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

The human teratocarcinoma cell line PA-1 was derived from culturing ascites fluid cells from a patient with an ovarian germ line tumor. We previously described a non-neoplastic variant cloned from the PA-1 human teratocarcinoma cell line, clone 6, which at passage 40 was resistant to transformation by activated ras oncogenes. However, these cells could be transformed by a plasmid containing both myc and ras. Another PA-1 cell variant, clone 1, isolated at passage 63 and used 50 passages later becomes tumorigenic in nude mice after transfection with an activated ras oncogene (Tainsky et al., Anticancer Res., 8, 899-914, 1988). We report here that the progression from ras resistance to ras susceptibility occurs in both clone 1 and clone 6 cells during 25 passages in culture. In the presence of epidermal growth factor, transforming growth factor-alpha, and basic fibroblast growth factor, the ras-transformable cells exhibit anchorage independent growth, whereas the ras-resistant cells can not be growth stimulated by these growth factors. Similarly, ornithine decarboxylase (ODC) activity was inducible in ras susceptible and ras transformed cells by these growth factors, but not in the ras resistant cells. These differences are not due to the level and activity of epidermal growth factor receptor or to the level of expression of 25 proto-oncogenes.
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PMID:Susceptibility to ras oncogene transformation is coregulated with signal transduction through growth factor receptors. 164 84

The effects of unsaturated fat and fiber (cellulose) on the growth of human colon cancer explanted to athymic nude mice was evaluated. Eighty-seven male nude mice bearing xenografts of human HT29 or WiDr colon cancer were divided into three groups of equal weight and tumor volume. Each group was fed one of three diets: normal fat/no fiber (N/N), high fat/no fiber (H/N) or high fat/high fiber (H/H). To equalize caloric intake, animals in the H/N group received 4 g of food per day and the other animals were fed 5 g of food per day. At sacrifice tumor volume and weight was recorded, and tumors were analyzed for protein and DNA content and ornithine decarboxylase activity. Tumor volume, weight, and protein were greater in the H/N group compared to the N/N group for both colon cancer cell lines. Tumor DNA content was greater in the HT29 H/N group compared to the N/N group (P less than 0.05) and tumor ornithine decarboxylase activity in the WiDr H/N group was greater than the N/N animals (P less than 0.002). The tumor growth-promoting effects of the high unsaturated fat diet were attenuated by the addition of fiber. Animal weight was higher in the H/N group compared to the N/N and H/H groups. This study suggested that a high-fat diet stimulated and fiber decreased the growth of human colon cancer explanted to athymic nude mice. The growth-promoting effects of a high-fat diet in colorectal cancer may be due in part to a circulating trophic factor since these tumors were remote from the large intestine.
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PMID:Effects of fat and fiber on human colon cancer xenografted to athymic nude mice. 165 57

Interspecific mouse hybrids that are viable and fertile provide a wealth of genetic variation that is useful for gene mapping. We are using this genetic variation to develop multilocus linkage maps of the mouse genome. As an outgrowth of this work, we have identified three repetitive probes that collectively identify 28 loci dispersed on 16 of the 19 mouse autosomes and the X chromosome. These loci establish a skeleton linkage map that can be used to detect linkage over much of the mouse genome. The molecular probes are derived from the mouse mammary tumor virus envelope gene, the ornithine decarboxylase gene, and the triose phosphate isomerase gene. The ability to scan the mouse genome quickly and efficiently in an interspecific cross using these three repetitive probes makes this system a powerful tool for identifying the chromosomal location of mutations that have yet to be cloned, mapping multigenic traits, and identifying recessive protooncogene loci associated with murine neoplastic disease. Ultimately, interspecific hybrids in conjunction with repetitive and single-copy probes will provide a rapid means to access virtually any gene of interest in the mouse genome at the molecular level.
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PMID:Identification and applications of repetitive probes for gene mapping in the mouse. 167 5

The inhibitory effect of dietary perilla oil rich in the n-3 polyunsaturated fatty acid alpha-linolenic acid against colon carcinogenesis was investigated in rats. Four groups of 26 F344 rats each received an intrarectal dose of 2 mg of N-methyl-N-nitrosourea 3 times a week for 2 weeks, and received a diet containing 12% perilla oil, 6% or 12% safflower oil (rich in the n-6 polyunsaturated fatty acid linoleic acid), or 12% palm oil (rich in saturated and monounsaturated fatty acids). At week 35, the incidence of colon cancer was significantly lower in perilla oil-fed rats than in other dietary groups; 19% vs. 46%, 56% and 58%. When examined at week 10, the concentration of fecal bile acids, known to be tumor promoters, was not significantly different among the dietary groups, and the intrarectal deoxycholic acid-induced colonic mucosal ornithine decarboxylase activity, a marker of tumor promotion, was significantly lower in perilla oil-fed group than in other groups. The serum and colonic mucosal fatty acid compositions and the blood plasma prostaglandin E2 level directly reflected the fatty acid composition of each dietary fat. The results suggest that the anti-tumor-promoting effect of dietary perilla oil was a result of a decreased sensitivity of colonic mucosa to tumor promoters arising from the altered fatty acid composition in membrane phospholipid of colonic epithelial cells, and was not a consequence of a decrease of promoters such as bile acids.
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PMID:Inhibitory effect of dietary perilla oil rich in the n-3 polyunsaturated fatty acid alpha-linolenic acid on colon carcinogenesis in rats. 168 47

alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, inhibited B16 melanoma-induced angiogenesis in chick embryo chorioallantoic membrane and subsequently the growth of the tumor on the chorioallantoic membrane. These inhibitions were reversed by exogenous putrescine and spermidine. DFMO also inhibited rapid neovascularization in yolk sac membrane of 4-day-old chick embryos and the inhibition was reversed by exogenous putrescine and spermidine. DFMO strongly inhibited DNA synthesis and proliferation of bovine pulmonary artery endothelial (BPAE) cells in culture and decreased their ornithine decarboxylase activity and intracellular polyamine concentrations. Addition of putrescine to the culture medium of DFMO-treated BPAE cells restored their intracellular putrescine and spermidine concentrations and their DNA synthesis and proliferation. Addition of spermidine to cultures of DFMO-treated BPAE cells restored their intracellular spermidine concentration and their DNA synthesis and proliferation. DFMO inhibited the proliferation of B16 melanoma cells in culture but the inhibitory effect was much less than that on BPAE cells. When one-half the monolayer of confluent cultures of BPAE cells had been peeled off, addition of DFMO to the cultures inhibited the proliferation and extension of the BPAE cells into the vacant area but had no effect on stationary cells in the remaining half of the monolayer, suggesting that it inhibited induction of proliferation of endothelial cells. These findings suggest that the antitumor activity of DFMO against solid tumors is probably due more to its inhibition of tumor-induced angiogenesis by inhibition of proliferation of endothelial cells induced by polyamine depletion than to a direct effect on tumor cell proliferation.
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PMID:Tumor angiogenesis and polyamines: alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, inhibits B16 melanoma-induced angiogenesis in ovo and the proliferation of vascular endothelial cells in vitro. 169 80

The ornithine decarboxylase-inducing factor (ODC factor) was purified about 1,000-fold in 42% yield from the ascites fluids of an Ehrlich ascites tumor by a combination of centrifugation and concanavalin A (ConA) treatment. A single ip injection of 0.5 micrograms of the purified factor per mouse resulted in half-maximum induction of liver ODC. The factor was found to be a trypsin- and chymotrypsin-resistant, acidic glycoprotein (pI about 4.43) with a minimum molecular weight of about 70 kilodaltons, containing a disulfide bond(s) in its functional domain. It did not react with ConA. This factor induced retrodifferentiation of liver function, causing a marked increase of prototype M2 isozyme of pyruvate kinase. It reduced liver catalase activity, and also modified thyroid hormone metabolism, reducing the serum levels of T4 and T3. These results suggest that the ODC factor is multifunctional and induces many of the changes observed in a tumor-bearing host.
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PMID:Purification of ornithine decarboxylase-inducing factor from cell-free ascites fluid of Ehrlich ascites tumor and its characteristics. 170 56

The enzyme ornithine decarboxylase (ODC) has been implicated in the control of cell growth, differentiation and tumor promotion. To further elucidate its precise role a murine ODC cDNA was inserted into the retrovirus-derived vector pMV7 and retrovirus-like particles were used to infect NIH3T3 and rat 6(R6) fibroblasts. Derivatives were obtained that stably express a 5-40 fold increase in ODC enzyme activity. Despite these high levels of enzyme activity the cells retained a normal morphology and displayed no major changes in growth properties in monolayer culture or in agar suspension. On the other hand, R6 cells that expressed high levels of ODC displayed a marked increase in susceptibility to morphologic transformation by an activated c-H-ras oncogene. These results provide the first evidence that ODC can cooperate with an activated oncogene in the process of cell transformation. Although the mechanism is not known, these findings may be relevant to the multistage carcinogenic process.
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PMID:Effects of overexpression of ornithine decarboxylase (ODC) on growth control and oncogene-induced cell transformation. 171 Nov 88

