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)

PSK, a protein-bound polysaccharide obtained from cultured mycelia of Coriolus versicolor in basidiomycetes, is a biological response modifier, diverse operations of which include an antitumor action. We have previously reviewed recent research which had demonstrated that in animals, PSK has a preventive effect on chemical carcinogen-induced, radiation-induced, and spontaneously developed carcinogenesis (Kobayashi et al., Cancer Epidemiol., Biomarkers & Prev., 2: 271-276, 1993). We now focus on the effects of PSK once the progression of carcinogenesis has begun, and review what is now known of the preventive action of PSK on cancer metastasis. Recent research reports that PSK suppresses pulmonary metastasis of methylcholanthrene-induced sarcomas, human prostate cancer DU145M, and lymphatic metastasis of mouse leukemia P388, and that it has prolonged the survival period in spontaneous metastasis models. PSK also suppresses the metastasis of rat hepatoma AH60C, mouse colon cancer colon 26, and mouse leukemia RL male 1 in artificial metastasis models. PSK influences the steps of cancer metastasis in a number of ways: (a) by suppression of intravasation through the inhibition of tumor invasion, adhesion and production of cell matrix-degrading enzymes; (b) by suppression of tumor cell attachment to endothelial cells through the inhibition of tumor cell-induced platelet aggregation; (c) by suppression of tumor cell migration after extravasation through the inhibition of tumor cell motility; and (d) by suppression of tumor growth after extravasation through the inhibition of angiogenesis, the modulation of cytokine production, and the augmentation of effector cell functions. In addition, PSK has suppressed the malignant progression of mouse tumor cells through superoxide trapping.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antimetastatic effects of PSK (Krestin), a protein-bound polysaccharide obtained from basidiomycetes: an overview. 760 3

The antitumor effects of muramyl tripeptide phosphatidylethanolamine, incorporated within the lipophilic phase of liposomes (lipMTP-PE) were studied using a model of liver metastasis of colon cancer in the rat. Intravenous immunotherapy with lipMTP-PE, when started 2 days before the inoculation of tumor cells and given twice a week, significantly reduced subsequent tumor growth in the liver. The main effect of treatment appeared to be a substantial local increase in the number of tumoricidal macrophages and lymphocytes. Tumor cell lysis by isolated macrophages in vitro, however, appeared not to be elevated above the level triggered by tumor growth alone. Therefore, the observed therapeutic effect of lipMTP-PE probably results from a combination of (1) an increase in the number of cytotoxic macrophages at the onset of metastatic growth in the liver, thus increasing the probability of lethal contacts between tumoricidal effectors and tumor cells and (2) indirect effects of lipMTP-PE, via the induction of cytokine production by liver macrophages, leading to increased numbers and/or activity of cytotoxic lymphocytes and natural killer cells.
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PMID:Antitumor reactivity induced by liposomal MTP-PE in a liver metastasis model of colon cancer in the rat. 764 18

The purpose of this study was to determine whether liver regeneration induced by partial hepatectomy (PH) influences the growth of human colon cancer (HCC) cells implanted into athymic nude mice. HCC KM12C cells were injected subcutaneously into nude mice and then the mice were randomized to undergo PH, laparotomy, or no surgery. The latent period to development of measurable tumors was shorter and the growth rate of HCC tumors was significantly faster in hepatectomized mice. Accelerated tumor growth directly coincided with liver regeneration. Peak mitotic activity in both the regenerating liver and HCC occurred on the second day following PH. No enhancement in growth of tumors occurred in mice implanted with HCC cells 3 weeks after PH (i.e. 2 weeks after completion of liver regeneration). The accelerated tumor growth was specific to HCC. We base this conclusion on results of control experiments where cells from human melanoma, colon, breast, prostate, and renal cancer were injected into nude mice that were then randomized to undergo PH or laparotomy. Only HCC grew faster in hepatectomized mice. No significant differences in expression of epidermal growth factor receptor (EGF-R) and c-met were found between HCC tumors in mice with PH or laparotomy, suggesting that over-expression of EGF-R or c-met is not an essential component of this phenomenon. The accelerated growth of HCC cells at a site distant from surgical trauma suggests that circulating growth factors involved in liver regeneration can specifically stimulate the growth of HCC cells.
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PMID:Accelerated growth of human colon cancer cells in nude mice undergoing liver regeneration. 765 29

