Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transport of thymidine has been characterized kinetically and thermodynamically in Novikoff rat hepatoma cells grown in culture and, less extensively, in mouse L cells, Chinese hamster ovary cells, P388 murine leukemia cells and HeLa cells. That the characterizations pertained to the transport system per se was ensured, (i) by employing recently developed methods for rapid sampling of cell/substrate mixtures in order to follow isotope movements within a few seconds after initial exposure of cells to substrate; (ii) by utilizing cells rendered, by genetic or chemical means, incapable of metabolizing thymidine; and (iii) by demonstrating conformity of the transport data to an integrated rate equation derived for a simple, carrier-mediated system. The results indicate that thymidine is transported into mammalian cells by a functionally symmetrical, non-concentrative system for which the carrier : substrate dissociation constant ranges from about 100 microM in Chinese hamster ovary cells, to 230 microM in Novikoff hepatoma cells. In all cell lines investigated, the velocity of transport was sufficient to nearly completely equilibrate low concentration of thymidine across the membrane membrane within 15 s. Temperature dependence of transport velocity and substrate : carrier dissociation were continuous (EA = 18.3 kcal/mol, delta H0' = 9.3 kcal/mol, respectively), and showed no evidence of abrupt transitions. Several natural and artificial nucleosides and nucleic acid bases inhibited influx of radiolabeled thymidine, apparently by competing with thymidine for the transport carrier.
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PMID:Thymidine transport in cultured mammalian cells. Kinetic analysis, temperature dependence and specificity of the transport system. 44 18

In recent literature numerous papers have been published concerning the accuracy of scintigraphic detection of liver metastases. Unfortunately however, the problem of false positive results is not particularly discussed in these papers. Because of the lack of information it was our aim to compare our own scintigraphic results with postmortem histopathological findings. Our investigations were carried out in 139 patients with various types of malignancy. Included in the investigations were 20 patients with primary liver tumor. The interval between scintigraphic examination and the histological verification ranged from 3 days to 1 year. In 62 of the patients with liver metastases, histopathology revealed liver metastases, while 77 patients showed no liver involvement. We arrived at the correct diagnosis "liver metastasis" in 50 out of 62 patients (80.6%). False negative scintigrams (19.4%) were found in most of the respective cases when diffuse malignant involvement such as leukemia and Hodgkin's disease was present, and also when the size of the metastases was less than 2 cm in diameter. Fifty six out of 77 patients (72.7%) without histopathological evidence of liver metastases revealed negative scintigrams. Twenty one (27.3%) false positive scintigrams were mostly due to (diffuse) nonmalignant disease e.g. fibrosis and cirrhosis. The overall accuracy of liver scintigraphy in our study was 76.2%. In 18 of 20 (90%) patients with focal liver disease correct diagnosis was established. 7 patients with benign liver tumors and 11 of 13 patients with hepatocellular carcinoma showed focal defects. Considering the fact that liver scintigraphy is a non-invasive procedure, it can be recommended as screening method. In connection with sonography and computer tomography liver scintigraphy can undoubtedly improve the diagnostic accuracy in detecting liver metastases and primary liver tumors.
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PMID:[Accuracy of liver scintigraphy in focal liver disease; a comparison with postmortem studies in 159 cases (author's transl)]. 53 Aug 44

Pyridine N-oxides having 1-(2-chloroethyl)-1-nitrosoureidoalkyl or 1-methyl-1-nitrosoureidoalkyl groups were evaluated for their antitumor activity against AH13 hepatoma and L1210 leukemia. Among them, 1-(2-chloroethyl)-1-nitroso-3-(2-pyridylmethyl)urea N-oxide (1), its tosylate (2), 1-(2-chloroethyl)-1-nitroso-3-(2-pyridylethyl)urea N-oxide (4), and 1-(2-chloroethyl)-1-nitroso-3-(3-pyridylmethyl)urea N-oxide (6) were highly active against both tumors in ip-ip system. These compounds were also active in ip-iv and ip-po systems of L1210. On the other hand, pyridine N-oxides having 1-methyl-1-nitrosoureidoalkyl group were all inactive against AH13 and weakly active against L1210. Effect on blood cells in Donryu rats bearing EDEN-5 erythroblastic leukemia cells was tested with these 1-(2-chloroethyl)-1-nitrosoureidoalkylureas. These compounds caused leucopenia and compound (4) was only slightly effective against EDEN-5.
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PMID:Antitumor effect of pyridine N-oxides having 1-(2-chloroethyl)-1-nitrosoureidoalkyl and 1-methyl-1-nitrosoureidoalkyl groups. 53 84

