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)

The effect of intestinal microflora on liver tumorigenesis was studied in gnotobiotic C3H/He male mice monoassociated, diassociated, or polyassociated with the following strains of intestinal bacteria: Escherichia coli, Streptococcus faecalis, Bifidobacterium adolescentis, Bifidobacterium infantis, Clostridium indolis, C. paraputrificum, C. perfringens, C. innocuum, C. nexile, C. ramosum, C. clostridiiforme, Bacteroides multiacidus, Bacteroides fragilis, Veillonella alcalescens, V. parvula, and Lactobacillus acidophilus. The incidence of liver tumors was higher in most of the gnotobiotes (67--100%) and conventionalized mice (82%) derived from the germfree mice than in the germfree mice (39%). The average incidence of tumor nodules in gnotobiotes associated with E. coli, S. faecalis, and C. paraputrificum was 2.9, which was significantly higher than that in the conventionalized animals (1.6). In contrast, the average incidence of tumor nodules in gnotobiotes associated with E. coli, S. faecalis, L. acidophilus, C. perfringens, and Bacteroides fragilis (0.9) was not significantly different from that in germfree animals (0.5). The present study demonstrated that the presence of certain intestinal bacteria is related to liver tumorigenesis in gnotobiotic C3H/He male mice.
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PMID:Effect of intestinal bacteria on incidence of liver tumors in gnotobiotic C3H/He male mice. 29 9

We have previously reported that abdominal irradiation prior to i.v. injection of syngeneic tumor cells reduced metastases in lung. Our report described an investigation of the significance of intestinal organisms in the radiation effect. We found that eliminating intestinal organisms with antibiotics totally abolished the radiation effect. Monoassociation of germ-free mice revealed that the radiation effect was observable only for Enterobacter cloacae, never for Streptococcus faecium, Bifidobacterium adlesentis, or Escherichia coli. After abdominal irradiation of regular mice, E. cloacae multiplied in cecal contents, adhered to mucous membranes, invaded the cecal wall, and translocated to mesenteric lymph nodes. Intravenous administration of E. cloacae in place of abdominal irradiation inhibited metastases. E. cloacae-monoassociated mice developed fewer metastases than germ-free mice, and the reduction was further enhanced by abdominal irradiation. We concluded that abdominal irradiation caused the invasion of E. cloacae from the mucous membrane of the intestine and inhibited formation of lung metastases.
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PMID:Significance of bacterial flora in abdominal irradiation-induced inhibition of lung metastases. 296 70

In order to investigate the antitumor activity of intestinal microflora, the constitution of normal flora was examined in humans, guinea pigs and mice. It was clarified that Eubacterium, Bifidobacterium and Bacteroides were the predominant bacterial genera in humans. In addition, neither Clostridium nor Enterobacteriaceae was detected in guinea pigs and neither Clostridium nor Bifidobacterium was present in mice. Total bacterial counts in tumor-bearing mice were reduced in comparison with those in normal mice. Especially, in the ileum of tumor-bearing mice, the incidence of anaerobic bacterial genera was strikingly decreased. From the bacteria found, 59 living and killed strains isolated from intestinal microflora were examined for antitumor activity against Ehrlich ascites tumor. It was observed that 11 of the tested strains had antitumor activity. Four of these were toxic to the host, and in particular, all mice injected with Pseudomonas aeruginosa (TYM-8) died within several days. Eubacterium lentum (TYH-11), Propionibacterium acnes (TYM-28), Proteus mirabilis (TYM-7) and Serratia marcescens (TY-142), in which antitumor activity was recognized with living and formalin-killed bacteria, cured the tumor-bearing mice, and the culture supernatant of S. marcescens contained apparent antitumor activity.
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PMID:Antitumor effect of normal intestinal microflora on Ehrlich ascites tumor. 312 98

Three kinds of morphologically distinct cell wall preparations were isolated from heat-killed Bifidobacterium infantis and examined for the relative antitumor efficacy with syngeneic Meth A fibrosarcoma in BALB/c mice. Ultrastructural examinations revealed that cell wall skeleton (CWS) did not retain morphologically recognizable cell wall structure but showed fibrous structure. By contrast, a new cell wall preparation, whole peptidoglycan (WPG), which was isolated from whole cells without being subjected to physically destructive methods, completely retained the intact cell wall structure. When WPG was disrupted by sonic treatment, it retained some degree of physical integrity of cell wall structure, as compared with CWS. The results of chemical analysis indicated that the three cell wall preparations had similar chemical properties. A single s.c. injection of either CWS, WPG, or sonicated WPG in a mixture with tumor cells resulted in a significant suppression of the tumor growth. They were of equally high activity. However, when WPG, sonicated WPG, or CWS was injected intralesionally five times into mice bearing 5-day-old tumors, the incidence of complete tumor regression was demonstrated to decrease in the order of 70, 40, and 20%, respectively. The in vitro cytotoxicity test excluded the possibility that the tumor cell destruction was the result of direct cytotoxicity of the cell wall preparations. From these findings, it was concluded that WPG was an active stimulator of host-mediated response at the tumor-growing sites.
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PMID:A new morphologically characterized cell wall preparation (whole peptidoglycan) from Bifidobacterium infantis with a higher efficacy on the regression of an established tumor in mice. 397 75

