Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin A level and the cytosol-binding proteins specific for vitamin A ere studied in human tumor and its surrounding tissue. The tissues examined were 10 hepatocellular carcinomas which were surgically removed, 4 other malignant tumors (2 metastatic liver cancer and one each of gastric cancer and glioma), and 3 human fetal livers. Compared with surrounding tissues, considerable decrease of vitamin A content was observed in the hepatocellular carcinoma suggesting local deficient state of the vitamin. In addition to cellular retinol-binding protein (CRBP) and retinoic acid-binding protein (CRABP), a new molecular species having affinity for both retinol and retinoic acid was detected in the cytosols obtained from hepatocellular carcinoma as well as glioma by means of gel filtration on Sephadex G-75. With regard to ligand specificity, the protein was found to be similar to cellular retinol-binding protein, F-type or CRBP(F) which was originally recognized in the fish eye cytosol. Since the protein was also demonstrated in human fetal liver, CRBP(F) is considered to be an oncofetal protein in nature. The present study further revealed that CRBP(F) was detected in 80% of hepatocellular carcinoma (whereas plasma alpha-fetoprotein was significantly elevated only in 50%), and hepatocellular carcinoma contained CRBP(F) in a larger amount than CRABP.
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PMID:Demonstration of a novel cellular retinol-binding protein, F-type, in hepatocellular carcinoma. 8 58

Synthetic aromatic analogs of retinoic acid were administered i.p. and p.o. to Fischer F344 rats bearing a transplantable chondrosarcoma. 35CO4 incorporation into glycosaminoglycans were compared for neoplastic and normal cartilage explants after removal from animals given various analogs. There was a direct relationship between [35S]glycosaminoglycan synthesis by chondrosarcoma chondrocytes and inhibition of tumor growth. The degree of inhibition of [35S]glycosaminoglycan synthesis in the neoplastic cartilage was dependent on the dose of the retinoid administered. At 20-mg/kg/day doses of retinoid for 4 weeks, 35SO4 incorporated into glycosaminoglycan by treated tumor explants was reduced as much as 95%. There was no reduction of [35S] glycosaminoglycan produced in normal costal cartilage of the same animals. Retinoid treatment of 20-mg/kg/day doses for 4 weeks resulted in a 75% reduction in glycosaminoglycan per mg of chondrosarcoma; there was no reduction in costal cartilage glycosaminoglycan. Retinoid (10- to 20-mg/kg/day doses) elevated collagen levels per mg of chondrosarcoma but had no effect on costal cartilage collagen. Combined in vitro and in vivo studies showed that retinoid administration modified neoplastic chondrocyte function but had no measurable effect on normal chondrocyte function.
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PMID:Effect of aromatic retinoids on rat chondrosarcoma glycosaminoglycan biosynthesis. 13 54

This paper reports the effect of vitamin A and its derivatives, the retinoids, on plasminogen activator (PA) synthesis in chick embryo fibroblast cultures (CEF). Low concentrations of retinoic acid (RA) (10(-6)-10(-10) M) and the retinoids stimulated PA synthesis in CEF; the maximal stimulation achieved, 9--10 fold, was somewhat lower than that obtained with optimal concentrations of the potent tumor promoter phorbol myristate acetate (PMA). This action of RA required protein and mRNA synthesis but, in contrast to enzyme induction by PMA and/or sarcoma virus transformation, retinoid effects were not significantly inhibited by elevated concentrations of cAMP. In inducing and/or stimulating PA production, the effects of RA and sarcoma virus transformation were synergistic rather than additive. Analogous synergism was observed between RA and PMA, but only at suboptimal concentrations of the latter. RA did not affect PA production in normal or transformed cultures maximally stimulated by PMA. These findings may help to elucidate the role of retinoids in promoting tumor growth, tissue remodeling and teratogenesis.
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PMID:Plasminogen activator in chick fibroblasts: induction of synthesis by retinoic acid; synergism with viral transformation and phorbol ester. 21 37

To explore the generality of the effects of sarcoma viruses, tumor-promoting phorbol esters and retinoic acid, we have studied plasminogen activator production in differentiating chick myogenic cultures. Although slightly higher than in chick fibroblast cultures, the level of spontaneously synthesized enzyme is low; it reaches a peak shortly after maximum cell fusion has been completed and then declines. Rous sarcoma virus (RSV) transformation of differentiating myotubes was accomplished by infecting myoblasts with a temperature-sensitive mutant, maintaining cultures at the nonpermissive temperature until completion of fusion and shifting to permissive temperatures at selected times thereafter. RSV transformation, phorbol myristate acetate (PMA) and retinoic acid all induced high levels of plasminogen activator production by differentiating myotubes in the absence of DNA synthesis. In comparison with fibroblasts, virus-induced enzyme synthesis by myogenic cultures proceeded more slowly but ultimately reached comparably high levels. Whereas cAMP strongly repressed RSV- and PMA-induced plasminogen activator production by chick fibroblasts, it weakly stimulated enzyme synthesis by myotubes. This suggests that enzyme induction by RSV and PMA is not mediated primarily through effects on cAMP metabolism.
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PMID:Plasminogen activator in chick embryo muscle cells: induction of enzyme by RSV, PMA and retinoic acid. 21 22

