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 apoptosis-resistant phenotype of cloned high-metastatic A11 and low-metastatic P29 cells isolated from Lewis lung carcinoma was compared. The results showed that A11 cells were more resistant to apoptosis induced by microenvironmental stresses such as serum starvation, glucose deprivation and hypoxia than P29 cells as judged by viability, DNA laddering, and chromatin condensation and fragmentation. Both cell lines were insensitive to tumor necrosis factor-alpha-mediated apoptosis. P29 cells expressed a much higher level of Fas antigen on the cell surface than A11 cells. However, both cell lines were also insensitive to Fas-mediated apoptosis. The apoptosis resistant phenotype of A11 cells was associated with the expression level of caspase-3, but not with those of Bcl-2, Bcl-X(L) Bax, p27Kip1 and DAP kinase. There was no difference between A11 and P29 cells in the expression of E-cadherin, the adhesiveness to the extracellular matrix components or the expression levels of metastasis-associated genes such as c-Ha-ras, c-jun, p53 and nm23. Furthermore, A11 cells exhibited lower motile and invasive abilities than P29 cells. These results suggest that the apoptosis-resistant phenotype is an important factor for determining the metastatic ability of A11 cells. Supporting this, P29 cells became more apoptosis-resistant after treatment of the cells with dimethylsulfoxide which is reported to enhance the experimental metastatic potential of the cells.
Clin Exp Metastasis 1999 Jul
PMID:Resistance to apoptosis induced by microenvironmental stresses is correlated with metastatic potential in Lewis lung carcinoma. 1065 7

Forty-two enucleated eyes of 42 patients with unilateral retinoblastoma were studied histologically, including histochemically examination with anti-nm23 polyclonal antibody which does not recognise cDNA but its product. Primary tumours of >15 mm diameter with less evidence of apoptosis and with the most pleomorphic and anaplastic nuclei were associated with an increased risk of distant metastasis, but rosette formation did not discriminate. A high intensity of nm23 staining also indicated a tendency to metastasize, consistent with childhood neuroblastoma but in contrast to findings in carcinoma of the breast, colon and uterine cervix.
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PMID:Nucleoside diphosphate kinase (nm23 protein) expression in retinoblastoma. 1075 38

The clinical implications of understanding the invasive and metastatic proclivities of an individual patient's tumour are substantial because the choice of systemic therapy needs to be guided by the likelihood of occult metastasis as well as by knowing when the metastases will become overt. Malignant potential is dynamic, progressing throughout the natural history of a tumour. Required of tumours is the development of critical phenotypic attributes: growth, angiogenesis, invasion and metastagenicity. Characterisation of the extent of tumour progression with regard to these major tumour phenotypes should allow the fashioning of individual therapy for each patient. To examine the clinical parameters and molecularly characterise the metastatic proclivity we have been studying a series of regionally treated breast cancer patients who received no systemic therapy and have long follow-up. Clinically we describe two parameters: metastagenicity - the metastatic proclivity of a tumour, and virulence--the rate at which these metastases appear. Both attributes increase with tumour size and nodal involvement. However, within each clinical group there is a cured population, even in those with extensive nodal involvement, underscoring the heterogeneity of breast cancers within each group and the need for further molecular characterisation. Using biomarkers that characterise the malignant phenotype we have determined that there is progression in the phenotypic changes. Angiogenesis and loss of nm23 are earlier events than the loss of E-cadherin, or abnormalities in TP53. The strongest biomarkers of poor prognosis are p53 and E-cadherin, but even when both are abnormal 42% of node-negative patients are cured indicating that other determinative steps need to occur before successful metastases are established. Identification of these critical later events will further increase the efficacy of determining the malignant capacities of individual tumours.
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PMID:Individual characterisation of the metastatic capacity of human breast carcinoma. 1095 49

