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)

Ornithine decarboxylase activity in the livers, spleens, and kidneys of tumor-bearing mice changed markedly during tumor growth. These changes in enzyme activity were not due to infiltration or metastasis of tumor cells in these organs. After i.p. inoculation of Ehrlich tumor cells, enzyme activity in the liver and spleen increased remarkedly, reaching a peak in 4 to 6 days and then quickly decreasing. Conversely, activity in the kidney, which was very high in normal mice, decreased markedly during tumor growth, nearly reaching zero on Day 6 and remaining very low until death. Upon injection of a cell-free homogenate of Ehrlich tumor or cell-free ascites fluid, enzyme activity in the liver and spleen also increased markedly, but that in the kidney did not change. These increases in activity were not due to the effects of living tumor cells. Similar increases in enzyme activity were also observed in the livers of mice given injections of homogenates of Sarcoma 180 or Act. S tumor, or plasma from tumor-bearing mice, but not in the livers of mice given injections of homogenates of various nontumorous tissues, such as liver, kidney, spleen, muscle, regenerating liver, and fetus, or plasma obtained from normal mice. A similar increase in enzyme activity in the liver after injection of a cell-free preparation of tumor cells was observed in hypophysectomized and adrenalectomized mice; thus, these endocrine systems are probably not involved in the increase in enzyme activity in the livers of tumor-bearing mice.
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PMID:A factor responsible for increases in ornithine decarboxylase activity in the livers of tumor-bearing mice. 97 47

The immunological properties of thymidine kinase from a variety of human tumors suggest that the form of the tumor enzyme resembles that found in the placenta and in the nondividing colonic flat mucosa. To examine the placenta-like characteristics of tumor thymidine kinase, the jejunum and colon from rats ranging in age from fetal to old and from animals treated with dimethylhydrazine (DMH), an intestinal carcinogen, have been studied. In normal jejunum, thymidine kinase activity decreased rapidly with age. Both the activity and the response to phospholipase C and to mercaptans in DMH-induced tumors resembled that of fetal gut, while those in abnormal appearing DMH-treated jejunum were intermediate between normal control of the same age and tumor. Similar but less pronounced changes were seen in the colon. In the jejunum, the level of another enzyme normally associated with rapid cell division, ornithine decarboxylase, was found to be over 100 times that of the liver, colon, and stomach. Treatment of the animals with acetylaminofluorene and with DMH resulted in elevated levels of the enzyme in liver and in colon, respectively, but had little effect on this enzyme in other tissues. The data presented indicate that there were premalignant changes in the levels of both of these enzymes in target tissues of animals treated with carcinogens.
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PMID:Biochemical changes in premalignant intestines. 97 9

DL-alpha-Hydrazino-delta-aminovaleric acid (DL-HAVA) is a potent and fairly specific inhibitor of ornithine decarboxylase (EC 4.1.1.17). Its effect on polyamine metabolism and cell proliferation was investigated in sarcoma-180, inoculated into the axillary region of mice. In the tumor tissues, the activities of ornithine and S-adenosyl-L-methionine decarboxylases and the putrescine level were much higher in the early stage of growth than those in normal mouse liver. Administration of DL-HAVA greatly depressed the putrescine level and putrescine formation from L-ornithine. It also suppressed DNA synthesis and increase in weight of the tumor tissue. However, it had little effect on RNA synthesis or the tissue concentration of spermidine and spermine. The inhibition of DNA synthesis and subsequent tumor development by DL-HAVA was effectively prevented by putrescine, but not by cadaverine or 1,7-diaminoheptane. From these results it is concluded that the suppression of DNA synthesis and neoplastic growth by DL-HAVA is due to decrease in the putrescine level by inhibition of ornithine decarboxylase.
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PMID:Effect of DL-alpha-hydrazino-delta-aminovaleric acid, an inhibitor of ornithine decarboxylase, on polyamine metabolism and growth of mouse sarcoma-180. 102 52