A strain of domestic bacteria, Bifidobacterium bifidum (Lac B), which is nonpathogenic and anerobic, selectively localized and proliferated in several types of mouse tumors following i.v. administration. None of the same bacilli could be detected in the tissues of healthy organs such as the liver, spleen, kidney, lung, blood, bone marrow, and muscle 48 or 96 hr after i.v. administration into tumor-bearing mice. Proliferation of Lac B in the tumor was artifically stimulated by i.p. administration of DDD-H-2s mice of a synthesized disaccharide, lactulose (4-O-beta-D-galactopyranosyl-D-fructofuranose), a sugar which is not metabolized by mammalian tissue cells. Lac B, which survices and proliferates selectively in the tumor following i.v. administration into the tumor-bearing host, should aid in diagnosis and selective therapy for cancer.
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PMID:Selective localization and growth of Bifidobacterium bifidum in mouse tumors following intravenous administration. 698 95

Intestinal Bifidobacterium species are thought to be beneficial in animal and human intestines. We studied the mechanisms of Bifidobacteria in antitumor activity using a cell wall preparation (WPG) of B. infantis (Cancer Res., 45, 1300, (1985)). WPG enhanced the in vitro antitumor activities of mouse peritoneal exudate cells elicited with proteose-peptone (P-PEC) and thioglycollate broth (TG-PEC), determined by cytostatic ([3H]thymidine uptake inhibition) and cytolytic ([3H]uridine release) assays. Tumor necrosis factor-alpha (TNF-alpha) and reactive nitrogen intermediates (RNI) play a role in such augmented cytotoxicity, because anti-TNF-alpha antibody almost completely blocked the increased cytolytic activity of P-PEC in the presence of WPG. Moreover, WPG induced RNI in the supernatant of TG-PEC in a dose-dependent manner. The mRNA expression of several cytokines (IL-1 beta, IL-6, IL-10, IFN-alpha and TNF-alpha) was induced in BALB/c mouse peritoneal cells 3 h after an intraperitoneal injection of WPG (3 h WPG-PEC). However, this expression disappeared from 24 h WPG-PEC, except for that of IFN-alpha. IFN-gamma was not induced. Kinetic studies of the tumor neutralizing activities of the WPG-PECs by means of the in vivo Winn assay revealed that the activity emerged at 1.5 h, became maximal at 3 h and disappeared at 24h. These results indicated that Bifidobacterial WPG is a Biological Response Modifier (BRM) with characteristics similar to those of other bacterial BRMs.
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PMID:Analysis of antitumor properties of effector cells stimulated with a cell wall preparation (WPG) of Bifidobacterium infantis. 753 75

PSK, a protein-bound polysaccharide derived from basidiomycetes, is a biological response modifier that exhibits a variety of activities following oral administration, including prevention of infection. In this study, the effects of oral administration of this drug on microbial flora of tumor-bearing mice were examined. Numbers of Staphylococcus, Streptococcus and Pseudomonas were increased, and those of Bifidobacterium and Lactobacillus were reduced in fresh feces of mice from later than 9 weeks after inoculation of sarcoma 180. However, these changes were prevented by oral administration of PSK. In mice bearing sarcoma 180, the increases in numbers of Staphylococcus and Pseudomonas and the decrease in those of Bifidobacterium were further enhanced by intraperitoneal administration of anticancer agent mitomycin C, but such changes were suppressed by oral administration of PSK. These results suggest that PSK has a preventive effect against abnormal conditions of the intestinal flora induced by tumor inoculation or the administration of anticancer agents.
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PMID:Effect of a biological response modifier, PSK, on intestinal flora of tumor-bearing mice. 836 70

