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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer metastasis, a complex and sequential network of cellular events involved in the migration and establishment of malignant cells from original site to distant foci, is an important and significant contributor to morbidity and mortality of cancer patients. Despite the clinical importance of cancer metastasis, its molecular and biochemical mechanism remains unclear. The identification of tumor suppressor gene confirmed that metastasis might involve the functional loss of genes that maintain the cellular differentiation optimally. Metastasis suppressor is defined by the ability to reduce the metastatic property of cancer cells without affecting its tumorigenesis. Since NM23 was first identified in 1988 as a metastasis suppressor, several metastasis suppressor genes have been identified and characterized. In this article, we review the complex and multi-step process of cancer metastasis and describe the recent progress of metastasis suppressors in the studies of identified. Consequently, we hope to introduce the new therapeutic target for the metastasis suppressors in cancer patients.
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PMID:[Cancer metastasis and metastasis suppressors]. 1474 45

The nm23 gene is a putative tumour and metastasis suppressor gene. A number of studies have found that reduction of its expression is associated with increased metastatic potential in several human malignancies. Similarly, clinical studies have shown correlation between reduced nm23 protein expression and a poor prognosis. The aim of this study was to determine if a relationship exists between nm23 expression in primary cutaneous melanomas with or without cerebral metastases. Paraffin-embedded tissues were retrieved from 21 patients with primary cutaneous melanomas (n=21) and who subsequently developed cerebral metastases (n=24). Primary cutaneous melanomas with no regional or organ metastases within a 10 year period were used as control cases (n=34). Nm23 staining was localized in the cytoplasm of the tumour cells. Most of the control cases showed strong expression, whereas the majority of the primary melanomas with cerebral metastases showed no or weak expression of nm23. The cerebral metastases mostly showed strong expression. In summary, the results of this study may have significant prognostic implications for patients presenting with cutaneous melanoma. Patients with cutaneous melanomas with a low expression of nm23 appear to be more at risk of developing brain metastases.
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PMID:Cytoplasmic expression of nm23 predicts the potential for cerebral metastasis in patients with primary cutaneous melanoma. 1509 Nov 90

Surgical material from 157 patients with lung carcinoma was studied. Immunohistochemical detection of the following oncomarkers was performed: Ki67, p53, CD34, CAS, Topoisomerase II alfa, nm23 protein, E-cadherin. The existence of association between proliferation, tumour cell apoptosis and formation of vessels in the tumour stroma is established. Angiogenesis correlated with proliferative activity of tumour cells this resulting from the effect of growth factors secreted by cells of both tumours and stroma. Angiogenesis in lung carcinoma may also be stimulated by mitogenetic factors accumulating in tumour tissue due to the "uncompleted" apoptosis. Low nm23 and E-cadherin expression is found in lung carcinoma with regional lymphogenic metastases indicating probably cancer metastases.
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PMID:[Correlation of proliferation, apoptosis, angiogenesis and metastasizing in various histogenetic types of pulmonary cancer (an immunohistochemical investigation)]. 1564 65

E-cadherin, a calcium-dependent cell-cell adhesion molecule, functions as maintenance of epithelial integrity. nm23, encoded by non-metastatic 23 gene, plays a key role in differentiation of many kinds of epithelium. Loss or dysfunction of E-cadherin and nm23 was frequently identified in many types of human cancers and is considered to correlate with invasive/metastatic phenotype. We previously reported that defective expression of E-cadherin might play a role in the development of the malignant phenotype in non-small cell lung cancer (NSCLC) [Q.Y. Fei, H.T. Zhang, X.F. Chen, et al., Defected expression of Ecadherin in non-small cell lung cancer, Lung Cancer 37 (2002) 147-152]. In an attempt to evaluate the significance of E-cadherin and nm23 in human non-small cell lung cancer, we performed mRNA expression and genetic structure analyses of the E-cadherin and nm23 genes in 54 NSCLCs and 46 normal lung tissues. The mRNA expression was determined by semi-quantitative RT-PCR, and genetic structure was examined through PCR-SSCP followed by sequencing. Although no mutation of the E-cadherin and nm23 genes was detected, the results obtained in the present study showed that reduction of E-cadherin and nm23 mRNA expression remarkably correlated with low histological differentiation, increasing stage as well as lymph node metastases (P<0.05). These data provide us with support for the idea that dysfunction of E-cadherin and nm23 has a role in progression of NSCLC and that the examination of E-cadherin and nm23 expression can provide experimental evidence for clinical treatment.
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PMID:Expression of E-cadherin and nm23 is associated with the clinicopathological factors of human non-small cell lung cancer in China. 1577 72

