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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen metabolites (ROM) have been postulated to contribute to the development of various carcinomas, including colon cancer. Indeed, the effects of ROM scavengers are being tested for chemoprevention of adenocarcinoma of the colon. However, there has been no evidence to indicate that high levels of ROM are indeed present in cancerous tissue. In this study, we used a chemiluminescence probe to estimate ROM levels in cancerous and neighboring noncancerous colonic tissues from seven patients with colon cancer. Cancerous tissues contained significantly (p less than 0.05) more luminol-enhanced chemiluminescence (4,808 +/- 2,282 counts/min/mg protein) than neighboring noncancerous tissues (2,175 +/- 1,111). The addition of an ROM scavenger, catalase (2, 4, and 8 micrograms/ml), to the tissue suspension inhibited chemiluminescence produced by both noncancerous (-74%, -85%, and -71%) and cancerous (-11%, -61%, and -53%) tissues. This study shows that colonic cancerous tissue contains high levels of ROM, which may play an important role in the pathogenesis of colon cancer.
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PMID:High levels of reactive oxygen metabolites in colon cancer tissue: analysis by chemiluminescence probe. 133 90

Described herein are structure-activity studies of new antitumor agents based on the pyrrolo[1,2-a]benzimidazole (PBI) ring system. These compounds were designed as new DNA cross-linkers mimicking the mitomycin antitumor agents. Actually, the PBI derivatives were found to have anthracycline-like features: (i) shared cross resistance with doxorubicin in a human myeloma line, (ii) cardiotoxicity, and (iii) excellent DNA strand cleaving capability. The DNA strand cleavage is thought to result from reductive alkylation of DNA followed by the generation of reactive oxygen radicals. The best antitumor agent studied is 6-N-aziridinyl-3-hydroxy-7-methyl-2,3-dihydro-1H-pyrrolo- [1,2-a]benzimidazole-5,8-dione 3-acetate (PBI-A), which possesses nanomolar IC50 values against various human ovarian and colon cancer cell lines.
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PMID:Structure-activity studies of antitumor agents based on pyrrolo[1,2-a]benzimidazoles: new reductive alkylating DNA cleaving agents. 192 Mar 49

This study was undertaken to investigate the effects of a single infusion of radiolabelled murine monoclonal antibody (MAb) on peripheral blood leukocytes in cancer patients. Eleven patients with disseminated colon cancer, malignant melanoma, or lung adenocarcinoma were infused with 111In-labelled anti-ZCE 025, anti-p97 type 96.5c, or LA 20207 MAb, respectively. Blood samples were obtained before infusion, immediately after infusion (1 hr), and at 4 and 7 days postinfusion. Flow cytometry analysis of CD3+, CD4+, CD8+, CD16+, and CD19+ lymphocytes showed increasing CD4:CD8 ratios in seven patients after infusion. This phenomenon was not restricted to antibody subclass or to type of cancer. Two of the remaining patients exhibited a marked post-infusion increase in CD8+ cells. In all three patients with malignant melanoma, decreasing levels of CD16+ lymphocytes were noted after infusion and natural killer cell cytotoxicity showed fluctuations which paralleled the changes in the CD16+ subpopulation. Oxygen radical production by phagocytic cells was markedly affected in three subjects. These results suggest that a single infusion of radiolabelled murine MAb may alter the balance of critical lymphocyte subpopulations and modulate other leukocyte responses in cancer patients.
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PMID:Effects of radiolabelled monoclonal antibody infusion on blood leukocytes in cancer patients. 196 68

This study was undertaken to determine whether infusion of a unique ZCE/CHA bifunctional antibody (BFA, 5-40 mg) could alter the composition and functions of peripheral blood leucocytes in 18 patients with colon cancer. The BFA is made by combining chemically the Fab' fragments of two murine monoclonal antibodies. One fragment (ZCE 025) binds to the carcino-embryonic antigen (CEA) and the other (CHA 225) to an epitope, present on an 111In-benzyl EDTA analog of bleomycin (BLEDTA IV) and on 111In-hydroxy-ethyl-thiourea benzyl EDTA (EOTUBE). The radiolabelled epitope (111In-BLEDTA IV or 111In-EOTUBE) was given 4 days after prelocalization with BFA. Peripheral blood samples were tested before BFA infusion, at the end of infusion (1 h later), and at 4 and 7 days post-infusion. A 50% or greater suppression in lymphocyte responsiveness to phytohaemagglutinin (PHA) and concanavalin A (Con A) was seen in 13 out of 18 and 12 out of 18 subjects, respectively, at some time after BFA infusion; this was especially evident in those patients with pre-infusion stimulation indices of greater than 50 (PHA) and/or greater than 10 (Con A). In contrast, natural killer (NK) cell cytotoxicity and oxygen radical production increased in five out of 15 and in seven out of 18 subjects, respectively. Little or no change was observed in CD3, CD4, CD8, CD16, and CD19 markers on lymphocyte subpopulations as determined by flow cytometry. These data suggest that significant changes in mitogen-induced lymphoproliferation. NK cell cytotoxicity, and oxygen radical production can occur in a substantial proportion of cancer patients after infusion of the ZCE/CHA bifunctional antibody system. The immunomodulation was unrelated to initial BFA dose, dose of BFA as a carrier, or to subsequent infusion of either form of the 111In epitope. The clinical significance of these phenomena, if any, remains to be determined.
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PMID:Changes in leucocyte populations following murine bifunctional antibody infusion in colon cancer patients. 202 55

