| 1. |
- Elmroth, Kerstin, 1970, et al.
(författare)
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Radiation and hypothermia: changes in DNA supercoiling in human diploid fibroblasts
- 1999
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Ingår i: Anticancer Res. - 0250-7005 .- 1791-7530. ; 19:6B, s. 5307-11
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Tidskriftsartikel (refereegranskat)abstract
- The influence of hypothermia (2 degrees, 15 degrees and 28 degrees C) upon the effect of X-irradiation on chromatin from human diploid fibroblast cells (AG1518) was studied using the fluorescent halo assay. Rewinding of supercoils was inhibited in a dose-dependent manner when cells were irradiated with 4, 8 or 16 Gy. This inhibition of rewinding was reduced when cells were irradiated at subnormal temperatures compared with cells irradiated at 37 degrees C. One hour's preincubation at low temperature did not influence rewinding. When AG1518 cells were irradiated at 37 degrees C in the presence of the radical scavenger DMSO (0.5 M), the radiation-induced damage was reduced. No additional protection of DMSO in hypothermic cells (2 degrees C) was found, possibly indicating that OH-radical-mediated effects are more temperature dependent. These results are similar to those recently found for the malignant MCF-7 cell line.
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| 2. |
- Larsson, D. E., et al.
(författare)
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Chromosomal damage in two X-ray irradiated cell lines: influence of cell cycle stage and irradiation temperature
- 2007
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:2, s. 749-53
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate if irradiation with X-rays in different cell cycle phases resulted in a different response as measured with the micronucleus technique. In addition, the influence of irradiation temperature was investigated. MATERIALS AND METHODS: Cells from a non-transformed human fibroblast cell line, HS2429, and a human breast cancer cell line, MCF-7, were synchronized by thymidine block and irradiated at either 2 degrees C or 37 degrees C in the G1-, S- and G2/M-phases. After cytokinesis-block by cytochalasin B, the frequency of micronuclei was determined. RESULTS: Clear dose-response relationships were found. More micronuclei were detected in fibroblast cells irradiated in G1 and S than in G2/M, while the differences were not as prominent in MCF-7 cells. The irradiation temperature had no significant influence on the formation of micronuclei in either of the cell lines. CONCLUSION: The formation of micronuclei varies with the cell cycle stage at the time of irradiation.
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| 3. |
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| 4. |
- Elmroth, Kerstin, 1970, et al.
(författare)
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Effect of hypothermic irradiation of the growth characteristics of two human cell lines
- 2000
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Ingår i: Anticancer Res. - 0250-7005. ; 20:5B, s. 3429-33
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Tidskriftsartikel (refereegranskat)abstract
- The effect of hypothermic irradiation on the growth characteristics of two human cell lines was investigated. Low temperature (2 degrees C) X-irradiation of MCF-7 cells (2, 3 and 4 Gy) resulted in higher surviving fractions compared to irradiation at 37 degrees C as assessed by the colony forming assay. The ratios for the surviving fraction between the two temperatures were 1.2, 1.5 and 1.7 at 2, 3 and 4 Gy, respectively. Correspondingly, the dose modifying factor was 1.23. The distribution of colony sizes (of those with more than 50 cells) was different with proportionally more small-sized colonies from cells irradiated at 2 degrees C. Colonies from diploid fibroblasts (HS27) were ill-defined and could not be counted. In conclusion, hypothermia during irradiation seems to influence the radioresponse in MCF-7 cells. The growth in multiwell plates of MCF-7 cells and human diploid fibroblasts (HS27) after irradiation with 3 and 4 Gy, respectively, at 2 degrees C or 37 degrees C was assessed by using the crystal violet growth assay. No difference between 2 degrees C or 37 degrees C irradiation was found for either of the two cell lines.
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| 5. |
- Gritli Linde, Amel, 1959, et al.
(författare)
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Effects of suramin on polyamine metabolism in B16 murine melanoma cells
- 1998
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Ingår i: Anticancer Res. - 0250-7005. ; 18:2A, s. 855-62
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Gritli Linde, Amel, 1959, et al.
(författare)
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Opposing effects of suramin and DL-alpha-difluoromethylornithine on polyamine metabolism contribute to a synergistic action on B16 melanoma cell growth in vitro
- 1998
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Ingår i: Anticancer Res. - 0250-7005. ; 18:2A, s. 863-70
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Hultborn, Ragnar, 1946, et al.
