Andreas Scorilas

The American Society for Biochemistry and Molecular Biology, Greece, New York, United States

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Publications (262)1125.62 Total impact

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    ABSTRACT: Bladder and renal cancer are two representative cases of tumors that respond differentially to gemcitabine. Previous studies have shown that gemcitabine can trigger apoptosis in various cancer cells. Herein, we sought to investigate the impact of gemcitabine on the expression levels of the BCL2 family members BCL2, BAX, and BCL2L12 and the apoptosis-related microRNAs miR-182, miR-96, miR-145, and miR-16 in the human bladder and kidney cancer cell lines T24 and Caki-1, respectively. Cancer cells' viability as well as the IC50 doses of gemcitabine were estimated by the MTT assay, while the detection of cleaved PARP via Western blotting was used as an indicator of apoptosis. Furthermore, T24 and Caki-1 cells' ability to recover from treatment was also monitored. Two different highly sensitive quantitative real-time RT-PCR methodologies were developed in order to assess the expression levels of BCL2 family genes and microRNAs. Exposure of cancer cells to gemcitabine produced the IC50 values of 30 and 3 nM for Caki-1 and T24 cells, correspondingly, while cleaved PARP was detected only in Caki-1 cells. T24 cells demonstrated the ability to recover from gemcitabine treatment, whereas Caki-1 cells' recovery capability was dependent on the initial time of exposure. BCL2 and BAX were significantly modulated in treated Caki-1 cells. Instead, T24 cells exhibited alterations only in the latter, as well as in all studied microRNAs. Therefore, according to our data, bladder and renal cancer cells' response to gemcitabine is accompanied by distinct alterations in the expression levels of their apoptosis-related genes and microRNAs.
    Tumor Biology 04/2015; DOI:10.1007/s13277-014-2190-8 · 2.84 Impact Factor
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    ABSTRACT: MicroRNA expression signatures can promote personalised care for non-small cell lung cancer (NSCLC) patients. Our aim was to evaluate the previously unexplored prognostic potential of miR-197, a key oncogenic molecule for NSCLC. Total RNA isolation (n=124 NSCLC and n=21 tumour-adjacent normal tissues), was performed using the QIAsymphony SP workstation. The quantity and quality of RNA were assessed by spectrophotometric analysis and an Agilent 2100 bioanalyzer. Polyadenylation and reverse transcription were subsequently carried out. MiR-197 expression levels were measured by qPCR, after quality control (inter-assay CV=7.8%). Internal validation procedures were followed by assigning training and test sets and robust biostatistical analyses were performed, including bootstrap resampling. MiR-197 is associated with larger tumours (P=0.042) and the squamous cell carcinoma histotype (P=0.032). Interestingly, after adjusting for important prognostic indicators, miR-197 expression was identified as a novel independent predictor of unfavourable prognosis for NSCLC patients (HR=1.97, 95% CI=1.10-3.38, P=0.013). We also demonstrate that miR-197 retains its prognostic performance in both early-stage I (P=0.045) and more advanced-stage individuals (P=0.036). The cost-effective expression analysis of miR-197 could constitute a novel molecular tool for NSCLC management.British Journal of Cancer advance online publication 31 March 2015; doi:10.1038/bjc.2015.119 www.bjcancer.com.
