Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Orotic acid, first discovered in ruminant milk, is an intermediate in the pyrimidine biosynthesis pathway of animal cells. Its synthesis is initiated by the formation of carbamoyl phosphate (CP) in the cytoplasm, with ammonia derived from glutamine. Ureotelic species also form CP in the first step of urea synthesis in liver mitochondria. For that, ammonia is derived from tissue fluid. When there is insufficient capacity for detoxifying the load of ammonia presented for urea synthesis, CP leaves the mitochondria and enters the pyrimidine pathway, where orotic acid biosynthesis is stimulated, orotic acid excretion in urine then increases. Orotic acid synthesis is abnormally high with hereditary deficiencies of urea-cycle enzymes or uridine monophosphate synthase. It is also elevated by ammonia intoxication and during feeding of diets high in protein, high in lysine with respect to arginine, or deficient in arginine, ornithine, and citrulline. Rats fed 1% orotic acid or diets deficient in urea-cycle amino acids develop fatty livers, which has not been demonstrated in other species. Humans consuming 6 g of orotic acid daily have not shown adverse effects. Rats fed 1% orotic acid or arginine-deficient diets also showed more and larger foci positive for gamma-glutamyl transpeptidase and more liver tumors after administration of carcinogens and partial hepatectomy. Orotic acid feeding was also associated with the tendency for development of larger mammary tumors induced by chemical carcinogens in rats and with development of urinary bladder calculi containing high concentrations of orotic acid in mice. Conditions that raise tissue orotic acid change purine-pyrimidine ratios. It is unknown whether tissue orotate concentrations play a role in the recently observed enhanced proliferation of cells in the colon of rats fed high-protein, high-fat diets or in the promotion of chemically induced colon cancer by intrarectal administration of ammonium acetate.
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PMID:Nitrogen-stimulated orotic acid synthesis and nucleotide imbalance. 154 44

The synthesis and release of the tumor marker carcinoembryonic antigen (CEA) from the colon cancer cell line LS180 has previously been reported to be enhanced during the later stages of in vitro culture after growth has stopped. It has been suggested that CEA expression was inversely related to the growth rate for these cells (Kahan, B.D.; Rutzky, L.P.; Legrue, S.J.; Tom, B.H. Methods Cancer Res. 18:197-275; 1979 and Shi, Z.R.; Tsao, D.; Kim, Y.S. Cancer Res. 43:4045-4049; 1983). Our studies indicate, however, that while certain environmental perturbations that halt growth (e.g., glucose starvation and elevated temperatures) do indeed stimulate CEA expression and release; other growth-arresting conditions, such as oxygen starvation, have no effect. Replacement of spent or conditioned medium with fresh medium during the later culture stages resulted in a 10-fold decrease in CEA release, indicating that either depleted nutrients or accumulating cellular products (such as lactate or ammonium) trigger enhanced CEA production.
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PMID:The effects of adverse growth conditions on the shedding of carcinoembryonic antigen from cultured LS180 colon cancer cells. 237 72

Effect of glutamine deprivation (GLN- medium) and of its replacement by 4mM ammonium chloride (GLN-/NH4+ medium) or by 4mM glutamate (GLN-/Gt+ medium) was studied on growth rate, morphology and metabolism of HT29 human colon cancer cells. Growth rates were modified as follows: at the first passage, growth of GLN- cells was strongly decreased (doubling time: 192 hr vs 32 hr in control cells grown in GLN+ medium); GLN-/NH4+ cells and GLN-/Gt+ cells were found to have doubling times of 72 and 70 hr, respectively. At the 8th passage, doubling times were decreased in all cases, being: 144 hr for GLN- cells, 60 hr for GLN-/NH4+ cells and 24 hr for GLN-/Gt+ cells, which indicates a capacity of adaptation of the cell-line to new culture conditions. GLN- cells and GLN-/NH4+ cells were found to exhibit an enterocytic type of differentiation (polarization of the cell layer with apical and cystic brush border and tight junctions); GLN-/Gt+ cells remained undifferentiated and comparable to control GLN+ cells. Glycogen level varied according to the phases of the culture, with a trend to lower level in glutamine deprived cells; glucose uptake and lactate production varied as a function of the medium composition and of the phases of the culture. At the 8th passage, all the glutamine deprived cells produced less lactate than control; GLN-/Gt+ cells were found to utilize less glucose than others.
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PMID:Effect of glutamine deprivation and glutamate or ammonium chloride addition on growth rate, metabolism and differentiation of human colon cancer cell-line HT29. 286 87