Thymidine kinase, dTMP kinase, and DNA polymerase activities were determined in cell lines of AH hepatoma, L1210 leukemia, and Yoshida sarcoma that were sensitive and resistant to 5-fluorouracil (5-FU). It was found that the levels of these enzymes in tumor cells were not consistently related to the property of sensitivity to 5-FU. A marked difference was observed between sensitive and resistant cell lines of L1210 leukemia and Yoshida sarcoma in the uptake of labeled 5-FU into the acid-soluble, nucleotide, and RNA fractions, the rate of incorporation of 5-FU into these fractions being 3 to 5 times greater in sensitive tumor cells than in resistant tumor cells. The radioactivities in the acid-soluble fractions of AH44 (sensitive) and AH109A (resistant) were similar after incubation of these cells with labeled 5-FU in vitro. However, a smaller volume of ascites and lower cell number were observed in AH44 (sensitive)-bearing rats than in AH109A (resistant)-bearing rats. These in vivo results indicate that the 5-FU injected intraperitoneally was diluted by ascites more in AH109A (resistant)-bearing rats than in AH44 (sensitive)-bearing rats.
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PMID:Metabolism of 5-fluorouracil in sensitive and resistant tumor cells. 55 50

The transport of thymidine into Chinese hamster ovary cells grown in suspension culture was measured under conditions in which thymidine was not metabolized, namely, when cells had been depleted of ATP. The system transporting thymidine was saturable (Kztm = 70 micron), rapid 50% of transmembrane equilibrium level attained within 8 sec), and was apparently shared by other nucleosides, but not thymine or hypoxanthine. 6([4-nitrobenzyl]thio)-9-beta-D-ribofuranosylpurine, "nitrobenzylthioinosine", inhibited thymidine transport in a simple, noncompetitive fashion with an apparent Ki = 1.0 nM (based on total concentration of inhibitor, which significnatly overestimates that of free inhibitor). The rate of expression of inhibition was slow (t 1/2 = 17 sec) relative to the rate of association of thymidine with its transporter, and thymidine partially protected the transport system against inhibition by nitrobenzylthioinosine. The dissociation constant for the inhibitor-transporter complex was estimated at about 0.1 nM, and the number of binding sites per cell at about 6 x 10(4). HeLa, P388 murine leukemia, and mouse L cells were as sensitive to nitrobenzylthioinosine inhibition of thymidine transport as Chinese hamster ovary cells; Novikoff rat hepatoma cells were much less sensitive.
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PMID:Properties of the thymidine transport system of Chinese hamster ovary cells as probed by nitrobenzylthioinosine. 56 78

Therapeutic properties of cis-dichlorodiammineplatinum (II) were studied on 12 strains of transplantable tumors and leukemias in mice. The compound is characterized by a wide spectrum of antitumor action. The greatest effect was gained in adenocarcinoma of the lage intestine (strain AKATOL), proventricular cancer (strain PRG) and adenocarcinoma of the mammary gland (strain Ca-755). The terms of survival in mice with leukemia (strain La and L-1210) and ascites hepatoma 22 are increased considerably. In some L-1210 animals the complete cure was noted. Cis-dichlorodiammineplatinum (II) may be effectively combined with sarcolysin. Much greater antitumor effect was obtained on 3 tumor strains (AKATOL, Ca-755 and sarcoma 37) with the combined therapy than with each drug used separately. The histological study of Ca-755 during chemotherapy indicated that immunocompetent cells of the organism play an important role in the mechanism of antitumor action of the platinum complex. This is manifested in the development of intensive lymphohistiocytic reaction around and inside the tumor. A damage to the convoluted tubules of the kidney and intestinal villi is one of the main adverse side-effects of the combination.
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PMID:[Antitumor action of cis-dichlorodiammineplatinum(II) and the effectiveness of a combination with sarcolysine]. 65 74

The adjuvant activity of the cell-wall skeletons prepared from eight species (ten strains) of Nocardia was determined by Brunner's method using allogeneic cell-mediated cytotoxicity test. The antitumor activity of the cell-wall skeleton of N. rubra, which showed the most potent adjuvant activity, was examined using EL-4 leukemia and MH-134 hepatoma cells in syngeneic mice. Its results suggest that the cell-wall skeleton of N. rubra is more potent than BCG cell-wall skeleton as the immunotherapeutic agent for cancer immunotherapy in man. The chemical properties of the cell-wall skeleton of N. rubra were also described.
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PMID:Adjuvant and antitumor activities of Nocardia cell-wall skeletons. 79 26

