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)

In A-Jax mice, the appearance of MCA-induced sarcomas in delayed by Vitamin A application. Continuous uptake of drinking water containing 0.05% of a retinol palmitate emulsion leads to a significant inhibition. Administration of ethylnitrosourea (ENU) to pregnant Swiss mice on the 17th day of gravidity results in the formation of lymphoblastoid leukemias from the beginning of the 12th week after birth, 90% of the animals dying within 25 weeks. In this case, continuous addition of 0.1% retinol palmitate emulsion to drinking water leads to a dramatic reduction of the tumor risk to about 50%. By additional administration of proteolytic enzymes of animal and plant origin this risk can be further reduced. The lung adenomas developing to 100% in the animals are not influenced by this treatment. Vitamin A, added to drinking water, exerts a strong inhibitory effect on transplacentally induced leukemia.
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PMID:Experimental cancer prophylaxis. 635 37

Administration of vitamin A (retinol palmitate) causes a reduction of transplacentally induced leukemias. Subsequent to a transplacental application of ENU, addition of vitamin A as a suspension to drinking water leads to a reduction of leukemia incidence to 50% as well as to a corresponding decrease of this disease as a cause of death. Yet there is no influence of vitamin A on the adenomas of the lung arising in this experimental design.
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PMID:Prevention of transplacentally induced malignant diseases. 670 Sep 32

In mice, administration of ethylnitrosourea (120 mg/kg body weight) on day 14 of pregnancy leads to a transplacentally induced and transplantable leukemia in a high percentage of the offspring. Moreover, 100% of the offspring develop, later on, adenomas of the lung. Application of retinol palmitate (daily dose 170,000 IU/kg) reduces leukemogenesis up to 50%, yet without influencing formation of lung adenomas.
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PMID:Influence of vitamin A on the formation of ethylnitrosourea (ENU)-induced leukemias. 686 90

The inhibition of the growth of HeLa cells in culture by 6-mercaptopurine was greatly enhanced in combination with retinol, retinal or retinol acetate, but not in combination with retinoic acid or retinol palmitate. The antitumor effect of retinol palmitate combined with 6-mercaptopurine was examined in BDF1 mice with L1210 leukemia. The blood level of retinol, a strong potentiator of 6-mercaptopurine among vitamin A compounds, was increased in BDF1 mice after retinol palmitate injection. Retinol palmitate was found to enhance the antitumor effect of 6-mercaptopurine against murine L1210 leukemia to a significant extent (69% increase in life span).
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PMID:Enhancement of the antitumor effect of 6-mercaptopurine by vitamin A. 719 7

Preclinical studies make fenretinide attractive for prevention and treatment of breast cancer. It inhibits mammary gland end bud formation in developing animals. Carcinogen-induced mammary cancer is suppressed by fenretinide, both at early and late stages of carcinogenesis, in young and mature rats. Fenretinide causes regression of invasive rat mammary cancer. Cytostatic activity has been demonstrated against human breast cancer cell lines. Autocrine stimulation of human breast cancer cell lines by tgf-alpha, insulin-like growth factors I and II is significantly abrogated by fenretinide. The human half-life is 24 hours. Absorption is markedly affected by meal content. Serum levels of 1 mM are achieved at doses of 200 mg/day. This dose significantly suppresses serum IGF-I levels in women. This concentration is capable of suppressing human breast cancer growth in vitro. A 3-day drug holiday is given each month in order to restore serum retinol levels. Under these circumstances, fenretinide is well tolerated. A phase III trial evaluating the efficacy of fenretinide for breast cancer prevention in high-risk women has been completed. Tamoxifen enhances the effectiveness of fenretinide in carcinogenesis models. The combination can be safely administered to women. A phase III adjuvant trial of tamoxifen, with or without fenretinide will be conducted in the United States.
Leukemia 1994
PMID:Breast cancer and fenretinide, an analogue of vitamin A. 780 27

