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Sample records for cancer subset enriched

  1. Characterization of a naturally occurring breast cancer subset enriched in EMT and stem cell characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Hennessy, Bryan T.; Gonzalez-Angulo, Ana-Maria; Stemke-Hale, Katherine; Gilcrease, Michael Z.; Krishnamurthy, Savitri; Lee, Ju-Seog; Fridlyand, Jane; Sahin, Aysegul; Agarwal, Roshan; Joy, Corwin; Liu, Wenbin; Stivers, David; Baggerly, Keith; Carey, Mark; Lluch, Ana; Monteagudo, Carlos; He, Xiaping; Weigman, Victor; Fan, Cheng; Palazzo, Juan; Hortobagyi, Gabriel N.; Nolden, Laura K.; Wang, Nicholas J.; Valero, Vicente; Gray, Joe W.; Perou, Charles M.; Mills, Gordon B.

    2009-05-19

    Metaplastic breast cancers (MBC) are aggressive, chemoresistant tumors characterized by lineage plasticity. To advance understanding of their pathogenesis and relatedness to other breast cancer subtypes, 28 MBCs were compared with common breast cancers using comparative genomic hybridization, transcriptional profiling, and reverse-phase protein arrays and by sequencing for common breast cancer mutations. MBCs showed unique DNA copy number aberrations compared with common breast cancers. PIK3CA mutations were detected in 9 of 19 MBCs (47.4%) versus 80 of 232 hormone receptor-positive cancers (34.5%; P = 0.32), 17 of 75 HER-2-positive samples (22.7%; P = 0.04), 20 of 240 basal-like cancers (8.3%; P < 0.0001), and 0 of 14 claudin-low tumors (P = 0.004). Of 7 phosphatidylinositol 3-kinase/AKT pathway phosphorylation sites, 6 were more highly phosphorylated in MBCs than in other breast tumor subtypes. The majority of MBCs displayed mRNA profiles different from those of the most common, including basal-like cancers. By transcriptional profiling, MBCs and the recently identified claudin-low breast cancer subset constitute related receptor-negative subgroups characterized by low expression of GATA3-regulated genes and of genes responsible for cell-cell adhesion with enrichment for markers linked to stem cell function and epithelial-to-mesenchymal transition (EMT). In contrast to other breast cancers, claudin-low tumors and most MBCs showed a significant similarity to a 'tumorigenic' signature defined using CD44{sup +}/CD24{sup -} breast tumor-initiating stem cell-like cells. MBCs and claudin-low tumors are thus enriched in EMT and stem cell-like features, and may arise from an earlier, more chemoresistant breast epithelial precursor than basal-like or luminal cancers. PIK3CA mutations, EMT, and stem cell-like characteristics likely contribute to the poor outcomes of MBC and suggest novel therapeutic targets.

  2. The CD44(high tumorigenic subsets in lung cancer biospecimens are enriched for low miR-34a expression.

    Directory of Open Access Journals (Sweden)

    Saroj K Basak

    Full Text Available Cellular heterogeneity is an integral part of cancer development and progression. Progression can be associated with emergence of cells that exhibit high phenotypic plasticity (including "de-differentiation" to primitive developmental states, and aggressive behavioral properties (including high tumorigenic potentials. We observed that many biomarkers that are used to identify Cancer Stem Cells (CSC can label cell subsets in an advanced clinical stage of lung cancer (malignant pleural effusions, or MPE. Thus, CSC-biomarkers may be useful for live sorting functionally distinct cell subsets from individual tumors, which may enable investigators to hone in on the molecular basis for functional heterogeneity. We demonstrate that the CD44(hi (CD44-high cancer cell subsets display higher clonal, colony forming potential than CD44(lo cells (n=3 and are also tumorigenic (n=2/2 when transplanted in mouse xenograft model. The CD44(hi subsets express different levels of embryonal (de-differentiation markers or chromatin regulators. In archived lung cancer tissues, ALDH markers co-localize more with CD44 in squamous cell carcinoma (n=5/7 than Adeno Carcinoma (n=1/12. MPE cancer cells and a lung cancer cell line (NCI-H-2122 exhibit chromosomal abnormalities and 1p36 deletion (n=3/3. Since miR-34a maps to the 1p36 deletion site, low miR-34a expression levels were detected in these cells. The colony forming efficiency of CD44(hi cells, characteristic property of CSC, can be inhibited by mir-34a replacement in these samples. In addition the highly tumorigenic CD44(hi cells are enriched for cells in the G2 phase of cell cycle.

  3. CLINICAL VALUE OF DETECTING T LYMPHOCYTE SUBSET AND NK CELL ACTIVITY IN PATIENTS WITH COLORECTAL CANCER

    Institute of Scientific and Technical Information of China (English)

    刘长安; 管增伟; 孙武; 邵玉霞; 李卓; 贾廷珍

    2001-01-01

    Objective To study on the expression and clinical significance of T lymphocyte subset and NK cell activity (NKA) in patients with colorectal cancer. Methods Fifty-seven cancer patients and 33 healthy controls were enrolled in this study. T lymphocyte subset was measured by SAP technique and NKA by LDH release assay based on K562 cells, which served as target cells.

  4. EWS and FUS bind a subset of transcribed genes encoding proteins enriched in RNA regulatory functions

    DEFF Research Database (Denmark)

    Luo, Yonglun; Friis, Jenny Blechingberg; Fernandes, Ana Miguel;

    2015-01-01

    IP-seq). Our results show that FUS and EWS bind to a subset of actively transcribed genes, that binding often is downstream the poly(A)-signal, and that binding overlaps with RNA polymerase II. Functional examinations of selected target genes identified that FUS and EWS can regulate gene expression...... at different levels. Gene Ontology analyses showed that FUS and EWS target genes preferentially encode proteins involved in regulatory processes at the RNA level. Conclusions The presented results yield new insights into gene interactions of EWS and FUS and have identified a set of FUS and EWS target genes...

  5. Human endotoxin tolerance is associated with enrichment of the CD14+ CD16+ monocyte subset.

    Science.gov (United States)

    Domínguez-Nieto, Aimée; Zentella, Alejandro; Moreno, José; Ventura, José L; Pedraza, Sigifredo; Velázquez, Juan R

    2015-01-01

    Prior exposure to lipopolysaccharides (LPS) induces a state of cell resistance to subsequent LPS restimulation, known as endotoxin tolerance, mainly by repressing the expression of pro-inflammatory cytokines. We established an endotoxin tolerance model in human monocytes Endotoxin-tolerant cells showed a decrease in IκBα degradation and diminished expression of Tumor necrosis factor (TNF) (both messenger RNA [mRNA] and protein content). The myeloid differentiation factor 88 (MyD88)/MyD88 splice variant (MyD88s) ratio, an indirect way to test the Toll-like receptor 4 (TLR4) MyD88-dependent signaling cascade, did not change in endotoxin-tolerant cells when compared to LPS-stimulated or -unstimulated ones. Remarkably, cell population analysis indicated a significant increase of the CD14+ CD16+ subset only under the endotoxin-tolerant condition. Furthermore, endotoxin-tolerant cells produced higher amounts of C-X-C motif chemokine 10 (CXCL10), a typical MyD88-independent cytokine.

  6. Activin signal promotes cancer progression and is involved in cachexia in a subset of pancreatic cancer.

    Science.gov (United States)

    Togashi, Yosuke; Kogita, Akihiro; Sakamoto, Hiroki; Hayashi, Hidetoshi; Terashima, Masato; de Velasco, Marco A; Sakai, Kazuko; Fujita, Yoshihiko; Tomida, Shuta; Kitano, Masayuki; Okuno, Kiyotaka; Kudo, Masatoshi; Nishio, Kazuto

    2015-01-28

    We previously reported that activin produces a signal with a tumor suppressive role in pancreatic cancer (PC). Here, the association between plasma activin A and survival in patients with advanced PC was investigated. Contrary to our expectations, however, patients with high plasma activin A levels had a significantly shorter survival period than those with low levels (median survival, 314 days vs. 482 days, P = 0.034). The cellular growth of the MIA PaCa-2 cell line was greatly enhanced by activin A via non-SMAD pathways. The cellular growth and colony formation of an INHBA (beta subunit of inhibin)-overexpressed cell line were also enhanced. In a xenograft study, INHBA-overexpressed cells tended to result in a larger tumor volume, compared with a control. The bodyweights of mice inoculated with INHBA-overexpressed cells decreased dramatically, and these mice all died at an early stage, suggesting the occurrence of activin-induced cachexia. Our findings indicated that the activin signal can promote cancer progression in a subset of PC and might be involved in cachexia. The activin signal might be a novel target for the treatment of PC.

  7. Differential Aspartate Usage Identifies a Subset of Cancer Cells Particularly Dependent on OGDH

    Directory of Open Access Journals (Sweden)

    Eric L. Allen

    2016-10-01

    Full Text Available Although aberrant metabolism in tumors has been well described, the identification of cancer subsets with particular metabolic vulnerabilities has remained challenging. Here, we conducted an siRNA screen focusing on enzymes involved in the tricarboxylic acid (TCA cycle and uncovered a striking range of cancer cell dependencies on OGDH, the E1 subunit of the alpha-ketoglutarate dehydrogenase complex. Using an integrative metabolomics approach, we identified differential aspartate utilization, via the malate-aspartate shuttle, as a predictor of whether OGDH is required for proliferation in 3D culture assays and for the growth of xenograft tumors. These findings highlight an anaplerotic role of aspartate and, more broadly, suggest that differential nutrient utilization patterns can identify subsets of cancers with distinct metabolic dependencies for potential pharmacological intervention.

  8. Circulating Lymphocyte Subsets 
in Patients with Lung Cancer and Their Prognostic Value

    Directory of Open Access Journals (Sweden)

    Jun LUO

    2011-08-01

    Full Text Available Background and objective Lung cancer is one of the most common malignancies. The aim of this study is to investigate the relationship between the change of lymphocyte subsets in the peripheral blood of lung cancer patients and the survival rate. Methods Flow cytometry was used to measure the percentages of lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells in peripheral blood obtained from 221 patients with primary lung cancer without any treatment and from 96 healthy blood donors as the control group. The result was combined with clinical and follow-up data and statistical analysis was conducted. Results The levels of CD3+ and CD8+ in the patient group are significantly lower compared with the control group, whereas the levels of CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells are significantly higher (P<0.05. CD8+ is significantly higher in the small cell lung cancer (SCLC group compared with the non-small cell lung cancer (NSCLC group. However, CD4+ and CD4+/CD8+ are lower in SCLC (P<0.05. There were no significant differences in different stages and differentiation (P>0.05 in the NSCLC group. The level of CD3+ was significantly higher compared with the pre-chemotherapy group, but NK cell, CD19+, and CD44+ were distinctly lower in the post-chemotherapy group (P<0.05. More survival opportunities will be obtained for patients with no increase in CD44+ after chemotherapy (P=0.021, but the other three indices have no obvious influence on survival. Conclusion Widespread changes of lymphocyte occur in the peripheral blood of patients with lung cancer. There is a significant correlation between the change of CD44+ and the prognosis after chemotherapy.

  9. Methylation of PTCH1a gene in a subset of gastric cancers

    Institute of Scientific and Technical Information of China (English)

    Peng Du; Hai-Rong Ye; Jun Gao; Wei Chen; Zhong-Chuan Wang; Hong-Hua Jiang; Ji Xu; Ji-We Zhang; Jian-Cheng Zhang; Long Cui

    2009-01-01

    AIM: To establish if PTCH1a transcriptional regulation region (TRR) is methylated in gastric cancer and its influence in gastric tumorigenesis. METHODS: The CpG islands in PTCH1a TRR were analyzed by Methyl Primer Express v1.0 software. The region from -643 to -355 bp (the transcription initiation site of PTCH1a was designated as 0) that contained 19 CpG sites was chosen for bisulfitesequencing PCR (BSP) and methylation-specific PCR (MSP) detection. The gastric cancer cell line AGS was treated with 5-aza-2'-deoxycytidine (5-Aza-dC; 1 μmol/L) for 3 d. Alterations in PTCH1a TRR methylation in treated AGS cells was measured through BSP clone sequences, and their PTCH1 expression was measured by quantitative RT-PCR. The cell cycle and apoptosis were observed with flow cytometry through propidium iodide (PI) staining or annexin V/PI double staining. The prevalence of PTCH1a TRR methylation was investigated in 170 gastric cancer tissue samples and the adjacent normal tissues by MSP. The correlation of PTCH1a TRR methylation with PTCH1 expression or with patients' clinical features was analyzed. RESULTS: Methylation of PTCH1a TRR was observed in AGS cells and a subset of gastric cancer tissues (32%, 55/170), while no methylation amplification products were observed in any normal tissues by MSP. The methylation of PTCH1a TRR was correlated negatively with PTCH1 expression (Spearman's r = -0.380, P = 0.000). However, methylation of PTCH1a TRR was not related to the gastric cancer patients' clinical features, such as sex, age of onset, clinical stage, lymph node metastasis or histological grade. The methylation of PTCH1a TRR in AGS cells was almost converted to non-methylation after 5-Aza-dC treatment, which increased PTCH1 expression (5.3 ± 2.5 times; n = 3) and apoptosis rate (3.0 ± 0.26 times; P < 0.05; n = 3). CONCLUSION: Methylation of PTCH1a TRR is present in a subset of gastric cancers and correlated negatively with PTCH1 expression. This may be an early event in

  10. Androgen receptors and serum testosterone levels identify different subsets of postmenopausal breast cancers

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    Secreto Giorgio

    2012-12-01

    Full Text Available Abstract Background Androgen receptors (AR are frequently expressed in breast cancers, but their implication in cancer growth is still controversial. In the present study, we further investigated the role of the androgen/AR pathway in breast cancer development. Methods AR expression was evaluated by immunochemistry in a cohort of 528 postmenopausal breast cancer patients previously examined for the association of serum testosterone levels with patient and tumor characteristics. AR expression was classified according to the percentage of stained cells: AR-absent (0% and AR-poorly (1%-30%, AR-moderately (>30%-60%, and AR-highly (>60% positive. Results Statistical analysis was performed in 451 patients who experienced natural menopause. AR-high expression was significantly related with low histologic grade and estrogen receptor (ER- and progesterone receptor (PR-positive status (P trendP=0.022, although a trend across the AR expression categories was not present. When women defined by ER status were analyzed separately, regression analysis in the ER-positive group showed a significant association of high testosterone levels with AR-highly-positive expression (OR 1.86; 95% CI, 1.10-3.16, but the association was essentially due to patients greater than or equal to 65 years (OR 2.42; 95% CI, 1.22-4.82. In ER-positive group, elevated testosterone levels appeared also associated with AR-absent expression, although the small number of patients in this category limited the appearance of significant effects (OR 1.92; 95% CI, 0.73–5.02: the association was present in both age groups ( Conclusions The findings in the present study confirm that testosterone levels are a marker of hormone-dependent breast cancer and suggest that the contemporary evaluation of ER status, AR expression, and circulating testosterone levels may identify different subsets of cancers whose growth may be influenced by androgens.

  11. MicroRNA-125b expands hematopoietic stem cells and enriches for the lymphoid-balanced and lymphoid-biased subsets.

    Science.gov (United States)

    Ooi, A G Lisa; Sahoo, Debashis; Adorno, Maddalena; Wang, Yulei; Weissman, Irving L; Park, Christopher Y

    2010-12-14

    MicroRNAs profoundly impact hematopoietic cells by regulating progenitor cell-fate decisions, as well as mature immune effector function. However to date, microRNAs that regulate hematopoietic stem cell (HSC) function have been less well characterized. Here we show that microRNA-125b (miR-125b) is highly expressed in HSCs and its expression decreases in committed progenitors. Overexpression of miR-125b in mouse HSC enhances their function, demonstrated through serial transplantation of highly purified HSC, and enriches for the previously described Slamf1(lo)CD34(-) lymphoid-balanced and the Slamf1(neg)CD34(-) lymphoid-biased cell subsets within the multipotent HSC (CD34-KLS) fraction. Mature peripheral blood cells derived from the miR-125b-overexpressing HSC are skewed toward the lymphoid lineage. Consistent with this observation, miR-125b overexpression significantly increases the number of early B-progenitor cells within the spleen and induces the expansion and enrichment of the lymphoid-balanced and lymphoid-biased HSC subset via an antiapoptotic mechanism, reducing the mRNA expression levels of two proapoptotic targets, Bmf and KLF13. The antiapoptotic effect of miR-125b is more pronounced in the lymphoid-biased HSC subset because of their intrinsic higher baseline levels of apoptosis. These effects of miR-125b are associated with the development of lymphoproliferative disease, marked by expansion of CD8(+) T lymphocytes. Taken together, these data reveal that miR-125b regulates HSC survival and can promote lymphoid-fate decisions at the level of the HSC by preferentially expanding lymphoid-balanced and lymphoid-biased HSC.

  12. Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients.

    Science.gov (United States)

    Simpson, K; Jones, R E; Grimstead, J W; Hills, R; Pepper, C; Baird, D M

    2015-06-01

    Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer.

  13. Influence of DC-CIK in advanced colorectal cancer patients on T lymphocyte subsets and cytokines

    Institute of Scientific and Technical Information of China (English)

    Rong Wang; Min Yi; Shi-Rong Yang; Li-Xia Chai; Mao Hua

    2016-01-01

    Objective:To explore the effects of dendritic cells (DC)-cytokine induced killer cells (CIK) treatment on T lymphocyte subsets and cytokines in patients with advanced colorectal cancer. Methods:A total of 84 cases patients with advanced colorectal cancer were divided into two groups according to random number table method, each 42 cases, both two groups were given FOLFOX scheme chemotherapy, on the basis, the observation group were given supplementary DC-CIK treatment, compared the T lymphocy te subgroup: CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines, interleukin-2 (IL-2) and interferon gamma-γ (FN-γ), Th2 cytokines:interleukin 6 (IL-6), interleukin 4 (IL-4) of the two groups before and after treatment. Results:Compared with before treatment, the CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines IL-2 and IFN-γin observation group were significantly higher than after treatment , the CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines IL-2 and IFN-γin control group were significantly lower than after treatment, and the differences were all statistically significant;The CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines IL-2 and IFN-γin observation group after treatment were significantly higher than those in control group after treatment with statistical difference;CD8+, Th2 cytokines IL-4, IL-6 in two groups had no statistical significance before and after treatment. Conclusion:Chemotherapy can cause the immune function restrained in patients with advanced colorectal cancer, and DC-CIK supplementary therapy can significantly improve the immune function, enhance the anti tumor immune responses.

  14. Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity

    OpenAIRE

    D’Angelo, Rosemarie C.; Ouzounova, Maria; Davis, April; Choi, Daejin; Tchuenkam, Stevie M.; Kim, Gwangil; Luther, Tahra; Quraishi, Ahmed A.; Senbabaoglu, Yasin; Conley, Sarah J; Shawn G Clouthier; Hassan, Khaled A.; Wicha, Max S; Korkaya, Hasan

    2015-01-01

    Developmental pathways such as Notch play a pivotal role in tissue specific stem cell self-renewal as well as in tumor development. However, the role of Notch signaling in breast cancer stem cells (CSC) remains to be determined. We utilized a lentiviral Notch reporter system to identify a subset of cells with a higher Notch activity (Notch+) or reduced activity (Notch-) in multiple breast cancer cell lines. Using in vitro and mouse xenotransplantation assays we investigated the role of Notch ...

  15. Upregulation of Glycans Containing 3’ Fucose in a Subset of Pancreatic Cancers Uncovered Using Fusion-Tagged Lectins

    OpenAIRE

    Singh, Sudhir; Pal, Kuntal; Yadav, Jessica; Tang, Huiyuan; Partyka, Katie; Kletter, Doron; Hsueh, Peter; Ensink, Elliot; Birendra, KC; Hostetter, Galen; Xu, H. Eric; Bern, Marshall; Smith, David F; Mehta, Anand S.; Brand, Randall

    2015-01-01

    The fucose post-translational modification is frequently increased in pancreatic cancer, thus forming the basis for promising biomarkers, but a subset of pancreatic cancer patients does not elevate the known fucose-containing biomarkers. We hypothesized that such patients elevate glycan motifs with fucose in linkages and contexts different from the known fucose-containing biomarkers. We used a database of glycan array data to identify the lectins CCL2 to detect glycan motifs with fucose in a ...

  16. Distribution of natural killer cells and T-lymphocyte subsets in peripheral blood, gallbladder cancer and surrounding tissue

    Institute of Scientific and Technical Information of China (English)

    Gang Liu; Hong Ren; Xue-Jun Sun; Jing-Sen Shi

    2007-01-01

    BACKGROUND:The patient with malignant tumor always show immunologic function drawback and ingravescent with tumor development, especially in the aspect of cell-mediated immunity. This study was undertaken to deifne the relationship between the immune function of local cells and cancer development by investigating the distribution of natural killer (NK) cells and T-lymphocyte subsets in peripheral blood, the cancer tissue and the tissue surrounding gallbladder carcinoma. METHODS:The numbers of CD4+and CD8+T-lymphocytes and NK cells were measured by lfow cytometry in samples taken from gallbladder cancer tissue, the surrounding tissues and peripheral blood of 38 patients, and compared with the numbers in the peripheral blood and gallbladder tissue of 30 patients with cholecystitis as controls. RESULTS:The numbers of CD4+and CD8+T-cells and NK cells in gallbladder cancer tissues were signiifcantly higher than those in the surrounding tissue and gallbladder with gallstone. However, the ratio of CD4+/CD8+was lower in the cancer tissue than that in the surrounding tissue and tissue from gallbladders with gallstones. The distribution of CD4+ and CD8+ T-cells and NK cells in mucous membrane of cholecystitis gallbladder and that in the tissue surrounding gallbladder cancer were signiifcantly different. CONCLUSIONS:Disproportionate and imbalanced distri-bution of NK cells and subsets of T-lymphocytes occurs in the mucous membrane proper of gallbladder cancer and surrounding tissue. Although gallbladder cancer tissue has higher expressions of CD4+, CD8+and NK cells, the immune function is low or in an inhibited state. In gallbladder cancer immunization therapy, local cellular immunological function should be enhanced and the protective barrier improved.

  17. ENRICH Forum: Ethical aNd Regulatory Issues in Cancer ResearcH

    Science.gov (United States)

    ENRICH Forum: Ethical aNd Regulatory Issues in Cancer ResearcH, designed to stimulate dialogue on ethical and regulatory issues in cancer research and promote awareness of developing policies and best practices.

  18. Combining FoxP3 and Helios with GARP/LAP markers can identify expanded Treg subsets in cancer patients.

    Science.gov (United States)

    Abd Al Samid, May; Chaudhary, Belal; Khaled, Yazan S; Ammori, Basil J; Elkord, Eyad

    2016-03-22

    Regulatory T cells (Tregs) comprise numerous heterogeneous subsets with distinct phenotypic and functional features. Identifying Treg markers is critical to investigate the role and clinical impact of various Treg subsets in pathological settings, and also for developing more effective immunotherapies. We have recently shown that non-activated FoxP3-Helios+ and activated FoxP3+/-Helios+ CD4+ T cells express GARP/LAP immunosuppressive markers in healthy donors. In this study we report similar observations in the peripheral blood of patients with pancreatic cancer (PC) and liver metastases from colorectal cancer (LICRC). Comparing levels of different Treg subpopulations in cancer patients and controls, we report that in PC patients, and unlike LICRC patients, there was no increase in Treg levels as defined by FoxP3 and Helios. However, defining Tregs based on GARP/LAP expression showed that FoxP3-LAP+ Tregs in non-activated and activated settings, and FoxP3+Helios+GARP+LAP+ activated Tregs were significantly increased in both groups of patients, compared with controls. This work implies that a combination of Treg-specific markers could be used to more accurately determine expanded Treg subsets and to understand their contribution in cancer settings. Additionally, GARP-/+LAP+ CD4+ T cells made IL-10, and not IFN-γ, and levels of IL-10-secreting CD4+ T cells were elevated in LICRC patients, especially with higher tumor staging. Taken together, our results indicate that investigations of Treg levels in different cancers should consider diverse Treg-related markers such as GARP, LAP, Helios, and others and not only FoxP3 as a sole Treg-specific marker.

  19. Changes in percentage of lymphocyte subsets after 131I treatment in patients with differentiated thyroid cancer

    Institute of Scientific and Technical Information of China (English)

    LUO Quan-Yong; CHEN Li-Bo; YU Yong-Li; LU Han-Kui; ZHU Rui-Sen

    2005-01-01

    To monitor the extent and the duration of lymphocyte subset changes in patients with thyroid carcinoma undergoing therapeutic 131I administration, the percentage of lymphocyte subsets were serially analyzed before and after 131I treatment. In patients who received 1850 MBq of 131I for ablation of thyroid remnants, only for NK cells and B cells showed a significant reduction. In patients received 3700 MBq of 131I for treatment of local lymph node metastases, NK cells, B cells and CD4+ were found decreased. In patients received 7400 MBq of 131I for treatment of distant metastases, NK cells, B cells and CD4+ and CD8+ were all affected. However, there is no significant reduction compared to the baseline in the percentage of all lymphocyte subsets three months after 131I treatment. The results show that the sensitivity of lymphocytes to 131I internal radiation depends upon lymphocyte phenotype and 131I activity. The immunosuppression effects are temporary and reversible.

  20. Gamma-secretase inhibition combined with platinum compounds enhances cell death in a large subset of colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Feller Stephan M

    2008-10-01

    Full Text Available Abstract Background Notch signalling is essential for the development and maintenance of the colonic epithelium. Its inhibition induces a differentiation phenotype in vivo and reduces adenomas in APCmin mice. Whether Notch signals are also required in colorectal cancer (CRC has remained elusive. Therefore, 64 CRC cell lines were analysed for the occurrence of proteolytically processed, active Notch. Results 63 CRC lines contained a fragment with approximately the size of the Notch1 intracellular domain (NICD, which is required for signalling. Subsequent analyses with an antibody that specifically recognises the free Val1744 residue generated by γ-secretase-mediated cleavage of Notch1 showed that a subset of CRC cells lacks this specific Val1744-NICD. Surprisingly, inhibition of Val1744-NICD signalling with different γ-secretase inhibitors (GSI did not lead to substantial effects on CRC cell line growth or survival. However, transient activation of Erk upon GSI treatment was detected. Since cisplatin relies on Erk activation for bioactivity in some cells, platinum compounds were tested together with GSI and enhanced cell killing in a subset of Val1744-NICD-positive CRC cell lines was detected. Erk inhibition ablated this combination effect. Conclusion We conclude that γ-secretase inhibition results in activation of the MAP kinases Erk1/2 and, when used in conjunction, enhances cell death induced by platinum compounds in a large subset of colorectal cancer cell lines. Furthermore the activation of Erk appears to be of particular importance in mediating the enhanced effect seen, as its inhibition abrogates the observed phenomenon. These findings do not only highlight the importance of signalling pathway crosstalk but they may also suggest a new avenue of combination therapy for some colorectal cancers.

  1. Heterogenous high-level HER-2 amplification in a small subset of colorectal cancers.

    Science.gov (United States)

    Marx, Andreas H; Burandt, Eike C; Choschzick, Matthias; Simon, Ronald; Yekebas, Emre; Kaifi, Jussuf T; Mirlacher, Martina; Atanackovic, Djordje; Bokemeyer, Carsten; Fiedler, Walter; Terracciano, Luigi; Sauter, Guido; Izbicki, Jakob R

    2010-11-01

    HER-2 is the molecular target for antibody-based treatment of breast cancer (trastuzumab). The potential benefit of anti-HER-2 therapy is currently investigated in several other HER-2 amplified cancers. For example, trastuzumab was recently shown to be effective in HER-2 positive gastric cancer. To address the potential applicability of anti-HER-2 therapy in colorectal cancer, tissue microarray sections and colorectal resection specimens of 1851 colorectal cancers were analyzed for HER-2 overexpression and amplification using FDA approved reagents for immunohistochemistry and fluorescence in situ hybridization. HER-2 amplification was seen in 2.5% and HER-2 overexpression in 2.7% of 1439 interpretable colorectal cancers. Amplification was often high level with HER-2 copies ranging from 4 to 60 per tumor cell and was strongly related to protein overexpression. HER-2 amplification and overexpression were unrelated to histological tumor type, tumor localization, grading, pT, pN, pM or survival. As heterogeneity of drug target expression could represent a major drawback for targeted cancer therapy we next studied HER-2 heterogeneity in selected cases. Extensive evaluation of all available large sections from patients with HER-2 positive colorectal cancer revealed heterogenous findings in 3 of 4 cases. In summary, high-level HER-2 amplification occurs in a small fraction of colorectal cancers. Heterogeneity of amplification may limit the utility of anti- HER-2 therapy in some of these tumors and therefore, adequate clinical trials are needed to further evaluate this approach.

  2. Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity.

    Science.gov (United States)

    D'Angelo, Rosemarie C; Ouzounova, Maria; Davis, April; Choi, Daejin; Tchuenkam, Stevie M; Kim, Gwangil; Luther, Tahra; Quraishi, Ahmed A; Senbabaoglu, Yasin; Conley, Sarah J; Clouthier, Shawn G; Hassan, Khaled A; Wicha, Max S; Korkaya, Hasan

    2015-03-01

    Developmental pathways such as Notch play a pivotal role in tissue-specific stem cell self-renewal as well as in tumor development. However, the role of Notch signaling in breast cancer stem cells (CSC) remains to be determined. We utilized a lentiviral Notch reporter system to identify a subset of cells with a higher Notch activity (Notch(+)) or reduced activity (Notch(-)) in multiple breast cancer cell lines. Using in vitro and mouse xenotransplantation assays, we investigated the role of the Notch pathway in breast CSC regulation. Breast cancer cells with increased Notch activity displayed increased sphere formation as well as expression of breast CSC markers. Interestingly Notch(+) cells displayed higher Notch4 expression in both basal and luminal breast cancer cell lines. Moreover, Notch(+) cells demonstrated tumor initiation capacity at serial dilutions in mouse xenografts, whereas Notch(-) cells failed to generate tumors. γ-Secretase inhibitor (GSI), a Notch blocker but not a chemotherapeutic agent, effectively targets these Notch(+) cells in vitro and in mouse xenografts. Furthermore, elevated Notch4 and Hey1 expression in primary patient samples correlated with poor patient survival. Our study revealed a molecular mechanism for the role of Notch-mediated regulation of breast CSCs and provided a compelling rationale for CSC-targeted therapeutics.

  3. Upregulation of glycans containing 3' fucose in a subset of pancreatic cancers uncovered using fusion-tagged lectins.

    Science.gov (United States)

    Singh, Sudhir; Pal, Kuntal; Yadav, Jessica; Tang, Huiyuan; Partyka, Katie; Kletter, Doron; Hsueh, Peter; Ensink, Elliot; Kc, Birendra; Hostetter, Galen; Xu, H Eric; Bern, Marshall; Smith, David F; Mehta, Anand S; Brand, Randall; Melcher, Karsten; Haab, Brian B

    2015-06-05

    The fucose post-translational modification is frequently increased in pancreatic cancer, thus forming the basis for promising biomarkers, but a subset of pancreatic cancer patients does not elevate the known fucose-containing biomarkers. We hypothesized that such patients elevate glycan motifs with fucose in linkages and contexts different from the known fucose-containing biomarkers. We used a database of glycan array data to identify the lectins CCL2 to detect glycan motifs with fucose in a 3' linkage; CGL2 for motifs with fucose in a 2' linkage; and RSL for fucose in all linkages. We used several practical methods to test the lectins and determine the optimal mode of detection, and we then tested whether the lectins detected glycans in pancreatic cancer patients who did not elevate the sialyl-Lewis A glycan, which is upregulated in ∼75% of pancreatic adenocarcinomas. Patients who did not upregulate sialyl-Lewis A, which contains fucose in a 4' linkage, tended to upregulate fucose in a 3' linkage, as detected by CCL2, but they did not upregulate total fucose or fucose in a 2' linkage. CCL2 binding was high in cancerous epithelia from pancreatic tumors, including areas negative for sialyl-Lewis A and a related motif containing 3' fucose, sialyl-Lewis X. Thus, glycans containing 3' fucose may complement sialyl-Lewis A to contribute to improved detection of pancreatic cancer. Furthermore, the use of panels of recombinant lectins may uncover details about glycosylation that could be important for characterizing and detecting cancer.

  4. Altered Expression of Natural Cytotoxicity Receptors and NKG2D on Peripheral Blood NK Cell Subsets in Breast Cancer Patients

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    Nayeli Goreti Nieto-Velázquez

    2016-10-01

    Full Text Available Human natural killer (NK cells are considered professional cytotoxic cells that are integrated into the effector branch of innate immunity during antiviral and antitumoral responses. The purpose of this study was to examine the peripheral distribution and expression of NK cell activation receptors from the fresh peripheral blood mononuclear cells of 30 breast cancer patients prior to any form of treatment (including surgery, chemotherapy, and radiotherapy, 10 benign breast pathology patients, and 24 control individuals. CD3−CD56dimCD16bright NK cells (CD56dim NK and CD3−CD56brightCD16dim/− NK cells (CD56bright NK were identified using flow cytometry. The circulating counts of CD56dim and CD56bright NK cells were not significantly different between the groups evaluated, nor were the counts of other leukocyte subsets between the breast cancer patients and benign breast pathology patients. However, in CD56dim NK cells, NKp44 expression was higher in breast cancer patients (P = .0302, whereas NKp30 (P = .0005, NKp46 (P = .0298, and NKG2D (P = .0005 expression was lower with respect to healthy donors. In CD56bright NK cells, NKp30 (P = .0007, NKp46 (P = .0012, and NKG2D (P = .0069 expression was lower in breast cancer patients compared with control group. Only NKG2D in CD56bright NK cells (P = .0208 and CD56dim NK cells (P = .0439 showed difference between benign breast pathology and breast cancer patients. Collectively, the current study showed phenotypic alterations in activation receptors on CD56dim and CD56bright NK cells, suggesting that breast cancer patients have decreased NK cell cytotoxicity.

  5. A Vulnerability of a Subset of Colon Cancers with Potential Clinical Utility

    NARCIS (Netherlands)

    Vecchione, Loredana; Gambino, Valentina; Raaijmakers, Jonne; Schlicker, Andreas; Fumagalli, Arianna; Russo, Mariangela; Villanueva, Alberto; Beerling, Evelyne; Bartolini, Alice; Mollevi, David G; El-Murr, Nizar; Chiron, Marielle; Calvet, Loreley; Nicolazzi, Céline; Combeau, Cécile; Henry, Christophe; Simon, Iris M; Tian, Sun; In 't Veld, Sjors; D'ario, Giovanni; Mainardi, Sara; Beijersbergen, Roderick L; Lieftink, Cor; Linn, Sabine; Rumpf-Kienzl, Cornelia; Delorenzi, Mauro; Wessels, Lodewyk; Salazar, Ramon; Di Nicolantonio, Federica; Bardelli, Alberto; van Rheenen, Jacco; Medema, René H; Tejpar, Sabine; Bernards, René

    2016-01-01

    BRAF(V600E) mutant colon cancers (CCs) have a characteristic gene expression signature that is also found in some tumors lacking this mutation. Collectively, they are referred to as "BRAF-like" tumors and represent some 20% of CCs. We used a shRNA-based genetic screen focused on genes upregulated in

  6. Epidemiology of doublet/multiplet mutations in lung cancers: evidence that a subset arises by chronocoordinate events.

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    Zhenbin Chen

    Full Text Available BACKGROUND: Evidence strongly suggests that spontaneous doublet mutations in normal mouse tissues generally arise from chronocoordinate events. These chronocoordinate mutations sometimes reflect "mutation showers", which are multiple chronocoordinate mutations spanning many kilobases. However, little is known about mutagenesis of doublet and multiplet mutations (domuplets in human cancer. Lung cancer accounts for about 25% of all cancer deaths. Herein, we analyze the epidemiology of domuplets in the EGFR and TP53 genes in lung cancer. The EGFR gene is an oncogene in which doublets are generally driver plus driver mutations, while the TP53 gene is a tumor suppressor gene with a more typical situation in which doublets derive from a driver and passenger mutation. METHODOLOGY/PRINCIPAL FINDINGS: EGFR mutations identified by sequencing were collected from 66 published papers and our updated EGFR mutation database (www.egfr.org. TP53 mutations were collected from IARC version 12 (www-p53.iarc.fr. For EGFR and TP53 doublets, no clearly significant differences in race, ethnicity, gender and smoking status were observed. Doublets in the EGFR and TP53 genes in human lung cancer are elevated about eight- and three-fold, respectively, relative to spontaneous doublets in mouse (6% and 2.3% versus 0.7%. CONCLUSIONS/SIGNIFICANCE: Although no one characteristic is definitive, the aggregate properties of doublet and multiplet mutations in lung cancer are consistent with a subset derived from chronocoordinate events in the EGFR gene: i the eight frameshift doublets (present in 0.5% of all patients with EGFR mutations are clustered and produce a net in-frame change; ii about 32% of doublets are very closely spaced (< or =30 nt; and iii multiplets contain two or more closely spaced mutations. TP53 mutations in lung cancer are very closely spaced (< or =30 nt in 33% of doublets, and multiplets generally contain two or more very closely spaced mutations. Work in

  7. The Role of Biomaterials on Cancer Stem Cell Enrichment and Behavior

    Science.gov (United States)

    Ordikhani, Faride; Kim, Yonghyun; Zustiak, Silviya P.

    2015-11-01

    The theory of cancer stem cells (CSCs) and their role in cancer metastasis, tumorigenicity and resistance to therapy is slowly shifting the emphasis on the search for cancer cure: more evidence is surfacing that a successful therapy should be geared against this rare cancer cell population. Unfortunately, CSCs are difficult to culture in vitro which severely limits the progress of CSC research. This review gives a brief overview of CSCs and their microenvironment, with particular focus on studies that used in vitro biomaterial-based models and biomaterial/CSC interfaces for the enrichment of CSCs. Biomaterial properties relevant to CSC behaviors are also addressed. While the discussed research field is still in its infancy, it appears that in vitro cancer models that include a biomaterial can support CSC enrichment and this has proved indispensable to the study of their biology as well as the development of novel cancer therapies.

  8. Effect of Yunpi Huoxue soup combined chemotherapy on T lymphocyte subsets and nutritional status in patients with advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Yi-Jiao Huang; Pei Xiang; Wei-Min Zhu

    2016-01-01

    Objective:To observe the effect of Yunpi Huoxue soup combined with chemotherapy on T lymphocyte subsets and nutritional status in patients with advanced gastric cancer.Methods:A total of 94 cases patients with advanced gastric cancer were randomly divided into the treatment group (49 cases) and the control group (45 cases) according to the results of the draw. The control group was given chemotherapy, the treatment group was given Yunpi Huoxue soup on the basis of the control group. Treated for 6 weeks, observed the changes of T cell subsets (CD3, CD4, CD8 and CD4/CD8) and nutrition indexes: total protein (TP), albumin (ALB), prealbumin (PA) and transferrin (TRF) in the two groups.Results:After treatment, CD3, CD4, CD8 and CD4/CD8 in the treatment group were (57.38±4.03), (31.63±4.26), (30.82±3.52) and (1.16±0.20 ) respectively, there were no significant differences compared with before treatment; After treatment, the levels of CD3, CD4, CD8 and CD4/CD8 in the control group were significantly lower than those before treatment, and the differences were statistically significant; After treatment, the levels of CD3, CD4, CD8 and CD4/CD8 in the treatment group were significant higher than those in the control group after treatment, and the differences were statistically significant. After treatment, TP, ALB, PA and TRF in the treatment group were(54.22±5.93) g/L, (32.47±4.97) g/L, (2.52±0.43) g/L and (1.66±0.40) g/L respectively, there were no significant differences compared with before treatment; After treatment, the levels of TP, ALB, PA and TRF in the control group were significantly lower than those before treatment; After treatment, the levels of TP, ALB, PA and TRF in the treatment group were significant higher than those in the control group after treatment, and the differences were statistically significant.Conclusion:When chemotherapy for patients with advanced gastric cancer, Yunpi Huoxue soup is helpful to maintain the immune function and

  9. Sub-sets of cancer stem cells differ intrinsically in their patterns of oxygen metabolism.

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    Luke Gammon

    Full Text Available The glycolytic response of hypoxic cells is primarily mediated by the hypoxia inducible factor alpha (HIF-1α but even in the presence of abundant oxygen tumours typically show high rates of glycolysis. Higher levels of HIF-1α in tumours are associated with a poorer prognosis and up-regulation of markers of epithelial mesenchymal transition (EMT due to HIF-1α actions. We have recently shown that EMT occurs within the CD44(high cancer stem cell (CSC fraction and that epithelial and EMT CSCs are distinguished by high and low ESA expression, respectively. We here show that hypoxia induces a marked shift of the CSC fraction towards EMT leading to altered cell morphology, an increased proportion of CD44(high/ESA(low cells, patterns of gene expression typical of EMT, and enhanced sphere-forming ability. The size of EMT fractions returned to control levels in normoxia indicating a reversible process. Surprisingly, however, even under normoxic conditions a fraction of EMT CSCs was present and maintained high levels of HIF-1α, apparently due to actions of cytokines such as TNFα. Functionally, this EMT CSC fraction showed decreased mitochondrial mass and membrane potential, consumed far less oxygen per cell, and produced markedly reduced levels of reactive oxygen species (ROS. These differences in the patterns of oxygen metabolism of sub-fractions of tumour cells provide an explanation for the general therapeutic resistance of CSCs and for the even greater resistance of EMT CSCs. They also identify potential mechanisms for manipulation of CSCs.

  10. Xmrk, kras and myc transgenic zebrafish liver cancer models share molecular signatures with subsets of human hepatocellular carcinoma.

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    Weiling Zheng

    Full Text Available Previously three oncogene transgenic zebrafish lines with inducible expression of xmrk, kras or Myc in the liver have been generated and these transgenic lines develop oncogene-addicted liver tumors upon chemical induction. In the current study, comparative transcriptomic approaches were used to examine the correlation of the three induced transgenic liver cancers with human liver cancers. RNA profiles from the three zebrafish tumors indicated relatively small overlaps of significantly deregulated genes and biological pathways. Nevertheless, the three transgenic tumor signatures all showed significant correlation with advanced or very advanced human hepatocellular carcinoma (HCC. Interestingly, molecular signature from each oncogene-induced zebrafish liver tumor correlated with only a small subset of human HCC samples (24-29% and there were conserved up-regulated pathways between the zebrafish and correlated human HCC subgroup. The three zebrafish liver cancer models together represented nearly half (47.2% of human HCCs while some human HCCs showed significant correlation with more than one signature defined from the three oncogene-addicted zebrafish tumors. In contrast, commonly deregulated genes (21 up and 16 down in the three zebrafish tumor models generally showed accordant deregulation in the majority of human HCCs, suggesting that these genes might be more consistently deregulated in a broad range of human HCCs with different molecular mechanisms and thus serve as common diagnosis markers and therapeutic targets. Thus, these transgenic zebrafish models with well-defined oncogene-induced tumors are valuable tools for molecular classification of human HCCs and for understanding of molecular drivers in hepatocarcinogenesis in each human HCC subgroup.

  11. Treg/Th17 polarization by distinct subsets of breast cancer cells is dictated by the interaction with mesenchymal stem cells

    OpenAIRE

    Patel, Shyam A.; Dave, Meneka A.; Bliss, Sarah A.; Giec-Ujda, Agata B.; Bryan, Margarette; Pliner, Lillian F.; Rameshwar, Pranela

    2014-01-01

    Breast cancer (BC) cells (BCCs) exist within a hierarchy beginning with cancer stem cells (CSCs). Unsorted BCCs interact with mesenchymal stem cells (MSCs) to induce regulatory T cells (Tregs). This study investigated how distinct BCC subsets interacted with MSCs to polarize T-cell response, Tregs versus T helper 17 (Th17). This study tested BC initiating cells (CSCs) and the relatively more mature early and late BC progenitors. CSCs interacted with the highest avidity to MSCs. This interacti...

  12. ALCHEMIST: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials

    Science.gov (United States)

    ALCHEMIST represents three integrated, precision medicine trials that are designed to identify people with early-stage lung cancer who have tumors that harbor certain uncommon genetic changes and evaluate whether drug treatments targeted against those mol

  13. Cancer bioinformatics: detection of chromatin states,SNP-containing motifs, and functional enrichment modules

    Institute of Scientific and Technical Information of China (English)

    Xiaobo Zhou

    2013-01-01

    In this editorial preface,I briefly review cancer bioinformatics and introduce the four articles in this special issue highlighting important applications of the field:detection of chromatin states; detection of SNP-containing motifs and association with transcription factor-binding sites; improvements in functional enrichment modules; and gene association studies on aging and cancer.We expect this issue to provide bioinformatics scientists,cancer biologists,and clinical doctors with a better understanding of how cancer bioinformatics can be used to identify candidate biomarkers and targets and to conduct functional analysis.

  14. Enriched transcription factor signatures in triple negative breast cancer indicates possible targeted therapies with existing drugs

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    Scooter Willis

    2015-06-01

    Conclusion: With the increasing number of large sample size breast cancer cohorts, an exploratory analysis of genes that are consistently enriched in TN sharing common promoter motifs allows for the identification of possible therapeutic targets with extensive validation in patient derived data sets.

  15. The culture of cancer cell lines as tumorspheres does not systematically result in cancer stem cell enrichment.

    Science.gov (United States)

    Calvet, Christophe Y; André, Franck M; Mir, Lluis M

    2014-01-01

    Cancer stem cells (CSC) have raised great excitement during the last decade and are promising targets for an efficient treatment of tumors without relapses and metastases. Among the various methods that enable to enrich cancer cell lines in CSC, tumorspheres culture has been predominantly used. In this report, we attempted to generate tumorspheres from several murine and human cancer cell lines: B16-F10, HT-29, MCF-7 and MDA-MB-231 cells. Tumorspheres were obtained with variable efficiencies from all cell lines except from MDA-MB-231 cells. Then, we studied several CSC characteristics in both tumorspheres and adherent cultures of the B16-F10, HT-29 and MCF-7 cells. Unexpectedly, tumorspheres-forming cells were less clonogenic and, in the case of B16-F10, less proliferative than attached cells. In addition, we did not observe any enrichment in the population expressing CSC surface markers in tumorspheres from B16-F10 (CD133, CD44 and CD24 markers) or MCF-7 (CD44 and CD24 markers) cells. On the contrary, tumorspheres culture of HT-29 cells appeared to enrich in cells expressing colon CSC markers, i.e. CD133 and CD44 proteins. For the B16-F10 cell line, when 1 000 cells were injected in syngenic C57BL/6 mice, tumorspheres-forming cells displayed a significantly lower tumorigenic potential than adherent cells. Finally, tumorspheres culture of B16-F10 cells induced a down-regulation of vimentin which could explain, at least partially, the lower tumorigenicity of tumorspheres-forming cells. All these results, along with the literature, indicate that tumorspheres culture of cancer cell lines can induce an enrichment in CSC but in a cell line-dependent manner. In conclusion, extensive characterization of CSC properties in tumorspheres derived from any cancer cell line or cancer tissue must be performed in order to ensure that the generated tumorspheres are actually enriched in CSC.

  16. Role of epithelial-mesenchymal transition in the enrichment of colorectal cancer stem cells

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    Jia-ping CHENG

    2016-10-01

    Full Text Available Objective  To explore whether the enrichment of cancer stem cells (CSCs in colorectal cancer by suspension culture method is involved with epithelial-mesenchymal transition (EMT. Methods  3D microspheres were cultured by suspension culture method to human colorectal cancer SW620 cells. The 3D microspheres and SW620 cells were used as the research objects. To clarify whether 3D microspheres were enriched with CSCs, we made tumorigenicity experiments in NOD/SCID mice, soft agar cloning experiments, and detected the expression levels of cancer stem cells markers CD44 and Ep-CAM by flow cytometry or by Western blotting. The protein expression levels of EMT markers such as E-cadherin, N-cadherin and vimentin were detected by Western blotting. Results  Compared with the parental SW620 cells, colony formation in vitro (P<0.01 and tumorigenicity in NOD/SCID mice were significantly enhanced, the percentage of CD44-positive cells and Ep-CAM protein expression levels was significantly increased (P<0.01 in 3D microspheres. The protein expression level of epithelial marker E-cadherin was obviously increased (P<0.01, while the protein expression levels of mesenchymal markers N-cadherin and vimentin were significantly decreased (P<0.01. Conclusions  Colorectal cancer stem cells can be enriched by suspension culture method, and the process may be related to EMT. DOI: 10.11855/j.issn.0577-7402.2016.09.03

  17. Enrichment and Function Research of Large Cell Lung Cancer Stem Cell-like Cells

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    Wenke YUE

    2011-06-01

    Full Text Available Background and objective There are no universal method to recognize and screen for lung cancer stem cell markers and indicators. Commonly used methods are flow Cytometry and learning from other cancer stem cell sorting tags to sort lung cancer stem cells. But this method has low specificity screening, the workload is huge. In this study, Serum-free suspension culture was used to enrich lung cancer stem cells, and explore method for lung cancer stem cell screening. Methods Human large lung cancer cell line-L9981 was cultured in serum-free and growth factors added medium, and spheres were obtained. Then the morphological differences of sphere cells and adherent L9981 cells cultured in serum-containing mediums are observed. Cell proliferation was analyzed by Vi-cell viability analyzer; invasion ability was tested by transwell assay; and in vivo tumorigenicity of the two groups of cells was studied in nude mouse. Results Compared with adherent L9981 cells cultured in serum-containing mediums, cells cultured in serum-free medium display sphere appearance. Doubling time of adherent cells and sphere cells are (56.05±1.95 h and (33.00±1.44 h respectively; Spheroid cells had higher invasion and tumorigenicity ability, 5 times and 20 times respectively, than adherent cells. Conclusion Suspension cultured L9981 in Serum-free medium could form spheroid populations. Cells in spheres had higher ability of invasion and Tumorigenicity than adherent L9981 cells. These results indicated spheroid L9981 cells contained enriched lung cancer stem cells, and Serum-free suspension culture can be a candidate method for enriching lung cancer stem cell.

  18. Enrichment of breast cancer stem cells using a keratinocyte serum-free medium

    Institute of Scientific and Technical Information of China (English)

    LIU Zhen-zhen; CHEN Ping; LU Zhen-duo; CUI Shu-de; DONG Zi-ming

    2011-01-01

    Background Keratinocyte serum-free medium (K-SFM) is a defined medium used to support the growth of primary keratinocytes and embryonic stem cell. The aim of this research was to optimize enrichment of breast cancer stem cells (CSCs) using K-SFM.Methods A K-SFM was used to enrich CSCs from two breast cancer cell lines and a primary culture of breast cancer.RPMI-1640 supplemented with 10% fetal calf serum (FCS) was used as a control. CSCs were identified with flow cytometry using CD44+/CD24-as molecular markers. The expression of a variety of CSC markers (Oct-4, ABCG2, Nanog,N-cadherin, and E-cadherin) was analyzed with real-time PCR.Results Much higher percentage of CSCs was achieved with K-SFM: 17.3% for MCF-7 cells, 17.4% for SKBR-3, and 20.0% for primary breast cancer culture. Less than 1% CSC was achieved using RPMI-1640 supplemented with 10% FCS. In comparison to the CSCs obtained with RPMI-1640, CSCs in the K-SFM expressed higher levels of Oct-4,ABCG2, Nanog and N-cadherin, and lower level of E-cadherin.Conclusion K-SFM is an optimal culture medium to maintain and to enrich breast CSCs.

  19. Enriched environment housing enhances the sensitivity of mouse pancreatic cancer to chemotherapeutic agents.

    Science.gov (United States)

    Wu, Yufeng; Gan, Yu; Yuan, Hui; Wang, Qing; Fan, Yingchao; Li, Guohua; Zhang, Jian; Yao, Ming; Gu, Jianren; Tu, Hong

    2016-04-29

    Living in an enriched housing environment is an established model of eustress and has been consistently shown to reduce the growth of transplanted tumors, including pancreatic cancer. Here, we further investigate the influence of an enriched environment (EE) on the efficacy of chemotherapy in pancreatic cancer. Male C57BL/6 mice were housed in EE or standard environment (SE) conditions and transplanted with syngeneic Panc02 pancreatic cancer cells. Tumor-bearing mice were treated with 5-fluorouracil (5-FU) or gemcitabine (GEM) to examine their sensitivities to chemotherapy. The results showed that both 5-FU and GEM exerted the dose dependent inhibition of tumor growth. The tumor inhibition rates of low-dose 5-FU and GEM were improved from 17.7% and 23.6% to 46.3% and 49.9% by EE housing. Importantly, tumor cells isolated from the pancreatic cancer xenografts of EE mice had significantly enhanced sensitivities to both 5-FU and GEM (IC50 for 5-FU: 2.8 μM versus 27.3 μM; IC50 for GEM: 0.8 μM versus 5.0 μM). Furthermore, using microarray analyses, we identified the "ATP-binding cassette (ABC) transporter" that was overrepresented among EE-induced down-regulated genes in pancreatic cancer. Particularly, the tumoral expression of ABC transporter A8b (ABCA8b) was confirmed to be significantly decreased by EE. Over-expression of ABCA8b in mouse pancreatic cancer cells led to a marked decrease in the sensitivity to chemotherapeutic drugs both in vitro and in vivo. In conclusion, our data indicate that benign stressful stimulation can synergistically boost the efficiency of chemotherapeutics in pancreatic cancer, which suggests a novel strategy for adjuvant cancer therapy.

  20. The culture of cancer cell lines as tumorspheres does not systematically result in cancer stem cell enrichment.

    Directory of Open Access Journals (Sweden)

    Christophe Y Calvet

    Full Text Available Cancer stem cells (CSC have raised great excitement during the last decade and are promising targets for an efficient treatment of tumors without relapses and metastases. Among the various methods that enable to enrich cancer cell lines in CSC, tumorspheres culture has been predominantly used. In this report, we attempted to generate tumorspheres from several murine and human cancer cell lines: B16-F10, HT-29, MCF-7 and MDA-MB-231 cells. Tumorspheres were obtained with variable efficiencies from all cell lines except from MDA-MB-231 cells. Then, we studied several CSC characteristics in both tumorspheres and adherent cultures of the B16-F10, HT-29 and MCF-7 cells. Unexpectedly, tumorspheres-forming cells were less clonogenic and, in the case of B16-F10, less proliferative than attached cells. In addition, we did not observe any enrichment in the population expressing CSC surface markers in tumorspheres from B16-F10 (CD133, CD44 and CD24 markers or MCF-7 (CD44 and CD24 markers cells. On the contrary, tumorspheres culture of HT-29 cells appeared to enrich in cells expressing colon CSC markers, i.e. CD133 and CD44 proteins. For the B16-F10 cell line, when 1 000 cells were injected in syngenic C57BL/6 mice, tumorspheres-forming cells displayed a significantly lower tumorigenic potential than adherent cells. Finally, tumorspheres culture of B16-F10 cells induced a down-regulation of vimentin which could explain, at least partially, the lower tumorigenicity of tumorspheres-forming cells. All these results, along with the literature, indicate that tumorspheres culture of cancer cell lines can induce an enrichment in CSC but in a cell line-dependent manner. In conclusion, extensive characterization of CSC properties in tumorspheres derived from any cancer cell line or cancer tissue must be performed in order to ensure that the generated tumorspheres are actually enriched in CSC.

  1. Enrichment of cancer stem cell-like cells by culture in alginate gel beads.

    Science.gov (United States)

    Xu, Xiao-xi; Liu, Chang; Liu, Yang; Yang, Li; Li, Nan; Guo, Xin; Sun, Guang-wei; Ma, Xiao-jun

    2014-05-10

    Cancer stem cells (CSCs) are most likely the reason of cancer reoccurrence and metastasis. For further elucidation of the mechanism underlying the characteristics of CSCs, it is necessary to develop efficient culture systems to culture and expand CSCs. In this study, a three-dimensional (3D) culture system based on alginate gel (ALG) beads was reported to enrich CSCs. Two cell lines derived from different histologic origins were encapsulated in ALG beads respectively and the expansion of CSCs was investigated. Compared with two-dimensional (2D) culture, the proportion of cells with CSC-like phenotypes was significantly increased in ALG beads. Expression levels of CSC-related genes were greater in ALG beads than in 2D culture. The increase of CSC proportion after being cultured within ALG beads was further confirmed by enhanced tumorigenicity in vivo. Moreover, increased metastasis ability and higher anti-cancer drug resistance were also observed in 3D-cultured cells. Furthermore, we found that it was hypoxia, through the upregulation of hypoxia-inducible factors (HIFs) that occurred in ALG beads to induce the increasing of CSC proportion. Therefore, ALG bead was an efficient culture system for CSC enrichment, which might provide a useful platform for CSC research and promote the development of new anti-cancer therapies targeting CSCs.

  2. Systematic enrichment analysis of gene expression profiling studies identifies consensus pathways implicated in colorectal cancer development

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    Jesús Lascorz

    2011-01-01

    Full Text Available Background: A large number of gene expression profiling (GEP studies on colorectal carcinogenesis have been performed but no reliable gene signature has been identified so far due to the lack of reproducibility in the reported genes. There is growing evidence that functionally related genes, rather than individual genes, contribute to the etiology of complex traits. We used, as a novel approach, pathway enrichment tools to define functionally related genes that are consistently up- or down-regulated in colorectal carcinogenesis. Materials and Methods: We started the analysis with 242 unique annotated genes that had been reported by any of three recent meta-analyses covering GEP studies on genes differentially expressed in carcinoma vs normal mucosa. Most of these genes (218, 91.9% had been reported in at least three GEP studies. These 242 genes were submitted to bioinformatic analysis using a total of nine tools to detect enrichment of Gene Ontology (GO categories or Kyoto Encyclopedia of Genes and Genomes (KEGG pathways. As a final consistency criterion the pathway categories had to be enriched by several tools to be taken into consideration. Results: Our pathway-based enrichment analysis identified the categories of ribosomal protein constituents, extracellular matrix receptor interaction, carbonic anhydrase isozymes, and a general category related to inflammation and cellular response as significantly and consistently overrepresented entities. Conclusions: We triaged the genes covered by the published GEP literature on colorectal carcinogenesis and subjected them to multiple enrichment tools in order to identify the consistently enriched gene categories. These turned out to have known functional relationships to cancer development and thus deserve further investigation.

