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Biomedical subjects

M R Berger

Publications and source records attributed to M R Berger.

At least 145 records · Page 8Linked to original sources
PubMed1985

Effect of different diets on the ratio of plasma lipids/vitamin A and E in female Sprague-Dawley rats with MNU-induced mammary carcinomas.

An inverse relationship between vitamin A uptake and cancer as well as serum cholesterol concentration and cancer has been shown. An inverse relationship between serum cholesterol and retinol has also been reported. In a study, in which female Sprague-Dawley rats with MNU-induced mammary tumors were fed diets containing different amounts of fat and vitamins A and E, the effect of these diets on the inverse association between the cancer risk and both plasma lipids and vitamin A, E was investigated. According to the data obtained there is not only a relationship between plasma cholesterol and vitamin A, but also a similar relationship between cholesterol and vitamin E. The relationship between triglycerides and the two vitamins was also parallel to that of the cholesterol-vitamin A relationship. The interactions between cancer, plasma lipids and vitamin A, E could be modified by certain diets. However, further studies will be needed to elucidate these interactions.

Animals↗
PubMed1984

Antineoplastic activity of ASTA Z 7557 (INN mafosfamide) in transplanted and autochthonous experimental rodent tumors.

The antineoplastic activities of ASTA Z 7557 and cyclophosphamide (CPA) were compared in advanced transplanted AKR lymphoma by determining the optimal dose using single dose and twofold applications. Autochthonous DMBA-induced leukemias and MNU-induced mammary carcinomas were treated with fractionated doses over 3 and 5 weeks, respectively. In the respective optimal dosages ASTA Z 7557 exhibited an antitumor effect comparable to that of CPA in all three models. The results obtained by treatment of the autochthonous models indicate that Z 7557 seems to have advantages over CPA in the treatment of malignancies with impaired bone marrow function as for instance acute leukemias and in fractionated dose schedules.

Animals↗
PubMed1984

A comparative study of therapeutic activity, myelotoxicity and DNA damage in the bone marrow of mice after cyclophosphamide and ASTA Z 7557 (INN mafosfamide).

This study compares the two oxazaphosphorine compounds ASTA Z 7557 (AZ) and cyclophosphamide (CP) in their therapeutic activity as well as in their myelotoxicity and DNA damage being induced after a single intraperitoneal injection. Therapeutic activity was determined towards methylnitrosourea-induced rat mammary carcinomas in vivo and in vitro, resulting in comparable efficacy of both compounds at their optimal doses, respectively, with the sensitivity of individual tumors being reflected by the degree of inhibition of 3H-thymidine uptake of these cells in vitro. Myelotoxicity was measured as inhibition of pluripotent (CFU-S) and macrophage-granulocyte committed (CFU-C) stem cells together with the extent of single strand breaks and DNA-DNA interstrand crosslinks in murine bone marrow. At equimolar base AZ was found to induce a higher level of DNA damage than CP in the bone marrow of mice 16 hours after a single intraperitoneal injection. Both compounds depressed the pluripotent stem cell compartment of the bone marrow to a similar extent, whereas AZ was significantly less toxic to the granulocyte cell lineage.

Animals↗
PubMed1984

The level of DNA interstrand crosslinking in bone marrow parallels the extent of myelosuppression in mice treated with four chloroethylnitrosoureas.

This study compares the level of DNA-DNA interstrand crosslinking in murine bone marrow with the decrease in mean number of blood progenitor cells in mice treated with chloroethylnitrosoureas. Male C57BL6 X C3HF1 mice were treated with single IP injections of 1-(2-chloroethyl)-1-nitroso-3-(methylene-carboxamido)-urea (acetamido-CNU), 1,2-bis(2-chloroethyl)-1-nitrosourea (BCNU), 2-[3-(2-chloroethyl)3-nitrosoureido]-beta-D-glucopyranose (chlorozotocin), or 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea (HECNU). After 16 h three aliquots of pooled bone marrow were assayed for DNA damage in the form of DNA-DNA interstrand crosslinks and myelosuppression in terms of the depletion of granulocyte-committed (CFU-C) and pluripotent (CFU-S) stem cell activity. Both acetamido-CNU and HECNU produced a dose-dependent increase in DNA-DNA interstrand crosslinking, which was paralleled by a marked inhibition of both types of progenitor cells. BCNU and chlorozotocin, however, were much less effective at crosslinking DNA, and were much less myelosuppressive in terms of CFU-C and CFU-S activity. These data suggest a correlation between the degree of myelosuppression at the level of the stem cell and the extent of DNA damage in murine bone marrow. The levels of haematosuppression did not parallel the acute single-dose toxicity in mice but rather reflected the relative antileukaemic activity of these agents. However, the degree of recovery of the stem cell compartments may be more relevant to the clinically important long-term toxicity after single and repeated doses.

