Synergismus von Adriamycin mit 5-Fluor-Uracil, mit Prednisolon und mit Cyclophosphamid am autochthonen Mammacarcinom der Ratte

Hh, Fiebig; Schmähl, D.

doi:10.1007/bf01488582

Cited by 7 publications

(5 citation statements)

References 8 publications

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“…Better comparable to the human situation are autoch thonous cancers such as spontaneous tumors or after induction with chemical carcinogens or oncogenic viruses [23][24][25], Especially autochthonous mammary cancers, in duced by aromatic hydrocarbons, and acute leukemias of the rat, induced by cthylnitrosourea, seem comparable to the human mammary cancer and the acute leukemia [8][9][10][11]36], However, experiments with autochthonous tu mors are very expensive. Until today no new drugs effec tive in the clinic have been identified by these test sys tems.…”

Section: Significance O F Xenografts In Comparison To Experimental Tumentioning

confidence: 99%

“…In mice, trans plantable tumors include the leukemias LI 210 and P388, the melanoma B16, the Lewis lung carcinoma, the Ehrlich carcinoma and transplantable colon and mammary can cers [14,33], In rats the most frequently used tumors were the Walker carcinosarcoma 256, the Yoshida sarcoma, the DS carcinoma and the leukemia L5222 [3,8,13,36], However, many of these tumors showed differences in the long-term passage in comparison to the original tumor and to human tumors of the same category. In most cases, these transplantable tumors cannot be considered as typical models for the human cancer.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Development and Characterization of 51 Human Tumor Models for Large Bowel, Stomach and Esophageal Cancers

Fiebig¹,

Widmer²,

Fiedler³

et al. 1984

Dig Surg

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Out of 83 human colorectal and 44 stomach cancers transplanted subcutaneously in nude mice, tumor take was observed in 78 and 68 %, respectively. Progressive tumor growth (product of two tumor diameters . > 60 mm² after 90 days) was found in 49 and 32%. Serial passage was done in 46 colorectal and 17 stomach cancers. In 5 out of 6 esophageal cancers tumor take was found, and serial passage was performed in 4 tumors. Tumor stage was the most important factor for the take rate. Metastasized or locally advanced tumors of the large bowel and stomach were grown in 89 and 54%, respectively, which was significantly higher than in the localized stage. The take rate was independent of the degree of differentiation, the amount of fibrous tissue, CEA content, sex and tumor localization, except for tumors originating in the cardia in comparison to other parts of the stomach. The similarity of the xenografts in serial passage in comparison to the donor tumor was shown by histological and immunological (CEA) examinations. The presence of human isoenzymes such as esterase-D and LDH demonstrate the human origin of the tumors. However, most of the xenografts were growing more rapidly in the serial passage than in early passages. 31 comparisons of tumor response in the patient and in nude mice were made in 20 different tumors. The highly correct prediction rate for resistance (100%) and sensitivity (86%) validates the xenograft system. 34 colorectal, 14 stomach and 3 esophageal cancers were selected and characterized as tumor models. This tumor panel is continuously available for therapeutic and biological studies. For surgical purposes the xenografts can also be grown in athymic nude rats. The most relevant model for the clinic is available if the human tumors are implanted at the site of tumor origin.

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Section: Significance O F Xenografts In Comparison To Experimental Tumentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development and Characterization of 51 Human Tumor Models for Large Bowel, Stomach and Esophageal Cancers

Fiebig¹,

Widmer²,

Fiedler³

et al. 1984

Dig Surg

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“…The DMBA induced mammary cancer of the rat is less sensitive to chemotherapy than human mammary cancer. However, a good correlation is given in single agent therapy as well as in combination therapy, when in the DMBA induced tumor system the rates of remissions plus no changes are com pared with the remission rate in human breast cancer [16], The DMBA induced mammary cancer of the rat therefore is a useful tumor model for endocrinologic and chemo therapeutic studies.…”

Section: Discussionmentioning

confidence: 99%

“…A marked agreement exists in biologic properties [15], in their responsiveness to chemotherapy [16] and endocrine therapy [17,18]. Furthermore, specific estrogen receptors could be demonstrated in DMBA induced mammary tumors [19], This experimental tumor, therefore, has been used to compare the effectiveness of ovariectomy, the antiestrogen tamoxifen and combination chemotherapy of adriamycin and 5-fluorouracil (5-FU) in premenopausal mammary cancer of the rat.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Ovariectomy, Tamoxifen and the Combination Adriamycin and 5-FU on 7,12-Dimethylbenz(a)anthracene Induced Mammary Cancer of the Rat

