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Entity | Non-Small Cell Lung Cancer (NSCLC) |
Note | Higher expression of ENO1 was demonstrated in NSCLC tissues as compared with normal lung tissues. Detection and expression level of ENO1 in primary tumors were the key factors contributing to overall patient's survival rates. Relatively higher ENO1 levels in tumors correlated with poorer survival outcomes and tumor recurrence. Other report suggests that ENO1 down-regulation in patients with NSCLC, predicts more aggressive biological behaviour. The patients whose tumors showed decreased ENO1 production had significantly poorer overall survival when compared with those without ENO1 reduction. Also in proteomic studies, ENO1 was one of the secreted proteins demonstrated to be overexpressed by NSCLC cell line A549 as compared to controls. Studies in vitro performed on NSCLC cell line H1299, revealed that MBP-1 overexpression correlated with decreased cell proliferation as compared with corresponding controls. Investigations in vivo demonstrated tumor suppressive properties of MBP-1. In mice with induced tumors (injection of H1299) administration of adenovirus MBP-1 construct significantly reduced tumor growth and prolonged animal survival rates. |
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Entity | Small Cell Lung Cancer |
Note | There is some evidence concerning the role of anti-alpha-enolase antibodies in cancer associated retinopathy with SCLC. In serum obtained from patient with a sudden loss of vision, the only detectable antibodies were those against a 35-kDa anti-retinal protein. Surgical treatment performed after 1 week and 1 month, led to changes in the antibody response from antibodies against p35kDa to alpha-enolase after tumor resection. SCLC may express high levels of alpha-enolase and anti-alpha-enolase antibodies are typically detected after diagnosis of cancer. |
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Entity | Thyroid carcinoma |
Note | In thyroid oncocytomas, which represent a subgroup of follicular thyroid carcinoma (FTC), the up-regulation of ENO1, GPI (glucose phosphate isomerase) and GAPDH (glyceraldehydes-3-phosphate dehydrogenase) was identified as metabolic signature of thyroid carcinoma. Important role of ENO1 in progression of thyroid carcinoma was also demonstrated for cell lines established from FTC. Pre-treatment of these cell lines with retinoic acid (RA) used in therapy and chemoprevention of solid cancers, led to decrease in ENO1 and MBP-1 expression, accompanied by reduced invasiveness of the thyroid carcinoma cells. Similar effects were also observed after silencing of common the MYC promoter-binding domain found in ENO1 and MBP-1. Both, RA-mediated and siRNA induced reduction of ENO1/MBP-1 resulted in down-regulation of c-Myc oncoprotein. It seems that in FTC the bi-functional role of ENO1 gene products is diminished and ENO1 posses the enzymatic activity only. It is worth to notice that ENO1 promoter contains two MYC binding sites (CACGTG). C-Myc over-expression and interaction with these sites may result in increased ENO1 expression and/or energy production. In well differentiated medullary thyroid carcinomas MTC the relatively high amount of alpha beta and gamma gamma enolase isoenzymes was observed, indicating presumed neuroectodermal origin of these tumors. In highly undifferentiated and anaplastic MTCs, the majority of enzyme was represented as alpha alpha-enolase while alpha gamma-enolase was only weakly detectable. |
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Entity | Hepatocellular carcinoma (HCC) |
Note | In proteomic studies performed on HCC cell lines and tissues, ENO1 was identified as a protein that showed stronger expression in tumor tissues when comparing to nontumorous samples. Additionally, expression of ENO1 increased with tumor dedifferentiation status. Significantly higher ENO1 expression was found in poorly differentiated HCC than in well differentiated HCC. Moreover, expression of ENO1 positively correlated with tumor size and venous invasion. Also reduction of ENO1 by specific siRNAs decreased the proliferation rates of HCC cell lines and prolonged the G2/M phase of the cell cycle. Investigations of MBP-1 revealed its significant reduction in cirrhosis and even more diminished expression in HCC. This reduction was surprisingly accompanied by decrease in c-myc expression. |
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Entity | Breast carcinoma |