    British Journal of Cancer 03/2015; DOI:10.1038/bjc.2015.119 · 4.82 Impact Factor
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    ABSTRACT: Accurate prognosis is a key-factor in establishing optimal therapeutic decisions; yet in the case of bladder cancer (BlCa) current prognostic indicators cannot ensure optimal disease management. Here we aimed to evaluate the previously unexplored clinical potential of the urological cancer-related miR-145, miR-143 and miR-224 in BlCa. A total of 279 bladder tissue specimens were included in this study (133 BlCa, 107 adjacent normal and 39 healthy samples). Total RNA was extracted from tissues, it was polyadenylated and reverse transcribed to cDNA. The expression of target molecules was measured via qPCR. The expression levels of both miR-143 and miR-145 were significantly decreased, whereas those of miR-224 were increased in BlCa. ROC curve analysis indicated a significant discriminatory capacity for miR-143/miR-145 levels. Important associations with disease aggressiveness were observed for all three miRNAs; elevated levels were observed in tumors of higher stage and grade, as well as in "high-risk" TaT1 patients. More importantly, high miR-143/145 levels could effectively prognose inferior overall survival for muscle-invasive patients and could independently predict the progression of superficial tumors. Finally, the combination of miR-143/145 overexpression with the widely used prognostic markers of EORTC-risk groups or recurrence at the first follow-up cystoscopy resulted to a superior positive prediction of NMIBC short-term progression compared to the use of the abovementioned markers alone. The cancer-related miR-143, miR-145 and miR-224 were investigated for the first time in the clinical setting of BlCa, and miR-143/145 cluster constitutes a novel marker helpful for providing an enhanced prediction of oncologic outcome for BlCa patients. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Carcinogenesis 03/2015; DOI:10.1093/carcin/bgv024 · 5.27 Impact Factor
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    ABSTRACT: Sunitinib and everolimus are two of the antineoplastic agents indicated for the management of metastatic renal cancer. Although both of the above compounds were primarily designed as antiangiogenic factors, preclinical studies claim that these drugs can also trigger apoptosis. Herein, we sought to evaluate the cytotoxic activity of sunitinib and everolimus against renal cancer cells Caki-1 and moreover to assess their impact on the expression levels of three BCL2 family members and three apoptosis-related microRNA clusters upon incubation with the drugs or following recovery from treatment. The cytotoxic effect of sunitinib and everolimus on Caki-1 cells' viability was estimated by the MTT assay, while cleaved PARP, assayed via Western Blotting, served as a marker of programmed cell death. As for the expression levels of the BCL2 family members BCL2, BAX and BCL2L12 and those of the mature microRNAs of the miR-183/96/182, miR-143/145, and miR-15a/16 clusters, they were quantified via real-time PCR. Our results showed that both agents induced a time- and dose-dependent decrease in cell viability and promoted cleavage of PARP. In parallel, significant modulations were observed in the expression levels of miR-145, miR-15a, and miR-16 in case of sunitinib, whereas BCL2, BAX, miR-145 and miR-15a expression was strongly affected by everolimus. Overall, our data support the notion that sunitinib and everolimus are able to directly induce cell death in renal cancer cells and simultaneously affect the expression levels of their apoptosis-related microRNAs and BCL2 family members upon this process. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    Biomedecine [?] Pharmacotherapy 03/2015; 70:33-40. DOI:10.1016/j.biopha.2014.12.043 · 2.11 Impact Factor
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    ABSTRACT: Renal cell carcinoma (RCC) is the most frequent type of kidney cancer. RCC patients frequently present with arterial hypertension due to various causes, including intrarenal dopamine deficiency. L-DOPA decarboxylase (DDC) is the gene encoding the enzyme that catalyzes the biosynthesis of dopamine in humans. Several studies have shown that the expression levels of DDC are significantly deregulated in cancer. Thus, we herein sought to analyze the mRNA levels of DDC and evaluate their clinical significance in RCC. DDC levels were analyzed in 58 surgically resected RCC tumors and 44 adjacent non-cancerous renal tissue specimens via real-time PCR. Relative levels of DDC were estimated by applying the 2(-ΔΔC)T method, while their diagnostic accuracy and correlation with the clinicopathological features of RCC tumors were assessed by comprehensive statistical analysis. DDC mRNA levels were found to be dramatically downregulated (p<0.001) in RCC tumors, exhibiting remarkable diagnostic accuracy as assessed by ROC curve analysis (AUC: 0.910; p<0.001) and logistic regression (OR: 0.678; p=0.001). Likewise, DDC was found to be differentially expressed between clear cell RCC and the group of non-clear cell subtypes (p=0.001) consisted of papillary and chromophobe RCC specimens. Furthermore, a statistically significant inverse correlation was also observed when the mRNA levels of DDC were analyzed in relation to tumor grade (p=0.049). Our data showed that DDC constitutes a highly promising molecular marker for RCC, exhibiting remarkable diagnostic accuracy and potential to discriminate between clear cell and non-clear cell histological subtypes of RCC. Copyright © 2015. Published by Elsevier Inc.
