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)

The nm23 gene was isolated as a metastasis suppressor gene that exhibits low expression in high-level metastatic cancer cells. Its gene is related to the prognosis of acute myelogenous leukemia (AML) and non-Hodgkin's lymphoma (NHL). In this study, we examined the expression of nm23-H1 protein on the lymphoma cell surface of NHL. In 28 of 108 cases (25.9%), we observed > or = 20% of cell surface nm23-H1 protein expression and expression was especially high in peripheral T cell lymphomas and extranodal NK/T cell lymphomas. We also observed a significant correlation between serum nm23-H1 level and cell surface nm23-H1 expression levels. In patients with high levels of cell surface nm23-H1 expression, overall and progression-free survival rates were significantly lower than those in patients with low surface nm23-H1 expression levels. When surface nm23-H1 and serum nm23-H1 were combined, patients with high levels of both exhibited a poorer prognosis than patients with a high level of one or the other. These results indicate that in addition to serum nm23-H1, cell surface nm23-H1 may be used as a prognostic factor in planning a treatment strategy. The nm23-H1 protein appears to be intimately related to biological aggressiveness of lymphoma and, therefore, might be a molecular target of NHL treatment.
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PMID:Clinical significance of nm23-H1 proteins expressed on cell surface in non-Hodgkin's lymphoma. 1252 78

The first metastasis suppressor gene identified was nm23. Transfection of nm23 into metastatic cell lines resulted in the inhibition of metastasis, but not primary tumor size in vivo. Using in vitro assays, nm23 overexpression resulted in reduced anchorage-independent colonization in response to TGF-beta, reduced invasion and motility in response to multiple factors, and increased differentiation. We hypothesize that the mechanism of action of Nm23 in metastasis suppression involves diminished signal transduction downstream of a particular receptor. Candidate biochemical mechanisms are identified and discussed herein.
Clin Exp Metastasis 2003
PMID:Inhibition of signal transduction by the nm23 metastasis suppressor: possible mechanisms. 1265 Jun 1

Metastasis is the manifestation most directly affecting survival for patients with colorectal carcinoma. Identification of high-risk markers for metastases would allow focused selection of patients for adjuvant chemotherapy. Reports of the relationship between the putative metastasis suppressor NM23 and metastasis and/or survival in colorectal cancer patients are conflicting. The purpose of this study was to separately assess expression of NM23-H1 and NM23-H2 in primary colon cancers and determine whether expression was associated with regional nodal disease and/or liver metastases. Four patient cohorts were selected on the basis of histopathological staging at primary surgery (lymph node status/liver metastasis): -/- (n = 46), +/- (n = 47), -/+ (n = 43), and +/+ (n = 46). Primary tumors were evaluated by semiquantitative immunohistochemical analysis of NM23-H1 and NM23-H2. NM23-H2 expression was not related to survival; however, there was a modest survival advantage with low expression of NM23-H1 (P = 0.027). NM23-H1 expression in the +/+ group was increased compared with the other groups (P < 0.001). The -/+ group had the lowest expression of NM23-H2 (P < 0.001). This analysis distinguishes two high-risk groups of colorectal cancer patients. Prior discrepancies regarding the usefulness of NM23 staining may be explained by the need to evaluate both serotypes in addition to standard histopathological analysis to identify specific "at-risk" groups.
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PMID:Analysis of both NM23-h1 and NM23-H2 expression identifies "at-risk" patients with colorectal cancer. 1267 75

