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  1. EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas.

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    Dongsheng Yue

    Full Text Available Squamous cell carcinomas (SCC account for approximately 30% of non-small cell lung cancer (NSCLC. Current staging methods do not adequately predict outcome for this disease. EMX2 is a homeo-domain containing transcription factor known to regulate a key developmental pathway. This study assessed the significance of EMX2 as a prognostic and predictive marker for resectable lung SCC.Two independent cohorts of patients with lung SCC undergoing surgical resection were studied. EMX2 protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. EMX2 expression levels in tissue specimens were scored and correlated with patient outcomes. Chemo-sensitivity of lung SCC cell lines stably transfected with EMX2 shRNAs to cisplatin, carboplatin, and docetaxel was examined in vitro.EMX2 expression was down-regulated in lung SCC tissue samples compared to their matched adjacent normal tissues. Positive EMX2 expression was significantly associated with improved overall survival in stage I lung SCC patients, and in stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. EMX2 expression was also associated with expression of EMT markers in both lung SCC cell lines and tissue samples. Knock-down of EMX2 expression in lung SCC cells promoted chemo-resistance and cell migration.EMX2 expression is down-regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT. EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy.

  2. EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas

    Science.gov (United States)

    Zhang, Yi; Tolani, Bhairavi; Mo, Minli; Zhang, Hua; Zheng, Qingfeng; Yang, Yue; Cheng, Runfen; Jin, Joy Q.; Luh, Thomas W.; Yang, Cathryn; Tseng, Hsin-Hui K.; Giroux-Leprieur, Etienne; Woodard, Gavitt A.; Hao, Xishan; Wang, Changli; Jablons, David M.; He, Biao

    2015-01-01

    Background Squamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer (NSCLC). Current staging methods do not adequately predict outcome for this disease. EMX2 is a homeo-domain containing transcription factor known to regulate a key developmental pathway. This study assessed the significance of EMX2 as a prognostic and predictive marker for resectable lung SCC. Methods Two independent cohorts of patients with lung SCC undergoing surgical resection were studied. EMX2 protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. EMX2 expression levels in tissue specimens were scored and correlated with patient outcomes. Chemo-sensitivity of lung SCC cell lines stably transfected with EMX2 shRNAs to cisplatin, carboplatin, and docetaxel was examined in vitro. Results EMX2 expression was down-regulated in lung SCC tissue samples compared to their matched adjacent normal tissues. Positive EMX2 expression was significantly associated with improved overall survival in stage I lung SCC patients, and in stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. EMX2 expression was also associated with expression of EMT markers in both lung SCC cell lines and tissue samples. Knock-down of EMX2 expression in lung SCC cells promoted chemo-resistance and cell migration. Conclusions EMX2 expression is down-regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT). EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. PMID:26132438

  3. Prediction of response to radiotherapy in the treatment of esophageal cancer using stem cell markers

    International Nuclear Information System (INIS)

    Background and purpose: In this study, we investigated whether cancer stem cell marker expressing cells can be identified that predict for the response of esophageal cancer (EC) to CRT. Materials and methods: EC cell-lines OE-33 and OE-21 were used to assess in vitro, stem cell activity, proliferative capacity and radiation response. Xenograft tumors were generated using NOD/SCID mice to assess in vivo proliferative capacity and tumor hypoxia. Archival and fresh EC biopsy tissue was used to confirm our in vitro and in vivo results. Results: We showed that the CD44+/CD24− subpopulation of EC cells exerts a higher proliferation rate and sphere forming potential and is more radioresistant in vitro, when compared to unselected or CD44+/CD24+ cells. Moreover, CD44+/CD24− cells formed xenograft tumors faster and were often located in hypoxic tumor areas. In a study of archival pre-neoadjuvant CRT biopsy material from EC adenocarcinoma patients (N = 27), this population could only be identified in 50% (9/18) of reduced-responders to neoadjuvant CRT, but never (0/9) in the complete responders (P = 0.009). Conclusion: These results warrant further investigation into the possible clinical benefit of CD44+/CD24− as a predictive marker in EC patients for the response to chemoradiation

  4. Transcription Profiles of Marker Genes Predict The Transdifferentiation Relationship between Eight Types of Liver Cell during Rat Liver Regeneration

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    Xiaguang Chen

    2015-07-01

    Full Text Available Objective: To investigate the transdifferentiation relationship between eight types of liver cell during rat liver regeneration (LR. Materials and Methods: 114 healthy Sprague-Dawley (SD rats were used in this experimental study. Eight types of liver cell were isolated and purified with percoll density gradient centrifugation and immunomagentic bead methods. Marker genes for eight types of cell were obtained by retrieving the relevant references and databases. Expression changes of markers for each cell of the eight cell types were measured using microarray. The relationships between the expression profiles of marker genes and transdifferentiation among liver cells were analyzed using bioinformatics. Liver cell transdifferentiation was predicted by comparing expression profiles of marker genes in different liver cells. Results: During LR hepatocytes (HCs not only express hepatic oval cells (HOC markers (including PROM1, KRT14 and LY6E, but also express biliary epithelial cell (BEC markers (including KRT7 and KRT19; BECs express both HOC markers (including GABRP, PCNA and THY1 and HC markers such as CPS1, TAT, KRT8 and KRT18; both HC markers (KRT18, KRT8 and WT1 and BEC markers (KRT7 and KRT19 were detected in HOCs. Additionally, some HC markers were also significantly upregulated in hepatic stellate cells ( HSCs, sinusoidal endothelial cells (SECs , Kupffer cells (KCs and dendritic cells (DCs, mainly at 6-72 hours post partial hepatectomy (PH. Conclusion: Our findings indicate that there is a mutual transdifferentiation relationship between HC, BEC and HOC during LR, and a tendency for HSCs, SECs, KCs and DCs to transdifferentiate into HCs.

  5. Circulating Tumor Cells in Metastatic Breast Cancer: A Prognostic and Predictive Marker

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    Sayyed Farshid Moussavi-Harami

    2014-05-01

    Full Text Available The role of circulating tumor cells (CTCs as a marker for disease progression in metastatic cancer is controversial. The current review will serve to summarize the evidence on CTCs as a marker of disease progression in patients with metastatic breast cancer. The immunohistochemistry (IHC-based CellSearch® is the only FDA-approved isolation technique for quantifying CTCs in patients with metastatic breast cancer. We searched PubMed and Web of Knowledge for clinical studies that assessed the prognostic and predictive value of CTCs using IHC-based isolation. The patient outcomes reported include median and Cox-proportional hazard ratios for overall survival (OS and progression-free survival (PFS. All studies reported shorter OS for CTC-positive patients versus CTC-negative. A subset of the selected trials reported significant lower median PFS for CTC-positive patients. The reported trials support the utility of CTC enumeration for patient prognosis. But further studies are required to determine the utility of CTC enumeration for guiding patient therapy. There are three clinical trials ongoing to test this hypothesis. These studies, and others, will further establish the role of CTCs in clinical practice.

  6. Embryonic Stem Cell Markers

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    Lan Ma; Liang Li; Wenxiu Zhao; Xiang Ji; Fangfang Zhang

    2012-01-01

    Embryonic stem cell (ESC) markers are molecules specifically expressed in ES cells. Understanding of the functions of these markers is critical for characterization and elucidation for the mechanism of ESC pluripotent maintenance and self-renewal, therefore helping to accelerate the clinical application of ES cells. Unfortunately, different cell types can share single or sometimes multiple markers; thus the main obstacle in the clinical application of ESC is to purify ES cells from other type...

  7. Gene expression markers in circulating tumor cells may predict bone metastasis and response to hormonal treatment in breast cancer

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    WANG, HAIYING; MOLINA, JULIAN; JIANG, JOHN; FERBER, MATTHEW; PRUTHI, SANDHYA; JATKOE, TIMOTHY; DERECHO, CARLO; RAJPUROHIT, YASHODA; ZHENG, JIAN; WANG, YIXIN

    2013-01-01

    Circulating tumor cells (CTCs) have recently attracted attention due to their potential as prognostic and predictive markers for the clinical management of metastatic breast cancer patients. The isolation of CTCs from patients may enable the molecular characterization of these cells, which may help establish a minimally invasive assay for the prediction of metastasis and further optimization of treatment. Molecular markers of proven clinical value may therefore be useful in predicting disease aggressiveness and response to treatment. In our earlier study, we identified a gene signature in breast cancer that appears to be significantly associated with bone metastasis. Among the genes that constitute this signature, trefoil factor 1 (TFF1) was identified as the most differentially expressed gene associated with bone metastasis. In this study, we investigated 25 candidate gene markers in the CTCs of metastatic breast cancer patients with different metastatic sites. The panel of the 25 markers was investigated in 80 baseline samples (first blood draw of CTCs) and 30 follow-up samples. In addition, 40 healthy blood donors (HBDs) were analyzed as controls. The assay was performed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) with RNA extracted from CTCs captured by the CellSearch system. Our study indicated that 12 of the genes were uniquely expressed in CTCs and 10 were highly expressed in the CTCs obtained from patients compared to those obtained from HBDs. Among these genes, the expression of keratin 19 was highly correlated with the CTC count. The TFF1 expression in CTCs was a strong predictor of bone metastasis and the patients with a high expression of estrogen receptor β in CTCs exhibited a better response to hormonal treatment. Molecular characterization of these genes in CTCs may provide a better understanding of the mechanism underlying tumor metastasis and identify gene markers in CTCs for predicting disease progression and

  8. Circulating tumor cells as a prognostic and predictive marker in gastrointestinal stromal tumors

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    Li, Qiang; Zhi, Xiaofei; Zhou, Jianping;

    2016-01-01

    BACKGROUND: Circulating tumor cells (CTC) are prognostic and predictive for several cancer types. Only limited data exist regarding prognostic or predictive impact of CTC on gastrointestinal stromal tumor (GIST) patients. The aim of our study was to elucidate the role of CTC in GIST patients. RES...

  9. Embryonic Stem Cell Markers

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    Lan Ma

    2012-05-01

    Full Text Available Embryonic stem cell (ESC markers are molecules specifically expressed in ES cells. Understanding of the functions of these markers is critical for characterization and elucidation for the mechanism of ESC pluripotent maintenance and self-renewal, therefore helping to accelerate the clinical application of ES cells. Unfortunately, different cell types can share single or sometimes multiple markers; thus the main obstacle in the clinical application of ESC is to purify ES cells from other types of cells, especially tumor cells. Currently, the marker-based flow cytometry (FCM technique and magnetic cell sorting (MACS are the most effective cell isolating methods, and a detailed maker list will help to initially identify, as well as isolate ESCs using these methods. In the current review, we discuss a wide range of cell surface and generic molecular markers that are indicative of the undifferentiated ESCs. Other types of molecules, such as lectins and peptides, which bind to ESC via affinity and specificity, are also summarized. In addition, we review several markers that overlap with tumor stem cells (TSCs, which suggest that uncertainty still exists regarding the benefits of using these markers alone or in various combinations when identifying and isolating cells.

  10. The Current Immunohistochemistry Markers in the Resected Tissues of Non-small Cell Lung Cancer Could Not Predict Prognosis

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    Luyan SHEN

    2016-03-01

    Full Text Available Background and objective It has been drawn much attention to identify the molecular markers by immunohistochemistry (IHC for evaluating the prognosis of non-small cell lung cancer (NSCLC following resection. The aim of this study is to retrospectively associate ever tested IHC markers and prognosis of NSCLC after resection. Methods A total of 722 NSCLC patients underwent surgery by single surgeon team from 2008 to 2013. Twelve molecular markers had been examined by IHC and the staining signals was re-scored with unified standard. Survival analysis by univariate and multivariate was carried out to assess the significance of these markers in prognosis of NSCLC in our prospective database with strict follow-up. Results The following twelve IHC markers had been tested between 2008 and 2013, including platelet-derived growth factor receptor (PDGFR(n=124, excision repair cross complementing 1 (ERCC1(n=124, epithelial growth factor receptor (EGFR(n=131, vascular endothelial growth factor receptor 3 (VEGFR3(n=142, NM23 (n=129, MRP (n=109, P170 (n=104, TS (n=143, Tubulin (n=133, ribonucleotide reductase M1 (RRM1(n=131, ribonucleotide reductase M1 (COX2(n=138, and TOPII (n=127. Only VEGFR3 expression was correlated with prognosis of the patients by univariate analysis, with 5-yrs survival rate being 77.6% and 65.0% (positive vs. negative respectively (P=0.042. However, VEGFR3 was not an independent prognostic factor for this series of NSCLC patients in multivariate analysis. Conclusion These twelve IHC markers could not predict prognosis of NSCLC patients after surgery in our series.

  11. Prediction of lung density changes after radiotherapy by cone beam computed tomography response markers and pre-treatment factors for non-small cell lung cancer patients

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    Bernchou, Uffe; Hansen, Olfred; Schytte, Tine; Bertelsen, Anders; Hope, Andrew; Moseley, Douglas; Brink, Carsten

    2015-01-01

    BACKGROUND AND PURPOSE: This study investigates the ability of pre-treatment factors and response markers extracted from standard cone-beam computed tomography (CBCT) images to predict the lung density changes induced by radiotherapy for non-small cell lung cancer (NSCLC) patients. METHODS AND...... MATERIALS: Density changes in follow-up computed tomography scans were evaluated for 135 NSCLC patients treated with radiotherapy. Early response markers were obtained by analysing changes in lung density in CBCT images acquired during the treatment course. The ability of pre-treatment factors and CBCT...... markers to predict lung density changes induced by radiotherapy was investigated. RESULTS: Age and CBCT markers extracted at 10th, 20th, and 30th treatment fraction significantly predicted lung density changes in a multivariable analysis, and a set of response models based on these parameters were...

  12. Efficient marker data utilization in genomic prediction

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    Edriss, Vahid

    Genomic prediction is a novel method to recognize the best animals for breeding. The aim of this PhD is to improve the accuracy of genomic prediction in dairy cattle by effeiently utilizing marker data. The thesis focuses on three aspects for improving the genomc prediction, which are: criteria of...... editing marker data, methods to handle missing genotypes and prediction using haplotypes constructed with an advanced method. The results of this study show that the accuracy of genomc prediction increases by: optimal criteria for marker data editing parameters, proper handling of missing genotypes using...

  13. Analyses of Potential Predictive Markers and Response to Targeted Therapy in Patients with Advanced Clear-cell Renal Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yan Song; Jing Huang; Ling Shan; Hong-Tu Zhang

    2015-01-01

    Background:Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC),but biomarkers of activity are lacking.The aim of this study was to investigate the association of Von Hippel-Lindau (VHL) gene status,vascular endothelial growth factor receptor (VEGFR) or stem cell factor receptor (KIT) expression,and their relationships with characteristics and clinical outcome of advanced ccRCC.Methods:A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute,Chinese Academy of Medical Sciences between January 2010 and November 2012.Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry.Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS) and ovcrall survival (OS) were calculated and then compared based on expression status.The Chi-square test,the KaplanMeier method,and the Lon-rank test were used for statistical analyses.Results:Of 59 patients,objective responses were observed in 28 patients (47.5%).The median PFS was 13.8 months and median OS was 39.9 months.There was an improved PFS in patients with the following clinical features:Male gender,number of metastatic sites 2 or less,VEGFR-2 positive or KIT positive.Eleven patients (18.6%) had evidence of VHL mutation,with an objective response rate of 45.5%,which showed no difference with patients with no VHL mutation (47.9%).VHL mutation status did not correlate with either overall response rate (P =0.938) or PFS (P =0.277).The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients,respectively,which was significantly longer than that of VEGFR-2 or KIT negative patients (P =0.026 and P =0.043).Conclusion:VHL mutation status could not predict

  14. Analyses of Potential Predictive Markers and Response to Targeted Therapy in Patients with Advanced Clear-cell Renal Cell Carcinoma

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    Yan Song

    2015-01-01

    Full Text Available Background: Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC, but biomarkers of activity are lacking. The aim of this study was to investigate the association of Von Hippel-Lindau (VHL gene status, vascular endothelial growth factor receptor (VEGFR or stem cell factor receptor (KIT expression, and their relationships with characteristics and clinical outcome of advanced ccRCC. Methods: A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute, Chinese Academy of Medical Sciences between January 2010 and November 2012. Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry. Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS and overall survival (OS were calculated and then compared based on expression status. The Chi-square test, the Kaplan-Meier method, and the Lon-rank test were used for statistical analyses. Results: Of 59 patients, objective responses were observed in 28 patients (47.5%. The median PFS was 13.8 months and median OS was 39.9 months. There was an improved PFS in patients with the following clinical features: Male gender, number of metastatic sites 2 or less, VEGFR-2 positive or KIT positive. Eleven patients (18.6% had evidence of VHL mutation, with an objective response rate of 45.5%, which showed no difference with patients with no VHL mutation (47.9%. VHL mutation status did not correlate with either overall response rate (P = 0.938 or PFS (P = 0.277. The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients, respectively, which was significantly longer than that of VEGFR-2 or KIT negative patients (P = 0.026 and P = 0.043. Conclusion

  15. Soluble Serum αKlotho Is a Potential Predictive Marker of Disease Progression in Clear Cell Renal Cell Carcinoma.

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    Gigante, Margherita; Lucarelli, Giuseppe; Divella, Chiara; Netti, Giuseppe Stefano; Pontrelli, Paola; Cafiero, Cesira; Grandaliano, Giuseppe; Castellano, Giuseppe; Rutigliano, Monica; Stallone, Giovanni; Bettocchi, Carlo; Ditonno, Pasquale; Gesualdo, Loreto; Battaglia, Michele; Ranieri, Elena

    2015-11-01

    Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies, and clear cell RCC (ccRCC), that has a high metastatic index and high relapse rate, is the most common histological subtype. The identification of new biomarkers in ccRCC is fundamental for stratifying patients into prognostic risk groups and to guide therapy. The renoprotective antiaging gene, αKlotho, has recently been found to work as a tumor suppressor in different human cancers. Here, we evaluated αKlotho expression in tissue and serum of ccRCC patients and correlated it with disease progression. Tissue αKlotho expression was studied by quantitative RT-PCR and immunohistochemistry. In addition, soluble serum αKlotho levels were preoperatively measured in 160 patients who underwent nephrectomy for RCC with ELISA. Estimates of cancer-specific (CSS) and progression-free survival (PFS) were calculated according to the Kaplan-Meier method. Multivariate analysis was performed to identify the most significant variables for predicting CSS and PFS. αKlotho protein levels were significantly decreased in RCC tissues compared with normal tissues (P < 0.01) and the more advanced the disease, the more evident the down-regulation. This trend was also observed in serum samples. Statistically significant differences resulted between serum αKlotho levels and tumor size (P = 0.003), Fuhrman grade (P = 0.007), and clinical stage (P = 0.0004). CSS and PFS were significantly shorter in patients with lower levels of αKlotho (P < 0.0001 and P = 0.0004, respectively). At multivariate analysis low serum levels of αKlotho were independent adverse prognostic factors for CSS (HR = 2.11; P = 0.03) and PFS (HR = 2.18; P = 0.03).These results indicate that a decreased αKlotho expression is correlated with RCC progression, and suggest a key role of declining αKlotho in the onset of cancer metastasis. PMID:26559258

  16. Can widely used cell type markers predict the suitability of immortalized or primary mammary epithelial cell models?

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    Ontsouka, Edgar; Bertschi, Janique Sabina; Huang, Xiao; Lüthi, Michael; Müller, Stefan Jürg; Albrecht, Christiane

    2016-01-01

    BACKGROUND Mammary cell cultures are convenient tools for in vitro studies of mammary gland biology. However, the heterogeneity of mammary cell types, e.g., glandular milk secretory epithelial or myoepithelial cells, often complicates the interpretation of cell-based data. The present study was undertaken to determine the relevance of bovine primary mammary epithelial cells isolated from American Holstein (bMECUS) or Swiss Holstein-Friesian (bMECCH) cows, and of primary bovine mammary alv...

  17. Can widely used cell type markers predict the suitability of immortalized or primary mammary epithelial cell models?

    OpenAIRE

    Ontsouka, Edgar Corneille; Bertschi, Janique Sabina; Huang, Xiao; Lüthi, Michael; Müller, Stefan; Albrecht, Christiane

    2016-01-01

    Background Mammary cell cultures are convenient tools for in vitro studies of mammary gland biology. However, the heterogeneity of mammary cell types, e.g., glandular milk secretory epithelial or myoepithelial cells, often complicates the interpretation of cell-based data. The present study was undertaken to determine the relevance of bovine primary mammary epithelial cells isolated from American Holstein (bMECUS) or Swiss Holstein–Friesian (bMECCH) cows, and of primary bovine mammary alveola...

  18. Galectin-7 as a potential predictive marker of chemo-and/or radio-therapy resistance in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Treatment of advanced oral squamous cell carcinoma (OSCC) requires the integration of multimodal approaches. The aim of this study was to identify predictors of tumor sensitivity to preoperative radiotherapy/chemotherapy for OSCC in order to allow oncologists to determine optimum therapeutic strategies without the associated adverse effects. Here, the protein expression profiles of formalin-fixed paraffin-embedded (FFPE) tissue samples from 18 OSCC patients, termed learning cases, who received preoperative chemotherapy and/or radiotherapy followed by surgery were analyzed by quantitative proteomics and validated by immunohistochemistry in 68 test cases as well as in the 18 learning cases. We identified galectin-7 as a potential predictive marker of chemotherapy and/or radiotherapy resistance, and the sensitivity and specificity of the galectin-7 prediction score (G7PS) in predicting this resistance was of 96.0% and 39.5%, respectively, in the 68 test cases. The cumulative 5-year disease-specific survival rate was 75.2% in patients with resistant prediction using G7PS and 100% in patients with sensitive prediction. In vitro overexpression of galectin-7 significantly decreased cell viability in OSCC cell line. Therefore, our findings suggest that galectin-7 is a potential predictive marker of chemotherapy and/or radiotherapy resistance in patients with OSCC. Identification of proteins differentially expressed in OSSC samples from patients sensitive or resistant. The samples were processed by LC-MS and analyzed with 2DICAL

  19. A Comparison of KL-6 and Clara Cell Protein as Markers for Predicting Bronchopulmonary Dysplasia in Preterm Infants

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    Keyi Wang

    2014-01-01

    Full Text Available Objectives. To evaluate the predictive characteristics of KL-6 and CC16 for bronchopulmonary dysplasia (BPD in preterm infants, either independently or in combination. Study Design. This prospective cohort study was performed from 2011 to 2013 with preterm neonates of gestational age ≤32 weeks and birth weight ≤1500 g. Serum KL-6 and CC16 levels were determined 7 and 14 days after birth. Results. Seventy-three preterm infants were studied. BPD was identified in 24 of these infants. After adjusting for potential confounders, serum KL-6 concentrations were found to be elevated in BPD infants at both time points relative to non-BPD infants, while serum CC16 concentrations were lower at 14 days. At both 7 d and 14 d of life the predictive power of KL-6 levels exceeded that of CC16 (area under receiver operating characteristic curve: at 7 d, 0.91 cf. 0.73, P=0.02; at 14 d, 0.95 cf. 0.85, P=0.05. The combination of these markers enhanced the sensitivity further. Conclusions. Serum KL-6 levels higher than 79.26 ng/mL at 14 days postpartum in preterm infants predict the occurrence of BPD. CC16 was less predictive than KL-6 at this time point, but KL-6 and CC16 together enhanced the prediction.

  20. Diffusion-weighted MRI in renal cell carcinoma: A surrogate marker for predicting nuclear grade and histological subtype

    International Nuclear Information System (INIS)

    Background: Though previous investigators have attempted to evaluate its utility in characterization of focal renal lesions, diffusion-weighted MR imaging (DW MRI) in renal diseases is still an evolving field and its role in predicting the aggressiveness of renal cell carcinoma (RCC) is yet to be established. Purpose: To assess whether apparent diffusion coefficient (ADC) values can be used to determine the nuclear grade and histological subtype of RCCs and to identify the tumor attributes contributing to variation in ADC values. Material and Methods: The institutional ethics committee waived the requirement of informed consent for this retrospective study. The study cohort consisted of 33 patients who underwent MRI (with diffusion-weighted imaging at b values of 0 and 500 s/mm2) and were found to have 36 pathologically-proven RCCs. ADC values were determined for solid portions of RCC, cystic/hemorrhagic areas, and normal renal parenchyma. Histological subtype, nuclear grade, and cell count were determined for each lesion. ADC values were compared between different grades and subtypes and correlation with cell count was investigated. Receiver operating characteristic curves were drawn to establish cut-off ADC values. Results: There were 23 low grade (grades I and II) and 13 high grade tumors (grades III and IV). There were 32 clear-cell and four non-clear-cell RCCs. A decreasing trend of ADC values was seen with increasing grade and mean ADC of high grade RCC was significantly lower than low grade (1.3145 vs 1.6982 x 10-3 mm2/s) (P = 0.005). Mean ADC for clear-cell RCC was significantly higher than non-clear-cell RCC (1.6245 vs. 1.0412 x 10-3 mm2/s) (P = 0.005). ADC values higher than 1.7960 x 10-3 mm2/s were seen only with low grade and values greater than 1.4904 x 10-3 mm2/s were seen only with clear-cell RCC. Conclusion: ADC values provide a non-invasive means to predict the nuclear grade and histological subtype of RCC. Cellularity and morphology are other

  1. Diffusion-weighted MRI in renal cell carcinoma: A surrogate marker for predicting nuclear grade and histological subtype

    Energy Technology Data Exchange (ETDEWEB)

    Goyal, Ankur; Sharma, Raju; Bhalla, Ashu S.; Gamanagatti, Shivanand (Dept. of Radiodiagnosis, All India Inst. of Medical Sciences (AIIMS), New Delhi (India)), Email: raju152@yahoo.com; Seth, Amlesh (Dept. of Urology, All India Inst. of Medical Sciences (AIIMS), New Delhi (India)); Iyer, Venkateswaran K.; Das, Prasenjit (Dept. of Pathology, All India Inst. of Medical Sciences (AIIMS), New Delhi (India))

    2012-04-15

    Background: Though previous investigators have attempted to evaluate its utility in characterization of focal renal lesions, diffusion-weighted MR imaging (DW MRI) in renal diseases is still an evolving field and its role in predicting the aggressiveness of renal cell carcinoma (RCC) is yet to be established. Purpose: To assess whether apparent diffusion coefficient (ADC) values can be used to determine the nuclear grade and histological subtype of RCCs and to identify the tumor attributes contributing to variation in ADC values. Material and Methods: The institutional ethics committee waived the requirement of informed consent for this retrospective study. The study cohort consisted of 33 patients who underwent MRI (with diffusion-weighted imaging at b values of 0 and 500 s/mm2) and were found to have 36 pathologically-proven RCCs. ADC values were determined for solid portions of RCC, cystic/hemorrhagic areas, and normal renal parenchyma. Histological subtype, nuclear grade, and cell count were determined for each lesion. ADC values were compared between different grades and subtypes and correlation with cell count was investigated. Receiver operating characteristic curves were drawn to establish cut-off ADC values. Results: There were 23 low grade (grades I and II) and 13 high grade tumors (grades III and IV). There were 32 clear-cell and four non-clear-cell RCCs. A decreasing trend of ADC values was seen with increasing grade and mean ADC of high grade RCC was significantly lower than low grade (1.3145 vs 1.6982 x 10-3 mm2/s) (P = 0.005). Mean ADC for clear-cell RCC was significantly higher than non-clear-cell RCC (1.6245 vs. 1.0412 x 10-3 mm2/s) (P = 0.005). ADC values higher than 1.7960 x 10-3 mm2/s were seen only with low grade and values greater than 1.4904 x 10-3 mm2/s were seen only with clear-cell RCC. Conclusion: ADC values provide a non-invasive means to predict the nuclear grade and histological subtype of RCC. Cellularity and morphology are other

  2. Predictive markers of honey bee colony collapse.

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    Benjamin Dainat

    Full Text Available Across the Northern hemisphere, managed honey bee colonies, Apis mellifera, are currently affected by abrupt depopulation during winter and many factors are suspected to be involved, either alone or in combination. Parasites and pathogens are considered as principal actors, in particular the ectoparasitic mite Varroa destructor, associated viruses and the microsporidian Nosema ceranae. Here we used long term monitoring of colonies and screening for eleven disease agents and genes involved in bee immunity and physiology to identify predictive markers of honeybee colony losses during winter. The data show that DWV, Nosema ceranae, Varroa destructor and Vitellogenin can be predictive markers for winter colony losses, but their predictive power strongly depends on the season. In particular, the data support that V. destructor is a key player for losses, arguably in line with its specific impact on the health of individual bees and colonies.

  3. Predictive Immunohistochemical Markers Related to Drug Selection for Patients Treated with Sunitinib or Sorafenib for Metastatic Renal Cell Cancer

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    Ma, Xin; Wang, Lei; Li, Hongzhao; Zhang, Yu; Gao, Yu; Guo, Gang; Liu, Kan; Meng, Qingyu; Zhao, Chaofei; Wang, Dianjun; Song, Zhigang; Zhang, Xu

    2016-01-01

    Targeted drug decisions in metastatic renal cell carcinoma are exclusively made on the basis of clinical criteria. We investigated whether these biomarkers (HIF-1α, HIF-2α, CAIX, VEGF, VEGFR1, VEGFR2, VEGFR3, PDGFB, PDGFRA, PDGFRB, CD31, CD44, bcl-xL, KIT, p21, CXCR4, PTEN, (CSF)-1R, RET, and FLT-3) can predictive the different effects between sunitinib and sorafenib treatments and are available to guide targeted drug selection. We enrolled all patients who underwent nephrectomy with postoperative sunitinib- or sorafenib-treatment at our institution from 2007 to 2012. Immunohistochemical approach was applied to assess the potential differential effects of immunostainings between sunitinib- and sorafenib-treated groups. We found that patients with high HIF-2α, CD31 expression showed greater relative PFS and OS benefit and patients with high CAIX expression presented greater relative OS benefit from sunitinib than from sorafenib, patients with high VEGFR1 or PDGFRB expression levels exhibited worse relative PFS benefit from sunitinib than from sorafenib. Namely high HIF-2α, CD31, and CAIX expression levels along with low VEGFR1 and PDGFRB expression levels improved the benefit of sunitinib treatment compared with sorafenib treatment. These results can identify whether patients can benefit more from sunitinib or sorafenib for drug selection guidance, eventually with precision medicine. PMID:27488093

  4. Mutant KRAS associated malic enzyme 1 expression is a predictive marker for radiation therapy response in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Advanced non-small cell lung cancer (NSCLC) is an aggressive tumor that is treated with a combination of chemotherapy and radiation if the patient is not a candidate for surgery. Predictive biomarkers for response to radiotherapy are lacking in this patient population, making it a non-tailored therapy regimen with unknown outcome. Twenty to 30 % of NSCLC harbor an activating mutation in KRAS that may confer radioresistance. We hypothesized that mutant KRAS can regulate glutamine metabolism genes in NSCLC and maintain tumor redox balance through transamination reactions that generate cytosolic NADPH via malic enzyme 1 (ME1), which may contribute to radioresistance. A doxycycline-inducible mouse model of KRASG12D driven NSCLC and patient data was analyzed from multiple publicly accessible databases including TCGA, CCLE, NCBI GEO and Project Achilles. ME1 expression was found to be mutant KRAS associated in both a NSCLC mouse model and human NSCLC cancer cell lines. Perturbing glutamine metabolism sensitized mutant KRAS, but not wild-type KRAS NSCLC cell lines to radiation treatment. NSCLC survival analysis revealed that patients with elevated ME1 and GOT1 expression had significantly worse outcomes after radiotherapy, but this was not seen after chemotherapy alone. KRAS driven glutamine metabolism genes, specifically ME1 and GOT1 reactions, may be a predictive marker and potential therapeutic target for radiotherapy in NSCLC. The online version of this article (doi:10.1186/s13014-015-0457-x) contains supplementary material, which is available to authorized users

  5. Lipid-related markers and cardiovascular disease prediction

    DEFF Research Database (Denmark)

    Di Angelantonio, Emanuele; Gao, Pei; Pennells, Lisa;

    2012-01-01

    The value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated.......The value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated....

  6. What makes cancer stem cell markers different?

    OpenAIRE

    Karsten, Uwe; Goletz, Steffen

    2013-01-01

    Since the cancer stem cell concept has been widely accepted, several strategies have been proposed to attack cancer stem cells (CSC). Accordingly, stem cell markers are now preferred therapeutic targets. However, the problem of tumor specificity has not disappeared but shifted to another question: how can cancer stem cells be distinguished from normal stem cells, or more specifically, how do CSC markers differ from normal stem cell markers? A hypothesis is proposed which might help to solve t...

  7. Assessment of circulating tumor cells and serum markers for progression-free survival prediction in metastatic breast cancer: a prospective observational study

    OpenAIRE

    Bidard, François-Clément; Hajage, David; Bachelot, Thomas; Delaloge, Suzette; Brain, Etienne; Campone, Mario; Cottu, Paul; Beuzeboc, Philippe; Rolland, Emilie; Mathiot, Claire; Pierga, Jean-Yves

    2012-01-01

    Introduction Circulating tumor cells (CTC) have been recently proposed as a new dynamic blood marker whose positivity at baseline is a prognostic factor and whose changes under treatment are correlated with progression-free survival (PFS) in metastatic breast cancer patients. However, serum marker levels are also used for the same purpose, and no clear comparison has been reported to date. Methods The IC 2006-04 enrolled prospectively 267 metastatic breast cancer patients treated by first lin...

  8. A Comparison of KL-6 and Clara Cell Protein as Markers for Predicting Bronchopulmonary Dysplasia in Preterm Infants

    OpenAIRE

    Keyi Wang; Xianmei Huang; Hui Lu; Zhiqun Zhang

    2014-01-01

    Objectives. To evaluate the predictive characteristics of KL-6 and CC16 for bronchopulmonary dysplasia (BPD) in preterm infants, either independently or in combination. Study Design. This prospective cohort study was performed from 2011 to 2013 with preterm neonates of gestational age ≤32 weeks and birth weight ≤1500 g. Serum KL-6 and CC16 levels were determined 7 and 14 days after birth. Results. Seventy-three preterm infants were studied. BPD was identified in 24 of these infants. After adj...

  9. Augmented telomerase activity, reduced telomere length and the presence of alternative lengthening of telomere in renal cell carcinoma: plausible predictive and diagnostic markers.

    Science.gov (United States)

    Pal, Deeksha; Sharma, Ujjawal; Khajuria, Ragini; Singh, Shrawan Kumar; Kakkar, Nandita; Prasad, Rajendra

    2015-05-15

    In this study, we analyzed 100 cases of renal cell carcinoma (RCC) for telomerase activity, telomere length and alternative lengthening of telomeres (ALT) using the TRAP assay, TeloTTAGGG assay kit and immunohistochemical analysis of ALT associated promyelocytic leukemia (PML) bodies respectively. A significantly higher (P=0.000) telomerase activity was observed in 81 cases of RCC which was correlated with clinicopathological features of tumor for instance, stage (P=0.008) and grades (P=0.000) but not with the subtypes of RCC (P = 0.355). Notwithstanding, no correlation was found between telomerase activity and subtypes of RCC. Strikingly, the telomere length was found to be significantly shorter in RCC (P=0.000) to that of corresponding normal renal tissues and it is well correlated with grades (P=0.016) but not with stages (P=0.202) and subtypes (P=0.669) of RCC. In this study, telomere length was also negatively correlated with the age of patients (r(2)=0.528; P=0.000) which supports the notion that it could be used as a marker for biological aging. ALT associated PML bodies containing PML protein was found in telomerase negative cases of RCC. It suggests the presence of an ALT pathway mechanism to maintain the telomere length in telomerase negative RCC tissues which was associated with high stages of RCC, suggesting a prevalent mechanism for telomere maintenance in high stages. In conclusion, the telomerase activity and telomere length can be used as a diagnostic as well as a predictive marker in RCC. The prevalence of ALT mechanism in high stages of RCC is warranted for the development of anti-ALT inhibitors along with telomerase inhibitor against RCC as a therapeutic approach. PMID:25769384

  10. Markers of beta cell failure predict poor glycemic response to GLP-1 receptor agonist therapy in type 2 diabetes

    Science.gov (United States)

    Jones, Angus G; McDonald, Timothy J; Shields, Beverley M; Hill, Anita V; Hyde, Christopher J; Knight, Bridget A; Hattersley, Andrew T

    2016-01-01

    Objective To assess whether clinical characteristics and simple biomarkers of beta cell failure are associated with individual variation in glycemic response to GLP-1 receptor agonist therapy in patients with type 2 diabetes. Research Design and Methods We prospectively studied 620 participants with type 2 diabetes and HbA1c ≥58mmol/mol (7.5%) commencing GLP-1 receptor agonist therapy as part of their usual diabetes care and assessed response to therapy over 6 months. We assessed the association between baseline clinical measurements associated with beta cell failure and glycemic response (HbA1c change 0 to 6 months, primary outcome) with change in weight (0 to 6 months) as a secondary outcome using linear regression and ANOVA with adjustment for baseline HbA1c and co-treatment change. Results Reduced glycemic response to GLP-1R agonists was associated with longer duration diabetes, insulin co-treatment, lower fasting C-peptide, lower post meal urine C-peptide creatinine ratio and positive GAD or IA2 islet autoantibodies (p≤0.01 for all). Participants with positive autoantibodies or severe insulin deficiency (fasting C-peptide ≤0.25nmol/L) had markedly reduced glycemic response to GLP-1RA therapy (autoantibodies: mean HbA1c change -5.2 vs -15.2 mmol/mol (-0.5 vs -1.4%), p=0.005 C-peptide diabetes. PMID:26242184

  11. BRCA1 mRNA expression as a predictive and prognostic marker in advanced esophageal squamous cell carcinoma treated with cisplatin- or docetaxel-based chemotherapy/chemoradiotherapy.

    Directory of Open Access Journals (Sweden)

    Yong Gao

    Full Text Available BACKGROUND: The molecular backgrounds that determine therapeutic effectiveness in esophageal cancer remain largely unknown. Breast cancer susceptibility gene 1 (BRCA1 expression has been found to switch the response to cisplatin- or paclitaxel-based chemotherapy. It remains unclear how variations in BRCA1 expression influence clinical outcomes in esophageal cancer. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qPCR was performed to examine BRCA1 mRNA expressions in paraffin-embedded specimens from 144 patients with advanced or metastatic esophageal squamous cell carcinoma who received cisplatin- or docetaxel-based first-line treatments. RESULTS: Low BRCA1 mRNA expression correlated with increased response rate (RR; P = 0.025 and 0.017, respectively and median overall survival (mOS; P = 0.002 and P<0.001, respectively in cisplatin-based chemotherapy or chemoradiotherapy group and also correlated with decreased RR (P = 0.017 and 0.024, respectively and mOS (both P<0.001 in docetaxel-based chemotherapy or chemoradiotherapy group. Multivariate analysis revealed that low BRCA1 expression was an independent prognostic factor in cisplatin-based chemotherapy (HR 0.29; 95%CI 0.12-0.71; P = 0.007 or chemoradiotherapy (HR 0.12; 95%CI 0.04-0.37; P<0.001 group and higher risk for mortality in docetaxel-based chemotherapy (HR 5.02; 95%CI 2.05-12.28; P<0.001 or chemoradiotherapy (HR 7.02; 95%CI 2.37-27.77; P<0.001 group. CONCLUSIONS: BRCA1 mRNA expression could be used as a predictive and prognostic marker in esophageal cancer who underwent first-line cisplatin- or docetaxel-based treatments.

  12. Soluble fms-like tyrosine kinase-1 and endothelial adhesion molecules (intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1) as predictive markers for blood pressure reduction after renal sympathetic denervation.

    Science.gov (United States)

    Dörr, Oliver; Liebetrau, Christoph; Möllmann, Helge; Gaede, Luise; Troidl, Christian; Rixe, Johannes; Hamm, Christian; Nef, Holger

    2014-05-01

    Renal sympathetic denervation (RSD) is a treatment option for patients with resistant arterial hypertension, but in some patients it is not successful. Predictive parameters on the success of RSD remain unknown. The angiogenic factors soluble fms-like tyrosine kinase-1 (sFLT-1), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are known to be associated with endothelial dysfunction, vascular remodeling, and hypertension. We evaluated whether sFLT-1, ICAM-1, and VCAM-1 are predictive markers for blood pressure reduction after RSD. Consecutive patients (n=55) undergoing renal denervation were included. Venous serum samples for measurement of sFlt-1, ICAM-1, and VCAM-1 were collected before and 6 months after RSD. A therapeutic response was defined as an office systolic blood pressure reduction of >10 mm Hg 6 months after RSD. A significant mean office systolic blood pressure reduction of 31.2 mm Hg was observed in 46 patients 6 months after RSD. Nine patients were classified as nonresponders, with a mean systolic blood pressure reduction of 4.6 mm Hg. At baseline, sFLT-1 levels were significantly higher in responders than in nonresponders (P<0.001) as were ICAM-1 (P<0.001) and VCAM-1 levels (P<0.01). The areas under the curve for sFLT-1, ICAM-1, and VCAM-1 were 0.82 (interquartile range, 0.718-0.921; P<0.001), 0.754 (0.654-0.854; P<0.001), and 0.684 (0.564-804; P=0.01), respectively, demonstrating prediction of an RSD response. Responders showed significantly higher serum levels of sFLT-1, ICAM-1, and VCAM-1 at baseline compared with nonresponders. Thus, this study identified for the first time potential biomarkers with a predictive value indicating a responder or nonresponder before renal denervation. PMID:24470464

  13. Instagram photos reveal predictive markers of depression

    CERN Document Server

    Reece, Andrew G

    2016-01-01

    Using Instagram data from 166 individuals, we applied machine learning tools to successfully identify markers of depression. Statistical features were computationally extracted from 43,950 participant Instagram photos, using color analysis, metadata components, and algorithmic face detection. Resulting models outperformed general practitioners' average diagnostic success rate for depression. These results held even when the analysis was restricted to posts made before depressed individuals were first diagnosed. Photos posted by depressed individuals were more likely to be bluer, grayer, and darker. Human ratings of photo attributes (happy, sad, etc.) were weaker predictors of depression, and were uncorrelated with computationally-generated features. These findings suggest new avenues for early screening and detection of mental illness.

  14. Use of molecular markers for predicting therapy response in cancer patients.

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    Predictive markers are factors that are associated with upfront response or resistance to a particular therapy. Predictive markers are important in oncology as tumors of the same tissue of origin vary widely in their response to most available systemic therapies. Currently recommended oncological predictive markers include both estrogen and progesterone receptors for identifying patients with breast cancers likely to benefit from hormone therapy, HER-2 for the identification of breast cancer patients likely to benefit from trastuzumab, specific K-RAS mutations for the identification of patients with advanced colorectal cancer unlikely to benefit from either cetuximab or panitumumab and specific EGFR mutations for selecting patients with advanced non-small-cell lung cancer for treatment with tyrosine kinase inhibitors such as gefitinib and erlotinib. The availability of predictive markers should increase drug efficacy and decrease toxicity, thus leading to a more personalized approach to cancer treatment.

  15. Genomic Predictions Using Combined Populations and SNP Marker Panels

    DEFF Research Database (Denmark)

    Brøndum, Rasmus Froberg

    Genomic prediction is an important tool for genetic evaluation of cattle, but Factors such as the size of the reference population and the density of the SNP marker panel used for prediction affects the accuracy. This thesis explores different strategies and models for scharing of data across...

  16. Molecular Markers for Breast Cancer: Prediction on Tumor Behavior

    OpenAIRE

    Bruna Karina Banin Hirata; Julie Massayo Maeda Oda; Roberta Losi Guembarovski; Carolina Batista Ariza; Carlos Eduardo Coral de Oliveira; Maria Angelica Ehara Watanabe

    2014-01-01

    Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical m...

  17. Cell Surface Markers in HTLV-1 Pathogenesis

    Directory of Open Access Journals (Sweden)

    Andrea K. Kress

    2011-08-01

    Full Text Available The phenotype of HTLV-1-transformed CD4+ T lymphocytes largely depends on defined viral effector molecules such as the viral oncoprotein Tax. In this review, we exemplify the expression pattern of characteristic lineage markers, costimulatory receptors and ligands of the tumor necrosis factor superfamily, cytokine receptors, and adhesion molecules on HTLV-1-transformed cells. These molecules may provide survival signals for the transformed cells. Expression of characteristic surface markers might therefore contribute to persistence of HTLV-1-transformed lymphocytes and to the development of HTLV-1-associated disease.

  18. Diagnostic markers for germ cell neoplasms

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, Ewa; Nielsen, John E; Skakkebaek, Niels E;

    2015-01-01

    This concise review summarises tissue and serum markers useful for differential diagnosis of germ cell tumours (GCTs), with focus on the most common testicular GCTs (TGCTs). GCTs are characterised by phenotypic heterogeneity due to largely retained embryonic pluripotency and aberrant somatic diff...

  19. AFP mRNA level in enriched circulating tumor cells from hepatocellular carcinoma patient blood samples is a pivotal predictive marker for metastasis.

    Science.gov (United States)

    Jin, Junhua; Niu, Xiaojuan; Zou, Lihui; Li, Lin; Li, Shugang; Han, Jingli; Zhang, Peiying; Song, Jinghai; Xiao, Fei

    2016-08-01

    Circulating tumor cells (CTCs) quantification may be helpful for evaluating cancer dissemination, predicting prognosis and assessing therapeutic effectiveness and safety. In the present study, CTCs from blood samples of 72 patients with hepatocellular carcinoma (HCC) were enriched with anti-EpCAM nanoparticles. AFP mRNA level was detected by nested polymerase chain reaction (PCR) after enrichment of CTCs from HCC blood samples at 0, 3, 6, 9 and 12 months after hepatectomy, respectively. AFP mRNA expression in CTCs was positive in 43 patients (59.7%) and negative in 29 patients (40.3%) before hepatectomy. Among 43 patients with positive AFP mRNA expression in CTCs before hepatectomy, 10 and 11 were diagnosed as intrahepatic/extrahepatic metastasis before and after hepatectomy, respectively. In addition, these 21 patients with metastasis had persisting positive AFP mRNA of CTCs during the whole tested year. Specifically, 3 patients with AFP mRNA negative in CTCs before hepatectomy changed to be positive at 6 and 9 months, and 2 of them were diagnosed as metastasis 12 months after hepatectomy. We conclude that the positive AFP mRNA of CTCs can be a pivotal predictor for HCC metastasis before and after hepatectomy. The release of AFP expression from hepatocellular carcinoma cells into circulation must be a major source of HCC metastasis. PMID:27160647

  20. The power and the promise of liver cancer stem cell markers.

    Science.gov (United States)

    Liu, Li-Li; Fu, Da; Ma, Yushui; Shen, Xi-Zhong

    2011-12-01

    Recently, there has been growing support for the cancer stem cell (CSC) hypothesis, which states that primary tumors are initiated and maintained by a small subpopulation of cancer cells that possess "stem-like" characteristics. CSCs have been identified in many tumor types, including hepatocellular carcinoma (HCC). The dye, Hoechst 33342, has been used to enrich CSCs into a side population. Alternatively, liver CSCs (LCSCs) can be identified by several cell surface antigens, including CD133, CD90, CD44, EpCAM, and CD13. In this review, we summarized the recent evidence regarding LCSC markers and discussed the origin and function of these markers. LCSC markers are essential to identify and isolate these cells, to develop future therapies targeting CSCs, and to predict prognosis and efficacy of these therapies. However, definite LCSC markers are still controversial, because none of these markers is exclusively expressed by LCSCs in HCC. By combining several positive or negative markers, it may be possible to isolate and identify CSC fractions beyond the ability of each individual assay. By grouping LCSC markers according to their cellular origin, the properties of LCSC markers may be better studied and new markers may be found. Lastly, markers could be used to estimate the number of LCSCs and therefore predict outcomes. From our point of view, selecting HCC tissue samples from patients with different prognoses and detecting expression patterns of marker combinations may be a new method to identify new and unique markers. PMID:21651381

  1. Joint Serum Tumor Markers Serve as survival predictive model of Erlotinib in the treatment of recurrent Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Lan SHAO

    2014-05-01

    Full Text Available Background and objective Molecular targeting therapy is the direction of individualized treatment of lung cancer, scholars has been established targeted therapy prediction models which provide more guidance for clinical individual therapy. This study investigated the relationship among pulmonary surfactant-associated protein D (SP-D, transforming growth factor α (TGF-α, matrix metalloproteinase 9 (MMP-9, tissue polypeptide specific antigen (TPS, and Krebs von den Lungen-6 (KL-6 and response as well as survival in the patients with recurrent non-small cell lung cancer, which Erlotinib was as second line treatment after failure to chemotherapy. This study also established a predictive prognostic model. Methods Serum levels of SP-D, TGF-α, MMP-9, TPS, and KL-6 in 114 patients before erlotinib treatment were detected by ELISA method. Combined with clinical factors, these levels were used to investigate the relationship with efficacy in erlotinib treatment and construct a predicted prognostic model by Kaplan-Meier curve and Cox proportional hazard model multivariate analysis. Results The objective response rate (ORR and disease control rate (DCR in the 114 patients, were 22.8% (26/114 and 72.8% (83/114, to Erlotinib treatment respectively. The median progression-free survival (PFS and one year survival rate with Erlotinib treatment were 5.13 months and 69.3%, respectively. Patients in the SP-D>110 ng/mL group exhibited more ORR (33.3% vs 13.3%, P=0.011 and DCR (83.3% vs 63.3%, P=0.017 than those in the ≤110 ng/mL group. Patients in the MMP-9≤535 ng/mL group showed more DCR (83.9% than those in the >535 ng/mL group (62.1% (P=0.009. Patients in the TPS110 ng/mL (5.95 months vs 3.25 months, P=0.009, MMP-9≤535 ng/mL (5.83 months vs 3.47 months, P=0.046, KL-6<500 U/mL (6.03 months vs 3.40 months, P=0.040, and TPS<80 U/L (6.15 months vs 2.42 months, P=0.014 groups showed better PFS. Multivariate analysis showed that current or ever-smoker, wild

  2. Identification of Prognostic and Predictive Markers in Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Suzanne M Russo

    2011-03-01

    Full Text Available Pancreatic cancer remains a significant cause of morbidity and mortality. While increasing treatment options have improved outcomes for many patients, they have also complicated decision-making for treatment. Unfortunately, most patients with pancreatic cancer die from their disease. Prognostic and predictive markers could play a role to improve treatment by identifying patients who may or may not require a given therapy, and determining those most likely to benefit from a therapy. At the 2011 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium held in San Francisco, January 2011, several interesting abstracts were presented that focused on prognostic and predictive markers associated with pancreatic adenocarcinomas. These abstracts discuss progress made in identifying molecular subtypes of pancreatic cancers that may provide insight into selection of patients likely to benefit from certain therapies.

  3. Emerging markers of cachexia predict survival in cancer patients

    OpenAIRE

    MONDELLO, PATRIZIA; Lacquaniti, Antonio; Mondello, Stefania; Bolignano, Davide; Pitini, Vincenzo; Aloisi, Carmela; Buemi, Michele

    2014-01-01

    Background Cachexia may occur in 40% of cancer patients, representing the major cause of death in more than 20% of them. The aim of this study was to investigate the role of leptin, ghrelin and obestatin as diagnostic and predictive markers of cachexia in oncologic patients. Their impact on patient survival was also evaluated. Methods 140 adults with different cancer diagnoses were recruited. Thirty healthy volunteers served as control. Serum ghrelin, obestatin and leptin were tested at basel...

  4. Predictive markers and risk factors in canine pyometra

    OpenAIRE

    Jitpean, Supranee

    2015-01-01

    Pyometra is a common and life-threatening disease in intact female dogs, which is generally treated by surgery. Early identification of dogs with high risk of complications or poor prognosis is valuable for optimising treatment and increase survival. The objectives of this thesis were to detect predictive markers for prognosis and outcome of pyometra by investigating clinical and pathophysiological responses and to explore the breed-dependent risk for pyometra and mammary tumours (MTs). ...

  5. Markers of small cell lung cancer

    OpenAIRE

    Sharma SK; Taneja Tarvinder

    2004-01-01

    Abstract Lung cancer is the number one cause of cancer death; however, no specific serum biomarker is available till date for detection of early lung cancer. Despite good initial response to chemotherapy, small-cell lung cancer (SCLC) has a poor prognosis. Therefore, it is important to identify molecular markers that might influence survival and may serve as potential therapeutic targets. The review aims to summarize the current knowledge of serum biomarkers in SCLC to improve diagnostic effi...

  6. Markers of small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Sharma SK

    2004-05-01

    Full Text Available Abstract Lung cancer is the number one cause of cancer death; however, no specific serum biomarker is available till date for detection of early lung cancer. Despite good initial response to chemotherapy, small-cell lung cancer (SCLC has a poor prognosis. Therefore, it is important to identify molecular markers that might influence survival and may serve as potential therapeutic targets. The review aims to summarize the current knowledge of serum biomarkers in SCLC to improve diagnostic efficiency in the detection of tumor progression in lung cancer. The current knowledge on the known serum cytokines and tumor biomarkers of SCLC is emphasized. Recent findings in the search for novel diagnostic and therapeutic molecular markers using the emerging genomic technology for detecting lung cancer are also described. It is believed that implementing these new research techniques will facilitate and improve early detection, prognostication and better treatment of SCLC.

  7. Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers.

    LENUS (Irish Health Repository)

    Jansen, Michael

    2010-07-01

    Over the past 10 years, there has been an increasing use of molecular markers in the assessment and management of adult malignant gliomas. Some molecular signatures are used diagnostically to help pathologists classify tumours, whereas others are used to estimate prognosis for patients. Most crucial, however, are those markers that are used to predict response to certain therapies, thereby directing clinicians to a particular treatment while avoiding other potentially deleterious therapies. Recently, large-scale genome-wide surveys have been used to identify new biomarkers that have been rapidly developed as diagnostic and prognostic tools. Given these developments, the pace of discovery of new molecular assays will quicken to facilitate personalised medicine in the setting of malignant glioma.

  8. Joint Serum Tumor Markers Serve as survival predictive model of Erlotinib in the treatment of recurrent Non-small Cell Lung Cancer

    OpenAIRE

    Lan SHAO; Hong, Wei; Zheng, Lei; He, Chunxiao; Beibei ZHANG; Xie, Fajun; Song, Zhengbo; Guangyuan LOU; Zhang, Yiping

    2014-01-01

    Background and objective Molecular targeting therapy is the direction of individualized treatment of lung cancer, scholars has been established targeted therapy prediction models which provide more guidance for clinical individual therapy. This study investigated the relationship among pulmonary surfactant-associated protein D (SP-D), transforming growth factor α (TGF-α), matrix metalloproteinase 9 (MMP-9), tissue polypeptide specific antigen (TPS), and Krebs von den Lungen-6 (KL-6) and respo...

  9. Expression of miRNA-106b in conventional renal cell carcinoma is a potential marker for prediction of early metastasis after nephrectomy

    Directory of Open Access Journals (Sweden)

    Slaby Ondrej

    2010-07-01

    Full Text Available Abstract Background MicroRNAs are endogenously expressed regulatory noncoding RNAs. Previous studies have shown altered expression levels of several microRNAs in renal cell carcinoma. Methods We examined the expression levels of selected microRNAs in 38 samples of conventional renal cell carcinoma (RCC and 10 samples of non-tumoral renal parenchyma using TaqMan real-time PCR method. Results The expression levels of miRNA-155 (p Conclusions We have confirmed previous observations obtained by miRNA microarray analysis using standardized real-time PCR method. For the first time, we have identified a prognostic significance of miRNA-106b, which, after validation on a larger group of patients, maybe useful as a promising biomarker in patients with RCC.

  10. Galectin-7 as a potential predictive marker of chemo-and/or radio-therapy resistance in oral squamous cell carcinoma

    OpenAIRE

    Matsukawa, Sho; Morita, Kei-ichi; Negishi, Ayako; Harada, Hiroyuki; Nakajima, Yusuke; Shimamoto, Hiroaki; Tomioka, Hirofumi; Tanaka, Kae; Ono, Masaya; Yamada, Tesshi; Omura, Ken

    2014-01-01

    Treatment of advanced oral squamous cell carcinoma (OSCC) requires the integration of multimodal approaches. The aim of this study was to identify predictors of tumor sensitivity to preoperative radiotherapy/chemotherapy for OSCC in order to allow oncologists to determine optimum therapeutic strategies without the associated adverse effects. Here, the protein expression profiles of formalin-fixed paraffin-embedded (FFPE) tissue samples from 18 OSCC patients, termed learning cases, who receive...

  11. A novel cell permeable DNA replication and repair marker

    OpenAIRE

    Herce, Henry D.; Rajan, Malini; Lättig-Tünnemann, Gisela; Fillies, Marion; Cardoso, M. Cristina

    2014-01-01

    Proliferating Cell Nuclear Antigen (PCNA) is a key protein in DNA replication and repair. The dynamics of replication and repair in live cells is usually studied introducing translational fusions of PCNA. To obviate the need for transfection and bypass the problem of difficult to transfect and/or short lived cells, we have now developed a cell permeable replication and/or repair marker. The design of this marker has three essential molecular components: (1) an optimized artificial PCNA bindin...

  12. Data defining markers of human neural stem cell lineage potential.

    Science.gov (United States)

    Oikari, Lotta E; Okolicsanyi, Rachel K; Griffiths, Lyn R; Haupt, Larisa M

    2016-06-01

    Neural stem cells (NSCs) and neural progenitor cells (NPCs) are self-renewing and multipotent cells, however, NPCs are considered to be more lineage-restricted with a reduced self-renewing capacity. We present data comparing the expression of 21 markers encompassing pluripotency, self-renewal (NSC) as well as neuronal and glial (astrocyte and oligodendrocyte) lineage specification and 28 extracellular proteoglycan (PG) genes and their regulatory enzymes between embryonic stem cell (ESC)-derived human NSCs (hNSC H9 cells, Thermo Fisher) and human cortex-derived normal human NPCs (nhNPCs, Lonza). The data demonstrates expression differences of multiple lineage and proteoglycan-associated genes between hNSC H9 cells and nhNPCs. Data interpretation of markers and proteoglycans defining NSC and neural cell lineage characterisation can be found in "Cell surface heparan sulfate proteoglycans as novel markers of human neural stem cell fate determination" (Oikari et al. 2015) [1]. PMID:26958640

  13. Urinary protein markers predict the severity of renal histological lesions in children with mesangial proliferative glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Li Yanhong

    2012-05-01

    Full Text Available Abstract Background Several renal histopathological features, including mesangial hypercellularity, glomerulosclerosis, tubular atrophy and interstitial fibrosis, are considered to be independent predictors of end-stage renal failure in patients with glomerular diseases. Mesangial proliferative glomerulonephritis (MesPGN is characterized by proliferations of mesangial cells with increase in mesangial matrix and/or deposits in mesangial region. The purpose of this study is to determine the association between urinary protein markers measured at the same time as renal biopsy and the severity of renal histological lesions in children with MesPGN, and to evaluate whether these markers could serve as predictors of severe renal histological lesions in this population. Methods Ninety-eight children with MesPGN (40 with IgA nephropathy, 37 with IgM nephropathy, and 21 with MesPGN without IgA/IgM deposition were enrolled. Urinary level of IgG, albumin, transferrin, α1-microglobulin, β2-microglobulin and N-acetyl-β-glucosaminidase from a morning sample before biopsy was measured. The scores of mesangial hypercellularity, glomerulosclerosis, and tubule-interstitial damage were used to semi-quantitatively evaluate renal histological lesions. Results The urine proteins, as independent factors associated with severe mesangial cellularity (> 5 mesangial cells/ mesangial area were transferrin, albumin, α1-microglobulin, IgG and 24-hour total protein, with severe glomerulosclerosis (≥ 10 % glomeruli showing segmental adhesions or sclerosis were transferrin and 24-hour total protein, and with severe tubule-interstitial damage (focal or diffuse tubular and interstitial lesions were transferrin and N-acetyl-β-glucosaminidase. Urinary transferrin achieved the area under-the-receiver-operating-characteristic curve (AUC of 0.86 and 0.82, respectively, for predicting severe mesangial cellularity and glomerulosclerosis. Urinary N

  14. Stathmin protein level, a potential predictive marker for taxane treatment response in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Henrica M J Werner

    Full Text Available Stathmin is a prognostic marker in many cancers, including endometrial cancer. Preclinical studies, predominantly in breast cancer, have suggested that stathmin may additionally be a predictive marker for response to paclitaxel. We first evaluated the response to paclitaxel in endometrial cancer cell lines before and after stathmin knock-down. Subsequently we investigated the clinical response to paclitaxel containing chemotherapy in metastatic endometrial cancer in relation to stathmin protein level in tumors. Stathmin level was also determined in metastatic lesions, analyzing changes in biomarker status on disease progression. Knock-down of stathmin improved sensitivity to paclitaxel in endometrial carcinoma cell lines with both naturally higher and lower sensitivity to paclitaxel. In clinical samples, high stathmin level was demonstrated to be associated with poor response to paclitaxel containing chemotherapy and to reduced disease specific survival only in patients treated with such combination. Stathmin level increased significantly from primary to metastatic lesions. This study suggests, supported by both preclinical and clinical data, that stathmin could be a predictive biomarker for response to paclitaxel treatment in endometrial cancer. Re-assessment of stathmin level in metastatic lesions prior to treatment start may be relevant. Also, validation in a randomized clinical trial will be important.

  15. Pancreatic cancer stem cell markers and exosomes - the incentive push.

    Science.gov (United States)

    Heiler, Sarah; Wang, Zhe; Zöller, Margot

    2016-07-14

    Pancreatic cancer (PaCa) has the highest death rate and incidence is increasing. Poor prognosis is due to late diagnosis and early metastatic spread, which is ascribed to a minor population of so called cancer stem cells (CSC) within the mass of the primary tumor. CSC are defined by biological features, which they share with adult stem cells like longevity, rare cell division, the capacity for self renewal, differentiation, drug resistance and the requirement for a niche. CSC can also be identified by sets of markers, which for pancreatic CSC (Pa-CSC) include CD44v6, c-Met, Tspan8, alpha6beta4, CXCR4, CD133, EpCAM and claudin7. The functional relevance of CSC markers is still disputed. We hypothesize that Pa-CSC markers play a decisive role in tumor progression. This is fostered by the location in glycolipid-enriched membrane domains, which function as signaling platform and support connectivity of the individual Pa-CSC markers. Outside-in signaling supports apoptosis resistance, stem cell gene expression and tumor suppressor gene repression as well as miRNA transcription and silencing. Pa-CSC markers also contribute to motility and invasiveness. By ligand binding host cells are triggered towards creating a milieu supporting Pa-CSC maintenance. Furthermore, CSC markers contribute to the generation, loading and delivery of exosomes, whereby CSC gain the capacity for a cell-cell contact independent crosstalk with the host and neighboring non-CSC. This allows Pa-CSC exosomes (TEX) to reprogram neighboring non-CSC towards epithelial mesenchymal transition and to stimulate host cells towards preparing a niche for metastasizing tumor cells. Finally, TEX communicate with the matrix to support tumor cell motility, invasion and homing. We will discuss the possibility that CSC markers are the initial trigger for these processes and what is the special contribution of CSC-TEX. PMID:27468191

  16. Pancreatic cancer stem cell markers and exosomes - the incentive push

    Science.gov (United States)

    Heiler, Sarah; Wang, Zhe; Zöller, Margot

    2016-01-01

    Pancreatic cancer (PaCa) has the highest death rate and incidence is increasing. Poor prognosis is due to late diagnosis and early metastatic spread, which is ascribed to a minor population of so called cancer stem cells (CSC) within the mass of the primary tumor. CSC are defined by biological features, which they share with adult stem cells like longevity, rare cell division, the capacity for self renewal, differentiation, drug resistance and the requirement for a niche. CSC can also be identified by sets of markers, which for pancreatic CSC (Pa-CSC) include CD44v6, c-Met, Tspan8, alpha6beta4, CXCR4, CD133, EpCAM and claudin7. The functional relevance of CSC markers is still disputed. We hypothesize that Pa-CSC markers play a decisive role in tumor progression. This is fostered by the location in glycolipid-enriched membrane domains, which function as signaling platform and support connectivity of the individual Pa-CSC markers. Outside-in signaling supports apoptosis resistance, stem cell gene expression and tumor suppressor gene repression as well as miRNA transcription and silencing. Pa-CSC markers also contribute to motility and invasiveness. By ligand binding host cells are triggered towards creating a milieu supporting Pa-CSC maintenance. Furthermore, CSC markers contribute to the generation, loading and delivery of exosomes, whereby CSC gain the capacity for a cell-cell contact independent crosstalk with the host and neighboring non-CSC. This allows Pa-CSC exosomes (TEX) to reprogram neighboring non-CSC towards epithelial mesenchymal transition and to stimulate host cells towards preparing a niche for metastasizing tumor cells. Finally, TEX communicate with the matrix to support tumor cell motility, invasion and homing. We will discuss the possibility that CSC markers are the initial trigger for these processes and what is the special contribution of CSC-TEX. PMID:27468191

  17. Molecular Pathogenesis and Diagnostic, Prognostic and Predictive Molecular Markers in Sarcoma.

    Science.gov (United States)

    Mariño-Enríquez, Adrián; Bovée, Judith V M G

    2016-09-01

    Sarcomas are infrequent mesenchymal neoplasms characterized by notable morphological and molecular heterogeneity. Molecular studies in sarcoma provide refinements to morphologic classification, and contribute diagnostic information (frequently), prognostic stratification (rarely) and predict therapeutic response (occasionally). Herein, we summarize the major molecular mechanisms underlying sarcoma pathogenesis and present clinically useful diagnostic, prognostic and predictive molecular markers for sarcoma. Five major molecular alterations are discussed, illustrated with representative sarcoma types, including 1. the presence of chimeric transcription factors, in vascular tumors; 2. abnormal kinase signaling, in gastrointestinal stromal tumor; 3. epigenetic deregulation, in chondrosarcoma, chondroblastoma, and other tumors; 4. deregulated cell survival and proliferation, due to focal copy number alterations, in dedifferentiated liposarcoma; 5. extreme genomic instability, in conventional osteosarcoma as a representative example of sarcomas with highly complex karyotype. PMID:27523972

  18. Expression of squamous cell carcinoma markers and adenocarcinoma markers in primary pulmonary neuroendocrine carcinomas.

    Science.gov (United States)

    Masai, Kyohei; Tsuta, Koji; Kawago, Mitsumasa; Tatsumori, Takahiro; Kinno, Tomoaki; Taniyama, Tomoko; Yoshida, Akihiko; Asamura, Hisao; Tsuda, Hitoshi

    2013-07-01

    Recent clinical trials have revealed that accurate histologic typing of non-small cell lung cancer is essential. Until now, squamous cell carcinoma (SQC) and adenocarcinoma (ADC) markers have not been thoroughly analyzed for pulmonary neuroendocrine carcinomas (NECs). We analyzed the expression of 8 markers [p63, cytokeratin (CK) 5/6, SOX2, CK7, desmocollin 3, thyroid transcription factor-1 (8G7G3/1 and SPT24), and napsin A] in 224 NECs. SOX2 (76.2%) had the greatest expression for NECs. CK5/6 (1.4%), desmocollin 3 (0.5%), and napsin A (0%) were expressed less or not at all in NECs. Although our investigated markers have been reported useful for differentiating between SQC and ADC, some of them were also present in a portion of pulmonary NECs. In our study, CK5/6 and desmocollin 3 were highly specific markers for SQC, and napsin A was highly specific for ADC. These markers are recommended for diagnosis of poorly differentiated non-small cell lung cancer. PMID:23060301

  19. Lack of correlation of stem cell markers in breast cancer stem cells

    OpenAIRE

    Liu, Y; Nenutil, R; Appleyard, M V; Murray, K; Boylan, M; Thompson, A. M.; Coates, P J

    2014-01-01

    Background: Various markers are used to identify the unique sub-population of breast cancer cells with stem cell properties. Whether these markers are expressed in all breast cancers, identify the same population of cells, or equate to therapeutic response is controversial. Methods: We investigated the expression of multiple cancer stem cell markers in human breast cancer samples and cell lines in vitro and in vivo, comparing across and within samples and relating expression with growth and t...

  20. Immune response markers in sentinel nodes may predict melanoma progression

    OpenAIRE

    Rodolfo, Monica; Castelli, Chiara; Rivoltini, Licia

    2014-01-01

    We recently reported that variable expression of immune-response genes distinguishes tumor positive sentinel nodes in melanoma patients with malignant progression from those with non-progressing disease. Our results depict sentinel nodes as sites in which immune functions are associated with metastatic disease and identify CD30 as a host immune-related cancer prognostic marker and potential therapeutic target.

  1. Cancer stem cell markers in common cancers - therapeutic implications

    DEFF Research Database (Denmark)

    Klonisch, Thomas; Wiechec, Emilia; Hombach-Klonisch, Sabine;

    2008-01-01

    Rapid advance in the cancer stem cell field warrants optimism for the development of more reliable cancer therapies within the next 2-3 decades. Below, we characterize and compare the specific markers that are present on stem cells, cancer cells and cancer stem cells (CSC) in selected tissues......, the last part of the review discusses future directions of this intriguing new research field in the context of new diagnostic and therapeutic opportunities....

  2. Markers

    Science.gov (United States)

    Healthy Schools Network, Inc., 2011

    2011-01-01

    Dry erase whiteboards come with toxic dry erase markers and toxic cleaning products. Dry erase markers labeled "nontoxic" are not free of toxic chemicals and can cause health problems. Children are especially vulnerable to environmental health hazards; moreover, schools commonly have problems with indoor air pollution, as they are more densely…

  3. Marker-free cell discrimination by holographic optical tweezers

    Science.gov (United States)

    Schaal, F.; Warber, M.; Zwick, S.; van der Kuip, H.; Haist, T.; Osten, W.

    2009-06-01

    We introduce a method for marker-free cell discrimination based on optical tweezers. Cancerous, non-cancerous, and drug-treated cells could be distinguished by measuring the trapping forces using holographic optical tweezers. We present trapping force measurements on different cell lines: normal pre-B lymphocyte cells (BaF3; "normal cells"), their Bcr-Abl transformed counterparts (BaF3-p185; "cancer cells") as a model for chronic myeloid leukaemia (CML) and Imatinib treated BaF3-p185 cells. The results are compared with reference measurements obtained by a commercial flow cytometry system.

  4. Combined-modality treatment and organ preservation in bladder cancer. Do molecular markers predict outcome?

    International Nuclear Information System (INIS)

    Purpose: in invasive bladder cancer, several groups have reported the value of organ preservation by a combined-treatment approach, including transurethral resection (TUR-BT) and radiochemotherapy (RCT). As more experience is acquired with this organ-sparing treatment, patient selection needs to be optimized. Clinical factors are limited in their potential to identify patients most likely to respond to RCT, thus, additional molecular markers for predicting treatment response of individual lesions are sorely needed. Patients and methods: the apoptotic index (AI) and Ki-67 index were evaluated by immunohistochemistry on pretreatment biopsies of 134 patients treated for bladder cancer by TUR-BT and RCT. Expression of each marker as well as clinicopathologic factors were then correlated with initial response, local control and cancer-specific survival with preserved bladder in univariate and multivariate analysis. Results: the median AI for all patients was 1.5% (range 0.2-7.4%). The percentage of Ki-67-positive cells in the tumors ranged from 0.2% to 85% with a median of 14.2%. A significant correlation was found for AI and tumor differentiation (G1/2: AI = 1.3% vs. G3/4: AI = 1.6%; p = 0.01). A complete response at restaging TUR-BT was achieved in 76% of patients. Factors predictive of complete response included T-category (p < 0.0001), resection status (p = 0.02), lymphovascular invasion (p = 0.01), and Ki-67 index (p = 0.02). For local control, AI (p = 0.04) and Ki-67 index (p = 0.05) as well as T-category (p = 0.005), R-status (p = 0.05), and lymphatic vessel invasion (p = 0.05) reached statistical significance. Out of the molecular markers only high Ki-67 levels were associated to cause-specific survival with preserved bladder. On multivariate analysis, T-category was the strongest independent factor for initial response, local control and cancer-specific survival with preserved bladder. Conclusion: The indices of pretreatment apoptosis and Ki-67 predict a

  5. Markers of Atherosclerosis and Inflammation for Prediction of Coronary Heart Disease in Older Adults

    OpenAIRE

    Rodondi, Nicolas; Marques-Vidal, Pedro; Butler, Javed; Sutton-Tyrrell, Kim; Cornuz, Jacques; Satterfield, Suzanne; Harris, Tamara; Bauer, Douglas C.; Ferrucci, Luigi; Vittinghoff, Eric; Newman, Anne B

    2010-01-01

    Although both inflammatory and atherosclerosis markers have been associated with coronary heart disease (CHD) risk, data directly comparing their predictive value are limited. The authors compared the value of 2 atherosclerosis markers (ankle-arm index (AAI) and aortic pulse wave velocity (aPWV)) and 3 inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)) in predicting CHD events. Among 2,191 adults aged 70–79 years at baseline (1997–1998) ...

