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 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron overload is found clinically in such conditions as hemochromatosis and sideroblastic anemia, and after long term repeated transfusion in aplastic anemia. An animal model of iron overload was successfully developed in rats and rabbits by repeated intraperitoneal injections of ferric nitrilotriacetate (Fe3+-NTA). This procedure induced a diabetic state with hyperglycemia, ketonemia, glycosuria and ketonuria. Blood venesection on these rats reduced the iron load in the liver and pancreas, and ameliorated the general diabetic symptoms. A single injection of Fe3+-NTA in rats induced a temporary elevation in plasma iron concentration, lipid peroxidation in the perfused liver homogenate expressed by malondialdehyde (MDA) formation, blood GOT, GPT, ALP and gamma-GTP sequentially. Fe3+-NTA uptake in the liver caused membrane lipid peroxidation, and subsequently produced a transit liberation of liver cell enzymes, although the incorporated liver Fe3+-NTA was only 1% of the injected dosage (7.5 mg iron/kg BW) at 3 hr after injection. The direct toxic effect of Fe3+-NTA to living cells was examined using cultured normal rat liver parenchymal cells (RL-34). Marked cytolysis was found in cells exposed to more than 25 micrograms of iron through Fe3+-NTA/ml. At 50 micrograms iron of Fe3+-NTA/ml, most cells were lethally injured and the remaining cells were piled up and aggregated at 15 days. They grew on soft agar culture, and when inoculated subcutaneously to five newly born rats a subcutaneous tumor developed in all animals within three weeks. Lung metastases were found in three of five inoculated rats. A spin trapping technique with electron spin resonance (ESR) on Fe3+-NTA employing 5, 5-dimethyl-l-pyrroline-N-oxide (DMPO) yielded a spin adduct with three doublets (DMPO-Z) which corresponded to singlet oxygen. By ESR in the presence of H2O2, the Fe3+-NTA solution strongly generated hydroxyl radical. The production of active oxygen species by Fe3+-NTA solution may explain the toxicity and carcinogenicity of Fe3+-NTA. The majority of stainable iron in the iron overloaded tissue was hemosiderin (Hs). We tried to purify the Hs from multi-transfused human spleen by the method of Weir et al. The purified Hs did not show a DMPO-OH adducts in the presence of H2O2 and DMPO on ESR measurement. The Hs iron was solubilized with several biological ligands in an acidic state in the presence of a reducing reagent like glutathione. Solubilized Hs iron produced iron chelate complexes which resulted in OH radicals production in the presence of H2O2 in acidic conditions below pH 5.5.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Pathogenesis and mechanism of iron overload: ferric nitrilotriacetate, hemosiderin, active oxygen, and carcinogenesis]. 268 76

Circulating immune complexes (CIC) were measured at the time of diagnosis in 81 patients with acute leukemia or blast crisis of chronic myeloid leukemia using precipitation by 3.75% polyethyleneglycol. Elevated CIC levels did not adversely influence complete remission duration and survival, patients with normal CIC levels exhibited mostly shorter remission and survival than those with elevated or borderline levels. No significant correlation was observed between CIC levels and Hb, WBC, CBC, platelet count, age, serum bilirubin, total protein, fibrinogen, AST and ALT levels, presence of hepatosplenomegaly and/or lymphadenopathy, HbSAg positivity, complete remission duration and survival. The lack of correlation may be caused by altered immune response in leukemic patients, but the obtained results may also be affected by the nonspecific nature of the method used for the detection. Simultaneous detection of CIC levels by multiple tests and evaluation not only of the number but also of the composition and size of CIC may decrease the incidence of false results. Nevertheless, only the establishment of antigen-specific assays may resolve the controversies in the detection of CIC and thus contribute to a more precise assessment of the role of CIC in prognosis of cancer, as well as to the verification of reliability of using CIC as a tumor marker.
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PMID:Circulating immune complexes in acute leukemia. 270 22

