UMLS:C0178874 - FACTA Search

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Query: UMLS:C0178874 (tumor progression)
40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The two nm23 genes, nm23-H1 and nm23-H2, are implicated in the metastatic process and tumor progression in some human tumors. Until now no data exist about nm23 expression in the different types of human renal tumors. To investigate if the nm23 genes play a central role in the progression of renal tumors, we have examined nm23-H1 and nm23-H2 gene expression using Northern-blot analysis and immunohistochemistry. We analysed clear cell type RCC, chromophilic RCC, chromophobic RCC, collecting duct type RCC and renal oncocytomas. Our results indicate that the nm23 genes do not play a central role in the prognosis of renal cell carcinoma in the analysed tumors.
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PMID:NM23-H1 and NM23-H2 gene expression in human renal tumors. 961 86

The human A and B subunits of nucleoside diphosphate kinase (NDP kinase), encoded by the nm23-H1 and nm23-H2 genes, respectively, associate as homo- or heterohexamers to be catalytically active for the synthesis of nucleoside triphosphates. Despite 88% identity, they appear to possess specific functions. The nm23-H1 gene is implicated in tumor progression and metastasis, and the nm23-H2 gene product is a transcription factor for c-myc. To determine if these distinct functions reflect different subcellular localizations, the distribution of the A and B NDP kinases was analyzed by immunocytofluorescence microscopy in human breast cancer cell lines (MCF-7 and MDA-MB-231) using highly specific polyclonal and monoclonal antibodies. Interphasic cells exhibited a granular and filamentous cytoplasmic staining, particularly intense around nuclei, with both anti-NDP kinase A and B antibodies. The filamentous component observed with either anti-A or anti-B antibodies was altered in parallel to tubulin labeling with compounds interacting with microtubules, such as taxol and colchicine. Confirming published biochemical data, a partial colocalization with the vimentin network was observed in the MDA-231 cell line. A nuclear and nucleolar localization of NDP kinase B was shown by confocal microscopy which was not observed with the A enzyme. In dividing cells, NDP kinase labeling was punctiform and was not colocalized with the mitotic spindle. In conclusion, the A and B NDP kinases are similarly distributed in cytosol, associated partly to microtubules supporting a role in nucleotide channeling. Only the B enzyme is present in nuclei in accord with its role as a DNA binding protein. Their altered localization in dividing cells suggests colocalization with yet unidentified structures which are not intermediate filament aggregates.
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PMID:Cytoskeletal association of the A and B nucleoside diphosphate kinases of interphasic but not mitotic human carcinoma cell lines: specific nuclear localization of the B subunit. 992 51

Downregulation of nm-23 antimetastasis gene has been associated with disease progression in some human tumors. NPD kinase A is the product of the H1 isotype of the nm23 gene and its value as a marker of metastatic potential is well worth investigating. The expression of the nm23-H1 gene peptide was immunohistochemically evaluated in 191 primary mammary cancer tissues. A three-step immunoperoxidase staining procedure was performed and any association of our results with several classical clinicopathologic indicators, including hormonal status and c-erbB-2 oncoprotein membrane immunoexpression, was examined. NDP kinase A-positive cytoplasmic immunolabeling was noticed in 64% of all specimens (123/191) which frequently demonstrated positive progesterone receptor (PgR) status (p = 0.001) and were furthermore characterized by high PgR immunoreactivity rates. This association was significant by both univariate and multivariate statistical analysis. The double nm23-H1 (+)/PgR(+) phenotype was more frequently detected than any other combined phenotype of these markers. The nm23-H1 gene peptide was generally detected in a remarkable proportion of malignant cells, either in the invasive or the intraductal tumor components. Notably, large-cell ductal carcinomas in situ were characterized by lower nm23-H1 immunoreactivity rates when compared with other in situ cancer types. Quantitatively increased nm23-H1 immunopositive staining was more frequently observed in special histologic types of infiltrating cancers, in high nuclear grade tumors, as well as in carcinomas with high PgR levels (p = 0.05). The nm23-H1 (-)/c-erbB-2(+) phenotype was more often detected in the cancers of this study than the nm23-H1(+)/c-erbB-2(+) one. The former phenotype was correlated to postmenopausal ages as well as to extensive axillary nodal involvement by univariate statistical analysis. It is noteworthy that nm23-H1(-) status, on its own, was not statistically associated either with the presence or with a high number of involved lymph nodes. On the contrary, nm23-H1 immunopositivity was, paradoxically, more frequently observed in tumors of relatively increased TN tumor stage. Tumor progression is thus more likely to depend on the c-erbB-2 gene's overexpression. Possibly, any favorable outcome in nm23-H1(+) cases might be due to the fact that they also express PgR, which is a marker of a more functionally differentiated phenotype.
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PMID:Nm-23, c-erbB-2, and progesterone receptor expression in invasive breast cancer: correlation with clinicopathologic parameters. 1040 1