Cellular drug resistance and increased metastatic potential are the major obstacles in the successful treatment of cancer with chemotherapy. The aim of this study was to investigate whether the immunohistochemical expression of two proteins implicated in drug resistance (P-glycoprotein and metallothionein) and the product of the suppressor gene nm23 could be related to prognosis in breast cancer. Seventy-two patients with palpable or occult breast carcinoma, not treated with chemotherapy or endocrine therapy, were examined. Immunohistochemical methods were used to determine the expression of P-glycoprotein (PG), metallothionein (MT), nm23, as well as the estrogen receptor (ER), the p53 status, and the Ki67 index. The results were correlated with clinical and morphological features. Cytoplasmic and membrane-specific immunostainings of PG were seen exclusively in tumor cells and identified in 14 of 72 cases (19.4%). Only a statistically significant association with metastases, (p = 0.06) and recurrences (p = 0.1) was observed. MT-positive reaction was identified in the cytoplasm of the tumor cells in 47 (65.3%) cases. Statistical significance was associated with metastases (p = 0.07), but not with death or recurrences. Specific immunostaining of nm23 protein was seen only in the cytoplasm of tumor cells. A positive reaction was observed in 55 of 72 (89.3%) cases. Although a significant association between nm23 protein expression and other morphologic and immunohistochemical variables did not exist, we observed a higher morbidity in patients with the MT-positive/nm23-negative tumor phenotype. Univariate analysis for survival selected the following variables: histologic grade (p = 0.001), ER (p = 0.002), mitotic index (p = 0.005), Ki 67 index (p = 0.068), MT (p = 0.046) and PG (p = 0.085). The Cox model provided the following independent variables: histologic grade (p = 0.021) and metallothionein (p = 0.03). These data confirm the prognosis observed in patients with PG or metallothionein expression as well as the independence of these two variables. It also suggests that nm23 is not necessarily involved in the development of an invasive phenotype.
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PMID:P-glycoprotein, metallothionein and NM23 protein expressions in breast carcinoma. 1098 18

Typical bronchial carcinoids are usually considered fairly benign tumors. Metastases do however occur, and up to 10% of the patients ultimately die from their disease. To identify prognostic markers, we immunostained 43 typical bronchial carcinoids with antibodies against 8 possibly relevant hormones, oncogenes, tumor suppressor genes, adhesion molecules, and proliferation markers. Altogether 12 patients (28%) had metastatic disease, of whom 10 had regional lymph node metastases at diagnosis. Distant metastases have occurred in 5 patients (12%); all of these have died from their disease. Patients with high expression of Ki-67 had shorter survival time (P < 0.01). None of the immunostained hormones correlated to distant metastases or shorter survival time, but gastrin-releasing peptide correlated to metastatic disease (P < 0.05). All patients who died had CD44-negative tumors (P < 0.001). Nuclear nm23 staining correlated to decreased risk for metastatic disease and distant metastases per se (P < 0.01). Bcl-2 and p53 were associated with increased risk for distant metastases (P < 0.05 and P < 0.01, respectively). We conclude that some patients with typical bronchial carcinoids die from their disease and that gastrin-releasing peptide, Bcl-2, and p53 may be of importance for the malignant transformation of the tumor. Moreover, CD44, nm23, and Ki-67 may give valuable prognostic information and help identify the patients at risk of disease-related death.
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PMID:Prognostic markers in patients with typical bronchial carcinoid tumors. 1099 44

NM23.H1 is a protein connected with tumor progression. Loss of heterozygosity and reduced expression of the gene have been associated with poor prognosis and increased incidence of metastases in many epithelial tumors. The aim of this study was to detect the presence of NM23.H1 point mutations or small deletions in human breast carcinomas by using the single-strand-conformation polymorphism (SSCP) technique. Mutational analysis was performed on 76 breast tumors, 10 of which had allelic deletion of the gene. The NM23.H1 mRNA content also was evaluated in each sample. Only a C-to-A transversion leading to a stop codon was found in the 5' untranslated region of exon 1. A polymorphic SSCP pattern was identified in exon 1; direct sequencing showed a C-to-T transition 30 nucleotides upstream from the 5' splice site flanking exon 1. None of the tumors analyzed presented both alleles inactivated. Our results suggest that NM23.H1 is rarely inactivated by point mutations.
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PMID:Mutational analysis of the NM23.H1 gene in human breast cancer. 1106 4