The influence of selenium on cis-diamminedichloroplatinum(II) (c-DDP) nephrotoxicity in mice and rats was assessed, using single doses of both compounds. Sodium selenite, 2 mg of selenium per kg, given 1 h before c-DDP, greatly reduced blood urea nitrogen and creatinine levels and morphological kidney damage in both BALB/c mice and Wistar rats, while administration 1 h after c-DDP did not. Liver toxicity of selenium was evaluated by measuring serum glutamic pyruvate transaminase and serum glutamic oxalate transaminase and by routine histology. No liver damage was observed in animals treated with sodium selenite, 2 mg of selenium per kg, and physiological saline or c-DDP. Pretreatment with sodium selenite did not reduce the antitumor activity of c-DDP against MPC 11 plasmacytoma or Prima breast tumor in BALB/c mice. The present results indicate that sodium selenite may provide protection against c-DDP nephrotoxicity, when it is given before c-DDP. Moreover, selenium has an antineoplastic activity against several tumors. The combination of these qualities may open new perspectives in cancer chemotherapy.
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PMID:Selenium-induced protection against cis-diamminedichloroplatinum(II) nephrotoxicity in mice and rats. 272 Jun 62

Over a 9-year period, major resection was successfully performed on 51 occasions with total vascular exclusion using supra- and infrahepatic caval and portal vein clamping. The main indications for hepatic resection were centrally located tumor in liver metastases (62%) and hepatocellular carcinoma with no evidence of co-existing cirrhosis (25%). Major resections included extended and regular right hepatectomy, extended left hepatectomy, and segmentectomy. The mean duration of vascular exclusion was 46.5 +/- 5.0 minutes (range 20 to 70 minutes) and mean blood transfusion requirement was 1.4 +/- 0.4 units during vascular exclusion. There were significant correlations between postoperative fall in factor II levels and the number of segments removed (r = 0.37, p = 0.015) and between serum alanine aminotransferase levels at day 2 and the duration of vascular exclusion (r = 0.35, p = 0.02). One patient died 45 days after the procedure of multi-organ failure and sepsis. Nonfatal complications occurred in 7 patients (14%) and included respiratory infection (7 patients), biliary fistula (3 patients), and collection at the site of hepatic resection (3 patients). Total vascular exclusion is a safe and useful technique in resection of major hepatic lesions that involve hepatic veins.
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PMID:Major hepatic resection under total vascular exclusion. 274 11

Lycobetaine (AT-1840), developed by our institute, is a new chemotherapeutic agent with relatively high percentage of remission on the treatment of ovary cancer and stomach cancer; no remarkable changes in blood picture, EKG and GPT, were observed. Early examination of the structure activity relationship of lycobetaine gave the following results: 1. A potential betaine and a methylenedioxy group in this compound may be critical for exhibiting antitumor activity; 2. Fission of the five membered ring of lycobetaine will not affect its antitumor activity. In order to see whether the distance between the phenolic oxygen and quaternary nitrogen affects its antitumor activity, compounds 7a-c, 8a-b were synthesized and screened against tumor in mice bearing EAC Preliminary experimental results showed that among the open ring analogs of lycobetaine, 7a, 7b and 8d possessed marked antitumor activity and 7c did not. The results indicate that changes in the distance of the betaine in lycobetaine obviously influence its antitumor activity.
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PMID:[Structure-activity-relationship study of the new anticancer drug lycobetaine (AT-1840)]. 281 92

Transcatheter arterial embolization was performed in a group of rabbits bearing VX2 tumor in the liver by injecting gelatin sponge (GS) with or without an anticancer agent (ACA) or Lipiodol with or without ACA. The antitumor effects as evaluated by tumor size and histological examination revealed that GS with or without ACA was most effective, followed in order by Lipiodol-ACA, aqueous solution of ACA and Lipiodol alone. On the other hand, severe normal tissue damage (necrosis of the liver and gallbladder) with elevation of plasma GOT, GPT, and LDH levels was more commonly observed in GS with or without ACA. Pharmacological analysis of plasma and tissue revealed that the antitumor effect of Lipiodol-ACA was due to prolonged release of ACA in addition to the embolization effect of Lipiodol, while the chemotherapeutic role of ACA was of little importance in GS-ACA.
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PMID:Experimental study of hepatic artery embolization: evaluation of various embolic materials. 282 39