Animals↗
PubMed1984

Evaluation of new estrogen-linked 2-chloroethylnitrosoureas. I. Short term anticancer efficacy in methylnitrosourea-induced rat mammary carcinoma and hormonal activity in mice.

Short-term treatment of N-methyl-N-nitrosourea-induced mammary carcinomas in Sprague-Dawley rats with estradiol-linked nitrosoureas shows that the compounds in which the cytotoxic group is linked to position 17 of estradiol are superior to the 3-ester analogue. Moreover, N-(2-chloroethyl)-N-nitroso-carbamoyl (CNC)-L-alanyl-L-alanine-estradiol-3-ester is more effective and less toxic than CNC-L-alanine-estradiol-3-ester, being equivalent to ovariectomy in its therapeutic efficacy. Unlinked CNC-amino acid or-dipeptide in admixture with estradiol is less effective. Linked compounds at therapeutic dosages display estrogenic activity.

Animals↗
PubMed1984

Negative dose-response study for carcinogenicity of orally administered rutin sulfate in Sprague-Dawley rats.

Rutin is a ubiquitous naturally occurring flavonoid, which is used in a number of drugs. It was tested for carcinogenicity in Sprague--Dawley rats as a water-soluble mixture of sodium salts of sulfuric acid esters. Over 2 years, doses ranging from 10 to 500 mg/kg body wt of rutin sulfate (expanding factor 2.66) were administered by gavage 3 times a week to 4 groups of rats comprising 12 males and 12 females each. A control group was treated with tap water. Age-adjusted analysis of tumor rates did not provide any evidence for rutin sulfate to be carcinogenic under the conditions of this bioassay.

Administration, Oral↗
PubMed1984

Intraosseously transplantable osteosarcoma with regularly disseminating pulmonary metastases in rats.

An intratibially transplantable osteogenic sarcoma in rats, that regularly disseminates osteogenic metastases in the lung, is described. The tumor take rates exceeded 90% 30 days after transplantation. Pulmonary metastases were diagnosed in about 99% of the animals, while metastases in the kidneys (14%), lymph nodes (13%) and liver (3%) occurred less frequently. The mean survival time of untreated animals varied between 36 and 48 days, depending on the age at transplantation. Histologic and scintigraphic findings are reported.

Animals↗
PubMed1984

Influence of the alkyllysophospholipid ET-18-OCH3 on methylnitrosourea-induced rat mammary carcinomas.

This study describes the efficacy of the alkyllysophospholipid 1-octadecyl-2-methoxy-Sn-racglycero-3-phosphocholine (ET-18-OCH3) in inhibiting the growth of methylnitrosourea-induced mammary carcinomas in Sprague-Dawley rats. In experiment A 2 X 10 mg/kg Et-18-OCH3 were administered daily for 10 weeks prior to manifestation of mammary carcinomas which resulted in a significant inhibition of median tumor number and median tumor volume per rat. Treatment of established tumors (experiment B) with 6 and 60 mg/kg ET-18-OCH3 daily for 3 weeks effected a stagnation in tumor growth for the higher dosage only with 90% tumor inhibition in comparison to untreated controls; at the same time, however, clear toxic effects were seen, thus indicating a narrow therapeutic index of ET-18-OCH3 in single-drug therapy. Combination of ET-18-OCH3 with compounds possessing a different toxicity spectrum is suggested.

Animals↗
PubMed1984

Chemically induced autochthonous tumor models in experimental chemotherapy.

