Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular retinol and retinoic acid binding proteins were detected in mouse skin papillomas, human adenocarcinoma HAD-1, Dunning Leukemia, Walker 256 carcinosarcoma and mammary adenocarcinoma MAC-1. A chondrosarcoma and Sarcoma 180 apparently contain only the cellular retinoic acid binding protein. Neither protein could be detected in Ehrlich carcinoma and L1210 leukemia. The presence of these proteins might be necessary for sensitivity to retinoid therapy.
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PMID:Presence of cellular rentinol and retinoic acid binding proteins in experimental rumors. 103 29

Retinoids have been successfully used in the treatment of some forms of leukaemia, suggesting that such cells have an efficient uptake mechanism for circulating retinoids. Therefore, we have studied the uptake of lipoprotein-associated retinyl esters in human leukocytes in vivo. After an oral load of 100 mumol retinyl palmitate (30,000 retinol equivalents) per square meter given to healthy adults, the concentration of retinoids in circulating leukocytes was determined. A peak was measured after 5 h, which coincided with a peak of retinyl esters in plasma. To test whether low-density lipoprotein receptors are necessary for the postprandial uptake of retinoids, we studied retinoid uptake in leukocytes from two patients homozygous for familial hypercholesterolaemia. After an oral load of retinoids we found that leukocytes from these patients took up at least as much retinoid as leukocytes in normal individuals, suggesting that uptake of chylomicron remnant retinyl esters may proceed independent of the low-density lipoprotein receptor. The expression of mRNA for the low density lipoprotein receptor-related protein, which is a putative chylomicron remnant receptor, was similar in leukocytes from a patient homozygous for familial hypercholesterolaemia and normal individuals. Six hours after vitamin A administration, recovery of unesterified retinol was 71% in normal leukocytes, however, only 9% unesterified retinol was recovered in leukocytes from the two patients with familial hypercholesterolaemia. Thus, the apparent rate of retinyl ester hydrolysis was markedly reduced in leukocytes from these patients, indicating different intracellular traffic of chylomicron remnants in normal individuals and patients homozygous for familial hypercholesterolaemia.
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PMID:Uptake of chylomicron remnant retinyl esters in human leukocytes in vivo. 149 39

We have studied the effects of retinyl esters in chylomicron remnants on cell growth and differentiation of myeloid and lymphoid leukaemic cells. Ten mumol l-1 retinyl ester in chylomicron remnants effectively reduced proliferation of the myeloid leukaemic cell lines HL60, U937 and KG-1, and induced differentiation of 68% and 53% of the HL60 and U937 cells, respectively, in 5 days. While no effect on cell growth of the lymphoid cell lines Daudi, Raji and SOS was observed, 10 mumol 1-1 retinyl esters in chylomicron remnants reduced the growth of the B lymphoid cell line Reh by more than 50%. Primary cell cultures from six patients with acute leukaemia (four non-lymphocytic and two lymphocytic) were incubated with chylomicron remnant retinyl esters and proliferation was measured by means of thymidine incorporation. Among the myeloid leukaemic cells, the monomyelocytic, the two promyelocytic and the monoblastic leukaemic cells were growth inhibited. Chylomicron remnants had no effect on the growth of the c-ALL primary culture, but reduced proliferation of the T-ALL primary culture by approximately 20% after 48 h. These data suggest that high doses of retinol may be used in the treatment of some forms of acute leukaemia.
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PMID:Retinyl esters in chylomicron remnants inhibit growth of myeloid and lymphoid leukaemic cells. 177 18

Specific [3H]retinoic acid (RA)-binding sites in nuclear and cytosolic extracts prepared from human myeloblastic leukemia HL-60 cells have been detected by sucrose density gradient sedimentation and size-exclusion high-performance liquid chromatography (HPLC) analyses. This RA-binding activity migrated as a single peak with an apparent molecular weight of 50,000 and greater than 95% of the total binding activity was associated with the nuclear extract. Nuclear extracts prepared from COS-1 cells transfected with an expression vector for the nuclear RA receptors RAR alpha or RAR beta were enriched (20- to 100-fold) with a RA-binding activity that coeluted by size-exclusion HPLC with the putative RAR from HL-60 cells. The HL-60 nuclear receptor exhibited high-affinity binding of RA and its benzoic acid analogs Ch55, Ch30, Ro 13-7410, and SRI 6409-40 and low-affinity binding of retinol, Ro 8-8717, and SRI 5442-60, correlating well with the biological activity of these compounds in HL-60 cells. Saturation binding and Scatchard plot analyses of the binding of RA to the nuclear HL-60 receptor yielded an apparent dissociation constant of approximately 0.46 nM and 1400 +/- 100 receptor sites per cell. Northern blot analyses of poly(A)+ RNA with cDNA probes specific for RAR alpha and RAR beta indicated that HL-60 cells contain predominantly transcripts encoded by the RAR alpha gene. Our results suggest that the observed nuclear RA-binding activity in HL-60 cells might mediate the action of RA in these cells.
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PMID:Identification and characterization of nuclear retinoic acid-binding activity in human myeloblastic leukemia HL-60 cells. 254 90