  6. Biological Markers Predictive of Invasive Recurrence in DCIS

    Directory of Open Access Journals (Sweden)

    Sharon Nofech-Mozes

    2008-01-01

    Full Text Available DCIS is a heterogeneous group of non-invasive cancers of the breast characterized by various degrees of differentiation and unpredictable propensity for transformation into invasive carcinoma. We examined the expression and prognostic value of 9 biological markers with a potential role in tumor progression in 133 patients with pure DCIS treated with breast conserving surgery alone, between 1982–2000. Histology was reviewed and immunohistochemical staining was performed. Pearson correlation coefficient was used to determine the associations between markers and histopathological features. Univariate and multivariate analysis examined associations between time to recurrence and clinico-pathologic features and biological markers.Median age at diagnosis was 55 years (25–85. With a median follow up of 8.91 years, 41/133 patients recurred (21 as invasive recurrence. In this cohort 13.5% had low, 43% intermediate and 42% high nuclear grade. Comedo necrosis was found in 65% of cases. Expression of ER (62.4%, PR (55.6%, HER2/neu (31.6%, MIB1 (39.8%, p53 (22.6%, p21 (39.8%, Cyclin D1 (95.5% calgranulin (20.5%, psoriasin (12%, was found in DCIS. HER2/neu was overexpressed in 45% that recurred as DCIS and 42.9% that recurred as invasive cancer, and only in 26.1% in cases that never recurred. On univariate analysis, HER2/neu overexpression was the only marker associated with an increased risk for any recurrence (p = 0.044. The hazard ratio for recurrence for HER2/neu positive DCIS was 1.927 (confidence interval 1.016–3.653 compared to HER2 negative DCIS. On multivariate analysis, HER2/neu overexpression remained the only independent variable significantly associated with any recurrence (p = 0.014 and with invasive recurrence (p = 0.044.This data suggest that HER2/neu testing may become an important parameter in the management of DCIS and the treatment of cases with positive HER2/neu status could be modified accordingly, similar to the current approach

  7. MicroRNA-194 is a Marker for Good Prognosis in Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Nofech-Mozes, Roy; Khella, Heba W Z; Scorilas, Andreas; Youssef, Leza; Krylov, Sergey N; Lianidou, Evi; Sidiropoulos, Konstantinos G; Gabril, Manal; Evans, Andrew; Yousef, George M

    2016-04-01

    Clear cell renal cell carcinoma (ccRCC) is the most prevalent adult kidney cancer. Prognostic markers are needed to guide patient management toward aggressive versus more conservative approaches, especially for small tumors ≤4 cm. miR-194 was reported to be downregulated in several cancers and is involved in epithelial to mesenchymal transition. We evaluated miR-194 as a prognostic marker in ccRCC. In a cohort of 234 patients with primary ccRCC, we correlated miR-194 expression level with multiple clinicopathological features including disease-free and overall survival, tumor size, clinical stage, and histological grade. Our results shows a stepwise decrease in miR-194 expression from normal kidney to primary ccRCC (P = 0.0032) and a subsequent decrease from primary to metastatic lesions. Additionally, patients with higher miR-194 expression has significantly longer disease-free survival (P = 0.041) and overall survival (P = 0.031) compared to those with lower expression. In multivariate analysis, miR-194-positive tumors retain significance in disease-free survival and overall survival, suggesting miR-194 is an independent marker for good prognosis in ccRCC. Moreover, miR-194 is a marker for good prognosis for patients with small renal masses (P = 0.014). These findings were validated on an independent data set from The Cancer Genome Atlas. We also compared miR-194 expression between RCC subtypes. ccRCC had the highest levels, whereas chromophobe RCC and oncocytoma had comparable lower levels. Target prediction coupled with pathway analysis show that miR-194 is predicted to target key molecules and pathways involved in RCC progression. miR-194 represents a prognostic biomarker in ccRCC. PMID:26860079

  8. Prediction of Physicochemical Properties of Indonesian Indica Rice Using Molecular Markers

    Directory of Open Access Journals (Sweden)

    PUJI LESTARI

    2014-06-01

    Full Text Available Physicochemical properties determine the palatability and cooking quality of rice, which must be determined efficiently in order to satisfy consumer demand. To date, little information exists on the use of molecular markers to predict physicochemical properties of the “indica” rice varieties found in Indonesia. The objective of this study was to investigate physicochemical properties and genetic variation of Indonesian rice varieties, and to formulate regression equations to analyze sets of DNA markers which could predict amylose content (AC, protein content (PC and pasting properties of the varieties. A total of 24 Indonesian indica rice varieties were chosen based on their genetic background and agricultural characteristics. We then measured selected physicochemical properties, and genotyped the varieties using 30 DNA markers. The chosen varieties showed favorable values for PC, AC, and six rapid viscosity analyzer (RVA pasting properties, which was supported by molecular data. As demonstrated by principal component analysis (PCA, markers could provide a complementary method for differentiating rice varieties, as an alternative to measuring physicochemical properties. PCA analysis also allowed us to establish marker sets using multiple regression analysis. We formulated eight model regression equations comprising data regarding 15 to 19 markers with high coefficients (R2=0.98-0.99. The formulas provided results that consistently correlated and therefore predicted the physicochemical properties of indica rice. Further validation of these marker sets may provide rapid and efficient means for predicting the physicochemical properties of Indonesian-bred indica rice in the future.

  9. Cancer Stem Cells, Epithelial to Mesenchymal Markers, and Circulating Tumor Cells in Small Cell Lung Cancer

    NARCIS (Netherlands)

    Pore, Milind; Meijer, Coby; de Bock, Geertruida H; Boersma-van Ek, Wytske; Terstappen, Leon W M M; Groen, Harry J M; Timens, Wim; Kruyt, Frank A E; Hiltermann, T Jeroen N

    2016-01-01

    BACKGROUND: Small cell lung cancer (SCLC) has a poor prognosis, and even with localized (limited) disease, the 5-year survival has only been around 20%. Elevated levels of circulating tumor cells (CTCs) have been associated with a worse prognosis, and markers of cancer stem cells (CSCs) and epitheli

  10. A novel cell permeable DNA replication and repair marker.

    Science.gov (United States)

    Herce, Henry D; Rajan, Malini; Lättig-Tünnemann, Gisela; Fillies, Marion; Cardoso, M Cristina

    2014-01-01

    Proliferating Cell Nuclear Antigen (PCNA) is a key protein in DNA replication and repair. The dynamics of replication and repair in live cells is usually studied introducing translational fusions of PCNA. To obviate the need for transfection and bypass the problem of difficult to transfect and/or short lived cells, we have now developed a cell permeable replication and/or repair marker. The design of this marker has three essential molecular components: (1) an optimized artificial PCNA binding peptide; (2) a cell-penetrating peptide, derived from the HIV-1 Trans Activator of Transcription (TAT); (3) an in vivo cleavable linker, linking the two peptides. The resulting construct was taken up by human, hamster and mouse cells within minutes of addition to the media. Inside the cells, the cargo separated from the vector peptide and bound PCNA effectively. Both replication and repair sites could be directly labeled in live cells making it the first in vivo cell permeable peptide marker for these two fundamental cellular processes. Concurrently, we also introduced a quick peptide based PCNA staining method as an alternative to PCNA antibodies for immunofluorescence applications. In summary, we present here a versatile tool to instantaneously label repair and replication processes in fixed and live cells. PMID:25484186

  11. Early molecular markers predictive of dengue hemorrhagic fever

    OpenAIRE

    Carlos E Calzavara-Silva; Ana L.V. Gomes; Rita C.C. Maia; Bartolomeu Acioli-Santos; Gil, Laura H.V.G.; Ernesto T.A. Marques Jr.

    2009-01-01

    The management of acute dengue patients during outbreaks is a challenging problem. Most of the dengue fever cases are benign, but some cases develop into a severe and possibly lethal vasculopathy, known as dengue hemorrhagic fever. Early symptoms of dengue and hemorrhagic fever are very similar. An early differential diagnosis is needed to predict which of these two clinical presentations is crucial to proper patient care and public health management. This study evaluates the predictive poten...

  12. Markers for Characterization of Bone Marrow Multipotential Stromal Cells

    Directory of Open Access Journals (Sweden)

    Sally A. Boxall

    2012-01-01

    Full Text Available Given the observed efficacy of culture-expanded multipotential stromal cells, also termed mesenchymal stem cells (MSCs, in the treatment of graft-versus host and cardiac disease, it remains surprising that purity and potency characterization of manufactured cell batches remains rather basic. In this paper, we will initially discuss surface and molecular markers that were proposed to serve as the indicators of the MSC potency, in terms of their proliferative potential or the ability to differentiate into desired lineages. The second part of this paper will be dedicated to a critical discussion of surface markers of uncultured (i.e., native bone marrow (BM MSCs. Although no formal consensus has yet been reached on which markers may be best suited for prospective BM MSC isolation, markers that cross-react with MSCs of animal models (such as CD271 and W8-B2/MSCA-1 may have the strongest translational value. Whereas small animal models are needed to discover the in vivo function on these markers, large animal models are required for safety and efficacy testing of isolated MSCs, particularly in the field of bone and cartilage tissue engineering.

  13. Cardiac and proinflammatory markers predict prognosis in cirrhosis

    DEFF Research Database (Denmark)

    Wiese, Signe; Mortensen, Christian; Gøtze, Jens P;

    2014-01-01

    BACKGROUND & AIMS: Inflammation and cardiac dysfunction plays an important role in the development of complications leading to increased mortality in patients with cirrhosis. Novel cardiac markers such as prohormone of ANP (proANP), copeptin and high-sensitivity troponin T (hs-TnT) and...... changes, and long-term survival. METHODS: One hundred and ninety-three stable cirrhotic patients (Child class: A = 46; B = 97; C = 50) had a full haemodynamic investigation performed with measurement of splanchnic and systemic haemodynamics and measurement of circulating levels of proBNP, proANP, copeptin...... copeptin correlated with indicators of disease severity in cirrhosis; ProANP and suPAR correlated with hepatic venous pressure gradient (r = 0.24 and r = 0.34; P < 0.001) and systemic vascular resistance (r = -0.24 and r = -0.33; P < 0.001). Cardiac (proANP, hs-TnT; P < 0.01) and proinflammatory (hs...

  14. Prediction of the preeclampsia: a view of biochemical markers

    Directory of Open Access Journals (Sweden)

    Mehmet Sühha Bostancı

    2013-10-01

    Full Text Available Preeclampsia is a diverse, multiorgan group of related disease processes that occurs in up to 5%-8% of pregnancies after 20 weeks’ gestation and it is one of the leading causes of maternal and fetal morbidity and mortality. Many molecular mechanisms are contributed to the pathogenesis of preeclampsia. Although it is unknown whether the mechanisms act independently or have synergistic effects. This review describes review of primary papers investigating blood based biomarker such as PAP-A, Inhibin A, sFlt1, and PP13 in general and first trimester biochemical markers and combinations of them specifically for preeclampsia.http://dx.doi.org/10.7175/rhc.v4i4.699

  15. Effect of marker-data editing on the accuracy of genomic prediction

    DEFF Research Database (Denmark)

    Edriss, Vahid; Guldbrandtsen, Bernt; Lund, Mogens Sandø;

    2013-01-01

    Genomic selection is a method to predict breeding values using genome-wide single-nucleotide polymorphism (SNP) markers. High-quality marker data are necessary for genomic selection. The aim of this study was to investigate the effect of marker-editing criteria on the accuracy of genomic predicti......Genomic selection is a method to predict breeding values using genome-wide single-nucleotide polymorphism (SNP) markers. High-quality marker data are necessary for genomic selection. The aim of this study was to investigate the effect of marker-editing criteria on the accuracy of genomic...... predictions in the Nordic Holstein and Jersey populations. Data included 4429 Holstein and 1071 Jersey bulls. In total, 48 222 SNP for Holstein and 44 305 SNP for Jersey were polymorphic. The SNP data were edited based on (i) minor allele frequencies (MAF) with thresholds of no limit, 0.001, 0.01, 0.02, 0.......05 and 0.10, (ii) deviations from Hardy–Weinberg proportions (HWP) with thresholds of no limit, chi-squared p-values of 0.001, 0.02, 0.05 and 0.10, and (iii) GenCall (GC) scores with thresholds of 0.15, 0.55, 0.60, 0.65 and 0.70. The marker data sets edited with different criteria were used for genomic...

  16. Expression of stem cell markers in the human fetal kidney.

    Directory of Open Access Journals (Sweden)

    Sally Metsuyanim

    Full Text Available In the human fetal kidney (HFK self-renewing stem cells residing in the metanephric mesenchyme (MM/blastema are induced to form all cell types of the nephron till 34(th week of gestation. Definition of useful markers is crucial for the identification of HFK stem cells. Because wilms' tumor, a pediatric renal cancer, initiates from retention of renal stem cells, we hypothesized that surface antigens previously up-regulated in microarrays of both HFK and blastema-enriched stem-like wilms' tumor xenografts (NCAM, ACVRIIB, DLK1/PREF, GPR39, FZD7, FZD2, NTRK2 are likely to be relevant markers. Comprehensive profiling of these putative and of additional stem cell markers (CD34, CD133, c-Kit, CD90, CD105, CD24 in mid-gestation HFK was performed using immunostaining and FACS in conjunction with EpCAM, an epithelial surface marker that is absent from the MM and increases along nephron differentiation and hence can be separated into negative, dim or bright fractions. No marker was specifically localized to the MM. Nevertheless, FZD7 and NTRK2 were preferentially localized to the MM and emerging tubules (50% of HFK cells and predominantly co-express EpCAM(bright, indicating they are mostly markers of differentiation. Furthermore, localization of NCAM exclusively in the MM and in its nephron progenitor derivatives but also in stroma and the expression pattern of significantly elevated renal stem/progenitor genes Six2, Wt1, Cited1, and Sall1 in NCAM(+EpCAM(- and to a lesser extent in NCAM(+EpCAM(+ fractions confirmed regional identity of cells and assisted us in pinpointing the presence of subpopulations that are putative MM-derived progenitor cells (NCAM(+EpCAM(+FZD7(+, MM stem cells (NCAM(+EpCAM(-FZD7(+ or both (NCAM(+FZD7(+. These results and concepts provide a framework for developing cell selection strategies for human renal cell-based therapies.

  17. Immunogold labels: cell-surface markers in atomic force microscopy

    NARCIS (Netherlands)

    Putman, Constant A.J.; Grooth, de Bart G.; Hansma, Paul K.; Hulst, van Niek F.; Greve, Jan

    1993-01-01

    The feasibility of using immunogold labels as cell-surface markers in atomic force microscopy is shown in this paper. The atomic force microscope (AFM) was used to image the surface of immunogold-labeled human lymphocytes. The lymphocytes were isolated from whole blood and labeled by an indirect imm

  18. Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Olsen, Jesper; Linnemann, Dorte;

    2015-01-01

    Colorectal cancer (CRC) still has one of the highest incidence and mortality rate among cancers. Therefore, improved differential diagnostics and personalized treatment are still needed. Several intestinal stem cell markers have been found to be associated with CRC and might have a prognostic and...

  19. Prognostic Cell Biological Markers in Cervical Cancer Patients Primarily Treated With (Chemo)radiation: A Systematic Review

    International Nuclear Information System (INIS)

    The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in ≥50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biological markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1α). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients.

  20. Molecular Markers with Predictive and Prognostic Relevance in Lung Cancer

    OpenAIRE

    Alphy Rose-James; TT, Sreelekha

    2012-01-01

    Lung cancer accounts for the majority of cancer-related deaths worldwide of which non-small-cell lung carcinoma alone takes a toll of around 85%. Platinum-based therapy is the stronghold for lung cancer at present. The discovery of various molecular alterations that underlie lung cancer has contributed to the development of specifically targeted therapies employing specific mutation inhibitors. Targeted chemotherapy based on molecular profiling has shown great promise in lung cancer treatment...

  1. Rescue of marker phenotypes mediated by somatic cell hybridization

    International Nuclear Information System (INIS)

    The effect of irradiation prior to virus-induced cell fusion on the frequency of hybrid production has been measured as a function of radiation dose. The Chinese hamster line wg3h (HGPRT-) was crossed with the TK- mutants; Chinese hamster A23 or mouse 3T34E, and hybrids were selected in HAT medium. Irradiation of one (marker rescue) or both (mutual rescue) partners before fusion yielded qualitatively different results. After X-irradiation, marker rescue curves were of single-hit type, with D0 values about five-fold greater than the irradiated parent cell. Mutual rescue curves were of the multi-hit type, with zero-dose extrapolation value (n) greater than that of the more resistant partner, but no significant alteration in D0. Qualitatively similar results were obtained after U.V.- irradiation, but the probability of rescue per surviving parent cell was

  2. BRCA1 Mutation: A Predictive Marker for Radiation Therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Kan, Charlene; Zhang, Junran, E-mail: Junran.zhang@case.edu

    2015-10-01

    DNA repair, in particular, DNA double-strand break (DSB) repair, is essential for the survival of both normal and cancer cells. An elaborate repair mechanism has been developed in cells to efficiently repair the damaged DNA. The pathways predominately involved in DSB repair are homologous recombination and classic nonhomologous end-joining, although the alternative NHEJ pathway, a third DSB repair pathway, could also be important in certain contexts. The protein of BRCA1 encoded by the tumor suppressor gene BRCA1 regulates all DSB repair pathways. Given that DSBs represent the most biologically significant lesions induced by ionizing radiation and that impaired DSB repair leads to radiation sensitivity, it has been expected that cancer patients with BRCA1 mutations should benefit from radiation therapy. However, the clinical data have been conflicting and inconclusive. We provide an overview about the current status of the data regarding BRCA1 deficiency and radiation therapy sensitivity in both experimental models and clinical investigations. In addition, we discuss a strategy to potentiate the effects of radiation therapy by poly(ADP-ribose) polymerase inhibitors, the pharmacologic drugs being investigated as monotherapy for the treatment of patients with BRCA1/2 mutations.

  3. BRCA1 Mutation: A Predictive Marker for Radiation Therapy?

    International Nuclear Information System (INIS)

    DNA repair, in particular, DNA double-strand break (DSB) repair, is essential for the survival of both normal and cancer cells. An elaborate repair mechanism has been developed in cells to efficiently repair the damaged DNA. The pathways predominately involved in DSB repair are homologous recombination and classic nonhomologous end-joining, although the alternative NHEJ pathway, a third DSB repair pathway, could also be important in certain contexts. The protein of BRCA1 encoded by the tumor suppressor gene BRCA1 regulates all DSB repair pathways. Given that DSBs represent the most biologically significant lesions induced by ionizing radiation and that impaired DSB repair leads to radiation sensitivity, it has been expected that cancer patients with BRCA1 mutations should benefit from radiation therapy. However, the clinical data have been conflicting and inconclusive. We provide an overview about the current status of the data regarding BRCA1 deficiency and radiation therapy sensitivity in both experimental models and clinical investigations. In addition, we discuss a strategy to potentiate the effects of radiation therapy by poly(ADP-ribose) polymerase inhibitors, the pharmacologic drugs being investigated as monotherapy for the treatment of patients with BRCA1/2 mutations

  4. Lactate Dehydrogenase A is a potential prognostic marker in clear cell renal cell carcinoma

    OpenAIRE

    Girgis, Hala; Masui, Olena; White, Nicole MA; Scorilas, Andreas; Rotondo, Fabio; Seivwright, Annetta; Gabril, Manal; Filter, Emily R; Girgis, Andrew HA; Bjarnason, Georg A.; Jewett, Michael AS; Evans, Andrew; Al-Haddad, Sahar; Siu, KW Michael; Yousef, George M.

    2014-01-01

    Background 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...

  5. Multi-Marker Strategy in Heart Failure: Combination of ST2 and CRP Predicts Poor Outcome.

    Science.gov (United States)

    Dupuy, Anne Marie; Curinier, Corentin; Kuster, Nils; Huet, Fabien; Leclercq, Florence; Davy, Jean Marc; Cristol, Jean Paul; Roubille, François

    2016-01-01

    Natriuretic peptides (BNP and NT-proBNP) are recognized as gold-standard predictive markers in Heart Failure (HF). However, currently ST2 (member of the interleukin 1 receptor family) has emerged as marker of inflammation, fibrosis and cardiac stress. We evaluated ST2 and CRP as prognostic markers in 178 patients with chronic heart failure in comparison with other classical markers such as clinical established parameters but also biological markers: NT-proBNP, hs-cTnT alone or in combination. In multivariate analysis, subsequent addition of ST2 led to age, CRP and ST2 as the only remaining predictors of all-cause mortality (HR 1.03, HR 1.61 and HR 2.75, respectively) as well as of cardiovascular mortality (HR 1.00, HR 2.27 and HR 3.78, respectively). The combined increase of ST2 and CRP was significant for predicting worsened outcomes leading to identify a high risk subgroup that individual assessment of either marker. The same analysis was performed with ST2 in combination with Barcelona score. Overall, our findings extend previous data demonstrating that ST2 in combination with CRP as a valuable tool for identifying patients at risk of death. PMID:27311068

  6. Immunogold labels: cell-surface markers in atomic force microscopy

    OpenAIRE

    Putman, Constant A.J.; Grooth, de, B.G.; Hansma, Paul K.; Hulst, van der, R.W.M.; Greve, Jan

    1993-01-01

    The feasibility of using immunogold labels as cell-surface markers in atomic force microscopy is shown in this paper. The atomic force microscope (AFM) was used to image the surface of immunogold-labeled human lymphocytes. The lymphocytes were isolated from whole blood and labeled by an indirect immunolabeling method using the monoclonal antibody anti-CD3 and a secondary antibody (Goat-anti-Mouse) linked to 30 nm colloidal gold particles. Some of the samples were enhanced by silver deposition...

  7. Novel Single-Nucleotide Polymorphism Markers Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin C., E-mail: jckim@amc.seoul.kr [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Ha, Ye J.; Roh, Seon A. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Cho, Dong H. [Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Graduate School of East-West Medical Science, Kyung Hee University, Gyeoggi-do (Korea, Republic of); Choi, Eun Y. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Tae W. [Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Department of Internal Medicine, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Jong H. [Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kang, Tae W. [Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Kim, Seon Y. [Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Kim, Yong S., E-mail: yongsung@kribb.re.kr [Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of)

    2013-06-01

    Purpose: Studies aimed at predicting individual responsiveness to preoperative chemoradiation therapy (CRT) are urgently needed, especially considering the risks associated with poorly responsive patients. Methods and Materials: A 3-step strategy for the determination of CRT sensitivity is proposed based on (1) the screening of a human genome-wide single-nucleotide polymorphism (SNP) array in correlation with histopathologic tumor regression grade (TRG); (2) clinical association analysis of 113 patients treated with preoperative CRT; and (3) a cell-based functional assay for biological validation. Results: Genome-wide screening identified 9 SNPs associated with preoperative CRT responses. Positive responses (TRG 1-3) were obtained more frequently in patients carrying the reference allele (C) of the SNP CORO2A rs1985859 than in those with the substitution allele (T) (P=.01). Downregulation of CORO2A was significantly associated with reduced early apoptosis by 27% (P=.048) and 39% (P=.023) in RKO and COLO320DM colorectal cancer cells, respectively, as determined by flow cytometry. Reduced radiosensitivity was confirmed by colony-forming assays in the 2 colorectal cancer cells (P=.034 and .015, respectively). The SNP FAM101A rs7955740 was not associated with radiosensitivity in the clinical association analysis. However, downregulation of FAM101A significantly reduced early apoptosis by 29% in RKO cells (P=.047), and it enhanced colony formation in RKO cells (P=.001) and COLO320DM cells (P=.002). Conclusion: CRT-sensitive SNP markers were identified using a novel 3-step process. The candidate marker CORO2A rs1985859 and the putative marker FAM101A rs7955740 may be of value for the prediction of radiosensitivity to preoperative CRT, although further validation is needed in large cohorts.

  8. Novel Single-Nucleotide Polymorphism Markers Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

    International Nuclear Information System (INIS)

    Purpose: Studies aimed at predicting individual responsiveness to preoperative chemoradiation therapy (CRT) are urgently needed, especially considering the risks associated with poorly responsive patients. Methods and Materials: A 3-step strategy for the determination of CRT sensitivity is proposed based on (1) the screening of a human genome-wide single-nucleotide polymorphism (SNP) array in correlation with histopathologic tumor regression grade (TRG); (2) clinical association analysis of 113 patients treated with preoperative CRT; and (3) a cell-based functional assay for biological validation. Results: Genome-wide screening identified 9 SNPs associated with preoperative CRT responses. Positive responses (TRG 1-3) were obtained more frequently in patients carrying the reference allele (C) of the SNP CORO2A rs1985859 than in those with the substitution allele (T) (P=.01). Downregulation of CORO2A was significantly associated with reduced early apoptosis by 27% (P=.048) and 39% (P=.023) in RKO and COLO320DM colorectal cancer cells, respectively, as determined by flow cytometry. Reduced radiosensitivity was confirmed by colony-forming assays in the 2 colorectal cancer cells (P=.034 and .015, respectively). The SNP FAM101A rs7955740 was not associated with radiosensitivity in the clinical association analysis. However, downregulation of FAM101A significantly reduced early apoptosis by 29% in RKO cells (P=.047), and it enhanced colony formation in RKO cells (P=.001) and COLO320DM cells (P=.002). Conclusion: CRT-sensitive SNP markers were identified using a novel 3-step process. The candidate marker CORO2A rs1985859 and the putative marker FAM101A rs7955740 may be of value for the prediction of radiosensitivity to preoperative CRT, although further validation is needed in large cohorts

  9. Quantitative trait loci markers derived from whole genome sequence data increases the reliability of genomic prediction.

    Science.gov (United States)

    Brøndum, R F; Su, G; Janss, L; Sahana, G; Guldbrandtsen, B; Boichard, D; Lund, M S

    2015-06-01

    This study investigated the effect on the reliability of genomic prediction when a small number of significant variants from single marker analysis based on whole genome sequence data were added to the regular 54k single nucleotide polymorphism (SNP) array data. The extra markers were selected with the aim of augmenting the custom low-density Illumina BovineLD SNP chip (San Diego, CA) used in the Nordic countries. The single-marker analysis was done breed-wise on all 16 index traits included in the breeding goals for Nordic Holstein, Danish Jersey, and Nordic Red cattle plus the total merit index itself. Depending on the trait's economic weight, 15, 10, or 5 quantitative trait loci (QTL) were selected per trait per breed and 3 to 5 markers were selected to tag each QTL. After removing duplicate markers (same marker selected for more than one trait or breed) and filtering for high pairwise linkage disequilibrium and assaying performance on the array, a total of 1,623 QTL markers were selected for inclusion on the custom chip. Genomic prediction analyses were performed for Nordic and French Holstein and Nordic Red animals using either a genomic BLUP or a Bayesian variable selection model. When using the genomic BLUP model including the QTL markers in the analysis, reliability was increased by up to 4 percentage points for production traits in Nordic Holstein animals, up to 3 percentage points for Nordic Reds, and up to 5 percentage points for French Holstein. Smaller gains of up to 1 percentage point was observed for mastitis, but only a 0.5 percentage point increase was seen for fertility. When using a Bayesian model accuracies were generally higher with only 54k data compared with the genomic BLUP approach, but increases in reliability were relatively smaller when QTL markers were included. Results from this study indicate that the reliability of genomic prediction can be increased by including markers significant in genome-wide association studies on whole genome

  10. Expression of biological markers in oral squamous cell carcinomas

    Directory of Open Access Journals (Sweden)

    Humberto Thomazi Gassen

    2012-01-01

    Full Text Available Squamous cell carcinomas are the most commonly diagnosed oral malignancy, accounting for about 90% of all malignant oral lesions. Detection of the condition at early stages is rare; as a result, the clinical and histological characteristics and prognosis of this tumor have not been extensively investigated. The objective of this study was to evaluate clinical and microscopic features of squamous cell carcinomas using immunohistochemical analysis and assessing biological markers of angiogenesis and tumor vascular activity (anti-CD31, anti-CD34, Factor VIII, cell proliferation (Ki-67, and loss of cell suppression (p53. Tolonium chloride 1% was used to determine the optimal biopsy site. Six patients seen at the Stomatology Service of a university hospital in Canoas, southern Brazil, with a suspected diagnosis of squamous cell carcinoma were analyzed. All patients were male, with a mean age of 56.6 years, and four had a white skin color. Lesions were detected in the tongue (4 and tonsillar pillar (2. All diagnoses were confi rmed by microscopy (hematoxylin-eosin staining. Immunohistochemical analysis revealed p53 expression in 5 of the cases, Ki-67 in 6, and anti-CD34 in 1; anti-CD31 and Factor VIII were not detected in any patient. Our fi ndings suggest an important contribution of tumor markers in the diagnosis and prognosis of these malignancies, as well as in treatment planning.

  11. Identification of cancer stem cell markers in human malignant mesothelioma cells

    International Nuclear Information System (INIS)

    Research highlights: → We performed serial transplantation of surgical samples and established new cell lines of malignant mesothelioma. → SP cell and expressions of CD9/CD24/CD26 were often observed in mesothelioma cell lines. → SP and CD24+ cells proliferated by asymmetric cell division-like manner. CD9+ and CD24+ cells have higher potential to generate spheroid colony. → The marker-positive cells have clear tendency to generate larger tumors in mice. -- Abstract: Malignant mesothelioma (MM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells and usually associated with long-term asbestos exposure. Recent studies suggest that tumors contain cancer stem cells (CSCs) and their stem cell characteristics are thought to confer therapy-resistance. However, whether MM cell has any stem cell characteristics is not known. To understand the molecular basis of MM, we first performed serial transplantation of surgical samples into NOD/SCID mice and established new cell lines. Next, we performed marker analysis of the MM cell lines and found that many of them contain SP cells and expressed several putative CSC markers such as CD9, CD24, and CD26. Interestingly, expression of CD26 closely correlated with that of CD24 in some cases. Sorting and culture assay revealed that SP and CD24+ cells proliferated by asymmetric cell division-like manner. In addition, CD9+ and CD24+ cells have higher potential to generate spheroid colony than negative cells in the stem cell medium. Moreover, these marker-positive cells have clear tendency to generate larger tumors in mouse transplantation assay. Taken together, our data suggest that SP, CD9, CD24, and CD26 are CSC markers of MM and could be used as novel therapeutic targets.

  12. Identification of cancer stem cell markers in human malignant mesothelioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Ghani, Farhana Ishrat; Yamazaki, Hiroto; Iwata, Satoshi; Okamoto, Toshihiro [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan); Aoe, Keisuke; Okabe, Kazunori; Mimura, Yusuke [Departments of Medical Oncology, Yamaguchi-Ube Medical Center, Yamaguchi (Japan); Fujimoto, Nobukazu; Kishimoto, Takumi [Department of Respiratory Medicine, Okayama Rosai Hospital, Okayama (Japan); Yamada, Taketo [Department of Pathology, Keio University School of Medicine, Tokyo (Japan); Xu, C. Wilson [Drug Development Program, Nevada Cancer Institute, Las Vegas, NV (United States); Morimoto, Chikao, E-mail: morimoto@ims.u-tokyo.ac.jp [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan); Drug Development Program, Nevada Cancer Institute, Las Vegas, NV (United States)

    2011-01-14

    Research highlights: {yields} We performed serial transplantation of surgical samples and established new cell lines of malignant mesothelioma. {yields} SP cell and expressions of CD9/CD24/CD26 were often observed in mesothelioma cell lines. {yields} SP and CD24{sup +} cells proliferated by asymmetric cell division-like manner. CD9{sup +} and CD24{sup +} cells have higher potential to generate spheroid colony. {yields} The marker-positive cells have clear tendency to generate larger tumors in mice. -- Abstract: Malignant mesothelioma (MM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells and usually associated with long-term asbestos exposure. Recent studies suggest that tumors contain cancer stem cells (CSCs) and their stem cell characteristics are thought to confer therapy-resistance. However, whether MM cell has any stem cell characteristics is not known. To understand the molecular basis of MM, we first performed serial transplantation of surgical samples into NOD/SCID mice and established new cell lines. Next, we performed marker analysis of the MM cell lines and found that many of them contain SP cells and expressed several putative CSC markers such as CD9, CD24, and CD26. Interestingly, expression of CD26 closely correlated with that of CD24 in some cases. Sorting and culture assay revealed that SP and CD24{sup +} cells proliferated by asymmetric cell division-like manner. In addition, CD9{sup +} and CD24{sup +} cells have higher potential to generate spheroid colony than negative cells in the stem cell medium. Moreover, these marker-positive cells have clear tendency to generate larger tumors in mouse transplantation assay. Taken together, our data suggest that SP, CD9, CD24, and CD26 are CSC markers of MM and could be used as novel therapeutic targets.

  13. Functional characteristics of neonatal rat β cells with distinct markers

    DEFF Research Database (Denmark)

    Martens, G A; Motté, E; Kramer, G; Stangé, G; Gaarn, L W; Hellemans, K; Nielsen, Jens Høiriis; Aerts, J M; Ling, Z; Pipeleers, D

    2014-01-01

    Neonatal β cells are considered developmentally immature and hence less glucose responsive. To study the acquisition of mature glucose responsiveness, we compared glucose-regulated redox state, insulin synthesis, and secretion of β cells purified from neonatal or 10-week-old rats with their...... had twofold lower expression of malate/aspartate-NADH shuttle and most glycolytic enzymes. Genome-wide profiling situated neonatal β cells at a developmental crossroad: they showed advanced endocrine differentiation when specifically analyzed for their mRNA/protein level of classical neuroendocrine...... high DLK1, but no association was found. In conclusion, the current study supports the importance of glycolytic NADH-shuttling in stimulus function coupling, presents basal hyperactivity as novel property of neonatal β cells, and provides potential markers to recognize intercellular developmental...

  14. SNPs in transporter and metabolizing genes as predictive markers for oxaliplatin treatment in colorectal cancer patients.

    Science.gov (United States)

    Kap, Elisabeth J; Seibold, Petra; Scherer, Dominique; Habermann, Nina; Balavarca, Yesilda; Jansen, Lina; Zucknick, Manuela; Becker, Natalia; Hoffmeister, Michael; Ulrich, Alexis; Benner, Axel; Ulrich, Cornelia M; Burwinkel, Barbara; Brenner, Hermann; Chang-Claude, Jenny

    2016-06-15

    Oxaliplatin is frequently used as part of a chemotherapeutic regimen with 5-fluorouracil in the treatment of colorectal cancer (CRC). The cellular availability of oxaliplatin is dependent on metabolic and transporter enzymes. Variants in genes encoding these enzymes may cause variation in response to oxaliplatin and could be potential predictive markers. Therefore, we used a two-step procedure to comprehensively investigate 1,444 single nucleotide polymorphisms (SNPs) from these pathways for their potential as predictive markers for oxaliplatin treatment, using 623 stage II-IV CRC patients (of whom 201 patients received oxaliplatin) from a German prospective patient cohort treated with adjuvant or palliative chemotherapy. First, all genes were screened using the global test that evaluated SNP*oxaliplatin interaction terms per gene. Second, one model was created by backward elimination on all SNP*oxaliplatin interactions of the selected genes. The statistical procedure was evaluated using bootstrap analyses. Nine genes differentially associated with overall survival according to oxaliplatin treatment (unadjusted p values analysis we show an improvement of the prediction error of 3.7% in patients treated with oxaliplatin. Several variants in genes involved in metabolism and transport could thus be potential predictive markers for oxaliplatin treatment in CRC patients. If confirmed, inclusion of these variants in a predictive test could identify patients who are more likely to benefit from treatment with oxaliplatin. PMID:26835885

  15. Prediction of Post-Operative Liver Dysfunction by Serum Markers of Liver Fibrosis in Hepatocellular Carcinoma

    Science.gov (United States)

    Shen, Yinghao; Shi, Guoming; Huang, Cheng; Zhu, Xiaodong; Chen, Si; Sun, Huichuan; Zhou, Jian; Fan, Jia

    2015-01-01

    Aim To investigate the role of biomarkers in predicting postoperative liver dysfunction in patients with hepatocellular carcinoma (HCC). Methods A total of 200 patients operated from July 2009 to June 2010 at Zhongshan Hospital, Fudan University for pathologically confirmed HCC were retrospectively analyzed for clinical data, HBD DNA level and serum biochemical markers for liver fibrosis. The patients were followed up to observersation end point. Correlation of the monitored parameters with postoperative liver dysfunction and patient survival was statistically analyzed. Results Preoperative hepatitis B virus (HBV) DNA level, serum prealbumin (PA) hyaluronic acid (HA), and laminin (LN) levels correlated with postoperative liver dysfunction. A predictive model was generated using these 4 parameters and validated in 89 HCC patients with sensitivity and specificity of 0.625 and 0.912, respectively. However, no correlation was identified between postoperative liver function and overall survival. Conclusion Liver fibrosis markers could be preoperatively used in predicting postoperative liver dysfunction in HCC patients. PMID:26501145

  16. Macrophage serum markers in pneumococcal bacteremia: Prediction of survival by soluble CD163

    DEFF Research Database (Denmark)

    Møller, Holger Jon; K. Moestrup, Søren; Wejse, Christian;

    2006-01-01

    probability of survival when sCD163 and CRP were known (p = .25). CONCLUSIONS: Macrophage marker response in pneumococcal bacteremia was compromised in old age. In patients <75 yrs old, sCD163 was superior to other markers, including C-reactive protein, in predicting fatal disease outcome....... pneumococcal bacteremia. DESIGN: Observational cohort study. SETTING: Five university hospitals in Denmark. PATIENTS: A total of 133 patients with Streptococcus pneumoniae bacteremia (positive blood culture) and 133 age- and gender-matched controls. INTERVENTIONS: Samples were collected for biochemical...

  17. Astrocytes derived from trisomic human embryonic stem cells express markers of astrocytic cancer cells and premalignant stem-like progenitors

    Directory of Open Access Journals (Sweden)

    Iverson Linda E

    2010-04-01

    Full Text Available Abstract Background Trisomic variants of human embryonic stem cells (hESCs arise spontaneously in culture. Although trisomic hESCs share many properties with diploid hESCs, they also exhibit features of cancer stem cells. Since most hESC-based therapies will utilize differentiated derivatives, it is imperative to investigate the potential of trisomic hESCs to undergo malignant transformation during differentiation prior to their use in the clinical setting. Methods Diploid and trisomic hESCs were differentiated into astrocytic progenitors cells (APCs, RNA extracted and hybridized to human exon-specific microarrays. Global gene expression profiles of diploid and trisomic APCs were compared to that of an astrocytoma cell line and glioblastoma samples, analyzed by others, using the same microarray platform. Results Bioinformatic analysis of microarray data indicates that differentiated trisomic APCs exhibit global expression profiles with similarities to the malignant astrocytoma cell line. An analogous trend is observed in comparison to glioblastoma samples indicating that trisomic APCs express markers of astrocytic cancer cells. The analysis also allowed identification of transcripts predicted to be differentially expressed in brain tumor stem cells. These data indicate that in vitro differentiation of trisomic hESCs along astrocytic pathways give rise to cells exhibiting properties of premalignant astrocytic stem/progenitor cells. Conclusions Given their occult nature, opportunities to study premalignant stem/progenitor cells in human have been few. The ability to propagate and direct the differentiation of aneuploid hESCs provides a powerful in vitro system for investigating biological properties of human cells exhibiting features of premalignant stem cells. This in vitro culture system can be used to elucidate changes in gene expression occurring enroute to malignant transformation and to identify molecular markers of cancer stem

  18. Specific Protein Markers for Stem Cell Cross-Talk with Neighboring Cells in the Environment

    OpenAIRE

    Park, Kyung Soo; Shin, Seung Won; Choi, Jeong-Woo; Um, Soong Ho

    2013-01-01

    A stem cell interacts with the neighboring cells in its environment. To maintain a living organism’s metabolism, either cell-cell or cell-environment interactions may be significant. Usually, these cells communicate with each other through biological signaling by interactive behaviors of primary proteins or complementary chemicals. The signaling intermediates offer the stem cell’s functionality on its metabolism. With the rapid advent of omics technologies, various specific markers by which s...

  19. Use of the gold markers method to predict the mechanisms of iron atmospheric corrosion

    Energy Technology Data Exchange (ETDEWEB)

    Burger, E., E-mail: emilien.burger@cea.f [CEA, DEN, DPC, SCCME, Laboratoire d' Etude de la Corrosion Aqueuse, F-91191 Gif-sur-Yvette (France); CEA, DSM, IRAMIS, SIS2M, Laboratoire, Archeomateriaux et revision de l' Alteration, UMR3299, F-91191 Gif-sur-Yvette (France); Fenart, M.; Perrin, S. [CEA, DEN, DPC, SCCME, Laboratoire d' Etude de la Corrosion Aqueuse, F-91191 Gif-sur-Yvette (France); Neff, D. [CEA, DSM, IRAMIS, SIS2M, Laboratoire, Archeomateriaux et revision de l' Alteration, UMR3299, F-91191 Gif-sur-Yvette (France); Dillmann, P. [CEA, DSM, IRAMIS, SIS2M, Laboratoire, Archeomateriaux et revision de l' Alteration, UMR3299, F-91191 Gif-sur-Yvette (France); LMC IRAMAT UMR5060 CNRS (France)

    2011-06-15

    Highlights: {yields} Corrosion mechanisms investigated by gold markers method coupled with microRaman imaging. {yields} Experimental highlighting of an important internal development of the rust layer. {yields} Microstructural evolution of the corrosion product layer during atmospheric treatment. {yields} Comparison with long-term corrosion layer microstructure. - Abstract: Iron corrosion under atmospheric conditions has been investigated by using the gold markers method. The corrosion experiments were performed in a climatic chamber with an accelerated treatment. The gold markers localization, carried out by scanning electron microscopy coupled with energy dispersive X-ray spectroscopy, revealed that the rust layer growth was essentially due to an internal development. Moreover, microRaman mappings allowed prediction of the mechanism of rust layer evolution during the ageing treatment. Finally these results were compared to samples corroded for several 100 years in order to extrapolate our observations to long term corrosion.

  20. Use of the gold markers method to predict the mechanisms of iron atmospheric corrosion

    International Nuclear Information System (INIS)

    Highlights: → Corrosion mechanisms investigated by gold markers method coupled with microRaman imaging. → Experimental highlighting of an important internal development of the rust layer. → Microstructural evolution of the corrosion product layer during atmospheric treatment. → Comparison with long-term corrosion layer microstructure. - Abstract: Iron corrosion under atmospheric conditions has been investigated by using the gold markers method. The corrosion experiments were performed in a climatic chamber with an accelerated treatment. The gold markers localization, carried out by scanning electron microscopy coupled with energy dispersive X-ray spectroscopy, revealed that the rust layer growth was essentially due to an internal development. Moreover, microRaman mappings allowed prediction of the mechanism of rust layer evolution during the ageing treatment. Finally these results were compared to samples corroded for several 100 years in order to extrapolate our observations to long term corrosion.

  1. Identification of stem-like cells and clinical significance of candidate stem cell markers in gastric cancer

    Science.gov (United States)

    Wang, Xiaofeng; Huang, Mingzhu; Gan, Lu; Wu, Zhenhua; Zhang, Jiejun; Wang, Hongqiang; Cheng, Yufan; Li, Jin; Guo, Weijian

    2016-01-01

    The existence of gastric cancer stem cells (CSCs) has not been definitively proven and specific cell surface markers for identifying gastric CSCs have largely not been identified. Our research aimed to isolate potential gastric CSCs and clarify their clinical significance, while defining markers for GCSC identification and verification. Here, we report that spheroid cells possess stem cell-like properties, and overexpress certain stem cell markers. CD133 or CD44-positive cells also exhibit properties of CSCs. The expression of Oct4, Sox2, Gli1, CD44, CD133, p-AKT, and p-ERK was significantly higher in metastatic lesions compared to that in primary lesions. Elevated expression of some of these proteins was correlated with a more aggressive phenotype and poorer prognosis, including Oct4, Sox2, Gli1, CD44, and p-ERK. Multivariate Cox proportional hazards model analysis showed that only CD44 is an independent factor. Knockdown of CD44 down-regulated the stem cell-like properties, which was accompanied by the down-regulation of p-ERK and Oct4. Oct4 overexpression could reverse the decreased CSCs properties induced by CD44 knockdown. Taken together, our research revealed that spheroid cell culture, and CD133 or CD44-labeled FACS methods can be used to isolate gastric CSCs. Some CSC markers have clinical significance in predicting the prognosis. CD44 is an independent prognostic factor and maintains the properties of CSCs in CD44-p-ERK-Oct4 positive feedback loop. PMID:26769843

  2. Serologic and laboratory markers in prediction of the disease course in inflammatory bowel disease

    OpenAIRE

    2010-01-01

    The search for biologic markers that can assess the natural history and perhaps predict the course of individual’s disease including response to treatments over time has become an important focus of inflammatory bowel disease research. The knowledge of an individual’s prognosis can help physicians and patients make important management decisions and aid communication on risk and benefits of disease and treatment.

  3. Role of Histological Criteria and Immunohistochemical Markers in Predicting Risk of Malignancy in Parathyroid Neoplasms.

    Science.gov (United States)

    Kumari, Niraj; Chaudhary, Nandita; Pradhan, Roma; Agarwal, Amit; Krishnani, Narendra

    2016-06-01

    Parathyroid carcinoma (PC) is a rare neoplasm accounting for 0.5-6 % of primary hyperparathyroidism. Histological criteria are currently considered as established means to diagnose malignancy in parathyroid neoplasms; however, it does not accurately predict the risk of aggressive behaviour of PC. Immunohistochemical (IHC) markers have been used in the literature with variable results. This work was planned to study whether IHC markers would have any added advantage over histology in predicting outcome in parathyroid neoplasms. Two hundred twenty-seven parathyroid neoplasms were reviewed according to older and revised histological criteria. IHC was performed for parafibromin, APC, galectin-3, PGP9.5 and Ki67. Diagnostic categories were correlated with clinical, biochemical, histological features and IHC markers. Chi-square test was used to analyse categorical variables. Review of histology by earlier and revised criteria showed a change in diagnosis of five cases of atypical adenoma (15.1 %), all of which were diagnosed as carcinoma according to earlier criteria. Change in diagnosis did not affect behaviour of disease as none of the cases showed recurrence or metastasis on follow-up. Combination of PF, Gal-3 and PGP9.5 showed 50 % sensitivity, 97.9 % specificity and 95.4 % predictive accuracy for PC. Histological criteria still remains the most established method for predicting risk of malignancy in parathyroid neoplasms irrespective of whether old or revised criteria are used. Combination of positive (Gal-3, PGP9.5) and negative (PF) IHC markers may be used as an adjunct to histology in histological, atypical and malignant parathyroid neoplasms to obviate the need for repeated follow-up. PMID:26984237

  4. Macrophage activation marker soluble CD163 may predict disease progression in hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Kazankov, Konstantin; Rode, Anthony; Simonsen, Kira;

    2016-01-01

    BACKGROUND: Tumor associated macrophages are present in hepatocellular carcinoma (HCC) and associated with a poor prognosis. The aim of the present study was to investigate the levels and dynamics of soluble (s)CD163, a specific macrophage activation marker, in patients with HCC. METHODS: In a......, baseline sCD163 appeared to predict a rapid HCC progression, as sCD163 increased during follow-up in HCC patients who showed progression....

  5. Role of maternal serum ferritin as a predictive marker in intrauterine growth restriction

    OpenAIRE

    Neeta Bindal; Zeepee Godha; Reema Kohli; V. K. Kadam

    2015-01-01

    Background: Intrauterine growth restriction (IUGR) is most common and distressing complication for both obstetrician and neonatologist. Measurement of maternal serum ferritin has also been used as a predictive marker of increase risk of IUGR. In pregnancy, ferritin level decreases with advancing gestation. Its lowest level is seen around 30-32 weeks of gestational age after which its concentration reaches plateau level. Methods: Total 326 antenatal women enrolled in the study. Maternal ser...

  6. Molecular markers for tumor cell dissemination in female cancers

    International Nuclear Information System (INIS)

    In the fight against cancer many advances have been made in early detection and treatment of the disease during the last few decades. Nevertheless, many patients still die of cancer due to metastatic spreading of the disease. Tumor cell dissemination may occur very early and usually is not discovered at the time of initial diagnosis. In these cases, the mere excision of the primary tumor is an insufficient treatment. Microscopic tumor residues will remain in the blood, lymph nodes, or the bone marrow and will cause disease recurrence. To improve the patient's prognosis, a sensitive tool for the detection of single tumor cells supplementing conventional diagnostic procedures is required. As the blood is more easily accessible than the bone marrow or tissue biopsies, we intended to identify gene markers for the detection of circulating tumor cells in the blood of cancer patients. We focused on patients with breast, ovarian, endometrial or cervical cancer. Starting from a genome-wide gene expression analysis of tumor cells and blood cells, we found six genes higher expression levels in cancer patients compared to healthy women. These findings suggest that an increased expression of these genes in the blood indicates the presence of circulating tumor cells inducing future metastases and thus the need for adjuvant therapy assisting the primary treatment. Measuring the expression levels of these six genes in the blood may supplement conventional diagnostic tests and improve the patient's prognosis. (author)

  7. Identification and Characterization of Renal Cell Carcinoma Gene Markers

    Directory of Open Access Journals (Sweden)

    Louis S. Liou

    2007-01-01

    Full Text Available Microarray gene expression profiling has been used to distinguish histological subtypes of renal cell carcinoma (RCC, and consequently to identify specific tumor markers. The analytical procedures currently in use find sets of genes whose average differential expression across the two categories differ significantly. In general each of the markers thus identifi ed does not distinguish tumor from normal with 100% accuracy, although the group as a whole might be able to do so. For the purpose of developing a widely used economically viable diagnostic signature, however, large groups of genes are not likely to be useful. Here we use two different methods, one a support vector machine variant, and the other an exhaustive search, to reanalyze data previously generated in our Lab (Lenburg et al. 2003. We identify 158 genes, each having an expression level that is higher (lower in every tumor sample than in any normal sample, and each having a minimum differential expression across the two categorie at a signifi cance of 0.01. The set is highly enriched in cancer related genes (p = 1.6 × 10 – 12, containing 43 genes previously associated with either RCC or other types of cancer. Many of the biomarkers appear to be associated with the central alterations known to be required for cancer transformation. These include the oncogenes JAZF1, AXL, ABL2; tumor suppressors RASD1, PTPRO, TFAP2A, CDKN1C; and genes involved in proteolysis or cell-adhesion such as WASF2, and PAPPA.

  8. Early diagnosis of breast cancer dissemination by tumor markers follow-up and method of prediction

    International Nuclear Information System (INIS)

    A mathematical model of prediction of progression was tested in patients with breast cancer employing long-term monitoring of tumor markers CEA, CA 15/3, MSA and TPA, erythrocyte sedimentation rate (FW), and the enzymes gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and lactate dehydrogenase (LD) in serum. At the same time, specificity, sensitivity, lead time and positive predictive value were evaluated along with false positivity for the all these parameters and their combinations. A model was proposed for the follow up of patients with breast cancer after the completion of basic therapy. (author)

  9. Prediction of metabolic syndrome among postmenopausal Ghanaian women using obesity and atherogenic markers

    Directory of Open Access Journals (Sweden)

    Arthur Fareed K N

    2012-08-01

    Full Text Available Abstract Background Metabolic syndrome (MetS is an important health problem which puts individuals at risk for cardiovascular diseases and type 2 diabetes as well as obesity-related cancers such as colon and renal cell in men, and endometrial and oesophageal in women. Objective This study was aimed at examining how obesity indicators and related determinants influence metabolic syndrome, and how the factors can be used to predict the syndrome and its cut-offs in postmenopausal Ghanaian women. Methods Two hundred and fifty (250 Ghanaian subjects were involved in the study with one hundred and forty-three (143 being premenopausal women and one hundred and seven (107 postmenopausal women. The influence of traditional metabolic risk factors including high blood pressure, dyslipidemia and glucose intolerance on obesity and atherogenic indices i.e. body mass index (BMI, waist circumference (WC, waist-to-hip ratio (WHR, Waist-to-thigh ratio (WTR, waist-to-height ratio (WHtR, high density lipoprotein cholesterol to total cholesterol ratio (HDL-C/TC, high density lipoprotein cholesterol to low density lipoprotein ratio (HDL-C/LDL-C and triglyceride to high density lipoprotein cholesterol ratio (TG/HDL-C were identified according to the Harmonization (H_MS criterion. Results The predominant anthropometric marker that significantly influence metabolic risk factors among the pre- and postmenopausal women was waist-to-hip ratio (premenopausal: p- 0.004, 0.026 and 0.002 for systolic blood pressure (SBP, fasting blood glucose (FBG and HDL-C; postmenopausal: p-0.012, 0.048, 0.007 and 0.0061 for diastolic blood pressure (DBP, FBG, triglyceride (TG and high density lipoprotein cholesterol (HDL-C respectively. Using the receiver operating characteristic (ROC analysis, the area under the curve for WC, WHR, TG/HDL-C and HDL-C/TC among postmenopausal women were estimated at 0.6, 0.6, 0.8 and 0.8 respectively. The appropriate cut-off values for WC, WHR, TG/HDL-C and

  10. Multidimensional profiling of cell surface proteins and nuclear markers

    Energy Technology Data Exchange (ETDEWEB)

    Han, Ju; Chang, Hang; Andarawewa, Kumari; Yaswen, Paul; Helen Barcellos-Hoff, Mary; Parvin, Bahram

    2009-01-30

    Cell membrane proteins play an important role in tissue architecture and cell-cell communication. We hypothesize that segmentation and multidimensional characterization of the distribution of cell membrane proteins, on a cell-by-cell basis, enable improved classification of treatment groups and identify important characteristics that can otherwise be hidden. We have developed a series of computational steps to (i) delineate cell membrane protein signals and associate them with a specific nucleus; (ii) compute a coupled representation of the multiplexed DNA content with membrane proteins; (iii) rank computed features associated with such a multidimensional representation; (iv) visualize selected features for comparative evaluation through heatmaps; and (v) discriminate between treatment groups in an optimal fashion. The novelty of our method is in the segmentation of the membrane signal and the multidimensional representation of phenotypic signature on a cell-by-cell basis. To test the utility of this method, the proposed computational steps were applied to images of cells that have been irradiated with different radiation qualities in the presence and absence of other small molecules. These samples are labeled for their DNA content and E-cadherin membrane proteins. We demonstrate that multidimensional representations of cell-by-cell phenotypes improve predictive and visualization capabilities among different treatment groups, and identify hidden variables.

  11. Molecular markers predicting radiotherapy response: Report and recommendations from an International Atomic Energy Agency technical meeting

    International Nuclear Information System (INIS)

    Purpose: There is increasing interest in radiogenomics and the characterization of molecular profiles that predict normal tissue and tumor radioresponse. A meeting in Amsterdam was organized by the International Atomic Energy Agency to discuss this topic on an international basis. Methods and Materials: This report is not completely exhaustive, but highlights some of the ongoing studies and new initiatives being carried out worldwide in the banking of tumor and normal tissue samples underpinning the development of molecular marker profiles for predicting patient response to radiotherapy. It is generally considered that these profiles will more accurately define individual or group radiosensitivities compared with the nondefinitive findings from the previous era of cellular-based techniques. However, so far there are only a few robust reports of molecular markers predicting normal tissue or tumor response. Results: Many centers in different countries have initiated tissue and tumor banks to store samples from clinical trials for future molecular profiling analysis, to identify profiles that predict for radiotherapy response. The European Society for Therapeutic Radiology and Oncology GENEtic pathways for the Prediction of the effects of Irradiation (GENEPI) project, to store, document, and analyze sample characteristics vs. response, is the most comprehensive in this regard. Conclusions: The next 5-10 years are likely to see the results of these and other correlative studies, and promising associations of profiles with response should be validated in larger definitive trials

  12. ICAM1 Is a Potential Cancer Stem Cell Marker of Esophageal Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Sheng-Ta Tsai

    Full Text Available Esophageal squamous cell carcinoma (ESCC accounts for about 90% of esophageal cancer diagnosed in Asian countries, with its incidence on the rise. Cancer stem cell (CSC; also known as tumor-initiating cells, TIC is inherently resistant to cytotoxic chemotherapy and radiation and associates with poor prognosis and therapy failure. Targeting therapy against cancer stem cell has emerged as a potential therapeutic approach to develop effective regimens. However, the suitable CSC marker of ESCC for identification and targeting is still limited. In this study, we screened the novel CSC membrane protein markers using two distinct stemness characteristics of cancer cell lines by a comparative approach. After the validation of RT-PCR, qPCR and western blot analyses, intercellular adhesion molecule 1 (ICAM1 was identified as a potential CSC marker of ESCC. ICAM1 promotes cancer cell migration, invasion as well as increasing mesenchymal marker expression and attenuating epithelial marker expression. In addition, ICAM1 contributes to CSC properties, including sphere formation, drug resistance, and tumorigenesis in mouse xenotransplantation model. Based on the analysis of ICAM1-regulated proteins, we speculated that ICAM1 regulates CSC properties partly through an ICAM1-PTTG1IP-p53-DNMT1 pathway. Moreover, we observed that ICAM1 and CD44 could have a compensation effect on maintaining the stemness characteristics of ESCC, suggesting that the combination of multi-targeting therapies should be under serious consideration to acquire a more potent therapeutic effect on CSC of ESCC.

  13. Should the markers on X chromosome be used for genomic prediction?

    DEFF Research Database (Denmark)

    Su, Guosheng; Guldbrandtsen, Bernt; Aamand, Gert Pedersen;

    2013-01-01

    traits based on 54K markerdata, imputed 54K for test animals, and imputed 54K for half of referenceanimals. GBLUP models with or without residual polygenic effect were used forgenomic prediction. For all three data sets, genomic prediction using allmarkers gave slightly higher reliability than prediction...... excluding the X chromosome.Averaged over 15 traits, the gains in reliability from the X chromosome rangedfrom 0.3% to 0.5% points among the three data sets and models. Using a model with a G-matrix accounting for sex-linkedrelationship appropriately or a model which divided genomic breeding value intoan...... autosomal component and an X chromosomal component did not led to betterprediction based on the present data where all animals were bulls. A modelincluding polygenic effect did not recover the loss of prediction accuracy dueto exclusion of the X chromosome. It is recommended using markers on the X...

  14. Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas

    Directory of Open Access Journals (Sweden)

    Olsson Björn

    2009-10-01

    Full Text Available Abstract Background Chemotherapy resistance remains a major obstacle in the treatment of women with ovarian cancer. Establishing predictive markers of chemoresponse would help to individualize therapy and improve survival of ovarian cancer patients. Chemotherapy resistance in ovarian cancer has been studied thoroughly and several non-overlapping single genes, gene profiles and copy number alterations have been suggested as potential markers. The objective of this study was to explore genetic alterations behind chemotherapy resistance in ovarian cancer with the ultimate aim to find potential predictive markers. Methods To create the best opportunities for identifying genetic alterations of importance for resistance, we selected a homogenous tumor material concerning histology, stage and chemotherapy. Using high-resolution whole genome array comparative genomic hybridization (CGH, we analyzed the tumor genomes of 40 fresh-frozen stage III ovarian serous carcinomas, all uniformly treated with combination therapy paclitaxel/carboplatin. Fisher's exact test was used to identify significant differences. Subsequently, we examined four genes in the significant regions (EVI1, MDS1, SH3GL2, SH3KBP1 plus the ABCB1 gene with quantitative real-time polymerase chain reaction (QPCR to evaluate the impact of DNA alterations on the transcriptional level. Results We identified gain in 3q26.2, and losses in 6q11.2-12, 9p22.3, 9p22.2-22.1, 9p22.1-21.3, Xp22.2-22.12, Xp22.11-11.3, and Xp11.23-11.1 to be significantly associated with chemotherapy resistance. In the gene expression analysis, EVI1 expression differed between samples with gain versus without gain, exhibiting higher expression in the gain group. Conclusion In conclusion, we detected specific genetic alterations associated with resistance, of which some might be potential predictive markers of chemotherapy resistance in advanced ovarian serous carcinomas. Thus, further studies are required to validate

  15. Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas

    International Nuclear Information System (INIS)

    Chemotherapy resistance remains a major obstacle in the treatment of women with ovarian cancer. Establishing predictive markers of chemoresponse would help to individualize therapy and improve survival of ovarian cancer patients. Chemotherapy resistance in ovarian cancer has been studied thoroughly and several non-overlapping single genes, gene profiles and copy number alterations have been suggested as potential markers. The objective of this study was to explore genetic alterations behind chemotherapy resistance in ovarian cancer with the ultimate aim to find potential predictive markers. To create the best opportunities for identifying genetic alterations of importance for resistance, we selected a homogenous tumor material concerning histology, stage and chemotherapy. Using high-resolution whole genome array comparative genomic hybridization (CGH), we analyzed the tumor genomes of 40 fresh-frozen stage III ovarian serous carcinomas, all uniformly treated with combination therapy paclitaxel/carboplatin. Fisher's exact test was used to identify significant differences. Subsequently, we examined four genes in the significant regions (EVI1, MDS1, SH3GL2, SH3KBP1) plus the ABCB1 gene with quantitative real-time polymerase chain reaction (QPCR) to evaluate the impact of DNA alterations on the transcriptional level. We identified gain in 3q26.2, and losses in 6q11.2-12, 9p22.3, 9p22.2-22.1, 9p22.1-21.3, Xp22.2-22.12, Xp22.11-11.3, and Xp11.23-11.1 to be significantly associated with chemotherapy resistance. In the gene expression analysis, EVI1 expression differed between samples with gain versus without gain, exhibiting higher expression in the gain group. In conclusion, we detected specific genetic alterations associated with resistance, of which some might be potential predictive markers of chemotherapy resistance in advanced ovarian serous carcinomas. Thus, further studies are required to validate these findings in an independent ovarian tumor series

  16. Laser-guidance based cell detection for identifying malignant cancerous cells without any fluorescent markers

    OpenAIRE

    Ma, Zhen; Gao, Bruce Z.

    2011-01-01

    Laser guidance technique employs the optical forces generated from a focused Gaussian laser beam incident on a biological cell to trap and guide the cell along the laser propagation direction. The optical force, which determines the guidance speed, is dependent on the cellular characteristics of the cell being guided, such as size, shape, composition and morphology. Different cell populations or subpopulations can be detected without any fluorescent markers by measuring their guidance speeds....

  17. Prediction of hybrid performance in maize using molecular markers and joint analyses of hybrids and parental inbreds.

    Science.gov (United States)

    Schrag, Tobias A; Möhring, Jens; Melchinger, Albrecht E; Kusterer, Barbara; Dhillon, Baldev S; Piepho, Hans-Peter; Frisch, Matthias

    2010-01-01

    The identification of superior hybrids is important for the success of a hybrid breeding program. However, field evaluation of all possible crosses among inbred lines requires extremely large resources. Therefore, efforts have been made to predict hybrid performance (HP) by using field data of related genotypes and molecular markers. In the present study, the main objective was to assess the usefulness of pedigree information in combination with the covariance between general combining ability (GCA) and per se performance of parental lines for HP prediction. In addition, we compared the prediction efficiency of AFLP and SSR marker data, estimated marker effects separately for reciprocal allelic configurations (among heterotic groups) of heterozygous marker loci in hybrids, and imputed missing AFLP marker data for marker-based HP prediction. Unbalanced field data of 400 maize dent x flint hybrids from 9 factorials and of 79 inbred parents were subjected to joint analyses with mixed linear models. The inbreds were genotyped with 910 AFLP and 256 SSR markers. Efficiency of prediction (R (2)) was estimated by cross-validation for hybrids having no or one parent evaluated in testcrosses. Best linear unbiased prediction of GCA and specific combining ability resulted in the highest efficiencies for HP prediction for both traits (R (2) = 0.6-0.9), if pedigree and line per se data were used. However, without such data, HP for grain yield was more efficiently predicted using molecular markers. The additional modifications of the marker-based approaches had no clear effect. Our study showed the high potential of joint analyses of hybrids and parental inbred lines for the prediction of performance of untested hybrids. PMID:19916002

  18. Expression Compilation of Several Putative Cancer Stem Cell Markers by Primary Ovarian Carcinoma

    OpenAIRE

    Di Jiabo; Yigit Refika; G. Figdor Carl; Duiveman-de Boer Tjitske; Massuger Leon; Torensma Ruurd

    2010-01-01

    Cancer stem cells (CSCs) or tumor initiating cells are rare cells that are able to establish a tumor or metastasis. Identification of those CSCs is, however, cumbersome even in established cell lines. Several cancer stem cell markers were reported to be expressed by ovarian cancer. Those cancer stem cells are gifted with lower vulnerability to irradiation and cytostatic drugs explaining the high incidence of recurrence after treatment. A variety of different cancer stem cell markers were desc...

  19. Plasmacytoma with aberrant expression of myeloid markers, T-cell markers, and cytokeratin

    DEFF Research Database (Denmark)

    Shin, J S; Stopyra, G A; Warhol, M J; Multhaupt, H A

    2001-01-01

    for myeloid markers such as CD13, CD33, CD38, and CD138. Significant negative markers include CD20 (L26), CD45RO (UCHL-1), and CD79alpha. The unusual phenotypic features of this plasmacytoma illustrate potential diagnostic pitfalls. It is important to fully study such lesions to correctly classify...

  20. Neurobiological markers predicting treatment response in anxiety disorders: A systematic review and implications for clinical application.

    Science.gov (United States)

    Lueken, Ulrike; Zierhut, Kathrin C; Hahn, Tim; Straube, Benjamin; Kircher, Tilo; Reif, Andreas; Richter, Jan; Hamm, Alfons; Wittchen, Hans-Ulrich; Domschke, Katharina

    2016-07-01

    Anxiety disorders constitute the largest group of mental disorders with a high individual and societal burden. Neurobiological markers of treatment response bear potential to improve response rates by informing stratified medicine approaches. A systematic review was performed on the current evidence of the predictive value of genetic, neuroimaging and other physiological markers for treatment response (pharmacological and/or psychotherapeutic treatment) in anxiety disorders. Studies published until March 2015 were selected through search in PubMed, Web of Science, PsycINFO, Embase, and CENTRAL. Sixty studies were included, among them 27 on genetic, 17 on neuroimaging and 16 on other markers. Preliminary evidence was found for the functional 5-HTTLPR/rs25531 genotypes, anterior cingulate cortex function and cardiovascular flexibility to modulate treatment outcome. Studies varied considerably in methodological quality. Application of more stringent study methodology, predictions on the individual patient level and cross-validation in independent samples are recommended to set the next stage of biomarker research and to avoid flawed conclusions in the emerging field of "Mental Health Predictomics". PMID:27168345

  1. Evaluation of Stem Cell Markers, CD44/CD24 in Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Masoud Hashemi Arabi

    2014-05-01

    Four breast cancer cell lines, MCF-7 ، T47D ، MDA-MB231 and MDA-MB468 were purchased from National cell Bank of Iran based in Iran Pasture Institute and were cultured in high glucose DMEM supplemented with 10% FCS. Cells were stained with antiCD44-PE and antiCD24-FITC antibodies and Status of CD44 and CD24 as markers of breast cancer stem cells were evaluated using flow cytometer and fluorescent microscopy.Evaluation of CD44 and CD24 as markers of breast cancer stem cells showed that MDA-MB231 with 97±1.2% CD44+/CD24-/low cells is significantly different from the others that they were mainly CD44 and CD24 positive cells(p

  2. Biological markers as predictive factors of response to neoadjuvant taxanes and anthracycline chemotherapy in breast carcinoma

    Institute of Scientific and Technical Information of China (English)

    ZHOU Bo; YANG De-qi; XIE Fei

    2008-01-01

    Background Neoadjuvant chemotherapy provides an excellent model for evaluation of potential predictive factors.The objective of this study was to evaluate the predictive value of different biological factors in breast cancer patients treated with neoadjuvant taxane and anthracycline chemotherapy.Methods One hundred and thirty-five patients treated with 4 cycles of neoadjuvant taxanes and anthracycline were included in this retrospective study.Using pretreatment biopsy materials,immunohistochemical studies were performed for estrogen receptor(ER),progesterone receptor(PgR),HER-2,Ki-67 and p53 protein expression.The associations among biological markers and clinical and pathological complete response (pCR)were analyzed.Results The overall clinical response was 86%,including 33%clinical complete response(cCR)and 53%clinical partial response.The pCR was iust 17%.In the univariate analysis,only HER-2 overexpression was predictive of cCR to neoadjuvant chemotherapy(P=0.018).No significant associations between other biological factors and cCR were found.Absence of ER,PgR expression and overexpression of HER-2 were predictive of the pCR(P=0.002,0.001,0.01,respectively).Ki-67 and p53 failed to show an association with pCR.In multivariate analysis,overexpression of HER-2remained as an independent variable in predicting the cCR(P=0.021).However,negative ER was the only parameter that maintained statistical significance in predicting the pCR(P=0.001).Conclusions Patients with overexoression of HER-2 and negative hormonal receptor status are much more likely to respond to neoadjuvant taxane and anthracycline chemotherapy than those with the opposite characte ristics.These factors could serve as predictive markers for this regimen.

  3. Serum Amyloid A as a Predictive Marker for Radiation Pneumonitis in Lung Cancer Patients

    International Nuclear Information System (INIS)

    Purpose: To investigate serum markers associated with radiation pneumonitis (RP) grade ≥3 in patients with lung cancer who were treated with radiation therapy. Methods and Materials: Pretreatment serum samples from patients with stage Ib-IV lung cancer who developed RP within 1 year after radiation therapy were analyzed to identify a proteome marker able to stratify patients prone to develop severe RP by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Dosimetric parameters and 3 biological factors were compared. Results: Serum samples from 16 patients (28%) with severe RP (grade 3-4) and 42 patients (72%) with no or mild RP (grade 0-2) were collected for analysis. All patients received a median of 54 Gy (range, 42-70 Gy) of three-dimensional conformal radiation therapy with a mean lung dose (MLD) of 1502 cGy (range, 700-2794 cGy). An m/z peak of 11,480 Da was identified by SELDI-TOF-MS, and serum amyloid A (SAA) was the primary splitter serum marker. The receiver operating characteristic area under the curve of SAA (0.94; 95% confidence interval [CI], 0.87-1.00) was higher than those of C-reactive protein (0.83; 95% CI, 0.72-0.94), interleukin-6 (0.79; 95% CI, 0.65-0.94), and MLD (0.57; 95% CI, 0.37-0.77). The best sensitivity and specificity of combined SAA and MLD for predicting RP were 88.9% and 96.0%, respectively. Conclusions: Baseline SAA could be used as an auxiliary marker for predicting severe RP. Extreme care should be taken to limit the lung irradiation dose in patients with high SAA

  4. Serum Amyloid A as a Predictive Marker for Radiation Pneumonitis in Lung Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yu-Shan [Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Department of Animal Science, National Ilan University, Ilan, Taiwan (China); Chang, Heng-Jui [Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Chang, Yue-Cune [Department of Mathematics, Tamkang University, Taipei, Taiwan (China); Huang, Su-Chen; Ko, Hui-Ling; Chang, Chih-Chia [Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Yeh, Yu-Wung; Jiang, Jiunn-Song [Department of Chest Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Lee, Cheng-Yen; Chi, Mau-Shin [Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Chi, Kwan-Hwa, E-mail: M006565@ms.skh.org.tw [Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Institute of Radiation Science and School of Medicine, National Yang-Ming University, Taipei, Taiwan (China)

    2013-03-01

    Purpose: To investigate serum markers associated with radiation pneumonitis (RP) grade ≥3 in patients with lung cancer who were treated with radiation therapy. Methods and Materials: Pretreatment serum samples from patients with stage Ib-IV lung cancer who developed RP within 1 year after radiation therapy were analyzed to identify a proteome marker able to stratify patients prone to develop severe RP by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Dosimetric parameters and 3 biological factors were compared. Results: Serum samples from 16 patients (28%) with severe RP (grade 3-4) and 42 patients (72%) with no or mild RP (grade 0-2) were collected for analysis. All patients received a median of 54 Gy (range, 42-70 Gy) of three-dimensional conformal radiation therapy with a mean lung dose (MLD) of 1502 cGy (range, 700-2794 cGy). An m/z peak of 11,480 Da was identified by SELDI-TOF-MS, and serum amyloid A (SAA) was the primary splitter serum marker. The receiver operating characteristic area under the curve of SAA (0.94; 95% confidence interval [CI], 0.87-1.00) was higher than those of C-reactive protein (0.83; 95% CI, 0.72-0.94), interleukin-6 (0.79; 95% CI, 0.65-0.94), and MLD (0.57; 95% CI, 0.37-0.77). The best sensitivity and specificity of combined SAA and MLD for predicting RP were 88.9% and 96.0%, respectively. Conclusions: Baseline SAA could be used as an auxiliary marker for predicting severe RP. Extreme care should be taken to limit the lung irradiation dose in patients with high SAA.

  5. Comparing the predictive abilities of phenotypic and marker-assisted selection methods in a biparental lettuce population

    Science.gov (United States)

    Breeding and selection for the traits with polygenic inheritance is a challenging task that can be done by phenotypic selection, by marker-assisted selection or by genome wide selection. We tested predictive ability of four selection models in a biparental population genotyped with 95 SNP markers an...