The angiogenesis inhibitor O-(chloroacetyl-carbamoyl)fumagillol (TNP-470) showed antitumor activity in three human cancer xenograft systems. TNP-470 potently inhibited the tumor growth of hormone-independent prostate cancer PC-3 cells and breast cancer MDA-MB-231 cells dose dependently at weekly s.c. doses of 50-200 mg/kg with maximum inhibition of 96 and 88% (tumor growth, 4 and 12% of that in the respective control). In experiments of combination therapy with chemotherapeutic agents, the combination of TNP-470 (100 mg/kg) and cisplatin (5 mg/kg) showed an additive antitumor effect (from treated versus control, 38 and 22% to 5%) against PC-3 carcinoma. 5-Fluorouracil and Adriamycin alone did not significantly inhibit MDA-MB-231 tumor growth (treated versus control, 131 and 64%, respectively). TNP-470 also inhibited tumor growth of WiDr colon cancer; although the inhibition was less marked (treated versus control, 39%) than that observed with the hormone-independent cancers used in this study. In an in vitro study, all the cell lines tested were considerably insensitive to TNP-470 in monolayer cultures (50% inhibitory concentration, approximately 5 micrograms/ml), whereas TNP-470 inhibited the anchorage-independent growth of PC-3 and MDA-MB-231 cells (50% inhibitory concentration, 0.05 and 470 ng/ml, respectively). The inhibitory activity of TNP-470 against anchorage-independent growth correlated well with the in vivo antitumor activity among the cell lines tested. Thus, this inhibitory action may partly contribute to the potent antitumor activity of the angiogenesis inhibitor TNP-470, at least in the case of PC-3 and MDA-MB-231. These results suggest that hormone-independent prostate and breast cancers may be appropriate target diseases for TNP-470 clinical trials.
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PMID:Angiogenesis inhibitor TNP-470 (AGM-1470) potently inhibits the tumor growth of hormone-independent human breast and prostate carcinoma cell lines. 769 35

Gastrin has been suggested to be involved in the promotion and progression of colon cancer. Mice colon cancers and colon-carcinoma cell lines are stimulated to grow by gastrin, and gastrin receptors have been found in the majority of human colon-tumor specimens. High serum gastrin levels have been reported in patients with colon polyps and cancers, together with increased ornithine decarboxylase (ODC) activity. Since gastrin stimulates ornithine decarboxylase in colon cancer cells in vitro it has been suggested that increased synthesis of intracellular polyamines is one of the mechanisms activated by the hormone. In order to confirm the presence of hypergastrinemia in colon cancer and to investigate the relationship between plasma gastrin and tumor growth, we used an animal model of colon carcinogenesis that minimizes the possible bias of human studies, related to varying diet, age and environmental factors. We evaluated blood gastrin levels in 35 rats with colon cancer induced by the carcinogen azoxymethane (AOM), and we correlated gastrinemia with tumor proliferation, assessed by thymidine-labeling index (TLI) and ODC activity; 6 animals constituted the control group. Gastrin levels in rats with AOM-induced tumors were significantly higher than in controls. Significantly higher TLI and ODC activity were found in the tumors of hypergastrinemic rats than in neoplasms of animals with normal gastrin levels. Our data provide additional evidence of a role for gastrin as trophic hormone for colon neoplastic cells.
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PMID:Hypergastrinemia in rats with azoxymethane-induced colon cancers. 770 52

