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  • 1
    Electronic Resource
    Electronic Resource
    Synergismus von Adriamycin mit 5-Fluor-Uracil, mit Prednisolon und mit Cyclophosphamid am autochthonen Mammacarcinom der Ratte (1977)
    Springer
    Journal of molecular medicine 55 (1977), S. 445-450 
    Details
    ISSN: 1432-1440
    Keywords: Experimental mammary cancer ; Adriamycin ; Single agent therapy ; Combination therapie ; Tierexperimentelles Mammakarzinom ; Adriamycin ; Monotherapie ; Kombinationstherapie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Am autochthonen Mammacarcinom der Ratte wurden in einer prospektiven, randomisierten Studie 7 klinisch wirksame Zytostatika in der Monotherapie und in Zweierkombinationen bei simultaner Gabe geprüft. In der Monotherapie zeigten alle 7 Zytostatika eine Tumorhemmung im Vergleich zur Kontrolle. Remissionsraten wie beim Mammacarcinom der Frau wurden mit den gewählten Dosierungen und Therapieschemen nicht erreicht. Ein in der Monotherapie vergleichbares, relatives Ansprechen wie in der Klinik wird erzielt, wenn neben den Remissionen die unter der Therapie stationär gebliebenen Tumoren als Therapieerfolg gewertet werden. Bei der Kombinationstherapie führten Adriamycin und 5-Fluor-Uracil in 62% (p〈0,05), Adriamycin und Prednisolon in 81% (p〈0,01), sowie Adriamycin und Cyclophosphamid in 54% zu Remissionen oder No Change gegenüber 30% bei der Monotherapie mit Adriamycin. Die drei genannten Kombinationen waren wirksamer als das Cooper-Schema. Nur die Kombination Adriamycin und Cyclophosphamid ergab eine Zunahme der Toxizität bei gleicher Dosierung wie bei der Monotherapie. Adriamycin und Vincristin zeigten keinen therapeutischen Synergismus. Die Kombinationstherapie führte zu höheren Remissions-No Change-Raten als die Monotherapie (p〈0,001). Wir schlagen vor, das Produkt der Parameter Respondrate und -dauer als Responderwartung zur Bewertung eines Therapieverfahrens in die Klinik einzuführen. Das vergleichbare relative Ansprechen in der Monotherapie sowie die Übereinstimmung mit zwei klinisch geprüften Kombinationen weisen auf die Übertragbarkeit chemotherapeutischer Ergebnisse vom autochthonen Mammacarcinom der Ratte auf das menschliche Mammacarcinom hin.
    Notes: Summary In a prospectively planned and randomised study 7 clinically active anti-cancer agents were tested as single-agents and in double-combinations by simultaneous application against the autochthonous mammary cancer of the rat. In single therapy all 7 anticancer agents displayed tumor inhibition in comparison to the control rats. Remission rates similar to those obtained in the mammary cancer of the woman could not be obtained at the dosages and schedules chosen. Single therapy produces an effectiveness which is relatively comparable to clinical treatment if, in addition to remissions the tumors remaining stationary are also considered as a therapeutic success. In combination chemotherapy, Adriamycin and 5-Fluor-Uracyl resulted in remission or no change in 62% (p〈0.05), Adriamycin and Prednisolone in 81% (p〈0.01), and Adriamycin and Cyclophosphamide in 54%; in contrast, the single therapy with Adriamycin showed remissions or no change in 30%. The 3 combinations above were more effective than the Cooper regimen. When a same dosage and schedule in combination therapy was used as in single therapy, only the combination of Adriamycin and Cyclophosphamide produced an increase of toxicity. Adriamycin and Vincristin showed no therapeutic synergism. Combination chemotherapy resulted in higher remission/no change rate than single therapy (p〈0.001). For clinical evaluation of treatment modalities we propose to introduce the product of responserate and response-duration as the response-expectation. The comparable relative effectiveness of the single therapy and the results of combination therapy which correspond to 2 clinically tested combinations suggest that the results of chemotherapeutic treatment of autochthonous mammary cancer of the rat can be extrapolated to human mammary cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01488582
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  • 2
    Electronic Resource
    Electronic Resource
    Synthesis, mechanism of action, and biological evaluation of mitosenes (1989)
    s.l. : American Chemical Society
    Journal of medicinal chemistry 32 (1989), S. 1612-1620 
    Details
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jm00127a035
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  • 3
    Electronic Resource
    Electronic Resource
    Short communication: Deletion 7q, trisomy 6 and 11 in a case of Merkel-cell carcinoma
    Amsterdam : Elsevier
    Cancer Genetics and Cytogenetics 33 (1988), S. 305-309 
    Details
    ISSN: 0165-4608
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0165-4608(88)90039-8
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  • 4
    Electronic Resource
    Electronic Resource
    Preclinical phase II study of ifosfamide in human tumour xenografts in vivo (1990)
