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K H Schmidt-Ruppin

Publications and source records attributed to K H Schmidt-Ruppin.

14 recordsLinked to original sources
PubMed1989

CGP 6809, a sugar-containing nitrosourea derivative: pharmacological and physicochemical properties.

CGP 6809 is a water-soluble nitrosourea derivative with quite distinct chemical and biological properties as compared with the well-known representatives of this class of compounds. It is related to the antibiotic streptozotocin, from which it is distinguished in the structure of the sugar moiety and the position of the methylnitrosourea residue. CGP 6809 possesses practically the same alkylating potential as streptozotocin; however, its carbamoylating activity is comparable with that of CCNU. In contrast to other nitrosourea derivatives, CGP 6809 showed relatively little activity in murine leukemias but was markedly active in solid transplantable melanomas (Harding-Passay, B16), in the 11095 prostate carcinoma, and in a substrain of Yoshida hepatoma (AH 7974) resistant to BCNU and CCNU. In the Ehrlich and Yoshida ascitic tumors complete responses were seen with no toxic death. Dose-dependent activity was found in the human lung carcinoma MBA 9812 and almost complete growth inhibition was achieved in the human melanoma WM 47 by both the oral and parenteral routes of administration. However, mammary tumor lines (Ca 755, 2661/61, R-3230AC), the Guerin-T8 uterus epithelioma, and the Rous sarcoma/S-R proved to be relatively refractory to this drug. This was also the case for the Lewis lung carcinoma implanted i.m. or s.c. However, development of lung metastases was markedly inhibited. Combination therapy using CGP 6809 with cyclophosphamide, 5-fluorouracil, or chlorambucil in the same model led to partial responses of the primary tumor as well as almost total eradication of lung metastases.

Alkylation↗
PubMed1984

beta-Lapachone: synthesis of derivatives and activities in tumor models.

In order to find a 3,4-dihydro-2H-naphtho[1,2-b]pyran-5,6-dione more potent than the naturally occurring 2,2-dimethyl derivative [beta-lapachone (10a)], we synthesized a series of analogous compounds with modifications at position 2 of the pyran ring or at positions 8 and 9 of the benzene ring. Of the compounds tested in vitro for inhibition of RNA-dependent DNA polymerase and in mice infected with Rauscher leukemia, all retained good enzyme activity. Inhibition of the reverse transcriptase activity of the 2,2-substituted derivatives 10b-e was as strong as 10a. However, only the 2-methyl-2-phenyl derivative 10e proved to be about as potent as the 2,2-dimethyl reference compound 10a in prolonging the mean survival time of mice with Rauscher leukemia virus induced leukemia.

Animals↗
PubMed1981

Ureido-ethyl-imidazolines active against autochtonous diethylnitrosamine-induced epidermoid, papillary and adenocarcinomatous tumors of the respiratory tract of Syrian hamsters and against human bronchogenic carcinomas in nu/nu mice.

The detection of a new class of tumor inhibiting substances is described. Employing a chemical reaction discovered several years ago, a series of imidazolinylureas were prepared. It was found that some compounds of this group were active against diethylnitrosamine (DENA)-induced tumours in hamsters. CGP 15720 A (1-[2-[2-(4-pyridyl)-2-imidazoline-1-yl]-ethyl]-3-(4-carboxy-phenyl)urea. Xb), the most active compound at present, was developed through a series of structural variations. CGP 15720 A inhibits significantly in oral or parenteral treatment with well tolerated doses (10-30 mg/kg) the progressive growth of autochthonous, DENA-induced papillary, epidermoid and adenocarcinomatous tumors of the respiratory system in Syrian hamsters and prolongs significantly the survival. The substance also inhibits significantly the growth of 2 poorly differentiated human epidermoid or anaplastic bronchogenic carcinomas in nu/nu Balb/c mice and prolongs the mean survival time. In these mice, the substance is also active against the rodent ascites tumors Ehrlich carcinoma, CrSa 180 and Yoshida Sa AH 66, although it is only marginally active or inactive against these tumors in normal mice or rats.-In the therapeutic trials, hamsters tolerated the highest dose administered for 4 weeks, 1000 mg/kg p.o., without signs or symptoms of toxicity.

Animals↗
PubMed1976

Methodoloigcal study on examiniation of primary tumors of the respiratory tract "in toto" and histologically.

The results of histological evaluation of DENA-induced tracheobronchial tumors in the Syrian golden hamster are described and compared with those of an in toto method of visualization. In 55 animals, roughly twice as many tumors were detected in the lungs in the in toto preparation as those found by the histological technique [92:42]. The examiniation of the respiratory tract, as a whole, would consequently appear to afford an efficient and economical means of quantifying the effects of, for instance, chemotherapeutic agents in the growth of such tumors, which can subsequently be complemented, especially in the qualitative sense, by histological techniques.

Animals↗
PubMed1976

Regression of "hormone-independent" DMBA-induced mammary carcinomas in response to GP 48989 and its effects on hormone receptors.

GP 48 989 causes regression of DMBA-induced mammary carcinomas of spayed ("hormone-independent"), non spayed (approximately 5% "hormone-dependent") rats and of tumors which had become refractory to estradiol treatment. Since no binding to the cytoplasmic estradiol receptor after prolonged intramuscular treatment was found, the compound does not act as a classical anti-estrogen.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1975

Herpes genitalis in guinea-pigs. I. Kinetic study in infection with Herpesvirus hominis type 2.

The kinetics of virus replication after vaginal infection of guinea-pigs with HVH 2/Angelotti were studied in relation to the appearance of local and general symptoms. Most virus was isolated from the genital tract 24-48 hours post infection. Virus was first isolated from the spinal cord 48-72 hours post infection. Penetration into the brain only occurred occasionally, and later. Under the experimental conditions employed, no virus was found in the blood, spleen, kidneys, adrenals or inguinal lymph nodes. The local symptoms (typical genital herpes) and the general symptoms (paralysis and death) started after maximum virus replication had been reached and seemed to be a consequence of neural, rather than of haematogenic or lymphogenic spread.

Animals↗
PubMed1975

Herpes genitalis in guinea-pigs. II. Morphological studies in female guinea-pigs infected with Herpesvirus hominis type 2.

Gross and microscopial morphological changes developing in female guinea-pigs after vaginal infection with HVH 2/Angelotti were studied. In the mucosa of the external genital tract there were inflammatory changes with formation of intra-epithelial vesicles, erosions and ulcerations. In the late stages of the infection signs of inflammatory dysplasia were also observed. The infection spread into the nervous system and produced characteristic inflammatory changes. The inflammation began as a bilateral posterior myelitis and ascended in the course of infection through the upper spinal-cord towards the brain-stem. The morphological changes were preceded by increased virus replication in the respective tissues and were correlated in time with clinical symptoms. The morphological changes seen at the site of inoculation in the external genital tract of the guinea-pig bore a certain resemblance to those seen in some cases of human infection with the same type of virus.

Animals↗