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)

The goal of this investigation was to identify the metabolic abnormalities in a group of colon cancer patients before and during 5-fluorouracil chemotherapy. Twenty-two colon cancer patients were prospectively enrolled into a Clinical Research Center for measurement of counter regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA), and leucine oxidation (LO). Both the cancer group and the normal volunteers were matched for nutrition status (109 +/- 5% of ideal body weight vs 104 +/- 4%, mean +/- SEM, respectively) and history of weight loss (6.3 +/- 2.6 kg vs 4.4 +/- 4.8). Plasma growth hormone was significantly elevated in the colon cancer patients (3.22 +/- 0.62 ng/mL vs 0.73 +/- 0.18, p < .05) despite the fact that insulin-like growth factor-1 levels were not different. Plasma glucose, insulin, cortisol, glucagon, epinephrine, and norepinephrine levels were not significantly different than those of the normal volunteers. Fasting HGP rates were slightly but not significantly elevated in the group of colon cancer patients compared with the normal volunteers (2.09 +/- 0.11 mg/kg per minute vs 1.79 +/- 0.10, p = .10). Plasma LA was not significantly elevated in the colon cancer group (63.3 +/- 3.0 mumol/kg per hour vs 57.7 +/- 4.2; p = .25). Five days of continuous 5-fluorouracil chemotherapy was associated with a significant elevation in both the fasting glucose level (97 +/- 3 mg/dL vs 106 +/- 5, p < .05), and HGP (2.09 +/- 0.11 mg/kg per minute vs 2.27 +/- 0.10; p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic response to chemotherapy in colon cancer patients. 128 27

Several somatostatin analogs with recently synthesized acetylated N terminus were assayed in vivo for their effects on sodium pentobarbital-stimulated growth hormone (GH) levels in fed male rats and gastrin-releasing peptide (14-27)-stimulated gastrin levels in fasted male rats. The binding characteristics of these analogs to somatostatin receptors were also examined in various human tumors and normal tissues. The analog RC-101-I, injected at a dose of 0.1 micrograms/100 g body wt, significantly suppressed GH release (P less than 0.01) for at least 2 hr. Analog RC-160-II caused the longest inhibition of GH release, greater than that induced by nonacetylated parent analog RC-160, with GH levels showing significant suppression (P less than 0.01) for more than 3 hr. Analogs RC-160-II and RC-101-I and RC-160, injected at a dose of 1.0 micrograms/100 g body wt, significantly (P less than 0.01) suppressed gastrin-releasing peptide (14-27)-stimulated serum gastrin. Analog RC-101-I was active in this test at a dose of 0.1 micrograms/100 g body wt. RC-160-II showed significant binding to somatostatin-14 receptors in all investigated tissues (human colon, human colon cancer, breast cancer, human pancreas and pancreatic cancer, human prostate and prostate cancer, and rat cerebral cortex), but there were marked variations in binding affinities among various normal and cancerous tissues. The highest affinity was found in membranes of colon cancer (Ka = 18.4 nM-1) and breast cancer (Ka = 12.46 nM-1). The binding affinity of RC-160-II to somatostatin receptors in membranes of the breast cancer was similar to that of RC-160. RC-101-I showed higher binding affinity to somatostatin-14 receptors than RC-160 in human breast, pancreatic, and prostate cancer. With the exception of breast cancer tissue, the binding affinity of RC-101-I was significantly lower than that of RC-160-II in membranes of all investigated tissues. It can be concluded that acetylated somatostatin analogs RC-101-I and RC-160-II possess prolonged and enhanced biological activities in suppressing serum GH and gastrin in rats. Significant variations in binding affinities for these analogs in different tissues and various tumors suggest that differences may exist between somatostatin receptors in normal versus malignant tissues. This raises the possibility that some of these analogs could be used more selectively in the treatment of various neoplasms.
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PMID:Biological activity and receptor binding characteristics to various human tumors of acetylated somatostatin analogs. 134 89

Growth hormone and its principal mediator insulinlike growth factor I are known promoters of normal growth. To determine whether excessive secretion of growth hormone is associated with an increased occurrence of benign and of malignant tumors, we studied records of 87 patients with acromegaly seen in the Lahey Clinic Medical Center (Burlington, Mass) from 1957 to 1988 and compared the rate of tumor occurrence with a control group of patients with pituitary tumors (198) and with findings from a cancer registry. Patients with acromegaly had a 2.45-fold increased rate of malignant tumors (95% confidence interval, 0.98 to 5.04) compared with findings from the tumor registry. Female patients had a higher rate than male patients. The rate of carcinoma of the thyroid was excessive and previously underscribed, but the rate of carcinoma of the colon was not increased as reported by others. Among benign lesions, goiters, predominantly nodular, were seen in 25% of patients in addition to a large number of mesenchymal lesions.
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PMID:Benign and malignant tumors in patients with acromegaly. 167 93