    Clinical Biochemistry 02/2015; DOI:10.1016/j.clinbiochem.2015.02.007 · 2.23 Impact Factor
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    ABSTRACT: The KLK13 gene is dysregulated in several carcinomas and its expression levels seem to be associated with disease prognosis. The aim of our study was to investigate the prognostic potential of KLK13 mRNA expression for patients with non-small cell lung cancer (NSCLC). Total RNA was isolated from cancerous and normal tissues from a cohort of 128 NSCLC patients. The KLK13 mRNA transcription levels were measured using a sensitive quantitative RT-PCR method. The results were normalized by dividing the KLK13 mRNA values with the geometric mean of mRNA expression from 4 reference genes: beta-actin, TATA-binding protein, hypoxanthine phosphoribosyltransferase 1 and acidic ribosomal phosphoprotein P0. The malignant tissues from the majority of patients (59.3%) contained significantly more KLK13 mRNA transcripts than did the paired non-malignant tissues (median difference: 11.1-fold; P = 0.008). KLK13 was expressed at higher levels in females than in males (P = 0.021). No other statistically significant association with clinicopathological data was observed. Kaplan-Meier survival analyses demonstrated that patients with KLK13-positive tumors survived significantly longer than those with KLK13-negative ones (P = 0.009). KLK13 expression was also shown to be able to stratify high-risk individuals among patients with early disease stages (P = 0.030). Multivariate Cox regression analysis showed that KLK13 expression is a favorable, independent prognostic indicator of overall survival (OS) (P = 0.024). Our results suggest that KLK13 mRNA expression constitutes a novel biomarker for the prediction of overall survival in NSCLC and that its quantitative assessment in tumor tissues can aid in treatment decision making.
    Tumor Biology 01/2015; DOI:10.1007/s13277-015-3148-1 · 2.84 Impact Factor
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    ABSTRACT: Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with unpredictable behavior. Clinical parameters are not always accurate for predicting prognosis. miR-126 is differentially expressed in many cancers, including RCC, and is down-regulated in metastatic versus primary ccRCC. We assessed the prognostic significance of miR-126 in 264 primary ccRCCs. We also compared its expression in normal kidney, primary and metastatic ccRCC, and RCC subtypes. We validated our results on an independent set of 481 ccRCCs. miR-126 was down-regulated in metastatic versus primary tumors and in tumors of higher stage (P = 0.005) or higher grade (P = 0.002). miR-126 up-regulation was associated with significantly prolonged disease-free survival (P < 0.001) and overall survival (P = 0.015). For larger tumors (>4 cm), patients with higher miR-126 expression had significantly longer survival. Restoration of miR-126 expression decreased cellular migration and proliferation in RCC cell lines. The ccRCCs exhibited the highest miR-126 expression, and papillary RCCs exhibited the lowest expression. We identified a number of miR-126 targets and pathways that are involved in carcinogenesis, including the apoptosis signaling pathway. miR-126 is a promising prognostic marker in ccRCC that can distinguish between clear cell and papillary subtypes. In addition, miR-126 has potential therapeutic applications. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
    American Journal Of Pathology 01/2015; DOI:10.1016/j.ajpath.2014.11.017 · 4.60 Impact Factor
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    ABSTRACT: Accurate assessment of prognosis of clear cell renal cell carcinoma (ccRCC) is key in optimizing management plans to fit individual patient needs. miRNAs are short noncoding single-stranded RNAs that control the expression of target genes and may act as cancer biomarkers. We analyzed the expression of miR-210 in 276 cases of primary ccRCC and compared its expression in 40 pairs of adjacent normal and cancerous tissues. We assessed its expression in primary and metastatic tumors, in the common RCC subtypes, and the benign oncocytoma. The results were validated with an independent data set from The Cancer Genome Atlas. miR-210 was significantly overexpressed in ccRCC compared with normal kidney. miR-210(+) patients had a statistically higher chance of disease recurrence [hazard ratio (HR), 1.82; P = 0.018] and shorter overall survival (HR, 2.46; P = 0.014). In multivariate analysis, miR-210 lost its statistically significant association with shorter disease-free survival and overall survival after adjusting for tumor size and tumor, node, metastasis stage. Papillary RCC showed comparable miR-210 overexpression, whereas decreased up-regulation was seen in chromophobe RCC and oncocytoma. A number of predicted targets that might be involved in carcinogenesis and aggressive tumor behavior were identified. miR-210 is a potential therapeutic target and independent marker of poor prognosis of ccRCC. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.