The prevention of cancer by agents in our diet has led to the concept that oxygen radicals are a necessary component of a variety of human cancers including breast, colon and prostatic cancer. These cancers are putatively promoted by estradiol, bile acids and androgens. Epidemiological studies have shown that these cancers are suppressed in vegetarian populations. Vegetable components that may be responsible for this cancer prevention are Vitamin A, retinoids and protease inhibitors (PIs). These agents have been shown to suppress the formation of hydrogen peroxide in promoter-induced neutrophils. They also have been shown to block two-stage carcinogenesis and breast cancer when fed to animals. PIs also suppress experimentally-induced colon cancer and spontaneous liver cancer. Moreover, a new series of cancer-preventive agents, Sarcophytols (isolated by Fujiki and co-workers), are capable of suppressing two-stage carcinogenesis, breast and colon cancers in rodents when given in low concentrations. Sarcophytols were also active suppressors of H2O2 formation of 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced neutrophils. These observations point to an essential role of oxygen radicals in carcinogenesis. Suppression of the oxygen radical response of neutrophils in relation to cancer preventive agents is a facile assay of these important substances. The mechanism of action of oxygen radicals in promoting carcinogenesis is a multiple one, including: (1) activation of oncogenes, (2) modification of DNA bases, and (3) formation of single-strand breaks leading to poly(ADP)ribose polymerase activation.
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PMID:Prevention of cancer by agents that suppress oxygen radical formation. 206 Aug 47

1. Oxygen consumption was investigated in two cultured subpopulations of either undifferentiated (Glc+ cells) or differentiated (Glc- cells) HT29 colon cancer cells and in the corresponding isolated mitochondria. In Glc+ cells, a decrease of the respiration is induced by the presence of glucose (Crabtree effect), whereas it is not the case in Glc- cells. 2. The oxidative phosphorylation rate of Glc- mitochondria is found to be much higher than that of Glc+ mitochondria, due to a higher efficiency to oxidize glutamine, glutamate, 2-oxoglutarate, succinate or malate. 3. In both types of mitochondria, respiration can be supported by the ADP formed by adenylate kinase or nucleotide diphosphate kinase, and, although to a lesser extent in Glc- mitochondria, by hexokinase. 4. Glc+ cells are characterized by a low respiration capacity and a high glycolytic flux leading to the Crabtree effect. Glc- cells are characterized by a better correlation between a moderate glycolytic flux and a high respiratory capacity.
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PMID:Respiration of mitochondria isolated from differentiated and undifferentiated HT29 colon cancer cells in the presence of various substrates and ADP generating systems. 215 27

This hypothesis paper reviews diverse evidence suggesting that intracolonic production of oxygen radicals may play a role in carcinogenesis. The hypothesis began to evolve when the author made the chance discovery that 1/10,000 dilutions of feces generated detectable quantities of highly reactive hydroxyl radicals (HO.). The rate of HO. formation, detected using DMSO as a molecular probe, was quite remarkable, corresponding to that which would be produced by over 10,000 rads of gamma irradiation per day, absorbed in the periphery of the fecal mass adjacent to the mucosa. The relatively high concentrations of iron in feces, together with the ability of bile pigments to act as iron chelators that support Fenton chemistry, may very well permit efficient HO. generation from superoxide and hydrogen peroxide produced by bacterial metabolism. Such free radical generation in feces could provide a missing link in our understanding of the etiology of colon cancer: the oxidation of procarcinogens either by fecal HO., or by secondary peroxyl radicals (ROO.) to form active carcinogens or mitogenic tumor promotors. Intracolonic free radical formation may explain the high incidence of cancer in the colon and rectum, compared to other regions of the GI tract, as well as the observed correlations of a higher incidence of colon cancer with red meat in the diet, which increases stool iron, and with excessive fat in the diet, which may increase the fecal content of procarcinogens and bile pigments.
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PMID:Free radicals and the etiology of colon cancer. 218 44

The mechanisms of cancer cell destruction by unelicited peripheral blood neutrophils has never been reported in a syngeneic model. We demonstrated that in vitro, unelicited polymorphonuclear neutrophils isolated from rat blood were toxic against syngeneic colon cancer cells. The tumor cell lysis was not due to oxygen metabolites released by PMNs, but was due to a cytolytic factor. This factor was spontaneously secreted by PMNs, was heat-stable and had a low molecular weight (less than 10 kD). Its partial inhibition by chymotrypsin and/or chymotrypsin-like proteases suggested a peptidic structure of this factor.
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PMID:Non-activated rat neutrophils kill syngeneic colon tumor cells by the release of a low molecular weight factor. 227 41

Estramustine (EM), a complex between estradiol-17 beta and nornitrogen mustard, is commonly used in the treatment of prostatic cancer. The exact mechanism of action is unknown but has previously been considered to be mediated through non-DNA targets, specifically with the mitotic spindle, and to be related to the intact EM complex. In the present study, using different cell-systems (monocyte phagocytosis transformed fibroblasts, colon cancer cells), the EM cytotoxicity was also found to involve direct interaxtion with DNA and cell membranes. The interaction with DNA was shown by a DNA precipitation assay using 3H- and 14C- thymidine, and the cell membrane damage by using 86Rb- accumulation as a sensitive marker for active potassium uptake. EM effects in the fibroblasts were inhibited by various metal chelators and radical scavengers. Involvement of free oxygen radicals was further indicated in a cell-free system with an oxygen electrode. The EM inhibition of monocyte phagocytosis was related to the engulfment, and was not at all influenced by radical scavengers. In contrast to EM, neither of its components alone, or together, affected monocyte engulfment. Finally, it was shown that the colon cancer cell-line HT-29 was resistant to both of the two suggested and separate mechanisms for EM toxicity: an interaction with the microtubuli system by the intact EM complex and a more unspecific action mediated by free-oxygen radicals.
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PMID:The effect of estramustine on microtubuli is different from the direct action via oxygen radicals on DNA and cell membrane. 234 5

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


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