Radioautographic studies of the protein synthesis in rat during protein deprivation and starvation.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
U Stenram
Publications and source records attributed to U Stenram.
Metal implants in the human body. A histopathological study.
Explore the source record for details and available documents.
Biopsy↗
Treatment of adenocarcinoma of the liver with mitomycin, hyaluronidase, and ethanol: an experimental study in the rat.
PURPOSE: To evaluate the effect of intratumorally injected ethanol, mitomycin, mitomycin with hyaluronidase, and hyaluronidase on tumor growth in an experimental model. METHODS: A suspension of 1 x 10(6) cells of chemically induced adenocarcinoma was implanted into the liver of 52 rats. Seven days later the rats were divided into groups according to treatment and injected via a midline laparotomy with ethanol, mitomycin, mitomycin with hyaluronidase, or hyaluronidase. A control group was treated with saline. The rats were killed 7 days after treatment. The tumor growth ratio was calculated, and the results compared for the different groups. Wilcoxon's rank sum test was used for statistical evaluation. RESULTS: The tumor growth ratio was significantly reduced after injection of mitomycin (p < 0.01) but not after ethanol. Hyaluronidase alone did not reduce the tumor growth ratio and had no synergetic effect with mitomycin. CONCLUSION: In an animal model intratumoral treatment of adenocarcinoma of the liver with mitomycin was significantly more efficient than similar treatment with saline or ethanol.
Adenocarcinoma↗
Nucleic acid labeling with [3H]orotic acid and nucleotide profile in rats in protein deprivation, enteral and parenteral essential amino acid administration, and 5-fluorouracil treatment.
Rats were fed a 0% casein diet for 1 week, with or without enteral or parenteral administration of essential amino acids, or a 25% casein diet, in one group supplemented with 5-fluorouracil treatment. Ninety minutes before sacrifice the rats were given a tracer of [3H]orotic acid. Incorporation into the acid soluble fraction, RNA, and DNA was determined in liver, small intestine, bone marrow, and kidney. Nucleotide profile was examined in liver and intestine. Protein deficiency caused inter alia a decrease in body weight; a decrease in RNA/DNA ratio and an increase in the specific RNA labeling in liver and kidney; an altered nucleotide profile in the liver; an increase in the nucleotide/DNA and RNA/DNA ratios and a decrease in the specific labeling of the acid soluble fraction, RNA, and DNA in the bone marrow. These changes were prevented to the same extent by giving essential amino acids, either orally or intravenously. The minor changes in intestinal nucleotide profile in protein deprivation were prevented to a slightly larger extent by amino acids orally than parenterally. 5-Fluorouracil treatment gave a decrease in the RNA/DNA ratio in the liver and kidney but an increase in the nucleotide/DNA and RNA/DNA ratios in the bone marrow. Nucleotide profiles were unaltered. The amount of DNA per gram of tissue decreased in bone marrow and increased in kidney. Parenteral administration per se resulted in almost no changes.
Amino Acids↗
Electrically mediated drug delivery for treatment of an adenocarcinoma transplanted into rat liver.
BACKGROUND: In this study, electrochemotherapy (ECT), i.e. tumour treatment based on local augmentation of intracellular drug delivery from short, intense electric pulses, was evaluated in rats with an adenocarcinoma implanted into the liver. Tumour response and concentrations of macrophages and T-lymphocytes (CD4 and CD8) in and around the tumour were measured. MATERIALS AND METHODS: Rats were treated with permeabilizing electric pulses, bleomycin, or both, eight days after implantation of the tumour, while one group received sham treatment. RESULTS: Treatment with electric pulses and bleomycin resulted in a significantly reduced lesion volume and 92% cure rate (12 out of 13, p<0.0002 compared to the other treatment groups). The highest concentration of CD8 lymphocytes was found in tumours treated with electric pulses and bleomycin. Macrophages were found mainly in tumours treated with electric pulses, with or without bleomycin. CONCLUSION: Electrochemotherapy using millisecond exponential pulses and bleomycin is efficient in a rat liver tumour model and appears to stimulate the host's immune system.
Adenocarcinoma↗
The antitumor effect of a novel nitrosourea, tauromustine, at intravenous administration in rat. Cure of hepatomas.
