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)

Treatment of nontransformed rat intestinal crypt epithelial IEC-6 cells with tetradecanoyl phorbol acetate (TPA) + calcium ionophore (A23187) induces both the synthesis of prostacyclin and the expression of the TIS10/PGS-2 gene, a primary response gene encoding a second form of prostaglandin synthase (PGS). In addition to pharmacological induction by TPA + A23187, TIS10/PGS-2 message is also induced by the inflammatory cytokine interleukin 1-beta (IL-1 beta). Transforming growth factor beta 1 (TGF-beta), a potent cytokine known to modulate a variety of biological responses, does not by itself induce either prostanoid accumulation or TIS10/PGS-2 gene expression. TGF-beta does, however, augment both induced prostacyclin accumulation and the induced synthesis and accumulation of TIS10/PGS-2 protein and message in IEC-6 cells. TGF-beta concentrations in the range of 0.1-1.0 ng/ml (4.0-40 pM) maximally augment accumulation of TIS10/PGS-2 message. In contrast, dexamethasone attenuates prostacyclin production, TIS10/PGS-2 protein accumulation, and TIS10/PGS-2 message induction in IEC-6 cells. These results suggest that steroids and cytokines such as TGF-beta may (i) modulate intestinal epithelial cell growth and differentiation and (ii) influence gastrointestinal diseases such as gastric ulcers and colon cancer by modulating eicosanoid production.
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PMID:TGF-beta 1 augments expression of the TIS10/prostaglandin synthase-2 gene in intestinal epithelial cells. 778 83

During the 1990s, research interest in the use of chemopreventive agents to reverse human colon carcinogenesis increased exponentially. In parallel, there has been an increase in the need for putative surrogate endpoint biomarkers (SEBs) of cancer risk. Since the hallmark studies of Lipkin et al. and Terpstra et al., among others, the rate and patterns of rectal mucosal proliferation have been established as intermediate biomarker endpoints for colon cancer risk, modulated by potential chemopreventive agents including calcium, wheat bran fiber, and nutritional stress diets. Researchers rely heavily on these rectal mucosal proliferation indices as surrogate endpoints to evaluate the relative efficacy of various chemopreventive intervention strategies. Standardization through quality control/quality assurance (QC/QA) programs which continuously validate the accuracy, reproducibility, and variability of these indices is increasingly needed. Along with many others, we have attempted to validate 3H-thymidine and bromodeoxyuridine labeling indices in rectal mucosal biopsies as reliable SEBs. In this manuscript we outline a series of QC/QA steps that can be followed in the validation process for new as well as "old" biomarkers prior to their use as primary efficacy surrogate endpoints for chemopreventive agent intervention trials.
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PMID:Validation of proliferation indices as surrogate endpoint biomarkers. 782 9

Data from two population-based case-control studies were used to investigate the effect of age on colon cancer risk. Dietary intake data were assessed from a study conducted in Utah (United States) between 1979 and 1983; reproductive data were assessed from a study conducted in Adelaide (Australia) between 1979 and 1980. Data from both studies were assessed for their impact on those less than 65 years of age and those 65 or more years of age. Intake of energy, fat, and protein had a greater impact on risk among older men than among younger men. Risk estimates for the upper quartile of intake relative to the lowest quartile of intake were 8.5 (95 percent confidence interval [CI] = 1.7-43.0) for energy, 8.2 (CI = 1.6-41.3) for protein, and 7.2 (CI = 1.6-31.4) for total fat for older men, while comparable risk estimates were 2.4 (CI = 0.6-9.1) for energy, 3.0 (CI = 0.7-13.6) for protein, and 1.9 (CI = 0.5-7.1) for total fat among younger men. Similar trends were seen for older women for energy and protein. beta-carotene decreased colon cancer risk among younger men (odds ratio [OR] = 0.4, CI = 0.1-1.2) and women (OR = 0.1, CI = 0.1-0.5), although not among older men (OR = 1.2, CI = 0.3-4.9) and women (OR = 1.9, CI = 0.6-64). Calcium decreased risk of colon cancer among older men (OR = 0.1, CI = < 0.1-0.8) and younger women (OR = 0.2, CI = < 0.1-0.7).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Age and risk factors for colon cancer (United States and Australia): are there implications for understanding differences in case-control and cohort studies? 782 43

