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)

Refeeding of patients with malignant tumors may induce tumor-cell DNA synthesis. The present study was aimed at evaluating whether induction of altered cell-cycle kinetics could be induced by intravenous total parenteral nutrition (TPN) in tumor biopsies from head and neck cancers. Nine malnourished patients with squamous cell carcinoma in the head-and-neck area were investigated before and after 5-7 d of continuous TPN. Tumor biopsies were taken in both fasted and fed states for determination of 1) ornithine decarboxylase (ODC) activity, which is rate limiting for polyamine synthesis; 2) flow-cytometric-DNA-distribution measurements; and 3) the fraction of proliferating cells expressed as immunohistochemical reactivity with the monoclonal antibody Ki-67. The histopathological differentiation, the fraction of aneuploidic cells, ODC activity, and Ki-67 reactivity were not significantly related to each other, although the number of aneuploidic cells in replicative phases correlated with the number of cells expressing the Ki-67 antigen (r = 0.86, P less than 0.01). Tumor cytokinetics showed no evidence of being changed by TPN administration.
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PMID:Tumor cytokinetic response to total parenteral nutrition in patients with head and neck cancers. 190 Mar 85

Polyamine synthesis is required in normal or neoplastic tissues if they are to continue to grow or divide. The highly inducible enzyme ornithine decarboxylase (ODC) catalyzes the conversion of ornithine to putrescine as the initial step in polyamine biosynthesis. The level of substrate pools of ornithine in cultured cells has been reported to markedly alter mitogen-induced ODC activity, putrescine accumulation, and DNA synthesis (V. Wu and C. V. Byus, Biochim. Biophys. Acta, 804: 89-99, 1984; V. Wu et al., Cancer Res., 41: 3384-3391, 1981). We attempted to limit the amount of ornithine available for polyamine biosynthesis in an animal by using a dietary approach. Since arginine serves as one of the intermediate biosynthetic precursors of ornithine, female CD-1 mice were placed on a special synthetic amino acid diet deficient in arginine. The ability of this arginine-free diet to alter epidermal ornithine and polyamine metabolism and tumorigenesis was assessed in the mouse two-stage model of skin carcinogenesis. The basal level of ornithine in the epidermis in control animals receiving the amino acid complete diet was very high compared to other tissues (155 nmol/mg protein). However, when the mice were fed the isocaloric arginine-free diet for a 2-week period, the levels of epidermal ornithine and arginine decreased by 40% (P less than 0.01). This reduction was blocked by the addition of 2% ornithine to the drinking water of the arginine-restricted animals. Acute administration of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) to the epidermis caused a transient (4 and 8 h) reduction in ornithine and arginine but not lysine in the animals receiving the control, and ornithine-supplemented diets. The animals fed the special arginine-free diet exhibited a 40-50% reduction in tumor multiplicity or papillomas/mouse (P less than 0.05) and had a significantly lower tumor incidence or percentage of animals with tumour throughout a 19-week promotion period (P less than 0.02). However, the major effect of arginine restriction was consistent with an increase in tumor latency. The addition of ornithine completely reversed the reduction in the rate and extent of tumorigenesis in the arginine-free animals. The accumulation of putrescine (but not spermidine or spermine) in the epidermis following a single administration of TPA was significantly reduced in the animals receiving the arginine-free diet. The papillomas or tumors from the animals deprived of arginine had markedly reduced (less than 35%) levels of putrescine compared to the tumors from control animals, and appeared to be more sensitive to dietary arginine restriction than was the chronically promoted but untransformed epidermis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of dietary arginine restriction upon ornithine and polyamine metabolism during two-stage epidermal carcinogenesis in the mouse. 190 27