Infection by LP-BM5 murine leukemia virus (MuLV) produces an AIDS-like condition in mice. The viral infection suppressed the percentage of peripheral blood cells showing surface markers for macrophages, activated macrophages, T lymphocytes and activated lymphoid cells. High dietary vitamin A (retinyl palmitate) caused increased numbers of activated macrophages. It also increased the percentage of cells with markers for Ia+ cells and macrophages in the retrovirally infected mice compared to infected controls. In uninfected mice retinyl palmitate stimulated the percentage of cells with activated lymphocytes bearing IL-2R, and T cytotoxic cells. These were associated with a retarded death rate during infection with LP-BM5 murine leukemia in C57BL/6 mice. By 25 weeks of infection and 20 weeks of retinyl palmitate supplementation 71.3% survived, while 45.0% virally infected controls survived. The mice also had elevated numbers of B cells measured in the blood after 4 and 8 weeks of dietary treatment. Vitamin A stimulation may play a role in the slower death rate for retrovirally infected mice.
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PMID:Enhanced survival by vitamin A supplementation during a retrovirus infection causing murine AIDS. 284 48

Human T-cell leukemia virus type I was induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 5-iodo-2'-deoxyuridine (ldUrd) in the MT-1 cell line. Virus expression was monitored by immunofluorescence microscopy with GIN-14, mouse monoclonal antibodies directed toward Mr 19,000 and Mr 28,000 protein-specific virus polypeptides. MNNG (0.1 micrograms/ml) and ldUrd (50 micrograms/ml) both induced virus synthesis in MT-1 cells. MNNG-induced virus expression peaked between 24 and 48 h of incubation, whereas ldUrd induced maximum virus expression between 48 and 72 h of incubation. Superinduction resulted when MNNG was added to cells induced 48 h previously with ldUrd, but not with concomitant treatment. 13-cis-Retinoic acid, retinol, retinol aldehyde, and retinol acetate (10(-6) to 10(-9)M) were concomitantly added with ldUrd to MT-1 cells for 24, 48, and 72 h incubation. All inhibited virus induction to various degrees. The retinoids were ranked as to inhibitory activity: retinol greater than retinoic acid greater than retinol aldehyde greater than retinol acetate. The most sensitive period for inhibiting ldUrd induction by retinoic acid was 24 h postinduction or with concomitant treatment. Vitamin C and vitamin E inhibited ldUrd induction most effectively with 48 h incubation. Retinol and vitamin C also inhibited virus induction by MNNG. None of the retinoids, vitamin C, or vitamin E significantly inhibited virus expression in noninduced cells or were toxic to the cells at the concentrations used in these experiments.
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PMID:Human T-cell leukemia virus I induction by 5-iodo-2'-deoxyuridine and N-methyl-N'-nitro-N-nitrosoguanidine: inhibition by retinoids, L-ascorbic acid, and DL-alpha-tocopherol. 299 Jun 71

Vitamin A has been shown to potentiate the cytotoxic action of anticancer agents like vincristine (VCR) against drug resistant mouse P388 leukaemia cells. In vitro tests showed enhancement by retinyl acetate of cytocidal activities of VCR against drug-sensitive leukaemia (P388/S) and VCR-resistant leukaemia (P388/VCR) cells in culture; retinyl acetate rather specifically potentiated VCR against cultured P388/VCR cells than P388/S cells. The cellular accumulation of radioactive VCR was significantly enhanced in cultured P388/VCR cells when retinyl acetate was present. The efflux of VCR from drug-resistant cells was blocked by retinyl acetate. The effect of the combination of vitamin A and VCR was also tested in vivo on the life-span of mice bearing P388/S or P388/VCR. Intraperitoneal administration of retinyl palmitate at 41.75 or 83.5 mg kg-1 was effective to potentiate the antileukaemic activity of VCR against P388/S bearing mice, and it also overcame vincristine-resistance in P388/VCR bearing mice.
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PMID:Potentiation of vincristine by vitamin A against drug-resistant mouse leukaemia cells. 366 74