  6. Contribution to the study of markers in lungs carcinogenesis and analysis of factors predicting the benefit of chemotherapy

    International Nuclear Information System (INIS)

    A better definition of early bio markers in lung carcinogenesis should enhance the development of molecular means to perform screening, diagnostic, and chemo-prevention of patients at high risk of lung cancer. We studied epigenetic deregulation of multiple promoters (p16(INK4a), HOX A9, MAGE A 1 et MAGE B2) in sputum samples from smokers at high risk and from patients with non-small cell lung cancer (N.S.C.L.C.). This molecular test, based on easily accessible sample,s can be modulated according to the aims of the investigator (e.g. screening or confirmation of diagnosis). Secondly, we have studied two candidate proteins as predictive markers of the benefit of adjuvant chemotherapy in patients with resected lung cancer. The multivariate analysis shows that tumor expression of the catalytic sub-unit of telomerase is not able to predict survival in patients included in the lAL T study' of adjuvant chemotherapy. However, tumor expression of the DNA repair protein ERCC1 identifies a sub-group of patients (ERCC1 negative) whose chances of survival are increased by 35% by means of cisplatin-based adjuvant chemotherapy. Further, tumor ERCC1 expression has a positive prognostic value in the non-treated control group. The need for a deeper understanding in cancerology of the physiological role of the ERCC1 endonuclease is discussed in this thesis. (author)

  7. Aneuploidy involving chromosome 1 may be an early predictive marker of intestinal type gastric cancer

    International Nuclear Information System (INIS)

    Intestinal type gastric cancer is a significant cause of mortality, therefore a better understanding of its molecular basis is required. We assessed if either aneuploidy or activity of the oncogenic transcription factor nuclear factor kappa B (NF-κB), increased incrementally during pre-malignant gastric histological progression and also if they correlated with each other in patient samples, as they are both induced by oxygen free radicals. In a prospective study of 54 (aneuploidy) and 59 (NF-κB) consecutive patients, aneuploidy was assessed by interphase fluorescent in situ hybridisation (FISH) for chromosome 1. NF-κB was assessed by expression of interleukin-8 (IL-8), and in a subset, by immunohistochemistry (IHC) for active p65. Aneuploidy levels increased incrementally across the histological series. 2.76% of cells with normal histology (95% CI, 2.14-3.38%) showed background levels of aneuploidy, this increased to averages of 3.78% (95% CI, 3.21-4.35%), 5.89% (95% CI, 3.72-8.06%) and 7.29% (95% CI, 4.73-9.85%) of cells from patients with gastritis, Helicobacter pylori positive gastritis and atrophy/intestinal metaplasia (IM) respectively. IL-8 expression was only increased in patients with current H. pylori infection. NF-κB analysis showed some increased p65 activity in inflamed tissues. IL-8 expression and aneuploidy level were not linked in individual patients. Aneuploidy levels increased incrementally during histological progression; were significantly elevated at very early stages of neoplastic progression and could well be linked to cancer development and used to assess cancer risk. Reactive oxygen species (ROS) induced in early gastric cancer are presumably responsible for the stepwise accumulation of this particular mutation, i.e. aneuploidy. Hence, aneuploidy measured by fluorescent in situ hybridisation (FISH) coupled to brush cytology, would be worthy of consideration as a predictive marker in gastric cancer and could be clinically useful in pre

  8. Aneuploidy involving chromosome 1 may be an early predictive marker of intestinal type gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Williams, L. [Royal Glamorgan Hospital, Ynysmaerdy, Llantrisant CF72 8XR (United Kingdom); Somasekar, A. [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom); Neath Port Talbot Hospital, Abertawe Bro Morgannwg University NHS Trust, Baglan Way, Port Talbot SA12 7BX (United Kingdom); Davies, D.J.; Cronin, J.; Doak, S.H. [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom); Alcolado, R. [Royal Glamorgan Hospital, Ynysmaerdy, Llantrisant CF72 8XR (United Kingdom); Williams, J.G. [Neath Port Talbot Hospital, Abertawe Bro Morgannwg University NHS Trust, Baglan Way, Port Talbot SA12 7BX (United Kingdom); Griffiths, A.P. [Department of Histopathology, Morriston Hospital, Abertawe Bro Morgannwg University NHS Trust, Morriston, SA66NL (United Kingdom); Baxter, J.N. [Department of Surgery, Morriston Hospital, Abertawe Bro Morgannwg University NHS Trust, Morriston, SA66NL (United Kingdom); Jenkins, G.J.S., E-mail: g.j.jenkins@swansea.ac.uk [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom)

    2009-10-02

    Intestinal type gastric cancer is a significant cause of mortality, therefore a better understanding of its molecular basis is required. We assessed if either aneuploidy or activity of the oncogenic transcription factor nuclear factor kappa B (NF-{kappa}B), increased incrementally during pre-malignant gastric histological progression and also if they correlated with each other in patient samples, as they are both induced by oxygen free radicals. In a prospective study of 54 (aneuploidy) and 59 (NF-{kappa}B) consecutive patients, aneuploidy was assessed by interphase fluorescent in situ hybridisation (FISH) for chromosome 1. NF-{kappa}B was assessed by expression of interleukin-8 (IL-8), and in a subset, by immunohistochemistry (IHC) for active p65. Aneuploidy levels increased incrementally across the histological series. 2.76% of cells with normal histology (95% CI, 2.14-3.38%) showed background levels of aneuploidy, this increased to averages of 3.78% (95% CI, 3.21-4.35%), 5.89% (95% CI, 3.72-8.06%) and 7.29% (95% CI, 4.73-9.85%) of cells from patients with gastritis, Helicobacter pylori positive gastritis and atrophy/intestinal metaplasia (IM) respectively. IL-8 expression was only increased in patients with current H. pylori infection. NF-{kappa}B analysis showed some increased p65 activity in inflamed tissues. IL-8 expression and aneuploidy level were not linked in individual patients. Aneuploidy levels increased incrementally during histological progression; were significantly elevated at very early stages of neoplastic progression and could well be linked to cancer development and used to assess cancer risk. Reactive oxygen species (ROS) induced in early gastric cancer are presumably responsible for the stepwise accumulation of this particular mutation, i.e. aneuploidy. Hence, aneuploidy measured by fluorescent in situ hybridisation (FISH) coupled to brush cytology, would be worthy of consideration as a predictive marker in gastric cancer and could be

  9. Waterlow score as a surrogate marker for predicting adverse outcome in acute pancreatitis.

    Science.gov (United States)

    Gillick, K; Elbeltagi, H; Bhattacharya, S

    2016-01-01

    Introduction Introduced originally to stratify risk for developing decubitus ulcers, the Waterlow scoring system is recorded routinely for surgical admissions. It is a composite score, reflecting patients' general condition and co-morbidities. The aim of this study was to investigate whether the Waterlow score can be used as an independent surrogate marker to predict severity and adverse outcome in acute pancreatitis. Methods In this retrospective analysis, a consecutive cohort was studied of 250 patients presenting with acute pancreatitis, all of whom had their Waterlow score calculated on admission. Primary outcome measures were length of hospital stay and mortality. Secondary outcome measures included rate of intensive care unit (ICU) admission and development of complications such as peripancreatic free fluid, pancreatic necrosis and pseudocyst formation. Correlation of the Waterlow score with some known markers of disease severity and outcomes was also analysed. Results The Waterlow score correlated strongly with the most commonly used marker of disease severity, the Glasgow score (analysis of variance, p=0.0012). Inpatient mortality, rate of ICU admission and length of hospital stay increased with a higher Waterlow score (Mann-Whitney U test, p=0.0007, p=0.049 and p=0.0002 respectively). There was, however, no significant association between the Waterlow score and the incidence of three known complications of pancreatitis: presence of peripancreatic fluid, pancreatic pseudocyst formation and pancreatic necrosis. Receiver operating characteristic curve analysis demonstrated good predictive power of the Waterlow score for mortality (area under the curve [AUC]: 0.73), ICU admission (AUC: 0.65) and length of stay >7 days (AUC: 0.64). This is comparable with the predictive power of the Glasgow score and C-reactive protein. Conclusions The Waterlow score for patients admitted with acute pancreatitis could provide a useful tool in prospective assessment of disease

  10. Preoperative serum liver enzyme markers for predicting early recurrence after curative resection of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zhong-Xia Wang; Chun-Ping Jiang; Yin Cao; Guang Zhang; Wei-Bo Chen; Yi-Tao Ding

    2015-01-01

    BACKGROUND:Early recurrence of hepatocellular carcinoma (HCC) is associated with worse prognosis after liver resection. This study aimed to investigate the prognostic value of com-mon liver enzyme markers in HCC early recurrence after cu-rative hepatectomy and to establish a simple predictive model for HCC early recurrence. METHODS:A total of 200 patients who had undergone curative resection for HCC were retrospectively analyzed. The patients were divided into early recurrence (within 2 years) and non-early recurrence groups. Demographical characteristics, preopera-tive liver function parameters, surgical factors and tumor related factors of the patients were assessed by univariate analysis to identify potential signiifcant predictors for early recurrence after resection of HCC. Parameters with statisti-cal signiifcance were entered into a Cox proportional hazard model to ifnd independent risk factors. Receiver operating characteristic analysis was done to determine optimal cut-off values and the number of combined factors in multi-factor predictive model. RESULTS:Of 13 potential risk factors for early recurrence identiifed by univariate analysis, high lactate dehydrogenase (LDH>206 U/L, HR=1.711,P=0.006), high aspartate amino-transferase (AST)/alanine aminotransferase (ALT) ratio (AST/ALT>0.96, HR=1.769,P=0.006), elevated alpha-fetoprotein (AFP>8.6 ng/mL, HR=2.079,P=0.007), small resection margin (≤1 cm, HR=2.354,P CONCLUSIONS:Preoperative common liver enzyme markers, LDH and AST/ALT ratio, were independently associated with early recurrence of HCC. The combination of serum liver en-zyme markers with AFP, resection margin and TNM stage bet-ter predicted early recurrence of HCC after curative resection in a simple multi-factor model.

  11. Association Between Serum C- Reactive Protein Levels and Other Important Predictive Markers of Outcome in COPD

    Directory of Open Access Journals (Sweden)

    Mohammad Shameem

    2011-01-01

    Full Text Available C-reactive protein (CRP is an acute-phase protein synthesized predominantly by the hepatocytes in response to tissue damage or inflammation. Levels of acute-phase proteins rise rapidly, during infection and after injury. We take up the study to correlate serum CRP levels with other important predictive markers of outcome in COPD. Patient with stable COPD (no exacerbation in the last two months were taken up for the study. Parameters taken to correlate were age, grade of dyspnea, FEV1. It was found the CRP is negatively correlated with FEV1 and grade of dyspnea but not correlated with age.

  12. Molecular markers in prostate cancer.Part I:predicting lethality

    Institute of Scientific and Technical Information of China (English)

    Sachin Agrawal; William D.Dunsmuir

    2009-01-01

    Assessing the lethality of 'early,' potentially organ-confined prostate cancer (PCa) is one of the central controversies in moderu-day urological clinical practice.Such cases are often considered for radical 'curative' treatment,although active surveillance may be equally appropriate for many men.Moreover,the balance between judicious intervention and overtreatment can be difficult to judge.The patient's age,comorbidities,family history and philosophy of self-health care can be weighed against clinical features such as the palpability of disease,the number and percentage of biopsy cores involved with the disease,histological grade,presenting prostate-specific antigen (PSA) and possible previous PSA kinetics.For many years,scientists and physicians have sought additional molecular factors that may be predictive for disease stage,progression and lethality.Usually,claims for a 'new' unique marker fall short of true clinical value.More often than not,such molecular markers are useful only in multivariate models.This review summarizes relevant molecular markers and models reported up to and including 2008.

  13. Clusters of conserved beta cell marker genes for assessment of beta cell phenotype.

    Directory of Open Access Journals (Sweden)

    Geert A Martens

    Full Text Available BACKGROUND AND METHODOLOGY: The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators. PRINCIPAL FINDINGS: A panel of 332 conserved beta cell biomarker genes was found to discriminate both isolated and laser capture microdissected beta cells from all other examined cell types. Of all conserved beta cell-markers, 15% were strongly beta cell-selective and functionally associated to hormone processing, 15% were shared with neuronal cells and associated to regulated synaptic vesicle transport and 30% with immune plus gut mucosal tissues reflecting active protein synthesis. Fasting specifically down-regulated the latter cluster, but preserved the neuronal and strongly beta cell-selective traits, indicating preserved differentiated state. Analysis of consensus binding site enrichment indicated major roles of CREB/ATF and various nutrient- or redox-regulated transcription factors in maintenance of differentiated beta cell phenotype. CONCLUSIONS: Conserved beta cell marker genes contain major gene clusters defined by their beta cell selectivity or by their additional abundance in either neural cells or in immune plus gut mucosal cells. This panel can be used as a template to identify changes in the differentiated state of beta cells.

  14. A generalized model for multi-marker analysis of cell cycle progression in synchrony experiments

    OpenAIRE

    Mayhew, Michael B.; Joshua W. Robinson; Jung, Boyoun; Haase, Steven B.; Alexander J Hartemink

    2011-01-01

    Motivation: To advance understanding of eukaryotic cell division, it is important to observe the process precisely. To this end, researchers monitor changes in dividing cells as they traverse the cell cycle, with the presence or absence of morphological or genetic markers indicating a cell's position in a particular interval of the cell cycle. A wide variety of marker data is available, including information-rich cellular imaging data. However, few formal statistical methods have been develop...

  15. Convoluted cells as a marker for maternal cell contamination in CVS cultures

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Jensen, P K; Therkelsen, A J

    1987-01-01

    In order to identify cells of maternal origin in CVS cultures, tissue from 1st trimester abortions were cultivated and the cultures stained in situ for X-chromatin. Convoluted cells and maternal fibroblasts were found to be positive. By chromosome analysis of cultures from 105 diagnostic placenta...... biopsies, obtained by the transabdominal route, metaphases of maternal origin were found in nine cases. In eight of these cases colonies of convoluted cells were observed. We conclude that convoluted cells are of maternal origin and are a reliable marker for maternal cell contamination in CVS cultures....

  16. Mesenchymal markers on human adipose stem/progenitor cells

    Science.gov (United States)

    Zimmerlin, Ludovic; Donnenberg, Vera S.; Rubin, J. Peter; Donnenberg, Albert D.

    2014-01-01

    The stromal-vascular fraction (SVF) of adipose tissue is a rich source of multipotent stem cells. We and others have described 3 major populations of stem/progenitor cells in this fraction, all closely associated with small blood vessels: endothelial progenitor cells (EPC, CD45−/CD31+/CD34+), pericytes (CD45−/CD31−/CD146+) and supra-adventitial adipose stromal cells (SA-ASC, CD45−/CD31−/CD146−/CD34+). EPC are luminal, pericytes are adventitial and SA-ASC surround the vessel like a sheath. The multipotency of the pericytes and SA-ASC compartments is strikingly similar to that of CD45−/CD34−/CD73+/CD105+/CD90+ bone marrow-derived mesenchymal stem cells (BM-MSC). Here we determine the extent to which this mesenchymal expression pattern is expressed on the 3 adipose stem/progenitor populations. Eight independent adipose tissue samples were analyzed in a single tube (CD105-FITC/CD73-PE/CD146-PETXR/CD14-PECY5/CD33-PECY5/CD235A-PECY5/CD31-PECY7/CD90-APC/CD34-A700/CD45-APCCY7/DAPI). Adipose EPC were highly proliferative with 14.3±2.8% (mean ± SEM) having >2N DNA. About half (53.1±7.6%) coexpressed CD73 and CD105, and 71.9±7.4% expressed CD90. Pericytes were less proliferative (8.2±3.4% >2N DNA) with a smaller proportion (29.6±6.9% CD73+/CD105+, 60.5±10.2% CD90+) expressing mesenchymal associated markers. However, the CD34+ subset of CD146+ pericytes, were both highly proliferative (15.1±3.6% with >2N DNA) and of uniform mesenchymal phenotype (93.3±3.7% CD73+/CD105+, 97.8±0.7% CD90+), suggesting transit amplifying progenitor cells. SA-ASC were the least proliferative (3.7 ± 0.8%>2N DNA) but were also highly mesenchymal in phenotype (94.4±3.2% CD73+/CD105+, 95.5±1.2% CD90+). These data imply a progenitor/progeny relationship between pericytes and SA-ASC, the most mesenchymal of SVF cells. Despite phenotypic and functional similarities to BM-MSC, SA-ASC are distinguished by CD34 expression. PMID:23184564

  17. The A3 adenosine receptor (A3AR): therapeutic target and predictive biological marker in rheumatoid arthritis.

    Science.gov (United States)

    Fishman, Pnina; Cohen, Shira

    2016-09-01

    The Gi protein-associated A3 adenosine receptor (A3AR) is over-expressed in inflammatory cells, and this high expression is also reflected in the peripheral blood mononuclear cells of patients with autoimmune inflammatory diseases such as rheumatoid arthritis, psoriasis, and Crohn's disease. CF101, a selective agonist with high affinity to the A3AR, is known to induce robust anti-inflammatory effect in experimental animal models of adjuvant-, collagen-, and tropomyosin-induced arthritis. The effect is mediated via a definitive molecular mechanism entailing deregulation of the nuclear factor-κB (NF-κB) and the Wnt signal transduction pathways resulting in apoptosis of inflammatory cells. CF101 was found to be safe and well tolerated in all preclinical, phase I, and phase II human clinical studies. In two phase II clinical studies where CF101 was administered to rheumatoid arthritis (RA) patients as a stand-alone drug, a significant anti-rheumatic effect and a direct significant correlation were found between receptor expression at baseline and patients' response to the drug, suggesting that A3AR may be utilized as a predictive biomarker. The A3AR is a promising therapeutic target in rheumatoid arthritis and can be used also as a biological marker to predict patients' response to CF101. This is a unique type of a personalized medicine approach which may pave the way for a safe and efficacious treatment for this patient population. PMID:26886128

  18. Differentiation factors that influence neuronal markers expression in vitro from human amniotic epithelial cells

    Directory of Open Access Journals (Sweden)

    H Niknejad

    2010-01-01

    Full Text Available The differentiation of neural cells from embryonic stem cells is influenced by several growth factors. Amniotic epithelial cells (AECs share many of the same characteristics as embryonic stem cells, and therefore those factors may similarly affect the derivation of neural cells from AECs. In this study, we examined the differentiation of neural cells in vitro from AECs following AECs treatment with retinoic acid (RA, basic fibroblast growth factor (bFGF as well as investigation of bFGF withdrawal on neuronal differentiation. We also studied whether blocking bone morphogenetic protein (BMP signaling using its antagonist, noggin, affects the derivation of neuronal cells from AECs. The effects of serum on the rate of neural markers expression were also examined. Analysis of AECs derived neurons was performed at some neural markers expression level by immunocytochemistry. All cultures treated with noggin showed the higher levels of neural markers expression than noggin free cultures. Combined treatment with bFGF and RA showed the highest level of neural markers in all treatment groups with or without noggin. bFGF withdrawal did not promote expression of neural markers, while its maintenance increased the expression of these markers. Serum-free condition decreased the viability of cells but increased the rate of neural markers expression. These results show the capability of AECs to express neural cell markers and this ability is affected by some factors including serum, noggin, bFGF and RA.

  19. Molecular Markers Predict Distant Metastases After Adjuvant Chemoradiation for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jun Won; Kim, Yong Bae [Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Choi, Jun Jeong [Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Koom, Woong Sub [Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Hoguen [Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Nam-Kyu [Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Ahn, Joong Bae [Department of Medical Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Ikjae; Cho, Jae Ho [Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Keum, Ki Chang, E-mail: kckeum@yuhs.ac [Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-12-01

    Purpose: The outcomes of adjuvant chemoradiation for locally advanced rectal cancer are nonuniform among patients with matching prognostic factors. We explored the role of molecular markers for predicting the outcome of adjuvant chemoradiation for rectal cancer patients. Methods and Materials: The study included 68 patients with stages II to III rectal adenocarcinoma who were treated with total mesorectal excision and adjuvant chemoradiation. Chemotherapy based on 5-fluorouracil and leucovorin was intravenously administered each month for 6-12 cycles. Radiation therapy consisted of 54 Gy delivered in 30 fractions. Immunostaining of surgical specimens for COX-2, EGFR, VEGF, thymidine synthase (TS), and Raf kinase inhibitor protein (RKIP) was performed. Results: The median follow-up was 65 months. Eight locoregional (11.8%) and 13 distant (19.1%) recurrences occurred. Five-year locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates for all patients were 83.9%, 78.7%, 66.7%, and 73.8%, respectively. LRFFS was not correlated with TNM stage, surgical margin, or any of the molecular markers. VEGF overexpression was significantly correlated with decreased DMFS (P=.045), while RKIP-positive results were correlated with increased DMFS (P=.025). In multivariate analyses, positive findings for COX-2 (COX-2+) and VEGF (VEGF+) and negative findings for RKIP (RKIP-) were independent prognostic factors for DMFS, DFS, and OS (P=.035, .014, and .007 for DMFS; .021, .010, and <.0001 for DFS; and .004, .012, and .001 for OS). The combination of both COX-2+ and VEGF+ (COX-2+/VEGF+) showed a strong correlation with decreased DFS (P=.007), and the combinations of RKIP+/COX-2- and RKIP+/VEGF- showed strong correlations with improved DFS compared with the rest of the patients (P=.001 and <.0001, respectively). Conclusions: Molecular markers can be valuable in predicting treatment outcome of adjuvant

  20. Prediction of body mass index in mice using dense molecular markers and a regularized neural network.

    Science.gov (United States)

    Okut, Hayrettin; Gianola, Daniel; Rosa, Guilherme J M; Weigel, Kent A

    2011-06-01

    Bayesian regularization of artificial neural networks (BRANNs) were used to predict body mass index (BMI) in mice using single nucleotide polymorphism (SNP) markers. Data from 1896 animals with both phenotypic and genotypic (12 320 loci) information were used for the analysis. Missing genotypes were imputed based on estimated allelic frequencies, with no attempt to reconstruct haplotypes based on family information or linkage disequilibrium between markers. A feed-forward multilayer perceptron network consisting of a single output layer and one hidden layer was used. Training of the neural network was done using the Bayesian regularized backpropagation algorithm. When the number of neurons in the hidden layer was increased, the number of effective parameters, γ, increased up to a point and stabilized thereafter. A model with five neurons in the hidden layer produced a value of γ that saturated the data. In terms of predictive ability, a network with five neurons in the hidden layer attained the smallest error and highest correlation in the test data although differences among networks were negligible. Using inherent weight information of BRANN with different number of neurons in the hidden layer, it was observed that 17 SNPs had a larger impact on the network, indicating their possible relevance in prediction of BMI. It is concluded that BRANN may be at least as useful as other methods for high-dimensional genome-enabled prediction, with the advantage of its potential ability of capturing non-linear relationships, which may be useful in the study of quantitative traits under complex gene action. PMID:21481292

  1. Can Preterm Labour Be Predicted in Low Risk Pregnancies? Role of Clinical, Sonographic, and Biochemical Markers

    Directory of Open Access Journals (Sweden)

    Reva Tripathi

    2014-01-01

    Full Text Available Background and Objectives. This is a prospective nested cohort study conducted over a period of 3 years. 2644 women were recruited, out of which final analysis was done for 1884 women. Methods. Cervicovaginal and blood samples were collected for all recruited women. Out of these, 137 women who delivered before 35 weeks were treated as cases and equal number of matched controls were chosen. Analysis of samples for serum G-CSF, AFP, ferritin, and cervicovaginal interleukin-6 and IGFBP-1 was done. Results. Poor orodental hygiene, which can be a social marker, was significantly more common in women who delivered preterm (P=0.008. Serum alkaline phosphatase and serum ferritin were found to be significantly associated with preterm deliveries. The 90th percentile value of these parameters was considered as cut-off as there is no specific cut-off. Conclusions. Our study did not prove usefulness of any predictive marker. Serum ferritin and alkaline phosphatase were found to have correlation but their values are affected in many conditions and need to be elucidated with caution. Larger studies are needed for predicting preterm labour in asymptomatic women.

  2. Establishing quiescence in human bone marrow stem cells leads to enhanced osteoblast marker expression

    DEFF Research Database (Denmark)

    Harkness, Linda; Rumman, Mohammad; Kassem, Moustapha;

    expression profiling of the cells demonstrated down-regulation of cyclin (CCNA2, CCND1, CCNE1, CCNB1) and proliferation markers (Ki67) markers during G0 and up-regulation of the osteogenic genes RUNX2 and OPN. RT-PCR analysis of osteogenic differentiation of cells post G0 demonstrated an increase...

  3. A new insight into cancer stem cell markers: Could local and circulating cancer stem cell markers correlate in colorectal cancer?

    Science.gov (United States)

    Mirzaei, Alireza; Tavoosidana, Gholamreza; Rad, Afshin Abdi; Rezaei, Farhad; Tavakoli-Yaraki, Masoumeh; Kadijani, Azade Amini; Khalili, Ehsan; Madjd, Zahra

    2016-02-01

    Cancer stem cell (CSC) markers could serve as potential prognostic procedure. This study is aimed to investigate the local expression of doublecortin-like kinase 1 (DCLK1) and Lgr5 in colorectal cancer tissues (CRC) at both protein and messenger RNA (mRNA) level, followed by providing a comparison of the local and circulating expression pattern of these markers, based on our present and previous study. The mRNA expression level of DCLK1 and Lgr5 was evaluated using comparative real-time PCR method applying 58 fresh tumor tissues and their correspondent normal margins. Immunohistochemistry was applied to analyze the protein expression level of DCLK1 and Lgr5 in paraffin-embedded CRC tissues. The correlation of DCLK1 and Lgr5 expression pattern with clinicopathological characteristics was assessed. A higher mRNA expression level of DCLK1 (3.28-fold change, p < 0.001) and Lgr5 (2.29-fold change, p < 0.001) was observed in CRC fresh tissues compared to the normal adjacent margins, and the expression level was higher in patients with higher grade and stages of disease and patients who underwent neoadjuvant chemoradiotherapy (CRT). The protein expression level of DCLK1 and Lgr5 was also increased significantly in tumor tissues compared to normal colon tissues which were positively correlated to tumor stage and grade and neoadjuvant CRT. Taken together, the results of protein analysis were in accordance with mRNA assessment. The local expression pattern of DCLK1 and Lgr5 was also in accordance with their expression level in circulation. However, some minor inconsistencies were observed which may be attributed to several factors including the possible effect of CRT on CSC reprogramming. PMID:26383518

  4. Sunitinib treatment for patients with clear-cell metastatic renal cell carcinoma: clinical outcomes and plasma angiogenesis markers

    International Nuclear Information System (INIS)

    Sunitinib is a protein tyrosine kinase-inhibitor targeting VEGFR, c-kit and PDGFR. It has been approved for the treatment of metastatic renal-cell carcinoma and gastrointestinal stromal tumors. Although it has been shown to prolong disease-free and overall survival in renal-cell carcinoma patients, only 70% of the treated population receive a clinical benefit (CB) from the treatment. Markers that could predict clinical benefit to sunitinib would be an important aid in monitoring and following their treatment. We assessed the outcome and plasma proangiogenic factors in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib in our institution. We have treated 42 patients with metastatic clear-cell renal carcinoma with sunitinib. Plasma concentrations of VEGF-A, sVEGFR2 and PDGF were determined by ELISA. At the time of analysis 39 patients were evaluable for response and 30 patients had obtained a clinical benefit (CB). Median progression-free survival was 268 days (8.93 months) and median overall survival was 487 days (16.23 months). Interestingly, disease stabilization or objective response resulted in comparable overall survival. Most treatment-related adverse events were of mild-to-moderate intensity with one treatment-related death. Plasma sVEGFR2 and PDGF levels had no predictive value. Fold-increase in plasma VEGF was significantly lower in patients that obtained a CB as compared to patients that progressed after two cycles of treatment. Plasma VEGF did not increase in patients with initial CB at the time of progression. Sunitinib showed substantial activity in mRCC. Disease stabilization or objective response resulted in comparable overall survival and both outcomes should be considered positive. Fold-increase in plasma VEGF predicts for CB and could be a candidate marker. Progression after initial CB is not associated with elevated plasma VEGF, implying a different mechanism of resistance

  5. Molecular marker-based prediction of hybrid performance in maize using unbalanced data from multiple experiments with factorial crosses.

    Science.gov (United States)

    Schrag, Tobias A; Möhring, Jens; Maurer, Hans Peter; Dhillon, Baldev S; Melchinger, Albrecht E; Piepho, Hans-Peter; Sørensen, Anker P; Frisch, Matthias

    2009-02-01

    In hybrid breeding, the prediction of hybrid performance (HP) is extremely important as it is difficult to evaluate inbred lines in numerous cross combinations. Recent developments such as doubled haploid production and molecular marker technologies have enhanced the prospects of marker-based HP prediction to accelerate the breeding process. Our objectives were to (1) predict HP using a combined analysis of hybrids and parental lines from a breeding program, (2) evaluate the use of molecular markers in addition to phenotypic and pedigree data, (3) evaluate the combination of line per se data with marker-based estimates, (4) study the effect of the number of tested parents, and (5) assess the advantage of haplotype blocks. An unbalanced dataset of 400 hybrids from 9 factorial crosses tested in different experiments and data of 79 inbred parents were subjected to combined analyses with a mixed linear model. Marker data of the inbreds were obtained with 20 AFLP primer-enzyme combinations. Cross-validation was used to assess the performance prediction of hybrids of which no or only one parental line was testcross evaluated. For HP prediction, the highest proportion of explained variance (R (2)), 46% for grain yield (GY) and 70% for grain dry matter content (GDMC), was obtained from line per se best linear unbiased prediction (BLUP) estimates plus marker effects associated with mid-parent heterosis (TEAM-LM). Our study demonstrated that HP was efficiently predicted using molecular markers even for GY when testcross data of both parents are not available. This can help in improving greatly the efficiency of commercial hybrid breeding programs. PMID:19048224

  6. Proliferating cell nuclear antigen: a marker for hepatocellular proliferation in rodents.

    OpenAIRE

    Eldrige, S R; Butterworth, B E; Goldsworthy, T L

    1993-01-01

    Two different markers for quantitating cell proliferation were evaluated in livers of control and chemically treated mice and rats. Proliferating cell nuclear antigen (PCNA), an endogenous cell replication marker, and bromodeoxyuridine (BrdU), an exogenously administered DNA precursor label, were detected in formalin-fixed, paraffin-embedded tissues using immunohistochemical techniques. The percentage of cells in S phase (labeling indexes, LI) evaluated as PCNA- or BrdU-positive hepatocellula...

  7. Simple blood tests as predictive markers of disease severity and clinical condition in patients with venous insufficiency.

    Science.gov (United States)

    Karahan, Oguz; Yavuz, Celal; Kankilic, Nazim; Demirtas, Sinan; Tezcan, Orhan; Caliskan, Ahmet; Mavitas, Binali

    2016-09-01

    Chronic venous insufficiency (CVI) is a progressive inflammatory disease. Because of its inflammatory nature, several circulating markers were investigated for predicting disease progression. We aimed to investigate simple inflammatory blood markers as predictors of clinical class and disease severity in patients with CVI. Eighty patients with CVI were divided into three groups according to clinical class (grade 1, 2 and 3) and score of disease severity (mild, moderate and severe). The basic inflammatory blood markers [neutrophil, lymphocyte, mean platelet volume (MPV), white blood cell (WBC), platelet, albumin, D-dimer, fibrinogen, fibrinogen to albumin ratio, and neutrophil to lymphocyte ratio] were investigated in each group. Serum neutrophil, lymphocyte, MPV, platelet count, D-dimer and neutrophil to lymphocyte ratio levels were similar among the groups (P > 0.05). Although the serum WBC levels were significant in the clinical severity groups (P < 0.05), it was useless to separate each severity class. However, albumin, fibrinogen and the fibrinogen to albumin ratio were significant predictors of clinical class and disease severity. Especially, the fibrinogen to albumin ratio was detected as an independent indicator for a clinical class and disease severity with high sensitivity and specificity (75% sensitivity and 87.5% specificity for clinical class and 90% sensitivity and 88.3% specificity for disease severity). Serum fibrinogen and albumin levels can be useful parameters to determine clinical class and disease severity in patients with CVI. Moreover, the fibrinogen to albumin ratio is a more sensitive and specific predictor of the progression of CVI. PMID:26650463

  8. Multiple Lineages of Human Breast Cancer Stem/Progenitor Cells Identified by Profiling with Stem Cell Markers

    OpenAIRE

    Hwang-Verslues, Wendy W.; Wen-Hung Kuo; Po-Hao Chang; Chi-Chun Pan; Hsing-Hui Wang; Sheng-Ta Tsai; Yung-Ming Jeng; Jin-Yu Shew; Kung, John T.; Chung-Hsuan Chen; Lee, Eva Y-H. P.; King-Jen Chang; Wen-Hwa Lee

    2009-01-01

    Heterogeneity of cancer stem/progenitor cells that give rise to different forms of cancer has been well demonstrated for leukemia. However, this fundamental concept has yet to be established for solid tumors including breast cancer. In this communication, we analyzed solid tumor cancer stem cell markers in human breast cancer cell lines and primary specimens using flow cytometry. The stem/progenitor cell properties of different marker expressing-cell populations were further assessed by in vi...

  9. Cell adhesion molecules and hyaluronic acid as markers of inflammation, fibrosis and response to antiviral therapy in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Esther Granot

    2001-01-01

    Full Text Available Objective: Cell adhesion molecules (intracellular adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 (VCAM-1 and hyaluronic acid, markers of inflammation and fibrosis were monitored in hepatitis C patients to determine whether changes in plasma levels, during antiviral treatment, can predict long-term response to therapy.

  10. Merging person-specific bio-markers for predicting oral cancer recurrence through an ontology.

    Science.gov (United States)

    Salvi, Dario; Picone, Marco; Arredondo, María Teresa; Cabrera-Umpierrez, María Fernanda; Esteban, Ángel; Steger, Sebastian; Poli, Tito

    2013-01-01

    One of the major problems related to cancer treatment is its recurrence. Without knowing in advance how likely the cancer will relapse, clinical practice usually recommends adjuvant treatments that have strong side effects. A way to optimize treatments is to predict the recurrence probability by analyzing a set of bio-markers. The NeoMark European project has identified a set of preliminary bio-markers for the case of oral cancer by collecting a large series of data from genomic, imaging, and clinical evidence. This heterogeneous set of data needs a proper representation in order to be stored, computed, and communicated efficiently. Ontologies are often considered the proper mean to integrate biomedical data, for their high level of formality and for the need of interoperable, universally accepted models. This paper presents the NeoMark system and how an ontology has been designed to integrate all its heterogeneous data. The system has been validated in a pilot in which data will populate the ontology and will be made public for further research. PMID:22955869

  11. Predictive Role of Serum Tumor Markers in Diagnosis of Pulmonary Tuberculosis

    Science.gov (United States)

    MA, Jingjing; XIA, Dan; HU, Jing; FU, Rui; XU, Lijun; ZHANG, Ying; ZHANG, Mengying; LI, Benhe; YANG, Jianghua; WEN, Yufeng

    2016-01-01

    Background: The diagnosis of pulmonary tuberculosis (PTB) is complicated and time-consuming currently. There was association of PTB with serum tumor markers. In this study we aimed to evaluate the predictive role of serum CA125, CA199 and CEA as diagnostic tools for PTB. Methods: This study was designed as a case-control study with 565 subjects who visited the Yijishan Hospital from Jun to Dec in 2014.This case-control study matched as for age and sex with 113 cases and 452 controls. Serum CA125, CA199 and CEA levels were detected by electrochemiluminescence instrument. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value on PTB. Results: Serum levels of CA125, CA199 and CEA in PTB patients were significantly higher than those in control group (P<0.001). There was no significantly different of three tumor markers between initial treatment group and retreatment group. The logistic regression analysis showed that CA125 was an impact factor to PTB. The ROC analysis revealed that AUC of CA125 was 0.966 (95%CI: 0.951–0.981), the sensitivity, specificity in serum and cut-off were 95.6%, 85.0% and 10.30 U/ml, respectively. Conclusion: The serum CA125 has potential good diagnostic performance for PTB. PMID:27252912

  12. Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes

    International Nuclear Information System (INIS)

    The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers

  13. Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Aires, M.B. [Departamento de Morfologia, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Santos, J.R.A. [Departamento de Enfermagem, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Souza, K.S.; Farias, P.S. [Departamento de Morfologia, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Santos, A.C.V. [Departamento de Enfermagem, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Fioretto, E.T. [Departamento de Morfologia, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Maria, D.A. [Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo, SP (Brazil)

    2015-07-10

    The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers.

  14. Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes

    Directory of Open Access Journals (Sweden)

    M.B. Aires

    2015-08-01

    Full Text Available The function of the visceral yolk sac (VYS is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g with induced diabetes (alloxan, 37 mg/kg on the 8th gestational day (gd 8. At gd 15, rats from control (n=5 and diabetic (n=5 groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05, CCR2 (P<0.001, and OCT3/4 (P<0.01, and significantly increased expression of CD90 (P<0.05, CD117 (P<0.01, and CD14 (P<0.05 were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers.

  15. Multiple lineages of human breast cancer stem/progenitor cells identified by profiling with stem cell markers.

    Directory of Open Access Journals (Sweden)

    Wendy W Hwang-Verslues

    Full Text Available Heterogeneity of cancer stem/progenitor cells that give rise to different forms of cancer has been well demonstrated for leukemia. However, this fundamental concept has yet to be established for solid tumors including breast cancer. In this communication, we analyzed solid tumor cancer stem cell markers in human breast cancer cell lines and primary specimens using flow cytometry. The stem/progenitor cell properties of different marker expressing-cell populations were further assessed by in vitro soft agar colony formation assay and the ability to form tumors in NOD/SCID mice. We found that the expression of stem cell markers varied greatly among breast cancer cell lines. In MDA-MB-231 cells, PROCR and ESA, instead of the widely used breast cancer stem cell markers CD44(+/CD24(-/low and ALDH, could be used to highly enrich cancer stem/progenitor cell populations which exhibited the ability to self renew and divide asymmetrically. Furthermore, the PROCR(+/ESA(+ cells expressed epithelial-mesenchymal transition markers. PROCR could also be used to enrich cells with colony forming ability from MB-361 cells. Moreover, consistent with the marker profiling using cell lines, the expression of stem cell markers differed greatly among primary tumors. There was an association between metastasis status and a high prevalence of certain markers including CD44(+/CD24(-/low, ESA(+, CD133(+, CXCR4(+ and PROCR(+ in primary tumor cells. Taken together, these results suggest that similar to leukemia, several stem/progenitor cell-like subpopulations can exist in breast cancer.

  16. Simultaneous detection of mRNA and protein stem cell markers in live cells

    Directory of Open Access Journals (Sweden)

    Bao Gang

    2009-04-01

    Full Text Available Abstract Background Biological studies and medical application of stem cells often require the isolation of stem cells from a mixed cell population, including the detection of cancer stem cells in tumor tissue, and isolation of induced pluripotent stem cells after eliciting the expression of specific genes in adult cells. Here we report the detection of Oct-4 mRNA and SSEA-1 protein in live carcinoma stem cells using respectively molecular beacon and dye-labeled antibody, aiming to establish a new method for stem cells detection and isolation. Results Quantification of Oct-4 mRNA and protein in P19 mouse carcinoma stem cells using respectively RT-PCR and immunocytochemistry confirmed that their levels drastically decreased after differentiation. To visualize Oct-4 mRNA in live stem cells, molecular beacons were designed, synthesized and validated, and the detection specificity was confirmed using control studies. We found that the fluorescence signal from Oct-4-targeting molecular beacons provides a clear discrimination between undifferentiated and retinoic acid-induced differentiated cells. Using deconvolution fluorescence microscopy, Oct-4 mRNAs were found to reside on one side of the cytosol. We demonstrated that, using a combination of Oct-4 mRNA-targeting molecular beacon with SSEA-1 antibody in flow cytometric analysis, undifferentiated stem cells can be clearly distinguished from differentiated cells. We revealed that Oct-4 targeting molecular beacons do not seem to affect stem cell biology. Conclusion Molecular beacons have the potential to provide a powerful tool for highly specific detection and isolation of stem cells, including cancer stem cells and induced pluripotent stem (iPS cells without disturbing cell physiology. It is advantageous to perform simultaneous detection of intracellular (mRNA and cell-surface (protein stem cell markers in flow cytometric analysis, which may lead to high detection sensitivity and efficiency.

  17. Characterization of cell subpopulations expressing progenitor cell markers in porcine cardiac valves.

    Directory of Open Access Journals (Sweden)

    Huan Wang

    Full Text Available Valvular interstitial cells (VICs are the main population of cells found in cardiac valves. These resident fibroblastic cells play important roles in maintaining proper valve function, and their dysregulation has been linked to disease progression in humans. Despite the critical functions of VICs, their cellular composition is still not well defined for humans and other mammals. Given the limited availability of healthy human valves and the similarity in valve structure and function between humans and pigs, we characterized porcine VICs (pVICs based on expression of cell surface proteins and sorted a specific subpopulation of pVICs to study its functions. We found that small percentages of pVICs express the progenitor cell markers ABCG2 (~5%, NG2 (~5% or SSEA-4 (~7%, whereas another subpopulation (~5% expresses OB-CDH, a type of cadherin expressed by myofibroblasts or osteo-progenitors. pVICs isolated from either aortic or pulmonary valves express most of these protein markers at similar levels. Interestingly, OB-CDH, NG2 and SSEA-4 all label distinct valvular subpopulations relative to each other; however, NG2 and ABCG2 are co-expressed in the same cells. ABCG2(+ cells were further characterized and found to deposit more calcified matrix than ABCG2(- cells upon osteogenic induction, suggesting that they may be involved in the development of osteogenic VICs during valve pathology. Cell profiling based on flow cytometry and functional studies with sorted primary cells provide not only new and quantitative information about the cellular composition of porcine cardiac valves, but also contribute to our understanding of how a subpopulation of valvular cells (ABCG2(+ cells may participate in tissue repair and disease progression.

  18. Predicted solar cell edge radiation effects

    International Nuclear Information System (INIS)

    The Advanced Solar Cell Orbital Test (ASCOT) will test six types of solar cells in a high energy proton environment. During the design of the experiment a question was raised about the effects of proton radiation incident on the edge of the solar cells and whether edge radiation shielding was required. Historical geosynchronous data indicated that edge radiation damage is not detectable over the normal end of life solar cell degradation; however because the ASCOT radiation environment has a much higher and more energetic fluence of protons, considerably more edge damage is expected. A computer analysis of the problem was made by modeling the expected radiation damage at the cell edge and using a network model of small interconnected solar cells to predict degradation in the cell's electrical output. The model indicated that the deepest penetration of edge radiation was at the top of the cell near the junction where the protons have access to the cell through the low density cell/cover adhesive layer. The network model indicated that the cells could tolerate high fluences at their edge as long as there was high electrical resistance between the edge radiated region and the contact system on top of the cell. The predicted edge radiation related loss was less than 2% of maximum power for GaAs/Ge solar cells. As a result, no edge radiation protection was used for ASCOT

  19. Uroplakins, specific membrane proteins of urothelial umbrella cells, as histological markers of metastatic transitional cell carcinomas.

    OpenAIRE

    Moll, R.; Wu, X. R.; Lin, J.H.; Sun, T. T.

    1995-01-01

    Uroplakins (UPs) Ia, Ib, II, and III, transmembrane proteins constituting the asymmetrical unit membrane of urothelial umbrella cells, are the first specific urothelial differentiation markers described. We investigated the presence and localization patterns of UPs in various human carcinomas by applying immunohistochemistry (avidin-biotin-peroxidase complex method), using rabbit antibodies against UPs II and III, to paraffin sections. Positive reactions for UP III (sometimes very focal) were...

  20. A bayesian mixed regression based prediction of quantitative traits from molecular marker and gene expression data.

    Directory of Open Access Journals (Sweden)

    Madhuchhanda Bhattacharjee

    Full Text Available Both molecular marker and gene expression data were considered alone as well as jointly to serve as additive predictors for two pathogen-activity-phenotypes in real recombinant inbred lines of soybean. For unobserved phenotype prediction, we used a bayesian hierarchical regression modeling, where the number of possible predictors in the model was controlled by different selection strategies tested. Our initial findings were submitted for DREAM5 (the 5th Dialogue on Reverse Engineering Assessment and Methods challenge and were judged to be the best in sub-challenge B3 wherein both functional genomic and genetic data were used to predict the phenotypes. In this work we further improve upon this previous work by considering various predictor selection strategies and cross-validation was used to measure accuracy of in-data and out-data predictions. The results from various model choices indicate that for this data use of both data types (namely functional genomic and genetic simultaneously improves out-data prediction accuracy. Adequate goodness-of-fit can be easily achieved with more complex models for both phenotypes, since the number of potential predictors is large and the sample size is not small. We also further studied gene-set enrichment (for continuous phenotype in the biological process in question and chromosomal enrichment of the gene set. The methodological contribution of this paper is in exploration of variable selection techniques to alleviate the problem of over-fitting. Different strategies based on the nature of covariates were explored and all methods were implemented under the bayesian hierarchical modeling framework with indicator-based covariate selection. All the models based in careful variable selection procedure were found to produce significant results based on permutation test.

  1. How to interpret a small increase in AUC with an additional risk prediction marker: Decision analysis comes through

    Science.gov (United States)

    Baker, Stuart G.; Schuit, Ewoud; Steyerberg, Ewout W.; Pencina, Michael J.; Vickers, Andew; Moons, Karel G. M.; Mol, Ben W.J.; Lindeman, Karen S.

    2014-01-01

    An important question in the evaluation of an additional risk prediction marker is how to interpret a small increase in the area under the receiver operating characteristic curve (AUC). Many researchers believe that a change in AUC is a poor metric because it increases only slightly with the addition of a marker with a large odds ratio. Because it is not possible on purely statistical grounds to choose between the odds ratio and AUC, we invoke decision analysis, which incorporates costs and benefits. For example a timely estimate of the risk of later non-elective operative delivery can help a woman in labor decide if she wants an early elective cesarean section to avoid greater complications from possible later non-elective operative delivery. A basic risk prediction model for later non-elective operative delivery involves only antepartum markers. Because adding intrapartum markers to this risk prediction model increases AUC by 0.02, we questioned whether this small improvement is worthwhile. A key decision-analytic quantity is the risk threshold, here the risk of later non-elective operative delivery at which a patient would be indifferent between an early elective cesarean section and usual care. For a range of risk thresholds, we found that an increase in the net benefit of risk prediction requires collecting intrapartum marker data on 68 to 124 women for every correct prediction of later non-elective operative delivery. Because data collection is non-invasive, this test tradeoff of 68 to 124 is clinically acceptable, indicating the value of adding intrapartum markers to the risk prediction model. PMID:24825728

  2. Phenotypic and functional markers for 1alpha,25-dihydroxyvitamin D(3)-modified regulatory dendritic cells

    DEFF Research Database (Denmark)

    Pedersen, A W; Holmstrøm, K; Jensen, S S; Fuchs, D; Rasmussen, S; Kvistborg, P; Claesson, M H; Zocca, M-B

    2009-01-01

    The clinical use of dendritic cells (DCs) to induce antigen-specific immune tolerance has been hampered by the lack of a widely acknowledged method for generating human regulatory DCs but even more so by the non-existence of reliable markers. Thus, we set out to find reliable markers that can be...

  3. Conservation of spermatogonial stem cell marker expression in undifferentiated felid spermatogonia.

    Science.gov (United States)

    Vansandt, Lindsey M; Livesay, Janelle L; Dickson, Melissa Joy; Li, Lei; Pukazhenthi, Budhan S; Keefer, Carol L

    2016-09-01

    Spermatogonial stem cells (SSCs) are distinct in their ability to self-renew, transmit genetic information, and persist throughout the life of an individual. These characteristics make SSCs a useful tool for addressing diverse challenges such as efficient transgenic production in nonrodent, biomedical animal models, or preservation of the male genome for species in which survival of frozen-thawed sperm is low. A requisite first step to access this technology in felids is the establishment of molecular markers. This study was designed to evaluate, in the domestic cat (Felis catus), the expression both in situ and following enrichment in vitro of six genes (GFRA1, GPR125, ZBTB16, POU5F1, THY1, and UCHL1) that had been previously identified as SSC markers in other species. Antibodies for surface markers glial cell line-derived neurotrophic factor family receptor alpha 1, G protein-coupled receptor 125, and thymus cell antigen 1 could not be validated, whereas Western blot analysis of prepubertal, peripubertal, and adult cat testis confirmed protein expression for the intracellular markers ubiquitin carboxy-terminal hydrolase 1, zinc finger and BTB domain-containing protein 16, and POU domain, class 5, transcription factor 1. Colocalization of the markers by immunohistochemistry revealed that several cells within the subpopulation adjacent to the basement membrane of the seminiferous tubules and identified morphologically as spermatogonia, expressed all three intracellular markers. Studies performed on cheetah (Acinonyx jubatus) and Amur leopard (Panthera pardus orientalis) testis exhibited a conserved expression pattern in protein molecular weights, relative abundance, and localization of positive cells within the testis. The expression of the three intracellular SSC marker proteins in domestic and wild cat testes confirms conservation of these markers in felids. Enrichment of marker transcripts after differential plating was also observed. These markers will

  4. Intestinal Stem Cell Markers in the Intestinal Metaplasia of Stomach and Barrett's Esophagus.

    Directory of Open Access Journals (Sweden)

    Bo Gun Jang

    Full Text Available Gastric intestinal metaplasia (IM is a highly prevalent preneoplastic lesion; however, the molecular mechanisms regulating its development remain unclear. We have previously shown that a population of cells expressing the intestinal stem cell (ISC marker LGR5 increases remarkably in IM. In this study, we further investigated the molecular characteristics of these LGR5+ cells in IM by examining the expression profile of several ISC markers. Notably, we found that ISC markers-including OLFM4 and EPHB2-are positively associated with the CDX2 expression in non-tumorous gastric tissues. This finding was confirmed in stomach lesions with or without metaplasia, which demonstrated that OLFM4 and EPHB2 expression gradually increased with metaplastic progression. Moreover, RNA in situ hybridization revealed that LGR5+ cells coexpress several ISC markers and remained confined to the base of metaplastic glands, reminiscent to that of normal intestinal crypts, whereas those in normal antral glands expressed none of these markers. Furthermore, a large number of ISC marker-expressing cells were diffusely distributed in gastric adenomas, suggesting that these markers may facilitate gastric tumorigenesis. In addition, Barrett's esophagus (BE-which is histologically similar to intestinal metaplasia-exhibited a similar distribution of ISC markers, indicating the presence of a stem cell population with intestinal differentiation potential. In conclusion, we identified that LGR5+ cells in gastric IM and BE coexpress ISC markers, and exhibit the same expression profile as those found in normal intestinal crypts. Taken together, these results implicate an intestinal-like stem cell population in the pathogenesis of IM, and provide an important basis for understanding the development and maintenance of this disease.

  5. Markers of stem cells in human ovarian granulosa cells: is there a clinical significance in ART?

    Directory of Open Access Journals (Sweden)

    Varras Michail

    2012-11-01

    Full Text Available Abstract Background The purpose of the study was to determine the incidence of gene expression of Oct-4 and DAZL, which are typical markers for stem cells, in human granulosa cells during ovarian stimulation in women with normal FSH levels undergoing IVF or ICSI and to discover any clinical significance of such expression in ART. Methods Twenty one women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded separately and granulosa cells were analyzed for each patient separately using quantitative reverse-transcription–polymerase chain reaction analysis for Oct-4 and DAZL gene expression with G6PD gene as internal standard. Results G6PD and Oct-4 mRNA was detected in the granulosa cells in 47.6% (10/21. The median of Oct-4 mRNA/G6PD mRNA was 1.75 with intra-quarteral range from 0.10 to 98.21. The OCT-4 mRNA expression was statistically significantly correlated with the number of oocytes retrieved; when the Oct-4 mRNA expression was higher, then more than six oocytes were retrieved (p=0.037, Wilcoxon rank-sum. No detection of DAZL mRNA was found in granulosa cells. There was no additional statistically significant correlation between the levels of Oct-4 expression and FSH basal levels or estradiol peak levels or dosage of FSH for ovulation induction. No association was found between the presence or absence of Oct-4 mRNA expression in granulosa cells and ovarian response to gonadotropin stimulation. Also, no influence on pregnancy was observed between the presence or absence of Oct-4 mRNA expression in granulosa cells or to its expression levels accordingly. Conclusions Expression of OCT-4 mRNA, which is a typical stem cell marker and absence of expression of DAZL mRNA, which is a typical germ cell marker, suggest that a subpopulation of luteinized granulosa cells in healthy ovarian follicles (47

  6. Association of cancer stem cell markers genetic variants with gallbladder cancer susceptibility, prognosis, and survival.

    Science.gov (United States)

    Yadav, Anu; Gupta, Annapurna; Rastogi, Neeraj; Agrawal, Sushma; Kumar, Ashok; Kumar, Vijay; Mittal, Balraj

    2016-02-01

    Genes important to stem cell progression have been involved in the genetics and clinical outcome of cancers. We investigated germ line variants in cancer stem cell (CSC) genes to predict susceptibility and efficacy of chemoradiotherapy treatment in gallbladder cancer (GBC) patients. In this study, we assessed the effect of SNPs in CSC genes (surface markers CD44, ALCAM, EpCAM, CD133) and (molecular markers NANOG, SOX-2, LIN-28A, ALDH1A1, OCT-4) with GBC susceptibility and prognosis. Total 610 GBC patients and 250 controls were genotyped by using PCR-RFLP, ARMS-PCR, and TaqMan allelic discrimination assays. Chemotoxicity graded 2-4 in 200 patients and tumor response was recorded in 140 patients undergoing neoadjuvant chemotherapy (NACT). Differences in genotype and haplotype frequency distributions were calculated by binary logistic regression. Gene-gene interaction model was analyzed by generalized multifactor dimensionality reduction (GMDR). Overall survival was assessed by Kaplan-Meier survival curve and multivariate Cox-proportional methods. ALCAM Ars1157Crs10511244 (P = 0.0035) haplotype was significantly associated with GBC susceptibility. In GMDR analysis, ALCAM rs1157G>A, EpCAM rs1126497T>C emerged as best significant interaction model with GBC susceptibility and ALDH1A1 rs13959T>G with increased risk of grade 3-4 hematological toxicity. SOX-2 rs11915160A>C, OCT-4 rs3130932T>G, and NANOG rs11055786T>C were found best gene-gene interaction model for predicting response to NACT. In both Cox-proportional and recursive partitioning ALCAM rs1157GA+AA genotype showed higher mortality and hazard ratio. ALCAM gene polymorphisms associated with GBC susceptibility and survival while OCT-4, SOX-2, and NANOG variants showed an interactive role with treatment response. PMID:26318430

  7. Identification of astrocytoma associated genes including cell surface markers

    International Nuclear Information System (INIS)

    Despite intense effort the treatment options for the invasive astrocytic tumors are still limited to surgery and radiation therapy, with chemotherapy showing little or no increase in survival. The generation of Serial Analysis of Gene Expression (SAGE) profiles is expected to aid in the identification of astrocytoma-associated genes and highly expressed cell surface genes as molecular therapeutic targets. SAGE tag counts can be easily added to public expression databases and quickly disseminated to research efforts worldwide. We generated and analyzed the SAGE transcription profiles of 25 primary grade II, III and IV astrocytomas [1]. These profiles were produced as part of the Cancer Genome Anatomy Project's SAGE Genie [2], and were used in an in silico search for candidate therapeutic targets by comparing astrocytoma to normal brain transcription. Real-time PCR and immunohistochemistry were used for the validation of selected candidate target genes in 2 independent sets of primary tumors. A restricted set of tumor-associated genes was identified for each grade that included genes not previously associated with astrocytomas (e.g. VCAM1, SMOC1, and thymidylate synthetase), with a high percentage of cell surface genes. Two genes with available antibodies, Aquaporin 1 and Topoisomerase 2A, showed protein expression consistent with transcript level predictions. This survey of transcription in malignant and normal brain tissues reveals a small subset of human genes that are activated in malignant astrocytomas. In addition to providing insights into pathway biology, we have revealed and quantified expression for a significant portion of cell surface and extra-cellular astrocytoma genes

  8. Identification of astrocytoma associated genes including cell surface markers

    Directory of Open Access Journals (Sweden)

    Eberhart Charles G

    2004-07-01

    Full Text Available Abstract Background Despite intense effort the treatment options for the invasive astrocytic tumors are still limited to surgery and radiation therapy, with chemotherapy showing little or no increase in survival. The generation of Serial Analysis of Gene Expression (SAGE profiles is expected to aid in the identification of astrocytoma-associated genes and highly expressed cell surface genes as molecular therapeutic targets. SAGE tag counts can be easily added to public expression databases and quickly disseminated to research efforts worldwide. Methods We generated and analyzed the SAGE transcription profiles of 25 primary grade II, III and IV astrocytomas 1. These profiles were produced as part of the Cancer Genome Anatomy Project's SAGE Genie 2, and were used in an in silico search for candidate therapeutic targets by comparing astrocytoma to normal brain transcription. Real-time PCR and immunohistochemistry were used for the validation of selected candidate target genes in 2 independent sets of primary tumors. Results A restricted set of tumor-associated genes was identified for each grade that included genes not previously associated with astrocytomas (e.g. VCAM1, SMOC1, and thymidylate synthetase, with a high percentage of cell surface genes. Two genes with available antibodies, Aquaporin 1 and Topoisomerase 2A, showed protein expression consistent with transcript level predictions. Conclusions This survey of transcription in malignant and normal brain tissues reveals a small subset of human genes that are activated in malignant astrocytomas. In addition to providing insights into pathway biology, we have revealed and quantified expression for a significant portion of cell surface and extra-cellular astrocytoma genes.

  9. Evaluation of a multi-marker immunomagnetic enrichment assay for the quantification of circulating melanoma cells

    Directory of Open Access Journals (Sweden)

    Freeman James B

    2012-09-01

    Full Text Available Abstract Background Circulating melanoma cells (CMCs are thought to be valuable in improving measures of prognosis in melanoma patients and may be a useful marker of residual disease to identify non-metastatic patients requiring adjuvant therapy. We investigated whether immunomagnetic enrichment targeting multiple markers allows more efficient enrichment of CMCs from patient peripheral blood than targeting a single marker. Furthermore, we aimed to determine whether the number of CMCs in patient blood was associated with disease stage. Methods We captured CMCs by targeting the melanoma associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5 and CD271, both individually and in combination, by immunomagnetic enrichment. CMCs were enriched and quantified from the peripheral blood of 10 non-metastatic and 13 metastatic melanoma patients. Results Targeting all markers in combination resulted in the enrichment of more CMCs than when any individual marker was targeted (p  Conclusions Our results demonstrated that a combination of markers should be targeted for optimal isolation of CMCs. In addition, there are significantly more CMCs in metastatic patients compared with non-metastatic patients and therefore quantification of CMCs may prove to be a useful marker of disease progression.

  10. Early markers of renal injury in predicting outcome in thermal burn patients

    International Nuclear Information System (INIS)

    Acute renal failure (ARF) is a well known complication of severe burn and is an important factor that can increase mortality. To determine the predictors of acute renal failure that occur in major burns, we studied 40 patients with moderate to severe thermal burn injury - second to third degree with > 20% of total body surface area. All patients were subjected to routine investigations including: Serum creatinine, blood urea nitrogen, fractional excretion of sodium, uri-nary malondialdehyde and microalbuminuria on day 0, 3, 7, 14 and 21 of hospitalization. Nine patients (22.5 %) developed acute renal failure; 4 patients required supportive dialysis. The group that developed ARF showed an increase of markers of glomerular damage with appearance of microalbuminuria on day 0 that reached 3 - 4 folds above its normal level on day 14 and remained constant with elevated serum creatinine and burn size in the 3 rd week of ARF, and progressed to overt proteinuria in 3 cases. Urinary malondialdehyde increased 3 folds above normal values before developing acute renal failure, and gradually increased on day 14, which coincided with the increased of microalbuminuria. Two cases (22.2%) in the ARF group who developed septicemia and required dialysis died on the 32nd and 36th days post-burn. Burn size and occurrence of septicemia were the only predictors of acute renal failure using multiple regression analysis (P value < 0.001 and < 0.0371, respectively). We conclude that acute renal failure complicates burn patients and is related to the size and depth of burn and occurrence of septicemia. Microalbuminuria and urinary malondialdehyde are useful markers for prediction of renal outcome in such group of patients. (author)

  11. Predictive value of neutrophil infiltration as a marker of Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Xiao-Qing Xu; Zhen-Hua Wang; Jing-Xian Liao; Xiao-Yu Chen; Wen-Zhong Liu; Shu-Dong Xiao; Hong Lu

    2012-01-01

    AIM:To evaluate the predictive value of neutrophil infiltration as a marker of Helicobacter pylori (H.pylori)infection.METHODS:A total of 315 patients with dyspepsia symptoms who underwent upper gastrointestinal endoscopy were enrolled in this study.Biopsies were evaluated using the updated Sydney system.The medication history of all patients in the preceding 4 wk was recorded.The diagnosis of H.pylori infection was based on 13C-urea breath test at least 4 wk after withdrawal of antisecretory drugs,antibiotics and related drugs.For the patients with subtotal gastrectomy,the diagnosis of H.pylori infection was based on anti-H.pylori immunoglobulin G (IgG) antibody.Serum anti-H.pylori IgG antibody was measured by enzyme-linked immunosorbent assays (Biohit,Finland).RESULTS:The sensitivity,specificity,positive predictive value and negative predictive value of neutrophil infiltration in the diagnosis of H.pylori infection were 92.3%,83.5%,77.4% and 94.7%,respectively.Neutrophil infiltration of gastric mucosa in the histological analysis was strongly associated with H.pylori infection (77.4% vs 5.3% in the neutrophil infiltration negative group,P =0.000).Moderate neutrophil infiltration was more frequent in H.pylori infection when compared to mild infiltration (81.8% and 75%,respectively),but did not reach statistical significance.For those patients with negative rapid urease test,H.pylori was detected in 73.2% of patients with positive neutrophil infiltration on histology.In patients with subtotal gastrectomy,the diagnostic accuracy of neutrophil infiltration in H.pylori infection was 50%.CONCLUSION:Neutrophil infiltration is closely associated with H.pylori and may be recognized as a sign of this infection.

  12. Gene expression profiles of hepatic cell-type specific marker genes in progression of liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Yoshiyuki Takahara; Mitsuo Takahashi; Hiroki Wagatsuma; Fumihiko Yokoya; Qing-Wei Zhang; Mutsuyo Yamaguchi; Hiroyuki Aburatani; Norifumi Kawada

    2006-01-01

    AIM: To determine the gene expression profile data for the whole liver during development of dimethylnitrosamine (DMN)-induced hepatic fibrosis.METHODS: Marker genes were identified for different types of hepatic cells, including hepatic stellate cells (HSCs), Kupffer cells (including other inflammatory cells),and hepatocytes, using independent temporal DNA microarray data obtained from isolated hepatic cells.RESULTS: The cell-type analysis of gene expression gave several key results and led to formation of three hypotheses: (1) changes in the expression of HSCspecific marker genes during fibrosis were similar to gene expression data in in vitro cultured HSCs, suggesting a major role of the self-activating characteristics of HSCs in formation of fibrosis; (2) expression of mast cell-specific marker genes reached a peak during liver fibrosis,suggesting a possible role of mast cells in formation of fibrosis; and (3) abnormal expression of hepatocytespecific marker genes was found across several metabolic pathways during fibrosis, including sulfur-containing amino acid metabolism, fatty acid metabolism, and drug metabolism, suggesting a mechanistic relationship between these abnormalities and symptoms of liver fibrosis.CONCLUSION: Analysis of marker genes for specific hepatic cell types can identify the key aspects of fibrogenesis. Sequential activation of inflammatory cells and the self-supporting properties of HSCs play an important role in development of fibrosis.

  13. Tracking neuronal marker expression inside living differentiating cells using molecular beacons

    DEFF Research Database (Denmark)

    Ilieva, Mirolyuba; Della Vedova, Paolo; Hansen, Ole;

    2013-01-01

    Monitoring gene expression is an important tool for elucidating mechanisms of cellular function. In order to monitor gene expression during nerve cell development, molecular beacon (MB) probes targeting markers representing different stages of neuronal differentiation were designed and synthesized...

  14. Detection of non-genotoxic hepatocarcinogens and prediction of their mechanism of action in rats using gene marker sets.

    Science.gov (United States)

    Kanki, Masayuki; Gi, Min; Fujioka, Masaki; Wanibuchi, Hideki

    2016-01-01

    Several studies have successfully detected hepatocarcinogenicity in rats based on gene expression data. However, prediction of hepatocarcinogens with certain mechanisms of action (MOAs), such as enzyme inducers and peroxisome proliferator-activated receptor α (PPARα) agonists, can prove difficult using a single model and requires a highly toxic dose. Here, we constructed a model for detecting non-genotoxic (NGTX) hepatocarcinogens and predicted their MOAs in rats. Gene expression data deposited in the Open Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System (TG-GATEs) was used to investigate gene marker sets. Principal component analysis (PCA) was applied to discriminate different MOAs, and a support vector machine algorithm was applied to construct the prediction model. This approach identified 106 probe sets as gene marker sets for PCA and enabled the prediction model to be constructed. In PCA, NGTX hepatocarcinogens were classified as follows based on their MOAs: cytotoxicants, PPARα agonists, or enzyme inducers. The prediction model detected hepatocarcinogenicity with an accuracy of more than 90% in 14- and 28-day repeated-dose studies. In addition, the doses capable of predicting NGTX hepatocarcinogenicity were close to those required in rat carcinogenicity assays. In conclusion, our PCA and prediction model using gene marker sets will help assess the risk of hepatocarcinogenicity in humans based on MOAs and reduce the number of two-year rodent bioassays. PMID:26961613

  15. Predicting Lymph Node Metastasis in Endometrial Cancer Using Serum CA125 Combined with Immunohistochemical Markers PR and Ki67, and a Comparison with Other Prediction Models.

    Directory of Open Access Journals (Sweden)

    Bingyi Yang

    Full Text Available We aimed to evaluate the value of immunohistochemical markers and serum CA125 in predicting the risk of lymph node metastasis (LNM in women with endometrial cancer and to identify a low-risk group of LNM. The medical records of 370 patients with endometrial endometrioid adenocarcinoma who underwent surgical staging in the Obstetrics & Gynecology Hospital of Fudan University were collected and retrospectively reviewed. Immunohistochemical markers were screened. A model using serum cancer antigen 125 (CA125 level, the immunohistochemical markers progesterone receptor (PR and Ki67 was created for prediction of LNM. A predicted probability of 4% among these patients was defined as low risk. The developed model was externally validated in 200 patients from Shanghai Cancer Center. The efficiency of the model was compared with three other reported prediction models. Patients with serum CA125 50% and Ki67 < 40% in cancer lesion were defined as low risk for LNM. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.82. The model classified 61.9% (229/370 of patients as being at low risk for LNM. Among these 229 patients, 6 patients (2.6% had LNM and the negative predictive value was 97.4% (223/229. The sensitivity and specificity of the model were 84.6% and 67.4% respectively. In the validation cohort, the model classified 59.5% (119/200 of patients as low-risk, 3 out of these 119 patients (2.5% has LNM. Our model showed a predictive power similar to those of two previously reported prediction models. The prediction model using serum CA125 and the immunohistochemical markers PR and Ki67 is useful to predict patients with a low risk of LNM and has the potential to provide valuable guidance to clinicians in the treatment of patients with endometrioid endometrial cancer.

  16. Tumor cell marker PVRL4 (nectin 4 is an epithelial cell receptor for measles virus.

    Directory of Open Access Journals (Sweden)

    Ryan S Noyce

    2011-08-01

    Full Text Available Vaccine and laboratory adapted strains of measles virus can use CD46 as a receptor to infect many human cell lines. However, wild type isolates of measles virus cannot use CD46, and they infect activated lymphocytes, dendritic cells, and macrophages via the receptor CD150/SLAM. Wild type virus can also infect epithelial cells of the respiratory tract through an unidentified receptor. We demonstrate that wild type measles virus infects primary airway epithelial cells grown in fetal calf serum and many adenocarcinoma cell lines of the lung, breast, and colon. Transfection of non-infectable adenocarcinoma cell lines with an expression vector encoding CD150/SLAM rendered them susceptible to measles virus, indicating that they were virus replication competent, but lacked a receptor for virus attachment and entry. Microarray analysis of susceptible versus non-susceptible cell lines was performed, and comparison of membrane protein gene transcripts produced a list of 11 candidate receptors. Of these, only the human tumor cell marker PVRL4 (Nectin 4 rendered cells amenable to measles virus infections. Flow cytometry confirmed that PVRL4 is highly expressed on the surfaces of susceptible lung, breast, and colon adenocarcinoma cell lines. Measles virus preferentially infected adenocarcinoma cell lines from the apical surface, although basolateral infection was observed with reduced kinetics. Confocal immune fluorescence microscopy and surface biotinylation experiments revealed that PVRL4 was expressed on both the apical and basolateral surfaces of these cell lines. Antibodies and siRNA directed against PVRL4 were able to block measles virus infections in MCF7 and NCI-H358 cancer cells. A virus binding assay indicated that PVRL4 was a bona fide receptor that supported virus attachment to the host cell. Several strains of measles virus were also shown to use PVRL4 as a receptor. Measles virus infection reduced PVRL4 surface expression in MCF7 cells, a

  17. Further evidence for population specific differences in the effect of DNA markers and gender on eye colour prediction in forensics

    OpenAIRE

    Pośpiech, Ewelina; Karłowska-Pik, Joanna; Ziemkiewicz, Bartosz; Kukla, Magdalena; Skowron, Małgorzata; Wojas-Pelc, Anna; Branicki, Wojciech

    2016-01-01

    The genetics of eye colour has been extensively studied over the past few years, and the identified polymorphisms have been applied with marked success in the field of Forensic DNA Phenotyping. A picture that arises from evaluation of the currently available eye colour prediction markers shows that only the analysis of HERC2-OCA2 complex has similar effectiveness in different populations, while the predictive potential of other loci may vary significantly. Moreover, the role of gender in the ...

  18. GWAS and Genomic Prediction Based on Markers of SNP-CHIPS and Sequence Data in Cattle Populations

    DEFF Research Database (Denmark)

    Wu, Xiaoping

    This thesis investigated the methods and models for genome wide association study and genomic prediction. The main conclusions are: 1) The power of QTL detection can be increased by increasing marker densities, and the Bayesian variable selection model together with the analysis of the QTL...

  19. Criteria of GenCall score to edit marker data and methods to handle missing markers have an influence on accuracy of genomic predictions

    DEFF Research Database (Denmark)

    Edriss, Vahid; Guldbrandtsen, Bernt; Lund, Mogens Sandø;

    2013-01-01

    The aim of this study was to investigate the effect of different strategies for handling low-quality or missing data on prediction accuracy for direct genomic values of protein yield, mastitis and fertility using a Bayesian variable model and a GBLUP model in the Danish Jersey population. The data...... contained 1071 Jersey bulls that were genotyped with the Illumina Bovine 50K chip. After preliminary editing, 39227 SNP remained in the dataset. Four methods to handle missing genotypes were: 1) BEAGLE: missing markers were imputed using Beagle 3.3 software, 2) COMMON: missing genotypes at a locus were...

  20. Association of expression levels of pluripotency/stem cell markers with the differentiation outcome of Wharton's jelly mesenchymal stem cells into insulin producing cells.

    Science.gov (United States)

    Kassem, Dina H; Kamal, Mohamed M; El-Kholy, Abd El-Latif G; El-Mesallamy, Hala O

    2016-08-01

    Recently, there has been much attention towards generation of insulin producing cells (IPCs) from stem cells, especially from Wharton's jelly mesenchymal stem cells (WJ-MSCs). However, generation of mature IPCs remains a challenge. Assessment of generation of IPCs was usually done by examining β-cell markers, however, assessment of pluripotency/stem cell markers drew less attention. Therefore, the purpose of this study was to investigate the levels of pluripotency/stem cell markers during differentiation of WJ-MSCs into IPCs and the association of these levels with differentiation outcomes. WJ-MSCs were isolated, characterized then induced to differentiate into IPCs using three different protocols namely A, B and C. Differentiated IPCs were assessed by the expression of pluripotency/stem cell markers, together with β-cell markers using qRT-PCR, and functionally by measuring glucose stimulated insulin secretion. Differentiated cells from protocol A showed lowest expression of pluripotency/stem cell markers and relatively best GSIS. However, protocol B showed concomitant expression of pluripotency/stem cell and β-cell markers with relatively less insulin secretion as compared to protocol A. Protocol C failed to generate glucose-responsive IPCs. In conclusion, sustained expression of pluripotency/stem cell markers could be associated with the incomplete differentiation of WJ-MSCs into IPCs. A novel finding for which further investigations are warranted. PMID:27265786

  1. Galectin-1 is a useful marker for detecting neoplastic squamous cells in oral cytology smears.

    Science.gov (United States)

    Noda, Yuri; Kondo, Yuko; Sakai, Manabu; Sato, Sunao; Kishino, Mitsunobu

    2016-06-01

    Cytologic diagnoses in the oral region are very difficult due to the small amount of cells in smears, which are also exposed to many stimulating factors and often show atypical changes. Galectin-1 (Gal1) is a β-galactoside binding protein that modulates tumor progression. Gal1 is very weakly expressed in normal cells, but is often overexpressed in neoplastic lesions. The aim of the present study was to determine whether it is possible to differentiate reactive changes from neoplastic changes in oral cytology smears based on the expression of Gal1. A total of 155 tissue biopsy specimens and 61 liquid-based cytology specimens were immunostained by an anti-Gal1 antibody, and Gal1 expression levels were subsequently evaluated. These samples consisted of oral squamous cell carcinomas, epithelial dysplasia, and oral mucosal diseases. The positive and negative expressions of Gal1 were examined in 37 specimens collected by scalpel and cytobrush biopsy. The sensitivity, specificity, and positive predictive value of Gal1 were also evaluated in smears. In tissue sections, the positive ratio of Gal1 in neoplastic lesions was high (72.3%). In cytology specimens, the positive ratio of Gal1 was higher in neoplastic lesions (79.0%) than in those negative for intraepithelial lesion or malignancy (22.2%). A correlation was found between immunocytochemical Gal1 expression and immunohistochemical Gal1 expression (P < .001). The sensitivity (75.0%), specificity (75.0%), and positive predictive value (91.3%) of Gal1 were also high in smears. In conclusion, Gal1 may be a useful marker for determining whether morphologic changes in cells are reactive or neoplastic. PMID:26980012

  2. Correlation between EGFR gene mutation, cytologic tumor markers, 18F-FDG uptake in non-small cell lung cancer

    OpenAIRE

    Cho, Arthur; Hur, Jin; Moon, Yong Wha; Hong, Sae Rom; Suh, Young Joo; Kim, Yun Jung; Im, Dong Jin; Hong, Yoo Jin; Lee, Hye-Jeong; Kim, Young Jin; Shim, Hyo Sup; Lee, Jae Seok; Kim, Joo-Hang; Choi, Byoung Wook

    2016-01-01

    Background EGFR mutation-induced cell proliferation causes changes in tumor biology and tumor metabolism, which may reflect tumor marker concentration and 18F-FDG uptake on PET/CT. Direct aspirates of primary lung tumors contain different concentrations of tumor markers than serum tumor markers, and may correlate better with EGFR mutation than serum tumor markers. The purpose of this study is to investigate an association between cytologic tumor markers and FDG uptake with EGFR mutation statu...

