| 1. |
- Hellstrand, Kristoffer, 1956, et al.
(författare)
-
Histamine in immunotherapy of advanced melanoma: a pilot study.
- 1994
-
Ingår i: Cancer immunology, immunotherapy : CII. - 0340-7004. ; 39:6, s. 416-9
-
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.
|
|
| 2. |
- Hafström, Lars-Olof, 1936, et al.
(författare)
-
Isolated hyperthermic liver perfusion with chemotherapy for liver malignancy.
- 1994
-
Ingår i: Surgical oncology. - 0960-7404. ; 3:2, s. 103-8
-
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.
|
|
| 3. |
|
|
| 4. |
- Holmberg, Stig B, 1946, et al.
(författare)
-
Cytotoxicity of liver macrophages against liver tumours. Influence of betamethasone, indomethacin and allopurinol.
- 1991
-
Ingår i: Anticancer research. - 0250-7005. ; 11:5, s. 1827-30
-
Tidskriftsartikel (refereegranskat)abstract
- Macrophage activation with zymosan has an inhibitory effect on tumour take and initial tumour growth in the rat liver. 91 rats with syngeneic transplanted hepatoma in the liver were treated with zymosan (46) or saline (45). Betamethasone (glucocorticoid), indomethacin (prostaglandin synthesis inhibitor), allopurinol (oxygen radical scavenger) or saline were administered concomitantly. Tumour take, tumour growth and relative spleen weight were used as in vivo parameters of liver macrophages cytotoxicity and general macrophage activation. Zymosan inhibition of tumour take was counteracted by betamethasone, indomethacin and allopurinol. Betamethasone increased the growth rate of the non-zymosan treated tumours during seven days. Indomethacin decreased the growth rate of the tumours in non-zymosan treated rats up to 14 days. Allopurinol significantly blocked the zymosan inhibition of tumour take and tumour growth after 7 and 14 days. Allopurinol blocked zymosan induced increased relative spleen weight. It is proposed that the liver macrophage cytotoxicity induced by zymosan is in part mediated via production of oxygen radicals.
|
|
| 5. |
- Lindnér, Per, 1956, et al.
(författare)
-
Biochemical modulation of intraperitoneal fluorouracil by allopurinol-the effect on an experimental adenocarcinoma in the liver.
- 1994
-
Ingår i: Anticancer research. - 0250-7005. ; 14:3A, s. 847-52
-
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.
|
|
| 6. |
- Lindnér, Per, 1956, et al.
(författare)
-
Hepatic artery occlusion and energy charge in rat liver tumour.
- 1994
-
Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - 0923-7534. ; 5:10, s. 961-3
-
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.
|
|
| 7. |
- Lindnér, Per, 1956, et al.
(författare)
-
Regional lymphatic drug exposure following intraperitoneal administration of 5-fluorouracil, carboplatin, and etoposide.
- 1993
-
Ingår i: Surgical oncology. - 0960-7404. ; 2:2, s. 105-12
-
Tidskriftsartikel (refereegranskat)abstract
- Intraperitoneal (i.p.) administration of chemoterapeutic agents results in greater total drug exposures in the peritoneal cavity than in plasma. A study on the drug exposure for i.p. lymphatics of pigs, receiving 5-fluorouracil (5-FU), etoposide (VP-16) and carboplatin (CBDCA) by the i.p. route was conducted. Drug concentrations in peritoneal fluid, plasma, and thoracic duct lymph were monitored over the ensuing 3 h. 5-FU appeared rapidly in thoracic duct, lymph and plasma. The lymph concentration declined after 20 min while the plasma concentration remained stable. CBDCA reached a stable concentration in lymph and plasma after 60 min. VP-16 peaked in the lymph after 20 min, whereas the plasma concentration continued to rise for 150 min; the peritoneal half-life for VP-16 was too long for clearance to be defined. Total drug exposure (AUC) was for 5-FU 5.7-fold greater for lymph than for plasma and for CBDCA equal in both compartments. VP-16 had a 2.1-fold higher AUC for lymph than for plasma. The results indicate that the i.p. route of administration results in a greater exposure of the lower thoracic duct lymph than the plasma to 5-FU, produces only a marginally increased exposure to VP-16, and results in no difference for CBDCA. The efficacy of 5-FU is a function of total drug exposure. The results reported provide a strong rationale for evaluating the adjuvant use of i.p. 5-FU in colorectal and gastric carcinoma.
|
|
| 8. |
- Naredi, Peter, 1955, et al.
(författare)
-
The effects of tumour necrosis factor alpha on the vascular bed and blood flow in an experimental rat hepatoma.
- 1993
-
Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 54:4, s. 645-9
-
Tidskriftsartikel (refereegranskat)abstract
- The influence of TNF alpha on tumour growth rate has been attributed to its effects on the vascular bed and blood flow. The aim of our study was to investigate the effects of pharmacological doses of TNF alpha on the tumour vascular bed and to quantify blood flow in an experimental hepatoma during a more extended period after TNF-alpha exposure than hitherto reported. In Lister rats, a syngeneic rat hepatoma was implanted on the dorsum of the right hind foot. TNF alpha was given i.v. The injection was repeated after 24 hr. Tumour blood flow was estimated before and 1, 24, and 96 hr after TNF-alpha administration with the 133Xe-washout technique. The passage of microspheres through the tumour vascular bed (non-entrapment), as a measure of vascular occlusion, was estimated 4 and 96 hr after TNF-alpha administration. Tumour growth rate was measured. The tumours were subjected to histological examination and the sensitivity to TNF alpha in vitro was tested. A reduction of tumour blood flow was observed in TNF-alpha-treated groups. Tumour growth rate was equally increased after 96 hr in both the TNF-alpha groups as compared with controls. There was no significant change in non-entrapment for the TNF-alpha-treated rats as compared with controls. Histology revealed extensive necrosis and thrombosis in tumours. TNF alpha had no effect on the viability of the cloned hepatoma cell line in vitro.
|
|
| 9. |
- Naredi, Peter, 1955, et al.
(författare)
-
The influence of hepatic artery ligation and of vasopressin on liver tumour blood flow in rats.
- 1992
-
Ingår i: Journal of surgical oncology. - : Wiley. - 0022-4790 .- 1096-9098. ; 50:2, s. 70-6
-
Tidskriftsartikel (refereegranskat)abstract
- The blood flow in an experimental adenocarcinoma in the rat liver was determined with the 133Xe-washout technique before and after hepatic artery ligation (HAL). There was an initial reduction of the washout of 50%. This was further reduced after 1 day by 50%, which was maintained for 7 days. Seven days after HAL or sham procedures the 133Xe-washout was of similar magnitude in the liver tumours, although after the sham procedure the tumours were larger (3.4 g vs. 1.5 g). The estimated tumour blood flow was then approximately 0.04 ml x min-1 x g-1. The influence on normal liver parenchyma of HAL was a reduction at 30 minutes, which was maintained for 7 days. Postacton--a synthetic vasopressin--did not influence the 133Xe-washout in normal liver parenchyma in non-tumour, as well as in tumour-bearing animals. There was no influence of Postacton on the 133Xe-washout in the liver tumours. Thirty minutes after HAL Postacton gave a reduction of blood flow in normal liver parenchyma of tumour-bearing animals, which is thus only from the portal vein. In tumours Postacton did not significantly reduce the tumour blood flow immediately after HAL.
|
|
