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)

The utilisation of three peripherally-administered intravenous nutritional regimens has been evaluated in 42 patients on the first four days following surgery for colorectal cancer. A standard dextrose-saline (DS) regimen (n = 16) has been compared with an amino-acid (AA) regimen (n = 12) and a regimen consisting of glucose, amino-acid and fat (GAF) (n = 14). Fat and carbohydrate oxidation was calculated pre- and post-operatively using indirect calorimetry. Patients receiving AA showed a fall in carbohydrate oxidation (p < 0.01) and a rise in fat oxidation (p < 0.05) post-operatively, whereas no significant changes in fat and carbohydrate oxidation occurred in the DS and GAF groups. Cumulative nitrogen balance (NB) for the first four post-operative days was significantly better (p < 0.01) in the AA group (-10.3 +/- 3.8 g; mean +/- s.e.m.) than in the DS group (-25.3 +/- 3.1 g), due to an improved NB in the AA group on the first and second days only. Cumulative NB in the GAF group (+7.7 +/- 2.3 g) was significantly better (p < 0.01) than in the other two groups. Where the provision of peripheral intravenous nutritional support is desired, the use of a combination of glucose, amino-acid and fat is recommended.
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PMID:The utilisation of peripherally-administered intravenous nutrient solutions. 1683 4

The metabolic effects of intravenous nutrition (IVN) with branched chain amino acid (BCAA) enriched solutions on skeletal muscle and tumor were investigated in patients with colorectal cancer. Patients (n = 26) undergoing surgical removal of clinically localized tumors were allocated to 3 treatment groups: fasted, conventional IVN or BCAA supplemented (30% of nitrogen as BCAA). Nutritional treatments started 20 h before surgery and protein synthesis was assessed in vivo using a flooding dose technique with L-[1-13C]leucine. The plasma level of most amino acids was higher in the fed groups than in the fasted group; the level of BCAA was increased in the BCAA fed group. Conventional IVN stimulated protein synthesis in tumor (+94%) and in skeletal muscle (+48%) compared to the fasted group; this effect was less pronounced in the BCAA group (+49% and +19% respectively). Anti-proliferative cell nuclear antigen (PCNA) expression in the tumors was increased in both fed groups compared to the fasted state, and correlated with the rate of protein synthesis. It is concluded that the rate of tumor growth can be influenced by the composition of nutrient infused. However, BCAA seems to provide no clear advantage over a conventional IVN, since lower stimulation of tumor protein synthesis was associated with a lower stimulation of muscle protein synthesis.
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PMID:Tumor and host tissue responses to branched-chain amino acid supplementation of patients with cancer M A McNurlan, S D Heys, K G M Park et al Clinical Science 1994; 86: 339-345. 1684 18

The goal of this study was to identify systematic alterations in key cell signaling and metabolic pathways that occur during colon cancer carcinogenesis and metastasis. Understanding gene expression changes in the context of specific pathways may increase our understanding of carcinogenesis and help guide treatment. Ten cases, with matched controls, were profiled for expression of >18,000 human transcripts using Affymetrix U133A chips. Data were filtered using GeneSifter. Gene expression levels for primary colon samples were compared to a normal colon while metastatic tissues were compared to the primary colon. Differentially regulated genes were associated using the Kyoto encyclopedia of genes and genome pathways to identify cell signaling and metabolic pathways altered during carcinogenesis and metastasis. Primary colon samples displayed high positive z-scores (indicating a gene ontology term that occurs more frequently than expected) for genes involved in Wnt-signaling (4.11), nitrogen metabolism (7.30) and inositol phosphate metabolism (2.47). Expression level changes for individual genes in each cluster were statistically significant (e.g. p=0.017 for cyclin D1 in the Wnt-signaling cluster). Metastatic tissue from the liver and omentum, but not the lung, displayed a decreased expression of genes important for oxidative phosphorylation. The metastatic tissue from all sites displayed a substantially decreased expression for genes involved in butanoate and propanoate metabolism and valine, leucine and isoleucine degradation. Our results demonstrate that systematic changes in gene expression occur for proteins involved in key cell signaling and metabolic pathways during the course of carcinogenesis and metastasis. These expression level changes complement the spectrum of mutations that characterize the progression of colorectal cancer.
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PMID:Tissue-dependent and -independent gene expression changes in metastatic colon cancer. 1809 2