To investigate whether the metabolism of the polyamines putrescine, spermidine and spermine is related to cellular growth rate, we have measured the activities of L-ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase as well as the levels of the polyamines in rat brain tumor cells at various stages of a 7-day in vitro growth period and correlated them with the continuous changes in specific growth rate ([dN[t]/dt]/N[t]). L-Ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase both exhibited their maximal activities at the time of most rapid growth. A high positive correlation between the activities of these enzymes and the specific growth rate of the tumor cells during the entire growth period was demonstrated statistically. The pattern of fluctuation of the spermidine content during the culture cycle was similar to those of the enzyme activities and likewise showed a high positive correlation with the specific growth rate of the tumor cells during the entire growth period. The putrescine content exhibited a low positive correlation, whereas the spermine content exhibited a somewhat higher, but negative correlation with the specific growth rate. The high correlation between the specific growth rate of the tumor cells and the synthesis of the polyamines indicates that these events are primarily associated with processes involved in cell replication. Putrescine and spermidine are thought to participate in the regulation of cellular growth rate; a high content may augment, and a low content may restrain, cellular growth rate.
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PMID:Polyamine metabolism in a rat brain tumor cell line: its relationship to the growth rate. 120 31

The ornithine decarboxylase [EC 4.1.1.17] activities in the liver and spleen of tumor-bearing mice increased remarkably, reaching a peak 4 to 6 days after inoculation of tumor cells. On the contrary, the enzyme activity in the kidney decreased during tumor growth and had almost disappeared on day 6 after tumor inoculation. Injection of cell-free tumor homogenate also raised the enzyme activities in the liver and spleen, but did not change the activity in the kidney. No increase in enzyme activity in the liver of mice was observed on injection of homogenates of normal tissues, such as liver, spleen, kidney, and muscle.
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PMID:Changes in ornithine decarboxylase activity in normal tissues of tumor-bearing mice during tumor growth. 127 Apr 12

Two enzymes were examined as potential indicators of early precancerous changes. Ornithine decarboxylase, an enzyme normally associated with rapid cell division, is low in the rapidly dividing, cancer-susceptible colon. The level of this enzyme was also very high in the nondividing cells of the small intestines. Administration of an intestinal carcinogen, dimethylhydrazine, led to a large increase in colonic ornithine decarboxylase but did not affect the enzyme in liver. A liver carcinogen, acetylaminofluorene, induced manyfold increases in ornithine decarboxylase of the liver but not of the colon. Studies of thymidine kinase of the gut showed that this enzyme changed quantitatively and qualitatively throughout the life of the animal, from fetal rat to newborn and adult. The tumor enzyme has many fetal-like properties. Long-term treatment with dimethylhydrazine led to changes in thymidine kinase reminiscent of the fetal enzyme. Short-term treatment caused sharp increases in the thymidine kinase of nondividing cells of the jejunum and the proximal end of the colon; similar changes in the distal end of the colon were slower in appearing and less pronounced.
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PMID:Biochemical changes in preneoplastic rodent intestines. 127 75

The polyamines are normal cell constituents considered to have an important role in the regulation of proliferation and differentiation. DFMO is an irreversible, enzyme-activated, suicide inhibitor of ornithine decarboxylase (ODC), the enzyme responsible for the first and rate-limiting step in mammalian polyamine synthesis. Preliminary data show that DFMO inhibits tumor cell growth in vitro and in vivo, and that it demonstrates chemopreventive activity in a variety of animal tumors. The prostate contains some of the highest concentrations of polyamines and of polyamine-synthetic enzymes (including ODC) in the mammalian organism. ODC activity in the prostate was shown to be more susceptible to DFMO inhibition than in other organs. We have found the ODC activity of the Dunning R3327 rat prostatic carcinomas to be as sensitive to inhibition by DFMO as the normal rat prostate. Furthermore, DFMO was inhibitory to the growth of the tumor both in vitro and in vivo. Given the slow growth rate and long latency period of human prostate cancer and the preliminary DFMO data, we suggest that clinical trials to evaluate the chemopreventive potential of DFMO in prostatic carcinoma deserve serious consideration.
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PMID:Chemoprevention in prostate cancer: the role of difluoromethylornithine (DFMO). 128 67