Metastatic disease remains a significant contributor to morbidity and mortality in patients with breast cancer. An improved molecular and biochemical understanding of the metastatic process is expected to fuel the development of new therapeutic approaches. The suppression of tumor metastasis, despite tumor cell expression of oncogenes and metastasis-promoting events, has become a diverse and fruitful field of investigation. Although many genetic events promote metastasis, several genes show relatively reduced expression levels in metastatic tumor cells in mouse model systems and in aggressive human tumors. Re-expression of a metastasis-suppressor gene in a metastatic tumor cell line results in a significant reduction in metastatic behavior in vivo with no effect on tumorigenicity. The known metastasis-suppressor gene products nm23, KAI1, mitogen-activated protein kinase kinase 4, breast cancer metastasis suppressor-1, KiSS1, RHOGDI2, CRSP3, and vitamin D3-upregulated protein/thioredoxin interacting protein exhibit unexpected biochemical functions that have shed new light on signaling events that are important in metastasis. Most metastasis suppressors function at the translationally important stage of outgrowth of micrometastatic tumor cells at a distant site. We hypothesize that elevation of metastasis suppressor gene expression in micrometastatic tumor cells in the adjuvant high-risk population of patients with breast cancer will halt metastatic colonization and have a clinical benefit. DNA methylation inhibitors have shown limited promise in increasing metastasis-suppressor gene expression, and ligands of the nuclear hormone receptor family are currently under investigation in vitro and in vivo. Clinical testing of agents that increase metastasis-suppressor gene expression is expected to require tailored trial designs.
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PMID:Metastasis suppressor genes: basic biology and potential clinical use. 1274 59

The erbB2 gene is often found amplified and/or overexpressed in breast cancer in which it has clinical relevance as prognostic and predictive factor. It is involved in growth regulation and has a role in the initial phases of cell proliferation, while in vivo and in vitro studies have suggested an involvement also in cell invasion and metastases. It is not clear if these two roles are mutually exclusive and little is known about the mechanisms by which erbB2 may be involved in the control of these processes. Our previous data on patient series suggested that erbB2 might be regulated in different ways depending on the neoplastic status of the cells and that it might be involved in different regulatory pathways. To test this hypothesis we have measured the serum-dependent regulation of erbB2 as a function of the expression of the antimetastatic gene, nm23, in a panel of breast cancer cell lines. The experimental model consisted of three cell lines having different proliferative and invasive potentials: a non-metastatic estrogen receptor (ER) positive cell line, MCF-7; a highly metastatic ER negative cell line, MDA-MB435; and the MDA-MB435 cell line transfected with the nm23-H1 antimetastatic gene (clone H1-177) which has lost the ability to invade and metastasize. We first analysed the serum concentration dependence of invasion and proliferation after 3-4 days of serum deprivation confirming the proliferative and invasive potential of the three cell lines. Modulation of erbB2 expression by different concentrations of serum was then studied. ErbB2 expression in MCF-7 cells showed a complex pattern due to serum modulation, whereas, it was not longer regulated by serum in the MDA-MB435 cell line. In H1-177 cells the erbB2 response to serum was restored and it was very similar to that observed in MCF-7. These data showed a tight association between nm23 and the regulation of erbB2 expression by serum factors suggesting that the role of erbB2 in invasion might be dependent on nm23 expression.
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PMID:ErbB2 and the antimetastatic nm23/NDP kinase in regulating serum induced breast cancer invasion. 1279 23

An in vivo melanoma spontaneous metastases model was adopted to study the molecular mechanisms of the anti-metastatic effect of Taxol. The morphology of melanoma cells in the melanoma tissue lesions was examined by hematoxylin/eosin (H&E) staining and electron microscopy. The in situ programmed cell death was tested by TUNEL analysis. Vascular endothelial growth factor (VEGF) and E-cadherin expression were detected by immunohistochemistry. The metastases suppressor gene nm23 mRNA expression level was analyzed by in situ hybridization. The results showed that i.p. injection of Taxol at 5 mg/kg per day for three weeks significantly inhibited metastases formation in the pulmonary of mice. Taxol induced melanogenesis and apoptosis in the melanoma cells, inhibited angiogenesis in melanoma tissue lesions, and reduced the expression of VEGF. Conversely, Taxol increased the expression of E-cadherin and nm23. In conclusion, administration of Taxol in the early stage of melanoma metastases can significantly inhibit melanoma metastases. This effect was possibly related to apoptosis induction, tumor angiogenesis inhibition, and restoration of the metastasis suppression ability.
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PMID:Taxol inhibits melanoma metastases through apoptosis induction, angiogenesis inhibition, and restoration of E-cadherin and nm23 expression. 1457 88