The nm23 gene, originally identified by differential hybridization of metastatic murine melanoma cell lines has been associated with decreased metastatic potential. In this study, we evaluated the utility of nm23 expression levels as a predictive and a prognostic biomarker for distal metastases and poor survival in a Chinese cohort of 168 breast cancer patients. Our study indicates that high nm23 expression is associated with older age (older than 35 years) and smaller tumor size. There is no statistically significant association between nm23 expression and pathologic type or axillary metastasis. High nm23 expression is associated with the absence of distal metastases. Nearly 80% of women with high nm23 expression are alive after 10 years compared to 25% with low expression; at five years the cumulative survival proportions are 86% and 46%, respectively. The Cox model for survival indicates that controlling for tumor size and presence of axillary metastases at diagnosis, the hazard for women with low nm23 expression is nearly 4 times that of women with high nm23 expression. Low nm23 expression is predictive of distal metastases and appears to be a risk factor that is independent of the presence or absence of positive axillary nodes at diagnosis.
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PMID:Loss of nm23 expression predicts distal metastases and poorer survival for breast cancer. 1117 91

One of the most important factor in prognosis of the patients with laryngeal cancer is presence of the metastases in lymph nodes of the neck. The main purpose of the paper was the evaluation of CD34 and FVIII antigens as angiogenesis markers, and nm23 protein and CD44 antigen expression as metastasis potential markers and description of their role in the tumour progression and making metastasis in the patients with laryngeal cancer. Paraffin-embedded tissue sections from 89 patients with laryngeal cancer were stained with a monoclonal antibody raised against CD34 and FVIII antigens, against nm 23 protein and against CD44 antigen. Measuring the density of the microvasculature in tumour was investigated. We found significant dependence between intensity of angiogenesis (IA) and pT, nodal metastasis, histological grading and survival. There were also significant correlation between nm23 protein expression and nodal metastasis, and between CD44 antigen expression and pT, nm23 protein expression and FVIII antigen expression. Evaluation of mentioned markers allowed to asses the aggressiveness of tumour cells and anticipate neck metastasis in the patients with laryngeal cancer.
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PMID:[Evaluation of CD44 adhesion molecule, nm23 gene product expression and intensity of angiogenesis in patients with laryngeal cancer]. 1126 74

NM23 is considered to be a metastasis suppressor gene the role of which as prognosticator in the case of malignant skin melanoma (MM) is highly controversial due to different results on gene, and protein expressions. Accordingly, we analyzed the protein expression of NM23 in 32 primary skin melanomas with a follow-up period of 5 years minimum. We found that NM23 expression was the lowest in the thickest primary tumors (based on the % of the positive cells and the incidence of low expressor tumors) but the difference was not significant statistically due to the extreme heterogeneity of the tumors. When primary tumors were grouped according to their biological behavior (non-metastatic; lymph-node (LN) metastatic; organ and LN metastatic tumors) we observed that the lowest NM23 protein expression (based on the % of positive tumor cells as well as on the incidence of low expressor tumors) was found in the LN metastatic tumors compared to other groups (p < 0.05). The NM23 phenotype of the primary tumors remained stable in the corresponding LN metastases in the case of the 5 analyzed tumors. There was no difference in the 5-year survival between patients with low (< 50% positive cells) or high NM23 protein expressing primary tumors. Collectively, these data suggest that the NM23 protein expression in the primary tumors of MM predicted lymphatic spread but did not affect 5-year survival because it did not correlate with organ metastasis.
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PMID:The loss of NM23 protein in malignant melanoma predicts lymphatic spread without affecting survival. 1126 86

A left atrial tumor, in which radical resection was impossible, demonstrated two processes: An inflammatory pseudotumor and cellular atypia suggestive of a sarcoma. Immunohistochemistry (proliferating cell nuclear antigen [PCNA], MIB-1 [Ki-67 antibody], bcl-2 positive; p53 negative, focal loss of nm23) was supportive for a malignant tumor. Despite no further therapy because of uncertainty in tumor classification, the patient remained in remission for 28 months. Thereafter, spine metastases and local regrowth were found, and the patient died 15 months later, after temporary remission by radiotherapy. This case stresses the impact immunohistochemistry may have on diagnosis of malignancy and the difficulty in predicting the biological behavior of cardiac sarcomas.
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PMID:A primary cardiac sarcoma with unusual histology and clinical course. 1138 22


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