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9841584
[ "Colonoscopic", "surveillance", "is", "an", "effective", "method", "of", "reducing", "risk", "for", "cancer", "in", "carriers", "of", "a", "mutation", "mutations", " ", "for", "hereditary", "nonpolyposis", "colorectal", "cancer", "is", "unclear." ]
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Colonoscopic surveillance is an effective method of reducing risk for cancer in carriers of a mutation mutations for hereditary nonpolyposis colorectal cancer is unclear.
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23132392
[ "Mediator", "complex", "participates", "in", "transcriptional", "regulation", "by", "connecting", "regulatory", "DNA", "sequences", "to", "the", "RNA", "polymerase", "II", "initiation", "complex.", "Recently,", "we", "discovered", "through", "exome", "sequencing", "that", "as", "many", "as", "70%", "of", "uterine", "leiomyomas", "harbour", "specific", "mutations", "in", "exon", "2", " ", "of", "mediator", "complex", "subunit", "12", "(MED12).", "In", "this", "work,", "we", "examined", "the", "role", "of", "MED12", "exon", "2", "mutations", "in", "other", "tumour", "types." ]
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Mediator complex participates in transcriptional regulation by connecting regulatory DNA sequences to the RNA polymerase II initiation complex. Recently, we discovered through exome sequencing that as many as 70% of uterine leiomyomas harbour specific mutations in exon 2 of mediator complex subunit 12 (MED12). In this work, we examined the role of MED12 exon 2 mutations in other tumour types.
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9609758
[ "Expression", "of", "transforming", "growth", "factor", "beta", "receptors", "in", "normal", "human", "colon", "and", "sporadic", "adenocarcinomas.", "\n\n\n", "##", "BACKGROUND", "&", "AIMS" ]
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Expression of transforming growth factor beta receptors in normal human colon and sporadic adenocarcinomas. ## BACKGROUND & AIMS
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20198339
[ "MUC2", "is", "a", "major", "secretory", "mucin", "normally", "expressed", "by", "goblet", "cells", "of", "the", "intestine,", "but", "is", "aberrantly", "expressed", "in", "colonic", "neoplasia.", "Bile", "acids", "have", "been", "implicated", "in", "colorectal", "carcinogenesis", "and,", "therefore,", "we", "sought", "to", "determine", "the", "effects", "of", "bile", "acids", "on", "MUC2", "expression", "and", "regulation", "in", "colon", "cancer", "cells.", "Since", "deoxycholic", "acid", "(DCA),", "a", "secondary", "bile", "acid,", "has", "been", "reported", "to", "be", "a", "potent", "mucin", "secretagogue", "and", "tumor", "promoter,", "DCA-treated", "HM3", "colon", "cancer", "cells", "were", "analyzed", "using", "promoter-reporter", "assays", "of", "the", "5'", "flanking", "region", "of", "the", "MUC2", "gene.", "Chemical", "inhibitors,", "mutant", "reporter", "constructs", "and", "EMSA", "showed", "that", "DCA", "upregulates", "MUC2", "transcription", "via", "multiple", "pathways", "involving", "activation", "of", "EGFR/PKC/Ras/Raf-1/MEK1/ERK/CREB,", "PI3/Akt/", "IkappaB", "JNK", "NF-kappaB", "IkappaB", "/NF-kappaB", "and", "p38/", "MSK1", "/CREB", "pathways", "and", "negative", "JNK/c-Jun/AP-1", "pathway." ]
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MUC2 is a major secretory mucin normally expressed by goblet cells of the intestine, but is aberrantly expressed in colonic neoplasia. Bile acids have been implicated in colorectal carcinogenesis and, therefore, we sought to determine the effects of bile acids on MUC2 expression and regulation in colon cancer cells. Since deoxycholic acid (DCA), a secondary bile acid, has been reported to be a potent mucin secretagogue and tumor promoter, DCA-treated HM3 colon cancer cells were analyzed using promoter-reporter assays of the 5' flanking region of the MUC2 gene. Chemical inhibitors, mutant reporter constructs and EMSA showed that DCA upregulates MUC2 transcription via multiple pathways involving activation of EGFR/PKC/Ras/Raf-1/MEK1/ERK/CREB, PI3/Akt/ IkappaB JNK NF-kappaB IkappaB /NF-kappaB and p38/ MSK1 /CREB pathways and negative JNK/c-Jun/AP-1 pathway.
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16396368
[ "HNPCC", "is", "a", "hereditary", "cancer", "syndrome", "of", "several", "organs", "but", "more", "particularly", "the", "colon", "and", "the", "uterus.", "It", "is", "characterized", "by", "microsatellite", "instability", " ", "(MSI)", "related", "to", "mutations", "MSI", ")", "related", "to", "mutations", "of", "DNA", "mismatch", "repair", "(MMR)", "genes.", "The", "role", "of", "the", "pathologist", "in", "the", "detection", "of", "colorectal", "cancer", "with", "MSI", " ", "phenotype", "is", "important.", "Among", "the", "available", "tests", "to", "detect", "MSI", ",", "immunohistochemistry", "appears", "being", "a", "sensitive,", "specific", "and", "inexpensive", "test.", "The", "detection", "of", "HNPCC", "syndrome", "by", "the", "genetic", "test", "among", "the", "MSI", " ", "cancers", "implies", "a", "coordination", "of", "the", "structures", "of", "health", "and", "requires", "a", "follow-up", "of", "the", "patients,", "during", "and", "after", "the", "genetic", "test.", "Ethical", "dimension", "related", "to", "these", "hereditary", "cancers", "must", "be", "considered", "without", "constituting", "a", "brake", "for", "their", "detection." ]
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HNPCC is a hereditary cancer syndrome of several organs but more particularly the colon and the uterus. It is characterized by microsatellite instability (MSI) related to mutations MSI ) related to mutations of DNA mismatch repair (MMR) genes. The role of the pathologist in the detection of colorectal cancer with MSI phenotype is important. Among the available tests to detect MSI , immunohistochemistry appears being a sensitive, specific and inexpensive test. The detection of HNPCC syndrome by the genetic test among the MSI cancers implies a coordination of the structures of health and requires a follow-up of the patients, during and after the genetic test. Ethical dimension related to these hereditary cancers must be considered without constituting a brake for their detection.
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22899730
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9731891
[ "Left", "and", "right", "colon", "carcinomas", "can", "display", "different", "clinical,", "pathologic,", "and", "genetic", "characteristics.", "The", "purpose", "of", "this", "study", "was", "to", "characterize", "multiple", "molecular", "genetic", "alterations", "in", "sporadic", "colon", "carcinoma", "and", "to", "correlate", "them", "with", "the", "location", "of", "the", "tumors", "and", "with", "lymph", "node", "metastasis." ]
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Left and right colon carcinomas can display different clinical, pathologic, and genetic characteristics. The purpose of this study was to characterize multiple molecular genetic alterations in sporadic colon carcinoma and to correlate them with the location of the tumors and with lymph node metastasis.
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14734469
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12534642
[ "In", "114", "samples,", "the", "most", "frequent", "CYP1A2", "SNPs", "were", "1545T-->C", "(38.2%", "of", "tested", "chromosomes),", "-164A-->C", "(CYP1A2*1F,", "33.3%)", "and", "-2464T-->delT", " ", "(", "CYP1A2*1D", ",", "4.82%).", "The", "SNPs", " ", "were", "in", "linkage", "disequilibrium:", "the", "most", "frequent", "constellations", "were", "found", "to", "be", "-3858G/-2464T/-740T/-164A/63C/1545T", " ", "(61.8%),", "-3858G/-2464T/-740T/-164C/63C/1545C", " ", "(33.3%),", "and", "-3858G/-2464delT/-740T/-164A/63C/1545C", " ", "(3.51%),", "with", "no", "significant", "frequency", "differences", "between", "cases", "and", "controls.", "In", "the", "phenotype", "analysis,", "lower", "caffeine", "metabolic", "ratios", "were", "detected", "in", "cases", "than", "in", "controls.", "This", "was", "significant", "in", "smokers", "(n", "=", "14,", "P", "=", "0.020),", "and", "in", "a", "subgroup", "of", "15", "matched", "case-control", "pairs", "(P", "=", "0.007),", "but", "it", "was", "not", "significant", "in", "nonsmokers", "(n", "=", "100,", "P", "=", "0.39).", "There", "was", "no", "detectable", "association", "between", "CYP1A2", "genotype", "and", "caffeine", "phenotype." ]
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In 114 samples, the most frequent CYP1A2 SNPs were 1545T-->C (38.2% of tested chromosomes), -164A-->C (CYP1A2*1F, 33.3%) and -2464T-->delT ( CYP1A2*1D , 4.82%). The SNPs were in linkage disequilibrium: the most frequent constellations were found to be -3858G/-2464T/-740T/-164A/63C/1545T (61.8%), -3858G/-2464T/-740T/-164C/63C/1545C (33.3%), and -3858G/-2464delT/-740T/-164A/63C/1545C (3.51%), with no significant frequency differences between cases and controls. In the phenotype analysis, lower caffeine metabolic ratios were detected in cases than in controls. This was significant in smokers (n = 14, P = 0.020), and in a subgroup of 15 matched case-control pairs (P = 0.007), but it was not significant in nonsmokers (n = 100, P = 0.39). There was no detectable association between CYP1A2 genotype and caffeine phenotype.