Fish or vegetable oils were fed during the promotion stage of a mouse skin carcinogenesis model in order to investigate the effects of dietary fat on tumor development. Two weeks after initiation with 10 nmol dimethylbenz[a]anthracene, SENCAR mice were divided into five groups and maintained on one of the following semipurified diets containing 10% total fat and varying the type of fat: 8.5% coconut oil (CT)/1.5% corn oil (CO); 1% menhaden oil (MO)/7.5% CT/1.5% CO; 4% MO/4.5% CT/1.5% CO; 8.5% MO/1.5% CO; or 10% CO. Promotion with twice-weekly applications of 40 mg benzoyl peroxide was begun 2 weeks later and continued for 52 weeks. No statistically significant differences in kcal food consumed or body weights were observed between diet groups. Papilloma latency, incidence and yield differed among the diet groups with the group fed the 8.5% CT/1.5% CO diet having the shortest latency and highest papilloma incidence and number. In addition, carcinoma latency and incidence was assessed and the first carcinoma appeared in the group fed 8.5% CT/1.5% CO after 20 weeks of benzoyl peroxide treatment; this group yielded the highest carcinoma incidence throughout the study. In comparison, the group fed the 10% CO diet had the longest latency period, and among the lowest papilloma and carcinoma incidence and fewest tumors. In parallel studies, ornithine decarboxylase activity, vascular permeability and hyperplasia were elevated in the epidermis of benzoyl peroxide-treated mice but the extent of the response did not correlate with the different rates of tumor formation observed among the diet groups. These data indicate that dietary fat modulates tumor promotion by benzoyl peroxide in this skin carcinogenesis model with the predominantly saturated fat diet producing the highest rates of papilloma and carcinogen formation and the polyunsaturated fat diet the lowest.
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PMID:The effect of dietary lipid on skin tumor promotion by benzoyl peroxide: comparison of fish, coconut and corn oil. 190 20

The oral administration of alpha-difluoromethylornithine (DFMO), an enzyme-activated inhibitor of ornithine decarboxylase (ODC), produced a marked decrease in the rate of growth of amelanotic Harding-Passey melanoma transplanted in mice. The half-life of this compound in Harding-Pasey melanoma was 30 min. A combined treatment of DFMO and hyperthermia did not show any synergistic effect on the inhibition of tumor growth, and no differences in the levels of tumor ODC, S-Adenosylmethionine decarboxylase (SAMDC) and polyamines were observed between single and combination treatments. DFMO-treatment alone produced a decrease of about 80% in spermidine concentration in melanoma, while in other tissues such as kidney, the diminution of spermidine was only moderate. ODC activity was reduced greatly in the kidney and moderately in melanoma. However, the activity of SAMDC increased up to 30-fold in DFMO-treated melanoma, while only a moderate increase was observed in the renal enzyme. Melanoma tyrosinase activity did not increase with the treatment with DFMO. These results indicate that the inhibition of amelanotic Harding-Passey melanoma growth by DFMO is not caused by the stimulation of cell differentiation, and that in this system polyamine depletion caused by this drug does not produce an enhancement in the heat-induced cytotoxicity.
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PMID:Effects of treatments with alpha-difluoromethylornithine and hyperthermia on the growth and polyamine metabolism of Harding-Passey murine melanoma. 190 4

Topical application of curcumin, the major yellow pigment in turmeric and curry, has a potent inhibitory effect on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion in mouse skin. The structurally related compounds chlorogenic acid, caffeic acid and ferulic acid are less potent inhibitors. Curcumin is a potent inhibitor of TPA-induced ornithine decarboxylase activity and inflammation in mouse skin whereas chlorogenic acid, caffeic acid and ferulic acid are only weakly active or inactive. Curcumin is a potent inhibitor of arachidonic acid-induced inflammation in vivo in mouse skin, and this compound is also a potent inhibitor of epidermal lipoxygenase and cyclooxygenase activity in vitro. Although chlorogenic acid is only weakly active as an inhibitor of epidermal lipoxygenase activity and TPA-induced ear inflammation, it is more active than caffeic acid and ferulic acid. The inhibitory effects of curcumin, chlorogenic acid, caffeic acid and ferulic acid on TPA-induced tumor promotion in mouse skin parallel their inhibitory effects on TPA-induced epidermal inflammation and epidermal lipoxygenase and cyclooxygenase activities. Examination of the structural features of curcumin required for its biological activity indicate that free hydroxyl groups on the benzene rings are not required for inhibition of TPA-induced ornithine decarboxylase activity and inflammation in mouse skin.
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PMID:Inhibitory effect of curcumin and some related dietary compounds on tumor promotion and arachidonic acid metabolism in mouse skin. 190 16