An inhibitor of soft agar colony formation by a human breast carcinoma-derived cell line was found to be present in latent form in the majority of cytology-positive human malignant effusions. Prior to dialysis, addition of human malignant effusions resulted in less than 10% alteration in efficiency of colony formation by the BT-20 human breast carcinoma cell line (mean efficiency 1 colony/4.3 cells plated at 14 days; mean colony diameter greater than 0.8 mm). After dialysis (membrane cutoff of 3500 molecular weight), 58 of 70 malignant effusions from patients with a variety of epithelial cell carcinomas resulted in 71% mean inhibition of colony formation (range 19.1-98% inhibition). Similar inhibition of anchorage-independent growth was observed for a human colon cancer-derived cell line (HCT-15) but not for polyoma and murine sarcoma virus-transformed rodent fibroblast lines. The malignant effusion-related transformed cell growth-inhibiting factor (TGIF) was sensitive to heat, sulfhydryl reduction, and protease treatment. TGIF-containing effusion resulted in parallel inhibition of thymidine incorporation in sensitive cell types in vitro. TGIF was precipitable in 28-34% ammonium sulfate with reconstitution of activity after resolubilization. TGIF was partially purified by chromatography on Biogel A-0.5 and Biogel P-100 which yielded two peaks of inhibitory activity. The predominant species had an approximate molecular weight of 110,000 and could be recovered as a single species from DEAE-cellulose at relatively high salt concentrations (0.4 M NaCl). A smaller amount of inhibitory activity was recovered from Biogel P-100 or Biogel P-60 with an apparent molecular weight of 55,000. The higher molecular-weight TGIF which appears to be a dimer of the Mr 55,000 protein is distinguishable from previously described growth-promoting and -inhibiting factors.
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PMID:Latent transformed growth-inhibiting factor in human malignant effusions. 325 64

An immunosuppressive substance was isolated from ascitic fluids of patients with advanced colon cancer by means of ammonium sulphate precipitation and preparative isoelectric focusing. This was a glycoprotein with an isoelectric point of pH 2.7-3.3, a molecular weight of about 52,000, and a sedimentation coefficient of 4.0S. The substance showed a single band on ordinary disc electrophoresis, but it was separated into several bands by gel isoelectric focusing, due to the structural variety of the sugar moiety. The results of physicochemical analysis indicate that the amino acid composition of this glycoprotein was indistinguishable from that of alpha 1-acid glycoprotein (alpha 1-AG), but its molecular weight, its carbohydrate content, and composition were distinctly different. Furthermore, this glycoprotein was found to have higher immunosuppressive activity than that of alpha 1-AG in both the in vitro and in vivo assays. This glycoprotein, which we called "IS substance," is a cancer-related substance synthesized in cancer patients.
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PMID:Purification and characterization of immunosuppressive (IS) substance obtained from ascitic fluids of patients with gastrointestinal cancer. 365 40

The LAI reactivity of a colon organ specific neoantigen (OSN) was recovered from the urine of advanced colon cancer patients. In this study three physico-chemical steps were employed; precipitation by 80% ammonium sulfate, ion exchange, and molecular sieve chromatography. Each isolate was tested for activity and specificity by the direct tube leukocyte adherence inhibition (LAI) assay employing leukocytes from colon and breast cancer patients. The OSN enriched isolate was then used to generate monoclonal antibodies (Mab). Hybridomas were screened by ELISA. One hybridoma designated Bac 18.1 reacted preferentially with colon OSN and not with the urine from normals or patients with breast cancer. Affinity purification of colon OSN was achieved and it was shown to consist of a single band in SDS-PAGE with an apparent molecular weight of 30,000. The eluted polypeptide was specifically reactive in ELISA as well as in the LAI assay.
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PMID:The isolation of colon cancer organ specific neoantigen by the use of the leukocyte adherence inhibition assay and monoclonal antibodies. 375 60

The human colon carcinoma cell line HT-29 was adapted to grow in chemically defined medium (CDM). The spent CDM (S-CDM) was concentrated by Amicon filtration and the crude HT-29 S-CDM purified by 40% saturated (NH4)2 SO4 precipitation. The purified antigen was tested by a microcomplement fixation (MCF) assay against the sera of cancer patients of various histologic types and against the sera of normal donors. Fifteen of 20 (75%) colon cancer, 16/20 (80%) breast cancer sera, 14/19 (74%) lung cancer sera, and 13/20 (65%) miscellaneous carcinoma sera were positive in the MCF. By contrast, 2/21 (10%) melanoma sera, 7/20 (35%) sarcoma sera, and 2/19 (11%) normal sera were positive. These data suggest the presence of a carcinoma-associated antigen in the spent CDM of the HT-29 colon carcinoma cell line adapted to grow in CDM.
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PMID:Presence of a carcinoma-associated antigen(s) in the spent chemically defined medium of a human colon carcinoma cell line. 615 28