Transplantability of mouse tumors superinfected with various kinds of membrane viruses was investigated in syngeneic hosts. Methylcholanthrene-induced fibrosarcomas in BALB/c mice, Meth A, and in C57BL/6 mice, BMT-, superinfected with Friend lymphatic leukemia virus in mice given neonatal injection of the virus, grew more slowly than uninfected tumors. The retardation of growths was not observed in mice that had been given injections of the virus at birth. Similarly, Meth A and a hepatoma in C3H/He mice, MH134, superinfected with Moloney murine sarcoma virus in nu/nu mice, had reduced their transplantability in respective syngeneic mice. Further, Meth A and MH134 superinfected with endogenous rat leukemia virus and human measles virus, respectively, in nu/nu mice also showed reduced transplantability, and some of the former were actually rejected by normal syngeneic hosts. On the other hand, the reduced transplantability was not found in irradiated mice, suggesting that the phenomenon was due to immunological events. However, a myelogenous leukemia in C57BL/6 mice, C1498, superinfected with Moloney sarcoma virus in nu/nu mice grew like uninfected tumor and did not show reduced transplantability at all.
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PMID:Reduced transplantability of syngenic mouse tumors superinfected with membrane viruses in nu/nu mice. 100 77

The cytotoxicities of 2 derivatives of artemisinin B and 2 derivatives of artemisic acid (designated as Compound A, B, C, and D) were investigated, using trypan blue dye exclusion test and colony-forming units assay. At the concentration of 5 micrograms.ml-1, the inhibition rates of these 4 compounds against murine leukemia cell line P388 were > 85%. When tested against human hepatoma cell line SMMC-7721 at 25 micrograms.ml-1, the inhibition rates of Compound A, B, C, and D were found to be 92.3%, 96.9%, 84%, and 82.1%, respectively, and 27%, 8%, 37.8%, 1.7% against normal human embryonic lung cell line WI-38, respectively. These 4 compounds all showed an inhibition rate of 100% against human gastric cancer cell line SGC-7901 at 50 micrograms.ml-1.
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PMID:[Antitumor activities of 4 derivatives of artemisic acid and artemisinin B in vitro]. 130 44

Biochemical and biological studies have been carried out with 2-desamino-2-methylaminopterin (dmAMT), which inhibits tumor cell growth in culture but is only a weak inhibitor of dihydrofolate reductase (DHFR). Since it was possible that the species responsible for growth inhibition are polyglutamylated metabolites, the di-, tri-, and tetraglutamates of dmAMT were synthesized and tested as inhibitors of purified recombinant human DHFR, murine L1210 leukemia thymidylate synthase (TS), chicken liver glycinamide ribonucleotide formyltransferase (GARFT), and murine L1210 leukemia aminoimidazolecarboxamide ribonucleotide formyltransferase (AICARFT). The compounds with three and four gamma-glutamyl residues were found to bind two orders of magnitude better than dmAMT itself to DHFR, TS, and AICARFT, with 50% inhibitory concentration values in the 200 to 300 nM range against all three enzymes. In contrast, at a concentration of 10 microM, dmAMT polyglutamates had no appreciable effect on GARFT activity. These findings support the hypothesis that dmAMT requires intracellular polyglutamylation for activity and indicate that replacement of the 2-amino group by 2-methyl is as acceptable a structural modification in antifolates targeted against DHFR as it is in antifolates targeted against TS. In growth assays against methotrexate (MTX)-sensitive H35 rat hepatoma cells and MTX-resistant H35 sublines with a transport defect, dmAMT was highly cross-resistant with MTX, but not with the TS inhibitors N10-propargyl-5,8-dideazafolic acid and N-(5-[N-(3,4-dihydro-2-methyl-4-ox-oquinazolin-6-yl)-N- methylamino]thenoyl)-L-glutamic acid, implicating DHFR rather than TS as the principal target for dmAMT polyglutamates in intact cells. On the other hand, an H35 subline resistant to 2'-deoxy-5-fluorouridine by virtue of increased TS activity was highly cross-resistant to N10-propargyl-5,8-dideazafolic acid and not cross-resistant to MTX, but showed partial cross-resistance to dmAMT. Both thymidine and hypoxanthine were required to protect H35 cells treated with concentrations of dmAMT and MTX that inhibited growth by greater than 90% relative to unprotected controls. In contrast, N10-propargyl-5,8-dideazafolic acid and N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-yl)-N-methylamino] thenoyl)- L-glutamic acid required only thymidine for protection. Like MTX, therefore, dmAMT appears to inhibit purine as well as pyrimidine de novo synthesis, and its effect on cell growth probably reflects the ability of dmAMT polyglutamates to not only block dihydrofolate reduction but also interfere with other steps of folate metabolism, either directly or indirectly via alteration of reduced folate pools.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Biochemical and biological studies on 2-desamino-2-methylaminopterin, an antifolate the polyglutamates of which are more potent than the monoglutamate against three key enzymes of folate metabolism. 131 37


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