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14645426
[ "##", "RESULTS" ]
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## RESULTS
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26925673
[ "##", "RESULTS" ]
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## RESULTS
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12000733
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Aberrant crypt foci (ACF) are postulated to be the earliest precursor lesion in colorectal carcinogenesis, and CpG island methylation has been described as an important molecular pathway. We therefore studied methylation in ACF from patients with familial adenomatous polyposis (FAP) or sporadic colorectal cancer. We assessed methylation status of the p16 tumor suppressor gene, MINT1 (methylated in tumor 1), MINT2, MINT31 , O(6)-methylguanine-DNA methyltransferase gene, and hMLH1 mismatch repair gene. We compared methylation to ACF histopathology, K-ras proto-oncogene mutation , loss of heterozygosity at chromosome 1p loss of heterozygosity at chromosome 1p, and microsatellite instability. Methylation was present in 34% (21 of 61) of ACF, including both FAP and sporadic types, but was more frequent in sporadic ACF [53% (18 of 34) versus 11% (3 of 27), P = 0.002], especially dysplastic sporadic ACF [75% (3 of 4) versus 8% (2 of 24), P = 0.004]. MINT31 was more frequently methylated in heteroplastic ACF than dysplastic ACF [35% (11 of 31) versus 7% (2 of 30), P = 0.01]. Strong associations of ACF methylation with K-ras mutation (P = 0.007) and with loss of chromosome 1p (P = 0.04) were observed, but methylation was the only molecular abnormality identified in 16% (10 of 61) of ACF. Our findings suggest that methylation in ACF is an early event in the pathogenesis of a subset of colorectal carcinomas, and that ACF from FAP patients and patients with sporadic colorectal cancer have distinct epigenetic changes MINT31 Methylation was present in 34% (21 of 61) of ACF, including both FAP and sporadic types, but was more frequent in sporadic ACF [53% (18 of 34) versus 11% (3 of 27), P = 0.002], especially dysplastic sporadic ACF [75% (3 of 4) versus 8% (2 of 24), P = 0.004]. MINT31 was more frequently methylated in heteroplastic ACF than dysplastic ACF [35% (11 of 31) versus 7% (2 of 30), P = 0.01]. Strong associations of ACF methylation methylated in heteroplastic ACF than dysplastic ACF [35% (11 of 31) versus 7% (2 of 30), P = 0.01]. Strong associations of ACF methylation with K-ras mutation K-ras mutation (P = 0.007) and with loss of chromosome 1p (P = 0.04) were observed, but methylation was the only molecular abnormality identified in 16% (10 of 61) of ACF. Our findings suggest that methylation microsatellite instability . Methylation was present in 34% (21 of 61) of ACF, including both FAP and sporadic types, but was more frequent in sporadic ACF [53% (18 of 34) versus 11% (3 of 27), P = 0.002], especially dysplastic sporadic ACF [75% (3 of 4) versus 8% (2 of 24), P = 0.004]. MINT31 was more frequently methylated in heteroplastic ACF than dysplastic ACF [35% (11 of 31) versus 7% (2 of 30), P = 0.01]. Strong associations of ACF methylation with K-ras mutation (P = 0.007) and with loss of chromosome 1p (P = 0.04) were observed, but methylation methylation CpG island methylation in aberrant crypt foci of the colorectum.
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17186357
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20646601
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Of 208 cases, 91 cases of K-ras gene mutation were detected. The 12 or 13 codon had a mutation rate of 43.8%. There were no significant differences in gender, tumor location, histopathological grading and Duke's stage between the wild and mutated groups.
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22810479
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: The K-ras gene is one of the commonly mutated oncogenes associated with colorectal cancer. However, its prognostic significance for patients with colorectal cancer remains inconclusive.
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22575968
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We show how to use reports of cancer in family members to discover additional genetic associations or confirm previous findings in genome-wide association (GWA) studies conducted in case-control, cohort, or cross-sectional studies. Our novel family history-based approach allows economical association studies for multiple cancers, without genotyping of relatives (as required in family studies), follow-up of participants (as required in cohort studies), or oversampling of specific cancer cases (as required in case-control studies). We empirically evaluate the performance of the proposed family history-based approach in studying associations with prostate and ovarian cancers, using data from GWA studies previously conducted within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The family history-based method may be particularly useful for investigating genetic susceptibility to rare diseases for which accruing cases may be very difficult, by using disease information from nongenotyped relatives of participants in multiple case-control and cohort studies designed primarily for other purposes.
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10962562
[ "Breast", "cancer", "susceptibility", "gene", "BRCA1", "has", "been", "implicated", "in", "the", "control", "of", "gene", "regulation", "and", "such", "regulated", "genes", "are", "thought", "to", "mediate", "the", "biological", "role", "of", "BRCA1.", "Overexpression", "of", "BRCA1", "induces", "GADD45,", "a", "p53-regulated", "and", "stress-inducible", "gene.", "However,", "the", "molecular", "mechanism", "by", "which", "BRCA1", "induces", "the", "expression", "GADD45", "remains", "unclear.", "In", "this", "report,", "we", "have", "shown", "that", "the", "GADD45", "promoter", "is", "strongly", "activated", "following", "expression", "of", "wild-type", "BRCA1.", "In", "contrast,", "both", "the", "tumor-derived", "BRCA1", "mutants", "(p1749R", "and", "Y1853insA)", "and", "truncated", "BRCA1", "mutant", "BRCA1", " ", "activation", "of", "the", "GADD45", "promoter." ]
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Breast cancer susceptibility gene BRCA1 has been implicated in the control of gene regulation and such regulated genes are thought to mediate the biological role of BRCA1. Overexpression of BRCA1 induces GADD45, a p53-regulated and stress-inducible gene. However, the molecular mechanism by which BRCA1 induces the expression GADD45 remains unclear. In this report, we have shown that the GADD45 promoter is strongly activated following expression of wild-type BRCA1. In contrast, both the tumor-derived BRCA1 mutants (p1749R and Y1853insA) and truncated BRCA1 mutant BRCA1 activation of the GADD45 promoter.
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9731891
[ "One", "hundred", "and", "twenty-five", "cases", "of", "sporadic", "colon", "carcinoma", "(50", "in", "the", "right", "colon", "and", "75", "in", "the", "left", "colon", "in", "patients", "with", "no", "family", "history", "of", "colon", "carcinoma)", "were", "studied.", "Status", "of", "the", "p53", "gene", "was", "assessed", "by", "polymerase", "chain", "reaction", "(PCR),", "single", "strand", "conformation", "polymorphism,", "and", "sequencing", "at", "exons", "5-8.", "Microsatellite", "instability", "was", "analyzed", "with", "five", "microsatellite", "markers", "at", "chromosome", "18.", "The", "mismatch", "repair", "genes", "hMLH1", "and", "hMSH2", "were", "studied", "in", "tumors", "found", "to", "have", "microsatellite", "instability", "by", "PCR", "and", "sequencing." ]
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One hundred and twenty-five cases of sporadic colon carcinoma (50 in the right colon and 75 in the left colon in patients with no family history of colon carcinoma) were studied. Status of the p53 gene was assessed by polymerase chain reaction (PCR), single strand conformation polymorphism, and sequencing at exons 5-8. Microsatellite instability was analyzed with five microsatellite markers at chromosome 18. The mismatch repair genes hMLH1 and hMSH2 were studied in tumors found to have microsatellite instability by PCR and sequencing.
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12534642
[ "In", "114", "samples,", "the", "most", "frequent", "CYP1A2", "SNPs", "were", "1545T-->C", "(38.2%", "of", "tested", "chromosomes),", "-164A-->C", "(CYP1A2*1F,", "33.3%)", "and", "-2464T-->delT", "(CYP1A2*1D,", "4.82%).", "The", "SNPs", "were", "in", "linkage", "disequilibrium:", "the", "most", "frequent", "constellations", "were", "found", "to", "be", "-3858G/-2464T/-740T/-164A/63C/1545T", "(61.8%),", "-3858G/-2464T/-740T/-164C/63C/1545C", "(33.3%),", "and", "-3858G/-2464delT/-740T/-164A/63C/1545C", "(3.51%),", "with", "no", "significant", "frequency", "differences", "between", "cases", "and", "controls.", "In", "the", "phenotype", "analysis,", "lower", "caffeine", "metabolic", "ratios", "were", "detected", "in", "cases", "than", "in", "controls.", "This", "was", "significant", "in", "smokers", "(n", "=", "14,", "P", "=", "0.020),", "and", "in", "a", "subgroup", "of", "15", "matched", "case-control", "pairs", "(P", "=", "0.007),", "but", "it", "was", "not", "significant", "in", "nonsmokers", "(n", "=", "100,", "P", "=", "0.39).", "There", "was", "no", "detectable", "association", "between", "CYP1A2", "genotype", "and", "caffeine", "phenotype." ]
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In 114 samples, the most frequent CYP1A2 SNPs were 1545T-->C (38.2% of tested chromosomes), -164A-->C (CYP1A2*1F, 33.3%) and -2464T-->delT (CYP1A2*1D, 4.82%). The SNPs were in linkage disequilibrium: the most frequent constellations were found to be -3858G/-2464T/-740T/-164A/63C/1545T (61.8%), -3858G/-2464T/-740T/-164C/63C/1545C (33.3%), and -3858G/-2464delT/-740T/-164A/63C/1545C (3.51%), with no significant frequency differences between cases and controls. In the phenotype analysis, lower caffeine metabolic ratios were detected in cases than in controls. This was significant in smokers (n = 14, P = 0.020), and in a subgroup of 15 matched case-control pairs (P = 0.007), but it was not significant in nonsmokers (n = 100, P = 0.39). There was no detectable association between CYP1A2 genotype and caffeine phenotype.
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24576032
[ "In", "general,", "laboratories", "performed", "well", "in", "microsatellite", "instability", "testing.", "This", "testing", "will", "continue", "to", "be", "important", "in", "screening", "patients", "with", "colorectal", "and", "other", "cancers", "for", "Lynch", "syndrome", "and", "guiding", "the", "management", "of", "patients", "with", "sporadic", "colorectal", "cancer." ]
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In general, laboratories performed well in microsatellite instability testing. This testing will continue to be important in screening patients with colorectal and other cancers for Lynch syndrome and guiding the management of patients with sporadic colorectal cancer.