Feces contain intestinal bacteria and exfoliated epithelial cells that may provide useful information concerning gastrointestinal tract health. Intestinal bacteria that synthesize or metabolize potential carcinogens and produce anti-tumorigenic products may have relevance to colorectal cancer, the second most common cause of cancer deaths in the USA. To facilitate epidemiological studies relating bacterial and epithelial cell DNA and RNA markers, preservative/extraction methods suitable for self-collection and shipping of fecal samples at room temperature were tested. Purification and PCR amplification of fecal DNA were compared after preservation of stool samples in RNAlater (R) or Paxgene (P), or after drying over silica gel (S) or on Whatman FTA cards (W). Comparisons were made to samples frozen in liquid nitrogen (N2). DNA purification methods included Whatman (accompanying FTA cards), Mo-Bio Fecal (MB), Qiagen Stool (QS), and others. Extraction methods were compared for amount of DNA extracted, DNA amplifiable in a real-time SYBR-Green quantitative PCR format, and the presence of PCR inhibitors. DNA can be extracted after room temperature storage for five days from W, R, S and P, and from N2 frozen samples. High amounts of total DNA and PCR-amplifiable Bacteroides spp. DNA (34%+/-9% of total DNA) with relatively little PCR inhibition were especially obtained with QS extraction applied to R preserved samples (method QS-R). DNA for human reduced folate carrier (SLC19A1) genomic sequence was also detected in 90% of the QS-R extracts. Thus, fecal DNA is well preserved by methods suitable for self-collection that may be useful in future molecular epidemiological studies of intestinal bacteria and human cancer markers.
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PMID:Fecal collection, ambient preservation, and DNA extraction for PCR amplification of bacterial and human markers from human feces. 1816 91

This review provides an overview of the synthesis and metal complexation chemistry of the nitrogen and sulphur donor bicyclic ligands or cages, and the key criteria that led to the design of sarar for the application for (64)Cu(II). Aspects of the high yielding synthesis of sarar and strategies for its conjugation to a range of antibodies for targeting colorectal cancer, neuroblastoma and melanoma are described. Free and conjugated to proteins sarar can complex (64)Cu(II) rapidly at room temperature and quantitatively; the latter leading to products of high specific activity and purity. The full occupation of the (64)Cu(II) ions 6 coordination sites by the sarar cage prevents the ready exchange of the (64)Cu(II) from the cage and is the rational for the extraordinary thermodynamic and kinetic stability of (64)Cu(II) labelled sarar and its conjugates. It's in vivo stability is further highlighted by the low uptake and retention of (64)Cu-sarar-conjugated antibodies in the liver. Finally, the prospects for the use of the sarar technology in the materials science arena for probing solid liquid interfaces, in particular, the quantification of functional groups on microspheres and in the engineering of novel materials are discussed.
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PMID:Sarar technology for the application of Copper-64 in biology and materials science. 1817 77