Organ-specific neoantigens (TA) shed from the tumours of patients with metastatic breast or colon cancer and which had filtered into the urine were partially purified by a combination of physicochemical methods and affinity chromatography. TA activity of the isolated materials was monitored by the blocking Tube LAI assay. Urinary protein was precipitated by 80% saturated ammonium sulphate. Albumin was removed by affinity chromatography with blue Sepharose CL-6B. Affinity columns of human IgG were prepared from sera of patients whose leucocytes were LAI+ to the breast- or colon-cancer extracts. The anti-breast-TA affinity column bound the TA in the urine of patients with metastatic breast cancer but not that of patients with metastatic colon cancer. The TA in urine of patients with metastatic colon cancer was bound by the anti-colon-TA affinity column. Analysis by SDS PAGE revealed that the isolates with and without TA activity were composed mostly of urinary protein which had bound nonspecifically to the human IgG affinity columns. With an affinity column of anti-NHS and Protein A, some of the contaminants were removed, to reveal SDD PAGE unique bands at about 38,000 and 12,000 mol. wt in the isolate with breast-TA activity. Rabbit antisera, raised to the material that had bound nonspecically to the anti-breast-TA affinity column, were used as an anti-nonspecific affinity column to remove the contaminants in the isolates from the affinity columns of anti-breast TA and anti-colon TA. After passage through the anti-nonspecific affinity column, the material that contained the putative breast or colon cancer TA revealed a unique band at about 38,000-40,000 mol. wt and residual fine bands at about 25,000-30,000 mol. wt. Both the control material and material with TA activity had similar bands at about 25,000 and 50,000 mol. wt. The specific activity of the putative colon or breast TAs, as measured by the blocking Tube LAI assay, was increased from about 30 to 5000-10,000 u/mg, a 125-400-fold enrichment.
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PMID:Partial purification of organ-specific neoantigens from human colon and breast cancer by affinity chromatography with human tumour-specific gamma-globulin. 736 81

Mutation of the adenomatous polyposis coli (APC) gene is responsible for familial adenomatous polyposis and is an etiologic factor for digestive tract malignancies. Although the APC gene product (APC) is believed to play a role in growth suppression of colonocytes, the underlying mechanism is not clear. However, recent evidence does suggest that APC is a microtubule-associated protein (MAP), and like other MAPs, it can be phosphorylated, as we have shown. To facilitate studies of APC function, we purified the APC protein. To purify the full-length APC protein, HCT116 human colon cancer cells were lysed and the particulate fraction from the lysate was extracted with ammonium sulfate followed by Sepharose 4B and DEAE-Sephacel column fractionation and then by sucrose zonal density gradient centrifugation. The final purified APC fraction was determined to be about 1000-fold enriched in APC. The availability of purified APC will be valuable in investigating possible growth-suppressing mechanisms of APC including specific sites of APC phosphorylation and APC's interaction with other cellular proteins.
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PMID:Purification of the adenomatous polyposis coli (APC) gene product. 748 82

Thermolyzed casein is known to promote the growth of aberrant crypt foci (ACF) and colon cancer when it is fed to rats that have been initiated with azoxymethane. We speculated that the promotion was a consequence of increased colonic protein fermentation (i.e., that the thermolysis of the casein decreases its digestibility, increases the amount of protein reaching the colon, and increases colonic protein fermentation and that the potentially toxic products of this fermentation promote colon carcinogenesis). We found that the thermolysis of casein reduces its digestibility and increases colonic protein fermentation, as assessed by fecal ammonium and urinary phenol, cresol, and indol-3-ol. Thermolysis of two other proteins, soy and egg white protein, also increases colonic protein fermentation with increased fecal ammonia and urinary phenols, and thermolysis of all three proteins increases the levels of ammonia and butyric, valeric, and i-valeric acids in the cecal contents. We found, however, that the increased protein fermentation observed with thermolysis is not associated with promotion of colon carcinogenesis. With casein, the kinetics of protein fermentation with increasing thermolysis time are clearly different from the kinetics of promotion of ACF growth. The formation of the fermentation products was highest when the protein was thermolyzed for one hour, whereas promotion was highest for protein that had been thermolyzed for two or more hours. With soy and egg white, thermolysis increased colonic protein fermentation but did not promote colon carcinogenesis. Thus, although thermolysis of dietary casein increases colonic protein fermentation, products of this fermentation do not appear to be responsible for the promotion of colon carcinogenesis. Indeed, the results suggest that protein fermentation products do not play an important role in colon cancer promotion.
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PMID:Colonic protein fermentation and promotion of colon carcinogenesis by thermolyzed casein. 760 87


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