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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was performed to determine the relationship between the expression of CD44, p53 and NM23 and the metastatic potential of colorectal cancer. Frozen sections of 56 cases of colorectal cancer were immunohistologically examined for the expression of CD44, p53 and NM23. Positive immunoreactivity was found in 30 of 56 cases (54%) in CD44, 26 of 56 (46%) in p53 and 20 of 56 in NM23 (36%), respectively. There was no significant relationship between the expression of these molecules and clinicopathological findings such as age, sex, size, location of tumor, histological type, serosal invasion, peritoneal dissemination, lymph node metastasis, extramural venous spread and tumor stage; however, when examining the relationship between the expression of these molecules and prognosis in terms of hepatic metastasis and recurrence after curative operation, a significant association was seen in the expression of CD44, but none in p53 and NM23. It was suggested that expression of CD44 could be used as a possible indicator to predict metastatic potential of colorectal cancer.
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PMID:Positive relationship between expression of CD44 and hepatic metastases in colorectal cancer. 753 7

The human nm23 gene, a candidate metastatic suppressor gene, consists of two genes, nm23-H1 and nm23-H2. The potential mutation in the nm23-H1 gene was examined in colorectal cancer using a reverse transcription polymerase chain reaction amplification followed by DNA sequencing analysis. Genomic alterations in the nm23 gene were also examined by Southern hybridization. Genetic alterations either as a deletion in the coding sequence of nm23-H1 or as an allelic deletion were detected in four among eight colorectal adenocarcinomas associated with metastases in lymph nodes, lung, or liver. No alteration was observed in 12 additional colorectal cancer specimens without metastasis. These results provide first evidence for novel mutation in the nm23 gene and demonstrate a correlation between the mutation in the nm23 gene and metastasis in colorectal oncogenesis which suggests that the nm23 gene plays a role in the causation of metastasis.
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PMID:Mutation in the nm23 gene is associated with metastasis in colorectal cancer. 833 71

We report here the use of multiplex fluorescent polymerase chain reaction (PCR) for quantitative allele loss detection using microsatellites with 2-5 base pair repeat motifs. Allele loss of APC, DCC, p53 and RB1 in colorectal tumours has been reported previously using a variety of methods. However, not all workers used intragenic markers. We have used microsatellite polymorphisms which map within, or are closely linked to, these tumour-suppressor gene loci in order to determine whether these loci are indeed the targets for alteration in colorectal cancer. In addition, we have assayed two other tumour-suppressor genes, WT1 and NF1, to see whether they play a role in colorectal carcinogenesis. The putative metastasis-suppressor gene, NM23, was also investigated since there have been conflicting reports about its involvement in colorectal carcinogenesis. Allele loss was detected at the DCC (29%), p53 (66%), RB1 (50%) and NF1 (14%) loci and in the APC/MCC region (50%), but not at the WT1 or NM23 loci. These rapid, and mostly gene-specific, fluorescent multiplex PCR assays for allele loss detection could be modified to devise a single molecular diagnostic test for the important lesions in colorectal cancer.
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PMID:Frequency of allele loss of DCC, p53, RBI, WT1, NF1, NM23 and APC/MCC in colorectal cancer assayed by fluorescent multiplex polymerase chain reaction. 794 85

It has been proposed that nm23-H1, a candidate suppressor gene for metastasis, plays an important role in metastasis formation of human tumours. In order to investigate its role in the progression of colorectal cancer, we analysed 22 liver metastases of this malignancy with respect to mutational changes, loss of heterozygosity and expression levels of nm23-H1. Although genetic alterations in nm23-H1 have recently been described in those colorectal adenocarcinomas which give rise to distant metastases, we were unable to detect any mutation in the coding sequence of nm23-H1 in the metastatic tissue itself. We further analysed the metastases with respect to allelic deletions at the chromosomal locus of nm23. However, no loss of heterozygosity could be detected in ten informative cases. Moreover, the mRNA expression levels of nm23-H1 in the metastatic tissues were not significantly different from those in normal colon mucosa. Thus, although nm23-H1 might be involved in metastasis suppression of certain tumour types, in colorectal tumour progression its role remains to be determined.
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PMID:Expression and mutational analysis of Nm23-H1 in liver metastases of colorectal cancer. 798 Oct 87

Alterations in multiple oncogenes and multiple tumor suppressor genes are observed in human gastro-intestinal cancer. Among them, the most frequently implicated in malignancy and metastasis of esophageal carcinoma may be amplification and overexpression of the human cyclin D gene. In gastric carcinoma, amplification and abnormal expression of the c-met gene encoding receptor for hepatocyte growth factor (HGF) may contribute to the tumor progression and metastasis. Interaction between cadherin in c-met overexpressed tumor cells and HGF from fibroblast may play an important role in morphogenesis of two histological types of stomach cancer. During stomach carcinogenesis the clone having critical p53 mutations may expand selectively to make up a finally advanced stage of malignancy and show metastasis. In colorectal cancer, loss of heterozygosity of the RB, p53 and DCC genes is frequently associated with liver metastasis. Overexpression of nm23 may participate in carcinogenesis and the reduction in nm23 expression is involved in metastasis in gastric and colorectal cancers.
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PMID:[Metastasis related genes and malignancy in human esophageal, gastric and colorectal cancers]. 809 50