  3. A Quantitative Perspective on Surface Marker Selection for the Isolation of Functional Tumor Cells.

    Science.gov (United States)

    Cahall, Calvin F; Lilly, Jacob L; Hirschowitz, Edward A; Berron, Brad J

    2015-01-01

    Much effort has gone into developing fluid biopsies of patient peripheral blood for the monitoring of metastatic cancers. One common approach is to isolate and analyze tumor cells in the peripheral blood. Widespread clinical implementation of this approach has been hindered by the current choice of targeting epithelial markers known to be highly variable in primary tumor sites. Here, we review current antigen-based tumor cell isolation strategies and offer biological context for commonly studied cancer surface markers. Expression levels of the most common markers are quantitated for three breast cancer and two non-small cell lung cancer (NSCLC) lineage models. These levels are contrasted with that present on healthy peripheral blood mononuclear cells (PBMC) for comparison to expected background levels in a fluid biopsy setting. A key feature of this work is establishing a metric of markers per square micrometer. This describes an average marker density on the cell membrane surface, which is a critical metric for emerging isolation strategies. These results serve to extend expression of key tumor markers in a sensitive and dynamic manner beyond traditional positive/negative immunohistochemical staining to guide future fluid biopsy targeting strategies. PMID:26309407

  4. Study of Pluripotency Markers in Zebrafish Embryos and Transient Embryonic Stem Cell Cultures

    OpenAIRE

    Robles, Vanesa; Martí, Mercé; Belmonte, Juan Carlos Izpisua

    2011-01-01

    Targeted genomic manipulation using embryonic stem (ES) cells has not yet been achieved in zebrafish, although methods for zebrafish ES cell culture has been described in literature. The knowledge of pluripotency markers in this species is almost nonexistent and this is a very limiting factor in the definition of the ideal culture conditions for ES cells. Here, we studied the expression of several genes associated with pluripotency in zebrafish embryonic cells versus differentiated cells and ...

  5. SOX9 is a novel cancer stem cell marker surrogated by osteopontin in human hepatocellular carcinoma

    Science.gov (United States)

    Kawai, Takayuki; Yasuchika, Kentaro; Ishii, Takamichi; Miyauchi, Yuya; Kojima, Hidenobu; Yamaoka, Ryoya; Katayama, Hokahiro; Yoshitoshi, Elena Yukie; Ogiso, Satoshi; Kita, Sadahiko; Yasuda, Katsutaro; Fukumitsu, Ken; Komori, Junji; Hatano, Etsuro; Kawaguchi, Yoshiya; Uemoto, Shinji

    2016-01-01

    The current lack of cancer stem cell (CSC) markers that are easily evaluated by blood samples prevents the establishment of new therapeutic strategies in hepatocellular carcinoma (HCC). Herein, we examined whether sex determining region Y-box 9 (SOX9) represents a new CSC marker, and whether osteopontin (OPN) can be used as a surrogate marker of SOX9 in HCC. In HCC cell lines transfected with a SOX9 promoter-driven enhanced green fluorescence protein gene, FACS-isolated SOX9+ cells were capable of self-renewal and differentiation into SOX9− cells, and displayed high proliferation capacity in vitro. Xenotransplantation experiments revealed that SOX9+ cells reproduced, differentiated into SOX9− cells, and generated tumors at a high frequency in vivo. Moreover, SOX9+ cells were found to be involved in epithelial-mesenchymal transition (EMT) and activation of TGFb/Smad signaling. Gain/loss of function experiments showed that SOX9 regulates Wnt/beta-catenin signaling, including cyclin D1 and OPN. Immunohistochemistry of 166 HCC surgical specimens and serum OPN measurements showed that compared to SOX9− patients, SOX9+ patients had significantly poorer recurrence-free survival, stronger venous invasion, and higher serum OPN levels. In conclusion, SOX9 is a novel HCC-CSC marker regulating the Wnt/beta-catenin pathway and its downstream target, OPN. OPN is a useful surrogate marker of SOX9 in HCC. PMID:27457505

  6. Predictive immunohistochemical indicators of regional metastasis of laryngeal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Kovtunenko A.V.

    2014-12-01

    Full Text Available Background. The comprehension of molecular events that underlie malignant transformation of squamous cell epithelium could not only extend the knowledge about the etiology of this process, but also is basic for predictive markers and target therapy. Objective. The article analyzes the predictive immunohistochemical indicators of regional metastasis of laryngeal squamous cell carcinoma. Methods. In the study we used the original biopsy material from 70 patients with laryngeal squamous cell carcinoma T3-4N0-3M0 (69 men and 1 woman aged from 33 to 74 during the period 2011-2014. The primary monoclonal antibodies for cyclin D1, CD34 and VEGF (TermoScientific, USA were used. Results. There were significant correlation between increased expression of markers cyclin D1 (р<0,0001, VEGF (р=0,018, extension of microvessel density (р=0,032 and presence of regional metastasis of laryngeal squamous cell carcinoma. Conclusion. The significant increase of microvessel density and expression of VEGF and cyclin D1markers in the laryngeal squamous cell carcinomas proves their predictive importance. Citation: Kovtunenko AV, Shportko BV, Shponka IS, Poslavska ОV. [Predictive immunohistochemical indicators of regional metastasis of laryngeal squamous cell carcinoma]. Morphologia. 2014;8(4:30-6. Ukrainian.

  7. Stem cell markers in the heart of the human newborn

    OpenAIRE

    Armando Faa; Elvira Podda; Vassilios Fanos

    2016-01-01

    The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. Several recent studies now show that the different cell types that characterize the adult human heart arise from a common ancestor. Human cardiac stem cells differentiate into cardiomyocytes, and, in lesser extent, into smooth muscle and endothelial cells. The characterization of human cardiac stem ...

  8. Surface Markers for Chondrogenic Determination: A Highlight of Synovium-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Douglas D. Campbell

    2012-11-01

    Full Text Available Cartilage tissue engineering is a promising field in regenerative medicine that can provide substantial relief to people suffering from degenerative cartilage disease. Current research shows the greatest chondrogenic potential for healthy articular cartilage growth with minimal hypertrophic differentiation to be from mesenchymal stem cells (MSCs of synovial origin. These stem cells have the capacity for differentiation into multiple cell lineages related to mesenchymal tissue; however, evidence exists for cell surface markers that specify a greater potential for chondrogenesis than other differentiation fates. This review will examine relevant literature to summarize the chondrogenic differentiation capacities of tested synovium-derived stem cell (SDSC surface markers, along with a discussion about various other markers that may hold potential, yet require further investigation. With this information, a potential clinical benefit exists to develop a screening system for SDSCs that will produce the healthiest articular cartilage possible.

  9. Serum CA125 is a novel predictive marker for pancreatic cancer metastasis and correlates with the metastasis-associated burden

    OpenAIRE

    Liu, Liang; Xu, Hua-Xiang; Wang, Wen-Quan; Wu, Chun-tao; Xiang, Jin-Feng; Liu, Chen; Long, Jiang; Xu, Jin; Fu, De-Liang; Ni, Quan-Xing; Houchen, Courtney W.; Postier, Russell G.; Li, Min; Yu, Xian-Jun

    2016-01-01

    This study evaluated potential of serum tumor markers to predict the incidence and intensity of pancreatic cancer metastasis as well as patient survival. Retrospective records from 905 patients and prospective data from 142 patients were collected from two high-volume institutions. The levels of eight serum tumor markers (CA19-9, CEA, CA242, CA72-4, CA50, CA125, CA153, and AFP) commonly used in gastroenterological cancer were analyzed in all stages of pancreatic cancer. Serum CA125 levels wer...

  10. Comparative Value of Simple Inflammatory Markers in the Prediction of Left Ventricular Systolic Dysfunction in Postacute Coronary Syndrome Patients

    Directory of Open Access Journals (Sweden)

    Panagiotis Aggelopoulos

    2009-01-01

    Full Text Available Objectives. We sought to assess the comparative value of inflammatory markers on the occurrence of left ventricular systolic dysfunction (LVSD after an acute coronary syndrome (ACS. Methods. During 2006–2008, 760 patients with an ACS were enrolled. C-reactive protein (CRP and white blood cell (WBC count were measured during the first 12 hours of hospital admission. Results. CRP levels and WBC count were significantly higher in those who developed LVSD compared to those who did not. The analysis revealed that a 10 mg/dL increase of CRP levels and a 1000/L increase in WBC are associated with a 6% and a 7% increase in the likelihood of developing LVSD, respectively. Furthermore, WBC count at entry and CRP have almost the same predictive value for development of LVSD after an ACS (2=0.109 versus 2=0.093. Conclusions. Serum CRP levels and WBC count at entry are almost equally powerful independent predictors of LVSD, after an ACS.

  11. ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias.

    Science.gov (United States)

    Ishibashi, Tomohiko; Yokota, Takafumi; Tanaka, Hirokazu; Ichii, Michiko; Sudo, Takao; Satoh, Yusuke; Doi, Yukiko; Ueda, Tomoaki; Tanimura, Akira; Hamanaka, Yuri; Ezoe, Sachiko; Shibayama, Hirohiko; Oritani, Kenji; Kanakura, Yuzuru

    2016-04-01

    Reliable markers are essential to increase our understanding of the biological features of human hematopoietic stem cells and to facilitate the application of hematopoietic stem cells in the field of transplantation and regenerative medicine. We previously identified endothelial cell-selective adhesion molecule (ESAM) as a novel functional marker of hematopoietic stem cells in mice. Here, we found that ESAM can also be used to purify human hematopoietic stem cells from all the currently available sources (adult bone marrow, mobilized peripheral blood, and cord blood). Multipotent colony-forming units and long-term hematopoietic-reconstituting cells in immunodeficient mice were found exclusively in the ESAM(High) fraction of CD34(+)CD38(-) cells. The CD34(+)CD38(-) fraction of cord blood and collagenase-treated bone marrow contained cells exhibiting extremely high expression of ESAM; these cells are likely to be related to the endothelial lineage. Leukemia cell lines of erythroid and megakaryocyte origin, but not those of myeloid or lymphoid descent, were ESAM positive. However, high ESAM expression was observed in some primary acute myeloid leukemia cells. Furthermore, KG-1a myeloid leukemia cells switched from ESAM negative to ESAM positive with repeated leukemia reconstitution in vivo. Thus, ESAM is a useful marker for studying both human hematopoietic stem cells and leukemia cells. PMID:26774386

  12. CEA serum level as early predictive marker of outcome during EGFR-TKI therapy in advanced NSCLC patients.

    Science.gov (United States)

    Facchinetti, Francesco; Aldigeri, Raffaella; Aloe, Rosalia; Bortesi, Beatrice; Ardizzoni, Andrea; Tiseo, Marcello

    2015-08-01

    Considering the role of carcinoembryonic antigen (CEA) serum levels as potential useful predictive marker during chemotherapy treatment, we studied its applicability in advanced non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs). Our retrospective cohort consists of 79 patients (33 EGFR mutated and 46 EGFR wild type or unknown) affected by advanced NSCLC, for whom CEA serum values at the beginning of TKI therapy and after the first month of treatment were available, regardless of treatment line. Baseline CEA value, percentage of CEA reduction after 1 month, and percentage of patients with ≥20 % CEA decrease after 1 month (CEA response) were correlated with disease control rate (DCR), progression-free (PFS), and overall (OS) survival, according to EGFR mutational status. Median baseline CEA levels were significantly higher in EGFR mutated (40.9 ng/ml; interquartile range (IQR) 8.9-197.6) than in wild-type cases (6.2 ng/ml; IQR 2.8-12.8; p = 0.003). Both percentage reduction in CEA levels (-10.7 vs. +13.4 %) and percentage of cases with CEA response (42 vs. 20 %) were significantly higher in mutated vs. wild-type/unknown patients (p = 0.007 and p = 0.027, respectively). In wild-type/unknown patients, CEA response was significantly correlated with DCR (p = 0.001) and resulted as a significant predictor of PFS both in univariate (p = 0.002) and in multivariate analyses (hazard ratio (HR) 0.27; 95 % confidence interval (CI) 0.11-0.66; p = 0.004); only a trend was found for OS prediction (p = 0.082). In EGFR-mutated group, CEA reduction did not show any correlation either with PFS or OS. CEA response after 1 month of EGFR-TKI therapy could be a useful marker, worthy to further studies, as early predictor of treatment outcome in EGFR wild-type/unknown unselected NSCLC cases for which no molecular predictor is yet available. PMID:25731731

  13. Cardiomyocyte Marker Expression in Mouse Embryonic Fibroblasts by Cell-Free Cardiomyocyte Extract and Epigenetic Manipulation

    Directory of Open Access Journals (Sweden)

    Tahereh Talaei-Khozani

    2014-03-01

    Full Text Available Background: The regenerative capacity of the mammalian heart is quite limited. Recent reports have focused on reprogramming mesenchymal stem cells into cardiomyocytes. We investigated whether fibroblasts could transdifferentiate into myocardium. Methods: Mouse embryonic fibroblasts were treated with Trichostatin A (TSA and 5-Aza-2-Deoxycytidine (5-aza-dC. The treated cells were permeabilized with streptolysin O and exposed to the mouse cardiomyocyte extract and cultured for 1, 10, and 21 days. Cardiomyocyte markers were detected by immunohistochemistry. Alkaline phosphatase activity and OCT4 were also detected in cells treated by chromatin-modifying agents. Results: The cells exposed to a combination of 5-aza-dC and TSA and permeabilized in the presence of the cardiomyocyte extract showed morphological changes. The cells were unable to express cardiomyocyte markers after 24 h. Immunocytochemical assays showed a notable degree of myosin heavy chain and α-actinin expressions after 10 days. The expression of the natriuretic factor and troponin T occurred after 21 days in these cells. The cells exposed to chromatin-modifying agents also expressed cardiomyocyte markers; however, the proportion of reprogrammed cells was clearly smaller than that in the cultures exposed to 5-aza-dC , TSA, and extract. Conclusion: It seems that the fibroblasts were able to eliminate the previous epigenetic markers and form new ones according to the factors existing in the extract. Since no beating was observed, at least up to 21 days, the cells may need an appropriate extracellular matrix for their function.

  14. Ovarian Cancer Stem Cell Markers: Prognostic and Therapeutic Implications

    OpenAIRE

    Burgos-Ojeda, Daniela; Rueda, Bo R.; Buckanovich, Ronald J.

    2012-01-01

    Cancer stem cells are rare chemotherapy resistant cells within a tumor which can serve to populate the bulk of a tumor with more differentiated daughter cells and potentially contribute to recurrent disease. Ovarian cancer is a disease for which at the time of initial treatment we can obtain complete clinical remission in the majority of patients. Unfortunately, most will relapse and succumb to their disease. This clinical course is in line with the cancer stem cell model. In the past five ye...

  15. Impact of stem cell marker expression on recurrence of TACE-treated hepatocellular carcinoma post liver transplantation

    Directory of Open Access Journals (Sweden)

    Zeng Zhen

    2012-12-01

    Full Text Available Abstract Background Liver transplantation is the most effective therapy for cirrhosis-associated hepatocellular carcinoma (HCC but its utility is limited by post-transplant tumor recurrence. Use of the Milan, size-based criteria, has reduced recurrence rate to less than 10% but many patients remain ineligible. Reduction of tumor size with local therapies has been used to “downstage” patients to allow them to qualify for transplantation, but the optimal criteria to predict tumor recurrence in these latter patients has not been established. The existence of a progenitor cell population, sometimes called cancer stem cells (CSCs, has been proposed to be one mechanism accounting for the chemotherapy resistance and recurrence of hepatocellular carcinoma. The aim of this study was to determine if transcatheter arterial chemoemolization (TACE treated tumors have increased CSC marker expression and whether these markers could be used to predict tumor recurrence. Methods Formalin fixed specimens were obtained from 39 HCC liver explants (23 with no treatment and 16 after TACE. Immunohistochemical staining was performed for EpCAM, CD44, CD90, and CD133. Staining for each marker was scored 0–3 by evaluating the number and intensity of positive tumor cells in 5 hpf of tumor in each specimen. Results TACE treated tumors displayed greater necrosis and fibrosis than non-TACE treated samples but there were no differences in morphology between the viable tumor cells of both groups. In TACE treated specimens, the staining of both EpCAM and CD133 was greater than in non-TACE specimens but CD44 and CD90 were the same. In the TACE group, the presence of high EpCAM staining was associated with tumor recurrence. Four of ten EpCAM high patients recurred while 0 of 6 EpCAM low patients recurred (P = 0.040. None of the other markers predicted recurrence. Conclusion High pre-transplant EpCAM staining predicted HCC recurrence. This suggests that the abundance of

  16. Impact of stem cell marker expression on recurrence of TACE-treated hepatocellular carcinoma post liver transplantation

    International Nuclear Information System (INIS)

    Liver transplantation is the most effective therapy for cirrhosis-associated hepatocellular carcinoma (HCC) but its utility is limited by post-transplant tumor recurrence. Use of the Milan, size-based criteria, has reduced recurrence rate to less than 10% but many patients remain ineligible. Reduction of tumor size with local therapies has been used to “downstage” patients to allow them to qualify for transplantation, but the optimal criteria to predict tumor recurrence in these latter patients has not been established. The existence of a progenitor cell population, sometimes called cancer stem cells (CSCs), has been proposed to be one mechanism accounting for the chemotherapy resistance and recurrence of hepatocellular carcinoma. The aim of this study was to determine if transcatheter arterial chemoemolization (TACE) treated tumors have increased CSC marker expression and whether these markers could be used to predict tumor recurrence. Formalin fixed specimens were obtained from 39 HCC liver explants (23 with no treatment and 16 after TACE). Immunohistochemical staining was performed for EpCAM, CD44, CD90, and CD133. Staining for each marker was scored 0–3 by evaluating the number and intensity of positive tumor cells in 5 hpf of tumor in each specimen. TACE treated tumors displayed greater necrosis and fibrosis than non-TACE treated samples but there were no differences in morphology between the viable tumor cells of both groups. In TACE treated specimens, the staining of both EpCAM and CD133 was greater than in non-TACE specimens but CD44 and CD90 were the same. In the TACE group, the presence of high EpCAM staining was associated with tumor recurrence. Four of ten EpCAM high patients recurred while 0 of 6 EpCAM low patients recurred (P = 0.040). None of the other markers predicted recurrence. High pre-transplant EpCAM staining predicted HCC recurrence. This suggests that the abundance of tumor cells with a CSC phenotype may be a critical factor in the

  17. [Anti mullerian hormone (AMH)--is it a new reliable marker of the ovarian reserve? Its role in predicting the ovarian response in assisted reproductive technology (ART)].

    Science.gov (United States)

    Alshiek, Jonia Amer; Lessing, Joseph B; Amit, Ami; Azem, Foad

    2012-07-01

    Anti-Müllerian hormone (AMH) is predominantly known for its important role in the differentiation of the male and female sexual system during the early embryonic period. Recently, many animal and human researches have been studying the role of the AMH in the postnatal ovarian function. In the female, AMH is produced by the granulosa cells of early developing follicles. It plays a major role in the folliculogenesis and seems to be able to inhibit the initiation of the growth of primordial follicles and FSH-induced follicles. As AMH is expressed throughout the folliculogenesis, from the primary follicular stage to the antral stage, the serum levels of AMH may represent both the quantity and the quality of ovarian follicles. Thus, the AMH levels may be useful as a new potential marker of the ovarian reserve. As compared to other ovarian reserve tests, the AMH has unique characteristics which make it a favorable marker. The measurement of AMH levels may be useful in the prediction of poor response and cycle cancellation as well as hyper-response and the ovarian hyperstimulation syndrome in assisted reproductive technology (ART). We assume that the measurement of AMH Levels may play a role in the individualization of treatment strategies among patients who are treated by ART. However, the AMH cannot predict the qualitative ovarian response in ART. In men, the AMH was not found to have satisfactory clinical utility as a single marker of spermatogenesis. PMID:23002694

  18. Identification of circulating fetal cell markers by microarray analysis

    DEFF Research Database (Denmark)

    Brinch, Marie; Hatt, Lotte; Singh, Ripudaman;

    2012-01-01

    cells identified by XY fluorescence in situ hybridization and confirmed by reverse-color fluorescence in situ hybridization were shot off microscope slides by laser capture microdissection. The expression pattern of a subset of expressed genes was compared between fetal cells and maternal blood cells...

  19. Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance

    International Nuclear Information System (INIS)

    Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 103 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 105 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, Si

  20. Response to induction chemotherapy as predictive marker of tumor response to radiotherapy and survival in oral cavity cancer

    Directory of Open Access Journals (Sweden)

    Surendra Kumar Saini

    2015-01-01

    Full Text Available Background: Trials have shown some statistically nonsignificant survival advantage of taxane, platin and 5-FU (TPF induction chemotherapy before definitive chemoradiation. We tried to find the role of induction chemotherapy in the prediction of tumor response to radiotherapy and survival in the treatment of oral cavity cancers. Patients and Methods: Patients of stage III and IV (M0 unresectable oral cavity squamous cell carcinoma were assigned to receive two cycles of TPF. On the basis of response to chemotherapy, two groups were made. Those who had partial or more than partial response and another group who had stable disease or disease progression during chemotherapy. Concurrent chemoradiotherapy was given to all patients after induction chemotherapy. Results: A total of 128 patients who received TPF, 29 (22.6% had complete response, 57 (44.5% had partial response, 38 (29.7% had stable disease and 4 (3.1% had progressive disease. Definitive chemoradiotherapy lead to complete response in 48 (55.8% patients who had partial or more than partial response (total 86 to chemotherapy and 10 (23.8% patients among those who had stable disease or disease progression during chemotherapy (total 42. This difference in response is statistically significant (P = 0.001. Three years survival was significantly better after treatment in patients who responded more than partial (hazard ratio 0.463, 95% confidence interval 0.2789-0.7689, with an estimated 3-year survival of 35% in patients in group 1 and 14% in group 2. Conclusion: Response to induction chemotherapy can be a predictive marker for response to subsequent chemoradiotherapy and survival, with acceptable toxicities.

  1. Nocodazole treatment decreases expression of pluripotency markers Nanog and Oct4 in human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Ade Kallas

    Full Text Available Nocodazole is a known destabiliser of microtubule dynamics and arrests cell-cycle at the G2/M phase. In the context of the human embryonic stem cell (hESC it is important to understand how this arrest influences the pluripotency of cells. Here we report for the first time the changes in the expression of transcription markers Nanog and Oct4 as well as SSEA-3 and SSEA-4 in human embryonic cells after their treatment with nocodazole. Multivariate permeabilised-cell flow cytometry was applied for characterising the expression of Nanog and Oct4 during different cell cycle phases. Among untreated hESC we detected Nanog-expressing cells, which also expressed Oct4, SSEA-3 and SSEA-4. We also found another population expressing SSEA-4, but without Nanog, Oct4 and SSEA-3 expression. Nocodazole treatment resulted in a decrease of cell population positive for all four markers Nanog, Oct4, SSEA-3, SSEA-4. Nocodazole-mediated cell-cycle arrest was accompanied by higher rate of apoptosis and upregulation of p53. Twenty-four hours after the release from nocodazole block, the cell cycle of hESC normalised, but no increase in the expression of transcription markers Nanog and Oct4 was detected. In addition, the presence of ROCK-2 inhibitor Y-27632 in the medium had no effect on increasing the expression of pluripotency markers Nanog and Oct4 or decreasing apoptosis or the level of p53. The expression of SSEA-3 and SSEA-4 increased in Nanog-positive cells after wash-out of nocodazole in the presence and in the absence of Y-27632. Our data show that in hESC nocodazole reversible blocks cell cycle, which is accompanied by irreversible loss of expression of pluripotency markers Nanog and Oct4.

  2. CD133: A cancer stem cells marker, is used in colorectal cancers

    OpenAIRE

    Fei Ren; Wei-Qi Sheng; Xiang Du

    2013-01-01

    Colorectal cancer is one of the most common malignant tumors worldwide. A model of cancer development involving cancer stem cells has been put forward because it provides a possible explanation of tumor hierarchy. Cancer stem cells are characterized by their proliferation, tumorigenesis, differentiation, and self-renewal capacities, and chemoradiotherapy resistance. Due to the role of cancer stem cells in tumor initiation and treatment failure, studies of cancer stem cell markers, such as CD1...

  3. Graphical assessment of incremental value of novel markers in prediction models: From statistical to decision analytical perspectives.

    Science.gov (United States)

    Steyerberg, Ewout W; Vedder, Moniek M; Leening, Maarten J G; Postmus, Douwe; D'Agostino, Ralph B; Van Calster, Ben; Pencina, Michael J

    2015-07-01

    New markers may improve prediction of diagnostic and prognostic outcomes. We aimed to review options for graphical display and summary measures to assess the predictive value of markers over standard, readily available predictors. We illustrated various approaches using previously published data on 3264 participants from the Framingham Heart Study, where 183 developed coronary heart disease (10-year risk 5.6%). We considered performance measures for the incremental value of adding HDL cholesterol to a prediction model. An initial assessment may consider statistical significance (HR = 0.65, 95% confidence interval 0.53 to 0.80; likelihood ratio p continuous net reclassification improvement (NRI) as a summary measure. When we focus on one particular decision threshold, the changes in sensitivity and specificity are central. We propose a net reclassification risk graph, which allows us to focus on the number of reclassified persons and their event rates. Summary measures include the binary AUC, the two-category NRI, and decision analytic variants such as the net benefit (NB). Various graphs and summary measures can be used to assess the incremental predictive value of a marker. Important insights for impact on decision making are provided by a simple graph for the net reclassification risk. PMID:25042996

  4. New serum markers for small-cell lung cancer. I. The ganglioside fucosyl-GM1

    DEFF Research Database (Denmark)

    Vangsted, A; Drivsholm, L; Andersen, E;

    1994-01-01

    The ganglioside fucosyl-GM1 (FucGM1) has been suggested as a marker for small-cell lung cancer (SCLC). Immunohistochemical analyses have shown the expression of the ganglioside in tumors in 75 to 90% of patients with SCLC. We have demonstrated that the ganglioside is shedded from SCLC cells both in...

  5. (poly)Phosphoinositide phosphorylation is a marker for plasma membrane in Friend erythroleukaemic cells

    NARCIS (Netherlands)

    Rawyler, A.J.; Roelofsen, B.; Wirtz, K.W.A.; Kamp, J.A.F. op den

    1982-01-01

    Upon subcellular fractionation of (murine) Friend erythroleukaemic cells (FELCs), purified plasma membranes were identified by their high enrichment in specific marker enzymes and typical plasma membrane lipids. When FELCs were incubated for short periods with 32Pi before cell fractionation, the lip

  6. Regional differences in expression of specific markers for human embryonic stem cells

    DEFF Research Database (Denmark)

    Laursen, Steen B; Møllgård, Kjeld; Olesen, Christian;

    2007-01-01

    Characterization of human embryonic stem cell (hESC) lines derived from the inner cell masses of blastocysts generally includes expression analysis of markers such as OCT4, NANOG, SSEA3, SSEA4, TRA-1-60 and TRA-1-81. Expression is usually detected by immunocytochemical staining of entire colonies...

  7. Expression of mesenchymal stem cell marker CD90 on dermal sheath cells of the anagen hair follicle in canine species

    OpenAIRE

    Gargiulo, A.M.; Pedini, V.; C. Dall’Aglio; Ceccarelli, P.; L. Pascucci; F Mercati

    2009-01-01

    The dermal sheath (DS) of the hair follicle is comprised by fibroblast-like cells and extends along the follicular epithelium, from the bulb up to the infundibulum. From this structure, cells with stem characteristics were isolated: they have a mesenchymal origin and express CD90 protein, a typical marker of mesenchymal stem cells. It is not yet really clear in which region of hair follicle these cells are located but some experimental evidence suggests that dermal stem cells are localized pr...

  8. Biology and Molecular Markers of Malignant Gonadal Germ Cell Tumors

    OpenAIRE

    Salonen, Jonna

    2009-01-01

    Germ cell tumors occur both in the gonads of both sexes and in extra-gonadal sites during adoles-cence and early adulthood. Malignant ovarian germ cell tumors are rare neoplasms accounting for less than 5% of all cases of ovarian malignancy. In contrast, testicular cancer is the most common malignancy among young males. Most of patients survive the disease. Prognostic factors of gonadal germ cell tumors include histology, clinical stage, size of the primary tumor and residua, and levels of tu...

  9. A new marker set that identifies fetal cells in maternal circulation with high specificity

    DEFF Research Database (Denmark)

    Hatt, Lotte; Brinch, Marie; Singh, Ripudaman;

    2014-01-01

    OBJECTIVE: Fetal cells from the maternal circulation (FCMBs) have the potential to replace cells from amniotic fluid or chorionic villi in a diagnosis of common chromosomal aneuploidies. Good markers for enrichment and identification are lacking. METHOD: Blood samples from 78 normal pregnancies...... were used for testing the marker-set CD105 and CD141 for fetal cell enrichment. Fetal cell candidates were subsequently stained by a cocktail of cytokeratin antibodies, and the gender of the fetal cells was explored by fluorescence in situ hybridization (FISH) of the X and Y chromosomes. RESULTS: Fetal...... cell candidates could be detected in 91% of the samples, and in 85% of the samples, it was possible to obtain X and Y chromosomal FISH results for gender determination. The concordance between gender determined by FISH on fetal cells in maternal blood and gender found at birth reached 100% if three or...

  10. Stem cell markers in the heart of the human newborn

    Directory of Open Access Journals (Sweden)

    Armando Faa

    2016-07-01

    Full Text Available The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. Several recent studies now show that the different cell types that characterize the adult human heart arise from a common ancestor. Human cardiac stem cells differentiate into cardiomyocytes, and, in lesser extent, into smooth muscle and endothelial cells. The characterization of human cardiac stem cells (CSCs has important clinical implications. In recent years, CD117 (c-kit has been reported to mark a subtype of stem/progenitor cells in the human heart, with stem cell-like properties, including the ability to self-renewal and clonogenicity multipotentiality. Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  11. Serum markers of macrophage activation in pre-eclampsia: no predictive value of soluble CD163 and neopterin

    DEFF Research Database (Denmark)

    Kronborg, Camilla S; Knudsen, Ulla Breth; Moestrup, Søren K;

    2007-01-01

    BACKGROUND: Alternatively activated macrophages expressing the CD163 and CD206 surface receptors are the dominant immune-cell type found in the placenta. The placental number and distribution of macrophages is altered in pre-eclampsia, and the generalised inflammatory reaction associated with pre......-eclampsia group (r=0.32, p=0.011). C-reactive protein was higher in pre-eclampsia than in healthy pregnancies by week 38 (159 versus 91 nmol/l, p=0.0189). CONCLUSIONS: The macrophage serum-markers sCD163 and neopterin are not pre-symptomatic nor prognostic markers for pre-eclampsia...

  12. Oxidized alpha-1 antitrypsin as a predictive risk marker of opisthorchiasis-associated cholangiocarcinoma.

    Science.gov (United States)

    Jamnongkan, Wassana; Techasen, Anchalee; Thanan, Raynoo; Duenngai, Kunyarat; Sithithaworn, Paiboon; Mairiang, Eimorn; Loilome, Watcharin; Namwat, Nisana; Pairojkul, Chawalit; Yongvanit, Puangrat

    2013-04-01

    The oxidized alpha-1 antitrypsin (ox-A1AT) is one modified form of A1AT, generated via oxidation at its active site by free radicals released from inflammatory cells which subsequently are unable to inhibit protease enzymes. The presence of ox-A1AT in human serum has been used as oxidative stress indicator in many diseases. As oxidative/nitrative damage is one major contributor in opisthorchiasis-driven cholangiocarcinogenesis, we determined A1AT and ox-A1AT expression in human cholangiocarcinoma (CCA) tissue using immunohistochemical staining and measured serum ox-A1AT levels by ELISA. A1AT and ox-A1AT were found to be expressed in the tumor of CCA patients. The group with high expression has a significant poor prognosis. Serum levels of ox-A1AT were also significantly higher in groups of patients with heavy Opisthorchis viverrini infection, advanced periductal fibrosis (APF) and CCA when compared with healthy controls (P < 0.001). Odds ratio (OR) analysis implicated high ox-A1AT levels as a risk predictor for APF and CCA (P < 0.001; OR = 140.5 and 22.0, respectively). In conclusion, as APF may lead to hepatobiliary diseases and an increased risk of CCA development, our results identified ox-A1AT as a potential risk indicator for opisthorchiasis-associated CCA. This marker could now be explored for screening of subjects living in endemic areas where the prevalence of opisthorchiasis still remains high. PMID:23188705

  13. Characterization of colon cancer cells: a functional approach characterizing CD133 as a potential stem cell marker

    International Nuclear Information System (INIS)

    Isolation and characterization of tumourigenic colon cancer initiating cells may help to develop novel diagnostic and therapeutic procedures. We characterized a panel of fourteen human colon carcinoma cell lines and their corresponding xenografts for the surface expression of potential stem cell markers CD133, CD24, CD44, CDCP1 and CXCR4. In five cell lines and nine xenografts, mRNA expression of these markers was determined. Tumour growth behaviour of CD133+, CD133- and unsorted SW620 cells was evaluated in vivo. All five putative stem cell markers showed distinct expression patterns in the tumours examined. Two patient-derived cell lines highly expressed CD133 (> 85% of positive cells) and three other cell lines had an expression level of about 50% whereas in long-term culture based models CD133 expression ranged only from 0 to 20%. In 8/14 cell lines, more than 80% of the cells were positive for CD24 and 11/14 were over 70% positive for CD44. 10/14 cell lines expressed CDCP1 on ≥ 83% of cells. CXCR4 expression was determined solely on 94 L and SW480. Analyses of the corresponding xenografts revealed a significant reduction of cell numbers expressing the investigated surface markers and showed single cell fractions expressing up to three markers simultaneously. Statistical analysis revealed that the CXCR4 mRNA level correlates negatively with the protein expression of CD133, CD44, CD24 and CDCP1 in cell lines and xenografts. A lower differentiation grade of donor material correlated with a higher CDCP1 mRNA expression level in the respective tumour model. In vivo growth behaviour studies of SW620 revealed significantly higher take rates and shorter doubling times in the tumour growth of CD133 positive subclones in comparison to the unsorted cell line or CD133 negative subclones. Our data revealed correlations in the expression of surface markers CD44 and CD24 as well as CD44 and CDCP1 and strongly suggest that CD133 is a stem cell marker within our colon

  14. High expression of markers of apoptosis in Langerhans cell histiocytosis

    DEFF Research Database (Denmark)

    Petersen, Bodil Laub; Lundegaard, Pia Rengtved; Bank, M I;

    2003-01-01

    develop organ dysfunction. In these cases the prognosis is poor. Our objective has been to study the immunohistochemical expression of Fas and Fas-ligand (Fas-L) in order to determine whether the level of expression of these proteins could predict the outcome of the disease. We also wanted to determine...

  15. Detection of embryonic stem cell markers in adult human adipose tissue-derived stem cells

    Directory of Open Access Journals (Sweden)

    Sarasa Bharati Arumugam

    2011-01-01

    Full Text Available Background: Bone marrow transplantation is already an established therapy, which is now widely used in medicine to treat leukemia, lymphoma, and several inherited blood disorders. The culture of multilineage cells from easily available adipose tissue is another source of multipotent mesenchymal stem cells, and is referred to as adipose tissue-derived stem cells (ADSCs. While ADSCs are being used to treat various conditions, some lacuna exists regarding the specific proteins in these. It was therefore decided to analyze the specific proteins of embryonic cells in ADSCs. Aims: To analyze the specific protein of embryonic stem cells (ESCs in ADSCs. Materials and Methods: Adult human adipose tissue-derived stem cells (ADSCs were harvested from 13 patients after obtaining patients′ consent. The specific markers of ESCs included surface proteins CD10, CD13, CD44, CD59, CD105, and CD166, and further nucleostemin,(NS NANOG, peroxisome proliferator-activated receptor-gγ, collagen type 1 (Coll1, alkaline phosphate, (ALP osteocalcin (OC, and core binding factor 1 (Cbfa1 were analyzed using by reverse transcription-polymerase chain reaction, (RT-PCR immunofluorescence (IF, and western blot. Results: All the proteins were expressed distinctly, except CD13 and OC. CD13 was found individually with different expressions, and OC expression was discernable. Conclusions: Although the ESC with its proven self-renewal capacity and pluripotency seems appropriate for clinical use, the recent work on ADSCs suggests that these adult stem cells would be a valuable source for future biotechnology, especially since there is a relative ease of procurement.

  16. Glow in the Dark: Fluorescent Proteins as Cell and Tissue-Specific Markers in Plants

    Institute of Scientific and Technical Information of China (English)

    Wenzislava Ckurshumova; Adriana E. Caragea; Rochelle S. Goldstein; Thomas Berleth

    2011-01-01

    Since the hallmark discovery of Aequorea victoria's Green Fluorescent Protein (GFP) and its adaptation for efficient use in plants,fluorescent protein tags marking expression profiles or genuine proteins of interest have been used to recognize plant tissues and cell types,to monitor dynamic cell fate selection processes,and to obtain cell type-specific transcriptomes.Fluorescent tagging enabled visualization in living tissues and the precise recordings of dynamic expression pattern changes.The resulting accurate recording of cell fate acquisition kinetics in space and time has strongly stimulated mathematical modeling of self-organizing feedback mechanisms.In developmental studies,the use of fluorescent proteins has become critical,where morphological markers of tissues,cell types,or differentiation stages are either not known or not easily recognizable.In this review,we focus on the use of fluorescent markers to identify and illuminate otherwise invisible cell states in plant development.

  17. Human Breast Cancer Cell Lines Co-Express Neuronal, Epithelial, and Melanocytic Differentiation Markers In Vitro and In Vivo

    OpenAIRE

    Qingbei Zhang; Hanli Fan; Jikun Shen; Hoffman, Robert M.; H Rosie Xing

    2010-01-01

    Differentiation programs are aberrant in cancer cells allowing them to express differentiation markers in addition to their tissue of origin. In the present study, we demonstrate the multi-lineage differentiation potential of breast cancer cell lines to express multiple neuronal/glial lineage-specific markers as well as mammary epithelial and melanocytic-specific markers. Multilineage expression was detected in luminal (MCF-7 and SKBR3) and basal (MDA-MB-231) types of human breast cancer cell...

  18. Microfluidic single-cell transcriptional analysis rationally identifies novel surface marker profiles to enhance cell-based therapies.

    Science.gov (United States)

    Rennert, Robert C; Januszyk, Michael; Sorkin, Michael; Rodrigues, Melanie; Maan, Zeshaan N; Duscher, Dominik; Whittam, Alexander J; Kosaraju, Revanth; Chung, Michael T; Paik, Kevin; Li, Alexander Y; Findlay, Michael; Glotzbach, Jason P; Butte, Atul J; Gurtner, Geoffrey C

    2016-01-01

    Current progenitor cell therapies have only modest efficacy, which has limited their clinical adoption. This may be the result of a cellular heterogeneity that decreases the number of functional progenitors delivered to diseased tissue, and prevents correction of underlying pathologic cell population disruptions. Here, we develop a high-resolution method of identifying phenotypically distinct progenitor cell subpopulations via single-cell transcriptional analysis and advanced bioinformatics. When combined with high-throughput cell surface marker screening, this approach facilitates the rational selection of surface markers for prospective isolation of cell subpopulations with desired transcriptional profiles. We establish the usefulness of this platform in costly and highly morbid diabetic wounds by identifying a subpopulation of progenitor cells that is dysfunctional in the diabetic state, and normalizes diabetic wound healing rates following allogeneic application. We believe this work presents a logical framework for the development of targeted cell therapies that can be customized to any clinical application. PMID:27324848

  19. Following damage, the majority of bone marrow-derived airway cells express an epithelial marker

    OpenAIRE

    MacPherson, Heather; Keir, Pamela A; Edwards, Carol J; Webb, Sheila; Dorin, Julia R.

    2006-01-01

    Adult-derived bone marrow stem cells are capable of reconstituting the haematopoietic system. However there is ongoing debate in the literature as to whether bone marrow derived cells have the ability to populate other tissues and express tissue specific markers. The airway has been an organ of major interest and was one of the first where this was demonstrated. We have previously demonstrated that the mouse airway can be repopulated by side population bone marrow transplanted cells. Here we ...

  20. CD10 is a marker for cycling cells with propensity to apoptosis in childhood ALL

    OpenAIRE

    G. Cutrona; Tasso, P; Dono, M; Roncella, S; M. ULIVI; Carpaneto, E M; Fontana, V; Comis, M; F. Morabito; Spinelli, M.; Frascella, E.; Boffa, L C; G. Basso; Pistoia, V.; Ferrarini, M.

    2002-01-01

    CD10 constitutes a favourable prognostic marker for childhood acute lymphoblastic leukaemia. Since correlations between CD10, cell cycle and apoptotic abilities were demonstrated in various cell types, we investigated whether differences existed in the cycling/apoptotic abilities of CD10-positive and CD10-negative B acute lymphoblastic leukaemia cells. Twenty-eight cases of childhood acute lymphoblastic leukaemia (mean age of 6.8 years) were subdivided into two groups according to high (17 ca...

  1. Cell surface carbohydrates as prognostic markers in human carcinomas

    DEFF Research Database (Denmark)

    Dabelsteen, Erik

    1996-01-01

    cell types; within a given tissue, variation in expression may be related to cell maturation. Tumour-associated carbohydrate structures often reflect a certain stage of cellular development; most of these moieties are structures normally found in other adult or embryonic tissues. There is no unique......Tumour development is usually associated with changes in cell surface carbohydrates. These are often divided into changes related to terminal carbohydrate structures, which include incomplete synthesis and modification of normally existing carbohydrates, and changes in the carbohydrate core...... tumour carbohydrate structure, since certain structures which are tumour-related in one organ may be normal constituents of other tissues. Tumour-associated carbohydrate changes have been used in the diagnosis of human cancers. Recently, however, it has been demonstrated that the expression of some...

  2. PDGFRβ Is a Novel Marker of Stromal Activation in Oral Squamous Cell Carcinomas

    Science.gov (United States)

    Han, Rong; Haines, Paul; Gallagher, George; Noonan, Vikki; Kukuruzinska, Maria; Monti, Stefano; Trojanowska, Maria

    2016-01-01

    Carcinoma associated fibroblasts (CAFs) form the main constituents of tumor stroma and play an important role in tumor growth and invasion. The presence of CAFs is a strong predictor of poor prognosis of head and neck squamous cell carcinoma. Despite significant progress in determining the role of CAFs in tumor progression, the mechanisms contributing to their activation remain poorly characterized, in part due to fibroblast heterogeneity and the scarcity of reliable fibroblast surface markers. To search for such markers in oral squamous cell carcinoma (OSCC), we applied a novel approach that uses RNA-sequencing data derived from the cancer genome atlas (TCGA). Specifically, our strategy allowed for an unbiased identification of genes whose expression was closely associated with a set of bona fide stroma-specific transcripts, namely the interstitial collagens COL1A1, COL1A2, and COL3A1. Among the top hits were genes involved in cellular matrix remodeling and tumor invasion and migration, including platelet-derived growth factor receptor beta (PDGFRβ), which was found to be the highest-ranking receptor protein genome-wide. Similar analyses performed on ten additional TCGA cancer datasets revealed that other tumor types shared CAF markers with OSCC, including PDGFRβ, which was found to significantly correlate with the reference collagen expression in ten of the 11 cancer types tested. Subsequent immunostaining of OSCC specimens demonstrated that PDGFRβ was abundantly expressed in stromal fibroblasts of all tested cases (12/12), while it was absent in tumor cells, with greater specificity than other known markers such as alpha smooth muscle actin or podoplanin (3/11). Overall, this study identified PDGFRβ as a novel marker of stromal activation in OSCC, and further characterized a list of promising candidate CAF markers that may be relevant to other carcinomas. Our novel approach provides for a fast and accurate method to identify CAF markers without the need for

  3. Quantitative trait loci markers derived from whole genome sequence data increases the reliability of genomic prediction

    DEFF Research Database (Denmark)

    Brøndum, Rasmus Froberg; Su, Guosheng; Janss, Luc;

    2015-01-01

    the aim of augmenting the custom low-density Illumina BovineLD SNP chip (San Diego, CA) used in the Nordic countries. The single-marker analysis was done breed-wise on all 16 index traits included in the breeding goals for Nordic Holstein, Danish Jersey, and Nordic Red cattle plus the total merit...... percentage point was observed for mastitis, but only a 0.5 percentage point increase was seen for fertility. When using a Bayesian model accuracies were generally higher with only 54k data compared with the genomic BLUP approach, but increases in reliability were relatively smaller when QTL markers were...

  4. Predictive and prognostic effect of CD133 and cancer-testis antigens in stage Ib-IIIA non-small cell lung cancer

    OpenAIRE

    SU, CHUNXIA; Xu, Ying; Xuefei LI; Ren, Shengxiang; Zhao, Chao; Hou, Likun; Ye, Zhiwei; Zhou, Caicun

    2015-01-01

    CD133 and cancer-testis antigens (CTAs) may be potential predicted markers of adjuvant chemotherapy or immune therapy, and they may be the independent prognostic factor of NSCLC. Nowadays, there is still no predictive biomarker identified for the use of adjuvant chemotherapy in non-small cell lung cancer (NSCLC) patients. To clarify the role of CD133 and CTAs as a predictive marker for adjuvant chemotherapy or prognostic factors of overall survival, we performed a retrospective study in 159 s...

  5. Cardiomyocyte marker expression in a human lymphocyte cell line using mouse cardiomyocyte extract.

    Science.gov (United States)

    Vojdani, Zahra; Tavakolinejad, Sima; Talaei-Khozani, Tahereh; Esmaeilpour, Tahereh; Rasooli, Manuchehr

    2011-03-01

    Cell transplantation shows potential for the treatment of cardiac diseases. Embryonic stem cells, cord blood and mesenchymal stem cells have been suggested as sources for transplantation therapy. Because of some technical limitations with the use of stem cells, transdifferentiation of fully differentiated cells is a potentially useful alternative. We investigated whether human peripheral blood cells could transdifferentiate into cardiomyocyte. Transdifferentiation was induced in a human B lymphocyte cell line (Raji). Cardiomyocyte extract was prepared from adult mouse cardiomyocytes. The cells were treated with 5-aza-2-deoxycytidine and trichostatin A, permeabilized with streptolysin O, and exposed to the mouse cardiomyocyte extract. They were cultured for 10 days, 3 weeks and 4 weeks. Cardiomyocyte markers were detected with immunohistochemistry and flow cytometry. Immunocytochemistry revealed that some cells expressed myosin heavy chain, α-actinin and cardiac troponin T after 3 and 4 weeks. Flow cytometry confirmed these data. In cells exposed to trichostatin A and 5-aza-2-deoxycytidine and permeabilized in the presence of the cardiomyocyte extract, troponin T expression was seen in 3.53% of the cells and 3.11% of them expressed α-actinin. After exposure to the cardiomyocyte extract, some permeabilized cells adhered to the plate loosely; however, the morphology did not change significantly, and they continued to show a rounded shape after 4 weeks. Our treated lymphocytes expressed cardiomyocyte markers. Our results suggest that lymphocytes may be useful in future research as a source of cells for reprogramming procedures. PMID:21547694

  6. LRRN4 and UPK3B are markers of primary mesothelial cells.

    Directory of Open Access Journals (Sweden)

    Mutsumi Kanamori-Katayama

    Full Text Available BACKGROUND: Mesothelioma is a highly malignant tumor that is primarily caused by occupational or environmental exposure to asbestos fibers. Despite worldwide restrictions on asbestos usage, further cases are expected as diagnosis is typically 20-40 years after exposure. Once diagnosed there is a very poor prognosis with a median survival rate of 9 months. Considering this the development of early pre clinical diagnostic markers may help improve clinical outcomes. METHODOLOGY: Microarray expression arrays on mesothelium and other tissues dissected from mice were used to identify candidate mesothelial lineage markers. Candidates were further tested by qRTPCR and in-situ hybridization across a mouse tissue panel. Two candidate biomarkers with the potential for secretion, uroplakin 3B (UPK3B, and leucine rich repeat neuronal 4 (LRRN4 and one commercialized mesothelioma marker, mesothelin (MSLN were then chosen for validation across a panel of normal human primary cells, 16 established mesothelioma cell lines, 10 lung cancer lines, and a further set of 8 unrelated cancer cell lines. CONCLUSIONS: Within the primary cell panel, LRRN4 was only detected in primary mesothelial cells, but MSLN and UPK3B were also detected in other cell types. MSLN was detected in bronchial epithelial cells and alveolar epithelial cells and UPK3B was detected in retinal pigment epithelial cells and urothelial cells. Testing the cell line panel, MSLN was detected in 15 of the 16 mesothelioma cells lines, whereas LRRN4 was only detected in 8 and UPK3B in 6. Interestingly MSLN levels appear to be upregulated in the mesothelioma lines compared to the primary mesothelial cells, while LRRN4 and UPK3B, are either lost or down-regulated. Despite the higher fraction of mesothelioma lines positive for MSLN, it was also detected at high levels in 2 lung cancer lines and 3 other unrelated cancer lines derived from papillotubular adenocarcinoma, signet ring carcinoma and transitional

  7. Compatibility of pedigree-based and marker-based relationships for single-step genomic prediction

    DEFF Research Database (Denmark)

    Christensen, Ole Fredslund

    2012-01-01

    marker-based relationship matrix is constructed assuming all allele frequencies equal to 0.5 and the pedigree-based relationship matrix is constructed using the unusual assumption that animals in the base population are related and inbreed with relationship coefficient alpha and inbreeding coefficient...

  8. Prediction of industrial tomato hybrids from agronomic traits and ISSR molecular markers.

    Science.gov (United States)

    Figueiredo, A S T; Resende, J T V; Faria, M V; Da-Silva, P R; Fagundes, B S; Morales, R G F

    2016-01-01

    Heterosis is a highly relevant phenomenon in plant breeding. This condition is usually established in hybrids derived from crosses of highly divergent parents. The success of a breeder in obtaining heterosis is directly related to the correct identification of genetically contrasting parents. Currently, the diallel cross is the most commonly used methodology to detect contrasting parents; however, it is a time- and cost-consuming procedure. Therefore, new tools capable of performing this task quickly and accurately are required. Thus, the purpose of this study was to estimate the genetic divergence in industrial tomato lines, based on agronomic traits, and to compare with estimates obtained using inter-simple sequence repeat (ISSR) molecular markers. The genetic divergence among 10 industrial tomato lines, based on nine morphological characters and 12 ISSR primers was analyzed. For data analysis, Pearson and Spearman correlation coefficients were calculated between the genetic dissimilarity measures estimated by Mahalanobis distance and Jaccard's coefficient of genetic dissimilarity from the heterosis estimates, combining ability, and means of important traits of industrial tomato. The ISSR markers efficiently detected contrasting parents for hybrid production in tomato. Parent RVTD-08 was indicated as the most divergent, both by molecular and morphological markers, that positively contributed to increased heterosis and by the specific combining ability in the crosses in which it participated. The genetic dissimilarity estimated by ISSR molecular markers aided the identification of the best hybrids of the experiment in terms of total fruit yield, pulp yield, and soluble solids content. PMID:27323023

  9. Streptozocin-Based Chemotherapy in Patients with Advanced Neuroendocrine Neoplasms – Predictive and Prognostic Markers for Treatment Stratification

    Science.gov (United States)

    Krug, Sebastian; Boch, Michael; Daniel, Hanna; Nimphius, Wilhelm; Müller, Daniela; Michl, Patrick; Rinke, Anja; Gress, Thomas Matthias

    2015-01-01

    Background and Aim Chemotherapy with streptozocin (STZ) in combination with 5-FU or doxorubicin (Dox) represents a standard of care for patients with metastatic pancreatic neuroendocrine neoplasms (pNEN). However, predictive markers for patient selection are still missing. The aim of this study was a retrospective evaluation of the clinicopathological characteristics of pNEN patients receiving STZ-based chemotherapies and to identify predictive and prognostic markers. Patients and Methods We retrospectively analyzed 77 patients treated at our center between 1995 and 2013. The median overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier and Cox regression methods, respectively. Uni- and multivariate analyses were performed. Results The median PFS (mPFS) in patients receiving STZ/5-FU/Dox was 16 months with a median OS (mOS) of 28 months. Objective response rate (ORR) and disease control rate (DCR) were 34% and 72%, respectively. Biochemical response and positive octreotide scintigraphy predicted objective response. Univariate analysis revealed Ki-67 > 10% and the absence of biochemical or objective response by imaging as independent risk factors for shorter PFS. Additionally, performance status (PS) and resection of the primary tumor were observed to influence mOS. Treatment was well tolerated with less than 10% grade 3 and 4 toxicities. Conclusions STZ-based chemotherapy is an effective and well-tolerated treatment option in patients with well differentiated neuroendocrine neoplasms. Positive octreotide scintigraphy and biochemical response predict objective response. PMID:26630134

  10. The autophagy-related marker LC3 can predict prognosis in human hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Yoo Jin Lee

    Full Text Available BACKGROUND: Defects of autophagy and endoplasmic reticulum (ER stress are related to many diseases and tumors. However, only a few studies have examined hepatocellular carcinoma (HCC as related to these processes. Therefore, in this study, we investigated the expression and extent of autophagy and ER stress-related markers in HCC and their influence on clinical characteristics and prognosis for each protein. METHODOLOGY: The expression of autophagy-related markers (LC3 and Beclin-1 and ER stress-related markers (GRP78 and CHOP was analyzed by immunohistochemistry on tissues from completely resected specimens of 190 HCC patients. Their influence on clinicopathologic features and prognosis were evaluated using the chi-square test and Kaplan-Meier analysis. Correlations of each protein were determined by Spearman's correlation analysis. PRINCIPAL FINDINGS: LC3 expression was not correlated with TNM, BCLC stage, or Edmonson-Steiner grading, whereas it was correlated with longer overall survival (OS (p = 0.039 and tended to be related with longer time to recurrence (TTR (p=0.068 although it did not show statistical significance. Multivariate analysis indicated that LC3 expression was a significantly independent prognostic factor of OS (HR, 0.42; 95% CI, 0.22-0.80; p-value=0.009 and TTR (HR, 0.54; 95% CI, 0.33-0.90; p=0.017. Expression of LC3 in advanced stages of TNM (III (p=0.045 and Edmonson-Steiner Grades (III and IV (p=0.043 was correlated with longer survival, but not in the early stages. A positive correlation was not observed between the expression of autophagy-related markers and ER stress-related markers. CONCLUSION: Our results suggest that the expression and extent of LC3 might be a strong prognostic factor of HCC, especially in patients with surgical resection.

  11. ABCG2 regulates self-renewal and stem cell marker expression but not tumorigenicity or radiation resistance of glioma cells

    Science.gov (United States)

    Wee, Boyoung; Pietras, Alexander; Ozawa, Tatsuya; Bazzoli, Elena; Podlaha, Ondrej; Antczak, Christophe; Westermark, Bengt; Nelander, Sven; Uhrbom, Lene; Forsberg-Nilsson, Karin; Djaballah, Hakim; Michor, Franziska; Holland, Eric C.

    2016-01-01

    Glioma cells with stem cell traits are thought to be responsible for tumor maintenance and therapeutic failure. Such cells can be enriched based on their inherent drug efflux capability mediated by the ABC transporter ABCG2 using the side population assay, and their characteristics include increased self-renewal, high stem cell marker expression and high tumorigenic capacity in vivo. Here, we show that ABCG2 can actively drive expression of stem cell markers and self-renewal in glioma cells. Stem cell markers and self-renewal was enriched in cells with high ABCG2 activity, and could be specifically inhibited by pharmacological and genetic ABCG2 inhibition. Importantly, despite regulating these key characteristics of stem-like tumor cells, ABCG2 activity did not affect radiation resistance or tumorigenicity in vivo. ABCG2 effects were Notch-independent and mediated by diverse mechanisms including the transcription factor Mef. Our data demonstrate that characteristics of tumor stem cells are separable, and highlight ABCG2 as a potential driver of glioma stemness. PMID:27456282

  12. The use of lectins as markers for differentiated secretory cells in planarians.

    Science.gov (United States)

    Zayas, Ricardo M; Cebrià, Francesc; Guo, Tingxia; Feng, Junjie; Newmark, Phillip A

    2010-11-01

    Freshwater planarians have reemerged as excellent models to investigate mechanisms underlying regeneration. The introduction of molecular tools has facilitated the study of planarians, but cell- and tissue-specific markers are still needed to examine differentiation of most cell types. Here we report the utility of fluorescent lectin-conjugates to label tissues in the planarian Schmidtea mediterranea. We show that 16 lectin-conjugates stain planarian cells or tissues; 13 primarily label the secretory cells, their cytoplasmic projections, and terminal pores. Thus, we examined regeneration of the secretory system using lectin markers and functionally characterized two genes expressed in the secretory cells: marginal adhesive gland-1 (mag-1) and Smed-reticulocalbin1 (Smed-rcn1). RNAi knockdown of these genes caused a dramatic reduction of secretory cell lectin staining, suggesting a role for mag-1 and Smed-rcn1 in secretory cell differentiation. Our results provide new insights into planarian secretory system regeneration and add new markers for labeling several planarian tissues. PMID:20865784

  13. Prognostic Value of Cancer Stem Cells Markers in Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Francesca Collina

    2015-01-01

    Full Text Available Triple-negative breast cancer (TNBC has a significant clinical relevance of being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. Increased aggressiveness of this tumor, as well as resistance to standard drug therapies, may be associated with the presence of stem cell populations within the tumor. Several stemness markers have been described for the various histological subtypes of breast cancer, such as CD44, CD24, CD133, ALDH1, and ABCG2. The role of these markers in breast cancer is not clear yet and above all there are conflicting opinions about their real prognostic value. To investigate the role of CSCs markers in TNBC cancerogenesis and tumor progression, we selected 160 TNBCs samples on which we detected protein expression of CD44, CD24, CD133, ALDH1, and ABCG2 by immunohistochemistry. Our results highlighted a real prognostic role only for CD44 in TNBCs. All other CSCs markers do not appear to be related to the survival of TNBC patients. In conclusion, despite the fact that the presence of the cancer stem cells in the tumor provides important information on its potential aggressiveness, today their detection by immunohistochemistry is not sufficient to confirm their role in carcinogenesis, because specific markers probably are not yet identified.

  14. Neuronal classification and marker gene identification via single-cell expression profiling of brainstem vestibular neurons subserving cerebellar learning

    OpenAIRE

    Kodama, Takashi; Guerrero, Shiloh; Shin, Minyoung; Moghadam, Seti; Faulstich, Michael; du Lac, Sascha

    2012-01-01

    Identification of marker genes expressed in specific cell types is essential for the genetic dissection of neural circuits. Here we report a new strategy for classifying heterogeneous populations of neurons into functionally distinct types and for identifying associated marker genes. Quantitative single-cell expression profiling of genes related to neurotransmitters and ion channels enables functional classification of neurons; transcript profiles for marker gene candidates identify molecular...

  15. Sex‐Specific Differences in the Predictive Value of Cholesterol Homeostasis Markers and 10‐Year Cardiovascular Disease Event Rate in Framingham Offspring Study Participants

    OpenAIRE

    Matthan, Nirupa R; Zhu, Lei; Pencina, Michael; D'Agostino, Ralph B.; Schaefer, Ernst J.; Lichtenstein, Alice H.

    2013-01-01

    Background Available data are inconsistent regarding factors influencing plasma cholesterol homeostasis marker concentrations and their value in predicting subsequent cardiovascular disease (CVD) events. Methods and Results To address this issue, the relationship between markers of cholesterol absorption (campesterol, sitosterol, cholestanol) and synthesis (squalene, desmosterol, lathosterol) and 10‐year CVD incidence was assessed in Framingham Offspring Study participants (cycle 6) who were ...

  16. A Quantitative Perspective on Surface Marker Selection for the Isolation of Functional Tumor Cells

    OpenAIRE

    Cahall, Calvin F; Lilly, Jacob L.; Hirschowitz, Edward A.; Berron, Brad J

    2015-01-01

    Much effort has gone into developing fluid biopsies of patient peripheral blood for the monitoring of metastatic cancers. One common approach is to isolate and analyze tumor cells in the peripheral blood. Widespread clinical implementation of this approach has been hindered by the current choice of targeting epithelial markers known to be highly variable in primary tumor sites. Here, we review current antigen-based tumor cell isolation strategies and offer biological context for commonly stud...

  17. Complementation of two related tumour cell classes during experimental metastasis tagged with different histochemical marker genes.

    OpenAIRE

    Lin, W.C.; O'Connor, K. L.; Culp, L. A.

    1993-01-01

    Intercellular complementation during tumour development and metastasis was analysed for two different oncogene (ras or sis) transformants of Balb/c 3T3 cells, tagged with different histochemical marker genes (lacZ or ALP to generate LZEJ or APSI cells, respectively), by localising them after their co-injection with specific double-staining protocols. This model evaluates whether limited progression of each tumour class can be facilitated reciprocally during co-localisation and co-growth in nu...

  18. (poly)Phosphoinositide phosphorylation is a marker for plasma membrane in Friend erythroleukaemic cells

    OpenAIRE

    Rawyler, A.J.; Roelofsen, B; Wirtz, K.W.A.; Kamp, J.A.F. op den

    1982-01-01

    Upon subcellular fractionation of (murine) Friend erythroleukaemic cells (FELCs), purified plasma membranes were identified by their high enrichment in specific marker enzymes and typical plasma membrane lipids. When FELCs were incubated for short periods with 32Pi before cell fractionation, the lipid-bound radioactivity was almost exclusively present in phosphatidylinositol-4-phosphate (DPI) and phosphatidylinositol-4,5-bisphosphate (TPI), and its distribution closely matched that of the pla...

  19. Effect of radiation on the expression of osteoclast marker genes in RAW264.7 cells

    OpenAIRE

    Yang, Bing; Zhou, Hui; Zhang, Xiao-Dong; Liu, Zheng; Fan, Fei-Yue; Sun, Yuan-Ming

    2012-01-01

    Cancer radiation therapy can cause skeletal complications, such as osteopenia and osteoporosis. To understand the mechanism responsible for the skeletal complications, the expression profiles of osteoclast marker genes in RAW264.7 cells were observed. Osteoclast formation was established by RAW264.7 cells that were treated with the receptor activator of nuclear factor (NF)-κB ligand (RANKL) and detected using immunochemistry and morphological observations. Quantitative real-time polymerase ch...

  20. Circulating levels of cell adhesion molecule L1 as a prognostic marker in gastrointestinal stromal tumor patients

    International Nuclear Information System (INIS)

    L1 cell adhesion molecule (CD171) is expressed in many malignant tumors and its expression correlates with unfavourable outcome. It thus represents a target for tumor diagnosis and therapy. An earlier study conducted by our group identified L1 expression levels in primary gastrointestinal stromal tumors (GIST) as a prognostic marker. The aim of the current study was to compare L1 serum levels of GIST patients with those of healthy controls and to determine whether levels of soluble L1 in sera could serve as a prognostic marker. Using a sensitive enzyme-linked immunosorbent assay (ELISA), soluble L1 was measured in sera of 93 GIST patients und 151 healthy controls. Soluble L1 levels were then correlated with clinicopathological data. Median levels of soluble L1 were significantly higher (p < 0.001; Mann-Whitney U test) in sera of GIST patients compared to healthy individuals. Median soluble L1 levels were particularly elevated in patients with recurrence and relapse (p < 0.05; Mann Whitney U test). These results suggest that high soluble L1 levels predict poor prognosis and may thus be a promising tumor marker that can contribute to individualise therapy

  1. Circulating levels of cell adhesion molecule L1 as a prognostic marker in gastrointestinal stromal tumor patients

    Directory of Open Access Journals (Sweden)

    Schachner Melitta

    2011-05-01

    Full Text Available Abstract Background L1 cell adhesion molecule (CD171 is expressed in many malignant tumors and its expression correlates with unfavourable outcome. It thus represents a target for tumor diagnosis and therapy. An earlier study conducted by our group identified L1 expression levels in primary gastrointestinal stromal tumors (GIST as a prognostic marker. The aim of the current study was to compare L1 serum levels of GIST patients with those of healthy controls and to determine whether levels of soluble L1 in sera could serve as a prognostic marker. Methods Using a sensitive enzyme-linked immunosorbent assay (ELISA, soluble L1 was measured in sera of 93 GIST patients und 151 healthy controls. Soluble L1 levels were then correlated with clinicopathological data. Results Median levels of soluble L1 were significantly higher (p p Conclusion These results suggest that high soluble L1 levels predict poor prognosis and may thus be a promising tumor marker that can contribute to individualise therapy.

  2. Serum trypsin and TCR as novel markers for predicting disease activity in IgG4-related disease

    OpenAIRE

    Fengqing, Wang; Qiang, Yi; Feng, Gao; Zehao, Zhuang; Yuefei, Ma; Jing, Chen; Guina, Wang; Bing, Hu; Jing, Zheng; Jingjing, Zhang; Danfeng, Lu; Rui, Ha; Qi-Cai, Liu

    2014-01-01

    Background IgG4-related disease (IgG4-RD) is a novel disease named in recent years. Because of its varied clinical manifestations, like tumor but not tumor, it brings a great challenge to clinical diagnosis. Trypsin and T-cell receptor (TCR) are thought to mediate the regulation of B cell maturation, survival and antibody production. In this study, we investigated the clinical features and important novel markers of IgG4-RD. Material and methods A prospective cohort study of 22 patients with ...

  3. Breast cancers radiation-resistance: key role of the cancer stem cells marker CD24

    International Nuclear Information System (INIS)

    This work focuses on the characterization of radiation-resistant breast cancer cells, responsible for relapse after radiotherapy. The 'Cancer Stem Cells' (CSC) theory describes a radiation-resistant cellular sub-population, with enhanced capacity to induce tumors and proliferate. In this work, we show that only the CSC marker CD24-/low defines a radiation resistant cell population, able to transmit the 'memory' of irradiation, expressed as long term genomic instability in the progeny of irradiated cells. We show that CD24 is not only a marker, but is an actor of radiation-response. So, CD24 expression controls cell proliferation in vitro and in vivo, and ROS level before and after irradiation. As a result, CD24-/low cells display enhanced radiation-resistance and genomic stability. For the first time, our results attribute a role to CD24-/low CSCs in the transmission of genomic instability. Moreover, by providing informations on tumor intrinsic radiation-sensitivity, CD24- marker could help to design new radiotherapy protocols. (author)

  4. Isopropanolic Cimicifuga racemosa is favorable on bone markers but neutral on an osteoblastic cell line.

    Science.gov (United States)

    García-Pérez, Miguel Angel; Pineda, Begoña; Hermenegildo, Carlos; Tarín, Juan J; Cano, Antonio

    2009-04-01

    Postmenopausal women treated with an isopropanolic extract of Cimicifuga racemosa underwent a decrease in the urinary concentration of N-telopeptides, a marker of bone resorption, and an increase in alkaline phosphatase, a marker of bone formation, at the third month of therapy. Serum from treated women did not modify the activity of alkaline phosphatase or the expression of three genes, runt-related transcription factor-2 (Runx-2), alkaline phosphatase, and osteocalcin, when added to the MC3T3-E1 osteoblastic cell line. PMID:18555220

  5. Predicting Impending Death: Inconsistency in Speed is a Selective and Early Marker

    OpenAIRE

    MacDonald, Stuart W. S.; Hultsch, David F.; Dixon, Roger A.

    2008-01-01

    Among older adults, deficits in both level and variability of speeded performance are linked to neurological impairment. This study examined whether and when speed (rate), speed (inconsistency), and traditional accuracy-based markers of cognitive performance foreshadow terminal decline and impending death. Victoria Longitudinal Study data spanning 12 years (5 waves) of measurement were assembled for 707 adults aged 59 to 95 years. Whereas 442 survivors completed all waves and relevant measure...

  6. Identification of Meflin as a Potential Marker for Mesenchymal Stromal Cells

    Science.gov (United States)

    Maeda, Keiko; Enomoto, Atsushi; Hara, Akitoshi; Asai, Naoya; Kobayashi, Takeshi; Horinouchi, Asuka; Maruyama, Shoichi; Ishikawa, Yuichi; Nishiyama, Takahiro; Kiyoi, Hitoshi; Kato, Takuya; Ando, Kenju; Weng, Liang; Mii, Shinji; Asai, Masato; Mizutani, Yasuyuki; Watanabe, Osamu; Hirooka, Yoshiki; Goto, Hidemi; Takahashi, Masahide

    2016-01-01

    Bone marrow-derived mesenchymal stromal cells (BM-MSCs) in culture are derived from BM stromal cells or skeletal stem cells. Whereas MSCs have been exploited in clinical medicine, the identification of MSC-specific markers has been limited. Here, we report that a cell surface and secreted protein, Meflin, is expressed in cultured MSCs, fibroblasts and pericytes, but not other types of cells including epithelial, endothelial and smooth muscle cells. In vivo, Meflin is expressed by immature osteoblasts and chondroblasts. In addition, Meflin is found on stromal cells distributed throughout the BM, and on pericytes and perivascular cells in multiple organs. Meflin maintains the undifferentiated state of cultured MSCs and is downregulated upon their differentiation, consistent with the observation that Meflin-deficient mice exhibit increased number of osteoblasts and accelerated bone development. In the bone and BM, Meflin is more highly expressed in primitive stromal cells that express platelet-derived growth factor receptor α and Sca-1 than the Sca-1-negative adipo-osteogenic progenitors, which create a niche for hematopoiesis. Those results are consistent with a decrease in the number of clonogenic colony-forming unit-fibroblasts within the BM of Meflin-deficient mice. These preliminary data suggest that Meflin is a potential marker for cultured MSCs and their source cells in vivo. PMID:26924503

  7. A novel strategy for enrichment and isolation of osteoprogenitor cells from induced pluripotent stem cells based on surface marker combination.

    Directory of Open Access Journals (Sweden)

    Hiromi Ochiai-Shino

    Full Text Available In this study, we developed a new method to stimulate osteogenic differentiation in tissue-nonspecific alkaline phosphatase (TNAP-positive cells liberated from human induced pluripotent stem cells (hiPSCs-derived embryoid bodies (EBs with 14 days long TGF-β/IGF-1/FGF-2 treatment. TNAP is a marker protein of osteolineage cells. We analyzed and isolated TNAP-positive and E-cadherin-negative nonepithelial cells by fluorescence-activated cell sorting. Treating the cells with a combination of transforming growth factor (TGF-β, insulin-like growth factor (IGF-1, and fibroblast growth factor (FGF-2 for 14 days greatly enhanced TNAP expression and maximized expression frequency up to 77.3%. The isolated cells expressed high levels of osterix, which is an exclusive osteogenic marker. Culturing these TNAP-positive cells in osteoblast differentiation medium (OBM led to the expression of runt-related transcription factor 2, type I collagen, bone sialoprotein, and osteocalcin (OCN. These cells responded to treatment with activated vitamin D3 by upregulating OCN. Furthermore, in OBM they were capable of generating many mineralized nodules with strong expression of receptor activator of NF-kappaB ligand and sclerostin (SOST. Real-time RT-PCR showed a significant increase in the expression of osteocyte marker genes, including SOST, neuropeptide Y, and reelin. Scanning electron microscopy showed dendritic morphology. Examination of semi-thin toluidine blue-stained sections showed many interconnected dendrites. Thus, TNAP-positive cells cultured in OBM may eventually become terminally differentiated osteocyte-like cells. In conclusion, treating hiPSCs-derived cells with a combination of TGF-β, IGF-1, and FGF-2 generated TNAP-positive cells at high frequency. These TNAP-positive cells had a high osteogenic potential and could terminally differentiate into osteocyte-like cells. The method described here may reveal new pathways of osteogenesis and provide a novel

  8. Lysophosphatidic Acid Receptor Is a Functional Marker of Adult Hippocampal Precursor Cells

    Directory of Open Access Journals (Sweden)

    Tara L. Walker

    2016-04-01

    Full Text Available Here, we show that the lysophosphatidic acid receptor 1 (LPA1 is expressed by a defined population of type 1 stem cells and type 2a precursor cells in the adult mouse dentate gyrus. LPA1, in contrast to Nestin, also marks the quiescent stem cell population. Combining LPA1-GFP with EGFR and prominin-1 expression, we have enabled the prospective separation of both proliferative and non-proliferative precursor cell populations. Transcriptional profiling of the isolated proliferative precursor cells suggested immune mechanisms and cytokine signaling as molecular regulators of adult hippocampal precursor cell proliferation. In addition to LPA1 being a marker of this important stem cell population, we also show that the corresponding ligand LPA is directly involved in the regulation of adult hippocampal precursor cell proliferation and neurogenesis, an effect that can be attributed to LPA signaling via the AKT and MAPK pathways.