  3. Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer.

    Science.gov (United States)

    Park, So Yeon; Seo, An Na; Jung, Hae Yoen; Gwak, Jae Moon; Jung, Namhee; Cho, Nam-Yun; Kang, Gyeong Hoon

    2014-01-01

    The changes in DNA methylation status in cancer cells are characterized by hypermethylation of promoter CpG islands and diffuse genomic hypomethylation. Alu and long interspersed nucleotide element-1 (LINE-1) are non-coding genomic repetitive sequences and methylation of these elements can be used as a surrogate marker for genome-wide methylation status. This study was designed to evaluate the changes of Alu and LINE-1 hypomethylation during breast cancer progression from normal to pre-invasive lesions and invasive breast cancer (IBC), and their relationship with characteristics of IBC. We analyzed the methylation status of Alu and LINE-1 in 145 cases of breast samples including normal breast tissue, atypical ductal hyperplasia/flat epithelial atypia (ADH/FEA), ductal carcinoma in situ (DCIS) and IBC, and another set of 129 cases of IBC by pyrosequencing. Alu methylation showed no significant changes during multistep progression of breast cancer, although it tended to decrease during the transition from DCIS to IBC. In contrast, LINE-1 methylation significantly decreased from normal to ADH/FEA, while it was similar in ADH/FEA, DCIS and IBC. In IBC, Alu hypomethylation correlated with negative estrogen receptor (ER) status, and LINE-1 hypomethylation was associated with negative ER status, ERBB2 (HER2) amplification and p53 overexpression. Alu and LINE-1 methylation status was significantly different between breast cancer subtypes, and the HER2 enriched subtype had lowest methylation levels. In survival analyses, low Alu methylation status tended to be associated with poor disease-free survival of the patients. Our findings suggest that LINE-1 hypomethylation is an early event and Alu hypomethylation is probably a late event during breast cancer progression, and prominent hypomethylation of Alu and LINE-1 in HER2 enriched subtype may be related to chromosomal instability of this specific subtype.

  4. Breast Cancer Stem Cell Culture and Enrichment Using Poly(ε-Caprolactone Scaffolds

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    Sònia Palomeras

    2016-04-01

    Full Text Available The cancer stem cell (CSC population displays self-renewal capabilities, resistance to conventional therapies, and a tendency to post-treatment recurrence. Increasing knowledge about CSCs’ phenotype and functions is needed to investigate new therapeutic strategies against the CSC population. Here, poly(ε-caprolactone (PCL, a biocompatible polymer free of toxic dye, has been used to fabricate scaffolds, solid structures suitable for 3D cancer cell culture. It has been reported that scaffold cell culture enhances the CSCs population. A RepRap BCN3D+ printer and 3 mm PCL wire were used to fabricate circular scaffolds. PCL design and fabrication parameters were first determined and then optimized considering several measurable variables of the resulting scaffolds. MCF7 breast carcinoma cell line was used to assess scaffolds adequacy for 3D cell culture. To evaluate CSC enrichment, the Mammosphere Forming Index (MFI was performed in 2D and 3D MCF7 cultures. Results showed that the 60° scaffolds were more suitable for 3D culture than the 45° and 90° ones. Moreover, 3D culture experiments, in adherent and non-adherent conditions, showed a significant increase in MFI compared to 2D cultures (control. Thus, 3D cell culture with PCL scaffolds could be useful to improve cancer cell culture and enrich the CSCs population.

  5. The use of targeted and non-targeted advertising to enrich skin cancer screening samples.

    Science.gov (United States)

    Katris, P; Donovan, R J; Gray, B N

    1996-08-01

    The purpose of this study was to determine whether the risk factor profile of persons attending skin cancer screening clinics could be enriched by appropriate advertising prior to the screening events. Eleven screening clinics were held in eight rural and three suburban communities. Matched communities were randomly assigned to either a target or non-target condition. Targeted communities received an advertisement designed to attract high-risk individuals. The advertisement listed a number of risk factors and encouraged readers with one or more of the listed risk factors to attend the screening. Non-targeted communities received a general advertisement requesting individuals who felt they were at risk of skin cancer to attend the clinic. Risk factor profiles of all participants were measured on the factors listed in the targeted advertisement. The risk factor profiles of screenees and the referral rates for skin lesions requiring attention were significantly higher in the targeted communities than in the non-targeted communities. Lesions suspicious of malignant melanoma or Hutchinson's melanotic freckle also were higher, but not statistically significant, in the targeted communities. Population samples attending community-based skin cancer screening clinics can be enriched by appropriate targeted advertising prior to the screening events. This has important implications for determining the potential cost-effectiveness of population screening programmes.

  6. Photoablative dilution with pre-enrichment for the clonal isolation of rare cancer cells

    Science.gov (United States)

    Zordan, Michael D.; Leary, James F.

    2009-02-01

    The clonal isolation of rare cells, especially cancer and stem cells, in a population is important to cell biology. We have demonstrated that the Laser-Enabled Analysis and Processing (LEAP, Cyntellect Inc., San Diego, CA) instrument can be used to efficiently produce clones by photoablative dilution. The LEAP instrument performs automated fluorescence imaging and real-time image analysis to classify cells. The instrument also features a pulsed laser that gives it the ability to purify a sample by eliminating unwanted cells via laser ablation or UV-induced apoptosis. In photoablative dilution, rare cells are deposited into a multiwell plate at 10 cells per well. Then one cell is chosen to clone, and the other cells present in the well are eliminated by laser ablation. We have successfully used LEAP to produce single cell clones in 95% of wells (originally containing 5+/-2.1 cells/well). While photoablative dilution is a very effective way of producing clonal cultures, it has a fundamental limitation in the low number of cells that can be processed. This can be overcome by performing a pre-enrichment to increase the frequency of the rare cells to be cloned. Another enrichment strategy is flow cytometry based cell sorting. Flow sorting can provide greater than 104 fold enrichment and cells can be sorted directly into a multiwell plate. With pre-enrichment, photoablative dilution can be used to clonally isolate rare cells. This is especially important in cases where the total number of potentially rare cells recovered by first stage enrichment sorting is only 10-200 cells. Such a situation which would normally preclude second pass sorting for purity by the high-throughput first stage cell separation technology.

  7. Expression of DNA ligase IV is linked to poor prognosis and characterizes a subset of prostate cancers harboring TMPRSS2:ERG fusion and PTEN deletion.

    Science.gov (United States)

    Grupp, Katharina; Roettger, Laura; Kluth, Martina; Hube-Magg, Claudia; Simon, Ronald; Lebok, Patrick; Minner, Sarah; Tsourlakis, Maria Christina; Koop, Christina; Graefen, Markus; Adam, Meike; Haese, Alexander; Wittmer, Corinna; Sauter, Guido; Wilczak, Waldemar; Huland, Hartwig; Schlomm, Thorsten; Steurer, Stefan; Krech, Till

    2015-09-01

    DNA ligases are essential for the maintenance of genome integrity as they are indispensable for DNA replication, recombination and repair. The present study was undertaken to gain insights into the prevalence and clinical significance of ligase IV (LIG4) expression in prostate cancer. A total of 11,152 prostate cancer specimens were analyzed by immunohistochemistry for LIG4 expression. Results were compared to follow-up data, ERG status and deletions at PTEN, 3p13, 5q21 and 6q15. LIG4 expression was predominantly localized in the nucleus of the cells with increased intensities in malignant as compared to benign prostate epithelium. In prostate cancer, LIG4 expression was found in 91% of interpretable tumors, including 12% cancers with weak, 23% with moderate and 56% with strong LIG4 positivity. Strong LIG4 expression was tightly linked to advanced Gleason score (P<0.0001) and positive nodal involvement (P=0.03). There was a remarkable accumulation of strong LIG4 expression in tumors harboring TMPRSS2:ERG fusion and PTEN deletions (P<0.0001 each). High LIG4 expression was also tightly related to early biochemical recurrence when all tumors (P<0.0001) or the subsets of ERG-negative (P=0.0004) or ERG-positive prostate cancers (P=0.006) were analyzed. Multivariate analysis including parameters that are available before surgery demonstrated independent association with biochemical recurrence for advanced Gleason grade on biopsy, high preoperative PSA level, high clinical stage (P<0.0001 each) and for LIG4 immunostaining (P=0.03). Our study identifies LIG4 as a predictor of an increased risk for early PSA recurrence in prostate cancer. Moreover, the strong association with TMPRSS2:ERG fusion and PTEN deletions suggest important interactions between these pathways in prostate cancers.

  8. Dietary, lifestyle and clinicopathological factors associated with BRAF and K-ras mutations arising in distinct subsets of colorectal cancers in the EPIC Norfolk study

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    McTaggart Alison

    2010-03-01

    Full Text Available Abstract Background BRAF and K-ras proto-oncogenes encode components of the ERK signalling pathway and are frequently mutated in colorectal cancer. This study investigates the associations between BRAF and K-ras mutations and clinicopathological, lifestyle and dietary factors in colorectal cancers. Methods 186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for BRAF and K-ras mutations. Diet and lifestyle data were collected prospectively using seven day food diaries. Results BRAF V600E mutation was found in 15.6% of colorectal cancers but at higher frequencies in cancers with proximal location, poor differentiation and microsatellite instability (MSI (all p K-ras mutation (mostly in codons 12 and 13 was found in 22.0% of colorectal cancers but at higher frequencies in cancers of more advanced Dukes' stage (p = 0.001, microsatellite stable (MSS status (p = 0.002 and in individuals with lower blood high-density lipoprotein concentrations (p = 0.04. Analysis of dietary factors demonstrated no link between BRAF mutation and any specific dietary constituent, however, K-ras mutation was found at higher frequencies in individuals with higher white meat consumption (p K-ras were observed at higher frequencies in individuals consuming lower amounts of fruit (p = 0.02. Conclusion These data support the model of BRAF and K-ras mutations arising in distinct colorectal cancer subsets associated with different clinicopathological and dietary factors, acting as mutually exclusive mechanisms of activation of the same signalling pathway.

  9. Effect of different anesthesia and analgesia methods on theT lymphocyte subsets, cytokines and stress hormone level in patients with breast cancer surgery

    Institute of Scientific and Technical Information of China (English)

    Yan Ma; Xi-Qiang He; Geng Wang

    2015-01-01

    Objective: To explore the effect of different anesthesia and analgesia methods on the T lymphocyte subsets, cytokines and the levels of the stress hormone in patients with breast cancer surgery.Methods: 86 cases of breast cancer were divided into two groups by random digits table, control group of 43 cases with total intravenous anesthesia, and the observation group of 43 cases with total intravenous anesthesia combined with epidural anesthesia and postoperative underwent analgesia. The T lymphocyte subsets, cytokines and the levels of the stress hormone were detected before and after operation and compared. Results:CD3+, CD4+ and CD4+/CD8+ of the two groups at T1 or T2 were significantly lower than those at T0, and those in the observation group were significantly lower than the control group, and the difference between the two groups has statistical significance. IL-6, CRP and TNF-α levels of the two groups at T1, T2 or T3 were significantly higher than those at T0, and those in the observation group were significantly lower than the control group, and the difference between the two groups has statistical significance. Each index of two groups at T4 were restored to T0, and the differences were no statistically significant. The cortisol levels of two groups at T1 or T2 were significantly increased compared with T0, and the increase in the observation group was less than that of the control group, the difference between the two groups has statistical significance. The cortisol levels of two groups at T4 were restored to T0, and the differences were no statistically significant.Conclusion:Epidural analgesia after the intravenous anesthesia combined with epidural anesthesia for breast cancer cure patients has lighter immunosuppression and stress reaction, has less influence on inflammatory factors, is an ideal anesthesia and analgesia.

  10. The effect of TACE combined with tumor interstitial therapy on immune globulin, complement and T lymphocyte subsets in patients with liver cancer

    Institute of Scientific and Technical Information of China (English)

    Bu-Tian Li; Sheng-Ping Zhang

    2016-01-01

    Objective:To explore the effect of TACE combined with interstitial therapy on immune globulin, complement and T lymphocyte subsets in patients with liver cancer.Methods:A total of 95 patients with liver cancer from March 2013 to April 2015 in the hospital were selected, and they were randomly divided into group A (n = 47) and group B (n=48), patients in group A were given simple TACE treatment, while patients in group B underwent TACE + tumor interstitial therapy (percutaneous liver tumor injection of lipiodol chemotherapy). Immune globulin, complement and T lymphocyte subsets in peripheral blood preoperative 1w and postoperative 4w were observed.Results: After treatment, the lipiodol deposition rate, local control rate and tumor reduction rate of group B were significantly higher than that in group A, which had statistically significant difference between the two groups. Compared with that before treatment, CD3+, CD4+, CD4+/CD8+ were significantly increased, CD8+ was significantly decreased after treatment. There were significantly differences in CD3+, CD4+, CD4+/CD8+, CD8+ between the two groups after treatment. The immune globulin and complement levels increased in group A after treatment, but had no significant difference. Immunoglobulin and complement levels increased significantly in group B, there were significantly differences in immunoglobulin and complement levels in the two groups after treatment.Conclusions:The results showed that single TACE treatment in patients with liver cancer could enhance immune function, which had little effect on the humoral immunity. TACE combined with interstitial therapy could improve patients' cellular immunity and humoral immunity, which was benefit for prognosis.

  11. Liver cancer stem cells are selectively enriched by low-dose cisplatin

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    H. Zhang

    2014-06-01

    Full Text Available Accumulating evidence has indicated the importance of cancer stem cells in carcinogenesis. The goal of the present study was to determine the effect of low-dose cisplatin on enriched liver cancer stem cells (LCSCs. Human hepatoblastoma HepG2 cells were treated with concentrations of cisplatin ranging from 1 to 5 μg/mL. Cell survival and proliferation were evaluated using a tetrazolium dye (MTT assay. LCSCs were identified using specific markers, namely aldehyde dehydrogenase-1 (ALDH1 and CD133. The percentage of ALDH1+ or CD133+ cells was examined by flow cytometric analysis. The expression of ALDH1 and/or CD133 in HepG2 cells was determined by immunocytochemical analysis. Low-dose cisplatin treatment significantly decreased cell survival in HepG2 cells after 24 or 72 h. However, the percentage of LCSCs in the surviving cells was greatly increased. The percentage of ALDH1+ or CD133+ cells was increased in a time- and dose-dependent manner after treatment with 1-4 μg/mL cisplatin, whereas 5 μg/mL cisplatin exposure slightly reduced the number of positive cells. These findings indicate that low-dose cisplatin treatment may efficiently enrich the LCSC population in HepG2 cells.

  12. Functional prostate-specific membrane antigen is enriched in exosomes from prostate cancer cells.

    Science.gov (United States)

    Liu, Tiancheng; Mendes, Desiree E; Berkman, Clifford E

    2014-03-01

    Developing simple and effective approaches to detect tumor markers will be critical for early diagnosis or prognostic evaluation of prostate cancer treatment. Prostate‑specific membrane antigen (PSMA) has been validated as an important tumor marker for prostate cancer progression including angiogenesis and metastasis. As a type II membrane protein, PSMA can be constitutively internalized from the cell surface into endosomes. Early endosomes can fuse with multivesicular bodies (MVB) to form and secrete exosomes (40-100 nm) into the extracellular environment. Herein, we tested whether some of the endosomal PSMA could be transferred to exosomes as an extracellular resource for PSMA. Using PSMA-positive LNCaP cells, the secreted exosomes were collected and isolated from the cultured media. The vesicular structures of exosomes were identified by electron microscopy, and exosomal marker protein CD9 and tumor susceptibility gene (TSG 101) were confirmed by western blot analysis. Our present data demonstrate that PSMA can be enriched in exosomes, exhibiting a higher content of glycosylation and partial proteolysis in comparison to cellular PSMA. An in vitro enzyme assay further confirmed that exosomal PSMA retains functional enzymatic activity. Therefore, our data may suggest a new role for PSMA in prostate cancer progression, and provide opportunities for developing non-invasive approaches for diagnosis or prognosis of prostate cancer.

  13. Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci.

    Science.gov (United States)

    Coetzee, Simon G; Shen, Howard C; Hazelett, Dennis J; Lawrenson, Kate; Kuchenbaecker, Karoline; Tyrer, Jonathan; Rhie, Suhn K; Levanon, Keren; Karst, Alison; Drapkin, Ronny; Ramus, Susan J; Couch, Fergus J; Offit, Kenneth; Chenevix-Trench, Georgia; Monteiro, Alvaro N A; Antoniou, Antonis; Freedman, Matthew; Coetzee, Gerhard A; Pharoah, Paul D P; Noushmehr, Houtan; Gayther, Simon A

    2015-07-01

    Understanding the regulatory landscape of the human genome is a central question in complex trait genetics. Most single-nucleotide polymorphisms (SNPs) associated with cancer risk lie in non-protein-coding regions, implicating regulatory DNA elements as functional targets of susceptibility variants. Here, we describe genome-wide annotation of regions of open chromatin and histone modification in fallopian tube and ovarian surface epithelial cells (FTSECs, OSECs), the debated cellular origins of high-grade serous ovarian cancers (HGSOCs) and in endometriosis epithelial cells (EECs), the likely precursor of clear cell ovarian carcinomas (CCOCs). The regulatory architecture of these cell types was compared with normal human mammary epithelial cells and LNCaP prostate cancer cells. We observed similar positional patterns of global enhancer signatures across the three different ovarian cancer precursor cell types, and evidence of tissue-specific regulatory signatures compared to non-gynecological cell types. We found significant enrichment for risk-associated SNPs intersecting regulatory biofeatures at 17 known HGSOC susceptibility loci in FTSECs (P = 3.8 × 10(-30)), OSECs (P = 2.4 × 10(-23)) and HMECs (P = 6.7 × 10(-15)) but not for EECs (P = 0.45) or LNCaP cells (P = 0.88). Hierarchical clustering of risk SNPs conditioned on the six different cell types indicates FTSECs and OSECs are highly related (96% of samples using multi-scale bootstrapping) suggesting both cell types may be precursors of HGSOC. These data represent the first description of regulatory catalogues of normal precursor cells for different ovarian cancer subtypes, and provide unique insights into the tissue specific regulatory variation with respect to the likely functional targets of germline genetic susceptibility variants for ovarian cancer.

  14. Use of Aleuria alantia Lectin Affinity Chromatography to Enrich Candidate Biomarkers from the Urine of Patients with Bladder Cancer

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    Sarah R. Ambrose

    2015-09-01

    Full Text Available Developing a urine test to detect bladder tumours with high sensitivity and specificity is a key goal in bladder cancer research. We hypothesised that bladder cancer-specific glycoproteins might fulfill this role. Lectin-ELISAs were used to study the binding of 25 lectins to 10 bladder cell lines and serum and urine from bladder cancer patients and non-cancer controls. Selected lectins were then used to enrich glycoproteins from the urine of bladder cancer patients and control subjects for analysis by shotgun proteomics. None of the lectins showed a strong preference for bladder cancer cell lines over normal urothlelial cell lines or for urinary glycans from bladder cancer patients over those from non-cancer controls. However, several lectins showed a strong preference for bladder cell line glycans over serum glycans and are potentially useful for enriching glycoproteins originating from the urothelium in urine. Aleuria alantia lectin affinity chromatography and shotgun proteomics identified mucin-1 and golgi apparatus protein 1 as proteins warranting further investigation as urinary biomarkers for low-grade bladder cancer. Glycosylation changes in bladder cancer are not reliably detected by measuring lectin binding to unfractionated proteomes, but it is possible that more specific reagents and/or a focus on individual proteins may produce clinically useful biomarkers.

  15. The cancer-testis antigen NY-ESO-1 is highly expressed in myxoid and round cell subset of liposarcomas.

    Science.gov (United States)

    Hemminger, Jessica A; Ewart Toland, Amanda; Scharschmidt, Thomas J; Mayerson, Joel L; Kraybill, William G; Guttridge, Denis C; Iwenofu, O Hans

    2013-02-01

    Liposarcomas are a heterogenous group of fat-derived sarcomas, and surgery with or without chemoradiation therapy remains the main stay of treatment. NY-ESO-1 is a cancer-testis antigen expressed in various cancers where it can induce both cellular and humoral immunity. Immunotherapy has shown promise in clinical trials involving NY-ESO-1-expressing tumors. Gene expression studies have shown upregulation of the gene for NY-ESO-1, CTAG1B, in myxoid and round cell liposarcomas. Herein, we evaluated the expression of NY-ESO-1 among liposarcoma subtypes by quantitative real-time PCR, western blot analysis, and immunohistochemistry. Frozen tissue for quantitative real-time PCR and western blot analysis was obtained for the following liposarcoma subtypes (n=15): myxoid and round cell (n=8); well-differentiated (n=4), and dedifferentiated (n=3). Formalin-fixed paraffin-embedded blocks were obtained for the following liposarcoma subtypes (n=44): myxoid and round cell (n=18); well-differentiated (n=10); dedifferentiated (n=10); and pleomorphic (n=6). Full sections were stained with monoclonal antibody NY-ESO-1, and staining was assessed for intensity (1-3+), percentage of tumor positivity, and location. In all, 7/8 (88%) and 16/18 (89%) myxoid and round cell expressed CTAG1B and NY-ESO-1 by quantitative real-time PCR and immunohistochemistry, respectively. Western blot correlated with mRNA expression levels. By immunohistochemistry, 94% (15/16) of positive cases stained homogenously with 2-3+ intensity. Also, 3/6 (50%) pleomorphic liposarcomas demonstrated a range of staining: 1+ intensity in 50% of cells; 2+ intensity in 5% of cells; and 3+ intensity in 90% of cells. One case of dedifferentiated liposarcoma showed strong, diffuse staining (3+ intensity in 75% of cells). Our study shows that both CTAG1B mRNA and protein are overexpressed with high frequency in myxoid and round cell liposarcoma, enabling the potential use of targeted immunotherapy in the treatment of this

  16. Integrative Analysis of Gene Expression Data Including an Assessment of Pathway Enrichment for Predicting Prostate Cancer

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    Pingzhao Hu

    2006-01-01

    Full Text Available Background: Microarray technology has been previously used to identify genes that are differentially expressed between tumour and normal samples in a single study, as well as in syntheses involving multiple studies. When integrating results from several Affymetrix microarray datasets, previous studies summarized probeset-level data, which may potentially lead to a loss of information available at the probe-level. In this paper, we present an approach for integrating results across studies while taking probe-level data into account. Additionally, we follow a new direction in the analysis of microarray expression data, namely to focus on the variation of expression phenotypes in predefined gene sets, such as pathways. This targeted approach can be helpful for revealing information that is not easily visible from the changes in the individual genes. Results: We used a recently developed method to integrate Affymetrix expression data across studies. The idea is based on a probe-level based test statistic developed for testing for differentially expressed genes in individual studies. We incorporated this test statistic into a classic random-effects model for integrating data across studies. Subsequently, we used a gene set enrichment test to evaluate the significance of enriched biological pathways in the differentially expressed genes identified from the integrative analysis. We compared statistical and biological significance of the prognostic gene expression signatures and pathways identified in the probe-level model (PLM with those in the probeset-level model (PSLM. Our integrative analysis of Affymetrix microarray data from 110 prostate cancer samples obtained from three studies reveals thousands of genes significantly correlated with tumour cell differentiation. The bioinformatics analysis, mapping these genes to the publicly available KEGG database, reveals evidence that tumour cell differentiation is significantly associated with many

  17. Impact of fish oil enriched total parenteral nutrition on elderly patients after colorectal cancer surgery

    Institute of Scientific and Technical Information of China (English)

    ZHU Ming-wei; TANG Da-nian; HOU Jing; WEI Jun-min; HUA Bin; SUN Jian-hua; CUI Hong-yuan

    2012-01-01

    Background Polyunsaturated omega-3 fatty acids may beneficially influence healing processes and patient outcomes.The aim of this research was to study the clinical efficacy of fish oil enriched total parenteral nutrition in elderly patients after colorectal cancer surgery.Methods Fifty-seven elderly patients with colorectal cancer were enrolled in this prospective,randomized,double-blind,controlled clinical trial.All patients received isocaloric and isonitrogenous total parenteral nutrition by continuous infusion (20-24 hours per day) for seven days after surgery.The control group (n=28) received 1.2 g/kg soybean oil per day,whereas the treatment group (n=29) received 0.2 g/kg fish oil and 1.0 g/kg soybean oil per day.Blood samples were taken pre-operatively,and at days one and eight after the operation.The plasma levels of CD4,CD8,CD4/CD8,interleukin 6 (IL-6) and tumor necrosis factor a (TNF-a) were measured.Clinical outcomes were then analysed.Results Patient characteristics were comparable between the two groups.At day eight post-surgery,IL-6,TNF-α and CD8 titres were lower in the treatment group when compared to the control group; these results reached statistical significance.In the treatment group,there were fewer infectious complications and incidences of systemic inflammatory response syndrome (SIRS),and shorter lengths of hospital stay were observed.The total cost of medical care was comparable for the two groups.No serious adverse events occurred in either group.Conclusions Fish oil 0.2 g/kg per day administrated to elderly patients after colorectal surgery was safe and may shorten the length of hospital stay and improve clinical outcomes.

  18. Pros and cons of HaloPlex enrichment in cancer predisposition genetic diagnosis

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    Agnès Collet

    2015-12-01

    Full Text Available Panel sequencing is a practical option in genetic diagnosis. Enrichment and library preparation steps are critical in the diagnostic setting. In order to test the value of HaloPlex technology in diagnosis, we designed a custom oncogenetic panel including 62 genes. The procedure was tested on a training set of 71 controls and then blindly validated on 48 consecutive hereditary breast/ovarian cancer (HBOC patients tested negative for BRCA1/2 mutation. Libraries were sequenced on HiSeq2500 and data were analysed with our academic bioinformatics pipeline. Point mutations were detected using Varscan2, median size indels were detected using Pindel and large genomic rearrangements (LGR were detected by DESeq. Proper coverage was obtained. However, highly variable read depth was observed within genes. Excluding pseudogene analysis, all point mutations were detected on the training set. All indels were also detected using Pindel. On the other hand, DESeq allowed LGR detection but with poor specificity, preventing its use in diagnostics. Mutations were detected in 8% of BRCA1/2-negative HBOC cases. HaloPlex technology appears to be an efficient and promising solution for gene panel diagnostics. Data analysis remains a major challenge and geneticists should enhance their bioinformatics knowledge in order to ensure good quality diagnostic results.

  19. Subset Analysis of a Multicenter, Randomized Controlled Trial to Compare Magnifying Chromoendoscopy with Endoscopic Ultrasonography for Stage Diagnosis of Early Stage Colorectal Cancer.

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    Tomonori Yamada

    Full Text Available Our recent prospective study found equivalent accuracy of magnifying chromoendoscopy (MC and endoscopic ultrasonography (EUS for diagnosing the invasion depth of colorectal cancer (CRC; however, whether these tools show diagnostic differences in categories such as tumor size and morphology remains unclear. Hence, we conducted detailed subset analysis of the prospective data.In this multicenter, prospective, comparative trial, a total of 70 patients with early, flat CRC were enrolled from February 2011 to December 2012, and the results of 66 lesions were finally analyzed. Patients were randomly allocated to primary MC followed by EUS or to primary EUS followed by MC. Diagnoses of invasion depth by each tool were divided into intramucosal to slight submucosal invasion (invasion depth <1000 μm and deep submucosal invasion (invasion depth ≥1000 μm, and then compared with the final pathological diagnosis by an independent pathologist blinded to clinical data. To standardize diagnoses among examiners, this trial was started after achievement of a mean κ value of ≥0.6 which was calculated from the average of κ values between each pair of participating endoscopists.Both MC and EUS showed similar diagnostic outcomes, with no significant differences in prediction of invasion depth in subset analyses according to tumor size, location, and morphology. Lesions that were consistently diagnosed as Tis/T1-SMS or ≥T1-SMD with both tools revealed accuracy of 76-78%. Accuracy was low in borderline lesions with irregular pit pattern in MC and distorted findings of the third layer in EUS (MC, 58.5%; EUS, 50.0%.MC and EUS showed the same limited accuracy for predicting invasion depth in all categories of early CRC. Since the irregular pit pattern in MC, distorted findings to the third layer in EUS and inconsistent diagnosis between both tools were associated with low accuracy, further refinements or even novel methods are still needed for such lesions

  20. The anti-oncogenic influence of ellagic acid on colon cancer cells in leptin-enriched microenvironment.

    Science.gov (United States)

    Yousef, Amany I; El-Masry, Omar S; Yassin, Eman H

    2016-10-01

    Ellagic acid (EA) has been proposed as a promising candidate for therapeutic use in colon cancer. Investigation of the effectiveness of EA in a leptin-enriched model might have been given a little interest. Here in, we investigated the anti-tumor effect of EA in the presence of leptin to reflect on therapeutic use of EA in obesity-linked colon cancer. Proven effective in leptin-enriched microenvironment, EA inhibited cell proliferation of HCT-116 and CaCo-2 cell lines, modulated cell cycle, translocated Bax to the mitochondrial fraction of cells, activated caspase-8, and reduced PCNA expression. The current study findings cast a beam of light on the potential therapeutic use of EA in obesity-related colon carcinogenesis.

  1. Stem cell marker aldehyde dehydrogenase 1 (ALDH1)-expressing cells are enriched in triple-negative breast cancer.

    Science.gov (United States)

    Li, Huihui; Ma, Fei; Wang, Haijuan; Lin, Chen; Fan, Ying; Zhang, Xueyan; Qian, Haili; Xu, Binghe

    2013-12-17

    The stem cell marker ALDH1 has been of particular interest to scientists since it has been successfully used as a marker to isolate cancer stem cells from breast cancers. However, little is known, especially in Chinese breast cancer patients, on whether ALDH1 enrichment is prevalent in certain subtypes of breast cancer. In this study, we performed flow cytometry and immunohistochemistry to measure the expression of ALDH1 in 10 breast cancer cell lines and in a set of tissue microarrays consisting of 101 breast cancer tissues from the Chinese population. The 101 breast cancer tissues included 4 cancer subtypes defined on bases of their ER, PR, and HER2 statuses: triple-negative (25 cases), luminal A (33 cases), luminal B (16 cases) and HER2-overexpressing (HER2-OE, 27 cases). We found that ALDH1 was expressed in 25 of the 101 cases of breast cancer tissues. When the analysis was stratified, we found that the expression of ALDH1 varied significantly among the 4 subtypes, with a higher expression in triple-negative breast cancer (TNBC, p=0.003) than in the other 3 subtypes. In a series of breast cancer cell lines, we also confirmed that ALDH1 activity was mainly found in TNBC cell lines compared with non-TNBC ones (15.6% ± 2.45% vs 5.5% ± 2.58%, p=0.026). These data support the concept that the expression of ALDH1 is higher in TNBC than non-TNBC, which may be clinically meaningful for a better understanding of the poor prognosis of TNBC patients.

  2. Subset selection in regression

    CERN Document Server

    Miller, Alan

    2002-01-01

    Originally published in 1990, the first edition of Subset Selection in Regression filled a significant gap in the literature, and its critical and popular success has continued for more than a decade. Thoroughly revised to reflect progress in theory, methods, and computing power, the second edition promises to continue that tradition. The author has thoroughly updated each chapter, incorporated new material on recent developments, and included more examples and references. New in the Second Edition:A separate chapter on Bayesian methodsComplete revision of the chapter on estimationA major example from the field of near infrared spectroscopyMore emphasis on cross-validationGreater focus on bootstrappingStochastic algorithms for finding good subsets from large numbers of predictors when an exhaustive search is not feasible Software available on the Internet for implementing many of the algorithms presentedMore examplesSubset Selection in Regression, Second Edition remains dedicated to the techniques for fitting...

  3. Side population rather than CD133+ cells distinguishes enriched tumorigenicity in hTERT-immortalized primary prostate cancer cells

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    Wolcott Karen

    2011-09-01

    Full Text Available Abstract Background Subpopulations of cancer cells with the capacity of generating solid tumors have been characterized. In various cancer types, including prostate cancer cells, a side population (SP and CD133-expressing cells have been proposed as containing a population cancer cells with stem-like ability. Therefore the aim of this work was to determine, in prostate cancer cell lines, the frequency and tumorigenic potential of SP and CD133+ cells. Results In vitro 2D colony-forming assay and sphere-forming assay, Flow cytometry analysis and magnetic cell sorting were utilized to sort CD133+, CD133- and Side population (SP cells. Our findings indicate that CD44 and integrin α-6 are uniformly expressed in the hTERT cell lines; however, CD133 is expressed only in a small population (in vitro and in vivo. Additionally, for the hTERT cells, SP rather than CD133 expression showed an 8-fold enhanced tumorigenic potential. The data suggest that SP cells, rather than those with CD133 marker, contain the rare population of CSC capable of producing prostate tumors. Conclusion Collectively, our data suggest that although CD133 is expressed only in a small population of hTERT-immortalized prostate cancer cells, it is not likely to be associated with stem cells, as CD133- and CD133+ cells exhibited similar tumorigenicity. However, SP isolated cells, appear to be enriched with tumorigenic stem-like cells capable of generating palpable tumors.

  4. Thrombopoietin mobilizes CD34+ cell subsets into peripheral blood and expands multilineage progenitors in bone marrow of cancer patients with normal hematopoiesis.

    Science.gov (United States)

    Murray, L J; Luens, K M; Estrada, M F; Bruno, E; Hoffman, R; Cohen, R L; Ashby, M A; Vadhan-Raj, S

    1998-03-01

    Thrombopoietin (TPO), the primary regulator of megakaryocytopoiesis, also mediates biologic effects in vitro on hematopoietic cells more primitive than those committed to the megakaryocyte (MK) lineage. To assess the spectrum of hematopoietic effects of recombinant human (rh)TPO in vivo, we evaluated its proliferative effect on bone marrow (BM) progenitor cells, its maturation effect on BM MKs, and its mobilizing effect on peripheral blood (PB) progenitor cells during a phase I clinical laboratory investigation in which rhTPO was administered to cancer patients with normal hematopoiesis. Twelve patients received a single dose of rhTPO (0.3, 0.6, 1.2, or 2.4 microg/kg of body weight) prior to chemotherapy. BM and PB samples from these patients were analyzed 1 to 2 days before (baseline) and 7 days after rhTPO administration. At higher doses (1.2-2.4 microg/kg), rhTPO produced increased concentrations of primitive CD34+Thy-1+Lin-cells (mean 2.1-fold), CD34+mpl+ cells (mean 5.2-fold), CD34+CD41+CD14- promegakaryoblasts (mean 2.9-fold), and myeloerythroid colony-forming cells (mean threefold) in BM. No significant increases in the frequency of BM colony-forming unit (CFU)-MK were observed. Elevated numbers of both immature (2N-8N) and more mature (64N and 128N) CD41+ MKs were detected in BM, with modal ploidy remaining at 16N. Higher doses of rhTPO (1.2-2.4 microg/kg) also induced increased concentrations of CD34+ cell subsets in PB, including both primitive CD34+Thy-1+Lin- (mean 8.8-fold) and MK lineage-committed CD34+CD41+CD14- cells (mean 14.6-fold) as well as various myeloerythroid colony-forming cells (mean 3.6- to 5.5-fold). These results demonstrate that rhTPO given as a single dose not only promotes proliferation and maturation of cells of the MK lineage, but also expands the pool of BM primitive hematopoietic cells. In addition, rhTPO induces mobilization of hematopoietic progenitors into peripheral circulation. The extent to which such multilineage effects on

  5. Human bladder cancer stem cells exist in epithelial membrane antigen-subset%人膀胱癌干细胞存在于EMA-细胞亚群

    Institute of Scientific and Technical Information of China (English)

    杨宇明; 畅继武

    2008-01-01

    BACKGROUND:Cancer stem cell (CSC) hypothesis suggests that tumorous clones are maintained by a rare fraction of cells with stem cell proprieties. Several kinds of CSCs of solid tumor have been isolated in recent years. However, there have been fewer studies on the objective existence of bladder cancer stem cells (BCSCs) and on the methods to effectively isolate and identify BCSCs. OBJECTIVE:To investigate possibilities of BCSC existence and of epithelial membrane antigen (EMA) used as a surface marker of BCSC. DESIGN:A control observation experiment. SETTING:Tianjin Institute of Urinary Surgery & Second Hospital of Tianjin Medical University. MATERIALS:This study was performed at the Room for Tumor Immunity of Tianjin Institute of Urinary Surgery (key laboratory for State "211 Project") from March 2006 to July 2007. Nine specimens of human bladder were obtained from patients who received treatment in the Second Hospital of Tianjin Medical University. These specimens corresponded to the diagnostic criteria of low malignant potential papillary urothelial neoplasm and low-grade papillary urothelial carcinoma. Additionally, 40 samples of human low malignant bladder transitional cell carcinomas (BTCC) and 10 samples of normal urothelium that were used for immunohistochemistry were obtained from the patients who received treatment in the Department of Urinary Surgery, Second Hospital of Tianjin Medical University. Written informed consent for the specimen providing was obtained from the patients, and the protocol was approved by the hospital’s Ethics Committee. METHODS:The genes that were differentially expressed between normal urothelium and BTCC were identified through a DNA array assay to preliminarily determine the existence of BTCC. Overpressed stem cell related genes, Bmi-1 and EZH2, were verified by immunohistochemistry. A total of 27 potential surface markers of BCSCs were assayed to determine the location of positive cells. EMA- subsets were obtained through

  6. Enrichment of prostate cancer stem-like cells from human prostate cancer cell lines by culture in serum-free medium and chemoradiotherapy.

    Science.gov (United States)

    Wang, Lei; Huang, Xing; Zheng, Xinmin; Wang, Xinghuan; Li, Shiwen; Zhang, Lin; Yang, Zhonghua; Xia, Zhiping

    2013-01-01

    The discovery of rare subpopulations of cancer stem cells (CSCs) has created a new focus in cancer research. As CSCs demonstrate resistance to chemoradiation therapy relative to other cancer cells, this allows the enrichment of CSC populations by killing apoptosis-susceptible cancer cells. In this study, three commonly used human prostate cancer (PCa) cell lines (DU145, PC-3 and LNCaP) were examined for their expression of the putative stem cell markers CD133 and CD44 via flow cytometric analysis. Under normal culture conditions, CD133(+)/CD44(+) cells were only present in the DU145 cell line, and comprised only a minor percentage (0.1% ± 0.01%) of the total population. However, the proportion of these CD133(+)/CD44(+) prostate CSCs could be increased in these cell lines via culture in serum-free medium (SFM), or through chemotherapy or radiotherapy. Indeed, after culture in SFM, the proportion of CD133(+)/CD44(+) cells in DU145 and PC-3 had increased to 10.3% and 3.0%, respectively. Moreover, the proportion had increased to 9.8% enriched by chemotherapy and 3.5% by radiotherapy in DU145. Colony-formation tests, cell invasion assays, and tumor xenografts in BALB/c nude mice were used to evaluate the stem cell properties of CD133(+)/CD44(+) PCa cells that were isolated via fluorescence-activated cell sorting (FACS). CD133(+)/CD44(+) cells had an enhanced colony-formation capability and invasive ability in vitro, and displayed greater tumorigenic properties in vivo. These results demonstrate the presence of CD133(+)/CD44(+) prostate CSCs in established PCa cell lines and that populations of these cells can be enriched by culture in SFM or chemoradiotherapy. Finding novel therapies to override chemoradiation resistance in the prostate CSCs is the key to improve long-term results in PCa management.

  7. Krüppel-Like Factor 4 Acts as an Oncogene in Colon Cancer Stem Cell-Enriched Spheroid Cells

    Science.gov (United States)

    Xia, Qinghua; Tan, Jun; Yue, Zhongyi; Chen, Jinhuang; Xi, Hailin; Li, Jie; Zheng, Hai

    2013-01-01

    Cancer stem cells (CSCs), a rare population in any type of cancers, including colon cancer, are tumorigenic. It has been thought that CSCs are responsible for cancer recurrence, metastasis, and drug resistance. Isolating CSCs in colon cancers is challenging, and thus the molecular mechanism regulating the self-renewing and differentiation of CSCs remains unknown. We cultured DLD-1 cells, one of types of cells derived from colon cancers, in serum-free medium to obtain spheroid cells. These cells possessed the characteristics of CSCs, with the expression of CD133, CD166, Lgr5, and ALDH1, higher capacities of chemo-resistance, migration, invasion, and tumorigenicity in vitro and in vivo than the adherent DLD-1 cells. Krüppel-like factor 4 (KLF4) is essential factor for maintaining self-renewal of adult and embryonic stem cells. It has been used to induce pluripotent stem cells (iPS) from somatic cells. Since KLF4 is expressed in colon cancer cells, we investigated its role in spheroid cells isolated from DLD-1 cells and found that KLF4 was overexpressed only in spheroid cells and reducing the expression of KLF4 by short-hairpin RNA significantly decreased the capacities of these cells to resist the chemicals, migrate, invade, and generate tumors in vitro and in vivo. The spheroid cells with reduced KLF4 expression also had decreased expression of CSCs markers and mesenchymal markers. Taken together, culturing DLD-1 cells in serum-free medium enriches CSCs and the expression of KLF4 is essential for the characteristics of CSCs in DLD-1; thus KLF4 can be a potential therapeutic target for treating colon cancer. PMID:23418515

  8. Kruppel-like factor 4 acts as an oncogene in colon cancer stem cell-enriched spheroid cells.

    Directory of Open Access Journals (Sweden)

    Zhengwei Leng

    Full Text Available Cancer stem cells (CSCs, a rare population in any type of cancers, including colon cancer, are tumorigenic. It has been thought that CSCs are responsible for cancer recurrence, metastasis, and drug resistance. Isolating CSCs in colon cancers is challenging, and thus the molecular mechanism regulating the self-renewing and differentiation of CSCs remains unknown. We cultured DLD-1 cells, one of types of cells derived from colon cancers, in serum-free medium to obtain spheroid cells. These cells possessed the characteristics of CSCs, with the expression of CD133, CD166, Lgr5, and ALDH1, higher capacities of chemo-resistance, migration, invasion, and tumorigenicity in vitro and in vivo than the adherent DLD-1 cells. Krüppel-like factor 4 (KLF4 is essential factor for maintaining self-renewal of adult and embryonic stem cells. It has been used to induce pluripotent stem cells (iPS from somatic cells. Since KLF4 is expressed in colon cancer cells, we investigated its role in spheroid cells isolated from DLD-1 cells and found that KLF4 was overexpressed only in spheroid cells and reducing the expression of KLF4 by short-hairpin RNA significantly decreased the capacities of these cells to resist the chemicals, migrate, invade, and generate tumors in vitro and in vivo. The spheroid cells with reduced KLF4 expression also had decreased expression of CSCs markers and mesenchymal markers. Taken together, culturing DLD-1 cells in serum-free medium enriches CSCs and the expression of KLF4 is essential for the characteristics of CSCs in DLD-1; thus KLF4 can be a potential therapeutic target for treating colon cancer.

  9. Enriched environment inhibits mouse pancreatic cancer growth and down-regulates the expression of mitochondria-related genes in cancer cells.

    Science.gov (United States)

    Li, Guohua; Gan, Yu; Fan, Yingchao; Wu, Yufeng; Lin, Hechun; Song, Yanfang; Cai, Xiaojin; Yu, Xiang; Pan, Weihong; Yao, Ming; Gu, Jianren; Tu, Hong

    2015-01-19

    Psycho-social stress has been suggested to influence the development of cancer, but it remains poorly defined with regard to pancreatic cancer, a lethal malignancy with few effective treatment modalities. In this study, we sought to investigate the impacts of enriched environment (EE) housing, a rodent model of "eustress", on the growth of mouse pancreatic cancer, and to explore the potential underlying mechanisms through gene expression profiling. The EE mice showed significantly reduced tumor weights in both subcutaneous (53%) and orthotopic (41%) models, while each single component of EE (inanimate stimulation, social stimulation or physical exercise) was not profound enough to achieve comparative anti-tumor effects as EE. The integrative transcriptomic and proteomic analysis revealed that in response to EE, a total of 129 genes in the tumors showed differential expression at both the mRNA and protein levels. The differentially expressed genes were mostly localized to the mitochondria and enriched in the citrate cycle and oxidative phosphorylation pathways. Interestingly, nearly all of the mitochondria-related genes were down-regulated by EE. Our data have provided experimental evidence in favor of the application of positive stress or of benign environmental stimulation in pancreatic cancer therapy.

  10. Multifaceted enrichment analysis of RNA-RNA crosstalk reveals cooperating micro-societies in human colorectal cancer.

    Science.gov (United States)

    Mazza, Tommaso; Mazzoccoli, Gianluigi; Fusilli, Caterina; Capocefalo, Daniele; Panza, Anna; Biagini, Tommaso; Castellana, Stefano; Gentile, Annamaria; De Cata, Angelo; Palumbo, Orazio; Stallone, Raffaella; Rubino, Rosa; Carella, Massimo; Piepoli, Ada

    2016-05-19

    Alterations in the balance of mRNA and microRNA (miRNA) expression profiles contribute to the onset and development of colorectal cancer. The regulatory functions of individual miRNA-gene pairs are widely acknowledged, but group effects are largely unexplored. We performed an integrative analysis of mRNA-miRNA and miRNA-miRNA interactions using high-throughput mRNA and miRNA expression profiles obtained from matched specimens of human colorectal cancer tissue and adjacent non-tumorous mucosa. This investigation resulted in a hypernetwork-based model, whose functional backbone was fulfilled by tight micro-societies of miRNAs. These proved to modulate several genes that are known to control a set of significantly enriched cancer-enhancer and cancer-protection biological processes, and that an array of upstream regulatory analyses demonstrated to be dependent on miR-145, a cell cycle and MAPK signaling cascade master regulator. In conclusion, we reveal miRNA-gene clusters and gene families with close functional relationships and highlight the role of miR-145 as potent upstream regulator of a complex RNA-RNA crosstalk, which mechanistically modulates several signaling pathways and regulatory circuits that when deranged are relevant to the changes occurring in colorectal carcinogenesis.

  11. A novel method for sample preparation of fresh lung cancer tissue for proteomics analysis by tumor cell enrichment and removal of blood contaminants

    OpenAIRE

    Orre Lotta; Bergman Per; Elmberger Göran; Pernemalm Maria; De Petris Luigi; Lewensohn Rolf; Lehtiö Janne

    2010-01-01

    Abstract Background In-depth proteomics analyses of tumors are frequently biased by the presence of blood components and stromal contamination, which leads to large experimental variation and decreases the proteome coverage. We have established a reproducible method to prepare freshly collected lung tumors for proteomics analysis, aiming at tumor cell enrichment and reduction of plasma protein contamination. We obtained enriched tumor-cell suspensions (ETS) from six lung cancer cases (two ade...

  12. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.

    OpenAIRE

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C.; Sampson, Joshua N.; Hoskins, Jason W; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S.; Abnet, Christian C.; Adjei, Andrew A.

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based...

  13. Exosomes enriched in stemness/metastatic-related mRNAS promote oncogenic potential in breast cancer

    OpenAIRE

    2015-01-01

    Cancer cells efficiently transfer exosome contents (essentially mRNAs and microRNAs) to other cell types, modifying immune responses, cell growth, angiogenesis and metastasis. Here we analyzed the exosomes release by breast tumor cells with different capacities of stemness/metastasis based on CXCR4 expression, and evaluated their capacity to generate oncogenic features in recipient cells. Breast cancer cells overexpressing CXCR4 showed an increase in stemness-related markers, and in prolifera...

  14. DNA-methyltransferase 3B 39179 G > T polymorphism and risk of sporadic colorectal cancer in a subset of Iranian population

    Directory of Open Access Journals (Sweden)

    Abdolreza Daraei

    2011-01-01

    Full Text Available Background: Epigenetic event is a biological regulation that influences the expression of various genes involved in cancer. DNA methylation is established by DNA methyltransferases, particularly DNAmethyltransferase 3B (DNMT3B. It seems to play an oncogenic role in the creation of abnormal methylation during tumorigenesis. The polymorphisms of the DNMT3B gene may influence DNMT3B activity in DNA methylation and increase the susceptibility to several cancers. These genetic polymorphisms have been studied in several cancers in different populations. Methods: In this study, we performed a case-control study with 125 colorectal cancer patients and 135 cancer-free controls to evaluate the association between DNMT3B G39179T polymorphism (rs1569686 in the promoter region and the risk of sporadic colorectal cancer. Up to now, few studies have investigated the role of this gene variant in sporadic colorectal cancer with no familial history. The genotypes of DNMT3B G39179T polymorphism was analyzed by PCR-RFLP. Results: We found that compared with G allele carriers, statistically the DNMT3B TT genotype (%34 was significantly associated with increased risk of colorectal cancer (adjusted OR, 3.993, 95% CI, 1.726-9.238, P = 0.001. Compared with DNMT3B TT genotype, the GT and GG genotypes had lower risk of developing sporadic colorectal cancer (OR = 0.848, 95% CI = 0.436-1.650. Conclusions: Our findings were consistent with that of previously reported case-control studies with colorectal cancer. These results suggest that the DNMT3B G39179T polymorphism influences DNMT3B expression, thus contributing to the genetic susceptibility to colorectal cancer. Further mechanistic studies are needed to unravel the causal molecular mechanisms.

  15. Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population.

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    Kazuyo Yasuda

    Full Text Available Cancer stem-like cells (CSCs/cancer-initiaiting cells (CICs are defined as a small population of cancer cells that have self-renewal capacity, differentiation potential and high tumor-initiating ability. CSCs/CICs of ovarian cancer have been isolated by side population (SP analysis, ALDEFLUOR assay and using cell surface markers. However, these approaches are not definitive markers for CSCs/CICs, and it is necessary to refine recent methods for identifying more highly purified CSCs/CICs. In this study, we analyzed SP cells and aldehyde dehydrogenese bright (ALDH(Br cells from ovarian cancer cells. Both SP cells and ALDH(Br cells exhibited higher tumor-initiating ability and higher expression level of a stem cell marker, sex determining region Y-box 2 (SOX2, than those of main population (MP cells and ALDH(Low cells, respectively. We analyzed an SP and ALDH(Br overlapping population (SP/ALDH(Br, and the SP/ALDH(Br population exhibited higher tumor-initiating ability than that of SP cells or ALDH(Br cells, enabling initiation of tumor with as few as 10(2 cells. Furthermore, SP/ADLH(Br population showed higher sphere-forming ability, cisplatin resistance, adipocyte differentiation ability and expression of SOX2 than those of SP/ALDH(Low, MP/ALDH(Br and MP/ALDH(Low cells. Gene knockdown of SOX2 suppressed the tumor-initiation of ovarian cancer cells. An SP/ALDH(Br population was detected in several gynecological cancer cells with ratios of 0.1% for HEC-1 endometrioid adenocarcinoma cells to 1% for MCAS ovary mucinous adenocarcinoma cells. Taken together, use of the SP and ALDH(Br overlapping population is a promising approach to isolate highly purified CSCs/CICs and SOX2 might be a novel functional marker for ovarian CSCs/CICs.

  16. Low adherent cancer cell subpopulations are enriched in tumorigenic and metastatic epithelial-to-mesenchymal transition-induced cancer stem-like cells.

    Science.gov (United States)

    Morata-Tarifa, Cynthia; Jiménez, Gema; García, María A; Entrena, José M; Griñán-Lisón, Carmen; Aguilera, Margarita; Picon-Ruiz, Manuel; Marchal, Juan A

    2016-01-11

    Cancer stem cells are responsible for tumor progression, metastasis, therapy resistance and cancer recurrence, doing their identification and isolation of special relevance. Here we show that low adherent breast and colon cancer cells subpopulations have stem-like properties. Our results demonstrate that trypsin-sensitive (TS) breast and colon cancer cells subpopulations show increased ALDH activity, higher ability to exclude Hoechst 33342, enlarged proportion of cells with a cancer stem-like cell phenotype and are enriched in sphere- and colony-forming cells in vitro. Further studies in MDA-MB-231 breast cancer cells reveal that TS subpopulation expresses higher levels of SLUG, SNAIL, VIMENTIN and N-CADHERIN while show a lack of expression of E-CADHERIN and CLAUDIN, being this profile characteristic of the epithelial-to-mesenchymal transition (EMT). The TS subpopulation shows CXCL10, BMI-1 and OCT4 upregulation, differing also in the expression of several miRNAs involved in EMT and/or cell self-renewal such as miR-34a-5p, miR-34c-5p, miR-21-5p, miR-93-5p and miR-100-5p. Furthermore, in vivo studies in immunocompromised mice demonstrate that MDA-MB-231 TS cells form more and bigger xenograft tumors with shorter latency and have higher metastatic potential. In conclusion, this work presents a new, non-aggressive, easy, inexpensive and reproducible methodology to isolate prospectively cancer stem-like cells for subsequent biological and preclinical studies.

  17. Exome Enrichment and SOLiD Sequencing of Formalin Fixed Paraffin Embedded (FFPE) Prostate Cancer Tissue

    Science.gov (United States)

    Menon, Roopika; Deng, Mario; Boehm, Diana; Braun, Martin; Fend, Falko; Boehm, Detlef; Biskup, Saskia; Perner, Sven

    2012-01-01

    Next generation sequencing (NGS) technologies have revolutionized cancer research allowing the comprehensive study of cancer using high throughput deep sequencing methodologies. These methods detect genomic alterations, nucleotide substitutions, insertions, deletions and copy number alterations. SOLiD (Sequencing by Oligonucleotide Ligation and Detection, Life Technologies) is a promising technology generating billions of 50 bp sequencing reads. This robust technique, successfully applied in gene identification, might be helpful in detecting novel genes associated with cancer initiation and progression using formalin fixed paraffin embedded (FFPE) tissue. This study’s aim was to compare the validity of whole exome sequencing of fresh-frozen vs. FFPE tumor tissue by normalization to normal prostatic FFPE tissue, obtained from the same patient. One primary fresh-frozen sample, corresponding FFPE prostate cancer sample and matched adjacent normal prostatic tissue was subjected to exome sequencing. The sequenced reads were mapped and compared. Our study was the first to show comparable exome sequencing results between FFPE and corresponding fresh-frozen cancer tissues using SOLiD sequencing. A prior study has been conducted comparing the validity of sequencing of FFPE vs. fresh frozen samples using other NGS platforms. Our validation further proves that FFPE material is a reliable source of material for whole exome sequencing. PMID:22942743

  18. Exome Enrichment and SOLiD Sequencing of Formalin Fixed Paraffin Embedded (FFPE Prostate Cancer Tissue

    Directory of Open Access Journals (Sweden)

    Saskia Biskup

    2012-07-01

    Full Text Available Next generation sequencing (NGS technologies have revolutionized cancer research allowing the comprehensive study of cancer using high throughput deep sequencing methodologies. These methods detect genomic alterations, nucleotide substitutions, insertions, deletions and copy number alterations. SOLiD (Sequencing by Oligonucleotide Ligation and Detection, Life Technologies is a promising technology generating billions of 50 bp sequencing reads. This robust technique, successfully applied in gene identification, might be helpful in detecting novel genes associated with cancer initiation and progression using formalin fixed paraffin embedded (FFPE tissue. This study’s aim was to compare the validity of whole exome sequencing of fresh-frozen vs. FFPE tumor tissue by normalization to normal prostatic FFPE tissue, obtained from the same patient. One primary fresh-frozen sample, corresponding FFPE prostate cancer sample and matched adjacent normal prostatic tissue was subjected to exome sequencing. The sequenced reads were mapped and compared. Our study was the first to show comparable exome sequencing results between FFPE and corresponding fresh-frozen cancer tissues using SOLiD sequencing. A prior study has been conducted comparing the validity of sequencing of FFPE vs. fresh frozen samples using other NGS platforms. Our validation further proves that FFPE material is a reliable source of material for whole exome sequencing.

  19. Exosomes enriched in stemness/metastatic-related mRNAS promote oncogenic potential in breast cancer

    Science.gov (United States)

    Rodríguez, Marta; Silva, Javier; Herrera, Alberto; Herrera, Mercedes; Peña, Cristina; Martín, Paloma; Gil-Calderón, Beatriz; Larriba, María Jesús; Coronado, Mª José; Soldevilla, Beatriz; Turrión, Víctor S.; Provencio, Mariano; Sánchez, Antonio; Bonilla, Félix; García-Barberán, Vanesa

    2015-01-01

    Cancer cells efficiently transfer exosome contents (essentially mRNAs and microRNAs) to other cell types, modifying immune responses, cell growth, angiogenesis and metastasis. Here we analyzed the exosomes release by breast tumor cells with different capacities of stemness/metastasis based on CXCR4 expression, and evaluated their capacity to generate oncogenic features in recipient cells. Breast cancer cells overexpressing CXCR4 showed an increase in stemness-related markers, and in proliferation, migration and invasion capacities. Furthermore, recipient cells treated with exosomes from CXCR4-cells showed increased in the same abilities. Moreover, inoculation of CXCR4-cell-derived exosomes in immunocompromised mice stimulated primary tumor growth and metastatic potential. Comparison of nucleic acids contained into exosomes isolated from patients revealed a “stemness and metastatic” signature in exosomes of patients with worse prognosis. Finally, our data supported the view that cancer cells with stem-like properties show concomitant metastatic behavior, and their exosomes stimulate tumor progression and metastasis. Exosomes-derived nucleic acids from plasma of breast cancer patients are suitable markers in the prognosis of such patients. PMID:26528758

  20. Induction of apoptosis by (-)-gossypol-enriched cottonseed oil in human breast cancer cells

    Science.gov (United States)

    Induction of apoptosis is one of the mechanisms of chemotherapeutic agents against breast cancer. In addition, recent studies have shown that diets containing polyphenolic components possess anticancer activities either in vitro or in vivo by inhibiting cell proliferation and inducing apoptosis. T...

