Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been reported that insulin-like growth factor (IGF) II is associated with human primary colorectal tumors and colon-carcinoma cell lines. Here, we examine alterations in circulating levels of IGFs and IGF binding proteins (IGFBPs) in patients with colorectal carcinoma, and compare them to age- and nutrition-adjusted references. We report (i) an increase in serum IGF-II concentrations (about 2-fold), whereas IGF-I concentrations are regarded as normal when aging is taken into account; (ii) an apparent increase in serum IGFBP-3 levels when compared to those of healthy elderly subjects, IGFBP-3 only being detected in the 150-kDa IGFBP ternary complex as in normal serum; (iii) abnormally elevated serum IGFBP-2 levels taking into account the apparent concentrations of IGFBP-3. This simultaneous elevation of IGFBP-3 and IGFBP-2 in the serum of patients with colorectal tumors appears to be unique in that it reflects a break in the inverse relationship between the serum IGFBP-3 and IGFBP-2 levels that is observed in normal and in several physiopathological conditions. Moreover, it enables a distinction to be made between 76.5% (13/17) of patients with colorectal carcinoma and normal adults, age-related healthy aged and malnourished patients. We propose that the disturbed serum IGFBP profile observed in the patients with colorectal cancer may be a consequence of oversecretion of IGF-II by the tumor cells. The usefulness of IGFs and IGFBPs as potential colorectal tumor-associated metabolic markers should be further investigated.
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PMID:Alterations in serum levels of insulin-like growth factors and insulin-like growth-factor-binding proteins in patients with colorectal cancer. 751 52

Expression of insulin-like growth factor-2 (IGF-2) has been reported in tissue specimens and cell lines of human colorectal cancers. However, the effects of IGF-2 in colorectal cancer patients are not well known. In this study, IGF-2 staining was performed on tissue samples from 92 patients with colorectal cancer, and the relationship of IGF-2 staining to clinicopathological variables, proliferating cell nuclear antigen (PCNA) staining and patient survival was analyzed. IGF-2 staining was correlated with tumor progression, PCNA staining and patient survival. Our results suggest that IGF-2 plays an important role in tumor progression and that IGF-2 staining is useful as a prognostic factor in colorectal cancer patients.
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PMID:Expression of insulin-like growth factor-2 can predict the prognosis of human colorectal cancer patients: correlation with tumor progression, proliferative activity and survival. 956 57

The limited proteolysis of insulin-like growth factor (IGF)-binding protein (IGFBP)-3 is a key event in the regulation of endocrine bioavailability of IGFs. Here, we investigated IGFBP-3 and IGFBP-3 proteolysis in serum from patients with colorectal cancer both before and at different times following surgery. In vivo IGFBP-3 proteolysis, estimated by immunoblot analysis of IGFBP-3 fragments in serum, and in vitro IGFBP-3 protease activity of serum, estimated by a 125I-IGFBP-3 degradation assay, allowed us to identify 2 groups of patients (IGF-M vs. IGF-NM) with respect to their status for mobilizing the IGF system. In IGF-M patients, in vivo and in vitro IGFBP-3 proteolysis were significantly elevated (156% and 181% of the age-matched control pool, respectively) and accompanied by a decrease in intact IGFBP-3 (38% of the control pool). The IGFBP-3 proteolytic processing was further increased in response to surgical ablation of the tumor (mean increase 45-55%), then gradually returned to levels comparable with controls. In contrast, IGF-NM patients exhibited a minimal alteration of in vitro IGFBP-3 protease activity and even an inhibition of in vivo IGFBP-3 proteolysis, whereas intact IGFBP-3 was unaltered when compared with controls. Moreover, this pattern was not further significantly altered in response to the surgical stress. None (0/6) of the IGF-M patients vs. 70% (5/7) of the IGF-NM patients developed a metastatic disease (median duration of follow-up 26 months). Neither elevated amounts of pro-IGF-II nor presence of detectable IGFBP-3 protease inhibitors in the circulation could explain the observed suppression of IGFBP-3 proteolytic processing in IGF-NM patients. These results indicate that inhibition of IGFBP-3 proteolysis and invasive properties of cancer cells are related in colorectal cancer patients.
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PMID:Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) proteolysis in patients with colorectal cancer: possible association with the metastatic potential of the tumor. 976 Nov 13