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19276868
[ "UA62784", "is", "a", "small", "molecule", "that", "selectively", "kills", "DPC4", "DPC4", "DPC4", ")-deficient", "pancreatic", "and", "colon", "cancer", "cells.", "\n\n\n", "##", "OBJECTIVES" ]
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UA62784 is a small molecule that selectively kills DPC4 DPC4 DPC4 )-deficient pancreatic and colon cancer cells. ## OBJECTIVES
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26925673
[ "To", "evaluate", "the", "impact", "of", "cellular", "genetic", "make-", "up", "of", "two", "colon", "cancer", "cell", "lines", "with", "different", "genetic", "backgrounds,", "HCT-116", "(K-Ras-/p53+)", "and", "Caco-2", "(K-Ras+/", "p53", "K-Ras", " ", "activation", "is", "an", "early", "event", "in", "colorectal", "carcinogenesis", "and", "associated", "mutations", "have", "been", "reported", "in", "about", "40%", "of", "colorectal", "cancer", "patients.", "These", "mutations", "have", "always", "been", "responsible", "for", "enhancing", "malignancy", "and", "silencing", "them", "is", "associated", "with", "attenuation", "of", "tumorigenicity.", "Among", "downstream", "effectors", "are", "the", "RAF/MEK/ERK", "and", "the", "PI3K/Akt", "signaling", "pathways.", "PI3K/Akt", "signaling", "leads", "to", "reduction", "of", "apoptosis,", "stimulated", "cell", "growth", "and", "enhanced", "proliferation.", "Ellagic", "acid", "(EA),", "a", "naturally", "occurring", "antioxidant,", "has", "recently", "emerged", "as", "a", "promising", "anti-cancer", "agent." ]
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To evaluate the impact of cellular genetic make- up of two colon cancer cell lines with different genetic backgrounds, HCT-116 (K-Ras-/p53+) and Caco-2 (K-Ras+/ p53 K-Ras activation is an early event in colorectal carcinogenesis and associated mutations have been reported in about 40% of colorectal cancer patients. These mutations have always been responsible for enhancing malignancy and silencing them is associated with attenuation of tumorigenicity. Among downstream effectors are the RAF/MEK/ERK and the PI3K/Akt signaling pathways. PI3K/Akt signaling leads to reduction of apoptosis, stimulated cell growth and enhanced proliferation. Ellagic acid (EA), a naturally occurring antioxidant, has recently emerged as a promising anti-cancer agent.
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27070770
[ "[Rare", "hereditary", "syndromes", "associated", "with", "polyposis", "and", "the", "development", "of", "malignant", "tumors].", "\n\n\n", "##", "UNLABELLED" ]
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[Rare hereditary syndromes associated with polyposis and the development of malignant tumors]. ## UNLABELLED
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19706845
[ "Sixteen", "tagSNPs", "were", "selected,", "and", "13", "were", "successfully", "genotyped.", "A", "novel", "CYP2E1", " ", "locus", "rs1329149", " ", "and", "a", "known", "ALDH2", " ", "locus", "rs671", " ", "were", "found", "to", "be", "significantly", "associated", "with", "CRC", "risk.", "The", "adjusted", "OR", "was", "1.86", "(95%", "CI,", "1.12-3.09)", "for", "the", "rs671", " ", "A/A", "genotype", "and", "4.04", "for", "the", "rs1329149", "T/T", "genotype", "(95%", "CI,", "2.44-6.70),", "compared", "with", "their", "common", "homozygous", "genotypes.", "Interaction", "was", "found", "between", "alcohol", "consumption", "and", "gene", "polymorphisms", "on", "CRC,", "the", "adjusted", "OR", "was", "7.17", "(95%", "CI,", "2.01-25.53)", "for", "drinking", "habits", "combined", "with", "rs671", "A/A", "or", "rs1329149", "T/T", "genotype." ]
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Sixteen tagSNPs were selected, and 13 were successfully genotyped. A novel CYP2E1 locus rs1329149 and a known ALDH2 locus rs671 were found to be significantly associated with CRC risk. The adjusted OR was 1.86 (95% CI, 1.12-3.09) for the rs671 A/A genotype and 4.04 for the rs1329149 T/T genotype (95% CI, 2.44-6.70), compared with their common homozygous genotypes. Interaction was found between alcohol consumption and gene polymorphisms on CRC, the adjusted OR was 7.17 (95% CI, 2.01-25.53) for drinking habits combined with rs671 A/A or rs1329149 T/T genotype.
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24435063
[ "##", "CONCLUSIONS" ]
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## CONCLUSIONS
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8495305
[ "An", "immunohistochemical", "method", "using", "Pab1801,", "a", "monoclonal", "antibody", "specific", "to", "the", "human", "p53", " ", "protein,", "was", "applied", "to", "detect", "p53", "expression", "in", "colorectal", "cancer", "and", "dysplasia", "complicating", "ulcerative", "colitis.", "Of", "20", "tissue", "samples", "with", "dysplasia,", "six", "showed", "positive", "immunoreactivity.", "Archival", "paraffin-embedded", "tissue", "blocks", "from", "21", "colitic", "cancers", "were", "analysed;", "11", "showed", "positive", "immunoreactivity,", "compared", "with", "ten", "of", "21", "samples", "from", "matched", "sporadic", "colorectal", "cancers", "(P", "not", "significant).", "Previous", "data", "suggesting", "that", "colorectal", "carcinoma", "complicating", "ulcerative", "colitis", "has", "a", "reduced", "frequency", "of", "c-Ki-ras", "mutation", " ", "compared", "with", "sporadic", "cancer", "have", "led", "to", "the", "hypothesis", "that", "different", "genetic", "lesions", "underlie", "colitic", "and", "sporadic", "colorectal", "carcinoma.", "The", "present", "results", "suggest", "that", "this", "is", "not", "the", "case", "with", "regard", "to", "p53", "gene", "alterations." ]
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An immunohistochemical method using Pab1801, a monoclonal antibody specific to the human p53 protein, was applied to detect p53 expression in colorectal cancer and dysplasia complicating ulcerative colitis. Of 20 tissue samples with dysplasia, six showed positive immunoreactivity. Archival paraffin-embedded tissue blocks from 21 colitic cancers were analysed; 11 showed positive immunoreactivity, compared with ten of 21 samples from matched sporadic colorectal cancers (P not significant). Previous data suggesting that colorectal carcinoma complicating ulcerative colitis has a reduced frequency of c-Ki-ras mutation compared with sporadic cancer have led to the hypothesis that different genetic lesions underlie colitic and sporadic colorectal carcinoma. The present results suggest that this is not the case with regard to p53 gene alterations.
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26416897
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
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19276868
[ "A", "lead", "molecule,", "UA62784,", "was", "identified", "to", "be", "selectively", "cytotoxic", "against", "cancer", "cells", "with", "deficient", "DPC4.", "UA62784", "preferentially", "induces", "cell", "cycle", "arrest", "and", "apoptosis", "in", "cells", "with", "deficient", "DPC4.", "It", "also", "selectively", "reduces", "the", "clonogenicity", "of", "DPC4-deficient", "cells", "on", "soft", "agar", "when", "compared", "with", "cells", "with", "wild", "type", "DPC4.", "We", "further", "demonstrate", "that", "UA62784", "induces", "CDC2", "kinase", "activity", "preferentially", "in", "DPC4-negative", "cells." ]
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A lead molecule, UA62784, was identified to be selectively cytotoxic against cancer cells with deficient DPC4. UA62784 preferentially induces cell cycle arrest and apoptosis in cells with deficient DPC4. It also selectively reduces the clonogenicity of DPC4-deficient cells on soft agar when compared with cells with wild type DPC4. We further demonstrate that UA62784 induces CDC2 kinase activity preferentially in DPC4-negative cells.
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9731891
[ "##", "METHODS" ]
[ 0, 0 ]
## METHODS
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12534642
[ "(i)", "CYP1A2", "polymorphisms", "are", "in", "linkage", "disequilibrium.", "Therefore,", "only", "-164A-->C", "(CYP1A2*1F)", "and", "-2464T-->delT", "(CYP1A2*1D)", "need", "to", "be", "analysed", "in", "the", "routine", "assessment", "of", "CYP1A2", "genotype;", "(ii)", "in", "vivo", "CYP1A2", "CYP1A2*1D", "),", "-740T-->G", "(CYP1A2*1E", "and", "*1G),", "-164A-->C", "(CYP1A2*1F),", "63C-->G", "(CYP1A2*2),", "and", "1545T-->C", "(alleles", "CYP1A2*1B,", "*1G,", "*1H", "and", "*3),", "using", "polymerase", "chain", "reaction-restriction", "fragment", "length", "polymorphism", "assays.", "All", "patients", "and", "controls", "were", "phenotyped", "for", "CYP1A2", "by", "h.p.l.c.", "analysis", "of", "urinary", "caffeine", "metabolites." ]
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(i) CYP1A2 polymorphisms are in linkage disequilibrium. Therefore, only -164A-->C (CYP1A2*1F) and -2464T-->delT (CYP1A2*1D) need to be analysed in the routine assessment of CYP1A2 genotype; (ii) in vivo CYP1A2 CYP1A2*1D ), -740T-->G (CYP1A2*1E and *1G), -164A-->C (CYP1A2*1F), 63C-->G (CYP1A2*2), and 1545T-->C (alleles CYP1A2*1B, *1G, *1H and *3), using polymerase chain reaction-restriction fragment length polymorphism assays. All patients and controls were phenotyped for CYP1A2 by h.p.l.c. analysis of urinary caffeine metabolites.
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20646601
[ "A", "total", "of", "208", "colorectal", "cancer", "tissue", "samples", "were", "collected", "from", "September", "2008", "to", "February", "2009.", "DNA", "was", "extracted", "with", "a", "genomic", "DNA", "miniprep", "kit.", "Then", "PCR", "was", "performed", "with", "the", "designed", "primers", "and", "the", "product", "directly", "sequenced", "by", "the", "Sanger", "method.", "Then", "the", "associations", "between", "K-ras", "mutation", "status", "and", "clinicopathological", "characteristics", "in", "colorectal", "cancer", "were", "analyzed." ]
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A total of 208 colorectal cancer tissue samples were collected from September 2008 to February 2009. DNA was extracted with a genomic DNA miniprep kit. Then PCR was performed with the designed primers and the product directly sequenced by the Sanger method. Then the associations between K-ras mutation status and clinicopathological characteristics in colorectal cancer were analyzed.
