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  • 1
    Electronic Resource
    Electronic Resource
    Investigations of droloxifene and other hormone manipulations onN-nitrosomethylurea-induced rat mammary tumours (1992)
    Springer
    Journal of cancer research and clinical oncology 119 (1992), S. 91-96 
    Details
    ISSN: 1432-1335
    Keywords: NMU-induced rat mammary tumours ; Hormonal manipulation ; Droloxifene ; Tumour growth behaviour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of droloxifene, a new anti-oestrogenic drug, onN-nitrosomethylurea-induced mammary tumours of Sprague-Dawley rats was investigated and compared with that of tamoxifen. The response of tumour growth to ovariectomy or to treatment with aminoglutethimide or high doses of oestradiol was also studied. Ovariectomy was by far the most effective treatment for mammary-tumour-bearing animals. More than 75% of the tumours in ovariectomized rats did not grow progressively but remained in remission for up to 12 weeks after castration when the experiment was terminated. The inhibitory effects of droloxifene and tamoxifen on mammary tumour growth were similar, but body weight loss of animals treated with tamoxifen was more marked than that of animals treated with droloxifene at the same dose and schedule.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01209662
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of sterically stabilized hexadecylphosphocholine liposomes versus conventional liposomes and free hexadecylphosphocholine in tumor-free and human breast carcinoma bearing mice (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 71-80 
    Details
    ISSN: 1573-7217
    Keywords: hexadecylphosphocholine ; human breast carcinoma ; pharmacokinetics ; sterically stabilized liposomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics of free and different liposomal formulations of hexadecylphosphocholine (HPC) was investigated in tumor-bearing (human mammary tumor MaTu) and tumor-free mice after intravenous and intraperitoneal administration. The levels of HPC were evaluated at different times in serum, normal tissues, and tumor. The purpose was to test the hypothesis that the enhanced therapeutic efficacy of sterically stabilized HPC liposomes in comparison to conventional vesicles and free HPC is due to its pharmacokinetics. Conventional non-compartmental pharmacokinetic analysis and an elaborate three- and four-compartmental model were used for explaining the experimental data. The serum levels of HPC obtained with sterically stabilized liposomes were only consistently higher in comparison to conventional vesicles and free HPC in the first 4 h. In the xenografted MaTu carcinoma, the differences of the HPC content between the different groups are unexpectedly low and do not reflect the high therapeutic activity [5] of sterically stabilized HPC liposomes. Detailed analysis shows that the liposomally encapsulated drug displays a modified pharmacokinetic behavior, which may also involve lymphatic absorption of the liposomal drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006224611505
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  • 3
    Electronic Resource
    Electronic Resource
    Antineoplastic activity of sterically stabilized alkylphosphocholine liposomes in human breast carcinomas (1997)
    Springer
    Breast cancer research and treatment 43 (1997), S. 237-246 
    Details
    ISSN: 1573-7217
    Keywords: alkylphosphocholine ; hexadecylphosphocholine ; human breast carcinoma ; sterically stabilized liposomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract New sterically stabilized liposomes derived from the antitumoragent hexadecylphosphocholine with reduced uptake by the mononuclearphagocyte system and improved antitumor activities were developedand tested. The bilayer of such sterically stabilizedliposomes consists of hexadecylphosphocholine, cholesterol and polyethylene glycol-linkedphosphoethanolamine. The measurement of carbon clearance in miceshows that these stabilized liposomes, in contrast toconventional alkylphosphocholine liposomes, are not largely engulfed bythe mononuclear phagocyte system. Their therapeutic activity onexperimental human breast carcinomas MaTu, MT-1 and MT-3was tested in nude mice. Especially in theMaTu models the sterically stabilized hexadecylphosphocholine liposomes resultedin significantly reduced tumor growth in comparison toconventional hexadecylphosphocholine liposomes or free hexadecylphosphocholine. The enhancedtherapeutic efficacy of sterically stabilized hexadecylphosphocholine liposomes isprobably related to the extended circulation time ofthe formulation and its accumulation in tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005798715192
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  • 4
    Electronic Resource
    Electronic Resource
    Investigations of droloxifene and other hormonal manipulations onN-nitrosomethylurea-induced rat mammary tumours (1992)
    Springer
    Journal of cancer research and clinical oncology 119 (1992), S. 97-100 
    Details
    ISSN: 1432-1335