    Springer
    Cancer chemotherapy and pharmacology 26 (1990), S. S7 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The in vivo effects of the oxazaphosphorine compound ifosfamide (IFO) on human tumour xenografts were assessed in thymus aplastic nude mice. The human origin of the tumours was confirmed by isoenzymatic and immunohistochemical methods. Tumour models were selected from a panel of 180 regularly growing, well-characterized xenografts. The maximum tolerated dose in tumour-bearing nude mice was determined to be 130 mg/kg per day given on days 1–3 and 15–17. After 21 days, lethality was 14% after i.p. and 6% after s.c. administration. A total of 43 human tumours were tested for antineoplastic activity, 15 of which (36%) showed regression: 4/5 breast cancer xenografts, 1/3 colon, 1/1 gastric, 2/7 non-small-cell lung cancers (NSCLC), 3/4 small-cell lung cancers (SCLC), 1/2 sarcomas and 3/3 testicular cancers. Two ovarian, two uterine and six renal cancer xenografts as well as three melanomas and five tumours of various histologies were resistant. In 30 human tumour xenografts, the antineoplastic efficacy of the two oxazaphosphorine derivatives cyclophosphamide and IFO was compared. The maximum tolerated dose of cyclophosphamide was 200 mg/kg per day given i.p. on days 1 and 15; it led to 17% lethality after 21 days. Cyclophosphamide induced tumour regression or remission in 10/30 xenografts (33%) and IFO in 13/30 (43%). In conclusion, the observed efficacy of IFO parallels the clinical situation. Breast, lung and testicular cancer and sarcomas proved to be responsive. The antitumoural activity of IFO shows similarities to that of cyclophosphamide; however, a higher response rate and lower toxicity were noted for the former. Preclinical phase II studies in nude mice seem to offer an effective way of identifying active drugs as well as sensitive tumour types for further clinical development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685408
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  • 5
    Electronic Resource
    Electronic Resource
    Development of meningeal leukemia in rats by intracerebral or intrameningeal inoculation of the acute transplantable leukemia L 5222 (1976)
    Springer
    Journal of cancer research and clinical oncology 86 (1976), S. 287-292 
    Details
    ISSN: 1432-1335
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Ein tierexperimentelles Modell einer meningiosis leucaemica bei der Ratte wird erreicht durch intracerebrale oder intrameningeale Verimpfung von Zellen der transplantablen akuten Rattenleukämie L 5222. Das histopathologische Bild entspricht demjenigen, wie es bei der menschlichen meningiosis leucemica gefunden wird. 2 Tage nach der intracerebralen Transplantation ist die Leukämie L 5222 generalisiert.
    Notes: Summary An experimental model of meningeal leukemia is developed by intracerebral or intrameningeal inoculation of cells from the transplantable acute rat leukemia L 5222. The histopathological pattern is similar to that observed in central nervous system leukemia in man. The leukemia L 5222 becomes systemic 2 days after intracerebral inoculation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00286947
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  • 6
    Electronic Resource
    Electronic Resource
    Examination of four newly synthesized 2-chloroethylnitrosoureas in comparison with BCNU, CCNU, MeCCNU, chlorozotocin and hydroxyethyl-CNU in preterminal rat leukemia L 5222 (1979)
    Springer
    Journal of cancer research and clinical oncology 95 (1979), S. 43-49 
    Details
    ISSN: 1432-1335
    Keywords: 2-Chloroethylnitrosoureas ; Leukemia L 5222 ; Rat ; 2-Chlorethylnitrosoharnstoffe ; Leukämie L 5222 ; Ratte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die therapeutische Aktivität der vier neusynthetisierten Nitrosoharnstoffe 1-(2-Chlorethyl)-1-nitroso(3-methylencarboxamido)-harnstoff (Acetamido-CNU), 1-(2-Chlorethyl)-1-nitroso-3-(4-morpholino)-harnstoff (Morpholino-CNU), 1-(2-Chlorethyl)-1-nitroso-3-(1-piperidino)-harnstoff (Piperidino-CNU) und 2-[3-(2-Chlorethyl)-3-nitrosoureido]-ethylmethansulfonat (Ethylmethansulfonato-CNU) wurde an der präterminalen Rattenleukämie L 5222 mit der Wirkung von BCNU, CCNU, MeCCNU, Chlorozotocin und Hydroxyethyl-CNU verglichen. MeCCNU war den anderen Substanzen im Hinblick auf den breiten Dosisbereich, in dem eine mediane Überlebenszeit von 〉90 Tagen bewirkt wurde, überlegen. Chlorozotocin dagegen bewirkte als einzige Substanz in dieser Versuchsanordnung keine Heilungen. Von den neu vorgestellten Substanzen waren die wasserlöslichen Verbindungen Acetamido-CNU und Morpholino-CNU im Hinblick auf die Breite des Dosisbereiches, in dem eine mediane Überlebenszeit von 〉90 Tagen erzielt wurde, annähernd dem CCNU vergleichbar. Piperidino-CNU und Ethylmethansulfonato-CNU bewirkten auch Heilungen; jedoch wurde nur mit einer Dosierung von Piperidino-CNU eine mediane Überlebenszeit von 〉90 Tagen erreicht.
