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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The carcinogenic process is usually multifactor in its causation and multistep in its evolution. It is likely that entirely different molecular mechanisms underlie the many steps in this process. In contrast to initiating carcinogens, the action of the tumor-promoting phorbol esters does not appear to involve covalent binding to cellular DNA and they are not mutagenic. Recent studies in cell culture have revealed two interesting biologic effects of the phorbol esters and related macrocyclic plant diterpenes. The first is that at nanomolar concentrations they induce several changes that resemble those seen in cells transformed by chemical carcinogens or tumor viruses. These include altered morphology and increased saturation density, altered cell surface fucose-glycopeptides, decrease in the LETS protein, increased transport of deoxyglucose, and increased levels of plasminogen activator and ornithine decarboxylase. In transformed cells exposed to phorbol esters the expression of these features is further accentuated. Phorbol esters do not induce normal cells to grow in agar but they do enhance the growth in agar of certain transformed cells. The second effect of the phorbol esters is inhibition of terminal differentiation. This effect extends to a variety of programs of differentiation and is reversible when the agent is removed. With certain cell culture systems induction of differentiation, rather than inhibition, is observed. Both the transformation mimetic and the differentiation effects are exerted by plant diterpenes that have tumor-promoting activity but not by congeners that lack such activity. The primary target of phorbol esters appears to be the cell membrane. Early membrane-related effects include enhanced uptake of 2-deoxyglucose and other nutrients, altered cell adhesion, induction of arachidonic acid release and prostaglandin synthesis, inhibition of the binding of epidermal growth factor to cell surface receptors, altered lipid metabolism, and modifications in the activities of other cell surface receptors. A model of "two stage" carcinogenesis encompassing the known molecular and cellular effects of initiating carcinogens and tumor promoters is presented. According to this model, initiating carcinogens induce stable alterations in the cellular genome but these are not manifested until tumor promoters modulate programs of gene expression and induce the clonal outgrowth of the initiated cell.
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PMID:Action of phorbol esters in cell culture: mimicry of transformation, altered differentiation, and effects on cell membranes. 39 70

Ornithine decarboxylase (ODC) production was used as an indicator of mitotic activity in neoplastic cells removed from murine hosts at progressive stages of growth. Cells from three ascites cancers and one fibrosarcoma were tested and showed declining ODC production with progressive growth. The cells were incubated with serum or malignant effusion fluid taken from the murine hosts at progressive stages of growth. For 2 to 3 weeks after tumor implantation, sera and, in particular, ascites fluids increasingly stimulated ODC production in cells at all stages of growth. With advancing disease, without the malignant growth having reached a stationary phase, the collected fluids decreasingly stimulated ODC production in the cells. The stimulating factor(s) in host serum and malignant effusion fluid were not tumor specific in the one combination tested.
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PMID:Endogenous tumor growth factor indicated by increased ornithine decarboxylase activity in malignant cells treated with host serum ascites fluid. 42 94

The effect of dietary L-arginine on the growth and development of transplantable Ehrlich Ascites tumor cells was examined. Growth of tumor bearing mice was significantly inhibited by feeding a purified casein diet supplemented with 5% arginine. This diet significantly reduced the total number of free tumor cells growing in the peritoneal cavity of mice. Total free tumor cell RNA, DNA, and protein were also significantly reduced. Supplemental arginine approximately doubled the length of time for 50% death of tumor bearing mice. Arginine did not alter respiration as measured by glucose or citrate oxidation. Varying the concentration of supplemental dietary arginine revealed that 3% arginine also significantly retarded the growth of Ehrlich Ascites Tumor Cells. Tumor ornithine decarboxylase activities were significantly reduced by dietary arginine supplementation. Supplemental dietary arginine at 3 or 5% did not significantly affect the growth of non-tumor bearing mice. Dietary arginine may play a critical role in growth of normal as well as neoplastic tissue.
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PMID:Inhibitory effect of dietary arginine on growth of Ehrlich ascites tumor cells in mice. 43 Feb 51