In many tumors an expression of nm23 gene products is associated with a lower metastatic potential. The aim was to evaluate whether nm23 gene expression in renal cell carcinoma was associated with clinicopathological findings and survival. In 41 patients, the expression of nm23 protein was analyzed in tumor and corresponding kidney cortex tissue by immunohistochemical analysis using a monoclonal nm23-H1 antibody. In all kidney cortex samples intense nm23 staining was found. Of 41 tumors, 15 had high, 12 intermediate, 5 low nm23 expression whereas 9 tumors showed none. There were no differences in nm23 staining between different stages, grades or size of tumor. No correlation between survival and nm23 expression was observed. However, diploid tumors had significantly less nm23 staining compared with aneuploid tumors, indicating that nm23 gene inactivation might be a favorable sign. The expression of nm23 gene products seems not to be correlated to tumor progression and metastatic ability in renal cell carcinoma.
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PMID:Clinical significance of nm23 expression in renal cell carcinoma. 1042 91

To investigate the expression of nm23-H1 gene in laryngeal squamous cell carcinoma, immunohistochemistry was carried out with a monoclonal antibody against nm23-H1. Of 48 cancer tissues tested, 35(72.9%) showed a positive immuno-reaction for nm23-H1. The percentage of nm23-H1 positivity was significantly lower (P < 0.01) in the tumors with cervical lymph node metastasis than in those without metastasis. Moreover, the percentage of nm23-H1 positivity was significantly lower (P < 0.05) in tumors of stages III-IV than in those of stages I-II. No significant correlation was found between nm23-H1 expression and tumor sites or histopathological grades. Analyzed with following up date, we found that the overall survival was better (P < 0.01) in patients with nm23-H1 expression than in those without expression. These results suggest that nm23-H1 gene may play a role in the suppression of lymph node metastasis and tumor progression in laryngeal carcinoma, and the expression of nm23-H1 gene is a useful predictor of prognosis.
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PMID:[Study on expression of nm23-H1 protein/NDPK-A in laryngeal carcinoma]. 1118 67

Reduced expression of the metastasis suppressor gene nm23-H1 has been previously correlated with high tumor metastatic potential and fatal clinical outcome in several types of human carcinomas. The aim of the study was to identify the expression of nm23-H1 in a variety of premalignant and malignant cervical lesions. The study comprised 106 cervical biopsies obtained from 106 women ranging in age from 23 to 68 (median 42) years. Histologic slides stained with H&E were evaluated blindly by two pathologists and a consensus diagnosis was established for each case. In addition, immunohistochemical stain was employed and a monoclonal antibody against nm23-H1 (YLEM Rome, Italy) was used. Twenty-five of the cervical biopsies showed changes of mild dysplasia (CIN I), whereas 28 demonstrated features of moderate dysplasia (CIN II) and 28 severe dysplasia (CIN III). In 25 cases infiltrating squamous cell carcinoma was identified. Expression of nm23-H1 was evident in 9/25 (36%) CIN I, 13/28 (46%) CIN II, 22/28 (78.5%) CIN III and 17/25 (68%) infiltrating carcinoma biopsies. Statistically significant differences were observed between CIN II and CIN III (p=0.003), and CIN II and infiltrating carcinoma (p=0.002) groups. Expression of the nm23-H1 gene in premalignant and malignant cervical lesions indicates that this gene may play a substantial role in carcinogenesis and tumor progression.
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PMID:Immunohistochemical analysis of nm23-H1 expression in human cervical lesions. 1119 46

