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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucocorticoid receptor levels and steroid induced inhibition of nucleic acid precursors have been examined in lymphocytes from 27 patients at different stages of chronic lymphatic leukaemia. No correlation can be found between the level of glucocorticoid receptors and the stage of the disease. On the other hand, a significant difference (P less than 0.02) was found between stage O and stage III/IV patients, in terms of the in vitro effect of dexamethasone on [3H] uridine incorporation.
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PMID:Chronic lymphatic leukaemia: cellular effects of glucocorticoids in vitro. 64 48

Tissue-culture-passaged, Friend leukemia virus (FV)-induced reticulum cell sarcomas from BALB/c mice (FVTCT-BALB) did not produce infectious FV, although retrieval of infectious FV occurred when these cells were co-cultivated with cell lines replicating non-defective murine leukemia viruses (MLVs). The level of FV expression in the FVTCT-BALB cell line was studied to understand better the process of FV retrieval. 3H-uridine labelling techniques and reverse transcriptase assays showed that FVTCT-BALB cells did not release C-type virus particles. Nucleic acid hybridization techniques demonstrated that the level of viral RNA synthesis in the FVTCT-BALB non-producer cell line was indistinguishable from that in cell lines productively infected with MLVs. These data suggest that in the FVTCT-BALB cell line the synthesis of FV is blocked in some late stage of virus assembly.
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PMID:Incomplete viral synthesis in Friend leukemia virus-induced reticulum cell sarcomas. 76 87

The therapeutic activity of ftorafur was compared to that of 5-fluorouracil (5-FU) in a number of tumor systems. The drugs were active against ip L1210 leukemia when administered ip, sc, or orally. Administration every fourth day x 3 proved to be the most effective treatment schedule for both drugs, although significant activity was seen on all treatment schedules tested. Both congeners had activity against sc implanted L1210 leukemia as well as a limited effect on the ic implanted tumor. 5-FU produced greater increases in lifespan of mice bearing L1210 leukemia than did ftorafur. 5-FU was also more effective against ip B16 melanoma and ip Gardner 6C3HED lymphosarcoma. Ftorafur was ineffective in the treatment of mice bearing ip P388 leukemia, a tumor which is quite sensitive to 5-FU. At approximately equimolar doses both drugs produced a persistent inhibition of 2'-deoxyuridine incorporation into DNA of L1210 cells in vivo. Ftorafur produced a greater inhibition of uridine incorporation into RNA than did 5-FU, which may account for the lower therapeutic activity of ftorafur. In combination chemotherapy of L1210 leukemia 5-FU plus ftorafur was no more effective than 5-FU alone, neither of the congeners was synergistic with either adriamycin or actinomycin D, and in combination with methotrexate therapeutic synergism was observed with 5-FU but not with ftorafur. After eight transplant generations of exposure to ftorafur, a subline of L1210 leukemia became totally resistant to ftorafur and simultaneously cross-resistant to 5-FU. Doses of ftorafur and 5-FU which were optimally effective in mice bearing the parental L1210 line were lethal to mice implanted with the ftorafur-resistant subline. When treatment of the resistant subline was discontinued after nine transplant generations of exposure to ftorafur, sensitivity to 5-FU returned after three transplant generations without ftorafur. The subline retained its resistance to ftorafur until eight transplant generations after cessation of ftorafur treatment. Another subline of L1210 leukemia exposed to 5-fU for 20 transplant generations proved to be completely resistant to 5-fu and cross-resistant to ftorafur. The mutual cross-resistance between ftorafur and 5-FU supports the contention that ftorafur acts primarily as a depot form of 5-FU.
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PMID:Comparison of 5-fluorouracil and ftorafur. II. Therapeutic response and development of resistance in murine tumors. 79 50

