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

The capability of carcinogens with different modes of action to affect replicative DNA synthesis in the human colon was tested with the use of organ culture of histologically normal mucosae from patients undergoing colectomy for colon cancer or diverticulosis. 1,2-Dimethylhydrazine, an organotropic carcinogen for the colon in rodents, inhibited DNA synthesis of mucosa at a concentration of 3.0 mM but not at 1.5 mM. Methylazoxymethanol acetate, a proximate carcinogen, inhibited DNA synthesis at a concentration of 1.5 mM. N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG), a direct-acting carcinogen, inhibited DNA synthesis at a concentration of 0.5 mM. No tissue toxicity was observed at the doses of these carcinogens used. The procarcinogen benzo[a]pyrene, which is not organotropic for the colon, caused no inhibition of DNA synthesis in colon explants at concentrations of 0.01--0.05 mM. These data indicate that replicative DNA synthesis in the human colon is most sensitive to the inhibitory effect of the direct-acting carcinogen MNNG.
 ...
PMID:Inhibition of DNA synthesis by carcinogens in human colon mucosa in organ culture. 29 4

Sera from 134 selected patients with various types of cancer were tested for soluble antigen-antibody complexes by the C1q binding method. Sera from 85 healthy blood bank donors served as normal controls. C1q binding activity (C1q BA) values above the 95th percentile for healthy subjects were found in 83% of sera from patients with neoplastic diseases. The incidence of abnormal C1q BA values among patients with malignant melanoma was 83%, with breast cancer 74%, with colon cancer 75%, with lung cancer 88%, with leukemia and lymphoma 85%, and with miscellaneous tumors 94%. High C1q BA values were found most frequently in sera of patients who had been diagnosed relatively recently (within 5 mo) and who had evident residual disease after surgical treatment. Recurrence or progression of tumor growth occurred significantly more frequently in lung cancer patients with high C1q BA. DNA was not detected in cancer patients' sera and treatment with DNase did not decrease in C1q BA. C1q BA in sera could not be explained by the presence of antiglobulin antibodies. Sucrose density gradient ultracentrifugation studies of the serum C1q BA in 4 cancer patients showed that the major binding activity was found between 19S and 7S.
 ...
PMID:The C1q binding test for soluble immune complexes: clinical correlations obtained in patients with cancer. 32 5

Cultured human malignant melanoma cells, when added to normal human lymphocytes stimulated to proliferate by mitogen or antigen, were found to inhibit the uptake of 3H-thymidine (3H-T) by the lymphocytes. A heat-labile factor present in the supernatants of the melanoma cultures is responsible for inhibition. Cell viability and blastogenesis are unimpaired in the lymphocyte cultures containing the inhibitor. Inhibition of 3H-deoxyuridine uptake was also noted indicating that both salvage and de novo pathways of DNA synthesis are involved. Lymphocytes appear to be preferentially affected as cultured colon cancer cells take up 3H-T normally in the presence of the inhibitor. Normal mitotic indices and biochemical estimation of DNA content in lymphocyte cultures containing the inhibitory factor indicate that DNA synthesis does proceed normally. The mechanisms of action of the inhibitor would appear to involve alteration of exogenous nucleoside rather than a metabolic inhibition of intracellular nucleic acid synthesis.
 ...
PMID:Characterisation of human malignant melanoma cell lines. VI. Inhibition of 3H-thymidine uptake by normal stimulated lymphocytes. 59 53

An abnormal zone of DNA synthesis at the surface and upper portion of colonic crypts has been thought to be related to future adenomatous polyp development and to express a regulatory defect in the mechanism that normally terminates synthesis in the upper third. As part of a screening program for early colon cancer detection, patients over 40 years of age found to have occult blood in their stool (Ho+) are evaluated by barium enema and colonscopy as well as isotopic incorporation studies of biopsy and lavage specimens. This proliferative abnormality occurred most frequently among patients with an adenoma or adenocarcinoma although the frequency varied among simultaneous biopsies from the same patient. Specimens from Ho+ patients with a tumor often contained small areas of focal atypism in the biopsy or fragments of atypical epithelial cells in the lavage sample. A small group of Ho+ patients in whom no overt neoplasm could be detected also demonstrated surface-labeled epithelial cells with morphological alteration of these cells. Based on the microscopic findings presented, continued surveillance of these patients is suggested, as well as extension of these studies to include other high risk groups.
 ...
PMID:Early detection of colonic neoplasia in patients at high risk. 59 71