Progesterone-associated endometrial protein (PAEP/PP14) is a 28-kD glycoprotein with sequence homology to beta-lactoglobulins containing a retinol-binding motif. PAEP/PP14 is present at nanomolar concentrations in human serum. It is produced by secretory and decidualized endometrium in women and by seminal vesicle epithelium in men. We report here that PAEP mRNA is constitutively expressed in normal hematopoietic tissue. Western immunoblotting of bone marrow cells with rabbit antibodies to PAEP gave a band at 28 kD, and immunocytochemical staining with monoclonal antibodies localized PAEP into the cytoplasm of erythroid precursors representing different stages of the normoblast series. PAEP was not detected in mature red blood cells, platelets, or in cells of the myeloid lineage. Untreated K562 leukemia cells did not contain PAEP, whereas treatment of the cells with tetradecanoylphorbol acetate (TPA) induced strong expression of PAEP mRNA and synthesis of the intact protein that was found both in the cytoplasm of the differentiating cells and in the supernatant of TPA-treated cultures. These findings add a new member to the growing family of genes that are constitutively expressed both in the reproductive tract and in the hematopoietic system.
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PMID:Progesterone-associated endometrial protein--a constitutive marker of human erythroid precursors. 802 74

Serum antioxidant vitamins A (retinol) and E (alpha-tocopherol), beta-carotene, zinc and selenium for 418 children with newly diagnosed malignancy were compared with those of 632 cancer-free controls. Incident cancer cases and controls were 1-16 years old and recruited in 1986-1989. Age- and sex-adjusted serum concentrations of retinol, beta-carotene and alpha-tocopherol were significantly inversely associated with cancer. In similar models, the odds ratio (OR) comparing the highest with the lowest quintile was 2.06 (95% confidence interval [CI] 1.40-3.02) for retinol, 3.87 (95% CI: 2.54-5.90) for beta-carotene, 2.15 (95% CI: 1.48-3.10) for alpha-tocopherol, 1.29 (95% CI: 0.75-2.23) for selenium, and 1.94 (95% CI: 1.17-2.23) for zinc. The cancer sites that were associated with serum beta-carotene were, in general, leukaemia, lymphoma, central nervous system, bone and renal tumours. Moreover, leukaemia was associated with low mean serum levels of retinol, selenium and zinc. Subjects with lymphoma, bone and renal tumours also had lower mean retinol and alpha-tocopherol levels than controls. Brain tumour patients had low vitamin E levels. Low serum values of antioxidant vitamins were associated with childhood neoplasm occurrence. Some site-specific effect was reported. Low peripheral nutrient levels are not considered as cancer promoters but rather as an impairment of the body's defence mechanism occurring during the cancer-related metabolic and nutritional disturbances and inflammation processes.
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PMID:Serum beta-carotene and antioxidant micronutrients in children with cancer. The 'Cancer in Children and Antioxidant Micronutrients' French Study Group. 828 53

14-Hydroxy-4,14-retro-retinol (14-HRR), first isolated from cultures of lymphoblastoid 5/2 and HeLa cells and characterized by NMR, UV, and CD, is a metabolite of retinol which promotes growth of B lymphocytes in culture and activation of T lymphocytes by antigen receptor-mediated signals. It is also produced by various tested cell lines: fibroblasts, leukemia, and Drosophila cells. 14-HRR is the first bioactive retro-retinoid to be discovered and, after retinal and retinoic acid, is the third intracellular messenger molecule derived from retinol. Physical properties and intracellular signaling activities of synthetic (14R)-HRR, (14S)-HRR, and racemic 14-HRR are described. CD spectra indicate that natural 14-HRR isolated previously was a mixture of enantiomers. B-cell survival and T-cell activation assays performed in the optimal range of (7-1.6) x 10(-7) M surprisingly showed that all 14-HRR compounds exhibit similar activity, with the 14R enantiomer exhibiting slightly higher activity in comparison to the 14S enantiomer. However, because of the semiquantitative nature of the assays, the conclusion as to which enantiomer is more active and which is the true ligand for the target receptor must await characterization of this protein.
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PMID:Intracellular signaling activity of synthetic (14R)-, (14S)-, and (14RS)-14-hydroxy-4,14-retro-retinol. 829 89