    The Journal of molecular diagnostics: JMD 12/2014; DOI:10.1016/j.jmoldx.2014.10.005 · 3.96 Impact Factor
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    ABSTRACT: Clear cell renal cell carcinoma (ccRCC) is associated with high mortality, although individual outcomes are highly variable. Identification of patients with increased risk of disease progression can guide customizing management plan according to disease severity. Profilin-1 (Pfn1) has been recently identified as overexpressed in metastatic ccRCC compared with primary tumors. We examined Pfn1 expression in a tissue microarray of 384 cases of histologically confirmed primary ccRCC with detailed clinical follow-up. Profilin-1 expression showed both cytoplasmic and nuclear staining patterns. The immunoexpression of Pfn1 was scored in a semiquantitative fashion. There was no significant difference in Pfn1 expression between normal kidney and kidney ccRCC. Our results show that strong cytoplasmic Pfn1 expression is associated with high-grade (P < .001) and high-stage (III-IV) (P = .018) disease. Univariate analysis of the data set showed that higher Pfn1 expression is associated with significantly shorter disease-free survival (hazard ratio 7.36, P = .047) and also lower overall survival. Kaplan-Meier analysis showed that high cytoplasmic expression of Pfn1 was also associated with a statistically significant lower disease-free survival (P = .018). It was also associated with lower overall survival, although this was not statistically significant. Profilin-1 lost its prognostic significance in the multivariate analysis when controlling for grade and stage. Profilin-1 expression was not associated with significant prognostic deference in the subgroup of patients with stage 1 disease. Our results suggest that the evaluation of Pfn1 by immunohistochemistry may help to identify patients with an increased risk of disease progression. We validated our results at the messenger RNA level on an independent patient cohort. Higher messenger RNA expression of Pfn1 is associated with significantly lower survival. Copyright © 2014 Elsevier Inc. All rights reserved.
    Human pathology 11/2014; DOI:10.1016/j.humpath.2014.11.007 · 2.81 Impact Factor
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    ABSTRACT: Colorectal adenocarcinoma constitutes the most frequent form of colorectal cancer and a serious cause of cancer‑related deaths. The expression of multiple miRNAs, including miR-224, is deregulated in colorectal adenocarcinoma. The aim of this study was the investigation of the prognostic value of miR-224 in colorectal adenocarcinoma. For this purpose, total RNA was isolated from 115 colorectal adenocarcinomas and 66 adjacent non-cancer mucosae. Total RNA (2 µg) was polyadenylated and reverse transcribed. A quantitative PCR method based on SYBR‑Green chemistry was developed and applied for the quantification of miR-224 levels, followed by extensive biostatistical analysis. miR-224 levels in malignant colorectal adenocarcinomas ranged between 1.81 and 187.75 RQU (miR-224 copies/1,000 SNORD48 copies) with a median of 34.27, and were significantly elevated, compared to miR-224 levels in adjacent non-cancer mucosae (p<0.001). Enhanced miR-224 expression constitutes a rather strong prognosticator in colorectal adenocarcinoma, predicting short-term relapse and poor overall survival in these patients (p=0.012 and p=0.005, respectively), independent of established clinicopathological parameters. In conclusion, miR-224 is significantly upregulated in malignant colorectal tumors compared to adjacent non-cancer mucosae, and its enhanced expression constitutes an independent predictor of short-term relapse and poor overall survival in colorectal adenocarcinoma patients.