The effect of intravenously injected tauromustine (TCNU) on tumor growth and body weight was studied in rats with subcutaneously implanted experimental carcinomas. With a colonic tumor, a single dose or that dose split on 4 consecutive days gave the same tumor growth delay but the body weight loss was less at the split dose. Injection of the single dose for 1 min, 30 min or 2 h each had the same effect. Rats of another strain were implanted with a hepatoma. 9 out of 10 rats were cured. A late effect was body weight loss due to disturbed growth of the teeth.
Animals↗
Hyaline cytoplasmic inclusions in human hepatoma. A case report.
A case of hepatoma in a 79-year old woman is reported. The patient had an enlarged liver and a pathological liver scintigram. Percutaneous liver biopsies were performed both with Menghini-and fine needles. The most prominent feature was the presence of hyaline cytoplasmic PAS-negative inclusions in liver parenchymal cells. There was no nuclear atypia. Electron microscopy disclosed two types of cytoplasmic changes. One consisted of a lamellar ultrastructure and was interpreted as a hyperplasia of smooth-surfaced endoplasmic reticulum. The other change consisted of smooth globular non-membrane limited regions containing amorphous or finely fibrillar material. This was interpreted as corresponding to the hyaline inclusions visible in the light microscope. The presence of PAS-negative hyaline cytoplasmic inclusions may thus be a sign of hepatoma. This may be of relevance for the diagnostic considerations of material obtained by fine needle biopsy.
Aged↗
Improved antitumor effect of the nitrosourea drugs tauromustine (TCNU) and carmustine (BCNU) on a rat liver adenocarcinoma after hepatic arterial administration with degradable starch microspheres.
The effect of the cytostatic nitrosourea drugs TCNU and BCNU on tumor growth was studied in rats with a transplantable colon adenocarcinoma implanted into the liver. The drugs were given as a single dose into the hepatic artery alone or together with degradable starch microspheres (DSM). The effect of the treatment on tumor growth was measured 7 days later. Compared to control animals, TCNU decreased tumor growth. BCNU alone did not significantly decrease tumor growth. The antitumor effect of both drugs was significantly improved by DSM. The addition of DSM to the drugs caused liver damage in a few rats. There were no differences between different treatment groups regarding body weight changes. DSM may protect bone marrow against BCNU toxicity. Injection of DSM alone had no effect either on tumor growth or on survival.
Adenocarcinoma↗
Hepatic vascular occlusion combined with adriamycin given by the hepatic artery in rats with adenocarcinoma in the liver.
Rats with an adenocarcinoma of the colon implanted into the liver were treated by a bolus injection of adriamycin by the hepatic artery. In addition, vascular occlusions were performed in the following three ways. 1. The hepatic artery was ligated (HAL) immediately after adriamycin injection. 2. The portal venous branch nourishing the tumor was ligated immediately after adriamycin injection. 3. The Pringle maneuvre (clamping of the hepatic artery, the portal vein and the common bile duct) was performed during 5 min before and 10 min after injection. Tumor size was measured at operation and 6 and 12 days later in the first experiment, 7 days later in the other two experiments. The combination of adriamycin and HAL retarded tumor growth at day 6 as compared to controls, adriamycin alone and HAL alone. The differences were not significant at day 12. The other vascular occlusions did not improve the antitumor effect of adriamycin.
Adenocarcinoma↗
Potentiation by dipyridamole of 5-fluorouridine antitumor activity against a rat adenocarcinoma in vivo.
Rats were inoculated subcutaneously into both flanks with a transplantable adenocarcinoma of the colon. They were treated intravenously with either 5-FUrd (5-fluorouridine) or 5-FdUrd (5-fluoro-2'-deoxyuridine) with or without addition of dipyridamole 20 and 30 min later, respectively, for 3 consecutive days. Dipyridamole improved the antitumor activity of 5-FUrd but decreased that of 5-FdUrd.
Adenocarcinoma↗
Incorporation of 5-fluorouracil into RNA of normal tissues and an adenocarcinoma in protein-deprived rats.
One of the main cytotoxic effects of 5-FU is its incorporation into RNA. In rats, protein deprivation increases the incorporation of labelled precursors into liver RNA. We examined the effect of protein deprivation on the incorporation of a therapeutic dose of 5-FU into the liver, small intestine, kidney and bone marrow and into an adenocarcinoma transplanted to the liver in the rat. The rats were fed either on a 25% or a 0% casein diet for one week. Some rats from both groups were given amino acids or glucose parenterally. Therapeutic 5-[3H]-FU was given in a 2 h infusion by the hepatic artery and the rats were sacrificed one h later. Incorporation into liver and intestinal RNA increased significantly with protein deprivation. The increase was largely eliminated by parenteral feeding of amino acids. No differences were found in incorporation into tumor and bone marrow RNA in protein deprivation. Incorporation into the acid soluble fraction and DNA is also reported.