Ornithine decarboxylase (ODC), a key enzyme in mammalian polyamine biosynthesis, has been proposed to be a marker of colonic epithelial cell proliferation and risk for colorectal cancer. We investigated the basal levels of ODC activity in sigmoid and rectal mucosae, and basal and tumor promoter 12-O-tetradecanoylphorbol-13-acetate-induced levels of skin ODC activity in individuals with a personal history of colon cancer (n = 9 colon; n = 58 skin), a family history of nonpolyposis hereditary colorectal cancer (n = 49; n = 42), adenomas (n = 16; n = 40), and healthy, family history-negative control subjects (n = 40; n = 79). Using a fresh tissue assay and samples obtained after a standard colon lavage preparation, colon mucosal ODC levels ranged from 0 to 192 pmol/mg/h (sigmoid, 0-163 pmol/mg/h; mean, 36 +/- 32 pmol/mg/h; rectum, 0-192 pmol/mg/h; mean, 35 +/- 32 pmol/mg/h). No differences among the four groups of subjects were found for either colon or skin ODC levels, and there were no sex differences overall or in any group. These results are not compatible with the suggestion that ODC levels are a useful marker of risk for colorectal cancer.
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PMID:Levels of colorectal ornithine decarboxylase activity in patients with colon cancer, a family history of nonpolyposis hereditary colorectal cancer, and adenomas. 130 5

Dietary fiber may affect the development of cancers of the gastrointestinal tract and the breast. The biological intermediates studied most have been fecal bile acids; both human and animal studies suggest a tumor-promoting role of bile acids in the development of colon tumors, although there are conflicting data from human studies. Short-chain fatty acids are major fermentation products of bacterial degradation of dietary fiber. If short-chain fatty acids explained the tumor-inhibiting properties of dietary fiber, the readily fermentable fibers such as guar and pectin would be more protective than cellulose and wheat bran, which has not been observed. Because these two hypotheses do not adequately explain modulation of tumor growth by dietary fiber, investigation of other intermediates is indicated. These include physical characteristics of the feces, such as abrasiveness; intestinal microflora; aqueous-phase bile acids, which may represent the bioavailable pool; alterations in mucins; mutagenicity of intestinal contents; alterations in mucosal cytokinetics; activities of enzymes, such as ornithine decarboxylase or aryl hydrocarbon hydroxylase; neurogenic effects caused by changes in intestinal bulk or short-chain fatty acids; gut hormones or other peptide growth factors (local or systemic); enterohepatic circulation of hormones; transit time; pH; or decreased availability of total dietary energy.
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PMID:Dietary fiber-mediated mechanisms in carcinogenesis. 131 88

The activation of polyamine biosynthesis, dependent on increased gene expression of ornithine decarboxylase, has been found to play an important role in the control of cell proliferation and differentiation. In this report it has been found that accumulation of ornithine decarboxylase mRNA also follows stimulation of human monocytes/macrophages by tumor necrosis factor. Human recombinant tumor necrosis factor (100 units/ml) also evoked an enhanced respiratory burst of macrophages. The respiratory burst response was inhibited in a dose-dependent manner with difluoromethylornithine, an inhibitor of ornithine decarboxylase, and methylglyoxal-bis(guanylhydrazone), an inhibitor of the formation of spermidine and spermine. The data presented in this paper suggest that polyamines may play a functional role in tumor necrosis factor-driven macrophage activation, and they are discussed in the context of their possible use as inhibitors of polyamine metabolism in tumor chemotherapy.
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PMID:Inhibitors of polyamine biosynthesis block tumor necrosis factor-induced activation of macrophages. 131 3


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