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Biomedical subjects

H P Fortmeyer

Publications and source records attributed to H P Fortmeyer.

At least 37 records · Page 2Linked to original sources
PubMed1988

New experimental possibilities in nutritive oncology by the model of human tumors, xenotransplanted and passaged into athymic nude mice.

The model of human tumors, heterotransplanted and subsequently passaged into athymic nude mice, enlarges the scale of possibilities in experimental oncology considerably. The model is mostly used in testing therapeutic schedules and principles. But the results of our research indicate that the model can be successfully used in nutritive oncology also. Tumor specific dependencies on dietary ingredients or on nutritive substances may be evaluated.

Animal Nutritional Physiological Phenomena↗
PubMed1987

Blood flow, oxygen consumption, and tissue oxygenation of human breast cancer xenografts in nude rats.

Human breast cancer xenografts in T-cell-deficient rnu/rnu rats permit the detailed and systematic study of blood flow, oxygen supply, and characterization of the cellular microenvironment of human tumors in vivo. Using an epigastric pouching technique, it is possible to obtain a tissue-isolated preparation which makes direct studies of blood flow and oxygen supply in human tumors feasible. So far, medullary and squamous cell carcinomas of the breast from patients have been investigated under well-defined systemic conditions. At comparable tumor sizes, the average blood flow rate through human breast cancer xenografts is higher in medullary than in squamous cell carcinomas (0.17 versus 0.10 ml X g-1 X min-1). Blood flow per unit tumor mass significantly decreases with increasing wet weight. No significant differences are obvious when comparing the flow values of pre- and postmenopausal tumors or of cancer tissues with different hormone receptor capacities. On the average, the oxygen consumption rates of human breast cancer xenografts are 10.4 in medullary and 7.7 microliter O2 X g-1 X min-1 in squamous cell carcinomas. With increasing tumor mass, the O2 consumption rate per unit weight significantly decreases. This decrease parallels the respective decline of tumor blood flow, implying that the O2 consumption rate of the cancer cells in vivo is mostly limited by the nutritive blood flow, i.e., by the O2 availability to the tumors. Due to a restricted blood supply, the O2 utilization of human breast cancer xenografts is high. Tissue oxygenation in microareas of human breast cancers xenotransplanted s.c. into nude rats is mostly inadequate. As a consequence, tissue hypoxia and anoxia are common findings even in very early growth stages. Due to marked intra- and intertumor variabilities in blood flow, heterogeneities in the tissue oxygenation are characteristic features of human breast cancer xenografts. From the results obtained it is concluded that human breast cancers growing as xenografts in rnu/rnu rats may be useful tools for cancer research, especially for investigations of blood flow, tissue oxygenation, and substrate turnover.

Animals↗
PubMed1987

L-glutamine: a major substrate for tumor cells in vivo?

From 65 human breast cancer xenografts investigated, a net glutamine uptake was found in 13 tumors (mean +/- SE: 15.7 +/- 4.5 nmol/g per min) whereas a net release (22.5 +/- 3.3 nmol/g per min) was observed in 40 tumors. In 12 tumors neither a significant net uptake nor a net release was obvious. There is experimental evidence that glutamine is taken up by cancer cells only at arterial concentrations greater than 0.5 mM. Another parameter determining glutamine utilization by tumor cells may be the tissue oxygenation. In hypoxic or anoxic tumor areas, glutamine oxidation is unlikely since oxygen is required for the reoxidation of coenzymes which are reduced in the course of this metabolic pathway. The pronounced net release could be due to proteolysis within the tumors investigated. In ascitic fluid (DS-carcinosarcoma), glutamine accumulated during growth, implicating a reduction in the glutamine consumption rate, proposedly also due to a worsening of the oxygen supply to the suspended tumor cells. Thus, the generally held opinion that L-glutamine is a (if not the) major substrate for the energy metabolism of rapidly growing tumor cells should be reconsidered since evidence for this hypothesis has been derived mainly from in vitro systems with abundant oxygen.

Animals↗
PubMed1985

Monoclonal antibody-defined circulating human tumor-associated antigen with epitope shared by cytokeratins.

Sera of human colonic carcinoma xenografted rnu/nu rats were used to immunize rnu/+rats in order to obtain an immune response against circulating human tumor-associated components. After fusion of rat spleen cells with mouse myeloma cells monoclonal antibody MAB 108 could be established which reacted with two 40 and 45 kD cytokeratins as well as with vimentin, with a soluble 37 kD protein apparently derived from the 45 kD protein and with a 37 kD protein released by tumor cells. The MAB 108-specific epitope was also detected in tissue polypeptide antigen (TPA), a human tumor-associated antigen originally described by Björklund et al. (22).