The accurate estimation of prognosis in patients with melanoma is of increasing importance with novel adjuvant therapies on the horizon. The current prediction of prognosis employs techniques involving sentinel lymph node biopsy, which carries an associated morbidity and is of little use in patients who develop direct distant metastases or direct in-transit metastases. New strategies or factors are therefore needed to improve the accuracy of determination of prognosis. nm23 is a putative metastasis suppressor; however, conflicting data exist as to its role in melanoma progression and its use as a potential prognostic marker. The purpose of this study was to use the technique of tissue microarray to study a cohort of melanoma patients with long-term follow-up data in order to ascertain its potential use as a prognostic marker. One hundred and twenty patients with primary cutaneous melanoma were included in the tissue microarray and a commercially available immunohistochemical marker for nm23 was used for protein detection. nm23 expression was strongly correlated with Clark's level (P<0.001), Breslow depth (P=0.002) and patient age (P=0.014). nm23 expression was significantly associated with a poor patient outcome (chi2=7.2219, P=0.0072). Further analysis revealed that the intensity of nm23 expression also correlated with patient outcome (chi2=11.3281, P=0.0035). However, on multivariate analysis, nm23 was shown not to be an independent marker of prognosis. The results of this study, when taken with the existing literature, suggest a role for nm23 in melanoma disease progression. However, its use as a prognostic marker in routine practice does not appear to be justified.
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PMID:nm23 as a prognostic marker in primary cutaneous melanoma: evaluation using tissue microarray in a patient group with long-term follow-up. 1617 71

KiSS-1 has been shown to function as a tumor metastasis suppressor gene and reduce the number of metastases in different cancers. The expression of KiSS-1 or KiSS1, like other tumor suppressor, is commonly reduced or completely ablated in a variety of cancers via an unknown mechanism. Here we show that the loss of KiSS-1 expression in highly metastatic breast cancer cell lines correlates directly with the expression levels of two transcription factors, activator protein-2alpha (AP-2alpha) and specificity protein 1 (Sp1), which synergistically activate the transcriptional regulation of KiSS-1 in breast cancer cells. Although the KiSS-1 promoter contains multiple AP-2alpha binding elements, AP-2alpha-mediated regulation occurs indirectly through Sp1 sites, as determined by deletion and mutation analysis. Overexpression of AP-2alpha into highly metastatic breast cell lines did not alter KiSS-1 promoter-driven luciferase gene activity. However, co-transfection of AP-2alpha wild-type or the dominant negative form of AP-2 lacking its C-terminal DNA-binding domain, AP-2B, together with Sp1, increased KiSS-1 promoter activity dramatically, suggesting that AP-2alpha regulation of KiSS-1 transcription does not require direct binding to the KiSS-1 promoter. Furthermore, we demonstrated that AP-2alpha directly interacted with Sp1 to form transcription complexes at two tandem Sp1-binding sites of the promoter to activate KiSS-1 transcription. Together, our results indicate that AP-2alpha and Sp1 are strong transcriptional regulators of KiSS-1 and that loss or decreased expression of AP-2alpha in breast cancer may account for the loss of tumor metastasis suppressor KiSS-1 expression and thus increased cancer metastasis.
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PMID:Regulation of KiSS-1 metastasis suppressor gene expression in breast cancer cells by direct interaction of transcription factors activator protein-2alpha and specificity protein-1. 1626 Apr 18

Twenty-nine cases of oral melanomas were investigated for nm23 and Ki67 antigen expression, as well as for the fraction of tumour cells in S-phase, using immunohistochemical techniques and DNA cytophotometry. Nm23 expression was significantly reduced and Ki67 antigen expression increased in primary tumours with either lymph node or organ metastases in comparison to tumours without metastases. The percentages of Ki67 immunoreactive tumour cells and cells in S-phase correlated positively with each other and negatively with the percentage of nm23-expressing cells. These data argue against a significant growth stimulatory function of the nm23H1 gene product nucleoside diphopshate kinase in the progression of oral melanomas. The functional relevance of nm23 in relation to increased proliferation and metastatic spread is discussed.
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PMID:Relationship of nm23 expression to proliferation and prognosis in malignant melanomas of the oral cavity. 1627 28