A cohort of 1041 men who were discharged from the hospital with a diagnosis of acromegaly were examined for subsequent cancer. With a mean follow-up time of 8.3 years, an increased rate of cancers of the digestive organs was observed (27 cases; standard incidence ratio [SIR], 2.0; 95% confidence interval [CI], 1.3 to 2.9). Rates were elevated for cancers of the esophagus (7 cases; SIR, 3.1), stomach (4 cases; SIR, 2.5), and colon (13 cases; SIR, 3.1). The increased risk of colon cancer in acromegaly is consistent with previous clinical reports and suggests opportunities for etiologic research and early cancer detection. It would seem prudent to also evaluate this risk in current research on the use of growth hormone in older individuals to increase muscle mass and reduce body fat.
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PMID:Acromegaly and gastrointestinal cancer. 191 7

We examined the cytosolic estrogen receptor (ER) level in tumor tissue from 77 patients: 36 meningiomas, 20 gliomas (12 glioblastomas, 2 cerebellar astrocytomas, 2 ependymomas, and 4 medulloblastomas), 8 neurinomas, 7 pituitary adenomas (2 prolactin-producing adenomas, 1 growth hormone-producing adenoma, and 4 nonfunctioning adenomas), and 6 metastatic brain tumors (1 from breast cancer, 4 from lung cancers, and 1 from colon cancer). Nuclear ER levels were assayed in 11 meningiomas and 2 glioblastomas. ER was determined by the dextran-coated charcoal method and calculated by Scatchard analysis. Cytosolic ER was detected in 100% of the pituitary adenomas, 50% of the meningiomas, 50% of the metastatic brain tumors, 25% of the neurinomas, and 15% of the gliomas. In gliomas, only medulloblastomas had ER activity. Nuclear ER was found in three premenopausal women with meningioma. The dissociation constant of the ER complex was, in each case, less than 10(-9) M. These observations suggest that some brain tumors may be responsive to estrogen via the cellular ER.
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PMID:Estrogen receptors in brain tumors. 650 47

Intestinal trefoil factor (ITF) is a small peptide bearing the unique motif of intrachain disulfide bonds characteristic of the trefoil family. Previous work had localized expression of ITF primarily within goblet cells in the small and large bowel, making it a candidate gene for the study of the molecular basis of intestinal and goblet cell-specific gene expression. In order to study the regulation of ITF expression, we have cloned the rat ITF gene and sequenced 1.7 kilobases of the 5'-flanking region. RNase protection analysis demonstrated a single transcriptional start site. Various lengths of the 5'-flanking region were linked to the reporter gene luciferase and transfected into the colon cancer cell lines LS174T and Caco-2, representing, respectively, cells with and without goblet cell-like phenotype. Expression in the goblet cell-like LS174T colon cancer cell line was nearly 10-fold greater than expression in Caco-2 cells which exhibit columnar enterocyte-like phenotype. The pattern of goblet cell-associated selective transcription required only 153 base pairs of the rat ITF 5'-flanking sequence. Transfection of a construct of human growth hormone under the control of the rat ITF promoter in the N2 subclone of HT-29 cells demonstrated expression of the reporter gene only in those cells exhibiting a goblet cell phenotype as assessed by expression of immunoreactive mucin. These initial studies of the 5'-flanking region of the ITF gene demonstrate the presence of cis-regulatory elements capable of directing goblet cell specific expression.
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PMID:Molecular cloning of the rat intestinal trefoil factor gene. Characterization of an intestinal goblet cell-associated promoter. 772 58

The primary nutritionally linked diseases are coronary heart disease, stroke and cancers of the stomach, colon, pancreas, prostate, breast, ovary, and endometrium. Dietary fats operate through a promoting mechanism. An S-shaped dose-response curve with a threshold has been demonstrated in models of breast and colon cancer in which the standard Western fat intake of 40% of energy yields a high level of promotion, and reduction of fat to 10% to 20% of energy (the traditional Japanese fat intake) has a low promoting action. In models of breast and colon cancer, saturated fats such as beef fat or lard, and monounsaturated oils, such as olive oil, display only a weak promoting effect, with the incidence of induced tumors being similar at intake levels of 40% and 10% of energy. On the other hand, the n-6-polyunsaturated oils display a strong promoting effect. Such findings may have a parallel in the low but definitely increasing slope of postmenopausal breast cancer incidence in the past 30 years as the American public decreased saturated fat intake to avoid heart disease and increased use of the n-6-polyunsaturated oils. Mechanisms underlying the cancer-promoting effect in the colon stem from increased hepatic production of bile acids, which are transferred to the intestinal tract via the bile. Ingestion of 40% fat calories yields higher concentrations of bile acids in the colon than lower levels of dietary fat ingestion. Cancer in the mammary gland is promoted through higher concentrations of fats and phospholipids in the gland as well as increased levels of estrogen secondary to production by the ovary and other endocrine tissues that, in turn, affect the generation of pituitary hormones such as prolactin and growth hormone. The n-3-fats, as found in fish and fish oils, have a pronounced inhibitory effect in models of colon and breast cancer, presumably through their shifting of prostaglandin metabolism to the generation of prostaglandins, which lower cell proliferation potential and, thus, decrease promotional effects. The role of dietary fat as a promoter can be modified by other nutritional components. Finally, one of the best pieces of evidence for an enhancing effect of many dietary fats in the nutritionally linked cancers is the current increase in the incidence of these diseases in Japan as the nutritional habits of people in that country become more Westernized.
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PMID:Dietary fat and risk of chronic disease: mechanistic insights from experimental studies. 921 63