Animals↗
PubMed1982

Synthesis and evaluation of catechol analogs of diethylstilbestrol on a hormone-dependent human mammary carcinoma implanted in nude mice.

3,4-Bis(3',4'-diacetoxyphenyl)hex-3-ene (5a), 4(4'-acetoxyphenyl)-3(3',4'-diacetoxyphenyl)hex-3-ene (5b), and 4(3'-acetoxyphenyl)-3(3',4'-diacetoxyphenyl)hex-3-ene (5c) were synthesized according to the method of Dodds et al. (1939). All compounds inhibited the interaction of 3H-estradiol with its receptor. The relative binding affinity (RBA) values increased in the order: 5a (1.0) less than 5c (7.6) less than 5b (21.7). In the immature mouse uterine weight bioassay, the uterotrophic activity of 5a-c was only weak. 5a and 5c, but not 5b, exhibited significant antiuterotrophic properties. All compounds significantly inhibited the growth of a postmenopausal hormone-dependent human mammary carcinoma serially implanted in nude mice.

Animals↗
PubMed1982

Mammary tumor inhibiting effect of 3,3'-diacetoxy-alpha, beta-dialkylstilbenes and of related stilbene oxides.

3,3'-Diacetoxy-alpha, beta-dialkylstilbenes (alkyl = CH3 to C4H9, 1-4) 3,3'-dihydroxy-alpha, beta-diethylstilbene (5), and their corresponding stilbene oxides (6-10) were synthesized. Compounds 1-10 competitively antagonized in vitro the interaction of [3H]estradiol with its receptor. 3,3'-Diacetoxy-alpha, beta-diethylstilbene (2), 3,3'-diacetoxy-alpha, beta-diethylstilbene oxide (7), and their phenolic analogues (5 and 10) were most effective. Shortening or lengthening the alkyl side chains led to a decrease in receptor affinity. Among the stilbenes and epoxides, those with C2H5 and C3H7 groups (2, 3, 5 and 7, 8, 10) caused the strongest inhibition of the growth of a hormone-dependent postmenopausal human mammary carcinoma serially implanted in nude mice. The strong antitumor activity of 5 and 10 was confirmed by experiments on the 9,10-dimethyl-1,2-benzanthracene-induced, hormone-dependent mammary carcinoma of the Sprague-Dawley rat.

Alkylating Agents↗
PubMed1982

1,1,2-triphenylbut-1-enes: relationship between structure, estradiol receptor affinity, and mammary tumor inhibiting properties.

1,1,2-Triphenylbut-1-enes, which are substituted with acetoxy groups on one, two, or three aromatic rings in the para and/or meta positions, were synthesized. The identity of the occurring E and Z isomers were established by 1H NMR spectroscopy. A study on structure-activity relationships was carried out with regard to estradiol receptor affinity and to inhibiting effects on the growth of a postmenopausal human mammary carcinoma implanted in nude mice. The para-substituted compounds generally exhibited a higher receptor affinity and a better antitumor activity than the corresponding meta-substituted ones. The E isomers were superior to the respective Z isomers in those two properties. The tumor-inhibiting effect of the mono- and disubstituted compounds was better than that of the trisubstituted ones. Except for the trisubstituted compounds, they all show a good correlation between estradiol receptor affinity and antitumor activity. One of the compounds was also tested on the 9,10-dimethylbenz[a]-anthracene-induced, hormone-dependent mammary carcinoma of the Sprague-Dawley rat, and the results corresponded to those obtained in the xenograft tumor.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

The tumor-inhibiting effect of diethylstilbestrol-3,4-oxide.

Diethylstilbestrol-3,4-oxide, (DES-3,4-oxide), one of the possible cancerogenic metabolites of the well-known estrogen diethylstilbestrol (DES), is a potential estrophilic cytostatic compound. It shows a very good affinity to the estrogen receptor. The uterotrophic activity determined in the mouse uterine weight bioassay is nearly identical with that of DES. Potential alkylating properties could neither be detected in the p-NBP test not in the prophage induction test. DES-3,4-oxide [0.01-1.0 mg/kg body weight (b. wt.)] markedly inhibited the growth of the DMBA-induced hormone-dependent mammary carcinoma of the SD rat, as well as the growth of a hormone-dependent postmenopausal (but not of a premenopausal) human mammary carcinoma serially transplanted in nude mice. However, DES-3,4-oxide had no significantly better effect on the DMBA-induced mammary carcinoma of the SD rat than DES.

9,10-Dimethyl-1,2-benzanthracene↗