The growth-inhibitory effect of 6-methylmercaptopurine riboside (MMPR) against leukemia L1210 cells in culture was dramatically potentiated by the addition of guanine nucleosides to the medium. In the presence of either deoxyguanosine or guanosine, the concentration of MMPR that caused 50% inhibition of growth was 35 times lower than in the absence of these nucleosides. Similar potentiation was also observed against Sarcoma 180 cells in culture by guanosine. The metabolic basis of this synergism was approached in a study of the incorporation of [14C]glycine into 5'-phosphoribosyl-N-formylglycinamide in Sarcoma 180 cells. The results show that the site of inhibition resulting in synergism is an early step in purine biosynthesis, probably phosphoribosyl pyrophosphate amidotransferase (EC 2.4.2.14). In the L1210 cell system, the addition of hypoxanthine to the medium prevented the potentiation of MMPR by guanine nucleosides supporting the conclusion that the site of the synergistic interaction involves purine biosynthesis de novo. While hypoxanthine partially reversed the growth-inhibitory effects of MMPR, an even higher degree of protection was observed in the presence of both uridine and hypoxanthine, suggesting that MMPR may have additional sites of action concerned with pyrimidine metabolism.
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PMID:Potentiation by guanine nucleosides of the growth-inhibitory effects of adenosine analogs on L1210 and sarcoma 180 cells in culture. 94 90

Velocity sedimentation of uridine-labelled cultures was found to be more reliable than isopycnic sedimentation in detecting oncornavirus production in lymphoid cells. Of 13 cell lines (including six derivea from Burkitt's lymphomas and two from leukaemic leukocytes) only one, the leukaemia-derived, Epstein-Barr virus-producing line QIMR-WIL, showed any activity. The nature of the QIMR-WIL particles was further defined by isolation of uridine-labelled 70S RNA and by the simultaneous assay for reverse transcriptase and 70S RNA, but production of such particles was detected in only three of 10 assays. Pretreatment of cells with 5'-iododeoxyuridine or culture in arginine-free medium did not induce particle production. Syncytia assays using XC cells were negative. Of 13 primary cultures (nine samples of leukaemic leukocytes and four of cord leukocytes) treated with mitogens and subjected to inducing conditions, one (leukocytes from a patient with acute myelogenous leukaemia) showed evidence in successive assays of oncornavirus synthesis. The low and transient yield of oncornavirus-like particles obtained in this work parallels that reported in previous studies of fresh lymphoid cells and primary cultures.
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PMID:Survey of human lymphoblastoid cell lines and primary cultures of normal and leukaemic leukocytes for oncornavirus production. 97 88

Peripheral lymphocytes from normal individuals and from patients with chronic lymphocytic leukemia (CLL) were cultured in vitro for 1-7 days. The growth response to phytohemagglutinin (PHA) was quantitated by the incorporation of tritiated uridine into RNA nucleotide during a 2-hr pulse with the radioisotope. While the maximum response in PHA-stimulated normal cultures appeared at 2-3 days, CLL cultures required 5-7 days to develop their maximal response, which was 50%-60% of the normal magnitude. Dilution of the number of normally reactive lymphocytes by culturing them with totally unreactive, mitomycin-treated cells produced a normal 72-hr maximal response, no matter what proportion of unreactive cells was included in the PHA-stimulated cultures. In addition, the response of peripheral lymphocytes from patients with myeloblastic leukemia, where large numbers of unreactive myeloblasts diluted the normal small lymphocytes, a depressed reaction occurred at the anticipated 2-3 days. Nylon fiber-adherent lymphocytes consisting of 85% immunoglobulin (Ig)-bearing cells responded minimally to PHA, but showed no evidence of a delay. When isolated from CLL patients, both fiber-adherent cells (Ig-bearing) as well as non-fiber-adherent (sheep erythrocyterosetting) cells responded to PHA in a delayed fashion. Similarly, a case of CLL, in which 93.5% of the circulating lymphocytes bore sheep red blood cell receptors, showed its peak response to PHA at 7 days. Therefore, using surface marker criteria considered characteristic of normal T cells and B cells, the delayed response to PHA on the part of CLL lymphocytes was independent of thymic or nonthymic origin.
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PMID:Further characterization of the circulating cell in chronic lymphocytic leukemia. 106 90