Since normal epithelial cell proliferation occurs chiefly in the lower two thirds of colonic crypts, the presence of aberrant DNA-synthesizing cells (tritiated thymidine labeled) at the mouth and on the surface of colonic crypts is being assessed as a predictive indicator of the development of neoplasia in patients at high risk. These would include patients with previous polyps or colon cancer or family history of either or both. Surface cells are obtained by pulsatile saline lavage of the lower bowel and incubated with tritiated thymidine ([3H]TdR) for autoradiographic observation. Findings in each high-risk category are presented and compared with [3H]TdR labeling data from a biopsy taken at the close of the procedure. The lavage technique has also been carried out on mice injected with the colon carcinogen 1,2-dimethylhydrazine (DMH). Mice were demonstrated to have [3H]TdR-labeled cells and cellular atypic while being hemoccult negative and asymptomatic for overt disease. Evaluation of human material preliminarily demonstrated the presence of surface-labeled epithelial cells in a high percentage of patients at risk for colon cancer.
 ...
PMID:[3H]thymidine-labeled colonic epithelial cells and mucosa in mice and man. 66 24

Relatives of patients with multiple polyposis are among those at high risk for development of neoplasms in the colon. Examination of 4 siblings, 3 men and 1 woman, of a patient with multiple polyposis was conducted for the possible presence of colonic polyps. All patients were over 40 years of age and received barium enemas for the radiological detection of excrescences. Proctoscopic examinations were also carried out during which time a biopsy and colonic wash were obtained. Polyps were absent on films as well as on endoscopy, and colonic cytologies of all 4 subjects were within normal limits. However, isotopic incorporation studies revealed the presence of an abnormal labeling pattern in some crypts of the biopsy incubated with TdR-3H of 1 family member. Along with normal crypts with label in the lower two-thirds of the colonic crypts, some were seen to have cells labeled at the surface, a proliferative lesion thought to precede the apperarance of a polyp. Among the surface cells removed by the colonic wash, some were found to be isotopically labeled, that is, engaged in DNA synthesis. Thus, a defect in the regulation of colonic epithelial cell replication was found, suggesting the need for close surveillance in the interest of early colon cancer detection.
 ...
PMID:The detection of aberrant DNA synthesis in a member of a high-risk cancer family. 116 21

In an effort to evaluate the possible correlation of the transforming ability of the known colon carcinogens dimethylhydrazine, 3-2'-dimethyl-4-aminobiphenyl, and methylazoxymethanolacetate to damage and repair of DNA, a series of compounds known to react with DNA-nitrogen mustard, methylmethanesulfonate, and mitomycin C--were administered to rats that had been prelabeled with 3H-thymidine. The DNA of crypt and villus of the jejunum and crypt and surface cells of the large bowel were analyzed by ultracentrifugation on an alkaline sucrose gradient. All fractions suffered degradation to such an extent that essentially no undamaged DNA was detectable. This was followed by repair and an increase in size. However, in the surface cells of the colon of animals that had received a carcinogenic insult there was far less rapid repair. Since this is the site where tumors would ultimately arise these data are supportive of the hypothesis that there is a relationship between decreased repair and carcinogenicity. In view of the age related incidence of colon cancer, repair in older animals was evaluated and was found to be less than that seen in the young. Since multiple treatment with the carcinogen dimethylhydrazine is required and there is a long latent period, the effect of this treatment on repair potential was evaluated. Similar to what was seen in the older animals, these treated rats had greatly reduced capacity to repair DNA. All these observations are consistent with the hypothesis that decreased repair of DNA alterations is a concomitant of carcinogenesis.
 ...
PMID:In vivo repair of rat intestinal DNA damage by alkylating agents. 121 55

Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) widely used for treatment of inflammatory arthritis. Recent experimental and clinical studies suggest that piroxicam, as well as other NSAIDs, may be useful for chemoprevention of colon cancer. While there is less information regarding NSAIDs for chemoprevention of urinary bladder malignancy, there are compelling data which suggest that this should be evaluated. A major effect of NSAIDs is inhibition of cyclooxygenase, the rate-limiting enzyme for conversion of arachidonic acid to important signal molecules, including prostaglandins, which profoundly affect cellular functions in many tissues. The initial enzyme reaction leading to formation of prostaglandin H can be accompanied by cooxidation of xenobiotics resulting in extrahepatic and local tissue production of reactive products which are carcinogenic. The end product prostaglandins, especially prostaglandin E2 (PGE2), are biological modifiers which can significantly affect cell proliferation and tumor growth. High levels of PGE2 stimulate growth of certain tumor cell lines while inhibition of prostaglandin synthesis with indomethacin or piroxicam can cause suppression. The mechanisms for this effect are unclear. Studies in cultured cells exposed to indomethacin show inhibition of G1-to-S phase progression of the cell cycle and a reduction in overall DNA synthesis. It is unclear whether this effect on cell growth results from some direct action of the NSAID or a reduction in prostaglandins or indirectly from modulation of important control signals, such as calcium flux. In addition to cyclooxygenase, NSAIDs can inhibit activity of other enzymes, including phosphodiesterases and cyclic GMP-AMP protein kinases, which may be central to cancer initiation and promotion. NSAIDs can also interfere with transmembrane ion fluxes and with cell-to-cell binding. Prostaglandins can modulate a variety of immunological responses and thereby play an important role in host antitumor immunity. For example, high levels of tissue PGE2 are frequently associated with suppression of immune surveillance and killing of malignant cells. Conversely, immune responses are generally enhanced by drugs that inhibit prostaglandin synthesis. PGE2 can act as a feedback inhibitor for cellular immune processes, such as T-cell proliferation, lymphokine production, and cytotoxicity. This effect is also seen for macrophage activity and natural killer cell toxicity. In general, either increased production of PGE2 or increased sensitivity to normal amounts of PGE2 results in depressed cellular immunity. Cyclooxygenase inhibitors (NSAIDs) such as piroxicam which decrease PGE2 production can stimulate cellular immune function both in vitro and in vivo. A variety of tumor cell lines and human malignancies produce large quantities of prostaglandins.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Piroxicam and other cyclooxygenase inhibitors: potential for cancer chemoprevention. 130 81

The p53 gene has been implicated as a tumor suppressor gene involved in the pathogenesis of lung cancer. Our previous study revealed that the p53 gene is frequently mutated with a distinct nucleotide substitution pattern in small cell lung cancer specimens in Japanese patients. In this study, we examined 30 primary, resected non-small cell lung cancer samples in Japanese patients using complementary DNA-polymerase chain reaction and sequencing. Mutations changing the p53 coding sequence were found in 14 of 30 tumor samples (47%), while G:C to T:A transversions which are uncommon in other cancers such as colon cancer were the most frequently observed mutations, in agreement with an earlier report on non-small cell lung cancer in American patients. Furthermore, the present study shows for the first time that in univariate and multivariate analyses, the presence of p53 mutations is closely associated with lifetime cigarette consumption.
 ...
PMID:p53 mutations in non-small cell lung cancer in Japan: association between mutations and smoking. 131 70

Transcriptional activation of human heat shock protein (HSP) genes by heat shock or other stresses is regulated by the activation of a heat shock factor (HSF). Activated HSF posttranslationally acquires DNA-binding ability. We previously reported that quercetin and some other flavonoids inhibited the induction of HSPs in HeLa and COLO 320DM cells, derived from a human colon cancer, at the level of mRNA accumulation. In this study, we examined the effects of quercetin on the induction of HSP70 promoter-regulated chloramphenicol acetyltransferase (CAT) activity and on the binding of HSF to the heat shock element (HSE) by a gel mobility shift assay with extracts of COLO 320DM cells. Quercetin inhibited heat-induced CAT activity in COS-7 and COLO 320DM cells which were transfected with plasmids bearing the CAT gene under the control of the promoter region of the human HSP70 gene. Treatment with quercetin inhibited the binding of HSF to the HSE in whole-cell extracts activated in vivo by heat shock and in cytoplasmic extracts activated in vitro by elevated temperature or by urea. The binding of HSF activated in vitro by Nonidet P-40 was not suppressed by the addition of quercetin. The formation of the HSF-HSE complex was not inhibited when quercetin was added only during the binding reaction of HSF to the HSE after in vitro heat activation. Quercetin thus interacts with HSF and inhibits the induction of HSPs after heat shock through inhibition of HSF activation.
 ...
PMID:Inhibition of the activation of heat shock factor in vivo and in vitro by flavonoids. 132 38


1 2 3 4 5 6 7 8 9 10 Next >>