Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A prospective study analysed the prognostic value of nm23-H1 allelic deletions in colorectal cancer. Of 21 patients with no evidence of distant metastases at initial operation, 11 showed nm23-H1 allelic deletions (including 1 homozygous deletion); 10 had no nm23-H1 deletions. After median follow-up of 25 months, distant metastases had developed in 8 of 11 (73%) patients with nm23-H1 deletions but in only 2 of 10 (20%) without nm23-H1 deletions (p less than 0.03). Tests with probe YNZ 22.1, near p53, showed no significant association with distant metastases. nm23-H1 may be, or may be located near, a late-acting suppressor gene in colorectal carcinoma, in which deletions may have prognostic value.
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PMID:Association of nm23-H1 allelic deletions with distant metastases in colorectal carcinoma. 167 68

Freshly resected human non-small cell lung cancer (NSCLC) has been successfully transplanted and propagated subcutaneously in nude mice (Cancer Letters 61 (1991) 53-60). We used this model to study the changes of the human metastasis suppressor genes, nm23-H1 and nm23-H2, through the process of propagation and metastasis of human NSCLC. Using a non-radioisotopic Southern analysis, the nm23-H1 and nm23-H2 genes were detected without evidence of deletion in the early generations of the tumor grafts. These genes, however, were absent from the tumor grafts sampled past 4 generations of propagation and from all the propagated metastases originated from the subcutaneous grafts. Further restriction analysis revealed that only mouse DNA, but no human Alu DNA, was present in the tumor specimens which lacked the human nm23 genes. Thus, there is a loss of human DNA but a gain of mouse DNA in the propagated tumors originated from the transplanted human NSCLC. The mechanisms of loss of human DNA in these propagated tumors in nude mice have yet to be delineated.
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PMID:Loss of nm23 and Alu DNA in human lung cancer propagated in nude mice. 749 58

The NM23 gene family (nm23-H1 and nm23-H2) has been reported as a measure of metastatic potential. The goal of this study was to discriminate nm23-H1 and nm23-H2 gene expression in benign and malignant human prostate tissue and to determine the relationship of their expression to tumor stages. Specimens included 5 benign prostatic hyperplasias (BPH), 11 primary prostate adenocarcinomas (CaP) (5 stage B, 5 stage C and 1 stage D1), 2 pelvic lymph nodes with metastases and 3 prostate cancer cell lines derived from metastatic lesions. Polymerase chain reaction analysis of mRNA (RNA/PCR) was used to amplify transcripts of both NM23 genes and a normalizing gene (c-N-ras) to determine the relative levels of expression. A significant difference was shown between the BPH specimens and the cell lines from metastatic prostate cancer for nm23-H2 expression (p = 0.037) and the nm23-H1/nm23-H2 gene expression ratio (p = 0.037). The nm23-H1/nm23-H2 ratio increased significantly (p = 0.026, tau-b = 0.377) from BPH, through the CaP stages, to the cell lines. The expression of nm23-H2 decreased significantly (p = 0.002, tau-b = -0.517) from BPH, through the CaP stages, to the cell lines. Thus, while nm23-H2 appears to be significant for characterizing stages of CaP, an understanding of the metastatic phenotype will require further analysis of both NM23 genes.
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PMID:Quantitation of NM23 expression in human prostate tissues. 751 52

The majority of cancer patients succumb to the consequences of metastatic disease. A correlation of increased nm23 expression to low metastatic potential has been established in several malignancies, based on published prognostic studies with tumour cohorts and transfection studies. Transfection of highly metastatic MDA-MB-435 human breast carcinoma cells with nm23-H1 cDNA resulted in a significant reduction in the metastatic potential in vivo. These transfections also showed inhibition of colonisation and motility, as well as morphological and biosynthetic differentiation in vitro. The biochemical mechanism of Nm23-H1 action, as well as the identity of proteins involved in its functional biochemical pathway, are still unknown. We summarise published and recent research concerning the role of the nm23 gene in metastasis and normal cellular differentiation.
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PMID:The potential roles of nm23 in cancer metastasis and cellular differentiation. 757 99