Insulin-like growth factors (IGFs) I and II are implicated in progression of various tumours including colorectal carcinomas. To interfere with the production of IGFs, we treated male nude mice bearing xenografts of HT-29 human colon cancer with various potent growth hormone-releasing hormone (GH-RH) antagonists. Twice daily injections of antagonist MZ-4-71, 10 microg intraperitoneally or 5 microg subcutaneously (s.c.) resulted in a significant 43-45% inhibition of tumour growth. Longer acting GH-RH antagonists, MZ-5-156 and JV-1-36 given once daily at doses of 20 microg s.c. produced a 43-58% decrease in volume and weight of cancers. Histological analyses of HT-29 cancers demonstrated that both a decreased cell proliferation and an increased apoptosis contributed to tumour inhibition. GH-RH antagonists did not change serum IGF-I or IGF-II levels, but significantly decreased IGF-II concentration and reduced mRNA expression for IGF-II in tumours. In vitro studies showed that HT-29 cells produced and secreted IGF-II into the medium, and addition of MZ-5-156 dose-dependently decreased IGF-II production by about 40% as well as proliferation of HT-29 cells. Our studies demonstrate that GH-RH antagonists inhibit growth of HT-29 human colon cancers in vivo and in vitro. The effect of GH-RH antagonists may be mediated through a reduced production and secretion of IGF-II by cancer cells.
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PMID:Antagonists of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers. 1081 10

cDNA representational difference analysis (cDNA RDA) is a PCR-based subtractive enrichment procedure for the cloning of differentially expressed genes. In this study, we have further developed the procedure to take advantage of solid-phase technology, and to facilitate the use of RDA when starting material is limited. Several parameters of the PCR-based generation of cDNA representations were investigated, and a solid-phase based purification step was introduced to simplify removal of digested adapter-ends and uncleaved fragments. The use of magnetic particles increased the speed of the method, and also eliminated the risk of carry-over contamination between iterative steps of subtraction and PCR amplification. The modified protocol was evaluated in monitoring differences in gene expression in (i) a rat system consisting of livers with and without growth hormone treatment, and in (ii) a human system consisting of normal colon and colon cancer.
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PMID:A cDNA RDA protocol using solid-phase technology suited for analysis in small tissue samples. 1104 71

Recent case-controlled studies have found increases in the serum levels of insulin-like growth factor-I (IGF-I) in subjects who had, or who eventually developed, prostate or premenopausal breast cancers. Since growth hormone (GH) increases IGF-I levels, concern has been raised regarding its potential role as a cancer initiation factor. The epidemiological studies, which indicate an association between serum IGF-I levels and cancer risk, have not established causality. In fact, several alternative explanations for the elevated serum IGF-I levels in cancer patients may be proposed based on human and animal models. First, an effect of IGF-I causing symptomatic benign tissue hyperplasia may result in an ascertainment bias leading to an initiation of procedures resulting in the diagnosis of asymptomatic cancers. Second, elevated serum IGF-I in cancer patients may originate within the tumor (as suggested by some animal studies). Thirdly, serum IGF-I may actually be a surrogate marker of tissue IGF-I levels or of nutritional factors, which are not under GH control and may be involved in cancer initiation. The role of GH in cancer initiation is further negated by the fact that in acromegaly, the incidence of cancer, other than possibly colonic neoplasia does not appear to be significantly increased. Furthermore, GH transgenic mice, with high IGF-I levels, do not develop breast, prostate, or colonic malignancies. It is known that IGFBP-3 can inhibit IGF action on cancer cells in vitro and also can induce apoptosis via an IGF-independent mechanism. Importantly, in addition to increasing IGF-I levels, GH also increases the serum levels of IGFBP-3 and serum IGFBP-3 levels have been shown to be negatively correlated with the risk of cancer in the above mentioned epidemiological studies and in a similar study on colon cancer. These studies suggest that cancer risk is increased in individuals in whom both high IGF-I levels and low IGFBP-3 levels are present. In subjects treated with GH, IGF-I and IGFBP-3 levels both rise together and are not within the elevated cancer-risk range, based on published studies. Long-term studies are needed to assess the potential risks, including the long-term cancer risk associated with GH therapy. These should take into account several factors, including the duration of exposure, the risk magnitude associated with the degree of serum IGF-I elevation, and the adjusted risk based on a concomitant increase in IGFBP-3 levels. Since GH treated patients often have sub-normal IGF-I serum levels, which normalize on therapy, one might predict that their cancer risk on GH therapy should not increase above the normal population. Until further research in the area dictates otherwise, on-going cancer surveillance and routine monitoring of serum IGF-I and IGFBP-3 levels in GH-recipients should be the standard of care. At present, the data that are available do not warrant a change in our current management of approved indications for GH therapy.
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PMID:Does the GH-IGF axis play a role in cancer pathogenesis? 1116 60


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