The expression of tumour promoter gene S100A4, metastasis suppressor gene nm23, oestrogen and progesterone receptors, and tumour grade and size have been investigated for their potential to predict breast cancer progression. The molecular and cellular data have been analysed using artificial neural networks to determine the potential of these markers to predict the presence of metastatic tumour in the regional lymph nodes. This study shows that tumour grade and size are poor predictors. The relative expression of S100A4 and nm23 genes is the single most effective predictor of nodal status. Inclusion of oestrogen- and progesterone-receptor status with tumour grade and size markers improves prediction; however, there may be some overlap between steroid receptors and molecular markers. This study also underscores the power of artificial neural network techniques to predict the potential of primary breast cancers to spread to axillary lymph nodes. This could aid the clinician in determining whether invasive procedures of axially node dissection can be obviated and whether conservative forms of treatment might be appropriate in the management of the patient.
Clin Exp Metastasis 2003
PMID:Prediction of nodal spread of breast cancer by using artificial neural network-based analyses of S100A4, nm23 and steroid receptor expression. 1459 84

Expression of proteins nm 23 and c-erbB-2 is observed in many human carcinomas and is associated with the disease progression. Immunohistochemical study of nm23 and c-erbB-2 expression was performed on 64 primary tumours, 19 metastases in the lymph nodes and 37 liver metastases. More pronounced expression of these proteins in the primary tumour cells is observed in cases with liver metastases. Expression of nm 23 was observed in 66% and that of c-erbB2 in 59% of liver metastases. Thus, expression of these proteins may reflect biological behaviour of the tumour and may appear to be an important factor in development of colorectal cancer metastases.
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PMID:[Expression of nm23 and c-erbB-2 proteins in cells of primary colorectal cancer and its metastases]. 1466 40

Melanoma prognosis is based on histological criteria such as tumor thickness (measured by Breslow index), level of invasion (Clarck's level), presence of ulceration and number of mitoses per mm2. However, these parameters do not provide a precise prognosis in all cases: thin melanomas may develop metastases and thick melanomas may remain focalized for many years. For these reasons, the search for other prognostic factors is still ongoing. Many molecules play a part in the invasiveness and metastatic dissemination of melanoma have now been identified. Expression of these molecules has been studied in primary melanoma and correlated with prognosis. An increase in the number of cells positive for Ki67 (detected by Mib1), cycline A, cycline D, p35, MMp-2, beta1 and beta3 integrins, osteonectin, the presence of an intense inflammatory infiltrate and capillary invasion are considered as factors of poor prognosis as well as the decrease in p16, p27, Melan A and nm23. The significance of CD44 modifications is still controversial. Only a small number of these different proteins has a prognostic value independent of tumor thickness. These results need to be confirmed on larger series of patients. Additional hope is given to new techniques such as the analysis of the genes implied in tumor progression by microarray technique in such a way as to provide a molecular map of each tumor.
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PMID:[Molecular markers associated to prognosis of melanoma]. 1472 37

Metastases of various malignancies have been shown to be inversely related to the abundance of nm23 protein expression. However, the downstream pathways involved in nm23-mediated suppression of metastasis have not been elucidated. In the present investigation, we used cDNA microarrays to identify novel genes and functional pathways in nm23-mediated spontaneous breast metastasis. Microarray experiments were performed in a pair of cell lines, namely, C-100 (only vector transfected; highly metastatic) and H1-177 (nm23 transfected; low metastatic), derived from human mammary carcinoma cell line MDA-MB-435. The cDNA microarray analysis using GeneSpring software revealed significant as well as consistent alterations in the expression (up- and downregulation) of 2158 genes in a total of 18889 genes between high and low metastatic cells. Some of these genes were grouped into 6 functional categories, namely, invasion and metastasis, apoptosis and senescence, signal transduction molecules and transcription factors, cell cycle and repair, adhesion, and angiogenesis to extrapolate an association between these genes and different functional pathways involved in nm23-regulated metastasis. The results suggest that nm23 gene plays a major role in metastasis and its mechanism of action of metastasis suppression may involve downregulation of genes associated with cell adhesion, motility (integrins alpha2, -8, -9, -L and -V, collagen type VIII alpha1, fibronectin 1, catenin, TGF-beta2, FGF7, MMP14 and 16, ErbB2) and possibly certain tumor/metastasis suppressors (2 members of SWI/SNF-related matrix-associated proteins 2 and 5 and PTEN).
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PMID:Expression profile of genes associated with antimetastatic gene: nm23-mediated metastasis inhibition in breast carcinoma cells. 1473 69


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