| 1. |
- Lindnér, Per, 1956, et al.
(författare)
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Hepatic artery occlusion and energy charge in rat liver tumour.
- 1994
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - 0923-7534. ; 5:10, s. 961-3
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Tidskriftsartikel (refereegranskat)abstract
- Hepatic artery ligation (HAL) is a model for inducing a vascular attack on liver tumours which causes a reduction in tumour growth. To determine in an experimental rat liver adenocarcinoma the duration and magnitude of changes in adenonucleotide concentration and energy charge (EC) after HAL, analyses of energy-rich nucleotides were performed at 1, 2, 24 and 168 hours after HAL or a SHAM procedure. There was a significant decrease of the ATP content and energy charge in the tumour one hour after HAL. Two hours after HAL this difference had decreased and with longer observation it was not detectable. Twenty-four hours of starvation did not significantly alter the effects of HAL on the tumour. HAL gives rise to a transient energy depletion of the tumour which is not completely compensated for by glycolysis after 1 hour, but is restored after 2 hours.
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| 2. |
- Hafström, Lars-Olof, 1936, et al.
(författare)
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Isolated hyperthermic liver perfusion with chemotherapy for liver malignancy.
- 1994
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Ingår i: Surgical oncology. - 0960-7404. ; 3:2, s. 103-8
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Tidskriftsartikel (refereegranskat)abstract
- In an open study of unresectable liver tumours, isolated regional perfusion with hyperthermia and cytotoxic drugs has been tested in 29 patients. Four patients had primary hepatocellular cancer, 10 patients had metastases from malignant melanoma, remaining from breast cancer, colorectal cancer, midgut carcinoids and miscellaneous primaries. At laparotomy the proper hepatic artery and portal vein were canulated and connected to a pump oxygenator. The inferior vena cava was canulated with a triple lumen catheter (Perfufix) allowing for porto-caval shunting, drainage of lower body and renal veins to the heart and separate drainage of liver veins to the pump oxygenator. Liver perfusion was performed with a mean flow of 900 ml per min. Melphalan and cis-platinum 0.5 mg/kg body-weight were added to the perfusate for 1 h after liver temperature reached 40 degrees C. Four patients died within 30 days of perfusion due to multiple organ failure. These patients had more than 50% of liver volume occupied by cancer. All surviving patients developed reversible hepato- and renal toxicity. Partial tumour regression was registered in 20% of the patients. Five patients have survived more than three years. Hyperthermic liver perfusion is feasible but in patients with massive liver tumour, there is a significant risk of developing multiple organ failure.
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| 3. |
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| 4. |
- Hellstrand, Kristoffer, 1956, et al.
(författare)
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Histamine in immunotherapy of advanced melanoma: a pilot study.
- 1994
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Ingår i: Cancer immunology, immunotherapy : CII. - 0340-7004. ; 39:6, s. 416-9
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Tidskriftsartikel (refereegranskat)abstract
- Sixteen patients with advanced metastatic malignant melanoma were treated with a high-dose infusion of interleukin-2 (IL-2; 18 x 10(6) IU/m-2 day-1) together with daily subcutaneous (s.c.) injections of interferon alpha (IFN alpha; 3 x 10(6) U/m-2 day-1) in 5-day cycles. Nine of these patients were given histamine (1 mg s.c.) twice daily during treatment with IL-2 and IFN alpha. In the seven patients who did not receive histamine, one partial response (that is a reduction of more than 50% in the total tumour burden) was observed in a patient with skin and lymph node melanoma. In the eight histamine-treated patients evaluable for response, four partial responses were observed. Two other patients showed regression at one site of metastasis but tumours remained unchanged at other sites. Two histamine-treated patients showed complete resolution of extensive liver metastasis. Sites of response in histamine-treated patients also included the subcutis, lymph nodes, skeleton, spleen and muscle. Lung melanoma did not respond to histamine/IL-2/IFN alpha. Three patients with lung tumours responded with significant (more than 50%) reduction of the volume of soft-tissue tumours, suggesting that the response to histamine may be organotropic. Survival was significantly prolonged in patients receiving histamine. Our data suggest that treatment with histamine may improve the antitumour efficacy of immunotherapy in metastatic melanoma.
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| 5. |
- Lindnér, Per, 1956, et al.