Nm23 is a putative metastasis suppressor gene and alterations in this gene have been reported in colorectal carcinomas suggestive of a role for nm23 in the dissemination of these tumours. In this study we used an affinity purified polyclonal antibody, ab-11, on formalin-fixed, paraffin-embedded sections of colorectal carcinomas from 46 patients in a three-stage avidin-biotin complex immunoperoxidase technique. Follow-up of these patients was until time of death or for 5 years, with a mean time of 31.2 months. Two observers scored the staining results from 1 to 3 according to the proportion of tumour cells positive. The association of nm23 staining with survival, sex, age, vascular invasion, and Dukes' stage was determined using Cox's regression model. The association of death from colorectal cancer and nm23 status reached marginal significance in this study (P = 0.0417). Moreover, there is some suggestion of a protective effect from nm23 as the relative risk of dying from colorectal cancer for each increment of nm23 positivity is 0.573 (95 per cent confidence limits 0.34-0.98).
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PMID:Nm23 'anti-metastatic' gene product expression in colorectal carcinoma. 819 29

The expression of nm23-H1 mRNA and protein was studied in colorectal cancers by Northern blotting and immunohistochemistry. All 21 colorectal cancers studied by Northern blotting had increased levels of nm23-H1 mRNA relative to the adjacent normal colonic mucosa. Increased nm23-H1 protein expression was also observed in all 36 colorectal cancer cases including those studied by Northern blotting. There was no significant correlation between nm23-H1 expression and tumour histology, serosal invasion, lymphatic invasion, venous invasion, or lymph node metastasis. However, the expression of both mRNA and protein was significantly lower in tumours associated with liver metastasis than in those without such metastasis. These observations indicate that the nm23 gene may play a role in the suppression of liver metastasis of colorectal cancer.
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PMID:Inverse association of nm23-H1 expression by colorectal cancer with liver metastasis. 821 91

To facilitate further mutational analysis of NM13-H1, a human metastasis suppressor gene, we have established its genomic organization. NM23-H1 is composed of five exons, spanning a genomic DNA fragment of 10 kb. Using oligonucleotide primers flanking each exon, PCR-SSCP analysis was performed on genomic DNAs of healthy individuals. A common polymorphism, a C to T transition, was detected 30 nucleotides upstream from the 5' splice site flanking exon 1. As NM23-H1 allele loss and altered expression have been reported in colorectal cancer, genomic DNAs of 20 colorectal tumors were analyzed for the presence of gene-specific mutations by PCR-SSCP: no abnormal sequences were detected within the coding and splice site regions of the NM23-H1 gene. This finding suggests that NM23-H1 mutations are rare events in human colorectal cancer.
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PMID:Genomic PCR-SSCP analysis of the metastasis associated NM23-H1 (NME1) gene: a study on colorectal cancer. 829 27

Allelic imbalance at the NME locus on chromosome 17q21 was analyzed in colorectal cancer patients using a highly polymorphic microsatellite repeat sequence within NME1 itself. Duplicate samples of carcinoma and adjacent normal tissue was obtained by microdissection from 6 to 7-microns paraffin sections of 94 primary carcinomas (treatment years 1979-1993) and available lymph node and liver secondaries. In 55 patients informative (heterozygous) at this locus, allelic imbalance was examined in primary and secondary carcinomas. Microsatellite instability prevented assessment of allelic balance in two cases, and there was no evidence of homozygous loss at NME1 in any case analyzed. Allelic imbalance at the NME locus in carcinomas was frequent (27/53; 51%), and concordant results were obtained between primary carcinoma and secondary deposits in 30 of 33 (91%) cases. Three discordant cases showed allelic imbalance in secondary deposits but not the primary lesion. Although frequent, allelic imbalance at NME1 had no relationship to Dukes' stage at presentation or with subsequent hepatic metastasis, nor with the primary carcinoma site (proximal versus distal), tumor size, or mitotic or apoptotic index. Moreover, neither disease-free nor overall survival differed between patients with carcinomas showing NME1 allelic imbalance and patients with carcinomas that did not. Our results show that although allelic imbalance is frequent at the NME locus in primary and secondary colorectal carcinomas, there is no evidence to link this with clinical or pathological features or with metastatic potential. Microsatellite PCR and microdissection of enriched populations of carcinoma cells allowed uniformly successful analysis of samples from archival formalin-fixed paraffin-embedded tissue up to 15 years old and clear assessment of allelic imbalance in tumor specimens. Target sequences (e.g., microsatellites and minisatellites) up to approximately 200-250 bp may be reliably analyzed for allelic balance, suggesting that this method is of general utility in the genetic analysis of primary and metastatic neoplasia.
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PMID:Allelic imbalance at NME1 in microdissected primary and metastatic human colorectal carcinomas is frequent but not associated with metastasis to lymph nodes or liver. 863 Oct 33

Nm23 gene codifies for a nucleoside diphosphate kinase allowing the intracellular transduction of the signals. In colorectal cancer nm23 protein expression seems related to the progression of the disease. By immunohistochemistry we have studied the intracytoplasmatic nm23 H1 protein expression in 20 patients affected by colorectal cancer at initial stage. In 12 cases it resulted elevated and in four the disease recurred. The overexpression was not correlated with other prognostic factors. Nm23 H1-positive patients affected by colorectal cancer at initial stage could be considered at risk for disease recurrence and included in a more frequent follow-up protocol.
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PMID:Early stage human colorectal cancer: prognostic value of nm23-H1 protein overexpression. 902 21


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