Studies have shown that trans fatty acids may play a role in the development of chronic diseases such as heart disease and cancer. The objective of the present project was to examine the effect of supplementation with 18:1 isomers, both positional and geometrical, as compared to 18:0 on the growth, membrane fatty acid composition and the phosphoinositide cycle of HT-29 human colon cancer cells. Cells were supplemented with 30 microM stearic acid (18:0), elaidic acid (18:1, n9, trans), oleic acid (18:1, n9, cis), vaccenic acid (18:1, n7, cis) or trans-vaccenic acid (18:1, n7, trans) as sodium salts complexed to fatty acid-free bovine serum. Cells were grown in these media for 9 days. Cell growth was examined by counting the number of cells and expressed as percentage of control (18:0 supplemented cells). The phosphoinositide (PI) cycle was examined by measuring the inositol phosphate (IP) released from phosphoinositides in the absence (basal) or presence of stimuli (0.1 mM carbachol, 0.1 mM A23187 or 20 mM NaF). The results obtained indicated that cis and trans n7 fatty acids inhibited the growth of HT-29 cells by 11% and 23%, respectively, as compared to 18:0 supplementation. 18:1, n9 had no effect on tumor growth. Supplementation with all forms of 18:1 resulted in an increase in IP and IP2 production as compared to 18:0 supplemented cells without influencing IP3. The presence of the double bond at the 9 position in the supplemented fatty acid increases total IP production by 59% and in the cis form by 37% above the control. The breakdown of phosphoinositides in the absence and presence of several stimuli supports the observed finding on IP. Trans fatty acid supplementation resulted in lower hydrolysis of PI as compared to cis fatty acids. It is concluded that the observed inhibition of tumor growth by the vaccenic acids may be mediated by their effect(s) on the PI cycle which may be associated with their incorporation into membrane lipids.
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PMID:18:1 n7 fatty acids inhibit growth and decrease inositol phosphate release in HT-29 cells compared to n9 fatty acids. 775 95

We have investigated the interaction between Cepharanthine (CEP), a multi-functional alkaloid that has the capacity to stabilize the cell membrane, and 5-fluorouracil (5-FU) against a human colon cancer cell line (RPMI 4788) transplanted into nude mice. Their anti-tumor effects were assessed in a group of 7 mice intravenously injected with CEP (5 mg/kg/day) and/or 5-FU (15 mg/kg/day) during a 3-week treatment. The results were compared with a control and a 5-FU group, which received saline solution and 5-FU alone, respectively. The tumors were harvested 2 h after 5-FU administration. On an additional 4 groups of 5 mice, the intratumoral concentration of 5-FU was assessed by a high performance liquid chromatographic (HPLC) method 2, 4, 6 and 12 h following CEP (5 mg/kg) injection 1 h prior to, simultaneously, and 1 h after injection of 5-FU (30 mg/kg). The mean (SD) intratumoral concentration of 5-FU was 0.16 (0.05) mu g/g, 0.32 (0.19) mu g/g, 0.32 (0.16) mu g/g and 0.21 (0.13) mu g/g in the control and the three other groups treated with CEP, respectively. This concentration was about twice as high in mice simultaneously treated with CEP compared to those treated by 5-FU alone. Relatively higher concentrations of 5-FU were noted up to 4 h following 5-FU injection in mice treated with CEP than in those injected only with 5-FU. CEP also enhanced the inhibitory effects of the 5-FU on tumor growth rate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo augmentation of the intratumoral concentration of 5-fluorouracil by cepharanthine--a biscoclaurine alkaloid. 780 9

