Library

X
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
    Electronic Resource
    Electronic Resource
    Tamoxifen stimulates in vivo growth of drug-resistant estrogen receptor-negative breast cancer (1993)
    Springer
    Cancer chemotherapy and pharmacology 32 (1993), S. 396-398 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An estrogen receptor-negative, multidrug-resistant MDA-MB-A1 human breast cancer cell line was grown in culture with and without a noninhibitory concentration (0.5 μM) of tamoxifen for 122 days. Tamoxifentreated and control cells were inoculated into opposite flanks of nine nude mice, where they produced measurable tumors in every case. Six of the animals were treated with tamoxifen at 500 μg/day for 22 days. Although no inhibitory nor stimulatory effect of tamoxifen was seen in vitro, tamoxifen had a clear tumor-growth-stimulating effect in mice. The most pronounced stimulatory effects were observed in the cells that had been cultured with tamoxifen. Within 3 weeks of the start of tamoxifen therapy, the cells grown in the presence of tamoxifen produced tumors with a mean size of 380 mm2, whereas the cells not pretreated with tamoxifen had tumors of 220 mm2. In contrast, in mice not receiving tamoxifen, the sizes of the tumors were 190 and 140 mm2, respectively. These preliminary results suggest that prolonged in vitro tamoxifen exposure induces cellular changes that result in tumors that are stimulated to grow faster in mice following tamoxifen treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00735926
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Reduced tamoxifen accumulation is not associated with stimulated growth in tamoxifen resistance (1994)
    Springer
    Cancer chemotherapy and pharmacology 35 (1994), S. 149-152 
    Details
    ISSN: 1432-0843
    Keywords: Breast Cancer ; Tamoxifen ; Resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To study tamoxifen resistance-stimulated growth, 30 female ovariectomized nude mice were implanted with tamoxifen-resistant tumors and treated with 10–1000 μg/day of tamoxifen citrate subcutaneously. Tamoxifen stimulated MCF-7 tumor growth in a dose-dependent manner, with tumoral tamoxifen concentrations increasing proportionally to the dose (1–13 nmol/g), as measured by high-performance liquid chromatography (HPLC). Flow-cytometric analysis revealed that tamoxifen-resistant tumors had a different DNA content as compared with wild-type MCF-7 cells. In contrast to earlier results, these data suggest that tamoxifen resistance-stimulated growth is associated with increasing rather than decreasing tumoral tamoxifen concentrations. Furthermore, the observed ploidy changes in the tamoxifen-resistant tumors imply that a genetic basis may exist for the development of tamoxifen resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686638
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Reduced tamoxifen accumulation is not associated with stimulated growth in tamoxifen resistance (1994)
    Springer
    Cancer chemotherapy and pharmacology 35 (1994), S. 149-152 
    Details
    ISSN: 1432-0843
    Keywords: Key words Breast Cancer ; Tamoxifen ; Resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To study tamoxifen resistance-stimulated growth, 30 female ovariectomized nude mice were implanted with tamoxifen-resistant tumors and treated with 10–1000 μg/day of tamoxifen citrate subcutaneously. Tamoxifen stimulated MCF-7 tumor growth in a dose-dependent manner, with tumoral tamoxifen concentrations increasing proportionally to the dose (1–13 nmol/g), as measured by high-performance liquid chromatography (HPLC). Flow-cytometric analysis revealed that tamoxifen-resistant tumors had a different DNA content as compared with wild-type MCF-7 cells. In contrast to earlier results, these data suggest that tamoxifen resistance-stimulated growth is associated with increasing rather than decreasing tumoral tamoxifen concentrations. Furthermore, the observed ploidy changes in the tamoxifen-resistant tumors imply that a genetic basis may exist for the development of tamoxifen resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686638
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Toremifene and its metabolites enhance doxorubicin accumulation in estrogen receptor negative multidrug resistant human breast cancer cells (1992)
    Springer
    Investigational new drugs 10 (1992), S. 63-71 
    Details
    ISSN: 1573-0646
    Keywords: multidrug resistance ; toremifene ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The enhanced accumulation of doxorubicin by agents known to reverse multidrug resistance provides a good functional test for evaluating modulating activity. In the present study, the non-steroidal triphenylethylene toremifene selectively increased doxorubicin accumulation in multidrug resistant estrogen receptor negative MDA A-1 human breast cells compared to the MDA 231 wild type cells. MDA A-1 cells were noted to be 1,000 fold resistant to doxorubicin (IC 50=〈 0.1μg/ml MDA 231; IC 50=100μg/ml MDA A-1). Total accumulation of doxorubicin, expressed as area under the time concentration curve (AUC), was increased significantly in doxorubicin resistant cells (156% increase) versus wild type MDA 