The multistep process of carcinogenesis implies the accumulation of multiple molecular defects. Alteration of tumor suppressor and metastasis suppressor genes are the important steps. Increasing experimental evidence indicates that decreased expression of tumor-metastasis/suppressor genes and gene products are involved in the progression of a variety of human malignancies. In the present study, we have extended this analysis to non-small cell lung carcinomas (NSCLC). The expression and prognostic significance of the tumor suppressor gene PTEN and metastasis suppressor genes nm23-H1 and KAI-1 was evaluated in NSCLCs. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissues from 53 bronchogenic adenocarcinomas and 51 squamous cell carcinomas using monoclonal antibodies against PTEN, nm23H-1, and KAI-1 proteins. Immunohistochemical results were correlated with tumor stage, grade, lymph nodes positivity, metastasis, and patient survival. Significant co-expression of PTEN, nm23-H1 and KAI-1 was observed in NSCLC (P<.001 to .002). The immunohistochemical expression of these proteins was significantly higher in stages 1 and 2 compared with stages 3 and 4 (P=.04 for PTEN and KAI-1, P=.039 for nm23-H1). When all stages were considered together, loss of immunoreactivity for PTEN, nm23-H1 and KAI-1 was found in advanced NCSCLs (P=.015 for PTEN, P=.001 for KAI-1, P=.004 for nm23-H1), which is suggestive of co-downregulation of these proteins in the process of tumor progression. On multivariate analysis, negative staining for PTEN (P=.014), KAI-1 (P=.034), and nm23-H1 (a trend toward association for nm23-H1 reached near significance P=.08) correlated with disease-related death. Positive lymph node status was associated with negative immunostaining for PTEN (P=.007) but no correlation was observed for nm23-H1 and KAI-1. Loss of expression was linked to distant metastasis (P=.006 for PTEN, P=.002 for nm23H1, P=.001 for KAI-1). On multivariate analysis, co-downregulation of PTEN (P=.009), KAI-1 (P=.02), and nm23-H1 (P=.011) independently predicted shortened survival in NSCLC. Although NSCLC exhibits strong co-expression of PTEN, nm23-H1 and KAI-1, there is a loss of these proteins in high-stage tumors. Co-downregulation of PTEN, KAI-1, and nm23-H1 significantly correlates with distant metastasis and predicts shortened survival. Our study supports a role of these tumor suppressor and metastasis suppressor genes in the evolution and progression of NSCLC.
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PMID:Co-downregulation of PTEN, KAI-1, and nm23-H1 tumor/metastasis suppressor proteins in non-small cell lung cancer. 1512 4

Recent studies indicated nm23-H1 played a role in cancer progression. Therefore, we investigated clinical significance of nm23-H1 expression in oral squamous cell carcinoma (OSCC). In total, 86 OSCC specimens were immunohistochemically stained with nm23-H1-specific monoclonal antibodies. Immunohistochemical staining of nm23-H1 was confirmed by immunoblotting. The relations between nm23-H1 expression and clinicopathologic variables were evaluated by chi(2) analysis. As increased size of primary tumour could escalate metastatic potential and the data of patients at the late T stage might confound statistical analyses, we thus paid special attention to 54 patients at the early T stage of OSCC. Statistical difference of survival was compared by a log-rank test. Immunohistochemically, nm23-H1 expression was detected in 48.8% (42 out of 86) of tumorous specimens. It positively correlated with larger primary tumour size (P=0.03) and inversely with cigarette-smoking habit (P=0.042). In patients at the early T stage, decreased nm23 expression was associated with increased incidence of lymph node metastasis (P=0.004) and indicated poor survival (P=0.014). Tumour nm23-H1 expression is a prognostic factor for predicting better survival in OSCC patients at the early T stage, which may reflect antimetastatic potential of nm23. Therefore, modulation of nm23-H1 expression in cancer cells can provide a novel possibility of improving therapeutic strategy at this stage. In addition, our results further indicated cigarette smoking could aggravate the extent of nm23-H1 expression and possibly disease progression of OSCC patients.
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PMID:Prognostic significance of nm23-H1 expression in oral squamous cell carcinoma. 1515 Jun 13