In recent years, a tumor suppressor gene nm23 has been found to be associated with decreased tumor metastatic potential. Allelic deletion, mutation and low expression of this gene has been correlated with tumor metastatic potential in a number of tumors. There are two known isotypes of human nm23 gene, named nm23-H1 and nm23-H2. We examined DNA from 23 cases of colorectal carcinomas and their corresponding normal mucosa using Southern blot hybridization with nm23-H1 cDNA probe. Five cases with allelic deletion of nm23-H1 gene were found, with allelic deletion rate of 57. 1% (4/7) in cases with metastasis to lymph node, liver or other organs, and 6.2% (1/16) in cases without metastases (P < 0.005). There is no correlation between allelic deletion and tumor size, location or differentiation. This result indicates that nm23-H1 gene plays an important role in the metastasis of colorectal carcinoma.
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PMID:[Correlation study of allelic gene deletion of nm23-H1 and human colorectal carcinoma metastasis]. 758 91

The genetic events involved in the development of metastases of epithelial ovarian cancer are largely unknown. One gene postulated to play a role in tumour metastasis suppression is NME1 (nm23-H1), and an inverse relationship between NME1 expression and metastatic potential has been observed for some solid tumours. In this study we have investigated the levels of mRNA expression of the 2 isoforms of the NME gene, NME1 and NME2. A maximum of 45 tumours samples from 33 patients were available for Northern blot analysis. We observed variable levels expression of NME1 and NME2 mRNA. The average level of NME1, but not NME2, mRNA expression was statistically higher in metastatic biopsies when compared with primary tumour biopsies. To examine the possible tumour suppressor gene role of NME1 in ovarian tumours, 76 patients were investigated by Southern blot analysis to determine the rate of allelic deletion. Allele loss at 5 other chromosome 17 loci (D17S5, TP53, NF1, D17S74, D17S4) was also evaluated for many of these 76 patients. Allele loss was observed in 22/30 (73%) informative patients at the NME1 locus. We also observed high rates of allele loss at the other loci evaluated. No correlations with clinical stage, histological subtype or patient survival were observed in either mRNA or DNA analyses. We have established that tumour progression in ovarian cancer is accompanied by over-expression of the NME1 gene; however, despite high rates of allele loss at the NME1 locus, the concept that NME1 may be a candidate tumour suppressor gene in ovarian cancer cannot be confirmed by this study.
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PMID:Increased expression of the NME1 gene is associated with metastasis in epithelial ovarian cancer. 762 7

Alteration of expression levels of the nm23 genes has previously been correlated with metastatic status of ovarian epithelial carcinoma. To elucidate the relevance of the qualitative changes of the nm23 genes to progression of ovarian carcinoma and/or to nm23 expression levels of the tumour, 41 samples of epithelial ovarian tumours [three benign, three low malignant potential (LMP), and 35 frankly malignant tumours] were studied for mutation of the nm23-H1 and the nm23-H2 genes using single-strand conformational polymorphism (SSCP) analysis. In addition, loss of heterozygosity (LOH) at the nm23 locus on chromosome 17q was studied by CA repeat polymorphism analysis. Mutation of the K-ras gene was also analysed in the same specimens. A novel mutation of the nm23 gene was found in one case of stage III serous carcinoma without lymph model metastases. Sequencing of the subcloned mutant cDNA revealed a missense mutation from TGG to CGG at codon 133 of the nm23-H2 gene, resulting in a change from Trp to Arg. LOH at the nm23 locus was detected in 5 of 23 (21.7%) informative cases of ovarian carcinoma. Mutation of the K-ras gene was detected in 2 of 35 (5.7%) carcinomas at codons 12 and 13 respectively. There was no correlation between clinical stage or metastatic status of ovarian carcinoma and nm23 mutation, LOH at the nm23 locus or K-ras mutation. The expression levels of both the nm23-H1 and the nm23-H2 genes were lower in the tumour with nm23-H2 mutation and higher in those with K-ras mutation. This suggests that mutation of the nm23 genes and the K-ras gene affects carcinogenesis or progression of ovarian carcinoma by modulating expression of the nm23 genes.
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PMID:Mutation of the nm23 gene, loss of heterozygosity at the nm23 locus and K-ras mutation in ovarian carcinoma: correlation with tumour progression and nm23 gene expression. 766 82