We assayed serum levels of certain enzymes and tumor markers in patients after transcatheter arterial embolization (TAE) to evaluate the effectiveness of this treatment. Twenty patients had hepatocellular carcinoma and two patients had metastases to the liver from colon cancer. Assays were first done immediately after TAE and were continued for the next 12 days. Glutamic oxaloacetic transaminase (GOT; EC 2.6.1.1, L-aspartate:2-oxoglutarate aminotransferase), glutamic pyruvic transaminase (GPT; EC 2.6.1.2, L-alanine:2-oxoglutarate aminotransferase), and lactate dehydrogenase (EC 1.1.1.27; (S)-lactate:NAD+ oxidoreductase) peaked 24 to 48 h after TAE and returned to the base lines in 7 to 10 days. Mitochondrial GOT (mGOT) and glutamate dehydrogenase (GLDH; EC 1.4.1.2, L-glutamate:NAD+ oxidoreductase) also peaked at the same time after TAE. alpha-Fetoprotein peaked 2 h after TAE and decreased to half of the baseline on day 7. Carcinoembryonic antigen peaked at 24 h and fell at 48 h only in the patients with colon cancer. The total amount of cytosolic GOT, GPT, mGOT, and GLDH released was correlated to the volume of the necrotic mass estimated by computed tomography scans. The correlation coefficients for mGOT and GLDH were r = 0.919 and r = 0.939 (both p less than 0.001), respectively. Assays of mGOT and GLDH may be useful to estimate the volume of the necrotic mass of a hepatoma or metastatic carcinoma in the liver.
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PMID:Changes in serum enzyme activity after transcatheter arterial embolization for hepatic neoplasm. 283 50

This paper describes a primary extraskeletal osteogenic sarcoma arising in the spleen of an 11-year-old, male, cross-bred Terrier. Initial diagnosis was made after surgical removal of a splenic mass, at which time the liver and other abdominal viscera appeared grossly normal. However, elevations in the activities of alanine aminotransferase and alkaline phosphatase in blood taken 7 days after laparotomy suggested that hepatic metastases were developing. This was confirmed when the dog died 3.5 months after surgery, with massive hepatic metastatic involvement. There appears to be no previous report of the spleen being the primary site of such a neoplasm in the dog.
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PMID:A primary extraskeletal osteogenic sarcoma arising in the spleen of a dog. 293 Mar 90

For the investigation of locoregional chemotherapy of liver neoplasms we developed a standardized animal model in the rat. Continuous infusion therapy or repeated bolus injections of FUDR or 5-FU were given via the hepatic artery, the portal vein or the vena cava in tumor-bearing animals. The efficacy of the treatment was determined by measuring the tumor volume 3 weeks after tumor cell implantation. For the evaluation of the local and systemic toxicity serum GOT, GPT, and total bilirubin were determined. DNA single strand breaks were assessed in isolated liver and bone marrow cells. Inhibition of colony formation of bone marrow stem cells was determined by CFU-C and CFU-S bioassay. A significant reduction of tumor growth was observed only after continuous infusion of FUDR via the hepatic artery. Systemic toxicity was lowest in this group for both compounds while the local liver toxicity was only slightly elevated.
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PMID:Experiments on the efficacy and toxicity of locoregional chemotherapy of liver tumors with 5-fluoro-2'-deoxyuridine (FUDR) and 5-fluorouracil (5-FU) in an animal model. 293 47

3',5'-Dioctanoyl-5-fluoro-2'-deoxyuridine (FdUrd-C8), one of the lipophilic prodrugs of 5-fluoro-2'-deoxyuridine (FdUrd) was dissolved in an oily lymphographic agent (Lipiodol Ultra-Fluid), which had been studied as a carrier of the anticancer drug for hepatic cancer. The prodrug was administered into the left proper hepatic artery of rabbits bearing VX-2 tumor in the liver in order to examine the anticancer effects and possible adverse effects on nontumorous hepatic cells. Lipiodol or FdUrd-C8*Lipiodol selectively remained in the hepatic cancer area but disappeared from nontumorous parts of the liver 7 days after injection. Tumor growth rates in 1 week of the untreated group, a group given injections of 0.2 ml of Lipiodol alone, and groups given injections of 0.2 ml of Lipiodol containing 30, 50, 70, and 100 mg of FdUrd-C8 were 636, 436, 34.8, 14.9, -2.4, and -10.4% of the size at the time of treatment, respectively. Pathological observation also showed that FdUrd-C8 had a strong anticancer effect on VX-2 tumor growing in the liver of the rabbits. In contrast to the effect on the cancerous cells, that on nontumorous hepatic cells was very slight. In pathological observation, necrosis or degeneration of nontumorous hepatic cells was hardly observed. Plasma glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase levels temporarily rose 1 day after injection but returned to the initial levels within 7 days in all groups.
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PMID:Selective anticancer effects of 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine, a lipophilic prodrug of 5-fluoro-2'-deoxyuridine, dissolved in an oily lymphographic agent on hepatic cancer of rabbits bearing VX-2 tumor. 302 18


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