  1. Exosomes enriched in stemness/metastatic-related mRNAS promote oncogenic potential in breast cancer.

    Science.gov (United States)

    Rodríguez, Marta; Silva, Javier; Herrera, Alberto; Herrera, Mercedes; Peña, Cristina; Martín, Paloma; Gil-Calderón, Beatriz; Larriba, María Jesús; Coronado, M Josés; Soldevilla, Beatriz; Turrión, Víctor S; Provencio, Mariano; Sánchez, Antonio; Bonilla, Félix; García-Barberán, Vanesa

    2015-12-01

    Cancer cells efficiently transfer exosome contents (essentially mRNAs and microRNAs) to other cell types, modifying immune responses, cell growth, angiogenesis and metastasis. Here we analyzed the exosomes release by breast tumor cells with different capacities of stemness/metastasis based on CXCR4 expression, and evaluated their capacity to generate oncogenic features in recipient cells. Breast cancer cells overexpressing CXCR4 showed an increase in stemness-related markers, and in proliferation, migration and invasion capacities. Furthermore, recipient cells treated with exosomes from CXCR4-cells showed increased in the same abilities. Moreover, inoculation of CXCR4-cell-derived exosomes in immunocompromised mice stimulated primary tumor growth and metastatic potential. Comparison of nucleic acids contained into exosomes isolated from patients revealed a "stemness and metastatic" signature in exosomes of patients with worse prognosis. Finally, our data supported the view that cancer cells with stem-like properties show concomitant metastatic behavior, and their exosomes stimulate tumor progression and metastasis. Exosomes-derived nucleic acids from plasma of breast cancer patients are suitable markers in the prognosis of such patients.

  2. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

    Science.gov (United States)

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C.; Sampson, Joshua N.; Hoskins, Jason W.; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S.; Abnet, Christian C.; Adjei, Andrew A.; Ahlbom, Anders; Albanes, Demetrius; Allen, Naomi E.; Ambrosone, Christine B.; Aldrich, Melinda; Amiano, Pilar; Amos, Christopher; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L.; Arici, Cecilia; Arslan, Alan A.; Austin, Melissa A.; Baris, Dalsu; Barkauskas, Donald A.; Bassig, Bryan A.; Beane Freeman, Laura E.; Berg, Christine D.; Berndt, Sonja I.; Bertazzi, Pier Alberto; Biritwum, Richard B.; Black, Amanda; Blot, William; Boeing, Heiner; Boffetta, Paolo; Bolton, Kelly; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Brennan, Paul; Brinton, Louise A.; Brotzman, Michelle; Bueno-de-Mesquita, H. Bas; Buring, Julie E.; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Cao, Guangwen; Caporaso, Neil E.; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chang, Gee-Chen; Chang, I-Shou; Chang-Claude, Jenny; Che, Xu; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chung-Hsing; Chen, Constance; Chen, Kuan-Yu; Chen, Yuh-Min; Chokkalingam, Anand P.; Chu, Lisa W.; Clavel-Chapelon, Francoise; Colditz, Graham A.; Colt, Joanne S.; Conti, David; Cook, Michael B.; Cortessis, Victoria K.; Crawford, E. David; Cussenot, Olivier; Davis, Faith G.; De Vivo, Immaculata; Deng, Xiang; Ding, Ti; Dinney, Colin P.; Di Stefano, Anna Luisa; Diver, W. Ryan; Duell, Eric J.; Elena, Joanne W.; Fan, Jin-Hu; Feigelson, Heather Spencer; Feychting, Maria; Figueroa, Jonine D.; Flanagan, Adrienne M.; Fraumeni, Joseph F.; Freedman, Neal D.; Fridley, Brooke L.; Fuchs, Charles S.; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; Garcia-Closas, Reina; Gastier-Foster, Julie M.; Gaziano, J. Michael; Gerhard, Daniela S.; Giffen, Carol A.; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M.; Gonzalez, Carlos; Gorlick, Richard; Greene, Mark H.; Gross, Myron; Grossman, H. Barton; Grubb, Robert; Gu, Jian; Guan, Peng; Haiman, Christopher A.; Hallmans, Goran; Hankinson, Susan E.; Harris, Curtis C.; Hartge, Patricia; Hattinger, Claudia; Hayes, Richard B.; He, Qincheng; Helman, Lee; Henderson, Brian E.; Henriksson, Roger; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Hosgood, H. Dean; Hsiao, Chin-Fu; Hsing, Ann W.; Hsiung, Chao Agnes; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Hunter, David J.; Inskip, Peter D.; Ito, Hidemi; Jacobs, Eric J.; Jacobs, Kevin B.; Jenab, Mazda; Ji, Bu-Tian; Johansen, Christoffer; Johansson, Mattias; Johnson, Alison; Kaaks, Rudolf; Kamat, Ashish M.; Kamineni, Aruna; Karagas, Margaret; Khanna, Chand; Khaw, Kay-Tee; Kim, Christopher; Kim, In-Sam; Kim, Jin Hee; Kim, Yeul Hong; Kim, Young-Chul; Kim, Young Tae; Kang, Chang Hyun; Jung, Yoo Jin; Kitahara, Cari M.; Klein, Alison P.; Klein, Robert; Kogevinas, Manolis; Koh, Woon-Puay; Kohno, Takashi; Kolonel, Laurence N.; Kooperberg, Charles; Kratz, Christian P.; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C.; Kurucu, Nilgun; Lan, Qing; Lathrop, Mark; Lau, Ching C.; Lecanda, Fernando; Lee, Kyoung-Mu; Lee, Maxwell P.; Le Marchand, Loic; Lerner, Seth P.; Li, Donghui; Liao, Linda M.; Lim, Wei-Yen; Lin, Dongxin; Lin, Jie; Lindstrom, Sara; Linet, Martha S.; Lissowska, Jolanta; Liu, Jianjun; Ljungberg, Börje; Lloreta, Josep; Lu, Daru; Ma, Jing; Malats, Nuria; Mannisto, Satu; Marina, Neyssa; Mastrangelo, Giuseppe; Matsuo, Keitaro; McGlynn, Katherine A.; McKean-Cowdin, Roberta; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Meltzer, Paul S.; Mensah, James E.; Miao, Xiaoping; Michaud, Dominique S.; Mondul, Alison M.; Moore, Lee E.; Muir, Kenneth; Niwa, Shelley; Olson, Sara H.; Orr, Nick; Panico, Salvatore; Park, Jae Yong; Patel, Alpa V.; Patino-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H. M.; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Picci, Piero; Pike, Malcolm C.; Porru, Stefano; Prescott, Jennifer; Pu, Xia; Purdue, Mark P.; Qiao, You-Lin; Rajaraman, Preetha; Riboli, Elio; Risch, Harvey A.; Rodabough, Rebecca J.; Rothman, Nathaniel; Ruder, Avima M.; Ryu, Jeong-Seon; Sanson, Marc; Schned, Alan; Schumacher, Fredrick R.; Schwartz, Ann G.; Schwartz, Kendra L.; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D.; Severi, Gianluca; Shen, Hongbing; Shen, Min; Shete, Sanjay; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesumaga, Luis; Sierri, Sabina; Loon Sihoe, Alan Dart; Silverman, Debra T.; Simon, Matthias; Southey, Melissa C.; Spector, Logan; Spitz, Margaret; Stampfer, Meir; Stattin, Par; Stern, Mariana C.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael Z.; Stram, Daniel O.; Strom, Sara S.; Su, Wu-Chou; Sund, Malin; Sung, Sook Whan; Swerdlow, Anthony; Tan, Wen; Tanaka, Hideo; Tang, Wei; Tang, Ze-Zhang; Tardon, Adonina; Tay, Evelyn; Taylor, Philip R.; Tettey, Yao; Thomas, David M.; Tirabosco, Roberto; Tjonneland, Anne; Tobias, Geoffrey S.; Toro, Jorge R.; Travis, Ruth C.; Trichopoulos, Dimitrios; Troisi, Rebecca; Truelove, Ann; Tsai, Ying-Huang; Tucker, Margaret A.; Tumino, Rosario; Van Den Berg, David; Van Den Eeden, Stephen K.; Vermeulen, Roel; Vineis, Paolo; Visvanathan, Kala; Vogel, Ulla; Wang, Chaoyu; Wang, Chengfeng; Wang, Junwen; Wang, Sophia S.; Weiderpass, Elisabete; Weinstein, Stephanie J.; Wentzensen, Nicolas; Wheeler, William; White, Emily; Wiencke, John K.; Wolk, Alicja; Wolpin, Brian M.; Wong, Maria Pik; Wrensch, Margaret; Wu, Chen; Wu, Tangchun; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xiang, Yong-Bing; Xu, Jun; Yang, Hannah P.; Yang, Pan-Chyr; Yatabe, Yasushi; Ye, Yuanqing; Yeboah, Edward D.; Yin, Zhihua; Ying, Chen; Yu, Chong-Jen; Yu, Kai; Yuan, Jian-Min; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Zhou, Baosen; Mirabello, Lisa; Savage, Sharon A.; Kraft, Peter; Chanock, Stephen J.; Yeager, Meredith; Landi, Maria Terese; Shi, Jianxin; Chatterjee, Nilanjan; Amundadottir, Laufey T.

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10−39; Region 3: rs2853677, P = 3.30 × 10−36 and PConditional = 2.36 × 10−8; Region 4: rs2736098, P = 3.87 × 10−12 and PConditional = 5.19 × 10−6, Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10−6; and Region 6: rs10069690, P = 7.49 × 10−15 and PConditional = 5.35 × 10−7) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10−18 and PConditional = 7.06 × 10−16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. PMID:25027329

  3. ATP-binding cassette transporters are enriched in non-caveolar detergent-insoluble glycosphingolipid-enriched membrane domains (DIGs) in human multidrug-resistant cancer cells

    NARCIS (Netherlands)

    Hinrichs, JWJ; Klappe, K; Hummel, [No Value; Kok, JW

    2004-01-01

    In this study we show that P-glycoprotein in multi-drug-resistant 2780AD human ovarian carcinoma cells and multidrug resistance-associated protein 1 in multi-drug-resistant HT29(col) human colon carcinoma cells are predominantly located in Lubrol-based detergent-insoluble glycosphingolipid-enriched

  4. Exercise and nutrition routine improving cancer health (ENRICH: The protocol for a randomized efficacy trial of a nutrition and physical activity program for adult cancer survivors and carers

    Directory of Open Access Journals (Sweden)

    Boyes Allison

    2011-04-01

    Full Text Available Abstract Background The Exercise and Nutrition Routine Improving Cancer Health (ENRICH study is investigating a novel lifestyle intervention aimed at improving the health behaviors of adult cancer survivors and their carers. The main purpose of the study is to determine the efficacy of lifestyle education and skill development delivered via group-based sessions on the physical activity and dietary behaviors of participants. This article describes the intervention development, study design, and participant recruitment. Methods/Design ENRICH is a randomized controlled trial, conducted in Australia, with two arms: an intervention group participating in six, two-hour face-to-face sessions held over eight weeks, and a wait-list control group. Intervention sessions are co-facilitated by an exercise physiologist and dietician. Content includes healthy eating education, and a home-based walking (utilizing a pedometer and resistance training program (utilizing elastic tubing resistance devices. The program was developed with reference to social cognitive theory and chronic disease self-management models. The study population consists of cancer survivors (post active-treatment and their carers recruited through community-based advertising and referral from health professionals. The primary outcome is seven-days of sealed pedometry. Secondary outcomes include: self-reported physical activity levels, dietary intake, sedentary behavior, waist circumference, body mass index, quality of life, and perceived social support. The outcomes will be measured at baseline (one week prior to attending the program, eight-weeks (at completion of intervention sessions, and 20-weeks. The intervention group will also be invited to complete 12-month follow-up data collection. Process evaluation data will be obtained from participants by questionnaire and attendance records. Discussion No trials are yet available that have evaluated the efficacy of group-based lifestyle

  5. Phospholipase C isozymes are deregulated in colorectal cancer--insights gained from gene set enrichment analysis of the transcriptome.

    Directory of Open Access Journals (Sweden)

    Stine A Danielsen

    Full Text Available Colorectal cancer (CRC is one of the most common cancer types in developed countries. To identify molecular networks and biological processes that are deregulated in CRC compared to normal colonic mucosa, we applied Gene Set Enrichment Analysis to two independent transcriptome datasets, including a total of 137 CRC and ten normal colonic mucosa samples. Eighty-two gene sets as described by the Kyoto Encyclopedia of Genes and Genomes database had significantly altered gene expression in both datasets. These included networks associated with cell division, DNA maintenance, and metabolism. Among signaling pathways with known changes in key genes, the "Phosphatidylinositol signaling network", comprising part of the PI3K pathway, was found deregulated. The downregulated genes in this pathway included several members of the Phospholipase C protein family, and the reduced expression of two of these, PLCD1 and PLCE1, were successfully validated in CRC biopsies (n = 70 and cell lines (n = 19 by quantitative analyses. The repression of both genes was found associated with KRAS mutations (P = 0.005 and 0.006, respectively, and we observed that microsatellite stable carcinomas with reduced PLCD1 expression more frequently had TP53 mutations (P = 0.002. Promoter methylation analyses of PLCD1 and PLCE1 performed in cell lines and tumor biopsies revealed that methylation of PLCD1 can contribute to reduced expression in 40% of the microsatellite instable carcinomas. In conclusion, we have identified significantly deregulated pathways in CRC, and validated repression of PLCD1 and PLCE1 expression. This illustrates that the GSEA approach may guide discovery of novel biomarkers in cancer.

  6. Pathways enrichment analysis for differentially expressed genes in squamous lung cancer.

    Science.gov (United States)

    Qian, Liqiang; Luo, Qingquan; Zhao, Xiaojing; Huang, Jia

    2014-01-01

    Squamous lung cancer (SQLC) is a common type of lung cancer, but its oncogenesis mechanism is not so clear. The aim of this study was to screen the potential pathways changed in SQLC and elucidate the mechanism of it. Published microarray data of GSE3268 series was downloaded from Gene Expression Omnibus (GEO). Significance analysis of microarrays was performed using software R, and differentially expressed genes (DEGs) were harvested. The functions and pathways of DEGs were mapped in Gene Otology and KEGG pathway database, respectively. A total of 2961 genes were filtered as DEGs between normal and SQLC cells. Cell cycle and metabolism were the mainly changed functions of SQLC cells. Meanwhile genes such as MCM, RFC, FEN1, and POLD may induce SQLC through DNA replication pathway, and genes such as PTTG1, CCNB1, CDC6, and PCNA may be involved in SQLC through cell cycle pathway. It is demonstrated that pathway analysis is useful in the identification of target genes in SQLC.

  7. Bacteria-human somatic cell lateral gene transfer is enriched in cancer samples.

    Directory of Open Access Journals (Sweden)

    David R Riley

    Full Text Available There are 10× more bacterial cells in our bodies from the microbiome than human cells. Viral DNA is known to integrate in the human genome, but the integration of bacterial DNA has not been described. Using publicly available sequence data from the human genome project, the 1000 Genomes Project, and The Cancer Genome Atlas (TCGA, we examined bacterial DNA integration into the human somatic genome. Here we present evidence that bacterial DNA integrates into the human somatic genome through an RNA intermediate, and that such integrations are detected more frequently in (a tumors than normal samples, (b RNA than DNA samples, and (c the mitochondrial genome than the nuclear genome. Hundreds of thousands of paired reads support random integration of Acinetobacter-like DNA in the human mitochondrial genome in acute myeloid leukemia samples. Numerous read pairs across multiple stomach adenocarcinoma samples support specific integration of Pseudomonas-like DNA in the 5'-UTR and 3'-UTR of four proto-oncogenes that are up-regulated in their transcription, consistent with conversion to an oncogene. These data support our hypothesis that bacterial integrations occur in the human somatic genome and may play a role in carcinogenesis. We anticipate that the application of our approach to additional cancer genome projects will lead to the more frequent detection of bacterial DNA integrations in tumors that are in close proximity to the human microbiome.

  8. A modified method by differential adhesion for enrichment of bladder cancer stem cells

    Directory of Open Access Journals (Sweden)

    Yong-tong Zhu

    Full Text Available ABSTRACT Purpose: In a previous study the vaccine was effective against bladder cancer in a mouse model. However, a small portion of tumors regrew because the vaccine could not eliminate bladder cancer stem cells (CSCs. In this study, we showed a modified method for the isolation of bladder CSCs using a combination of differential adhesion method and serum-free culture medium (SFM method. Materials and Methods: Trypsin-resistant cells and trypsin-sensitive cells were isolated from MB49, EJ and 5637 cells by a combination of differential adhesion method and SFM method. The CSCs characterizations of trypsin-resistant cells were verified by the flow cytometry, the western blotting, the quantitative polymerase chain reaction, the resistance to chemotherapy assay, the transwell assay, and the tumor xenograft formation assay. Results: Trypsin-resistant cells were isolated and identified in CSCs characters, with high expression of CSCs markers, higher resistance to chemotherapy, greater migration in vitro, and stronger tumorigenicity in vivo. Conclusion: Trypsin-resistant cells displayed specific CSCs properties. Our study showed trypsin-resistant cells were isolated successfully with a modified method using a combination of differential adhesion method and SFM method.

  9. Increased CD4 and CD8-positive T cell infiltrate signifies good prognosis in a subset of triple-negative breast cancer.

    Science.gov (United States)

    Matsumoto, Hirofumi; Thike, Aye Aye; Li, Huihua; Yeong, Joe; Koo, Si-Lin; Dent, Rebecca Alexandra; Tan, Puay Hoon; Iqbal, Jabed

    2016-04-01

    Tumour-infiltrating lymphocytes (TILs) signify immune response to tumour in a variety of cancers including breast cancer. However, earlier studies examining the clinical significance of TILs in breast cancers have generated mixed results. There are only a few that address the relationship between TILs and clinical outcomes in triple-negative breast cancers (TNBC). The aim of this study is to evaluate the clinical significance of TILs that express CD4 + and CD8 + , in TNBC. Immunohistochemical staining of CD4 and CD8 was performed on tissue microarrays of 164 cases of TNBC. TILs were counted separately as intratumoral when within the cancer cell nests (iTILs) and as stromal when within cancer stroma (sTILs). High CD8 + iTILs and sTILs, and CD4 + iTILs correlated with histologic grade. On Kaplan-Meier analysis, a significantly better survival rate was observed in high CD8 + iTIL (disease-free survival, DFS: P = 0.004, overall survival, OS: P = 0.02) and both high CD4 + iTILs (DFS: P = 0.025, OS: P = 0.023) and sTILs (DFS: P = 0.01, OS: P = 0.002). In multivariate analysis, CD8 + iTILs (DFS: P = 0.0095), CD4 + sTILs (DFS: P = 0.0084; OS: P = 0.0118), and CD4 (high) CD8 (high) CD8 iTILs (DFS: P = 0.0121; OS: P = 0.0329) and sTILs (DFS: P = 0.0295) showed significantly better survival outcomes. These results suggest that high levels of both CD8 + iTILs and CD4 + sTILs as well as CD4 (high) CD8 (high) iTILs and sTILs are independent prognostic factors in TNBC.

  10. Cancer stem-like cells enriched with CD29 and CD44 markers exhibit molecular characteristics with epithelial-mesenchymal transition in squamous cell carcinoma.

    Science.gov (United States)

    Geng, Songmei; Guo, Yuanyuan; Wang, Qianqian; Li, Lan; Wang, Jianli

    2013-01-01

    Increasing evidences have indicated that only a phenotypic subset of cancer cells, termed as the cancer stem cells (CSCs), is capable of initiating tumor growth and provide a reservoir of cells that cause tumor recurrence after therapy. Epithelial-mesenchymal transition (EMT), a cell type change from an epithelial cobblestone phenotype to an elongated fibroblastic phenotype, plays a critical role not only in tumor metastasis but also in tumor recurrence and contributes to drug resistance. Accumulating evidence has shown that cells with an EMT phenotype are rich sources for CSCs, suggesting a biological link between EMT and CSCs; thus study on the link will help understand the cellular and molecular mechanisms of tumor metastasis and drug resistance. CD29 is involved in EMT through cross-talk with cadherins and CD44 has been reported as a successful used marker for CSCs. Here, we try to address whether combination of CD29 and CD44 could be used to identify cancer stem-like cells undergoing EMT in squamous cell carcinoma (SCC) and compare the molecular differences between CD29high/CD44high and CD29low/CD44low cells in SCC. Expression pattern of CD29 and CD44 was analyzed in tissues of skin SCC and cultured A431 cells by immunostaining. Subtype cells of CD29high/CD44high and CD29low/CD44low A431 were sorted by fluorescence-activated cell sorting and proliferating abilities were assayed by cell counting, colony forming and tumorigenicity in NOD/SCID mice. Finally, to probe more deeply into the molecular differences between CD29high/CD44high and CD29low/CD44low A431 cells, gene microarray analysis was applied to compare gene expression profiling. Staining of CD29 and CD44 showed similar heterogeneous expression pattern with positive cells located in the invasion front of SCC tissue as well as in cultured A431 cells. Sorted CD29high/CD44high A431 cells had higher proliferating ability in vitro and in NOD/SCID mice as compared with CD29low/CD44low cells. Gene profiling

  11. Prediction based on mean subset

    DEFF Research Database (Denmark)

    Øjelund, Henrik; Brown, P. J.; Madsen, Henrik;

    2002-01-01

    , it is found that the proposed mean subset method has superior prediction performance than prediction based on the best subset method, and in some settings also better than the ridge regression and lasso methods. The conclusions drawn from the Monte Carlo study is corroborated in an example in which prediction......Shrinkage methods have traditionally been applied in prediction problems. In this article we develop a shrinkage method (mean subset) that forms an average of regression coefficients from individual subsets of the explanatory variables. A Bayesian approach is taken to derive an expression of how...

  12. An Increase in N-Ras Expression is Associated with Development of Hormone Refractory Prostate Cancer in a Subset of Patients

    Directory of Open Access Journals (Sweden)

    Pamela Traynor

    2008-01-01

    Full Text Available Protein expression of H, K and N-Ras was assessed in hormone sensitive and hormone refractory prostate tumour pairs from 61 patients by immunohistochemistry. Expression of H-Ras and K- Ras was not associated with any known clinical parameters. In contrast an increase in N-Ras membrane expression in the transition from hormone sensitive to hormone refractory prostate cancer was associated with shorter time to relapse (p = 0.01 and shorter disease specific survival (p = 0.008. In addition, patients with an increase in N-Ras membrane expression had lower levels of PSA at relapse (p = 0.02 and expression correlated with phosphorylated MAP kinase (p = 0.010 and proliferation index (Ki67, p = 0.02. These results suggest that in a subgroup patients N-Ras expression is associated with development of hormone refractory prostate cancer via activation of the MAP kinase cascade.

  13. Identification of Distinct Breast Cancer Stem Cell Populations Based on Single-Cell Analyses of Functionally Enriched Stem and Progenitor Pools

    Directory of Open Access Journals (Sweden)

    Nina Akrap

    2016-01-01

    Full Text Available The identification of breast cancer cell subpopulations featuring truly malignant stem cell qualities is a challenge due to the complexity of the disease and lack of general markers. By combining extensive single-cell gene expression profiling with three functional strategies for cancer stem cell enrichment including anchorage-independent culture, hypoxia, and analyses of low-proliferative, label-retaining cells derived from mammospheres, we identified distinct stem cell clusters in breast cancer. Estrogen receptor (ERα+ tumors featured a clear hierarchical organization with switch-like and gradual transitions between different clusters, illustrating how breast cancer cells transfer between discrete differentiation states in a sequential manner. ERα− breast cancer showed less prominent clustering but shared a quiescent cancer stem cell pool with ERα+ cancer. The cellular organization model was supported by single-cell data from primary tumors. The findings allow us to understand the organization of breast cancers at the single-cell level, thereby permitting better identification and targeting of cancer stem cells.

  14. Anti-protozoal and anti-bacterial antibiotics that inhibit protein synthesis kill cancer subtypes enriched for stem cell-like properties.

    Science.gov (United States)

    Cuyàs, Elisabet; Martin-Castillo, Begoña; Corominas-Faja, Bruna; Massaguer, Anna; Bosch-Barrera, Joaquim; Menendez, Javier A

    2015-01-01

    Key players in translational regulation such as ribosomes might represent powerful, but hitherto largely unexplored, targets to eliminate drug-refractory cancer stem cells (CSCs). A recent study by the Lisanti group has documented how puromycin, an old antibiotic derived from Streptomyces alboniger that inhibits ribosomal protein translation, can efficiently suppress CSC states in tumorspheres and monolayer cultures. We have used a closely related approach based on Biolog Phenotype Microarrays (PM), which contain tens of lyophilized antimicrobial drugs, to assess the chemosensitivity profiles of breast cancer cell lines enriched for stem cell-like properties. Antibiotics directly targeting active sites of the ribosome including emetine, puromycin and cycloheximide, inhibitors of ribosome biogenesis such as dactinomycin, ribotoxic stress agents such as daunorubicin, and indirect inhibitors of protein synthesis such as acriflavine, had the largest cytotoxic impact against claudin-low and basal-like breast cancer cells. Thus, biologically aggressive, treatment-resistant breast cancer subtypes enriched for stem cell-like properties exhibit exacerbated chemosensitivities to anti-protozoal and anti-bacterial antibiotics targeting protein synthesis. These results suggest that old/existing microbicides might be repurposed not only as new cancer therapeutics, but also might provide the tools and molecular understanding needed to develop second-generation inhibitors of ribosomal translation to eradicate CSC traits in tumor tissues.

  15. Anti-protozoal and anti-bacterial antibiotics that inhibit protein synthesis kill cancer subtypes enriched for stem cell-like properties

    Science.gov (United States)

    Cuyàs, Elisabet; Martin-Castillo, Begoña; Corominas-Faja, Bruna; Massaguer, Anna; Bosch-Barrera, Joaquim; Menendez, Javier A

    2015-01-01

    Key players in translational regulation such as ribosomes might represent powerful, but hitherto largely unexplored, targets to eliminate drug-refractory cancer stem cells (CSCs). A recent study by the Lisanti group has documented how puromycin, an old antibiotic derived from Streptomyces alboniger that inhibits ribosomal protein translation, can efficiently suppress CSC states in tumorspheres and monolayer cultures. We have used a closely related approach based on Biolog Phenotype Microarrays (PM), which contain tens of lyophilized antimicrobial drugs, to assess the chemosensitivity profiles of breast cancer cell lines enriched for stem cell-like properties. Antibiotics directly targeting active sites of the ribosome including emetine, puromycin and cycloheximide, inhibitors of ribosome biogenesis such as dactinomycin, ribotoxic stress agents such as daunorubicin, and indirect inhibitors of protein synthesis such as acriflavine, had the largest cytotoxic impact against claudin-low and basal-like breast cancer cells. Thus, biologically aggressive, treatment-resistant breast cancer subtypes enriched for stem cell-like properties exhibit exacerbated chemosensitivities to anti-protozoal and anti-bacterial antibiotics targeting protein synthesis. These results suggest that old/existing microbicides might be repurposed not only as new cancer therapeutics, but also might provide the tools and molecular understanding needed to develop second-generation inhibitors of ribosomal translation to eradicate CSC traits in tumor tissues. PMID:25970790

  16. Effect of endostar combined with paclitaxel liposome and radiotherapy simultaneously on serum CYFRA21-1, CEA, SCCA, CA125, IL-8 and T lymphocyte subsets in patients with advanced cervical cancer

    Institute of Scientific and Technical Information of China (English)

    Wen-Jing Yang; Lu Wang

    2016-01-01

    Objective:To study the effect of endostar combined with paclitaxel liposome and radiotherapy simultaneously on serum CYFRA21-1, CEA, SCCA, CA125, IL-8 and T lymphocyte subsets in patients with advanced cervical cancer.Methods:A total of 72 patients with advanced cervical cancer in our hospital from January 2014 to February 2016 were enrolled in this study. The subjects were divided into control group (n=36) and experiment group (n=36) randomly. The control group were treated with radiotherapy, the experiment group were treated with endostar combined with paclitaxel liposome and radiotherapy simultaneously. 3 weeks for a period of treatment and the two groups were treated for 4 periods. The serum CYFRA21-1, CEA, SCCA, CA125, IL-8 levels and peripheral blood CD3+, CD4+ and CD8+ cells of the two groups before and after treatment were compared.Results:There were no significantly differences of the serum CYFRA21-1, CEA, SCCA, CA125, IL-8 levels and peripheral blood CD3+, CD4+ and CD8+ cells of the two groups before treatment. The serum CYFRA21-1, CEA, SCCA, CA125 and IL-8 levels of the two groups after treatment were significantly lower than before treatment, and that of experiment were significantly lower than control group. The peripheral blood CD3+, CD4+ cells of the two groups after treatment were significantly lower than before treatment, CD8+ cells of the two groups after treatment were significantly higher than before treatment, and that of experiment group were significantly better than control group.Conclusion: Endostar combined with paclitaxel liposome and radiotherapy simultaneously can significantly reduce the serum CYFRA21-1, CEA, SCCA, CA125 and IL-8 levels, improve peripheral blood CD3+, CD4+ and CD8+ levels of patients with advanced cervical cancer, and it was worthy clinical application.

  17. Effect of paclitaxel liposome combined with nedaplatin on serum HE4, CA125, CA19-9, AFP, CEA and T lymphocyte subsets in patients with advanced ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Su-Yu Zhu; Jie Tan; Chen-Lu Zhang; Qun-Ying Wu; Xue-Xin Xie; Hua-Fang Yin

    2016-01-01

    Objective:To study the effect of paclitaxel liposome combined with nedaplatin on serum HE4, CA125, CA19-9, AFP, CEA and T lymphocyte subsets in patients with advanced ovarian cancer.Methods:A total of 80 patients with advanced ovarian cancer in our hospital from December 2012 to December 2015 were enrolled in this study. The subjects were divided into control group (n=40) and experiment group (n=40) randomly. The control group were treated with paclitaxel and cisplatin, the experiment group were treated with paclitaxel liposome combined with nedaplatin. 21 days for a period of treatment and the two groups were treated for 3 periods. The serum HE4, CA125, CA19-9, AFP, CEA levels and peripheral blood CD3+, CD4+, CD8+ and NK cells of the two groups before and after treatment were compared. Results:There were no significantly differences of the serum HE4, CA125, CA19-9, AFP, CEA level and peripheral blood CD3+, CD4+, CD8+ and NK cells of the two groups before treatment (P>0.05). The serum HE4, CA125, CA19-9, AFP and CEA level of the two groups after treatment were significantly lower than before treatment (P<0.05), and that of experiment were significantly lower than control group (P<0.05). The peripheral blood CD3+, CD4+, CD8+and NK cells of the two groups after treatment were significantly lower than before treatment (P<0.05), and that of experiment were significantly higher than control group (P<0.05). Conclusions:Paclitaxel liposome combined with nedaplatin can significantly reduce the serum HE4, CA125, CA19-9, AFP and CEA levels, improve peripheral blood CD3+, CD4+, CD8+ and NK levels of patients with advanced ovarian cancer, and it was worthy clinical application.

  18. Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells

    Directory of Open Access Journals (Sweden)

    Kim Yoon-Keun

    2009-11-01

    Full Text Available Abstract Background Various cancer cells, including those of colorectal cancer (CRC, release microvesicles (exosomes into surrounding tissues and peripheral circulation. These microvesicles can mediate communication between cells and affect various tumor-related processes in their target cells. Results We present potential roles of CRC cell-derived microvesicles in tumor progression via a global comparative microvesicular and cellular transcriptomic analysis of human SW480 CRC cells. We first identified 11,327 microvesicular mRNAs involved in tumorigenesis-related processes that reflect the physiology of donor CRC cells. We then found 241 mRNAs enriched in the microvesicles above donor cell levels, of which 27 were involved in cell cycle-related processes. Network analysis revealed that most of the cell cycle-related microvesicle-enriched mRNAs were associated with M-phase activities. The integration of two mRNA datasets showed that these M-phase-related mRNAs were differentially regulated across CRC patients, suggesting their potential roles in tumor progression. Finally, we experimentally verified the network-driven hypothesis by showing a significant increase in proliferation of endothelial cells treated with the microvesicles. Conclusion Our study demonstrates that CRC cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells, suggesting that microvesicles of cancer cells can be involved in tumor growth and metastasis by facilitating angiogenesis-related processes. This information will help elucidate the pathophysiological functions of tumor-derived microvesicles, and aid in the development of cancer diagnostics, including colorectal cancer.

  19. Metabolic response to feeding in weight-losing pancreatic cancer patients and its modulation by a fish-oil-enriched nutritional supplement.

    Science.gov (United States)

    Barber, M D; McMillan, D C; Preston, T; Ross, J A; Fearon, K C

    2000-04-01

    Weight-losing patients with advanced cancer often fail to gain weight with conventional nutritional support. This suboptimal response might be explained, in part, by an increased metabolic response to feeding. It has been suggested that eicosapentaenoic acid (EPA) can modify beneficially the metabolic response to cancer. The aim of the present study was to examine the metabolic response to feeding in cancer and the effects of an EPA-enriched oral food supplement on this response. A total of 16 weight-losing, non-diabetic patients with unresectable pancreatic adenocarcinoma and six healthy, weight-stable controls were studied by indirect calorimetry in the fasting and fed states. Body composition was estimated by bioimpedence analysis. Cancer patients were then given a fish-oil-enriched nutritional supplement providing 2 g of EPA and 2550 kJ daily, and underwent repeat metabolic study after 3 weeks of such supplementation. At baseline, resting energy expenditure whether expressed per kg body weight, lean body mass or body cell mass was significantly greater in the cancer patients compared with controls. Fat oxidation was significantly higher in the fasting state in cancer patients [median 1.26 g.kg(-1).min(-1) (interquartile range 0.95-1.38)] than in controls [0.76 g.kg(-1). min(-1) (0.62-0.92); Pfeeding period, changes in insulin and glucose concentrations in cancer patients suggested relative glucose intolerance. In response to oral meal feeding, the percentage change in the area under the curve of energy expenditure was significantly lower in the cancer patients [median 7.9% (interquartile range 3.4-9.0)] than in controls [12.6% (9.9-15.1); Ppatients had increased and the energy expenditure in response to feeding had risen significantly [9.6% (6. 3-12.4)], such that it was no different from baseline healthy control values. Similarly, fasting fat oxidation fell to 1.02 g. kg(-1).min(-1) (0.8-1.18), again no longer significantly different from baseline healthy

  20. Loss of post-transcriptional regulation of DNMT3b by microRNAs: a possible molecular mechanism for the hypermethylation defect observed in a subset of breast cancer cell lines.

    Science.gov (United States)

    Sandhu, Rupninder; Rivenbark, Ashley G; Coleman, William B

    2012-08-01

    A hypermethylation defect associated with DNMT hyperactivity and DNMT3b overexpression characterizes a subset of breast cancers and breast cancer cell lines. We analyzed breast cancer cell lines for differential expression of regulatory miRs to determine if loss of miR-mediated post-transcriptional regulation of DNMT3b represents the molecular mechanism that governs the overexpression of DNMT3b that drives the hypermethylation defect in breast cancer. MicroRNAs (miRs) that regulate (miR-29a, miR-29b, miR-29c, miR-148a, miR-148b) or are predicted (miR-26a, miR-26b, miR-203, miR-222) to regulate DNMT3b were examined among 10 hypermethylator and 6 non-hypermethylator breast cancer cell lines. Hypermethylator cell lines express diminished levels of miR-29c, miR-148a, miR-148b, miR-26a, miR-26b, and miR-203 compared to non-hypermethylator cell lines. miR expression patterns correlate inversely with methylation-sensitive gene expression (r=-0.66, p=0.0056) and directly with the methylation status of these genes (r=0.72, p=0.002). To determine the mechanistic role of specific miRs in the dysregulation of DNMT3b among breast cancer cell lines, miR levels were modulated by transfection of pre-miR precursors for miR-148b, miR-26b, and miR-29c into hypermethylator cell lines (Hs578T, HCC1937, SUM185) and transfection of antagomirs directed against miR-148b, miR-26b, and miR-29c into non-hypermethylator cell lines (BT20, MDA-MB-415, MDA-MB-468). Antagomir-mediated knock-down of miR-148b, miR-29c, and miR-26b significantly increased DNMT3b mRNA in non-hypermethylator cell lines, and re-expression of miR-148b, miR-29c, and miR-26b following transfection of pre-miR precursors significantly reduced DNMT3b mRNA in hypermethylator cell lines. These findings strongly suggest that: i) post-transcriptional regulation of DNMT3b is combinatorial, ii) diminished expression of regulatory miRs contributes to DNMT3b overexpression, iii) re-expression of regulatory miRs reduces DNMT3b m

  1. Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research.

    Science.gov (United States)

    Grover, P K; Cummins, A G; Price, T J; Roberts-Thomson, I C; Hardingham, J E

    2014-08-01

    Increasing evidence suggests that circulating tumour cells (CTCs) are responsible for metastatic relapse and this has fuelled interest in their detection and quantification. Although numerous methods have been developed for the enrichment and detection of CTCs, none has yet reached the 'gold' standard. Since epithelial cell adhesion molecule (EpCAM)-based enrichment of CTCs offers several advantages, it is one of the most commonly used and has been adapted for high-throughput technology. However, emerging evidence suggests that CTCs are highly heterogeneous: they consist of epithelial tumour cells, epithelial-to-mesenchymal transition (EMT) cells, hybrid (epithelial/EMT(+)) tumour cells, irreversible EMT(+) tumour cells, and circulating tumour stem cells (CTSCs). The EpCAM-based approach does not detect CTCs expressing low levels of EpCAM and non-epithelial phenotypes such as CTSCs and those that have undergone EMT and no longer express EpCAM. Thus, the approach may lead to underestimation of the significance of CTCs, in general, and CTSCs and EMT(+) tumour cells, in particular, in cancer dissemination. Here, we provide a critical review of research literature on the evolving concept of CTCs and the inadequacy of their enrichment by EpCAM-based technology for basic and clinical cancer research. The review also outlines future perspectives in the field.

  2. Mitosis Phase Enrichment with Identification of Mitotic Centromere-Associated Kinesin As a Therapeutic Target in Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Sircar, Kanishka; Huang, Heng; Hu, Limei; Liu, Yuexin; Dhillon, Jasreman; Cogdell, David; Aprikian, Armen; Efstathiou, Eleni; Navone, Nora; Troncoso, Patricia; Zhang, Wei

    2012-01-01

    The recently described transcriptomic switch to a mitosis program in castration-resistant prostate cancer (CRPC) suggests that mitotic proteins may be rationally targeted at this lethal stage of the disease. In this study, we showed upregulation of the mitosis-phase at the protein level in our cohort of 51 clinical CRPC cases and found centrosomal aberrations to also occur preferentially in CRPC compared with untreated, high Gleason–grade hormone-sensitive prostate cancer (P<0.0001). Expression profiling of chemotherapy-resistant CRPC samples (n = 25) was performed, and the results were compared with data from primary chemotherapy-naïve CRPC (n = 10) and hormone-sensitive prostate cancer cases (n = 108). Our results showed enrichment of mitosis-phase genes and pathways, with progression to both castration-resistant and chemotherapy-resistant disease. The mitotic centromere-associated kinesin (MCAK) was identified as a novel mitosis-phase target in prostate cancer that was overexpressed in multiple CRPC gene-expression datasets. We found concordant gene expression of MCAK between our parent and murine CRPC xenograft pairs and increased MCAK protein expression with clinical progression of prostate cancer to a castration-resistant disease stage. Knockdown of MCAK arrested the growth of prostate cancer cells suggesting its utility as a potential therapeutic target. PMID:22363599

  3. Mitosis phase enrichment with identification of mitotic centromere-associated kinesin as a therapeutic target in castration-resistant prostate cancer.

    Directory of Open Access Journals (Sweden)

    Kanishka Sircar

    Full Text Available The recently described transcriptomic switch to a mitosis program in castration-resistant prostate cancer (CRPC suggests that mitotic proteins may be rationally targeted at this lethal stage of the disease. In this study, we showed upregulation of the mitosis-phase at the protein level in our cohort of 51 clinical CRPC cases and found centrosomal aberrations to also occur preferentially in CRPC compared with untreated, high Gleason-grade hormone-sensitive prostate cancer (P<0.0001. Expression profiling of chemotherapy-resistant CRPC samples (n = 25 was performed, and the results were compared with data from primary chemotherapy-naïve CRPC (n = 10 and hormone-sensitive prostate cancer cases (n = 108. Our results showed enrichment of mitosis-phase genes and pathways, with progression to both castration-resistant and chemotherapy-resistant disease. The mitotic centromere-associated kinesin (MCAK was identified as a novel mitosis-phase target in prostate cancer that was overexpressed in multiple CRPC gene-expression datasets. We found concordant gene expression of MCAK between our parent and murine CRPC xenograft pairs and increased MCAK protein expression with clinical progression of prostate cancer to a castration-resistant disease stage. Knockdown of MCAK arrested the growth of prostate cancer cells suggesting its utility as a potential therapeutic target.

  4. Integrative ChIP-seq/microarray analysis identifies a CTNNB1 target signature enriched in intestinal stem cells and colon cancer.

    Directory of Open Access Journals (Sweden)

    Kazuhide Watanabe

    Full Text Available BACKGROUND: Deregulation of canonical Wnt/CTNNB1 (beta-catenin pathway is one of the earliest events in the pathogenesis of colon cancer. Mutations in APC or CTNNB1 are highly frequent in colon cancer and cause aberrant stabilization of CTNNB1, which activates the transcription of Wnt target genes by binding to chromatin via the TCF/LEF transcription factors. Here we report an integrative analysis of genome-wide chromatin occupancy of CTNNB1 by chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq and gene expression profiling by microarray analysis upon RNAi-mediated knockdown of CTNNB1 in colon cancer cells. RESULTS: We observed 3629 CTNNB1 binding peaks across the genome and a significant correlation between CTNNB1 binding and knockdown-induced gene expression change. Our integrative analysis led to the discovery of a direct Wnt target signature composed of 162 genes. Gene ontology analysis of this signature revealed a significant enrichment of Wnt pathway genes, suggesting multiple feedback regulations of the pathway. We provide evidence that this gene signature partially overlaps with the Lgr5+ intestinal stem cell signature, and is significantly enriched in normal intestinal stem cells as well as in clinical colorectal cancer samples. Interestingly, while the expression of the CTNNB1 target gene set does not correlate with survival, elevated expression of negative feedback regulators within the signature predicts better prognosis. CONCLUSION: Our data provide a genome-wide view of chromatin occupancy and gene regulation of Wnt/CTNNB1 signaling in colon cancer cells.

  5. The Low Chamber Pancreatic Cancer Cells Had Stem-Like Characteristics in Modified Transwell System: Is It a Novel Method to Identify and Enrich Cancer Stem-Like Cells?

    Directory of Open Access Journals (Sweden)

    Dongqing Wang

    2014-01-01

    Full Text Available Cancer stem cells (CSCs or cancer-initiating cells (CICs play an important role in tumor initiation, progression, metastasis, chemoresistance, and recurrence. It is important to construct an effective method to identify and isolate CSCs for biotherapy of cancer. During the past years, many researchers had paid more attention to it; however, this method was still on seeking. Therefore, compared to the former methods that were used to isolate the cancer stem cell, in the present study, we tried to use modified transwell system to isolate and enrich CSCs from human pancreatic cancer cell lines (Panc-1. Our results clearly showed that the lower chamber cells in modified transwell system were easily forming spheres; furthermore, these spheres expressed high levels of stem cell markers (CD133/CD44/CD24/Oct-4/ESA and exhibited chemoresistance, underwent epithelial-to-mesenchymal transition (EMT, and possessed the properties of self-renewal in vitro and tumorigenicity in vivo. Therefore, we speculated that modified transwell assay system, as a rapid and effective method, can be used to isolate and enrich CSCs.

  6. Evaluation of phosphopeptide enrichment strategies for quantitative TMT analysis of complex network dynamics in cancer-associated cell signalling

    Directory of Open Access Journals (Sweden)

    Benedetta Lombardi

    2015-03-01

    Full Text Available Defining alterations in signalling pathways in normal and malignant cells is becoming a major field in proteomics. A number of different approaches have been established to isolate, identify and quantify phosphorylated proteins and peptides. In the current report, a comparison between SCX prefractionation versus an antibody based approach, both coupled to TiO2 enrichment and applied to TMT labelled cellular lysates, is described. The antibody strategy was more complete for enriching phosphopeptides and allowed the identification of a large set of proteins known to be phosphorylated (715 protein groups with a minimum number of not previously known phosphorylated proteins (2.

  7. B cell subsets in atherosclerosis

    Directory of Open Access Journals (Sweden)

    Heather M. Perry

    2012-12-01

    Full Text Available Atherosclerosis, the underlying cause of heart attacks and strokes, is a chronic inflammatory disease of the artery wall. Immune cells, including lymphocytes modulate atherosclerotic lesion development through interconnected mechanisms. Elegant studies over the past decades have begun to unravel a role for B cells in atherosclerosis. Recent findings provide evidence that B cell effects on atherosclerosis may be subset-dependent. B-1a B cells have been reported to protect from atherosclerosis by secretion of natural IgM antibodies. Conventional B-2 B cells can promote atherosclerosis through less clearly defined mechanism that may involve CD4 T cells. Yet, there may be other populations of B cells within these subsets with different phenotypes altering their impact on atherosclerosis. Additionally, the role of B cell subsets in atherosclerosis may depend on their environmental niche and/or the stage of atherogenesis. This review will highlight key findings in the evolving field of B cells and atherosclerosis and touch on the potential and importance of translating these findings to human disease.

  8. Inhibitory effects of polyphenol-enriched extract from Ziyang tea against human breast cancer MCF-7 cells through reactive oxygen species-dependent mitochondria molecular mechanism

    Directory of Open Access Journals (Sweden)

    Wenfeng Li

    2016-07-01

    Full Text Available A polyphenol-enriched extract from selenium-enriched Ziyang green tea (ZTP was selected to evaluate its antitumor effects against human breast cancer MCF-7 cells. In ZTP, (−-epigallocatechin gallate (28.2% was identified as the major catechin, followed by (−-epigallocatechin (5.7% and (−-epicatechin gallate (12.6%. ZTP was shown to inhibit MCF-7 cell proliferation (half maximal inhibitory concentration, IC50 = 172.2 μg/mL by blocking cell-cycle progression at the G0/G1 phase and inducing apoptotic death. Western blotting assay indicated that ZTP induced cell-cycle arrest by upregulation of p53 and reduced the expression of CDK2 in MCF-7 cells. ZTP-caused cell apoptosis was associated with an increase in Bax/Bcl-2 ratio, and activation of caspase-3 and -9. MCF-7 cells treated with ZTP also showed an overproduction of reactive oxygen species, suggesting that reactive oxygen species played an important role in the induction of apoptosis in MCF-7 cells. This is the first report showing that ZTP is a potential novel dietary agent for cancer chemoprevention or chemotherapy.

  9. Domino: Extracting, Comparing, and Manipulating Subsets across Multiple Tabular Datasets

    Science.gov (United States)

    Gratzl, Samuel; Gehlenborg, Nils; Lex, Alexander; Pfister, Hanspeter; Streit, Marc

    2016-01-01

    Answering questions about complex issues often requires analysts to take into account information contained in multiple interconnected datasets. A common strategy in analyzing and visualizing large and heterogeneous data is dividing it into meaningful subsets. Interesting subsets can then be selected and the associated data and the relationships between the subsets visualized. However, neither the extraction and manipulation nor the comparison of subsets is well supported by state-of-the-art techniques. In this paper we present Domino, a novel multiform visualization technique for effectively representing subsets and the relationships between them. By providing comprehensive tools to arrange, combine, and extract subsets, Domino allows users to create both common visualization techniques and advanced visualizations tailored to specific use cases. In addition to the novel technique, we present an implementation that enables analysts to manage the wide range of options that our approach offers. Innovative interactive features such as placeholders and live previews support rapid creation of complex analysis setups. We introduce the technique and the implementation using a simple example and demonstrate scalability and effectiveness in a use case from the field of cancer genomics. PMID:26356916

  10. THE FEATURE SUBSET SELECTION ALGORITHM

    Institute of Scientific and Technical Information of China (English)

    Liu Yongguo; Li Xueming; Wu Zhongfu

    2003-01-01

    The motivation of data mining is how to extract effective information from huge data in very large database. However, some redundant and irrelevant attributes, which result in low performance and high computing complexity, are included in the very large database in general.So, Feature Subset Selection (FSS) becomes one important issue in the field of data mining. In this letter, an FSS model based on the filter approach is built, which uses the simulated annealing genetic algorithm. Experimental results show that convergence and stability of this algorithm are adequately achieved.

  11. Investigation of Human Cancers for Retrovirus by Low-Stringency Target Enrichment and High-Throughput Sequencing

    DEFF Research Database (Denmark)

    Vinner, Lasse; Mourier, Tobias; Friis-Nielsen, Jens;

    2015-01-01

    Although nearly one fifth of all human cancers have an infectious aetiology, the causes for the majority of cancers remain unexplained. Despite the enormous data output from high-throughput shotgun sequencing, viral DNA in a clinical sample typically constitutes a proportion of host DNA that is too......-stringency in-solution hybridization method enables detection of discovery of hitherto unknown viral sequences by high-throughput sequencing. The sensitivity was sufficient to detect retroviral...

  12. Flaxseed enriched diet-mediated reduction in ovarian cancer severity is correlated to the reduction of prostaglandin E(2) in laying hen ovaries.

    Science.gov (United States)

    Eilati, Erfan; Hales, Karen; Zhuge, Yan; Ansenberger Fricano, Kristine; Yu, Rui; van Breemen, Richard B; Hales, Dale Buchanan

    2013-09-01

    Prevention of ovarian cancer is the best approach for reducing the impact of this deadly disease. The laying hen is a robust model of spontaneous ovarian cancer that recapitulates the human disease. Dietary intervention with flaxseed, the richest vegetable source of omega-3 fatty acids (OM-3FAs) and phytoestrogen lignans, demonstrate the potential for effective prevention and amelioration of ovarian cancer by targeting inflammatory prostaglandin pathways. Prostaglandin E2 (PGE2) is the most pro-inflammatory ecoisanoid and one of the downstream products of two isoforms of cyclooxygenase (COX) enzymes: COX-1 and COX-2. Our objective was to investigate the effect of flaxseed supplementation for one year on ovarian cancer and correlate its effects to expression of COX enzymes and concentrations of prostaglandins. White Leghorn hens were fed 10% flaxseed-enriched or standard diet for one year. The severity of ovarian cancer was determined by gross pathology and histology. COX-1 and COX-2 localization and protein and mRNA expression and PGE2 and PGE3 concentrations in ovaries were measured by IHC, western blot, quantitative real-time PCR and LC-MS-MS, respectively. The results demonstrated a significant reduction in late stage ovarian tumors in the flaxseed-fed hens compared with the control diet-fed hens. In correlation with decreased ovarian cancer severity, concentrations of PGE2 and expression of COX-2 were diminished in ovaries of flaxseed-fed hens. PGE3 concentrations were below the level of detection. The results demonstrated that in normal ovaries, COX-1 was localized to the granulosa cell layer surrounding the follicles and ovarian surface epithelium (OSE) whereas COX-2 protein was localized to the granulosa cell layer in the follicle. Extensive COX-1 and COX-2 protein expression was found throughout the ovarian carcinoma. Our findings suggest that the flaxseed-mediated reduction in the severity of ovarian cancer in hens is correlated to the reduction in PGE2 in

  13. Enrichment of Breast Cancer Stem Cells by Serum-free Shaking Suspension Culture%无血清摇动悬浮培养富集乳腺癌干细胞

    Institute of Scientific and Technical Information of China (English)

    闫文星; 陈玉丙; 张红梅; 国春龙; 王铁君

    2011-01-01

    Objective To investigate the characteristics of division of breast cancer MCF-7 cells under various conditions so as to develop a rapid and effective method for enrichment of breast cancer stem cells. Methods MCF-7 cells were subjected to static culture in complete medium (group A), shaking culture in complete medium (group B), static culture with cytokine (group C) and shaking culture with cytokine (group D) respectively, for 12, 24 and 36 h, then observed for division under inverted phase contrast microscope, based on which clone formation rate was calculated, and determined for the percentage of CD44+/CD24"/low lymphocyte subsets. Results In groups B and C, rod-like divisions were observed in both about 30% of cells 12 h, and in about 50% and about 60% of cells respectively 24 h, while large cell clones were formed 36 h after culture. However, in group D, rod-like division was observed in about 50% of cells 12 h, and in about 80% of cells 24 h when several cell clones appeared, while the number of cell clones decreased 36 h after culture. The percentage of CD44+/CD24"/km lymphocyte subsets 12 h after culture in group D (8. 05%) was 8 times of those in group B (0. 99%) and 2. 1 times of those in group C (3. 80%). However, the percentage 24 h after culture in group D (15. 24%) was 3 times of those in group B (4. 83%) and 6 times of those in group C (2. 30%). The percentage in group D decreased to 9. 68% 36 h after culture, which was about 9 times of those in groups B (0. 95%) and C (1. 03%). Conclusion The mitotic division of MCF-7 cells was accelerated in shaking culture with cytokine, while the percentage of CD44+/CD24'/low lymphocyte subsets increased rapidly, and stem cell pool increased significantly, indicating serum-free shaking suspension culture a rapid and effective method for enrichment of breast cancer stem cells.%目的 探讨不同培养条件下乳腺癌MCF-7细胞的分裂特点,建立快速、有效的乳腺癌干细胞富集方法.方法 将MCF-7

  14. Size-based enrichment of exfoliated tumor cells in urine increases the sensitivity for DNA-based detection of bladder cancer.

    Directory of Open Access Journals (Sweden)

    Elin Andersson

    Full Text Available Bladder cancer is diagnosed by cystoscopy, a costly and invasive procedure that is associated with patient discomfort. Analysis of tumor-specific markers in DNA from sediments of voided urine has the potential for non-invasive detection of bladder cancer; however, the sensitivity is limited by low fractions and small numbers of tumor cells exfoliated into the urine from low-grade tumors. The purpose of this study was to improve the sensitivity for non-invasive detection of bladder cancer by size-based capture and enrichment of tumor cells in urine. In a split-sample set-up, urine from a consecutive series of patients with primary or recurrent bladder tumors (N = 189 was processed by microfiltration using a membrane filter with a defined pore-size, and sedimentation by centrifugation, respectively. DNA from the samples was analyzed for seven bladder tumor-associated methylation markers using MethyLight and pyrosequencing assays. The fraction of tumor-derived DNA was higher in the filter samples than in the corresponding sediments for all markers (p<0.000001. Across all tumor stages, the number of cases positive for one or more markers was 87% in filter samples compared to 80% in the corresponding sediments. The largest increase in sensitivity was achieved in low-grade Ta tumors, with 82 out of 98 cases positive in the filter samples (84% versus 74 out of 98 in the sediments (75%. Our results show that pre-analytic processing of voided urine by size-based filtration can increase the sensitivity for DNA-based detection of bladder cancer.

  15. Mining Representative Subset Based on Fuzzy Clustering

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hongfang; FENG Boqin; L(U) Lintao

    2007-01-01

    Two new concepts-fuzzy mutuality and average fuzzy entropy are presented. Then based on these concepts, a new algorithm-RSMA (representative subset mining algorithm) is proposed, which can abstract representative subset from massive data.To accelerate the speed of producing representative subset, an improved algorithm-ARSMA(accelerated representative subset mining algorithm) is advanced, which adopt combining putting forward with backward strategies. In this way, the performance of the algorithm is improved. Finally we make experiments on real datasets and evaluate the representative subset. The experiment shows that ARSMA algorithm is more excellent than RandomPick algorithm either on effectiveness or efficiency.

  16. A novel method for sample preparation of fresh lung cancer tissue for proteomics analysis by tumor cell enrichment and removal of blood contaminants

    Directory of Open Access Journals (Sweden)

    Orre Lotta

    2010-02-01

    Full Text Available Abstract Background In-depth proteomics analyses of tumors are frequently biased by the presence of blood components and stromal contamination, which leads to large experimental variation and decreases the proteome coverage. We have established a reproducible method to prepare freshly collected lung tumors for proteomics analysis, aiming at tumor cell enrichment and reduction of plasma protein contamination. We obtained enriched tumor-cell suspensions (ETS from six lung cancer cases (two adenocarcinomas, two squamous-cell carcinomas, two large-cell carcinomas and from two normal lung samples. The cell content of resulting ETS was evaluated with immunocytological stainings and compared with the histologic pattern of the original specimens. By means of a quantitative mass spectrometry-based method we evaluated the reproducibility of the sample preparation protocol and we assessed the proteome coverage by comparing lysates from ETS samples with the direct lysate of corresponding fresh-frozen samples. Results Cytological analyses on cytospin specimens showed that the percentage of tumoral cells in the ETS samples ranged from 20% to 70%. In the normal lung samples the percentage of epithelial cells was less then 10%. The reproducibility of the sample preparation protocol was very good, with coefficient of variation at the peptide level and at the protein level of 13% and 7%, respectively. Proteomics analysis led to the identification of a significantly higher number of proteins in the ETS samples than in the FF samples (244 vs 109, respectively. Albumin and hemoglobin were among the top 5 most abundant proteins identified in the FF samples, showing a high contamination with blood and plasma proteins, whereas ubiquitin and the mitochondrial ATP synthase 5A1 where among the top 5 most abundant proteins in the ETS samples. Conclusion The method is feasible and reproducible. We could obtain a fair enrichment of cells but the major benefit of the method

  17. In vitro antiproliferative/cytotoxic activity on cancer cell lines of a cardanol and a cardol enriched from Thai Apis mellifera propolis

    Directory of Open Access Journals (Sweden)

    Teerasripreecha Dungporn

    2012-03-01

    Full Text Available Abstract Background Propolis is a complex resinous honeybee product. It is reported to display diverse bioactivities, such as antimicrobial, anti-inflammatory and anti-tumor properties, which are mainly due to phenolic compounds, and especially flavonoids. The diversity of bioactive compounds depends on the geography and climate, since these factors affect the floral diversity. Here, Apis mellifera propolis from Nan province, Thailand, was evaluated for potential anti-cancer activity. Methods Propolis was sequentially extracted with methanol, dichloromethane and hexane and the cytotoxic activity of each crude extract was assayed for antiproliferative/cytotoxic activity in vitro against five human cell lines derived from duet carcinoma (BT474, undifferentiated lung (Chaco, liver hepatoblastoma (Hep-G2, gastric carcinoma (KATO-III and colon adenocarcinoma (SW620 cancers. The human foreskin fibroblast cell line (Hs27 was used as a non-transformed control. Those crude extracts that displayed antiproliferative/cytotoxic activity were then further fractionated by column chromatography using TLC-pattern and MTT-cytotoxicity bioassay guided selection of the fractions. The chemical structure of each enriched bioactive compound was analyzed by nuclear magnetic resonance and mass spectroscopy. Results The crude hexane and dichloromethane extracts of propolis displayed antiproliferative/cytotoxic activities with IC50 values across the five cancer cell lines ranging from 41.3 to 52.4 μg/ml and from 43.8 to 53.5 μg/ml, respectively. Two main bioactive components were isolated, one cardanol and one cardol, with broadly similar in vitro antiproliferation/cytotoxicity IC50 values across the five cancer cell lines and the control Hs27 cell line, ranging from 10.8 to 29.3 μg/ml for the cardanol and . Conclusion This is the first report that Thai A. mellifera propolis contains at least two potentially new compounds (a cardanol and a cardol with potential anti-cancer

  18. Doxorubicin-enriched, ALDHbr mouse breast cancer stem cells are treatable to oncolytic herpes simplex virus type 1

    Directory of Open Access Journals (Sweden)

    Zhuang Xiufen

    2012-11-01

    Full Text Available Abstract Background The primary objective of this study was to test whether oncolytic herpes simplex virus type 1 (HSV1 could eradicate chemoresistant cancer stem cells (CSCs. Methods The fluorescent aldefluor reagent-based technique was used to identify and isolate ALDHbr cells as CSCs from the 4T1 murine breast cancer cell line. The presence of ALDHbr 4T1 cells was also examined in 4T1 breast cancer transplanted in immune-competent syngeneic mice. Results Compared with ALDHlo cells, ALDHbr cells had a markedly higher ability to form tumor spheres in vitro and a higher tumorigenic potential in vivo. ALDHbr cells also exhibited increased doxorubicin resistance in vitro, which correlated with a selective increase in the percentage of ALDHbr cells after doxorubicin treatment and an increased expression of P-glycoprotein (P-gp, a known chemoresistance factor. In contrast, oncolytic HSV1 was able to kill ALDHbr cells in vitro and even more markedly in vivo. Furthermore, in in vivo studies, systemic administration of doxorubicin followed by intratumoral injection of oncolytic HSV1 resulted in much more significant suppression of tumor growth with increased median survival period compared with each treatment given alone (p+ T lymphocytes were induced by oncolytic HSV1, no significant specific T cell response against CSCs was detected in vivo. Conclusions These results suggested that the use of oncolytic HSV1 following doxorubicin treatment may help eradicate residual chemoresistant CSCs in vivo.

