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)

Activation of C-Ki-ras oncogene by point mutation within codon 12,13 was determined by Polymerase Chain Reaction (PCR) using specific oligonucleotide probes. In 9 of 42 colon cancer specimens point mutations in codon 12 of C-Ki-ras oncogene were found. The point mutations identified were GGT(Gly)----GAT(Asp) (4 cases), GGT (Gly)----TGT (Cys) (3 cases) and GGT(Gly)----GTT(Val) (2 cases), respectively. Two types of point mutations (GGT----GAT, GGT----TGT) were found simultaneously in one specimen. The results showed that there was no relationship between the point mutation of C-Ki-ras oncogene and patient's sex, age, state of metastasis or prognosis.
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PMID:[Detection of point mutations of C-Ki-ras oncogene in colon cancer by PCR using specific oligonucleotide probes]. 139 73

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

In 98 patients affected by colorectal cancer (43 patients with colon cancer, 55 patients with rectosigmoid cancer) the specificity of some tumor markers (CEA, GICA, TPA, alpha-FP, FpA, gamma-GT) has been tested in evidencing the coexistence of liver metastases and the site of the primary tumor, i.e. the rectosigmoid region (rectum + 15 cm of the adjacent sigmoid colon) vs the rest of the colon. Liver metastases, present in 19 patients with colon cancer and in 24 with recto-sigmoid cancer, were previously ascertained by various instrumental investigations. Unlike previous studies which indicated CEA or alpha-FP as the most reliable markers to suggest the coexistence of liver metastases in such patients, the reported results allow the following sequence, in decreasing order of sensitivity, to be proposed: gamma-GT; FpA; CEA and GICA to a similar degree; TPA, which increases only when liver metastases from colon cancer are present; lastly, alpha-FP, which rises only in very few cases of massive hepatic involvement.
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PMID:Specificity of tumor markers (CEA, GICA, TPA, alpha-FP, FpA, gamma-GT) for the diagnosis of hepatic metastases from large bowel cancers. 247 62

The effect of butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) on the carcinogenicity in rats of aflatoxin B1 (AFB1) was investigated. AFB1 was administered by gastric intubation to male F344 rats at 25 micrograms/kg body wt three times a week such that a total dose of 1.5 mg/kg (0.48 mmol/kg) body wt was given over a period of 20 weeks and diets containing either 1000 or 6000 p.p.m. BHA or BHT were fed starting one more week before carcinogen, during administration and for one week after cessation. Animals were killed during exposure and at intervals up to 24 weeks after cessation. Liver altered foci and neoplasms were quantified using the exclusion of cellular iron after iron-loading and gamma-glutamyl transpeptidase reaction, as well as conventional staining for identification. Exposure to AFB1 alone induced substantial numbers of altered foci after 20 weeks, and at 24 weeks after cessation of exposure, the incidence of hepatocellular neoplasms was 63%. In the groups receiving BHA or BHT together with AFB1, the numbers of altered foci were decreased at all time points and at termination, the final incidence of liver cell neoplasms and number of neoplasms per animal were also reduced in a dose-related manner. Neoplasms in other organs were rare and were not affected by antioxidant treatment, except for a possible reduction of colon cancer. Thus, BHA and BHT inhibited the hepatocarcinogenesis of concurrently administered AFB1 without shifting the organotropism.
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PMID:Dose-related inhibition of aflatoxin B1 induced hepatocarcinogenesis by the phenolic antioxidants, butylated hydroxyanisole and butylated hydroxytoluene. 287 75