Pendolmycin, isolated from Nocardiopsis, is a compound structurally similar to teleocidin A, one of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters. Pendolmycin has a C5 dimethyl allyl group attached to C-7 of (-)-indolactam-V, whereas teleocidin A has a C10 linalyl group attached to the molecule. The structure-activity relationships of a hydrophobic moiety attached to (-)-indolactam-V were studied in four compounds, (-)-indolactam-V, pendolmycin, teleocidin A and newly synthesized 7-(nerolidyl)-(-)-indolactam-V in tests on inhibition of the specific [3H]TPA binding to a particulate fraction of mouse skin, activation of protein kinase C and induction of both adhesion of HL-60 cells and ornithine decarboxylase in mouse skin. The potencies of the compounds for these activities increased mainly depending on the length of the hydrophobic group. Pendolmycin had a tumor-promoting activity on mouse skin initiated with a single application of 7,12-dimethyl-benz[a]anthracene, and its potency was just between those of (-)-indolactam-V and teleocidin A. The role of the hydrophobic moiety is discussed with particular emphasis on the results obtained with 7-(nerolidyl)-(-)-indolactam-V.
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PMID:Pendolmycin, a new tumor promoter of the teleocidin A class on skin of CD-1 mice. 190 44

Cepharanthine, isolated from Stephania cepharantha, is one of the bisbenzylisoquinoline-type alkaloids. We have found that it inhibits tumor promotion after topical application in two-stage carcinogenesis in mouse skin. Epidermal ornithine decarboxylase activities inhibited by topical application of cepharanthine, with an 5 micrograms/mouse) and mezerein (5 micrograms/mouse) were found to be inhibited by topical application of cepharanthine, with a ED50 of 1.2 mumol and 1.4 mumol respectively. These inhibitory effects of cepharanthine are considered to be related to its antitumor activity in two-stage carcinogenesis in mouse skin. Cell-mediated immunosuppression by TPA was unaffected by topical application of cepharanthine. A diet containing 0.005% cepharanthine (about 0.5 mg mouse-1 day-1) slightly suppressed the two-stage promotion of skin tumors by twice-weekly applications of 2.5 micrograms TPA for 2 weeks (first stage) followed by twice-weekly applications of 2.5 micrograms mezerein for 23 weeks (second stage) in ICR mice following initiation by 50 micrograms 7,12-dimethylbenz[a]anthracene. Oral administration of cepharanthine inhibits the tumor promotion in two-stage carcinogenesis in mouse skin.
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PMID:Cepharanthine inhibits two-stage tumor promotion by 12-O-tetradecanoylphorbol 13-acetate and mezerein on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene. 190 98

Pretreatment of CD-1 mouse skin with prostratin (12-deoxyphorbol 13-acetate) inhibited biological response to phorbol 12-myristate 13-acetate. The three responses examined were hyperplasia, induction of ornithine decarboxylase, and edema; the characteristics of inhibition depended on the specific response. Hyperplasia is the best short-term correlate of tumor promotion. Two or more pretreatments with 2.56 mumol (1 mg) prostratin, administered at intervals of 1-4 days, almost completely blocked the hyperplasia induced by phorbol 12-myristate 13-acetate applied 15 min to 6 h after the last pretreatment. Inducibility of hyperplasia was partially restored at 2 days and recovered by 4 days. Prostratin was more potent for inhibition of ornithine decarboxylase induction (50% inhibitory dose = 25.6 nmol) than it was for hyperplasia: the inhibition was largely attained by the first application, and the recovery from inhibition was slower (8 days). Edema was partially inhibited by prostratin (dose giving 50% of maximal inhibition = 512 nmol). We have previously demonstrated that prostratin is a protein kinase C activator. Our present results show that prostratin is a functional antagonist for a class of protein kinase C mediated responses. The findings emphasize the diversity of biological outcome for protein kinase C activators, presumably driven by the extensive heterogeneity in the protein kinase C pathway.
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PMID:Prostratin, a nonpromoting phorbol ester, inhibits induction by phorbol 12-myristate 13-acetate of ornithine decarboxylase, edema, and hyperplasia in CD-1 mouse skin. 191 57