  9. Novel tumor markers in the serum of testicular germ cell cancer patients: a review

    Directory of Open Access Journals (Sweden)

    Syring I

    2014-09-01

    Full Text Available Isabella Syring, Stefan C Müller, Jörg Ellinger Department for Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany Abstract: Serum tumor markers have an important role in the management of patients with testicular cancer. They are useful for diagnosis, staging and risk assessment, follow-up, evaluation of response, and early detection of relapse. Alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are established serum markers in testicular cancer, but they have a limited sensitivity. Ongoing research may lead to the identification of novel biomarkers. Therefore, we review the experimental analyses for nucleic acids, circulating tumor cells, and proteins as potential biomarkers in the serum of testicular germ cell cancer patients. Keywords: biomarker, serum, testicular germ cell cancer

  10. Effect of age on expression of spermatogonial markers in bovine testis and isolated cells.

    Science.gov (United States)

    Giassetti, Mariana Ianello; Goissis, Marcelo Demarchi; Moreira, Pedro Vale; de Barros, Flavia Regina Oliveira; Assumpção, Mayra Elena Ortiz D'Ávila; Visintin, José Antônio

    2016-07-01

    Spermatogonial stem cells (SSC) are the most undifferentiated germ cell present in adult male testes and, it is responsible to maintain the spermatogenesis. Age has a negative effect over stem cell, but the aging effect on SSC is not elucidated for bovine. The present study aim to evaluate the effect of age on the expression of undifferentiated spermatogonial markers in testis and in enriched testicular cells from prepubertal calves and adult bulls. In this matter, testicular parenchyma from calves (3-5 months) (n=5) and bulls with 3 years of age (n=5) were minced and, isolated cells were obtained after two enzymatic digestions. Differential platting was performed for two hours onto BSA coated dish. Cell viability was assessed by Trypan Blue solution exclusion method and testicular cells enriched for SSC was evaluated by expression of specific molecular markers by qRT-PCR (POU5F1, GDNF, CXCR4, UCHL1, ST3GAL, SELP, ICAM1 and ITGA6) and flow cytometry (GFRA1, CXCR4 and ITGA6). CXCR4 and UCHL1 expression was evaluated in fixated testes by immunohistochemistry. We observed that age just affected the expression of selective genes [SELP (Fold Change=5.61; p=0.0023) and UCHL1 (Fold Change=4.98; p=0.0127)]. By flow cytometry, age affected only the proportion of ITGA6+ cells (P<0.001), which was higher in prepubertal calves when compared to adult bulls. In situ, we observed an effect of age on the number of UCHL1+ (p=0.0006) and CXCR4+ (p=0.0139) cells per seminiferous tubule. At conclusion, age affects gene expression and the population of cells expressing specific spermatogonial markers in the bovine testis. PMID:27180120

  11. Stem cell markers in neuroblastoma: An emerging role for LGR5

    Directory of Open Access Journals (Sweden)

    Helen eForgham

    2015-12-01

    Full Text Available The prognostic value of cancer stem cell markers in various cancer subtypes is a well documented research area. Our findings show that the stem cell marker Lgr5 is associated with an aggressive phenotype in neuroblastoma. Here, we discuss these findings within the context of recent studies in several cancers such as lung, colorectal and intestinal cancer, glioblastoma and ewing’s sarcoma.Neuroblastoma continues to be an elusive disease, due to its heterogeneous presentation ranging from spontaneous regression to aggressive metastatic disease and intertwined genetic variability. Currently, the most significant prognostic marker of high risk disease and poor prognosis is amplification of the MYCN oncogene, which is found in approximately 25% of cases [1]. With this in mind, there is still much to learn about the driving mechanisms of this aggressive paediatric tumour. Neuroblastoma development is thought to be the result of aberrant differentiation of the cell of origin, embryonic neural crest cells which then migrate and invade during the developmental stage[2]. Aberrant cells are those which would, under normal conditions form the mature tissues of the sympathetic ganglia and adrenal medulla. Tumours are known to develop indiscriminately along the radius of the sympathetic ganglia, although it is well established that the adrenal glands are fundamentally the most common primary site [3

  12. Prospective Isolation of Murine and Human Bone Marrow Mesenchymal Stem Cells Based on Surface Markers

    Directory of Open Access Journals (Sweden)

    Yo Mabuchi

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSCs are currently defined as multipotent stromal cells that undergo sustained in vitro growth and can give rise to cells of multiple mesenchymal lineages, such as adipocytes, chondrocytes, and osteoblasts. The regenerative and immunosuppressive properties of MSCs have led to numerous clinical trials exploring their utility for the treatment of a variety of diseases (e.g., acute graft-versus-host disease, Crohn’s disease, multiple sclerosis, osteoarthritis, and cardiovascular diseases including heart failure and myocardial infarction. On the other hand, conventionally cultured MSCs reflect heterogeneous populations that often contain contaminating cells due to the significant variability in isolation methods and the lack of specific MSC markers. This review article focuses on recent developments in the MSC research field, with a special emphasis on the identification of novel surface markers for the in vivo localization and prospective isolation of murine and human MSCs. Furthermore, we discuss the physiological importance of MSC subtypes in vivo with specific reference to data supporting their contribution to HSC niche homeostasis. The isolation of MSCs using selective markers (combination of PDGFRα and Sca-1 is crucial to address the many unanswered questions pertaining to these cells and has the potential to enhance their therapeutic potential enormously.

  13. Markers of coagulation activation and acute kidney injury in patients after hematopoietic cell transplantation.

    Science.gov (United States)

    Hingorani, S R; Seidel, K; Pao, E; Lawler, R; McDonald, G B

    2015-05-01

    Acute kidney injury (AKI) is common after hematopoietic cell transplant (HCT). The etiology of AKI is unknown because biopsies are rarely performed. The pathophysiology of injury is inferred from clinical data. Thrombotic microangiopathy (TMA) is often invoked as the cause of renal injury. Patients >2 years old undergoing their first HCT at Fred Hutchinson Cancer Research Center participated in this study. We prospectively measured plasma markers of coagulation activation, (PAI-1 and tPA) and fibrinolyis (D-dimer) weekly in 149 patients during the first 100 days post transplant. Cox proportional hazards modeling was used to determine associations between these markers and AKI (doubling of baseline serum creatinine). Kruskal-Wallis test was used to determine the associations between day 100 urinary albumin to creatinine ratios and these markers. Thirty one percent of patients developed AKI. Though elevations in these markers occurred frequently, neither PAI-1 nor tPA were associated with the development of AKI. D-dimer was associated with a slightly increased risk of AKI (relative risk=1.76; P-value 0.04). None of these markers were associated with micro- or macroalbuminuria at day 100. The lack of an association with AKI suggests that endothelial injury in the form of TMA is not a common cause of AKI early after transplant. PMID:25665045

  14. Prediction of epigenetically regulated genes in breast cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Loss, Leandro A; Sadanandam, Anguraj; Durinck, Steffen; Nautiyal, Shivani; Flaucher, Diane; Carlton, Victoria EH; Moorhead, Martin; Lu, Yontao; Gray, Joe W; Faham, Malek; Spellman, Paul; Parvin, Bahram

    2010-05-04

    panel of breast cancer cell lines. Subnetwork enrichment of these genes has identifed 35 common regulators with 6 or more predicted markers. In addition to identifying epigenetically regulated genes, we show evidence of differentially expressed methylation patterns between the basal and luminal subtypes. Our results indicate that the proposed computational protocol is a viable platform for identifying epigenetically regulated genes. Our protocol has generated a list of predictors including COL1A2, TOP2A, TFF1, and VAV3, genes whose key roles in epigenetic regulation is documented in the literature. Subnetwork enrichment of these predicted markers further suggests that epigenetic regulation of individual genes occurs in a coordinated fashion and through common regulators.

  15. Nuclear Import Analysis of Two Different Fluorescent Marker Proteins into Hepatocyte Cell Lines (HuH-7 Cell

    Directory of Open Access Journals (Sweden)

    Aris Haryanto

    2015-10-01

    Full Text Available The application of fluorescent proteins as expression markers and protein fusion partners has provedimmensely valuable for resolving the organization of biological events in living cells. EGFP and DsRed2 arecommonly fluorescent marker protein which is used for biotechnology and cell biology research. The presentstudy was designed to identify the expression vector that suitable to ligate with DNA encoding HBV coreprotein for intracellular localization study in hepatocyte cell, which were expressed as fusion proteins. We alsocompared and quantified the expressed fluorescent protein which predominantly localized in the cellcompartment. The results indicated that DsRed2 shown as less than ideal for intracellular localization study ofthan EGFP, because of its tetrameric structure of the fluorescent protein and when fused to a protein of interest,the fusion protein often forms aggregates in the living cells. In contrast, EGFP fluorescent protein shown a muchhigher proportion of cytoplasmic localization, thus being more suitable for analysis of intracellular localizationthan DsRed2 fluorescent protein. EGFP fluorescent protein is also capable to produce a strong green fluorescencewhen excited by blue light, without any exogenously added substrate or cofactor, events inside living cell canthus be visualized in a non-invasive way. Based on our present quantitative data and some reasons above shownthat EGFP is more suitable than DsRed2 as a fluorescent marker protein for intracellular localization study intoHuH-7 cell.Keywords: EGFP, DsRed2 fluorescent protein , HuH-7 cell, HBV, intracellular localization

  16. Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells

    DEFF Research Database (Denmark)

    Jørgensen, N; Rajpert-De Meyts, E; Graem, N;

    1995-01-01

    BACKGROUND: It has been hypothesized that carcinoma in situ of the testis (CIS), which is the precursor of invasive testicular germ cell tumours, may arise from fetal germ cells during fetal development rather than later in life. In order to corroborate this hypothesis, we undertook the present...... alternative explanation. However, we speculate that a transformation of normal fetal germ cells into CIS cells may take place before the end of the 9th week of fetal development. Furthermore, the expression of c-kit in early human fetal germ cells indicates that the c-kit and its ligand play a role in the......-like alkaline phosphatase, the protooncogene c-kit protein product, and the antigens for the monoclonal antibodies TRA-1-60 and M2A. The relative numbers of fetal germ cells that demonstrated positive reaction with the markers were calculated. RESULTS: The vast majority of the germ cells (75-100%) in the first...

  17. Cancer predictive value of cytogenetic markers used in occupational health surveillance programs

    DEFF Research Database (Denmark)

    Hagmar, L; Bonassi, S; Strömberg, U; Mikoczy, Z; Lando, C; Hansteen, I L; Montagud, A H; Knudsen, Lisbeth E.; Norppa, H; Reuterwall, C; Tinnerberg, H; Brøgger, A; Forni, A; Högstedt, B; Lambert, B; Mitelman, F; Nordenson, I; Salomaa, S; Skerfving, S

    1998-01-01

    It has not previously been clear whether cytogenetic biomarkers in healthy subjects will predict cancer. Earlier analyses of a Nordic and an Italian cohort indicated predictivity for chromosomal aberrations (CAS) but not for sister chromatid exchanges (SCES). A pooled analysis of the updated...

  18. Markers for sebaceoma show a spectrum of cell cycle regulators, tumor suppressor genes, and oncogenes

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2015-01-01

    Full Text Available Background: Sebaceoma is a tumor for which the causative oncogenes are not well-understood. Sebaceomas demonstrate some histopathologic features similar to basal cell carcinoma (BCC, such as palisading borders and basaloid cells with additional features, including foamy cytoplasm and indented nuclei. Aims: We examine multiple cell-cycle, oncogene, and tumor suppressor gene markers in sebaceomas, to try to find some suitable biological markers for this tumor, and compare with other published studies. Materials and Methods: We investigated a panel of immunohistochemical (IHC stains that are important for cellular signaling, including a cell cycle regulator, tumor suppressor gene, oncogene, hormone receptor, and genomic stability markers in our cohort of sebaceomas. We collected 30 sebaceomas from three separate USA dermatopathology laboratories. The following IHC panel: Epithelial membrane antigen (EMA/CD227, cytokeratin AE1/AE3, cyclin D1, human breast cancer 1 protein (BRCA-1, C-erb-2, Bcl-2, human androgen receptor (AR, cyclin-dependent kinase inhibitor 1B (p27 kip1 , p53, topoisomerase II alpha, proliferating cell nuclear antigen, and Ki-67 were tested in our cases. Results: EMA/CD227 was positive in the well-differentiated sebaceomas (13/30. Cyclin-dependent kinase inhibitor 1B was positive in tumors with intermediate differentiation (22/30. The less well-differentiated tumors failed to stain with EMA and AR. Most of the tumors with well-differentiated palisaded areas demonstrated positive staining for topoisomerase II alpha, p27 kip1 , and p53, with positive staining in tumoral basaloid areas (22/30. Numerous tumors were focally positive with multiple markers, indicating a significant degree of variability in the complete group. Conclusions: Oncogenes, tumor suppressor genes, cell cycle regulators, and hormone receptors are variably expressed in sebaceomas. Our results suggest that in these tumors, selected marker staining seems to correlate

  19. Identification of CD90 as Putative Cancer Stem Cell Marker and Therapeutic Target in Insulinomas.

    Science.gov (United States)

    Buishand, Floryne O; Arkesteijn, Ger J A; Feenstra, Laurien R; Oorsprong, Claire W D; Mestemaker, Margiet; Starke, Achim; Speel, Ernst-Jan M; Kirpensteijn, Jolle; Mol, Jan A

    2016-06-01

    The long-term prognosis after surgical resection of malignant insulinoma (INS) is poor. Novel adjuvant therapies, specifically targeting cancer stem cells (CSCs), are warranted. Therefore, the goal of this study was to characterize and target putative INS CSCs. Using fluorescence-activated cell sorting, human INS cell line CM and pancreatic carcinoid cell line BON1 were screened for the presence of stem cell-associated markers. CD90, CD166, and GD2 were identified as potential CSC markers. Only CD90(+) INS cells had an increased tumor-initiating potential in athymic nude mice. Anti-CD90 monoclonal antibodies decreased the viability and metastatic potential of injected cells in a zebrafish embryo INS xenograft model. Primary INS stained positive for CD90 by immunohistochemistry, however also intratumoral fibroblasts and vascular endothelium showed positive staining. The results of this study suggest that anti-CD90 monoclonals form a potential novel adjuvant therapeutic modality by targeting either INS cells directly, or by targeting the INS microenvironment. PMID:27049037

  20. Cisplatinum dose dependent response in germ cell cancer evaluated by tumour marker modelling

    DEFF Research Database (Denmark)

    Carl, J; Christensen, T B; von der Maase, H

    1992-01-01

    This study presents an analysis on longitudinal tumour marker series in twenty-two patients with non-seminomatous germ cell cancers treated with cisplatinum (DDP) based combination chemotherapy. Series of alphafoetoprotein (AFP), human chorionic gonadotrophin (HCG) and lactate dehydrogenase (LDH...... faster than AFP producing cells, and were 3-5-fold more sensitive to the chemotherapy given than AFP producing cells. Treatment response versus DDP dose appeared to be bi-phasic, but with no significant change in treatment efficiency within the given range of DDP doses....

  1. A multi-gene transcriptional profiling approach to the discovery of cell signature markers

    OpenAIRE

    Wada, Youichiro; Li, Dan; Merley, Anne; Zukauskas, Andrew; Aird, William C.; Dvorak, Harold F.; Shih, Shou-Ching

    2010-01-01

    A profile of transcript abundances from multiple genes constitutes a molecular signature if the expression pattern is unique to one cell type. Here we measure mRNA copy numbers per cell by normalizing per million copies of 18S rRNA and identify 6 genes (TIE1, KDR, CDH5, TIE2, EFNA1 and MYO5C) out of 79 genes tested as excellent molecular signature markers for endothelial cells (ECs) in vitro. The selected genes are uniformly expressed in ECs of 4 different origins but weakly or not expressed ...

  2. Further evidence for population specific differences in the effect of DNA markers and gender on eye colour prediction in forensics.

    Science.gov (United States)

    Pośpiech, Ewelina; Karłowska-Pik, Joanna; Ziemkiewicz, Bartosz; Kukla, Magdalena; Skowron, Małgorzata; Wojas-Pelc, Anna; Branicki, Wojciech

    2016-07-01

    The genetics of eye colour has been extensively studied over the past few years, and the identified polymorphisms have been applied with marked success in the field of Forensic DNA Phenotyping. A picture that arises from evaluation of the currently available eye colour prediction markers shows that only the analysis of HERC2-OCA2 complex has similar effectiveness in different populations, while the predictive potential of other loci may vary significantly. Moreover, the role of gender in the explanation of human eye colour variation should not be neglected in some populations. In the present study, we re-investigated the data for 1020 Polish individuals and using neural networks and logistic regression methods explored predictive capacity of IrisPlex SNPs and gender in this population sample. In general, neural networks provided higher prediction accuracy comparing to logistic regression (AUC increase by 0.02-0.06). Four out of six IrisPlex SNPs were associated with eye colour in the studied population. HERC2 rs12913832, OCA2 rs1800407 and SLC24A4 rs12896399 were found to be the most important eye colour predictors (p forensics and provided additional evidence for population specific differences in the predictive importance of the IrisPlex SNPs and gender. PMID:27221533

  3. Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma.

    Science.gov (United States)

    Rowe, Casey J; Tang, Fiona; Hughes, Maria Celia B; Rodero, Mathieu P; Malt, Maryrose; Lambie, Duncan; Barbour, Andrew; Hayward, Nicholas K; Smithers, B Mark; Green, Adele C; Khosrotehrani, Kiarash

    2016-08-01

    Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics and carries rare but significant morbidity. Previous studies have linked markers of tumour biology to patient survival. In this study, we aimed to combine the predictive value of established biomarkers in addition to clinical parameters as indicators of survival in addition to or instead of sentinel node biopsy in a cohort of high-risk melanoma patients. Patients with locally invasive melanomas undergoing sentinel lymph node biopsy were ascertained and prospectively followed. Information on mortality was validated through the National Death Index. Immunohistochemistry was used to analyse proteins previously reported to be associated with melanoma survival, namely Ki67, p16 and CD163. Evaluation and multivariate analyses according to REMARK criteria were used to generate models to predict disease-free and melanoma-specific survival. A total of 189 patients with available archival material of their primary tumour were analysed. Our study sample was representative of the entire cohort (N = 559). Average Breslow thickness was 2.5 mm. Thirty-two (17%) patients in the study sample died from melanoma during the follow-up period. A prognostic score was developed and was strongly predictive of survival, independent of sentinel node status. The score allowed classification of risk of melanoma death in sentinel node-negative patients. Combining clinicopathological factors and established biomarkers allows prediction of outcome in locally invasive melanoma and might be implemented in addition to or in cases when sentinel node biopsy cannot be performed. PMID:26990817

  4. CT-based abdominal aortic calcification score as a surrogate marker for predicting the presence of asymptomatic coronary artery disease

    International Nuclear Information System (INIS)

    To assess the value of a CT-based abdominal aortic calcification (AAC) score as a surrogate marker for the presence of asymptomatic coronary artery disease (CAD). The AAC scores of 373 patients without cardiac symptoms who underwent both screening coronary CT angiography and abdominal CT within one year were calculated according to the Agatston method. Logistic regression was used to derive two multivariate models from traditional cardiovascular risk factors, with and without AAC scores, to predict the presence of CAD. The AAC score and the two multivariate models were compared by calculating the area under the receiver operating characteristic curve (AUC) and the net reclassification improvement (NRI). The AAC score alone showed a marginally higher AUC (0.823 vs. 0.767, P = 0.061) and significantly better risk classification (NRI = 0.158, P = 0.048) than the multivariate model without AAC. The multivariate model using traditional factors and AAC did not show a significantly higher AUC (0.832 vs. 0.823, P = 0.616) or NRI (0.073, P = 0.13) than the AAC score alone. The optimal cutoff value of the AAC score for predicting CAD was 1025.8 (sensitivity, 79.5 %; specificity, 75.9 %). AAC scores may serve as a surrogate marker for the presence or absence of asymptomatic CAD. (orig.)

  5. CT-based abdominal aortic calcification score as a surrogate marker for predicting the presence of asymptomatic coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    An, Chansik; Lee, Hye-Jeong; Ahn, Sung Soo; Choi, Byoung Wook; Kim, Myeong-Jin; Chung, Yong Eun [Severance Hospital, Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, 50 Yonsei-Ro, Seodaemun-Gu, Seoul (Korea, Republic of); Lee, Hye Sun [Yonsei University College of Medicine, Biostatistics Collaboration Unit, Department of Research Affairs, Seoul (Korea, Republic of)

    2014-10-15

    To assess the value of a CT-based abdominal aortic calcification (AAC) score as a surrogate marker for the presence of asymptomatic coronary artery disease (CAD). The AAC scores of 373 patients without cardiac symptoms who underwent both screening coronary CT angiography and abdominal CT within one year were calculated according to the Agatston method. Logistic regression was used to derive two multivariate models from traditional cardiovascular risk factors, with and without AAC scores, to predict the presence of CAD. The AAC score and the two multivariate models were compared by calculating the area under the receiver operating characteristic curve (AUC) and the net reclassification improvement (NRI). The AAC score alone showed a marginally higher AUC (0.823 vs. 0.767, P = 0.061) and significantly better risk classification (NRI = 0.158, P = 0.048) than the multivariate model without AAC. The multivariate model using traditional factors and AAC did not show a significantly higher AUC (0.832 vs. 0.823, P = 0.616) or NRI (0.073, P = 0.13) than the AAC score alone. The optimal cutoff value of the AAC score for predicting CAD was 1025.8 (sensitivity, 79.5 %; specificity, 75.9 %). AAC scores may serve as a surrogate marker for the presence or absence of asymptomatic CAD. (orig.)

  6. A multi-gene transcriptional profiling approach to the discovery of cell signature markers.

    Science.gov (United States)

    Wada, Youichiro; Li, Dan; Merley, Anne; Zukauskas, Andrew; Aird, William C; Dvorak, Harold F; Shih, Shou-Ching

    2011-01-01

    A profile of transcript abundances from multiple genes constitutes a molecular signature if the expression pattern is unique to one cell type. Here we measure mRNA copy numbers per cell by normalizing per million copies of 18S rRNA and identify 6 genes (TIE1, KDR, CDH5, TIE2, EFNA1 and MYO5C) out of 79 genes tested as excellent molecular signature markers for endothelial cells (ECs) in vitro. The selected genes are uniformly expressed in ECs of 4 different origins but weakly or not expressed in 4 non-EC cell lines. A multi-gene transcriptional profile of these 6 genes clearly distinguishes ECs from non-ECs in vitro. We conclude that (i) a profile of mRNA copy numbers per cell from a well-chosen multi-gene panel can act as a sensitive and accurate cell type signature marker, and (ii) the method described here can be applied to in vivo cell fingerprinting and molecular diagnosis. PMID:20972619

  7. Defining the expression of marker genes in equine mesenchymal stromal cells

    Directory of Open Access Journals (Sweden)

    Deborah J Guest

    2008-11-01

    Full Text Available Deborah J Guest1, Jennifer C Ousey1, Matthew RW Smith21Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU; 2Reynolds House Referrals, Greenwood Ellis and Partners, 166 High Street, Newmarket, Suffolk, CB8 9WS, UKAbstract: Mesenchymal stromal (MS cells have been derived from multiple sources in the horse including bone marrow, adipose tissue and umbilical cord blood. To date these cells have been investigated for their differentiation potential and are currently being used to treat damage to horse musculoskeletal tissues. However, no work has been done in horse MS cells to examine the expression profile of proteins and cell surface antigens that are expressed in human MS cells. The identification of such profiles in the horse will allow the comparison of putative MS cells isolated from different laboratories and different tissues. At present it is difficult to ascertain whether equivalent cells are being used in different reports. Here, we report on the expression of a range of markers used to define human MS cells. Using immunocytochemistry we show that horse MS cells homogenously express collagens, alkaline phosphatase activity, CD44, CD90 and CD29. In contrast, CD14, CD79α and the embryonic stem cell markers Oct-4, SSEA (stage specific embryonic antigen -1, -3, -4, TRA (tumor rejection antigen -1–60 and -1–81 are not expressed. The MS cells also express MHC class I antigens but do not express class II antigens, although they are inducible by treatment with interferon gamma (IFN-γ.Keywords: mesenchymal stem cells, equine, gene expression

  8. Immune development and regulation in young children - Potential markers for prediction of health and disease.

    OpenAIRE

    Reubsaet, L.L.

    2014-01-01

    The human immune system is complex and is formed and shaped during life by many triggers. Different subsets of T helper cells are involved in immunity against pathogens, but can also play a role in inflammatory diseases like allergy, asthma and allo-reactive disease. The regulation of these inflammatory responses is mediated by the regulatory T cell (Treg). During our whole life these different T cell subsets try to maintain a balance within the immune system. Graft-versus-Host disease Alloge...

  9. BSND and ATP6V1G3: Novel Immunohistochemical Markers for Chromophobe Renal Cell Carcinoma

    OpenAIRE

    SHINMURA, KAZUYA; Igarashi, Hisaki; Kato, Hisami; Koda, Kenji; Ogawa, Hiroshi; Takahashi, Seishiro; Otsuki, Yoshiro; Yoneda, Tatsuaki; Kawanishi, Yuichi; Funai, Kazuhito; Takayama, Tatsuya; Ozono, Seiichiro; Sugimura, Haruhiko

    2015-01-01

    Abstract Differentiating between chromophobe renal cell carcinoma (RCC) and other RCC subtypes can be problematic using routine light microscopy. This study aimed to identify novel immunohistochemical markers useful for a differential diagnosis between chromophobe RCC and other RCC subtypes. We selected 3 genes (including BSND and ATP6V1G3) that showed specific transcriptional expression in chromophobe RCC using expression data (n = 783) from The Cancer Genome Atlas (TCGA) database. A subsequ...

  10. Identification of Interconnected Markers for T-Cell Acute Lymphoblastic Leukemia

    OpenAIRE

    Emine Guven Maiorov; Ozlem Keskin; Ozden Hatirnaz Ng; Ugur Ozbek; Attila Gursoy

    2013-01-01

    Hindawi Publishing Corporation BioMed Research International Volume 2013, Article ID 210253, 20 pages http://dx.doi.org/10.1155/2013/210253 Research Article Identification of Interconnected Markers for T-Cell Acute Lymphoblastic Leukemia Emine Guven Maiorov,1 Ozlem Keskin,1 Ozden Hatirnaz Ng,2 Ugur Ozbek,2 and Attila Gursoy1 1 Center for Computational Biology and Bioinformatics and College of Engineering, Koc¸ University, Rumelifeneri Yolu, Sariyer, 34450 Istanbu...

  11. Functionality and specificity of gene markers for skin sensitization in dendritic cells

    OpenAIRE

    Lambrechts, Nathalie; Nelissen, Inge; van Tendeloo, Viggo; Witters, Hilda; Den Heuvel, Rosette; Hooyberghs, Jef; Schoeters, Greet

    2011-01-01

    Transcriptomic analyses revealed a discriminating gene expression profile in human CD34(+) progenitor-derived dendritic cells (DC) after exposure to skin sensitizers versus non-sensitizers. Starting from the differential expression in a small set of genes, a preliminary classification model (VITOSENS (R)) has been developed to identify chemicals as (non-)sensitizing. The objective of the current study is to gain knowledge on the role of the VITOSENS (R) markers in the DC maturation process, a...

  12. Prognostic Value of Cancer Stem Cells Markers in Triple-Negative Breast Cancer

    OpenAIRE

    Collina, Francesca; Di Bonito, Maurizio; Li Bergolis, Valeria; De Laurentiis, Michelino; Vitagliano, Carlo; Cerrone, Margherita; Nuzzo, Francesco; Cantile, Monica; Botti, Gerardo

    2015-01-01

    Triple-negative breast cancer (TNBC) has a significant clinical relevance of being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. Increased aggressiveness of this tumor, as well as resistance to standard drug therapies, may be associated with the presence of stem cell populations within the tumor. Several stemness markers have been described for the various histological subtypes of breast cancer, such as...

  13. Markers of stemness in equine mesenchymal stem cells: a plea for uniformity.

    Science.gov (United States)

    De Schauwer, Catharina; Meyer, Evelyne; Van de Walle, Gerlinde R; Van Soom, Ann

    2011-05-01

    Mesenchymal stromal cells (MSC) are a very promising subpopulation of adult stem cells for cell-based regenerative therapies in veterinary medicine. Despite major progress in the knowledge on adult stem cells during recent years, a proper identification of MSC remains a challenge. In human medicine, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy (ISCT) recently proposed three criteria to define MSC. Firstly, cells must be plastic-adherent when maintained under standard culture conditions. Secondly, MSC must express CD73, CD90 and CD105, and lack expression of CD34, CD45, CD14 or CD11b, CD79α or CD19 and MHC class II antigens. Thirdly, MSC must be able to differentiate into osteoblasts, adipocytes and chondroblasts in vitro. Successful isolation and differentiation of equine MSC from different sources such as bone marrow, fat tissue, umbilical cord blood, Wharton's Jelly or peripheral blood has been widely reported. However, their unequivocal immunophenotyping is hampered by the lack of a single specific marker and the limited availability of monoclonal anti-horse antibodies, which are two major factors complicating successful research on equine MSC. Detection of gene expression on mRNA level is hereby a valuable alternative, although the need still exists to test several antibody clones in search for cross-reactivity. To date, commercial antibodies recognizing equine epitopes are only available for CD13, CD44 and MHC-II. Moreover, as the expression of certain adult stem cell markers may differ between species, it is mandatory to define a set of CD markers which can be uniformly applied for the identification of equine MSC. PMID:21196039

  14. Adipose derived mesenchymal stem cells express keratinocyte lineage markers in a co-culture model.

    Science.gov (United States)

    Irfan-Maqsood, M; Matin, M M; Heirani-Tabasi, A; Bahrami, M; Naderi-Meshkin, H; Mirahmadi, M; Hassanzadeh, H; Sanjar Moussavi, N; Raza-Shah, H; Raeesolmohaddeseen, M; Bidkhori, H; Bahrami, A R

    2016-01-01

    Cutaneous wound healing is a complex type of biological event involving proliferation, differentiation, reprograming, trans/de-differentiation, recruitment, migration, and apoptosis of a number of cells (keratinocytes, fibroblasts, endothelial cells, nerve cells and stem cells) to regenerate a multi-layered tissue that is damaged by either internal or external factors. The exact regeneration mechanism of damaged skin is still unknown but the epithelial and other kinds of stem cells located in skin play crucial roles in the healing process. In this work, a co-culture model composed of adipose derived mesenchymal stem cells and keratinocytes was developed to understand the cellular differentiation behaviour in wound healing. Human mesenchymal stem cells were isolated from waste lipoaspirates. Keratinocytes were isolated from neonatal rats skin as well from human adult skin. Both types of cells were cultured and their culturing behaviour was observed microscopically under regular intervals of time. The identity of both cells was confirmed by flow cytometry and qRT-PCR. Cells were co-cultured under the proposed co-culturing model and the model was observed for 7, 14 and 21 days. The cellular behaviour was studied based on change in morphology, colonization, stratification, migration and expression of molecular markers. Expression of molecular markers was studied at transcriptional level and change in cellular morphology and migration capabilities was observed under the invert microscope regularly. Successfully isolated and characterized mesenchymal stem cells were found to express keratinocyte lineage markers i.e. K5, K10, K14, K18, K19 and Involucrin when co-cultured with keratinocytes after 14 and 21 days. Their expression was found to increase by increasing the time span of cell culturing. The keratinocyte colonies started to disappear after 10 days of culturing which might be due to stratification process initiated by possibly transdifferentiated stem cells. It can

  15. Radiation Dose-effects on Cell Cycle, Apoptosis, and Marker Expression of Ataxia Telangiectasia-Heterozygous Human Breast Epithelial Cells

    Science.gov (United States)

    Cruz, A.; Bors, K.; Jansen, H.; Richmond, R.

    2003-01-01

    Ataxia-telangiectasia (A-T) is a radiation-sensitive genetic condition. AT-heterozygous human mammary epithelial cells (HMEC) were irradiated using a Cs137 source in order to compare cell cycle, apoptosis, and marker expression responses across 3 radiation doses. No differences in cell cycle and apoptosis were found with any of the radiation doses used (30, 60, and 90 rads) compared with the unirradiated control (0 rad). At the same doses, however, differences were found in marker expression, such as keratin 18 (kl8), keratin 14 (k14), insulin-like growth factor I receptor (IGF-IR), and connexin 43 (cx43). This may indicate that radiation sensitivity in the heterozygous state may be initiated through signal transduction responses.

  16. Improved prediction of complex diseases by common genetic markers: state of the art and further perspectives.

    Science.gov (United States)

    Müller, Bent; Wilcke, Arndt; Boulesteix, Anne-Laure; Brauer, Jens; Passarge, Eberhard; Boltze, Johannes; Kirsten, Holger

    2016-03-01

    Reliable risk assessment of frequent, but treatable diseases and disorders has considerable clinical and socio-economic relevance. However, as these conditions usually originate from a complex interplay between genetic and environmental factors, precise prediction remains a considerable challenge. The current progress in genotyping technology has resulted in a substantial increase of knowledge regarding the genetic basis of such diseases and disorders. Consequently, common genetic risk variants are increasingly being included in epidemiological models to improve risk prediction. This work reviews recent high-quality publications targeting the prediction of common complex diseases. To be included in this review, articles had to report both, numerical measures of prediction performance based on traditional (non-genetic) risk factors, as well as measures of prediction performance when adding common genetic variants to the model. Systematic PubMed-based search finally identified 55 eligible studies. These studies were compared with respect to the chosen approach and methodology as well as results and clinical impact. Phenotypes analysed included tumours, diabetes mellitus, and cardiovascular diseases. All studies applied one or more statistical measures reporting on calibration, discrimination, or reclassification to quantify the benefit of including SNPs, but differed substantially regarding the methodological details that were reported. Several examples for improved risk assessments by considering disease-related SNPs were identified. Although the add-on benefit of including SNP genotyping data was mostly moderate, the strategy can be of clinical relevance and may, when being paralleled by an even deeper understanding of disease-related genetics, further explain the development of enhanced predictive and diagnostic strategies for complex diseases. PMID:26839113

  17. DDX4 (DEAD box polypeptide 4) colocalizes with cancer stem cell marker CD133 in ovarian cancers

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Hyung [Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan (Korea, Republic of); Biomedical Research Institute and Pusan Cancer Center, Pusan National University Hospital, Busan (Korea, Republic of); Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun [Department of Parasitology and Genetics, Kosin University College of Medicine, Busan (Korea, Republic of); Moon, Soo Hyun; Suh, Dong Soo; Yoon, Man Soo [Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan (Korea, Republic of); Biomedical Research Institute and Pusan Cancer Center, Pusan National University Hospital, Busan (Korea, Republic of); Park, Eun-Sil [Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, MA (United States); Jeong, Namkung [Department of Obstetrics and Gynecology, The Catholic University, Seoul (Korea, Republic of); Eo, Wan-Kyu [Department of Internal Medicine, Kyung Hee University, Seoul (Korea, Republic of); Kim, Heung Yeol, E-mail: hykyale@yahoo.com [Department of Obstetrics and Gynecology, Kosin University College of Medicine, Busan (Korea, Republic of); Cha, Hee-Jae, E-mail: hcha@kosin.ac.kr [Department of Parasitology and Genetics, Kosin University College of Medicine, Busan (Korea, Republic of); Institute for Medical Science, Kosin University College of Medicine, Busan (Korea, Republic of)

    2014-05-02

    Highlights: • Germ cell marker DDX4 was significantly increased in ovarian cancer. • Ovarian cancer stem cell marker CD133 was significantly increased in ovarian cancer. • DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. • CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4. • Germ cell marker DDX4 has the potential of ovarian cancer stem cell marker. - Abstract: DDX4 (DEAD box polypeptide 4), characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), is an RNA helicase which is implicated in various cellular processes involving the alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. DDX4 is known to be a germ cell-specific protein and is used as a sorting marker of germline stem cells for the production of oocytes. A recent report about DDX4 in ovarian cancer showed that DDX4 is overexpressed in epithelial ovarian cancer and disrupts a DNA damage-induced G2 checkpoint. We investigated the relationship between DDX4 and ovarian cancer stem cells by analyzing the expression patterns of DDX4 and the cancer stem cell marker CD133 in ovarian cancers via tissue microarray. Both DDX4 and CD133 were significantly increased in ovarian cancer compared to benign tumors, and showed similar patterns of expression. In addition, DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. Furthermore, almost all CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4, suggesting a strong possibility that DDX4 plays an important role in cancer stem cells, and/or can be used as an ovarian cancer stem cell marker.

  18. DDX4 (DEAD box polypeptide 4) colocalizes with cancer stem cell marker CD133 in ovarian cancers

    International Nuclear Information System (INIS)

    Highlights: • Germ cell marker DDX4 was significantly increased in ovarian cancer. • Ovarian cancer stem cell marker CD133 was significantly increased in ovarian cancer. • DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. • CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4. • Germ cell marker DDX4 has the potential of ovarian cancer stem cell marker. - Abstract: DDX4 (DEAD box polypeptide 4), characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), is an RNA helicase which is implicated in various cellular processes involving the alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. DDX4 is known to be a germ cell-specific protein and is used as a sorting marker of germline stem cells for the production of oocytes. A recent report about DDX4 in ovarian cancer showed that DDX4 is overexpressed in epithelial ovarian cancer and disrupts a DNA damage-induced G2 checkpoint. We investigated the relationship between DDX4 and ovarian cancer stem cells by analyzing the expression patterns of DDX4 and the cancer stem cell marker CD133 in ovarian cancers via tissue microarray. Both DDX4 and CD133 were significantly increased in ovarian cancer compared to benign tumors, and showed similar patterns of expression. In addition, DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. Furthermore, almost all CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4, suggesting a strong possibility that DDX4 plays an important role in cancer stem cells, and/or can be used as an ovarian cancer stem cell marker

  19. Predicting Arithmetic Abilities: The Role of Preparatory Arithmetic Markers and Intelligence

    Science.gov (United States)

    Stock, Pieter; Desoete, Annemie; Roeyers, Herbert

    2009-01-01

    Arithmetic abilities acquired in kindergarten are found to be strong predictors for later deficient arithmetic abilities. This longitudinal study (N = 684) was designed to examine if it was possible to predict the level of children's arithmetic abilities in first and second grade from their performance on preparatory arithmetic abilities in…

  20. Maternal Characteristics, Mean Arterial Pressure and Serum Markers in Early Prediction of Preeclampsia

    OpenAIRE

    Kuc, Sylwia; Maria P. H. Koster; Franx, Arie; Schielen, Peter C. J. I.; Visser, Gerard H. A.

    2013-01-01

    Objectives In a previous study, we have described the predictive value of first-trimester Pregnancy-Associated Plasma Protein-A (PAPP-A), free β-subunit of human Chorionic Gonadotropin (fβ-hCG), Placental Growth Factor (PlGF) and A Disintegrin And Metalloprotease 12 (ADAM12) for early onset preeclampsia (EO-PE; delivery

  1. Automated detection of residual cells after sex-mismatched stem-cell transplantation – evidence for presence of disease-marker negative residual cells

    Directory of Open Access Journals (Sweden)

    Johannes Tilman

    2009-05-01

    Full Text Available Abstract Background A new chimerism analysis based on automated interphase fluorescence in situ hybridization (FISH evaluation was established to detect residual cells after allogene sex-mismatched bone marrow or blood stem-cell transplantation. Cells of 58 patients were characterized as disease-associated due to presence of a bcr/abl-gene-fusion or a trisomy 8 and/or a simultaneous hybridization of gonosome-specific centromeric probes. The automatic slide scanning platform Metafer with its module MetaCyte was used to analyse 3,000 cells per sample. Results Overall 454 assays of 58 patients were analyzed. 13 of 58 patients showed residual recipient cells at one stage of more than 4% and 12 of 58 showed residual recipient cells less than 4%, respectively. As to be expected, patients of the latter group were associated with a higher survival rate (48 vs. 34 month. In only two of seven patients with disease-marker positive residual cells between 0.1–1.3% a relapse was observed. Besides, disease-marker negative residual cells were found in two patients without relapse at a rate of 2.8% and 3.3%, respectively. Conclusion The definite origin and meaning of disease-marker negative residual cells is still unclear. Overall, with the presented automatic chimerism analysis of interphase FISH slides, a sensitive method for detection of disease-marker positive residual cells is on hand.

  2. One Step Quick Detection of Cancer Cell Surface Marker by Integrated NiFe-based Magnetic Biosensing Cell Cultural Chip

    Institute of Scientific and Technical Information of China (English)

    Chenchen Bao; Lei Chen; Tao Wang; Chong Lei; Furong Tian; Daxiang Cui; Yong Zhou

    2013-01-01

    RGD peptides has been used to detect cell surface integrin and direct clinical effective therapeutic drug selection. Herein we report that a quick one step detection of cell surface marker that was realized by a specially designed NiFe-based magnetic biosensing cell chip combined with functionalized magnetic nanoparti-cles. Magnetic nanoparticles with 20-30 nm in diameter were prepared by coprecipitation and modified with RGD-4C, and the resultant RGD-functionalized magnetic nanoparticles were used for targeting cancer cells cul-tured on the NiFe-based magnetic biosensing chip and distinguish the amount of cell surface receptor-integrin. Cell lines such as Calu3, Hela, A549, CaFbr, HEK293 and HUVEC exhibiting different integrin expression were chosen as test samples. Calu3, Hela, HEK293 and HUVEC cells were successfully identified. This approach has advantages in the qualitative screening test. Compared with traditional method, it is fast, sensitive, low cost, easy-operative, and needs very little human intervention. The novel method has great potential in applications such as fast clinical cell surface marker detection, and diagnosis of early cancer, and can be easily extended to other biomedical applications based on molecular recognition.

  3. Expression of cancer stem cell surface markers after chemotherapeutic drug treatment to reflect breast cancer cell regrowth

    Institute of Scientific and Technical Information of China (English)

    Qing Liu; Wings Tjing Yung Loo; Louis Wing Cheong Chow; Kelly Wei Yu Rui

    2014-01-01

    Objective To detect the cell viability and the expressions of stem cell surface markers after chemotherapeutic drug treatment. Methods We observed the cytotoxic effects of three chemotherapeutic agents [ epirubicin ( Epi ) , fluorouracil ( 5-FU ) and cyclophosphamide ( Cyc ) ] in three cell lines, and the cell viabilities after removed these chemotherapeutic agents. Expressions of stem cell surface markers CD44, CD24, CD90, CD14 and aldehyde dehydrogenase1(ALDH1) in breast cancer cells were analyzed by real-time PCR. The post hoc analysis (Tukey’s tests) in conjunction with one-way ANOVA was used for statistical analysis. Results The initial cytotoxic efficacy was most notable. After the treatment of the same therapeutic agents, cell viability was decreased by 64. 8% 35. 14%, 32. 25% in BT-483 cells, 66. 4%, 22. 94% and 45. 88% in MDA-MB-231 cells, 97. 1%, 99. 5% and 76. 4% in MCF cells. The difference was significant compared with that before treatment ( P=0. 000 ) . However, the inhibitory effects were diminished after chemotherapeutic agent withdrawal. Cell viabilities were increased to 167. 9%, 212. 04% and 188. 66% in MDA-MB-231 cells at 48 h after withdrawal. At 72 h after withdrawal, cell viability was increased with a significant difference in three cell lines (all P values=0. 000). Expressions of CD44 and ALDH1 were most prevalent for MDA-MB-231, BT-483 and MCF-7 cells. ALDH1 mRNA level was significant higher in BT-483 ( HER-2 overexpression cell line) than MDA-MB-231 ( triple negative cell line ) ( P = 0. 012 ) . CD14 mRNA level in MCF-7 cells were significantly lower than that in MDA-MB-231 and BT-483 (P=0. 003, 0. 001). BT-483 showed significantly higher level of CD44 than MDA-MB-231 and MCF-7 cell line (P= 0.013, 0.020), and no significant difference was detected between MDA-MB-231 and MCF-7 breast cancer cells ( P=0. 955 ) . CD90 mRNA expressions were detected in MDA-MB-231 cells and MCF-7 cells, but not in BT-483 cells. Conclusion Some malignant

  4. Expression of Stem Cell and Epithelial-Mesenchymal Transition Markers in Circulating Tumor Cells of Breast Cancer Patients

    OpenAIRE

    Natalia Krawczyk; Franziska Meier-Stiegen; Malgorzata Banys; Hans Neubauer; Eugen Ruckhaeberle; Tanja Fehm

    2014-01-01

    Evaluation and characterization of circulating tumor cells (CTCs) have become a major focus of translational cancer research. Presence of CTCs predicts worse clinical outcome in early and metastatic breast cancer. Whether all cells from the primary tumor have potential to disseminate and form subsequent metastasis remains unclear. As part of the metastatic cascade, tumor cells lose their cell-to-cell adhesion and undergo epithelial-mesenchymal transition (EMT) in order to enter blood circulat...

  5. Actin marker lines in grapevine reveal a gatekeeper function of guard cells.

    Science.gov (United States)

    Guan, Xin; Buchholz, Günther; Nick, Peter

    2014-08-15

    Resistance to abiotic and biotic stress is a central topic for sustainable agriculture, especially in grapevine, one of the field crops with the highest economic output per acreage. As early cellular factors for plant defense, actin microfilaments (AF) are of high relevance. We therefore generated a transgenic actin marker line for grapevine by expressing a fusion protein between green fluorescent protein and the second actin-binding domain of Arabidopsis (Arabidopsis thaliana) fimbrin, AtFIM1. Based on this first cytoskeletal-marker line in grapevine, the response of AFs to phytopathogenic microorganisms could be followed in vivo. Upon inoculation with fluorescently labeled strains of phytopathogenic bacteria, actin responses were confined to the guard cells. In contrast, upon contact with zoospores of Plasmopara viticola, not only the guard cells, but also epidermal pavement cells, where no zoospores had attached responded with the formation of a perinuclear actin basket. Our data support the hypothesis that guard cells act as pacemakers of defense, dominating the responses of the remaining epidermal cells. PMID:24973589

  6. Napsin A is a specific marker for ovarian clear cell adenocarcinoma.

    Science.gov (United States)

    Yamashita, Yoriko; Nagasaka, Tetsuro; Naiki-Ito, Aya; Sato, Shinya; Suzuki, Shugo; Toyokuni, Shinya; Ito, Masafumi; Takahashi, Satoru

    2015-01-01

    Ovarian clear cell adenocarcinoma has a relatively poor prognosis among the ovarian cancer subtypes because of its high chemoresistance. Differential diagnosis of clear cell adenocarcinoma from other ovarian surface epithelial tumors is important for its treatment. Napsin A is a known diagnostic marker for lung adenocarcinoma, and expression of napsin A is reported in a certain portion of thyroid and renal carcinomas. However, napsin A expression in ovarian surface epithelial tumors has not previously been examined. In this study, immunohistochemical analysis revealed that in 71 of 86 ovarian clear cell adenocarcinoma patients (83%) and all of the 13 patients with ovarian clear cell adenofibroma, positive napsin A staining was evident. No expression was observed in 30 serous adenocarcinomas, 11 serous adenomas or borderline tumors, 19 endometrioid adenocarcinomas, 22 mucinous adenomas or borderline tumors, 10 mucinous adenocarcinomas, or 3 yolk sac tumors of the ovary. Furthermore, expression of napsin A was not observed in the normal surface epithelium of the ovary, epithelia of the fallopian tubes, squamous epithelium, endocervical epithelium, or the endometrium of the uterus. Therefore, we propose that napsin A is another sensitive and specific marker for distinguishing ovarian clear cell tumors (especially adenocarcinomas) from other ovarian tumors. PMID:24721826

  7. Premorbid multivariate markers of neurodevelopmental instability in the prediction of adult schizophrenia-spectrum disorder

    DEFF Research Database (Denmark)

    Golembo-Smith, Shana; Schiffman, Jason; Kline, Emily;

    2012-01-01

    . Participants were grouped into three categories indicating level of genetic risk: children with a parent with schizophrenia (n=94); children with a parent with a non-psychotic mental health diagnosis (n=84); and children with a parent with no records of psychiatric hospitalization (n=66). Variables measured......The authors examined whether multiple childhood indicators of neurodevelopmental instability known to relate to schizophrenia-spectrum disorders could predict later schizophrenia-spectrum outcomes. A standardized battery of neurological and intellectual assessments was administered to a sample of...... correctly classified 73% (24 of 33) of the participants who eventually developed a schizophrenia-spectrum outcome in adulthood. Results suggest that, with replication, multivariate premorbid prediction could potentially be a useful complementary approach to identifying individuals at risk for developing a...

  8. Overexpression of the novel senescence marker β-galactosidase (GLB1 in prostate cancer predicts reduced PSA recurrence.

    Directory of Open Access Journals (Sweden)

    Jennifer Wagner

    Full Text Available Senescence is a terminal growth arrest that functions as a tumor suppressor in aging and precancerous cells and is a response to selected anticancer compounds. Lysosomal-β-galactosidase (GLB1 hydrolyzes β-galactose from glycoconjugates and is the origin of senescence-associated β-gal activity (SA-β-gal. Using a new GLB1 antibody, senescence biology was investigated in prostate cancer (PCa tissues.In vitro characterization of GLB1 was determined in primary prostate epithelial cell cultures passaged to replicative senescence and in therapy-induced senescence in PCa lines using chemotherapeutic agents. FFPE tissue microarrays were subjected to immunofluorescent staining for GLB1, Ki67 and HP1γ and automated quantitative imaging initially using AQUA in exploratory samples and Vectra in a validation series.GLB1 expression accumulates in replicative and induced senescence and correlates with senescent morphology and P16 (CDKN2 expression. In tissue arrays, quantitative imaging detects increased GLB1 expression in high-grade prostatic intraepithelial neoplasia (HGPIN, known to contain senescent cells, and cancer compared to benign prostate tissues (p<0.01 and senescent cells contain low Ki67 and elevated HP1γ. Within primary tumors, elevated GLB1 associates with lower T stage (p=0.01, localized versus metastatic disease (p=0.0003 and improved PSA-free survival (p=0.03. Increased GLB1 stratifies better PSA-free survival in intermediate grade PCa (0.01. Tissues that elaborate higher GLB1 display increased uniformity of expression.Increased GLB1 is a valuable marker in formalin-fixed paraffin-embedded (FFPE tissues for the senescence-like phenotype and associates with improved cancer outcomes. This protein addresses a lack of senescence markers and should be applicable to study the biologic role of senescence in other cancers.

  9. Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders

    OpenAIRE

    Lester Kathryn J; Eley Thalia C

    2013-01-01

    Abstract Considerable variation is evident in response to psychological therapies for mood and anxiety disorders. Genetic factors alongside environmental variables and gene-environment interactions are implicated in the etiology of these disorders and it is plausible that these same factors may also be important in predicting individual differences in response to psychological treatment. In this article, we review the evidence that genetic variation influences psychological treatment outcomes...

  10. Differential Expression of Stem Cell Markers in Ocular Surface Squamous Neoplasia.

    Science.gov (United States)

    Mishra, Dilip Kumar; Veena, Uppala; Kaliki, Swathi; Kethiri, Abhinav Reddy; Sangwan, Virender S; Ali, Mohammed Hasnat; Naik, Milind N; Singh, Vivek

    2016-01-01

    Ocular Surface Squamous Neoplasm (OSSN) is the neoplasia arising from the conjunctiva, cornea and limbus. OSSN ranges from mild, moderate, severe dysplasia, carcinoma in situ (CIS) to squamous cell carcinoma (SCC). Recent findings on cancer stem cells theory indicate that population of stem-like cell as in neoplasia determines its heterogeneity and complexity leading to varying tumor development of metastatic behavior and recurrence. Cancer stem cell markers are not much explored in the cases of OSSN. In the present study, we aim to evaluate the expression of stem cells using stem cell markers mainly p63, ABCG2, c-KIT (CD117) and CD44 in OSSN tissue, which could have prognostic significance. The present study tries for the first time to explore expression of these stem markers in the cases of OSSN. These cases are subdivided into two groups. One group comprises of carcinoma in situ (n = 6) and the second group comprises of invasive carcinoma (n = 6). The mean age at presentation was 52 years; with 53 years for CIS group and 52 years for SCC group. From each group section from the paraffin block were taken for the IHC staining of p63, c-Kit, ABCG2 and CD44. Our experiments show high expression of P63 and CD44 in the cases of CIN and SCC. Both CIS and SCC displayed positive staining with p63, with more than 80% cells staining positive. However minimal expression of c-kit in both CIN and SCC. But surprisingly we got high expression of ABCG2 in cases of carcinoma in situ as compared to that of invasive squamous cell carcinoma. More than 50% of cells showed CD44 positivity in both CIS and SCC groups. Our results show for the first time that these four stem cells especially the limbal epithelium stem cells play a vital role in the genesis of OSSN but we need to explore more cases before establishing its clinical and biological significance. PMID:27584160

  11. A novel predictive marker for the recurrence of nasal polyposis following endoscopic sinus surgery.

    Science.gov (United States)

    Boztepe, Osman Fatih; Gün, Taylan; Demir, Meltem; Gür, Özer Erdem; Ozel, Deniz; Doğru, Harun

    2016-06-01

    We aimed to determine the value of neutrophil-to-lymphocyte (NLR) ratio for prediction of recurrence in patients subjected to endoscopic sinus surgery. Higher neutrophil counts mean more chronic inflammation so the NLR value could show the inflammatory level resulting with higher incidence of recurrence. From January 2011 to March 2013, we performed a retrospective review of the complete blood count samples from 192 patients with chronic sinusitis who underwent endoscopic sinus surgery. The patients were divided into two groups based on the presence of nasal polyps. NLR and platelet-to-lymphocyte (PLR) ratios were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value for significant differences in variables between the recurrence and non-recurrence groups. The ROC analysis results revealed an NLR cut-off of 3.13 and a PLR cut-off of 208.75. Our analysis revealed that NLR is an independent risk factor for recurrence of chronic sinusitis in patients subjected to endoscopic sinus surgery (p = 0.006), whereas the PLR was not a predictive factor for recurrence (p = 0.167). Our study revealed that the NLR could be used to predict disease recurrence before endoscopic sinus surgery. However, additional studies are needed to confirm these results. PMID:26285781

  12. Temperature multiscale entropy analysis: a promising marker for early prediction of mortality in septic patients.

    Science.gov (United States)

    Papaioannou, V E; Chouvarda, I G; Maglaveras, N K; Baltopoulos, G I; Pneumatikos, I A

    2013-11-01

    A few studies estimating temperature complexity have found decreased Shannon entropy, during severe stress. In this study, we measured both Shannon and Tsallis entropy of temperature signals in a cohort of critically ill patients and compared these measures with the sequential organ failure assessment (SOFA) score, in terms of intensive care unit (ICU) mortality. Skin temperature was recorded in 21 mechanically ventilated patients, who developed sepsis and septic shock during the first 24 h of an ICU-acquired infection. Shannon and Tsallis entropies were calculated in wavelet-based decompositions of the temperature signal. Statistically significant differences of entropy features were tested between survivors and non-survivors and classification models were built, for predicting final outcome. Significantly reduced Tsallis and Shannon entropies were found in non-survivors (seven patients, 33%) as compared to survivors. Wavelet measurements of both entropy metrics were found to predict ICU mortality better than SOFA, according to a combination of area under the curve, sensitivity and specificity values. Both entropies exhibited similar prognostic accuracy. Combination of SOFA and entropy presented improved the outcome of univariate models. We suggest that reduced wavelet Shannon and Tsallis entropies of temperature signals may complement SOFA in mortality prediction, during the first 24 h of an ICU-acquired infection. PMID:24149496

  13. Temperature multiscale entropy analysis: a promising marker for early prediction of mortality in septic patients

    International Nuclear Information System (INIS)

    A few studies estimating temperature complexity have found decreased Shannon entropy, during severe stress. In this study, we measured both Shannon and Tsallis entropy of temperature signals in a cohort of critically ill patients and compared these measures with the sequential organ failure assessment (SOFA) score, in terms of intensive care unit (ICU) mortality. Skin temperature was recorded in 21 mechanically ventilated patients, who developed sepsis and septic shock during the first 24 h of an ICU-acquired infection. Shannon and Tsallis entropies were calculated in wavelet-based decompositions of the temperature signal. Statistically significant differences of entropy features were tested between survivors and non-survivors and classification models were built, for predicting final outcome. Significantly reduced Tsallis and Shannon entropies were found in non-survivors (seven patients, 33%) as compared to survivors. Wavelet measurements of both entropy metrics were found to predict ICU mortality better than SOFA, according to a combination of area under the curve, sensitivity and specificity values. Both entropies exhibited similar prognostic accuracy. Combination of SOFA and entropy presented improved the outcome of univariate models. We suggest that reduced wavelet Shannon and Tsallis entropies of temperature signals may complement SOFA in mortality prediction, during the first 24 h of an ICU-acquired infection. (paper)

  14. Expression Profile of Apoptotic Mediators and Proliferative Markers in Oral Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Oral squamous cell carcinoma (OSCC) represents a major health problem worldwide. It is therefore essential to develop a deeper understanding of its biology. Beside the recent hypothesis of cancer stem cells, the consideration of its cell death and cell proliferation has emerged as important diagnostic and prognostic tools. Purpose of the Study: Detection of the proportion of cell loss monitored by apoptosis-related genes, p53, p21 and Bcl2, and their relationship to the pathological proliferation parameter, PCNA in OSCC. Furthermore, discussion of the hypothesis of cancer stem cell biology in OSCC would be anticipated. Material and Methods: Archival 35 tissue embedded paraffin blocks, that were previously diagnosed as well to moderately differentiated OSCC, were immunohistochemically stained using a panel of antibodies including apoptotic mediators, p53, p21, Bcl2, and proliferation marker, PCNA. Immuno expression was scored using a semiquantitative scale and statistically analyzed. Results: The clinico-pathological data revealed that mean age was 46.9±8.2 and the tongue was the most affected site, followed by the palate then the floor of the mouth. There was no significant difference between metastasizing and non-metastasizing patients regarding age or gender (p=0.174, 0.404, respectively). On the other hand, variable profile patterns of the investigated indicators existed, where PCNA positively immunostaining cells was 100% while P21 recorded the higher percentage of negatively immunoreactive cells (42.9%). A common trait for the studied cell cycle indicators was that the basal and supra basal epithelial cells as well as the peripheral cells of the invading nests were the harbor of immunoreactivity. Meanwhile, Pca immuno positivity was revealed in all epithelial layers plus stromal cells. Conclusions: Assessment of the studied cell cycle regulators may be valuable to judge tumorigenesis of Osac. Furthermore, deregulation of cell cycle control might aid in the

  15. Usefulness of C-Reactive Protein as a Marker for Prediction of Future Coronary Events in the Asian Indian Population: Indian Atherosclerosis Research Study

    OpenAIRE

    Rao, Veena S.; Kadarinarasimhiah, Natesha B.; Shibu John; Sridhara Hebbagodi; Jayashree Shanker; Kakkar, Vijay V.

    2010-01-01

    Inflammation plays a pivotal role in all stages of atherosclerosis. Numerous inflammatory, lipid, and cytokines markers have been associated with coronary artery disease (CAD) risk but data directly comparing their predictive value are limited. Studies were carried to elucidate the role of high-sensitivity C-reactive protein (hsCRP), other inflammatory as well as lipid markers and their associations. Among 1021 subjects, comprising 774 CAD affected members from Indian Atherosclerosis Research...

  16. Proteomic profiling of pretreatment serum from HIV-infected patients identifies candidate markers predictive of lymphoma development

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Ludvigsen, Maja; Bendix, Knud;

    2016-01-01

    Objective: HIV-infected individuals have an increased risk of developing lymphoma. We sought to identify markers predictive of lymphoma development by comparing protein expression patterns in serum obtained at the time of HIV diagnosis from patients who later developed malignant lymphoma or benig...... protein spots were detected. Using principal components analysis, spots containing immunoglobulin J chain, apolipoprotein A-I, procollagen C-endopeptidase enhancer-1 and complement C4-A were associated with lymphoma development (P...... lymphadenopathy, with samples from patients with no subsequent history of neoplasia. Design: All patients were identified retrospectively from the Danish HIV cohort. Methods: Serum samples (N=21), obtained at time of HIV diagnosis, were subjected to high-resolution two-dimensional gel electrophoresis...

  17. Co-Expression of Cancer Stem Cell Markers Corresponds to a Pro-Tumorigenic Expression Profile in Pancreatic Adenocarcinoma.

    Science.gov (United States)

    Skoda, Jan; Hermanova, Marketa; Loja, Tomas; Nemec, Pavel; Neradil, Jakub; Karasek, Petr; Veselska, Renata

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Its dismal prognosis is often attributed to the presence of cancer stem cells (CSCs) that have been identified in PDAC using various markers. However, the co-expression of all of these markers has not yet been evaluated. Furthermore, studies that compare the expression levels of CSC markers in PDAC tumor samples and in cell lines derived directly from those tumors are lacking. Here, we analyzed the expression of putative CSC markers-CD24, CD44, epithelial cell adhesion molecule (EpCAM), CD133, and nestin-by immunofluorescence, flow cytometry and quantitative PCR in 3 PDAC-derived cell lines and by immunohistochemistry in 3 corresponding tumor samples. We showed high expression of the examined CSC markers among all of the cell lines and tumor samples, with the exception of CD24 and CD44, which were enriched under in vitro conditions compared with tumor tissues. The proportions of cells positive for the remaining markers were comparable to those detected in the corresponding tumors. Co-expression analysis using flow cytometry revealed that CD24+/CD44+/EpCAM+/CD133+ cells represented a significant population of the cells (range, 43 to 72%) among the cell lines. The highest proportion of CD24+/CD44+/EpCAM+/CD133+ cells was detected in the cell line derived from the tumor of a patient with the shortest survival. Using gene expression profiling, we further identified the specific pro-tumorigenic expression profile of this cell line compared with the profiles of the other two cell lines. Together, CD24+/CD44+/EpCAM+/CD133+ cells are present in PDAC cell lines derived from primary tumors, and their increased proportion corresponds with a pro-tumorigenic gene expression profile. PMID:27414409

  18. Molecular biology of breast cancer metastasis Molecular expression of vascular markers by aggressive breast cancer cells

    International Nuclear Information System (INIS)

    During embryogenesis, the formation of primary vascular networks occurs via the processes of vasculogenesis and angiogenesis. In uveal melanoma, vasculogenic mimicry describes the 'embryonic-like' ability of aggressive, but not nonaggressive, tumor cells to form networks surrounding spheroids of tumor cells in three-dimensional culture; these recapitulate the patterned networks seen in patients' aggressive tumors and correlates with poor prognosis. The molecular profile of these aggressive tumor cells suggests that they have a deregulated genotype, capable of expressing vascular phenotypes. Similarly, the embryonic-like phenotype expressed by the aggressive human breast cancer cells is associated with their ability to express a variety of vascular markers. These studies may offer new insights for consideration in breast cancer diagnosis and therapeutic intervention strategies

  19. Human Lyb-2 homolog CD72 is a marker for progenitor B-cell leukemias.

    Science.gov (United States)

    Schwarting, R; Castello, R; Moldenhauer, G; Pezzutto, A; von Hoegen, I; Ludwig, W D; Parnes, J R; Dörken, B

    1992-11-01

    S-HCL 2 is the prototype antibody of the recently defined CD72 cluster (human Lyb-2). Under nonreducing conditions, S-HCL 2 monoclonal antibody (mAb) precipitates a glycoprotein of 80-86 kDa. Under reducing conditions, a dimer of 43 and 39 kDa, with core proteins of 40 and 36 kDa, is precipitated. CD72 expression in normal and malignant tissues is different from expression of all other previously described human B-cell antigens. In peripheral blood and bone marrow, the antigen appears to be present on all B lymphocytes, with the exception of plasma cells. In tissue, immunohistochemical staining revealed positivity for all known B-cell compartments; however, pulpa macrophages of the spleen and von Kupffer cells exhibited distinct positivity for CD72 also. Among 83 malignant non-Hodgkin's lymphomas examined by immunohistochemistry (alkaline phosphatase anti-alkaline phosphatase technique), all 54 B-cell lymphomas, including precursor B-cell lymphomas, Burkitt's lymphomas, germinal center lymphomas, chronic lymphocytic leukemias, and hairy cell leukemias, were CD72 positive, but no T-cell lymphomas were. Flow cytometry study of more than 80 mainly acute leukemias (52 B-cell leukemias) showed reactivity with S-HCL 2 mAb over the full range of B-cell differentiation. In particular, very early B cells in cytoplasmic Ig (cIg)-negative, CD19-positive pre-pre-B-cell leukemias and hybrid leukemias (mixed myeloid and B-cell type) were consistently positive for CD72 on the cell surface. Therefore, CD72 may become an important marker for progenitor B-cell leukemias. PMID:1384316

  20. Immune development and regulation in young children - Potential markers for prediction of health and disease.

    NARCIS (Netherlands)

    Reubsaet, L.L.

    2014-01-01

    The human immune system is complex and is formed and shaped during life by many triggers. Different subsets of T helper cells are involved in immunity against pathogens, but can also play a role in inflammatory diseases like allergy, asthma and allo-reactive disease. The regulation of these inflamma

  1. Immune infiltrates as predictive markers of survival in pancreatic cancer patients

    Directory of Open Access Journals (Sweden)

    Maria Pia eProtti

    2013-08-01

    Full Text Available Pancreatic cancer is a devastating disease with dismal prognosis. The tumor microenvironment is composed by multiple cell types, molecular factors and extracellular matrix forming a strong desmoplastic reaction, which is a hallmark of the disease. A complex cross-talk between tumor cells and the stroma exists with reciprocal influence that dictates tumor progression and ultimately the clinical outcome. In this context, tumor infiltrating immune cells through secretion of chemokine and cytokines exert an important regulatory role. Here we review the correlation between the immune infiltrates, evaluated on tumor samples of pancreatic cancer patients underwent surgical resection, and disease free and/or overall survival after surgery. Specifically, we focus on tumor infiltrating lymphocytes, mast cells and macrophages that all contribute to a Th2-type inflammatory and immunosuppressive microenvironment. In these patients tumor immune infiltrates not only do not contribute to disease eradication but rather the features of Th2-type inflammation and immunosuppression is significantly associated with more rapid disease progression and reduced survival.

  2. CD133 is a temporary marker of cancer stem cells in small cell lung cancer, but not in non-small cell lung cancer.

    Science.gov (United States)

    Cui, Fei; Wang, Jian; Chen, Duan; Chen, Yi-Jiang

    2011-03-01

    Lung cancer is the most common cause of cancer-related death worldwide. Current investigations in the field of cancer research have intensively focused on the 'cancer stem cell' or 'tumor-initiating cell'. While CD133 was initially considered as a stem cell marker only in the hematopoietic system and the nervous system, the membrane antigen also identifies tumorigenic cells in certain solid tumors. In this study, we investigated the human lung cancer cell lines A549, H157, H226, Calu-1, H292 and H446. The results of real-time PCR analysis after chemotherapy drug selection and the fluorescence-activated cell sorting analysis showed that CD133 only functioned as a marker in the small cell lung cancer line H446. The sorted CD133+ subset presented stem cell-like features, including self-renewal, differentiation, proliferation and tumorigenic capacity in subsequent assays. Furthermore, a proportion of the CD133+ cells had a tendency to remain stable, which may explain the controversies arising from previous studies. Therefore, the CD133+ subset should provide an enriched source of tumor-initiating cells among H446 cells. Moreover, the antigen could be used as an investigative marker of the tumorigenic process and an effective treatment for small cell lung cancer. PMID:21174061

  3. Pan B and T cell markers in cutaneous tuberculosis: An immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Padmavathy L

    2007-01-01

    Full Text Available Histopathology of tuberculosis and leprosy is expected to correlate with the clinical and gross pathological aspects of the disease. However, this may not be the case, particularly in tuberculosis. This reflects our inadequate interpretation of the cellular events in tissues. The advent of immunocytochemistry for finding the cell types in lesions and some of their functions have helped in the interpretation of these changes. Immunocytochemical studies using monoclonal antibodies have shown consistent relationship between histology and lymphocyte organization in leprosy, a related mycobacterial disease. The study of the patterns of cellular responses in the granuloma per se from the different clinical expressions of tuberculosis is essential to comprehend the different immunopathogenic mechanisms in each. CD stands for cluster designation and is a nomenclature for the identification of specific cell surface antigens defined as monoclonal antibodies. This procedure can be applied to both formalin-fixed and frozen tissues. It is very helpful in identifying subpopulations of T and B cell lymphocytes. CD3 T cell is marked by receptors for antigen recognition, while CD20 is meant for Pan B cells and dendritic cells. Since CMI is the preeminent immune response to the Mycobacterium tuberculosis infection, interaction of antigen-presenting cells with antigen specific B and T lymphocytes is of paramount importance, which should be accompanied by cytokine production and liberation. The present study is undertaken for evaluating the cell types in lesions of cutaneous tuberculosis and some of their functions using B and T cell markers.

  4. Fluorescent membrane markers elucidate the association of Borrelia burgdorferi with tick cell lines.

    Science.gov (United States)

    Teixeira, R C; Baêta, B A; Ferreira, J S; Medeiros, R C; Maya-Monteiro, C M; Lara, F A; Bell-Sakyi, L; Fonseca, A H

    2016-06-20

    This study aimed to describe the association of Borrelia burgdorferi s.s. with ixodid tick cell lines by flow cytometry and fluorescence and confocal microscopy. Spirochetes were stained with a fluorescent membrane marker (PKH67 or PKH26), inoculated into 8 different tick cell lines and incubated at 30°C for 24 h. PKH efficiently stained B. burgdorferi without affecting bacterial viability or motility. Among the tick cell lines tested, the Rhipicephalus appendiculatus cell line RA243 achieved the highest percentage of association/internalization, with both high (90%) and low (10%) concentrations of BSK-H medium in tick cell culture medium. Treatment with cytochalasin D dramatically reduced the average percentage of cells with internalized spirochetes, which passed through a dramatic morphological change during their internalization by the host cell as observed in time-lapse photography. Almost all of the fluorescent bacteria were seen to be inside the tick cells. PKH labeling of borreliae proved to be a reliable and valuable tool to analyze the association of spirochetes with host cells by flow cytometry, confocal and fluorescence microscopy. PMID:27332772

  5. Transmembrane adaptor molecules: a new category of lymphoid-cell markers.

    Science.gov (United States)

    Tedoldi, Sara; Paterson, Jennifer C; Hansmann, Martin-Leo; Natkunam, Yasodha; Rüdiger, Thomas; Angelisova, Pavla; Du, Ming Q; Roberton, Helen; Roncador, Giovanna; Sanchez, Lydia; Pozzobon, Michela; Masir, Noraidah; Barry, Richard; Pileri, Stefano; Mason, David Y; Marafioti, Teresa; Horejsí, Václav

    2006-01-01

    Transmembrane adaptor proteins (of which 7 have been identified so far) are involved in receptor signaling in immune cells. They have only a short extracellular region, with most of the molecule comprising a substantial intracytoplasmic region carrying multiple tyrosine residues that can be phosphorylated by Src- or Syk-family kinases. In this paper, we report an immunohistologic study of 6 of these molecules in normal and neoplastic human tissue sections and show that they are restricted to subpopulations of lymphoid cells, being present in either T cells (LAT, LIME, and TRIM), B cells (NTAL), or subsets of both cell types (PAG and SIT). Their expression in neoplastic lymphoid cells broadly reflects that of normal lymphoid tissue, including the positivity of plasma cells and myeloma/plasmacytoma for LIME, NTAL, PAG, and SIT. However, this study also revealed some reactions that may be of diagnostic/prognostic value. For example, lymphocytic lymphoma and mantle-cell lymphoma showed similar profiles but differed clearly from follicle-center lymphoma, whereas PAG tended to be selectively expressed in germinal center-derived subsets of diffuse large B-cell lymphoma. These molecules represent a potentially important addition to the panel of immunophenotypic markers detectable in routine biopsies that can be used in hematopathologic studies. PMID:16160011

  6. From cell to man: Evaluation of osteopontin as a possible bio-marker of uranium exposure

    International Nuclear Information System (INIS)

    Background: Ore workers are conventionally monitored for exposure by measuring the uranium in their urine, but specific bio-markers of kidney damage still remain to be discovered. A recent toxico-genomics study allowed us to focus on osteopontin (OSTP) normally excreted in human urine and linked to mineral metabolism. Objectives: We examined the association between osteopontin and uranium exposure both in vitro, in a human kidney cell model, and in the urine of exposed individuals. Methods: OSTP was measured in supernatants of uranium-exposed HK2 cells to establish a dose-response curve and a time course experiment. Its role was studied through a gene extinction experiment. Uranium and OSTP were then monitored in the urine of exposed nuclear fuel industry workers and a chronically exposed population. These levels were compared with those found in a non-exposed population. Results: The study of HK2 cells indicated that OSTP secretion decreased after uranium exposure in a concentration and time dependent manner, but its suppression does not affect cell sensitivity to uranium. In spite of wide inter-individual variability, this parameter decreases also in human urine when urinary uranium exceeds 30 μg/L after an acute exposure, a value considered to be critical for kidney damage. Conclusion: This study reports how toxico-genomics can highlight putative toxicity bio-markers in an easy to access biological fluid. The decrease of urinary osteopontin in response to uranium exposure suggests kidney damage and would thus be complementary to current markers. (authors)

  7. Identification and characterization of 2 testicular germ cell markers, Glut3 and CyclinA2.

    Science.gov (United States)

    Howitt, Brooke E; Brooks, James D; Jones, Sunita; Higgins, John P T

    2013-10-01

    Testicular germ cell tumors (TGCT) are the most common type of testicular tumor and encompass different histologic types that greatly influence treatment and prognosis. Immunohistochemical studies may be required for accurate classification, particularly when these tumors present at extragonadal sites, and to aid in distinguishing histologic types. Traditional markers for identifying and distinguishing TGCT include PLAP, CD117, AFP, and CD30. More recently, the addition of OCT3/4 and SALL4 has increased sensitivity for immunohistochemical detection of germ cell tumors. We examined gene expression data from a previously published microarray study that compared normal testis mRNA expression to various TGCT. We also performed a search of the literature to identify less well-characterized markers. Glut3 and cyclinA2 showed promise as TGCT markers. Therefore, we evaluated expression of glut3 and cyclinA2 by immunohistochemistry using tissue microarrays (TMAs). Of 66 seminomas included in the TMA, 64 (97%) showed positive nuclear staining for cyclinA2 and 58 (88%) were strongly positive. Strong positive staining for cyclinA2 was also seen in the spermatocytic seminoma. All 20 of the embryonal carcinomas stained positively with cyclinA2, and 19 (95%) displayed strong nuclear staining for cyclinA2. Twenty of the 20 embryonal carcinomas stained for glut3 in a strong membranous pattern. Of 8 yolk sac tumors, 100% stained with glut3. We also evaluated glut3 and cyclinA2 staining on a general TMA containing 486 samples representing 156 different tumors. CyclinA2 stained a number of other tumor types, but the majority of these were weak or focal staining. Glut3 was rarely positive in other tumors; interestingly, most of these were of ovarian origin. We conclude that glut3 is a sensitive (96%) and specific (92%) marker for embryonal carcinomas and yolk sac tumors. Although cyclinA2 is a sensitive marker of seminomas and embryonal carcinomas (98%), its specificity is lower if

  8. Identification of Stage-Specific Surface Markers in Early B Cell Development Provides Novel Tools for Identification of Progenitor Populations.

    Science.gov (United States)

    Jensen, Christina T; Lang, Stefan; Somasundaram, Rajesh; Soneji, Shamit; Sigvardsson, Mikael

    2016-09-01

    Whereas the characterization of B lymphoid progenitors has been facilitated by the identification of lineage- and stage-specific surface markers, the continued identification of differentially expressed proteins increases our capacity to explore normal and malignant B cell development. To identify novel surface markers with stage-specific expression patterns, we explored the reactivity of CD19(+) B cell progenitor cells to Abs targeted to 176 surface proteins. Markers with stage-specific expression were identified using a transgenic reporter gene system subdividing the B cell progenitors into four surface IgM(-) stages. This approach affirmed the utility of known stage-specific markers, as well as identifying additional proteins that selectively marked defined stages of B cell development. Among the stage-specific markers were the cell adhesion proteins CD49E, CD11A, and CD54 that are highly expressed selectively on the most immature progenitors. This work identifies a set of novel stage-specific surface markers that can be used as a complement to the classical staining protocols to explore B lymphocyte development. PMID:27456481

  9. Pre-treatment prediction of chemoresistance in second-line chemotherapy of ovarian carcinoma: value of serological tumor marker determination (tetranectin, YKL-40, CASA, CA 125)

    DEFF Research Database (Denmark)

    Grønlund, B; Høgdall, E V S; Christensen, Ib Jarle;

    2006-01-01

    biochemical tumor markers tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The serum tumor marker levels at time of relapse were correlated with response status at landmark time after 4 cycles of second-line chemotherapy. Univariate and multivariate logistic regression analyses...... (chemoresistant vs non-chemoresistant disease) were performed. RESULTS: At landmark time, 26% of patients had progression according to the GCIG (Gynecologic Cancer Intergroup) progression criteria. In univariate logistic regression analysis, the tumor markers tetranectin (OR 0.4; 95% CI: 0.2-0.8; p=0.008), YKL-40...... (OR 1.8; 95% CI: 1.0-3.3; p=0.045), and CASA (OR 1.8; 95% CI: 1.2-2.7; p=0.007) had predictive value for second-line chemoresistance, whereas serum CA 125 had no predictive value. In a multivariate logistic regression analysis, serum tetranectin and CASA both had independent predictive value for...