Rapidly labelled high molecular weight nuclear RNA from lymphocytes of chronic lymphocytic leukaemia was analysed for ribonuclease-stable adenylate-rich and double-stranded regions. The polyadenylate content corresponds to 0.4-0.5 percent and the content of double-stranded sequences to 2-4 percent of the total nucleotides. Partial association of polyadenylate segments with double-stranded regions was found by comparative analysis of (3H)-adenosine and (3H)-uridine labelled ribonuclease-stable RNA before and after thermal denaturation. Comparison with normal lymphocytes shows lower proportions of polyadenylate-containing RNA binding to poly(U)-Sepharose in leukaemia cells than in normals. Partial degradation of rapidly labelled high molecular weight RNA was found in leukaemia cases with low white cell counts.
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PMID:Heterogeneous nuclear rna from lymphocytes of chronic lymphocytic leukaemia: adenylate-rich and double-stranded regions. 112 45

Lewis lung adenocarcinoma growth was retarded by the oral administration of delta9-tetrahydrocannabinol (delta9-THC), delta8-tetrahydrocannabinol (delta8-THC), and cannabinol (CBN), but not cannabidiol (CBD). Animals treated for 10 consecutive days with delta9-THC, beginning the day after tumor implantation, demonstrated a dose-dependent action of retarded tumor growth. Mice treated for 20 consecutive days with delta8-THC and CBN had reduced primary tumor size. CBD showed no inhibitory effect on tumor growth at 14, 21, or 28 days. Delta9-THC, delta8-THC, and CBN increased the mean survival time (36% at 100 mg/kg, 25% at 200 mg/kg, and 27% at 50 mg/kg, respectively), whereas CBD did not. Delta9-THC administered orally daily until death in doses of 50, 100, or 200 mg/kg did not increase the life-spans of (C57BL/6 times DBA/2)F1 (BDF1) mice hosting the L1210 murine leukemia. However, delta9-THC administered daily for 10 days significantly inhibited Friend leukemia virus-induced splenomegaly by 71% at 200 mg/kg as compared to 90.2% for actinomycin D. Experiments with bone marrow and isolated Lewis lung cells incubated in vitro with delta9-THC and delta8-THC showed a dose-dependent (10(-4)-10(-7)) inhibition (80-20%, respectively) of tritiated thymidine and 14C-uridine uptake into these cells. CBD was active only in high concentrations (10(-4)).
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PMID:Antineoplastic activity of cannabinoids. 115 36

Bikaverin and its derivatives have been found to affect precursor utilization of nucleic acid and protein synthesis in the cells of Ehrlich ascites carcinoma (EAC). Mainly the uridine incorporation into EAC cells was inhibited. This is in agreement with the known concept that anthraquinones, to which bikaverin may also be assigned, intervene into RNA synthesis. The substances followed exerted a cytotoxic effect on in vitro proliferating cells of the three studied tumors. The ED50 values found for cells of these tumors were: EAC 0.5 mug/ml; leukemia L 5178 1.4 mug/ml; sarcoma 37 4.2 mug/ml.
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PMID:New potential cytotoxic and antitumor substances I. In vitro effect of bikaverin and its derivatives on cells of certain tumors. 117 1

A series of benzo-2,1,3-oxadiazoles (benzofurazans) and their N-oxides (benzofuroxans) inhibit incorporation of precursors into nucleic acids and protein by murine leukemia cells. At slighly higher levels, substantial single- and double-strand DNA breakage was observed. At still higher concentrations, inhibition of phosphorylation of uridine and thymidine was found. Structure-activity relationships show that only compounds bearing appropriate substitutions at positions 4 and 7 were effective inhibitors of biosynthetic pathways. Such compounds appear to interact with a wide variety of biological systems and may be useful in elucidating modes of macromolecule synthesis.
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PMID:Effects of 4-nitrobenzofurazans and their N-oxides on synthesis of protein and nucleic acid by murine leukemia cells. 123 68


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