The ability of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to induce the enzyme ornithine decarboxylase (ODC) and to stimulate DNA synthesis was studied in four different cell types in vitro. The effects of this agent on each cell type were different: (a) in hamster embryo cells, TPA induced ODC but had no effect on DNA synthesis; (b) TPA induced ODC and stimulated DNA synthesis in BALB/c 3T3 mouse cells; (c) it did not induce ODC in human fibroblasts but did stimulate DNA synthesis; and (d) it induced neither ODC nor DNA synthesis in rat embryo fibroblasts. In contrast to the effects of TPA, ODC was induced and DNA synthesis was stimulated in all cell types by fresh serum-containing medium. Treatment of the cells with a combination of fresh medium and TPA resulted in an approximate summation of the effects of treatment with each agent alone. These results emphasize the differences in the responses of various cells to TPA. They also show that in some cells, at least, the induction of ODC and stimulation of DNA synthesis following TPA treatment can be regulated independently.
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PMID:Ornithine decarboxylase activity and DNA synthesis after treatment of cells in culture with 12-O-tetradecanoylphorbol-13-acetate. 49 78

The reactivity of normal and tumor host lymphocytes incubated with normal serum or with serum or malignant ascites fluid from tumor hosts was measured by the ability of the lymphocytes to synthesize ornithine decarboxylase after phytohemagglutinin stimulation. Each of three tumors tested (a solid fibrosarcoma, an ascites mammary carcinoma, and an ascites ovarian carcinoma) caused increasing unresponsiveness in the lymphocytes of mice with progressing syngeneic neoplastic growth. The sera and particularly the malignant ascites fluids from mice given implants of the ascites cancers became progressively inhibitory to the activation of lymphocytes from tumor hosts as well as from normal mice. The serum from mice carrying s.c. implants of the fibrosarcoma enhanced the activation of lymphocytes from tumor hosts and from normal mice during early tumor growth before it also became inhibitory.
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PMID:Effect of progressive neoplastic growth on the decarboxylation of DL-[1-14C]ornithine by lymphocytes from C3H/He tumor hosts. 66 20

The tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA), a highly active comitogen in phytohemagglutinin-treated bovine lymphocytes, induces an 11-fold increase in ornithine decarboxylase activity over cultures treated with the lectin alone. This synergistic action of TPA could be antagonized by the simultaneous addition of the acyclic sesquiterpene, insect juvenile hormone III. Retinoic acid (vitamin A acid), an inhibitor of the tumor-promoting action of TPA in mice, was also an effective antagonist but required administration to lectin-activated lymphocytes 1 hr prior to TPA. These data suggest that metabolic activation of retinoic acid is required in order to exert its antagonistic action. Comparison of the responses in the lymphocytes and mouse skin suggests that the lymphocytes provide an excellent system for studying the molecular processes through which phorbol esters and retinoids influence the growth and differentiation of both normal and premalignant cells.
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PMID:Effects of retinoic acid and juvenile hormone on the induction of ornithine decarboxylase activity by 12-O-tetradecanoylphorbol-13-acetate. 67 97

A factor responsible for stimulating an increase in ornithine decarboxylase activity in the liver of mice was found in tumor cell-free ascites fluid of mice 3 days after inoculation of tumor cells. The factor was purified about 70-fold in 25% yield from tumor cell-free ascites fluid. As little as 1 microgram of protein of purified fraction, injected intraperitoneally into normal mice, significantly increased the activity of ornithine decarboxylase in the liver. The most active preparation of the factor formed two major protein bands on analytical polyacrylamide gel electrophoresis and both these bands stained with periodic acid-Schiff's reagent. The factor was a heat-labile, alkaline-stable, acidic protein with a molecular weight of more than 300 000. It was inactivated by treatment with 10 mM dithiothreitol, 5 M urea, pronase or mixed glycosidase, but was stable on treatment with DNAase, RNAase or neuraminidase.
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PMID:Partial purificationand characterizationof a factor which stimulates an increase in ornithine decarboxylase activity in the liver from tumor cell-free ascites fluid. 76 Aug 23