Adenocarcinoma↗
Modulation of 5-fluorouracil toxicity by uridine, deoxyuridine, orotate and dipyridamole in normal tissues of rats with liver adenocarcinoma.
The cytotoxicity of 5-FU, given by the hepatic artery, was measured by its incorporation into the acid soluble fraction, RNA and DNA in normal tissues and an adenocarcinoma transplanted into the liver in rats. Other substances were simultaneously administered by the portal vein to modulate the cytotoxicity. None of them had any significant influence on the incorporation of 5-FU into tumor. Dipyridamole decreased the incorporation of 5-FU into liver RNA and increased the nucleotide/DNA and RNA/DNA ratios so that the incorporation into mg RNA per liver cell was unchanged. Dipyridamole decreased the incorporation into the acid soluble fraction, RNA and DNA of the small intestine and also into RNA per mg DNA. It increased the nucleotide/RNA and RNA/DNA ratios in the bone marrow. Orotate decreased the incorporation into liver and intestinal RNA. Uridine increased the incorporation into liver RNA. The results obtained with dipyridamole were the most pronounced. Studies are continuing with this and other membrane transport inhibitors.
Adenocarcinoma↗
Modulation of 5-fluorouracil and 5-fluorouridine toxicity by membrane transport inhibitors in normal tissues of rats with liver adenocarcinoma.
The cytotoxicity of 5-FU and 5-FUrd, given via the hepatic artery, was measured by its incorpotation into the acid soluble fraction, RNA and DNA in normal tissues and an adenocarcinoma transplanted into the liver in rats. Drugs inhibiting the membrane transport of, especially, nucleosides were simultaneously administered by a femoral vein to modulate the cytotoxicity. None of them (dipyridamole, lidoflazine nor dilazep) had any statistically significant influence on the tumour. Dipyridamole and lidoflazine decreased the incorporation of 5-FU into the acid soluble fraction, RNA and DNA of the intestine. Dipyridamole probably decreased the incorporation of 5-FUrd into the acid soluble fraction and RNA of the intestine. Lidoflazine has not been tested with 5-FUrd. Dipyridamole increased the incorporation of 5-FU into the acid soluble fraction of liver, bone marrow and kidney, and of 5-FUrd into the acid soluble fraction of liver and bone marrow and liver RNA. Lidoflazine had fewer adverse effects. Both dipyridamole and lidoflazine increased the combined peak of UTP and FUTP in the liver, and dipyridamole also in the intestine of 5-FU treated rats. Dipyridamole which undergoes an enterohepatic circulation increased the combined peak of UDP-glucuronic acid and FUDP-glucuronic acid in 5-FU and 5-FUrd treated rats, as well as UDP-glucuronic acid in rats given neither 5-FU nor 5-FUrd in the liver. Membrane transport inhibitors seem to offer the opportunity to protect normal tissues from the cytotoxicity of 5-fluoropyrimidines, but the tissues can also be more exposed.
Adenocarcinoma↗
Chemical sclerosis of the gallbladder. An experimental study in pigs of the effect of absolute ethanol and polidocanol on gallbladder epithelium.
Chemical ablation of the gallbladder with absolute ethanol and polidocanol 3% was attempted in 23 and 10 pigs, respectively, after open transhepatic cholecystostomy. Absolute ethanol caused complete necrosis of the gallbladder epithelium in 10 pigs and partial necrosis with focally present gallbladder epithelium in 9. An intact epithelium was observed in 4 pigs but it was not possible to determine whether this epithelium was the original one, not affected by the ethanol, or regenerated after previous damage. Gallbladders with hemorrhage and hydrops were frequently encountered. Gallbladders treated with polidocanol all had an intact epithelium.
Animals↗
Effect of N-phosphonacetyl-L-aspartate and D-glucosamine on the incorporation of 5-fluorouridine into normal tissues and an adenocarcinoma in the rat.
