Biomedical subjects

B Gustavsson

Publications and source records attributed to B Gustavsson.

113 records · Page 7Linked to original sources

PubMedDate not supplied

Effects of local microwave hyperthermia and 5-fluorouracil in treatment of experimental liver cancer.

The effect of combined treatment with local hyperthermia and i.v. infusion of 5-fluorouracil was studied in 39 Wistar rats with a transplanted adenocarcinoma inoculated in the liver. Ten to 13 days later the rats were divided into three groups. Group A1 was subjected to local microwave hyperthermia (42 degrees C) for 1 h. During the hyperthermia, an i.v. infusion of 5-FU (20 mg/kg body weight) was given. In group A2 5-FU was administered under normothermic conditions. Group A3 received saline infusion under normothermic conditions. The mortality after infusion of 5-fluorouracil and hyperthermia increased during the first week after treatment. In group A1, a significant growth retardation of liver tumor was registered seven days after treatment. This effect was not superior to that of hyperthermia alone as previously described for the same experimental model. Studies of 5-FU pharmacokinetics in plasma were performed in another 20 Wistar rats. Ten rats were given an i.v. infusion of 5-FU during local hyperthermia, while the other 10 were infused under normothermic conditions. Plasma concentration of 5-FU was determined by isotachophoretic separation. The hyperthermia caused a faster decline in serum concentration of 5-FU, probably because of accelerated catabolism of the drug.

Adenocarcinoma↗

PubMedDate not supplied

5-Fluorouracil sensitive adenocarcinoma--a new experimental model in the rat.

Transplantable nitrosoguanidine-induced rat colonic carcinoma was transplanted into the liver of 49 rats in six different series during three years. Tumor growth in vivo was surveyed by repeated laparotomy at day eight and day seventeen, and 25 rats were treated with 5-fluorouracil (30 mg/kg body weight) once a day, between day 8 and day 17. Tumor take was one hundred per cent and the tumor growth rate was similar throughout the experimental period. No animals died due to treatment or due to progressive tumor growth. The animals treated with 5-fluorouracil revealed a 5 per cent weight loss compared to the controls but no other signs of health deterioration were observed. The tumors treated with 5-fluorouracil had a 70 per cent decrease of growth rate compared to control rats. Exposure of the tumor cells in vitro to 5-fluorouracil induced a dose--related decrease in surviving cells with a 50 per cent reduction of surviving cells 48 hours after exposure to 0.01 mg/ml of 5-fluorouracil. Thus, we present here a new, feasible and reproducible animal model, excellently suited to in vivo and in vitro studies of fluorinated pyrimidines and solid tumor growth.

Adenocarcinoma↗

PubMedDate not supplied

Biochemical modulation of intraperitoneal fluorouracil by allopurinol-the effect on an experimental adenocarcinoma in the liver.

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.

Adenocarcinoma↗

PubMedDate not supplied

5-fluorouracil (5-FU) and 5,10-methylene tetrahydrofolate (5,10-CH2FH4) as adjuvant therapy in an experimental rodent colon carcinoma model.

Eradication of micrometastases is the goal for adjuvant therapy following a radical surgical procedure for cancer. We report an experimental study with 5,10-methylenetetrahydrofolate (5,10-CH2FH4) modulation of 5-fluorouracil (5-FU) cytotoxicity in adjuvant treatment. A colon adenocarcinoma cell suspension was inoculated intrahepatically in a rodent experimental model. Intravenous 5-FU (30 mg/kg) in combination with 5,10-CH2FH4 (15 mg/kg or 30 mg/kg) was administered after 1, 2, 3, 4 and 7 days. 5-FU alone reduced the tumor take to fifty percent compared to one hundred percent tumor take in control animals (p < 0.05), while 5-FU in combination with 5,10-CH2FH4 (regardless of folate-dose) eliminated tumor take (p < 0.0001). This makes 5,10-CH2FH4 a promising agent for modulation of 5-FU cytotoxicity in adjuvant cancer treatment.

Adenocarcinoma↗

PubMedDate not supplied

Novel mutations in the APC gene and clinical features in Swedish patients with polyposis coli.

The adenomatous polyposis coli (APC) gene was investigated in Swedish patients with familial adenomatous polyposis (FAP). A combination of analyses including single stranded conformation polymorphism (SSCP), heteroduplex (HD), protein truncation test (PTT) and direct sequencing was used to enable optimal mutation detection. Three novel mutations in the gene were identified, i.e. nt2644C- > T (giving an Arg876Stop mutation), nt4025del173 (leading to premature truncation of the protein at codon 1337) and nt3526insG (giving truncation at codon 1178). In addition, one previously described mutation, i.e. the 5-bp-deletion nt3942del5(AAAGA) in codon 1309 (giving a premature termination of the protein at codon 1314) was detected. All four mutations were located in the 5'-half of exon 15. The two latter mutations were associated with the CHRPE (congenital hypertrophy of retina pigment epithelium) phenotype (CHRPE was not examined in the other two cases). The patients with mutations in codon 1309 and 1336 had a more severe FAP phenotype.

Adenomatous Polyposis Coli↗