  10. Predicting prognosis of rectal cancer patients with total mesorectal excision using molecular markers

    Institute of Scientific and Technical Information of China (English)

    Jun-Jie Peng; San-Jun Cai; Hong-Feng Lu; Guo-Xiang Cai; Peng Lian; Zu-Qing Guan; Ming-He Wang; Ye Xu

    2007-01-01

    AIM: To explore the prognostic variables in rectal cancer patients undergoing curative total mesorectal excision and the effect of postoperative chemotherapy in advanced rectal cancer.METHODS: A total of 259 consecutive rectal cancer patients treated with curative total mesorectal excision between 1999 and 2004 were collected, p53, p21, PCNA,and CD44v6 were examined using immunohistochemistry (IHC). The correlation between clinicopathological or molecular variables and clinical outcomes, including local recurrence, metastasis, disease-free survival and overall survival, was analyzed.RESULTS: The median follow-up was 44 mo. Fiveyear survival rates and 5-year disease free survival rates were 75.43% and 70.32%, respectively. Multi-analysis revealed TNM staging, preoperative CEA, and CD44v6 level were independent risk factors predicting overall survival or disease free survival. The hazard ratio of peroperative CEA was 2.65 (95% CI 1.4-5) and 3.10 (95% CI 1.37-6.54) for disease free survival and overall survival, respectively. The hazard ratio of CD44v6 was 1.93 (95% CI 1.04-3.61) and 2.21 (95% CI 1.01-4.88)for disease free survival and overall survival, respectively.TNM staging was the only risk factor predicting local recurrence. Postoperative chemotherapy without radiotherapy did not improve patients' outcome.CONCLUSION: TNM staging, preoperative CEA and CD44v6 were independent prognostic factors for rectal cancer patients with total mesorectal excision.Postoperative chemotherapy may be only used together with radiotherapy for rectal cancer patients.

  11. B7-H3 is a new cancer-specific endothelial marker in clear cell renal cell carcinoma

    OpenAIRE

    Qin XJ; Zhang HL; Ye DW; Dai B; Zhu Y; Shi GH

    2013-01-01

    Xiaojian Qin,1,2 Hailiang Zhang,1,2 Dingwei Ye,1,2 Bo Dai,1,2 Yao Zhu,1,2 Guohai Shi1,2 1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; 2Department of Oncology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China Background: The purpose of this study was to validate B7-H3 as a new cancer-specific endothelial marker in clear cell renal cell carcinoma. Methods: B7-H3 expression patterns were compared betw...

  12. Osteoclasts derive from hematopoietic stem cells according to marker, giant lysosomes of beige mice

    International Nuclear Information System (INIS)

    To ascertain the origin of multinucleated osteoclasts from hematopoietic stem cells, giant lysosomes peculiar to cells of beige mice (bg bg) were used as marker cells of that provenance. Radiation chimeras were established reciprocally between bg bg mice and osteopetrotic mi mi mice with defective osteoclasts. As a result, all the derivative cells of the hematopoietic stem cell would depend on the donor's cell line, whereas osteogenesis would remain the province of the host. It was affirmed in the chimeras mi mi/bg bg that the osteopetrosis was cured within six weeks. Thereafter the definitive osteoclasts of the chimeras contained giant lysosomes attributable to the beige cell line. However, the cure was well advanced before donor osteoclasts were prominent, for which several reasons are offered. In the mouse chimeras, bg bg/mi mi, there was a delay of some six weeks before osteopetrosis became evident, histologically before radiologically, at the major metaphyseal growth centers. During the period one to two months after establishment, osteoclasts appeared to be a mixture of two cell lines according to quantitative assessments for giant lysosomes. Assessments consisted of measurements of the percentage area of osteoclasts occupied by lysosomes over 1 micrometer diameter. The means were 0.018% +/- 0.008% for nonbeige stock and 2.09% +/- 0.58% for beige stock

  13. Cancer Stem Cells: Cell Culture, Markers and Targets for New Therapies

    OpenAIRE

    Gilbert, Candace A.; Ross, Alonzo H.

    2009-01-01

    A cancer stem cell is defined as an undifferentiated cell with the ability to self-renew, differentiate to multiple lineages and initiate tumors that mimic the parent tumor. In this review, we focus on glioblastomas, describing recent progress and problems in characterizing these cells. There have been advances in cancer stem cell culture, but tumor cell heterogeneity has made purification of cancer stem cells difficult. Indeed, it may be that cancer stem cells significantly vary from tumor t...

  14. Image findings and bone metabolic markers of bone involvement by oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kameta, Ayako; Tsuchimochi, Makoto; Harada, Mikiko; Katada, Tsutomu; Sasaki, Yoshihiko; Hayama, Kazuhide [Nippon Dental Univ. (Japan). School of Dentistry at Niigata

    2000-01-01

    Recently it has been reported that the circulating pyridinoline cross-linked carboxyl-terminal telopeptide of type I collagen (ICTP) and carboxyl-terminal propeptide of type I procollagen (PICP) are useful markers for detecting metastasis of malignancies to bone. Since ICTP and PICP are related to collagen metabolism, respectively breaking down and synthesizing type I collagen, elevated blood concentrations of these markers may reflect direct jaw bone destruction by oral cancer. The purpose of this study was to clarify the relationship between serum ICTP and PICP levels and bone invasion associated with oral cancer. Bone invasion was evaluated in 41 patients with oral squamous cell carcinoma (SCC) by panoramic radiography and {sup 99m}Tc-methylene diphosphonate (MDP) scintigraphy. We also assayed serum levels of parathyroid hormone-related protein (PTHrP) and compared them with concentrations of bone metabolic markers and imaging findings. There was no significant relationship between serum ICTP and PICP levels and bone invasion. However, in three of the five cases that showed remarkably high serum ICTP levels, {sup 99m}Tc-MDP uptake in the lesion was intensely increased. This suggests that serum ICTP levels may be elevated when bone metabolic changes caused by cancer involving the bone are extensive. We could find no significant correlation among serum levels of ICTP, PICP, and PTHrP. ICTP and PICP do not appear to be good indicators of direct bone invasion by oral SCC in early stages. (author)

  15. INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Mashima, Hirosato, E-mail: hmashima1-tky@umin.ac.jp [Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan); Ohno, Hideki [Division of Advanced Medical Science, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Yamada, Yumi; Sakai, Toshitaka; Ohnishi, Hirohide [Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan)

    2013-03-22

    Highlights: ► INSL5 is expressed in enteroendocrine cells along the colorectum. ► INSL5 is expressed increasingly from proximal colon to rectum. ► INSL5 co-localizes rarely with chromogranin A. ► All rectal neuroendocrine tumors examined expressed INSL5. -- Abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5–RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors.

  16. INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

    International Nuclear Information System (INIS)

    Highlights: ► INSL5 is expressed in enteroendocrine cells along the colorectum. ► INSL5 is expressed increasingly from proximal colon to rectum. ► INSL5 co-localizes rarely with chromogranin A. ► All rectal neuroendocrine tumors examined expressed INSL5. -- Abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5–RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors

  17. Predictable factors for lymph node metastasis in early gastric cancer analysis of clinicopathologic factors and biological markers.

    Science.gov (United States)

    Wang, Yi-Wei; Zhu, Mei-Ling; Wang, Rui-Fen; Xue, Wen-Ji; Zhu, Xue-Ru; Wang, Li-Feng; Zheng, Lei-Zhen

    2016-07-01

    Predicting lymph node metastasis (LNM) accurately is very important to decide treatment strategies preoperatively. The aim of this study was to explore risk factors that predict the presence of LNM in early gastric cancer (EGC). A total of 230 patients with EGC who underwent curative gastrectomy with lymph adenectomy at Xinhua Hospital from January 2006 to July 2014 were retrospectively reviewed. We studied the relationship between clinicopathological factors, biological markers (p53, ki67, nm23, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), E-cadherin (E-cad), beta-catenin (b-catenin), glutathione S-transferase (GST), and topoisomerase II (Topo II)), and LNM of EGC patients by chi-square test and logistic regression analysis. Meta-analyses were further conducted to review the effects of the proteins (P53, ki67, E-cad, and b-catenin) on LNM in ECG patients. LNM was detected in 42 (18.3 %) of 230 patients. Incidences of LNM was distinct in different tumor size (p = 0.044), depth of submucosal invasion (p validation in single large studies. PMID:26733174

  18. Expression of Excision Repair Cross-Complementation Group 1 as Predictive Marker for Nasopharyngeal Cancer Treated With Concurrent Chemoradiotherapy

    International Nuclear Information System (INIS)

    Purpose: Cisplatin-based concurrent chemoradiotherapy is the standard treatment of nasopharyngeal cancer. The expression of excision repair cross-complementation group 1 (ERCC1) has been reported to be associated with resistance to platinum-based chemotherapy. We evaluated whether ERCC1 expression could predict the treatment response and survival outcome of patients with locally advanced nasopharyngeal cancer who were treated with cisplatin-based concurrent chemoradiotherapy. Methods and Materials: Immunohistochemistry was used to examine the expression of ERCC1 in nasopharyngeal tumor tissue. Patients were categorized into either a resistant or sensitive group depending on their treatment response outcome. A total of 77 patients were assessed in the present study. Results: The resistant and sensitive groups included 25 and 52 patients, respectively. ERCC1 expression was positive in the tumor tissue for 39 of the 77 patients (51%). Significantly more ERCC1-negative tumors were in the sensitive group than in the resistant group (p = .035). In terms of survival outcome, univariate analysis determined that patients with ERCC1-negative tumors had longer disease-free survival (p = .076) and overall survival (p = .013) than patients with ERCC1-positive tumors. Multivariate analysis determined that negative ERCC expression in tumors was an independent predictor for prolonged overall survival (hazard ratio, 0.14; 95% confidence interval, 0.03-0.71). Conclusion: These results suggest that ERCC1 expression might be a useful predictive marker in patients with locally advanced nasopharyngeal cancer who are under consideration for cisplatin-based concurrent chemoradiotherapy.

  19. Use of novel serum markers in clinical follow-up of Sertoli-Leydig cell turnours

    OpenAIRE

    Lenhard, Miriam; Kuemper, Caroline; DITSCH, NINA; Diebold, Joachim; Stieber, Petra; Friese, Klaus; Burges, Alexander

    2007-01-01

    Background: Sertoli-Leyclig cell tumours of the ovary account for only 0.2% of malignant ovarian tumours. Two-thirds of all patients become apparent due to the tumour's hormone production. Methods: A 41-year-old patient (gravida 4, para 4) presented with dyspnoea, enlarged abdominal girth and melaena. Diagnostic imaging was suspicious for an ovarian cancer. The standard tumour marker for ovarian cancer (CA 125) was elevated to 984 U/mL. Results: Surgical exploration of the abdomen revealed a ...

  20. Rearrangements of the tal-1 locus as clonal markers for T cell acute lymphoblastic leukemia.

    OpenAIRE

    Jonsson, O G; Kitchens, R. L.; Baer, R J; Buchanan, G. R.; Smith, R G

    1991-01-01

    Normal and aberrant immune receptor gene assembly each produce site-specific DNA rearrangements in leukemic lymphoblasts. In either case, these rearrangements provide useful clonal markers for the leukemias in question. In the t(1;14)(p34;q11) translocation associated with T cell acute lymphoblastic leukemia (T-ALL), the breakpoints on chromosome 1 interrupt the tal-1 gene. A site-specific deletion interrupts the same gene in an additional 26% of T-ALL. Thus, nearly one-third of these leukemi...

  1. Novel Molecular Tumor Cell Markers in Regional Lymph Nodes and Blood Samples from Patients Undergoing Surgery for Non-Small Cell Lung Cancer

    OpenAIRE

    Oddmund Nordgård; Gurpartap Singh; Steinar Solberg; Lars Jørgensen; Ann Rita Halvorsen; Rune Smaaland; Odd Terje Brustugun; Åslaug Helland

    2013-01-01

    INTRODUCTION: Recent evidence suggests that microscopic lymph node metastases and circulating tumor cells may have clinical importance in lung cancer. The purpose of this study was to identify new molecular markers for tumor cells in regional lymph nodes (LNs) and peripheral blood (PB) from patients with non-small cell lung cancer (NSCLC). METHODS: Candidate markers were selected based on digital transcript profiling and previous literature. KRT19, CEACAM5, EPCAM, DSG3, SFTPA, SFTPC and SFTPB...

  2. High-resolution analyses of two different classes of tumor cells in situ tagged with alternative histochemical marker genes.

    OpenAIRE

    Lin, W.C.; Pretlow, T. P.; Pretlow, T. G.; Culp, L. A.

    1992-01-01

    To evaluate interactions of two different tumor cell classes during the establishment of micrometastases at the single-cell level, two different BALB/c 3T3 tumor cell derivatives were established that harbor different histochemical marker genes: bacterial lacZ in a EJ-Harvey ras transformant (abbreviated LZEJ cells) and human placental alkaline phosphatase (ALP) gene in a human c-sis transformant (APSI cells). Several different histochemical staining methods were evaluated, using the distinct...

  3. Co-Expression of Cancer Stem Cell Markers Corresponds to a Pro-Tumorigenic Expression Profile in Pancreatic Adenocarcinoma

    Science.gov (United States)

    Skoda, Jan; Hermanova, Marketa; Loja, Tomas; Nemec, Pavel; Neradil, Jakub; Karasek, Petr; Veselska, Renata

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Its dismal prognosis is often attributed to the presence of cancer stem cells (CSCs) that have been identified in PDAC using various markers. However, the co-expression of all of these markers has not yet been evaluated. Furthermore, studies that compare the expression levels of CSC markers in PDAC tumor samples and in cell lines derived directly from those tumors are lacking. Here, we analyzed the expression of putative CSC markers—CD24, CD44, epithelial cell adhesion molecule (EpCAM), CD133, and nestin—by immunofluorescence, flow cytometry and quantitative PCR in 3 PDAC-derived cell lines and by immunohistochemistry in 3 corresponding tumor samples. We showed high expression of the examined CSC markers among all of the cell lines and tumor samples, with the exception of CD24 and CD44, which were enriched under in vitro conditions compared with tumor tissues. The proportions of cells positive for the remaining markers were comparable to those detected in the corresponding tumors. Co-expression analysis using flow cytometry revealed that CD24+/CD44+/EpCAM+/CD133+ cells represented a significant population of the cells (range, 43 to 72%) among the cell lines. The highest proportion of CD24+/CD44+/EpCAM+/CD133+ cells was detected in the cell line derived from the tumor of a patient with the shortest survival. Using gene expression profiling, we further identified the specific pro-tumorigenic expression profile of this cell line compared with the profiles of the other two cell lines. Together, CD24+/CD44+/EpCAM+/CD133+ cells are present in PDAC cell lines derived from primary tumors, and their increased proportion corresponds with a pro-tumorigenic gene expression profile. PMID:27414409

  4. Heavy-ion irradiation induced alteration in histopathology and cancer stem cell markers

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate whether carbon ion irradiation had beneficial effects by targeting cancer stem cells, human colon cancer cells were treated in vitro and in vivo by carbon ion or X-rays irradiation. The relative biological effectiveness (RBE) value of carbon ion relative to X-rays was calculated to be 1.6 in vitro (D10 survival fraction) and 3.82 in vivo (tumor regrowth delay). FACS data provide evidence that cancer stem-like CD133+, CD44+ and EpCAM+ cells were highly enriched after low linear energy transfer (LET) X-rays compared to high LET carbon ion irradiation in a dose-dependent manner. At an isodose of 30 Gy, carbon ion irradiation predominantly induced xenograft tumor cell cavitation and fibrosis, whereas X-rays irradiation only partially destroyed the tumor cell mass. The expression of cancer stem-like cell markers, CD133, EpCAM, and CD44 were significantly suppressed following carbon ion irradiation. In contrast, X-rays actually increased the expression of these proteins. Heavy ion irradiation has a great potential to effectively target radioresistant cancer stem cells. This is considered to be one of the major contributing factors for the high radiocurability of heavy ion cancer treatment. (author)

  5. Class III β-tubulin is a predictive marker for taxane-based chemotherapy in recurrent and metastatic gastric cancer

    International Nuclear Information System (INIS)

    Class III β-tubulin (TUBB3) is a prognostic marker in various tumors, but the role of TUBB3 in advanced gastric cancer is not clearly defined. We analyzed the significance of TUBB3 expression, along with that of excision repair cross-complementation group 1 (ERCC1) in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy. We reviewed the cases of 146 patients with advanced gastric adenocarcinoma who received taxane-based first-line palliative chemotherapy between 2004 and 2010 at Chonnam National University Hwasun Hospital (Gwangju, Korea). Immunohistochemical staining for TUBB3 and ERCC1 was performed using paraffin wax-embedded tumor tissues. We evaluated the patients’ response to chemotherapy, progression-free survival (PFS), and overall survival (OS). In total, 146 patients with advanced gastric cancer received docetaxel and cisplatin (n = 15) or paclitaxel and cisplatin (n = 131). The median PFS was significantly shorter for patients with high-level TUBB3 expression than for patients with low-level TUBB3 expression (3.63 vs. 6.67 months, P = 0.001). OS was not associated with TUBB3 expression (13.1 vs. 13.1 months, P = 0.769). By multivariate analysis, only TUBB3 was related to a shorter PFS (HR 2.74, 95% CI 1.91-3.91, P = 0.001). Patients with high-level ERCC1 expression showed a lower response rate than patients with low-level ERCC1 expression (24 vs. 63.2%, P = 0.001); however, ERCC1 had no clinical effect on PFS or OS. TUBB3 was a strong predictive marker in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy. No clinical impact of ERCC1 was evident in this setting

  6. Fluorodeoxyglucose positron emission tomography and chemotherapy-related tumor marker expression in non-small cell lung cancer

    International Nuclear Information System (INIS)

    The chemotherapy resistance of non-small cell lung cancer (NSCLC) remains a clinic challenge and is closely associated with several biomarkers including epidermal growth factor receptor (EGFR) (Drugs 72(Suppl 1):28–36, 012.), p53 (Med Sci Monit 11(6):HY11–HY20, 2005.) and excision repair cross complementing gene 1 (ERCC1) (J Thorac Oncol 8(5):582–586, 2013.). Fluorodeoxyglucose positron emission tomography (FDG–PET) is the best non-invasive surrogate for tumor biology with the maximal standardized uptake values (SUVmax) being the most important paradigm. However, there are limited data correlating FDG-PET with the chemotherapy resistant tumor markers. The purpose of this study was to determine the correlation of chemotherapy related tumor marker expression with FDG–PET SUVmax in NSCLC. FDG–PET SUVmax was calculated in chemotherapy naïve patients with NSCLC (n = 62) and immunohistochemical analysis was performed for EGFR, p53 or ERCC1 on the intraoperative NSCLC tissues. Each tumor marker was assessed independently by two pathologists using common grading criteria. The SUVmax difference based on the histologic characteristics, gender, differentiation, grading and age as well as correlation analysis among these parameters were performed. Multiple stepwise regression analysis was further performed to determine the primary predictor for SUVmax and the receiver operating characteristics (ROC) curve analysis was performed to detect the optimized sensitivity and specificity for SUVmax in suggesting chemotherapy resistant tumor markers. The significant tumor type (P = 0.045), differentiation (P = 0.021), p53 (P = 0.000) or ERCC1 (P = 0.033) positivity dependent differences of SUVmax values were observed. The tumor differentiation is significantly correlated with SUVmax (R = -0.327), tumor size (R = -0.286), grading (R = -0.499), gender (R = 0.286) as well as the expression levels for p53 (R = -0.605) and ERCC1 (R = -0.644). The expression level of p53 is

  7. The relationship between glasgow prognostic score and serum tumor markers in patients with advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Glasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non–small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC. We included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21–1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted. Median levels of CYFRA21–1 were 1.5 ng/ml (0.1–3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7–35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4–89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9–134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (P < 0.05). Similar results were found for median levels of CEA and TPS in healthy controls and NSCLC patients (P < 0.05). In NSCLC patients, positive correlations were found between CYFRA21-1 and GPS, CEA and GPS, TPS and GPS. The Spearman’s rank correlation coefficient were 0.67 (P < 0.05), 0.61 (P < 0.05) and 0.55 (P < 0.05), respectively. Survival analyses showed GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC. Our results showed GPS were positive correlated

  8. Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

    Directory of Open Access Journals (Sweden)

    Montzka Katrin

    2009-03-01

    Full Text Available Abstract Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as

  9. Are globoseries glycosphingolipids SSEA-3 and -4 markers for stem cells derived from human umbilical cord blood?

    Institute of Scientific and Technical Information of China (English)

    Heli Suila; Jari Natunen; Saara Laitinen; Leena Valmu; Virve Pitk(a)nen; Tia Hirvonen; Annamari Heiskanen; Heidi Anderson; Anita Laitinen; Suvi Natunen; Halina Miller-Podraza; Tero Satomaa

    2011-01-01

    Umbilical cord blood (UCB) is an efficient and valuable source of hematopoietic stem cells (HSCs) for transplantation. In addition to HSCs it harbours low amounts of mesenchymal stem cells (MSCs). No single marker to identify cord blood-derived stem cells, or to indicate their multipotent phenotype, has been characterized so far. SSEA-3 and -4 are cell surface globoseries glycosphingolipid epitopes that are commonly used as markers for human embryonic stem cells, where SSEA-3 rapidly disappears when the cells start to differentiate. Lately SSEA-3 and -4 have also been observed in MSCs. As there is an ongoing discussion and variation of stem-cell markers between laboratories, we have now comprehensively characterized the expression of these epitopes in both the multipotent stem-cell types derived from UCB. We have performed complementary analysis using gene expression analysis, mass spectrometry and immunochemical methods, including both flow cytometry and immunofluoresence microscopy. SSEA-4, but not SSEA-3, was expressed on MSCs but absent from HSCs. Our findings indicate that SSEA-3 and/or -4 may not be optimal markers for multipotency in the case of stem cells derived from cord blood, as their expression may be altered by cell-culture conditions.

  10. Clinical Significance of Immuno phenotypic Markers in Pediatric T-cell Acute Lymphoblastic Leukemia

    International Nuclear Information System (INIS)

    Background: Cell-marker profiling has led to conflicting conclusions about its prognostic significance in T-ALL. Aim: To investigate the prevalence of the expression of CD34, CD10 and myeloid associated antigens (CD13/ CD33) in childhood T-ALL and to relate their presence to initial clinical and biologic features and early response to therapy. Patients and Methods: This study included 67 consecutive patients with newly diagnosed T-ALL recruited from the Children's Cancer Hospital in Egypt during the time period from July 2007 to June 2008. Immuno phenotypic markers and minimal residual disease (MRD) were studied by five-color flow cytometry. Results: The frequency of CD34 was 34.9%, CD10 33.3%, while CD13/CD33 was 18.8%. No significant association was encountered between CD34, CD10 or myeloid antigen positivity and the presenting clinical features as age, sex, TLC and CNS leukemia. Only CD10+ expression had significant association with initial CNS involvement (p=0.039). CD34 and CD13/CD33 expression was significantly associated with T-cell maturation stages (p<0.05). No relationship was observed for age, TLC, gender, NCI risk or CNS involvement with early response to therapy illustrated by BM as well as MRD day 15 and day 42. CD34+, CD13/CD33+ and early T-cell stage had high MRD levels on day 15 that was statistically highly significant (p<0.01), but CD10+ had statistically significant lower MRD level on day 15 (p=0.049). However, only CD34 retained its significance at an MRD cut-off level of 0.01%. Conclusion: CD34, CD10, CD13/CD33 expression, as well as T-cell maturation stages, may have prognostic significance in pediatric T-ALL as they have a significant impact on early clearance of leukemic cells detected by MRD day 15.

  11. Expression of mesenchymal stem cell marker CD90 on dermal sheath cells of the anagen hair follicle in canine species

    Directory of Open Access Journals (Sweden)

    F. Mercati

    2009-09-01

    Full Text Available The dermal sheath (DS of the hair follicle is comprised by fibroblast-like cells and extends along the follicular epithelium, from the bulb up to the infundibulum. From this structure, cells with stem characteristics were isolated: they have a mesenchymal origin and express CD90 protein, a typical marker of mesenchymal stem cells. It is not yet really clear in which region of hair follicle these cells are located but some experimental evidence suggests that dermal stem cells are localized prevalently in the lower part of the anagen hair follicle. As there are no data available regarding DS stem cells in dog species, we carried out a morphological analysis of the hair follicle DS and performed both an immunohistochemical and an immunocytochemical investigation to identify CD90+ cells. We immunohistochemically evidenced a clear and abundant positivity to CD90 protein in the DS cells located in the lower part of anagen hair follicle. The positive cells showed a typical fibroblast-like morphology. They were flat and elongated and inserted among bundles of collagen fibres. The whole structure formed a close and continuous sleeve around the anagen hair follicle. Our immunocytochemical study allowed us to localize CD90 protein at the cytoplasmic membrane level.

  12. In vitro cell motility as a potential mesenchymal stem cell marker for multipotency.

    Science.gov (United States)

    Bertolo, Alessandro; Gemperli, Armin; Gruber, Marco; Gantenbein, Benjamin; Baur, Martin; Pötzel, Tobias; Stoyanov, Jivko

    2015-01-01

    Mesenchymal stem cells (MSCs) are expected to have a fundamental role in future cell-based therapies because of their high proliferative ability, multilineage potential, and immunomodulatory properties. Autologous transplantations have the "elephant in the room" problem of wide donor variability, reflected by variability in MSC quality and characteristics, leading to uncertain outcomes in the use of these cells. We propose life imaging as a tool to characterize populations of human MSCs. Bone marrow MSCs from various donors and in vitro passages were evaluated for their in vitro motility, and the distances were correlated to the adipogenic, chondrogenic, and osteogenic differentiation potentials and the levels of senescence and cell size. Using life-image measuring of track lengths of 70 cells per population for a period of 24 hours, we observed that slow-moving cells had the higher proportion of senescent cells compared with fast ones. Larger cells moved less than smaller ones, and spindle-shaped cells had an average speed. Both fast cells and slow cells were characterized by a low differentiation potential, and average-moving cells were more effective in undergoing all three lineage differentiations. Furthermore, heterogeneity in single cell motility within a population correlated with the average-moving cells, and fast- and slow-moving cells tended toward homogeneity (i.e., a monotonous moving pattern). In conclusion, in vitro cell motility might be a useful tool to quickly characterize and distinguish the MSC population's differentiation potential before additional use. PMID:25473086

  13. Response to induction chemotherapy as predictive marker of tumor response to radiotherapy and survival in oral cavity cancer

    OpenAIRE

    Surendra Kumar Saini; Shelly Srivastava; Shanbhu Nath Prasad

    2015-01-01

    Background: Trials have shown some statistically nonsignificant survival advantage of taxane, platin and 5-FU (TPF) induction chemotherapy before definitive chemoradiation. We tried to find the role of induction chemotherapy in the prediction of tumor response to radiotherapy and survival in the treatment of oral cavity cancers. Patients and Methods: Patients of stage III and IV (M0) unresectable oral cavity squamous cell carcinoma were assigned to receive two cycles of TPF. On the basis of r...

  14. Characterization of inflammatory markers and transcriptome profiles of differentially activated embryonic stem cell-derived microglia.

    Science.gov (United States)

    Beins, Eva; Ulas, Thomas; Ternes, Svenja; Neumann, Harald; Schultze, Joachim L; Zimmer, Andreas

    2016-06-01

    Microglia, the immune cells of the CNS, are highly adaptive cells that can acquire different pro- and anti-inflammatory activation states with distinct functions in CNS homeostasis and pathologies. To study microglial function in vitro, primary microglia or immortalized cell lines are commonly used. An alternative to these cells are embryonic stem cell-derived microglia (ESdM). ESdM have previously been shown to be very similar to primary microglia in terms of expression profiles and surface molecules. In this study, ESdM and primary microglia were treated with different inflammatory stimulants to analyze their ability to adopt different activation states. Using quantitative real-time PCR, comparative transcriptomics, ELISA, and flow cytometry, we found that different activation states can be induced in ESdM, which are similar to those found in primary microglia. These states are characterized by specific sets of inflammatory marker molecules and differential transcriptome signatures. Our results show that ESdM are a valuable alternative cell model to study microglial functions and neuroinflammatory mechanisms. GLIA 2016;64:1007-1020. PMID:26959607

  15. Circulating tumor cells in prostate cancer: a potential surrogate marker of survival.

    Science.gov (United States)

    Doyen, Jérôme; Alix-Panabières, Catherine; Hofman, Paul; Parks, Scott K; Chamorey, Emmanuel; Naman, Hervé; Hannoun-Lévi, Jean-Michel

    2012-03-01

    Prostate-specific antigen (PSA) levels in blood are widely used in prostate cancer (PCa) for the management of this disease at every stage of progression. Currently, PSA levels combined with clinical stage and Gleason score provide the best predictor of survival and the main element to monitor treatment efficiency. However, these areas could be improved by utilizing emerging biomarkers. Recently, circulating tumor cells (CTCs) and disseminating tumor cells (DTCs) have been detected in PCa and may be a new surrogate candidate. Here we provide a systematic review of the literature in order to describe the current evidence of CTC/DTC surrogacy regarding outcome of prostate cancer patients. We also discuss several markers that could be used to increase the sensitivity and specificity of CTC/DTC detection. CTC/DTC detection is performed using a wide variety of techniques. Initially, reverse transcriptase polymerase chain reaction (RT-PCR) based methods were utilized with weak correlation between their positive detection and patients' outcome. More recent immunological techniques have indicated a reproducible correlation with outcome. Such surrogate markers may enable clinicians to provide early detection for inefficient treatments and patients with poor prognosis that are candidates for treatment intensification. Dissecting the micrometastasis phenomenon in CTCs/DTCs is a key point to increase surrogacy of this biomarker. PMID:21680196

  16. Neuropsychological and neuroimaging markers in prediction of cognitive impairment after ischemic stroke: a prospective follow-up study

    Directory of Open Access Journals (Sweden)

    Mehrabian S

    2015-10-01

    Full Text Available Shima Mehrabian,1 Margarita Raycheva,1 Neli Petrova,2 Armina Janyan,3,4 Mariya Petrova,1 Latchezar Traykov1 1Clinic of Neurology, University Hospital Alexandrovska, Sofia, 2Clinic of Neurology, MHAT “Ruse”, Ruse, 3Research Center for Cognitive Science, Department of Cognitive Science and Psychology, New Bulgarian University, Sofia, Bulgaria; 4Laboratory for Cognitive Studies in Language, National Research Tomsk State University, Tomsk, Russia Background: There are few longitudinal studies with controversial results examining delayed changes in cognition after ischemic stroke and predictive values of neuropsychological and neuroimaging markers. Objective: The objectives of this study were to evaluate the delayed changes in cognition in poststroke patients and their relationship to the neuropsychological and neuroimaging markers measured during the acute poststroke phase. Methods: Eighty-five first-ever stroke inpatients (mean age 65.6±5.6 years without previous cognitive complaints were prospectively evaluated with a comprehensive neuropsychological battery at the 5th day and the 1st, 6th, and 12th months. A wide range of clinical, radiological, and neuropsychological variables were examined. Results: Our results showed significantly poorer performance on mini–mental state examination, memory, attention/executive functions, and processing speed in patients with stroke in comparison with stroke-free cognitively intact controls. Multiple regression analysis revealed that hippocampal atrophy is the strongest predictor of delayed cognitive impairment. Secondary divided subgroups according to Isaacs Set Test (IST score showed that patients with IST score ≤28 had different patterns of cognitive and neurological impairment after 1 year. Baseline impairments in attention/executive functions and memory were associated with development of dementia in poststroke patients. Conclusion: Executive functioning deficit appears to have a predictive power

  17. Pre-treatment prediction of chemoresistance in second-line chemotherapy of ovarian carcinoma: value of serological tumor marker determination (tetranectin, YKL-40, CASA, CA 125)

    DEFF Research Database (Denmark)

    Grønlund, B; Høgdall, E V S; Christensen, Ib Jarle;

    2006-01-01

    biochemical tumor markers tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The serum tumor marker levels at time of relapse were correlated with response status at landmark time after 4 cycles of second-line chemotherapy. Univariate and multivariate logistic regression analyses...... (OR 1.8; 95% CI: 1.0-3.3; p=0.045), and CASA (OR 1.8; 95% CI: 1.2-2.7; p=0.007) had predictive value for second-line chemoresistance, whereas serum CA 125 had no predictive value. In a multivariate logistic regression analysis, serum tetranectin and CASA both had independent predictive value for...... chemoresistance. The combined determination of tetranectin and CASA had a specificity of 90% with 33% sensitivity for the prediction of chemoresistance (area under the receiver operating characteristic curve = 0.78; 95% CI: 0.66-0.91; p=0.001). CONCLUSION: Low serum levels of tetranectin, or high serum levels of...

  18. Origin of Ameloblastoma From Basal Cells of the Oral Epithelium- Establishing the Relation Using Neuroectodermal Markers

    Science.gov (United States)

    Suneela, S; Narayan, T V; Shreedhar, Balasundari; Mohanty, Leeky; Shenoy, Sadhana; Swaminathan, Uma

    2014-01-01

    Background and Objectives: Basal cell layer of the oral epithelium has been rightfully regarded as a potential source of odontogenic tumours and cysts, but, without substantial evidence. Also, whether the basal cell layer retains within it, some properties of ectomesenchyme, which was imbibed during the early embryogenesis and hence its neuroectodermal relation, is not known. Here, an attempt is made to establish the hidden neuroectodermal potential of the oral epithelium, especially the basal layer, by observing the expression of known neuroectodermal markers, NSE (Neuron Specific Enolase), Synaptophysin and CD99. The expression of the same markers has also been studied in Ameloblastoma, connecting it with oral epithelium, in turn establishing basal cell layer as a potential source of Ameloblastoma. Materials and Methods: Sections of formalin fixed, paraffin embedded tissue samples of 20 cases of Ameloblastoma and 10 cases of Normal Retromolar mucosa, were stained immunohistochemically with NSE, Synaptophysin, CD99 and also with CK-19 and evaluated for positive expression. Results: Positive reaction was obtained in all the cases of Ameloblastoma and NRM (Normal Retromolar mucosa) with NSE, all the cases of Ameloblastoma and eight cases of NRM with Synaptophysin and in six cases of Ameloblastoma and NRM with CD99. The staining was diffuse and more marked in case of NSE than Synaptophysin and CD99. CK19 staining done to assure that the tissue antigenicity was maintained was positive in all the samples. Interpretation and Conclusion: A strong relationship between the neuroectoderm, Ameloblastoma and the basal layer of the oral epithelium is established by the study. It favours the hypothesis that the basal cell layer of oral mucosa may be the sought out culprit in most cases of the Ameloblastomas, especially those occurring in the non-tooth bearing area. This would call for the need to incorporate additional therapy in the form of mucosal striping along with the

  19. Predicting the Effect of Accelerated Fractionation in Postoperative Radiotherapy for Head and Neck Cancer Based on Molecular Marker Profiles: Data From a Randomized Clinical Trial

    International Nuclear Information System (INIS)

    Purpose: To determine the prognostic and predictive values of molecular marker expression profiles based on data from a randomized clinical trial of postoperative conventional fractionation (p-CF) therapy versus 7-day-per-week postoperative continuous accelerated irradiation (p-CAIR) therapy for squamous cell cancer of the head and neck. Methods and Materials: Tumor samples from 148 patients (72 p-CF and 76 p-CAIR patients) were available for molecular studies. Immunohistochemistry was used to assess levels of EGFR, nm23, Ki-67, p-53, and cyclin D1 expression. To evaluate the effect of fractionation relative to the expression profiles, data for locoregional tumor control (LRC) were analyzed using the Cox proportional hazard regression model. Survival curves were compared using the Cox f test. Results: Patients who had tumors with low Ki-67, low p-53, and high EGFR expression levels and oral cavity/oropharyngeal primary cancer sites tended to benefit from p-CAIR. A joint score for the gain in LRC from p-CAIR based of these features was used to separate the patients into two groups: those who benefited significantly from p-CAIR with respect to LRC (n = 49 patients; 5-year LRC of 28% vs. 68%; p = 0.01) and those who did not benefit from p-CAIR (n = 99 patients; 5-year LRC of 72% vs. 66%; p = 0.38). The nm23 expression level appeared useful as a prognostic factor but not as a predictor of fractionation effect. Conclusions: These results support the studies that demonstrate the potential of molecular profiles to predict the benefit from accelerated radiotherapy. The molecular profile that favored accelerated treatment (low Ki-67, low p-53, and high EGFR expression) was in a good accordance with results provided by other investigators. Combining individual predictors in a joint score may improve their predictive potential.

  20. Predicting Breed Composition Using Breed Frequencies of 50,000 Markers from the U.S. Meat Animal Research Center 2,000 Bull Project

    Science.gov (United States)

    Our objective was to evaluate whether breed composition of crossbred cattle could be predicted using reference breed frequencies of SNP markers on the BovineSNP50 array. Semen DNA samples of over 2,000 bulls from 16 common commercial beef breeds were genotyped using the array and used to estimate cu...

  1. The use of novel lymphatic endothelial cell-specific immunohistochemical markers to differentiate cutaneous angiosarcomas in dogs.

    Science.gov (United States)

    Halsey, C H C; Worley, D R; Curran, K; Charles, J B; Ehrhart, E J

    2014-03-01

    Lymphangiosarcomas are uncommon vascular neoplasms that arise from lymphatic endothelial cells (LECs). They efface and replace normal subcutaneous tissue and are characterised by arborising, vascular channels lined by a single layer of pleomorphic endothelial cells and a paucity of erythrocytes. Lymphangiosarcomas are architecturally similar to hemangiosarcomas, a common malignancy of vascular origin arising from blood vascular endothelial cells. Common immunohistochemical markers for vascular endothelium, such as Factor VIII-related antigen (F8RA) and CD31, have traditionally been used to confirm the diagnosis of tumours of vascular origin. However, these markers fail to differentiate between lymphangiosarcoma and hemangiosarcoma, which often show overlapping morphologic features, disparate clinical behaviour and require different treatment modalities. Here we describe the use of two novel LEC-specific markers, lymphatic vessel endothelial receptor-1 (LYVE-1) and prospero-related homeobox gene-1 (PROX-1), to further differentiate between vascular tumours of lymphatic (lymphangiosarcoma) and blood (hemangiosarcoma) endothelial cell origin in the dog. PMID:24593773

  2. Clusters of conserved beta cell marker genes for assessment of beta cell phenotype

    DEFF Research Database (Denmark)

    Martens, Geert A; Jiang, Lei; Hellemans, Karine H;

    2011-01-01

    of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser......The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...... capture microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators....

  3. Ischemia-induced neural stem/progenitor cells express pyramidal cell markers

    NARCIS (Netherlands)

    Clausen, Martijn; Nakagomi, Takayuki; Nakano-Doi, Akiko; Saino, Orie; Takata, Masashi; Taguchi, Akihiko; Luiten, Paul; Matsuyama, Tomohiro

    2011-01-01

    Adult brain-derived neural stem cells have acquired a lot of interest as an endurable neuronal cell source that can be used for central nervous system repair in a wide range of neurological disorders such as ischemic stroke. Recently, we identified injury-induced neural stem/progenitor cells in the

  4. AMINOACYL FUCOSIDES AS POSSIBLE BIOCHEMICAL MARKERS OF TUMORIGENIC AND METASTATIC POTENTIAL IN HERPES SIMPLEX VIRUS TYPE 2-TRANSFORMED RAT CELLS

    Science.gov (United States)

    Two classes of aminoacyl fucosides termed F13 and F14 were studied as possible markers of tumorigenic and metastatic potential in herpes simplex virus type 2 transformed rat cells. In the present study, clonal cell lines of transformed highly tumorigenic and metastatic (t-REF-G-2...

  5. Human Blood and Mucosal Regulatory T Cells Express Activation Markers and Inhibitory Receptors in Inflammatory Bowel Disease.

    Directory of Open Access Journals (Sweden)

    James D Lord

    Full Text Available FOXP3+ regulatory T cells (Tregs are critical for preventing intestinal inflammation. However, FOXP3+ T cells are paradoxically increased in the intestines of patients with the inflammatory bowel disease (IBD ulcerative colitis (UC or Crohn's disease (CD. We determined whether these FOXP3+ cells in IBD patients share or lack the phenotype of such cells from patients without IBD.We quantified and characterized FOXP3+ Treg populations, as well as FOXP3- CD4+ T cells, in the lamina propria lymphocytes (LPL of intestine surgically resected from patients with and without IBD, and in the blood of controls or Crohn's patients with or without disease activity.In all samples, a similar fraction of FOXP3+ cells expressed the "natural" Treg (nTreg marker Helios, suggesting that, in IBD, these cells are not entirely "induced" Tregs (iTregs derived from activated effector T cells. Helios+ and Helios- FOXP3+ T cells demonstrated similar expression of maturation markers, activation markers, and inhibitory molecules between IBD patients and controls, while FOXP3- cells paradoxically expressed more of the inhibitory receptors CD39, CTLA4, and PD-1 in inflamed mucosa. Greater expression of activation markers was also seen in both Helios+ and Helios- Tregs, relative to FOXP3- cells, in both IBD patients and controls, indicating that Tregs are effectively activated by antigen in IBD.Extensive immunophenotyping revealed that Helios+ and Helios- mucosal Tregs exist at a similar frequency, and have a similar expression of inhibitory molecules and activation markers in patients with IBD as in healthy controls.

  6. Prediction of single-cross hybrid performance for grain yield and grain dry matter content in maize using AFLP markers associated with QTL.

    Science.gov (United States)

    Schrag, T A; Melchinger, A E; Sørensen, A P; Frisch, M

    2006-10-01

    Prediction methods to identify single-cross hybrids with superior yield performance have the potential to greatly improve the efficiency of commercial maize (Zea mays L.) hybrid breeding programs. Our objectives were to (1) identify marker loci associated with quantitative trait loci for hybrid performance or specific combining ability (SCA) in maize, (2) compare hybrid performance prediction by genotypic value estimates with that based on general combining ability (GCA) estimates, and (3) investigate a newly proposed combination of the GCA model with SCA predictions from genotypic value estimates. A total of 270 hybrids was evaluated for grain yield and grain dry matter content in four Dent x Flint factorial mating experiments, their parental inbred lines were genotyped with 20 AFLP primer-enzyme combinations. Markers associated significantly with hybrid performance and SCA were identified, genotypic values and SCA effects were estimated, and four hybrid performance prediction approaches were evaluated. For grain yield, between 38 and 98 significant markers were identified for hybrid performance and between zero and five for SCA. Estimates of prediction efficiency (R (2)) ranged from 0.46 to 0.86 for grain yield and from 0.59 to 0.96 for grain dry matter content. Models enhancing the GCA approach with SCA estimates resulted in the highest prediction efficiency if the SCA to GCA ratio was high. We conclude that it is advantageous for prediction of single-cross hybrids to enhance a GCA-based model with SCA effects estimated from molecular marker data, if SCA variances are of similar or larger importance as GCA variances. PMID:16896712

  7. BSND and ATP6V1G3: Novel Immunohistochemical Markers for Chromophobe Renal Cell Carcinoma

    Science.gov (United States)

    Shinmura, Kazuya; Igarashi, Hisaki; Kato, Hisami; Koda, Kenji; Ogawa, Hiroshi; Takahashi, Seishiro; Otsuki, Yoshiro; Yoneda, Tatsuaki; Kawanishi, Yuichi; Funai, Kazuhito; Takayama, Tatsuya; Ozono, Seiichiro; Sugimura, Haruhiko

    2015-01-01

    Abstract Differentiating between chromophobe renal cell carcinoma (RCC) and other RCC subtypes can be problematic using routine light microscopy. This study aimed to identify novel immunohistochemical markers useful for a differential diagnosis between chromophobe RCC and other RCC subtypes. We selected 3 genes (including BSND and ATP6V1G3) that showed specific transcriptional expression in chromophobe RCC using expression data (n = 783) from The Cancer Genome Atlas (TCGA) database. A subsequent immunohistochemical examination of 186 RCCs obtained in our patient series resulted in a strong diffuse positivity of BSND and ATP6V1G3 proteins (both of which are involved in the regulation of membrane transport) in all the chromophobe RCC specimens (23/23 cases, 100%) but not in the clear cell RCC specimens (0/153 cases, 0%) or the papillary RCC specimens (0/10 cases, 0%). BSND and ATP6V1G3 protein expressions were also detected in renal oncocytoma (13/14 cases, 92.9%) and in the distal nephron, including the collecting duct, in the normal kidney. A computational analysis of TCGA data suggested that DNA methylation was involved in the differential expression pattern of both genes among RCC subtypes. Finally, an immunohistochemical analysis showed lung carcinomas were negative (0/85 cases, 0%) for the expression of both proteins. These results suggest that BSND and ATP6V1G3 are excellent novel immunohistochemical markers for differentiating between chromophobe RCC and other subtypes of RCC, including clear cell and papillary RCCs.

  8. BSND and ATP6V1G3: Novel Immunohistochemical Markers for Chromophobe Renal Cell Carcinoma.

    Science.gov (United States)

    Shinmura, Kazuya; Igarashi, Hisaki; Kato, Hisami; Koda, Kenji; Ogawa, Hiroshi; Takahashi, Seishiro; Otsuki, Yoshiro; Yoneda, Tatsuaki; Kawanishi, Yuichi; Funai, Kazuhito; Takayama, Tatsuya; Ozono, Seiichiro; Sugimura, Haruhiko

    2015-06-01

    Differentiating between chromophobe renal cell carcinoma (RCC) and other RCC subtypes can be problematic using routine light microscopy. This study aimed to identify novel immunohistochemical markers useful for a differential diagnosis between chromophobe RCC and other RCC subtypes. We selected 3 genes (including BSND and ATP6V1G3) that showed specific transcriptional expression in chromophobe RCC using expression data (n = 783) from The Cancer Genome Atlas (TCGA) database. A subsequent immunohistochemical examination of 186 RCCs obtained in our patient series resulted in a strong diffuse positivity of BSND and ATP6V1G3 proteins (both of which are involved in the regulation of membrane transport) in all the chromophobe RCC specimens (23/23 cases, 100%) but not in the clear cell RCC specimens (0/153 cases, 0%) or the papillary RCC specimens (0/10 cases, 0%). BSND and ATP6V1G3 protein expressions were also detected in renal oncocytoma (13/14 cases, 92.9%) and in the distal nephron, including the collecting duct, in the normal kidney. A computational analysis of TCGA data suggested that DNA methylation was involved in the differential expression pattern of both genes among RCC subtypes. Finally, an immunohistochemical analysis showed lung carcinomas were negative (0/85 cases, 0%) for the expression of both proteins. These results suggest that BSND and ATP6V1G3 are excellent novel immunohistochemical markers for differentiating between chromophobe RCC and other subtypes of RCC, including clear cell and papillary RCCs. PMID:26091477

  9. Protein markers of cancer-associated fibroblasts and tumor-initiating cells reveal subpopulations in freshly isolated ovarian cancer ascites

    Directory of Open Access Journals (Sweden)

    Wintzell My

    2012-08-01

    Full Text Available Abstract Background In ovarian cancer, massive intraperitoneal dissemination is due to exfoliated tumor cells in ascites. Tumor-initiating cells (TICs or cancer stem cells and cells showing epithelial-mesenchymal-transition (EMT are particularly implicated. Spontaneous spherical cell aggregates are sometimes observed, but although similar to those formed by TICs in vitro, their significance is unclear. Methods Cells freshly isolated from malignant ascites were separated into sphere samples (S-type samples, n=9 and monolayer-forming single-cell suspensions (M-type, n=18. Using western blot, these were then compared for expression of protein markers of EMT, TIC, and of cancer-associated fibroblasts (CAFs. Results S-type cells differed significantly from M-type by expressing high levels of E-cadherin and no or little vimentin, integrin-β3 or stem cell transcription factor Oct-4A. By contrast, M-type samples were enriched for CD44, Oct-4A and for CAF markers. Independently of M- and S-type, there was a strong correlation between TIC markers Nanog and EpCAM. The CAF marker α-SMA correlated with clinical stage IV. This is the first report on CAF markers in malignant ascites and on SUMOylation of Oct-4A in ovarian cancer. Conclusions In addition to demonstrating potentially high levels of TICs in ascites, the results suggest that the S-type population is the less tumorigenic one. Nanoghigh/EpCAMhigh samples represent a TIC subset which may be either M- or S-type, and which is separate from the CD44high/Oct-4Ahigh subset observed only in M-type samples. This demonstrates a heterogeneity in TIC populations in vivo which has practical implications for TIC isolation based on cell sorting. The biological heterogeneity will need to be addressed in future therapeutical strategies.

  10. Protein markers of cancer-associated fibroblasts and tumor-initiating cells reveal subpopulations in freshly isolated ovarian cancer ascites

    International Nuclear Information System (INIS)

    In ovarian cancer, massive intraperitoneal dissemination is due to exfoliated tumor cells in ascites. Tumor-initiating cells (TICs or cancer stem cells) and cells showing epithelial-mesenchymal-transition (EMT) are particularly implicated. Spontaneous spherical cell aggregates are sometimes observed, but although similar to those formed by TICs in vitro, their significance is unclear. Cells freshly isolated from malignant ascites were separated into sphere samples (S-type samples, n=9) and monolayer-forming single-cell suspensions (M-type, n=18). Using western blot, these were then compared for expression of protein markers of EMT, TIC, and of cancer-associated fibroblasts (CAFs). S-type cells differed significantly from M-type by expressing high levels of E-cadherin and no or little vimentin, integrin-β3 or stem cell transcription factor Oct-4A. By contrast, M-type samples were enriched for CD44, Oct-4A and for CAF markers. Independently of M- and S-type, there was a strong correlation between TIC markers Nanog and EpCAM. The CAF marker α-SMA correlated with clinical stage IV. This is the first report on CAF markers in malignant ascites and on SUMOylation of Oct-4A in ovarian cancer. In addition to demonstrating potentially high levels of TICs in ascites, the results suggest that the S-type population is the less tumorigenic one. Nanoghigh/EpCAMhigh samples represent a TIC subset which may be either M- or S-type, and which is separate from the CD44high/Oct-4Ahigh subset observed only in M-type samples. This demonstrates a heterogeneity in TIC populations in vivo which has practical implications for TIC isolation based on cell sorting. The biological heterogeneity will need to be addressed in future therapeutical strategies

  11. MGMT Promoter Methylation and BRAF V600E Mutations Are Helpful Markers to Discriminate Pleomorphic Xanthoastrocytoma from Giant Cell Glioblastoma.

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    Laura-Nanna Lohkamp

    Full Text Available Giant Cell Glioblastoma (gcGBM and Pleomorphic Xanthoastrocytoma (PXA are rare astroglial tumors of the central nervous system. Although they share certain histomorphological and immunohistochemical features, they are characterized by different clinical behavior and prognosis. Nevertheless, few cases remain uncertain, as their histomorphological hallmarks and immunophenotypes do correspond to the typical pattern neither of gcGBM nor PXA. Therefore, in addition to the routinely used diagnostic histochemical and immunohistochemical markers like Gömöri, p53 and CD34, we analyzed if genetic variations like MGMT promoter methylation, mutations in the IDH1/2 genes, or BRAF mutations, which are actually used as diagnostic, prognostic and predictive molecular markers in anaplastic glial tumors, could be helpful in the differential diagnostic of both tumor entities. We analyzed 34 gcGBM and 20 PXA for genetic variations in the above-named genes and found distinct distributions between both groups. MGMT promoter hypermethylation was observed in 3 out of 20 PXA compared to 14 out of 34 gcGBM (15% vs. 41.2%, p-value 0.09. BRAF V600E mutations were detected in 50% of the PXA but not in any of the gcGBM (50% vs. 0%, p-value < 0.001. IDH1 R132 and IDH R172 mutations were not present in any of the PXA and gcGBM cases. Our data indicate, that in addition to the histological and immunohistochemical evaluation, investigation of MGMT promoter methylation and in particular BRAF V600E mutations represent reliable additional tools to sustain differentiation of gcGBM from PXA on a molecular basis. Based on these data specific BRAF kinase inhibitors could represent a promising agent in the therapy of PXA and their use should be emphasized.

  12. MGMT Promoter Methylation and BRAF V600E Mutations Are Helpful Markers to Discriminate Pleomorphic Xanthoastrocytoma from Giant Cell Glioblastoma.

    Science.gov (United States)

    Lohkamp, Laura-Nanna; Schinz, Maren; Gehlhaar, Claire; Guse, Katrin; Thomale, Ulrich-Wilhelm; Vajkoczy, Peter; Heppner, Frank L; Koch, Arend

    2016-01-01

    Giant Cell Glioblastoma (gcGBM) and Pleomorphic Xanthoastrocytoma (PXA) are rare astroglial tumors of the central nervous system. Although they share certain histomorphological and immunohistochemical features, they are characterized by different clinical behavior and prognosis. Nevertheless, few cases remain uncertain, as their histomorphological hallmarks and immunophenotypes do correspond to the typical pattern neither of gcGBM nor PXA. Therefore, in addition to the routinely used diagnostic histochemical and immunohistochemical markers like Gömöri, p53 and CD34, we analyzed if genetic variations like MGMT promoter methylation, mutations in the IDH1/2 genes, or BRAF mutations, which are actually used as diagnostic, prognostic and predictive molecular markers in anaplastic glial tumors, could be helpful in the differential diagnostic of both tumor entities. We analyzed 34 gcGBM and 20 PXA for genetic variations in the above-named genes and found distinct distributions between both groups. MGMT promoter hypermethylation was observed in 3 out of 20 PXA compared to 14 out of 34 gcGBM (15% vs. 41.2%, p-value 0.09). BRAF V600E mutations were detected in 50% of the PXA but not in any of the gcGBM (50% vs. 0%, p-value < 0.001). IDH1 R132 and IDH R172 mutations were not present in any of the PXA and gcGBM cases. Our data indicate, that in addition to the histological and immunohistochemical evaluation, investigation of MGMT promoter methylation and in particular BRAF V600E mutations represent reliable additional tools to sustain differentiation of gcGBM from PXA on a molecular basis. Based on these data specific BRAF kinase inhibitors could represent a promising agent in the therapy of PXA and their use should be emphasized. PMID:27253461

  13. Tissue regeneration and biomineralization in sea urchins: role of Notch signaling and presence of stem cell markers.

    Directory of Open Access Journals (Sweden)

    Helena C Reinardy

    Full Text Available Echinoderms represent a phylum with exceptional regenerative capabilities that can reconstruct both external appendages and internal organs. Mechanistic understanding of the cellular pathways involved in regeneration in these animals has been hampered by the limited genomic tools and limited ability to manipulate regenerative processes. We present a functional assay to investigate mechanisms of tissue regeneration and biomineralization by measuring the regrowth of amputated tube feet (sensory and motor appendages and spines in the sea urchin, Lytechinus variegatus. The ability to manipulate regeneration was demonstrated by concentration-dependent inhibition of regrowth of spines and tube feet by treatment with the mitotic inhibitor, vincristine. Treatment with the gamma-secretase inhibitor DAPT resulted in a concentration-dependent inhibition of regrowth, indicating that both tube feet and spine regeneration require functional Notch signaling. Stem cell markers (Piwi and Vasa were expressed in tube feet and spine tissue, and Vasa-positive cells were localized throughout the epidermis of tube feet by immunohistochemistry, suggesting the existence of multipotent progenitor cells in these highly regenerative appendages. The presence of Vasa protein in other somatic tissues (e.g. esophagus, radial nerve, and a sub-population of coelomocytes suggests that multipotent cells are present throughout adult sea urchins and may contribute to normal homeostasis in addition to regeneration. Mechanistic insight into the cellular pathways governing the tremendous regenerative capacity of echinoderms may reveal processes that can be modulated for regenerative therapies, shed light on the evolution of regeneration, and enable the ability to predict how these processes will respond to changing environmental conditions.

  14. Human breast cancer cell lines co-express neuronal, epithelial, and melanocytic differentiation markers in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Qingbei Zhang

    Full Text Available Differentiation programs are aberrant in cancer cells allowing them to express differentiation markers in addition to their tissue of origin. In the present study, we demonstrate the multi-lineage differentiation potential of breast cancer cell lines to express multiple neuronal/glial lineage-specific markers as well as mammary epithelial and melanocytic-specific markers. Multilineage expression was detected in luminal (MCF-7 and SKBR3 and basal (MDA-MB-231 types of human breast cancer cell lines. We also observed comparable co-expression of these three cell lineage markers in MDA-MB-435 cells in vitro, in MDA-MB-435 primary tumors derived from parental and single cell clones and in lung metastases in vivo. Furthermore, ectoderm multi-lineage transdifferentiation was also found in human melanoma (Ul-MeL and glioblastoma cell lines (U87 and D54. These observations indicate that aberrant multi-lineage transdifferentiation or lineage infidelity may be a wide spread phenomenon in cancer.

  15. Response of the plasma hypoxia marker osteopontin to in vitro hypoxia in human tumor cells

    International Nuclear Information System (INIS)

    Background: Osteopontin (OPN) is recognized as a tumor-associated protein and has recently been shown to be a potential plasma marker of tumor hypoxia in head and neck cancer patients. We sought to detect patterns of OPN accumulation and secretion in human tumor cells during in vitro hypoxia. Materials and methods: The human tumor cell lines A 549 lung carcinoma, U 87 malignant glioma, HT 1080 fibrosarcoma, FaDu pharyngeal carcinoma and HT 29 and HCT 116 colorectal carcinoma were treated with 1, 6 or 24 h of hypoxia (0.1% O2) or 24 h followed by 4 h or 20 of reoxygenation. OPN concentration in the supernatant was measured by ELISA, OPN protein and mRNA levels by Western and Northern blotting. Results: In FaDu, HT 29 and HCT 116, OPN levels in the supernatant remained below 10 ng/ml under all conditions. In A 549, HT 1080 and U 87, mean aerobic OPN concentrations were 2296, 164 and 115 ng/ml, respectively. No increase of OPN in the medium during 24 h of hypoxia, but moderate increases during subsequent 24-hour-reoxygenation were observed in these three cell lines. Intracellular OPN protein was present to a similar extent in all six-cell lines under aerobic conditions and also did not accumulate during hypoxia treatment. OPN mRNA response to hypoxia and reoxygenation was very heterogeneous between cell lines. Conclusion: Reoxygenation rather than hypoxia appears to induce OPN secretion from human tumor cells in a cell-type specific manner

  16. Detection of embryonic stem cell markers in adult human adipose tissue-derived stem cells

    OpenAIRE

    Sarasa Bharati Arumugam; Omana A Trentz; Devi Arikketh; Vijayalakshmi Senthinathan; Barry Rosario; P. V. A Mohandas

    2011-01-01

    Background: Bone marrow transplantation is already an established therapy, which is now widely used in medicine to treat leukemia, lymphoma, and several inherited blood disorders. The culture of multilineage cells from easily available adipose tissue is another source of multipotent mesenchymal stem cells, and is referred to as adipose tissue-derived stem cells (ADSCs). While ADSCs are being used to treat various conditions, some lacuna exists regarding the specific proteins in these. It was ...

  17. Serum Advanced Oxidation Protein Products in Oral Squamous Cell Carcinoma: Possible Markers of Diagnostic Significance

    Directory of Open Access Journals (Sweden)

    Abhishek Singh Nayyar

    2013-07-01

    Full Text Available Background: The aim of this study was to measure the concentrations (levels ofserum total proteins and advanced oxidation protein products as markers of oxidantmediated protein damage in the sera of patients with oral cancers.Methods: The study consisted of the sera analyses of serum total protein andadvanced oxidation protein products’ levels in 30 age and sex matched controls, 60patients with reported pre-cancerous lesions and/or conditions and 60 patients withhistologically proven oral squamous cell carcinoma. One way analyses of variance wereused to test the difference between groups. To determine which of the two groups’ meanswere significantly different, the post-hoc test of Bonferroni was used. The results wereaveraged as mean ± standard deviation. In the above test, P values less than 0.05 weretaken to be statistically significant. The normality of data was checked before thestatistical analysis was performed.Results: The study revealed statistically significant variations in serum levels ofadvanced oxidation protein products (P<0.001. Serum levels of total protein showedextensive variations; therefore the results were largely inconclusive and statisticallyinsignificant.Conclusion: The results emphasize the need for more studies with larger samplesizes to be conducted before a conclusive role can be determined for sera levels of totalprotein and advanced oxidation protein products as markers both for diagnosticsignificance and the transition from the various oral pre-cancerous lesions and conditionsinto frank oral cancers.

  18. GENETIC ALTERRATIONS OF MICROSATELLITE MARKERS AT CHROMOSOME 17 IN NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    GUO; Xue-jun

    2001-01-01

    [1]Froudarakis ME, Bouros D, Spandidos DA, et al. Microsatellite instability and loss of heterozygosity at chromosomes 17 in non-small cell lung cancer [J]. Chest 1998; 113:1091.[2]Fong KM, Zimmerman PV, Smith PJ. Microsatellite instability and other molecular abnormalities in non-small cell lung cancer [J]. Cancer Res 1994; 54:2098.[3]Mountain CF. A new international staging system for lung cancer [J]. Chest 1986; 89(suppl):225.[4]Shridhar V, Siegfried J, Hunt J, et al. Genetic instability of microsatellite sequences in many non-small cell lung carcinomas [J]. Cancer Res 1994; 54:2084.[5]Loeb LA. Microsatellite instability: Marker of a mutator phenotype in cancer [J]. Cancer Res 1994; 54:5059.[6]Sanchez CM, Monzo M, Rosell R, et al. Detection of chromosome 3p alterations in serum DNA of non-small cell lung cancer patients [J]. Ann Oncol 1989; 113.

  19. Comprehensive transcriptomic and proteomic characterization of human mesenchymal stem cells reveals source specific cellular markers.

    Science.gov (United States)

    Billing, Anja M; Ben Hamidane, Hisham; Dib, Shaima S; Cotton, Richard J; Bhagwat, Aditya M; Kumar, Pankaj; Hayat, Shahina; Yousri, Noha A; Goswami, Neha; Suhre, Karsten; Rafii, Arash; Graumann, Johannes

    2016-01-01

    Mesenchymal stem cells (MSC) are multipotent cells with great potential in therapy, reflected by more than 500 MSC-based clinical trials registered with the NIH. MSC are derived from multiple tissues but require invasive harvesting and imply donor-to-donor variability. Embryonic stem cell-derived MSC (ESC-MSC) may provide an alternative, but how similar they are to ex vivo MSC is unknown. Here we performed an in depth characterization of human ESC-MSC, comparing them to human bone marrow-derived MSC (BM-MSC) as well as human embryonic stem cells (hESC) by transcriptomics (RNA-seq) and quantitative proteomics (nanoLC-MS/MS using SILAC). Data integration highlighted and validated a central role of vesicle-mediated transport and exosomes in MSC biology and also demonstrated, through enrichment analysis, their versatility and broad application potential. Particular emphasis was placed on comparing profiles between ESC-MSC and BM-MSC and assessing their equivalency. Data presented here shows that differences between ESC-MSC and BM-MSC are similar in magnitude to those reported for MSC of different origin and the former may thus represent an alternative source for therapeutic applications. Finally, we report an unprecedented coverage of MSC CD markers, as well as membrane associated proteins which may benefit immunofluorescence-based applications and contribute to a refined molecular description of MSC. PMID:26857143

  20. Label-free nonlinear optical microscopy detects early markers for osteogenic differentiation of human stem cells

    Science.gov (United States)

    Hofemeier, Arne D.; Hachmeister, Henning; Pilger, Christian; Schürmann, Matthias; Greiner, Johannes F. W.; Nolte, Lena; Sudhoff, Holger; Kaltschmidt, Christian; Huser, Thomas; Kaltschmidt, Barbara

    2016-05-01

    Tissue engineering by stem cell differentiation is a novel treatment option for bone regeneration. Most approaches for the detection of osteogenic differentiation are invasive or destructive and not compatible with live cell analysis. Here, non-destructive and label-free approaches of Raman spectroscopy, coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy were used to detect and image osteogenic differentiation of human neural crest-derived inferior turbinate stem cells (ITSCs). Combined CARS and SHG microscopy was able to detect markers of osteogenesis within 14 days after osteogenic induction. This process increased during continued differentiation. Furthermore, Raman spectroscopy showed significant increases of the PO43‑ symmetric stretch vibrations at 959 cm‑1 assigned to calcium hydroxyapatite between days 14 and 21. Additionally, CARS microscopy was able to image calcium hydroxyapatite deposits within 14 days following osteogenic induction, which was confirmed by Alizarin Red-Staining and RT- PCR. Taken together, the multimodal label-free analysis methods Raman spectroscopy, CARS and SHG microscopy can monitor osteogenic differentiation of adult human stem cells into osteoblasts with high sensitivity and spatial resolution in three dimensions. Our findings suggest a great potential of these optical detection methods for clinical applications including in vivo observation of bone tissue–implant-interfaces or disease diagnosis.

  1. A population of human brain cells expressing phenotypic markers of more than one lineage can be induced in vitro to differentiate into mesenchymal cells

    International Nuclear Information System (INIS)

    Proliferating astrocytic cells from germinal, as well as mature areas of brain parenchyma, have the characteristics of neural stem/progenitor cells and are capable of generating both neurons and glia. We previously reported that primary fetal human brain cells, designated as Normal Human Astrocytes (NHA), expressed, in addition to GFAP, Vimentin and Nestin, low levels of βIII-Tubulin, an early neuronal marker, and differentiated into neurons and astrocytes in vitro. Here, we showed that primary NHA cells co-express low levels of mesenchymal markers Fibronectin and Collagen-1 in culture. These cells transitioned into mesenchymal-like cells when cultured in adherent conditions in serum containing media. The mesenchymal-like derivatives of these cells were characterized based on their morphological changes, high expression of Vimentin and extracellular matrix (ECM) proteins, Collagen-1 and Fibronectin, and decline of neural markers. When incubated in osteogenic and adipogenic induction media, the mesenchymal-like cells differentiated into osteoblasts and adipocytes. Furthermore, NHA cells express markers of neural crest cells, SOX-10 and p75. These data support the idea of ectoderm-derived mesenchymal lineages. These findings suggest that a population of primitive fetal brain cells with neural/neural crest/mesenchymal phenotype, resembles the remarkable phenotypic plasticity of neural crest cells, and differentiates into adipocytes and osteocytes under the influence of environmental factors

  2. Serum tumor marker CYFRA 21-1 in the diagnostics of squamous cell lung cancer - comparison with CEA

    International Nuclear Information System (INIS)

    The aim of the study was to test the diagnostic value tumor marker CYFRA 21-1 for squamous cell lung cancer (SQCLC) in comparison with carcinoembryonic antigen (CEA). Ninety-one patients were induced in this study: 56 with SQCLC - Group I, 25 with other types of lung cancer - Group II, 10 with benign respiratory tract diseases - Group III. Median CYFRA 21-1 serum concentration (ng/ml) was: in Group I: 4.52 (0.94 - >16), in Group II: 3.58 (1.72 - >16), in Group III: 2.05 (0.99 - 3.41). Median CEA serum concentration (ng/ml) was: in Group I: 4.49 (076- >20), in Group II: 3.32 (1.17 - >20), in Group III: 3.09 (1.84 - 6.37). There was a highly significant difference between the levels of CYFRA 21-1 in group I and Group III (p < 0.001), but there was no statistically significant difference between the levels of CEA in Group I and III. Sensitivity of CYFRA 21-1 by the cut-off 3.33 ng/ml in the diagnostics of SQCLC was 0.68, specificity 0.090, positive predictive value 0.91, negative predictive value 0.65. Sensitivity of CEA by cut-off 4.61 ng/ml was 0.5 by the same specificity 0.90. CYFRA 21-1 has high sensitivity, specificity and positive predictive value in the diagnostics of SQCLC. Sensitivity of CYFRA 21-1 is significantly higher than sensitivity of CEA in this settings. (author)

  3. Genomic breeding value prediction for simple maize hybrid yield using total effects of associated markers, under different imbalance levels and environments.

    Science.gov (United States)

    Cantelmo, N F; Von Pinho, R G; Balestre, M

    2016-01-01

    The main objective of a maize breeding program is to generate hybrid combinations that are more productive than those pre-existing in the market. However, the number of parents, and consequently the number of crosses, increases so rapidly that the phenotypic evaluation of all the possible combinations becomes economically and technically infeasible. In this context, predicting the performance of the most promising genotypes may increase the genetic gains with increased selection intensity and reduced breeding cycles. Thus, the present study aimed to use the total effects of associated markers method to predict genomic breeding values (GBVs) via cross-validation and by using different imbalance levels (10, 30, 50, and 70%). A set of 51 genotyped strains was used with 79 microsatellite markers and 273 hybrids that were generated by a partial diallel. A total of 186 and 272 hybrids were analyzed in the experiments within the southern and central regions of Brazil, respectively. The GBVs were, thus, predicted for each location in both the regions, and for training in one region and validation in another region. The correlation between the predicted and observed GBVs ranged from 0.48 to 0.91, depending on the imbalance level and the region analyzed. Overall, the results obtained in the present study were promising, particularly considering that a small number of markers were used and that the training and predictions occurred in the very distinct regions of southern and central Brazil. PMID:26985952

  4. Effects of the number of markers per haplotype and clustering of haplotypes on the accuracy of QTL mapping and prediction of genomic breeding values

    Directory of Open Access Journals (Sweden)

    Schrooten Chris

    2009-01-01

    Full Text Available Abstract The aim of this paper was to compare the effect of haplotype definition on the precision of QTL-mapping and on the accuracy of predicted genomic breeding values. In a multiple QTL model using identity-by-descent (IBD probabilities between haplotypes, various haplotype definitions were tested i.e. including 2, 6, 12 or 20 marker alleles and clustering base haplotypes related with an IBD probability of > 0.55, 0.75 or 0.95. Simulated data contained 1100 animals with known genotypes and phenotypes and 1000 animals with known genotypes and unknown phenotypes. Genomes comprising 3 Morgan were simulated and contained 74 polymorphic QTL and 383 polymorphic SNP markers with an average r2 value of 0.14 between adjacent markers. The total number of haplotypes decreased up to 50% when the window size was increased from two to 20 markers and decreased by at least 50% when haplotypes related with an IBD probability of > 0.55 instead of > 0.95 were clustered. An intermediate window size led to more precise QTL mapping. Window size and clustering had a limited effect on the accuracy of predicted total breeding values, ranging from 0.79 to 0.81. Our conclusion is that different optimal window sizes should be used in QTL-mapping versus genome-wide breeding value prediction.

  5. Interleukin 8 as a vaso-occlusive marker in Brazilian patients with sickle cell disease.

    Science.gov (United States)

    Gonçalves, M S; Queiroz, I L; Cardoso, S A; Zanetti, A; Strapazoni, A C; Adorno, E; Albuquerque, A; Sant'Ana, A; dos Reis, M G; Barral, A; Barral Netto, M

    2001-10-01

    Sickle cell disease has a worldwide distribution and is a public health problem in Brazil. Although vaso-occlusive crisis (VOC) is one of the most important clinical features of the disease, there are still several steps of its pathogenesis which are unknown. The increase of the chemotactic factor interleukin 8 (IL-8) has been reported to be involved in sickle cell disease crisis, but this has not been demonstrated conclusively. In the present study we analyzed serum IL-8 levels by ELISA and hematological parameters and hemoglobin patterns by standard techniques in 23 (21 SS and 2 SC) Brazilian patients with sickle cell syndromes during VOC caused by different inducing factors, 22 (21 SS and 1 SC) sickle cell patients out of crisis, and 11 healthy controls. Increased IL-8 levels were observed in 19 of 23 VOC patients (79.2%), 3 of them with more than 1,000 pg/ml. Seventeen of 22 (77.3%) non-crisis patients showed low IL-8 levels (less than 15 pg/ml). Healthy controls had low IL-8 levels. A significant difference in serum IL-8 levels was observed between crisis and non-crisis sickle cell patients (P<0.0001). There was no correlation between IL-8 levels and hematological data or hemoglobin patterns. High serum IL-8 levels were observed in VOC patients independently of the crisis-inducing factor. We conclude that in the studied population, IL-8 concentration may be a useful VOC marker, although the mechanism of the pathogenic process of sickle cell VOC syndromes remains unclear. PMID:11593306

  6. Human breast cancer stem cell markers CD44 and CD24: enriching for cells with functional properties in mice or in man?

    OpenAIRE

    Fillmore, Christine; Kuperwasser, Charlotte

    2007-01-01

    Identification of breast cancer stem cells as the cells within breast tumors that have the ability to give rise to cells that make up the bulk of the tumor mass has shifted the focus of cancer research. However, there is still much debate concerning the unique nature of the markers that distinguish cancer stem cells in the breast. As such, understanding whether CD44+/CD24- breast cancer cells are merely more successful in overcoming an engraftment incompatibility that exists when injecting hu...

  7. Myrtucommulone-A treatment decreases pluripotency- and multipotency-associated marker expression in bladder cancer cell line HTB-9.