231 cells (6% increase). Correction of the accumulation defect to doxorubicin in drug resistant cells required a 18–20 hour pre-incubation with toremifene. The effects of toremifene on cell cycle in MDA A-1 cells was analyzed by flow cytometric techniques. Toremifene had a dose response relationship in blocking cells in G0–G1 reducing the number of cells entering S phase of the cell cycle. This effect was maximal at concentrations which increased the accumulation of doxorubicin in MDA A-1 cells. Several metabolites of toremifene were also noted to increase doxorubicin accumulation in MDA A-1 doxorubicin resistant cells. Tore XVIII (deaminocarboxytoremifene), Tore IV (4-hydroxy-N-desmethyltoremifene) and N-desmethyltoremifene all increased the accumulation of doxorubicin significantly (114%, 128% and 42% respectively). Finally, we show evidence that toremifene and its active metabolites are present in high concentrations in human plasma following a single 200 mg oral dose. Toremifene remains a very promising agent for modulating doxorubicin cytotoxicity in multidrug resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00873119
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    A bioassay for antiestrogenic activity — potential utility in drug development and monitoring effectivein vivo dosing (1992)
    Springer
    Breast cancer research and treatment 24 (1992), S. 35-41 
    Details
    ISSN: 1573-7217
    Keywords: antiestrogens ; bioassay ; tamoxifen ; toremifene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Monitoring effective antiestrogenic activity of the triphenylethylenes in patients with breast cancer is usually determined by the duration of response. The pharmacokinetics of toremifene and tamoxifen have been shown to be highly variable but patient specific. In the present study, we developed a method to accurately assess the antiestrogenic activity of these agents using plasma specimens, cell culture, and cell cycle measurements. Plasma specimens (4–5mls) obtained from patients receiving toremifene (360mg/day for 5 days in a phase I trial) or tamoxifen (20mg/day) were extracted and reconstituted in tissue culture media (4–5mls), and growth inhibition was determined in estrogen responsive MCF-7 cells. Additionally, plasma specimens were quantified for toremifene or tamoxifen concentrations using HPLC. Growth inhibition of plasma specimens containing either toremifene or tamoxifen and their metabolites was also examined. Cell cycle measurements were determined followingin vitro exposure with flow cytometric techniques. Our results show that a dose-response relationship exists between cell growth inhibition and cell cycle measurements for human plasma with added toremifene or tamoxifen, and also for human plasma specimens containing drug and its metabolites after treatment. Our antiestrogenic bioassay can address clinical research problems such as patient-specific pharmacokinetics, dosing compliance, and acquired antiestrogen resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01832356
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Monitoring the chemosensitizing effects of toremifene with flow cytometry in estrogen receptor negative multidrug resistant human breast cancer cells (1992)
    Springer
    Breast cancer research and treatment 24 (1992), S. 43-49 
    Details
    ISSN: 1573-7217
    Keywords: multidrug resistance ; toremifene ; flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The clinical study of compounds that modulate multidrug resistance in cancer cells has been hindered by both the toxicities of these agents and the inability to monitor their effectiveness at a cellular level. The non-steroidal triphenylethylene toremifene is well tolerated clinically and can sensitize multidrug resistant cells to the effects of doxorubicin in vitro. The chemosensitizing properties of toremifene in estrogen receptor negative, multidrug resistant MDA-A1 human breast cancer cells were studied using flow cytometric analysis. Cell cycle kinetics of MDA-A1 cells were not significantly affected by treatment with either toremifene or doxorubicin alone, as the majority of cells remained in G0/G1. However, preincubation with toremifene for 70 hours followed by treatment with doxorubicin caused a marked shift of cells to G2, as cells appeared to be blocked in that phase of the cell cycle. This result was nearly identical to the effect of doxorubicin alone on doxorubicin-sensitive MDA-MB-231 breast cancer cells and can be interpreted as a "resensitization" by toremifene of MDA-A1 cells to doxorubicin. This chemosensitizing effect of toremifene was accompanied by an enhanced accumulation of doxorubicin in MDA-A1 cells (+110% after 70 hours pre-incubation with toremifene), and by a depression in protein kinase C activity in MDA-A1 cells that was maximal following 70 hours incubation with toremifene. Flow cytometry is a widely available technique that might be applied clinically to monitor at the cellular level the chemosensitizing effects of toremifene and other modulators of multidrug resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01832357
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Flow cytometry: Potential utility in monitoring drug effects in breast cancer (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 57-65 