Cellular methylation imbalance is associated with tumor progression, hepatic cancer, and cardiovascular disease. S-Adenosylhomocysteine (SAH) is an inhibitor of cellular methyltransferases, and increasing evidence suggests that SAH rather than homocysteine (Hcy) plays a crucial role in mediating these disorders related to methylation imbalance. The anti-metastatic gene nm23-H1 was recently identified in murine and human cancer lines, and the expressions of nm23-H1 mRNA and protein have been shown to be useful tumor invasion markers. We investigated the relationships of tumor cell invasion activities with the intracellular levels of SAH and Hcy and the level of DNA methylation (measured as the cellular content of 5-methyldeoxycytidine, 5-mdc) in four hepatocarcinoma cell lines (Sk-Hep1, J5, Hep-G2, Hep-3B) and one normal liver cell line (Chang's liver cells) with different invasion activities (Sk-Hep1 > J5 > Hep-G2 = Hep-3B > Chang's liver cells). We found that the intracellular level of SAH was the highest in SK-Hep1 cells and was correlated with the invasion activities (r = 0.75, P = 0.008), whereas the level of intracellular Hcy was the highest in Chang's liver cells and was not significantly correlated with the invasion activities of these cell lines (r = 0.24, P = 0.38). The levels of 5-mdc increased with decreasing invasion activities of these cell lines (r = 0.82, P = 0.002), that is, the order of DNA hypomethylation in these cell lines was Sk-Hep1 > J5 > Hep-G2 = Hep-3B > Chang's liver cells, because the lower levels of 5-mdc% represent the higher DNA hypomethylation. Thus, our results demonstrate that SAH rather than Hcy is associated with invasion activities of hepatoma cells, and they suggest that SAH may play an important role in the invasion activities through DNA hypomethylation.
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PMID:Intracellular levels of S-adenosylhomocysteine but not homocysteine are highly correlated to the expression of nm23-H1 and the level of 5-methyldeoxycytidine in human hepatoma cells with different invasion activities. 1704 78

Human telomerase reverse transcriptase (hTERT) and human nonmetastatic clone 23 (nm23-H1) may be separately involved in tumor progression of uterine cervix. We therefore investigate the correlations of hTERT and nm23-H1 in cervical carcinogenesis and further check their application. One hundred and twenty-eight cervical tissues, including 48 squamous cell carcinoma (SCC), 36 high-grade cervical intraepithelial neoplasia (CIN) (CIN 2 and CIN 3), 20 low-grade CIN 1, and 24 normal cases, were collected for immunohistochemical expression of hTERT and nm23-H1. Spearman rank correlation analysis was applied to assess their correlation in these samples. The Fisher exact or Chi-square test was used to evaluate the expression of hTERT or nm23-H1 among each subgroup. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and accuracy of hTERT and/or nm23-H1 were calculated for the prediction of high-grade CIN and SCC. We found normal cervix and CIN 1 samples had concurrent low expression of hTERT and nm23-H1, whereas high-grade CIN and SCC samples had concurrent high immunoreactivities. The hTERT alone and hTERT or nm23-H1 in combination had better sensitivity, NPV, and accuracy. The nm23-H1 alone as well as hTERT and nm23-H1 in combination had better specificity and PPV. Our results reveal a significantly positive relationship between expression of hTERT and nm23-H1 in normal and neoplastic tissues of uterine cervix. We suggest high expression of hTERT alone and hTERT or nm23-H1 in combination can be offered additional molecular information correlated with high-grade CIN and SCC.
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PMID:Concurrent high expression of human telomerase reverse transcriptase and human nonmetastatic clone 23 in high-grade squamous intraepithelial neoplasia and squamous cell carcinoma of uterine cervix. 1735 90

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