(författare)
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Efficacy of pamidronate in breast cancer with bone metastases: a randomized, double-blind placebo-controlled multicenter study
- 1999
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Ingår i: Anticancer Res. - 0250-7005. ; 19:4C, s. 3383-92
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the efficacy of pamidronate 60 mg i.v. q 4 weeks in women with advanced breast cancer with skeletal metastases. PATIENTS AND METHODS: 404 woman with skeletal metastases from breast cancer in Sweden and Norway were included in a randomized, placebo-controlled, multicenter study. Except for the study medication, other palliative treatment was chosen at the discretion of the physician. Skeletal related events, i.e. increased pain, treatment of hypercalcemia, pathologic fractures of long bones or pelvis, paralyses due to vertebral compression, palliative radiotherapy for skeletal metastases, surgery on bone and change of antitumor therapy were recorded every third month as well as a self-estimated pain-score using visual Analog Scales and analgesic consumption. RESULTS: There was a significantly increased time to progression of pain (p < 0.01), to hypercalcemic events (p < 0.05) as well as for the cumulative number of skeletal related events (p < 0.01) in favor for the pamidronate group. No statistically significant reduction of pathologic fractures of long bones or pelvis, or pareses due to vertebral compression occurred. No statistically significant differences were found for the need of radiotherapy and surgery on bone. The pamidronate group faired better regarding performance status (p < 0.05). There was a statistically not significant lower consumption of opioid analgesics in the pamidronate group (p = 0.14). CONCLUSION: Pamidronate 60 mg i.v. q 4 weeks reduces skeletal events and improves the quality of life in women with bone metastases from breast cancer.
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| 8. |
- Hultborn, Ragnar, 1946, et al.
(författare)
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Prevalence of Klinefelter's syndrome in male breast cancer patients
- 1997
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Ingår i: Anticancer Res. - 0250-7005. ; 17:6D, s. 4293-7
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Lundgren-Eriksson, L., et al.
(författare)
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Hypothermic modulation of doxorubicin, cisplatin and radiation cytotoxicity in vitro
- 2001
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Ingår i: Anticancer Res. - 0250-7005. ; 21:5, s. 3275-80
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The influence of hypothermia on doxorubicin, cisplatin and radiation cytotoxicity was investigated in vitro. MATERIALS AND METHODS: A human glioma cell line (251MG) in early exponential growth was exposed to doxorubicin or cisplatin at various concentrations for 4 hours, or X-irradiation at 28 degrees C or 37 degrees C. The cells continued growing in multi-well plates at 37 degrees C and were counted every third day until the end of the logarithmic phase, on day 13. RESULTS: Exposure to doxorubicin 0.05-0.5 microg/ml or cisplatin 1-10 microg/ml caused a dose-dependent inhibition of cell growth with a significantly reduced toxicity when exposed at 28 degrees C as compared to 37 degrees C. Irradiation with 4 Gy also resulted in less toxicity during hypothermia. Chlorpromazine 0.01-10 microg/ml, used to induce hypothermia in vivo (1), neither influenced, cellular growth itself nor interacted with doxorubicin, cisplatin or irradiation. CONCLUSION: Moderate hypothermia (28 degrees C) appears to protect against the cellular insult of doxorubicin, cisplatin and ionising irradiation and their consequences.
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| 10. |
- Lundgren-Eriksson, L., et al.
(författare)
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Radio-and chemotoxicity in mice during hypothermia
- 2001
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Ingår i: Anticancer Res. - 0250-7005. ; 21:5, s. 3269-74
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The influence of hypothermia induced by chlorpromazine (10-15 mg/kg given intra-peritoneally) on the survival from radiation and chemotherapy exposure in C57B1-mice, with or without tumour inoculation, was studied. MATERIALS AND METHODS: The mice were exposed to either whole body irradiation (8 Gy), or doxorubicin (15 or 17.5 mg/kg i.p.), or cisplatin (20 mg/kg i. p.) and followed to ensuing death. The control mice maintained a rectal temperature of 38 degres C while those receiving chlorpromazine developed moderate hypothermia of 28 degrees C or 36 degrees C, dependent on the ambient temperature. RESULTS: Hypothermia of 28 degrees C protected the mice from radiation-induced death and acute doxorubicin toxicity, with males gaining more protection than females. The effects appeared dependent on temperature, not on chlorpromazine. Hypothermia protected the mice from acute cisplatin toxicity and increased the anti-tumour effects in both genders. Chlorpromazine itself did not cause toxicity, neither did it change the natural course of tumour progression. CONCLUSION: Hypothermia of 28 degrees C induced by chlorpromazine profoundly reduces radiation, doxorubicin-and cisplatin-induced toxicity in mice with males benefiting more than females. The hypothermia itself, not the chlorpromazine, was responsible for these effects. The anti-neoplastic activity was not compromised; rather, it was enhanced, particularly for cisplatin.
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