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26416897
[ "TBK1", "rs7486100", "was", "significantly", "associated", "with", "overall", "survival", "in", "95", "KRAS", "wild-type", "patients", "of", "TRIBE", "cohort", "in", "univariate", "analysis", "and", "had", "a", "strong", "trend", "in", "multivariable", "analysis;", "furthermore,", "the", "association", "of", "the", "T", "allele", "was", "observed", "for", "progression-free", "survival", "(PFS)", "in", "both", "univariate", "and", "multivariable", "analyses", "in", "FIRE3-bevacizumab", "but", "not", "cetuximab", "cohort.", "CCL2", "rs4586,", "CCL18", "rs14304,", "and", "IRF3", "rs2304205", "had", "univariate", "and", "multivariable", "correlations", "with", "PFS", "in", "KRAS", "mutant", "patients", "of", "the", "TRIBE", "cohort,", "whereas", "they", "had", "no", "correlations", "in", "KRAS", "IRF3", "CCR2", ",", "HRG,", "PIGF,", "NFKB1,", "TBK1,", "CCL18,", "and", "IRF3)", "were", "tested", "for", "associations", "with", "clinical", "outcomes", "in", "a", "discovery", "cohort", "of", "228", "participants", "in", "TRIBE", "trial", "(NCT00719797),", "then", "validated", "in", "248", "KRAS", "exon2", "(KRAS)", "wild-type", "participants", "in", "FIRE3", "trial", "(NCT00433927).", "FIRE3-cetuximab", "cohort", "served", "as", "a", "negative", "control." ]
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TBK1 rs7486100 was significantly associated with overall survival in 95 KRAS wild-type patients of TRIBE cohort in univariate analysis and had a strong trend in multivariable analysis; furthermore, the association of the T allele was observed for progression-free survival (PFS) in both univariate and multivariable analyses in FIRE3-bevacizumab but not cetuximab cohort. CCL2 rs4586, CCL18 rs14304, and IRF3 rs2304205 had univariate and multivariable correlations with PFS in KRAS mutant patients of the TRIBE cohort, whereas they had no correlations in KRAS IRF3 CCR2 , HRG, PIGF, NFKB1, TBK1, CCL18, and IRF3) were tested for associations with clinical outcomes in a discovery cohort of 228 participants in TRIBE trial (NCT00719797), then validated in 248 KRAS exon2 (KRAS) wild-type participants in FIRE3 trial (NCT00433927). FIRE3-cetuximab cohort served as a negative control.
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Colorectal cancer has become the third leading cause of death from cancer in Taiwan. Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by the presence of multiple adenomatous polyps in the colon and rectum. The gene responsible for FAP (APC) was cloned in 1991. Extensive analyses of the mutation spectra in FAP kindreds have been performed in different countries, but the results have been highly variable (30-80%). In this study, we used denaturing high-performance liquid chromatography (DHPLC) followed by automatic sequencing in an effort to establish the mutation spectrum of APC from DNA of peripheral blood cells. Among the 6 FAP probands analyzed, mutations were detected in 3 (50%), 2 of which were novel. The first novel mutation was at codon 2166, with a C to T transition, resulting in a stop codon. The second novel mutation was at codon 1971, with a C to G transversion, resulting in an amino acid change from serine to cysteine. The third mutation involved an A insertion mutation spectra in FAP kindreds have been performed in different countries, but the results have been highly variable (30-80%). In this study, we used denaturing high-performance liquid chromatography (DHPLC) followed by automatic sequencing in an effort to establish the mutation spectrum of APC from DNA of peripheral blood cells. Among the 6 FAP probands analyzed, mutations were detected in 3 (50%), 2 of which were novel. The first novel mutation was at codon 2166, with a C to T transition, resulting in a stop codon. The second novel mutation was at codon 1971, with a C to G transversion, resulting in an amino acid change from serine to cysteine. The third mutation involved an A insertion in the sequence of -AAAAAA- at codons 1554-1556, which created a downstream stop codon ( codon 1558 C to T transition , resulting in a stop codon. The second novel mutation was at codon 1971 , with a C to G transversion mutation spectrum of APC from DNA of peripheral blood cells. Among the 6 FAP probands analyzed, mutations were detected in 3 (50%), 2 of which were novel. The first novel mutation was at codon 2166 , with a C to T transition, resulting in a stop codon. The second novel mutation was at codon 1971, with a C to G transversion, resulting in an amino acid change from serine to cysteine. The third mutation involved an A insertion in the sequence of -AAAAAA- at codons 1554-1556, which created a downstream stop codon (codon 1558). This study is the first to report mutation analysis in Taiwanese FAP probands.
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10962562
[ "BRCA1", "activation", "of", "the", "GADD45", "promoter." ]
[ 0, 0, 0, 0, 0, 0 ]
BRCA1 activation of the GADD45 promoter.
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[ 1, 1, 1, 1, 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, 0, 0, 0, 0, -100 ]
9439149
[]
[]
[ 2, 3 ]
[ 0, 0 ]
[ 1, 1 ]
[ -100, -100 ]
26925673
[ "Cellular", "proliferation,", "morphology", "and", "cell", "cycle", "analysis", "were", "carried", "out", "in", "addition", "to", "Western", "blotting", "for", "detecting", "total", "Akt", "and", "p-Akt", "(at", "Thr308", "and", "Ser473)", "in", "the", "presence", "and", "absence", "of", "different", "concentrations", "of", "EA.", "Cell", "proliferation", "was", "also", "assessed", "in", "cells", "transfected", "with", "different", "concentrations", "of", "K-Ras", " ", "siRNA", "or", "incubated", "with", "ellagic", "acid", "following", "transfection." ]
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Cellular proliferation, morphology and cell cycle analysis were carried out in addition to Western blotting for detecting total Akt and p-Akt (at Thr308 and Ser473) in the presence and absence of different concentrations of EA. Cell proliferation was also assessed in cells transfected with different concentrations of K-Ras siRNA or incubated with ellagic acid following transfection.
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19706845
[ "The", "results", "of", "this", "study", "suggest", "that", "rs671", "A/A", "and", "the", "first", "reported", "locus", "rs1329149", "T/T", "genotypes", "increase", "the", "susceptibility", "to", "CRC,", "and", "gene-environmental", "interaction", "between", "the", "two", "loci", "and", "alcohol", "use", "existed", "for", "CRC", "in", "Southwestern", "Chinese.", "Larger", "studies", "are", "warranted", "to", "verify", "our", "findings." ]
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The results of this study suggest that rs671 A/A and the first reported locus rs1329149 T/T genotypes increase the susceptibility to CRC, and gene-environmental interaction between the two loci and alcohol use existed for CRC in Southwestern Chinese. Larger studies are warranted to verify our findings.
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24576032
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
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[ -100, 0, 0, 0, -100 ]
26925673
[ "##", "PURPOSE" ]
[ 0, 0 ]
## PURPOSE
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[ -100, 0, 0, 0, -100 ]
26416897
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
[ 2, 7, 7, 2274, 3 ]
[ 0, 0, 0, 0, 0 ]
[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
22899730
[ "The", "presence", "of", "a", "BRAF", "c.1799T>A", "MSI", ")", "and", "are", "associated", "with", "other", "prognostic", "factors.", "The", "independent", "association", "between", "BRAF", "mutation", "status", "and", "CRC", "survival,", "however,", "remains", "unclear." ]
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The presence of a BRAF c.1799T>A MSI ) and are associated with other prognostic factors. The independent association between BRAF mutation status and CRC survival, however, remains unclear.
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8431846
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
[ 2, 7, 7, 4355, 3 ]
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22388025
[ "Editorial:", "sessile", "serrated", "adenomas", "and", "their", "pit", "patterns:", "we", "must", "first", "see", "the", "forest", "through", "the", "trees." ]
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Editorial: sessile serrated adenomas and their pit patterns: we must first see the forest through the trees.
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9731891
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
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[ -100, 0, 0, 0, -100 ]
22545919
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
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25374237
[ "The", "relation", "between", "colon", "cancer", "and", "survivin", "-31", "G/C", "(rs9904341),", "-241", "C/T", "(rs17878467)", "and", "-625", "C/G", "(rs8073069)", "polymorphism", "in", "promotor", "site", "of", "survivin", "gene", "associated", "with", "apoptosis", "was", "investigated", "using", "the", "polymerase", "chain", "reaction-restriction", "fragment", "length", "polymorphism", "(PCR-RFLP)", "method." ]
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The relation between colon cancer and survivin -31 G/C (rs9904341), -241 C/T (rs17878467) and -625 C/G (rs8073069) polymorphism in promotor site of survivin gene associated with apoptosis was investigated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
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26416897
[ "Variations", "in", "genes", "regulating", "tumor-associated", "macrophages", "(TAMs)", "to", "predict", "outcomes", "of", "bevacizumab-based", "treatment", "in", "patients", "with", "metastatic", "colorectal", "cancer:", "results", "from", "TRIBE", "and", "FIRE3", "trials.", "\n\n\n", "##", "BACKGROUND" ]
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Variations in genes regulating tumor-associated macrophages (TAMs) to predict outcomes of bevacizumab-based treatment in patients with metastatic colorectal cancer: results from TRIBE and FIRE3 trials. ## BACKGROUND
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14645426
[ "Endometrial", "cancer", "patients", "(N", "=", "58),", "who", "were", "diagnosed", "at", "less", "than", "50", "years", "of", "age,", "were", "included", "and", "questioned", "about", "their", "family", "history.", "Mutation", "analysis", "of", "the", "MLH1,", "MSH2,", "and", "MSH6", "genes", "was", "performed", "(denaturing", "gradient", "gel", "electrophoresis", "and", "sequence", "analysis", "to", "detect", "small", "mutations", "and", "multiplex", "ligation-dependent", "probe", "amplification", "to", "detect", "large", "deletions", "or", "duplications).", "For", "MSI", "analysis,", "five", "consensus", "markers", "were", "used,", "and", "immunostaining", "of", "the", "three", "MMR", "proteins", "was", "performed." ]
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Endometrial cancer patients (N = 58), who were diagnosed at less than 50 years of age, were included and questioned about their family history. Mutation analysis of the MLH1, MSH2, and MSH6 genes was performed (denaturing gradient gel electrophoresis and sequence analysis to detect small mutations and multiplex ligation-dependent probe amplification to detect large deletions or duplications). For MSI analysis, five consensus markers were used, and immunostaining of the three MMR proteins was performed.