In order to discover potential markers of prognosis in colorectal cancer (CRC) we have determined gene expression profiles, using cDNA microarrays in CRC samples obtained from 19 patients in Dukes stages C and D, with favorable clinical course (Dukes C patients, survival >5 years after surgery, group A, n=7) or unfavorable clinical course (Dukes stage C and D patients, survival <5 years after surgery, group B, n=12). Gene expression was measured in RNA from each tumor, using a pool of equal amounts of RNA from all tumors as a reference. To identify and rank differentially expressed genes we used three different analytical methods: (i) Significance Analysis of Microarrays (SAM), (ii) Cox's Proportional Hazard Model, and (iii) Trend Filter (a mathematical method for the assessment of numerical trends). The level of expression of a gene in an individual tumor was regarded as of interest when that gene was identified as differentially expressed by at least two of these three methods. By these stringent criteria we identified eight genes (ITGB2, MRPS11, NPR1, TXNL2, PHF10, PRSS8, KCNK3, JAK3) that were correlated with prolonged survival after surgery. Pathway analysis showed that patients with favorable prognosis had several activated metabolic pathways (carbon metabolism, transcription, amino acid and nitrogen metabolism, signaling and fibroblast growth factor receptor pathways). To further validate individual gene expression findings, the RNA level of each gene identified as a marker with microarrays was measured by real-time RT-PCR in CRC samples from an independent group of 55 patients. In this set of patients the Cox Proportional Hazard Model analysis demonstrated a significant association between increased patient survival and low expression of ITGB2 (p = 0.011) and NPR1 (p = 0.023) genes.
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PMID:Analysis of gene expression profiles reveals novel correlations with the clinical course of colorectal cancer. 1830 33

Oxidative stress has been implicated in the etiology of neurodegenerative disease, cancer and aging. Indeed, accumulation of reactive oxygen and nitrogen species generated by inflammatory cells that created oxidative stress is thought to be one of the major factor by which chronic inflammation contributes to neoplastic transformation as well as many other diseases. We have recently reported that mice lacking nuclear factor-erythroid 2-related factor 2 (Nrf2) are more susceptible to dextran sulfate sodium (DSS)-induced colitis and colorectal carcinogenesis. Nrf2 is a basic leucine zipper redox-sensitive transcriptional factor that plays a center role in ARE (antioxidant response element)-mediated induction of phase II detoxifying and antioxidant enzymes. We found that increased susceptibility of Nrf2 deficient mice to DSS-induced colitis and colorectal cancer was associated with decreased expression of antioxidant/phase II detoxifying enzymes in parallel with upregulation of pro-inflammatory cytokines/biomarkers. These findings suggest that Nrf2 may play an important role in defense against oxidative stress possibly by activation of cellular antioxidant machinery as well as suppression of pro-inflammatory signaling pathways. In addition, in vivo and in vitro data generated from our laboratory suggest that many dietary compounds can differentially regulate Nrf2-mediated antioxidant/anti-inflammatory signaling pathways as the first line defense or induce apoptosis once the cells have been damaged. In this review, we will summarize our thoughts on the potential cross-talks between Nrf2 and NFkappaB pathways. Although the mechanisms involved in the cross-talk between these signaling pathways are still illusive, targeting Nrf2-antioxidative stress signaling is an ideal strategy to prevent or treat oxidative stress-related diseases.
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PMID:Activation of Nrf2-antioxidant signaling attenuates NFkappaB-inflammatory response and elicits apoptosis. 1869 32

One unintentional result of widespread adoption of nitrogen application to croplands over the past 50 years has been nitrate contamination of drinking water with few studies evaluating the risk of colorectal cancer. In our population-based case-control study of 475 women age 20-74 years with colorectal cancer and 1447 community controls living in rural Wisconsin, drinking water nitrate exposure were interpolated to subjects residences based on measurements which had been taken as part of a separate water quality survey in 1994. Individual level risk factor data was gathered in 1990-1992 and 1999-2001. Logistic regression models estimated the risk of colorectal cancer for the study period, separately and pooled. In the pooled analyses, an overall colorectal cancer risk was not observed for exposure to nitrate-nitrogen in the highest category (> or =10 ppm) compared to the lowest category (<0.5 ppm). However, a 2.9 fold increase risk was observed for proximal colon cancer cases in the highest compared to the lowest category. Statistically significant increased distal colon or rectal cancer risk was not observed. These results suggest that if an association exists with nitrate-nitrogen exposure from residential drinking water consumption, it may be limited to proximal colon cancer.
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PMID:Nitrogen-nitrate exposure from drinking water and colorectal cancer risk for rural women in Wisconsin, USA. 1910 61

