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)

Glutathione (GSH) has been shown to modulate the cytotoxicity of a variety of chemotherapeutic agents. The effect of mitomycin C (MMC) treatment duration and the effect of GSH depletion on in vitro cytotoxicity against the human colon cancer cell line HT-29 was studied under aerobic conditions. Continuous-exposure experiments revealed that the cytotoxicity of 0.1 microM MMC, as measured by clonogenic cell survival, exhibited a shoulder until exposure time was at least 12 h, after which time exponential cytotoxicity was observed. Lowering GSH levels to less than 3% of control using buthionine sulfoximine (BSO) did not enhance cytotoxicity of MMC given for 1 h or continuously for less than 12 h. However, GSH depletion did enhance cytotoxicity of MMC given continuously for at least 12 h, with a dose-modifying factor at 1% survival of 1.4 for a 24-h treatment. GSH depletion under these conditions enhanced cytotoxicity of even minimally cytotoxic MMC concentrations (0.02 microM). Absolute levels of GSH-related enzymes, including glutathione-S-transferase, and the MMC-metabolizing enzyme DT-diaphorase did not change appreciably. A tetrazolium [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay was used to verify the results further and to determine the optimal sequence of BSO administration with a 24-h MMC treatment. BSO added simultaneously with MMC did not increase cytotoxicity, compared to MMC alone. BSO added and then removed prior to MMC was effective (dose-modifying factor at 50% survival = 1.3), but the greatest cytotoxicity was noted when BSO was present before and during MMC treatment (dose-modifying factor = 1.5). GSH depletion in another cell line (SW480) showed similar enhancement of 24-h MMC cytotoxicity. These studies show that aerobic cytotoxicity of MMC is improved by administration of the drug in continuous fashion for at least 12 h, as opposed to continuous administration for shorter periods or 1-h bolus administration. Cytotoxicity of continuous (at least 12-h) MMC treatment can be modestly enhanced by GSH depletion, which must precede MMC exposure in order to be effective.
Cancer Res 1992 Sep 01
PMID:Effect of treatment duration and glutathione depletion on mitomycin C cytotoxicity in vitro. 151 28

It has been predicted that low affinity antibodies (Abs) should penetrate into tumors more readily than high affinity Abs. However, the absolute uptake and residence time of a high affinity Ab may be better. It is, therefore, not clear whether a high affinity Ab would have a therapeutic advantage. This is particularly relevant with 125I radioimmunotherapy, where targeting of every cell is important. This study compared the uptake kinetics and toxicity in multicell spheroids of two murine monoclonal Abs labeled with 125I. 17-1A was produced by immunization with a human colon cancer cell line and has an affinity of 5.15 x 10(7) M-1. 323/A3 was produced by immunization with a human breast cancer cell line and has an affinity of 1.87 x 10(9) M-1. Binding of both Abs to LS174T spheroids was similar at 4 degrees C, but binding of 17-1A was 8-10-fold less than that of 323/A3 at 37 degrees C. Despite this difference, the toxicity of 125I-17-1A in spheroids after 7 days of incubation was similar to that of 125I-323/A3. Autoradiography showed that 17-1A penetrated the spheroids much more deeply and evenly than did 323/A3. It appears that much of the radiation dose to spheroids treated with 125I-323/A3 was wasted because of the uneven Ab distribution. This study demonstrates the potential advantage of using Abs of lower affinity for 125I radioimmunotherapy, because of their more even distribution. It also suggests that a large number of binding sites per cell may be a disadvantage if more 125I is bound than is necessary to kill the cell, because this may slow Ab penetration.
Cancer Res 1992 Sep 01
PMID:Comparisons between two monoclonal antibodies that bind to the same antigen but have differing affinities: uptake kinetics and 125I-antibody therapy efficacy in multicell spheroids. 151 38