Oral calcium supplementation is thought to be a useful interventional agent to decrease colon cancer risk. This is supposedly due, at least in part, to the binding of bile acids and fatty acids by calcium in the colon, thus prohibiting the damaging effects of these substances to the epithelium. To determine the effects of calcium supplementation on fecal fat excretion, 24 subjects kept a fat and calcium constant diet for one week and were supplemented with either 0, 2 or 4 g elemental calcium as calcium carbonate in a double-blind fashion. At the end of the week 72-hour feces was collected, and total fat, neutral fat, fatty acids and the ratio of polyunsaturated and saturated fatty acids (P/S ratio) were measured. Calcium dose-dependently increased the percentual excretion of total fat as related to fat intake: 6.8 +/- 0.9% during 0 g, 7.4 +/- 1.0% during 2 g and 10.2 +/- 1.4% during 4 g, r = 0.44, p = 0.03. This was due to increased fatty acid excretion, excretion of neutral fat was not affected, nor was the P/S ratio. It is concluded that calcium supplementation modestly increases fecal fatty acid excretion. No adverse metabolic effects are to be expected from this in case of long-term calcium supplementation in subjects at increased risk for colon cancer.
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PMID:Effects of supplemental dietary calcium on quantitative and qualitative fecal fat excretion in man. 783 78

A population-based case-control study was conducted in 726 incident cases with colorectal cancer and 1400 controls matched on age and sex in Shanghai, to explore the possible difference in associations between colorectal cancer and dietary fiber and calcium of various sources. The results showed reverse correlation between intake of vegetable fiber and ascending and descending colon cancer and rectal cancer, and between intake of fruit fiber and ascending colon cancer only. Dietary intake of calcium from animal sources could reduce the relative risk of ascending and descending colon cancer. These associations still existed after adjustment of the effects of the factors such as age, sex, intakes of total calorie, vitamin C, saturated fatty acid, etc. with logistic regression model, which indicated all of those variables were independent of other ones. Intake of dietary fiber from grains and calcium from plant sources had no significant protection from colorectal cancer. This study also showed the protective effects of dietary fiber and calcium on colorectal cancer not only correlated to their intake, but also closely to their sorts and sources.
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PMID:[A case-control study on colorectal cancer and dietary fiber and calcium of various sources]. 784 76

Activity of ornithine decarboxylase (ODC), one of the rate-limiting enzymes in the pathway of polyamine biosynthesis, is regulated by various factors. In this study, we examined the role of Ca2+ in the regulation of ODC enzyme activity in mouse colon cancer cells (MC-26). KCl, a membrane-depolarizing agent that opens the voltage-dependent Ca(2+)-channel to increase intracellular Ca2+, decreased serum-induced ODC enzyme activity in MC-26 cells in a dose-dependent, reversible fashion. Both verapamil and nifedipine, inhibitors of the L-type voltage-dependent Ca(2+)-channel, decreased serum-induced ODC enzyme activity. W-7, a calmodulin inhibitor, decreased ODC enzyme activity in a dose-dependent, reversible fashion while trifluoperazine, another calmodulin inhibitor, failed to affect ODC enzyme activity in MC-26 cells. Our findings indicate that intracellular Ca2+ participates in the regulatory mechanism of ODC enzyme activity in MC-26 cells, although the exact role of Ca2+ is still unclear.
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PMID:Role of calcium in the regulation of ornithine decarboxylase enzyme activity in mouse colon cancer cells. 787 72

An analogue of 1,25-dihydroxyvitamin D3, 22(S)-24-homo-26,26,26,27,27,27-hexafluoro-1 alpha,22,25-trihydroxyvitamin D3 (DD-003), showed 10-fold greater inhibiting effect than 1,25-dihydroxyvitamin D3 on the growth of HT-29 human colonic adenocarcinoma cells in culture. To examine the anticancer activity of DD-003 in vivo, a fibrin clot of HT-29 cells was prepared with fibrinogen and thrombin and implanted under the renal capsule of the severe combined immunodeficient mouse. Starting 7 days after implantation of HT-29 tumor, mice were given 3 micrograms/kg body weight of DD-003 or the vehicle i.p. every other day for 5 times. The HT-29 tumor grew rapidly in control mice; malignant growth was clearly observed with mitosis, massive tumor angiogenesis, and invasion into normal kidney tissue. Tumors in DD-003 treated mice were smaller with less invasion compared to the control. Administration of DD-003 inhibited growth of HT-29 tumor by 63%. Serum calcium concentrations and body weights of the treated mice were similar to those of the control. DD-003 inhibited growth of HT-29 tumor in a dose-dependent manner over the range of 0.1-10 micrograms/kg body weight, with no increase of serum calcium concentration observed at any dose level. When DD-003 was withdrawn after 2 weeks of treatment, tumor growth resumed. Since chemosensitivity tested by the subrenal capsule assay correlates well with clinical response, DD-003 may be clinically applicable in procedures such as postsurgical chemotherapy of colon cancer.
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PMID:Inhibition of HT-29 human colon cancer growth under the renal capsule of severe combined immunodeficient mice by an analogue of 1,25-dihydroxyvitamin D3, DD-003. 792 32