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20198339
[ "MUC2", "is", "a", "major", "secretory", "mucin", "normally", "expressed", "by", "goblet", "cells", "of", "the", "intestine,", "but", "is", "aberrantly", "expressed", "in", "colonic", "neoplasia.", "Bile", "acids", "have", "been", "implicated", "in", "colorectal", "carcinogenesis", "and,", "therefore,", "we", "sought", "to", "determine", "the", "effects", "of", "bile", "acids", "on", "MUC2", "MUC2", " ", "transcription", "in", "colon", "cancer", "cells", "via", "positive", "EGFR/PKC/Ras/ERK/CREB,", "PI3K/Akt/IkappaB/NF-kappaB", "and", "p38/MSK1/CREB", "pathways", "and", "negative", "JNK/c-Jun/AP-1", "pathway." ]
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MUC2 is a major secretory mucin normally expressed by goblet cells of the intestine, but is aberrantly expressed in colonic neoplasia. Bile acids have been implicated in colorectal carcinogenesis and, therefore, we sought to determine the effects of bile acids on MUC2 MUC2 transcription in colon cancer cells via positive EGFR/PKC/Ras/ERK/CREB, PI3K/Akt/IkappaB/NF-kappaB and p38/MSK1/CREB pathways and negative JNK/c-Jun/AP-1 pathway.
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7669575
[]
[]
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24196785
[ "##", "CONCLUSION" ]
[ 0, 0 ]
## CONCLUSION
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12534642
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
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9841584
[ "Predisposition", "genetic", "testing", "is", "now", "possible", "for", "many", "hereditary", "cancer", "syndromes,", "including", "hereditary", "nonpolyposis", "colorectal", "cancer.", "The", "optimal", "management", "of", "the", "elevated", "risk", "for", "cancer", "in", "carriers", "of", "mutations", "for", "hereditary", "nonpolyposis", "colorectal", "cancer", "is", "unclear." ]
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Predisposition genetic testing is now possible for many hereditary cancer syndromes, including hereditary nonpolyposis colorectal cancer. The optimal management of the elevated risk for cancer in carriers of mutations for hereditary nonpolyposis colorectal cancer is unclear.
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25374237
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
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9731891
[ "In", "the", "125", "cases", "studied,", "there", "were", "53", "tumors", "with", "mutations", "of", "the", "p53", "gene.", "p53", "mutations", "correlated", "with", "lymph", "node", "metastases", "from", "right", "colon", "carcinoma", "cases", "(61%),", "and", "all", "cases", "with", "p53", "mutations", "and", "microsatellite", "instability", "were", "AJCC/UICC", "Stage", "III", "(Dukes", "Stage", "C).", "In", "the", "right", "colon", "carcinoma", "cases", "the", "rate", "of", "microsatellite", "instability", "was", "related", "to", "the", "tumor", "size", "(19%", "in", "tumors", "measuring", "<", "4", "cm,", "and", "34%", "in", "tumors", "measuring", ">", "4", "cm).", "No", "correlation", "between", "microsatellite", "instability", "and", "p53", "mutations", "was", "detected.", "In", "the", "left", "colon", "carcinoma", "cases,", "p53", "mutations", "were", "detected", "in", "41%", "of", "tumors", "and", "microsatellite", "instability", "in", "14%;", "neither", "finding", "was", "related", "to", "the", "tumor", "size.", "Mutations", "of", "the", "hMLH1", "and", "hMSH2", "mismatch", "repair", "genes", "were", "detected", "in", "7", "of", "24", "cases", "with", "marked", "microsatellite", "instability." ]
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In the 125 cases studied, there were 53 tumors with mutations of the p53 gene. p53 mutations correlated with lymph node metastases from right colon carcinoma cases (61%), and all cases with p53 mutations and microsatellite instability were AJCC/UICC Stage III (Dukes Stage C). In the right colon carcinoma cases the rate of microsatellite instability was related to the tumor size (19% in tumors measuring < 4 cm, and 34% in tumors measuring > 4 cm). No correlation between microsatellite instability and p53 mutations was detected. In the left colon carcinoma cases, p53 mutations were detected in 41% of tumors and microsatellite instability in 14%; neither finding was related to the tumor size. Mutations of the hMLH1 and hMSH2 mismatch repair genes were detected in 7 of 24 cases with marked microsatellite instability.
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9731891
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
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9609758
[ "Both", "receptors", "were", "overexpressed", "in", "tumors", "compared", "with", "normal", "samples.", "There", "was", "a", "relationship", "between", "the", "abundance", "of", "type", "II", "receptor", "expression", "and", "the", "degree", "of", "differentiation", "of", "the", "tumors", "but", "not", "the", "Dukes'", "staging", "or", "the", "localization", "of", "the", "neoplasias.", "No", "mutation", "was", "observed", "in", "the", "microsatellite-like", "regions", "of", "receptor", "II", "in", "any", "of", "the", "samples." ]
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Both receptors were overexpressed in tumors compared with normal samples. There was a relationship between the abundance of type II receptor expression and the degree of differentiation of the tumors but not the Dukes' staging or the localization of the neoplasias. No mutation was observed in the microsatellite-like regions of receptor II in any of the samples.
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25374237
[ "##", "MATERIALS", "AND", "METHODS" ]
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## MATERIALS AND METHODS
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22899730
[ "##", "RESULTS" ]
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## RESULTS
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23259783
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25421761
[ "Targeted", "agents", "increase", "response", "rates", "and", "improved", "overall", "survival", "in", "treatment", "of", "metastatic", "gastrointestinal", "cancer.", "Therefore,", "physicians", "pay", "more", "attention", "to", "the", "role", "of", "targeted", "agents", "in", "treatment", "of", "local", "advanced", "gastrointestinal", "cancer.", "The", "clinical", "trials", "are", "ongoing", "to", "evaluate", "the", "efficacy", "of", "Trastuzumab", "in", "neoadjuvant", "treatment", "of", "local", "advanced", "gastric", "cancer", "with", "HER-2", "gene", "over", "expression.", "Many", "studies", "reported", "Cetuximab", "plus", "chemotherapy", "as", "a", "conversion", "treatment", "improve", "R0", "resection", "rates", "and", "prolonged", "overall", "survival", "of", "the", "patients", "with", "potentially", "resectable", "colorectal", "cancer", "liver", "metastasis", "with", "wild", "type", "KRAS", "gene", "status.", "A", "phase", "III(", "clinical", "trial", "is", "assessing", "the", "conversion", "efficacy", "of", "Bevacizumab", "in", "unresectable", "disease", "with", "KRAS", "gene", "mutation", "HER-2", " ", "gene", "over", "expression.", "Many", "studies", "reported", "Cetuximab", "plus", "chemotherapy", "as", "a", "conversion", "treatment", "improve", "R0", "resection", "rates", "and", "prolonged", "overall", "survival", "of", "the", "patients", "with", "potentially", "resectable", "colorectal", "cancer", "liver", "metastasis", "with", "wild", "type", "KRAS", " ", "gene", "status.", "A", "phase", "III(", "clinical", "trial", "is", "assessing", "the", "conversion", "efficacy", "of", "Bevacizumab", "in", "unresectable", "disease", "with", "KRAS", " ", "gene", "mutation.", "Current", "evidence", "showed", "that", "neoadjuvant", "therapy", "of", "targeted", "agents", "did", "not", "prolong", "survival", "of", "patients", "with", "resectable", "liver", "metastasis.", "However,", "this", "is", "controversial.", "In", "neoadjuvant", "therapy", "of", "local", "advanced", "rectal", "cancer,", "Cetuximab", "did", "not", "improve", "the", "rates", "of", "pathological", "complete", "response", "in", "most", "of", "the", "phase", "II(", "trials.", "Furthermore,", "there", "are", "no", "phase", "III(", "trials", "to", "assess", "the", "role", "of", "Bevacizumab.", "Compared", "to", "chemotherapy", "alone", "for", "metastatic", "cancer,", "it", "is", "more", "important", "to", "evaluate", "the", "interaction", "and", "synergistic", "action", "of", "targeted", "agents,", "cytotoxic", "drugs,", "surgery", "and", "radiation,", "to", "make", "a", "scientific", "multidisciplinary", "model", "in", "comprehensive", "treatment", "of", "local", "advanced", "cancer." ]
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Targeted agents increase response rates and improved overall survival in treatment of metastatic gastrointestinal cancer. Therefore, physicians pay more attention to the role of targeted agents in treatment of local advanced gastrointestinal cancer. The clinical trials are ongoing to evaluate the efficacy of Trastuzumab in neoadjuvant treatment of local advanced gastric cancer with HER-2 gene over expression. Many studies reported Cetuximab plus chemotherapy as a conversion treatment improve R0 resection rates and prolonged overall survival of the patients with potentially resectable colorectal cancer liver metastasis with wild type KRAS gene status. A phase III( clinical trial is assessing the conversion efficacy of Bevacizumab in unresectable disease with KRAS gene mutation HER-2 gene over expression. Many studies reported Cetuximab plus chemotherapy as a conversion treatment improve R0 resection rates and prolonged overall survival of the patients with potentially resectable colorectal cancer liver metastasis with wild type KRAS gene status. A phase III( clinical trial is assessing the conversion efficacy of Bevacizumab in unresectable disease with KRAS gene mutation. Current evidence showed that neoadjuvant therapy of targeted agents did not prolong survival of patients with resectable liver metastasis. However, this is controversial. In neoadjuvant therapy of local advanced rectal cancer, Cetuximab did not improve the rates of pathological complete response in most of the phase II( trials. Furthermore, there are no phase III( trials to assess the role of Bevacizumab. Compared to chemotherapy alone for metastatic cancer, it is more important to evaluate the interaction and synergistic action of targeted agents, cytotoxic drugs, surgery and radiation, to make a scientific multidisciplinary model in comprehensive treatment of local advanced cancer.
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26925673
[ "Cellular", "proliferation,", "morphology", "and", "cell", "cycle", "analysis", "were", "carried", "out", "in", "addition", "to", "Western", "blotting", "for", "detecting", "total", "Akt", "and", "p-Akt", "(at", "Thr308", "Ak", "t", "(at", "Thr308", "and", "Ser473)", "in", "the", "presence", "and", "absence", "of", "different", "concentrations", "of", "EA.", "Cell", "proliferation", "was", "also", "assessed", "in", "cells", "transfected", "with", "different", "concentrations", "of", "K-Ras", "siRNA", "or", "incubated", "with", "ellagic", "acid", "following", "transfection." ]
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Cellular proliferation, morphology and cell cycle analysis were carried out in addition to Western blotting for detecting total Akt and p-Akt (at Thr308 Ak t (at Thr308 and Ser473) in the presence and absence of different concentrations of EA. Cell proliferation was also assessed in cells transfected with different concentrations of K-Ras siRNA or incubated with ellagic acid following transfection.