Activation of the cellular oncogene c-N-ras has been frequently observed in DNA from leukemic cells in acute myeloid leukemia (AML). Ras gene activation sufficient to mediate in vitro transformation and rodent tumorigenesis usually results from point mutations and amino acid substitutions in the 12th or 61st codons. In AML and the related myelodysplastic syndromes, amino acid substitution at the 13th codon has been observed. An activated c-N-ras gene from a 45-year-old patient with AML was isolated by transfection analysis and subjected to molecular cloning and sequence analysis. A point mutation of the 12th codon (GGT to GAT) resulting in aspartic acid substitution for glycine was observed. In other neoplasms such as colon cancer, specific ras mutations occur predominantly (e.g., K-ras, codon 12). This predominance has been of demonstrable value in analyzing large cohorts for ras activation with techniques that are rapid and economical, such as oligonucleotide hybridization. It had previously been thought that such a predominance for activation of c-N-ras at codon 13 existed in AML; however, this study in concert with others underscores the importance of 12th codon c-N-ras mutations, along with 13th and 61st codon mutations in the molecular pathogenesis of AML. Guanylate to adenylate transition mutations are commonly observed in AML and may provide insight into potential environmental leukemogens. Addressing all commonly prevalent ras activating mutations bears impact in the future design of molecular surveys of the role of ras activation in leukemogenesis.
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PMID:12th codon mutation resulting in c-N-ras activation in acute myelogenous leukemia. 327 72

Carcinoembryonic antigen and activities of glucosephosphate isomerase (EC 5.3.1.9), gamma-glutamyltransferase (EC 2.3.2.2), and lactate dehydrogenase (EC 1.1.1.27) were measured in aqueous extracts of fetal, normal adult, and malignant human colon tissues. Fetal colon, as well as primary and metastatic colon tumor tissue, showed higher activities of these analytes than did normal adult human colon. Liver metastases of colon cancer gave the highest values, normal adult human colon the lowest. Statistically, these differences were more striking in the case of carcinoembryonic antigen and glucosephosphate isomerase than for gamma-glutamyltransferase or lactate dehydrogenase. In contrast to the other markers, gamma-glutamyltransferase activity was lower in fetal organs than in normal adult colon and colon tumors. These results are consistent with earlier observations that activities of these markers are significantly increased in the blood of patients with metastatic colon cancer.
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PMID:Concurrent measurements of carcinoembryonic antigen, glucosephosphate isomerase, gamma-glutamyltransferase, and lactate dehydrogenase in malignant, normal adult, and fetal colon tissues. 610 67

The Dukes' and TNM systems for staging carcinoma of the colon and rectum are still the best pathologic classifications, but they do not apply to all patients and do not distinguish between patients who will die and patients who will be cured by the same therapeutic procedure. A new approach to this problem should be to establish a biochemical automatic classification, complementary to the morphologic one, which allow us to classify every patient before and after the first and subsequent treatments. By using several nonspecific tumor markers, such as CEA, AAT, AF, AAG, GGT and transferrine, a discriminant analysis was executed among the groups of patients with LD, RD and DD. Our initial results with only 12.8 per cent of incorrect classifications, that is patients classified in a less advanced group, suggest that this system may be quite useful in order to select those patients with carcinoma of the rectum who should benefit from preoperative radiotherapy as well as those who should receive adjuvant therapy after the first treatment. On the other hand, for patients classified in a more advanced group than the pathologic grading, we may well be able to identify those patients with occult disease for which the frequency of revisions should be shorter.
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PMID:Automatic preoperative classification of carcinoma of the colon and rectum. 671 Mar 17