  19. Screening Key Genes Associated with the Development and Progression of Non-small Cell Lung Cancer Based on Gene-enrichment Analysis and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Wenwu HE

    2012-07-01

    Full Text Available Background and objective Non-small cell lung cancer (NSCLC is one of the most common malignant tumors; however, its causes are still not completely understood. This study was designed to screen the key genes and pathways related to NSCLC occurrence and development and to establish the scientific foundation for the genetic mechanisms and targeted therapy of NSCLC. Methods Both gene set-enrichment analysis (GSEA and meta-analysis (meta were used to screen the critical pathways and genes that might be corretacted with the development and progression of lung cancer at the transcription level. Results Using the GSEA and meta methods, focal adhesion and regulation of actin cytoskeleton were determined to be the more prominent overlapping significant pathways. In the focal adhesion pathway, 31 genes were statistically significant (P<0.05, whereas in the regulation of actin cytoskeleton pathway, 32 genes were statistically significant (P<0.05. Conclusion The focal adhesion and the regulation of actin cytoskeleton pathways might play important roles in the occurrence and development of NSCLC. Further studies are needed to determine the biological function for the positiue genes.

  20. CUDA Enabled Graph Subset Examiner

    Energy Technology Data Exchange (ETDEWEB)

    2016-12-22

    Finding Godsil-McKay switching sets in graphs is one way to demonstrate that a specific graph is not determined by its spectrum--the eigenvalues of its adjacency matrix. An important area of active research in pure mathematics is determining which graphs are determined by their spectra, i.e. when the spectrum of the adjacency matrix uniquely determines the underlying graph. We are interested in exploring the spectra of graphs in the Johnson scheme and specifically seek to determine which of these graphs are determined by their spectra. Given a graph G, a Godsil-McKay switching set is an induced subgraph H on 2k vertices with the following properties: I) H is regular, ii) every vertex in G/H is adjacent to either 0, k, or 2k vertices of H, and iii) at least one vertex in G/H is adjacent to k vertices in H. The software package examines each subset of a user specified size to determine whether or not it satisfies those 3 conditions. The software makes use of the massive parallel processing power of CUDA enabled GPUs. It also exploits the vertex transitivity of graphs in the Johnson scheme by reasoning that if G has a Godsil-McKay switching set, then it has a switching set which includes vertex 1. While the code (in its current state) is tuned to this specific problem, the method of examining each induced subgraph of G can be easily re-written to check for any user specified conditions on the subgraphs and can therefore be used much more broadly.

  1. Almost Chebyshev set with respect to bounded subsets

    Institute of Scientific and Technical Information of China (English)

    李冲; 王兴华

    1997-01-01

    The uniqueness and existence of restricted Chebyshev center with respect to arbitrary subset are investigated. The concept of almost Chebyshev sets with respect to bounded subsets is introduced. It is proved that each closed subset in a reflexive locally uniformly convex (uniformly convex, respectively) Banach space is an almost Chebyshev subset with respect to compact convex subsets (bounded convex subsets and bounded subsets, respectively).

  2. Establishment and characterization of a highly tumourigenic and cancer stem cell enriched pancreatic cancer cell line as a well defined model system.

    Directory of Open Access Journals (Sweden)

    Johannes Fredebohm

    Full Text Available Standard cancer cell lines do not model the intratumoural heterogeneity situation sufficiently. Clonal selection leads to a homogeneous population of cells by genetic drift. Heterogeneity of tumour cells, however, is particularly critical for therapeutically relevant studies, since it is a prerequisite for acquiring drug resistance and reoccurrence of tumours. Here, we report the isolation of a highly tumourigenic primary pancreatic cancer cell line, called JoPaca-1 and its detailed characterization at multiple levels. Implantation of as few as 100 JoPaca-1 cells into immunodeficient mice gave rise to tumours that were histologically very similar to the primary tumour. The high heterogeneity of JoPaca-1 was reflected by diverse cell morphology and a substantial number of chromosomal aberrations. Comparative whole-genome sequencing of JoPaca-1 and BxPC-3 revealed mutations in genes frequently altered in pancreatic cancer. Exceptionally high expression of cancer stem cell markers and a high clonogenic potential in vitro and in vivo was observed. All of these attributes make this cell line an extremely valuable model to study the biology of and pharmaceutical effects on pancreatic cancer.

  3. Efficient enrichment of hepatic cancer stem-like cells from a primary rat HCC model via a density gradient centrifugation-centered method.

    Directory of Open Access Journals (Sweden)

    Wei-hui Liu

    Full Text Available BACKGROUND: Because few definitive markers are available for hepatic cancer stem cells (HCSCs, based on physical rather than immunochemical properties, we applied a novel method to enrich HCSCs. METHODOLOGY: After hepatic tumor cells (HTCs were first isolated from diethylinitrosamine-induced F344 rat HCC model using percoll discontinuous gradient centrifugation (PDGC and purified via differential trypsinization and differential attachment (DTDA, they were separated into four fractions using percoll continuous gradient centrifugation (PCGC and sequentially designated as fractions I-IV (FI-IV. Morphological characteristics, mRNA and protein levels of stem cell markers, proliferative abilities, induced differentiation, in vitro migratory capacities, in vitro chemo-resistant capacities, and in vivo malignant capacities were determined for the cells of each fraction. FINDINGS: As the density of cells increased, 22.18%, 11.62%, 4.73% and 61.47% of primary cultured HTCs were segregated in FI-FIV, respectively. The cells from FIII (density between 1.041 and 1.062 g/ml displayed a higher nuclear-cytoplasmic ratio and fewer organelles and expressed higher levels of stem cell markers (AFP, EpCAM and CD133 than cells from other fractions (P<0.01. Additionally, in vitro, the cells from FIII showed a greater capacity to self-renew, differentiate into mature HTCs, transit across membranes, close scratches, and carry resistance to chemotherapy than did cells from any other fraction; in vivo, injection of only 1×10(4 cells from FIII could generate tumors not only in subcutaneous tissue but also in the livers of nude mice. CONCLUSIONS: Through our novel method, HCSC-like cells were successfully enriched in FIII. This study will greatly contribute to two important areas of biological interest: CSC isolation and HCC therapy.

  4. Cancer

    Science.gov (United States)

    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  5. Digital Image Correlation with Dynamic Subset Selection

    Science.gov (United States)

    Hassan, Ghulam Mubashar; MacNish, Cara; Dyskin, Arcady; Shufrin, Igor

    2016-09-01

    The quality of the surface pattern and selection of subset size play a critical role in achieving high accuracy in Digital Image Correlation (DIC). The subset size in DIC is normally selected by testing different subset sizes across the entire image, which is a laborious procedure. This also leads to the problem that the worst region of the surface pattern influences the performance of DIC across the entire image. In order to avoid these limitations, a Dynamic Subset Selection (DSS) algorithm is proposed in this paper to optimize the subset size for each point in an image before optimizing the correlation parameters. The proposed DSS algorithm uses the local pattern around the point of interest to calculate a parameter called the Intensity Variation Ratio (Λ), which is used to optimize the subset size. The performance of the DSS algorithm is analyzed using numerically generated images and is compared with the results of traditional DIC. Images obtained from laboratory experiments are also used to demonstrate the utility of the DSS algorithm. Results illustrate that the DSS algorithm provides a better alternative to subset size "guessing" and finds an appropriate subset size for each point of interest according to the local pattern.

  6. Some Properties of α-Subsets

    Institute of Scientific and Technical Information of China (English)

    LONG Xi-qing; XU Yang; GU Xiu-mei

    2006-01-01

    In this paper, the concept of α - subsets is introduced in a lattice implication algebra and some properties are discussed. Then we prove that an α- subset is a lattice ideal of L. In the end, we discuss the properties of annihilator.

  7. Development of a synchronous subset of AADL

    DEFF Research Database (Denmark)

    Filali, Mamoun; Lawall, Julia

    2010-01-01

    We study the definition and the mapping of an AADL subset: the so called synchronous subset. We show that the data port protocol used for delayed and immediate connections between periodic threads can be interpreted in a  synchronous way. In this paper, we formalize this interpretation and study...

  8. A Submodularity Framework for Data Subset Selection

    Science.gov (United States)

    2013-09-01

    evaluate novel data subset selection algorithms that are based on the framework of submodular functions, a class of mathematical functions that have...data selection to the problems of automatic speech recognition (ASR) and machine translation (MT). Data subset selection algorithms were used to

  9. Subsets of configurations and canonical partition functions

    DEFF Research Database (Denmark)

    Bloch, J.; Bruckmann, F.; Kieburg, M.;

    2013-01-01

    We explain the physical nature of the subset solution to the sign problem in chiral random matrix theory: the subset sum over configurations is shown to project out the canonical determinant with zero quark charge from a given configuration. As the grand canonical chiral random matrix partition...

  10. Growth inhibition and antioxidative status induced by selenium-enriched broccoli extract and selenocompounds in DNA mismatch repair-deficient human colon cancer cells.

    Science.gov (United States)

    Tsai, Cheng-Fang; Ou, Bor-Rung; Liang, Yu-Chuan; Yeh, Jan-Ying

    2013-08-15

    The effects of enzymatic-digested Se-enriched broccoli extracts (SeB) and selenocompounds on growth and antioxidative status in human colon cancer cells was investigated in this study. HCT116 and HCT116+Chr.3 cells were treated with selenocompounds (sodium selenite, sodium selenate, Se-Met, MeSeCys) or SeB [high-Se (H-SeB) or low-Se (L-SeB)]. The cytotoxicity induced by selenocompounds in HCT116 cells was not associated with cellular H2O2 level, while the differential cytotoxicity observed by sodium selenite between HCT116 and HCT116+Chr.3 cell lines was related to cellular H2O2 production with the change in antioxidative enzyme activity, and the restoration of chromosome 3. H-SeB was found to reduce the cellular H2O2 content in HCT116+Chr.3 cells. The results in this study indicate that regardless of Se content, the cytotoxicity in HCT116 cells of both SeB forms appeared to be H2O2-independent, whereas the cytotoxicity in HCT116+Chr.3 of either SeB form appeared to be H2O2-dependent with an increase in antioxidative ability for H-SeB.

  11. Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line

    Directory of Open Access Journals (Sweden)

    Martins-Neves Sara R

    2012-04-01

    Full Text Available Abstract Background Osteosarcoma is a bone-forming tumor of mesenchymal origin that presents a clinical pattern that is consistent with the cancer stem cell model. Cells with stem-like properties (CSCs have been identified in several tumors and hypothesized as the responsible for the relative resistance to therapy and tumor relapses. In this study, we aimed to identify and characterize CSCs populations in a human osteosarcoma cell line and to explore their role in the responsiveness to conventional therapies. Methods CSCs were isolated from the human MNNG/HOS cell line using the sphere formation assay and characterized in terms of self-renewal, mesenchymal stem cell properties, expression of pluripotency markers and ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to conventional chemotherapeutic agents and to irradiation was analyzed and related with cell cycle-induced alterations and apoptosis. Results The isolated CSCs were found to possess self-renewal and multipotential differentiation capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs were relatively more resistant to both chemotherapy and irradiation. None of the treatments have induced significant cell-cycle alterations and apoptosis in CSCs. Conclusions MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation. This resistant phenotype appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosarcoma.

  12. Consumption of soy isoflavone enriched bread in men with prostate cancer is associated with reduced proinflammatory cytokines and immunosuppressive cells.

    Science.gov (United States)

    Lesinski, Gregory B; Reville, Patrick K; Mace, Thomas A; Young, Gregory S; Ahn-Jarvis, Jennifer; Thomas-Ahner, Jennifer; Vodovotz, Yael; Ameen, Zeenath; Grainger, Elizabeth; Riedl, Kenneth; Schwartz, Steven; Clinton, Steven K

    2015-11-01

    We hypothesized that soy phytochemicals may have immunomodulatory properties that may affect prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 patients with prostate cancer with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to two slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of β-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on day 56 versus baseline. Subgroup analysis indicated reduced TH1 (P = 0.028) and myeloid-derived suppressor cell (MDSC)-associated cytokines (P = 0.035). TH2 and TH17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8(+) or CD4(+) T cells but showed increased CD56(+) natural killer (NK) cells (P = 0.038). The percentage of cells with a T regulatory cell phenotype (CD4(+)CD25(+)FoxP3(+)) was significantly decreased after 56 days of soy bread (P = 0.0136). Significantly decreased monocytic (CD33(+)HLADR(neg)CD14(+)) MDSC were observed in patients consuming soy bread (P = 0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required.

  13. Variable and subset selection in PLS regression

    DEFF Research Database (Denmark)

    Høskuldsson, Agnar

    2001-01-01

    The purpose of this paper is to present some useful methods for introductory analysis of variables and subsets in relation to PLS regression. We present here methods that are efficient in finding the appropriate variables or subset to use in the PLS regression. The general conclusion...... is that variable selection is important for successful analysis of chemometric data. An important aspect of the results presented is that lack of variable selection can spoil the PLS regression, and that cross-validation measures using a test set can show larger variation, when we use different subsets of X, than...

  14. Alterations in p53-specific T cells and other lymphocyte subsets in breast cancer patients during vaccination with p53-peptide loaded dendritic cells and low-dose interleukin-2

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Pedersen, Anders E; Nikolajsen, Kirsten;

    2008-01-01

    We have previously established a cancer vaccine using autologous DCs, generated by in vitro stimulation with IL-4 and GM-CSF, and pulsed with six HLA-A*0201 binding wild-type p53 derived peptides. This vaccine was used in combination with low-dose interleukin-2 in a recently published clinical...... Phase II trial where 26 HLA-A2+ patients with progressive late-stage metastatic breast cancer (BC) were included. Almost 1/3rd of the patients obtained stable disease or minor regression during treatment with a positive correlation to tumour over-expression of p53. In the present study, we performed...... (CD44high, CCR-7low and CD62Llow). Furthermore, fresh blood from 18 cancer patients included in the vaccination trial were prospectively examined for more general treatment associated quantitative and qualitative changes in T cell subpopulations. We found that the frequency of CD4+ CD25high regulatory...

  15. SUPPORTING AND SEPARATING SUBSETS FOR INVEX BODIES

    Institute of Scientific and Technical Information of China (English)

    H.K. EI-Sayied

    2008-01-01

    Invex bodies represent an important class of bodies which are considered as ageneralization of convex bodies. In this article, the author studies the supporting for thisclass of bodies as well as the separating subsets of two bodies.

  16. Curvatures for Parameter Subsets in Nonlinear Regression

    OpenAIRE

    1986-01-01

    The relative curvature measures of nonlinearity proposed by Bates and Watts (1980) are extended to an arbitrary subset of the parameters in a normal, nonlinear regression model. In particular, the subset curvatures proposed indicate the validity of linearization-based approximate confidence intervals for single parameters. The derivation produces the original Bates-Watts measures directly from the likelihood function. When the intrinsic curvature is negligible, the Bates-Watts parameter-effec...

  17. Identification of enriched driver gene alterations in subgroups of non-small cell lung cancer patients based on histology and smoking status.

    Directory of Open Access Journals (Sweden)

    She-Juan An

    Full Text Available BACKGROUND: Appropriate patient selection is needed for targeted therapies that are efficacious only in patients with specific genetic alterations. We aimed to define subgroups of patients with candidate driver genes in patients with non-small cell lung cancer. METHODS: Patients with primary lung cancer who underwent clinical genetic tests at Guangdong General Hospital were enrolled. Driver genes were detected by sequencing, high-resolution melt analysis, qPCR, or multiple PCR and RACE methods. RESULTS: 524 patients were enrolled in this study, and the differences in driver gene alterations among subgroups were analyzed based on histology and smoking status. In a subgroup of non-smokers with adenocarcinoma, EGFR was the most frequently altered gene, with a mutation rate of 49.8%, followed by EML4-ALK (9.3%, PTEN (9.1%, PIK3CA (5.2%, c-Met (4.8%, KRAS (4.5%, STK11 (2.7%, and BRAF (1.9%. The three most frequently altered genes in a subgroup of smokers with adenocarcinoma were EGFR (22.0%, STK11 (19.0%, and KRAS (12.0%. We only found EGFR (8.0%, c-Met (2.8%, and PIK3CA (2.6% alterations in the non-smoker with squamous cell carcinoma (SCC subgroup. PTEN (16.1%, STK11 (8.3%, and PIK3CA (7.2% were the three most frequently enriched genes in smokers with SCC. DDR2 and FGFR2 only presented in smokers with SCC (4.4% and 2.2%, respectively. Among these four subgroups, the differences in EGFR, KRAS, and PTEN mutations were statistically significant. CONCLUSION: The distinct features of driver gene alterations in different subgroups based on histology and smoking status were helpful in defining patients for future clinical trials that target these genes. This study also suggests that we may consider patients with infrequent alterations of driver genes as having rare or orphan diseases that should be managed with special molecularly targeted therapies.

  18. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

    DEFF Research Database (Denmark)

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may pl...

  19. Improved Subset Autoregression: With R Package

    Directory of Open Access Journals (Sweden)

    A. I. McLeod

    2008-07-01

    Full Text Available The FitAR R (R Development Core Team 2008 package that is available on the Comprehensive R Archive Network is described. This package provides a comprehensive approach to fitting autoregressive and subset autoregressive time series. For long time series with complicated autocorrelation behavior, such as the monthly sunspot numbers, subset autoregression may prove more feasible and/or parsimonious than using AR or ARMA models. The two principal functions in this package are SelectModel and FitAR for automatic model selection and model fitting respectively. In addition to the regular autoregressive model and the usual subset autoregressive models (Tong 1977, these functions implement a new family of models. This new family of subset autoregressive models is obtained by using the partial autocorrelations as parameters and then selecting a subset of these parameters. Further properties and results for these models are discussed in McLeod and Zhang (2006. The advantages of this approach are that not only is an efficient algorithm for exact maximum likelihood implemented but that efficient methods are derived for selecting high-order subset models that may occur in massive datasets containing long time series. A new improved extended {BIC} criterion, {UBIC}, developed by Chen and Chen (2008 is implemented for subset model selection. A complete suite of model building functions for each of the three types of autoregressive models described above are included in the package. The package includes functions for time series plots, diagnostic testing and plotting, bootstrapping, simulation, forecasting, Box-Cox analysis, spectral density estimation and other useful time series procedures. As well as methods for standard generic functions including print, plot, predict and others, some new generic functions and methods are supplied that make it easier to work with the output from FitAR for bootstrapping, simulation, spectral density estimation and Box

  20. T-cell subsets in the germinal center.

    Science.gov (United States)

    Ramiscal, Roybel R; Vinuesa, Carola G

    2013-03-01

    T cells are known to migrate to B-cell-enriched follicles and germinal centers within secondary lymphoid organs to provide help to B cells. Cognate T:B interactions that take place at the T:B border and subsequently within germinal centers are essential for B-cell priming, differentiation into germinal center B cells, and selection of mutated cells into memory B cells or memory plasma cells. In recent years, different stages of maturation within B-cell helper T cells, collectively known as B-follicular helper T (Tfh) cells, as well as heterogeneity amid germinal center T cells are becoming clear. Indeed, germinal centers support not only bona fide Tfh cells but also CD4(+) and CD8(+) follicular regulatory T (Tfr) cells that act to suppress germinal center responses and B-cell helper natural killer T cells. There is a growing need for more precise phenotypic and functional distinction of these specialized T-cell subsets. In this review, we summarize current knowledge on the ontogeny, molecular identity, and functional relevance of the various subsets of germinal center T cells.

  1. Feature subset selection based on relevance

    Science.gov (United States)

    Wang, Hui; Bell, David; Murtagh, Fionn

    In this paper an axiomatic characterisation of feature subset selection is presented. Two axioms are presented: sufficiency axiom—preservation of learning information, and necessity axiom—minimising encoding length. The sufficiency axiom concerns the existing dataset and is derived based on the following understanding: any selected feature subset should be able to describe the training dataset without losing information, i.e. it is consistent with the training dataset. The necessity axiom concerns the predictability and is derived from Occam's razor, which states that the simplest among different alternatives is preferred for prediction. The two axioms are then restated in terms of relevance in a concise form: maximising both the r( X; Y) and r( Y; X) relevance. Based on the relevance characterisation, four feature subset selection algorithms are presented and analysed: one is exhaustive and the remaining three are heuristic. Experimentation is also presented and the results are encouraging. Comparison is also made with some well-known feature subset selection algorithms, in particular, with the built-in feature selection mechanism in C4.5.

  2. Subset specification of central serotonergic neurons

    Directory of Open Access Journals (Sweden)

    Marten P Smidt

    2013-10-01

    Full Text Available The last decade the serotonin (5-hydroxytryptamine; 5-HT system has received enormous attention due to its role in regulation of behavior, exemplified by the discovery that increased 5-HT tone in the central nervous system is able to alleviate affective disorders. Here, we review the developmental processes, with a special emphasis on subset specification, leading to the formation of the 5-HT system in the brain. Molecular classification of 5-HT neuronal groups leads to the definition of two independent rostral groups positioned in rhombomere 1 and 2/3 and a caudal group in rhombomere 5-8. In addition, more disperse refinement of these subsets is present as shown by the selective expression of the 5-HT1A autoreceptor, indicating functional diversity between 5-HT subsets. The functional significance of the molecular coding differences is not well known and the molecular basis of described specific connectivity patterns remain to be elucidated. Recent developments in genetic lineage tracing models will provide these data and form a major step-up towards the full understanding of the importance of developmental programming and function of 5-HT neuronal subsets.

  3. Calibration with empirically weighted mean subset

    DEFF Research Database (Denmark)

    Øjelund, Henrik; Madsen, Henrik; Thyregod, Poul

    2002-01-01

    In this article a new calibration method called empirically weighted mean subset (EMS) is presented. The method is illustrated using spectral data. Using several near-infrared (NIR) benchmark data sets, EMS is compared to partial least-squares regression (PLS) and interval partial least-squares r......In this article a new calibration method called empirically weighted mean subset (EMS) is presented. The method is illustrated using spectral data. Using several near-infrared (NIR) benchmark data sets, EMS is compared to partial least-squares regression (PLS) and interval partial least...... is obtained by calculating the weighted mean of all coefficient vectors for subsets of the same size. The weighting is proportional to SSgamma-omega, where SSgamma is the residual sum of squares from a linear regression with subset gamma and omega is a weighting parameter estimated using cross......-validation. This construction of the weighting implies that even if some coefficients will become numerically small, none will become exactly zero. An efficient algorithm has been implemented in MATLAB to calculate the EMS solution and the source code has been made available on the Internet....

  4. 人胆管癌CD24+ CD44+ EpCAMhigh细胞亚群的分选及其肿瘤干细胞样特性的鉴定%Sorting of CD24+ CD44+ EpCAMhigh subset cells in human human cholangiocardnoma and the identificantion of their cancer stem cell-like properties

    Institute of Scientific and Technical Information of China (English)

    朱峰; 王敏; 秦仁义; 申铭; 王欣; 田锐; 江建新; 石程剑

    2010-01-01

    Objective To sort CD24+ CD44+ EpCAMhigh subset cells in human cholangiocarcinoma and identify their cancer stem cell-like properties. Methods The expression and rate of CD24, CD44 and EpCAM in 6 cases of human cholangiocacinomas were assayed by flow cytometry. The fresh specimens from two cases of cholangiocarcinoma were obtained and implanted subcutaneously into NOD/SCID mice for the establishment of xenografts model. CD24+ CD44+ EpCAMhigh subset cells were sorted from xenografts by flow cytometry and their tumorigenic potential, self-renewal ability and differentiation ability were assessed. Results The expression rate of CD24+ CD44+ EpCAMhigh cells ranged from 0. 58% to 2.43% (mean= 0. 94% ) in 6 cholangiocarcinoma specimens and 2 xenografts. CD24+ CD44+ EpCAMhigh subset cells sorted from 2 xenografts were found to be highly tumorigenic in NOD/SCID mice. CD24+ CD44+ EpCAMhigh cells consistently formed tumors with 1000 cells in 3/8 mice. In contrast, CD24+ CD44+ EpCAMhigh tumor cells were less tumorigenic and formed tumors with 50 000 cells in 1/8 mice. CD24+ CD44+ EpCAMhigh cells were passaged in NOD/SCID mice and formed tumors that recapitulated the histological features and heterogeneity of the original patient tumor. Conclusion CD24+ CD44+ EpCAMhigh subset cells were discriminated in human cholangiocarcinoma, and they had highly tumorigenic, self-renewal ability and differentiation ability. It was first confirmed that CD24+ CD44+ EpCAMhigh cells may be human cholangiocarcinoma cancer stem cells.%目的 检测及分选人胆管癌中的CD24+ CD44+ EpCAMhigh细胞亚群,探讨其是否具有肿瘤干细胞样生物学特性.方法 流式细胞术检测6例人胆管癌中CD24、CD44、EpCAM的表达率;取2例人胆管癌新鲜标本种植到NOD/SCID鼠皮下,建立荷人胆管癌小鼠模型.流式细胞术分选CD24+ CD44+ EpCAMhigh亚群细胞,NOD/SCID鼠移植瘤试验鉴定其成瘤和分化能力.结果 6例人胆管癌组织标本和2例移植瘤中,CD24

  5. Flavonol-enriched fraction from Vaccinium macrocarpon fruit inhibits matrix metalloproteinase-2, matrix metalloproteinase-9 and urokinase-type plasminogen activator expression in human prostate cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    James MacPhee

    2014-11-01

    Full Text Available Background: Prostate cancer, amongst other cancer types has a genetic and environmental component, which can contribute to prostate cancer development and progression. Vaccinum macrocarpon (American cranberry is a botanical that contains several phytochemicals which have been suggested to play a role in preventing cardiovascular disease, cancer, and urinary tract infections as well as in the maintenance of oral health. Context and purpose of this study: This investigation evaluated the effects of a flavonolenriched fraction (FL from the American cranberry (Vaccinium macrocarpon containing quercetin and myricetin glycosides on matrix metalloproteinase (MMP and urokinase-type plasminogen activator (uPA activities and their associated regulatory proteins in DU145 human prostate cancer cells in vitro. Results: A flavonol-enriched fraction (FL was prepared from Vaccinium macrocarpon berries and the effect of this fraction on prostate cancer cell behaviour was assessed using biochemical and molecular approaches including cytotoxicity assays and Western blot analysis to determine protein expression. Cranberry FL decreased cellular viability of DU145 cells at a concentration of 25 ug/ml by 20% after 6 hours of treatment. Further investigations determined that associated with this cytotoxicity, cranberry FL decreases matrix metalloproteinase (MMP ( specifically MMP-2 and MMP-9 activity and urokinase plasminogen activator (uPA activity through effects on specific temporal MMP regulators and uPA regulators and by affecting either the phosphorylation status and/or expression of specific MAP kinase, PI-3 kinase, NF-kB and AP-1 pathway associated proteins. Conclusion: This study demonstrates, for the first time, the ability of Vaccinium macrocarpon flavonols to modulate cellular pathways associated with migration, invasion, and proliferation, suggesting that cranberry (Vaccinium macrocarpon is a viable candidate for further research as a natural product that

  6. Product-free subsets of profinite groups

    CERN Document Server

    Bardestani, Mohammad

    2012-01-01

    Gowers in his paper on quasirandom groups studies a question of Babai and Sos asking whether there exists a constant $c > 0$ such that every finite group $G$ has a product-free subset of size at least $c|G|$. Answering the question negatively, he proves that for sufficiently large prime $p$, the group $\\mathrm{PSL}_2(\\mathbb{F}_p)$ has no product-free subset of size $cn^{8/9}$, where $n$ is the order of $\\mathrm{PSL}_2(\\mathbb{F}_p)$. We will consider the problem for compact groups and in particular for profinite groups $\\SL_k(\\ZZ_p)$ obtain lower and upper exponential bounds for the supremal measure of the product-free sets. The proof involves establishing a lower bound for the dimension of non-trivial representations of the finite groups $\\SL_k(\\Z{p^n})$.

  7. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors

    Science.gov (United States)

    Sutton, Lesley-Ann; Young, Emma; Baliakas, Panagiotis; Hadzidimitriou, Anastasia; Moysiadis, Theodoros; Plevova, Karla; Rossi, Davide; Kminkova, Jana; Stalika, Evangelia; Pedersen, Lone Bredo; Malcikova, Jitka; Agathangelidis, Andreas; Davis, Zadie; Mansouri, Larry; Scarfò, Lydia; Boudjoghra, Myriam; Navarro, Alba; Muggen, Alice F.; Yan, Xiao-Jie; Nguyen-Khac, Florence; Larrayoz, Marta; Panagiotidis, Panagiotis; Chiorazzi, Nicholas; Niemann, Carsten Utoft; Belessi, Chrysoula; Campo, Elias; Strefford, Jonathan C.; Langerak, Anton W.; Oscier, David; Gaidano, Gianluca; Pospisilova, Sarka; Davi, Frederic; Ghia, Paolo; Stamatopoulos, Kostas; Rosenquist, Richard

    2016-01-01

    We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (BIRC3, MYD88, NOTCH1, SF3B1 and TP53) and cytogenetic aberrations, we reveal a subset-biased acquisition of gene mutations. More specifically, the frequency of NOTCH1 mutations was found to be enriched in subsets expressing unmutated immunoglobulin genes, i.e. #1, #6, #8 and #59 (22–34%), often in association with trisomy 12, and was significantly different (Pimmunoglobulin genes). Interestingly, subsets harboring a high frequency of NOTCH1 mutations were found to carry few (if any) SF3B1 mutations. This starkly contrasts with subsets #2 and #3 where, despite their immunogenetic differences, SF3B1 mutations occurred in 45% and 46% of cases, respectively. In addition, mutations within TP53, whilst enriched in subset #1 (16%), were rare in subsets #2 and #8 (both 2%), despite all being clinically aggressive. All subsets were negative for MYD88 mutations, whereas BIRC3 mutations were infrequent. Collectively, this striking bias and skewed distribution of mutations and cytogenetic aberrations within specific chronic lymphocytic leukemia subsets implies that the mechanisms underlying clinical aggressiveness are not uniform, but rather support the existence of distinct genetic pathways of clonal evolution governed by a particular stereotyped B-cell receptor selecting a certain molecular lesion(s). PMID:27198719

  8. CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver.

    Science.gov (United States)

    Stegmann, Kerstin A; Robertson, Francis; Hansi, Navjyot; Gill, Upkar; Pallant, Celeste; Christophides, Theodoros; Pallett, Laura J; Peppa, Dimitra; Dunn, Claire; Fusai, Giuseppe; Male, Victoria; Davidson, Brian R; Kennedy, Patrick; Maini, Mala K

    2016-05-23

    Natural killer cells (NK) are highly enriched in the human liver, where they can regulate immunity and immunopathology. We probed them for a liver-resident subset, distinct from conventional bone-marrow-derived NK. CXCR6+ NK were strikingly enriched in healthy and diseased liver compared to blood (p hi)Eomes(lo)(CXCR6-) and T-bet(lo)Eomes(hi)(CXCR6+); the latter was virtually absent in the periphery. The small circulating CXCR6+ subset was predominantly T-bet(hi)Eomes(lo), suggesting its lineage was closer to CXCR6- peripheral than CXCR6+ liver NK. These data reveal a large subset of human liver-resident T-bet(lo)Eomes(hi) NK, distinguished by their surface expression of CXCR6, adapted for hepatic tolerance and inducible anti-viral immunity.

  9. EWS and FUS bind a subset of transcribed genes encoding proteins enriched in RNA regulatory functions

    DEFF Research Database (Denmark)

    Luo, Yonglun; Friis, Jenny Blechingberg; Fernandes, Ana Miguel;

    2015-01-01

    and involved in the human neurological diseases amyotrophic lateral sclerosis and fronto-temporal lobar degeneration. Results To determine the gene regulatory functions of FUS and EWS at the level of chromatin, we have performed chromatin immunoprecipitation followed by next generation sequencing (Ch...

  10. Immunity to pathogens taught by specialized human dendritic cell subsets.

    Directory of Open Access Journals (Sweden)

    Jens A. E. Geginat

    2015-10-01

    Full Text Available Dendritic cells (DC are specialized antigen-presenting cells (APC that have a key role in immune responses, because they bridge the innate and adaptive arms of the immune system. They mature upon recognition of pathogens and up-regulate MHC molecules and co-stimulatory receptors to activate antigen-specific CD4+ and CD8+ T-cells. It is now well established that DC are not a homogeneous population, but are composed of different subsets with specialized functions in immune responses to specific pathogens. Upon viral infections, plasmacytoid DC (pDC rapidly produce large amounts of IFN-α, which has potent anti-viral functions and activates several other immune cells. However, pDC are not particularly potent APC and induce the tolerogenic cytokine IL-10 in CD4+ T-cells. In contrast, myeloid DC (mDC are very potent APC and possess the unique capacity to prime naïve T-cells and consequently to initiate a primary adaptive immune response. Different subsets of myeloid DC with specialized functions have been identified. In mice, CD8α+ mDC capture antigenic material from necrotic cells, secrete high levels of IL-12, and prime Th1 and cytotoxic T cell responses to control intracellular pathogens. Conversely, CD8α- mDC preferentially prime CD4+ T-cells and promote Th2 or Th17 differentiation. BDCA-3+ mDC2 are the human homologue of CD8α+ mDC, since they share the expression of several key molecules, the capacity to cross-present antigens to CD8+ T-cells and to produce IFN-λ. However, although several features of the DC network are conserved between humans and mice, the expression of several relevant toll-like receptors as well as the production of cytokines that regulate T-cell differentiation are different. Intriguingly, recent data suggests specific roles for human DC subsets in immune responses against individual pathogens. The biology of human DC subsets holds the promise to be exploitable in translational medicine, in particular for the

  11. Dense subsets of products of finite trees

    CERN Document Server

    Dodos, Pandelis; Tyros, Konstantinos

    2011-01-01

    We prove a "uniform" version of the finite density Halpern-L\\"{a}uchli Theorem. Specifically, we say that a tree $T$ is homogeneous if it is uniquely rooted and there is an integer $b\\geq 2$, called the branching number of $T$, such that every $t\\in T$ has exactly $b$ immediate successors. We show the following. For every integer $d\\geq 1$, every $b_1,...,b_d\\in\\mathbb{N}$ with $b_i\\geq 2$ for all $i\\in\\{1,...,d\\}$, every integer $k\\meg 1$ and every real $0<\\epsilon\\leq 1$ there exists an integer $N$ with the following property. If $(T_1,...,T_d)$ are homogeneous trees such that the branching number of $T_i$ is $b_i$ for all $i\\in\\{1,...,d\\}$, $L$ is a finite subset of $\\mathbb{N}$ of cardinality at least $N$ and $D$ is a subset of the level product of $(T_1,...,T_d)$ satisfying \\[|D\\cap \\big(T_1(n)\\times ...\\times T_d(n)\\big)| \\geq \\epsilon |T_1(n)\\times ...\\times T_d(n)|\\] for every $n\\in L$, then there exist strong subtrees $(S_1,...,S_d)$ of $(T_1,...,T_d)$ of height $k$ and with common level set such ...

  12. Hierarchical modeling for rare event detection and cell subset alignment across flow cytometry samples.

    Directory of Open Access Journals (Sweden)

    Andrew Cron

    Full Text Available Flow cytometry is the prototypical assay for multi-parameter single cell analysis, and is essential in vaccine and biomarker research for the enumeration of antigen-specific lymphocytes that are often found in extremely low frequencies (0.1% or less. Standard analysis of flow cytometry data relies on visual identification of cell subsets by experts, a process that is subjective and often difficult to reproduce. An alternative and more objective approach is the use of statistical models to identify cell subsets of interest in an automated fashion. Two specific challenges for automated analysis are to detect extremely low frequency event subsets without biasing the estimate by pre-processing enrichment, and the ability to align cell subsets across multiple data samples for comparative analysis. In this manuscript, we develop hierarchical modeling extensions to the Dirichlet Process Gaussian Mixture Model (DPGMM approach we have previously described for cell subset identification, and show that the hierarchical DPGMM (HDPGMM naturally generates an aligned data model that captures both commonalities and variations across multiple samples. HDPGMM also increases the sensitivity to extremely low frequency events by sharing information across multiple samples analyzed simultaneously. We validate the accuracy and reproducibility of HDPGMM estimates of antigen-specific T cells on clinically relevant reference peripheral blood mononuclear cell (PBMC samples with known frequencies of antigen-specific T cells. These cell samples take advantage of retrovirally TCR-transduced T cells spiked into autologous PBMC samples to give a defined number of antigen-specific T cells detectable by HLA-peptide multimer binding. We provide open source software that can take advantage of both multiple processors and GPU-acceleration to perform the numerically-demanding computations. We show that hierarchical modeling is a useful probabilistic approach that can provide a

  13. A Study on Peripheral T Cell Subsets in Patients with Thyroid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Soo [Pusan National University College of Medicine, Pusan (Korea, Republic of)

    1991-03-15

    To elucidate alteration of peripheral T cell subsets in thyroid tumors, the author enumerated T cell subsets in peripheral blood by indirect immunofluorescent method, using monoclonal antibodies (CD3, CD4 and CD8) in 17 cases of thyroid cancer, 12 cases of thyroid adenoma, and 16 cases of adult healthy subjects as controls. Diagnoses were confirmed histopathologically in thyroid cancer and adenoma, and were established on the basis of commonly accepted clinical and biochemical criteria in Hashimoto's thyroiditis. The blood was drawn from veins of (he patients and control subjects in Pusan National University Hospital during the period of January to October 1990. The results obtained were summarized as follow: 1) The percentage of CD3+ cells was significantly decreased in thyroid cancer as compared with healthy subjects. 2) The percentage of CD4+ cells was not different among thyroid cancer, thyroid adenoma, hashimoto's thyroiditis and control subjects each other. 3) The percentage of CD8+ cells was significantly decreased in thyroid cancer as compared with adult healthy subjects, and tended to be decreased as compared with thyroid adenoma and Hashimoto's thyroiditis. 4) The CD/CDH ratio was significantly increased in thyroid cancer as compared with control subjects, and tended to be increased as compared with thyroid adenoma and Hashimoto's thyroiditis. On the basis of (the results, it can be suggested that the immunodysfunction may be due to decreased suppressor/cytotoxic T cells in thyroid cancer.

  14. Sensor Placement for Modal Parameter Subset Estimation

    DEFF Research Database (Denmark)

    Ulriksen, Martin Dalgaard; Bernal, Dionisio; Damkilde, Lars

    2016-01-01

    The present paper proposes an approach for deciding on sensor placements in the context of modal parameter estimation from vibration measurements. The approach is based on placing sensors, of which the amount is determined a priori, such that the minimum Fisher information that the frequency...... responses carry on the selected modal parameter subset is, in some sense, maximized. The approach is validated in the context of a simple 10-DOF mass-spring-damper system by computing the variance of a set of identified modal parameters in a Monte Carlo setting for a set of sensor configurations, whose......). It is shown that the widely used Effective Independence (EI) method, which uses the modal amplitudes as surrogates for the parameters of interest, provides sensor configurations yielding theoretical lower bound variances whose maxima are up to 30 % larger than those obtained by use of the max-min approach....

  15. Dissimilarity-Based Sparse Subset Selection.

    Science.gov (United States)

    Elhamifar, Ehsan; Sapiro, Guillermo; Sastry, S Shankar

    2016-11-01

    Finding an informative subset of a large collection of data points or models is at the center of many problems in computer vision, recommender systems, bio/health informatics as well as image and natural language processing. Given pairwise dissimilarities between the elements of a 'source set' and a 'target set,' we consider the problem of finding a subset of the source set, called representatives or exemplars, that can efficiently describe the target set. We formulate the problem as a row-sparsity regularized trace minimization problem. Since the proposed formulation is, in general, NP-hard, we consider a convex relaxation. The solution of our optimization finds representatives and the assignment of each element of the target set to each representative, hence, obtaining a clustering. We analyze the solution of our proposed optimization as a function of the regularization parameter. We show that when the two sets jointly partition into multiple groups, our algorithm finds representatives from all groups and reveals clustering of the sets. In addition, we show that the proposed framework can effectively deal with outliers. Our algorithm works with arbitrary dissimilarities, which can be asymmetric or violate the triangle inequality. To efficiently implement our algorithm, we consider an Alternating Direction Method of Multipliers (ADMM) framework, which results in quadratic complexity in the problem size. We show that the ADMM implementation allows to parallelize the algorithm, hence further reducing the computational time. Finally, by experiments on real-world datasets, we show that our proposed algorithm improves the state of the art on the two problems of scene categorization using representative images and time-series modeling and segmentation using representative models.

  16. Lymphocytes subsets in children with febrile convulsions.

    Science.gov (United States)

    Tuncer, Oğuz; Karaman, Sait; Caksen, Hüseyin; Oner, Ahmet Faik; Odabas, Dursun; Yilmaz, Cahide; Atas, Bülent

    2007-07-01

    In this study, lymphocytes subsets including blood CD3, CD4, CD8, CD16, CD19, and CD56 values were analyzed in children with febrile convulsion (FC) to determine whether there was the association of lymphocytes subsets in the pathogenesis of FC. The study includes 48 children with FC, and 55 healthy age matched control subjects, followed in Yüzüncü Yil University, Faculty of Medicine, Department of Pediatrics between October 2003 and June 2004. Blood CD3, CD4, CD8, CD16, CD19, and CD56 values were examined in the study and control groups. The analyses were performed in the Hematology Laboratory, Yüzüncü Yil University Faculty of Medicine, with flow cytometer device (Coulter Epics XL2, Flow Cytometer). A total of 48 children [17 girls (35.5%) and 31 boys (64.5%)], aged 6 months to 60 months (mean 22.20 +/- 13.75 months) with FC and 55 healthy children [28 girls (51%) and 27 boys (49%)], aged 6 months to 60 months (mean 28.87 +/- 17.04 months) were included in the study. When compared with the control group, the study found significantly decreased blood CD3 and CD4 values in the study group (p .05). When comparing the children with and without positive family history for FC, the study did not find any difference for all CD values between the groups (p >.05). Similarly, there was not significant difference in CD values between the children with simple and complex FC (p >.05). The findings suggested that decreased blood CD3 and CD4 values might be responsible for the infections connected with FC or that they might be related to the pathogenesis of FC in some children.

  17. 新辅助化疗对局部晚期非小细胞肺癌肿瘤标记物和淋巴细胞亚群的影响%Effect of neoadjuvant chemotherapy on locally advanced non-small cell lung cancer tumor markers and lymphocyte subsets

    Institute of Scientific and Technical Information of China (English)

    王纯; 卢宏达

    2014-01-01

    目的:观察新辅助化疗对不同病理类型的局部晚期非小细胞肺癌(NSCLC )肿瘤标记物、淋巴细胞亚群的影响。方法选取该院新辅助化疗的局部晚期NSCLC患者为研究对象,共计40例,选取20例体检的健康人群为对照组,比较不同病理类型的NSCLC肿瘤标记物癌胚抗原(CEA)、糖类蛋白-125(CA-125)、细胞角蛋白19可溶性片段(CYFRA21-1)的水平以及淋巴细胞亚群CD3+、CD4+、CD8+比例。分析不同疗效的NSCLC患者肿瘤标记物水平及淋巴细胞亚群的差异。结果(1)腺癌、鳞癌患者CEA、CA-125和CYFRA21-1水平均显著高于健康人群(P<0.05);鳞癌患者CEA升高水平低于腺癌,而鳞癌CA-125和CYFRA21-1升高水平高于腺癌(P<0.05);相对于健康人群,腺癌、鳞癌患者CD3+、CD4+、CD4+/CD8+均显著降低,而CD8+升高(P<0.05);但鳞癌、腺癌患者CD3+、CD4+、CD8+、CD4+/CD8+差异无统计学意义(P>0.05)。(2)经2个周期化疗后,缓解和部分缓解共18例,稳定和进展共22例。新辅助化疗有效的鳞癌患者血清CA-125和CYFRA21-1水平显著降低(P<0.05),新辅助化疗有效的腺癌患者血清CEA 和 CYFRA21-1水平显著降低(P<0.05)。新辅助化疗有效鳞癌、腺癌患者CD3+、CD4+、CD4+/CD8+升高,CD8+降低。结论不同病理类型的晚期NSCLC患者血清肿瘤标记物表达水平具有一定的差异,血清标记物与淋巴细胞亚群的变化均可作为评价新辅助化疗疗效的指标。%Objective To observe and analyze the effect of neoadjuvant chemotherapy on locally advanced non-small cell lung cancer tumor markers and lymphocyte subsets of different pathological type .Methods A total number of 40 NSCLC patients which received neoadjuvant chemotherapy and 20 normal people were selected in our study .To compare the differences of CEA ,CA-125 , CYFRA21-1 and

  18. A method for high purity sorting of rare cell subsets applied to TDC.

    Science.gov (United States)

    Kuka, Mirela; Ashwell, Jonathan D

    2013-12-31

    T(DC) are a recently described subset of polyclonal αβ T-cells with dendritic cell properties. Because of their low number in peripheral immune compartments, isolation and characterization of T(DC) with existing purification methods are technically challenging. Here we describe a customized gating strategy and a flow cytometry-based cell sorting protocol for isolation of T(DC). The protocol was developed because, despite very conservative gating for dead-cell and doublet exclusion, cells obtained with normal sorting procedures were enriched for T(DC) but not pure. Re-sorting the output of the first round of sorting results in highly pure T(DC). Cells obtained with this method are viable and can be used for in vitro characterization. Moreover, this double-round sorting strategy can be universally applied to the isolation of other rare cell subsets.

  19. Anti-protozoal and anti-bacterial antibiotics that inhibit protein synthesis kill cancer subtypes enriched for stem cell-like properties

    OpenAIRE

    2015-01-01

    Key players in translational regulation such as ribosomes might represent powerful, but hitherto largely unexplored, targets to eliminate drug-refractory cancer stem cells (CSCs). A recent study by the Lisanti group has documented how puromycin, an old antibiotic derived from Streptomyces alboniger that inhibits ribosomal protein translation, can efficiently suppress CSC states in tumorspheres and monolayer cultures. We have used a closely related approach based on Biolog Phenotype Microarray...

  20. Identification of polarized macrophage subsets in zebrafish.

    Science.gov (United States)

    Nguyen-Chi, Mai; Laplace-Builhe, Béryl; Travnickova, Jana; Luz-Crawford, Patricia; Tejedor, Gautier; Phan, Quang Tien; Duroux-Richard, Isabelle; Levraud, Jean-Pierre; Kissa, Karima; Lutfalla, Georges; Jorgensen, Christian; Djouad, Farida

    2015-07-08

    While the mammalian macrophage phenotypes have been intensively studied in vitro, the dynamic of their phenotypic polarization has never been investigated in live vertebrates. We used the zebrafish as a live model to identify and trail macrophage subtypes. We generated a transgenic line whose macrophages expressing tumour necrosis factor alpha (tnfa), a key feature of classically activated (M1) macrophages, express fluorescent proteins Tg(mpeg1:mCherryF/tnfa:eGFP-F). Using 4D-confocal microscopy, we showed that both aseptic wounding and Escherichia coli inoculation triggered macrophage recruitment, some of which started to express tnfa. RT-qPCR on Fluorescence Activated Cell Sorting (FACS)-sorted tnfa(+) and tnfa(-) macrophages showed that they, respectively, expressed M1 and alternatively activated (M2) mammalian markers. Fate tracing of tnfa(+) macrophages during the time-course of inflammation demonstrated that pro-inflammatory macrophages converted into M2-like phenotype during the resolution step. Our results reveal the diversity and plasticity of zebrafish macrophage subsets and underline the similarities with mammalian macrophages proposing a new system to study macrophage functional dynamic.

  1. Large convexly independent subsets of Minkowski sums

    CERN Document Server

    Swanepoel, Konrad J

    2010-01-01

    Let $E_d(n)$ be the maximum number of pairs that can be selected from a set of $n$ points in $R^d$ such that the midpoints of these pairs are convexly independent. We show that $E_2(n)\\geq \\Omega(n\\sqrt{\\log n})$, which answers a question of Eisenbrand, Pach, Rothvo\\ss, and Sopher (2008) on large convexly independent subsets in Minkowski sums of finite planar sets, as well as a question of Halman, Onn, and Rothblum (2007). We also show that $\\lfloor\\frac{1}{3}n^2\\rfloor\\leq E_3(n)\\leq \\frac{3}{8}n^2+O(n^{3/2})$. Let $W_d(n)$ be the maximum number of pairwise nonparallel unit distance pairs in a set of $n$ points in some $d$-dimensional strictly convex normed space. We show that $W_2(n)=\\Theta(E_2(n))$ and for $d\\geq 3$ that $W_d(n)\\sim\\frac12\\left(1-\\frac{1}{a(d)}\\right)n^2$, where $a(d)\\in N$ is related to strictly antipodal families. In fact we show that the same asymptotics hold without the requirement that the unit distance pairs form pairwise nonparallel segments, and also if diameter pairs are considere...

  2. Arithmetic progressions in Salem-type subsets of the integers

    CERN Document Server

    Potgieter, Paul

    2010-01-01

    Given a subset of the integers of zero density, we define the weaker notion of fractional density of such a set. It is shown how this notion corresponds to that of the Hausdorff dimension of a compact subset of the reals. We then show that a version of a theorem of {\\L}aba and Pramanik on 3-term arithmetic progressions in subsets of the unit interval also holds for subsets of the integers with fractional density and satisfying certain Fourier-decay conditions.

  3. A novel HMM-based method for detecting enriched transcription factor binding sites reveals RUNX3 as a potential target in pancreatic cancer biology.

    Directory of Open Access Journals (Sweden)

    Liron Levkovitz

    Full Text Available BACKGROUND: Pancreatic adenocarcinoma (PAC is one of the most intractable malignancies. In order to search for potential new therapeutic targets, we relied on computational methods aimed at identifying transcription factor binding sites (TFBSs over-represented in the promoter regions of genes differentially expressed in PAC. Though many computational methods have been implemented to accomplish this, none has gained overall acceptance or produced proven novel targets in PAC. To this end we have developed DEMON, a novel method for motif detection. METHODOLOGY: DEMON relies on a hidden Markov model to score the appearance of sequence motifs, taking into account all potential sites in a promoter of potentially varying binding affinities. We demonstrate DEMON's accuracy on simulated and real data sets. Applying DEMON to PAC-related data sets identifies the RUNX family as highly enriched in PAC-related genes. Using a novel experimental paradigm to distinguish between normal and PAC cells, we find that RUNX3 mRNA (but not RUNX1 or RUNX2 mRNAs exhibits time-dependent increases in normal but not in PAC cells. These increases are accompanied by changes in mRNA levels of putative RUNX gene targets. CONCLUSIONS: The integrated application of DEMON and a novel differentiation system led to the identification of a single family member, RUNX3, which together with four of its putative targets showed a robust response to a differentiation stimulus in healthy cells, whereas this regulatory mechanism was absent in PAC cells, emphasizing RUNX3 as a promising target for further studies.

  4. T-lymphocyte subsets in recurrent aphthous ulceration

    DEFF Research Database (Denmark)

    Pedersen, A; Klausen, B; Hougen, H P;

    1989-01-01

    Peripheral T-lymphocyte subsets: T-helper (OKT4) and T-suppressor (OKT8) cells were studied quantitatively in 20 patients with recurrent aphthous ulceration (RAU) in ulcerative, as well as inactive, stages of the disease. The figures were compared with T-lymphocyte subsets from matched control do...

  5. Uranium Conversion & Enrichment

    Energy Technology Data Exchange (ETDEWEB)

    Karpius, Peter Joseph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-02-06

    The isotopes of uranium that are found in nature, and hence in ‘fresh’ Yellowcake’, are not in relative proportions that are suitable for power or weapons applications. The goal of conversion then is to transform the U3O8 yellowcake into UF6. Conversion and enrichment of uranium is usually required to obtain material with enough 235U to be usable as fuel in a reactor or weapon. The cost, size, and complexity of practical conversion and enrichment facilities aid in nonproliferation by design.

  6. Enriching the Catalog

    Science.gov (United States)

    Tennant, Roy

    2004-01-01

    After decades of costly and time-consuming effort, nearly all libraries have completed the retrospective conversion of their card catalogs to electronic form. However, bibliographic systems still are really not much more than card catalogs on wheels. Enriched content that Amazon.com takes for granted--such as digitized tables of contents, cover…

  7. Progressive Enrichment of Stemness Features and Tumor Stromal Alterations in Multistep Hepatocarcinogenesis.

    Science.gov (United States)

    Yoo, Jeong Eun; Kim, Young-Joo; Rhee, Hyungjin; Kim, Haeryoung; Ahn, Ei Yong; Choi, Jin Sub; Roncalli, Massimo; Park, Young Nyun

    2017-01-01

    Cancer stem cells (CSCs), a subset of tumor cells, contribute to an aggressive biological behavior, which is also affected by the tumor stroma. Despite the role of CSCs and the tumor stroma in hepatocellular carcinoma (HCC), features of stemness have not yet been studied in relation to tumor stromal alterations in multistep hepatocarcinogenesis. We investigated the expression status of stemness markers and tumor stromal changes in B viral carcinogenesis, which is the main etiology of HCC in Asia. Stemness features of tumoral hepatocytes (EpCAM, K19, Oct3/4, c-KIT, c-MET, and CD133), and tumor stromal cells expressing α-smooth muscle actin (α-SMA), CD68, CD163, and IL-6 were analyzed in 36 low grade dysplastic nodules (DNs), 48 high grade DNs, 30 early HCCs (eHCCs), and 51 progressed HCCs (pHCCs) by immunohistochemistry or real-time PCR. Stemness features (EpCAM and K19 in particular) were progressively acquired during hepatocarcinogenesis in combination with enrichment of stromal cells (CAFs, TAMs, IL-6+ cells). Stemness features were seen sporadically in DNs, more consistent in eHCCs, and peaked in pHCCs. Likewise, stromal cells were discernable in DNs, showed up as consistent cell densities in eHCCs and peaked in pHCCs. The stemness features and tumor stromal alterations also peaked in less differentiated or larger HCCs. In conclusion, progression of B viral multistep hepatocarcinogenesis is characterized by an enrichment of stemness features of neoplastic hepatocytes and a parallel alteration of the tumor stroma. The modulation of neoplastic hepatocytes and stromal cells was at low levels in precancerous lesions (DNs), consistently increased in incipient cancer (eHCCs) and peaked in pHCCs. Thus, in B viral hepatocarcinogenesis, interactions between CSCs and the tumor stroma, although starting early, seem to play a major role in tumor progression.