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26925673
[ "To", "evaluate", "the", "impact", "of", "cellular", "genetic", "make-", "up", "of", "two", "colon", "cancer", "cell", "lines", "with", "different", "genetic", "backgrounds,", "HCT-116", "(K-Ras-/p53+)", "and", "Caco-2", "(K-Ras+/", "p53-),", "on", "response", "to", "potential", "anti-tumour", "effects", "of", "EA.", "In", "addition,", "the", "influence", "of", "K-Ras", "silencing", "in", "HCT-", "116", "cells", "was", "investigated." ]
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To evaluate the impact of cellular genetic make- up of two colon cancer cell lines with different genetic backgrounds, HCT-116 (K-Ras-/p53+) and Caco-2 (K-Ras+/ p53-), on response to potential anti-tumour effects of EA. In addition, the influence of K-Ras silencing in HCT- 116 cells was investigated.
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24196785
[ "We", "previously", "conducted", "gene", "expression", "microarray", "analyses", "to", "identify", "novel", "indicators", "for", "colorectal", "cancer", "(CRC)", "metastasis", "and", "prognosis", "from", "which", "we", "identified", "PVT-1", "as", "a", "candidate", "gene.", "PVT-1,", "which", "encodes", "a", "long", "noncoding", "RNA,", "mapped", "to", "chromosome", "8q24", "whose", "copy-number", "amplification", " ", "is", "one", "of", "the", "most", "frequent", "events", "in", "a", "wide", "variety", "of", "malignant", "diseases.", "However,", "PVT-1", " ", "molecular", "mechanism", "of", "action", "remains", "unclear." ]
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We previously conducted gene expression microarray analyses to identify novel indicators for colorectal cancer (CRC) metastasis and prognosis from which we identified PVT-1 as a candidate gene. PVT-1, which encodes a long noncoding RNA, mapped to chromosome 8q24 whose copy-number amplification is one of the most frequent events in a wide variety of malignant diseases. However, PVT-1 molecular mechanism of action remains unclear.
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14734469
[ "We", "observed", "a", "strong", "correlation", "of", "BRAF", "mutation", "with", "hMLH1", "promoter", "methylation.", "BRAF", "mutations", "were", "present", "in", "13", "of", "15", "(87%)", "of", "the", "colorectal", "cell", "lines", "and", "cancers", "with", "methylated", "hMLH1,", "whereas", "only", "4", "of", "91", "(4%)", "of", "the", "cell", "lines", "and", "cancers", "with", "unmethylated", "hMLH1", "carried", "the", "mutations", "(P", "<", "0.00001).", "Sixteen", "of", "17", "mutations", "were", "at", "residue", "599", "(V599E).", "A", "BRAF", "mutation", "was", "also", "identified", "at", "residue", "463", "(G463V)", "in", "one", "cell", "line.", "In", "addition,", "BRAF", "mutations", "BRAF", " ", "mutations", "in", "26", "colorectal", "cancer", "cell", "lines,", "80", "sporadic", "colorectal", "cancers,", "and", "20", "tumors", "from", "HNPCC", "patients", "by", "DNA", "sequencing", "and", "sequence-specific", "PCR.", "The", "methylation", "status", "of", "the", "hMLH1", "gene", "was", "measured", "by", "either", "sequencing", "or", "restriction", "enzyme", "digestion", "after", "NaHSO(3)", "treatment." ]
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We observed a strong correlation of BRAF mutation with hMLH1 promoter methylation. BRAF mutations were present in 13 of 15 (87%) of the colorectal cell lines and cancers with methylated hMLH1, whereas only 4 of 91 (4%) of the cell lines and cancers with unmethylated hMLH1 carried the mutations (P < 0.00001). Sixteen of 17 mutations were at residue 599 (V599E). A BRAF mutation was also identified at residue 463 (G463V) in one cell line. In addition, BRAF mutations BRAF mutations in 26 colorectal cancer cell lines, 80 sporadic colorectal cancers, and 20 tumors from HNPCC patients by DNA sequencing and sequence-specific PCR. The methylation status of the hMLH1 gene was measured by either sequencing or restriction enzyme digestion after NaHSO(3) treatment.
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22810479
[ "##", "OBJECTIVE" ]
[ 0, 0 ]
## OBJECTIVE
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[ 1, 1, 1, 1, 1 ]
[ -100, 0, 0, 0, -100 ]
22545919
[ "##", "METHODS" ]
[ 0, 0 ]
## METHODS
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26302849
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
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18184403
[ "Expression", "of", "beclin-1,", "an", "autophagy-related", "protein,", "in", "gastric", "and", "colorectal", "cancers." ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
Expression of beclin-1, an autophagy-related protein, in gastric and colorectal cancers.
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26925673
[ "The", "results", "of", "the", "present", "study", "revealed", "that", "EA", "exerts", "anti-proliferative", "and", "dose-dependent", "pro-apoptotic", "effects.", "Cytostatic", "and", "cytotoxic", "effects", "were", "also", "observed.", "p-Akt", "(at", "Thr308", "and", "Ser473)", "was", "downregulated.", "Moreover,", "EA", "treatment", "was", "found", "to", "(i)", "reduce", "K-Ras", "K-Ras", "-/p53+)", "and", "Caco-2", "(K-Ras+/", "p53-),", "on", "response", "to", "potential", "anti-tumour", "effects", "of", "EA.", "In", "addition,", "the", "influence", "of", "K-Ras", "silencing", "in", "HCT-", "116", "cells", "was", "investigated." ]
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The results of the present study revealed that EA exerts anti-proliferative and dose-dependent pro-apoptotic effects. Cytostatic and cytotoxic effects were also observed. p-Akt (at Thr308 and Ser473) was downregulated. Moreover, EA treatment was found to (i) reduce K-Ras K-Ras -/p53+) and Caco-2 (K-Ras+/ p53-), on response to potential anti-tumour effects of EA. In addition, the influence of K-Ras silencing in HCT- 116 cells was investigated.
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24568449
[ "These", "findings", "supported", "that", "the", "miR-196a2", "rs11614913", "and", "miR-149", "rs2292832", "rs11614913", "rs2292832", "single", "nucleotide", "polymorphisms", " ", "in", "miR-146a,", "miR-196a", "miR-146a", ",", "miR-196a,", "miR-149", "and", "miR-499", "miR-149", " ", "and", "miR-499", "with", "colorectal", "cancer", "susceptibility.", "\n\n\n", "##", "BACKGROUND" ]
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These findings supported that the miR-196a2 rs11614913 and miR-149 rs2292832 rs11614913 rs2292832 single nucleotide polymorphisms in miR-146a, miR-196a miR-146a , miR-196a, miR-149 and miR-499 miR-149 and miR-499 with colorectal cancer susceptibility. ## BACKGROUND
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12534642
[ "(i)", "CYP1A2", "polymorphisms", "are", "in", "linkage", "disequilibrium.", "Therefore,", "only", "-164A-->C", "(CYP1A2*1F)", "and", "-2464T-->delT", "(CYP1A2*1D)", "need", "to", "be", "analysed", "in", "the", "routine", "assessment", "of", "CYP1A2", "CYP1A2", "single", "nucleotide", "polymorphisms", " ", "(SNPs)", "of", "the", "cytochrome", "P450", "enzyme", "1A2", "gene", "(CYP1A2)", "have", "been", "reported.", "Here,", "frequencies,", "linkage", "disequilibrium", "and", "phenotypic", "consequences", "of", "six", "SNPs", "are", "described." ]
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(i) CYP1A2 polymorphisms are in linkage disequilibrium. Therefore, only -164A-->C (CYP1A2*1F) and -2464T-->delT (CYP1A2*1D) need to be analysed in the routine assessment of CYP1A2 CYP1A2 single nucleotide polymorphisms (SNPs) of the cytochrome P450 enzyme 1A2 gene (CYP1A2) have been reported. Here, frequencies, linkage disequilibrium and phenotypic consequences of six SNPs are described.
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25374237
[ "This", "study", "provides", "the", "first", "evidence", "that", "survivin", "-31", "G/C", "and", "-241", "C/T", "SNP", "-31", "G/C", " ", "and", "-241", "C/T", "-241", "C/T", " ", "(rs17878467)", "and", "-625", "C/G", "(rs8073069)", "polymorphism", "in", "promotor", "site", "-625", "C/G", " ", "(rs8073069)", "polymorphism", "in", "promotor", "site", "of", "survivin", "gene", "associated", "with", "apoptosis", "was", "investigated", "using", "the", "polymerase", "chain", "reaction-restriction", "fragment", "length", "polymorphism", "(PCR-RFLP)", "method." ]
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This study provides the first evidence that survivin -31 G/C and -241 C/T SNP -31 G/C and -241 C/T -241 C/T (rs17878467) and -625 C/G (rs8073069) polymorphism in promotor site -625 C/G (rs8073069) polymorphism in promotor site of survivin gene associated with apoptosis was investigated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
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6300869
[ "Two", "human", "neuroendocrine", "tumor", "cell", "lines", "derived", "from", "a", "colon", "carcinoma", "contain", "either", "numerous", "double", "minute", "chromosomes", "(COLO", "320", "DM)", "or", "a", "homogeneously", "staining", "marker", "chromosome", "(COLO", "320", "HSR).", "We", "found", "amplification", "and", "enhanced", "expression", "of", "the", "cellular", "oncogene", "c-myc", "in", "both", "COLO", "320", "DM", "and", "HSR", "cells,", "and", "we", "were", "able", "to", "show", "that", "the", "homogeneously", "staining", "regions", "of", "the", "COLO", "320", "HSR", "marker", "chromosome", "contain", "amplified", "c-myc.", "From", "previous", "and", "present", "karyotypes,", "it", "appears", "that", "the", "homogeneously", "staining", "regions", "reside", "on", "a", "distorted", "X", "chromosome.", "Therefore,", "amplification", "of", "c-myc", "has", "been", "accompanied", "by", "translocation", " ", "of", "the", "gene", "from", "its", "normal", "position", "on", "chromosome", "8", "(8q24).", "Because", "double", "minute", "chromosomes", "were", "features", "of", "primary", "cultures", "from", "the", "original", "tumor,", "it", "seems", "reasonable", "to", "suspect", "that", "amplification", "of", "c-myc", "c-myc", ")", "in", "malignant", "neuroendocrine", "cells", "from", "a", "human", "colon", "carcinoma." ]
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Two human neuroendocrine tumor cell lines derived from a colon carcinoma contain either numerous double minute chromosomes (COLO 320 DM) or a homogeneously staining marker chromosome (COLO 320 HSR). We found amplification and enhanced expression of the cellular oncogene c-myc in both COLO 320 DM and HSR cells, and we were able to show that the homogeneously staining regions of the COLO 320 HSR marker chromosome contain amplified c-myc. From previous and present karyotypes, it appears that the homogeneously staining regions reside on a distorted X chromosome. Therefore, amplification of c-myc has been accompanied by translocation of the gene from its normal position on chromosome 8 (8q24). Because double minute chromosomes were features of primary cultures from the original tumor, it seems reasonable to suspect that amplification of c-myc c-myc ) in malignant neuroendocrine cells from a human colon carcinoma.