Lactic acid bacteria (LAB) are proposed to have several beneficial effects, including the inactivation of carcinogens. We have studied the potential of Lactobacillus acidophilus (from a commercially available yogurt), Lactobacillus gasseri (P79), Lactobacillus confusus (DSM20196), Streptococcus thermophilus (NCIM 50083), Bifidobacterium breve and Bifidobacterium longum (from human infant stool) to prevent the induction of DNA damage by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 7.5 mg/kg body wt) in colon cells of the rat. Using the new technique of single cell microgel electrophoresis, all investigated strains were antigenotoxic toward MNNG after a single dose of 10(10) viable cells/kg body wt p.o. eight hours before the carcinogen. One-half and one-tenth of this initial dose resulted in a loss of protective activity. High doses of heat-treated L. acidophilus strains were also not antigenotoxic. One mechanism of the preventive effect could be that bacterial metabolites or components are responsible. Accordingly, selected examples were investigated in vitro in colon cells of the rat. Metabolically active L. acidophilus cells, as well as an acetone extract of the culture, prevented MNNG-induced DNA damage. Different cell fractions from L. acidophilus (cytoplasm, cell wall skeleton, cell wall) were devoid of antigenotoxic activity, whereas the peptidoglycan fraction and whole freeze-dried cells were antigenotoxic. As a second carcinogen, 1,2-dimethylhydrazine (DMH) was used. A dose- and time-response study was first performed to assess the effects of DMH in several segments of the gastrointestinal (GI) tract. Exposure for 16 hours to 15 or 25 mg DMH/kg body wt p.o. induced DNA damage in cells of the distal colon of rats, whereas no cytotoxicity was seen. Pretreatment orally with LAB on four consecutive mornings before DMH gavage (8 hours after the last LAB application) revealed that L. acidophilus, L. confusus, L. gasseri, B. longum, and B. breve inhibited the genotoxic effect of DMH. One of four S. thermophilus and one of three Lactobacillus delbrueckeii ssp. bulgaricus strains were also protective. Heat-treated L. acidophilus did not inhibit DMH-induced genotoxicity. A few aliquots of the colon cells were processed immunohistochemically for the presence of the "proliferation cell nuclear antigen" (PCNA). DMH treatment did not increase PCNA, nor was there any modulation by LAB. The effect of L. acidophilus on foreign compound-metabolizing enzymes (Phase I and Phase II) in liver and colon cells of rats revealed only one parameter to be modulated, namely, a two- to three-fold increase in the levels of NADPH-cytochrome P-450 reductase. The meaning of this finding, in terms of possible chemoprevention by LAB, remains unclear. In conclusion, our studies show that most, but not all, LAB tested could strongly inhibit genotoxicity in the GI tract of the rat and that viable LAB organisms are required for the protective effect in vivo. The comet assay technique is a powerful tool to elucidate such in vivo antigenotoxic activities in tumor target tissues.
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PMID:Lactobacillus- and bifidobacterium-mediated antigenotoxicity in the colon of rats. 891 Sep 18

The human colon can be described as a complex microbial ecosystem, comprising several hundred bacterial species. Some of these enteric bacteria are beneficial to the host and have been shown to exert antimutagenic and anticarcinogenic properties. We have investigated the colon tumor inhibitory activity of Bifidobacterium longum, a lactic acid-producing enterobacterium. The modifying effects of this lactic culture on colonic mucosal and/or tumor cell proliferation, ODC activity and ras-p21 oncoprotein expression in colon carcinogenesis were also analyzed. Male F344 rats were fed a modified AIN-76A diet containing 0 or 2% lyophilized cultures of B. longum and s.c. administered azoxymethane (AOM) dissolved in normal saline at a dose of 15 mg/kg body wt, once weekly for 2 weeks. Vehicle controls received an equal volume of normal saline s.c. Animals were maintained on control or experimental diets until termination of the study. Animals intended for analysis of cell proliferation were killed 20 weeks after the second AOM injection, whereas animals intended for colon tumor analysis and measurement of ODC activity and ras-p21 expression were killed 40 weeks after the last AOM injection. The data demonstrate that dietary administration of lyophilized cultures of B. longum resulted in significant suppression of colon tumor incidence and tumor multiplicity and also reduced tumor volume. Results also revealed that ingestion of B. longum significantly inhibited AOM-induced cell proliferation, ODC activity and expression of ras-p21 oncoprotein. Data suggest that oral administration of probiotic B. longum exerts strong antitumor activity, as indicated by modulation of the intermediate biomarkers of colon cancer, and consequently reduced tumor outcome.
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PMID:Bifidobacterium longum, a lactic acid-producing intestinal bacterium inhibits colon cancer and modulates the intermediate biomarkers of colon carcinogenesis. 911 Dec 22

Previous studies in our laboratory suggested that Lactobacillus acidophilus strain DDS-1 (LA1) has a suppressive effect on chemically induced tumors in experimental animals. In an effort to understand the possible mechanisms underlying this effect, we investigated the ability of LA1 to induce the production of interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha), which have potent cytocidal and cytostatic effects on tumor cells. The mouse macrophage cell line RAW264.7 was incubated with live or heat-killed cells of four strains of L. acidophilus or Bifidobacterium bifidum. Escherichia coli was used as a source of lipopolysaccharide that is known to induce the above cytokines. The amount of the cytokines present in the culture fluid was quantitated by an enzyme-linked immunosorbent assay. LA1 induced the production of higher levels of IL-1 alpha and TNF-alpha than other lactobacilli and bifidobacteria. Stimulation of the production of the cytokines was not due to the lipopolysaccharide (LPS) component, since LPS at concentrations equivalent to, or 100-fold greater than, that of LA1 induced only negligible amounts of IL-1 alpha and TNF-alpha. These results reveal that non-LPS component(s) of LA1 stimulate(s) the production of IL-1 alpha and TNF-alpha by macrophages, indicating that this organism stimulates the production of immunologic factors.
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PMID:Nonlipopolysaccharide component(s) of Lactobacillus acidophilus stimulate(s) the production of interleukin-1 alpha and tumor necrosis factor-alpha by murine macrophages. 929 Jan 17


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