Vitamin A (VA) protects the small intestine from methotrexate (MTX)-induced damage. However, before VA can be used as a remedy to protect cancer patients from MTX-induced damage to the intestine, it is essential to clarify whether or not it disturbs the antitumor activity of MTX. This study investigated the effect of VA on the antitumor activity of MTX in vitro in L1210 murine leukemia cells. The incorporation of [6-3H]-thymidine and [6-3H]-uridine, [5-3H]-uridine, and [4,5-3H]-leucine into DNA, RNA, and proteins, respectively, was examined to evaluate this effect. The incorporation of thymidine, the uridines, and leucine decreased dose-dependently in MTX-treated L1210 cells and profoundly in the MTX plus VA-treated L1210 cells, since VA itself had a cell-killing activity. Thus, MTX depressed the growth of L1210 cells dose-dependently and this depression was not affected by the presence of VA. The present study proved in L1210 murine leukemia cells in vitro that VA did not disturb the antitumor activity of MTX.
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PMID:Effect of vitamin A on methotrexate cytotoxicity in L1210 murine leukemia cells in culture. 832 67

Since their introduction 15 years ago, retinoids have been increasingly used for topical and systemic treatment of psoriasis and other hyperkeratotic and parakeratotic skin disorders, keratotic genodermatoses, severe acne and acne-related dermatoses, and also for therapy and/or chemoprevention of skin cancer and other neoplasia. Oxidative metabolites of vitamin A (retinol) are natural retinoids present at low levels in the peripheral blood. Synthetic retinoids are classified into 3 generations including nonaromatic, monoaromatic and polyaromatic compounds. They are detectable in plasma 30-60 minutes after systemic administration, and reach maximum concentrations 2 to 4 hours later. Elimination half-life is 10 to 20 hours for isotretinoin, 80 to 175 days for etretinate and 2 to 4 days for, trans-acitretin; the latter, however, partially converts into etretinate. Retinoid concentrations in skin are rather low in contrast to subcutaneous fat tissue. Intracellularly, retinoids interact with cytosolic proteins and specific nuclear receptors. Two classes of nuclear receptors have been suggested to mediate retinoid activity at the molecular level, RARs and RXRs. The expression of retinoid receptors is tissue specific; skin mainly espresses RAR gamma and RXR alpha. Retinoids affect epidermal cell growth and differentiation as well as sebaceous gland activity and exhibit immunomodulatory and anti-inflammatory properties. Current retinoid research targets the development of receptor-selective retinoids for tailoring and/or improving their therapeutic profile. Currently, tretinoin is used systemically for acute promyelocytic leukaemia, etretinate and acitretin for psoriasis and related disorders, as well as other disorders of keratinisation and isotretinoin for seborrhoea, severe acne, rosacea and acneiform dermatoses. Systemic retinoids are also applied for chemoprevention of epithelial skin cancer and cutaneous T cell lymphoma. The major adverse effect of retinoids is teratogenicity; all other adverse effects are dose-dependent and controllable. Contraception is, therefore, essential during retinoid treatment in women of child-bearing age. Clinical monitoring requires physical examination for adverse effects every 3 to 4 weeks and proper laboratory investigations, also including analysis of retinoid bioavailability in selected cases. Topical retinoids are rapidly developing at present and seem promising for the future; their clinical application includes acne, aging, photodamage, precanceroses, skin cancer and disorders of skin pigmentation. The development of receptor-specific retinoids for topical treatment of psoriasis and/or acne may lead to interesting new compounds based on our current concepts of retinoid function.
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PMID:Current use and future potential role of retinoids in dermatology. 907 40


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