Free cytosolic [Ca2+] ([Ca2+]f) was measured at the single cell level using digitized video-intensified fluorescence microscopy and the fluorescent Ca2+ indicator, fura-2. Cells were irradiated at 1-4 Gy (dose rate of 6 Gy/min) with a 90Sr eye applicator mounted on the microscope. HeLa cells responding to ionizing radiation exhibited a maximal 3-4-fold transient rise in cytosolic and nuclear [Ca2+]f immediately upon irradiation, which persisted for at least 5 min before returning to baseline in most but not all cells. The radiation-induced rise in [Ca2+]f was blocked by 1 mM La3+, 100 nM nifedipine, or membrane potential depolarization, suggesting that HeLa cells possess a voltage-dependent Ca2+ channel that mediates the response to radiation. Experiments with Mn2+, a paramagnetic probe for extracellular Ca2+, showed that radiation stimulated an increase in Mn2+ influx, as witnessed by loss of fura-2 fluorescence. Thapsigargin and ryanodine, inhibitors of intracellular Ca2+ mobilization, also completely blocked the radiation effect, implying a linkage between the radiation-induced influx and mobilization of internal Ca2+ stores. Not all cells in an asynchronous culture responded identically to radiation. Upon synchronization with thymidine/aphidicolin, cells in the S- and G2/M-phase exhibited radiation-induced changes in [Ca2+]f, whereas G1-phase cells did not. In addition, the increased [Ca2+]f of irradiated G2/M phase cells did not fully return to pretreatment levels. Further studies utilizing MDA-MB-231 and MCF-7 human breast and HT-29 human colon cancer cell lines indicate that radiation can alter Ca2+ homeostasis in other epithelial cell types. In the case of MDA-MB-231 and HT-29 cells, oscillations in cytosolic [Ca2+]f levels were observed that persisted for up to 50 min. The kinetics and inhibitor sensitivities differed from HeLa cells, indicating a different type of mechanism for the radiation effects on cell [Ca2+]f. Survival studies with HeLa and MDA-MB-231 cells did not reveal a connection between the radiation effects on cellular Ca2+ homeostasis and cell survival.
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PMID:Ionizing radiation induces a transient increase in cytosolic free [Ca2+] in human epithelial tumor cells. 792 44

The detergent Triton X-100 (TX100) was used with the intention to establish a model for necrotic cell death. However, TX100 was found to induce apoptotic and necrotic death in prostate and colon cancer cell lines. Apoptosis was characterized by the typical morphological features and internucleosomal DNA fragmentation. The rapid onset within 60 min and the lack of inhibition by cycloheximide indicated that apoptosis induced by TX100 was not dependent on protein synthesis. Removal of extracellular calcium blocked internucleosomal DNA fragmentation. This pattern of cell death shows a striking similarity to the effect of cytotoxic lymphocytes on their target cells.
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PMID:The detergent Triton X-100 induces a death pattern in human carcinoma cell lines that resembles cytotoxic lymphocyte-induced apoptosis. 792 36

To examine whether the consumption of fermented dairy products or the dietary intake of calcium decreases colon cancer risk, a case-control study was conducted in the The Netherlands. Dietary patterns were assessed in detail (for cases before diagnosis or symptoms occurred) using a structured dietary history questionnaire. After adjustment for potential confounding variables, consumption of fermented dairy products, hard cheese and unfermented dairy products was not significantly associated with risk of colon cancer: an odds ratio (OR) of 1.1 was found for individuals consuming more than one serving of fermented dairy products per day as compared to those consuming less than 10% of one serving a day. Adjustment for dietary calcium attenuated the associations. Total dietary calcium was positively but non-significantly associated with colon cancer risk after adjustment for age, gender, urbanization level and total energy intake. Additional adjustment for a positive family history of colorectal cancer, cholecystectomy and energy-adjusted intake of total fat, dietary fibre, vitamin C and alcohol increased the association. No differences were observed between calcium from fermented and from unfermented dairy sources. The observed associations for fermented dairy products and dietary calcium differed between men and women: positive significant associations were observed in men, while in women non-significant inverse associations were found. Our results do not support the hypothesis that an increased intake of commercially available, commonly used fermented dairy products or dietary calcium decreases the risk of colon cancer.
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PMID:Fermented dairy products, dietary calcium and colon cancer: a case-control study in The Netherlands. 792 14


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