Retinoic acid-binding protein (RABP) has been detected in the nuclei of chick embryo skin and Lewis lung tumor. The nuclear binding component showed the same ligand specificity and sedimentation value as the cytosol RABP. Whereas pronase completely digested the nuclear binding component, DNase showed 40%, and RNase showed negligible digestive action. Retinoic acid binding to the nuclear RABP was completely inhibited by a mercurial, and the inhibition was reversed by dithiothreitol. The nonspecific uptake of retinoic acid by Lewis drug nuclei and chick embryo skin nuclei was inhibited up to 50% by cytosol RABP. The maximal inhibitory effect produced by cytosol RABP was after 45-min incubation. Incubation of Lewis lung tumor with [3H]retinoic acid resulted in the appearance of nuclear RABP: [3H]retinoic acid in the nuclei. The complex formed was weak, and most of the bound retinoic acid could be removed by dialysis.
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PMID:Localization of retinoic acid-binding protein in nuclei and the nuclear uptake of retinoic acid. 22 Nov 5

Infection of differentiated mouse embryo cells by simian virus 40 (SV40) leads to the production of the early mRNAs and the tumor (T) antigens that they encode. In contrast, undifferentiated F-9 murine teratocarcinoma cells do not support these early stages of the SV40 cycle. This block results from the inability to accumulate stable processed early SV40 mRNAs. It has recently been shown that vitamin A and its derivatives can induce in vitro differentiation of stem cells. Undifferentiated F-9 cells, upon treatment with a low concentration of retinoic acid, exhibited pronounced morphologic changes as well as the appearance of the H-2 surface antigens. After differentiation, the susceptibility of F9 cells to SV40 infection could be demonstrated by the appearance of large T and small T antigens, as shown by immunofluorescence and immunoprecipitation. Furthermore, SI nuclease mapping of early SV40 transcripts confirmed the presence of the two spliced early mRNAs. These results indicate that the undifferentiated F-9 stem cells contain the genetic information needed for generating stable processed early SV40 mRNAs but are blocked in the production of functional species.
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PMID:Differentiation as a requirement for simian virus 40 gene expression in F-9 embryonal carcinoma cells. 23 Apr 84

The ability of retinoic acid (RA), a potent antitumor agent, to stimulate cell-mediated cytotoxicity (CMC) in mice was investigated. Low doses of RA (5-300 micrograms/mouse/day) administered ip into C57BL/6 mice for 5 days daily or for 1--3 months three times a week before immunization in vivo or in vitro with allogeneic BALB/c S194 myeloma cells led to an enhanced cytotoxic activity of their spleen effector cells. Similarly, in a syngeneic situation injection of RA into C57BL/6 or BALB/c mice before in vitro challenge with EL 4 (C57BL/6) or S194 (BALB/c) tumor cells strongly stimulated CMC. The enhanced cytotoxic activity was effected by thymus-derived lymphocytes (T-cells) and specific for the H-2 histocompatibility antigens in the case of the allogeneic sensitization or specific for tumor antigens in the case of the syngeneic sensitization. Because RA had no effect on the effector step of CMC, RA likely enhanced the induction step of T-CMC. The action of RA was antigen-dependent, and it is therefore a true adjuvant rather than a nonspecific stimulator or polyclonal activator of cytotoxic T-cells.
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PMID:Retinoic acid stimulation of the induction of mouse killer T-cells in allogeneic and syngeneic systems. 30 67