(författare)
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Biochemical modulation of intraperitoneal fluorouracil by allopurinol-the effect on an experimental adenocarcinoma in the liver.
- 1994
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Ingår i: Anticancer research. - 0250-7005. ; 14:3A, s. 847-52
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Tidskriftsartikel (refereegranskat)abstract
- In a rat liver tumour system with a nitrosoguanidine-induced carcinoma and in an in vitro system with the same tumour, the effect of allopurinol on the toxicity and antitumour effect of 5-fluorouracil (5-FU) was explored. Two doses of 5-FU, 30 and 60 mg/kg b.w. intraperitoneally (i.p.), were tested with a large dose of allopurinol subcutaneously (s.c.( (300 mg) in rats. The drugs were given for three consecutive days. The lethal toxicity of 60 mg 5-FU i.p. could not be counteracted by allopurinol. Allopurinol and 30 mg 5-FU reduced the tumour growth rate more than 5-FU alone. The spleen was smaller, as a sign of increased toxicity, without allopurinol. The concentration of allopurinol and its metabolites in the general circulation was high. In vitro, there was no additive or specific effect of allopurinol. These results indicate some in vivo metabolic modulation of 5-FU efficacy by allopurinol if 5-FU is administered intraperitoneally and allopurinol systemically.
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| 6. |
- Naredi, Peter, 1955, et al.
(författare)
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Cross-resistance between cisplatin and antimony in a human ovarian carcinoma cell line.
- 1994
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Ingår i: Cancer research. - 0008-5472. ; 54:24, s. 6464-8
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Tidskriftsartikel (refereegranskat)abstract
- The metal compound cisplatin (DDP) is a widely used anticancer agent but naturally occurring and acquired resistance to DDP limits its effectiveness. Resistance is associated with a decreased accumulation of DDP and increased levels of glutathione and metallothioneins. Such changes also serve as protective and detoxification mechanisms for other metal salts in prokaryotes and lower eukaryotes. The aim of this study was to find metal salts for which the cross-resistance profile was the same as for DDP in sublines of the parental 2008 human ovarian carcinoma cells selected with either DDP (2008/C13*5.25) or CdCl2 and ZnCl2 (2008/MT). Among the metal salts tested the resistance profile of trivalent antimony most closely resembled that of DDP. DDP-selected cells were 15-fold resistant to DDP and 4.4-fold cross-resistant to antimony potassium tartrate, whereas of the cations tested (Cd2+, Zn2+, Ni2+ and Co2+) cross-resistance was observed only for Cd2+ (2.4-fold). When 2008 cells were selected for resistance to antimony (6.6-fold) they were found to be 16-fold cross-resistant to DDP. Accumulation of the DDP analogue cis-[3H]dichloro(ethylenediamine)platinum(II) was 59% lower in the DDP-selected subline and 48% lower in the antimony-selected variant than in the parental cell line. We conclude from the mutual cross-resistance to DDP and antimony potassium tartrate and from the impaired uptake of [3H]DEP in both the DDP and antimony-selected variants that DDP and antimony share a common mechanism of resistance. The significance of this observation lies in the fact that several evolutionarily conserved mechanisms for antimony detoxification are already known in lower organisms which may point the way to identification of additional DDP resistance mechanisms in mammalian cells.
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| 7. |
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| 8. |
- Svensson, G, et al.
(författare)
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Quantitative measurements of collateral arterial blood flow in nonarterialized rat liver grafts.
- 1994
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - 0934-0874. ; 7:2, s. 136-9
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Tidskriftsartikel (refereegranskat)abstract
- The early development of arterial blood flow in the grafted liver after orthotopic liver transplantation in the rat without reconstruction of the hepatic artery was studied. Arterial liver blood flow was measured on day 21 after transplantation with NEN-TRAC microspheres (size 15.5 +/- 0.1 microns) and labelled with 103Ru. The arterial liver blood flow in the grafted liver was 0.778 +/- 0.247 ml/min per gram for transplanted rats after 21 days. One day after transplantation, the blood flow was only 0.006 +/- 0.002 ml/min per gram. The results of this study demonstrate that there was no arterial blood flow on day 1 after transplantation, as expected, but that there was a high arterial blood flow in the transplanted liver by day 21. This was also supported by the angiographic findings. The early development of arterial blood flow via collaterals may account for the excellent results that we and others have attained in orthotopic liver transplantation without rearterialization in the rat.
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