    Science.gov (United States)

    Iskender, Banu; Izgi, Kenan; Karaca, Halit; Canatan, Halit

    2015-10-01

    Cancer and stem cells exhibit similar features, including self-renewal, differentiation and immortality. The expression of stem-cell-related genes in cancer cells is demonstrated to be potentially correlated with cancer cell behaviour, affecting both drug response and tumor recurrence. There is an emerging body of evidence that subpopulations of tumors carry a distinct molecular sign and are selectively resistant to chemotherapy. Therefore, it is important to find novel therapeutic agents that could suppress the stem-like features of cancer cells while inhibiting their proliferation. Myrtucommulone-A (MC-A) is an active compound of a nonprenylated acylphloroglucinol isolated from the leaves of myrtle. Here we have investigated the potential of MC-A in inhibiting the expression of self-renewal regulatory factors and cancer stem cell markers in a bladder cancer cell line HTB-9. We used RT-PCR, immunocytochemistry, flow cytometry and western blotting to examine the expression of pluripotency- and multipotency-associated markers with or without treatment with MC-A. Treatment with MC-A not only decreased cancer cell viability and proliferation but also resulted in a decrease in the expression of pluripotency- and multipotency-associated markers such as NANOG, OCT-4, SOX-2, SSEA-4, TRA-1-60, CD90, CD73 and CD44. MC-A treatment was also observed to decrease the sphere-forming ability of HTB-9 cells. In summary, this study provides valuable information on the presence of stem-cell marker expression in HTB-9 cells and our results imply that MC-A could be utilized to target cancer cells with stem-like characteristics. PMID:26054707

  8. Evaluation of a new tumour marker in patients with non-small-cell lung cancer: Cyfra 21.1.

    OpenAIRE

    van der Gaast, A; Schoenmakers, C. H.; Kok, T.C.; Blijenberg, B. G.; Cornillie, F.; Splinter, T A

    1994-01-01

    The Cyfra 21.1 assay is a newly developed test which measures in serum a fragment of cytokeratin 19. We evaluated this marker in 212 patients with non-small-cell lung cancer (NSCLC), predominantly stage 3a-b and 4, and compared it with three other markers: carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and tissue polypeptide antigen (TPA). Sensitivities for Cyfra 21.1, TPA, CEA and SCC (using cut-off levels corresponding to a 95% specificity for benign lung diseases) we...

  9. Potentiation of reactive oxygen species is a marker for synergistic cytotoxicity of MS-275 and 5-azacytidine in leukemic cells

    Science.gov (United States)

    Gao, Shan; Mobley, Aaron; Miller, Claudia; Boklan, Jessica; Chandra, Joya

    2008-01-01

    Epigenetic modifiers are currently in clinical use for various tumor types. Recently, numerous studies supporting the combination of histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors have emerged, encouraging early clinical trials of these agents together. Here we show that MS-275, an HDACi, and 5-azacytidine, a methyltransferase inhibitor, display synergistic cytotoxicity and apoptosis in AML and ALL cells. Intracellular production of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, is a novel marker for this synergism in ALL cells. These data suggest that assessment of oxidative stress can serve as a marker of the concerted action of MS-275 and 5-azacytidine. PMID:18031811

  10. Bax expression measured by AQUAnalysis is an independent prognostic marker in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Resistance to apoptosis is a hallmark of cancer and proteins regulating apoptosis have been proposed as prognostic markers in several malignancies. However, the prognostic impact of apoptotic markers has not been consistently demonstrated in oral squamous cell carcinoma (OSCC). This inconsistency in reported associations between apoptotic proteins and prognosis can be partly attributed to the intrinsic low resolution and misclassification associated with manual, semi-quantitative methods of biomarker expression measurement. The aim of this study was to examine the association between apoptosis-regulating proteins and clinical outcomes in oral squamous cell carcinoma (OSCC) using the quantitative fluorescence immunohistochemistry (IHC) based AQUAnalysis technique. Sixty-nine OSCC patients diagnosed between 1998–2005 in Calgary, Alberta, Canada were included in the study. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin embedded pre-treatment tumour tissue. Bax, Bcl-2 and Bcl-XL protein expression was quantified using fluorescent IHC and AQUA technology in normal oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Survival was analyzed using Kaplan-Meier plots and the Cox proportional hazard model. Bax expression was predominantly nuclear in OCSE and almost exclusively cytoplasmic in OSCC. No similar differences in localization were observed for Bcl-2 or Bcl-XL. Only Bax expression associated with disease-specific survival (DSS), with 5-year survival estimates of 85.7% for high Bax versus 50.3% for low Bax (p = 0.006), in univariate analysis. High Bax expression was also significantly associated with elevated Ki67 expression, indicating that increased proliferation might lead to an improved response to radiotherapy in patients with elevated Bax expression. In multivariate analyses, Bax protein expression remained an independent

  11. Bax expression measured by AQUAnalysis is an independent prognostic marker in oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Bose Pinaki

    2012-08-01

    Full Text Available Abstract Background Resistance to apoptosis is a hallmark of cancer and proteins regulating apoptosis have been proposed as prognostic markers in several malignancies. However, the prognostic impact of apoptotic markers has not been consistently demonstrated in oral squamous cell carcinoma (OSCC. This inconsistency in reported associations between apoptotic proteins and prognosis can be partly attributed to the intrinsic low resolution and misclassification associated with manual, semi-quantitative methods of biomarker expression measurement. The aim of this study was to examine the association between apoptosis-regulating proteins and clinical outcomes in oral squamous cell carcinoma (OSCC using the quantitative fluorescence immunohistochemistry (IHC based AQUAnalysis technique. Methods Sixty-nine OSCC patients diagnosed between 1998–2005 in Calgary, Alberta, Canada were included in the study. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs were assembled from triplicate cores of formalin-fixed paraffin embedded pre-treatment tumour tissue. Bax, Bcl-2 and Bcl-XL protein expression was quantified using fluorescent IHC and AQUA technology in normal oral cavity squamous epithelium (OCSE and OSCC tumour samples. Survival was analyzed using Kaplan-Meier plots and the Cox proportional hazard model. Results Bax expression was predominantly nuclear in OCSE and almost exclusively cytoplasmic in OSCC. No similar differences in localization were observed for Bcl-2 or Bcl-XL. Only Bax expression associated with disease-specific survival (DSS, with 5-year survival estimates of 85.7% for high Bax versus 50.3% for low Bax (p = 0.006, in univariate analysis. High Bax expression was also significantly associated with elevated Ki67 expression, indicating that increased proliferation might lead to an improved response to radiotherapy in patients with elevated Bax expression. In multivariate analyses

  12. Functional canine dendritic cells can be generated in vitro from peripheral blood mononuclear cells and contain a cytoplasmic ultrastructural marker.

    Science.gov (United States)

    Ibisch, C; Pradal, G; Bach, J M; Lieubeau, B

    2005-03-01

    For physiological and practical reasons the dog is a large animal model used increasingly to study the pathogenesis of human diseases and new therapeutic approaches, in particular for immune disorders. However, some immunological resources are lacking in this model, especially concerning dendritic cells. The aim of our study was to develop an efficient method to generate dendritic cells (DC) in vitro from dog peripheral blood mononuclear cells (PBMC) and to characterize their functional, structural and ultrastructural properties. PBMC were cultured in vitro with IL-4 and GM-CSF. After 1 week of culture, a great proportion of non-adherent cells displayed typical cytoplasmic processes, as evidenced both by optical and electron microscopy. Cytometric analysis revealed the presence of 41.7+/-24.6% CD14+ cells expressing both CD11c and MHC class II molecules. Allogeneic mixed lymphocyte reactions confirmed the ability of these cultures to stimulate the proliferation of allogeneic lymphocytes as already reported as a characteristic of DC in other species. In addition, we describe for the first time the presence in canine DC of cytoplasmic periodic microstructures (PMS) that could represent ultrastructural markers of canine DC. In conclusion, our study provides an easy method to generate DC from PBMC in sufficient numbers for immunological in vitro investigations in dogs, a pre-clinical model for many human diseases. PMID:15847807

  13. Effects of Electromagnetic Stimulation on Cell Density and Neural Markers in Murine Enteric Cell Cultures

    International Nuclear Information System (INIS)

    Availability of adult stem cells from several organs like bone marrow, umbilical cord blood or peripheral blood has become a powerful therapeutic tool for many chronic diseases. Potential of adult stem cells for regeneration extents to other tissues among them the nervous system. However two obstacles should be resolved before such cells could be currently applied in clinical practice: a) slow growth rate and b) ability to form enough dense colonies in order to populate a specific injury or cellular deficiency. Many approaches have been explored as genetic differentiation programs, growth factors, and supplemented culture media, among others. Electromagnetic field stimulation of differentiation, proliferation, migration, and particularly on neurogenesis is little known. Since the biological effects of ELF-EMF are well documented, we hypothesize ELF-EMF could affect growth and maturation of stem cells derived of enteric tissue

  14. Effects of Electromagnetic Stimulation on Cell Density and Neural Markers in Murine Enteric Cell Cultures

    Science.gov (United States)

    Carreón-Rodríguez, A.; Belkind-Gerson, J.; Serrano-Luna, G.; Cañedo-Dorantes, L.

    2008-08-01

    Availability of adult stem cells from several organs like bone marrow, umbilical cord blood or peripheral blood has become a powerful therapeutic tool for many chronic diseases. Potential of adult stem cells for regeneration extents to other tissues among them the nervous system. However two obstacles should be resolved before such cells could be currently applied in clinical practice: a) slow growth rate and b) ability to form enough dense colonies in order to populate a specific injury or cellular deficiency. Many approaches have been explored as genetic differentiation programs, growth factors, and supplemented culture media, among others. Electromagnetic field stimulation of differentiation, proliferation, migration, and particularly on neurogenesis is little known. Since the biological effects of ELF-EMF are well documented, we hypothesize ELF-EMF could affect growth and maturation of stem cells derived of enteric tissue.

  15. Reticulated platelets as a marker of platelet recovery after allogeneic stem cell transplantation.

    Science.gov (United States)

    Michur, H; Maślanka, K; Szczepiński, A; Mariańska, B

    2008-12-01

    Reticulated platelets (RP) are the youngest forms of platelets in blood and reflect the rate of bone marrow platelet production. In the present study, we used flow cytometric analysis to determine the percentage of RPs in patients undergoing allogeneic stem cell transplantation. We investigated 10 patients after transplantation from HLA identical siblings: five with acute myeloid leukemia (AML), four with chronic myeloid leukemia (CML), and one patient with myelodysplastic syndrome (MDS). Of the patients examined, four patients underwent allogeneic bone marrow transplantation and six patients underwent peripheral blood stem cell transplantation. It was observed that the initially reduced percentage of RPs (2.9 +/- 1.7%; mean +/- SD) was significantly higher (P = 0.0109) in all patients (13.6 +/- 6.4%) in the following 10-26 days. The RP percentage peak preceded the recovery of peripheral platelet count up to 45.6 x 10(9)/l on average by 3 days. We found no difference in RP% between the AML and CML patients but we did observe that in CML patients the RP percentage increased on average 7 days earlier than in AML patients. The elevated RP percentage reflects increased bone marrow regeneration and can be considered an additional marker of thrombopoietic recovery in the patients undergoing allogeneic stem cell transplantation. PMID:18983304

  16. Prognostic and Predictive Value of Baseline and Posttreatment Molecular Marker Expression in Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy

    International Nuclear Information System (INIS)

    Purpose: To evaluate expression of a panel of molecular markers, including p53, p21, MLH1, MSH2, MIB-1, thymidylate synthase, epidermal growth factor receptor (EGFR), and tissue vascular endothelial growth factor (VEGF), before and after treatment in patients treated with neoadjuvant chemoradiotherapy for locally advanced rectal cancer, to correlate the constitutive profile and dynamics of expression with pathologic response and outcome. Methods and Materials: Expression of biomarkers was evaluated by immunohistochemistry in tumor samples from 91 patients with clinical Stage II and III rectal cancer treated with preoperative pelvic radiotherapy (50 Gy) plus concurrent 5-fluorouracil by continuous intravenous infusion. Results: A pathologic complete remission was observed in 14 patients (15.4%). Patients with MLH1-positive tumors had a higher pathologic complete response rate (24.3% vs. 9.4%; p = 0.055). Low expression of constitutive p21, absence of EGFR expression after chemoradiotherapy, and high Dworak's tumor regression grade (TRG) were significantly associated with improved disease-free survival and overall survival. A high MIB-1 value after chemoradiotherapy was significantly associated with worse overall survival. Multivariate analysis confirmed the prognostic value of constitutive p21 expression as well as EGFR expression and MIB-1 value after chemoradiotherapy among patients not achieving TRG 3-4. Conclusions: In our study, we observed the independent prognostic value of EGFR expression after chemoradiotherapy on disease-free survival. Moreover, our study suggests that a constitutive high p21 expression and a high MIB-1 value after neoadjuvant chemoradiotherapy treatment could predict worse outcome in locally advanced rectal cancer

  17. Prediction for steatosis in type-2 diabetes: clinico-biological markers versus {sup 1}H-MR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Guiu, Boris; Krause, Denis; Cercueil, Jean-Pierre [University of Burgundy, INSERM U866, BP 87900, Dijon (France); CHU (University Hospital), Department of Radiology, 2 boulevard Marechal de Lattre de Tassigny, BP 77908, Dijon (France); Crevisy-Girod, Elodie [CHU (University Hospital), Department of Endocrinology, Diabetology, and Metabolic Diseases, BP 77908, Dijon (France); Binquet, Christine [University of Burgundy, INSERM U866, BP 87900, Dijon (France); CHU (University Hospital), Department of Biostatistics and Medical Informatics, BP 77908, Dijon (France); Duvillard, Laurence [University of Burgundy, INSERM U866, BP 87900, Dijon (France); Masson, David [University of Burgundy, INSERM U866, BP 87900, Dijon (France); CHU (University Hospital), Department of Biochemistry, BP 77908, Dijon (France); Lepage, Come; Hamza, Samia; Minello, Anne; Hillon, Patrick [University of Burgundy, INSERM U866, BP 87900, Dijon (France); CHU (University Hospital), Department of Hepatology, BP 77908, Dijon (France); Verges, Bruno; Petit, Jean-Michel [University of Burgundy, INSERM U866, BP 87900, Dijon (France); CHU (University Hospital), Department of Endocrinology, Diabetology, and Metabolic Diseases, BP 77908, Dijon (France)

    2012-04-15

    The SteatoTest, fatty liver index (FLI) and hepatic steatosis index (HSI) are clinico-biological scores of steatosis validated in general or selected populations. Serum adiponectin (s-adiponectin) and retinol binding protein 4 (s-RBP4) are adipokines that could predict liver steatosis. We investigated whether the Steatotest, FLI, HSI, s-adiponectin and s-RBP4 could be valid predictors of liver steatosis in type-2 diabetic (T2D) patients. We enrolled 220 consecutive T2D patients. Reference standard was 3.0 T {sup 1}H-MR spectroscopy (corrected for T1 and T2 decays). Intraclass correlation coefficients (ICCs), Kappa statistic measures of agreement, receiver operating characteristic (ROC) curves were assessed. Median liver fat content was 91 mg triglyceride/g liver tissue (range: 0-392). ICCs among the Steatotest, FLI, HSI, s-adiponectin, s-RBP4 and spectroscopy were low: 0.384, 0.281, 0.087, -0.297 and 0.048. Agreement between scores and spectroscopy was poor (Kappa range: 0.042-0.281). The areas under the ROC curves were low: 0.674, 0.647, 0.637, 0.616 and 0.540. S-adiponectin and s-RBP4 levels were strongly related to the presence of diabetic nephropathy (P = 0.0037 and P = 0.004; Mann-Whitney). The SteatoTest, FLI, HSI, s-adiponectin, s-RBP4 are not valid predictors of steatosis in T2D patients. Clino-biological markers cannot replace {sup 1}H-MR spectroscopy for the assessment of liver fat in this population. (orig.)

  18. Prediction for steatosis in type-2 diabetes: clinico-biological markers versus 1H-MR spectroscopy

    International Nuclear Information System (INIS)

    The SteatoTest, fatty liver index (FLI) and hepatic steatosis index (HSI) are clinico-biological scores of steatosis validated in general or selected populations. Serum adiponectin (s-adiponectin) and retinol binding protein 4 (s-RBP4) are adipokines that could predict liver steatosis. We investigated whether the Steatotest, FLI, HSI, s-adiponectin and s-RBP4 could be valid predictors of liver steatosis in type-2 diabetic (T2D) patients. We enrolled 220 consecutive T2D patients. Reference standard was 3.0 T 1H-MR spectroscopy (corrected for T1 and T2 decays). Intraclass correlation coefficients (ICCs), Kappa statistic measures of agreement, receiver operating characteristic (ROC) curves were assessed. Median liver fat content was 91 mg triglyceride/g liver tissue (range: 0-392). ICCs among the Steatotest, FLI, HSI, s-adiponectin, s-RBP4 and spectroscopy were low: 0.384, 0.281, 0.087, -0.297 and 0.048. Agreement between scores and spectroscopy was poor (Kappa range: 0.042-0.281). The areas under the ROC curves were low: 0.674, 0.647, 0.637, 0.616 and 0.540. S-adiponectin and s-RBP4 levels were strongly related to the presence of diabetic nephropathy (P = 0.0037 and P = 0.004; Mann-Whitney). The SteatoTest, FLI, HSI, s-adiponectin, s-RBP4 are not valid predictors of steatosis in T2D patients. Clino-biological markers cannot replace 1H-MR spectroscopy for the assessment of liver fat in this population. (orig.)

  19. Single-cell differences in matrix gene expression do not predict matrix deposition

    OpenAIRE

    Cote, Allison J.; McLeod, Claire M.; Farrell, Megan J.; McClanahan, Patrick D.; Dunagin, Margaret C.; Raj, Arjun; Mauck, Robert L.

    2016-01-01

    Mesenchymal stem cells (MSCs) display substantial cell-to-cell heterogeneity, complicating their use in regenerative medicine. However, conventional bulk assays mask this variability. Here we show that both chondrocytes and chondrogenically induced MSCs exhibit substantial mRNA expression heterogeneity. Single-molecule RNA FISH to measure mRNA expression of differentiation markers in single cells reveals that sister cell pairs have high levels of mRNA variability, suggesting that marker expre...

  20. The ROCK inhibitor Y-27632 improves recovery of human embryonic stem cells after fluorescence-activated cell sorting with multiple cell surface markers.

    Directory of Open Access Journals (Sweden)

    Nil Emre

    Full Text Available BACKGROUND: Due to the inherent sensitivity of human embryonic stem cells (hESCs to manipulations, the recovery and survival of hESCs after fluorescence-activated cell sorting (FACS can be low. Additionally, a well characterized and robust methodology for performing FACS on hESCs using multiple-cell surface markers has not been described. The p160-Rho-associated coiled kinase (ROCK inhibitor, Y-27632, previously has been identified as enhancing survival of hESCs upon single-cell dissociation, as well as enhancing recovery from cryopreservation. Here we examined the application of Y-27632 to hESCs after FACS to improve survival in both feeder-dependent and feeder-independent growth conditions. METHODOLOGY/PRINCIPAL FINDINGS: HESCs were sorted using markers for SSEA-3, TRA-1-81, and SSEA-1. Cells were plated after sorting for 24 hours in either the presence or the absence of Y-27632. In both feeder-dependent and feeder-independent conditions, cell survival was greater when Y-27632 was applied to the hESCs after sort. Specifically, treatment of cells with Y-27632 improved post-sort recovery up to four fold. To determine the long-term effects of sorting with and without the application of Y-27632, hESCs were further analyzed. Specifically, hESCs sorted with and without the addition of Y-27632 retained normal morphology, expressed hESC-specific markers as measured by immunocytochemistry and flow cytometry, and maintained a stable karyotype. In addition, the hESCs could differentiate into three germ layers in vitro and in vivo in both feeder-dependent and feeder-independent growth conditions. CONCLUSIONS/SIGNIFICANCE: The application of Y-27632 to hESCs after cell sorting improves cell recovery with no observed effect on pluripotency, and enables the consistent recovery of hESCs by FACS using multiple surface markers. This improved methodology for cell sorting of hESCs will aid many applications such as removal of hESCs from secondary cell types

  1. Differential expression of CXCR4 and CXCR7 with various stem cell markers in paired human primary and recurrent glioblastomas.

    Science.gov (United States)

    Flüh, Charlotte; Hattermann, Kirsten; Mehdorn, H Maximilian; Synowitz, Michael; Held-Feindt, Janka

    2016-04-01

    The chemokine CXCL12 (also termed SDF-1, stromal cell-derived factor-1) and its receptors CXCR4 and CXCR7 are known to play a pivotal role in tumor progression including glioblastomas (GBM). Previous investigations focused on the expression and functional roles of CXCR4 and CXCR7 in different GBM cell subpopulations, but comparative analysis in matched primary versus recurrent GBM samples are still lacking. Thus, here we investigated the expression of CXCR4 and CXCR7 on mRNA and protein level using matched primary and recurrent GBM pairs. Additionally, as GBM CXCR4-positive stem-like cells are supposed to give rise to recurrence, we compared the expression of both receptors in primary and recurrent GBM cells expressing either neural (MUSASHI-1) or embryonic stem cell markers (KLF-4, OCT-4, SOX-2, NANOG). We were able to show that both CXCR4 and CXCR7 were expressed at considerable mRNA and protein levels. CXCR7 was downregulated in relapse cases, and different groups regarding CXCR4/CXCR7 expression differences between primary and recurrent samples could be distinguished. A co-expression of both receptors was rare. In line with this, CXCR4 was co-expressed with all investigated neural and embryonic stem cell markers in both primary and recurrent tissues, whereas CXCR7 was mostly found on stem cell marker-negative cells, but was co-expressed with KLF-4 on a distinct GBM cell subpopulation. These results point to an individual role of CXCR4 and CXCR7 in stem cell marker-positive GBM cells in glioma progression and underline the opportunity to develop new therapeutic tools for GBM intervention. PMID:26821357

  2. Calbindin and parvalbumin are early markers of non-mitotically regenerating hair cells in the bullfrog vestibular otolith organs

    Science.gov (United States)

    Steyger, P. S.; Burton, M.; Hawkins, J. R.; Schuff, N. R.; Baird, R. A.

    1997-01-01

    Earlier studies have demonstrated hair cell regeneration in the absence of cell proliferation, and suggested that supporting cells could phenotypically convert into hair cells following hair cell loss. Because calcium-binding proteins are involved in gene up-regulation, cell growth, and cell differentiation, we wished to determine if these proteins were up-regulated in scar formations and regenerating hair cells following gentamicin treatment. Calbindin and parvalbumin immunolabeling was examined in control or gentamicin-treated (GT) bullfrog saccular and utricular explants cultured for 3 days in amphibian culture medium or amphibian culture medium supplemented with aphidicolin, a blocker of nuclear DNA replication in eukaryotic cells. In control cultures, calbindin and parvalbumin immunolabeled the hair bundles and, less intensely, the cell bodies of mature hair cells. In GT or mitotically-blocked GT (MBGT) cultures, calbindin and parvalbumin immunolabeling was also seen in the hair bundles, cuticular plates, and cell bodies of hair cells with immature hair bundles. Thus, these antigens were useful markers for both normal and regenerating hair cells. Supporting cell immunolabeling was not seen in control cultures nor in the majority of supporting cells in GT cultures. In MBGT cultures, calbindin and parvalbumin immunolabeling was up-regulated in the cytosol of single supporting cells participating in scar formations and in supporting cells with hair cell-like characteristics. These data provide further evidence that non-mitotic hair cell regeneration in cultures can be accomplished by the conversion of supporting cells into hair cells.

  3. ABCC3 as a marker for multidrug resistance in non-small cell lung cancer

    OpenAIRE

    Yanbin Zhao; Hailing Lu; An Yan; Yanmei Yang; Qingwei Meng; Lichun Sun; Hui Pang; Chunhong Li; Xiaoqun Dong; Li Cai

    2013-01-01

    Multidrug resistance (MDR) contributes to the failure of chemotherapy and high mortality in non-small cell lung cancer (NSCLC). We aim to identify MDR genes that predict tumor response to chemotherapy. 199 NSCLC fresh tissue samples were tested for chemosensitivity by MTT assay. cDNA microarray was done with 5 samples with highest resistance and 6 samples with highest sensitivity. Expression of ABCC3 mRNA and protein was detected by real-time PCR and immunohistochemisty, respectively. The ass...

  4. Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer

    OpenAIRE

    Iqbal, Sobuhi; Vishnubhatla, Sreenivas; Raina, Vinod; Sharma, Surabhi; Gogia, Ajay; Suryanarayana S.V. Deo; Mathur, Sandeep; Shukla, Nutan Kumar

    2015-01-01

    The aim of our study was to look for alternative predictive biomarkers for breast cancer management in limited resource setup. A comprehensive analysis of circulating cell-free DNA (CCFD) in serum at baseline was performed to assess its prognostic potential. Quantitative polymerase chain reaction (qPCR) of ALU sequences using ALU115 and ALU247 primers was carried out in patients (N: baseline 148, postoperative 47) and 51 healthy controls. Mean serum DNA integrity, levels of ALU 247 and levels...

  5. What is the clinical value of cancer stem cell markers in gliomas?

    DEFF Research Database (Denmark)

    Dahlrot, Rikke Hedegaard; Hermansen, Simon Kjær; Hansen, Steinbjørn;

    2013-01-01

    . This review summarizes current reports on putative glioma CSC markers and reviews the prognostic value of the individual immunohistochemical markers reported in the literature. Using the Pubmed database, twenty-seven CSC studies looking at membrane markers (CD133, podoplanin, CD15, and A2B5), filament...... markers (nestin), RNA-binding proteins (Musashi-1) and transcription factors (BMI1, SOX2, Id1 and Oct-4) qualified for this review. The level of CD133 and nestin increased with increasing malignancy grade, and for both markers a prognostic significance was identified in the majority of the studies...... promising. For the remaining markers CD15, A2B5, BMI1, SOX2, Id1 and Oct4, no prognostic value was found regarding overall survival in this review. In conclusion we find that CD133, nestin, CD133/nestin, podoplanin, Musashi-1 and Musashi-1/MIB1 are the most promising markers for future investigation...

  6. Estimation of groin recurrence risk in patients with squamous cell vulvar carcinoma by the assessment of marker gene expression in the lymph nodes

    International Nuclear Information System (INIS)

    Regional lymph node (LN) status is a well-known prognostic factor for vulvar carcinoma (VC) patients. Although the reliable LN assessment in VC is crucial, it presents significant diagnostic problems. We aimed to identify specific mRNA markers of VC dissemination in the LN and to address the feasibility of predicting the risk of nodal recurrence by the patterns of gene expression. Sentinel and inguinal LN samples from 20 patients who had undergone surgery for stage T1-3, N0-2, M0 primary vulvar squamous cell carcinoma were analyzed. Gene expression profiles were assessed in four metastatic [LN(+)] and four histologically negative [LN(−)] lymph node samples obtained from four VC patients, by the Affymetrix U133 Plus 2.0 gene expression microarrays. Of the set of genes of the highest expression in the metastatic LNs compared to LN(−), seven candidate marker genes were selected: PERP, S100A8, FABP5, SFN, CA12, JUP and CSTA, and the expression levels of these genes were further analyzed by the real-time reverse transcription polymerase chain reaction (qRT-PCR) in 71 LN samples. All of the seven genes in question were significantly increased in LN(+) compared to LN(−) samples. In the initial validation of the seven putative markers of metastatic LN, the Cox proportional hazard model pointed to SFN, CA12 and JUP expression to significantly relate to the time to groin recurrence in VC patients. Our findings first provided evidence that SFN, CA12 and JUP have a potential of marker genes for the prediction of the groin recurrence LN in VC patients

  7. FolR1: a novel cell surface marker for isolating midbrain dopamine neural progenitors and nascent dopamine neurons.

    Science.gov (United States)

    Gennet, Nicole; Tamburini, Claudia; Nan, Xinsheng; Li, Meng

    2016-01-01

    Cell type-specific surface markers offer a powerful tool for purifying defined cell types for restorative therapies and drug screenings. Midbrain dopaminergic neurons (mesDA) are the nerve cells preferentially lost in the brains of Parkinson's disease patients. Clinical trials of transplantation of fetal neural precursors suggest that cell therapy may offer a cure for this devastating neurological disease. Many lines of preclinical studies demonstrate that neural progenitors committed to dopaminergic fate survive and integrate better than postmitotic DA neurons. We show that the folate-receptor 1 (FolR1), a GPI-anchored cell surface molecule, specifically marks mesDA neural progenitors and immature mesDA neurons. FolR1 expression superimposes with Lmx1a, a bona-fide mesDA lineage marker, during the active phase of mesDA neurogenesis from E9.5 to E14.5 during mouse development, as well as in ESC-derived mesDA lineage. FolR1(+) neural progenitors can be isolated by FACS or magnetic sorting (MAC) which give rise to dopamine neurons expressing TH and Pitx3, whilst FolR1 negative cells generate non-dopaminergic neurons and glia cells. This study identifies FolR1 as a new cell surface marker selectively expressed in mesDA progenitors in vivo and in vitro and that can be used to enrich in vitro differentiated TH neurons. PMID:27580818

  8. The macrophage activation marker sCD163 combined with markers of the Enhanced Liver Fibrosis (ELF) score predicts clinically significant portal hypertension in patients with cirrhosis

    DEFF Research Database (Denmark)

    Sandahl, T D; McGrail, R; Møller, H J;

    2016-01-01

    predict portal hypertension in patients with cirrhosis. METHODS: We measured sCD163 and the ELF components (hyaluronic acid, tissue inhibitor of metalloproteinase-1 and procollagen-III aminopeptide) in two separate cohorts of cirrhosis patients that underwent hepatic vein catheterisation. To test the...

  9. Quantifying and comparing dynamic predictive accuracy of joint models for longitudinal marker and time-to-event in presence of censoring and competing risks

    DEFF Research Database (Denmark)

    Blanche, Paul; Proust-Lima, Cécile; Loubère, Lucie;

    2015-01-01

    Thanks to the growing interest in personalized medicine, joint modeling of longitudinal marker and time-to-event data has recently started to be used to derive dynamic individual risk predictions. Individual predictions are called dynamic because they are updated when information on the subject's...... psychometric tests to predict dementia in the elderly, accounting for the competing risk of death. Models are estimated on the French Paquid cohort and predictive accuracies are evaluated and compared on the French Three-City cohort.......'s health profile grows with time. We focus in this work on statistical methods for quantifying and comparing dynamic predictive accuracy of this kind of prognostic models, accounting for right censoring and possibly competing events. Dynamic area under the ROC curve (AUC) and Brier Score (BS) are used to...

  10. Detection of cancer cells and tumor markers in gastric lavage of patients with gastric cancer: Do these findings have a clinicopathological significance and oncological implication?

    Science.gov (United States)

    Virgilio, Edoardo; Giarnieri, Enrico; Montagnini, Monica; D'Urso, Rosaria; Proietti, Antonella; Mesiti, Alessandra; Giovagnoli, Maria Rosaria; Mercantini, Paolo; Cavallini, Marco; Balducci, Genoveffa

    2016-09-01

    Although decreasing in the incidence over the last years, currently gastric adenocarcinoma represents the second cause of cancer related-death worldwide. Further knowledge and novel therapies are desperately needed in order to make the prognosis of these patients more acceptable. Infact, even though in recent years numerous staging parameters have been largely studied and unanimously recognized for their clinical and prognostic value, today too many shadows still exist around the capacity to predict exactly the natural history or post-treatment behavior of this cancer even among patients of the same stage. This study has identified the presence of isolated cancer cells as well as tumor markers (CEA, Ca 19.9, Ca 72.4 and Ca 50) from the gastric lavage of patients affected by gastric adenocarcinoma. Such findings led to the hypothesis that endoluminal exfoliation of neoplastic cells and the release of their products (tumor markers) into the gastric juice might be an expression of neoplastic behavior as well as aggressive malignancy. Should this hypothesis become a reality, some important progress could be made in the knowledge, staging, prediction as well as management and follow-up of this inauspicious type of cancer. PMID:27515187

  11. Anthropometric markers and their association with incident type 2 diabetes mellitus: which marker is best for prediction? Pooled analysis of four German population-based cohort studies and comparison with a nationwide cohort study

    Science.gov (United States)

    Hartwig, Saskia; Kluttig, Alexander; Tiller, Daniel; Fricke, Julia; Müller, Grit; Schipf, Sabine; Völzke, Henry; Schunk, Michaela; Meisinger, Christa; Schienkiewitz, Anja; Heidemann, Christin; Moebus, Susanne; Pechlivanis, Sonali; Werdan, Karl; Kuss, Oliver; Tamayo, Teresa; Haerting, Johannes; Greiser, Karin Halina

    2016-01-01

    Objective To compare the association between different anthropometric measurements and incident type 2 diabetes mellitus (T2DM) and to assess their predictive ability in different regions of Germany. Methods Data of 10 258 participants from 4 prospective population-based cohorts were pooled to assess the association of body weight, body mass index (BMI), waist circumference (WC), waist-to-hip-ratio (WHR) and waist-to-height-ratio (WHtR) with incident T2DM by calculating HRs of the crude, adjusted and standardised markers, as well as providing receiver operator characteristic (ROC) curves. Differences between HRs and ROCs for the different anthropometric markers were calculated to compare their predictive ability. In addition, data of 3105 participants from the nationwide survey were analysed separately using the same methods to provide a nationally representative comparison. Results Strong associations were found for each anthropometric marker and incidence of T2DM. Among the standardised anthropometric measures, we found the strongest effect on incident T2DM for WC and WHtR in the pooled sample (HR for 1 SD difference in WC 1.97, 95% CI 1.75 to 2.22, HR for WHtR 1.93, 95% CI 1.71 to 2.17 in women) and in female DEGS participants (HR for WC 2.24, 95% CI 1.91 to 2.63, HR for WHtR 2.10, 95% CI 1.81 to 2.44), whereas the strongest association in men was found for WHR among DEGS participants (HR 2.29, 95% CI 1.89 to 2.78). ROC analysis showed WHtR to be the strongest predictor for incident T2DM. Differences in HR and ROCs between the different markers confirmed WC and WHtR to be the best predictors of incident T2DM. Findings were consistent across study regions and age groups (<65 vs ≥65 years). Conclusions We found stronger associations between anthropometric markers that reflect abdominal obesity (ie, WC and WHtR) and incident T2DM than for BMI and weight. The use of these measurements in risk prediction should be encouraged. PMID:26792214

  12. The value of serum tumour markers in the prediction of aetiology and follow up of patients with pericardial effusion

    OpenAIRE

    Bildirici, U; Celikyurt, U; ACAR, E.; Sahin, T.; Kozdag, G; Ural, D; Bulut, O

    2012-01-01

    Background The aim of this study was to evaluate the value of tumour markers in the differential diagnosis of pericardial effusions and to assess their changing levels during follow up. Methods Sixty-nine patients who were admitted to hospital with a diagnosis of pericardial effusion were included in the study. Serum tumour markers were measured on admission and after a mean of 18 ± 7 months’ follow up. An aetiological diagnosis was made on clinical evaluation, imaging techniques and biochemi...

  13. Nuclear expression of β-catenin and stem cell markers as potential prognostic indicators in medulloblastoma

    Directory of Open Access Journals (Sweden)

    Kiran Krishne Gowda

    2012-01-01

    Full Text Available Aims: To study the prognostic role of β-catenin and stem cell markers in medulloblastoma (MB. Materials and Methods: Sixty cases of MB were retrospectively analyzed to study the expression of β-catenin, CD15, and CD133 by immunohistochemistry. Their expression was correlated with histological subtypes and event-free survival (EFS. Patients were divided into Group 1 and 2 based on non-occurrence and occurrence of events during the follow-up period. Results: Fifty of the 60 cases were of classic type of MB while nine were of desmoplastic subtype and one case showed chondroid and rhabdomyoblastic differentiation. Immunoreactivity for β-catenin was observed as nuclear and/or cytoplasmic positivity within the tumor cells. Forty-one (68.3% cases showed cytoplasmic positivity, while nuclear positivity was seen in 21 (35% cases. There was a significant correlation between nuclear expression of β-catenin and different histological subtypes by Chi-square test (P value<0.05. A statistically significant positive correlation of β-catenin nuclear positivity with EFS was observed. Among 60 cases, 37 cases (67.3% showed presence of CD15+ tumor cells with percentage of positivity varying between 0.1 to 17.1%. Overall, 42 of 60 (70% cases showed presence of CD133+ cells. The percentage of positivity varied between 0.1 to 16.5%. A statistically significant negative correlation of CD15 and CD133 positivity with EFS was observed. Conclusions: Nucleopositive β-catenin cases were associated with a favorable outcome on univariate analysis. Both CD15 and CD133 positivity were associated with a worse outcome on univariate analysis.

  14. Expression of Putative Stem Cell Marker, Hepatocyte Nuclear Factor 4 Alpha, in Mammary Gland of Water Buffalo.

    Science.gov (United States)

    Choudhary, Ratan K; Choudhary, Shanti; Kaur, Harmanjot; Pathak, Devendra

    2016-01-01

    Buffaloes account for more than 56% of total milk production in India. Cyclic remodeling of mammary glands of human, mice, cow, sheep, and goat is determined by mammary stem cells. It is logical to assume that buffalo mammary gland will have mammary stem/progenitor cells. Thus far, no report exists on identification of buffalo mammary stem cells. Hepatocyte nuclear factor 4 alpha (HNF4A) is a candidate marker for hepatic progenitor cells and has recently been suggested as a marker of bovine mammary stem/progenitor cells. We hypothesized that ( 1 ) HNF4A identifies putative buffalo mammary stem/progenitor cells and ( 2 ) the number of HNF4A-positive cells increases during mastitis. Sixteen buffalo mammary samples were collected from a local slaughterhouse. Hematoxylin and eosin staining were performed on 5-micron thick sections and on the basis of gross examination and histomorphology of the mammary glands, physiological stages of the animals were estimated as non-lactating (n = 4), mastitis (n = 9), and prepubertal (n = 3). In total, 24048 cells were counted (5-10 microscopic fields/animal; n = 16 animals) of which, 40% cells were mammary epithelial cells (MEC) and 60% cells were the stromal cells. The percentage of MEC in non-lactating animals was higher compared to mastitic animals (47.3% vs. 37.3%), which was likely due to loss of MEC in mastitis. HNF4A staining was observed in nuclei of MEC of ducts, alveoli, and stromal cells. Basal location and low frequency of HNF4A-positive MEC (ranges from 0.4-4.5%) were consistent with stem cell characteristics. Preliminary study showed coexpression of HNF4A with MSI1 (a mammary stem cell marker in sheep), suggesting HNF4A was likely to be a putative mammary stem/progenitor cell marker in buffalo. HNF4A-positive MEC (basal and luminal; light and dark stained) tended to be higher in non-lactating than the mastitic animals (8.73 ± 1.71% vs. 4.29 ± 1.19%; P = 0.07). The first hypothesis that HNF4A identify

  15. Neoadjuvant therapy affects tumor growth markers in early stage non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Chorostowska-Wynimko J

    2009-12-01

    Full Text Available Abstract Introduction While adjuvant therapy of early-stage non-small-cell lung cancer (NSCLC is widely accepted, literature data concerning neoadjuvant treatment provide contradictory results with both improved and unaffected survival rates. Also, data concerning potential effects of neo-adjuvant therapy on cellular level are scarce. Objective The aim of present study was to analyze the effect of chemotherapy followed by surgical resection on several key biological markers of tumor growth (TGF-β, VEGF, apoptosis (sAPO-1/Fas/CD95 and invasiveness (TIMP-1 assessed in the sera of NSCLC early-stage patients (IB-IIIA. Materials and methods Measurements were performed by ELISA method in blood serum from 24 NSCLC patients (I-IIIA collected prior therapy, one day before surgery and 3 days after. Results TGF-β serum concentrations were significantly lower after both chemotherapy (P Conclusion Neoadjuvant treatment of early-stage NSCLC affects mostly mechanisms responsible for tumor growth and vascularization. Its effect on cancer cells apoptotic activity needs further evaluation.

  16. Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma

    DEFF Research Database (Denmark)

    Jakobsen, Kristine Raaby; Paulsen, Birgitte Sandfeld; Bæk, Rikke;

    2015-01-01

    Background: Lung cancer is one of the leading causes of cancer-related death. At the time of diagnosis, more than half of the patients will have disseminated disease and, yet, diagnosing can be challenging. New methods are desired to improve the diagnostic work-up. Exosomes are cell-derived vesic......Background: Lung cancer is one of the leading causes of cancer-related death. At the time of diagnosis, more than half of the patients will have disseminated disease and, yet, diagnosing can be challenging. New methods are desired to improve the diagnostic work-up. Exosomes are cell...... control subjects based on the differential display of exosomal protein markers. Methods: Plasma was isolated from 109 NSCLC patients with advanced stage (IIIa–IV) disease and 110 matched control subjects initially suspected of having cancer, but diagnosed to be cancer free. The Extracellular Vesicle Array...... (EV Array) was used to phenotype exosomes directly from the plasma samples. The array contained 37 antibodies targeting lung cancer-related proteins and was used to capture exosomes, which were visualised with a cocktail of biotin-conjugated CD9, CD63 and CD81 antibodies. Results: The EV Array...

  17. Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma

    DEFF Research Database (Denmark)

    Jakobsen, Kristine R; Paulsen, Birgitte S; Bæk, Rikke;

    2015-01-01

    BACKGROUND: Lung cancer is one of the leading causes of cancer-related death. At the time of diagnosis, more than half of the patients will have disseminated disease and, yet, diagnosing can be challenging. New methods are desired to improve the diagnostic work-up. Exosomes are cell-derived vesic......BACKGROUND: Lung cancer is one of the leading causes of cancer-related death. At the time of diagnosis, more than half of the patients will have disseminated disease and, yet, diagnosing can be challenging. New methods are desired to improve the diagnostic work-up. Exosomes are cell...... control subjects based on the differential display of exosomal protein markers. METHODS: Plasma was isolated from 109 NSCLC patients with advanced stage (IIIa-IV) disease and 110 matched control subjects initially suspected of having cancer, but diagnosed to be cancer free. The Extracellular Vesicle Array...... (EV Array) was used to phenotype exosomes directly from the plasma samples. The array contained 37 antibodies targeting lung cancer-related proteins and was used to capture exosomes, which were visualised with a cocktail of biotin-conjugated CD9, CD63 and CD81 antibodies. RESULTS: The EV Array...

  18. Differential Regulation of Gene Expression of Alveolar Epithelial Cell Markers in Human Lung Adenocarcinoma-Derived A549 Clones

    Directory of Open Access Journals (Sweden)

    Hiroshi Kondo

    2015-01-01

    Full Text Available Stem cell therapy appears to be promising for restoring damaged or irreparable lung tissue. However, establishing a simple and reproducible protocol for preparing lung progenitor populations is difficult because the molecular basis for alveolar epithelial cell differentiation is not fully understood. We investigated an in vitro system to analyze the regulatory mechanisms of alveolus-specific gene expression using a human alveolar epithelial type II (ATII cell line, A549. After cloning A549 subpopulations, each clone was classified into five groups according to cell morphology and marker gene expression. Two clones (B7 and H12 were further analyzed. Under serum-free culture conditions, surfactant protein C (SPC, an ATII marker, was upregulated in both H12 and B7. Aquaporin 5 (AQP5, an ATI marker, was upregulated in H12 and significantly induced in B7. When the RAS/MAPK pathway was inhibited, SPC and thyroid transcription factor-1 (TTF-1 expression levels were enhanced. After treatment with dexamethasone (DEX, 8-bromoadenosine 3′5′-cyclic monophosphate (8-Br-cAMP, 3-isobutyl-1-methylxanthine (IBMX, and keratinocyte growth factor (KGF, surfactant protein B and TTF-1 expression levels were enhanced. We found that A549-derived clones have plasticity in gene expression of alveolar epithelial differentiation markers and could be useful in studying ATII maintenance and differentiation.

  19. A Unique Procedure to Identify Cell Surface Markers Through a Spherical Self-Organizing Map Applied to DNA Microarray Analysis

    Science.gov (United States)

    Sugii, Yuh; Kasai, Tomonari; Ikeda, Masashi; Vaidyanath, Arun; Kumon, Kazuki; Mizutani, Akifumi; Seno, Akimasa; Tokutaka, Heizo; Kudoh, Takayuki; Seno, Masaharu

    2016-01-01

    To identify cell-specific markers, we designed a DNA microarray platform with oligonucleotide probes for human membrane-anchored proteins. Human glioma cell lines were analyzed using microarray and compared with normal and fetal brain tissues. For the microarray analysis, we employed a spherical self-organizing map, which is a clustering method suitable for the conversion of multidimensional data into two-dimensional data and displays the relationship on a spherical surface. Based on the gene expression profile, the cell surface characteristics were successfully mirrored onto the spherical surface, thereby distinguishing normal brain tissue from the disease model based on the strength of gene expression. The clustered glioma-specific genes were further analyzed by polymerase chain reaction procedure and immunocytochemical staining of glioma cells. Our platform and the following procedure were successfully demonstrated to categorize the genes coding for cell surface proteins that are specific to glioma cells. Our assessment demonstrates that a spherical self-organizing map is a valuable tool for distinguishing cell surface markers and can be employed in marker discovery studies for the treatment of cancer. PMID:26966393

  20. Expression of stem cell marker CD133 during neuroendocrine transdifferentiation of prostate cancer cells

    Czech Academy of Sciences Publication Activity Database

    Pernicová, Zuzana; Lincová, Eva; Kozubík, Alois; Souček, Karel

    Oslo, 2009. s. 69. [Second Norwegian Cancer Symposium 2009 - Frontiers in Cancer Stem Cell Research: From basic science towards a cure . 02.12.2009-04.12.2009, Oslo] R&D Projects: GA ČR(CZ) GA204/07/0834; GA ČR(CZ) GA310/07/0961 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : neuroendocrine differentiation * CD133 * senescence Subject RIV: BO - Biophysics

  1. Isolation and differentiation of chondrocytic cells derived from human embryonic stem cells using dlk1/FA1 as a novel surface marker

    DEFF Research Database (Denmark)

    Harkness, Linda; Taipaleenmaki, Hanna; Mahmood, Amer;

    2009-01-01

    cells when cultured as micromass pellets in a xeno-free system containing TGFbeta1. In conclusion, we identified dlk1/FA1 as a novel marker of chondroprogenitor cells that undergo embryonic lineage progression from proliferation to the prehypertrophic stage. Tracking dlk1/FA1 expression as a mesoderm...

  2. The acute effects of strength training on inflammatory markers predicting atherosclerosis: a study on inactive middle-aged men

    Directory of Open Access Journals (Sweden)

    Bizheh N

    2011-06-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Cardiovascular diseases, especially atherosclerosis, are the main causes of morbidity and mortality worldwide. The disease has had an increasing prevalence in Iran in recent years. Homocysteine and C-reactive protein (CRP are two novel cardiovascular risk factors that independently predict risks of atherosclerosis. The purpose of this study was to investigate the effects of one session of circuit resistance training on the blood levels of the aforesaid inflammatory markers in inactive middle-aged men."n"nMethods: The participants of this study included twenty-three healthy but inactive middle-aged men who were overweight and were randomly divided into two experimental (n=14 and control (n=9 groups. The activity included doing exercises with the subjects' 35% one-repetition maximum (1-RM intensity at ten different stations. Blood levels of homocysteine and hs-CRP were measured before and after the exercise."n"nResults: Analysis of data using independent samples t-test showed a significant increment in the serum levels of homocysteine and hs-CRP after training in the experimental (P<0.05 versus the control group."n"nConclusion: Elevation of homocysteine levels is due to the increase in protein metabolism

  3. Circulating cell-free DNA: an up-coming molecular marker in exercise physiology.

    Science.gov (United States)

    Breitbach, Sarah; Tug, Suzan; Simon, Perikles

    2012-07-01

    The phenomenon of circulating cell-free DNA (cfDNA) concentrations is of importance for many biomedical disciplines including the field of exercise physiology. Increases of cfDNA due to exercise are described to be a potential hallmark for the overtraining syndrome and might be related to, or trigger adaptations of, immune function induced by strenuous exercise. At the same time, exercise provides a practicable model for studying the phenomenon of cfDNA that is described to be of pathophysiological relevance for different topics in clinical medicine like autoimmune diseases and cancer. In this review, we are summarizing the current knowledge of exercise-based acute and chronic alterations in cfDNA levels and their physiological significance. The effects of acute exercise on cfDNA concentrations have been investigated in resistance exercises and in continuous, stepwise and interval endurance exercises of different durations. cfDNA concentrations peaked immediately after acute exercise and showed a rapid return to baseline levels. Typical markers of skeletal muscle damage (creatine kinase, uric acid, C-reactive protein) show delayed kinetics compared with the cfDNA peak response. Exercise parameters such as intensity, duration or average energy expenditure do not explain the extent of increasing cfDNA concentrations after strenuous exercise. This could be due to complex processes inside the human organism during and after physical activity. Therefore, we hypothesize composite effects of different physiological stress parameters that come along with exercise to be responsible for increasing cfDNA concentrations. We suggest that due to acute stress, cfDNA levels increase rapidly by a spontaneous active or passive release mechanism that is not yet known. As a result of the rapid and parallel increase of cfDNA and lactate in an incremental treadmill test leading to exhaustion within 15-20 minutes, it is unlikely that cfDNA is released into the plasma by typical necrosis

  4. The cell birth marker BrdU does not affect recruitment of subsequent cell divisions in the adult avian brain.

    Science.gov (United States)

    Cattan, Anat; Ayali, Amir; Barnea, Anat

    2015-01-01

    BrdU is commonly used to quantify neurogenesis but also causes mutation and has mitogenic, transcriptional, and translational effects. In mammalian studies, attention had been given to its dosage, but in birds such examination was not conducted. Our previous study suggested that BrdU might affect subsequent cell divisions and neuronal recruitment in the brain. Furthermore, this effect seemed to increase with time from treatment. Accordingly, we examined whether BrdU might alter neurogenesis in the adult avian brain. We compared recruitment of [(3)H]-thymidine(+) neurons in brains of zebra finches (Taeniopygia guttata) when no BrdU was involved and when BrdU was given 1 or 3 months prior to [(3)H]-thymidine. In nidopallium caudale, HVC, and hippocampus, no differences were found between groups in densities and percentages of [(3)H]-thymidine(+) neurons. The number of silver grains per [(3)H]-thymidine(+) neuronal nucleus and their distribution were similar across groups. Additionally, time did not affect the results. The results indicate that the commonly used dosage of BrdU in birds has no long-term effects on subsequent cell divisions and neuronal recruitment. This conclusion is also important in neuronal replacement experiments, where BrdU and another cell birth marker are given, with relatively long intervals between them. PMID:25759813

  5. Cinnamon extract reduces symptoms, inflammatory mediators and mast cell markers in murine IL-10(-/-) colitis.

    Science.gov (United States)

    Hagenlocher, Yvonne; Hösel, Angela; Bischoff, Stephan C; Lorentz, Axel

    2016-04-01

    Inflammatory bowel disease (IBD) shows an increasing prevalence and harm in western countries. Conventional therapies are associated with bad compliance and adverse side effects. Natural substances like cinnamon extract (CE) could be an additional therapy. We found recently that CE acts anti-inflammatory on mast cells - discussed of being relevant in IBD. Here, we analysed the effects of CE on murine IL-10(-/-) colitis as model for IBD. Mice were treated 12 weeks with or without CE in drinking water. Clinical scores and disease activity index were assessed. Colonic tissue samples were analysed for infiltration, tissue damage, bowel wall thickness, expression of pro-inflammatory mediators, mast cell proteases, tight junction proteins, and NF-κB signaling. Following treatment with CE, symptoms of murine colitis as well as increased infiltration of immune cells, tissue damage and bowel wall thickness in colon tissue of IL-10(-/-) mice were diminished significantly. MIP-2, TNF, IFNγ, CCL2, CCL3, CCL4 and IL-1β as well as MC-CPA, MCP-1 and MCP-4 were strongly upregulated in IL-10(-/-) mice compared to WT, but noteworthy not in CE group. Expression of tight junction proteins was not influenced by CE. Phosphorylation of IκB was slightly down-regulated in CE treated IL-10(-/-) mice compared to IL-10(-/-) controls. In summary, CE decreases inflammatory symptoms and expression of inflammatory markers in murine IL-10(-/-) colitis. CE has no influence on tight junction proteins, but seems acting via reducing pro-inflammatory mediators and recruitment of neutrophil granulocytes probably by inhibiting NF-κB signaling. PMID:27012624

  6. Molecular markers of trichloroethylene-induced toxicity in human kidney cells

    International Nuclear Information System (INIS)

    Difficulties in evaluation of trichloroethylene (TRI)-induced toxicity in humans and extrapolation of data from laboratory animals to humans are due to the existence of multiple target organs, multiple metabolic pathways, sex-, species-, and strain-dependent differences in both metabolism and susceptibility to toxicity, and the lack or minimal amount of human data for many target organs. The use of human tissue for mechanistic studies is thus distinctly advantageous. The kidneys are one target organ for TRI and metabolism by the glutathione (GSH) conjugation pathway is responsible for nephrotoxicity. The GSH conjugate is processed further to produce the cysteine conjugate, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), which is the penultimate nephrotoxic species. Confluent, primary cultures of human proximal tubular (hPT) cells were used as the model system. Although cells in log-phase growth, which are undergoing more rapid DNA synthesis, would give lower LD50 values, confluent cells more closely mimic the in vivo proximal tubule. DCVC caused cellular necrosis only at relatively high doses (>100 μM) and long incubation times (>24 h). In contrast, both apoptosis and enhanced cellular proliferation occurred at relatively low doses (10-100 μM) and early incubation times (2-8 h). These responses were associated with prominent changes in expression of several proteins that regulate apoptosis (Bcl-2, Bax, Apaf-1, Caspase-9 cleavage, PARP cleavage) and cellular growth, differentiation and stress response (p53, Hsp27, NF-κB). Effects on p53 and Hsp27 implicate function of protein kinase C, the mitogen activated protein kinase pathway, and the cytoskeleton. The precise pattern of expression of these and other proteins can thus serve as molecular markers for TRI exposure and effect in human kidney

  7. Epidermal Cells Expressing Putative Cell Markers in Nonglabrous Skin Existing in Direct Proximity with the Distal End of the Arrector Pili Muscle

    Science.gov (United States)

    Rufaut, N. W.; Jones, L.; Sinclair, R.

    2016-01-01

    Inconsistent with the view that epidermal stem cells reside randomly spread along the basal layer of the epidermal rete ridges, we found that epidermal cells expressing stem cell markers in nonglabrous skin exist in direct connection with the distal end of the arrector pili muscle. The epidermal cells that express stem cell markers consist of a subpopulation of basal keratinocytes located in a niche at the lowermost portion of the rete ridges at the distal arrector pili muscle attachment site. Keratinocytes in the epidermal stem cell niche express K15, MCSP, and α6 integrin. α5 integrin marks the distal end of the APM colocalized with basal keratinocytes expressing stem cell markers located in a well-protected and nourished environment at the lowermost point of the epidermis; these cells are hypothesized to participate directly in epidermal renewal and homeostasis and also indirectly in wound healing through communication with the hair follicle bulge epithelial stem cell population through the APM. Our findings, plus a reevaluation of the literature, support the hierarchical model of interfollicular epidermal stem cell units of Fitzpatrick. This new view provides insights into epidermal control and the possible involvement of epidermal stem cells in nonmelanoma skin carcinogenesis.

  8. Upregulation of circulating cancer stem cell marker, DCLK1 but not Lgr5, in chemoradiotherapy-treated colorectal cancer patients.

    Science.gov (United States)

    Mirzaei, Alireza; Tavoosidana, Gholamreza; Modarressi, Mohammad Hossein; Rad, Afshin Abdi; Fazeli, Mohammad Sadegh; Shirkoohi, Reza; Tavakoli-Yaraki, Masoumeh; Madjd, Zahra

    2015-06-01

    Cancer stem cell (CSC) markers have attracted considerable attention in tumor diagnostic, prognostic, and therapeutic implications. Detection of cancer stem cells in circulating blood using cancer stem cell markers has received remarkable attention recently. In this study, we aimed to investigate the messenger RNA (mRNA) expression level of Lgr5 and DCLK1 as most proposed colorectal CSC markers in blood circulation also determine the subsequent association to patients' clinical and pathological findings. Peripheral blood mononuclear cells (PBMCs) of 58 patients with colorectal cancer at stage I-IV with 33 out of 58 patients undergoing preoperative chemoradiotherapy (CRT), as well as 58 healthy controls have been isolated and the extracted RNAs were analyzed using real-time PCR. The mRNA expression pattern of CSC markers of patients and controls was compared using ΔΔCt method. The expression level of Lgr5 was significantly higher in colorectal cancer (CRC) patients comparing to healthy group (4.8-fold change, p < 0.001). Also there was a significant increase in expression level of Lgr5 in patients at stages III and IV comparing to stages I and II (p = 0.031) and higher grades (p = 0.039) of CRC. The expression of DCLK1 was also elevated in patients significantly (2.7-fold change, p < 0.001) and the related expression was increased by increasing disease stage (p = 0.025). Combination of DCLK1 and Lgr5 markers was analyzed by logistic regression and proved to be a slightly better marker compared to each marker alone. Interestingly the DCLK1 expression level was significantly higher in patients undergoing preoperative CRT (p = 0.041); however, no association to neoadjuvant CRT was observed for Lgr5. Considering the over-expression of DCLK1 and Lgr5 in circulating blood of CRC patients comparing to controls, our results might emphasize on the presence of CSCs in blood of these patients which might be attributed to their clinical and

  9. A spectrum of cutaneous toxicities from erlotinib may be a robust clinical marker for non-small-cell lung therapy: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Jin F

    2015-04-01

    Full Text Available Feng Jin,1 Hui Zhu,2 Li Kong,2 Jinming Yu2 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, University of Jinan, Jinan, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, People’s Republic of China Abstract: Some literature suggests that an EGFR inhibition-induced rash can be used as a clinical marker, but few studies report the correlation between a spectrum of cutaneous toxicities from EGFR inhibition and drug efficacy. We report about a woman with a stage IV lung adenocarcinoma using erlotinib monotherapy, who experienced a spectrum of cutaneous toxicities, including papulopustular rash, mucositis, pruritus, xerosis, paronychia, and facial hirsutism. With treatment, her metastatic lesions shrunk remarkably. This report suggests that some non-small-cell lung cancer patients experiencing a spectrum of cutaneous toxicities might have a good tumor response using erlotinib monotherapy. Our findings may provide a method for clinicians to predict erlotinib efficacy in non-small-cell lung cancer therapy without knowledge of the EGFR mutation status. Keywords: cutaneous toxicity, epidermal growth factor receptor inhibition, erlotinib, clinical marker, non-small-cell lung cancer 

  10. In silico quantitative prediction of B-cell epitope

    Directory of Open Access Journals (Sweden)

    Raúl Isea

    2015-11-01

    Full Text Available This paper shows a computational approach for quantitative prediction of B cell epitopes. The function was defined, which reflects the average value of B epitopes, according to eight predictors of different B epitopes, as well as structural and energetic considerations of the origin protein. The proposed methodology could be useful to develop both dengue and chikungunya vaccines

  11. In silico quantitative prediction of B-cell epitope

    OpenAIRE

    Raúl Isea

    2015-01-01

    This paper shows a computational approach for quantitative prediction of B cell epitopes. The function was defined, which reflects the average value of B epitopes, according to eight predictors of different B epitopes, as well as structural and energetic considerations of the origin protein. The proposed methodology could be useful to develop both dengue and chikungunya vaccines

  12. Advances of Drug Resistance Marker of Gemcitabine for Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Baorui LIU

    2011-05-01

    Full Text Available With the development of pharmacogenomics and pharmacogenetics, personal therapy based on genes has become one of the most effective ways to enhance chemotherapeutic effect on non-small cell lung cancer (NSCLC patients. Much attention has been paid to validate the predictive biomarkers of chemotherapy in order to guide chemotherapy and enhance effect in general. Gemcitabine is one of the common agents treating NSCLC recently. This review is mainly about the recent reports on potential biomarkers of Gemcitabine in tailored therapy of NSCLC.

  13. Prediction of cell penetrating peptides by support vector machines.

    Directory of Open Access Journals (Sweden)

    William S Sanders

    2011-07-01

    Full Text Available Cell penetrating peptides (CPPs are those peptides that can transverse cell membranes to enter cells. Once inside the cell, different CPPs can localize to different cellular components and perform different roles. Some generate pore-forming complexes resulting in the destruction of cells while others localize to various organelles. Use of machine learning methods to predict potential new CPPs will enable more rapid screening for applications such as drug delivery. We have investigated the influence of the composition of training datasets on the ability to classify peptides as cell penetrating using support vector machines (SVMs. We identified 111 known CPPs and 34 known non-penetrating peptides from the literature and commercial vendors and used several approaches to build training data sets for the classifiers. Features were calculated from the datasets using a set of basic biochemical properties combined with features from the literature determined to be relevant in the prediction of CPPs. Our results using different training datasets confirm the importance of a balanced training set with approximately equal number of positive and negative examples. The SVM based classifiers have greater classification accuracy than previously reported methods for the prediction of CPPs, and because they use primary biochemical properties of the peptides as features, these classifiers provide insight into the properties needed for cell-penetration. To confirm our SVM classifications, a subset of peptides classified as either penetrating or non-penetrating was selected for synthesis and experimental validation. Of the synthesized peptides predicted to be CPPs, 100% of these peptides were shown to be penetrating.

  14. Marker-and-cell and Chorin finite difference modeling for fluid flow in a single fracture

    Institute of Scientific and Technical Information of China (English)

    Duoxing Yang

    2009-01-01

    It is important to set up a detailed dynamic model of the fluid flow through fractures for understanding many fluid processes in Earth sciences. Numerical simulation is a popular tool for exploring these processes. The objective of this study is to understand fluid flow in fractures. Contrary to the conventional macro-scale modeling approach, micro-scale simulation is carried out. The Navior-Stokes equation solver was developed by a staggered marker-and-cell and the Chorin pressure iterating finite difference approach. We analyze the effects of the Reynolds number and the frequency of pressure fluctuations on flow mainly through visualization. A significant result is that the effect of pressure fluctuation-induced fluid flow can be observed in a broader frequency range. The peak velocity shifts along the spatial axis depending upon the frequency of the pressure fluctuation. An effective frequency band of the pressure fluctuation was identified which dominates dynamic behavior of the flow. Another major finding is that there exits a critical frequency of the pressure fluctuation which controls approximately the flow dynamic behavior. We conclude that it is only possible to estimate the flow behavior from pressure fluctuation, if effective frequency range is properly accounted for.

  15. Matrix Metalloproteinase-2 Promoter Genotype as a Marker of Cutaneous T-Cell Lymphoma Early Stage

    Directory of Open Access Journals (Sweden)

    Anna Vasku

    2010-01-01

    Full Text Available The aim of the study was to investigate the DNA polymorphic genotype in MMP-2 promoter gene as a potential candidate region for the development of the cutaneous T-cell lymphoma (CTCL and/or its progression. A total of 89 Czech patients with CTCL (including 23 patients with large plaque parapsoriasis were compared to 198 controls of similar age and sex distribution, without personal or family history of chronic skin diseases and without personal history of malignancy. The three selected polymorphisms in the promoter of MMP-2 gene (−1575G/A, −1306C/T, and −790T/G were determined using the PCR-based methodology with RFLP. In our cohort, the associated GGCCTT MMP-2 promoter genotype was highly significantly more frequent in CTCL-Ia stage patients compared to patients with parapsoriasis, the tests having high sensitivity and specificity (78%, 83%, resp.. To conclude, use of associated MMP-2 promoter genotype as a DNA marker might make it possible to distinguish between the patients with parapsoriasis and those with CTCL stage Ia, which could substantially improve possibilities of clinical diagnostics, therapy design, and prognosis of this serious condition in the early stages.

  16. Nucleated red blood cells and early EEG: predicting Sarnat stage and two year outcome.

    LENUS (Irish Health Repository)

    Walsh, B H

    2012-01-31

    AIMS: Hypoxic Ischaemic Encephalopathy (HIE) causes characteristic changes of the electroencephalogram (EEG), and a raised Nucleated Red Blood Cell (NRBC) count compared to controls. We wished to examine whether combining these markers could improve their ability to predict HIE severity in the first 24h. METHODS: Term infants with HIE were recruited. NRBC count and continuous multi-channel EEG were recorded within the first 24h. Neurological assessment was carried out at 24 months. A control population with NRBC counts in the first 24h was recruited. RESULTS: 44 infants with HIE and 43 control infants were recruited. Of the HIE population 39 completed a 2 year follow-up. The median NRBC count differed significantly between the controls and those with HIE (3\\/100 WBC [range of 0-11] vs 12.3\\/100 WBC [0-240]) (p<0.001). Within the HIE population the median NRBC count was significantly greater in infants with moderate\\/severe HIE than mild (16\\/100 WBC [range of 0-240] vs 8\\/100 WBC [1-23]) (p=0.016), and among infants with abnormal outcome compared to normal (21.3\\/100 WBC [1-239.8] vs 8.3\\/100 WBC [0-50])(p=0.03). The predictive ability of EEG changed with time post-delivery, therefore results are given at both 12 and 24h of age. At both time points the combined marker had a stronger correlation than EEG alone; with HIE severity (12h: r=0.661 vs r=0.622), (24h: r=0.645 vs r=0.598), and with outcome at 2 years (12h: r=0.756 vs r=0.652), (24h: r=0.802 vs r=0.746). CONCLUSION: Combining early EEG and NRBC count to predict HIE severity and neurological outcome, improved the predictive ability of either in isolation.

  17. Lin28B is an oncofetal circulating cancer stem cell-like marker associated with recurrence of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Shu-Wen Cheng

    Full Text Available By using an expressed sequence tag bioinformatic algorithm, we identified that Lin28 homolog B (Lin28B may have an oncofetal expression pattern which may facilitate detecting cancer cells in adults. It is also reported to be a potential marker for cancer stem cells. Therefore, we sought to verify oncofetal-stemness characters of Lin28B and test its potential as a circulating cancer stem cell-like marker in adult HCC patients. Lin28B mRNA was examined in a panel of fetal tissue, adult tissue and tumors. Lin28B was over-expressed or knocked down in HepG2 cells to evaluate its potential as a stem cell-like marker. RT-qPCR for Lin28B was performed in the peripheral blood mononuclear cells from patients with HCC receiving surgery (n=96 and non-HCC controls (n=60 and analyzed its clinical significance. Lin28B showed an oncofetal expression pattern. Its overexpression could upregulate stemness markers (OCT4, Nanog and SOX2 and enhance tumorsphere formation in vitro. Lin28B knockdown had opposite effects. Circulating Lin28B was detected in peripheral blood mononuclear cells in 3 cases (5% of non-HCC controls and 32 cases (33.3% of HCC patients. In HCC patients, circulating Lin28B was associated with high tumor grade (P=0.046, large size (P=0.005, high AJCC stage (P=0.044 and BCLC stage (P=0.017. Circulating Lin28B was significantly associated with decreased recurrence-free survival (P<0.001. Circulating Lin28B separated early stage HCC into 2 recurrence-free survival curves (P=0.003. In multivariate analysis, circulating Lin28B was an independent variable associated with early recurrence (P=0.045 and recurrence in early stage HCC (P=0.006. In conclusion, the oncofetal gene Lin28B is a potential oncofetal cancer-stem-cell-like circulating tumor cell marker that correlates with HCC recurrence after hepatectomy. Circulating Lin28B could refine early AJCC stages. Our finding supports the possible use of a TNMC (C for circulating tumor cells staging system

  18. Lin28B is an oncofetal circulating cancer stem cell-like marker associated with recurrence of hepatocellular carcinoma.

    Science.gov (United States)

    Cheng, Shu-Wen; Tsai, Hung-Wen; Lin, Yih-Jyh; Cheng, Pin-Nan; Chang, Yu-Chung; Yen, Chia-Jui; Huang, Hsuan-Pang; Chuang, Yun-Pei; Chang, Ting-Tsung; Lee, Chung-Ta; Chao, Anning; Chou, Cheng-Yang; Chan, Shih-Huang; Chow, Nan-Haw; Ho, Chung-Liang

    2013-01-01

    By using an expressed sequence tag bioinformatic algorithm, we identified that Lin28 homolog B (Lin28B) may have an oncofetal expression pattern which may facilitate detecting cancer cells in adults. It is also reported to be a potential marker for cancer stem cells. Therefore, we sought to verify oncofetal-stemness characters of Lin28B and test its potential as a circulating cancer stem cell-like marker in adult HCC patients. Lin28B mRNA was examined in a panel of fetal tissue, adult tissue and tumors. Lin28B was over-expressed or knocked down in HepG2 cells to evaluate its potential as a stem cell-like marker. RT-qPCR for Lin28B was performed in the peripheral blood mononuclear cells from patients with HCC receiving surgery (n=96) and non-HCC controls (n=60) and analyzed its clinical significance. Lin28B showed an oncofetal expression pattern. Its overexpression could upregulate stemness markers (OCT4, Nanog and SOX2) and enhance tumorsphere formation in vitro. Lin28B knockdown had opposite effects. Circulating Lin28B was detected in peripheral blood mononuclear cells in 3 cases (5%) of non-HCC controls and 32 cases (33.3%) of HCC patients. In HCC patients, circulating Lin28B was associated with high tumor grade (P=0.046), large size (P=0.005), high AJCC stage (P=0.044) and BCLC stage (P=0.017). Circulating Lin28B was significantly associated with decreased recurrence-free survival (P<0.001). Circulating Lin28B separated early stage HCC into 2 recurrence-free survival curves (P=0.003). In multivariate analysis, circulating Lin28B was an independent variable associated with early recurrence (P=0.045) and recurrence in early stage HCC (P=0.006). In conclusion, the oncofetal gene Lin28B is a potential oncofetal cancer-stem-cell-like circulating tumor cell marker that correlates with HCC recurrence after hepatectomy. Circulating Lin28B could refine early AJCC stages. Our finding supports the possible use of a TNMC (C for circulating tumor cells) staging system in HCC

  19. Coxsackie-adenovirus receptor as a novel marker of stem cells in treatment-resistant non-small cell lung cancer

    International Nuclear Information System (INIS)

    Background: Treatment resistance resulting from the presence of cancer stem cells (CSCs) remains a challenge in cancer treatment. Little is known about possible markers of CSCs in treatment-resistant non-small cell lung cancer (NSCLC). We explored the coxsackie-adenovirus receptor (CAR) as one such marker of CSCs in models of treatment-resistant NSCLC. Materials and methods: Resistant H460 and A549 cell lines were established by repeated exposure to paclitaxel or fractionated radiation. CSC markers were measured by Western blotting and flow cytometry. We also established stable CAR-overexpressing and stable shRNA-CAR-knockdown cell lines and assessed their survival, invasiveness, and tumorigenic capabilities with clonogenic, telomerase, Matrigel, and tumor formation assays. Results: CAR expression was associated with CSC phenotype both in vitro and in vivo. CAR-overexpressing cells were more treatment-resistant, self-renewing, and tumorigenic than were parental cells, and shRNA-mediated knockdown of CAR expression was sufficient to inhibit these functions. CAR expression also correlated with the epithelial–mesenchymal transition. Conclusions: We showed for the first time that CAR is a marker of CSCs and may affect the activities of CSCs in treatment-resistant NSCLC. CAR may prove to be a target for CSC treatment and a predictor of treatment response in patients with NSCLC.

  20. Podocalyxin-like protein 1 is a relevant marker for human c-kit(pos) cardiac stem cells.

    Science.gov (United States)

    Moscoso, Isabel; Tejados, Naiara; Barreiro, Olga; Sepúlveda, Pilar; Izarra, Alberto; Calvo, Enrique; Dorronsoro, Akaitz; Salcedo, Juan Manuel; Sádaba, Rafael; Díez-Juan, Antonio; Trigueros, César; Bernad, Antonio

    2016-07-01

    Cardiac progenitor cells (CPCs) from adult myocardium offer an alternative cell therapy approach for ischaemic heart disease. Improved clinical performance of CPCs in clinical trials requires a comprehensive definition of their biology and specific interactions with the environment. In this work we characterize specific human CPC surface markers and study some of their related functions. c-kit(pos) human CPCs (hCPCs) were characterized for cell surface marker expression, pluripotency, early and late cardiac differentiation markers and therapeutic activity in a rat model of acute myocardial infarction. The results indicate that hCPCs are a mesenchymal stem cell (MSC)-like population, with a similar immunoregulatory capacity. A partial hCPC membrane proteome was analysed by liquid chromatography-mass spectrometry/mass spectrometry and 36 proteins were identified. Several, including CD26, myoferlin and podocalyxin-like protein 1 (PODXL), have been previously described in other stem-cell systems. Suppression and overexpression analysis demonstrated that PODXL regulates hCPC activation, migration and differentiation; it also modulates their local immunoregulatory capacity. Therefore, hCPCs are a resident cardiac population that shares many features with hMSCs, including their capacity for local immunoregulation. Expression of PODXL appears to favour the immature state of hCPCs, while its downregulation facilitates their differentiation. Copyright © 2016 John Wiley & Sons, Ltd. PMID:23897803

  1. Decreased levels of serum cytokeratin 19 fragment CYFRA 21-1 predict objective response to chemotherapy in patients with non-small cell lung cancer

    OpenAIRE

    Pang, Li; Jing WANG; Jiang, Yanwen; Chen, Liangan

    2013-01-01

    Diagnostic tools capable of predicting early responses to chemotherapy are required to improve the individual management of cancer patients. The present study aimed to evaluate the prognostic significance of the serum tumor markers CYFRA 21-1, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), carbohydrate antigen (CA) 125, and CA 19-9 for predicting responses to different chemotherapy regimens in patients with non-small cell lung cancer (NSCLC). A total of 276 patients with posto...