    International Journal of Oncology 11/2014; 46(2). DOI:10.3892/ijo.2014.2775 · 2.77 Impact Factor
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    ABSTRACT: l-DOPA decarboxylase (DDC) is a multiply-regulated gene which encodes the enzyme that catalyzes the biosynthesis of dopamine in humans. MicroRNAs comprise a novel class of endogenously transcribed small RNAs that can post-transcriptionally regulate the expression of various genes. Given that the mechanism of microRNA target recognition remains elusive, several genes, including DDC, have not yet been identified as microRNA targets. Nevertheless, a number of specifically designed bioinformatic algorithms provide candidate miRNAs for almost every gene, but still their results exhibit moderate accuracy and should be experimentally validated. Motivated by the above, we herein sought to discover a microRNA that regulates DDC expression. By using the current algorithms according to bibliographic recommendations we found that miR-145 could be predicted with high specificity as a candidate regulatory microRNA for DDC expression. Thus, a validation experiment followed by firstly transfecting an appropriate cell culture system with a synthetic miR-145 sequence and sequentially assessing the mRNA and protein levels of DDC via real-time PCR and Western blotting, respectively. Our analysis revealed that miR-145 had no significant impact on protein levels of DDC but managed to dramatically downregulate its mRNA expression. Overall, the experimental and bioinformatic analysis conducted herein indicate that miR-145 has the ability to regulate DDC mRNA expression and potentially this occurs by recognizing its mRNA as a target.
    Gene 10/2014; DOI:10.1016/j.gene.2014.10.043 · 2.08 Impact Factor
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    ABSTRACT: BCL2-like 12 (BCL2L12) is a new member of BCL2 gene family which was discovered and cloned by members of our group and found to be expressed in the mammary gland. Many genes of the BCL2 family were found to be implicated in breast carcinogenesis and to serve as possible prognostic markers. The aim of the present study was the quantification of BCL2L12 mRNA expression in order to assess its value as a prognostic tissue biomarker in breast cancer (BC). Design and Methods BCL2L12 mRNA levels were determined in a statistically significant sample size of cancerous (N=108) and adjacent non-cancerous (N=71) breast tissues using a highly sensitive quantitative real-time polymerase chain reaction (qRT-PCR) method. Relative quantification analysis was conducted using the comparative CT (2(-ddC)T) method, whereas the association between BCL2L12 expression and clinopathological data, disease free survival (DFS) and overall survival (OS) were estimated by statistical analysis.
    Clinical Biochemistry 09/2014; DOI:10.1016/j.clinbiochem.2014.09.008 · 2.23 Impact Factor
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    ABSTRACT: The Notch signaling pathway controls cell fates through interactions between neighboring cells by positively or negatively affecting the processes of proliferation, differentiation and apoptosis in a context-dependent manner. This pathway has been implicated in human cancer as both an oncogene and a tumor suppressor. Here we report new inactivating mutations in Notch pathway components in over 40% of human bladder cancers examined. Bladder cancer is the fourth most commonly diagnosed malignancy in the male population of the United States. Thus far, driver mutations in fibroblast growth factor receptor 3 (FGFR3) and, less commonly, in RAS proteins have been identified. We show that Notch activation in bladder cancer cells suppresses proliferation both in vitro and in vivo by directly upregulating dual-specificity phosphatases (DUSPs), thus reducing the phosphorylation of ERK1 and ERK2 (ERK1/2). In mouse models, genetic inactivation of Notch signaling leads to Erk1/2 phosphorylation, resulting in tumorigenesis in the urinary tract. Collectively our findings show that loss of Notch activity is a driving event in urothelial cancer.