    Details
    ISSN: 1573-7217
    Keywords: antiestrogens ; breast cancer ; drug resistance ; flow cytometry ; tamoxifen ; toremifene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Flow cytometric analysis of DNA ploidy and S-phase fraction are well recognized prognostic indicators in breast cancer. The present paper deals with the widening of the applications of flow cytometry to monitoring the effectiveness of antiestrogen therapy, detecting clonal selection and emergence of drug resistance, and monitoring chemosensitizing properties of drugs. Antiestrogen activity can be studied by DNA flow cytometry to address clinical research problems such as patient-specific pharmacokinetics, dosing compliance, and acquired antiestrogen resistance. Patient plasma specimens containing various concentrations of triphenylethylenes can be monitored for drug-induced effects using cell cycle measurements and correlated toin vivo drug levels. DNA flow cytometry has also been instrumental in the study of the effects of prolonged low-dose (0.5 µM for 〉 100 days) tamoxifen treatment on human estrogen receptor negative MDA-MB-231 cells, where it was shown that tamoxifen may significantly alter cell cycle kinetics and tumorigenicity of these cells, selecting a new, more aggressive, and rapidly growing clone. Lastly, it has been shown that the chemosensitizing properties of another triphenylethylene antiestrogen, toremifene, on estrogen receptor negative, multidrug resistant MDA-MB-231-A1 human breast cancer cells can be studied using flow cytometric analysis. Toremifene (and its metabolites N-desmethyltoremifene and toremifene IV) are able to “resensitize” MDA-MB-231-A1 cells to vinblastine and doxorubicin, as reflected in a marked shift of cells to G2/M phase of the cell cycle. Flow cytometry is a widely available technique that might be applied clinically to monitor, at the cellular level, drug effects on tumors, including the modulators of drug resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666206
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 8
    Electronic Resource
    Electronic Resource
    Changes in drug sensitivity of a human astrocytoma clone previously treated with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea in vitro (1988)
    Springer
    Investigational new drugs 6 (1988), S. 293-298 
    Details
    ISSN: 1573-0646
    Keywords: drug resistance ; astrocytoma ; radiation ; nitrosourea ; adriamycin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have shown in earlier studies that repeated weekly exposures of a human astrocytoma clone (AST 3–4) to MeCCNU (10 μg/ml for 1 h per week) produced a linear decrease in survival over the first 3 weekly treatments. But, after that time these cells became progressively more resistant to the 10 μg/ml concentration of the agent. In the studies reported here we show that these previously treated cells were also less responsive to other doses ranging from 1 to 30 μg MeCCNU/ml. This change in sensitivity to MeCCNU was accompanied by collateral changes in response to other agents: resistance to BCNU and Galactitol, increased sensitivity to Adriamycin, and no change to ionizing radiation. These experiments suggest that once repeated treatments with a single agent cause a tumor cell population to become more resistant, sensitivity to other agents may also change unpredictably.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00173647
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 9
    Electronic Resource
    Electronic Resource
    Schedule dependent potentiation of antitumor drug effects by α-difluoromethylornithine in human gastric carcinoma cells in vitro (1990)
    Springer
    Investigational new drugs 8 (1990), S. S9 
    Details
    ISSN: 1573-0646
    Keywords: stomach cancer ; polyamines ; αDFMO ; heterogeneity ; cell killing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A clone of human gastric cancer cells (AGS-6) and the parental line (AGS-P) from which it was isolated were used in cell survival studies to determine whether pretreatment for 24, 48 or 72h with α-difluoromethylornithine (DFMO, 5mM) would increase the cell's sensitivity to 5-Fluorouracil (5FU), Adriamycin (Adria), 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (MeCCNU), or Bleomycin (Bleo). Generally, the AGS parental cells were most sensitive to the anticancer agents after exposures to DFMO. However, there was no way to predict in advance from DFMO-induced changes in ornithine decarboxylase (ODC), polyamine or cell kinetics values, how long an exposure to DFMO was required before sensitization to an anticancer agent occurred. The degree of potentiation for a single drug was variable from time to time during exposure to DFMO, and broad differences in the sensitizations were demonstrated among the four anticancer drugs. The AGS-6 clone exhibited little or no increased sensitivity as a result of pretreatment with DFMO, even though the DFMO-induced reductions in ODC and polyamine values in these cells were similar to those produced in the more sensitive parental line.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00171979
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...