Previous studies indicated that the potent tumor promoter 12--0--tetradecanoyl-phorbol-13-acetate (TPA) enhances transformation of rat embryo cells (2 degrees RE) by a mutant of human Ad5 (H5ts125). This study examines the effect of TPA, its structural analogs and epidermal growth factor (EGF) on anchorage-independent growth of a cloned population of H5ts125-transformed 2 degrees RE cells (clone E11). Both TPA and EGF (approximately 10(-8) M) induced a 3--5 fold increase in agar cloning efficiency of E11 cells. In addition, macroscopic colonies appeared earlier and were larger and more diffuse. The TPA analogs phorbol--12,13--didecanoate (PDD) and ingenol--3,20--dibenzoate also enhanced growth in agar of E11 cells, whereas phorbol, 4 alpha PDD and 4--0--meTPA, which are inactive as tumor promoters, failed to enhance agar growth. In contrast to the results obtained with E11 cells, TPA, PDD or ingenol--3,20--bidenzoate failed to induce growth in agar of normal 2 degrees RE cells. Dexamethasone (10(-5)--10(-6) M), trans retinoic acid (10(-5)--10(-6) M) and the protease inhibitors leupeptin, antipain and elastatinol did not inhibit the ability of TPA to enhance the growth of E11 cells in agar. The TPA-enhanced anchorage independence was a stable property, since subclones of E11 cells isolated from TPA-agar plates had a higher agar cloning efficiency than the parental E11 cells when retested in the absence of TPA. This effect of TPA does not appear to reflect simple selection of a subpopulation of cells. When the parental E11 cells were first cloned in monolayer culture in the absence of TPA, all ten randomly picked clones showed enhanced growth in agar in the presence of TPA. In addition, prior growth of E11 cells in monolayer culture in the presence of TPA did not enhance their subsequent growth in agar. This system therefore provides an example in which TPA appears to enhance the acquisition of a stable cell property, and thus may be a useful model for studying mechanisms of tumor promotion and progression.
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PMID:Tumor promoters and epidermal growth factor stimulate anchorage-independent growth of adenovirus-tranformed rat embryo cells. 31 62

Retinoic acid (RA), a vitamin A derivative with anti-tumor activity, was assayed for its effects on the immune system in mice. High doses of this compound (1000 microgram/mouse/day) have toxic effects and cause depletion on the peripheral lymphoid organs (spleen, thymus) while leaving the bone marrow cells unaffected. Both the in vivo and in vitro induction of cell-mediated cytotoxicity (CMC) to allogeneic tumor cells is stimulated at least tenfold by low doses (25--300 microgram/mouse/day) of RA while high doses suppress CMC induction. RA is shown to be a specific adjuvant for the induction of cytotoxic thymus-derived lymphocytes (T cells) and not a general T cell mitogen or adjuvant. It does not enhance the proliferative response in the mixed lymphocyte culture nor does it stimulate lymphocyte proliferation in response to the mitogens concanavalin A and phytohemagglutinin. The induction of cooperating T cells and the delayed-type hypersensitivity reaction are also not stimulated by RA. In contrast to the reported stimulatory effects of retinyl palmitate and retinyl acetate, RA does not stimulate the humoral response to erythrocytes. The strong adjuvant effects that RA has on the induction of CMC at low doses may be responsible for its anti-tumor activity.
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PMID:Effects of retinoic acid on the immune system: stimulation of T killer cell induction. 34 57

Clinical observations and epidemiologic studies indicate that the sun is the primary stimus for most human skin can formation. However, investigations directly confirming this association as well as defining the action spectra, time-dose relationships, energy level requirements, etc., have been confined to animal experimentation. Studies in which gross methods are used indicate that the experimental carcinogenic action spectrum falls primarily between 280 and 320 nm. Quantitative studies and tumor promotion investigations indicate that UV-induced cancer formation begins with the initial exposure. Heat, wind, and moisture stimulate UV carcinogenesis. Also, exogenous chemicals may influence carcinogenesis as photosensitizers such as 8-MOP, as additive carcinogens as noted with DMBA, or as promoters as described for Croton oil, retinoic acid, and BCNU. Qualitative studies indicate that progressive alterations occur in the epidermal-dermal basement membrane and dermal conncecive tissue and mucopolysaccharides associated with the progressive development of epidermal cancers. Malignant melanomas have also been induced experimentally in hairless mice with UV energy. Mechanistically, immunologic alterations and effects on DNA have received the most attention. Tumor-specific antigenicity as well as antigen deletion has been demonstrated. Immune suppression by antilymphocyte serum and certain chemicals has led to stimulation of tumor development. Perhaps the most exciting new information relates to the demonstration that chronically UV-irradiated mice have not rejected highly antigenic UV-induced cancers. This indicated that UV irradiation specifically altered the immunologic responses of the animals to these tumors. Within recent years, the influence of DNA injury and repair on cutaneous carcinogenesis has received a great deal of attention. This has been partly due to the demonstration of defective repair of UV-induced DNA damage in patients with XP. The primary photosensitive problem in these patients is an inordinate sensitivity to the carcinogenic effects of sunlight. However, correlation of DNA injury and repair directly with cancer formation has not been accomplished.
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PMID:Photocarcinogenesis: a review. 38 36


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