The induction of ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase in mouse epidermis by various classes of tumor-promoting and nonpromoting compounds has been studied in order to determine the specificity of this response for tumor promotion. The effect of topical applications of a series of phorbol esters on these enzyme activities correlated well with their promoting abilities. Iodoacetic acid, anthralin, and Tween 60, all promoting compounds, also stimulated both of these enzyme activities after single and multiple applications. The hyperplastic agents acetic acid, cantharidin, and ethyl phenylpropriolate, however, had little effect on ornithine decarboxylase activity but a pronounced effect on epidermal S-adenosyl-L-methionine decarboxylase activity. The specificity of the ornithine decarboxylase response for tumor promotion was suggested by the results of the above experiments as well as the stimulatory effect of a completely carcinogenic dose of 7,12-dimethylbenz[a]anthracene; a lower initiating dose had no effect. In addition, epidermal tumors produced by a two-stage procedure showed consistently high levels of ornithine decarboxylase activity but variable levels of S-adenosyl-L-methionine decarboxylase activity.
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PMID:Induction of the polyamine-biosynthetic enzymes in mouse epidermis and their specificity for tumor promotion. 80 25

The kinetics of cell proliferation and polyamine synthesis during Ehrlich ascites tumor growth were studied. The steady deceleration of the specific growth rate with increasing tumor mass that was observed was attributable to a prolongation of the cell cycle, particularly of the S and G2 phases. The cell cycle time (Tc) was 43.3 hr (TG1 equals 10.8, TS equals 26.8, and TG2 equals 5.7 hr) on the seventh day of growth and 76.0 hr (TG1 equals 14.0, TS equals 52.0, and TG2 equals 10.0 hr) on the tenth day of growth. The growth fraction showed a decrease from 0.77 to 0.60 during the 7- to 10-day tumor growth interval. The cell death rate remained low and essentially unchanged during this period. A high correlation was found between polyamine synthesis (ornithine decarboxylase activity) and the specific growth rate; the correlation coefficient was 0.985. There was also a high positive correlation between the cellular polyamine (spermidine and spermine) and nucleic acid content (spermidine: DNA equals 0.916, spermine: DNA equals 0.947, spermidine:RNA equals 0.907, and spermine: RNA equals 0.881). These observations suggest that there may be a functional coupling between polyamines and nucleic acids, and they support the hypothesis that polyamines play an important role in DNA replication and cell division.
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PMID:Kinetics of cell proliferation and polyamine synthesis during Ehrlich ascites tumor growth. 92 27

The induction of mouse epidermal ornithine decarboxylase, 1 of the earliest and largest phenotypic changes following treatment of mouse skin with the tumor-promoting agent, 12-O-tetradecanoyl-phorbol-13-acetate, can be inhibited by prior administration of colchicine. Maximal inhibition of this enzyme induction was observed when colchicine was injected i.p. 90 or 120 min before promoter treatment, although time intervals up to 20 hr between colchicine and promoter treatment were effective. The effect of colchicine was dose dependent, with a dose as low as 25 nmoles/mouse causing an inhibition of 35%. Other microtubule-disrupting agents, vinblastine, vincristine, and Colcemid, had a similar effect on ornithine decarboxylase activity. However, beta, gamma-lumicolchicine, a photochemical derivative of colchicine with no antimitotic or microtubule-disrupting ability, and cytochalasin B, an inhibitor of microfilament-dependent processes, had no effect. N6, O2'-dibutyryl 3',5'-cyclic adenosine monophosphate, when administered just before colchicine, blocked the inhibitory action of colchicine. The results of these studies suggest that colchicine-sensitive structures, most likely containing microtubules, may be mediating elements between the binding of tumor promoters, perhaps to specific cell surface receptors, and the subsequent induction of ornithine decdaboxylase.
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PMID:The effect of colchicine on the induction of ornithine decarboxylase by 12-O-tetradecanoyl-phorbol-13-acetate. 95 2


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