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Biomedical subjects

G Winterfeld

Publications and source records attributed to G Winterfeld.

8 recordsLinked to original sources
PubMed1992

Investigations of droloxifene and other hormone manipulations on N-nitrosomethylurea-induced rat mammary tumours. 1. Influence on tumour growth.

The effect of droloxifene, a new anti-oestrogenic drug, on N-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.

Animals↗
PubMed1992

Investigations of droloxifene and other hormonal manipulations on N-nitrosomethylurea-induced rat mammary tumours. 2. Influence on oestrogen receptor.

In N-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 in breast tumour tissue of human beings. In summary: receptor investigations of N-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.

Aminoglutethimide↗
PubMed1990

Development of a mitoxantrone-resistant P 388 in vivo: approaches to overcome resistance.

A normally, relatively sensitive P 388 developed resistance within few passages (P 388/Mitox) by in vivo treatment with suboptimal doses (1 mg/kg i.v.) of mitoxantrone. This resistance remained stable over 50 generations without further drug treatment. Immunization with irradiated cells (30 Gy) 7 days before tumor challenge led to partial rejection, proving that there was a higher immunogenicity of the resistant line in comparison to the parenteral P 388 line. The P 388/Mitox showed cross-resistance towards doxorubicin, daunorubicin and vincristine. Cis-DDP and bleomycin had in the resistant line significantly better antineoplastic efficacy than in the source P 388 and should be taken into consideration as second-line therapy following development of clinical mitoxantrone resistance. Nifedipine, a calcium channel blocker, and the immunosuppressive agent ciclosporin A were able to overcome resistance partially, but the mechanisms are still unclear. The P 388/Mitox can be considered as an interesting in vivo model for further research concerning resistance mechanisms and reversal of resistance.

Animals↗
PubMed1976

[Studies for a mathematical model of the proliferation kinetics of mammary carcinomas by means of electronic data processing (author's transl)].

Continuing an earlier publication in which the growth of spontaneous mammary carcinomas in female mice of a C3H inbred strain was described, in the present paper the growth rate is expressed by a mathematical function, and is adapted by electronic data processing to the experimental values of 60 tumors classified into seven "growth types". For mathematical description the tumors were conveniently assumed to have a spherical shape, and the main reason for the reduction in volume increase with increasing tumor size was thought to be insufficient supply with oxygen and the essential nutrients S. Including the experimental data of all carcinomas investigated, the minimum concentration of S necessary for mitotic activity of the tumor cells was calculated to be 65% of the normal level. As the average for all the tumors investigated, a time of at least 33 hrs is required for the tumor volume to double.

Animals↗
PubMed1975

[Studies on the growth rate of spontaneous mammary carcinomas in C3H inbred mice (author's transl)].

The incidence of spontaneous mammary carcinomas was determined in the C3H mouse inbred colony reared in Berlin-Buch over the past three years. Only female animals reaching a lifespan of no less than 170 days, corresponding to the longevity of the shortest lived animal in which a mammary carcinoma developed, were included in the study. A 50% incidence of mammary carcinomas was found with female animals above one year of age. The median age for the incidence of tumours was 446 days. Related to tumour-free females which at least have reached the median tumours age, the proportion of females developing mammary carcinomas was 86.8%. With increasing litters the tumour latency decreased from 491 for monoparous females to 383 days for mothers with 7 to 8 litters. The growth rate of 60 tumours under observation was found to vary grossly. With the minimum volume doubling time being the same in all cases, the growth rate of the tumours varied according to longer or shorter phases of stagnation or delay. Tumours having approximately equal growth rates throughout the period of investigation were classified as a "growth type". Altogether, seven growth types for spontaneous mammary carcinomas were established.

Animals↗
PubMed1975

[Possible quantification of vascularization and of non-proliferating, hypoxic and nerotic proportions of lung cancer in man (author's transl)].

In hematoxylin-eosin stained quatorial sections of 14 human bronchial tumors, the relative proportions of different tissue elements were determined in two perpendicular planes, 500 and 200 mu wide, using the target principle. Data characterizing the level of necrotization of these tumors have revealed a poor supply of oxygen and nutritive substances to tumors in which large stroma areas were alternating with large fields of tumor parenchyma. As anticipated, necrotization increases with increasing size of the tumor. A network of narrow stroma strips in the tumor affords a more favourable supply of the cells. The proportions of necrotic, hypoxic and GO areas were calculated.

Blood Vessels↗