Glutathione transferases (GSTs) have been shown to play an important role in multiple drug resistance in cancer chemotherapy. The inactivation of GST isoforms could lead to an enhanced activity of cytotoxic drugs. Thus, we have developed glutathione phosphono analogs [(S)-gamma-glutamyl-(2RS)-(+/-)-2-amino-(dialkoxyphosphinyl)-ac etylgl ycines], which were previously shown to be inhibitors of GSTP1-1. In the present study, the inhibition characteristics of these analogs, including isoenzyme specificities, type of inhibition, and determination of K(i) values, were determined. The inhibition of class alpha GSTs was competitive towards GSH. A mixed-type, non-competitive inhibition of class mu and pi GSTs was observed. The K(i) values varied between 880 +/- 210 and 0.45 +/- 0.1 microM. The inhibitors were most effective towards class mu GSTs. In order to investigate the potential use of these GST inhibitors in intact cellular systems, two additional approaches were examined. Firstly, the metabolic stability was tested with purified gamma-glutamyl transpeptidase and cell homogenates as well as during incubation of cell lines. No appreciable degradation was observed in any of the tested systems. Secondly, to facilitate cellular uptake, three derivatives were synthesized in which the glycine carboxylic group was esterified. Uptake and a possible intracellular cleavage to the corresponding free acids were monitored by HPLC analysis. The esters were effectively transported into HT29 (colon cancer) and EPG85-257P (gastric cancer) cells, respectively, and readily converted into the more active free acids. In conclusion, the tested inhibitors may be regarded as model compounds for the development of modulating agents in cancer chemotherapy.
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PMID:Phosphono analogs of glutathione: inhibition of glutathione transferases, metabolic stability, and uptake by cancer cells. 1069 62

K-ras mutation is the most common oncogenic alteration in various human cancers including colorectal carcinomas. Point mutations have the potential to activate the K-ras gene if they occur in the critical coding sequences. Almost all of these mutations have been localized in codons 12, 13 and 61. We report a case of colon cancer presenting point mutations at both codons 12 and 22 of the K-ras gene. PCR-SSCP and subsequent sequencing revealed that GGT (glycine, wild-type) to AGT (serine) substitution at codon 12 and CAG (glutamine, wild-type) to CGG (arginine) substitution at codon 22 occurred in the same allele.
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PMID:Concurrent mutations of K-ras oncogene at codons 12 and 22 in colon cancer. 1211 Jun 40

To elucidate early molecular events related to colon carcinogenesis, we examined alterations in the expression of colon cancer-related genes such as cyclooxygenase (COX)-2, APC and c-Myc, cell proliferation and apoptosis in the background colon mucosa, and K-ras mutation at aberrant crypt foci (ACF) in the colons of azoxymethane (AOM)-treated rats 4 weeks after the first exposure to AOM. About 40 ACF/colon were induced in the colons of rats treated with AOM (Group 1); however, rats not treated with AOM (Group 2) showed no ACF formation in the colon. The level of AgNORs in the colonic mucosa was significantly higher in Group 1 than in Group 2 (P<0.01). The colonic mucosa in Group 1 looked macroscopically and histologically normal, but the proliferative activity of the mucosa of rats treated with AOM was clearly elevated. COX-2 mRNA expression was not detected in normal colonic mucosa in Group 2, but 3 out of 10 rats in Group 1 showed COX-2 mRNA expression in their colons by reverse transcription (RT)-polymerase chain reaction (PCR). There was a tendency toward an increased expression level of COX-2 in the AOM-treated group. The level of APC mRNA expression in Group 1 was significantly lower than that in Group 2 (P<0.01). Moreover, the level of c-Myc mRNA expression in Group 1 was significantly higher than that in Group 2 (P<0.01). An average of 0.034+/-0.006% apoptosis in colonic mucosa was detected in Group 1; the incidence of apoptosis in Group 2 was 0.021+/-0.005%. The difference between Groups 1 and 2 was significant (P<0.01). These results indicate that apoptosis was possibly induced to eliminate cells damaged by AOM administration. Six out of 22 (27%) ACF with 4 or more crypts showed K-ras mutations at codon 12; all mutations were G to A transitions (GGT to GAT). ACF with 1-3 crypts showed no mutations in the K-ras gene. In conclusion, AOM caused an increase in COX-2 and c-Myc mRNA expression, a decrease in APC mRNA expression, induction of apoptosis in normal-appearing colonic mucosa, and a K-ras mutation in ACF with 4 or more crypts. These findings may help to identify key targets in the early steps of colon carcinogenesis, against which drugs that would be broadly effective for chemoprevention of colon cancer could be developed.
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PMID:Molecular changes in the early stage of colon carcinogenesis in rats treated with azoxymethane. 1214 79


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