Epidemiological and animal studies suggest a role for calcium in the chemoprevention of colorectal neoplasia. This study was designed to investigate whether supplemental oral calcium has a suppressant effect on colonic mucosal ornithine decarboxylase (ODC) and tyrosine kinase activities in patients with adenomatous polyps or a history of adenomatous polyps and whether this is affected by age. ODC and tyrosine kinase activities were measured in rectal mucosal biopsies of 19 male patients (age, years 46-85 years; mean, 66 years) with adenomatous polyps or a history of adenomatous polyps before and after 1 week of calcium supplementation p.o. (CaCO3; 2500 mg/day) and 2 weeks after cessation of calcium treatment. The basal rectal mucosal ODC activity of patients greater than or equal to 64 years old was nearly 4-fold higher than that of patients less than 64 years old (P less than 0.005). In patients greater than or equal to 64 years old, there was a significant decrease in rectal mucosal ODC activity following 1 week of calcium p.o. compared to those age less than 64 years (P less than 0.05). Overall tyrosine kinase activity did not differ significantly in either patient group before or after calcium supplementation p.o. However, the concentration of phosphotyrosine membrane proteins with molecular weights between 40,000 and 60,000 and between 80,000 and 100,000 were suppressed in patients age greater than or equal to 64 years after 1 week of calcium treatment p.o. These patients also had a corresponding decrease in their rectal mucosal ODC activity. Alternatively, patients whose ODC was not affected by calcium showed no apparent change in the relative concentration of rectal mucosal phosphotyrosine membrane proteins. Our data indicate that there is an age-related increase in basal rectal mucosal ODC activity in patients with adenomatous polyps which can be suppressed with calcium supplementation p.o., suggesting a role for dietary calcium in the chemoprevention of colorectal neoplasia.
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PMID:Supplemental calcium suppresses colonic mucosal ornithine decarboxylase activity in elderly patients with adenomatous polyps. 171 10

In this work deviation of liver metabolism by cytokines, especially recombinant human interleukin 1-alpha (rhIL1-alpha), was investigated. Administration of rhIL1-alpha or recombinant human tumor necrosis factor (rhTNF/cachectin) to normal mice resulted in rapid, dose-dependent induction of high liver ornithine decarboxylase (ODC) activity. The effects of these cytokines on liver ODC were not indirect effects mediated by eicosanoids. The induction of liver ODC by rhIL1-alpha was at least partly a direct effect on hepatocytes, and was due to increase in de novo synthesis of the enzyme protein after increase in ODC mRNA. No specific protein was required for increase in the level of ODC-mRNA. On IL1 treatment, actinomycin D caused superinduction of liver ODC, which was at least partly due to increased stability of the ODC enzyme, because actinomycin D doubled the apparent half-life (from 50 to 95 min). Daily administration of 2 x 10(3) U of rhIL1-alpha to mice for 3 days also caused decrease in the level of the differentiated type of pyruvate kinase isozyme (PK-L) and marked increase in that of the prototype isozyme (PK-M2) in the liver, but did not cause significant change in the isozyme patterns of the kidney, thymus, and spleen. RhIL1-alpha also induced hypertrophy of the spleen. These results indicate that rhIL1-alpha causes metabolic deviation of the liver similar to that in tumor-bearing hosts.
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PMID:Metabolic deviation of mouse liver by RhIL1-alpha or RhTNF/cachectin. 171 39

Nordihydroguaiaretic acid (NDGA), which occurs in the resinous exudates of many plants is used as an antioxidant in fats and oils. In this study we show that NDGA inhibited the mutagenicity of methyl methanesulfonate, benzo[a]pyrene (BP), 2-aminofluorene, and aflatoxin B1 in Salmonella typhimurium strain TA100 or TA98 in the absence and presence of rat hepatic microsomal activation system. The addition of NDGA during and after nitrosation of methylurea (MU) resulted in a dose-dependent inhibition of mutagenicity induced by nitrosation products of MU. In a two-stage skin tumorigenesis protocol using 7,12-dimethylbenz[a]anthracene (DMBA) as the initiating agent followed by twice weekly applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) as tumor promoter, pretreatment of animals with NDGA prior to DMBA application, afforded significant protection against skin tumorigenicity in female SENCAR mice. In additional studies, skin application of NDGA also inhibited the binding of topically applied [3H]BP and [3H]DMBA to epidermal DNA. When assessed in the anti-tumor promotion protocol, pretreatment of animals with NDGA before each application of TPA in DMBA-initiated mouse skin, resulted in 72% decrease in the total number of tumors when compared to non-NDGA pretreated animals. The possible mechanism(s) of the antimutagenic and anti-tumorigenic activities may be due to the multiple effects of NDGA as inhibitor of the carcinogen metabolism and DNA-adduct formation, scavenger of carcinogen free radicals, and as inhibitor of TPA-induced ornithine decarboxylase activity.
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PMID:Antimutagenic and antitumorigenic activities of nordihydroguaiaretic acid. 171 6


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