    Notes: Summary The newly synthesized nitrosoureas 1-(2-chloroethyl)-1-nitroso-3-(methylenecarboxamido)-urea (Acetamido-CNU), 1-(2-chloroethyl)-1-nitroso-3-(4-morpholino)-urea (Morpholino-CNU), 1-(2-chloroethyl)-1-nitroso-3-(1-piperidino)-urea (Piperidino-CNU), and 2-[3-(2-chloroethyl)-3-nitrosoureido]-ethylmethanesulfonate (Ethylmethanesulfonato-CNU) were compared in their chemotherapeutic activity against preterminal rat leukemia L 5222 with BCNU, CCNU, MeCCNU, Chlorozotocin, and Hydroxyethyl-CNU. With respect to the dose range effecting a median survival time of more than 90 days, MeCCNU was superior to the other substances. Chlorozotocin, on the other hand, was the only substance which achieved no cures in this experimental arrangement. From the four newly introduced substances the water-soluble substances Acetamido-CNU and Morpholino-CNU were approximately comparable to CCNU with regard to the dose range effecting a median survival time of 〉90 days. Piperidino-CNU and Ethylmethanesulfonato-CNU also effected cures; however, only Piperidino-CNU in one dosage effected a median survival time of 〉90 days.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00411108
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  • 7
    Electronic Resource
    Electronic Resource
    Some new congeners of the anticancer agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) synthesis of bifunctional analogs and water soluble derivatives and preliminary evaluation of their chemotherapeutic potential (1976)
    Springer
    Journal of cancer research and clinical oncology 86 (1976), S. 279-286 
    Details
    ISSN: 1432-1335
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Synthese neuer Analoge von BCNU wird beschrieben. Sie beruht auf der Herstellung von N-(2-Chloräthyl)-N-nitrosocarbamoyl Azid und dessen Umsetzung mit aliphatischen Diaminen und Aminoalkoholen zu den entsprechenden 1,1′-Polymethylenbis-3-(2-chloräthyl)-3-nitrosoharnstoffen, sowie 1-(ω-Hydroxyalkyl)-3-(2-chloräthyl) 3-nitrosoharnstoffen. Die Prüfung der chemotherapeutischen Wirksamkeit der neu synthetisierten Nitrosoharnstoffe gegen die Rattenleukämie L 5222 und gegen das s.c. Walker Carcinosarkom 256 ergab bemerkenswerte Unterschiede zwischen den einzelnen Verbindungen. Der wasserlösliche 1-(2-Hydroxyäthyl)-3-(2-chloräthyl)-3-nitrosoharnstoff war die wirksamste Verbindung dieser Reihe; er ergab 90% Heilungen bei der Rattenleukämie L 5222.