    Nature Medicine 09/2014; 20(10). DOI:10.1038/nm.3678 · 28.05 Impact Factor
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    ABSTRACT: Abstract A large number of prostate cancer (PCa) patients receive treatment without significant benefits, strengthening the need for accurate prognosis, which can be supported by the study of miRNAs. In silico specificity analysis was performed for the identification of miRNAs able to regulate KLK2 and KLK4 expression. Total RNA was extracted from prostate tissues obtained from PCa and benign prostate hyperplasia patients. Thereafter, RNA was polyadenylated and reverse transcribed to cDNA, which was used for qPCR analysis. miR-378 was predicted to target both KLK2 and KLK4 and downregulated levels detected in PCa patients (p=0.050). The reduction of miR-378 was correlated with higher Gleason score (p=0.018), larger diameter tumors (p=0.034), and elevated serum PSA (p=0.006). Regarding prognosis, miR-378 was able to improve risk stratification according to Gleason score or tumor stage, while higher risk to recur highlighted for the patients expressing lower miR-378 levels. Finally, the loss of miR-378 was able to predict the short-term relapse of 'high'- and 'very high'-recurrence-risk patients, independent of Gleason score, tumor stage, PSA, and age as indicated by Kaplan-Meier survival curves (p=0.030) and multivariate Cox regression analysis (p=0.018). In conclusion, loss of miR-378 expression increases the risk for PCa progression and relapse, despite active treatment.
    Biological Chemistry 09/2014; 395(9):1095-1104. DOI:10.1515/hsz-2014-0150 · 2.69 Impact Factor
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    ABSTRACT: Abstract KLK6 is a secreted trypsin-like serine protease. KLK6 mRNA expression and its association with colon cancer (CC) progression was studied using quantitative real-time PCR. We examined the expression of KLK6 in 232 colon tissues (cancerous, non-cancerous, and adenomatous). We proved that KLK6 expression in CC behaves as a continuous variable, as its expression correlates significantly with increasing tumor stage (p=0.004) and histological grade (p=0.007). Interestingly, the expression of KLK6 in adenomas was significantly higher than that in the cancerous or non-cancerous tissues examined (p<0.001). Cox proportional hazard regression model using univariate analysis revealed that positive KLK6 expression is a significant factor for disease-free survival (DFS) (p=0.017) and overall survival (OS) (p=0.002) of patients. Kaplan-Meier survival curves demonstrated that KLK6-negative expression is significantly associated with longer DFS (p=0.009) and OS (p=0.001). ROC analysis showed that KLK6 expression has significant discriminatory power in distinguishing cancerous from non-cancerous colon tissues (p<0.001), or cancerous from adenoma tissues (p=0.001), or adenoma from non-cancerous colon tissues (p<0.001). Additionally, strong KLK6 immunostaining was seen in the cancer cells of selected CC sections, as well as in glandular cells and inflammatory cells of adenomas. In conclusion, KLK6 may represent a potential unfavorable prognostic biomarker for CC.
    Biological Chemistry 09/2014; 395(9):1105-1117. DOI:10.1515/hsz-2014-0166 · 2.69 Impact Factor
  • Andreas Scorilas, Konstantinos Mavridis
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    ABSTRACT: Kallikrein-related peptidases (KLKs) form a cancer-related ensemble of serine proteases. This multigene family hosts the most widely used cancer biomarker that is PSA-KLK3, with millions of tests performed annually worldwide. The present report provides an overview of the biomarker potential of the extended KLK family (KLK1-KLK15) in various disease settings and envisages approaches that could lead to additional KLK-driven applications in future molecular diagnostics. Particular focus is given on the inclusion of KLKs into multifaceted cancer biomarker panels that provide enhanced diagnostic, prognostic and/or predictive accuracy in several human malignancies. Such panels have been described so far for prostate, ovarian, lung and colorectal cancers. The role of KLKs as biomarkers in non-malignant disease settings, such as Alzheimer's disease and multiple sclerosis, is also commented upon. Predictions are given on the challenges and future directions regarding clinically oriented KLK research.
    Expert Review of Molecular Diagnostics 06/2014; DOI:10.1586/14737159.2014.928207 · 4.27 Impact Factor
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    ABSTRACT: Dysregulated expression of several KLK family members has been observed in colorectal adenocarcinoma. In the present study, the prognostic value of KLK11 mRNA expression as a molecular tissue biomarker in colorectal adenocarcinoma was examined.