The nm23 gene products/nucleoside diphosphate (NDP) kinase expression in prostate carcinomas and benign hyperplasias was evaluated immunohistochemically. Monoclonal antibodies against nm23-H1 and nm23-H2 proteins were prepared using the corresponding proteins fused with glutathione S-transferase as immunogens. Of the 80 cases of nonmetastatic prostate carcinoma examined, 74% (59/80) and 60% (48/80) were immunoreactive for nm23-H1 or nm23-H2 protein, respectively. Negative staining for nm23-H1 occurred in 83% of metastatic lesions, while 34% were negative for nm23-H2. All primary tumors corresponding to the metastases examined showed positive immunostaining for nm23-H1, indicating an inverse relationship between expression of this protein and metastatic status. nm23-H2 protein was detected in 83% of primary tumors and its expression appeared to be significantly correlated to the degree of histological differentiation. In contrast, all cases of benign prostatic hyperplasia showed elevated levels of both nm23-H1 and nm23-H2 expression. These data suggest that the nm23/NDP kinase may play a role in suppressing the expression of malignant potential in prostate carcinomas.
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PMID:Expression of nm23-H1 and nm23-H2 proteins in prostate carcinoma. 769 35

A series of sublines of a murine melanoma B16 of C57BL/6 origin were established and examined regarding their metastatic capacity and expression of nm23. The number of pulmonary metastases developed by these sublines was inversely correlated with the expression of two isotypes of nm23, nm23-M1 and nm23-M2. The cDNAs of nm23-M1, nm23-M2, and a combination of both were transfected into the highly metastatic melanoma subline FE7, with low nm23 expression. FE7 transfectants of any of these cDNAs expressed transfected genes, and their metastatic capacity was suppressed when compared with parental FE7 or FE7 transfected with a control neo gene. These cell lines, however, did not change in terms of in vitro growth in the presence of 3 or 10% fetal bovine serum and in vivo growth when injected s.c. into C57BL/6-nu/nu mice. Similar experiments were also performed using FE7 transfectants of human nm23 genes. Transfectants of nm23-H1, nm23-H2, and their combination did not present altered metastatic potential. These findings indicated that two murine isotypes of nm23 but not those of humans are intimately related with the suppression of metastasis in the murine body.
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PMID:Two isotypes of murine nm23/nucleoside diphosphate kinase, nm23-M1 and nm23-M2, are involved in metastatic suppression of a murine melanoma line. 772 68

Our previous study revealed that mutations of the p53 gene were detected by cDNA sequencing in one of four (25%) primary gastric tumors and in five of six (83%) gastric cancer cell lines. It was of interest that all five cell lines established from metastatic lesions had p53 gene mutations, while the single cell line established from a primary tumor lacked an abnormality. Thus, the current study was initiated to determine the frequency of p53 mutations in 10 pairs of samples from primary gastric carcinomas and their lymph node metastases, in addition to morphologically normal gastric mucosa. In addition, we correlated the findings with other relevant molecular markers including the metastasis associated nm23-H1 gene and loss of heterozygosity (LOH) using multiple polymorphic markers for chromosome 17p and sequencing the entire open reading frame (ORF) of the p53 gene. Five of ten (50%) patients were constitutionally heterozygous for one or more 17p and/or p53 probes (pYNZ 22, BamHI RFLP; pMct35.1, Mspl RFLP; php53cl, Bg/II RFLP), while none had LOH at the 17p and/or p53. A Bg/II RFLP for analysis of possible nm23-H1 somatic allelic deletion revealed no LOH out of four informative cases. One paired sample demonstrated the substitution of valine for isoleucine at codon 41 (GTT to ATT) in both primary gastric tumor and metastasis. Another metastatic sample demonstrated the substitution of proline for threonine at codon 278 (CCT to C/ACT) in addition to a non-mutated codon, while only the wild-type p53 sequence was present in the paired primary gastric tumor tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of p53 gene mutations in paired primary and metastatic gastric tumor tissues. 790 5


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