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R Hultborn

Publications and source records attributed to R Hultborn.

60 records · Page 4Linked to original sources

Effects of oophorectomy on interstitial fluid pressure, blood flow and vascularity in a rat mammary tumour.

Interstitial fluid pressure (IFP), tumour size, blood flow and vascularity were measured in dimethyl-benz-alpha-anthracene-induced rat mammary tumours after oophorectomy. IFP was measured in the tumours by the wick-in-needle technique, blood flow by the labelled microsphere technique and vascularity by fluorescence vascular staining. Tumour volume was determined by measuring two diameters. Oophorectomy resulted in a decrease in tumour volume preceded by a decrease in IFP, while no significant change was observed in total tumour blood flow. The vascular cross-sectional area seemed to decrease. Cell proliferation may be of importance for the high interstitial fluid pressure in this hormone dependent tumour. A reduced metabolic requirement in the regressing tissue, down-regulating the vascular capacity, may camouflage the influence of the reduced tissue pressure on blood perfusion.

9,10-Dimethyl-1,2-benzanthracene↗

Prevalence of Klinefelter's syndrome in male breast cancer patients.

Klinefelter's syndrome (KS, XXY) as a risk factor for developing breast cancer was evaluated in a retrospective study of 93 unselected male breast cancer patients from the Healthcare region of Western Sweden. Archival normal material from lymph nodes or skin and subcutaneous tissue was examined using the FISH (fluorescence in situ hybridisation)-technique. The best yield of intact nuclei was obtained from lymph node tissue. The prevalence rate of KS in males with breast cancer was found to be 7.5 per cent, a much higher rate than previously reported (approximately 3 per cent). Methodological differences are suggested to cause the increased prevalence rate. Based on our finding and on the prevalence of KS in the normal population as well as on the incidence of MBC, a 50-fold increased risk of developing breast cancer in males with KS relative to normal males was found. The same median age at diagnosis, 72 years, was established for both groups of patients. No differences in survival were seen.

Aged↗

Growth and clonogenic assays compared for irradiated MCF-7 and Colo-205 cell lines.

Clonogenic assays have been the golden standard for the assessment of cytotoxic injury from irradiation or drugs. Since such assays are time consuming, growth assays, often with automatic quantifying equipment, are frequently used. Since these procedures do not immediately reflect loss of clonogenic capacity, it was considered important to validate the two procedures using gamma-irradiation (0, 2 and 4 Gy) of two human cell lines (MCF-7 and Colo-205). The cells were growing exponentially in 96-well plates and crystal violet staining resulted in optical densities proportional to cell number. The homogeneity of optical densities within the plates was optimal if the wells to be measured were surrounded by liquid-containing ones. The slopes of the exponential growth curves were decreased upon irradiation. An "apparent cell survival", the mean of the three lowest ratios between irradiated and control cells, was defined. It was compared with the SF2 and SF4 as found in parallel Courtenay-Mills assays. In this work we found a modest underestimation of cell survival using the growth assay, ranging from 0 to 17 per cent in absolute terms.

Cell Division↗

Effects of suramin on polyamine metabolism in B16 murine melanoma cells.

Polyamines and their biosynthetic enzymes, such as ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), are crucial for normal and neoplastic cell growth and differentiation. Suramin inhibits the growth of several tumor cells by affecting various intracellular targets, but its effects on polyamines are not known. In this study, the effects of suramin on some parameters of polyamine metabolism in B16 melanoma cells were investigated in vitro. Suramin increased cellular ODC activity and ODC mRNA levels, whereas the drug was directly inhibitory to the enzyme. AdoMetDC was not affected. Cellular putrescine levels were enhanced by suramin, whereas spermidine and spermine pools were unaltered. Cells cultured in the presence of suramin showed decreased cellular polyamine transport, but no direct inhibitory effect on the polyamine transporter could be found. Fluorescence spectroscopy demonstrated a direct interaction between suramin and spermine. It may be concluded that suramin affects polyamine metabolism, and that its effects in some respects are opposite to those of alpha-difluoromethylomithine (DFMO), a specific inhibitor of ODC.

Adenosylmethionine Decarboxylase↗

Opposing effects of suramin and DL-alpha-difluoromethylornithine on polyamine metabolism contribute to a synergistic action on B16 melanoma cell growth in vitro.

Polyamines are crucial for normal and neoplastic cell growth. Treatment with the polyanionic drug suramin has pronounced antigrowth activity in several tumor cell lines, but its clinical use has been hampered by its toxicity. We have earlier shown that suramin affects cellular polyamine metabolism and transport, and that these effects were, in some respects, opposite to those of alpha-difluoromethylomithine (DFMO), a specific inhibitor to ornithine decarboxylase, a key metabolic enzyme for polyamines. DFMO has been used in anticancer trials, although with limited success. Combinations of suramin and DFMO were, hence, evaluated in vitro and were found to strongly inhibit B16 melanoma cell proliferation. DFMO alone induced melanoma cell differentiation, and suramin used in combination with DFMO did not abrogate this DFMO-induced differentiation. Synergy analysis demonstrated a pronounced growth-inhibitory synergism between suramin and DFMO. The results suggest that the efficacy of combinations of DFMO with suramin or its analogues should be further explored, especially in cells requiring high levels of polyamines for their growth.

Animals↗

Effects of the alpha-particle emitter At-211 and low-dose-rate gamma-radiation on the human cell line Colo-205 as studied with a growth assay.

BACKGROUND: The aim of this study was to investigate the biological effect of the alpha-particle-emitting isotope astatine-211 on the human cell line Colo-205 and to compare it with that of low-dose-rate gamma-radiation. MATERIALS AND METHODS: Plastic (PMMA) rotating phantoms were constructed, allowing precise dosimetry on a cellular level for both types of radiation. Growth assays using 96-well plates were used to estimate apparent cell survival for the two types of radiation. From this, the relative biological effect (RBE) could be estimated. RESULTS: Irradiation of the cells with 211At resulted in an RBE of 25.1 +/- 6.7 at 37% survival, and 17.3 +/- 2.5 at 10% survival, when compared with low-dose-rate gamma-irradiation. The absorbed dose at 37% survival, 0.12 Gy, corresponds to 2.2 traversals of alpha-particles through the cell nuclei. For cells irradiated with gamma-radiation (1 and 2 Gy), an apparent cell survival above unity was observed up to 50 hours post-irradiation, indicating a possible radiation hormesis effect. CONCLUSIONS: The RBE of 211At found in this growth-assay study was significantly higher than previously presented values. The difference might be due to the use of low-dose-rate gamma-radiation as reference. The RBE presented here could prove valuable when evaluating 211At-labelled compounds for radiotherapy.

Alpha Particles↗