Haggitt's classification is a useful guide in the management of patients with large bowel polyps which contain invasive adenocarcinoma in that patients with levels 1 to 3 require no operation. Nuclear morphometry has been shown to be a useful prognostic discriminant for patients with invasive carcinoma of the large bowel. The nuclear shape factor of 44 polyps with invasive carcinoma was studied to determine whether this parameter was of value to define those patients with Haggitt level 4 who should have a resection. The shape factor of 50 interphase nuclei was obtained through the use of image analysis by tracing the nuclear profiles as digitized on a video screen. The nuclear shape factor was defined as the degree of circularity of the nucleus, a perfect circle recorded as 1.0. Our previous experience showed a nuclear shape factor greater than 0.84 was associated with a poor outcome. The overall mean shape factor was 0.71 (0.59-0.85). There was a tendency for the patients with residual disease to have values in the upper range. Our findings suggest that nuclear morphometry fails to add any predictive information in this clinical situation.
J Surg Oncol 1992 Sep
PMID:The value of nuclear morphometry in the management of patients with colorectal polyps that contain invasive adenocarcinoma. 151 94

Screening of large populations for colon malignancy has been advocated in several countries to detect cancers at earlier, curable stages and/or prevent cancer by detecting and removing premalignant polyps. Ideal screening would identify subjects with the highest risk of cancer and target sensitive screening tests at this population. Recent data suggesting that environmental factors and genetic alterations contribute to increased cell proliferation in colonic mucosa provide several avenues for identification of high-risk subjects. This review examines the current literature regarding colon cancer risk factors, focusing on new ways to identify individuals who may benefit from targeted screening.
Am J Gastroenterol 1992 Sep
PMID:Targeted colon cancer screening: a concept whose time has almost come. 151 64

In a retrospective study, the frequency of occurrence of gallstones and cholecystectomy in 479 patients with colorectal cancer was compared with that of 483 matched control patients with other malignancies. The mean interval between cholecystectomy and colon cancer diagnosis was 15.1 +/- 9.9 yr (range 2-53 yr), and there was no statistically significant difference, compared with the control group at 13.9 +/- 8.2 yr (range 2-31 yr). In patients with colon cancer, the general increased relative risk of concomitant diagnosed gallstones (relative risk 1.73, p = 0.0123) and the relative risk of cholecystectomy (relative risk 2.08, p = 0.0074) was statistically significant. However, when the data with regard to sex were analyzed, significant differences were observed only in women. Women affected by right colon cancer also had a statistically significant higher incidence of previous cholecystectomy (relative risk 2.86, p = 0.0096), but no significantly higher incidence of concomitant gallstones. The general increased relative risk in patients with right colon cancer and decreased risk in patients with left colon cancer of concomitant gallstones and prior cholecystectomy was statistically significant. Our data provide evidence for the hypothesis that both gallstones and cholecystectomy increase the general risk of large bowel cancer. Therefore, they are also compatible with the possibility that common risk factors causes the association between gallstones and large bowel cancer.
Am J Gastroenterol 1992 Sep
PMID:Increased incidence of gallstones and prior cholecystectomy in patients with large bowel cancer. 824 94

The diets of 746 colon cancer cases in Los Angeles County, California (USA) were compared with those of 746 controls matched on age, sex, race, and neighborhood. In both genders, total energy intake was associated with significantly increased risk, and calcium intake was associated with significantly decreased risk. These effects were reduced only slightly after adjustment for the nondietary risk factors (weight, physical activity, family history, and, if female, pregnancy history). In men, total fat and alcohol intakes were responsible for the calorie effect; in women, no individual source of calories was associated independently with risk. Neither saturated fat nor fat from animal sources was responsible for the fat effect. There were no additional independent significant effects for sucrose, fiber, cruciferous vegetables, beta-carotene, other vitamins, or any other nutrient or micronutrient. In univariate analyses, meats, poultry, breads, and sweets were associated with excess risk, and yogurt was protective. After adjustment for sources of calories, no individual food was associated with excess risk, but yogurt remained significantly protective. Total calories were associated with excess risk throughout the colon while the effects of calcium, fat, and alcohol appeared somewhat stronger in the distal colon. After adjustment, crude fiber was significantly protective in the ascending colon but not even weakly protective in the distal colon.
Cancer Causes Control 1992 Sep
PMID:Diet and colon cancer in Los Angeles County, California. 152 27

A patient with recurrent sigmoid colon cancer developed an arterial-vaginal fistula after multiple surgeries and postoperative radiotherapy. Angiography revealed a fistula between the hypogastric artery and vaginal wall. Gelfoam and coil embolization controlled the hemorrhage and she recovered without incident. This case illustrates development of malignant fistula and intervention with embolization in a patient with multiple surgeries and postoperative irradiation in the pelvis.
Gynecol Oncol 1992 Sep
PMID:Hypogastric arterial-vaginal fistula following multiple surgeries and pelvic radiotherapy. 152 17