Cytostatic treatment of liver metastases from colorectal cancer has been of limited value. Higher drug levels in the target substances of the tumor may improve the results. It was the aim of this investigation to examine the effect of PALA (N-phosphonacetyl-L-aspartate) and D-glucosamine on the level of uracil nucleotides in the liver and in an N-methyl-N-nitrosoguanidine-induced adenocarcinoma of the colon transplanted to the liver of rats, and on the incorporation of 3H-FUrd into the acid-soluble fraction, the RNA and the DNA of the tumor and of several normal tissues. Combined treatment with PALA and D-glucosamine reduced the UTP pool in the liver and the tumor. D-glucosamine alone increased UDP-N-acetyl-hexosamine in liver tissue. Pretreatment with PALA and D-glucosamine increased incorporation of 3H-FUrd into RNA of the liver and kidney, and into the DNA fraction of the liver, but had no effect on 3H-FUrd incorporation in the tumor.
Adenocarcinoma↗
Interferon and the incorporation of 5-fluorouracil into RNA of normal tissues and a secondary liver carcinoma in rat.
The cytotoxicity of 5-fluorouracil (5-FU) has been related to its incorporation into RNA and blocking of DNA synthesis. Interferon may enhance the therapeutic efficacy of 5-FU in colorectal cancer. In a model of secondary liver cancer in the rat, the incorporation of 5-FU into the acid-soluble fraction (ASF), RNA and DNA of several normal tissues and the tumor was determined. The liver nucleotide profile and NADPH-cytochrome c reductase activity was examined. A therapeutic dose of 5-FU was given for 2 h via the hepatic artery and the rats were killed 1 h later. Half of them were pretreated with the interferon inducer polyinosinic-polycytidylic acid (poly(I)-poly(C) and interferon. Pretreatment increased the nucleotide (NT)/DNA and RNA/DNA ratios, decreased the cellularity and left the specific RNA labelling unchanged in the bone marrow. In the liver the pretreatment decreased the NT/DNA and RNA/DNA ratios, (F)UTP, and the NADPH-cytochrome c reductase activity. The 5-FU incorporation into liver DNA decreased. No changes were found in the tumor. The pretreated rats decreased in body weight. A decreased RNA synthesis in the liver might indicate a decreased 5-FU metabolism, explaining the increased 5-FU AUC in the clinic at interferon treatment.
Adenocarcinoma↗
Cure of hepatoma in rat with the nitrosourea carmustine (BCNU).
Two experiments were performed with a chemically induced hepatoma in the rat. In the first, tumors were inoculated subcutaneously into both flanks. After 10 days, when all rats had tumors, treatment was given intravenously on two successive days with 10 mg carmustine/kg body weight/day. All control rats displayed growing tumors and had to be killed 12 days after treatment. Treated rats initially lost weight with a slight increase in tumor size. After 3 weeks all tumors disappeared and the rats grew normally. After 4 months the rats were killed and had no tumors. In a second experiment, tumors were inoculated under the liver capsule. Treatment was given via the hepatic artery. Control rats had large tumors after 2 weeks and had to be killed. All treated rats were without tumors at sacrifice. One of them developed a liver cyst and was killed after 3 months, the others after 4 months.
Animals↗
Degradable starch microspheres in cytostatic treatment of a liver carcinoma; experimental studies in rats with 5-fluorouracil, tauromustine, carmustine, doxorubicin and RSU-1069.
The degradable starch microspheres (DSM) used have a size of 45 microns and are dissolved by amylase in blood. After intraarterial administration of a mixture of DSM and cytostatic drugs the coinjected drugs remain for a longer time in the target tissue/tumor. A transient hypoxia occurs. Systemic exposure of drugs is decreased. Rats with a carcinoma implanted into the liver were given DSM and drugs via the hepatic artery. DSM did not significantly increase the incorporation of 5-fluorouracil (5-FU) into liver tumor RNA. The incorporation of 5-FU into intestinal and bone marrow RNA increased. DSM increased the antitumor effect of doxorubicin, tauromustine, carmustine and RSU-1069 (aziridine 2-nitroimidazole). Side effects, such as liver and gastric necroses and body weight loss, appeared in some rats. The toxic overspill to the stomach seemed to be reduced by giving the DSM in two parts, with all the cytotoxic drug in the first part. The effect on liver and tumor was not decreased by this procedure. DSM alone had no anti-tumor effect. DSM alone decreased liver UDP-glucuronic acid in tumor-free rats, given either by the hepatic artery or, in the double dose, by the portal vein. DSM alone did not increase liver NADPH-cytochrome c reductase activity or serum ASAT (aspartate-aminotransferase) or ALAT (alanine-aminotransferase), indicating that the DSM are inert to the liver, when infused into the tributary vessels.
Adenosine Triphosphate↗