The presence of lymphoid aggregates within the muscularis propria or pericolic fibroadipose tissue apposing invasive colorectal carcinoma, termed the Crohn's-like lymphoid reaction, has been related to improved patient length of survival according to univariate statistical analysis. We tested the Crohn's-like lymphoid reaction as an indicator of prognosis in a multivariate statistical analysis of 344 resected right-sided colonic cancers. Improved 5-year survival in univariate analysis was associated with low tumor grade, regular tubule configuration, expanding tumor growth pattern, prominent peritumoral lymphocytic infiltration, absence of tumoral invasion of extramural veins, all levels of intramural and extramural invasion short of widespread local tumor permeation, conspicuous Crohn's-like lymphoid reaction, and absence of both nodal metastasis and nodal-independent tumor nodules in pericolic fat. By the Cox proportional hazard model using the stepwise method, depth of tumor invasion, lymph node metastasis, Crohn's-like lymphoid reaction, and metastatic tumor nodules in pericolic fat retained independent prognostic significance. Combining the four variables to formulate pathological prognostic categories yielded a highly favorable prognostic group-92% 5-year survival and 95% confidence limits (88% to 96%)--encompassing 53% of the study population. It included all Dukes' stage A carcinomas, 66% of Dukes' stage B adenocarcinomas, and 11% of Dukes' stage C cancers. Lymph node metastases coupled with intramural and extramural extent of tumor invasion are the cornerstones of colorectal cancer staging. Addition of other variables improves prognostication for the cecum and ascending colon. From this study the Crohn's-like lymphoid reaction and metastatic tumor nodules in pericolic fat emerge as significant independent indicators of prognosis for right-sided colon cancer. Complex correlations of both indicators with nonselected variables were observed.
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PMID:Impact of the Crohn's-like lymphoid reaction on staging of right-sided colon cancer: results of multivariate analysis. 782 14

Epidemiologic studies have linked diets high in animal fat with colon carcinogenesis. A number of animal tumor models have shown that diets rich in omega-3 fatty acids inhibit colon carcinogenesis while diets rich in omega-6 fatty acids promote tumor growth. This study examines whether modification of the membrane fatty acid composition of both moderately (CX-1) and poorly differentiated (MIP-101 and Clone A) human colorectal carcinoma cells alters their interaction with Kupffer cells and extracellular matrix proteins (collagen type IV, fibronectin and laminin). The cells were treated with 15-16 micrograms/ml of docosahexanoic acid (22:6, omega 3) or linoleic acid (18:2,omega 6). Gas chromatography showed significant alterations in the membrane fatty acid composition of the human colorectal cancer cell lines. Binding assays were performed by measuring adherence of 51Cr-labelled tumor cells to Kupffer cell monolayers or to immobilized proteins. Omega-3 treatment significantly decreased the Kupffer cell binding of only the CX-1 line while omega-6 treatment decreased binding of all three cell lines. In contrast both omega-3 and omega-6 treatment of MIP-101 cells decreased binding to the extracellular matrix proteins with the omega-6 effect being more pronounced. These results indicate that the binding characteristics of the colon cancer cells to both Kupffer cells and extracellular matrix proteins may be determined in part by the membrane fatty acid composition. Decreased adherence to extracellular matrix proteins may lead to increased cell motility and invasiveness. Since Kupffer cell binding precedes tumor cell phagocytosis and killing, decreased binding may improve tumor cell survival.
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PMID:Effect of membrane free fatty acid alterations on the adhesion of human colorectal carcinoma cells to liver macrophages and extracellular matrix proteins. 788 22

A widespread from of transglutaminase, tissue transglutaminase, has been identified in a number of mammalian cell types, both normal and transformed cells; its biological role is not well understood. We investigated the effect of experimentally induced colon cancer on transglutaminase activity in the rat. Azoxymethane (15 mg/kg for six weeks), given by a course of weekly intraperitoneal injections, produces tumors almost exclusively confined to the intestinal tract. Transglutaminase activity was assayed on tissue homogenates both during the period of treatment and, when the cancer had developed, on tumor tissue and on microscopically uninjured adjacent tissue. A transient proliferative phase was present in the intestine during azoxymethane treatment: in this phase we found a coincidentally increased transglutaminase levels. Transglutaminase activity in tumors of both small and large intestine was significantly higher than in adjacent tissue. Immunohistochemistry revealed higher levels of transglutaminase in tumors, mainly localized in the extracellular matrix, than in adjacent tissues, where it was widely distributed. The present study shows that transglutaminase, besides its potential role in intracellular process during early proliferative phase of carcinogenesis, may also play an important role in matrix processing during tumor growth and differentiation.
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PMID:Transglutaminase in azoxymethane-induced colon cancer in the rat. 789 66


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