Human breast cancer cells with high metastatic potential show reduced expression of the metastasis-suppressor gene NME1. There are two polymorphic sites for the restriction enzymes BglII and EcoRI, both detectable by Southern blot analysis. Although the BglII site has been analyzed for loss of heterozygosity, the biallelic EcoRI site polymorphism has not been studied in association with breast cancer, complications or metastasis. We analyzed EcoRI site allele frequencies in Mexican patients with breast cancer, using polymerase chain reaction -restriction fragment length polymorphisms. The polymorphic allelic frequencies in the cases and reference groups were 0.4215 and 0.3375, respectively; this difference was not statistically significant (chi2=0.8687, p=0.3512). Thus, EcoR1 polymorphic site was not associated with breast cancer in this series, but could be analyzed in association with metastases and might be informative in the evaluation of loss of heterozygosity in women with breast cancer.
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PMID:EcoRI polymorphism of the metastasis-suppressor gene NME1 in Mexican patients with breast cancer. 1631 82

The cytological dilemma of distinguishing malignant cells from proliferating mesothelium has generated volumes of research but no clear consensus regarding an optimal staining panel. nm23 has been frequently described in malignant cells as a metastasis suppressor, but its mechanism of action and the relationship between nm23 expression, metastases, and prognosis is controversial. This is the first study to apply nm23 immunostaining in the setting of effusion cytology. One hundred samples of effusions (56 malignant and 44 benign) were immunostained with nm23 using the biotin-avidin technique and diaminobenzidine as a chromogen. Additionally, a mucicarmine stain was performed on most samples, all of which were evaluated for nm23 expression and mucin in a blinded fashion. After all the samples were reviewed, the diagnoses were disclosed and staining patterns evaluated. From the malignant cases, 51 of 56 cases were positive for nm23 in at least 5% of malignant cells, while 27 of 44 reactive mesothelium cases were also positive in at least 5% of cells. Of the malignant cases, all non-adenocarcinomas expressed nm23. We conclude that nm23 is a highly sensitive marker for detecting malignant cells. Its relatively high rate of expression in reactive mesothelium supports previous studies that suggest nm23 is expressed in proliferating cells.
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PMID:nm23 is expressed in reactive mesothelium and is not useful for detection of malignant cells in serous effusions. 1632 38

Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are difficult both from the diagnostic and patient management standpoint because they cannot be classified as benign or malignant by conventional histologic criteria. This study's aim was to determine the diagnostic utility of allelic imbalance (AI) analysis in uterine smooth muscle tumors. Using microdissection and genotyping, we tested 5 leiomyomas, 6 STUMPs, and 10 leiomyosarcomas with follow-up for AI across a panel of seven tumor suppressor genes (p16, p21, p53, VHL, XRCC3, RB, and NM-23). None of the 6 patients with STUMP experienced recurrent disease, whereas 8 of the 10 patients diagnosed with leiomyosarcoma died of disease at follow-up. The mean frequency of allelic loss (FAL) for leiomyomas (18%) was not significantly different from that of STUMPs (21%) (P = 1), whereas leiomyosarcomas displayed a significantly higher FAL (52%) than both leiomyomas (P = 0.001) and STUMPs (P = 0.002). Loss of NM-23, a reported tumor metastasis suppressor gene, was found only in leiomyosarcomas (5 of 9, or 56%), and 4 of 5 (80%) of these were the only cases that demonstrated distant metastases (P = 0.04). Additionally, an FAL of >50% correlated with both NM-23 loss (P = 0.008) and distant metastatic disease (P = 0.04). In conclusion, leiomyomas and STUMPs displayed similar mean FALs and all were clinically benign, whereas uterine leiomyosarcomas had significantly higher frequencies of allelic loss than both leiomyomas and STUMPs. Molecular profiling may thus provide a valuable tool in assessment of malignancy in uterine smooth muscle tumors. Additionally, NM-23 is a promising candidate gene for determination of metastatic potential in these tumors.
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PMID:Analysis of allelic loss as an adjuvant tool in evaluation of malignancy in uterine smooth muscle tumors. 1633 Sep 48


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