  8. Human NK Cell Subsets in Pregnancy and Disease: Toward a New Biological Complexity

    Science.gov (United States)

    Cristiani, Costanza Maria; Palella, Eleonora; Sottile, Rosa; Tallerico, Rossana; Garofalo, Cinzia; Carbone, Ennio

    2016-01-01

    In humans, NK cells are mainly identified by the surface expression levels of CD56 and CD16, which differentiate between five functionally different NK cell subsets. However, nowadays NK cells are considered as a more heterogeneous population formed by various subsets differing in function, surface phenotype, and anatomic localization. In human CMV- and hantaviruses-infected subjects, an increased frequency of a NKG2A−CD57+NKG2C+ NK cell subset has been observed, while the phenotype of the NK cell subpopulation associated with cancer may vary according to the specific kind of tumor and its anatomical location. The healthy human lymph nodes contain mainly the CD56bright NK cell subset while in melanoma metastatic lymph nodes the CD56dimCD57+KIR+CCR7+ NK cell subpopulation prevails. The five NK cell subpopulations are found in breast cancer patients, where they differ for expression pattern of chemokine receptors, maturation stage, functional capabilities. In pregnancy, uterine NK cells show a prevalence of the CD56brightCD16− NK cell compartment, whose activity is influenced by KIRs repertoire. This NK cell subset’s super specialization could be explained by (i) the expansion of single mature CD56dim clones, (ii) the recruitment and maturation of CD56bright NK cells through specific stimuli, and (iii) the in situ development of tumor-resident NK cells from tissue-resident CD56bright NK cells independently of the circulating NK cell compartment. This new and unexpected biological feature of the NK cell compartment could be an important source of new biomarkers to improve patients’ diagnosis. PMID:28082990

  9. Stem cell-like gene expression in ovarian cancer predicts type II subtype and prognosis.

    Directory of Open Access Journals (Sweden)

    Matthew Schwede

    Full Text Available Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age, the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further

  10. Multiparametric profiling of non–small-cell lung cancers reveals distinct immunophenotypes

    Science.gov (United States)

    Lizotte, Patrick H.; Ivanova, Elena V.; Awad, Mark M.; Jones, Robert E.; Keogh, Lauren; Liu, Hongye; Dries, Ruben; Herter-Sprie, Grit S.; Santos, Abigail; Feeney, Nora B.; Paweletz, Cloud P.; Kulkarni, Meghana M.; Bass, Adam J.; Rustgi, Anil K.; Yuan, Guo-Cheng; Kufe, Donald W.; Jänne, Pasi A.; Hammerman, Peter S.; Sholl, Lynette M.; Hodi, F. Stephen; Richards, William G.; Bueno, Raphael; English, Jessie M.; Bittinger, Mark A.

    2016-01-01

    BACKGROUND. Immune checkpoint blockade improves survival in a subset of patients with non–small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. METHODS. We performed comprehensive flow cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next-generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). RESULTS. Cytometric profiling identified an immunologically “hot” cluster with abundant CD8+ T cells expressing high levels of PD-1 and TIM-3 and an immunologically “cold” cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers. The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster. Additionally, approximately 20% of cases had high B cell infiltrates with a subset producing IL-10. CONCLUSIONS. Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer. FUNDING. The Robert A. and Renée E. Belfer Family Foundation, Expect Miracles Foundation, Starr Cancer Consortium, Stand Up to Cancer Foundation, Conquer Cancer Foundation, International Association for the Study of Lung Cancer, National Cancer Institute (R01 CA205150), and the Damon Runyon Cancer Research Foundation. PMID:27699239

  11. Reliability analysis and updating of deteriorating systems with subset simulation

    DEFF Research Database (Denmark)

    Schneider, Ronald; Thöns, Sebastian; Straub, Daniel

    2017-01-01

    Bayesian updating of the system deterioration model. The updated system reliability is then obtained through coupling the updated deterioration model with a probabilistic structural model. The underlying high-dimensional structural reliability problems are solved using subset simulation, which...

  12. Semilinear elliptic problems on unbounded subsets of the Heisenberg group

    Directory of Open Access Journals (Sweden)

    K. Tintarev

    2001-03-01

    Full Text Available In this paper we discuss the applications of an abstract version of concentration compactness to minimax problems. In particular, we prove the existence of solutions to semilinear elliptic problems on unbounded subsets of the Heisenberg group.

  13. Codings of separable compact subsets of the first Baire class

    CERN Document Server

    Dodos, Pandelis

    2008-01-01

    Let $X$ be a Polish space and $K$ a separable compact subset of the first Baire class on $X$. For every sequence $\\bs$ dense in $\\kk$, the descriptive set-theoretic properties of the set \\[ \\lbf=\\{L\\in[\

  14. Ineffective oesophageal motility: Manometric subsets exhibit different symptom profiles

    Institute of Scientific and Technical Information of China (English)

    Horst Gunter Haack; Ross David Hansen; Allison Malcolm; John Edward Kellow

    2008-01-01

    AIM: To compare the demographic and clinical features of different manometric subsets of ineffective oesophageal motility (IOM; defined as ≥30% wet swallows with distal contractile amplitude <30 mmHg), and to determine whether the prevalence of gastro-oesophageal reflux differs between IOM subsets.METHODS: Clinical characteristics of manometric subsets were determined in 100 IOM patients (73 female, median age 58 years) and compared to those of 100 age-and gender-matched patient controls with oesophageal symptoms, but normal manometry. Supine oesophageal manometry was performed with an eight-channel DentSleeve water-perfused catheter, and an ambulatory pH study assessed gastrooesophageal reflux.RESULTS: Patients in the IOM subset featuring a majority of low-amplitude simultaneous contractions (LASC) experienced less heartburn (prevalence 26%), but more dysphagia (57%) than those in the IOM subset featuring low-amplitude propagated contractions (LAP; heartburn 70%, dysphagia 24%; both P≤0.01). LASC patients also experienced less heartburn and more dysphagia than patient controls (heartburn 68%, dysphagia 11%; both P<0.001). The prevalence of heartburn and dysphagia in IOM patients featuring a majority of non-transmitted sequences (NT) was 54% (P=0.04 vs LASC) and 36% (P<0.01 vs controls), respectively. No differences in age and gender distribution, chest pain prevalence, acid exposure time (AET) and symptom/reflux association existed between IOM subsets, or between subsets and controls.CONCLUSION: IOM patients with LASC exhibit a different symptom profile to those with LAP, but do not differ in gastro-oesophageal reflux prevalence. These findings raise the possibility of different pathophysiological mechanisms in IOM subsets, which warrants further investigation.

  15. Origin of CD8+ Effector and Memory T Cell Subsets

    Institute of Scientific and Technical Information of China (English)

    Christian Stemberger; Michael Neuenhahn; Veit R.Buchholz; Dirk H.Busch

    2007-01-01

    It is well accepted that CD8+ T cells play a pivotal role in providing protection against infection with intracellular pathogens and some tumors. In many cases protective immunity is maintained for long periods of time (immunological memory). Over the past years, it has become evident that in order to fulfill these multiple tasks,distinct subsets of effector and memory T cells have to be generated. Until today, however, little is known about the underlying mechanisms of subset differentiation and the timing of lineage fate decisions. In this context, it is of special importance to determine at which level of clonal expansion functional and phenotypical heterogeneity is achieved. Different models for T cell subset diversification have been proposed; these differ mainly in the time point during priming and clonal expansion (prior, during, or beyond the first cell division) when differentiation programs are induced. Recently developed single-cell adoptive transfer technology has allowed us to demonstrate that individual precursor cell still bears the full plasticity to develop into a plethora different T cell subsets. This observation targets the shaping of T cell subset differentiation towards factors that are still operative beyond the first cell division. These findings have important implications for vaccine development, as the modulation of differentiation patterns towards distinct subsets could become a powerful strategy to enhance the efficacy and quality of vaccines.

  16. Multi-lingual search engine to access PubMed monolingual subsets: a feasibility study.

    Science.gov (United States)

    Darmoni, Stéfan J; Soualmia, Lina F; Griffon, Nicolas; Grosjean, Julien; Kerdelhué, Gaétan; Kergourlay, Ivan; Dahamna, Badisse

    2013-01-01

    PubMed contains many articles in languages other than English but it is difficult to find them using the English version of the Medical Subject Headings (MeSH) Thesaurus. The aim of this work is to propose a tool allowing access to a PubMed subset in one language, and to evaluate its performance. Translations of MeSH were enriched and gathered in the information system. PubMed subsets in main European languages were also added in our database, using a dedicated parser. The CISMeF generic semantic search engine was evaluated on the response time for simple queries. MeSH descriptors are currently available in 11 languages in the information system. All the 654,000 PubMed citations in French were integrated into CISMeF database. None of the response times exceed the threshold defined for usability (2 seconds). It is now possible to freely access biomedical literature in French using a tool in French; health professionals and lay people with a low English language may find it useful. It will be expended to several European languages: German, Spanish, Norwegian and Portuguese.

  17. Variance optimal sampling based estimation of subset sums

    CERN Document Server

    Cohen, Edith; Kaplan, Haim; Lund, Carsten; Thorup, Mikkel

    2008-01-01

    From a high volume stream of weighted items, we want to maintain a generic sample of a certain limited size $k$ that we can later use to estimate the total weight of arbitrary subsets. This is the classic context of on-line reservoir sampling, thinking of the generic sample as a reservoir. We present a reservoir sampling scheme providing variance optimal estimation of subset sums. More precisely, if we have seen $n$ items of the stream, then for any subset size $m$, our scheme based on $k$ samples minimizes the average variance over all subsets of size $m$. In fact, the optimality is against any off-line sampling scheme tailored for the concrete set of items seen: no off-line scheme based on $k$ samples can perform better than our on-line scheme when it comes to average variance over any subset size. Our scheme has no positive covariances between any pair of item estimates. Also, our scheme can handle each new item of the stream in $O(\\log k)$ time, which is optimal even on the word RAM.

  18. Chemokine-mediated distribution of dendritic cell subsets in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Meyer Werner

    2010-10-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC represents one of the most immunoresponsive cancers. Antigen-specific vaccination with dendritic cells (DCs in patients with metastatic RCC has been shown to induce cytotoxic T-cell responses associated with objective clinical responses. Thus, clinical trials utilizing DCs for immunotherapy of advanced RCCs appear to be promising; however, detailed analyses concerning the distribution and function of DC subsets in RCCs are lacking. Methods We characterized the distribution of the different immature and mature myeloid DC subsets in RCC tumour tissue and the corresponding normal kidney tissues. In further analyses, the expression of various chemokines and chemokine receptors controlling the migration of DC subsets was investigated. Results The highest numbers of immature CD1a+ DCs were found within RCC tumour tissue. In contrast, the accumulation of mature CD83+/DC-LAMP+ DCs were restricted to the invasive margin of the RCCs. The mature DCs formed clusters with proliferating T-cells. Furthermore, a close association was observed between MIP-3α-producing tumour cells and immature CCR6+ DC recruitment to the tumour bed. Conversely, MIP-3β and SLC expression was only detected at the tumour border, where CCR7-expressing T-cells and mature DCs formed clusters. Conclusion Increased numbers of immature DCs were observed within the tumour tissue of RCCs, whereas mature DCs were found in increased numbers at the tumour margin. Our results strongly implicate that the distribution of DC subsets is controlled by local lymphoid chemokine expression. Thus, increased expression of MIP-3α favours recruitment of immature DCs to the tumour bed, whereas de novo local expression of SLC and MIP-3β induces accumulation of mature DCs at the tumour margin forming clusters with proliferating T-cells reflecting a local anti-tumour immune response.

  19. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  20. Discovering cancer genes by integrating network and functional properties

    Directory of Open Access Journals (Sweden)

    Davis David P

    2009-09-01

    Full Text Available Abstract Background Identification of novel cancer-causing genes is one of the main goals in cancer research. The rapid accumulation of genome-wide protein-protein interaction (PPI data in humans has provided a new basis for studying the topological features of cancer genes in cellular networks. It is important to integrate multiple genomic data sources, including PPI networks, protein domains and Gene Ontology (GO annotations, to facilitate the identification of cancer genes. Methods Topological features of the PPI network, as well as protein domain compositions, enrichment of gene ontology categories, sequence and evolutionary conservation features were extracted and compared between cancer genes and other genes. The predictive power of various classifiers for identification of cancer genes was evaluated by cross validation. Experimental validation of a subset of the prediction results was conducted using siRNA knockdown and viability assays in human colon cancer cell line DLD-1. Results Cross validation demonstrated advantageous performance of classifiers based on support vector machines (SVMs with the inclusion of the topological features from the PPI network, protein domain compositions and GO annotations. We then applied the trained SVM classifier to human genes to prioritize putative cancer genes. siRNA knock-down of several SVM predicted cancer genes displayed greatly reduced cell viability in human colon cancer cell line DLD-1. Conclusion Topological features of PPI networks, protein domain compositions and GO annotations are good predictors of cancer genes. The SVM classifier integrates multiple features and as such is useful for prioritizing candidate cancer genes for experimental validations.

  1. Optimal Orderings of k-subsets for Star Identification

    CERN Document Server

    Mueller, Joerg H; Simões, Luís F; Izzo, Dario

    2016-01-01

    Finding the optimal ordering of k-subsets with respect to an objective function is known to be an extremely challenging problem. In this paper we introduce a new objective for this task, rooted in the problem of star identification on spacecrafts: subsets of detected spikes are to be generated in an ordering that minimizes time to detection of a valid star constellation. We carry out an extensive analysis of the combinatorial optimization problem, and propose multiple algorithmic solutions, offering different quality-complexity trade-offs. Three main approaches are investigated: exhaustive search (branch and prune), goal-driven (greedy scene elimination, minimally intersecting subsets), and stateless algorithms which implicitly seek to satisfy the problem's goals (pattern shifting, base unrank). In practical terms, these last algorithms are found to provide satisfactory approximations to the ideal performance levels, at small computational costs.

  2. A short and valid measure of work-family enrichment.

    Science.gov (United States)

    Kacmar, K Michele; Crawford, Wayne S; Carlson, Dawn S; Ferguson, Merideth; Whitten, Dwayne

    2014-01-01

    The stream of research concerning work-family enrichment has generated a significant body of research because it plays an important role in occupational health (Masuda, McNall, Allen, & Nicklin, 2012). work-family enrichment has been defined as "the extent to which experiences in one role improve the quality of life in the other role" (Greenhaus & Powell, 2006, p. 73). Within work-family enrichment, there are two directions: work to family and family to work. Carlson, Kacmar, Wayne, and Grzywacz (2006) developed an 18-item scale to measure this construct. Although the scale has been shown to be both reliable and valid, it also requires work-family researchers to include a proportionally large number of items to capture this construct in a study. The goal of the current study was to isolate a subset of the items in this measure that produces results similar to the full version thereby providing a more streamlined scale for researchers. Using a five-sample study that follows the scale reduction procedures offered by Stanton, Sinar, Balzer, and Smith (2002), we provide evidence that scales containing only three items for each direction of enrichment produce results equivalent to the full scale with respect to reliability and discriminant, convergent, and predictive validity. Reducing the original scale by two thirds, without losing explanatory power, allows scholars to measure enrichment in the work and family domains more efficiently, which should help minimize survey time, lower refusal rates, and generate less missing data.

  3. Investigating evolutionary conservation of dendritic cell subset identity and functions

    Directory of Open Access Journals (Sweden)

    Thien-Phong eVu Manh

    2015-06-01

    Full Text Available Dendritic cells (DC were initially defined as mononuclear phagocytes with a dendritic morphology and an exquisite efficiency for naïve T cell activation. DC encompass several subsets initially identified by their expression of specific cell surface molecules and later shown to excel in distinct functions and to develop under the instruction of different transcription factors or cytokines. Very few cell surface molecules are expressed in a specific manner on any immune cell type. Hence, to identify cell types, the sole use of a small number of cell surface markers in classical flow cytometry can be deceiving. Moreover, the markers currently used to define mononuclear phagocyte subsets vary depending on the tissue and animal species studied and even between laboratories. This has led to confusion in the definition of DC subset identity and in their attribution of specific functions. There is a strong need to identify a rigorous and consensus way to define mononuclear phagocyte subsets, with precise guidelines potentially applicable throughout tissues and species. We will discuss the advantages, drawbacks and complementarities of different methodologies: cell surface phenotyping, ontogeny, functional characterization and molecular profiling. We will advocate that gene expression profiling is a very rigorous, largely unbiased and accessible method to define the identity of mononuclear phagocyte subsets, which strengthens and refines surface phenotyping. It is uniquely powerful to yield new, experimentally testable, hypotheses on the ontogeny or functions of mononuclear phagocyte subsets, their molecular regulation and their evolutionary conservation. We propose defining cell populations based on a combination of cell surface phenotyping, expression analysis of hallmark genes and robust functional assays, in order to reach a consensus and integrate faster the huge but scattered knowledge accumulated by different laboratories on different cell types

  4. A community study of T lymphocyte subsets and malaria parasitaemia

    DEFF Research Database (Denmark)

    Lisse, I M; Aaby, P; Whittle, H

    1994-01-01

    In a community survey of 312 children aged 3-6 years in urban Guinea-Bissau, we examined Plasmodium falciparum parasitaemia and T cell subsets. 183 children (59%) had parasites in their blood, 13 had fever > or = 37.5 degrees C, and 9 (3%) had fever and a parasite density > 5000/microL (clinical...... parasites (P = 0.024), whereas there was no association with CD8 cell percentage or the CD4/CD8 ratio. Asymptomatic parasitaemia may be an important confounder in general community studies of T cell subsets in the tropics....

  5. On the size of the subset partial order

    DEFF Research Database (Denmark)

    Elmasry, Amr Ahmed Abd Elmoneim

    2012-01-01

    Given a family of k sets with cardinalities S 1,S 2,⋯, S k and N=Σ k i=1S i, we show that the size of the partial order graph induced by the subset relation (called the subset graph) is O(Σ si≤B 2si+N/lgN·Σ si>Blg(s i/B)), 2 where B=lg(N/lg 2N). This implies a simpler proof to the O(N 2/lg 2N...

  6. Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes

    DEFF Research Database (Denmark)

    Johnatty, Sharon E; Tyrer, Jonathan P; Kar, Siddhartha;

    2015-01-01

    PURPOSE: Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome. EXPERIMENTAL DESIGN: We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment...... for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent first-line treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with ≥ 4 cycles of paclitaxel and carboplatin...... at standard doses. We evaluated the top SNPs in 4,434 EOC patients, including patients from The Cancer Genome Atlas. In addition, we conducted pathway analysis of all intragenic SNPs and tested their association with PFS and OS using gene set enrichment analysis. RESULTS: Five SNPs were significantly...

  7. Thermal breeder fuel enrichment zoning

    Science.gov (United States)

    Capossela, Harry J.; Dwyer, Joseph R.; Luce, Robert G.; McCoy, Daniel F.; Merriman, Floyd C.

    1992-01-01

    A method and apparatus for improving the performance of a thermal breeder reactor having regions of higher than average moderator concentration are disclosed. The fuel modules of the reactor core contain at least two different types of fuel elements, a high enrichment fuel element and a low enrichment fuel element. The two types of fuel elements are arranged in the fuel module with the low enrichment fuel elements located between the high moderator regions and the high enrichment fuel elements. Preferably, shim rods made of a fertile material are provided in selective regions for controlling the reactivity of the reactor by movement of the shim rods into and out of the reactor core. The moderation of neutrons adjacent the high enrichment fuel elements is preferably minimized as by reducing the spacing of the high enrichment fuel elements and/or using a moderator having a reduced moderating effect.

  8. Clustering, Seriation, and Subset Extraction of Confusion Data

    Science.gov (United States)

    Brusco, Michael J.; Steinley, Douglas

    2006-01-01

    The study of confusion data is a well established practice in psychology. Although many types of analytical approaches for confusion data are available, among the most common methods are the extraction of 1 or more subsets of stimuli, the partitioning of the complete stimulus set into distinct groups, and the ordering of the stimulus set. Although…

  9. Directed Subset Feedback Vertex Set is Fixed-Parameter Tractable

    CERN Document Server

    Chitnis, Rajesh; Hajiaghayi, MohammadTaghi; Marx, Dániel

    2012-01-01

    Given a graph $G$ and an integer $k$, the \\textsc{Feedback Vertex Set} (\\textsc{FVS}) problem asks if there is a vertex set $T$ of size at most $k$ that hits all cycles in the graph. Bodlaender (WG '91) gave the first fixed-parameter algorithm for \\textsc{FVS} in undirected graphs. The fixed-parameter tractability status of \\textsc{FVS} in directed graphs was a long-standing open problem until Chen et al. (STOC '08) showed that it is fixed-parameter tractable by giving an $4^{k}k!n^{O(1)}$ algorithm. In the subset versions of this problems, we are given an additional subset $S$ of vertices (resp. edges) and we want to hit all cycles passing through a vertex of $S$ (resp. an edge of $S$). Indeed both the edge and vertex versions are known to be equivalent in the parameterized sense. Recently the \\textsc{Subset Feedback Vertex Set} in undirected graphs was shown to be FPT by Cygan et al. (ICALP '11) and Kakimura et al. (SODA '12). We generalize the result of Chen et al. (STOC '08) by showing that \\textsc{Subset...

  10. RECEIVE ANTENNA SUBSET SELECTION BASED ON ORTHOGONAL COMPONENTS

    Institute of Scientific and Technical Information of China (English)

    Lan Peng; Liu Ju; Gu Bo; Zhang Wei

    2007-01-01

    A new receive antenna subset selection algorithm with low complexity for wireless Multiple-Input Multiple-Output (MIMO) systems is proposed, which is based on the orthogonal components of the channel matrix. Larger capacity is achieved compared with the existing antenna selection methods. Simulation results of quasi-static flat fading channel demonstrate the significant performance of the proposed selection algorithm.

  11. Combinatorial Identities Via Phi Functions and Relatively Prime Subsets

    CERN Document Server

    Bachraoui, Mohamed El

    2010-01-01

    Let $n$ be a positive integer and let $A$ be nonempty finite set of positive integers. We say that $A$ is relatively prime if $\\gcd(A) =1$ and that $A$ is relatively prime to $n$ if $\\gcd(A,n)=1$. In this work we count the number of nonempty subsets of $A$ which are relatively prime and the number of nonempty subsets of $A$ which are relatively prime to $n$. Related formulas are also obtained for the number of such subsets having some fixed cardinality. This extends previous work for the cases where $A$ is an interval or a set in arithmetic progression. Applications include: a) An exact formula is obtained for the number of elements of $A$ which are co-prime to $n$; note that this number is $\\phi(n)$ if $A=[1,n]$. b) Algebraic characterizations are found for a nonempty finite set of positive integers to have elements which are all pairwise co-prime and consequently a formula is given for the number of nonempty subsets of $A$ whose elements are pairwise co-prime. c) We provide combinatorial formulas involving ...

  12. Effects of a Simulated Tennis Match on Lymphocyte Subset Measurements

    Science.gov (United States)

    Schafer, Mark; Kell, Holly; Navalta, James; Tibana, Ramires; Lyons, Scott; Arnett, Scott

    2014-01-01

    Tennis is an activity requiring both endurance and anaerobic components, which could have immunosuppressive effects postexercise. Purpose: The purpose of this investigation was to determine the effect of a simulated tennis match on apoptotic and migratory markers on lymphocyte subsets. Method: Male high school (n = 5) and college (n = 3) tennis…

  13. Modelling subset multivariate ARCH model via the AIC principle

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    In this paper we consider the problem of identifying a parsimonious subset multivariate ARCH model based on the AIC principle. The proposed approach can reduce the number of parameters in the final ARCH specification and allows for non-constant correlations between the components. Some simulation results illustrate the viability of the proposed procedure.

  14. IL-10 conditioning of human skin affects the distribution of migratory dendritic cell subsets and functional T cell differentiation.

    Science.gov (United States)

    Lindenberg, Jelle J; Oosterhoff, Dinja; Sombroek, Claudia C; Lougheed, Sinéad M; Hooijberg, Erik; Stam, Anita G M; Santegoets, Saskia J A M; Tijssen, Henk J; Buter, Jan; Pinedo, Herbert M; van den Eertwegh, Alfons J M; Scheper, Rik J; Koenen, Hans J P M; van de Ven, Rieneke; de Gruijl, Tanja D

    2013-01-01

    In cancer patients pervasive systemic suppression of Dendritic Cell (DC) differentiation and maturation can hinder vaccination efficacy. In this study we have extensively characterized migratory DC subsets from human skin and studied how their migration and T cell-stimulatory abilities were affected by conditioning of the dermal microenvironment through cancer-related suppressive cytokines. To assess effects in the context of a complex tissue structure, we made use of a near-physiological skin explant model. By 4-color flow cytometry, we identified migrated Langerhans Cells (LC) and five dermis-derived DC populations in differential states of maturation. From a panel of known tumor-associated suppressive cytokines, IL-10 showed a unique ability to induce predominant migration of an immature CD14(+)CD141(+)DC-SIGN(+) DC subset with low levels of co-stimulatory molecules, up-regulated expression of the co-inhibitory molecule PD-L1 and the M2-associated macrophage marker CD163. A similarly immature subset composition was observed for DC migrating from explants taken from skin overlying breast tumors. Whereas predominant migration of mature CD1a(+) subsets was associated with release of IL-12p70, efficient Th cell expansion with a Th1 profile, and expansion of functional MART-1-specific CD8(+) T cells, migration of immature CD14(+) DDC was accompanied by increased release of IL-10, poor expansion of CD4(+) and CD8(+) T cells, and skewing of Th responses to favor coordinated FoxP3 and IL-10 expression and regulatory T cell differentiation and outgrowth. Thus, high levels of IL-10 impact the composition of skin-emigrated DC subsets and appear to favor migration of M2-like immature DC with functional qualities conducive to T cell tolerance.

  15. IL-10 conditioning of human skin affects the distribution of migratory dendritic cell subsets and functional T cell differentiation.

    Directory of Open Access Journals (Sweden)

    Jelle J Lindenberg

    Full Text Available In cancer patients pervasive systemic suppression of Dendritic Cell (DC differentiation and maturation can hinder vaccination efficacy. In this study we have extensively characterized migratory DC subsets from human skin and studied how their migration and T cell-stimulatory abilities were affected by conditioning of the dermal microenvironment through cancer-related suppressive cytokines. To assess effects in the context of a complex tissue structure, we made use of a near-physiological skin explant model. By 4-color flow cytometry, we identified migrated Langerhans Cells (LC and five dermis-derived DC populations in differential states of maturation. From a panel of known tumor-associated suppressive cytokines, IL-10 showed a unique ability to induce predominant migration of an immature CD14(+CD141(+DC-SIGN(+ DC subset with low levels of co-stimulatory molecules, up-regulated expression of the co-inhibitory molecule PD-L1 and the M2-associated macrophage marker CD163. A similarly immature subset composition was observed for DC migrating from explants taken from skin overlying breast tumors. Whereas predominant migration of mature CD1a(+ subsets was associated with release of IL-12p70, efficient Th cell expansion with a Th1 profile, and expansion of functional MART-1-specific CD8(+ T cells, migration of immature CD14(+ DDC was accompanied by increased release of IL-10, poor expansion of CD4(+ and CD8(+ T cells, and skewing of Th responses to favor coordinated FoxP3 and IL-10 expression and regulatory T cell differentiation and outgrowth. Thus, high levels of IL-10 impact the composition of skin-emigrated DC subsets and appear to favor migration of M2-like immature DC with functional qualities conducive to T cell tolerance.

  16. Common fragile site profiling in epithelial and erythroid cells reveals that most recurrent cancer deletions lie in fragile sites hosting large genes.

    Science.gov (United States)

    Le Tallec, Benoît; Millot, Gaël Armel; Blin, Marion Esther; Brison, Olivier; Dutrillaux, Bernard; Debatisse, Michelle

    2013-08-15

    Cancer genomes exhibit numerous deletions, some of which inactivate tumor suppressor genes and/or correspond to unstable genomic regions, notably common fragile sites (CFSs). However, 70%-80% of recurrent deletions cataloged in tumors remain unexplained. Recent findings that CFS setting is cell-type dependent prompted us to reevaluate the contribution of CFS to cancer deletions. By combining extensive CFS molecular mapping and a comprehensive analysis of CFS features, we show that the pool of CFSs for all human cell types consists of chromosome regions with genes over 300 kb long, and different subsets of these loci are committed to fragility in different cell types. Interestingly, we find that transcription of large genes does not dictate CFS fragility. We further demonstrate that, like CFSs, cancer deletions are significantly enriched in genes over 300 kb long. We now provide evidence that over 50% of recurrent cancer deletions originate from CFSs associated with large genes.

  17. Chemoresistance of CD133+ cancer stem cells in laryngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    YANG Jing-pu; LIU Yan; ZHONG Wei; YU Dan; WEN Lian-ji; JIN Chun-shun

    2011-01-01

    Background Mounting evidence suggests that tumors are histologically heterogeneous and are maintained by a small population of tumor cells termed cancer stem cells. CD133 has been identified as a candidate marker of cancer stem cells in laryngeal carcinoma. This study aimed to analyze the chemoresistance of CD133+ cancer stem cells.Methods The response of Hep-2 cells to different chemotherapeutic agents was investigated and the expression of CD133 was studied. Fluorescence-activated cell sorting analysis was used to identify CD133,and the CD133+ subset of cells was separated and analyzed in colony formation assays,cell invasion assays,chemotherapy resistance studies,and analyzed for the expression of the drug resistance gene ABCG2.Results About 1%-2% of Hep-2 cells were CD133+ cells,and the CD133+ proportion was enriched by chemotherapy.CD133+ cancer stem cells exhibited higher potential for clonogenicity and invasion,and were more resistant to chemotherapy. This resistance was correlated with higher expression of ABCG2.Conclusions This study suggested that CD133+ cancer stem cells are more resistant to chemotherapy. The expression of ABCG2 could be partially responsible for this. Targeting this small population of CD133+ cancer stem cells could be a strategy to develop more effective treatments for laryngeal carcinoma.

  18. Hydrogen-enriched fuels

    Energy Technology Data Exchange (ETDEWEB)

    Roser, R. [NRG Technologies, Inc., Reno, NV (United States)

    1998-08-01

    NRG Technologies, Inc. is attempting to develop hardware and infrastructure that will allow mixtures of hydrogen and conventional fuels to become viable alternatives to conventional fuels alone. This commercialization can be successful if the authors are able to achieve exhaust emission levels of less than 0.03 g/kw-hr NOx and CO; and 0.15 g/kw-hr NMHC at full engine power without the use of exhaust catalysts. The major barriers to achieving these goals are that the lean burn regimes required to meet exhaust emissions goals reduce engine output substantially and tend to exhibit higher-than-normal total hydrocarbon emissions. Also, hydrogen addition to conventional fuels increases fuel cost, and reduces both vehicle range and engine output power. Maintaining low emissions during transient driving cycles has not been demonstrated. A three year test plan has been developed to perform the investigations into the issues described above. During this initial year of funding research has progressed in the following areas: (a) a cost effective single-cylinder research platform was constructed; (b) exhaust gas speciation was performed to characterize the nature of hydrocarbon emissions from hydrogen-enriched natural gas fuels; (c) three H{sub 2}/CH{sub 4} fuel compositions were analyzed using spark timing and equivalence ratio sweeping procedures and finally; (d) a full size pick-up truck platform was converted to run on HCNG fuels. The testing performed in year one of the three year plan represents a baseline from which to assess options for overcoming the stated barriers to success.

  19. CLEAN: CLustering Enrichment ANalysis

    Directory of Open Access Journals (Sweden)

    Medvedovic Mario

    2009-07-01

    Full Text Available Abstract Background Integration of biological knowledge encoded in various lists of functionally related genes has become one of the most important aspects of analyzing genome-wide functional genomics data. In the context of cluster analysis, functional coherence of clusters established through such analyses have been used to identify biologically meaningful clusters, compare clustering algorithms and identify biological pathways associated with the biological process under investigation. Results We developed a computational framework for analytically and visually integrating knowledge-based functional categories with the cluster analysis of genomics data. The framework is based on the simple, conceptually appealing, and biologically interpretable gene-specific functional coherence score (CLEAN score. The score is derived by correlating the clustering structure as a whole with functional categories of interest. We directly demonstrate that integrating biological knowledge in this way improves the reproducibility of conclusions derived from cluster analysis. The CLEAN score differentiates between the levels of functional coherence for genes within the same cluster based on their membership in enriched functional categories. We show that this aspect results in higher reproducibility across independent datasets and produces more informative genes for distinguishing different sample types than the scores based on the traditional cluster-wide analysis. We also demonstrate the utility of the CLEAN framework in comparing clusterings produced by different algorithms. CLEAN was implemented as an add-on R package and can be downloaded at http://Clusteranalysis.org. The package integrates routines for calculating gene specific functional coherence scores and the open source interactive Java-based viewer Functional TreeView (FTreeView. Conclusion Our results indicate that using the gene-specific functional coherence score improves the reproducibility of the

  20. Implementing Modifed Burg Algorithms in Multivariate Subset Autoregressive Modeling

    Directory of Open Access Journals (Sweden)

    A. Alexandre Trindade

    2003-02-01

    Full Text Available The large number of parameters in subset vector autoregressive models often leads one to procure fast, simple, and efficient alternatives or precursors to maximum likelihood estimation. We present the solution of the multivariate subset Yule-Walker equations as one such alternative. In recent work, Brockwell, Dahlhaus, and Trindade (2002, show that the Yule-Walker estimators can actually be obtained as a special case of a general recursive Burg-type algorithm. We illustrate the structure of this Algorithm, and discuss its implementation in a high-level programming language. Applications of the Algorithm in univariate and bivariate modeling are showcased in examples. Univariate and bivariate versions of the Algorithm written in Fortran 90 are included in the appendix, and their use illustrated.

  1. Myeloid-derived suppressor cell heterogeneity and subset definition.

    Science.gov (United States)

    Peranzoni, Elisa; Zilio, Serena; Marigo, Ilaria; Dolcetti, Luigi; Zanovello, Paola; Mandruzzato, Susanna; Bronte, Vincenzo

    2010-04-01

    Myeloid derived suppressor cells (MDSCs) are defined in mice on the basis of CD11b and Gr-1 marker expression and the functional ability to inhibit T lymphocyte activation. Nevertheless the term 'heterogeneous' remains the first, informal feature commonly attributed to this population. It is clear that CD11b(+)Gr-1(+) cells are part of a myeloid macropopulation, which comprises at least two subsets of polymorphonuclear and monocytic cells with different immunosuppressive properties. While recent literature shows substantial agreement on the immunoregulatory property of the monocytic MDSC subset, there is still contrasting evidence on the role of the granulocytic fraction. Moreover, this dichotomy holds true for human MDSCs. We attempt here to summarize conflicting findings in the field and provide some possible, unifying explanations.

  2. Subset Feature Learning for Fine-Grained Category Classification

    OpenAIRE

    Ge, Zongyuan; McCool, Christopher; Sanderson, Conrad; Corke, Peter

    2015-01-01

    Fine-grained categorisation has been a challenging problem due to small inter-class variation, large intra-class variation and low number of training images. We propose a learning system which first clusters visually similar classes and then learns deep convolutional neural network features specific to each subset. Experiments on the popular fine-grained Caltech-UCSD bird dataset show that the proposed method outperforms recent fine-grained categorisation methods under the most difficult sett...

  3. Cortistain is expressed in a distinct subset of cortical interneurons

    OpenAIRE

    Lecea Flores de Lemus, Luis de; Río Fernández, José Antonio del; Alcántara Horrillo, Soledad; Criado, José R.; Morales, Marisela; Danielson, Patria E.; Henriksen, Steven J.; Soriano García, Eduardo; Sutcliffe, J. Gregor

    1997-01-01

    Cortistatin is a presumptive neuropeptide that shares 11 of its 14 amino acids with somatostatin. In contrast to somatostatin, administration of cortistatin into the rat brain ventricles specifically enhances slow wave sleep, apparently by antagonizing the effects of acetylcholine on cortical excitability. Here we show that preprocortistatin mRNA is expressed in a subset of GABAergic cells in the cortex and hippocampus that partially overlap with those containing somatostatin. A significant p...

  4. Differentiable structure of ω-subsets of symplectic groups

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In this paper, we study the differentiable structure of theω-subset of Sp(2n), which is formed by all matrices in Sp(2n) possessing ω as an eigenvalue, for ω on the unit circle in the complex plane. Based on this result the ω-index theory parametrized by all ω on the unit circle for arbitrary symplectic paths is defined.

  5. Subset Simulation Method for Rare Event Estimation: An Introduction

    OpenAIRE

    2015-01-01

    This paper provides a detailed introductory description of Subset Simulation, an advanced stochastic simulation method for estimation of small probabilities of rare failure events. A simple and intuitive derivation of the method is given along with the discussion on its implementation. The method is illustrated with several easy-to-understand examples. For demonstration purposes, the MATLAB code for the considered examples is provided. The reader is assumed to be familiar only with elementary...

  6. Lymphocyte subset reference intervals in blood donors from northeastern Brazil

    Directory of Open Access Journals (Sweden)

    ALEX J.L. TORRES

    2015-06-01

    Full Text Available The reference intervals for leukocytes and lymphocytes currently used by most clinical laboratories present limitations as they are primarily derived from individuals of North American and European origin. The objective this study was to determine reference values for peripheral blood B lymphocytes, T lymphocyte subsets (CD4+, CD8+, naïve, memory, regulatory, TCRαβ and TCRγδ+ and NK cells from blood donors in Salvador-Bahia, Brazil. Results: The proportion of included male subjects was 73.7% and the median ages of males (34 and females (35 were found to be similar. Absolute counts total lymphocytes subsets to both gender was 1,956 (1,060-4,186 cells and relative values 34%. The T CD4+ and T CD8+ lymphocytes relative values was 51% (20-62 and 24% (9-28, respectively. The most statistically significant finding observed was a higher percentage of B lymphocytes (p=0.03 in females. Commonly cited subset reference intervals were found to be consistent with values in several populations from different geographic areas.

  7. Preparation of Internal Quality Control Material for Lymphocyte Subset Analysis.

    Science.gov (United States)

    Roh, Eun Youn; Shin, Sue; Yoon, Jong Hyun; Oh, Sohee; Park, Kyoung Un; Lee, Nuri; Song, Eun Young

    2016-07-01

    Lymphocyte subset analysis is widely used in clinical laboratories, and more than two levels of daily QC materials are required for reliable results. Commercially available, expensive QC materials have short shelf lives and may not be suitable in resource-poor settings. We compared different methods for preparing homemade QC material, including fixation with 1%, 2%, or 4% paraformaldehyde (PFA); freezing with 10% dimethylsulfoxide (DMSO), 0.1% bovine serum albumin-phosphate buffered saline, or after ethanolic dehydration; and using cryopreservation temperatures of -20°C, -80°C, or -196°C. We found an optimal experimental condition, which is 'fixation with 4% PFA, freezing with 10% DMSO, and storage at 80°C'. To evaluate long-term stability of QC materials prepared in this optimal condition, two levels of QC materials (QM1 and QM2) were thawed after 30, 33, 35, 37, 60, 62, 64, and 67 days of cryopreservation. Lymphocyte subset was analyzed with BD Multitest IMK kit (BD Biosciences, USA). QM1 and QM2 were stable after 1-2 months of cryopreservation (CV materials for lymphocyte subset analysis in resource-poor settings.

  8. T Helper Cell Subsets in Clinical Manifestations of Psoriasis

    Directory of Open Access Journals (Sweden)

    Marco Diani

    2016-01-01

    Full Text Available Psoriasis is a chronic inflammatory skin disease, which is associated with systemic inflammation and comorbidities, such as psoriatic arthritis and cardiovascular diseases. The autoimmune nature of psoriasis has been established only recently, conferring a central role to epidermal CD8 T cells recognizing self-epitopes in the initial phase of the disease. Different subsets of helper cells have also been reported as key players in the psoriasis pathogenesis. Here, we reviewed the knowledge on the role of each subset in the psoriatic cascade and in the different clinical manifestations of the disease. We will discuss the role of Th1 and Th17 cells in the initiation and in the amplification phase of cutaneous inflammation. Moreover, we will discuss the recently proposed role of tissue resident Th22 cells in disease memory in sites of recurrent psoriasis and the possible involvement of Th9 cells. Finally, we will discuss the hypothesis of a link between T helper cell subsets recirculating from the skin and the systemic manifestations of psoriasis.

  9. T Helper Cell Subsets in Clinical Manifestations of Psoriasis

    Science.gov (United States)

    Diani, Marco; Altomare, Gianfranco

    2016-01-01

    Psoriasis is a chronic inflammatory skin disease, which is associated with systemic inflammation and comorbidities, such as psoriatic arthritis and cardiovascular diseases. The autoimmune nature of psoriasis has been established only recently, conferring a central role to epidermal CD8 T cells recognizing self-epitopes in the initial phase of the disease. Different subsets of helper cells have also been reported as key players in the psoriasis pathogenesis. Here, we reviewed the knowledge on the role of each subset in the psoriatic cascade and in the different clinical manifestations of the disease. We will discuss the role of Th1 and Th17 cells in the initiation and in the amplification phase of cutaneous inflammation. Moreover, we will discuss the recently proposed role of tissue resident Th22 cells in disease memory in sites of recurrent psoriasis and the possible involvement of Th9 cells. Finally, we will discuss the hypothesis of a link between T helper cell subsets recirculating from the skin and the systemic manifestations of psoriasis. PMID:27595115

  10. Dysregulation of microRNA expression drives aberrant DNA hypermethylation in basal-like breast cancer.

    Science.gov (United States)

    Sandhu, Rupninder; Rivenbark, Ashley G; Mackler, Randi M; Livasy, Chad A; Coleman, William B

    2014-02-01

    Basal-like breast cancers frequently express aberrant DNA hypermethylation associated with concurrent silencing of specific genes secondary to DNMT3b overexpression and DNMT hyperactivity. DNMT3b is known to be post-transcriptionally regulated by microRNAs. The objective of the current study was to determine the role of microRNA dysregulation in the molecular mechanism governing DNMT3b overexpression in primary breast cancers that express aberrant DNA hypermethylation. The expression of microRNAs (miRs) that regulate (miR-29a, miR-29b, miR-29c, miR-148a and miR-148b) or are predicted to regulate DNMT3b (miR‑26a, miR-26b, miR-203 and miR-222) were evaluated among 70 primary breast cancers (36 luminal A-like, 13 luminal B-like, 5 HER2‑enriched, 16 basal-like) and 18 normal mammoplasty tissues. Significantly reduced expression of miR-29c distinguished basal-like breast cancers from other breast cancer molecular subtypes. The expression of aberrant DNA hypermethylation was determined in a subset of 33 breast cancers (6 luminal A-like, 6 luminal B-like, 5 HER2-enriched and 16 basal-like) through examination of methylation‑sensitive biomarker gene expression (CEACAM6, CDH1, CST6, ESR1, GNA11, MUC1, MYB, TFF3 and SCNN1A), 11/33 (33%) cancers exhibited aberrant DNA hypermethylation including 9/16 (56%) basal-like cancers, but only 2/17 (12%) non-basal-like cancers (luminal A-like, n=1; HER2-enriched, n=1). Breast cancers with aberrant DNA hypermethylation express diminished levels of miR-29a, miR-29b, miR-26a, miR-26b, miR-148a and miR-148b compared to cancers lacking aberrant DNA hypermethylation. A total of 7/9 (78%) basal-like breast cancers with aberrant DNA hypermethylation exhibit diminished levels of ≥6 regulatory miRs. The results show that i) reduced expression of miR-29c is characteristic of basal-like breast cancers, ii) miR and methylation-sensitive gene expression patterns identify two subsets of basal-like breast cancers, and iii) the subset of basal

  11. The Vast Universe of T Cell Diversity: Subsets of Memory Cells and Their Differentiation.

    Science.gov (United States)

    Jandus, Camilla; Usatorre, Amaia Martínez; Viganò, Selena; Zhang, Lianjun; Romero, Pedro

    2017-01-01

    The T cell receptor confers specificity for antigen recognition to T cells. By the first encounter with the cognate antigen, reactive T cells initiate a program of expansion and differentiation that will define not only the ultimate quantity of specific cells that will be generated, but more importantly their quality and functional heterogeneity. Recent achievements using mouse model infection systems have helped to shed light into the complex network of factors that dictate and sustain memory T cell differentiation, ranging from antigen load, TCR signal strength, metabolic fitness, transcriptional programs, and proliferative potential. The different models of memory T cell differentiation are discussed in this chapter, and key phenotypic and functional attributes of memory T cell subsets are presented, both for mouse and human cells. Therapeutic manipulation of memory T cell generation is expected to provide novel unique ways to optimize current immunotherapies, both in infection and cancer.

  12. Cancer

    Science.gov (United States)

    ... uses a surgical tool to remove the tumor.Mohs' surgery. Layers of cancer cells are removed one ... usually have not been approved by the U.S. Food and Drug Administration (FDA). The medicine may have ...

  13. Characterization of a chromosome-specific chimpanzee alpha satellite subset: Evolutionary relationship to subsets on human chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Warburton, P.E.; Gosden, J.; Lawson, D. [Western General Hospital, Edinburgh (United Kingdom)] [and others

    1996-04-15

    Alpha satellite DNA is a tandemly repeated DNA family found at the centromeres of all primate chromosomes examined. The fundamental repeat units of alpha satellite DNA are diverged 169- to 172-bp monomers, often found to be organized in chromosome-specific higher-order repeat units. The chromosomes of human (Homo sapiens (HSA)), chimpanzee (Pan troglodytes (PTR) and Pan paniscus), and gorilla (Gorilla gorilla) share a remarkable similarity and synteny. It is of interest to ask if alpha satellite arrays at centromeres of homologous chromosomes between these species are closely related (evolving in an orthologous manner) or if the evolutionary processes that homogenize and spread these arrays within and between chromosomes result in nonorthologous evolution of arrays. By using PCR primers specific for human chromosome 17-specific alpha satellite DNA, we have amplified, cloned, and characterized a chromosome-specific subset from the PTR chimpanzee genome. Hybridization both on Southern blots and in situ as well as sequence analysis show that this subset is most closely related, as expected, to sequences on HSA 17. However, in situ hybridization reveals that this subset is not found on the homologous chromosome in chimpanzee (PTR 19), but instead on PTR 12, which is homologous to HSA 2p. 40 refs., 3 figs.

  14. Influenza a virus induces an immediate cytotoxic activity in all major subsets of peripheral blood mononuclear cells.

    Directory of Open Access Journals (Sweden)

    Sanda Sturlan

    Full Text Available BACKGROUND: A replication defective influenza A vaccine virus (delNS1 virus was developed. Its attenuation is due to potent stimulation of the innate immune system by the virus. Since the innate immune system can also target cancer cells, we reasoned that delNS1 virus induced immune-stimulation should also lead to the induction of innate cytotoxic effects towards cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: Peripheral blood mononuclear cells (PBMCs, isolated CD56+, CD3+, CD14+ and CD19+ subsets and different combinations of the above subsets were stimulated by delNS1, wild type (wt virus or heat inactivated virus and co-cultured with tumor cell lines in the presence or absence of antibodies against the interferon system. Stimulation of PBMCs by the delNS1 virus effectively induced cytotoxicity against different cancer cell lines. Surprisingly, virus induced cytotoxicity was exerted by all major subtypes of PBMCs including CD56+, CD3+, CD14+ and CD19+ cells. Virus induced cytotoxicity in CD3+, CD14+ and CD19+ cells was dependent on virus replication, whereas virus induced cytotoxicity in CD56+ cells was only dependent on the binding of the virus. Virus induced cytotoxicity of isolated cell cultures of CD14+, CD19+ or CD56+ cells could be partially blocked by antibodies against type I and type II (IFN interferon. In contrast, virus induced cytotoxicity in the complete PBMC preparation could not be inhibited by blocking type I or type II IFN, indicating a redundant system of activation in whole blood. CONCLUSIONS/SIGNIFICANCE: Our data suggest that apart from their well known specialized functions all main subsets of peripheral blood cells also initially exert a cytotoxic effect upon virus stimulation. This closely links the innate immune system to the adaptive immune response and renders delNS1 virus a potential therapeutic tool for viro-immunotherapy of cancer.

  15. Ex vivo generation of interstitial and Langerhans cell-like dendritic cell subset-based vaccines for hematological malignancies.

    Science.gov (United States)

    Hutten, Tim; Thordardottir, Soley; Hobo, Willemijn; Hübel, Jessica; van der Waart, Anniek B; Cany, Jeannette; Dolstra, Harry; Hangalapura, Basav N

    2014-06-01

    Autologous, patient-specific, monocyte-derived dendritic cell (MoDC) vaccines have been successfully applied in the clinical studies so far. However, the routine application of this strategy has been hampered by the difficulties in generating sufficient numbers of DC and the poor DC vaccine quality because of pathology or prior treatment received by the patients. The immunotherapeutic potential of other subsets of DC has not been thoroughly investigated because of their rarity in tissues and difficulties associated with their ex vivo generation. The high expansion and differentiation potential of CD34 hematopoietic progenitor cells (HPC), isolated from umbilical cord blood (UCB), into different DC subsets make them an attractive alternative DC source for cancer immunotherapy. Therefore, the aim of this study was to generate a large number of different DC subsets from CD34 HPC and evaluate their functionality in comparison with MoDC. Our culture protocol generated a clinically relevant number of mature CD1a myeloid DC and CD207 Langerhans cells (LC)-like DC subsets from CD34 HPC with >95% purity. Both DC subsets exhibited a cytokine profile that favors cytotoxic T-cell responses. Furthermore, UCB-DC and UCB-LC demonstrated superior induction of proliferation of both allogeneic as well as viral antigen-specific CD8 T cells, both in vitro and in vivo. Additional studies revealed that UCC-DC and UCB-LC can efficiently expand minor histocompatibility antigen (MiHA) HA-1-specific cytotoxic T cells in the peripheral blood of leukemia patients and prime MiHA HA-1-specific and HA-2-specific cytotoxic T cells in vitro. These preclinical findings support the pharmaceutical development of the described culture protocol for clinical evaluation.

  16. T lymphocyte subset imbalances in patients contribute to ankylosing spondylitis.

    Science.gov (United States)

    Wang, Chenggong; Liao, Qiande; Hu, Yihe; Zhong, DA

    2015-01-01

    Ankylosing spondylitis is a chronic inflammatory rheumatic disease, which is characterized by inflammation of the spine and the sacroiliac joints. To date, the disease etiology remains unclear. In the present study, the correlation of T lymphocyte subset changes with the progression of ankylosing spondylitis was investigated. A total of 55 patients with ankylosing spondylitis (22 severe and 23 mild cases) and 20 healthy individuals were selected. Firstly, the punctured cells in the lesions and the serum were collected, and the lymphocytes and the peripheral blood mononuclear cells were prepared. Secondly, quantitative PCR, ELISA and flow cytometry analyses were carried out to detect the levels of a series of immunoglobulins, complements, helper T cells, cytotoxic T cells, regulatory cells and cytokines. The expression levels of α-globulin, γ-globulin, immunoglobulin (Ig)G, IgA, IgM, serum complement C3, and complement C4 were found to be significantly increased in ankylosing spondylitis patients. In addition, the percentage of Th1 and Th17 cells was found to be significantly higher in the ankylosing spondylitis groups (mild and severe) compared with the healthy individuals. As a result, the Th1/Th2 and Th17/Treg ratios were significantly higher in patients with ankylosing spondylitis. In addition, T lymphocyte subset ratio imbalances contributed to an increased expression of immune mediators, including interferon (IFN)-γ and interleukin (IL)-17A. The mRNA and protein expression levels of IFN-γ and IL-17A were found to be higher in the ankylosing spondylitis groups compared with the control group. The present study provided further evidence on the function and underlying mechanism of T lymphocyte subsets, which may be useful in the diagnosis and treatment of ankylosing spondylitis.

  17. Cytokine profile and lymphocyte subsets in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    C.O. Francisco

    2016-01-01

    Full Text Available Type 2 diabetes mellitus (T2D is a metabolic disease with inflammation as an important pathogenic background. However, the pattern of immune cell subsets and the cytokine profile associated with development of T2D are unclear. The objective of this study was to evaluate different components of the immune system in T2D patients' peripheral blood by quantifying the frequency of lymphocyte subsets and intracellular pro- and anti-inflammatory cytokine production by T cells. Clinical data and blood samples were collected from 22 men (51.6±6.3 years old with T2D and 20 nonsmoking men (49.4±7.6 years old who were matched for age and sex as control subjects. Glycated hemoglobin, high-sensitivity C-reactive protein concentrations, and the lipid profile were measured by a commercially available automated system. Frequencies of lymphocyte subsets in peripheral blood and intracellular production of interleukin (IL-4, IL-10, IL-17, tumor necrosis factor-α, and interferon-γ cytokines by CD3+ T cells were assessed by flow cytometry. No differences were observed in the frequency of CD19+ B cells, CD3+CD8+ and CD3+CD4+ T cells, CD16+56+ NK cells, and CD4+CD25+Foxp3+ T regulatory cells in patients with T2D compared with controls. The numbers of IL-10- and IL-17-producing CD3+ T cells were significantly higher in patients with T2D than in controls (P<0.05. The frequency of interferon-γ-producing CD3+ T cells was positively correlated with body mass index (r=0.59; P=0.01. In conclusion, this study shows increased numbers of circulating IL-10- and IL-17-producing CD3+ T cells in patients with T2D, suggesting that these cytokines are involved in the immune pathology of this disease.

  18. Profiling leucocyte subsets in tuberculosis-diabetes co-morbidity.

    Science.gov (United States)

    Kumar, Nathella Pavan; Moideen, Kadar; Dhakshinraj, Sharmila D; Banurekha, Vaithilingam V; Nair, Dina; Dolla, Chandrakumar; Kumaran, Paul; Babu, Subash

    2015-10-01

    The immune system plays an important role in the pathogenesis of pulmonary tuberculosis-type 2 diabetes mellitus (PTB-DM) co-morbidity. However, the phenotypic profile of leucocyte subsets at homeostasis in individuals with active or latent tuberculosis (LTB) with coincident diabetes is not known. To characterize the influence of diabetes on leucocyte phenotypes in PTB or LTB, we examined the frequency (Fo ) of leucocyte subsets in individuals with TB with (PTB-DM) or without (PTB) diabetes; individuals with latent TB with (LTB-DM) or without (LTB) diabetes and non-TB-infected individuals with (NTB-DM) or without (NTB) diabetes. Coincident DM is characterized by significantly lower Fo of effector memory CD4(+) T cells in LTB individuals. In contrast, DM is characterized by significantly lower Fo of effector memory CD8(+) T cells and significantly higher Fo of central memory CD8(+) T cells in PTB individuals. Coincident DM resulted in significantly higher Fo of classical memory B cells in PTB and significantly higher Fo of activated memory and atypical B cells in LTB individuals. Coincident DM resulted in significantly lower Fo of classical and intermediate monocytes in PTB, LTB and NTB individuals. Finally, DM resulted in significantly lower Fo of myeloid and plasmacytoid dendritic cells in PTB, LTB and NTB individuals. Our data reveal that coincident diabetes alters the cellular subset distribution of T cells, B cells, dendritic cells and monocytes in both individuals with active TB and those with latent TB, thus potentially impacting the pathogenesis of this co-morbid condition.

  19. 促甲状腺激素抑制疗法对老年甲状腺癌患者血清sIL-2 R、CD44 V6、TSGF及外周血T淋巴细胞亚群影响研究%Effect of TSH inhibition on sIL-2 R, TSGF, CD44 V6 and T lymphocyte subsets in elderly patients with thyroid cancer

    Institute of Scientific and Technical Information of China (English)

    吴伟宏; 王丰平

    2015-01-01

    Objective To analyze the effect of TSH inhibition on soluble interleukin 2 receptor ( sIL-2R), interleukin 44 variant 6 (CD44V6), tumor specific growth factor (TSGF) and T lymphocyte subsets in elderly patients with thyroid cancer.Methods 50 elderly patients with thyroid cancer in our hospital were collected.The patients were randomly assigned to experimental and control groups, 25 cases in each group, patients in the experimental group were given TSH suppression therapy after surgery , patients in control group were given thyroxine replacement therapy after operation, treatment for 1 month, serum SIL-2R, CD44v6, TSGF and peripheral blood T lymphocyte subsets situation were detected in all patients with .ResuIts After treatment, compared with the control group, ①in the experimental group, the level of serum sIL-2R was significantly lower, the difference was statistically significant(P<0.05);②the serum CD44V6 level was lower in the experimental group (P<0.05);③the serum TSGF level was lower in the experimental group (P<0.05);③in the experimental group,the levels of CD3 + and CD4 +were higher, levels of CD8 + were lower ( P<0.05 ) .ConcIusions TSH suppression therapy can reduce senile thyroid cancer patients serum SIL-2R, CD44v6, TSGF and CD8 +lymphocyte level, peripheral blood T lymphocyte CD3 +, CD4 +levels were elevated,and improve the immune function of patients , the clinical has guiding significance .%目的:探讨促甲状腺激素( thyroid stimulating hormone,TSH)抑制疗法对老年甲状腺癌患者血清可溶性白细胞介素-2受体(soluble interleukin-2 receptor,sIL-2R)、白细胞分化抗原44变异型6(CD44V6)、肿瘤特异性生长因子(tumors pecific growth factor , TSGF)及外周血T淋巴细胞亚群( peripheral blood T lymphocyte subsets,PBTLS)影响。方法收集的本院收治的老年甲状腺癌患者50例,随机分为对照组和实验组,每组各25例,实验组术后给予TSH抑制

  20. Microbial deprivation, inflammation and cancer.

    Science.gov (United States)

    von Hertzen, Leena C; Joensuu, H; Haahtela, T

    2011-06-01

    Dysregulated immune function is involved in the pathogenesis of many common human diseases. Living in urban, microbe-poor environment may have a profound influence on the immune function and eventually also on carcinogenesis. Unfortunately, few studies have thus far addressed the role of exposure to the environmental microbiota on the risk of cancer. Which mechanisms are broken in individuals prone to develop chronic inflammation in response to exposure that does not cause harm in others? Recent work in immunology has revealed that Th17 cells, a third subset of Th cells, and inflammatory cytokines, particularly IL-23, are closely linked with tumour-associated inflammation. Albeit the precise role of Th17 cells in cancer is still unclear and a matter of debate, accumulating evidence shows that Th17 cells are enriched in a wide range of human tumours, and that these tumour-derived Th17 cells may promote angiogenesis, tumour growth and inflammation. Regulatory T cells, in turn, appear to have counter-regulatory effects on Th17 cells and can inhibit their function. Thus, the regulatory network, induced and strengthened by continuous exposure to environmental microbiota, may play an important role in tumour immunobiology in preventing the establishment of chronic inflammation in its early phases. In addition, the discovery of the Toll-like receptor (TLR) system has brought micro-organisms to new light; continuous signalling via these TLRs and other receptors that sense microbial components is necessary for epithelial cell integrity, tissue repair, and recovery from injury. In this communication, we summarise the epidemiological data of living in environments with diverse microbial exposures and the risk of cancer, and discuss the related immunological mechanisms, focusing on the links between environmental microbiota, the Th17/IL-23 axis and cancer-associated inflammation.