Two autochthonous chemically induced tumor models (leukemias and mammary carcinomas) are described. Differences between autochthonous and transplanted tumors with regard to growth kinetics and chemotherapeutic sensitivity are pointed out. The significance of different tumor models for experimental chemotherapy will be discussed.

Acute Disease↗
PubMed1984

[Experimental toxicologic and therapeutic studies on the activity of the CMF(cyclophosphamide-methotrexate-5-fluorouracil) scheme versus the VMF(vincristine-methotrexate-5-fluorouracil) scheme].

Experimental administration of the CMF scheme, which is used in adjuvant chemotherapy in humans, resulted in carcinogenic effects in rats. When substituting cyclophosphamide by vincristine, no carcinogenic activity was observed. The therapeutic effect of the VMF scheme was approximately equivalent to that of the CMF scheme in various experimental designs. It is discussed whether in adjuvant chemotherapy combinations should rather be used which lack any long-term toxicity such as carcinogenic effects.

Animals↗
PubMed1975

[Somatic segregation and Fanconi's anemia].

The chromosome marrow cells of two patients suffering from Fanconi's anemia were studied. Abnormal clones were found, pseudodiploid in one case, aneuploid in another. The analysis of these clones showed that somatic segregation occurred, resulting in partial homozygosity.

Adolescent↗
PubMedDate not supplied

Fingertip dressings.

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Accidents, Home↗
PubMedDate not supplied

Implications of the carcinogenic hazard of low doses of three hepatocarcinogenic N-nitrosamines.

The data of a large-scale experiment on single and combination effects of very low doses of the hepatocarcinogenic N-nitrosamines N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR), and N-nitrosodiethanolamine (NDElA) were modeled by new statistical methods to derive implications of the carcinogenic hazard of dose ranges so low as to result in long-term toxic effects only slightly different from the background. According to this model a linear relationship was found to exist between daily exposure to low N-nitrosamine levels and time to death with liver tumor. Extrapolation of these data to zero exposure suggested the occurrence of one to ten percent of spontaneous liver tumors in animals surviving more than 1000 days. At this advanced age a further reduction of carcinogen-induced liver tumor incidence does not contribute to a longer overall survival due to competitive, probably independent, causes of death. A quasi-threshold in terms of a "no-observed-effect level" can thus be derived from the data. The observed combination effect indicates a mere additivity in liver tumor occurrence, even at very low doses which alone cause no significant carcinogenic effect during the animal's lifetime. Within the combination of NDEA, NPYR and NDElA, N-nitrosodiethylamine was found to be the most carcinogenic agent: it contributes by at least 17 orders of magnitude more to the relative risk of dying with liver tumor than the other two compounds, if the daily dose is increased by one unit (0.1 mg/kg). Likewise, NDEA shows the steepest slope when assessing the relationship between daily carcinogen doses and time to liver tumor occurrence; relative to NDElA--the least potent carcinogen on a weight basis--and NPYR a 40-fold and 9-fold quicker appearance of liver tumors has to be expected, if the daily doses are increased by an equivalent amount.

Animals↗
PubMedDate not supplied

Extended staging results from the detection of isolated tumor cells in the liver of colorectal cancer patients.

Liver metastasis, as well as local recurrence, are delineating factors of postoperative survival in patients suffering from colorectal cancer. We set up a PCR-RFLP assay to detect K-ras mutated cells in liver tissue as an indicator of possible isolated tumor cells (ITC) or micro-metastasis at the time of surgery. Sixty-four patients with K-ras codons 12 or 13 mutated colorectal cancer were clinically diagnosed for liver metastasis, as well as by PCR-RFLP assay of DNA from liver biopsies. Macro-metastasis was observed in the liver of 7 patients (11%), with no additional evidence of ITC. Likewise, in the liver of 14 patients (22%) only ITC, but no macro-metastasis was detected. In another 7 patients (11%) there was both, ITC and macro-metastasis. No macro-metastasis or ITC were found in 36 patients (56%). Thus, the PCR-RFLP assay added 14 cases (22%) with potential liver-metastasis to the 14 cases (22%) detected by clinical diagnostic means. T and N status were related to the refined detection and extended classification of liver involvement. We conclude that clinical and PCR-RFLP methods supplement each other and can increase the detection of cases with liver involvement, if applied together.

Adenocarcinoma↗