  2. A Predictive Model for Yeast Cell Polarization in Pheromone Gradients

    Science.gov (United States)

    Calvez, Vincent; Voituriez, Raphaël; Gonçalves-Sá, Joana; Guo, Chin-Lin; Jiang, Xingyu; Murray, Andrew; Meunier, Nicolas

    2016-01-01

    Budding yeast cells exist in two mating types, a and α, which use peptide pheromones to communicate with each other during mating. Mating depends on the ability of cells to polarize up pheromone gradients, but cells also respond to spatially uniform fields of pheromone by polarizing along a single axis. We used quantitative measurements of the response of a cells to α-factor to produce a predictive model of yeast polarization towards a pheromone gradient. We found that cells make a sharp transition between budding cycles and mating induced polarization and that they detect pheromone gradients accurately only over a narrow range of pheromone concentrations corresponding to this transition. We fit all the parameters of the mathematical model by using quantitative data on spontaneous polarization in uniform pheromone concentration. Once these parameters have been computed, and without any further fit, our model quantitatively predicts the yeast cell response to pheromone gradient providing an important step toward understanding how cells communicate with each other. PMID:27077831

  3. A Predictive Model for Yeast Cell Polarization in Pheromone Gradients.

    Science.gov (United States)

    Muller, Nicolas; Piel, Matthieu; Calvez, Vincent; Voituriez, Raphaël; Gonçalves-Sá, Joana; Guo, Chin-Lin; Jiang, Xingyu; Murray, Andrew; Meunier, Nicolas

    2016-04-01

    Budding yeast cells exist in two mating types, a and α, which use peptide pheromones to communicate with each other during mating. Mating depends on the ability of cells to polarize up pheromone gradients, but cells also respond to spatially uniform fields of pheromone by polarizing along a single axis. We used quantitative measurements of the response of a cells to α-factor to produce a predictive model of yeast polarization towards a pheromone gradient. We found that cells make a sharp transition between budding cycles and mating induced polarization and that they detect pheromone gradients accurately only over a narrow range of pheromone concentrations corresponding to this transition. We fit all the parameters of the mathematical model by using quantitative data on spontaneous polarization in uniform pheromone concentration. Once these parameters have been computed, and without any further fit, our model quantitatively predicts the yeast cell response to pheromone gradient providing an important step toward understanding how cells communicate with each other. PMID:27077831

  4. Usefulness of non-invasive serum markers for predicting liver fibrosis in Egyptian patients with chronic HCV infection.

    Science.gov (United States)

    El Guesiry, Dalal; Moez, Pacinte; Hossam, Nermine; Kassem, Mohamed

    2011-01-01

    Accurate monitoring of liver fibrosis changes in patients with hepatitis C virus (HCV) infection would be helpful in defining the need to intervene, implement the appropriate response in treatment and to minimize the use of liver biopsy. We aimed to evaluate the diagnostic utility of the different serum markers and indices in detecting liver fibrosis in study patients. Initial liver biopsy, routine liver function tests, estimation of hyaluronic acid, MMP-1, and PIIINP levels was performed for 30 Egyptian patients with HCV and 15 controls. Marker algorithms based on common laboratory such APRI score, Fibrotest and Actitest. PIIINP and MMP-1 serum markers were combined and entered into a stepwise logistic regression analysis with formulation of a score equation for fibrosis staging. Combined PIIINP and MMP-1 yielded different cut off scores to estimate two clinically relevant fibrosis stages: "significant fibrosis" versus "extensive fibrosis. Apri score also showed AUC of 1.0 with 100 % sensitivity and specificity to exclude the presence of cirrhosis and was significantly correlated to Metavair fibrosis stage in early fibrosis. On the other hand, PIIINP, Fibrotest and acti test were significantly correlated to Metavair fibrosis stage in both early and late fibrosis. In conclusion, integrating PIIINP/MMP-1 score was able to provide reliable information about the degree of liver fibrosis in chronic hepatitis C patients using different cut-offs values. A combination of liver markers as well as its related indices is an emerging tool to differentiate early from advanced liver fibrosis in HCV patients. PMID:23082465

  5. A functional MRI marker may predict the outcome of electroconvulsive therapy in severe and treatment-resistant depression

    NARCIS (Netherlands)

    J.A. van Waarde; H.S. Scholte; L.J.B. van Oudheusden; B. Verwey; D. Denys; G.A. van Wingen

    2014-01-01

    Electroconvulsive therapy (ECT) is effective even in treatment-resistant patients with major depression. Currently, there are no markers available that can assist in identifying those patients most likely to benefit from ECT. In the present study, we investigated whether resting-state network connec

  6. Increased serum cell-free DNA levels in relation to inflammation are predictive of distant metastasis of esophageal squamous cell carcinoma

    OpenAIRE

    TOMOCHIKA, SHINOBU; Iizuka, Norio; Watanabe, Yusaku; TSUTSUI, MASAHITO; Takeda, Shigeru; Yoshino, Shigefumi; ICHIHARA, KIYOSHI; Oka, Masaaki

    2010-01-01

    Distant metastasis hinders a favorable outcome for patients with esophageal squamous cell carcinoma (ESCC) by limiting the surgical cure. The levels of cell-free DNA (cfDNA) in the blood have served as a predictor for metastasis and recurrence in distant organs in liver cancer. Thus, this study tested the clinical efficacy of serum cfDNA levels as a predictive marker for distant metastasis of ESCC. We investigated cfDNA levels in a cohort of 101 ESCC patients and 46 age- and gender-matched co...

  7. Prediction of renal function (GFR) from cystatin C and creatinine in children: Body cell mass increases accuracy of the estimate

    DEFF Research Database (Denmark)

    Andersen, Trine Borup; Jødal, Lars; Bøgsted, Martin; J. Erlandsen, Erland; Eskild-Jensen, Anni; Frøkiær, Jørgen; Brøchner-Mortensen, Jens

    using robust regression in a forward, stepwise procedure. GFR (mL/min) was the dependent variable. The accuracy and precision of the prediction model were compared to other prediction models from the literature, using k-fold cross-validation. Local constants and coefficients were calculated for all...... glomerular filtration followed by catabolization in the tubular cells. We hypothesized that production rate is proportional to body cell mass (BCM) and inferred GFR (mL/min) to be proportional to BCM/CysC. MATERIAL AND METHODS: GFR was determined with 51Cr-EDTA-clearance in 131 children (52 girls, 79 boys....... CONCLUSION: The new equation predicts GFR with higher accuracy than other equations. Endogenous methods are, however, still not accurate enough to replace exogenous markers when GFR must be determined with high accuracy....

  8. Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions

    Science.gov (United States)

    Lin, Shu-Hai; Liu, Tengfei; Ming, Xiaoyan; Tang, Zhi; Fu, Li; Schmitt-Kopplin, Philippe; Kanawati, Basem; Guan, Xin-Yuan; Cai, Zongwei

    2016-02-01

    Cancer was hypothesized to be driven by cancer stem cells (CSCs), but the metabolic determinants of CSC-like phenotype still remain elusive. Here, we present that hexosamine biosynthetic pathway (HBP) at least in part rescues cancer cell fate with inactivation of glycolysis. Firstly, metabolomic analysis profiled cellular metabolome in CSCs of hepatocellular carcinoma using CD133 cell-surface marker. The metabolic signatures of CD133-positive subpopulation compared to CD133-negative cells highlighted HBP as one of the distinct metabolic pathways, prompting us to uncover the role of HBP in maintenance of CSC-like phenotype. To address this, CSC-like phenotypes and cell survival were investigated in cancer cells under low glucose conditions. As a result, HBP inhibitor azaserine reduced CD133-positive subpopulation and CD133 expression under high glucose condition. Furthermore, treatment of N-Acetylglucosamine in part restores CD133-positive subpopulation when either 2.5 mM glucose in culture media or glycolytic inhibitor 2-deoxy-D-glucose in HCC cell lines was applied, enhancing CD133 expression as well as promoting cancer cell survival. Together, HBP might be a key metabolic determinant in the functions of hepatic CSC marker CD133.

  9. PTK7 as a potential prognostic and predictive marker of response to adjuvant chemotherapy in breast cancer patients, and resistance to anthracycline drugs.

    Science.gov (United States)

    Ataseven, Beyhan; Gunesch, Angela; Eiermann, Wolfgang; Kates, Ronald E; Högel, Bernhard; Knyazev, Pjotr; Ullrich, Axel; Harbeck, Nadia

    2014-01-01

    Biomarkers predicting resistance to particular chemotherapy regimens could play a key role in optimally individualized treatment concepts. PTK7 (protein tyrosine kinase 7) belongs to the receptor tyrosine kinase family involved in several physiological, but also malignant, cell behaviors. Recent studies in acute myeloid leukemia have associated PTK7 expression with resistance to anthracycline therapy. PTK7 mRNA expression in primary tumor tissue (PTT) and corresponding lymph node tissue (LNT) were retrospectively measured in 117 patients with early breast cancer; PTK7 expression was available in 103 PTT and 108 LNT samples. Median age was 60 years (range, 27-87 years). At a median follow-up of 28.5 months, 6 deaths and 16 recurrences had occurred. PTK7 expression correlations with clinicopathological features were computed and PTK7 expression effects on patient outcome were analyzed in three cohorts defined by adjuvant treatment: anthracycline-based treatment, other chemotherapy regimens (including taxane or other substances), or no chemotherapy. Association of PTK7 expression with clinicopathological features was seen only for age in PTT and nodal stage in LNT. High LN PTK7 was associated with poorer disease-free survival (DFS) in the total population (3-year DFS: low [81.7%] versus high [70.4%]; P=0.016) and in patients without adjuvant chemotherapy (3-year DFS: low [91.7%] versus high [22.3%]; P<0.001), but not in patients receiving adjuvant chemotherapy (P=0.552). DFS stratified by PTK7 expression was compared in treatment cohorts: In patients with low LN PTK7 expression, neither chemotherapy cohort showed significantly better survival than the no-chemotherapy cohort. In patients with high LN PTK7 expression, those receiving chemotherapy, including substances other than anthracyclines, but not those receiving only anthracycline-based chemotherapy, showed significantly better DFS than those receiving no chemotherapy (P=0.001). Our results support earlier

  10. [3H]GABA uptake as a marker for cell type in primary cultures of cerebellum and olfactory bulb

    International Nuclear Information System (INIS)

    Uptake of [3H]GABA into cell cultures of rat cerebellum and olfactory bulb was studied by autoradiography, using β-alanine and aminocyclohexane carboxylic acid to distinguish neuronal-specific and glial-specific uptake. Neurons and astrocytes were also labelled by tetanus toxin and anti-GFAP respectively. This combination of markers allowed identification and quantification of several cell types. Cerebellar cultures were found to contain 77% granule neurons, 7.5% inhibitory neurons (probably stellate and basket cells) and 15% astrocytes. Olfactory bulb cultures were over 50% in small neurons which accumulated GABA, the olfactory bulb granule neuron being GABAergic in vivo. (Auth.)

  11. Is TrpM5 a reliable marker for chemosensory cells? Multiple types of microvillous cells in the main olfactory epithelium of mice

    Directory of Open Access Journals (Sweden)

    Finger Thomas E

    2008-12-01

    Full Text Available Abstract Background In the past, ciliated receptor neurons, basal cells, and supporting cells were considered the principal components of the main olfactory epithelium. Several studies reported the presence of microvillous cells but their function is unknown. A recent report showed cells in the main olfactory epithelium that express the transient receptor potential channel TrpM5 claiming that these cells are chemosensory and that TrpM5 is an intrinsic signaling component of mammalian chemosensory organs. We asked whether the TrpM5-positive cells in the olfactory epithelium are microvillous and whether they belong to a chemosensory system, i.e. are olfactory neurons or trigeminally-innervated solitary chemosensory cells. Results We investigated the main olfactory epithelium of mice at the light and electron microscopic level and describe several subpopulations of microvillous cells. The ultrastructure of the microvillous cells reveals at least three morphologically different types two of which express the TrpM5 channel. None of these cells have an axon that projects to the olfactory bulb. Tests with a large panel of cell markers indicate that the TrpM5-positive cells are not sensory since they express neither neuronal markers nor are contacted by trigeminal nerve fibers. Conclusion We conclude that TrpM5 is not a reliable marker for chemosensory cells. The TrpM5-positive cells of the olfactory epithelium are microvillous and may be chemoresponsive albeit not part of the sensory apparatus. Activity of these microvillous cells may however influence functionality of local elements of the olfactory system.

  12. A population of serumdeprivation-induced bone marrow stem cells (SD-BMSC) expresses marker typical for embryonic and neural stem cells

    International Nuclear Information System (INIS)

    The bone marrow represents an easy accessible source of adult stem cells suitable for various cell based therapies. Several studies in recent years suggested the existence of pluripotent stem cells within bone marrow stem cells (BMSC) expressing marker proteins of both embryonic and tissue committed stem cells. These subpopulations were referred to as MAPC, MIAMI and VSEL-cells. Here we describe SD-BMSC (serumdeprivation-induced BMSC) which are induced as a distinct subpopulation after complete serumdeprivation. SD-BMSC are generated from small-sized nestin-positive BMSC (S-BMSC) organized as round-shaped cells in the top layer of BMSC-cultures. The generation of SD-BMSC is caused by a selective proliferation of S-BMSC and accompanied by changes in both morphology and gene expression. SD-BMSC up-regulate not only markers typical for neural stem cells like nestin and GFAP, but also proteins characteristic for embryonic cells like Oct4 and SOX2. We hypothesize, that SD-BMSC like MAPC, MIAMI and VSEL-cells represent derivatives from a single pluripotent stem cell fraction within BMSC exhibiting characteristics of embryonic and tissue committed stem cells. The complete removal of serum might offer a simple way to specifically enrich this fraction of pluripotent embryonic like stem cells in BMSC cultures

  13. Effects of hypoxia on expression of a panel of stem cell and chemosensitivity markers in glioblastoma cell line-derived spheroids

    DEFF Research Database (Denmark)

    Kolenda, Jesper; Jensen, Stine Skov; Aaberg-Jessen, Charlotte;

    entire immunohistochemical panel included hypoxia (HIF-1α, HIF-2α), proliferation (Ki-67) and stem cell (CD133, nestin, podoplanin, Bmi-1, Sox-2) markers as well as markers related to chemosensitivity (MGMT, MDR-1, TIMP-1, Lamp-1). Since spheroids derived in hypoxia were smaller than in normoxia, a set...... differences were found for podoplanin, nestin and TIMP-1 as well as for Ki-67. Hif-2α, Sox-2, MGMT and MDR-1 were not detectable in normoxic and hypoxic U87 spheroids. In conclusion, the expression of tumor stem cell and chemosensitivity markers seems to depend on the oxygen tension suggesting that future...... oxygen tensions below 1-5% O2 has been attributed to play a crucial role in tumorigenesis and therapeutic resistance in glioblastoma. This is in contrast to most in vitro experiments in this field being performed in atmospheric air with 21% O2. In this study the influence of hypoxia on the expression of...

  14. Expression of peanut agglutinin-binding mucin-type glycoprotein in human esophageal squamous cell carcinoma as a marker

    Directory of Open Access Journals (Sweden)

    Balakrishnan Ramathilakam

    2003-11-01

    Full Text Available Abstract Background The TF (Thomson – Friedenreich blood group antigen behaves as an onco-foetal carcinoma-associated antigen, showing increased expression in malignancies and its detection and quantification can be used in serologic diagnosis mainly in adenocarcinomas. This study was undertaken to analyze the sera and tissue level detectable mucin-type glycoprotein (TF-antigen by Peanut agglutinin (PNA and its diagnostic index in serum as well tissues of human esophageal squamous cell carcinoma as marker. Results We examined 100 patients for serological analysis by Enzyme Linked Lectin Assay (ELISA and demonstrated a sensitivity of 87.5%, specificity of 90% and a positive predictive value of 95%. The immuno-histochemical localization of TF antigen by Fluorescence Antigen Technique (FAT in 25 specimens of normal esophageal squamous epithelium specimens and 92 specimens with different grades of, allowed a quicker and more precise identification of its increased expression and this did not correlate with gender and tumor size. There was a positive correlation between membrane bound TF antigen expression with different histological progression, from well differentiated to poorly differentiated, determined by PNA binding. Specimens showed morphological changes and a pronounced increase in PNA binding in Golgi apparatus, secretory granules of the cytosol of well differentiated and an increased cell membrane labeling in moderately and poorly differentiated, when compared with ESCC and normal tissues. Conclusion The authors propose that the expression of TF-antigen in human may play an important role during tumorigenesis establishing it as a chemically well-defined carcinoma-associated antigen. Identification of the circulating TF-antigen as a reactive form and as a cryptic form in the healthy individuals, using PNA-ELLA and Immunohistochemical analysis of TF antigen by FAT is positively correlated with the different histological grades as a simple

  15. Cell proliferation index predicts relapse of brain metastases in non-irradiated patients

    DEFF Research Database (Denmark)

    Peev, N A; Tonchev, A B; Penkowa, M;

    2008-01-01

    BACKGROUND: Brain metastasis is a common complication and a major cause of morbidity and mortality in human malignancies. We investigated whether the proliferating cell index of surgically treated single brain metastasis would predict the relapse at a location remote from the initial resection site...... subsequently by radiotherapy to the whole brain were stained by immunohistochemistry for the marker CDC47 and the proliferation index was calculated. The index was then analysed with respect to clinical parameters, including the incidence of brain relapse within 2 months of the first resection, the timing of...... the patients with lesions which had not relapsed or which had relapsed more than 2 months after first craniotomy (n = 12). The synchronous brain metastasis (that is, those occurring before or within 2 months of the primary cancer diagnosis) had a significantly higher proliferation index than the...

  16. Transcription factor AP-2gamma is a developmentally regulated marker of testicular carcinoma in situ and germ cell tumors

    DEFF Research Database (Denmark)

    Hoei-Hansen, Christina E; Nielsen, John E; Almstrup, Kristian;

    2004-01-01

    . CONCLUSIONS: AP-2gamma is developmentally regulated and associated with the undifferentiated phenotype in germ cells. This transcription factor may be involved in self-renewal and survival of immature germ cells and tissue-specific stem cells. AP-2gamma is a novel marker of testicular CIS and CIS-derived...... protein level in normal human tissues and a panel of tumors and tumor-derived cell lines. In the gonads, we established the ontogeny of expression of AP-2gamma in normal and dysgenetic samples. We also investigated the regulation of AP-2gamma by steroids and retinoic acid. RESULTS: We detected abundant AP......-2gamma in testicular CIS and in testicular germ cell tumors of young adults and confirmed differential expression of AP-2gamma in somatic tumors. We found that AP-2gamma expression was regulated by retinoic acid in an embryonal carcinoma cell line (NT2). The investigation of ontogeny of AP-2gamma...

  17. The thrombopoietin receptor, c-Mpl, is a selective surface marker for human hematopoietic stem cells

    Directory of Open Access Journals (Sweden)

    Kerr William G

    2006-02-01

    from mid-fetal through adult life. This study extends our previous work documenting human B-lineage, myeloid and CD34+ cell repopulation by c-mpl+ progenitors to show that c-mpl+ HSC/PC are also capable of significant T-lineage reconstitution in vivo. These results suggest that c-mpl merits consideration as a selective surface marker for the identification and isolation of human HSC in both basic research and clinical settings.

  18. Feasibility of proposed single-nucleotide polymorphisms as predictive markers for targeted regimens in metastatic colorectal cancer

    OpenAIRE

    Kim, J. C.; Ha, Y J; Roh, S A; Choi, E. Y.; Yoon, Y.S.; Kim, K P; Hong, Y S; Kim, T. W.; Cho, D H; Kim, S. Y.; Kim, Y.S.

    2013-01-01

    Background: Surrogate biomarkers for metastatic colorectal cancer (mCRC) are urgently needed to achieve the best outcomes for targeted therapy. Methods: A clinical association analysis was performed to examine the three single-nucleotide polymorphisms (SNPs) that were previously proposed as markers of chemosensitivity to the cetuximab (124 patients) and bevacizumab regimens (100 patients) in mCRC patients. In addition, biological correlations were examined for the candidate SNPs in terms of t...

  19. mRNA and protein dataset of autophagy markers (LC3 and p62) in several cell lines.

    Science.gov (United States)

    Gómez-Sánchez, Rubén; Yakhine-Diop, Sokhna M S; Rodríguez-Arribas, Mario; Bravo-San Pedro, José M; Martínez-Chacón, Guadalupe; Uribe-Carretero, Elisabet; Pinheiro de Castro, Diana C J; Pizarro-Estrella, Elisa; Fuentes, José M; González-Polo, Rosa A

    2016-06-01

    We characterized the dynamics of autophagy in vitro using four different cell systems and analyzing markers widely used in this field, i.e. LC3 (microtubule-associated protein 1 light chain 3; protein recruited from the cytosol (LC3-I) to the autophagosomal membrane where it is lipidated (LC3-II)) and p62/SQSTM1 (adaptor protein that serves as a link between LC3 and ubiquitinated substrates), (Klionsky et al., 2016) [1]. Data provided include analyses of protein levels of LC3 and p62 by Western-blotting and endogenous immunofluorescence experiments, but also p62 mRNA levels obtained by quantitative PCR (qPCR). To monitor the turnover of these autophagy markers and, thus, measure the flux of this pathway, cells were under starvation conditions and/or treated with bafilomycin A1 (Baf. A1) to block fusion of autophagosomes with lysosomes. PMID:27054171

  20. The utility of a novel triple marker (combination of TTF1, napsin A, and p40) in the subclassification of non–small cell lung cancer

    OpenAIRE

    Ao, Ming-Hui; Zhang, Hui; Sakowski, Lynne; Sharma, Rajni; Illei, Peter B.; Gabrielson, Edward; Askin, Frederic; Li, Qing Kay

    2014-01-01

    In lung cancer, targeted therapies depend on accurate histological subclassification of the tumor. The majority of lung cancers can be subclassified based on hematoxylin and eosin staining; however, classification may be difficult in small biopsies. In this study, we investigated the utility of a newly developed triple marker (combination of TTF1/Napsin A/p40) and compared the sensitivity and specificity of this novel marker with individual markers in the subclassification of non–small cell l...

  1. Epigenetic regulation of cardiac progenitor cells marker c-kit by stromal cell derived factor-1α.

    Directory of Open Access Journals (Sweden)

    Zhongpu Chen

    Full Text Available BACKGROUND: Cardiac progenitor cells (CPCs have been proven suitable for stem cell therapy after myocardial infarction, especially c-kit(+CPCs. CPCs marker c-kit and its ligand, the stem cell factor (SCF, are linked as c-kit/SCF axis, which is associated with the functions of proliferation and differentiation. In our previous study, we found that stromal cell-derived factor-1α (SDF-1α could enhance the expression of c-kit. However, the mechanism is unknown. METHODS AND RESULTS: CPCs were isolated from adult mouse hearts, c-kit(+ and c-kit(- CPCs were separated by magnetic beads. The cells were cultured with SDF-1α and CXCR4-selective antagonist AMD3100, and c-kit expression was measured by qPCR and Western blotting. Results showed that SDF-1α could enhance c-kit expression of c-kit(+CPCs, made c-kit(-CPCs expressing c-kit, and AMD3100 could inhibit the function of SDF-1α. After the intervention of SDF-1α and AMD3100, proliferation and migration of CPCs were measured by CCK-8 and transwell assay. Results showed that SDF-1α could enhance the proliferation and migration of both c-kit(+ and c-kit(- CPCs, and AMD3100 could inhibit these functions. DNA methyltransferase (DNMT mRNA were measured by qPCR, DNMT activity was measured using the DNMT activity assay kit, and DNA methylation was analyzed using Sequenom's MassARRAY platform, after the CPCs were cultured with SDF-1α. The results showed that SDF-1α stimulation inhibited the expression of DNMT1 and DNMT3β, which are critical for the maintenance of regional DNA methylation. Global DNMT activity was also inhibited by SDF-1α. Lastly, SDF-1α treatment led to significant demethylation in both c-kit(+ and c-kit(- CPCs. CONCLUSIONS: SDF-1α combined with CXCR4 could up-regulate c-kit expression of c-kit(+CPCs and make c-kit(-CPCs expressing c-kit, which result in the CPCs proliferation and migration ability improvement, through the inhibition of DNMT1 and DNMT3β expression and global DNMT

  2. Relationship of CD86 surface marker expression and cytotoxicity on dendritic cells exposed to chemical allergen

    International Nuclear Information System (INIS)

    Human peripheral blood-derived dendritic cells (DC) respond to a variety of chemical allergens by up-regulating expression of the co-stimulatory molecule CD86. It has been postulated that this measure might provide the basis for an in vitro alternative approach for the identification of skin sensitizing chemicals. We recently reported that DC, exposed in culture to the highest non-cytotoxic concentrations of various chemical allergens, displayed marginal up-regulation of membrane CD86 expression; the interpretation being that such changes were insufficiently sensitive for the purposes of hazard identification. For the work presented here, immature DC were derived from human monocytes and treated with the chemical allergens 2,4-dinitrobenzenesulfonic acid (DNBS), nickel sulfate (NiSO4), p-phenylenediamine (PPD), Bandrowski's base (BB), hydroquinone (HQ) and propyl gallate (PG) for 48 h at concentrations which induced both no to slight to moderate cytotoxicity. For comparison, DC were treated with the irritants sodium dodecyl sulfate (SDS), benzoic acid (BA), and benzalkonium chloride (BZC) at concentrations resulting in comparable levels of cytotoxicity. CD86 expression, as measured by flow cytometry, was consistently up-regulated (ranging from 162 to 386% control) on DC treated with concentrations of chemical allergens that induced approximately 10-15% cytotoxicity. The irritants BA and BZC did not induce up-regulation of CD86 expression when tested at concentrations that induced similar levels of cytotoxicity. SDS, however, up-regulated CD86 expression to 125-138% of control in 2/4 preparations when tested at concentrations which induced similar toxicity. Our results confirm that chemical allergens up-regulate CD86 expression on blood-derived DC and illustrate further that up-regulation of CD86 surface marker expression is more robust when DC are treated with concentrations of chemical allergen that induce slight to moderate cytotoxicity

  3. Changes in embryonic stem cell colony morphology and early differentiation markers driven by colloidal crystal topographical cues

    Directory of Open Access Journals (Sweden)

    L Ji

    2012-02-01

    Full Text Available The use of materials properties to guide cell behaviour is an attractive option for regenerative medicine, where controlling stem cell behaviour is important for the establishment of a functioning cell population. A wide range of materials properties have been shown to influence many types of cells but little is known about the effects of topography on embryonic stem cells (ESCs. In order to advance this knowledge, we synthesised and characterised substrates formed of silica colloidal crystal (SCC microspheres to present highly ordered and reproducible topographical features from 120-600 nm in diameter. We found that, compared to cells cultured on flat glass, cells cultured on the SCC substrates retained transcription of stem cell (Dppa5a, Nanog, and Pou5f1 and endoderm (Afp, Gata4, Sox17, and Foxa2 markers more similar to undifferentiated ESCs, suggesting the substrates are restricting differentiation, particularly towards the endoderm lineage. Additionally, five days after seeding, we observed strikingly different colony morphology, with cells on the SCC substrates growing in spherical colonies approximately ten cells thick, while cells on glass were growing in flat monolayers. Colonies on the SCC substrates developed a central pit, which was never observed in cells cultured on glass, and expressed proteins related to epithelialisation. Together, these data demonstrate the potential of using topographical cues to control stem cell behaviour in vitro.

  4. Cell surface marker profiling of human tracheal basal cells reveals distinct subpopulations, identifies MST1/MSP as a mitogenic signal, and identifies new biomarkers for lung squamous cell carcinomas

    OpenAIRE

    Van de Laar, Emily; Clifford, Monica; Hasenoeder, Stefan; Kim, Bo Ram; Wang, Dennis; Lee, Sharon; Paterson, Josh; Vu, Nancy M; Waddell, Thomas K; Keshavjee, Shaf; Tsao, Ming-sound; Ailles, Laurie; Moghal, Nadeem

    2014-01-01

    Background The large airways of the lungs (trachea and bronchi) are lined with a pseudostratified mucociliary epithelium, which is maintained by stem cells/progenitors within the basal cell compartment. Alterations in basal cell behavior can contribute to large airway diseases including squamous cell carcinomas (SQCCs). Basal cells have traditionally been thought of as a uniform population defined by basolateral position, cuboidal cell shape, and expression of pan-basal cell lineage markers l...

  5. CLCA2 as a Novel Immunohistochemical Marker for Differential Diagnosis of Squamous Cell Carcinoma from Adenocarcinoma of the Lung

    OpenAIRE

    Kazuya Shinmura; Hisaki Igarashi; Hisami Kato; Yuichi Kawanishi; Yusuke Inoue; Satoki Nakamura; Hiroshi Ogawa; Takashi Yamashita; Akikazu Kawase; Kazuhito Funai; Haruhiko Sugimura

    2014-01-01

    Recent progress in targeted therapy for lung cancer has revealed that accurate differential diagnosis between squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the lung is essential. To identify a novel immunohistochemical marker useful for differential diagnosis between the two subtypes of lung cancer, we first selected 24 SCC-specific genes and 6 ADC-specific genes using data (case number, 980) from the Cancer Genome Atlas (TCGA) database. Among the genes, we chose the CLCA2 gene,...

  6. Nuclear nano-morphology markers of histologically normal cells detect the “field effect” of breast cancer

    OpenAIRE

    Bista, Rajan K.; Wang, Pin; Bhargava, Rohit; Uttam, Shikhar; Douglas J Hartman; Randall E Brand; Liu, Yang

    2012-01-01

    Accurate detection of breast malignancy from histologically normal cells (“field effect”) has significant clinical implications in a broad base of breast cancer management, such as high-risk lesion management, personalized risk assessment, breast tumor recurrence, and tumor margin management. More accurate and clinically applicable tools to detect markers characteristic of breast cancer “field effect” that are able to guide the clinical management are urgently needed. We have recently develop...

  7. Molecular characterization of clear cell renal cell carcinoma identifies CSNK2A1, SPP1 and DEFB1 as promising novel prognostic markers

    DEFF Research Database (Denmark)

    Rabjerg, Maj; Bjerregaard, Henriette; Halekoh, Ulrich; Jensen, Boye L; Walter, Steen; Marcussen, Niels

    2016-01-01

    The prognosis associated with clear cell renal carcinoma (ccRCC) can vary widely and novel molecular prognostic markers are needed to assess prognosis at an earlier stage. Several gene products have been investigated for this purpose, but none of them have been implemented in clinical practice...

  8. Grid cells and theta as oscillatory interference: theory and predictions.

    Science.gov (United States)

    Burgess, Neil

    2008-01-01

    The oscillatory interference model [Burgess et al. (2007) Hippocampus 17:801-802] of grid cell firing is reviewed as an algorithmic level description of path integration and as an implementation level description of grid cells and their inputs. New analyses concern the relationships between the variables in the model and the theta rhythm, running speed, and the intrinsic firing frequencies of grid cells. New simulations concern the implementation of velocity-controlled oscillators (VCOs) with different preferred directions in different neurons. To summarize the model, the distance traveled along a specific direction is encoded by the phase of a VCO relative to a baseline frequency. Each VCO is an intrinsic membrane potential oscillation whose frequency increases from baseline as a result of depolarization by synaptic input from speed modulated head-direction cells. Grid cell firing is driven by the VCOs whose preferred directions match the current direction of motion. VCOs are phase-reset by location-specific input from place cells to prevent accumulation of error. The baseline frequency is identified with the local average of VCO frequencies, while EEG theta frequency is identified with the global average VCO frequency and comprises two components: the frequency at zero speed and a linear response to running speed. Quantitative predictions are given for the inter-relationships between a grid cell's intrinsic firing frequency and grid scale, the two components of theta frequency, and the running speed of the animal. Qualitative predictions are given for the properties of the VCOs, and the relationship between environmental novelty, the two components of theta, grid scale and place cell remapping. PMID:19021256

  9. Prediction of cell-penetrating peptides with feature selection techniques.

    Science.gov (United States)

    Tang, Hua; Su, Zhen-Dong; Wei, Huan-Huan; Chen, Wei; Lin, Hao

    2016-08-12

    Cell-penetrating peptides are a group of peptides which can transport different types of cargo molecules such as drugs across plasma membrane and have been applied in the treatment of various diseases. Thus, the accurate prediction of cell-penetrating peptides with bioinformatics methods will accelerate the development of drug delivery systems. The study aims to develop a powerful model to accurately identify cell-penetrating peptides. At first, the peptides were translated into a set of vectors with the same dimension by using dipeptide compositions. Secondly, the Analysis of Variance-based technique was used to reduce the dimension of the vector and explore the optimized features. Finally, the support vector machine was utilized to discriminate cell-penetrating peptides from non-cell-penetrating peptides. The five-fold cross-validated results showed that our proposed method could achieve an overall prediction accuracy of 83.6%. Based on the proposed model, we constructed a free webserver called C2Pred (http://lin.uestc.edu.cn/server/C2Pred). PMID:27291150

  10. Predicted efficiency of Si wire array solar cells

    OpenAIRE

    Kelzenberg, M. D.; Putnam, M. C.; Turner-Evans, D. B.; Lewis, N. S.; Atwater, H. A.

    2010-01-01

    Solar cells based on arrays of CVD-grown Si nano- or micro-wires have attracted interest as potentially low-cost alternatives to conventional wafer-based Si photovoltaics [1-6], and single-wire solar cells have been reported with efficiencies of up to 3.4% [7]. We recently presented device physics simulations which predicted efficiencies exceeding 17%, based on experimentally observed diffusion lengths within our wires [8]. However, this model did not take into account the optical properties ...

  11. Characterization of carbonic anhydrase IX (CA IX) as an endogenous marker of chronic hypoxia in live human tumor cells

    International Nuclear Information System (INIS)

    Purpose: Published clinical studies provide conflicting data regarding the prognostic significance of carbonic anhydrase IX (CA IX) overexpression as an endogenous marker of tumor hypoxia and its comparability with other methods of hypoxia detection. We performed a systematic analysis of CA IX protein levels under various in vitro conditions of tumor hypoxia in HT 1080 human fibrosarcoma and FaDu human pharyngeal carcinoma cells. Because sorting of live CA IX positive cells from tumors provides a tool to study the radiosensitivity of chronically hypoxic cells, we modified and tested a CA IX flow cytometry protocol on mixed hypoxic/aerobic suspensions of HT 1080 and FaDu cells. Methods and materials: HT 1080 and FaDu cells were treated with up to 24 h of in vitro hypoxia and up to 96 h of reoxygenation. To test the effect of nonhypoxic stimuli, glucose and serum availability, pH and cell density were modified. CA IX protein was quantified in Western blots of whole-cell lysates. Mixed suspensions with known percentages of hypoxic cells were prepared for CA IX flow cytometry. The same mixtures were assayed for clonogenic survival after 10 Gy. Results: Hypoxia-induced CA IX protein expression was seen after >6 h at ≤5% O2, and protein was stable over 96 h of reoxygenation in both cell lines. Glucose deprivation abolished the hypoxic CA IX response, and high cell density caused CA IX induction under aerobic conditions. Measured percentages of CA IX-positive cells in mixtures closely reflected known percentages of hypoxic cells in HT 1080 and were associated with radioresistance of mixtures after 10 Gy. Conclusion: CA IX is a stable marker of current or previous chronic hypoxia but influenced by nonhypoxic stimuli. Except the time course of accumulation, all properties of this marker resembled our previous findings for hypoxia-inducible factor-1α. A modified flow cytometry protocol provided good separability of CA IX-negative and -positive cells in vitro and can be

  12. Changes in Markers of T-Cell Senescence and Exhaustion With Atazanavir-, Raltegravir-, and Darunavir-Based Initial Antiviral Therapy: ACTG 5260s.

    Science.gov (United States)

    Kelesidis, Theodoros; Moser, Carlee; Stein, James H; Brown, Todd T; Tran, Thuy Tien T; Ribaudo, Heather J; Dube, Michael P; Yang, Otto O; Currier, Judith S; McComsey, Grace A

    2016-09-01

    It is unclear whether differential roles of CD4(+) versus CD8(+) T-cell senescence/exhaustion and effects of antiretroviral therapy (ART) on these processes may contribute to morbidity in treated human immunodeficiency virus type 1 (HIV) infection. In a prospective 96-week trial, 328 HIV-infected ART-naive participants were randomly assigned to receive tenofovir-emtricitabine plus either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir. Markers of CD4(+) T-cell senescence (ie, the percentage of CD28(-)CD57(+) cells among CD4(+) T cells ) and CD4(+)/CD8(+) T-cell exhaustion (ie, the percentage of PD-1(+) cells among CD4(+)/CD8(+) T cells) decreased after ART. There were no changes in markers of CD8(+) T-cell senescence after ART and no differential changes in all markers in ART groups. Senescent CD4(+) and CD8(+) T cells may have differential roles in HIV pathogenesis. PMID:27354367

  13. Effects of hypoxia on expression of a panel of stem cell and chemoresistance markers in glioblastoma-derived spheroids

    DEFF Research Database (Denmark)

    Kolenda, Jesper; Jensen, Stine Skov; Aaberg-Jessen, Charlotte;

    2011-01-01

    ). Spheroids were formed in 21% and 1% O(2) in serum-free medium. The immunohistochemical panel included hypoxia (HIF-1α, HIF-2α), proliferation (Ki-67), and stem cell markers (CD133, podoplanin, Bmi-1, nestin, Sox-2) as well as markers related to chemoresistance (MGMT, TIMP-1, Lamp-1, MRP1, MDR-1). As...... spheroids derived in hypoxia were smaller than in normoxia, a set of experiments was included in which the culturing time of hypoxic spheroids was extended to obtain equally sized spheroids. The results showed that expression of HIF-1α and HIF-2α was increased in hypoxia, whereas Ki-67 was reduced....... Expression of stem cell markers CD133, podoplanin, Bmi-1, and nestin was increased in hypoxia, whereas Sox-2 was increased in SJ-1 only. TIMP-1 and Lamp-1 were increased in both SJ-1 and U87. In conclusion, the tumor cell phenotype related to stemness, and thereby potentially to chemoresistance, seems to...

  14. High expression of FER tyrosine kinase predicts poor prognosis in clear cell renal cell carcinoma

    OpenAIRE

    Wei, Can; WU, SONG; Li, Xianxin; Wang, Yadong; Ren, Rui; LAI, YONGQING; YE, JIONGXIAN

    2012-01-01

    FER tyrosine kinase (FER) has been demonstrated to play a critical role in tumorigenesis and metastasis; however, its potential value as a novel prognostic marker for clear cell renal cell carcinoma (ccRCC) remains unclear. In 48 paired samples of ccRCCs and normal adjacent tissues (ADTs), real-time PCR was used to evaluate the expression of FER mRNA. The expression of FER protein was assessed in 87 ADTs and 206 samples of ccRCC using immunohistochemical methods. Statistical analysis was used...

  15. Protein p16 as a marker of dysplastic and neoplastic alterations in cervical epithelial cells

    International Nuclear Information System (INIS)

    Cervical carcinomas are second most frequent type of women cancer. Success in diagnostics of this disease is due to the use of Pap-test (cytological smear analysis). However Pap-test gives significant portion of both false-positive and false-negative conclusions. Amendments of the diagnostic procedure are desirable. Aetiological role of papillomaviruses in cervical cancer is established while the role of cellular gene alterations in the course of tumor progression is less clear. Several research groups including us have recently named the protein p16INK4a as a possible diagnostic marker of cervical cancer. To evaluate whether the specificity of p16INK4a expression in dysplastic and neoplastic cervical epithelium is sufficient for such application we undertook a broader immunochistochemical registration of this protein with a highly p16INK4a-specific monoclonal antibody. Paraffin-embedded samples of diagnostic biopsies and surgical materials were used. Control group included vaginal smears of healthy women and biopsy samples from patients with cervical ectopia. We examined 197 samples in total. Monoclonal antibody E6H4 (MTM Laboratories, Germany) was used. In control samples we did not find any p16INK4a-positive cells. Overexpression of p16INK4a was detected in samples of cervical dysplasia (CINs) and carcinomas. The portion of p16INK4a-positive samples increased in the row: CIN I – CIN II – CIN III – invasive carcinoma. For all stages the samples were found to be heterogeneous with respect to p16INK4a-expression. Every third of CINs III and one invasive squamous cell carcinoma (out of 21 analyzed) were negative. Overexpression of the protein p16INK4a is typical for dysplastic and neoplastic epithelium of cervix uteri. However p16INK4a-negative CINs and carcinomas do exist. All stages of CINs and carcinomas analyzed are heterogeneous with respect to p16INK4a expression. So p16INK4a-negativity is not a sufficient reason to exclude a patient from the high risk

  16. Protein p16 as a marker of dysplastic and neoplastic alterations in cervical epithelial cells

    Directory of Open Access Journals (Sweden)

    Spitkovsky Dimitry

    2004-08-01

    Full Text Available Abstract Background Cervical carcinomas are second most frequent type of women cancer. Success in diagnostics of this disease is due to the use of Pap-test (cytological smear analysis. However Pap-test gives significant portion of both false-positive and false-negative conclusions. Amendments of the diagnostic procedure are desirable. Aetiological role of papillomaviruses in cervical cancer is established while the role of cellular gene alterations in the course of tumor progression is less clear. Several research groups including us have recently named the protein p16INK4a as a possible diagnostic marker of cervical cancer. To evaluate whether the specificity of p16INK4a expression in dysplastic and neoplastic cervical epithelium is sufficient for such application we undertook a broader immunochistochemical registration of this protein with a highly p16INK4a-specific monoclonal antibody. Methods Paraffin-embedded samples of diagnostic biopsies and surgical materials were used. Control group included vaginal smears of healthy women and biopsy samples from patients with cervical ectopia. We examined 197 samples in total. Monoclonal antibody E6H4 (MTM Laboratories, Germany was used. Results In control samples we did not find any p16INK4a-positive cells. Overexpression of p16INK4a was detected in samples of cervical dysplasia (CINs and carcinomas. The portion of p16INK4a-positive samples increased in the row: CIN I – CIN II – CIN III – invasive carcinoma. For all stages the samples were found to be heterogeneous with respect to p16INK4a-expression. Every third of CINs III and one invasive squamous cell carcinoma (out of 21 analyzed were negative. Conclusions Overexpression of the protein p16INK4a is typical for dysplastic and neoplastic epithelium of cervix uteri. However p16INK4a-negative CINs and carcinomas do exist. All stages of CINs and carcinomas analyzed are heterogeneous with respect to p16INK4a expression. So p16INK4a-negativity is

  17. GENETIC ALTERRATIONS OF MICROSATELLITE MARKERS AT CHROMOSOME 17 IN NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To analyse the microsatellite instability (MI) and loss of heterozygosity (LOH) in non-small cell lung cancer (NSCLC). Methods: MI and LOH at chromosome 17 were checked in 35 cases of NSCLC tumor-normal paired tissues using four microsatellite markers TP53 (17p13.1), THRA1 (17q11.2-12), D17S579 (17q12-21) and D17S855 (17q21) by PCR based analysis. Mutations of P53 exons 5-8 were also tested using PCR-single strand conformation polymorphism (PCR-SSCP) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) analysis. Results: 22 of 35 tumors (62.8%) displayed MI or LOH. 14 tumors (40.0%) exhibited MI, 11 tumors (31.4%) exhibited LOH, while 3 tumors (8.6%) exhibited MI and LOH concurrently. 23 tumors (65.7%) exhibited P53 gene mutations. The frequency of MI or LOH was obviously higher in the early-stage (stages I and II, 78.9%) than in the advanced-stage (stage III, 43.8%). However, the frequency of MI or LOH had no difference either between high-grade (75.0%) and low-grade (52.6%) differentiated NSCLC or between the tumors with P53 mutations (59.1%) and those without P53 mutations (69.2%). No relationship was observed between the presence of MI or LOH and the histologic subtype of NSCLC. Conclusion: The results suggest that MI and LOH at chromosome 17 may play a alterations on chromosome 17 in tumors of non-small cell lung cancer (NSCLC). In addition, studies reported contradictory results concerning the incidence of these alterations and the relationship between these genetic alterations and the clinical behavior of NSCLC. The aim of this study was to investigate the incidence of MI and LOH at chromosome 17 in tumors of patients with NSCLC and its association with clinical and histologic features of NSCLC.

  18. Nanoparticles-cell association predicted by protein corona fingerprints

    Science.gov (United States)

    Palchetti, S.; Digiacomo, L.; Pozzi, D.; Peruzzi, G.; Micarelli, E.; Mahmoudi, M.; Caracciolo, G.

    2016-06-01

    In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a ``protein corona'' layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ~ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells.In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a ``protein corona'' layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ~ 100-250 nm) and surface

  19. Limited Clinical Value of Periablative Changes of Serum Markers in the Prediction of Biochemical Remission in Patients with Papillary Thyroid Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Heeyoung; Kim, Seongjang; Kim, Injoo; Kim, Keunyoung; Kim, Sojung; Kim, Bo Hyun; Kim, Sang Soo; Kyung, Jeon Yoon [Pusan National Univ., Busan (Korea, Republic of)

    2013-12-15

    Remnant thyroid ablation and 1-year stimulated thyroglobulin (sTg) measurement are recommended for those who have undergone total thyroidectomy for differentiated thyroid cancer. The serum Tg kinetics in such patients are still unclear. This study was designed to evaluate whether the periablative change in serum markers can predict biochemical remission in papillary thyroid cancer (PTC) patients. We reviewed the medical records of 185 patients who were given high-dose radioactive iodine ablation therapy from January 2006 to December 2008. Serum Tg, TSH, and anti-Tg antibody (TgAb) were measured on the day and the following 10th day of radioactive iodine administration. We defined preablative sTg as Tg-1, postablative Tg measured on the 10th day of ablation as Tg-2, and the 1-year sTg as Tg-3. ΔTg means Tg2-Tg1. The same definition was applied to TgAb. A biochemical remission defined as Tg-3 < 2 ng/ml was achieved in 144 patients. Among the patients who achieved biochemical remission, PTC recurred in six during a median follow-up of 54 months. Tg-1<3.3 ng/ml (p<0.0001) predicted biochemical remission. Neither the ΔTg nor ΔTgAb was useful for predicting biochemical remission. On the evaluation of recurrence after biochemical remission, Tg-1 > 5.32 (p<0.0001) and Tg-3 > 2.9 (p=0.01) were proven to be statistically significant cutoff values for predicting recurrence. The ΔTg and ΔTgAb were not able to predict recurrence. For the prediction of biochemical remission or recurrence after biochemical remission, preablative sTg was demonstrated to be a statistically significant serum marker. However, short-term changes in biochemical markers including Tg and TgAb around the day of ablation could not provide useful clinical information about biochemical remission or disease recurrence. In conclusion, 1-year sTg measurement cannot be omitted with short-term change.

  20. IMPORTANCE OF APOPTOSIS MARKERS (MDM2, BCL-2 AND Bax) IN CONVENTIONAL RENAL CELL CARCINOMA.

    Science.gov (United States)

    Saker, Z; Tsintsadze, O; Jiqia, I; Managadze, L; Chkhotua, A

    2015-12-01

    The goal of the current study was to analyze the expression of Bcl-2, MDM2 and Bax in benign and malignant renal tissue samples and assess their possible association with different clinical parameters. Prognostic significance of the markers in recurrence-free and cancer-specific survivals has also been evaluated. Activity of MDM2, Bcl-2 and Bax was evaluated in: 24 normal human kidney tissues resected from the patients of different ages (range: 21-80 years), and in 52 conventional RCC samples. Intensity of the markers' expression was compared between the groups and correlation was analyzed with different clinical parameters. Activity of anti-apoptotic MDM2 and Bcl-2 was significantly elevated while activity of pro-apoptotic Bax was decreased in RCC as compared with normal kidney tissues. Bax expression was positively correlated with patient age. Significant association has been detected between the evaluated markers and cancer clinical parameters like: tumor stage, grade, lymph node and distant metastases. The markers' activity was associates with the tumor morphological features, in particular: presence of tumor necrosis and microvascular invasion. Disease recurrence and 5-year patient survival were associated with the markers' activity. Cox regression analyses have shown that tumor size, pathological stage and grade are the risk factors for disease recurrence and patient death. Expression of MDM2 and Bcl-2 is significantly up-regulated, while Bax is down-regulated in RCC as compared with normal kidney tissue. Intensity of the markers'activities is associated with the tumor pathological and clinical parameters (stage, grade, lymph node and distant metastases, tumor recurrence and patient survival). Further studies with more patients and longer follow-up will uncover the clinical importance of the evaluated markers in RCC. PMID:26719546

  1. DNA methylation markers for breast cancer prognosis

    OpenAIRE

    Dedeurwaerder, Sarah; Fuks, François

    2012-01-01

    Currently, most of the prognostic and predictive gene expression signatures emerging for breast cancer concern the tumor component. In Dedeurwaerder et al. we show that DNA methylation profiling of breast tumors is a particularly sensitive means of capturing features of the immune component of breast tumors. Most importantly, correlation is observed between T-cell marker genes and breast cancer clinical outcome.

  2. Progenitor cells from the porcine neural retina express photoreceptor markers after transplantation to the subretinal space of allorecipients

    DEFF Research Database (Denmark)

    Klassen, Henry; Kiilgaard, Jens Folke; Zahir, Tasneem;

    2007-01-01

    immune suppression. Grafted cells expressed transducin, recoverin, and rhodopsin in the pig subretinal space, suggestive of differentiation into photoreceptors or, in a few cases, migrated into the neural retina and extended processes, the latter typically showing radial orientation. These results......Work in rodents has shown that cultured retinal progenitor cells (RPCs) integrate into the degenerating retina, thus suggesting a potential strategy for treatment of similar degenerative conditions in humans. To demonstrate the relevance of the rodent work to large animals, we derived progenitor...... cells from the neural retina of the domestic pig and transplanted them to the laser-injured retina of allorecipients. Prior to grafting, immunocytochemical analysis showed that cultured porcine RPCs widely expressed neural cell adhesion molecule, as well as markers consistent with immature neural cells...

  3. Expression Patterns of Cancer Stem Cell Markers During Specific Celecoxib Therapy in Multistep Rat Colon Carcinogenesis Bioassays.

    Science.gov (United States)

    Salim, Elsayed I; Hegazi, Mona M; Kang, Jin Seok; Helmy, Hager M

    2016-01-01

    The purpose of this study was to investigate the role of colon cancer stem cells (CSCs) during chemicallyinduced rat multi-step colon carcinogenesis with or without the treatment with a specific cyclooxygenase-2 inhibitor drug (celecoxib). Two experiments were performed, the first, a short term 12 week colon carcinogenesis bioassay in which only surrogate markers for colon cancer, aberrant crypt foci (ACF) lesions, were formed. The other experiment was a medium term colon cancer rat assay in which tumors had developed after 32 weeks. Treatment with celecoxib lowered the numbers of ACF, as well as the tumor volumes and multiplicities after 32 weeks. Immunohistochemical proliferating cell nuclear antigen (PCNA) labeling indexes LI (%) were downregulated after treatment by celecoxib. Also different cell surface antigens known to associate with CSCs such as the epithelial cell adhesion molecule (EpCAM), CD44 and CD133 were compared between the two experiments and showed differential expression patterns depending on the stage of carcinogenesis and treatment with celecoxib. Flow cytometric analysis demonstrated that the numbers of CD133 cells were increased in the colonic epithelium after 12 weeks while those of CD44 but not CD133 cells were increased after 32 weeks. Moreover, aldehyde dehydrogenase-1 activity levels in the colonic epithelium (a known CSC marker) detected by ELISA assay were found down-regulated after 12 weeks, but were up-regulated after 32 weeks. The data have also shown that the protective effect of celecoxib on these specific markers and populations of CSCs and on other molecular processes such as apoptosis targeted by this drug may vary depending on the genetic and phenotypic stages of carcinogenesis. Therefore, uncovering these distinction roles of CSCs during different phases of carcinogenesis and during specific treatment could be useful for targeted therapy. PMID:27039721

  4. Enhanced Wound Healing, Kinase and Stem Cell Marker Expression in Diabetic Organ-Cultured Human Corneas Upon MMP-10 and Cathepsin F Gene Silencing

    OpenAIRE

    Saghizadeh, Mehrnoosh; Epifantseva, Irina; Hemmati, David M.; Ghiam, Chantelle A.; Brunken, William J; Ljubimov, Alexander V

    2013-01-01

    Adenovirus-driven shRNA silencing of select proteinases upregulated in diabetic corneas restored normal wound healing time, the expression of diabetes-altered markers including limbal stem cell markers, and patterns of activated EGFR and Akt in human diabetic corneal organ cultures. The maximum effect was obtained combining proteinase shRNA with c-met overexpression.

  5. Ki-S1, a novel proliferative marker: flow cytometric assessment of staining in human breast carcinoma cells.

    OpenAIRE

    Camplejohn, R. S.; Brock, A.; Barnes, D. M.; Gillett, C; Raikundalia, B.; Kreipe, H.; Parwaresch, M R

    1993-01-01

    There is considerable interest in immunohistochemical markers of proliferation which are suitable for use on routinely fixed clinical material. The novel proliferation-associated antibody Ki-S1 shows promise in this respect. In this study we have: (i) defined the pattern of Ki-S1 labelling relative to the cell cycle phase; (ii) investigated the labelling pattern with Ki-S1 on a human breast cell line (ZR75) under varying proliferative conditions induced by serum deprivation and refeeding; (ii...

  6. Spatial expression of CLAVATA3 in the shoot apical meristem suggests it is not a stem cell marker in soybean

    OpenAIRE

    Wong, Chui E; Mohan B. Singh; Bhalla, Prem L

    2013-01-01

    CLAVATA3 (CLV3), a stem cell marker in Arabidopsis thaliana, encodes a secreted peptide that maintains the stem cell population within the shoot apical meristem. This work investigated the CLV3 orthologue in a major legume crop, soybean (GmCLV3). Instead of being expressed in the three outermost layers of the meristem as in Arabidopsis, GmCLV3 was expressed deeper in the central zone beneath the fourth layer (L4) of the meristem, overlapping with the expression of soybean WUSCHEL. Subsequent ...

  7. HER2 and TOP2A as predictive markers for anthracycline-containing chemotherapy regimens as adjuvant treatment of breast cancer: a meta-analysis of individual patient data

    DEFF Research Database (Denmark)

    Di Leo, Angelo; Desmedt, Christine; Bartlett, John M S;

    2011-01-01

    Prediction of response to anthracycline-based therapy for breast cancer is challenging. We aimed to assess the value of HER2 and TOP2A as predictive markers of response to anthracycline-based adjuvant therapy in patients with early breast cancer.......Prediction of response to anthracycline-based therapy for breast cancer is challenging. We aimed to assess the value of HER2 and TOP2A as predictive markers of response to anthracycline-based adjuvant therapy in patients with early breast cancer....

  8. Nanoparticles-cell association predicted by protein corona fingerprints.

    Science.gov (United States)

    Palchetti, S; Digiacomo, L; Pozzi, D; Peruzzi, G; Micarelli, E; Mahmoudi, M; Caracciolo, G

    2016-07-01

    In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø≈ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells. PMID:27279572

  9. Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma

    Directory of Open Access Journals (Sweden)

    Wallwiener Diethelm

    2011-01-01

    cell factor SOX2 is expressed in a variety of early stage postmenopausal breast carcinomas and metastatic lymph nodes. Our data suggest that SOX2 plays an early role in breast carcinogenesis and high expression may promote metastatic potential. Further studies are needed to explore whether SOX2 can predict metastatic potential at an early tumor stage.

  10. Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma

    International Nuclear Information System (INIS)

    The SRY-related HMG-box family of transcription factors member SOX2 has been mainly studied in embryonic stem cells as well as early foregut and neural development. More recently, SOX2 was shown to participate in reprogramming of adult somatic cells to a pluripotent stem cell state and implicated in tumorigenesis in various organs. In breast cancer, SOX2 expression was reported as a feature of basal-like tumors. In this study, we assessed SOX2 expression in 95 primary tumors of postmenopausal breast cancer patients. Samples from 95 patients diagnosed and treated at the University of Tuebingen Institute of Pathology and Women's Hospital were analyzed by immunohistochemistry for SOX2 expression in the primary tumor samples and in corresponding lymph node metastasis, where present. Furthermore, SOX2 amplification status was assessed by FISH in representative samples. In addition, eighteen fresh frozen samples were analyzed for SOX2, NANOG and OCT4 gene expression by real-time PCR. SOX2 expression was detected in 28% of invasive breast carcinoma as well as in 44% of ductal carcinoma in situ (DCIS) lesions. A score of SOX2 expression (score 0 to 3) was defined in order to distinguish SOX2 negative (score 0) from SOX2 positive samples (score 1-3) and among latter the subgroup of SOX2 high expressors (score 3 > 50% positive cells). Overall, the incidence of SOX2 expression (score 1-3) was higher than previously reported in a cohort of lymph node negative patients (28% versus 16.7%). SOX2 expression was detected across different breast cancer subtypes and did not correlate with tumor grading. However, high SOX2 expression (score 3) was associated with larger tumor size (p = 0.047) and positive lymph node status (0.018). Corresponding metastatic lymph nodes showed higher SOX2 expression and were significantly more often SOX2 positive than primary tumors (p = 0.0432). In this report, we show that the embryonic stem cell factor SOX2 is expressed in a variety of early

  11. Usefulness of DNA repair genes in prediction and potentiation of radiosensitivity in tumor cells

    International Nuclear Information System (INIS)

    tumor cells. From the survival fraction it was found that the pretreatment of NU7026 alone did not have any significant effect on survival fraction of the cells. But in the cells which are treated together with NU7026 and radiation showed a synergistic reduction in survival fraction. Similarly, synergistic sensitization was observed when both DNA-PK and PARP (a protein involved in base excision repair) were inhibited together. Our results, point to the fact that the genes involved in DNA repair can be a good markers for predicting the radiosensitivity of tumor cells and also inhibitors of those proteins can be potentially combined with cancer radiotherapy. (author)

  12. Identification of alanyl aminopeptidase (CD13) as a surface marker for isolation of mature gastric zymogenic chief cells.

    Science.gov (United States)

    Moore, Benjamin D; Jin, Ramon U; Osaki, Luciana; Romero-Gallo, Judith; Noto, Jennifer; Peek, Richard M; Mills, Jason C

    2015-12-15

    Injury and inflammation in the gastric epithelium can cause disruption of the pathways that guide the differentiation of cell lineages, which in turn can cause persistent alterations in differentiation patterns, known as metaplasia. Metaplasia that occurs in the stomach is associated with increased risk for cancer. Methods for isolating distinct gastric epithelial cell populations would facilitate dissection of the molecular and cellular pathways that guide normal and metaplastic differentiation. Here, we identify alanyl aminopeptidase (CD13) as a specific surface marker of zymogenic chief cells (ZCs) in the gastric epithelium. We show that 1) among gastric epithelial cells alanyl aminopeptidase expression is confined to mature ZCs, and 2) its expression is lost en route to metaplasia in both mouse and human stomachs. With this new marker coupled with new techniques that we introduce for dissociating gastric epithelial cells and overcoming their constitutive autofluorescence, we are able to reliably isolate enriched populations of ZCs for both molecular analysis and for the establishment of ZC-derived ex vivo gastroid cultures. PMID:26514774

  13. Improved site-specific recombinase-based method to produce selectable marker- and vector-backbone-free transgenic cells

    Science.gov (United States)

    Yu, Yuan; Tong, Qi; Li, Zhongxia; Tian, Jinhai; Wang, Yizhi; Su, Feng; Wang, Yongsheng; Liu, Jun; Zhang, Yong

    2014-02-01

    PhiC31 integrase-mediated gene delivery has been extensively used in gene therapy and animal transgenesis. However, random integration events are observed in phiC31-mediated integration in different types of mammalian cells; as a result, the efficiencies of pseudo attP site integration and evaluation of site-specific integration are compromised. To improve this system, we used an attB-TK fusion gene as a negative selection marker, thereby eliminating random integration during phiC31-mediated transfection. We also excised the selection system and plasmid bacterial backbone by using two other site-specific recombinases, Cre and Dre. Thus, we generated clean transgenic bovine fetal fibroblast cells free of selectable marker and plasmid bacterial backbone. These clean cells were used as donor nuclei for somatic cell nuclear transfer (SCNT), indicating a similar developmental competence of SCNT embryos to that of non-transgenic cells. Therefore, the present gene delivery system facilitated the development of gene therapy and agricultural biotechnology.

  14. Prediction markers for respiratory distress syndrome: evaluation of the stable microbubble test, surfactant protein-A and hepatocyte growth factor levels in amniotic fluid.

    Directory of Open Access Journals (Sweden)

    Kumazawa K

    2003-02-01

    Full Text Available Surfactant treatment in infants with respiratory distress syndrome (RDS has decreased neonatal mortality. With the advent of this therapy, it has become important to predict accurately the fetal lung maturity of a fetus before delivery. We evaluated the stable microbubble test (SMT, surfactant protein-A (SP-A and hepatocyte growth factor (HGF in amniotic fluid as predicting markers for RDS. Of 55 amniotic fluid samples obtained by amniocentesis from women less than 37 weeks pregnant, the SMT values were as follows: sensitivity 76.5%, specificity 84.2%, positive predictive value 68.4%, negative predictive value 88.9% and overall accuracy 81.8%. For SP-A, the values were 88.2%, 65.8%, 53.6%, 92.6% and 72.7%, respectively. If we used both SMT and SP-A, we could diagnose with 100% accuracy that a case with measurements of SMT > or = 2 and SP-A > or = 420 ng/ml would not complicate with RDS (24/24. However, the RDS diagnostic accuracy of HGF does not equal to those of SMT and SP-A levels. We concluded that the rapidity, simplicity and reliability of SMT was very useful during 24-36 weeks of gestation as a bedside procedure to predict fetuses likely to develop RDS. We also noted the additive effect of SP-A in improving the accuracy of lung maturity diagnosis.

  15. Prediction of the effect of atrasentan on renal and heart failure outcomes based on short-term changes in multiple risk markers

    DEFF Research Database (Denmark)

    Schievink, Bauke; de Zeeuw, Dick; Smink, Paul A;

    2016-01-01

    0.75 and 1.25 mg/day (+2% vs. +7%). Selecting patients with >30% albuminuria reduction from baseline (responders) improved renal outcome to almost 50% risk reduction, whereas non-responders showed no renal benefit. CONCLUSIONS: Based on the RADAR/JAPAN study, with short-term changes in risk markers......, hemoglobin, and increases body weight in patients with type 2 diabetes and nephropathy. We previously developed an algorithm, the Parameter Response Efficacy (PRE) score, which translates short-term drug effects into predictions of long-term effects on clinical outcomes. DESIGN: We used the PRE score on data......, atrasentan is expected to decrease renal risk without increased risk of heart failure. Within this population albuminuria responders appear to contribute to the predicted improvements, whereas non-responders showed no benefit. The ongoing hard outcome trial (SONAR) in type 2 diabetic patients with >30...

  16. PTK7 as a potential prognostic and predictive marker of response to adjuvant chemotherapy in breast cancer patients, and resistance to anthracycline drugs

    Directory of Open Access Journals (Sweden)

    Ataseven B

    2014-10-01

    Full Text Available Beyhan Ataseven,1,2 Angela Gunesch,2 Wolfgang Eiermann,3 Ronald E Kates,4 Bernhard Högel,5 Pjotr Knyazev,6 Axel Ullrich,6 Nadia Harbeck4 1Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany; 2Department of Gynecology and Obstetrics, Rotkreuzklinikum Munich, Munich, Germany; 3Department of Gynecology and Oncology, Interdisciplinary Oncology Center Munich, Munich, Germany; 4Breast Center, Department of Gynecology and Obstetrics, Ludwig-Maximilian-University Munich, Munich, Germany; 5Department of Pathology, Rotkreuzklinikum Munich, Munich, Germany; 6Department of Molecular Biology, Max-Planck-Institute of Biochemistry, Martinsried, Germany Abstract: Biomarkers predicting resistance to particular chemotherapy regimens could play a key role in optimally individualized treatment concepts. PTK7 (protein tyrosine kinase 7 belongs to the receptor tyrosine kinase family involved in several physiological, but also malignant, cell behaviors. Recent studies in acute myeloid leukemia have associated PTK7 expression with resistance to anthracycline therapy. PTK7 mRNA expression in primary tumor tissue (PTT and corresponding lymph node tissue (LNT were retrospectively measured in 117 patients with early breast cancer; PTK7 expression was available in 103 PTT and 108 LNT samples. Median age was 60 years (range, 27–87 years. At a median follow-up of 28.5 months, 6 deaths and 16 recurrences had occurred. PTK7 expression correlations with clinicopathological features were computed and PTK7 expression effects on patient outcome were analyzed in three cohorts defined by adjuvant treatment: anthracycline-based treatment, other chemotherapy regimens (including taxane or other substances, or no chemotherapy. Association of PTK7 expression with clinicopathological features was seen only for age in PTT and nodal stage in LNT. High LN PTK7 was associated with poorer disease-free survival (DFS in the total population (3-year

  17. Modified FOLFOX-6 chemotherapy in advanced gastric cancer: Results of phase II study and comprehensive analysis of polymorphisms as a predictive and prognostic marker

    Directory of Open Access Journals (Sweden)

    Lee Se-Hoon

    2008-05-01

    Full Text Available Abstract Background The objective of this study was to evaluate the efficacy and toxicity of infusional 5-fluorouracil (5-FU, folinic acid and oxaliplatin (modified FOLFOX-6 in patients with advanced gastric cancer (AGC, as first-line palliative combination chemotherapy. We also analyzed the predictive or prognostic value of germline polymorphisms of candidate genes associated with 5-FU and oxaliplatin. Methods Seventy-three patients were administered a 2 hour infusion of oxaliplatin (100 mg/m2 and folinic acid (100 mg/m2 followed by a 46 hour continuous infusion of 5-FU (2,400 mg/m2. Genomic DNA from the patients' peripheral blood mononuclear cells was extracted. Ten polymorphisms within five genes were investigated including TS, GSTP, ERCC, XPD and XRCC. Results The overall response rate (RR was 43.8%. Median time to progression (TTP and overall survival (OS were 6.0 months and 12.6 months, respectively. Toxicities were generally tolerable and manageable. The RR was significantly higher in patients with a 6-bp deletion homozygote (-6 bp/-6 bp in TS-3'UTR (55.0% vs. 30.3% in +6 bp/+6 bp or +6 bp/-6 bp, p = 0.034, and C/A or A/A in XPD156 (52.0% vs. 26.1% in C/C, p = 0.038. The -6 bp/-6 bp in TS-3'UTR was significantly associated with a prolonged TTP and OS. In a multivariate analysis, the 6-bp deletion in TS-3'UTR was identified as an independent prognostic marker of TTP (hazard ratio = 0.561, p = 0.032. Conclusion Modified FOLFOX-6 chemotherapy appears to be active and well tolerated as first line chemotherapy in AGC patients. The 6-bp deletion in TS-3'UTR might be a candidate to select patients who are likely to benefit from 5-FU based modified FOLFOX-6 in future large scale trial.

  18. Modified FOLFOX-6 chemotherapy in advanced gastric cancer: Results of phase II study and comprehensive analysis of polymorphisms as a predictive and prognostic marker

    International Nuclear Information System (INIS)

    The objective of this study was to evaluate the efficacy and toxicity of infusional 5-fluorouracil (5-FU), folinic acid and oxaliplatin (modified FOLFOX-6) in patients with advanced gastric cancer (AGC), as first-line palliative combination chemotherapy. We also analyzed the predictive or prognostic value of germline polymorphisms of candidate genes associated with 5-FU and oxaliplatin. Seventy-three patients were administered a 2 hour infusion of oxaliplatin (100 mg/m2) and folinic acid (100 mg/m2) followed by a 46 hour continuous infusion of 5-FU (2,400 mg/m2). Genomic DNA from the patients' peripheral blood mononuclear cells was extracted. Ten polymorphisms within five genes were investigated including TS, GSTP, ERCC, XPD and XRCC. The overall response rate (RR) was 43.8%. Median time to progression (TTP) and overall survival (OS) were 6.0 months and 12.6 months, respectively. Toxicities were generally tolerable and manageable. The RR was significantly higher in patients with a 6-bp deletion homozygote (-6 bp/-6 bp) in TS-3'UTR (55.0% vs. 30.3% in +6 bp/+6 bp or +6 bp/-6 bp, p = 0.034), and C/A or A/A in XPD156 (52.0% vs. 26.1% in C/C, p = 0.038). The -6 bp/-6 bp in TS-3'UTR was significantly associated with a prolonged TTP and OS. In a multivariate analysis, the 6-bp deletion in TS-3'UTR was identified as an independent prognostic marker of TTP (hazard ratio = 0.561, p = 0.032). Modified FOLFOX-6 chemotherapy appears to be active and well tolerated as first line chemotherapy in AGC patients. The 6-bp deletion in TS-3'UTR might be a candidate to select patients who are likely to benefit from 5-FU based modified FOLFOX-6 in future large scale trial

  19. Markers of T cell infiltration and function associate with favorable outcome in vascularized high-grade serous ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Katelin N Townsend

    Full Text Available BACKGROUND: When T cells infiltrate the tumor environment they encounter a myriad of metabolic stressors including hypoxia. Overcoming the limitations imposed by an inadequate tumor vasculature that contributes to these stressors may be a crucial step to immune cells mounting an effective anti-tumor response. We sought to determine whether the functional capacity of tumor infiltrating lymphocytes (TIL could be influenced by the tumor vasculature and correlated this with survival in patients with ovarian cancer. METHODOLOGY AND PRINCIPAL FINDINGS: In 196 high-grade serous ovarian tumors, we confirmed that the tumor vascularity as measured by the marker CD31 was associated with improved patient disease-specific survival. We also found that tumors positive for markers of TIL (CD8, CD4 and forkhead box P3 (FoxP3 and T cell function (granzyme B and T-cell restricted intracellular antigen-1 (TIA-1 correlated significantly with elevated vascularity. In vitro, hypoxic CD8 T cells showed reduced cytolytic activity, secreted less effector cytokines and upregulated autophagy. Survival analysis revealed that patients had a significant improvement in disease-specific survival when FoxP3 expressing cells were present in CD31-high tumors compared to patients with FoxP3 expressing cells in CD31-low tumors [HR: 2.314 (95% CI 1.049-5.106; p = 0.0377]. Patients with high vascular endothelial growth factor (VEGF expressing tumors containing granzyme B positive cells had improved survival compared to patients with granzyme B positive cells in VEGF-low tumors [HR: 2.522 (95% CI 1.097-5.799; p = 0.0294]. SIGNIFICANCE: Overall, this data provides a rationale for developing strategies aimed at improving the adaptability and function of TIL to hypoxic tumor conditions.

  20. Time-dependent effect of hypoxia on tumor progression and liver progenitor cell markers in primary liver tumors.

    Directory of Open Access Journals (Sweden)

    Eliene Bogaerts

    Full Text Available Expression of liver progenitor cell (LPC characteristics has been proposed as a negative prognostic marker in primary liver tumors. Hypoxia has been linked to activation of the Notch pathway which is responsible for activation and proliferation of LPCs and hypoxia-induced LPC activation has been shown in hepatocellular carcinoma. Our aim was to elucidate the time-dependent effects of hypoxia on the LPC niche in hepatocellular carcinoma which could aid in determining a safe time frame for use of hypoxia inducing therapies.We used dimethyloxaloylglycine to mimic a hypoxic reaction in mice by stabilizing hypoxia-inducible factor 1 alpha at three distinct time points in diethylnitrosamine induced hepatocarcinogenesis. LPC, metastasis and Notch pathway markers were determined by quantitative PCR and (immunehistochemistry (heamatoxillin-eosin, reticulin, Sirius red and cytokeratin 19 staining.Activating the hypoxia inducible pathway early in hepatocarcinogenesis resulted in an increased incidence of both cholangioma and hepatocellular lesions, associated with high expression of LPC, metastatic and Notch pathway markers. Adversely, activating the hypoxic response during tumor development resulted in decreased incidence of hepatocellular lesions and increased cholangioma incidence, with an unaltered gene expression profile of LPC-, Notch pathway- and metastatic markers. A hypoxic insult at advanced stages of hepatocarcinogenesis severely increased the expression of LPC characteristics, however without increased expression of actors of the Notch pathway and metastatic markers and minor changes in incidence of hepatocellular and cholangioma lesions.Our results indicate that increased hypoxia at the onset of tumor development has detrimental effects on tumor progression; patients with HCC developed in a background of fibrosis/cirrhosis might therefore represent a more difficult treatment group. In contrast, hypoxia during tumor development appears to favor

  1. Mapping of the vaccinia virus DNA polymerase gene by marker rescue and cell-free translation of selected RNA

    International Nuclear Information System (INIS)

    The previous demonstration that a phosphonoacetate (PAA)-resistant (PAA/sup r/) vaccinia virus mutant synthesized an altered DNA polymerase provided the key to mapping this gene. Marker rescue was performed in cells infected with wild-type PAA-sensitive (PAA/sup s/) vaccinia by transfecting with calcium phosphate-precipitated DNA from a PAA/sup r/ mutant virus. Formation of PAA/sup r/ recombinants was measured by plaque assay in the presence of PAA. Of the 12 HindIII fragments cloned in plasmid or cosmid vectors, only fragment E conferred the PAA/sup r/ phenotype. Successive subcloning of the 15-kilobase HindIII fragment E localized the marker within a 7.5-kilobase BamHI-HindIII fragment and then within a 2.9-kilobase EcoRI fragment. The location of the DNA polymerase gene, about 57 kilobases from the left end of the genome, was confirmed by cell-free translation of mRNA selected by hybridization to plasmids containing regions of PAA/sup r/ vaccinia DNA active in marker rescue. A 100,000-dalton polypeptide that comigrated with authentic DNA polymerase was synthesized. Correspondence of the in vitro translation product with purified vaccinia DNA polymerase was established by peptide mapping

  2. The role of inflammation in cardiovascular diseases: the predictive value of neutrophil-lymphocyte ratio as a marker in peripheral arterial disease.

    Science.gov (United States)

    Paquissi, Feliciano Chanana

    2016-01-01

    Peripheral arterial disease (PAD) is an important manifestation of atherosclerosis, with increasing prevalence worldwide. A growing body of evidence shows that the systemic inflammatory response is closely related to the development, progression, and prognosis of atherosclerosis. In the last decade, several studies have suggested the role of measured inflammatory biomarkers as predictors of severity and prognosis in PAD in an effort to stratify the risk of these patients, to improve treatment selection, and to predict the results after interventions. A simple inflammatory marker, more available than any other, is the neutrophil-lymphocyte ratio (NLR), which can be easily obtained in clinical practice, based on the absolute count of neutrophils and lymphocytes from the differential leukocytes count. Many researchers evaluated vigorously the NLR as a potential prognostic biomarker predic