  1. A novel cell subset:Interferon-producing killer dendritic cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Recent reports introduce a novel cell subset of DCs with antigenic phenotypes shared by both NK cells and B cells, but without surface markers of pDCs and T cells, appearing to be a chimera of NK cells and DCs, namely interferon-producing killer dendritic cells(IKDCs).IKDCs not only secret type I and type II interferons to recognize and kill tumor cells effectively, but also express MHC-II molecules to present antigens.Thus, IKDCs are considered as important immunosurveilance cells for tumors, providing a link between innate and adaptive immunity.

  2. Feature Subset Selection by Estimation of Distribution Algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Cantu-Paz, E

    2002-01-17

    This paper describes the application of four evolutionary algorithms to the identification of feature subsets for classification problems. Besides a simple GA, the paper considers three estimation of distribution algorithms (EDAs): a compact GA, an extended compact GA, and the Bayesian Optimization Algorithm. The objective is to determine if the EDAs present advantages over the simple GA in terms of accuracy or speed in this problem. The experiments used a Naive Bayes classifier and public-domain and artificial data sets. In contrast with previous studies, we did not find evidence to support or reject the use of EDAs for this problem.

  3. A maximum feasible subset algorithm with application to radiation therapy

    DEFF Research Database (Denmark)

    Sadegh, Payman

    1999-01-01

    inequalities. Special classes of this problem are of interest in a variety of areas such as pattern recognition, machine learning, operations research, and medical treatment planning. This problem is generally solvable in exponential time. A heuristic polynomial time algorithm is presented in this paper......Consider a set of linear one sided or two sided inequality constraints on a real vector X. The problem of interest is selection of X so as to maximize the number of constraints that are simultaneously satisfied, or equivalently, combinatorial selection of a maximum cardinality subset of feasible...

  4. Cytokine-producing T cell subsets in human leishmaniasis

    DEFF Research Database (Denmark)

    Kemp, Kåre

    2000-01-01

    Leishmania specific Th1/Th2 cells have been identified in humans as well as in mice. There is a correlation between the clinical outcome of the infection and the cytokine response profile. Generally, the production of Th2 cytokines leads to severe infection, whereas the production of Th1 cytokine...... cells mutually down-regulate each other. However, the presence of antigen specific regulatory T cell subsets may provide an environment that allows the presence of both Th1 and Th2 cells....

  5. CD163 positive subsets of blood dendritic cells

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan; Møller, Holger Jon; Moestrup, Søren Kragh

    2006-01-01

    expression in dendritic cells (DCs) was investigated using multicolor flow cytometry in peripheral blood from 31 healthy donors and 15 HIV-1 patients in addition to umbilical cord blood from 5 newborn infants. Total RNA was isolated from MACS purified DCs and CD163 mRNA was determined with real-time reverse...... transcriptase polymerase chain reaction. The effect of glucocorticoid and phorbol ester stimulation on monocyte and dendritic cell CD163 and CD91 expression was investigated in cell culture of mononuclear cells using multicolor flow cytometry. We identified two CD163+ subsets in human blood with dendritic cell...

  6. On filling families of finite subsets of the Cantor set

    CERN Document Server

    Dodos, Pandelis

    2008-01-01

    Let $\\ee>0$ and $\\fff$ be a family of finite subsets of the Cantor set $\\ccc$. Following D. H. Fremlin, we say that $\\fff$ is $\\ee$-filling over $\\ccc$ if $\\fff$ is hereditary and for every $F\\subseteq\\ccc$ finite there exists $G\\subseteq F$ such that $G\\in\\fff$ and $|G|\\geq\\ee |F|$. We show that if $\\fff$ is $\\ee$-filling over $\\ccc$ and $C$-measurable in $[\\ccc]^{<\\omega}$, then for every $P\\subseteq\\ccc$ perfect there exists $Q\\subseteq P$ perfect with $[Q]^{<\\omega}\\subseteq\\fff$. A similar result for weaker versions of density is also obtained.

  7. Individual discriminative face recognition models based on subsets of features

    DEFF Research Database (Denmark)

    Clemmensen, Line Katrine Harder; Gomez, David Delgado; Ersbøll, Bjarne Kjær

    2007-01-01

    of the face recognition problem. The elastic net model is able to select a subset of features with low computational effort compared to other state-of-the-art feature selection methods. Furthermore, the fact that the number of features usually is larger than the number of images in the data base makes feature...... selection techniques such as forward selection or lasso regression become inadequate. In the experimental section, the performance of the elastic net model is compared with geometrical and color based algorithms widely used in face recognition such as Procrustes nearest neighbor, Eigenfaces, or Fisher...

  8. 5-Azacytidine Induces Anoikis, Inhibits Mammosphere Formation and Reduces Metalloproteinase 9 Activity in MCF-7 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hsueh-Wei Chang

    2014-03-01

    Full Text Available Cancer stem cells are a subset of cancer cells that initiate the growth of tumors. Low levels of cancer stem cells also exist in established cancer cell lines, and can be enriched in serum-free tumorsphere cultures. Since cancer stem cells have been reported to be resilient to common chemotherapeutic drugs in comparison to regular cancer cells, screening for compounds selectively targeting cancer stem cells may provide an effective therapeutic strategy. We found that 5-azacytidine (5-AzaC selectively induced anoikis of MCF-7 in suspension cultures with an EC50 of 8.014 µM, and effectively inhibited tumorsphere formation, as well as the migration and matrix metalloproteinases-9 (MMP-9 activity of MCF-7 cells. Furthermore, 5-AzaC and radiation collaboratively inhibited MCF-7 tumorsphere formation at clinically relevant radiation doses. Investigating the underlying mechanism may provide insight into signaling pathways crucial for cancer stem cell survival and pave the way to novel potential therapeutic targets.

  9. Notch inhibition suppresses nasopharyngeal carcinoma by depleting cancer stem-like side population cells.

    Science.gov (United States)

    Yu, Shudong; Zhang, Ruxin; Liu, Fenye; Wang, Hong; Wu, Jing; Wang, Yanqing

    2012-08-01

    The cancer stem cell (CSC) is responsible for the initiation, proliferation and radiation resistance. Side population (SP) cells are a rare subset of cells enriched with CSCs. The targeting of key signaling pathways that are active in CSCs is a therapeutic approach to treating cancer. Notch signaling is important for the self-renewal and maintenance of stem cells. Our previous studies demonstrated that downregulation of Notch signaling could enhance radiosensitivity of nasopharyngeal carcinoma (NPC) cells. In this study, we found that Notch signaling was highly activated in SP cells compared with that of non-SP (NSP) cells of NPC. Therefore, Notch inhibition could reduce the proportion of SP cells. As SP cells decreased, proliferation, anti-apoptosis and tumorigenesis were also decreased. This study shows that Notch inhibition may be a promising clinical approach in CSC-targeting therapy for NPC.

  10. Peripheral blood and milk leukocytes subsets of lactating Sarda ewes

    Directory of Open Access Journals (Sweden)

    Piero Bonelli

    2013-05-01

    Full Text Available Leukocytes subpopulations in blood and milk of lactating Sarda ewes were investigated. Animals characterized by a SSC level <500×103cells/mL and a negative bacteriological examination were sampled in early, mid and late lactation. Milk differential cell count evidenced that macrophage represented the main population (42.8%±3.5 followed by lymphocytes (40.2%±3.4 and neutrophils (8,6%±2.1. Flow cytometry analysis showed that lymphocytes subsets in milk were quite different from blood. High CD8+ and low CD4+ lymphocytes percentages determined a CD4/CD8 ratio inversion in milk compared to blood (0.3%±0.03 vs 1.8%±0.08. CD8+ decreased while, conversely, CD4+ increased in late lactation. γδ T cells were more represented in milk (12.6%±1.3 than in blood (6.8%±0.3 and their proportions appeared similar throughout lactation in both compartments. IL-2 receptor was mainly expressed in milk on T cytotoxic lymphocytes. Data obtained in uninfected mammary glands could allow an early discrimination between physiological and pathological changes occurring in ewe milk. Further phenotypical and functional studies on milk leukocytes subsets might help to understand defense mechanisms of the ovine mammary gland against IMI.

  11. A Hybrid Feature Subset Selection using Metrics and Forward Selection

    Directory of Open Access Journals (Sweden)

    K. Fathima Bibi

    2015-04-01

    Full Text Available The aim of this study is to design a Feature Subset Selection Technique that speeds up the Feature Selection (FS process in high dimensional datasets with reduced computational cost and great efficiency. FS has become the focus of much research on decision support system areas for which data with tremendous number of variables are analyzed. Filters and wrappers are proposed techniques for the feature subset selection process. Filters make use of association based approach but wrappers adopt classification algorithms to identify important features. Filter method lacks the ability of minimization of simplification error while wrapper method burden weighty computational resource. To pull through these difficulties, a hybrid approach is proposed combining both filters and wrappers. Filter approach uses a permutation of ranker search methods and a wrapper which improves the learning accurateness and obtains a lessening in the memory requirements and finishing time. The UCI machine learning repository was chosen to experiment the approach. The classification accuracy resulted from our approach proves to be higher.

  12. A subset of interneurons required for Drosophila larval locomotion.

    Science.gov (United States)

    Yoshikawa, Shingo; Long, Hong; Thomas, John B

    2016-01-01

    Efforts to define the neural circuits generating locomotor behavior have produced an initial understanding of some of the components within the spinal cord, as well as a basic understanding of several invertebrate motor pattern generators. However, how these circuits are assembled during development is poorly understood. We are defining the neural circuit that generates larval locomotion in the genetically tractable fruit fly Drosophila melanogaster to study locomotor circuit development. Forward larval locomotion involves a stereotyped posterior-to-anterior segmental translocation of body wall muscle contraction and is generated by a relatively small number of identified muscles, motor and sensory neurons, plus an unknown number of the ~270 bilaterally-paired interneurons per segment of the 1st instar larva. To begin identifying the relevant interneurons, we have conditionally inactivated synaptic transmission of interneuron subsets and assayed for the effects on locomotion. From this screen we have identified a subset of 25 interneurons per hemisegment, called the lateral locomotor neurons (LLNs), that are required for locomotion. Both inactivation and constitutive activation of the LLNs disrupt locomotion, indicating that patterned output of the LLNs is required. By expressing a calcium indicator in the LLNs, we found that they display a posterior-to-anterior wave of activity within the CNS corresponding to the segmental translocation of the muscle contraction wave. Identification of the LLNs represents the first step toward elucidating the circuit generating larval locomotion.

  13. Mast cell subsets and neuropeptides in leprosy reactions

    Directory of Open Access Journals (Sweden)

    Antunes Sérgio Luiz Gomes

    2003-01-01

    Full Text Available The immunohistochemical identification of neuropeptides (calcitonin gene-related peptide, vasoactive intestinal polypeptide, substance P, alpha-melanocyte stimulating hormone and gamma-melanocyte stimulating hormone quantification of mast cells and their subsets (tryptase/chymase-immunoreactive mast cells = TCMC and tryptase-immunoreactive mast cells = TMC were determined in biopsies of six patients with leprosy reactions (three patients with type I reaction and three with type II. Biopsies were compared with those taken from the same body site in the remission stage of the same patient. We found a relative increase of TMC in the inflammatory infiltrate of the reactional biopsies compared to the post-reactional biopsy. Also, the total number of mast cells and the TMC/TCMC ratio in the inflammatory infiltrate was significantly higher than in the intervening dermis of the biopsies of both periods. No significant difference was found regarding neuroptide expression in the reactional and post-reactional biopsies. The relative increase of TMC in the reactional infiltrates could implicate this mast cell subset in the reported increase of the immune response in leprosy reactions.

  14. Monocyte Subsets in Schistosomiasis Patients with Periportal Fibrosis

    Directory of Open Access Journals (Sweden)

    Jamille Souza Fernandes

    2014-01-01

    Full Text Available A major issue with Schistosoma mansoni infection is the development of periportal fibrosis, which is predominantly caused by the host immune response to egg antigens. Experimental studies have pointed to the participation of monocytes in the pathogenesis of liver fibrosis. The aim of this study was to characterize the subsets of monocytes in individuals with different degrees of periportal fibrosis secondary to schistosomiasis. Monocytes were classified into classical (CD14++CD16−, intermediate (CD14++CD16+, and nonclassical (CD14+CD16++. The expressions of monocyte markers and cytokines were assessed using flow cytometry. The frequency of classical monocytes was higher than the other subsets. The expression of HLA-DR, IL-6, TNF-α, and TGF-β was higher in monocytes from individuals with moderate to severe fibrosis as compared to other groups. Although no differences were observed in receptors expression (IL-4R and IL-10R between groups of patients, the expression of IL-12 was lower in monocytes from individuals with moderate to severe fibrosis, suggesting a protective role of this cytokine in the development of fibrosis. Our data support the hypothesis that the three different monocyte populations participate in the immunopathogenesis of periportal fibrosis, since they express high levels of proinflammatory and profibrotic cytokines and low levels of regulatory markers.

  15. Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity

    DEFF Research Database (Denmark)

    Kim, Jiyoung; Villadsen, René; Sørlie, Therese;

    2012-01-01

    The majority of human breast cancers exhibit luminal epithelial differentiation. However, most aggressive behavior, including invasion and purported cancer stem cell activity, are considered characteristics of basal-like cells. We asked the following questions: Must luminal-like breast cancer cells...... become basal-like to initiate tumors or to invade? Could luminally differentiated cells within a basally initiated hierarchy also be tumorigenic? To answer these questions, we used rare and mutually exclusive lineage markers to isolate subsets of luminal-like and basal-like cells from human breast tumors....... We enriched for populations with or without prominent basal-like traits from individual tumors or single cell cloning from cell lines and recovered cells with a luminal-like phenotype. Tumor cells with basal-like traits mimicked phenotypic and functional behavior associated with stem cells assessed...

  16. Distinct Gene Expression Signatures in Lynch Syndrome and Familial Colorectal Cancer Type X

    DEFF Research Database (Denmark)

    Valentin, Mev; Therkildsen, Christina; Veerla, Srinivas;

    2013-01-01

    Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects.......Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects....

  17. An Architecture for End-User TV Content Enrichment

    Directory of Open Access Journals (Sweden)

    A.J. Jansen

    2007-01-01

    Full Text Available This paper proposes an extension to the television-watching paradigm that permits an end-user to enrich broadcast content. Examples of this enriched content are: virtual edits that allow the order of presentation within the content to be changed or that allow the content to be subsetted; conditional text, graphic or video objects that can be placed to appear within content and triggered by viewer interaction; additional navigation links that can be added to structure how other users view the base content object. The enriched content can be viewed directly within the context of the TV viewing experience. It may also be shared with other users within a distributed peer group. Our architecture is based on a model that allows the original content to remain unaltered, and which respects DRM restrictions on content reuse. The fundamental approach we use is to define an intermediate content enhancement layer that is based on the W3C′s SMIL language. Using a pen-based enhancement interface, end-users can manipulate content that is saved in a home PDR setting. This paper describes our architecture and it provides several examples of how our system handles content enhancement. We also describe a reference implementation for creating and viewing enhancements.

  18. 凸模糊子集的再定义%Convex Fuzzy Subsets Redefined

    Institute of Scientific and Technical Information of China (English)

    鞠红梅; 袁学海; 陈图云

    2001-01-01

    Definition of convex subsets based on t-norm is introduced. The properties of homomorphic image of this kind of convex subsets are discussed. Tm-convex fuzzy subsets generated by convex subset and Tm-convex fuzzy subsets generated by functions are studied. It is proved that each T∧-convex fuzzy subset is a Tm-convex fuzzy subset generated by convex subset.%给出基于t-范上的凸模糊子集的定义,讨论这种凸模糊子集的同态像性质,重点研究Tm-凸模糊子集的生成性,证明每一个T∧-凸模糊子集为凸子集生成的Tm-凸模糊子集。

  19. Enrichment of light hydrocarbon mixture

    Science.gov (United States)

    Yang; Dali; Devlin, David; Barbero, Robert S.; Carrera, Martin E.; Colling, Craig W.

    2010-08-10

    Light hydrocarbon enrichment is accomplished using a vertically oriented distillation column having a plurality of vertically oriented, nonselective micro/mesoporous hollow fibers. Vapor having, for example, both propylene and propane is sent upward through the distillation column in between the hollow fibers. Vapor exits neat the top of the column and is condensed to form a liquid phase that is directed back downward through the lumen of the hollow fibers. As vapor continues to ascend and liquid continues to countercurrently descend, the liquid at the bottom of the column becomes enriched in a higher boiling point, light hydrocarbon (propane, for example) and the vapor at the top becomes enriched in a lower boiling point light hydrocarbon (propylene, for example). The hollow fiber becomes wetted with liquid during the process.

  20. mIL-2R, T cell subsets & hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Chao-Pin Li; Ke-Xia Wang; Jian Wang; Bo-Rong Pan

    2002-01-01

    AIM: To study the levels of membrane interleukin-2 receptor(mIL-2R ) and T cell subsets in peripheral bloodmononuclear cells (PBMC) from patients with hepatitis Cand their role in the pathogenesis of hepatitis C.METHODS: The levels of mlL-2R and T cells subsets in PBMCWere detected by biotin- streptstividin (BSA) technique beforeand after stimulation with PHA in 203 patients with hepatitis Cwith HCV-RNA( + ), anti-HCV( + ), anti-HCV(-).RESULTS: The total expressive levels of mlL-2R before andafter stimulation with PHA(0.03 ± 0.01, 0.03 ± 0.02, 0.04 ± 0.02, 0.36±0.03), and Tcell subsets in PBMC (0.62±0.06,0.37 ± 0.05, 0.35 ± 0.07) were all lower in patients withhepatitis C than those in normal controls (0.66 ± 0.07, 0.41± 0.06, 0.31 ± 0.05, P < 0.01 ). Among the patients, thelevels of mlL-2R were lower in silence than those in situationof PHA inducting (P< 0.01). However, the levels of mlL-2Rwere similar in acute hepatitis C to that in chronic hepatitis C(P>0.05). The levels of CD3+, CD4+, CD4 +/CD8+ Were lov erand CD8 + was higher in patients with acute and chronichepatitis C with anti-HCV( + ) than those in normal controls (0.62±0.06, 0.37±0.05, 0.35±0.07, 1.18±0.30, 0.61±0.07, 0.37±0.05, 1.39±0.33, 0.31±0.05, P<0.05-P<0.01).CONCLUSION: The cellular immunity is obviously changed inpatients with hepatitis C. The levels of mlL-2R end activationof T cells am closely associated with chronicity of hepatitis C.

  1. Changes in T lymphocyte subsets after severe traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Yulu Miao; Mingxia Zhang; Yulin Nie; Wan Zhao; Bin Huang; Zhengming Jiang; Shaoxiong Yu; Zhibin Huang; Hongjin Fu

    2007-01-01

    BACKGROUND: Besides local changes of cranial parenchymal cells, hemorrhage, etc., severe traumatic brain injuries also cause the changes of total body fluid and various functions, and the changes of lymphocytes and T lymphocyte subsets should be paid more attention to.OBJECTIVE: To reveal the changing laws of T lymphocyte subsets after severe traumatic brain injury, and compare with mild to moderate brain injury.DESIGN: A comparative observation.SETTINGS: Department of Neurosurgery, Longgang District Buji People's Hospital of Shenzhen City;Central Laboratory of Shenzhen Hospital of Prevention and Cure for Chronic Disease.PARTICIPANTS: All the subjects were selected from the Department of Neurosurgery, Longgang District Buji People's Hospital of Shenzhen City from August 2002 to August 2005. Thirty patients with severe brain injury, whose Glasgow coma score (GCS) was ≤ 8 points, were taken as the experimental group, including 21 males and 9 females, aging 16 - 62 years. Meanwhile, 30 patients with mild traumatic brain injury were taken as the control group (GCS ranged 14 - 15 points), including 18 males and 12 females, aging 15 - 58 years. All the subjects were in admission at 6 hours after injury, without disease of major organs before injury.Informed consents were obtained from all the patients or their relatives.conditions of pulmonaryinfections were observed at 4 days after injury. The differences of measurement data were compared with the t test.MAIN OUTCOME MEASURES: Changes of T lymphocytes subsets at 1 - 14 days after severe and mild or moderate traumatic injury.RESULTS: Finally, 28 and 25 patients with mild to moderate traumatic brain injury, whereas 25 and 21 patients with severe traumatic brain injury were analyzed at 7 and 14 days respectively, and the missed ones CD3, CD4, CD8, CD4/CD8 began to decrease, whereas CD8 increased in the experimental group, which were very significantly different from those in the control group (t =2.77 - 3.26, P < 0

  2. 31 CFR 540.316 - Uranium enrichment.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Uranium enrichment. 540.316 Section... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY HIGHLY ENRICHED URANIUM (HEU) AGREEMENT ASSETS CONTROL REGULATIONS General Definitions § 540.316 Uranium enrichment. The term uranium enrichment means the process...

  3. The semigroup of nonempty finite subsets of rationals

    Directory of Open Access Journals (Sweden)

    Reuben Spake

    1988-01-01

    Full Text Available Let Q be the additive group of rational numbers and let ℛ be the additive semigroup of all nonempty finite subsets of Q. For X∈ℛ, define AX to be the basis of 〈X−min(X〉 and BX the basis of 〈max(X−X〉. In the greatest semilattice decomposition of ℛ, let (X denote the archimedean component containing X. In this paper we examine the structure of ℛ and determine its greatest semilattice decomposition. In particular, we show that for X,Y∈ℛ, (X=(Y if and only if AX=AY and BX=BY. Furthermore, if X is a non-singleton, then the idempotent-free (X is isomorphic to the direct product of a power joined subsemigroup and the group Q.

  4. Urofacial syndrome: A subset of neurogenic bladder dysfunction syndromes?

    Directory of Open Access Journals (Sweden)

    K N Stamatiou

    2010-01-01

    Full Text Available The urofacial syndrome is probably a subset of neurogenic bladder dysfunction syndromes characterized by detrusor-sphincter discoordination along with a characteristic inversion of facial expression with laughing. This characteristic facial expression can facilitate early detection of this disorder, which leads to poor bladder emptying with high residual urine, hydro-nephrosis with vesico-ureteral reflux and potentially renal failure if left untreated. The etiology of the urofacial syndrome is unknown. In our case, a 12-year-old boy of Middle-Eastern origin presented to the Outpatient Department of our hospital with left pyelonephritis, hydronephrosis and bladder dilatation. Voiding cystourethrography performed 15 days later revealed left vesicoureteral reflux. Cystoscopy revealed bladder trabeculation however an anatomic urethral obstruction was not noticed. Both, neurological examination and radiography of the lumbosacral spine were normal. Urodynamic evaluation revealed the typical findings of detrusor-sphincter discoordination.

  5. REST represses a subset of the pancreatic endocrine differentiation program

    DEFF Research Database (Denmark)

    Martin, David; Kim, Yung-Hae; Sever, Dror

    2015-01-01

    To contribute to devise successful beta-cell differentiation strategies for the cure of Type 1 diabetes we sought to uncover barriers that restrict endocrine fate acquisition by studying the role of the transcriptional repressor REST in the developing pancreas. Rest expression is prevented...... in neurons and in endocrine cells, which is necessary for their normal function. During development, REST represses a subset of genes in the neuronal differentiation program and Rest is down-regulated as neurons differentiate. Here, we investigate the role of REST in the differentiation of pancreatic...... endocrine cells, which are molecularly close to neurons. We show that Rest is widely expressed in pancreas progenitors and that it is down-regulated in differentiated endocrine cells. Sustained expression of REST in Pdx1(+) progenitors impairs the differentiation of endocrine-committed Neurog3...

  6. Seronegative necrolytic acral erythema: A distinct clinical subset?

    Directory of Open Access Journals (Sweden)

    Panda S

    2010-01-01

    Full Text Available A patient was referred to us with asymptomatic, erythematous, nonitchy, scaly lesions present bilaterally on the dorsa of his feet and toes since the last 2 months. Both the legs had pitting edema as well. There were hyperkeratosis, focal parakeratosis, acanthosis and scattered spongiosis in the epidermis, and proliferation of capillaries with perivascular infiltration of lymphomononuclear cells in the dermis. There was no serological evidence of hepatitis C virus. Laboratory investigations revealed hypoalbuminemia and low-normal serum zinc. On clinicopathological correlation, we made a diagnosis of necrolytic acral erythema (NAE. The lesions responded dramatically to oral zinc sulfate and topical clobetasol propionate within 3 weeks with disappearance of edema and scaling and only a minimal residual erythema. This is the first reported case of NAE from Eastern India. NAE with negative serology for hepatitis C may be viewed as a distinct subset of the condition that had been originally described.

  7. On curves contained in convex subsets of the plane

    CERN Document Server

    Coppersmith, Don; Ravsky, Alex

    2012-01-01

    If K' and K are convex bodies of the plane such that K' is a subset of K then the perimeter of K' is not greater than the perimeter of K. We obtain the following generalization of this fact. Let K be a convex compact body of the plane with the perimeter p and the diameter d and r>1 be an integer. Let s be the smallest number such that for any curve of length greater than s contained in K there is a straight line intersecting the curve at least in r+1 different points. Then s=rp/2 if r is even and s=(r-1)p/2+d if r is odd.

  8. Urofacial syndrome: A subset of neurogenic bladder dysfunction syndromes?

    Science.gov (United States)

    Stamatiou, K. N.; Karakos, C. D.

    2010-01-01

    The urofacial syndrome is probably a subset of neurogenic bladder dysfunction syndromes characterized by detrusor-sphincter discoordination along with a characteristic inversion of facial expression with laughing. This characteristic facial expression can facilitate early detection of this disorder, which leads to poor bladder emptying with high residual urine, hydro-nephrosis with vesico-ureteral reflux and potentially renal failure if left untreated. The etiology of the urofacial syndrome is unknown. In our case, a 12-year-old boy of Middle-Eastern origin presented to the Outpatient Department of our hospital with left pyelonephritis, hydronephrosis and bladder dilatation. Voiding cystourethrography performed 15 days later revealed left vesicoureteral reflux. Cystoscopy revealed bladder trabeculation however an anatomic urethral obstruction was not noticed. Both, neurological examination and radiography of the lumbosacral spine were normal. Urodynamic evaluation revealed the typical findings of detrusor-sphincter discoordination. PMID:21369396

  9. Plasticity of T helper cell subsets: Implications in periodontal disease

    Directory of Open Access Journals (Sweden)

    Avaneendra Talwar

    2013-01-01

    Full Text Available T helper (Th cells have an important role in host defence as well in the pathogenesis of periodontal disease. Th cells differentiate from naive cells into various subsets, each of which is associated with a set of inducing and effector cytokines. Previously, it was thought that this differentiation was an irreversible event. Recent evidence suggest that even differentiated Th cells, retain the flexibility to transform from one lineage to another, a phenomenon referred to as plasticity. This plasticity is thought to be brought about by epigenetic modifications that are regulated by external and internal signals in the micro-environment of these cells. The factors and mechanisms which affect the plasticity of these cells and their potential role in the etio-pathogenesis of periodontal disease has been described in this article.

  10. Thermal hypersensitivity in a subset of irritable bowel syndrome patients

    Institute of Scientific and Technical Information of China (English)

    QiQi Zhou; Roger B Fillingim; Joseph L Riley III; G Nicholas Verne

    2009-01-01

    AIM: To characterize thermal hypersensitivity in patients with constipation- and diarrhea-predominant irritable bowel syndrome (IBS). METHODS: Thermal pain sensitivity was tested among patients with diarrhea-predominant IBS (D-IBS) and constipation-predominant IBS (C-IBS) compared to healthy subjects. A total of 42 patients (29 female and patients (16 female and eight male; mean age 32.5participated in the study. Thermal stimuli were delivered using a Medoc Thermal Sensory Analyzer with a 3 cm heat pain tolerance (HPTo) were assessed on the left ventral forearm and left calf using an ascending method of limits. The Functional Bowel Disease Severity Index (FBDSI) was also obtained for all subjects. RESULTS: Controls were less sensitive than C-IBS and D-IBS (both at P < 0.001) with no differences between C-IBS and D-IBS for HPTh and HPTo. Thermal hyperalgesia was present in both groups of IBS patients relative to controls, with IBS patients reporting significantly lower pain threshold and pain tolerance at both test sites. Cluster analysis revealed the presence of subgroups of IBS patients based on thermal hyperalgesia. One cluster (17% of the sample) showed a profile of heat pain sensitivity very similar to that of healthy controls; a second cluster (47% of the sample) showed moderate heat pain sensitivity; and a third cluster (36% of the sample) showed a very high degree of thermal hyperalgesia.CONCLUSION: A subset of IBS patients had thermal hypersensitivity compared to controls, who reported significantly lower HPTh and HPTo. All IBS patients had a higher score on the FBDSI than controls. Interestingly, the subset of IBS patients with high thermal sensitivity (36%) had the highest FBDSI score compared to the other two groups of IBS patients.

  11. Dysregulation of CD4(+) T Cell Subsets in Intracranial Aneurysm.

    Science.gov (United States)

    Zhang, Hai-Feng; Zhao, Ming-Guang; Liang, Guo-Biao; Yu, Chun-Yong; He, Wenxiu; Li, Zhi-Qing; Gao, Xu

    2016-02-01

    Intracranial aneurysms (IAs) and potential IA rupture are one of the direct causes of permanent brain damage and mortality. Interestingly, the major risk factors of IA development, including hemodynamic stress, hypertension, smoking, and genetic predispositions, are closely associated with a proinflammatory immune status. Therefore, we examined the roles of CD4(+) T cells in IA pathogenesis. IA patients exhibited peripheral CD4(+) T-cell imbalance, with overrepresented T helper 1 (Th1) and Th17 activities and underrepresented Th2 and regulatory T (Treg) activities, including increased IFN-γ, TNF-α, and IL-17 production and decreased IL-10 production from total CD4(+) T cells. Chemokine receptors CXCR3 and CCR6 were used to identify Th1, Th2, and Th17 cell subsets, and CD4(+)CD25(hi) was used to identify Treg cells. Based on these markers, the data then showed altered cytokine production by each cell type and shifted subpopulation frequency. Moreover, this shift in frequency was directly correlated with IA severity. To examine the underlying mechanism of CD4(+) T cell skewing, we cocultured CD4(+) T cells with autologous monocytes and found that coculture with monocytes could significantly increase IFN-γ and IL-17 production through contact-independent mechanisms, demonstrating that monocytes could potentially contribute to the altered CD4(+) T cell composition in IA. Analyzing mRNA transcripts revealed significantly upregulated IL-1β and TNF-α expression by monocytes from IA patients. We found a loss of CD4(+) T cell subset balance that was likely to promote a higher state of inflammation in IA, which may exacerbate the disease through a positive feedback loop.

  12. CANCER

    Directory of Open Access Journals (Sweden)

    N. Kavoussi

    1973-09-01

    Full Text Available There are many carcinogenetic elements in industry and it is for this reason that study and research concerning the effect of these materials is carried out on a national and international level. The establishment and growth of cancer are affected by different factors in two main areas:-1 The nature of the human or animal including sex, age, point and method of entry, fat metabolism, place of agglomeration of carcinogenetic material, amount of material absorbed by the body and the immunity of the body.2 The different nature of the carcinogenetic material e.g. physical, chemical quality, degree of solvency in fat and purity of impurity of the element. As the development of cancer is dependent upon so many factors, it is extremely difficult to determine whether a causative element is principle or contributory. Some materials are not carcinogenetic when they are pure but become so when they combine with other elements. All of this creates an industrial health problem in that it is almost impossible to plan an adequate prevention and safety program. The body through its system of immunity protects itself against small amounts of carcinogens but when this amount increases and reaches a certain level the body is not longer able to defend itself. ILO advises an effective protection campaign against cancer based on the Well –equipped laboratories, Well-educated personnel, the establishment of industrial hygiene within factories, the regular control of safety systems, and the implementation of industrial health principles and research programs.

  13. CLEC12A-Mediated Antigen Uptake and Cross-Presentation by Human Dendritic Cell Subsets Efficiently Boost Tumor-Reactive T Cell Responses.

    Science.gov (United States)

    Hutten, Tim J A; Thordardottir, Soley; Fredrix, Hanny; Janssen, Lisanne; Woestenenk, Rob; Tel, Jurjen; Joosten, Ben; Cambi, Alessandra; Heemskerk, Mirjam H M; Franssen, Gerben M; Boerman, Otto C; Bakker, Lex B H; Jansen, Joop H; Schaap, Nicolaas; Dolstra, Harry; Hobo, Willemijn

    2016-10-01

    Potent immunotherapies are urgently needed to boost antitumor immunity and control disease in cancer patients. As dendritic cells (DCs) are the most powerful APCs, they are an attractive means to reinvigorate T cell responses. An appealing strategy to use the effective Ag processing and presentation machinery, T cell stimulation and cross-talk capacity of natural DC subsets is in vivo tumor Ag delivery. In this context, endocytic C-type lectin receptors are attractive targeting molecules. In this study, we investigated whether CLEC12A efficiently delivers tumor Ags into human DC subsets, facilitating effective induction of CD4(+) and CD8(+) T cell responses. We confirmed that CLEC12A is selectively expressed by myeloid cells, including the myeloid DC subset (mDCs) and the plasmacytoid DC subset (pDCs). Moreover, we demonstrated that these DC subsets efficiently internalize CLEC12A, whereupon it quickly translocates to the early endosomes and subsequently routes to the lysosomes. Notably, CLEC12A Ab targeting did not negatively affect DC maturation or function. Furthermore, CLEC12A-mediated delivery of keyhole limpet hemocyanin resulted in enhanced proliferation and cytokine secretion by keyhole limpet hemocyanin-experienced CD4(+) T cells. Most importantly, CLEC12A-targeted delivery of HA-1 long peptide resulted in efficient Ag cross-presentation by mDCs and pDCs, leading to strong ex vivo activation of HA-1-specific CD8(+) T cells of patients after allogeneic stem cell transplantation. Collectively, these data indicate that CLEC12A is an effective new candidate with great potential for in vivo Ag delivery into mDCs and pDCs, thereby using the specialized functions and cross-talk capacity of these DC subsets to boost tumor-reactive T cell immunity in cancer patients.

  14. Characterization of HPV and host genome interactions in primary head and neck cancers

    Science.gov (United States)

    Parfenov, Michael; Pedamallu, Chandra Sekhar; Gehlenborg, Nils; Freeman, Samuel S.; Danilova, Ludmila; Bristow, Christopher A.; Lee, Semin; Hadjipanayis, Angela G.; Ivanova, Elena V.; Wilkerson, Matthew D.; Protopopov, Alexei; Yang, Lixing; Seth, Sahil; Song, Xingzhi; Tang, Jiabin; Ren, Xiaojia; Zhang, Jianhua; Pantazi, Angeliki; Santoso, Netty; Xu, Andrew W.; Mahadeshwar, Harshad; Wheeler, David A.; Haddad, Robert I.; Jung, Joonil; Ojesina, Akinyemi I.; Issaeva, Natalia; Yarbrough, Wendell G.; Hayes, D. Neil; Grandis, Jennifer R.; El-Naggar, Adel K.; Meyerson, Matthew; Park, Peter J.; Chin, Lynda; Seidman, J. G.; Hammerman, Peter S.; Kucherlapati, Raju; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Butterfield, Yaron S.N.; Carlsen, Rebecca; Cheng, Dean; Chu, Andy; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Lee, Darlene; Li, Haiyan I.; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Wong, Tina; Protopopov, Alexei; Santoso, Netty; Lee, Semin; Parfenov, Michael; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Haseley, Psalm; Zeng, Dong; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Bristow, Christopher; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Casasent, Tod; Liu, Wenbin; Lu, Yiling; Mills, Gordon; Motter, Thomas; Weinstein, John; Diao, Lixia; Wang, Jing; Fan, You Hong; Liu, Jinze; Wang, Kai; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Buda, Elizabeth; Hayes, D. Neil; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Kimes, Patrick K.; Marron, J.S.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Parker, Joel S.; Perou, Charles M.; Prins, Jan F.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Singh, Darshan; Soloway, Mathew G.; Tan, Donghui; Veluvolu, Umadevi; Walter, Vonn; Waring, Scot; Wilkerson, Matthew D.; Wu, Junyuan; Zhao, Ni; Cherniack, Andrew D.; Hammerman, Peter S.; Tward, Aaron D.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Jung, Joonil; Ojesina, Akinyemi I.; Carter, Scott L.; Zack, Travis I.; Schumacher, Steven E.; Beroukhim, Rameen; Freeman, Samuel S.; Meyerson, Matthew; Cho, Juok; Chin, Lynda; Getz, Gad; Noble, Michael S.; DiCara, Daniel; Zhang, Hailei; Heiman, David I.; Gehlenborg, Nils; Voet, Doug; Lin, Pei; Frazer, Scott; Stojanov, Petar; Liu, Yingchun; Zou, Lihua; Kim, Jaegil; Lawrence, Michael S.; Sougnez, Carrie; Lichtenstein, Lee; Cibulskis, Kristian; Lander, Eric; Gabriel, Stacey B.; Muzny, Donna; Doddapaneni, HarshaVardhan; Kovar, Christie; Reid, Jeff; Morton, Donna; Han, Yi; Hale, Walker; Chao, Hsu; Chang, Kyle; Drummond, Jennifer A.; Gibbs, Richard A.; Kakkar, Nipun; Wheeler, David; Xi, Liu; Ciriello, Giovanni; Ladanyi, Marc; Lee, William; Ramirez, Ricardo; Sander, Chris; Shen, Ronglai; Sinha, Rileen; Weinhold, Nils; Taylor, Barry S.; Aksoy, B. Arman; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Reva, Boris; Schultz, Nikolaus; Sumer, S. Onur; Sun, Yichao; Chan, Timothy; Morris, Luc; Stuart, Joshua; Benz, Stephen; Ng, Sam; Benz, Christopher; Yau, Christina; Baylin, Stephen B.; Cope, Leslie; Danilova, Ludmila; Herman, James G.; Bootwalla, Moiz; Maglinte, Dennis T.; Laird, Peter W.; Triche, Timothy; Weisenberger, Daniel J.; Van Den Berg, David J.; Agrawal, Nishant; Bishop, Justin; Boutros, Paul C.; Bruce, Jeff P; Byers, Lauren Averett; Califano, Joseph; Carey, Thomas E.; Chen, Zhong; Cheng, Hui; Chiosea, Simion I.; Cohen, Ezra; Diergaarde, Brenda; Egloff, Ann Marie; El-Naggar, Adel K.; Ferris, Robert L.; Frederick, Mitchell J.; Grandis, Jennifer R.; Guo, Yan; Haddad, Robert I.; Hammerman, Peter S.; Harris, Thomas; Hayes, D. Neil; Hui, Angela BY; Lee, J. Jack; Lippman, Scott M.; Liu, Fei-Fei; McHugh, Jonathan B.; Myers, Jeff; Ng, Patrick Kwok Shing; Perez-Ordonez, Bayardo; Pickering, Curtis R.; Prystowsky, Michael; Romkes, Marjorie; Saleh, Anthony D.; Sartor, Maureen A.; Seethala, Raja; Seiwert, Tanguy Y.; Si, Han; Tward, Aaron D.; Van Waes, Carter; Waggott, Daryl M.; Wiznerowicz, Maciej; Yarbrough, Wendell; Zhang, Jiexin; Zuo, Zhixiang; Burnett, Ken; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candance; Shelton, Troy; Sherman, Mark; Yena, Peggy; Black, Aaron D.; Bowen, Jay; Frick, Jessica; Gastier-Foster, Julie M.; Harper, Hollie A.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Baboud, Julien; Jensen, Mark A.; Kahn, Ari B.; Pihl, Todd D.; Pot, David A.; Srinivasan, Deepak; Walton, Jessica S.; Wan, Yunhu; Burton, Robert; Davidsen, Tanja; Demchok, John A.; Eley, Greg; Ferguson, Martin L.; Shaw, Kenna R. Mills; Ozenberger, Bradley A.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Saller, Charles; Tarvin, Katherine; Chen, Chu; Bollag, Roni; Weinberger, Paul; Golusiński, Wojciech; Golusiński, Paweł; Ibbs, Matthiew; Korski, Konstanty; Mackiewicz, Andrzej; Suchorska, Wiktoria; Szybiak, Bartosz; Wiznerowicz, Maciej; Burnett, Ken; Curley, Erin; Gardner, Johanna; Mallery, David; Penny, Robert; Shelton, Troy; Yena, Peggy; Beard, Christina; Mitchell, Colleen; Sandusky, George; Agrawal, Nishant; Ahn, Julie; Bishop, Justin; Califano, Joseph; Khan, Zubair; Bruce, Jeff P; Hui, Angela BY; Irish, Jonathan; Liu, Fei-Fei; Perez-Ordonez, Bayardo; Waldron, John; Boutros, Paul C.; Waggott, Daryl M.; Myers, Jeff; Lippman, Scott M.; Egea, Sophie; Gomez-Fernandez, Carmen; Herbert, Lynn; Bradford, Carol R.; Carey, Thomas E.; Chepeha, Douglas B.; Haddad, Andrea S.; Jones, Tamara R.; Komarck, Christine M.; Malakh, Mayya; McHugh, Jonathan B.; Moyer, Jeffrey S.; Nguyen, Ariane; Peterson, Lisa A.; Prince, Mark E.; Rozek, Laura S.; Sartor, Maureen A.; Taylor, Evan G.; Walline, Heather M.; Wolf, Gregory T.; Boice, Lori; Chera, Bhishamjit S.; Funkhouser, William K.; Gulley, Margaret L.; Hackman, Trevor G.; Hayes, D. Neil; Hayward, Michele C.; Huang, Mei; Rathmell, W. Kimryn; Salazar, Ashley H.; Shockley, William W.; Shores, Carol G.; Thorne, Leigh; Weissler, Mark C.; Wrenn, Sylvia; Zanation, Adam M.; Chiosea, Simion I.; Diergaarde, Brenda; Egloff, Ann Marie; Ferris, Robert L.; Romkes, Marjorie; Seethala, Raja; Brown, Brandee T.; Guo, Yan; Pham, Michelle; Yarbrough, Wendell G.

    2014-01-01

    Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twenty-five cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter- and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis. PMID:25313082

  15. Ultraconservation identifies a small subset of extremely constrained developmental enhancers

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Visel, Axel; Prabhakar, Shyam; Akiyama, Jennifer A.; Shoukry, Malak; Lewis, Keith D.; Holt, Amy; Plajzer-Frick, Ingrid; Afzal, Veena; Rubin, Edward M.; Pennacchio, Len A.

    2007-10-01

    While experimental studies have suggested that non-coding ultraconserved DNA elements are central nodes in the regulatory circuitry that specifies mammalian embryonic development, the possible functional relevance of their>200bp of perfect sequence conservation between human-mouse-rat remains obscure 1,2. Here we have compared the in vivo enhancer activity of a genome-wide set of 231 non-exonic sequences with ultraconserved cores to that of 206 sequences that are under equivalently severe human-rodent constraint (ultra-like), but lack perfect sequence conservation. In transgenic mouse assays, 50percent of the ultraconserved and 50percent of the ultra-like conserved elements reproducibly functioned as tissue-specific enhancers at embryonic day 11.5. In this in vivo assay, we observed that ultraconserved enhancers and constrained non-ultraconserved enhancers targeted expression to a similar spectrum of tissues with a particular enrichment in the developing central nervous system. A human genome-wide comparative screen uncovered ~;;2,600 non-coding elements that evolved under ultra-like human-rodent constraint and are similarly enriched near transcriptional regulators and developmental genes as the much smaller number of ultraconserved elements. These data indicate that ultraconserved elements possessing absolute human-rodent sequence conservation are not distinct from other non-coding elements that are under comparable purifying selection in mammals and suggest they are principal constituents of the cis-regulatory framework of mammalian development.

  16. MicroRNA profiling of cisplatin-resistant oral squamous cell carcinoma cell lines enriched with cancer-stem-cell-like and epithelial-mesenchymal transition-type features

    Science.gov (United States)

    Ghosh, Ruma Dey; Ghuwalewala, Sangeeta; Das, Pijush; Mandloi, Sapan; Alam, Sk Kayum; Chakraborty, Jayanta; Sarkar, Sajal; Chakrabarti, Saikat; Panda, Chinmoy Kumar; Roychoudhury, Susanta

    2016-01-01

    Oral cancer is of major public health problem in India. Current investigation was aimed to identify the specific deregulated miRNAs which are responsible for development of resistance phenotype through regulating their resistance related target gene expression in oral squamous cell carcinoma (OSCC). Cisplatin-resistant OSCC cell lines were developed from their parental human OSCC cell lines and subsequently characterised. The resistant cells exhibited enhanced proliferative, clonogenic capacity with significant up-regulation of P-glycoprotein (ABCB1), c-Myc, survivin, β-catenin and a putative cancer-stem-like signature with increased expression of CD44, whereas the loss of E-cadherin signifies induced EMT phenotype. A comparative analysis of miRNA expression profiling in parental and cisplatin-resistant OSCC cell lines for a selected sets (deregulated miRNAs in head and neck cancer) revealed resistance specific signature. Moreover, we observed similar expression pattern for these resistance specific signature miRNAs in neoadjuvant chemotherapy treated and recurrent tumours compared to those with newly diagnosed primary tumours in patients with OSCC. All these results revealed that these miRNAs play an important role in the development of cisplatin-resistance mainly through modulating cancer stem-cell-like and EMT-type properties in OSCC. PMID:27045798

  17. Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Aaron Topol

    2016-05-01

    Full Text Available Converging evidence indicates that microRNAs (miRNAs may contribute to disease risk for schizophrenia (SZ. We show that microRNA-9 (miR-9 is abundantly expressed in control neural progenitor cells (NPCs but also significantly downregulated in a subset of SZ NPCs. We observed a strong correlation between miR-9 expression and miR-9 regulatory activity in NPCs as well as between miR-9 levels/activity, neural migration, and diagnosis. Overexpression of miR-9 was sufficient to ameliorate a previously reported neural migration deficit in SZ NPCs, whereas knockdown partially phenocopied aberrant migration in control NPCs. Unexpectedly, proteomic- and RNA sequencing (RNA-seq-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together, these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients.

  18. Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells.

    Science.gov (United States)

    Topol, Aaron; Zhu, Shijia; Hartley, Brigham J; English, Jane; Hauberg, Mads E; Tran, Ngoc; Rittenhouse, Chelsea Ann; Simone, Anthony; Ruderfer, Douglas M; Johnson, Jessica; Readhead, Ben; Hadas, Yoav; Gochman, Peter A; Wang, Ying-Chih; Shah, Hardik; Cagney, Gerard; Rapoport, Judith; Gage, Fred H; Dudley, Joel T; Sklar, Pamela; Mattheisen, Manuel; Cotter, David; Fang, Gang; Brennand, Kristen J

    2016-05-01

    Converging evidence indicates that microRNAs (miRNAs) may contribute to disease risk for schizophrenia (SZ). We show that microRNA-9 (miR-9) is abundantly expressed in control neural progenitor cells (NPCs) but also significantly downregulated in a subset of SZ NPCs. We observed a strong correlation between miR-9 expression and miR-9 regulatory activity in NPCs as well as between miR-9 levels/activity, neural migration, and diagnosis. Overexpression of miR-9 was sufficient to ameliorate a previously reported neural migration deficit in SZ NPCs, whereas knockdown partially phenocopied aberrant migration in control NPCs. Unexpectedly, proteomic- and RNA sequencing (RNA-seq)-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together, these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients.

  19. How do 2D fingerprints detect structurally diverse active compounds? Revealing compound subset-specific fingerprint features through systematic selection.

    Science.gov (United States)

    Heikamp, Kathrin; Bajorath, Jürgen

    2011-09-26

    In independent studies it has previously been demonstrated that two-dimensional (2D) fingerprints have scaffold hopping ability in virtual screening, although these descriptors primarily emphasize structural and/or topological resemblance of reference and database compounds. However, the mechanism by which such fingerprints enrich structurally diverse molecules in database selection sets is currently little understood. In order to address this question, similarity search calculations on 120 compound activity classes of varying structural diversity were carried out using atom environment fingerprints. Two feature selection methods, Kullback-Leibler divergence and gain ratio analysis, were applied to systematically reduce these fingerprints and generate alternative versions for searching. Gain ratio is a feature selection method from information theory that has thus far not been considered in fingerprint analysis. However, it is shown here to be an effective fingerprint feature selection approach. Following comparative feature selection and similarity searching, the compound recall characteristics of original and reduced fingerprint versions were analyzed in detail. Small sets of fingerprint features were found to distinguish subsets of active compounds from other database molecules. The compound recall of fingerprint similarity searching often resulted from a cumulative detection of distinct compound subsets by different fingerprint features, which provided a rationale for the scaffold hopping potential of these 2D fingerprints.

  20. A taxonomy of epithelial human cancer and their metastases

    Directory of Open Access Journals (Sweden)

    De Moor Bart

    2009-12-01

    Full Text Available Abstract Background Microarray technology has allowed to molecularly characterize many different cancer sites. This technology has the potential to individualize therapy and to discover new drug targets. However, due to technological differences and issues in standardized sample collection no study has evaluated the molecular profile of epithelial human cancer in a large number of samples and tissues. Additionally, it has not yet been extensively investigated whether metastases resemble their tissue of origin or tissue of destination. Methods We studied the expression profiles of a series of 1566 primary and 178 metastases by unsupervised hierarchical clustering. The clustering profile was subsequently investigated and correlated with clinico-pathological data. Statistical enrichment of clinico-pathological annotations of groups of samples was investigated using Fisher exact test. Gene set enrichment analysis (GSEA and DAVID functional enrichment analysis were used to investigate the molecular pathways. Kaplan-Meier survival analysis and log-rank tests were used to investigate prognostic significance of gene signatures. Results Large clusters corresponding to breast, gastrointestinal, ovarian and kidney primary tissues emerged from the data. Chromophobe renal cell carcinoma clustered together with follicular differentiated thyroid carcinoma, which supports recent morphological descriptions of thyroid follicular carcinoma-like tumors in the kidney and suggests that they represent a subtype of chromophobe carcinoma. We also found an expression signature identifying primary tumors of squamous cell histology in multiple tissues. Next, a subset of ovarian tumors enriched with endometrioid histology clustered together with endometrium tumors, confirming that they share their etiopathogenesis, which strongly differs from serous ovarian tumors. In addition, the clustering of colon and breast tumors correlated with clinico-pathological characteristics

  1. 术前热疗联合灌注化疗对非小细胞肺癌患者T淋巴细胞亚群及血清P53抗体水平的影响%Effects of preoperative infusion chemotherapy combined with hyperthermia on T lymphocyte subsets and serum P53 antibody level of non-small cell lung cancer patients

    Institute of Scientific and Technical Information of China (English)

    祝淮阳; 熊瑜

    2012-01-01

    目的:评估术前热疗联合灌注化疗对非小细胞肺癌患者免疫功能的影响.方法:选取中晚期非小细胞肺癌患者68例,31例(A组)术前给予单纯顺铂和丝裂霉素动脉灌注化疗;余37例(B组)灌注化疗前1 h和注药24 h后,用体外高频热疗机热疗1次.2组分别于灌注化疗前、术前1 天、术后第10天采集静脉血,应用间接免疫荧光法测定T淋巴细胞亚群;分别于灌注化疗前,术前1天,术后第10、30、60和90天抽取清晨空腹静脉血,应用ELISA法检测P53抗体水平.结果:A组术前CD3、CD4水平较灌注化疗前降低,CD8、CD4/CD8轻微升高;术后CD3、CD4及CD4/CD8水平升高,CD8降低.B组术前CD3、CD4水平较灌注化疗前明显增高,CD8降低,CD4/CD8升高;术后上述指标变化趋势未发生改变(P均<0.001).2组术后血清P53抗体水平均逐渐降低,B组较A组降低明显(F组间=52.735,F时间=9.297,F交互=4.219,P<0.001).结论:术前热疗联合灌注化疗可以改善晚期非小细胞肺癌患者的免疫力.%Aim:To study the effect of preoperalive infusion chemoltherapy combined with hyperlhermia on the immunnily of non-small cell lung cancer( NSCLC ) patients. Methods:A total of 68 patients with intermediate and advanced NSCLC were divided into ttwo groups. Croup A( n =31 ) was treated with inlervenlional arterial infusion chemotherapy alone. Group B( n = 37 ) was treated with transcatheter arterial infusion chemotherapy combined with hyperlhermia. The levels of the subsets of the peripheral blood T lymphocytes( CD3,CD4,CD8 )and the P53 antibody were delected by indirect immunofluorescence lech-nique and ELISA,respectively. Results:The CD3 and CD4 levels before operation were significantly lower than those before infusion chemotherapy in group A, CDS and CD4/CD8 were higher; but CD3, CD4 level and CD4/CD8 increased, and CD8 level decreased after operation. As to group li,CD3,CD4 and CD4/CD8 levels before operation were significantly higher than

  2. Leukocyte subsets and neutrophil function after short-term spaceflight

    Science.gov (United States)

    Stowe, R. P.; Sams, C. F.; Mehta, S. K.; Kaur, I.; Jones, M. L.; Feeback, D. L.; Pierson, D. L.

    1999-01-01

    Changes in leukocyte subpopulations and function after spaceflight have been observed but the mechanisms underlying these changes are not well defined. This study investigated the effects of short-term spaceflight (8-15 days) on circulating leukocyte subsets, stress hormones, immunoglobulin levels, and neutrophil function. At landing, a 1.5-fold increase in neutrophils was observed compared with preflight values; lymphocytes were slightly decreased, whereas the results were variable for monocytes. No significant changes were observed in plasma levels of immunoglobulins, cortisol, or adrenocorticotropic hormone. In contrast, urinary epinephrine, norepinephrine, and cortisol were significantly elevated at landing. Band neutrophils were observed in 9 of 16 astronauts. Neutrophil chemotactic assays showed a 10-fold decrease in the optimal dose response after landing. Neutrophil adhesion to endothelial cells was increased both before and after spaceflight. At landing, the expression of MAC-1 was significantly decreased while L-selectin was significantly increased. These functional alterations may be of clinical significance on long-duration space missions.

  3. Optimal Features Subset Selection and Classification for Iris Recognition

    Directory of Open Access Journals (Sweden)

    Roy Kaushik

    2008-01-01

    Full Text Available Abstract The selection of the optimal features subset and the classification have become an important issue in the field of iris recognition. We propose a feature selection scheme based on the multiobjectives genetic algorithm (MOGA to improve the recognition accuracy and asymmetrical support vector machine for the classification of iris patterns. We also suggest a segmentation scheme based on the collarette area localization. The deterministic feature sequence is extracted from the iris images using the 1D log-Gabor wavelet technique, and the extracted feature sequence is used to train the support vector machine (SVM. The MOGA is applied to optimize the features sequence and to increase the overall performance based on the matching accuracy of the SVM. The parameters of SVM are optimized to improve the overall generalization performance, and the traditional SVM is modified to an asymmetrical SVM to treat the false accept and false reject cases differently and to handle the unbalanced data of a specific class with respect to the other classes. Our experimental results indicate that the performance of SVM as a classifier is better than the performance of the classifiers based on the feedforward neural network, the k-nearest neighbor, and the Hamming and the Mahalanobis distances. The proposed technique is computationally effective with recognition rates of 99.81% and 96.43% on CASIA and ICE datasets, respectively.

  4. Optimal Features Subset Selection and Classification for Iris Recognition

    Directory of Open Access Journals (Sweden)

    Prabir Bhattacharya

    2008-06-01

    Full Text Available The selection of the optimal features subset and the classification have become an important issue in the field of iris recognition. We propose a feature selection scheme based on the multiobjectives genetic algorithm (MOGA to improve the recognition accuracy and asymmetrical support vector machine for the classification of iris patterns. We also suggest a segmentation scheme based on the collarette area localization. The deterministic feature sequence is extracted from the iris images using the 1D log-Gabor wavelet technique, and the extracted feature sequence is used to train the support vector machine (SVM. The MOGA is applied to optimize the features sequence and to increase the overall performance based on the matching accuracy of the SVM. The parameters of SVM are optimized to improve the overall generalization performance, and the traditional SVM is modified to an asymmetrical SVM to treat the false accept and false reject cases differently and to handle the unbalanced data of a specific class with respect to the other classes. Our experimental results indicate that the performance of SVM as a classifier is better than the performance of the classifiers based on the feedforward neural network, the k-nearest neighbor, and the Hamming and the Mahalanobis distances. The proposed technique is computationally effective with recognition rates of 99.81% and 96.43% on CASIA and ICE datasets, respectively.

  5. Immunophenotype of normal and myelomatous plasma cell subsets

    Directory of Open Access Journals (Sweden)

    Nelly eRobillard

    2014-03-01

    Full Text Available Plasma-cells are essentially characterized by the co-expression of CD138 and CD38, which allows their identification in flow cytometry in bone marrow, peripheral blood or cell suspensions from tissues. These terminally differentiated B-cells may lose the expression of surface CD19 and that of CD20 while retaining CD27. When malignant, they can gain a number of other markers such as CD28, CD33, CD56 or CD117 and lose CD27. Moreover, since each plasma cell is only able to produce a single type of immunoglobulins, they display isotypic restriction and clonal malignant plasma cells can be further characterized by their homogeneous expression of either kappa or lambda light chains. In multiple myeloma (MM, such plasma cell clones produce the immunoglobulin identified in plasma as an abnormal peak. In the bone marrow where they essentially accumulate, these plasma cells may however display various immunophenotypes. The latter were explored in a two-way approach. Firstly the various subsets delineated by the selective or common expression of CD19 together with combined CD56/CD28 were explored in normal and MM bone marrow. Then other aberrant markers’ expression was investigated, i.e. CD20, CD27, CD33, CD56, CD117. These data were compared to literature information. They underline the vast heterogeneity of MM plasma cells possibly accounting for the various answers to therapy of MM patients.