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9731891
[ "##", "CONCLUSIONS" ]
[ 0, 0 ]
## CONCLUSIONS
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26416897
[]
[]
[ 2, 3 ]
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[ 1, 1 ]
[ -100, -100 ]
1319833
[ "We", "have", "previously", "observed", "that", "the", "frequency", "of", "loss", "of", "heterozygosity", "(", "LOH", "loss", "of", "heterozygosity", " ", "(LOH)", "on", "chromosome", "18q", "was", "low", "in", "adenomas", "and", "intramucosal", "carcinomas,", "whereas", "invasive", "carcinomas", "exhibited", "a", "high", "frequency", "in", "familial", "adenomatous", "polyposis", "patients", "(M.", "Miyaki", "et", "al.,", "Cancer", "Res.,", "50:", "7166-7173,", "1990).", "In", "the", "present", "study,", "LOH", "at", "the", "DCC", " ", "locus", "on", "chromosome", "18q", "and", "the", "expression", "of", "DCC", "gene", "into", "mRNA", "were", "analyzed", "in", "colorectal", "tumors", "with", "distinct", "histopathological", "types.", "The", "carcinomas", "that", "showed", "18q", "LOH", "Loss", " ", "of", "expression", "of", "the", "DCC", "gene", "during", "progression", "of", "colorectal", "carcinomas", "in", "familial", "adenomatous", "polyposis", "and", "non-familial", "adenomatous", "polyposis", "patients." ]
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We have previously observed that the frequency of loss of heterozygosity ( LOH loss of heterozygosity (LOH) on chromosome 18q was low in adenomas and intramucosal carcinomas, whereas invasive carcinomas exhibited a high frequency in familial adenomatous polyposis patients (M. Miyaki et al., Cancer Res., 50: 7166-7173, 1990). In the present study, LOH at the DCC locus on chromosome 18q and the expression of DCC gene into mRNA were analyzed in colorectal tumors with distinct histopathological types. The carcinomas that showed 18q LOH Loss of expression of the DCC gene during progression of colorectal carcinomas in familial adenomatous polyposis and non-familial adenomatous polyposis patients.
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23132392
[ "Somatic", "MED12", "mutations", "in", "uterine", "leiomyosarcoma", "and", "colorectal", "cancer.", "\n\n\n", "##", "BACKGROUND" ]
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Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer. ## BACKGROUND
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9731891
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In the 125 cases studied, there were 53 tumors with mutations of the p53 gene. p53 mutations correlated with lymph node metastases from right colon carcinoma cases (61%), and all cases with p53 mutations and microsatellite instability were AJCC/UICC Stage III (Dukes Stage C). In the right colon carcinoma cases the rate of microsatellite instability was related to the tumor size (19% in tumors measuring < 4 cm, and 34% in tumors measuring > 4 cm). No correlation between microsatellite instability p53 mutations in sporadic right and left colon carcinoma: different clinical and molecular implications. ## BACKGROUND
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15987719
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Inherited biallelic mutations in the human MUTYH gene are responsible for the recessive syndrome--adenomatous colorectal polyposis (MUTYH associated polyposis, MAP)--which significantly increases the risk of colorectal cancer (CRC). Defective MUTYH activity causes G:C to T:A transversions in tumour APC and other genes thereby altering genomic integrity. We report that of the four established cell lines, derived from patients with the MAP phenotype and containing biallelic MUTYH mutations, three contain altered expressions of MUTYH protein (MUTYH Y165C(-/-), MUTYH mutations , three contain altered expressions of MUTYH protein (MUTYH Y165C(-/-), MUTYH 1103delC/G382D and MUTYH Y165C/G382D but not MUTYH MUTYH Y165C(-/-), MUTYH 1103delC/G382D and MUTYH Y165C/G382D but not MUTYH G382D(-/-)), but that all four cell lines have wild type levels of MUTYH mRNA. Mutant MUTYH MUTYH Y165C/G382D but not MUTYH G382D(-/-)), but that all four cell lines have wild type levels of MUTYH mRNA. Mutant MUTYH proteins in these four cell lines possess significantly lowered binding and cleavage activities with heteroduplex oligonucleotides containing A.8-oxoG and 8-oxoA.G A.8-oxoG APC and other genes thereby altering genomic integrity. We report that of the four established cell lines, derived from patients with the MAP phenotype and containing biallelic MUTYH mutations, three contain altered expressions of MUTYH protein (MUTYH Y165C(-/-), MUTYH 1103delC/G382D and MUTYH Y165C/G382D but not MUTYH G382D(-/-) ), but that all four cell lines have wild type levels of MUTYH mRNA. Mutant MUTYH proteins in these four cell lines possess significantly lowered binding and cleavage activities with heteroduplex oligonucleotides containing A.8-oxoG and 8-oxoA.G mispairs. Transfection of mitochondrial or nuclear MUTYH cDNAs partially correct altered MUTYH expression and activity in these defective cell lines. Finally, we surprisingly find that defective MUTYH MUTYH MUTYH gene are defective in DNA damage binding and repair.
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19706845
[ "##", "RESULTS" ]
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23497483
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In order to understand the role of somatic mutations in human colorectal cancers, we characterized the mutation spectrum in two colorectal tumor tissues and their matched normal tissues, by analyzing deep-sequenced transcriptome data.
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12534642
[ "##", "RESULTS" ]
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## RESULTS
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9731891
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In the 125 cases studied, there were 53 tumors with mutations of the p53 gene. p53 mutations correlated with lymph node metastases from right colon carcinoma cases (61%), and all cases with p53 mutations and microsatellite instability exons 5-8 p53 gene was assessed by polymerase chain reaction (PCR), single strand conformation polymorphism, and sequencing at exons 5-8. Microsatellite instability was analyzed with five microsatellite markers at chromosome 18. The mismatch repair genes hMLH1 and hMSH2 were studied in tumors found to have microsatellite instability by PCR and sequencing.
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9609758
[ "##", "RESULTS" ]
[ 0, 0 ]
## RESULTS
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22899730
[ "Among", "1,980", "cases", "tested,", "12%", "were", "BRAF", "c.1799T>A", "(p.V600E)", "mutation-positive", "(n", "=", "247).", "BRAF-mutated", "CRC", "was", "associated", "with", "poorer", "disease-specific", "survival", "adjusting", "for", "age,", "sex,", "time", "from", "diagnosis", "to", "enrollment,", "stage,", "and", "MSI", "status", "(HR,", "1.43;", "95%", "CI,", "1.05-1.95).", "This", "association", "was", "limited", "to", "cases", "diagnosed", "at", "ages", "<50", "(HR,", "3.06;", "95%", "CI,", "1.70-5.52)", "and", "was", "not", "evident", "in", "cases", "with", "MSI-high", "tumors", "(HR,", "0.94;", "95%", "CI,", "0.44-2.03).", "Associations", "with", "overall", "survival", "were", "similar." ]
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Among 1,980 cases tested, 12% were BRAF c.1799T>A (p.V600E) mutation-positive (n = 247). BRAF-mutated CRC was associated with poorer disease-specific survival adjusting for age, sex, time from diagnosis to enrollment, stage, and MSI status (HR, 1.43; 95% CI, 1.05-1.95). This association was limited to cases diagnosed at ages <50 (HR, 3.06; 95% CI, 1.70-5.52) and was not evident in cases with MSI-high tumors (HR, 0.94; 95% CI, 0.44-2.03). Associations with overall survival were similar.
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17234021
[ "Cost-effectiveness", "of", "surveillance", "programs", "for", "families", "at", "high", "and", "moderate", "risk", "of", "hereditary", "non-polyposis", "colorectal", "cancer.", "\n\n\n", "##", "OBJECTIVES" ]
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Cost-effectiveness of surveillance programs for families at high and moderate risk of hereditary non-polyposis colorectal cancer. ## OBJECTIVES
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25029911
[ "As", "a", "novel", "candidate", "metastasis", "suppressor", "gene,", "Nasopharyngeal", "carcinoma-associated", "gene", "6", "(NGX6)", "is", "involved", "in", "cellular", "growth,", "cell", "cycle", "progression", "and", "tumor", "angiogenesis.", "Previous", "studies", "have", "shown", "that", "NGX6", "gene", "is", "down-regulated", "in", "colorectal", "cancer", "(CRC).", "However,", "little", "is", "known", "about", "its", "transcriptional", "regulation." ]
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As a novel candidate metastasis suppressor gene, Nasopharyngeal carcinoma-associated gene 6 (NGX6) is involved in cellular growth, cell cycle progression and tumor angiogenesis. Previous studies have shown that NGX6 gene is down-regulated in colorectal cancer (CRC). However, little is known about its transcriptional regulation.