An alternative to a cell-kill strategy for eradication of acute myelogenous leukemia, is to restore normal differentiation. Vitamin A derivatives demonstrate differentiation-inducing activity both in vitro and in vivo on promyelocytic leukemic cells. We tested the ability of 13-cis retinoic acid to reduce proliferation and induce differentiation in 10 samples from patients with acute non-promyelocytic leukemia. DNA synthesis and leukemia colony formation were affected to varying degrees by a prolonged exposure to the vitamin A compound. Morphologically and cytochemically no differentiation was determined either after 48 h in suspension cultures or 7 additional days in semi-solid cultures. Alkaline leukocyte phosphatase, a biochemical marker of differentiation, was significantly increased in five samples. DNA synthesis in these samples was significantly reduced as compared to samples failing to express alkaline leukocyte phosphatase following 13-cis retinoic acid treatment. DNA synthesis of these same 5 samples was also strongly inhibited by Ara-C. Expression of alkaline leukocyte phosphatase following 13-cis retinoic acid exposure may be a useful indicator for cells amenable to 13-cis retinoic acid or Ara-C treatment.
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PMID:Effects of 13-cis retinoic acid and Ara-C on differentiation and proliferation of non-promyelocytic acute myelogenous leukemia. 386 17

Combinations of retinol palmitate (RP) and six different anticancer agents were examined to determine their effects on the life-span of mice bearing ascites sarcoma 180 or P388 leukemia. With ascites sarcoma 180, administration of a fixed dose of RP (3.3 mg/kg) considerably enhanced the antitumor effects of 5-fluorouracil (5-FU) (5 mg/kg, or 20 mg/kg), methotrexate (MTX) (0.5 mg/kg, or 1 mg/kg) and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) (12.5 mg/kg), when given by intraperitoneal injection. However RP failed to potentiate the antitumor effects of adriamycin (ADM) and 6-mercaptopurine (6-MP) against sarcoma 180. With P388 leukemia, RP (167 mg/kg, or 333 mg/kg) enhanced the antitumor effects of 6-MP (25 mg/kg, or 50 mg/kg), MTX (1 mg/kg, or 2 mg/kg), ADM (0.2 mg/kg), ACNU (5 mg/kg) and cis-dichlorodiammine-platinum (CDDP) (1 mg/kg) to a considerable extent, but it did not potentiate the antitumor effect of 5-FU. The combination of RP with ACNU or CDDP was particularly effective against P388 leukemia.
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PMID:Potentiation by vitamin A of the action of anticancer agents against murine tumors. 393 88

Vitamin A and its analogues (retinoids) affect normal and malignant hematopoietic cells. We examined the effect of retinoids on the clonal growth in vitro of myeloid leukemia cells. Retinoic acid inhibited the clonal growth of the KG-1, acute myeloblastic leukemia, and the HL-60, acute promyelocytic leukemia, human cell lines. The KG-1 cells were extremely sensitive to retinoic acid, with 50% of the colonies inhibited by 2.4-nM concentrations of the drug. A 50% growth inhibition of HL-60 was achieved by 25 nM retinoic acid. Complete inhibition of growth of both leukemia cell lines was seen with 1 microM retinoic acid. Exposure of KG-1 cells to retinoic acid for only 3-5 d was sufficient to inhibit all clonal growth. The all-trans and 13-cis forms of retinoic acid were equally effective in inhibiting proliferation. Retinal, retinyl acetate, and retinol (vitamin A) were less potent inhibitors. Clonal growth of the human K562 and mouse M-1 myeloid leukemic cell lines was not affected by 10 microM retinoic acid. Retinoic acid also inhibited the clonal growth of leukemia cells from five of seven patients with acute myeloid leukemia. Retinoic acid at concentrations of 5 nM to 0.3 microM inhibited 50% clonal growth, and 1 microM retinoic acid inhibited 64-98% of the leukemic colonies. The inhibition of clonal growth of KG-1 and HL-60 cell lines and of leukemic cells from two patients was not associated with the presence of a specific cytoplasmic retinoic acid-binding protein. Our study suggests that retinoic acid may prove to be effective in the treatment of human myeloid leukemia.
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PMID:Retinoic acid. Inhibition of the clonal growth of human myeloid leukemia cells. 627 39


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