  6. Alteration of peripheral blood lymphocyte subsets in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Miroslawa Pietruczuk; Milena I Dabrowska; Urszula Wereszczynska-Siemiatkowska; Andrzej Dabrowski

    2006-01-01

    AIM: To evaluate peripheral blood lymphocyte subsets in patients with acute pancreatitis (AP).METHODS: Twenty patients with mild AP (M-AP) and 15 with severe AP (S-AP) were included in our study. Peripheral blood lymphocytes were examined at d 1-3, 5,10 and 30 by means of flow cytometry.RESULTS: A significant depletion of circulating lymphocytes was found in AP. In the early AP, the magnitude of depletion was similar for T- and B- lymphocytes. In the late course of S-AP, B-lymphocytes were much more depleted than T-lymphocytes. At d 10, strong shift in the CD7+/CD19+ ratio implicating predominance of Tover B-lymphocytes in S-AP was found. Among T-lymphocytes, the significant depletion of the CD4+ population was observed in M-AP and S-AP, while CD8+ cells were in the normal range. Lymphocytes were found to strongly express activation markers: CD69, CD25, CD28,CD38 and CD122. Serum interleukin-2 (IL-2), IL-4, IL-5,IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α(TNF-α) levels were significantly increased in both forms of AP. The magnitude of elevation of cytokines known to be produced by Th2 was much higher than cytokines produced by Th1 cells.CONCLUSION: AP in humans is characterized by significant reduction of peripheral blood T- and B-lymphocytes.

  7. NK cell subset redistribution during the course of viral infections

    Directory of Open Access Journals (Sweden)

    Enrico eLugli

    2014-08-01

    Full Text Available Natural killer (NK cells are important effectors of innate immunity that play a critical role in the control of human viral infections. Indeed, given their capability to directly recognize virally infected cells without the need of specific antigen presentation, NK cells are on the first line of defense against these invading pathogens. By establishing cellular networks with a variety of cell types such as dendritic cells, NK cells can also amplify anti-viral adaptive immune responses. In turn, viruses evolved and developed several mechanisms to evade NK cell-mediated immune activity. It has been reported that certain viral diseases, including human immunodeficiency virus-1 (HIV-1 as well as cytomegalovirus (CMV infections, are associated with a pathologic redistribution of NK cell subsets in the peripheral blood. In particular, it has been observed the expansion of unconventional CD56neg NK cells, whose effector functions are significantly impaired as compared to that of conventional CD56pos NK cells. In this review, we address the impact of chronic viral infections on the functional and phenotypic perturbations of human NK cell compartment.

  8. PRODH mutations and hyperprolinemia in a subset of schizophrenic patients.

    Science.gov (United States)

    Jacquet, Hélène; Raux, Grégory; Thibaut, Florence; Hecketsweiler, Bernadette; Houy, Emmanuelle; Demilly, Caroline; Haouzir, Sadeq; Allio, Gabrielle; Fouldrin, Gael; Drouin, Valérie; Bou, Jacqueline; Petit, Michel; Campion, Dominique; Frébourg, Thierry

    2002-09-15

    The increased prevalence of schizophrenia among patients with the 22q11 interstitial deletion associated with DiGeorge syndrome has suggested the existence of a susceptibility gene for schizophrenia within the DiGeorge syndrome chromosomal region (DGCR) on 22q11. Screening for genomic rearrangements of 23 genes within or at the boundaries of the DGCR in 63 unrelated schizophrenic patients and 68 unaffected controls, using quantitative multiplex PCR of short fluorescent fragments (QMPSF), led us to identify, in a family including two schizophrenic subjects, a heterozygous deletion of the entire PRODH gene encoding proline dehydrogenase. This deletion was associated with hyperprolinemia in the schizophrenic patients. In addition, two heterozygous PRODH missense mutations (L441P and L289M), detected in 3 of 63 schizophrenic patients but in none among 68 controls, were also associated with increased plasma proline levels. Segregation analysis within the two families harboring respectively the PRODH deletion and the L441P mutation showed that the presence of a second PRODH nucleotide variation resulted in higher levels of prolinemia. In two unrelated patients suffering from severe type I hyperprolinemia with neurological manifestations, we identified a homozygous L441P PRODH mutation, associated with a heterozygous R453C substitution in one patient. These observations demonstrate that type I hyperprolinemia is present in a subset of schizophrenic patients, and suggest that the genetic determinism of type I hyperprolinemia is complex, the severity of hyperprolinemia depending on the nature and number of hits affecting the PRODH locus.

  9. Zone diagrams in compact subsets of uniformly convex normed spaces

    CERN Document Server

    Kopecká, Eva; Reich, Simeon

    2010-01-01

    A zone diagram is a relatively new concept which has emerged in computational geometry and is related to Voronoi diagrams. Formally, it is a fixed point of a certain mapping, and neither its uniqueness nor its existence are obvious in advance. It has been studied by several authors, starting with T. Asano, J. Matousek and T. Tokuyama, who considered the Euclidean plane with singleton sites, and proved the existence and uniqueness of zone diagrams there. In the present paper we prove the existence of zone diagrams with respect to finitely many pairwise disjoint compact sites contained in a compact and convex subset of a uniformly convex normed space. The proof is based on the Schauder fixed point theorem, the Curtis-Schori theorem regarding the Hilbert cube, and on recent results concerning the characterization of Voronoi cells as a collection of line segments and their geometric stability with respect to small changes of the corresponding sites. Along the way we obtain the continuity of the Dom mapping as wel...

  10. Bayesian Subset Modeling for High-Dimensional Generalized Linear Models

    KAUST Repository

    Liang, Faming

    2013-06-01

    This article presents a new prior setting for high-dimensional generalized linear models, which leads to a Bayesian subset regression (BSR) with the maximum a posteriori model approximately equivalent to the minimum extended Bayesian information criterion model. The consistency of the resulting posterior is established under mild conditions. Further, a variable screening procedure is proposed based on the marginal inclusion probability, which shares the same properties of sure screening and consistency with the existing sure independence screening (SIS) and iterative sure independence screening (ISIS) procedures. However, since the proposed procedure makes use of joint information from all predictors, it generally outperforms SIS and ISIS in real applications. This article also makes extensive comparisons of BSR with the popular penalized likelihood methods, including Lasso, elastic net, SIS, and ISIS. The numerical results indicate that BSR can generally outperform the penalized likelihood methods. The models selected by BSR tend to be sparser and, more importantly, of higher prediction ability. In addition, the performance of the penalized likelihood methods tends to deteriorate as the number of predictors increases, while this is not significant for BSR. Supplementary materials for this article are available online. © 2013 American Statistical Association.

  11. Comparative genomics analysis of mononuclear phagocyte subsets confirms homology between lymphoid tissue-resident and dermal XCR1(+) DCs in mouse and human and distinguishes them from Langerhans cells.

    Science.gov (United States)

    Carpentier, Sabrina; Vu Manh, Thien-Phong; Chelbi, Rabie; Henri, Sandrine; Malissen, Bernard; Haniffa, Muzlifah; Ginhoux, Florent; Dalod, Marc

    2016-05-01

    Dendritic cells (DC) are mononuclear phagocytes which exhibit a branching (dendritic) morphology and excel at naïve T cell activation. DC encompass several subsets initially identified by their expression of cell surface molecules and later shown to possess distinct functions. DC subset differentiation is orchestrated by transcription factors, growth factors and cytokines. Identifying DC subsets is challenging as very few cell surface molecules are uniquely expressed on any one of these cell populations. There is no standard consensus to identify mononuclear phagocyte subsets; varying antigens are employed depending on the tissue and animal species studied and between laboratories. This has led to confusion in how to accurately define and classify DCs across tissues and between species. Here we report a comparative genomics strategy that enables universal definition of DC and other mononuclear phagocyte subsets across species. We performed a meta-analysis of several public datasets of human and mouse mononuclear phagocyte subsets isolated from blood, spleen, skin or cutaneous lymph nodes, including by using a novel and user friendly software, BubbleGUM, which generates and integrates gene signatures for high throughput gene set enrichment analysis. This analysis demonstrates the equivalence between human and mouse skin XCR1(+) DCs, and between mouse and human Langerhans cells.

  12. Enrichment of lanthanides in aragonite

    Institute of Scientific and Technical Information of China (English)

    瞿成利; 路波; 刘刚

    2009-01-01

    Using the constant addition technique,the coprecipitation of lanthanum,gadolinium,and lutetium with aragonite in seawater was experimentally investigated at 25 ℃.Their concentrations in aragonite overgrowths were determined by inductive coupled plasma mass spectrometer.All these lanthanides were strongly enriched in aragonite overgrowths.The amount of lanthanum,gadolinium,and lutetium incorporated into aragonite accounted for 57%-99%,50%-89%,and 40%-91% of their initial total amount,respectively.With the in...

  13. Differential expression of HLA-DR antigens in subsets of human CFU-GM.

    Science.gov (United States)

    Griffin, J D; Sabbath, K D; Herrmann, F; Larcom, P; Nichols, K; Kornacki, M; Levine, H; Cannistra, S A

    1985-10-01

    Expression of HLA-DR surface antigens by granulocyte/monocyte colony-forming cells (CFU-GM) may be important in the regulation of proliferation of these cells. Using immunological techniques to enrich for progenitor cells, we investigated the expression of HLA-DR in subsets of CFU-GM. "Early" (day 14) CFU-GM express higher levels of HLA-DR than do "late" (day 7) CFU-GM. Among late CFU-GM, cells destined to form monocyte (alpha-naphthyl acetate esterase-positive) colonies express higher levels of HLA-DR than do CFU-GM destined to form granulocyte (chloroacetate esterase-positive) colonies. Because high-level expression of DR antigen was a marker for monocyte differentiation, we examined several lymphokines for their effects on both DR expression and in vitro commitment to monocyte differentiation by myeloid precursor cells. DR antigen density could be increased by more than twofold over 48 hours upon exposure to gamma-interferon (gamma-IFN), whereas colony-stimulating factors had no effect. This was associated with a dose-dependent inhibition of total CFU-GM number, and a relative, but not absolute, increase in the ratio of monocyte colonies to granulocyte colonies. Similarly, in day 7 suspension cultures of purified myeloid precursor cells, gamma-IFN inhibited cell proliferation and increased the ratio of monocytes to granulocytes. Thus, despite the induction of high levels of HLA-DR antigen on precursor cells (a marker of monocyte commitment), the dominant in vitro effect of gamma-IFN was inhibition of granulocyte differentiation.

  14. Enrichment and aggression in primates.

    Science.gov (United States)

    Honess, P E; Marin, C M

    2006-01-01

    There is considerable evidence that primates housed under impoverished conditions develop behavioural abnormalities, including, in the most extreme example, self-harming behaviour. This has implications for all contexts in which primates are maintained in captivity from laboratories to zoos since by compromising the animals' psychological well-being and allowing them to develop behavioural abnormalities their value as appropriate educational and research models is diminished. This review examines the extensive body of literature documenting attempts to improve living conditions with a view to correcting behavioural abnormalities and housing primates in such a way that they are encouraged to exhibit a more natural range and proportion of behaviours, including less self-directed and social aggression. The results of housing, feeding, physical, sensory and social enrichment efforts are examined with specific focus on their effect on aggressive behaviour and variation in their use and efficacy. It is concluded that while inappropriate or poorly distributed enrichment may encourage aggressive competition, enrichment that is species, sex, age and background appropriate can dramatically reduce aggression, can eliminate abnormal behaviour and substantially improve the welfare of primates maintained in captivity.

  15. Phenotypic and functional distinctions between the TH2+ and JRA+ T cell subsets in man.

    Science.gov (United States)

    Reinherz, E L; Strelkauskas, A J; O'Brien, C; Schlossman, S F

    1979-07-01

    Prior work has demonstrated the existence of distinct human peripheral blood T cell subsets by utilizing heterologous as well as autoimmune antisera. In the present study, the relationship between the TH2+ and JRA+ T cell subsets was examined. T cells were purified with Sephadex G-200 anti-F(ab)2' affinity chromatography and E-rosetting technique, and subsequently fractionated into TH2+ and TH2- subsets by utilizing indirect immunofluorescence on FACS. Approximately 40 to 45% of the TH2- subset was shown to be JRA+, whereas less than 5% of the TH2+ subset was JRA+. In reciprocal studies, T cells were fractionated into JRA+ and JRA- subsets and reacted with heterologous antisera with anti-TH2+ specificity and indirect immunofluorescence. FACS analysis demonstrated that the JRA+ population contained no TH2+ T cells. In contrast, the JRA- population contained TH2+ T cells and accounted for the entire TH2+ subset found in the unfractionated T cell population. Functional studies showed that the TH2+ subset, and not the JRA+ subset, contain the effector population for cell-mediated lympholysis. It is concluded that the TH2+ and JRA+ T cell subsets define distinct and different T cell populations in man.

  16. Network-based functional enrichment

    Directory of Open Access Journals (Sweden)

    Poirel Christopher L

    2011-11-01

    Full Text Available Abstract Background Many methods have been developed to infer and reason about molecular interaction networks. These approaches often yield networks with hundreds or thousands of nodes and up to an order of magnitude more edges. It is often desirable to summarize the biological information in such networks. A very common approach is to use gene function enrichment analysis for this task. A major drawback of this method is that it ignores information about the edges in the network being analyzed, i.e., it treats the network simply as a set of genes. In this paper, we introduce a novel method for functional enrichment that explicitly takes network interactions into account. Results Our approach naturally generalizes Fisher’s exact test, a gene set-based technique. Given a function of interest, we compute the subgraph of the network induced by genes annotated to this function. We use the sequence of sizes of the connected components of this sub-network to estimate its connectivity. We estimate the statistical significance of the connectivity empirically by a permutation test. We present three applications of our method: i determine which functions are enriched in a given network, ii given a network and an interesting sub-network of genes within that network, determine which functions are enriched in the sub-network, and iii given two networks, determine the functions for which the connectivity improves when we merge the second network into the first. Through these applications, we show that our approach is a natural alternative to network clustering algorithms. Conclusions We presented a novel approach to functional enrichment that takes into account the pairwise relationships among genes annotated by a particular function. Each of the three applications discovers highly relevant functions. We used our methods to study biological data from three different organisms. Our results demonstrate the wide applicability of our methods. Our algorithms are

  17. NEAT: an efficient network enrichment analysis test

    OpenAIRE

    Signorelli, Mirko; Vinciotti, Veronica; Wit, Ernst C

    2016-01-01

    Background Network enrichment analysis is a powerful method, which allows to integrate gene enrichment analysis with the information on relationships between genes that is provided by gene networks. Existing tests for network enrichment analysis deal only with undirected networks, they can be computationally slow and are based on normality assumptions. Results We propose NEAT, a test for network enrichment analysis. The test is based on the hypergeometric distribution, which naturally arises ...

  18. Molecular subsets in the gene expression signatures of scleroderma skin.

    Directory of Open Access Journals (Sweden)

    Ausra Milano

    Full Text Available BACKGROUND: Scleroderma is a clinically heterogeneous disease with a complex phenotype. The disease is characterized by vascular dysfunction, tissue fibrosis, internal organ dysfunction, and immune dysfunction resulting in autoantibody production. METHODOLOGY AND FINDINGS: We analyzed the genome-wide patterns of gene expression with DNA microarrays in skin biopsies from distinct scleroderma subsets including 17 patients with systemic sclerosis (SSc with diffuse scleroderma (dSSc, 7 patients with SSc with limited scleroderma (lSSc, 3 patients with morphea, and 6 healthy controls. 61 skin biopsies were analyzed in a total of 75 microarray hybridizations. Analysis by hierarchical clustering demonstrates nearly identical patterns of gene expression in 17 out of 22 of the forearm and back skin pairs of SSc patients. Using this property of the gene expression, we selected a set of 'intrinsic' genes and analyzed the inherent data-driven groupings. Distinct patterns of gene expression separate patients with dSSc from those with lSSc and both are easily distinguished from normal controls. Our data show three distinct patient groups among the patients with dSSc and two groups among patients with lSSc. Each group can be distinguished by unique gene expression signatures indicative of proliferating cells, immune infiltrates and a fibrotic program. The intrinsic groups are statistically significant (p<0.001 and each has been mapped to clinical covariates of modified Rodnan skin score, interstitial lung disease, gastrointestinal involvement, digital ulcers, Raynaud's phenomenon and disease duration. We report a 177-gene signature that is associated with severity of skin disease in dSSc. CONCLUSIONS AND SIGNIFICANCE: Genome-wide gene expression profiling of skin biopsies demonstrates that the heterogeneity in scleroderma can be measured quantitatively with DNA microarrays. The diversity in gene expression demonstrates multiple distinct gene expression programs

  19. Enriching Music and Language Arts Experiences

    Science.gov (United States)

    Flohr, John W.

    2006-01-01

    The article focuses on enriching music and language arts experiences of students. Music can enrich literature and language arts, poetry, theater arts, transitions, science, and math, as well as help meet special learner needs. A well-understood example of enrichment is the alphabet song. A music or classroom teacher using the alphabet song helps…

  20. How Did the IGM Become Enriched?

    CERN Document Server

    Aguirre, A; Aguirre, Anthony; Schaye, Joop

    2006-01-01

    The enrichment of the intergalactic medium with heavy elements is a process that lies at the nexus of poorly-understood aspects of physical cosmology. We review current understanding of the processes that may remove metals from galaxies, the basic predictions of these models, the key observational constraints on enrichment, and how intergalactic enrichment may be used to test cosmological simulations.

  1. Hereditary colorectal cancer diagnostics

    DEFF Research Database (Denmark)

    Klarskov, Louise; Holck, Susanne; Bernstein, Inge

    2012-01-01

    BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid...... in the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated with FCCTX...

  2. Supervised Feature Subset Selection based on Modified Fuzzy Relative Information Measure for classifier Cart

    Directory of Open Access Journals (Sweden)

    K.SAROJINI,

    2010-06-01

    Full Text Available Feature subset selection is an essential task in data mining. This paper presents a new method for dealing with supervised feature subset selection based on Modified Fuzzy Relative Information Measure (MFRIM. First, Discretization algorithm is applied to discretize numeric features to construct the membership functions of each fuzzy sets of a feature. Then the proposed MFRIM is applied to select the feature subset focusing on boundary samples. The proposed method can select feature subset with minimum number of features, which are relevant to get higher average classification accuracy for datasets. The experimental results with UCI datasets show that the proposed algorithm is effective and efficient in selecting subset with minimum number of features getting higher average classification accuracy than the consistency based feature subset selection method.

  3. Identification of Suitable Reference Genes for Peripheral Blood Mononuclear Cell Subset Studies in Multiple Sclerosis

    DEFF Research Database (Denmark)

    Oturai, D B; Søndergaard, H B; Börnsen, L;

    2016-01-01

    Quantitative real-time PCR (qPCR) involves the need of a proper standard for normalizing the gene expression data. Different studies have shown the validity of reference genes to vary greatly depending on tissue, cell subsets and experimental context. This study aimed at the identification...... of suitable reference genes for qPCR studies using different peripheral blood cell subsets (whole blood (WB) cells, peripheral blood mononuclear cells (PBMCs) and PBMC subsets (CD4(+) T cells, CD8(+) T cells, NK cells, monocytes, B cells and dendritic cells) from healthy controls (HC), patients with relapsing...... stable combination for analyses of cell subsets between HC and RRMS patients, while the combination of UBC and YWHAZ was superior for analysis of cell subsets between HC, RRMS and RRMS-IFN-β groups. GAPDH was generally unsuitable for blood cell subset studies in multiple sclerosis. In conclusion, we...

  4. Comprehensive annotation of bidirectional promoters identifies co-regulation among breast and ovarian cancer genes.

    Directory of Open Access Journals (Sweden)

    Mary Q Yang

    2007-04-01

    Full Text Available A "bidirectional gene pair" comprises two adjacent genes whose transcription start sites are neighboring and directed away from each other. The intervening regulatory region is called a "bidirectional promoter." These promoters are often associated with genes that function in DNA repair, with the potential to participate in the development of cancer. No connection between these gene pairs and cancer has been previously investigated. Using the database of spliced-expressed sequence tags (ESTs, we identified the most complete collection of human transcripts under the control of bidirectional promoters. A rigorous screen of the spliced EST data identified new bidirectional promoters, many of which functioned as alternative promoters or regulated novel transcripts. Additionally, we show a highly significant enrichment of bidirectional promoters in genes implicated in somatic cancer, including a substantial number of genes implicated in breast and ovarian cancers. The repeated use of this promoter structure in the human genome suggests it could regulate co-expression patterns among groups of genes. Using microarray expression data from 79 human tissues, we verify regulatory networks among genes controlled by bidirectional promoters. Subsets of these promoters contain similar combinations of transcription factor binding sites, including evolutionarily conserved ETS factor binding sites in ERBB2, FANCD2, and BRCA2. Interpreting the regulation of genes involved in co-expression networks, especially those involved in cancer, will be an important step toward defining molecular events that may contribute to disease.

  5. Comparative Study of Green Sub- and Supercritical Processes to Obtain Carnosic Acid and Carnosol-Enriched Rosemary Extracts with in Vitro Anti-Proliferative Activity on Colon Cancer Cells.

    Science.gov (United States)

    Sánchez-Camargo, Andrea Del Pilar; García-Cañas, Virginia; Herrero, Miguel; Cifuentes, Alejandro; Ibáñez, Elena

    2016-12-07

    In the present work, four green processes have been compared to evaluate their potential to obtain rosemary extracts with in vitro anti-proliferative activity against two colon cancer cell lines (HT-29 and HCT116). The processes, carried out under optimal conditions, were: (1) pressurized liquid extraction (PLE, using an hydroalcoholic mixture as solvent) at lab-scale; (2) Single-step supercritical fluid extraction (SFE) at pilot scale; (3) Intensified two-step sequential SFE at pilot scale; (4) Integrated PLE plus supercritical antisolvent fractionation (SAF) at pilot scale. Although higher extraction yields were achieved by using PLE (38.46% dry weight), this extract provided the lowest anti-proliferative activity with no observed cytotoxic effects at the assayed concentrations. On the other hand, extracts obtained using the PLE + SAF process provided the most active rosemary extracts against both colon cancer cell lines, with LC50 ranging from 11.2 to 12.4 µg/mL and from 21.8 to 31.9 µg/mL for HCT116 and HT-29, respectively. In general, active rosemary extracts were characterized by containing carnosic acid (CA) and carnosol (CS) at concentrations above 263.7 and 33.9 mg/g extract, respectively. Some distinct compounds have been identified in the SAF extracts (rosmaridiphenol and safficinolide), suggesting their possible role as additional contributors to the observed strong anti-proliferative activity of CA and CS in SAF extracts.

  6. Comparative Study of Green Sub- and Supercritical Processes to Obtain Carnosic Acid and Carnosol-Enriched Rosemary Extracts with in Vitro Anti-Proliferative Activity on Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Andrea del Pilar Sánchez-Camargo

    2016-12-01

    Full Text Available In the present work, four green processes have been compared to evaluate their potential to obtain rosemary extracts with in vitro anti-proliferative activity against two colon cancer cell lines (HT-29 and HCT116. The processes, carried out under optimal conditions, were: (1 pressurized liquid extraction (PLE, using an hydroalcoholic mixture as solvent at lab-scale; (2 Single-step supercritical fluid extraction (SFE at pilot scale; (3 Intensified two-step sequential SFE at pilot scale; (4 Integrated PLE plus supercritical antisolvent fractionation (SAF at pilot scale. Although higher extraction yields were achieved by using PLE (38.46% dry weight, this extract provided the lowest anti-proliferative activity with no observed cytotoxic effects at the assayed concentrations. On the other hand, extracts obtained using the PLE + SAF process provided the most active rosemary extracts against both colon cancer cell lines, with LC50 ranging from 11.2 to 12.4 µg/mL and from 21.8 to 31.9 µg/mL for HCT116 and HT-29, respectively. In general, active rosemary extracts were characterized by containing carnosic acid (CA and carnosol (CS at concentrations above 263.7 and 33.9 mg/g extract, respectively. Some distinct compounds have been identified in the SAF extracts (rosmaridiphenol and safficinolide, suggesting their possible role as additional contributors to the observed strong anti-proliferative activity of CA and CS in SAF extracts.

  7. Lymphoid organ-resident dendritic cells exhibit unique transcriptional fingerprints based on subset and site.

    Directory of Open Access Journals (Sweden)

    Kutlu G Elpek

    Full Text Available Lymphoid organ-resident DC subsets are thought to play unique roles in determining the fate of T cell responses. Recent studies focusing on a single lymphoid organ identified molecular pathways that are differentially operative in each DC subset and led to the assumption that a given DC subset would more or less exhibit the same genomic and functional profiles throughout the body. Whether the local milieu in different anatomical sites can also influence the transcriptome of DC subsets has remained largely unexplored. Here, we interrogated the transcriptional relationships between lymphoid organ-resident DC subsets from spleen, gut- and skin-draining lymph nodes, and thymus of C57BL/6 mice. For this purpose, major resident DC subsets including CD4 and CD8 DCs were sorted at high purity and gene expression profiles were compared using microarray analysis. This investigation revealed that lymphoid organ-resident DC subsets exhibit divergent genomic programs across lymphoid organs. Interestingly, we also found that transcriptional and biochemical properties of a given DC subset can differ between lymphoid organs for lymphoid organ-resident DC subsets, but not plasmacytoid DCs, suggesting that determinants of the tissue milieu program resident DCs for essential site-specific functions.

  8. Contributions of cell subsets to cytokine production during normal and impaired wound healing.

    Science.gov (United States)

    Mirza, Rita E; Koh, Timothy J

    2015-02-01

    The objective of this study was to determine the relative contributions of different cell subsets to the production of cytokines and growth factors during normal and impaired wound healing. Cells were isolated from wounds of non-diabetic and diabetic mice and separated by magnetic sorting into neutrophils/T cells/B cells (NTB cell subset), monocytes/macrophages (Mo/Mp subset) and non-leukocytic cells including keratinocyte/fibroblast/endothelial cells (KFE subset). On both per cell and total contribution bases, the Mo/Mp subset was the dominant producer of pro-inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6 in both non-diabetic and diabetic mice and was a significant producer of vascular endothelial cell growth factor (VEGF)-A, insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-β1. The NTB subset was also a significant producer of TNF-α and IL-10 whereas the KFE subset contributed significant amounts of VEGF, IGF-1 and TGF-β1. Sustained production of pro-inflammatory cytokines and impaired production of healing-associated factors were evident in each subset in diabetic mice. These data will be useful for further experimental and modeling studies on the role of cell subsets in wound healing as well as for designing therapeutic strategies for improving healing.

  9. Enrichment planting without soil treatment

    Energy Technology Data Exchange (ETDEWEB)

    Hagner, Mats

    1998-12-31

    Where enrichment planting had been carried out with either of the two species Picea abies and Pinus contorta, the survival of the planted seedlings was at least as good as after planting in a normal clear cut area treated with soil scarification. This was in spite of the fact that the seedlings were placed shallow in the humus layer without any soil treatment. However, they were sheltered from insects by treatment before planting. Where enrichment planting was carried out with Pinus sylvestris the survival in dense forest was poor, but in open forest the survival was good. The growth of planted seedlings was enhanced by traditional clearing and soil treatment. However, this was for Pinus sylvestris not enough to compensate for the loss of time, 1-2 years, caused by arrangement of soil scarification. The growth of seedlings planted under crown cover was directly related to basal area of retained trees. However, the variation in height growth among individual seedlings was very big, which meant that some seedlings grow well also under a fairly dense forest cover. The pioneer species Pinus sylvestris reacted more strongly to basal area of retained trees than did the shade tolerant species Picea abies. Enrichment planting seems to be a necessary tool for preserving volume productivity, at places where fairly intensive harvest of mature trees has been carried out in stands of ordinary forest type in central Sweden. If double seedlings, with one Picea abies and one Pinus sylvestris, are used, the probability for long term establishment is enhanced 13 refs, 20 figs, 4 tabs

  10. Survival and signaling changes in antigen presenting cell subsets after radiation

    Science.gov (United States)

    Parker, Jennifer Janell

    Radiation therapy is a widely used cancer treatment that has the potential to influence anti-tumor immune responses. Both myeloablative and non-myeloablative radiation are often used as part of preparatory regimens for hematopoetic stem cell transplantation, in combination with other chemotherapy or immuno-modulatory (e.g. Anti-thymocyte globulin (ATG)) therapies for both cytotoxic and immune modulatory purposes. However, the mechanisms responsible for the effect of radiation on antigen presenting cell (APC) responsiveness and radioresistance are poorly understood. The first studies described in this thesis were designed to identify and characterize early radiation-induced signaling changes in antigen presenting cells and to determine the effects of these signaling changes on APC receptor expression and function. The NFkappaB pathway in antigen presenting cells was chosen for study because it is activated by radiation in a wide range of other cell types and plays a vital role in the maintenance and regulation of the immune system. The effects of therapeutically relevant doses radiation (2 and 20 Gy) were compared at various timepoints in the human monocytic cell line (U937) using phospho-flow cytometry staining methods and cytometric analysis. These studies demonstrated that radiation-induced changes in the phosphorylation state of NFkappaB family members that were p53 independent. However, these changes were dependent upon activation of ATM in response to single or double-stranded breaks in DNA, as shown in experiments using an inhibitor of ATM and ATM siRNA knockdown U937 cells. In addition, studies examining the effect of radiation on co-stimulatory receptors with and without inhibition of the NFkappaB pathway via phospho-flow cytometry revealed that radiation-induced phosphorylation of NEMO promoted the activation and functional maturation of U937 cells. Furthermore, functional studies using both phospho-flow cytometry and/or mixed lymphocyte reactions to

  11. Boron enrichment in martian clay.

    Directory of Open Access Journals (Sweden)

    James D Stephenson

    Full Text Available We have detected a concentration of boron in martian clay far in excess of that in any previously reported extra-terrestrial object. This enrichment indicates that the chemistry necessary for the formation of ribose, a key component of RNA, could have existed on Mars since the formation of early clay deposits, contemporary to the emergence of life on Earth. Given the greater similarity of Earth and Mars early in their geological history, and the extensive disruption of Earth's earliest mineralogy by plate tectonics, we suggest that the conditions for prebiotic ribose synthesis may be better understood by further Mars exploration.

  12. Bi-directional SIFT predicts a subset of activating mutations.

    Science.gov (United States)

    Lee, William; Zhang, Yan; Mukhyala, Kiran; Lazarus, Robert A; Zhang, Zemin

    2009-12-14

    Advancements in sequencing technologies have empowered recent efforts to identify polymorphisms and mutations on a global scale. The large number of variations and mutations found in these projects requires high-throughput tools to identify those that are most likely to have an impact on function. Numerous computational tools exist for predicting which mutations are likely to be functional, but none that specifically attempt to identify mutations that result in hyperactivation or gain-of-function. Here we present a modified version of the SIFT (Sorting Intolerant from Tolerant) algorithm that utilizes protein sequence alignments with homologous sequences to identify functional mutations based on evolutionary fitness. We show that this bi-directional SIFT (B-SIFT) is capable of identifying experimentally verified activating mutants from multiple datasets. B-SIFT analysis of large-scale cancer genotyping data identified potential activating mutations, some of which we have provided detailed structural evidence to support. B-SIFT could prove to be a valuable tool for efforts in protein engineering as well as in identification of functional mutations in cancer.

  13. Environmental enrichment for primates in laboratories

    Science.gov (United States)

    Buchanan-Smith, H. M.

    2010-06-01

    Environmental enrichment is a critical component of Refinement, one of the 3Rs underlying humane experimentation on animals. In this paper I discuss why primates housed in laboratories, which often have constraints of space and study protocols, are a special case for enrichment. I outline a framework for categorising the different types of enrichment, using the marmoset as a case study, and summarise the methods used to determine what animals want/prefer. I briefly review the arguments that enrichment does not negatively affect experimental outcomes. Finally I focus on complexity and novelty, choice and control, the underlying features of enrichment that makes it successful, and how combined with a thorough understanding of natural history we can put effective enrichment into practice in laboratories. Throughout the paper I emphasise the need to evaluate enrichment to ensure it is having the desired effect.

  14. Hypermutation In Pancreatic Cancer.

    Science.gov (United States)

    Humphris, Jeremy L; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J; Johns, Amber L; McKay, Skye; Chang, David K; Miller, David K; Pajic, Marina; Kassahn, Karin S; Quinn, Michael C J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Stone, Andrew; Wilson, Peter J; Anderson, Matthew; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Mead, Ronald S; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Nagrial, Adnan M; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Rooman, Ilse; Giry-Laterriere, Marc; Samra, Jaswinder S; Kench, James G; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; McKay, Colin J; Carter, C Ross; Dickson, Euan J; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Morton, Jennifer P; Sansom, Owen J; Grützmann, Robert; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Rusev, Borislav; Corbo, Vincenzo; Salvia, Roberto; Cataldo, Ivana; Tortora, Giampaolo; Tempero, Margaret A; Hofmann, Oliver; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Gill, Anthony J; Pearson, John V; Grimmond, Sean M; Waddell, Nicola; Biankin, Andrew V

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.

  15. [Cellular immunity changes after total parenteral nutrition enriched with glutamine in patients with sepsis and malnutrition].

    Science.gov (United States)

    Słotwiński, R; Pertkiewicz, M; Lech, G; Szczygieł, B

    2000-06-01

    The influence of glutamine on human immune system is multidirectional but the exact changes still remain unclear. In this study the effect of total parenteral nutrition (TPN) enriched with glutamine on some selected immunological and nutritional parameters was examined in twelve surgical patients with sepsis and malnutrition. The reason for glutamine supplementation was lack of clinical improvement after standard TPN. All patients received TPN enriched with glutamine for 10 days. Phenotypic analysis of peripheral blood mononuclear subsets (CD4, CD8, CD16, CD56, HLA-DR) were measured before, during (on days 2, 4, 6) glutamine administration and two days after (day 12) glutamine withdrawal. Simultaneously some nutritional parameters were assessed. The number and percentage of CD4, CD16, CD56 mononuclear subsets increased significantly on day 2 and stayed on the same level during observation (with exception in CD4 on day 6, 12 and CD56 on day 4). No significant differences in CD8 and HLA-DR number and percentages were observed after TPN enriched with glutamine. BIA examination revealed on days 2 and 12 significant decrease of total body water and significant increase of body cell mass, intracellular water on day 12. It was correlated with significant higher total lymphocytes count and significantly higher total protein, serum albumin, transferrin, cholesterol and CRP concentration. Results demonstrated that TPN supplemented with glutamine improved rapidly some immunological and nutritional parameters in surgical, malnutrition patients with sepsis.

  16. Overexpression of the stathmin gene in a subset of human breast cancer.

    OpenAIRE

    Bièche, I.; Lachkar, S.; Becette, V; Cifuentes-Diaz, C; Sobel, A.; Lidereau, R; Curmi, P A

    1998-01-01

    Stathmin is a highly conserved cytosolic phosphoprotein that destabilizes microtubules. Stathmin, which has been proposed as a relay protein integrating diverse cell signalling pathways, acts in vitro as a tubulin-sequestering protein, and its activity is dramatically reduced by phosphorylation. Interestingly, stathmin expression and phosphorylation are regulated during the control of cell growth and differentiation, and there is much evidence suggesting that in vivo stathmin plays a role in ...

  17. T-lymphocyte subsets in West African children: impact of age, sex, and season

    DEFF Research Database (Denmark)

    Lisse, I M; Aaby, P; Whittle, H;

    1997-01-01

    OBJECTIVE: There has been no reference material for T-lymphocyte subsets for normal children in developing countries. We therefore used T-lymphocyte subset determinations among children in three different studies in Guinea-Bissau to construct age-related reference material and to examine possible...

  18. A class of compact subsets for non-sober topological spaces

    CERN Document Server

    Poncet, Paul

    2009-01-01

    We define a class of subsets of a topological space which coincides with the class of compact saturated subsets when the space is sober, and with enough good properties when the space is not sober. This class is introduced especially in view of applications to capacity theory.

  19. Phenotypic, ultra-structural and functional characterization of bovine peripheral blood dendritic cell subsets

    Science.gov (United States)

    Dendritic cells (DC) are multifunctional cells that bridge the gap between innate and adaptive immune systems. In bovine, significant information is lacking on the precise identity and role of peripheral blood DC subsets. In this study, we identify and characterize bovine peripheral blood DC subsets...

  20. Wnt/beta-Catenin, Foxa2, and CXCR4 Axis Controls Prostate Cancer Progression

    Science.gov (United States)

    2014-07-01

    al. Spiculated periosteal response induced by intraosseous injection of 22Rv1 prostate cancer cells resembles subset of bone metastases in prostate cancer patients. Prostate 2005; 65(4): 347-54. Appendice None

  1. Innate-like functions of natural killer T cell subsets result from highly divergent gene programs.

    Science.gov (United States)

    Engel, Isaac; Seumois, Grégory; Chavez, Lukas; Samaniego-Castruita, Daniela; White, Brandie; Chawla, Ashu; Mock, Dennis; Vijayanand, Pandurangan; Kronenberg, Mitchell

    2016-06-01

    Natural killer T cells (NKT cells) have stimulatory or inhibitory effects on the immune response that can be attributed in part to the existence of functional subsets of NKT cells. These subsets have been characterized only on the basis of the differential expression of a few transcription factors and cell-surface molecules. Here we have analyzed purified populations of thymic NKT cell subsets at both the transcriptomic level and epigenomic level and by single-cell RNA sequencing. Our data indicated that despite their similar antigen specificity, the functional NKT cell subsets were highly divergent populations with many gene-expression and epigenetic differences. Therefore, the thymus 'imprints' distinct gene programs on subsets of innate-like NKT cells that probably impart differences in proliferative capacity, homing, and effector functions.

  2. Canine Mammary Cancer Stem Cells are Radio- and Chemo- Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype.

    Science.gov (United States)

    Pang, Lisa Y; Cervantes-Arias, Alejandro; Else, Rod W; Argyle, David J

    2011-03-30

    Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs) can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelial to mesenchymal transition (EMT) has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype. Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGFβ and that these cells have an increased ability to form tumorspheres. Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology.

  3. Canine Mammary Cancer Stem Cells are Radio- and Chemo-Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Lisa Y., E-mail: lisa.pang@ed.ac.uk; Cervantes-Arias, Alejandro; Else, Rod W.; Argyle, David J. [Royal (Dick) School of Veterinary Studies and Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG (United Kingdom)

    2011-03-30

    Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs) can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelial to mesenchymal transition (EMT) has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype. Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGFβ and that these cells have an increased ability to form tumorspheres. Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology.

  4. Comparative oncogenomic analysis of copy number alterations in human and zebrafish tumors enables cancer driver discovery.

    Directory of Open Access Journals (Sweden)

    GuangJun Zhang

    2013-08-01

    Full Text Available The identification of cancer drivers is a major goal of current cancer research. Finding driver genes within large chromosomal events is especially challenging because such alterations encompass many genes. Previously, we demonstrated that zebrafish malignant peripheral nerve sheath tumors (MPNSTs are highly aneuploid, much like human tumors. In this study, we examined 147 zebrafish MPNSTs by massively parallel sequencing and identified both large and focal copy number alterations (CNAs. Given the low degree of conserved synteny between fish and mammals, we reasoned that comparative analyses of CNAs from fish versus human MPNSTs would enable elimination of a large proportion of passenger mutations, especially on large CNAs. We established a list of orthologous genes between human and zebrafish, which includes approximately two-thirds of human protein-coding genes. For the subset of these genes found in human MPNST CNAs, only one quarter of their orthologues were co-gained or co-lost in zebrafish, dramatically narrowing the list of candidate cancer drivers for both focal and large CNAs. We conclude that zebrafish-human comparative analysis represents a powerful, and broadly applicable, tool to enrich for evolutionarily conserved cancer drivers.

  5. Environmental enrichment in farm, zoo, companion and experimental animals

    Directory of Open Access Journals (Sweden)

    Vučinić Marijana

    2009-01-01

    Full Text Available The paper deals with environmental enrichment for domestic animals at farms, animals in zoos, experimental animals and pet animals. Also, the paper defines and describes different strategies of environmental enrichment. Environmental enrichment is a simple and effective mean of prevention of boredom, behavioral disorders as well as an effective mean of improving animal welfare in farm, zoo, companion and experimental animals. Different items and materials may be used for environmental enrichment. They need to be evaluated for use by taking into account the following: the species of an animal, its needs, habits and capabilities, the type of an enrichment device, the device's ability to stimulate the animal's interest and the safety of the device. Enrichment programmes should always include two forms of enrichment: behavioral enrichment and environmental enrichment. Enrichment comes in many forms such as structural or physical enrichment, sensory enrichment (auditory and olfactory stimulation, dietary enrichment, manipulatable enrichment and social enrichment.

  6. Evaluación de la eficacia de un suplemento oral en polvo enriquecido con ácido eicosapentaenoico en un grupo de pacientes con cáncer Efficacy evaluation of an oral powder supplement enriched with eicosapentaenoic acid in cancer patients

    Directory of Open Access Journals (Sweden)

    C. Gómez-Candela

    2011-12-01

    Full Text Available Introducción: El efecto beneficioso del ácido eicosapentaenoico en pacientes con cáncer está ampliamente descrito sobre todo en lo que respecta a su rol en la caquexia tumoral. Objetivo: Evaluar la eficacia de la administración de un nuevo suplemento oral en polvo con adición de este componente frente a un suplemento líquido estándar en un grupo de pacientes oncológicos. Pacientes y métodos: 61 adultos mayores de 18 años de ambos sexos con cáncer, fueron aleatorizados en dos grupos para recibir durante un mes 600 kcal extras añadidas a su alimentación; uno a través de un suplemento oral en polvo con 1,5 g de ácido eicosapentaenoico/día (RSI y el otro con un producto líquido estándar (RE. Tanto al inicio como al final del estudio se realizaron las siguientes medidas: valoración global subjetiva generada por el paciente (VGS-gp, parámetros antropométricos (Pliegues, circunferencia del brazo y bioimpedancia, dietéticos (registro alimentario de 72 horas, bioquímicos e inflamatorios (bioquímica básica, citoquinas, prealbúmina y PCR. La calidad de vida fue valorada mediante el cuestionario SF-36. Así mismo se emplearon escalas de percepción sensorial, tolerancia de los productos y motivación y saciedad al comer durante el estudio. Resultados: Finalizaron el estudio 40 pacientes. Tras la intervención ambos grupos mantuvieron sus parámetros antropométricos y aumentaron significativamente la prealbúmina (RSI 16,11 ± 5,66 mg/dl vs 19.81 ± 6.75 mg/dl p Background and objectives: The beneficial effect of eicosapentaenoic acid in cancer patients is widely described especially in relation to its role in tumour cachexia. The aim of the study was to evaluate the efficacy of administration of a new oral powder supplement enriched with eicosapentaenoic acid compared to a standard liquid supplement in cancer patients. Patients and methods: A total of 61 cancer patients, aged more than 18 years, were randomized to receive during

  7. Identifying cancer genes from cancer mutation profiles by cancer functions

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    It is of great importance to identify new cancer genes from the data of large scale genome screenings of gene mutations in cancers. Considering the alternations of some essential functions are indispensable for oncogenesis, we define them as cancer functions and select, as their approximations, a group of detailed functions in GO (Gene Ontology) highly enriched with known cancer genes. To evaluate the efficiency of using cancer functions as features to identify cancer genes, we define, in the screened genes, the known protein kinase cancer genes as gold standard positives and the other kinase genes as gold standard negatives. The results show that cancer associated functions are more efficient in identifying cancer genes than the selection pressure feature. Furthermore, combining cancer functions with the number of non-silent mutations can generate more reliable positive predictions. Finally, with precision 0.42, we suggest a list of 46 kinase genes as candidate cancer genes which are annotated to cancer functions and carry at least 3 non-silent mutations.

  8. Dynamic Changes of Signs During the Development of Rats' Liver Cancer under the Intervention Treatment of Oxymatrine and Selenium Enriched Yeast%苦参素联合富硒酵母干预大鼠肝癌变进程中体征的动态变化

    Institute of Scientific and Technical Information of China (English)

    刘丹丹; 马明霞; 乔丹; 王美娟; 王亚威; 金白洁; 张红绪

    2012-01-01

    Animal models of every pathologic stage during the development of SD rats' liver cancer were established by the gavage with n-nitroso-diethylamin (DENA). Meanwhile, treatment groups were administrated by oxymatrine and selenium enriched yeast(OMT+Se). After observing the related signs, animals were sacrificed respectively at 2, 4, 6, 8, 10, 12, 14, 16 and 18 week from the first day of gavage and livers were harvested for pathological grading to explore the dynamic changes of signs and histopathological structures during the development of rats' liver cancer as well as the intervention treatment of OMT+Se. Results showed that the treatment group was better than the induced group on the weight, liver appearance and the microscopic structures. From the 11th week, the weights of the treatment group were significantly more than the induced group (P<0. 01). It hinted that the treatment group was slow than the induced group in the progress of hepatocarcinogenesis and the qualities of life in the treatment group were much better especially in precancerosis and liver cancer. Furthermore, it suggested the intervention of OMT+Se reduced the carcmogenicity of DENA and delayed the progress of hepatocarcinogenesis to some extent.%以二乙基亚硝胺(n-nitroso-diethylamin,DENA)为诱变剂建立SD大鼠肝癌变动物模型,同时用苦参素(oxymatrine,OMT)联合富硒酵母(selenium enriched yeast)对其进行干预.自诱癌之日起,分别在2、4、6、8、10、12、14、16、18周观察相关体征后,处死大鼠,取其肝脏组织,制作病理切片,对大鼠在肝癌演进及药物干预过程中的体征及组织病理学的动态变化进行研究.结果显示,干预组大鼠在体重、毛色、精神状态、肝脏外形及组织显微结构等方面均优于诱癌组,且从11w开始干预组体重极显著高于诱癌组(P<0.01).说明干预组大鼠在肝癌变进程上要滞缓于诱癌组,在癌前病变及肝癌期的生存质量明显优于诱癌组.提示

  9. Screening Key Genes Associated with the Development and Progression of Non-small Cell Lung Cancer Based on Gene-enrichment Analysis and Meta-analysis%基因富集及meta分析筛选非小细胞肺癌发生发展关键基因的研究

    Institute of Scientific and Technical Information of China (English)

    何文武; 冼磊; 王永勇; 胡艳玲; 陈铭伍

    2012-01-01

    Background and objective Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors; however, its causes are still not completely understood. This study was designed to screen the key genes and pathways related to NSCLC occurrence and development and to establish the scientific foundation for the genetic mechanisms and targeted therapy of NSCLC. Methods Both gene set-enrichment analysis (GSEA) and meta-analysis (meta) were used to screen the critical pathways and genes that might be corretacted with the development and progression of lung cancer at the transcription level. Results Using the GSEA and meta methods, focal adhesion and regulation of act in cytoskeleton were determined to be the more prominent overlapping significant pathways. In the focal adhesion pathway, 31 genes were statistically significant (P<0.05), whereas in the regulation of actin cytoskeleton pathway, 32 genes were statistically significant (P<0.05). Conclusion The focal adhesion and the regulation of actin cytoskeleton pathways might play important roles in the occurrence and development of NSCLC. Further studies are needed to determine the biological function for the positiue genes.%背景与目的 非小细胞肺癌(non-small cell lung cancer,NSCLC)是全球最常见的恶性肿瘤之一,其发病遗传机制仍不清楚.本研究旨在筛选影响NSCLC发生发展的关键基因和通路,为NSCLC发病遗传机制及靶向治疗的研究奠定科学基础.方法 运用基因组富集分析(gene set enrichment analysis,GSEA)以及对单套数据集单个基因元分析(meta-analysis,meta)的方法,筛选出在转录水平上影响NSCLC发生发展的关键通路和基因.结果 通过GSEA和meta两种分析方法得出的通路中,重叠性较高的主要为粘着斑通路和细胞骨架肌动蛋白调控通路.在粘着斑通路中31个基因具有统计学意义(P<0.05);细胞骨架肌动蛋白调控通路中32个基因具有统计学意义(P<0.05).结论 粘着

  10. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling.

    Science.gov (United States)

    Eyerich, Stefanie; Eyerich, Kilian; Pennino, Davide; Carbone, Teresa; Nasorri, Francesca; Pallotta, Sabatino; Cianfarani, Francesca; Odorisio, Teresa; Traidl-Hoffmann, Claudia; Behrendt, Heidrun; Durham, Stephen R; Schmidt-Weber, Carsten B; Cavani, Andrea

    2009-12-01

    Th subsets are defined according to their production of lineage-indicating cytokines and functions. In this study, we have identified a subset of human Th cells that infiltrates the epidermis in individuals with inflammatory skin disorders and is characterized by the secretion of IL-22 and TNF-alpha, but not IFN-gamma, IL-4, or IL-17. In analogy to the Th17 subset, cells with this cytokine profile have been named the Th22 subset. Th22 clones derived from patients with psoriasis were stable in culture and exhibited a transcriptome profile clearly separate from those of Th1, Th2, and Th17 cells; it included genes encoding proteins involved in tissue remodeling, such as FGFs, and chemokines involved in angiogenesis and fibrosis. Primary human keratinocytes exposed to Th22 supernatants expressed a transcriptome response profile that included genes involved in innate immune pathways and the induction and modulation of adaptive immunity. These proinflammatory Th22 responses were synergistically dependent on IL-22 and TNF-alpha. Furthermore, Th22 supernatants enhanced wound healing in an in vitro injury model, which was exclusively dependent on IL-22. In conclusion, the human Th22 subset may represent a separate T cell subset with a distinct identity with respect to gene expression and function, present within the epidermal layer in inflammatory skin diseases. Future strategies directed against the Th22 subset may be of value in chronic inflammatory skin disorders.

  11. An information theoretic approach to select alternate subsets of predictors for data-driven hydrological models

    Science.gov (United States)

    Taormina, R.; Galelli, S.; Karakaya, G.; Ahipasaoglu, S. D.

    2016-11-01

    This work investigates the uncertainty associated to the presence of multiple subsets of predictors yielding data-driven models with the same, or similar, predictive accuracy. To handle this uncertainty effectively, we introduce a novel input variable selection algorithm, called Wrapper for Quasi Equally Informative Subset Selection (W-QEISS), specifically conceived to identify all alternate subsets of predictors in a given dataset. The search process is based on a four-objective optimization problem that minimizes the number of selected predictors, maximizes the predictive accuracy of a data-driven model and optimizes two information theoretic metrics of relevance and redundancy, which guarantee that the selected subsets are highly informative and with little intra-subset similarity. The algorithm is first tested on two synthetic test problems and then demonstrated on a real-world streamflow prediction problem in the Yampa River catchment (US). Results show that complex hydro-meteorological datasets are characterized by a large number of alternate subsets of predictors, which provides useful insights on the underlying physical processes. Furthermore, the presence of multiple subsets of predictors-and associated models-helps find a better trade-off between different measures of predictive accuracy commonly adopted for hydrological modelling problems.

  12. Functionalized diamond nanopowder for phosphopeptides enrichment from complex biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, Dilshad [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Najam-ul-Haq, Muhammad, E-mail: najamulhaq@bzu.edu.pk [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 80-82, A-6020 Innsbruck (Austria); Jabeen, Fahmida; Ashiq, Muhammad N.; Athar, Muhammad [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Rainer, Matthias; Huck, Christian W.; Bonn, Guenther K. [Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 80-82, A-6020 Innsbruck (Austria)

    2013-05-02

    Graphical abstract: -- Highlights: •Derivatization of diamond nanopowder as IMAC and RP. •Characterization with SEM, EDX and FT-IR. •Phosphopeptide enrichment from standard as well as real samples. •Desalting and human serum profiling with reproducible results. •MALDI-MS analysis with database identification. -- Abstract: Diamond is known for its high affinity and biocompatibility towards biomolecules and is used exclusively in separation sciences and life science research. In present study, diamond nanopowder is derivatized as Immobilized Metal Ion Affinity Chromatographic (IMAC) material for the phosphopeptides enrichment and as Reversed Phase (C-18) media for the desalting of complex mixtures and human serum profiling through MALDI-TOF-MS. Functionalized diamond nanopowder is characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy. Diamond-IMAC is applied to the standard protein (β-casein), spiked human serum, egg yolk and non-fat milk for the phosphopeptides enrichment. Results show the selectivity of synthesized IMAC-diamond immobilized with Fe{sup 3+} and La{sup 3+} ions. To comprehend the elaborated use, diamond-IMAC is also applied to the serum samples from gall bladder carcinoma for the potential biomarkers. Database search is carried out by the Mascot program ( (www.matrixscience.com)) for the assignment of phosphorylation sites. Diamond nanopowder is thus a separation media with multifunctional use and can be applied to cancer protein profiling for the diagnosis and biomarker identification.

  13. Feature subset selection based on mahalanobis distance: a statistical rough set method

    Institute of Scientific and Technical Information of China (English)

    Sun Liang; Han Chongzhao

    2008-01-01

    In order to select effective feature subsets for pattern classification, a novel statistics rough set method is presented based on generalized attribute reduction. Unlike classical reduction approaches, the objects in universe of discourse are signs of training sample sets and values of attributes are taken as statistical parameters. The binary relation and discernibility matrix for the reduction are induced by distance function. Furthermore, based on the monotony of the distance function defined by Mahalanobis distance, the effective feature subsets are obtained as generalized attribute reducts. Experiment result shows that the classification performance can be improved by using the selected feature subsets.

  14. Student science enrichment training program

    Energy Technology Data Exchange (ETDEWEB)

    Sandhu, S.S.

    1994-08-01

    This is a report on the Student Science Enrichment Training Program, with special emphasis on chemical and computer science fields. The residential summer session was held at the campus of Claflin College, Orangeburg, SC, for six weeks during 1993 summer, to run concomitantly with the college`s summer school. Fifty participants selected for this program, included high school sophomores, juniors and seniors. The students came from rural South Carolina and adjoining states which, presently, have limited science and computer science facilities. The program focused on high ability minority students, with high potential for science engineering and mathematical careers. The major objective was to increase the pool of well qualified college entering minority students who would elect to go into science, engineering and mathematical careers. The Division of Natural Sciences and Mathematics and engineering at Claflin College received major benefits from this program as it helped them to expand the Departments of Chemistry, Engineering, Mathematics and Computer Science as a result of additional enrollment. It also established an expanded pool of well qualified minority science and mathematics graduates, which were recruited by the federal agencies and private corporations, visiting Claflin College Campus. Department of Energy`s relationship with Claflin College increased the public awareness of energy related job opportunities in the public and private sectors.

  15. 21 CFR 137.350 - Enriched rice.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Enriched rice. 137.350 Section 137.350 Food and... Related Products § 137.350 Enriched rice. (a) The foods for which definitions and standards of identity are prescribed by this section are forms of milled rice (except rice coated with talc and glucose...

  16. A Component Analysis of Marriage Enrichment.

    Science.gov (United States)

    Buston, Beverley G.; And Others

    Although marriage enrichment programs have been shown to be effective for many couples, a multidimensional approach to assessment is needed in investigating these groups. The components of information and social support in successful marriage enrichment programs were compared in a completely crossed 2 x 2 factorial design with repeated measures.…

  17. Inoculation Stress Hypothesis of Environmental Enrichment

    Science.gov (United States)

    Crofton, Elizabeth J.; Zhang, Yafang; Green, Thomas A.

    2014-01-01

    One hallmark of psychiatric conditions is the vast continuum of individual differences in susceptibility vs. resilience resulting from the interaction of genetic and environmental factors. The environmental enrichment paradigm is an animal model that is useful for studying a range of psychiatric conditions, including protective phenotypes in addiction and depression models. The major question is how environmental enrichment, a non-drug and non-surgical manipulation, can produce such robust individual differences in such a wide range of behaviors. This paper draws from a variety of published sources to outline a coherent hypothesis of inoculation stress as a factor producing the protective enrichment phenotypes. The basic tenet suggests that chronic mild stress from living in a complex environment and interacting non-aggressively with conspecifics can inoculate enriched rats against subsequent stressors and/or drugs of abuse. This paper reviews the enrichment phenotypes, mulls the fundamental nature of environmental enrichment vs. isolation, discusses the most appropriate control for environmental enrichment, and challenges the idea that cortisol/corticosterone equals stress. The intent of the inoculation stress hypothesis of environmental enrichment is to provide a scaffold with which to build testable hypotheses for the elucidation of the molecular mechanisms underlying these protective phenotypes and thus provide new therapeutic targets to treat psychiatric/neurological conditions. PMID:25449533

  18. Dorsal horn-enriched genes identified by DNA microarray, in situ hybridization and immunohistochemistry

    Directory of Open Access Journals (Sweden)

    Koblan Kenneth S

    2002-08-01

    Full Text Available Abstract Background Neurons in the dorsal spinal cord play important roles in nociception and pain. These neurons receive input from peripheral sensory neurons and then transmit the signals to the brain, as well as receive and integrate descending control signals from the brain. Many molecules important for pain transmission have been demonstrated to be localized to the dorsal horn of the spinal cord. Further understanding of the molecular interactions and signaling pathways in the dorsal horn neurons will require a better knowledge of the molecular neuroanatomy in the dorsal spinal cord. Results A large scale screening was conducted for genes with enriched expression in the dorsal spinal cord using DNA microarray and quantitative real-time PCR. In addition to genes known to be specifically expressed in the dorsal spinal cord, other neuropeptides, receptors, ion channels, and signaling molecules were also found enriched in the dorsal spinal cord. In situ hybridization and immunohistochemistry revealed the cellular expression of a subset of these genes. The regulation of a subset of the genes was also studied in the spinal nerve ligation (SNL neuropathic pain model. In general, we found that the genes that are enriched in the dorsal spinal cord were not among those found to be up-regulated in the spinal nerve ligation model of neuropathic pain. This study also provides a level of validation of the use of DNA microarrays in conjunction with our novel analysis algorithm (SAFER for the identification of differences in gene expression. Conclusion This study identified molecules that are enriched in the dorsal horn of the spinal cord and provided a molecular neuroanatomy in the spinal cord, which will aid in the understanding of the molecular mechanisms important in nociception and pain.

  19. Bonzo/CXCR6 expression defines type 1–polarized T-cell subsets with extralymphoid tissue homing potential

    Science.gov (United States)

    Kim, Chang H.; Kunkel, Eric J.; Boisvert, Judie; Johnston, Brent; Campbell, James J.; Genovese, Mark C.; Greenberg, Harry B.; Butcher, Eugene C.