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25029911
[ "We", "defined", "the", "minimal", "promoter", "of", "NGX6", "gene", "in", "a", "186-bp", "region", "(from-86", "to", "+100)", "through", "mutation", "construct", "methods", "and", "luciferase", "assays.", "Results", "from", "Electrophoretic", "mobility", "shift", "assays", "(EMSA)", "and", "Chromatin", "immunoprecipitation", "(ChIP)", "revealed", "that", "Early", "growth", "response", "gene", "1", "(Egr-1)", "binds", "to", "the", "Sp1/Egr-1", "overlapping", "site", "of", "NGX6", "minimal", "promoter.", "Overexpression", "of", "Egr-1", "increased", "the", "promoter", "activity", "and", "mRNA", "level", "of", "NGX6", "gene;", "while", "knock-down", "of", "endogenous", "Egr-1", "decreased", "mRNA", "expression", "of", "NGX6", "gene." ]
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We defined the minimal promoter of NGX6 gene in a 186-bp region (from-86 to +100) through mutation construct methods and luciferase assays. Results from Electrophoretic mobility shift assays (EMSA) and Chromatin immunoprecipitation (ChIP) revealed that Early growth response gene 1 (Egr-1) binds to the Sp1/Egr-1 overlapping site of NGX6 minimal promoter. Overexpression of Egr-1 increased the promoter activity and mRNA level of NGX6 gene; while knock-down of endogenous Egr-1 decreased mRNA expression of NGX6 gene.
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9439149
[ "To", "obtain", "a", "better", "understanding", "of", "the", "molecular", "mechanism", "of", "gastric", "carcinogenesis,", "microsatellite", "instability", " ", "was", "examined", "at", "6", "gene", "loci", "(", "D2S71", ",", "D2S119,", "D3S1067,", "D6S87,", "D8S87", ",", "D11S905)", "in", "77", "gastric", "carcinomas", "(40", "cases", "of", "young", "patients", "and", "37", "cases", "of", "elderly", "patients)." ]
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To obtain a better understanding of the molecular mechanism of gastric carcinogenesis, microsatellite instability was examined at 6 gene loci ( D2S71 , D2S119, D3S1067, D6S87, D8S87 , D11S905) in 77 gastric carcinomas (40 cases of young patients and 37 cases of elderly patients).
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1347643
[ "Carcinogenesis", "is", "a", "multistage", "process", "that", "has", "been", "characterized", "both", "by", "the", "activation", "of", "cellular", "oncogenes", "and", "by", "the", "loss", "of", "function", "of", "tumor", "suppressor", "genes.", "Colorectal", "cancer", "has", "been", "associated", "with", "the", "activation", "of", "ras", "oncogenes", "and", "with", "the", "deletion", " ", "of", "multiple", "chromosomal", "regions", "including", "chromosomes", "5q,", "17p,", "and", "18q.", "Such", "chromosome", "loss", " ", "is", "often", "suggestive", "of", "the", "deletion", "or", "loss", "of", "function", "deletion", " ", "or", "loss", "of", "function", "of", "tumor", "suppressor", "genes.", "The", "candidate", "tumor", "suppressor", "genes", "from", "these", "regions", "are,", "respectively,", "MCC", " ", "and/or", "APC,", "p53,", "and", "DCC.", "In", "order", "to", "further", "our", "understanding", "of", "the", "molecular", "and", "genetic", "mechanisms", "involved", "in", "tumor", "progression", "and,", "thereby,", "of", "normal", "cell", "growth,", "it", "is", "important", "to", "determine", "whether", "defects", "in", "one", "or", "more", "of", "these", "loci", "contribute", "functionally", "in", "the", "progression", "to", "malignancy", "in", "colorectal", "cancer", "and", "whether", "correction", "of", "any", "of", "these", "defects", "restores", "normal", "growth", "control", "in", "vitro", "and", "in", "vivo.", "To", "address", "this", "question,", "we", "have", "utilized", "the", "technique", "of", "microcell-mediated", "chromosome", "transfer", "to", "introduce", "normal", "human", "chromosomes", "5,", "17,", "and", "18", "individually", "into", "recipient", "colorectal", "cancer", "cells.", "Additionally,", "chromosome", "15", "was", "introduced", "into", "SW480", "cells", "as", "an", "irrelevant", "control", "chromosome.", "While", "the", "introduction", "of", "chromosome", "17", "into", "the", "tumorigenic", "colorectal", "cell", "line", "SW480", "yielded", "no", "viable", "clones,", "cell", "lines", "were", "established", "after", "the", "introduction", "of", "chromosomes", "15,", "5,", "and", "18", "APC", ",", "p53,", "and", "DCC.", "In", "order", "to", "further", "our", "understanding", "of", "the", "molecular", "and", "genetic", "mechanisms", "involved", "in", "tumor", "progression", "and,", "thereby,", "of", "normal", "cell", "growth,", "it", "is", "important", "to", "determine", "whether", "defects", "in", "one", "or", "more", "of", "these", "loci", "contribute", "functionally", "in", "the", "progression", "to", "malignancy", "in", "colorectal", "cancer", "and", "whether", "correction", "of", "any", "of", "these", "defects", "restores", "normal", "growth", "control", "in", "vitro", "and", "in", "vivo.", "To", "address", "this", "question,", "we", "have", "utilized", "the", "technique", "of", "microcell-mediated", "chromosome", "transfer", "to", "introduce", "normal", "human", "chromosomes", "5,", "17,", "and", "18", "p53", "loss", "of", "function", " ", "of", "tumor", "suppressor", "genes.", "Colorectal", "cancer", "has", "been", "associated", "with", "the", "activation", "of", "ras", "oncogenes", "and", "with", "the", "deletion", "of", "multiple", "chromosomal", "regions", "including", "chromosomes", "5q,", "17p,", "and", "18q.", "Such", "chromosome", "loss", "is", "often", "suggestive", "of", "the", "deletion", "or", "loss", "of", "function", "of", "tumor", "suppressor", "genes.", "The", "candidate", "tumor", "suppressor", "genes", "from", "these", "regions", "are,", "respectively,", "MCC", "and/or", "APC,", "p53,", "and", "DCC", "transfer", "." ]
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Carcinogenesis is a multistage process that has been characterized both by the activation of cellular oncogenes and by the loss of function of tumor suppressor genes. Colorectal cancer has been associated with the activation of ras oncogenes and with the deletion of multiple chromosomal regions including chromosomes 5q, 17p, and 18q. Such chromosome loss is often suggestive of the deletion or loss of function deletion or loss of function of tumor suppressor genes. The candidate tumor suppressor genes from these regions are, respectively, MCC and/or APC, p53, and DCC. In order to further our understanding of the molecular and genetic mechanisms involved in tumor progression and, thereby, of normal cell growth, it is important to determine whether defects in one or more of these loci contribute functionally in the progression to malignancy in colorectal cancer and whether correction of any of these defects restores normal growth control in vitro and in vivo. To address this question, we have utilized the technique of microcell-mediated chromosome transfer to introduce normal human chromosomes 5, 17, and 18 individually into recipient colorectal cancer cells. Additionally, chromosome 15 was introduced into SW480 cells as an irrelevant control chromosome. While the introduction of chromosome 17 into the tumorigenic colorectal cell line SW480 yielded no viable clones, cell lines were established after the introduction of chromosomes 15, 5, and 18 APC , p53, and DCC. In order to further our understanding of the molecular and genetic mechanisms involved in tumor progression and, thereby, of normal cell growth, it is important to determine whether defects in one or more of these loci contribute functionally in the progression to malignancy in colorectal cancer and whether correction of any of these defects restores normal growth control in vitro and in vivo. To address this question, we have utilized the technique of microcell-mediated chromosome transfer to introduce normal human chromosomes 5, 17, and 18 p53 loss of function of tumor suppressor genes. Colorectal cancer has been associated with the activation of ras oncogenes and with the deletion of multiple chromosomal regions including chromosomes 5q, 17p, and 18q. Such chromosome loss is often suggestive of the deletion or loss of function of tumor suppressor genes. The candidate tumor suppressor genes from these regions are, respectively, MCC and/or APC, p53, and DCC transfer .
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24568449
[ "##", "METHODOLOGY/PRINCIPAL", "FINDINGS" ]
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## METHODOLOGY/PRINCIPAL FINDINGS
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26925673
[ "Cellular", "genetic", "makeup", "(K-Ras-/p53-)", "was", "not", "likely", "to", "impose", "limitations", "on", "targeting", "EA", "in", "treatment", "of", "colon", "cancer.", "EA", "had", "a", "multi-disciplinary", "pro-apoptotic", "anti-proliferative", "approach,", "having", "inhibited", "Akt", "phosphorylation,", "induced", "cell", "cycle", "arrest", "and", "showed", "an", "anti-proliferative", "potential", "in", "HCT-116", "cells", "(expressing", "mutant", "K-Ras)." ]
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Cellular genetic makeup (K-Ras-/p53-) was not likely to impose limitations on targeting EA in treatment of colon cancer. EA had a multi-disciplinary pro-apoptotic anti-proliferative approach, having inhibited Akt phosphorylation, induced cell cycle arrest and showed an anti-proliferative potential in HCT-116 cells (expressing mutant K-Ras).
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26416897
[ "Our", "study", "demonstrates", "for", "the", "first", "time", "that", "variations", "TBK1", ",", "CCL18,", "and", "IRF3)", "were", "tested", "for", "associations", "with", "clinical", "outcomes", "in", "a", "discovery", "cohort", "of", "228", "participants", "in", "TRIBE", "trial", "(NCT00719797),", "then", "validated", "in", "248", "KRAS", "exon2", "(KRAS)", "wild-type", "participants", "in", "FIRE3", "trial", "(NCT00433927).", "FIRE3-cetuximab", "cohort", "served", "as", "a", "negative", "control." ]
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Our study demonstrates for the first time that variations TBK1 , CCL18, and IRF3) were tested for associations with clinical outcomes in a discovery cohort of 228 participants in TRIBE trial (NCT00719797), then validated in 248 KRAS exon2 (KRAS) wild-type participants in FIRE3 trial (NCT00433927). FIRE3-cetuximab cohort served as a negative control.
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25029911
[ "##", "RESULTS" ]
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## RESULTS
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22810479
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: The pooled HR for the association between K-ras gene mutations and overall survival in patients with colorectal cancer was 1.04 (95% CI: 0.99-1.10, p = 0.11). Subgroup analysis showed significant reductions in the overall survival associated with mutations at K-ras codon 12, the articles that reported HR directly, and the studies published before and after 2005, although publication bias was present. All the associations disappeared after adjustment with the trim-and-fill method. The pooled HR of 3 studies examining mutations at K-ras codon 13 was 1.47 (95% CI: 1.09-1.97, p = 0.02), and no publication bias was observed. No significant association was observed in different study regions.
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24435063
[ "##", "METHODS" ]
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## METHODS
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9731891
[ "##", "CONCLUSIONS" ]
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## CONCLUSIONS
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