    Keywords: Droloxifene ; Endocrine-acting drugs ; NMU-induced rat mammary carcinoma ; oestradiol receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary InN-nitrosomethylurea-induced rat mammary tumours, tamoxifen is found to compete at the binding sites of the oestradiol receptor if a receptor determination is performed 1 day following the last drug application to animals. Despite a higher binding affinity of droloxifene (3-OH-tamoxifen) to oestradiol receptor, compared to tamoxifen, its influence on the measurable receptor quantity is only very weak or not demonstrable. Therefore, binding affinity is not a valid explanation for the different influences of the two anti-oestrogens on the receptor. These only can be attributed to different behaviour patterns of both substances in relation to their half-lives and metabolism and accumulation in the organism. Owing to the short half-life of droloxifene, even 1 day after the last application too little drug is available to compete for oestradiol binding sites. In the case of both anti-oestrogenic substances, cessation of drug application for 8 weeks abolished any influence on the oestradiol receptor. Furthermore, failure of aminoglutethimide to influence the oestradiol receptor could be observed because this substance does not act via this receptor. The experiments performed confirm literature data regarding the effect of aminoglutethimide therapy on oestradiol receptors breast tumour tissue of human beings. In summary: receptor investigations ofN-nitrosomethylurea-induced rat mammary tumours, used as a model to test therapy regimens with droloxifene or other drugs with a short half-life, may be of limited value only.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01209663
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  • 5
    Electronic Resource
    Electronic Resource
    Antineoplastic activity of alkylphosphocholines (APC) in human breast carcinomasin vivo andin vitro; use of liposomes (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 269-279 
    Details
    ISSN: 1573-7217
    Keywords: alkykphosphocholines ; breast carcinoma ; eicosanylphosphocholine ; hexadecylphosphocholine ; liposomes ; nude mice ; octadecylphosphocholine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study examines thein vitro andin vivo activity of alkylphosphocholines (APC) in experimental human breast carcinomas. Three analogs, hexadecylphosphocholine (HPC), octadecylphosphocholine (OPC) and eicosanylphosphocholine (EPC) were investigated. Three hormone receptor negative cell lines were sensitive to all three APCsin vitro whereas the receptor positive MCF-7 line was more resistant. Sensitivity was seen in 4/6 hormone receptor negative tumorsin vivo, with HPC being the most active analog. There were no antitumor effects in the four receptor positive models. The reasons for these differences in response between hormone receptor negative and -positive lines are not yet understood and require further study. Gastrointestinal toxicity and hemolysis, the major side effects of the APCs, were reduced by the use of liposomal preparations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666004
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  • 6
    Electronic Resource
    Electronic Resource
    Characterization of two human mammary carcinomas, MT-1 and MT-3, suitable forin vivo testing of ether lipids and their derivatives (1992)
    Springer
    Breast cancer research and treatment 23 (1992), S. 87-95 
    Details
    ISSN: 1573-7217
    Keywords: experimental chemotherapy ; ether lipids ; human mammary carcinoma ; nude mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The human mammary carcinomas MT-1 and MT-3 originate from surgical material and were transplanted in nude mice. Both tumors have been classified as estradiol- and progesterone receptor-negative. Therapeutic doses of hormones and anti-hormones remained without growth inhibitory effect. MT-1 and MT-3 proved to be sensitive to conventional cytostatic drugs used for treatment of mammary carcinomas; striking is their sensitivity to ether lipids. Therefore, they are considered suitable tumor models for this class of substances.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01831480
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  • 7
    Electronic Resource
    Electronic Resource
    Differences in immunoreactivity of estrogen receptor (ER) in tamoxifen-sensitive and -resistant breast carcinomas: preclinical and first clinical investigations (2000)
    Springer
    Breast cancer research and treatment 60 (2000), S. 81-92 
    Details
    ISSN: 1573-7217
    Keywords: breast carcinoma ; estrogen receptor ; immuno assay ; tamoxifen ; xenograft
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Inherited or acquired tamoxifen resistance is a major constraint in the endocrinological treatment of breast carcinomas. We developed an enzyme-immunoassay that discriminates between tamoxifen-sensitive and -resistant tumors. The procedure was established and standardized using two xenografted breast carcinomas – 3366 (highly sensitive to tamoxifen) and 3366/TAM (acquired tamoxifen resistance). The latter model was developed by treatment of 3366 tumor-bearing nude mice during serial passaging over 3 years with tamoxifen. Both lines were estrogen receptor (ER) positive (101 or 82 fmol/mg protein), and revealed no differences in the nucleotide sequences of the hormone binding domain of the ER protein. However, while in the sensitive tumors an upregulation of ER levels was registered after estradiol treatment of tumor bearing nude mice, the ER expression in the resistant line remained unchanged. The tamoxifen sensitive and -resistant breast carcinoma 3366 differed, additionally, in their immunoreactivity of ER to mAB H222. While an incubation with estradiol or tamoxifen of immobilized ER prepared from cytosols of the sensitive tumors 3366 led to a significant increase in immunoreactivity, samples of resistant tumors failed in the exposition of additional immunologically reactive epitopes. These results were the basis for the development of an assay for determination of the tamoxifen response in patients. Our retrospective results with 38 breast tumors from a tumor bank indicated that patients with an increase of immunoreactivity of ER more rarely had a recurrence while under going tamoxifen therapy compared with patients expecting no increase. However, the data indicate interesting changes occurring with the ER of tam-resistant tumors that are to be explained by further mutational or protein-chemical analysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006334131241
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