Loss of imprinting (LOI) is an epigenetic alteration of some cancers involving loss of parental origin-specific expression of imprinted genes. We observed LOI of the insulin-like growth factor-II gene in twelve of twenty-seven informative colorectal cancer patients (44%), as well as in the matched normal colonic mucosa of the patients with LOI in their cancers, and in peripheral blood samples of four patients. Ten of eleven cancers (91%) with microsatellite instability showed LOI, compared with only two of sixteen tumors (12%) without microsatellite instability (P < 0.001). Control patients without cancer showed LOI in colonic mucosa of only two of sixteen cases (12%, P < 0.001) and two of fifteen blood samples (13%, P < 0.001). These data suggest that LOI in tumor and normal tissue identifies most colorectal cancer patients with microsatellite instability in their tumors, and that LO! may identify an important subset of the population with cancer or at risk of developing cancer.
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PMID:Loss of imprinting in normal tissue of colorectal cancer patients with microsatellite instability. 980 40

Interest in the role of the insulin-like growth factor (IGF) axis in growth control and carcinogenesis has recently been increased by the finding of elevated serum insulin-like growth factor I (IGF-I) levels in association with three of the most prevalent cancers in the United States: prostate cancer, colorectal cancer, and lung cancer. IGFs serve as endocrine, autocrine, and paracrine stimulators of mitogenesis, survival, and cellular transformation. These actions are mediated through the type 1 IGF-receptor (IGF-1R), a tyrosine kinase that resembles the insulin receptor. The availability of free IGF for interaction with the IGF-1R is modulated by the insulin-like growth factor-binding proteins (IGFBPs). IGFBPs, especially IGFBP-3, also have IGF-independent effects on cell growth. IGF-independent growth inhibition by IGFBP-3 is believed to occur through IGFBP-3-specific cell surface association proteins or receptors and involves nuclear translocation. IGFBP-3-mediated apoptosis is controlled by numerous cell cycle regulators in both normal and disease processes. IGFBP activity is also regulated by IGFBP proteases, which affect the relative affinities of IGFBPs, IGFs and IGF-1R. Perturbations in each level of the IGF axis have been implicated in cancer formation and progression in various cell types.
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PMID:Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. 1069 60

The activity of our group is focused on the conduction of chemoprevention clinical trials of breast cancer in at-risk subjects, among which we include women on hormone replacement therapy (HRT). The role of the insulin-like growth factor (IGF) system and of mammographic breast density as surrogate biomarkers for breast cancer prevention is also being investigated. The IGF system is involved in human carcinogenesis of several solid tumors. IGF-I is a potent mitogen for breast cancer cells; elevated circulating IGF-I levels have been associated with a higher risk of premenopausal breast cancer, prostate and colorectal cancer in prospective studies. Both tamoxifen and the synthetic retinoid fenretinide (4-HPR) have been shown to decrease plasma IGF-I levels. A trial of their combination is ongoing in premenopausal women with increased risk for breast cancer. Mammographic breast density has also been associated with an increased risk of breast cancer in several prospective studies. In this article, we discuss the rationale for selection of appropriate cohorts, candidate agents, and putative surrogate biomarkers in our breast cancer prevention trials. Moreover, updated results of the secondary prevention trial of 4-H PR and of the primary prevention trial of tamoxifen are presented. Finally, the rationale for a reduction of tamoxifen dose in future prevention trials is provided.
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PMID:Chemoprevention of breast cancer: the Italian experience. 1076 20