Cl.16E, a stably differentiated clonal derivative of the human colonic cancer cell line HT29, was used to investigate the structure of oligosaccharide chains of mucins in colonic cancer. Secretory mucins were purified by equilibrium density gradient centrifugation in CsCl. Oligosaccharide side chains were isolated after beta-elimination. Compositional analysis of oligosaccharide-alditols performed after purification by gel filtration on a Bio-gel P-6 column showed 1) that GalNAc residues were located exclusively at the reducing ends of the chains, and 2) that fucose was absent from the preparation. Oligosaccharide-alditols were separated by high performance liquid chromatography (HPLC) on quaternary amine packings into a minor neutral fraction representing about 6.5% by weight of released oligosaccharides and four acidic fractions. Two acidic fractions, namely FI and FII encompassing mono- and disialylated structures, respectively, and containing 78% of total oligosaccharide alditols, were separated by HPLC. Structural determinations were carried out using methylation analysis, 1H NMR spectroscopy, and fast atom bombardment-mass spectrometry. Twelve oligosaccharide structures were determined which ranged in size from 3 to 8 residues. These oligosaccharides were based on core types 1, 2, and 4. Elongation of oligosaccharide chains was terminated by addition of sialic acid in alpha 2-3 linkage to Gal beta 1-3R and to Gal beta 1-4R residues. The predominant structure was a hexasaccharide (fraction FII-4). This contrasts with normal colonic mucins whose oligosaccharides were previously found to be based on core 3 structures and carry sialic acids in alpha (2-6) linkage to Gal beta 1-3R, to Gal beta 1-4R, and to GalNAc alpha-R (Podolsky, D.K. (1985) J. Biol. Chem. 260, 8262-8271; Podolsky, D.K. (1985) J. Biol. Chem. 260, 15510-15515). Collectively our findings suggest that Cl.16E colon cancer cells are able to synthesize mucin oligosaccharides of gastric type whose elongation is truncated by premature sialylation.
J Biol Chem 1992 Sep 25
PMID:Oligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E. 152 47

Flow cytometric DNA analysis of nuclear suspensions from formalin-fixed, paraffin-embedded tissue often fails to detect aneuploid cell populations present in corresponding fresh tissue. Nuclear suspensions were prepared by 8 different modifications and standard Hedley's method using 50-microns sections of tissue blocks from 8 breast and 8 colonic carcinomas, all previously known to be DNA aneuploid by analysis of fresh tumor. Pepsin solutions of three different enzymatic activities were used to release nuclei using three different tissue digest formats. DNA aneuploidy was demonstrated overall in 7 of 72 different colon tumor experiments and 25 of 72 breast cancer experiments. Modifications yielded aneuploid populations not detected by the standard Hedley method; DNA aneuploidy of 4 breast and 2 colon cancers was detected by modifications compared to 2 breast and 1 colon cancer demonstrated by the standard. No single method consistently demonstrated DNA aneuploidy. High histogram baselines, presumably from debris, contributed to the marked loss of sensitivity in detecting most DNA aneuploid populations. Detection of DNA aneuploidy was most closely associated with specific cases, regardless of the method of nuclear suspension preparation. Recovery of DNA aneuploid nuclei seems to depend primarily on tissue processing or innate characteristics of the tumor cells, not on the method used to prepare the nuclear suspension.
Am J Clin Pathol 1992 Sep
PMID:Comparison of eight modifications of Hedley's method for flow cytometric DNA ploidy analysis of paraffin-embedded tissue. 152 60

Thirty-eight patients with multiple carcinomas of large bowel were encountered during 32 years period in our hospital. The incidence of synchronous carcinomas (SC) was 1.5% (22/1430) and metachronous carcinomas (MC) 1.1% (16/1430). Thirty-one patients were found to have two primary carcinomas and seven patients have three primary malignancies. Among the 38 patients, six also had cancers in ether organs. The authors discussed the diagnosis, tumor distribution, the cancer association with familial colonic polyposis, and hereditary colon cancer. The 5 years survival rate with SC treated by surgery was 35.7% (5/14), and was 93% (15/16) with MC. It is the authors' opinion that surgical resection should always be attempted in patients with SC and MC.
Zhonghua Wai Ke Za Zhi 1991 Sep
PMID:[Multiple carcinomas of large bowel]. 166 16


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