Note | Increased expression of ENO1 was found in HER-2/neu positive breast tumors and cell lines when compared with corresponding controls. HER-2/neu is the receptor tyrosine kinase found to be overexpressed in up to 30% of breast cancers and is associated with increased metastasis rate and poor prognosis. Introduction of MBP-1 gene into human breast carcinoma cells MDA-MB-231 and MCF-7 reduced their ability to penetrate basement membrane matrix and suppressed tumor formation in athymic nude mice. It is worth to notice that MCF-7 cell line is estrogen receptor positive and estrogen dependent for tumorigenicity. It was demonstrated that translation of ENO1 mRNA in MCF-7 cell line is glucose concentration-dependent. Low glucose concentrations increased the level of MBP-1 protein accompanied by reduced proliferation rates. The levels of ENO1 mRNA remained unaffected. This suggests that effects induced by low glucose concentrations are mediated by preferential translation of MBP-1 (using the down-stream ATG codon). In contrast, physiologic or high glucose concentrations correlated with reduced levels of MBP-1 protein and markedly induced growth of the cells. Interestingly the low glucose group exhibited a dramatic increase in c-Myc expression, not observed in physiologic or high glucose conditions. As demonstrated for follicular thyroid carcinoma cells, also in this case c-Myc might directly transactivate ENO1 promoter, resulting in an increase in glucose uptake and elevated proliferation rates. |
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Entity | Prostate cancer |
Note | Investigations performed on human prostate cancer cells PC3, revealed that tumor suppressive function of MBP-1 is diminished. Reduction of endogenous MBP-1 by employing specific siRNAs resulted in decreased proliferation rates accompanied by inhibition of cyclin A1 and cyclin B1 expression. Additionally, the cell size increased after depletion of MBP-1. Introduction of exogenous MBP-1 restored cyclins expression, leading to dose-dependent increase in cyclin A1 and B1 levels. |
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Entity | Brain tumors |
Note | Generally, the increased levels and activity of alpha alpha-enolase correlate with brain tumorigenicity. In astrocytomas with different degrees of malignancy, oligodendrogliomas, meningiomas and ependymomas, alpha alpha-enolase was more abundant than in normal brain tissues. Among astrocytic tumors, glioblastomas revealed the highest proportion of alpha alpha-enolase as compared with control tissues. Introduction of full length, exogenous ENO1 sequence into 1p-deleted or other neuroblastoma cell lines, led to reduction of cell growth. This suggests that in this cell lines ENO1 is preferentially translated as MBP-1 and probably does not posses the enolase enzyme activity. |
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Entity | Multiple myeloma (plasma cell myeloma, Kahler's disease) |
Note | It was demonstrated, that interleukin 6 (IL-6) is implicated in the in vivo proliferation of malignant plasma cells in multiple myeloma. Studies in vitro revealed that myeloma cell line U266 treated with IL-6, responded with increased levels of MBP-1 and XBP-1 (X-box binding protein). |
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Entity | Acute lung inflammation (pneumonia) |
Note | Increased ENO1 cell-surface expression on peripheral blood monocytes (PBMs) and strong ENO1 production in mononuclear cells in the alveolar space were demonstrated for pneumonia patients when compared with healthy volunteers. Elevated cell-surface expression of ENO1 on PBMs and on human leukemic monocyte lymphoma cell line U937, led to increased plasmin generation, enhanced monocyte migration through epithelial monolayers and promoted matrix degradation. |
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Entity | Vasculitis |
Note | In sera from patients with clinically proven vaculitis, anti-neutrophil cytoplasmic antibodies (ANCA) reacted with proteins present in the granules of human neutrophils. 37.3 % of these sera contained the antibodies raised against 48kDa protein, identified further as cytoplasmic alpha-enolase. Antibodies directed against enolase protein, recognised only alpha isoform and were detected in sera giving ANCA staining pattern. |
Disease | Vasculitis (inflammatory destruction of blood vessels). |
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Entity | Nephritis |
Note | In two independent studies antibodies raised against alpha-enolase were detected in 10/41 and 9/33 sera of patients with clinically proved SLE, respectively. 80% of patients from the first report and 66.7% from the second one, suffered from active nephritis. |
Disease | Nephritis (renal disease) caused by systemic lupus erythematosus (SLE, chronic autoimmune connective tissue disease that can affect any part of the body). |
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Entity | Ulcerative colitis |
Note | Alpha-enolase antibodies were found in about 10% of ulcerative colitis patients. |
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Entity | Crohn's disease |
Note | Alpha-enolase antibodies were found in about 18% of patients with Crohn's disease. |
Disease | Crohn's disease (autoimmune, inflammatory disease of the intestines that may affect any part of the gastrointestinal tract). |
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Entity | Primary biliary cirrhosis and autoimmune hepatitis |
Note | Alpha-enolase antibodies were present in 28.6% of patients with primary biliary cirrhosis and in 31.6% with autoimmune hepatitis. Normal subjects revealed significantly lower levels of alpha-enolase antibodies when compared with both diseases. Note that antibodies against beta and gamma enolases were not found in any serum sample analysed. |
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