Fiebig¹,

Schmähl²

1977

Oncology

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This study was carried out in order to compare the therapeutic effect of ovariectomy, of the antiestrogen tamoxifen and of the combination adriamycin and 5-fluorouracil (5-FU) in 7,12-dimethylbenz (a) anthracene (DMBA) induced premenopausal mammary cancer. 74 rats were randomized to receive (A) ovariectomy, (B) tamoxifen 14 mg/m², day 1–21, per os, (C) Tamoxifen 2,1 mg/m2, day 1–21, per os, (D) combination chemotherapy of adriamycin and 5-FU and (E) no therapy. 72 rats were evaluable. Ovariectomy was the most effective treatment resulting in five (36 %) complete and seven (50 %) partial remissions out of 14. Tamoxifen (B) yielded one (7 %) partial remission and seven (47 %) no changes out of 13 treated rats. Median tumor size was 0.5 g after ovariectomy and 3.9 g after tamoxifen (B) respectively. The level of significance was p < 0.001 for remmission rate and p < 0.001 for tumor size in favor of ovariectomy. Regimen (C) of tamoxifen showed marginal activity. Only minimal toxic effects could be observed after treatment with tamoxifen. The combination of adriamycin and 5-FU was somewhat more effective than tamoxifen but significantly (p < 0.05) less active than ovariectomy. The results obtained in this experimental model for mammary cancer suggest that tamoxifen cannot replace ovariectomy as the first endocrine therapy in the treatment of advanced mammary cancer in premenopausal women.

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“…Procedures for transplantation of Walker carcinosarcoma 256, induction of mammary tumors by DMBA as well as the experimental arrangement for therapy and evaluation parameters were described recently [7,[14][15][16]. Therapeutic indices (LD50/E D S0) were cal culated for subcutaneously implanted Walker 256.…”

Section: Tumorsmentioning

confidence: 99%

Anticancer Activity of New Nitrosoureas against Walker Carcinosarcoma 256 and DMBA-Induced Mammary Cancer of the Rat

Fiebig¹,

Eisenbrand²,

Zeller³

et al. 1980

Oncology

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Three new nitrosoureas and chlorozotocin were screened for anticancer activity against Walker carcinoma 256 and DMBA-induced mammary cancer of the rat. High single doses (80% of LD₅₀) of water-soluble l-(2-chloroethyl)-l-nitroso-3-(methylencarboxamido)urea and 2-[3-(2-chloroethyl)-3-nitrosoureido]ethyl-methansulfonate effected a similar tumor weight inhibition than BCNU in treatment of subcutaneously implanted Walker 256. In dose-response studies low doses of the new analogs effected a higher tumor weight inhibition than BCNU in the treatment of subcutaneously implanted Walker 256. The therapeutic index calculated as LD₅₀/ED₅₀, was 2.7 and 2.4 for the new compounds in comparison to BCNU with 2.1. Chlorozotocin and l-(methylenecarboxyethyl)-l-nitroso-3-phenylurea were not active. Against DMBA-induced mammary cancer the new BCNU analogs yielded a greater tumor weight inhibition than adriamycin and BCNU. At a dose-level of approximately LD10, the remission rates of individual tumors, which were at least 0.6 g at the beginning of treatment were 46% (13/28) for therapy with 2-[3-(2-chloroethyl)-3-nitrosoureido]ethylmethanesulfonate, 32% (9/28) for l-(2-chloroethyl)-l-nitroso-3-(methylenecarboxamido)urea, 26% (6/23) for chlorozotocin, 21% (7/33) for adriamycin and 17% for BCNU, respectively. As single agents the 2 new analogs 2-[3-(l-chloroethyl)-3-nitrossureido]ethylmethanesulfonate, the water-soluble 1-(2-chloroethyl)-l-nitroso-3-(methylenecarboxamido)urea and chlorozotocin were the most effective compounds against DMBA-induced mammary cancer of the rat.

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Synergismus von Adriamycin mit 5-Fluor-Uracil, mit Prednisolon und mit Cyclophosphamid am autochthonen Mammacarcinom der Ratte

Cited by 7 publications

References 8 publications

Development and Characterization of 51 Human Tumor Models for Large Bowel, Stomach and Esophageal Cancers

Development and Characterization of 51 Human Tumor Models for Large Bowel, Stomach and Esophageal Cancers

The Effect of Ovariectomy, Tamoxifen and the Combination Adriamycin and 5-FU on 7,12-Dimethylbenz(a)anthracene Induced Mammary Cancer of the Rat

Anticancer Activity of New Nitrosoureas against Walker Carcinosarcoma 256 and DMBA-Induced Mammary Cancer of the Rat

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