    Biomarkers in Medicine 06/2014; 8(5):671-85. DOI:10.2217/bmm.13.151 · 2.86 Impact Factor
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    Athanasia Pavlopoulou, Andreas Scorilas
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    ABSTRACT: The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin superfamily and codes for a vast number of glycoproteins that differ greatly both in amino acid composition and function. The CEA family is divided into two groups, the carcinoembryonic antigen - related cell adhesion molecules (CEACAMs) and the pregnancy-specific glycoproteins (PSGs). The CEA family members are implicated in pleiotropic (patho)physiological functions including cell-cell adhesion, pregnancy, immunity, neovascularization, regulation of insulin homeostasis and carcinogenesis. In general, the CEA-encoding proteins are composed of an extracellular region with immunoglobulin variable and constant-like domains and a cytoplasmic region containing signaling motifs. Of particular interest, the well-studied human and mouse CEA genes are arranged in clusters in a single chromosome. Taking into account this characteristic, we made an effort to reconstruct the evolutionary history of the CEA gene family. Towards this end, the publicly available genomes were searched extensively for CEA homologs. The domain organization of the retrieved protein sequences was analyzed and, subsequently, comprehensive phylogenetic analyses of the entire length CEA homologous proteins were performed. A series of evolutionarily conserved amino acid residues, functionally important, were identified. The relative positioning of these residues on the modeled tertiary structure of novel CEA protein domains revealed that they are, also, spatially conserved. Furthermore, the chromosomal arrangement of CEA genes was examined and it was found that the CEA genes are preserved in terms of position, transcriptional orientation and number in all species under investigation.
    Genome Biology and Evolution 05/2014; DOI:10.1093/gbe/evu103 · 4.53 Impact Factor
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    ABSTRACT: Over 90% of cancer-related deaths in clear cell renal cell carcinoma (RCC) are caused by tumor relapse and metastasis. Thus, there is an urgent need for new molecular markers that can potentiate the efficacy of the current clinical-based models of prognosis assessment. The objective of this study is to evaluate the potential significance of lactate dehydrogenase A (LDHA), assessed by immunohistochemical staining, as a prognostic marker in clear cell renal cell carcinoma in relation to clinicopathological features and clinical outcome.
    Molecular Cancer 05/2014; 13(1):101. DOI:10.1186/1476-4598-13-101 · 5.40 Impact Factor

Publication Stats

6k Citations
1,125.62 Total Impact Points

Institutions

  • 2004–2015
    • The American Society for Biochemistry and Molecular Biology
      Greece, New York, United States
  • 2007–2014
    • Harokopion University of Athens
      Athínai, Attica, Greece
  • 2013
    • Technische Universität München
      München, Bavaria, Germany
  • 2006–2012
    • National and Kapodistrian University of Athens
      • Department of Biochemistry and Molecular Biology
      Athínai, Attica, Greece
    • Attikon University Hospital
      Athínai, Attica, Greece
    • Lund University
      • Department of Laboratory Medicine
      Lund, Skane, Sweden
  • 1997–2012
    • Saint Savvas Hospital
      Athínai, Attica, Greece
  • 2010
    • Centre of Biotechnology of Sfax (CBS)
      Şafāqis, Şafāqis, Tunisia
  • 1999–2009
    • University of Toronto
      • Department of Laboratory Medicine and Pathobiology
      Toronto, Ontario, Canada
  • 2002–2007
    • IPC Systems, Inc
      New York, New York, United States
    • University of Ioannina
      Yannina, Epirus, Greece
  • 2001–2006
    • National Center for Scientific Research Demokritos
      Athínai, Attica, Greece
  • 2003–2004
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
  • 1999–2003
    • Mount Sinai Hospital, Toronto
      • Department of Pathology and Laboratory Medicine
      Toronto, Ontario, Canada
  • 2000
    • 401 GSNA
      Athínai, Attica, Greece