    Notes: Summary The synthesis of new analogs of the anticancer agent BCNU is described. It involves the preparation of N-(2-chloroethyl)-N-nitrosocarbamoylazide and its reaction with aliphatic diamines and aminoalcohols to yield 1,1′-polymethylenebis 3-(2-chloroethyl)-3-nitrosoureas and 1-(ω-hydroxyalkyl)-3-(2-chloroethyl)-3-nitrosoureas. Screening for chemotherapeutic activities of the newly synthesized nitrosoureas against rat leukemia L 5222 and s.c. Walker carcinosarcoma 256 revealed remarkable differences between individual compounds. The water soluble 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea was the most active compound of this series, effecting 90% cures in i.p. inoculated L 5222 leukemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00286946
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  • 8
    Electronic Resource
    Electronic Resource
    Experimental chemotherapy with N′N′-bis(2-chloroethyl)-N-nitrosourea (BCNU) in autochthonous neurogenic tumors of the rat transplacentally induced by ethylnitrosourea (1982)
    Springer
    Journal of cancer research and clinical oncology 104 (1982), S. 89-98 
    Details
    ISSN: 1432-1335
    Keywords: Autochthonous primary neurogenic tumors ; Rat ; Transplacental induction ; Chemotherapy ; BCNU
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Autochthonous neurogenic tumors of the rat induced by transplacental application of ethylnitrosourea were used for the first time to study their suitability as tumor models for experimental chemotherapy. Of 189 transplacentally treated rats, 87% developed neurogenic tumors. After the initial clinical diagnosis of a neurogenic tumor, additional malignant tumors often occurred. The mean number of neurogenic tumors from 62 untreated control rats increased from 1.0 per rat at the time of randomization to 1.2 as revealed by autopsy and 1.5 tumors by histological examinations. Out of all neurogenic tumors, tumors of the brain were observed in 31%, tumors of cranial nerves in 36% (90% tumors of trigeminal nerve), tumors of spinal cord in 21%, and tumors of peripheral nerves in 10%. The median survival time until natural death of 62 control rats was 228 days. Rats with tumors of peripheral nerves lived shortest, followed by rats with tumors of cranial nerves, tumors of the spinal cord, and brain tumors. Brain tumors were mainly astrocytomas and oligodendrogliomas. The survival time of untreated rats from randomization to natural death was longest for those with brain tumors, followed by tumors of peripheral nerves, cranial nerves, and tumors of the spinal cord. There was great variation in survival time from a few days to more than 6 months. To study the responsiveness to chemotherapy, 62 rats received BCNU as a single intravenous dose of 9 and later 10 mg/kg. Sixty-two untreated control rats had a median survival time of 36 days (95% confidence interval 26–52 days), the treated rats 43.5 days (26–62 days) The difference was not statistically significant. BCNU produced a remission or a no change of neurologic symptoms in 60% (37 out of 62) in comparison to 39% (24 out of 62) in the control group (p〈0.05). The advantages and disadvantages of the present models are discussed. Due to methodical problems and the marginal response to BCNU, autochthonous neurogenic tumors of the rat are not suitable as models for chemotherapeutic studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402057
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  • 9
    Electronic Resource
    Electronic Resource
    Clonal growth of human tumor xenografts (1984)
    Springer
    Journal of cancer research and clinical oncology 108 (1984), S. 233-235 
    Details
    ISSN: 1432-1335
    Keywords: Clonal growth ; Human tumor xenografts ; Drug testing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human tumors growing as nude mice xenografts were investigated for growth in a clonogenic assay. Colony formation of more than 30 colonies per plate was obtained in 47 of 63 tumors examined (74.6%). The growth rate was enhanced by raising the concentration of fetal calf serum in the culture medium. Plating efficiency ranged from 0.0003% to 5.5%. To study the applicability of this model for screening new anticancer drugs, preliminary studies in drug sensitivity were conducted with continuous incubation of different anticancer drugs in a dose range of 1/10 to 10 times the maximum achievable plasma level. The highest concentration almost always led to a complete suppression of colony growth. In our opinion the procedure described may be a useful combination of two methods in predictive drug testing, provided drug concentration and mode of drug incubation are adequately considered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402473
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  • 10
    Electronic Resource
    Electronic Resource
    L1210 leukemia i. v. implanted as a model for testing short-chain nitrosourea analogs (1986)
    Springer
    Journal of cancer research and clinical oncology 111 (1986), S. 31-34 
    Details
    ISSN: 1432-1335
    Keywords: Nitrosourea analogs ; L1210 Leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A total of 11 newly synthesized 2-chloroethyl-nitrosoureas and 1 2-fluoroethylnitrosourea with short-chain substituents were tested for their cytostatic activity on the L1210 mouse leukemia in comparison to clinically used nitrosoureas. Initial experiments showed advantages of the i.v. route for tumor inoculation. Therefore, the anatomical generalisation of tumor cells after i.v. injection was studied by bio-assay. Tumor cell determinations in different organs were 10 to 100 times higher compared with i.p. implantation. Of the new compounds 10 showed marked cytostatic activity in this tumor model by producing cures, and 5 of them must be considered as superior to BCNU, the most commonly used nitrosourea.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402772
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