In a search for more selective anticancer drugs, we have designed nitrogen mustard and nitrosourea conjugates leading to a series of N-4-aryl-N'-2-chloroethylureas (CEUs). The iodinated derivative N-4-iodophenyl-N'-2-chloroethylurea (4-ICEU) has demonstrated significant antineoplastic and antiangiogenic potency in preclinical evaluations. In this study, 4-ICEU was radiolabelled with [(125)I]iodide in order to carry out a comparative study of its in vivo behavior profile. 4-[(125)I]-ICEU was synthesized by direct electrophilic radioiodination with 80% radiochemical yield and 97% radiopurity. Three different routes of administration (intraperitoneal (ip), intravenous (iv) and intratumoral (it)) were tested in mice bearing subcutaneously implanted CT-26 murine colon carcinoma. The results clearly established that 4-ICEU was more stable to biotransformation than previously studied CEUs congeners. It was readily bioavailable and reached the CT-26 colorectal tumor regardless of the route of administration. Additionally, the colon mucosa was an important target tissue where 4-ICEU accumulated and remained largely untransformed. In conclusion, these results justify further investigations for developing 4-ICEU as a new chemotherapeutic agent for colorectal cancer.
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PMID:N-4-iodophenyl-N'-2-chloroethylurea, a novel potential anticancer agent with colon-specific accumulation: radioiodination and comparative in vivo biodistribution profiles. 1920 25

Polyphenol oxidase (PPO) in conditioned red clover (ensiled or cut and crushed) reduces both proteolysis and lipolysis in the herbage, which has led to increases in N use efficiency and polyunsaturated fatty acid (PUFA) content of milk when offered to dairy cows. In damaged plant cells, PPO is activated and binds protein through the formation of protein-bound phenols. This study investigated a) whether freshly cut red clover could increase N use efficiency and milk PUFA concentrations in dairy cows or whether PPO enzymes require prior activation before feeding to elicit a response, and b) apparent whole-tract amino acid digestibility to help determine the effect of PPO on amino acid utilization. Six multiparous Holstein x Friesian dairy cows in mid-lactation were allocated at random to 1 of 3 dietary treatments in a 3 x 3 Latin square: a control treatment of grass (low PPO, G); red clover (high PPO, RC), and conditioned red clover (high fully activated PPO, CRC). The CRC herbage was cut and chopped in the field and then transported with the G and RC herbages to the animal house. Each period consisted of a 2-wk adaptation to diet and a week of measuring dietary effects (N balance and milk collection). The PPO activity was greatest in the RC treatment as fed, whereas activation of latent PPO enzyme and protein-bound phenol levels were greatest in the CRC diet. Dry matter and total fatty acid intakes were comparable across treatments (18.8 kg/d and 550 g/d, respectively). Milk yields and total fatty acid content were similar across treatments (32.6 kg/d and 34.8 mg/mL, respectively). Cows offered either RC or CRC had greater levels of protein, C18 PUFA and total long-chain PUFA in their milk than animals offered grass with no difference between RC and CRC. Nitrogen intakes, and output in milk, urine, and feces were greater in cows offered the 2 red clover treatments than G, with no difference between RC and CRC. However, there were no differences in N use efficiency among diets as measured by the proportion of feed N converted into milk N, possibly as the result of the excessive supply of N with the red clover diets. Amino acid apparent whole-tract digestibilities were greater when on RC than G diets and intermediate when on CRC for all amino acids, with the exception of Met, which was reduced in cows on both red clover diets compared with G. It is proposed that the PPO trait could show more benefit to ruminants if red clover was fed in combination with lesser N-containing forages or if red clover was bred to contain less N.
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PMID:Effect of feeding fresh or conditioned red clover on milk fatty acids and nitrogen utilization in lactating dairy cows. 1923 6


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