The insulin-like growth factor (IGF) type 1 receptor is required for growth, transformation, and protection from apoptosis. IGFs can enhance cell migration, which is known to be influenced via regulation of the E-cadherin/beta-catenin complex. We sought to investigate whether IGF-1 modulated the interaction between E-cadherin and beta-catenin in human colorectal cancer cells. We used the C10 cell line, which we established and have previously shown to lack adenomatous polyposis coli, E-cadherin, or beta-catenin mutations. We found that IGF-1 stimulation enhanced tyrosine phosphorylation of two proteins, beta-catenin and insulin-receptor substrate 1, which formed a complex with E-cadherin. Tyrosine phosphorylation of beta-catenin was accompanied by rapid (<1 min) dissociation from E-cadherin at the plasma membrane, followed by relocation to the cellular cytoplasm. IGF-1 also enhanced the stability of beta-catenin protein. Despite this, we observed no enhancement of transcriptional activity in complex with T-cell factor 4 (Tcf-4) in human embryonic kidney 293 cells treated with IGF-1 or insulin alone. IGF-1 did, however, enhance transcriptional activity in combination with lithium chloride, an inhibitor of glycogen synthase kinase 3 beta, which also stabilizes beta-catenin. In conclusion, we have shown that IGF-1 causes tyrosine phosphorylation and stabilization of beta-catenin. These effects may contribute to transformation, cell migration, and a propensity for metastasis in vivo.
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PMID:Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. 1103 89

Angiomodulin (tumor-derived adhesion factor/mac25/insulin-like growth factor binding protein-7), a cell-adhesive glycoprotein, is secreted by cancer cells and vascular endothelial cells. It may be involved in angiogenesis and modulation of the vascular functions necessary for tumor development. Although angiomodulin is expressed in colon cancer, there is limited information on it concerning cancer progression. In the present immunohistochemical study, we examined expression of angiomodulin in human colorectal cancer and its relationship with prognosis. A group of 89 surgically resected colorectal cancers was investigated immunohistochemically. In 37 cases (41.6%), angiomodulin was expressed in invading cancer cells. Early recurrence within 12 months after surgery was higher in patients with angiomodulin-expressing cancer than in those without (p < 0.05). The Kaplan-Meier life table revealed that patients with angiomodulin-positive tumor cells had a shorter survival time than those with negative cells (p < 0.01). The prognosis of patients with Dukes' C and angiomodulin-positive cells was apparently worse than that of patients with Dukes' D and angiomodulin-negative cells. Multivariate analysis with logistic regression indicated that only angiomodulin expression in cancer cells, lymph node metastasis and age remained significant prognostic variables for survival (p < 0.05). Angiomodulin showed correlations with poor prognosis, indicating that it may be a useful prognostic marker in patients with colorectal cancer.
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PMID:Expression of angiomodulin (tumor-derived adhesion factor/mac25) in invading tumor cells correlates with poor prognosis in human colorectal cancer. 1140 Jan 13

The growth hormone (GH)-insulin-like growth factor (IGF)-I axis is an important modulator of growth and development, but in addition to their classical role as endocrine hormones, its components also regulate a wide range of biological functions through paracrine and autocrine mechanisms. Their potent mitogenic and anti-apoptotic effects play a critical role in the regulation of rapidly renewing epithelial cell populations such as those found in the colon. Recent evidence suggests an association between inappropriate regulation of the GH-IGF-I axis and the development of colorectal cancer. However, the molecular mechanisms and signalling pathways responsible are only beginning to be unravelled, as are the relative contributions of the endocrine and autocrine or paracrine effects.
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PMID:The growth hormone-insulin-like growth factor-I axis and colorectal cancer. 1159 19

The purpose of this review is to examine recent evidence that investigates the role of the insulin-like growth factor (IGF) system in colorectal cancer. We concentrate on the evidence that makes the case for the investigation of strategies that might be used to disrupt the IGF system in prevention and treatment. Even though the weight of evidence suggests that components of the IGF system may be appropriate targets, there are a lack of studies that make a systematic characterisation of all the system components in human colorectal cancer. It is anticipated that this information, and the new therapeutic molecules which follow, will impact on the prevention and treatment of patients with this disease.
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PMID:The insulin-like growth factor system as a therapeutic target in colorectal cancer. 1199 63


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