The ability of the hyperplasiogenic irritant ethyl phenylpropiolate (EPP) to act as a tumor promoter in two-stage carcinogenesis and to stimulate cellular events commonly cited as markers of tumor promoter action was evaluated. Treatment of adult, inbred SENCAR (SSIN) mice, initiated with 7,12-dimethylbenz(a)anthracene, with 5 mg of EPP twice weekly resulted in 100% of the mice developing tumors (4.8 tumors/mouse) after 40 weeks of promotion. Treatment with 3 mg EPP (twice weekly) resulted in 52% of the mice developing tumors (0.9 tumor/mouse). This treatment regimen with EPP produces a sustained epidermal hyperplasia without being overtly toxic. In addition, a 5-mg dose of EPP induced ornithine decarboxylase activity to a level comparable to that induced by the tumor promoter phorbol 12-myristate 13-acetate (PMA): 2.3 nmol CO2/mg protein/h for EPP versus 4.5 nmol CO2/mg protein/h for PMA versus 0.04 nmol CO2/mg protein/h for acetone control. Likewise, the time course of ornithine decarboxylase induction by EPP was the same as that seen with PMA (maximum induction at approximately 6 h). Vascular permeability of the dorsal skin increased significantly in response to EPP (8 times that seen in acetone controls) and exhibited the same kinetics as that seen after exposure to PMA. Activity of protein kinase C (PKC), the cellular receptor for PMA, decreased by 75 to 95% 48 h after treatment with PMA. In contrast, EPP treatment resulted in less than a 20% decrease in PKC activity 48 h after treatment. This slight decrease in PKC activity is thought to be an indirect effect caused by the hyperproliferative and inflammatory reactions, because EPP was found to be inactive as an in vitro activator of PKC. These results indicate not only that EPP is a good tumor promoter that causes morphological and biochemical responses similar to those induced by PMA, but also that the action of EPP is apparently mediated via a mechanism that does not involve direct interaction with PKC.
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PMID:Tumor-promoting activity of ethyl phenylpropiolate. 191 82

To investigate the effects of two levels of dietary corn oil on tumorigenesis, semipurified diets containing 5% or 10% corn oil were fed during the promotion stage of a mouse skin carcinogenesis model. Sencar mice were initiated with 10 nmol dimethylbenz[a]anthracene (DMBA) and promoted with either 1 microgram 12-O-tetradecanoylphorbol-13-acetate (TPA) or 40 mg benzoyl peroxide twice weekly for 24 or 52 weeks, respectively. No significant differences in kilocalories of food consumed or body weights were observed between the diet groups during the study. Fatty acid profiles of the epidermal phospholipids reflected dietary fat intake. For example, high levels of linoleate and low levels of arachidonate were found in the phosphatidylcholine fraction from mice fed the 10% corn oil diet compared with 5% corn oil. When the diets were fed during TPA promotion, the papilloma incidence after 11 weeks of treatment for the 5% corn oil group was 77% and 37% for the 10% corn oil group. By 15 weeks of TPA treatment, papilloma incidence between the diet groups was similar, and later, carcinoma incidence and yield were not different between the two groups. For the animals treated with benzoyl peroxide, there was only a slight but not significant difference in papilloma and carcinoma appearance. In parallel studies, ornithine decarboxylase activity, vascular permeability, hyperplasia, and prostaglandin E2 (PGE2) levels were elevated in the epidermis after promoter treatment, but only hyperplasia and PGE2 synthesis tended to reflect the dietary effects on tumor appearance. These data suggest that the quantity of dietary corn oil at the two levels tested, 5% and 10%, altered epidermal phospholipid fatty acid composition and PGE2 levels and had modest effects on the modulation of tumorigenesis in this skin model.
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PMID:The effect of the level of dietary corn oil on mouse skin carcinogenesis. 192 5


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