    2001-01-01

    Chemokine receptor expression is finely controlled during T-cell development. We show that newly identified chemokine receptor Bonzo/CXCR6 is expressed by subsets of Th1 or T-cytotoxic 1 (Tc1) cells, but not by Th2 or Tc2 cells, establishing Bonzo as a differential marker of polarized type 1 T cells in vitro and in vivo. Priming of naive T cells by dendritic cells induces expression of Bonzo on T cells. IL-12 enhances this dendritic cell–dependent upregulation, while IL-4 inhibits it. In blood, 35–56% of Bonzo+ CD4 T cells are Th1 cells, and 60–65% of Bonzo+ CD8 T cells are Tc1 cells, while few Bonzo+ cells are type 2 T cells. Almost all Bonzo+ Tc1 cells contain preformed granzyme A and display cytotoxic effector phenotype. Most Bonzo+ T cells lack L-selectin and/or CCR7, homing receptors for lymphoid tissues. Instead, Bonzo+ T cells are dramatically enriched among T cells in tissue sites of inflammation, such as rheumatoid joints and inflamed livers. Bonzo may be important in trafficking of effector T cells that mediate type 1 inflammation, making it a potential target for therapeutic modulation of inflammatory diseases. PMID:11238560

  20. Enriching an effect calculus with linear types

    DEFF Research Database (Denmark)

    Egger, Jeff; Møgelberg, Rasmus Ejlers; Simpson, Alex

    2009-01-01

    We define an ``enriched effect calculus'' by conservatively extending  a type theory for computational effects with primitives from linear logic. By doing so, we obtain a generalisation of linear type theory, intended as a formalism for expressing linear aspects of effects. As a worked example, we...... formulate  linearly-used continuations in the enriched effect calculus. These are captured by a fundamental translation of the enriched effect calculus into itself, which extends existing call-by-value and call-by-name linearly-used CPS translations. We show that our translation is involutive. Full...... completeness results for the various linearly-used CPS translations  follow. Our main results, the conservativity of enriching the effect calculus with linear primitives, and the involution property of the fundamental translation, are proved using a category-theoretic semantics for the enriched effect calculus...

  1. Identification of vitamin D3 target genes in human breast cancer tissue.

    Science.gov (United States)

    Sheng, Lei; Anderson, Paul H; Turner, Andrew G; Pishas, Kathleen I; Dhatrak, Deepak J; Gill, Peter G; Morris, Howard A; Callen, David F

    2016-11-01

    Multiple epidemiological studies have shown that high vitamin D3 status is strongly associated with improved breast cancer survival. To determine the molecular pathways influenced by 1 alpha, 25-dihydroxyvitamin D3 (1,25D) in breast epithelial cells we isolated RNA from normal human breast and cancer tissues treated with 1,25D in an ex vivo explant system. RNA-Seq revealed 523 genes that were differentially expressed in breast cancer tissues in response to 1,25D treatment, and 127 genes with altered expression in normal breast tissues. GoSeq KEGG pathway analysis revealed 1,25D down-regulated cellular metabolic pathways and enriched pathways involved with intercellular adhesion. The highly 1,25D up-regulated target genes CLMN, SERPINB1, EFTUD1, and KLK6were selected for further analysis and up-regulation by 1,25D was confirmed by qRT-PCR analysis in breast cancer cell lines and in a subset of human clinical samples from normal and cancer breast tissues. Ketoconazole potentiated 1,25D-mediated induction of CLMN, SERPINB1, and KLK6 mRNA through inhibition of 24-hydroxylase (CYP24A1) activity. Elevated expression levels of CLMN, SERPINB1, and KLK6 are associated with prolonged relapse-free survival for breast cancer patients. The major finding of the present study is that exposure of both normal and malignant breast tissue to 1,25D results in changes in cellular adhesion, metabolic pathways and tumor suppressor-like pathways, which support epidemiological data suggesting that adequate vitamin D3 levels may improve breast cancer outcome.

  2. NK ACTIVITY OF LYMPHOCYTE SUBSETS AND THE EFFECTS OF LOW DOSE RADIATION

    Institute of Scientific and Technical Information of China (English)

    Su Liaoyuan; Tian Hailin; Xu Yingdong; Geng Yongzhi

    1998-01-01

    Objective: To determine the NK activity of lymphocyte subsets and the effects of low dose radiation.Methods: Lymphocyte subsets were separated by monoclonal antibodies. The NK activity of each subset on tumor cells was detected by radioactive release method.Results: The results showed that besides NK cells, CD4,CD8 and B cells alone can kill tumor cells. But the cellkilling activity of NK cells appeared to be strongest.There was synergistic effect between CD4 and NK cells.The activity of mixed lymphocytes was more than that of only one subset. The effect of low dose radiation (LDR)on NK activity of panlymphocytes or NK cells was different. Conclusion: This paper demonstrated that NK activity of mononuclear cells was called "NK activity of lymphocytes", but it is not true. Only when NK cells were separated by monoclonal antibodies, its killer activity can be called "activity of NK cells".

  3. Nfil3 is required for the development of all innate lymphoid cell subsets.

    Science.gov (United States)

    Seillet, Cyril; Rankin, Lucille C; Groom, Joanna R; Mielke, Lisa A; Tellier, Julie; Chopin, Michael; Huntington, Nicholas D; Belz, Gabrielle T; Carotta, Sebastian

    2014-08-25

    Innate lymphoid cell (ILC) populations protect against infection and are essential for lymphoid tissue formation and tissue remodeling after damage. Nfil3 is implicated in the function of adaptive immune lineages and NK cell development, but it is not yet known if Nfil3 regulates other innate lymphoid lineages. Here, we identify that Nfil3 is essential for the development of Peyer's patches and ILC2 and ILC3 subsets. Loss of Nfil3 selectively reduced Peyer's patch formation and was accompanied by impaired recruitment and distribution of lymphocytes within the patches. ILC subsets exhibited high Nfil3 expression and genetic deletion of Nfil3 severely compromised the development of all subsets. Subsequently, Nfil3(-/-) mice were highly susceptible to disease when challenged with inflammatory or infectious agents. Thus, we demonstrate that Nfil3 is a key regulator of the development of ILC subsets essential for immune protection in the lung and gut.

  4. The cell biology of cross-presentation and the role of dendritic cell subsets.

    Science.gov (United States)

    Lin, Ming-Lee; Zhan, Yifan; Villadangos, Jose A; Lew, Andrew M

    2008-01-01

    The cell biology of cross-presentation is reviewed regarding exogenous antigen uptake, antigen degradation and entry into the major histocompatibility complex class I pathway. Whereas cross-presentation is not associated with enhanced phagocytic ability, certain receptors may favour uptake for cross-presentation for example mannose receptor for soluble glycoproteins. Perhaps, the defining property of the cross-presenting cell is some specialization in host machinery for handling and transport of antigen across organelles. Both cytosolic and vacuolar pathways are discussed. Which dendritic cell (DC) subset is the cross-presenting cell is explored. Cross-presentation is found within the CD8(+) subset resident in lymphoid organs. The role of other DC subsets (especially the migratory CD8(-) DC) and the route of antigen delivery are also discussed. Further consideration is given to antigen transfer between DC subsets and differential presentation to naive vs memory T cells.

  5. Differential control of Helios+/− Treg development by monocyte subsets through disparate inflammatory cytokines

    OpenAIRE

    Zhong, Hui; Yazdanbakhsh, Karina

    2013-01-01

    Control of Helios+/− Treg subset development is mediated through distinct cytokines and monocyte subpopulations.CD16+ monocytes inhibit Helios+ Treg proliferation through IL-12, whereas CD16− monocytes suppress Helios− Treg development through TNF-α.

  6. Tailored immune responses: novel effector helper T cell subsets in protective immunity.

    Directory of Open Access Journals (Sweden)

    Ervin E Kara

    2014-02-01

    Full Text Available Differentiation of naïve CD4⁺ cells into functionally distinct effector helper T cell subsets, characterised by distinct "cytokine signatures," is a cardinal strategy employed by the mammalian immune system to efficiently deal with the rapidly evolving array of pathogenic microorganisms encountered by the host. Since the T(H1/T(H2 paradigm was first described by Mosmann and Coffman, research in the field of helper T cell biology has grown exponentially with seven functionally unique subsets having now been described. In this review, recent insights into the molecular mechanisms that govern differentiation and function of effector helper T cell subsets will be discussed in the context of microbial infections, with a focus on how these different helper T cell subsets orchestrate immune responses tailored to combat the nature of the pathogenic threat encountered.

  7. Tailored immune responses: novel effector helper T cell subsets in protective immunity.

    Science.gov (United States)

    Kara, Ervin E; Comerford, Iain; Fenix, Kevin A; Bastow, Cameron R; Gregor, Carly E; McKenzie, Duncan R; McColl, Shaun R

    2014-02-01

    Differentiation of naïve CD4⁺ cells into functionally distinct effector helper T cell subsets, characterised by distinct "cytokine signatures," is a cardinal strategy employed by the mammalian immune system to efficiently deal with the rapidly evolving array of pathogenic microorganisms encountered by the host. Since the T(H)1/T(H)2 paradigm was first described by Mosmann and Coffman, research in the field of helper T cell biology has grown exponentially with seven functionally unique subsets having now been described. In this review, recent insights into the molecular mechanisms that govern differentiation and function of effector helper T cell subsets will be discussed in the context of microbial infections, with a focus on how these different helper T cell subsets orchestrate immune responses tailored to combat the nature of the pathogenic threat encountered.

  8. LAP TGF-Beta Subset of CD4+CD25+CD127− Treg Cells is Increased and Overexpresses LAP TGF-Beta in Lung Adenocarcinoma Patients

    Science.gov (United States)

    Islas-Vazquez, Lorenzo; Prado-Garcia, Heriberto; Aguilar-Cazares, Dolores; Meneses-Flores, Manuel; Galicia-Velasco, Miriam; Romero-Garcia, Susana; Camacho-Mendoza, Catalina; Lopez-Gonzalez, Jose Sullivan

    2015-01-01

    Lung cancer is the leading cause of cancer death worldwide. Adenocarcinoma, the most commonly diagnosed histologic type of lung cancer, is associated with smoking. Cigarette smoke promotes inflammation on the airways, which might be mediated by Th17 cells. This inflammatory environment may contribute to tumor development. In contrast, some reports indicate that tumors may induce immunosuppressive Treg cells to dampen immune reactivity, supporting tumor growth and progression. Thus, we aimed to analyze whether chronic inflammation or immunosuppression predominates at the systemic level in lung adenocarcinoma patients, and several cytokines and Th17 and Treg cells were studied. Higher proportions of IL-17-producing CD4+ T-cells were found in smoking control subjects and in lung adenocarcinoma patients compared to nonsmoking control subjects. In addition, lung adenocarcinoma patients increased both plasma concentrations of IL-2, IL-4, IL-6, and IL-10, and proportions of Latency Associated Peptide (LAP) TGF-β subset of CD4+CD25+CD127− Treg cells, which overexpressed LAP TGF-β. This knowledge may lead to the development of immunotherapies that could inhibit the suppressor activity mediated by the LAP TGF-β subset of CD4+CD25+CD127− Treg cells to promote reactivity of immune cells against lung adenocarcinoma cells. PMID:26582240

  9. LAP TGF-Beta Subset of CD4+CD25+CD127− Treg Cells is Increased and Overexpresses LAP TGF-Beta in Lung Adenocarcinoma Patients

    Directory of Open Access Journals (Sweden)

    Lorenzo Islas-Vazquez

    2015-01-01

    Full Text Available Lung cancer is the leading cause of cancer death worldwide. Adenocarcinoma, the most commonly diagnosed histologic type of lung cancer, is associated with smoking. Cigarette smoke promotes inflammation on the airways, which might be mediated by Th17 cells. This inflammatory environment may contribute to tumor development. In contrast, some reports indicate that tumors may induce immunosuppressive Treg cells to dampen immune reactivity, supporting tumor growth and progression. Thus, we aimed to analyze whether chronic inflammation or immunosuppression predominates at the systemic level in lung adenocarcinoma patients, and several cytokines and Th17 and Treg cells were studied. Higher proportions of IL-17-producing CD4+ T-cells were found in smoking control subjects and in lung adenocarcinoma patients compared to nonsmoking control subjects. In addition, lung adenocarcinoma patients increased both plasma concentrations of IL-2, IL-4, IL-6, and IL-10, and proportions of Latency Associated Peptide (LAP TGF-β subset of CD4+CD25+CD127− Treg cells, which overexpressed LAP TGF-β. This knowledge may lead to the development of immunotherapies that could inhibit the suppressor activity mediated by the LAP TGF-β subset of CD4+CD25+CD127− Treg cells to promote reactivity of immune cells against lung adenocarcinoma cells.

  10. Studying the Role for CD4+ T Cell Subsets in Human Lupus

    Science.gov (United States)

    2013-07-01

    subsets in human lupus PRINCIPAL INVESTIGATOR: Insoo Kang, M.D. CONTRACTING...SUBTITLE 5a. CONTRACT NUMBER Studying the role for CD4+ T cell subsets in human lupus 5b. GRANT NUMBER W81XWH-10-1-0150 5c. PROGRAM ELEMENT NUMBER...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT We have investigated whether and how autoimmune complex (AIC) in SLE ( lupus ) can

  11. Deuterium enrichment of interstellar dusts

    Science.gov (United States)

    Das, Ankan; Chakrabarti, Sandip Kumar; Majumdar, Liton; Sahu, Dipen

    2016-07-01

    High abundance of some abundant and simple interstellar species could be explained by considering the chemistry that occurs on interstellar dusts. Because of its simplicity, the rate equation method is widely used to study the surface chemistry. However, because the recombination efficiency for the formation of any surface species is highly dependent on various physical and chemical parameters, the Monte Carlo method is best suited for addressing the randomness of the processes. We carry out Monte-Carlo simulation to study deuterium enrichment of interstellar grain mantle under various physical conditions. Based on the physical properties, various types of clouds are considered. We find that in diffuse cloud regions, very strong radiation fields persists and hardly a few layers of surface species are formed. In translucent cloud regions with a moderate radiation field, significant number of layers would be produced and surface coverage is mainly dominated by photo-dissociation products such as, C, CH_3, CH_2D, OH and OD. In the intermediate dense cloud regions (having number density of total hydrogen nuclei in all forms ˜2 × 10^4 cm^{-3}), water and methanol along with their deuterated derivatives are efficiently formed. For much higher density regions (˜10^6 cm^{-3}), water and methanol productions are suppressed but surface coverage of CO, CO_2, O_2, O_3 are dramatically increased. We find a very high degree of fractionation of water and methanol. Observational results support a high fractionation of methanol but surprisingly water fractionation is found to be low. This is in contradiction with our model results indicating alternative routes for de-fractionation of water.

  12. A novel hypothesis-unbiased method for Gene Ontology enrichment based on transcriptome data

    Science.gov (United States)

    Fruzangohar, Mario; Ebrahimie, Esmaeil; Adelson, David L.

    2017-01-01

    Gene Ontology (GO) classification of statistically significantly differentially expressed genes is commonly used to interpret transcriptomics data as a part of functional genomic analysis. In this approach, all significantly expressed genes contribute equally to the final GO classification regardless of their actual expression levels. Gene expression levels can significantly affect protein production and hence should be reflected in GO term enrichment. Genes with low expression levels can also participate in GO term enrichment through cumulative effects. In this report, we have introduced a new GO enrichment method that is suitable for multiple samples and time series experiments that uses a statistical outlier test to detect GO categories with special patterns of variation that can potentially identify candidate biological mechanisms. To demonstrate the value of our approach, we have performed two case studies. Whole transcriptome expression profiles of Salmonella enteritidis and Alzheimer’s disease (AD) were analysed in order to determine GO term enrichment across the entire transcriptome instead of a subset of differentially expressed genes used in traditional GO analysis. Our result highlights the key role of inflammation related functional groups in AD pathology as granulocyte colony-stimulating factor receptor binding, neuromedin U binding, and interleukin were remarkably upregulated in AD brain when all using all of the gene expression data in the transcriptome. Mitochondrial components and the molybdopterin synthase complex were identified as potential key cellular components involved in AD pathology. PMID:28199395

  13. HUMAN PAPILLOMAVIRUS INFECTIONS IN LARYNGEAL CANCER

    NARCIS (Netherlands)

    Torrente, Mariela C.; Rodrigo, Juan P.; Haigentz, Missak; Dikkers, Frederik G.; Rinaldo, Alessandra; Takes, Robert P.; Olofsson, Jan; Ferlito, Alfio

    2011-01-01

    Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we revie

  14. Profile of World Uranium Enrichment Programs-2009

    Energy Technology Data Exchange (ETDEWEB)

    Laughter, Mark D [ORNL

    2009-04-01

    It is generally agreed that the most difficult step in building a nuclear weapon is acquiring fissile material, either plutonium or highly enriched uranium (HEU). Plutonium is produced in a nuclear reactor, whereas HEU is produced using a uranium enrichment process. Enrichment is also an important step in the civil nuclear fuel cycle, in producing low enriched uranium (LEU) for use as fuel for nuclear reactors to generate electricity. However, the same equipment used to produce LEU for nuclear reactor fuel can also be used to produce HEU for weapons. Safeguards at an enrichment plant are the array of assurances and verification techniques that ensure uranium is not diverted or enriched to HEU. There are several techniques for enriching uranium. The two most prevalent are gaseous diffusion, which uses older technology and requires a lot of energy, and gas centrifuge separation, which uses more advanced technology and is more energy efficient. Gaseous diffusion plants (GDPs) provide about 40% of current world enrichment capacity but are being phased out as newer gas centrifuge enrichment plants (GCEPs) are constructed. Estimates of current and future enrichment capacity are always approximate, due to the constant upgrades, expansions, and shutdowns occurring at enrichment plants, largely determined by economic interests. Currently, the world enrichment capacity is approximately 56 million kilogram separative work units (SWU) per year, with 22.5 million in gaseous diffusion and more than 33 million in gas centrifuge plants. Another 34 million SWU/year of capacity is under construction or planned for the near future, almost entirely using gas centrifuge separation. Other less-efficient techniques have also been used in the past, including electromagnetic and aerodynamic separations, but these are considered obsolete, at least from a commercial perspective. Laser isotope separation shows promise as a possible enrichment technique of the future but has yet to be

  15. Potential usefulness of an EPA-enriched nutritional supplement on chemotherapy tolerability in cancer patients without overt malnutrition Uso potencial de un suplemento nutricional enriquecido en EPA en la tolerabilidad a la quimioterapia en pacientes con cáncer sin desnutrición manifiesta

    Directory of Open Access Journals (Sweden)

    Joan Trabal

    2010-10-01

    Full Text Available Objectives: To assess the effect of an intervention with an Eicosapentaenoic Acid-enriched oral nutritional supplement on chemotherapy tolerability in patients with advanced colorectal cancer. Methods: Thirteen patients diagnosed with stage IV colorectal cancer were included. Patients in the experimental group received 2 packs of supplement per day during 12 weeks plus dietary counseling. The control group only received dietary counseling. Patients were assessed for nutritional status, dietary intake, health related quality of life (HRQOL and chemotherapy compliance. Results: Only patients in the supplemented group significantly increased their weight after the intervention. They also had better scores in important domains of HRQOL, compared to controls. Although not statistically significant, the supplemented group did not experience interruptions in their chemotherapy treatment compared to the control group, with more interruptions due to toxicity. Conclusions: The present study, although limited by sample size, points out towards a positive effect of the intervention on chemotherapy tolerability.Objetivos: Valorar el efecto de una intervención con un suplemento nutricional oral enriquecido en Ácido Eicosapentaenoico sobre la tolerabilidad a la quimioterapia en pacientes con cáncer colorrectal avanzado. Métodos: Se incluyeron 13 pacientes diagnosticados con cáncer colorrectal en estadio IV. Los pacientes en el grupo experimental recibieron 2 briks de suplemento al día durante 12 semanas junto a consejo dietético. El grupo control solo recibió consejo dietético. Se valoró el estado nutricional, ingesta dietética, calidad de vida relacionada con la salud (CVRS y el cumplimento de la quimioterapia de los pacientes. Resultados: Solo los pacientes en el grupo suplementado incrementaron su peso significativamente tras la intervención. También obtuvieron mejores puntuaciones en importantes dominios de la CVRS, comparado con los controles

  16. Circulating TFH subset distribution is strongly affected in lupus patients with an active disease.

    Directory of Open Access Journals (Sweden)

    Carole Le Coz

    Full Text Available Follicular helper T cells (TFH represent a distinct subset of CD4(+ T cells specialized in providing help to B lymphocytes, which may play a central role in autoimmune diseases having a major B cell component such as systemic lupus erythematosus. Recently, TFH subsets that share common phenotypic and functional characteristics with TFH cells from germinal centers, have been described in the peripheral blood from healthy individuals. The aim of this study was to analyze the distribution of such populations in lupus patients. Circulating TFH cell subsets were defined by multicolor flow cytometry as TFH17 (CXCR3(-CCR6(+, TFH1 (CXCR3 (+ CCR6(- or TFH2 (CXCR3(-CCR6(- cells among CXCR5 (+ CD45RA(-CD4(+ T cells in the peripheral blood of 23 SLE patients and 23 sex and age-matched healthy controls. IL-21 receptor expression by B cells was analyzed by flow cytometry and the serum levels of IL-21 and Igs were determined by ELISA tests. We found that the TFH2 cell subset frequency is strongly and significantly increased in lupus patients with an active disease (SLEDAI score>8, while the TFH1 cell subset percentage is greatly decreased. The TFH2 and TFH1 cell subset frequency alteration is associated with the presence of high Ig levels and autoantibodies in patient's sera. Moreover, the TFH2 cell subset enhancement correlates with an increased frequency of double negative memory B cells (CD27(-IgD(-CD19(+ cells expressing the IL-21R. Finally, we found that IgE levels in lupus patients' sera correlate with disease activity and seem to be associated with high TFH2 cell subset frequency. In conclusion, our study describes for the first time the distribution of circulating TFH cell subsets in lupus patients. Interestingly, we found an increased frequency of TFH2 cells, which correlates with disease activity. Our results suggest that this subset might play a key role in lupus pathogenesis.

  17. Separable Bilayer Microfiltration Device for Viable Label-free Enrichment of Circulating Tumour Cells

    Science.gov (United States)

    Zhou, Ming-Da; Hao, Sijie; Williams, Anthony J.; Harouaka, Ramdane A.; Schrand, Brett; Rawal, Siddarth; Ao, Zheng; Brennaman, Randall; Gilboa, Eli; Lu, Bo; Wang, Shuwen; Zhu, Jiyue; Datar, Ram; Cote, Richard; Tai, Yu-Chong; Zheng, Si-Yang

    2014-12-01

    The analysis of circulating tumour cells (CTCs) in cancer patients could provide important information for therapeutic management. Enrichment of viable CTCs could permit performance of functional analyses on CTCs to broaden understanding of metastatic disease. However, this has not been widely accomplished. Addressing this challenge, we present a separable bilayer (SB) microfilter for viable size-based CTC capture. Unlike other single-layer CTC microfilters, the precise gap between the two layers and the architecture of pore alignment result in drastic reduction in mechanical stress on CTCs, capturing them viably. Using multiple cancer cell lines spiked in healthy donor blood, the SB microfilter demonstrated high capture efficiency (78-83%), high retention of cell viability (71-74%), high tumour cell enrichment against leukocytes (1.7-2 × 103), and widespread ability to establish cultures post-capture (100% of cell lines tested). In a metastatic mouse model, SB microfilters successfully enriched viable mouse CTCs from 0.4-0.6 mL whole mouse blood samples and established in vitro cultures for further genetic and functional analysis. Our preliminary studies reflect the efficacy of the SB microfilter device to efficiently and reliably enrich viable CTCs in animal model studies, constituting an exciting technology for new insights in cancer research.

  18. Profile of World Uranium Enrichment Programs - 2007

    Energy Technology Data Exchange (ETDEWEB)

    Laughter, Mark D [ORNL

    2007-11-01

    It is generally agreed that the most difficult step in building a nuclear weapon is acquiring weapons grade fissile material, either plutonium or highly enriched uranium (HEU). Plutonium is produced in a nuclear reactor, while HEU is produced using a uranium enrichment process. Enrichment is also an important step in the civil nuclear fuel cycle, in producing low enriched uranium (LEU) for use in fuel for nuclear reactors. However, the same equipment used to produce LEU for nuclear fuel can also be used to produce HEU for weapons. Safeguards at an enrichment plant are the array of assurances and verification techniques that ensure uranium is only enriched to LEU, no undeclared LEU is produced, and no uranium is enriched to HEU or secretly diverted. There are several techniques for enriching uranium. The two most prevalent are gaseous diffusion, which uses older technology and requires a lot of energy, and gas centrifuge separation, which uses more advanced technology and is more energy efficient. Gaseous diffusion plants (GDPs) provide about 40% of current world enrichment capacity, but are being phased out as newer gas centrifuge enrichment plants (GCEPs) are constructed. Estimates of current and future enrichment capacity are always approximate, due to the constant upgrades, expansions, and shutdowns occurring at enrichment plants, largely determined by economic interests. Currently, the world enrichment capacity is approximately 53 million kg-separative work units (SWU) per year, with 22 million in gaseous diffusion and 31 million in gas centrifuge plants. Another 23 million SWU/year of capacity are under construction or planned for the near future, almost entirely using gas centrifuge separation. Other less-efficient techniques have also been used in the past, including electromagnetic and aerodynamic separations, but these are considered obsolete, at least from a commercial perspective. Laser isotope separation shows promise as a possible enrichment technique

  19. Azacytidine and decitabine induce gene-specific and non-random DNA demethylation in human cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Sabine Hagemann

    Full Text Available The DNA methyltransferase inhibitors azacytidine and decitabine represent archetypal drugs for epigenetic cancer therapy. To characterize the demethylating activity of azacytidine and decitabine we treated colon cancer and leukemic cells with both drugs and used array-based DNA methylation analysis of more than 14,000 gene promoters. Additionally, drug-induced demethylation was compared to methylation patterns of isogenic colon cancer cells lacking both DNA methyltransferase 1 (DNMT1 and DNMT3B. We show that drug-induced demethylation patterns are highly specific, non-random and reproducible, indicating targeted remethylation of specific loci after replication. Correspondingly, we found that CG dinucleotides within CG islands became preferentially remethylated, indicating a role for DNA sequence context. We also identified a subset of genes that were never demethylated by drug treatment, either in colon cancer or in leukemic cell lines. These demethylation-resistant genes were enriched for Polycomb Repressive Complex 2 components in embryonic stem cells and for transcription factor binding motifs not present in demethylated genes. Our results provide detailed insights into the DNA methylation patterns induced by azacytidine and decitabine and suggest the involvement of complex regulatory mechanisms in drug-induced DNA demethylation.

  20. Cytokeratin 15 marks basal epithelia in developing ureters and is upregulated in a subset of urothelial cell carcinomas.

    Directory of Open Access Journals (Sweden)

    Guangping Tai

    Full Text Available The mammalian ureter contains a water-tight epithelium surrounded by smooth muscle. Key molecules have been defined which regulate ureteric bud initiation and drive the differentiation of ureteric mesenchyme into peristaltic smooth muscle. Less is known about mechanisms underlying the developmental patterning of the multilayered epithelium characterising the mature ureter. In skin, which also contains a multilayered epithelium, cytokeratin 15 (CK15, an acidic intermediate filament protein, marks cells whose progeny contribute to epidermal regeneration following wounding. Moreover, CK15+ precursor cells in skin can give rise to basal cell carcinomas. In the current study, using transcriptome microarrays of embryonic wild type mouse ureters, Krt15, coding for CK15, was detected. Quantitative polymerase chain reaction analyses confirmed the initial finding and demonstrated that Krt15 levels increased during the fetal period when the ureteric epithelium becomes multilayered. CK15 protein was undetectable in the ureteric bud, the rudiment from which the ureter grows. Nevertheless, later in fetal development, CK15 was immunodetected in a subset of basal urothelial cells in the ureteric stalk. Superficial epithelial cells, including those positive for the differentiation marker uroplakin III, were CK15-. Transformation-related protein 63 (P63 has been implicated in epithelial differentiation in murine fetal urinary bladders. In wild type fetal ureters, CK15+ cells were positive for P63, and p63 homozygous null mutant ureters lacked CK15+ cells. In these mutant ureters, sections of the urothelium were monolayered versus the uniform multilayering found in wild type littermates. Human urothelial cell carcinomas account for considerable morbidity and mortality. CK15 was upregulated in a subset of invasive ureteric and urinary bladder cancers. Thus, in ureter development, the absence of CK15 is associated with a structurally simplified urothelium whereas

  1. Comparison of Subset-Based Local and Finite Element-Based Global Digital Image Correlation

    KAUST Repository

    Pan, Bing

    2015-02-12

    Digital image correlation (DIC) techniques require an image matching algorithm to register the same physical points represented in different images. Subset-based local DIC and finite element-based (FE-based) global DIC are the two primary image matching methods that have been extensively investigated and regularly used in the field of experimental mechanics. Due to its straightforward implementation and high efficiency, subset-based local DIC has been used in almost all commercial DIC packages. However, it is argued by some researchers that FE-based global DIC offers better accuracy because of the enforced continuity between element nodes. We propose a detailed performance comparison between these different DIC algorithms both in terms of measurement accuracy and computational efficiency. Then, by measuring displacements of the same calculation points using the same calculation algorithms (e.g., correlation criterion, initial guess estimation, subpixel interpolation, optimization algorithm and convergence conditions) and identical calculation parameters (e.g., subset or element size), the performances of subset-based local DIC and two FE-based global DIC approaches are carefully compared in terms of measurement error and computational efficiency using both numerical tests and real experiments. A detailed examination of the experimental results reveals that, when subset (element) size is not very small and the local deformation within a subset (element) can be well approximated by the shape function used, standard subset-based local DIC approach not only provides better results in measured displacements, but also demonstrates much higher computation efficiency. However, several special merits of FE-based global DIC approaches are indicated.

  2. 77 FR 13367 - General Electric-Hitachi Global Laser Enrichment, LLC, Proposed Laser-Based Uranium Enrichment...

    Science.gov (United States)

    2012-03-06

    ... COMMISSION General Electric-Hitachi Global Laser Enrichment, LLC, Proposed Laser-Based Uranium Enrichment...- Hitachi Global Laser Enrichment, LLC (GLE) Uranium Enrichment Facility. On June 26, 2009, GLE submitted a... uranium enrichment facility (the ``proposed action''). The GLE proposes to locate the facility on...

  3. Proteomic profiling of patient-derived glioblastoma xenografts identifies a subset with activated EGFR: implications for drug development.

    Science.gov (United States)

    Brown, Kristine E; Chagoya, Gustavo; Kwatra, Shawn G; Yen, Timothy; Keir, Stephen T; Cooter, Mary; Hoadley, Katherine A; Rasheed, Ahmed; Lipp, Eric S; Mclendon, Roger; Ali-Osman, Francis; Bigner, Darell D; Sampson, John H; Kwatra, Madan M

    2015-06-01

    The development of drugs to inhibit glioblastoma (GBM) growth requires reliable pre-clinical models. To date, proteomic level validation of widely used patient-derived glioblastoma xenografts (PDGX) has not been performed. In the present study, we characterized 20 PDGX models according to subtype classification based on The Cancer Genome Atlas criteria, TP53, PTEN, IDH 1/2, and TERT promoter genetic analysis, EGFR amplification status, and examined their proteomic profiles against those of their parent tumors. The 20 PDGXs belonged to three of four The Cancer Genome Atlas subtypes: eight classical, eight mesenchymal, and four proneural; none neural. Amplification of EGFR gene was observed in 9 of 20 xenografts, and of these, 3 harbored the EGFRvIII mutation. We then performed proteomic profiling of PDGX, analyzing expression/activity of several proteins including EGFR. Levels of EGFR phosphorylated at Y1068 vary considerably between PDGX samples, and this pattern was also seen in primary GBM. Partitioning of 20 PDGX into high (n = 5) and low (n = 15) groups identified a panel of proteins associated with high EGFR activity. Thus, PDGX with high EGFR activity represent an excellent pre-clinical model to develop therapies for a subset of GBM patients whose tumors are characterized by high EGFR activity. Further, the proteins found to be associated with high EGFR activity can be monitored to assess the effectiveness of targeting EGFR. The development of drugs to inhibit glioblastoma (GBM) growth requires reliable pre-clinical models. We validated proteomic profiles using patient-derived glioblastoma xenografts (PDGX), characterizing 20 PDGX models according to subtype classification based on The Cancer Genome Atlas (TCGA) criteria, TP53, PTEN, IDH 1/2, and TERT promoter genetic analysis, EGFR amplification status, and examined their proteomic profiles against those of their parent tumors. Proteins found to be associated with high EGFR activity represent potential

  4. Management's Ecstasy and Disparity Over Job Enrichment

    Science.gov (United States)

    King, Albert S.

    1976-01-01

    A case study analyzing job enrichment schemes and manager expectations of increased productivity is presented. It was found that it was the managers' expectations of increased productivity, not the reorganization of work, that led to higher productivity. (EC)

  5. Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects.

    Science.gov (United States)

    Pandya, Jayesh M; Lundell, Anna-Carin; Hallström, Magnus; Andersson, Kerstin; Nordström, Inger; Rudin, Anna

    2016-10-01

    The pathogenic role and frequency of T cell subtypes in early rheumatoid arthritis are still unclear. We therefore performed a comprehensive analysis of the circulating T cell subtype pattern in patients with untreated early rheumatoid arthritis compared to healthy control subjects. Peripheral blood mononuclear cells were obtained from 26 patients with untreated early rheumatoid arthritis and from with 18 age- and sex-matched healthy control subjects. T helper cell types Th0, Th1, Th2, Th17, and Th1/17 and nonclassic T helper subsets were defined by flow cytometry based on the expression of chemokine receptors CCR4, CCR6, and CXCR3. Regulatory T cells were defined by expression of CD25(+) CD127(low) and also FOXP3 CXCR5(+) cells among regulatory and nonregulatory T cells were defined as T follicular regulatory and T follicular helper cells, respectively. The phenotype of T cell subsets was confirmed by transcription factor and cytokine secretion analyses. Multivariate discriminant analysis showed that patients with untreated early rheumatoid arthritis were segregated from healthy control subjects based on the circulating T cell subset profile. Among the discriminator subsets, CCR4(+)CXCR3(-) (Th2 and Th17), CTLA4(+) and FOXP3(+) subsets were present in significantly higher frequencies, whereas CCR4(-) (Th1/Th17, CCR6(+)CCR4(-)CXCR3(-), and Th1) subsets were present in lower frequencies in patients with untreated early rheumatoid arthritis compared with healthy control subjects. The proportions of Th2 and Th17 subsets associated positively with each other and negatively with the CXCR3(+)/interferon γ-secreting subsets (Th1 and Th1/Th17) in patients with untreated rheumatoid arthritis. The proportions of Th2 cells increased with age in patients with untreated early rheumatoid arthritis and healthy control subjects. The dominance of circulating CCR4(+)CXCR3(-) T helper subsets (Th2 and Th17) in untreated early rheumatoid arthritis point toward a pathogenic role of

  6. Integrated exon level expression analysis of driver genes explain their role in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Mohammad Azhar Aziz

    Full Text Available Integrated analysis of genomic and transcriptomic level changes holds promise for a better understanding of colorectal cancer (CRC biology. There is a pertinent need to explain the functional effect of genome level changes by integrating the information at the transcript level. Using high resolution cytogenetics array, we had earlier identified driver genes by 'Genomic Identification of Significant Targets In Cancer (GISTIC' analysis of paired tumour-normal samples from colorectal cancer patients. In this study, we analyze these driver genes at three levels using exon array data--gene, exon and network. Gene level analysis revealed a small subset to experience differential expression. These results were reinforced by carrying out separate differential expression analyses (SAM and LIMMA. ATP8B1 was found to be the novel gene associated with CRC that shows changes at cytogenetic, gene and exon levels. Splice index of 29 exons corresponding to 13 genes was found to be significantly altered in tumour samples. Driver genes were used to construct regulatory networks for tumour and normal groups. There were rearrangements in transcription factor genes suggesting the presence of regulatory switching. The regulatory pattern of AHR gene was found to have the most significant alteration. Our results integrate data with focus on driver genes resulting in highly enriched novel molecules that need further studies to establish their role in CRC.

  7. 围手术期免疫增强型全肠外营养对胃肠恶性肿瘤患者术后免疫功能的影响%Effects of Immune-Enriched Total Parenteral Nutrition on Postoperative Immune Function in Patients with Gastrointestinal Cancer

    Institute of Scientific and Technical Information of China (English)

    殷庆章; 洪亮; 殷琛庆; 齐翀; 汤承辉

    2011-01-01

    目的:评价免疫增强型全肠外营养对胃肠恶性肿瘤患者术后免疫功能、营养状况及预后的影响.方法:120例消化道恶性肿瘤手术患者随机分为A组(术前和术后应用免疫增强型全肠外营养组)、B组(术后应用免疫增强型全肠外营养组)和对照组(常规全肠外营养组).于入院时、术后第1天和第6天时分别检测各项免疫、营养及预后指标.结果:与入院时比较,3组免疫和营养指标于术后第1天降低,术后第6天均有所恢复.术后第6天,A、B组中的淋巴细胞总数和IgA、IgM、IgG、CD3、CD4、CD4/CD8值及中性数细胞吞噬率均显著高于C组,A、B组的术后感染性并发症发生率显著低于C组,平均住院时间则显著长于C组(P<0.05),而A组和B组间各项免疫及预后指标无显著差异(P>0.05).研究期间各组白蛋白、前白蛋白和转铁蛋白血清浓度无显著差异(P>0.05).结论:免疫增强型全肠外营养可增强胃肠恶性肿瘤患者术后机体免疫功能并改善预后.%Objective:To study the effect of Immune-enriched total parenteral nutrition (TPN) on the postoperative immune function, nutritional status and prognosis in the patients with gastrointestinal cancer. Methods: A hundred and twenty patients with gastrointestinal cancer were randomly divided into three groups. One group was given TPN supplemented with glutamine and arginine before and after operation( Group A), One group was given TPN supplemented with glutamine and arginine only after operation( Group B), and the other group was given conventional parenteral nutrition after operation as the control group (Group C). The nutrition status, immune function and prognostic indicators were measured on admission day,on the first day and the sixth day after operation respectively. Results: Compared with the admission day, the levels of most humoral and cellular immune parametes declined on the first day, but they resumed on the sixth day after

  8. Label-free haemogram using wavelength modulated Raman spectroscopy for identifying immune-cell subset

    Science.gov (United States)

    Ashok, Praveen C.; Praveen, Bavishna B.; Campbell, Elaine C.; Dholakia, Kishan; Powis, Simon J.

    2014-03-01

    Leucocytes in the blood of mammals form a powerful protective system against a wide range of dangerous pathogens. There are several types of immune cells that has specific role in the whole immune system. The number and type of immune cells alter in the disease state and identifying the type of immune cell provides information about a person's state of health. There are several immune cell subsets that are essentially morphologically identical and require external labeling to enable discrimination. Here we demonstrate the feasibility of using Wavelength Modulated Raman Spectroscopy (WMRS) with suitable machine learning algorithms as a label-free method to distinguish between different closely lying immune cell subset. Principal Component Analysis (PCA) was performed on WMRS data from single cells, obtained using confocal Raman microscopy for feature reduction, followed by Support Vector Machine (SVM) for binary discrimination of various cell subset, which yielded an accuracy >85%. The method was successful in discriminating between untouched and unfixed purified populations of CD4+CD3+ and CD8+CD3+ T lymphocyte subsets, and CD56+CD3- natural killer cells with a high degree of specificity. It was also proved sensitive enough to identify unique Raman signatures that allow clear discrimination between dendritic cell subsets, comprising CD303+CD45+ plasmacytoid and CD1c+CD141+ myeloid dendritic cells. The results of this study clearly show that WMRS is highly sensitive and can distinguish between cell types that are morphologically identical.

  9. Spatial-temporal subset based digital image correlation considering the temporal continuity of deformation

    Science.gov (United States)

    Wang, Xian; Liu, Xuejin; Zhu, Haibin; Ma, Shaopeng

    2017-03-01

    An improved digital image correlation (DIC) scheme termed spatial-temporal subset-based DIC (STS-DIC) that incorporates the temporal continuity of deformation is proposed. Provided that displacement at a certain physical point on a specimen in several successive frames is temporally continuous and can be expressed as a linear relationship over time, the STS-DIC scheme is constructed between the reference subset and spatial-temporal deformed subset consisting of several subsets from a period of successive frames. The proposed method is verified by simulated speckle images and experimental tests featuring different types of deformation. Compared to the traditional subset-based DIC, the STS-DIC proposed in this paper takes advantage of noise suppression so as to improve the accuracy, especially for speckle images with larger noise. More importantly, it is found that the computational demand of STS-DIC is much lower than that of mesh-based (global) DIC incorporating the temporal continuity, despite achieving comparable accuracy. Therefore, STS-DIC is expected to be useful as a practical and flexible tool in complex-environment measurements with low signal-to-noise-ratio speckle images.

  10. Merging transcriptomics and metabolomics - advances in breast cancer profiling

    Directory of Open Access Journals (Sweden)

    Bathen Tone F

    2010-11-01

    Full Text Available Abstract Background Combining gene expression microarrays and high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS of the same tissue samples enables comparison of the transcriptional and metabolic profiles of breast cancer. The aim of this study was to explore the potential of combining these two different types of information. Methods Breast cancer tissue from 46 patients was analyzed by HR MAS MRS followed by gene expression microarrays. Two strategies were used to combine the gene expression and metabolic data; first using multivariate analyses to identify different groups based on gene expression and metabolic data; second correlating levels of specific metabolites to transcripts to suggest new hypotheses of connections between metabolite levels and the underlying biological processes. A parallel study was designed to address experimental issues of combining microarrays and HR MAS MRS. Results In the first strategy, using the microarray data and previously reported molecular classification methods, the majority of samples were classified as luminal A. Three subgroups of luminal A tumors were identified based on hierarchical clustering of the HR MAS MR spectra. The samples in one of the subgroups, designated A2, showed significantly lower glucose and higher alanine levels than the other luminal A samples, suggesting a higher glycolytic activity in these tumors. This group was also enriched for genes annotated with Gene Ontology (GO terms related to cell cycle and DNA repair. In the second strategy, the correlations between concentrations of myo-inositol, glycine, taurine, glycerophosphocholine, phosphocholine, choline and creatine and all transcripts in the filtered microarray data were investigated. GO-terms related to the extracellular matrix were enriched among the genes that correlated the most to myo-inositol and taurine, while cell cycle related GO-terms were enriched for the genes that correlated the most

  11. A systems biology approach to the analysis of subset-specific responses to lipopolysaccharide in dendritic cells.

    Directory of Open Access Journals (Sweden)

    David G Hancock

    Full Text Available Dendritic cells (DCs are critical for regulating CD4 and CD8 T cell immunity, controlling Th1, Th2, and Th17 commitment, generating inducible Tregs, and mediating tolerance. It is believed that distinct DC subsets have evolved to control these different immune outcomes. However, how DC subsets mount different responses to inflammatory and/or tolerogenic signals in order to accomplish their divergent functions remains unclear. Lipopolysaccharide (LPS provides an excellent model for investigating responses in closely related splenic DC subsets, as all subsets express the LPS receptor TLR4 and respond to LPS in vitro. However, previous studies of the LPS-induced DC transcriptome have been performed only on mixed DC populations. Moreover, comparisons of the in vivo response of two closely related DC subsets to LPS stimulation have not been reported in the literature to date. We compared the transcriptomes of murine splenic CD8 and CD11b DC subsets after in vivo LPS stimulation, using RNA-Seq and systems biology approaches. We identified subset-specific gene signatures, which included multiple functional immune mediators unique to each subset. To explain the observed subset-specific differences, we used a network analysis approach. While both DC subsets used a conserved set of transcription factors and major signalling pathways, the subsets showed differential regulation of sets of genes that 'fine-tune' the network Hubs expressed in common. We propose a model in which signalling through common pathway components is 'fine-tuned' by transcriptional control of subset-specific modulators, thus allowing for distinct functional outcomes in closely related DC subsets. We extend this analysis to comparable datasets from the literature and confirm that our model can account for cell subset-specific responses to LPS stimulation in multiple subpopulations in mouse and man.

  12. On Maximal Ranges of Vector Measures for Subsets and Purification of Transition Probabilities

    CERN Document Server

    Dai, Peng

    2010-01-01

    Consider a measurable space with an atomless finite vector measure. This measure defines a mapping of the $\\sigma$-field into an Euclidean space. According to the Lyapunov convexity theorem, the range of this mapping is a convex compactum. Similar ranges are also defined for measurable subsets of the space. Two subsets with the same vector measure may have different ranges. We investigate the question whether, among all the subsets having the same given vector measure, there always exists a set with the maximal range of the vector measure. The answer to this question is positive for two-dimensional vector measures and negative for higher dimensions. We use this fact to prove that for two-dimensional vector measures the Dvoretzky-Wald-Wolfowitz purification theorem holds for the case of a countable image set.

  13. Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation

    Directory of Open Access Journals (Sweden)

    Michael Schnoor

    2015-01-01

    Full Text Available Leukocyte extravasation is one of the essential and first steps during the initiation of inflammation. Therefore, a better understanding of the key molecules that regulate this process may help to develop novel therapeutics for treatment of inflammation-based diseases such as atherosclerosis or rheumatoid arthritis. The endothelial adhesion molecules ICAM-1 and VCAM-1 are known as the central mediators of leukocyte adhesion to and transmigration across the endothelium. Engagement of these molecules by their leukocyte integrin receptors initiates the activation of several signaling pathways within both leukocytes and endothelium. Several of such events have been described to occur during transendothelial migration of all leukocyte subsets, whereas other mechanisms are known only for a single leukocyte subset. Here, we summarize current knowledge on regulatory mechanisms of leukocyte extravasation from a leukocyte and endothelial point of view, respectively. Specifically, we will focus on highlighting common and unique mechanisms that specific leukocyte subsets exploit to succeed in crossing endothelial monolayers.

  14. Leukocyte Subset Changes in Response to a 164-km Road Cycle Ride in a Hot Environment

    Science.gov (United States)

    LUK, HUI-YING; MCKENZIE, AMY L.; DUPLANTY, ANTHONY A.; BUDNAR, RONALD G.; LEVITT, DANIELLE; FERNANDEZ, ALEX; LEE, ELAINE C.; ARMSTRONG, LAWRENCE E.; VINGREN, JAKOB L.

    2016-01-01

    The purpose of this observational study was to determine the circulating leukocyte subset response to completing the 2013 Hotter’N Hell Hundred recreational 164-km road cycle event in a hot and humid environmental condition. Twenty-eight men and four women were included in this study. Whole blood samples were obtained 1–2 hours before (PRE) and immediately after (POST) the event. Electronic sizing/sorting and cytometry were used to determine complete blood counts (CBC) including neutrophil, monocyte, and lymphocyte subsets. The concentration of circulating total leukocytes (103·μL−1) increased 134% from PRE to POST with the greatest increase in neutrophils (319%, pexercise in stressful environmental conditions affects the complement of circulating immune cells, although activational state and characterization of specific leukocyte subsets remains unclear. The observed increase in circulating cell sub-populations suggests that the circulating immune surveillance system may be acutely affected by exercise in hot and humid conditions. PMID:27293505

  15. Digital image correlation involves an inverse problem: A regularization scheme based on subset size constraint

    Science.gov (United States)

    Zhan, Qin; Yuan, Yuan; Fan, Xiangtao; Huang, Jianyong; Xiong, Chunyang; Yuan, Fan

    2016-06-01

    Digital image correlation (DIC) is essentially implicated in a class of inverse problem. Here, a regularization scheme is developed for the subset-based DIC technique to effectively inhibit potential ill-posedness that likely arises in actual deformation calculations and hence enhance numerical stability, accuracy and precision of correlation measurement. With the aid of a parameterized two-dimensional Butterworth window, a regularized subpixel registration strategy is established, in which the amount of speckle information introduced to correlation calculations may be weighted through equivalent subset size constraint. The optimal regularization parameter associated with each individual sampling point is determined in a self-adaptive way by numerically investigating the curve of 2-norm condition number of coefficient matrix versus the corresponding equivalent subset size, based on which the regularized solution can eventually be obtained. Numerical results deriving from both synthetic speckle images and actual experimental images demonstrate the feasibility and effectiveness of the set of newly-proposed regularized DIC algorithms.

  16. Data mining a small molecule drug screening representative subset from NIH PubChem.

    Science.gov (United States)

    Xie, Xiang-Qun; Chen, Jian-Zhong

    2008-03-01

    PubChem is a scientific showcase of the NIH Roadmap Initiatives. It is a compound repository created to facilitate information exchange and data sharing among the NIH Roadmap-funded Molecular Library Screening Center Network (MLSCN) and the scientific community. However, PubChem has more than 10 million records of compound information. It will be challenging to conduct a drug screening of the whole database of millions of compounds. Thus, the purpose of the present study was to develop a data mining cheminformatics approach in order to construct a representative and structure-diverse sublibrary from the large PubChem database. In this study, a new chemical diverse representative subset, rePubChem, was selected by whole-molecule chemistry-space matrix calculation using the cell-based partition algorithm. The representative subset was generated and was then subjected to evaluations by compound property analyses based on 1D and 2D molecular descriptors. The new subset was also examined and assessed for self-similarity analysis based on 2D molecular fingerprints in comparing with the source compound library. The new subset has a much smaller library size (540K compounds) with minimum similarity and redundancy without loss of the structural diversity and basic molecular properties of its parent library (5.3 million compounds). The new representative subset library generated could be a valuable structure-diverse compound resource for in silico virtual screening and in vitro HTS drug screening. In addition, the established subset generation method of using the combined cell-based chemistry-space partition metrics with pairwised 2D fingerprint-based similarity search approaches will also be important to a broad scientific community interested in acquiring structurally diverse compounds for efficient drug screening, building representative virtual combinatorial chemistry libraries for syntheses, and data mining large compound databases like the PubChem library in general.

  17. Technical Note: Proximal Ordered Subsets Algorithms for TV Constrained Optimization in CT Image Reconstruction

    CERN Document Server

    Rose, Sean; Sidky, Emil Y; Pan, Xiaochuan

    2016-01-01

    This article is intended to supplement our 2015 paper in Medical Physics titled "Noise properties of CT images reconstructed by use of constrained total-variation, data-discrepancy minimization", in which ordered subsets methods were employed to perform total-variation constrained data-discrepancy minimization for image reconstruction in X-ray computed tomography. Here we provide details regarding implementation of the ordered subsets algorithms and suggestions for selection of algorithm parameters. Detailed pseudo-code is included for every algorithm implemented in the original manuscript.

  18. Longterm decrease in the CD57 lymphocyte subset in a patient with chronic Lyme disease.

    Science.gov (United States)

    Stricker, Raphael B; Burrascano, Joseph; Winger, Edward

    2002-01-01

    Lyme disease is a tickborne illness caused by the spirochete Borrelia burgdorferi. In a previous report we described a decrease in the CD57 lymphocyte subset in patients with chronic Lyme disease. We have now identified a patient with chronic relapsing and remitting symptoms of Lyme disease who had decreased levels of CD57 lymphocytes over 10 years. This observation represents the longest duration of an immunologic abnormality ever documented in chronic Lyme disease. The CD57 lymphocyte subset appears to be a useful marker of longterm infection with the Lyme disease spirochete.

  19. Gamma-Ray Bursts Subset and Supernova Remnants Low Radio-Frequency Turnover

    Institute of Scientific and Technical Information of China (English)

    LIU Xiang

    2000-01-01

    Durations of gamma-ray bursts (GRB's) are featured by >2s subset and <2s one, with initial corresponding energy ratio being 20:1. It is found that supernova remants(SNR 's) turnover frequencies peak at 100 and 500 MHz. After assuming that GRB's originate from hypernova and making an analysis on the evolution of GRB's, we find that the initial energy of two GRB subsets leads to a different radio-frequency turnover of their remnant spectra, which accords positively with the turnover-frequency ratio of SNR's.

  20. How to create order in large closed subsets of WordNet-type dictionaries

    Directory of Open Access Journals (Sweden)

    Ahti Lohk

    2013-04-01

    Full Text Available This article presents a new two-step method to handle and study large closed subsets of WordNet-type dictionaries with the goal of finding possible structural inconsistencies. The notion of closed subset is explained using a WordNet tree. A novel and very fast method to order large relational systems is described and compared with some other fast methods. All the presented methods have been tested using Estonian1 and Princeton WordNet2 largest closed sets.DOI: http://dx.doi.org/10.5128/ERYa9.10

  1. 3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood.

    Science.gov (United States)

    Zheng, Siyang; Lin, Henry K; Lu, Bo; Williams, Anthony; Datar, Ram; Cote, Richard J; Tai, Yu-Chong

    2011-02-01

    Detection of circulating tumor cells has emerged as a promising minimally invasive diagnostic and prognostic tool for patients with metastatic cancers. We report a novel three dimensional microfilter device that can enrich viable circulating tumor cells from blood. This device consists of two layers of parylene membrane with pores and gap precisely defined with photolithography. The positions of the pores are shifted between the top and bottom membranes. The bottom membrane supports captured cells and minimize the stress concentration on cell membrane and sustain cell viability during filtration. Viable cell capture on device was investigated with scanning electron microscopy, confocal microscopy, and immunofluorescent staining using model systems of cultured tumor cells spiked in blood or saline. The paper presents and validates this new 3D microfiltration concept for circulation tumor cell enrichment application. The device provides a highly valuable tool for assessing and characterizing viable enriched circulating tumor cells in both research and clinical settings.

  2. CD45/CD11b Positive Subsets of Adult Lung Anchorage-Independent Cells Harness Epithelial Stem Cells

    Science.gov (United States)

    Peter, Yakov; Sen, Namita; Levantini, Elena; Keller, Steven; Ingenito, Edward P; Ciner, Aaron; Sackstein, Robert; Shapiro, Steven D

    2015-01-01

    Compensatory growth is mediated by multiple cell types that interact during organ repair. To elucidate the relationship between the stem/progenitor cells that proliferate or differentiate and the somatic cells of lung, we utilized a novel ex vivo pneumoexplant system. Applying this technique, we identified a sustained culture of repopulating adult progenitors in the form of free floating anchorage-independent cells (AICs). AICs did not express integrin proteins α5, β3, and β7, and constituted 37% of the total culture at day 14, yielding a mixed yet conserved population that recapitulated RNA expression patterns of the healthy lung. AICs exhibited rapid proliferation manifested by a marked 60-fold increase in cell numbers by day 21. Over 50% of the AIC population was cKit+ or double-positive for CD45+ and CD11b+ antigenic determinants, consistent with cells of hematopoietic origin. The latter subset was found to be enriched with prosurfactant protein-C and SCGB1A1 expressing putative stem cells and with aquaporin-5 producing cells, characteristic of terminally differentiated alveolar epithelial type-1 pneumocytes. AICs undergo remodeling to form a cellular lining at the air/gel interface, and TGFβ1 treatment modifies protein expression, implying direct-differentiation of this population. These data confirm the active participation of clonogenic hematopietic stem cells in a mammalian model of lung repair and validate mixed stem/somatic cell cultures, which embrace sustained cell viability, proliferation, and differentiation, for use in studies of compensatory pulmonary growth. PMID:22585451

  3. Enrichment of Acinetobacter spp. from food samples.

    Science.gov (United States)

    Carvalheira, Ana; Ferreira, Vânia; Silva, Joana; Teixeira, Paula

    2016-05-01

    Relatively little is known about the role of foods in the chain of transmission of acinetobacters and the occurrence of different Acinetobacter spp. in foods. Currently, there is no standard procedure to recover acinetobacters from food in order to gain insight into the food-related ecology and epidemiology of acinetobacters. This study aimed to assess whether enrichment in Dijkshoorn enrichment medium followed by plating in CHROMagar™ Acinetobacter medium is a useful method for the isolation of Acinetobacter spp. from foods. Recovery of six Acinetobacter species from food spiked with these organisms was compared for two selective enrichment media (Baumann's enrichment and Dijkshoorn's enrichment). Significantly (p Acinetobacter was applied to detect Acinetobacter spp. in different foods. Fourteen different presumptive acinetobacters were recovered and assumed to represent nine different strains on the basis of REP-PCR typing. Eight of these strains were identified by rpoB gene analysis as belonging to the species Acinetobacter johnsonii, Acinetobacter calcoaceticus, Acinetobacter guillouiae and Acinetobacter gandensis. It was not possible to identify the species level of one strain which may suggests that it represents a distinct species.

  4. Profile of World Uranium Enrichment Programs-2009

    Energy Technology Data Exchange (ETDEWEB)

    Laughter, Mark D [ORNL

    2009-04-01

    It is generally agreed that the most difficult step in building a nuclear weapon is acquiring fissile material, either plutonium or highly enriched uranium (HEU). Plutonium is produced in a nuclear reactor, whereas HEU is produced using a uranium enrichment process. Enrichment is also an important step in the civil nuclear fuel cycle, in producing low enriched uranium (LEU) for use as fuel for nuclear reactors to generate electricity. However, the same equipment used to produce LEU for nuclear reactor fuel can also be used to produce HEU for weapons. Safeguards at an enrichment plant are the array of assurances and verification techniques that ensure uranium is not diverted or enriched to HEU. There are several techniques for enriching uranium. The two most prevalent are gaseous diffusion, which uses older technology and requires a lot of energy, and gas centrifuge separation, which uses more advanced technology and is more energy efficient. Gaseous diffusion plants (GDPs) provide about 40% of current world enrichment capacity but are being phased out as newer gas centrifuge enrichment plants (GCEPs) are constructed. Estimates of current and future enrichment capacity are always approximate, due to the constant upgrades, expansions, and shutdowns occurring at enrichment plants, largely determined by economic interests. Currently, the world enrichment capacity is approximately 56 million kilogram separative work units (SWU) per year, with 22.5 million in gaseous diffusion and more than 33 million in gas centrifuge plants. Another 34 million SWU/year of capacity is under construction or planned for the near future, almost entirely using gas centrifuge separation. Other less-efficient techniques have also been used in the past, including electromagnetic and aerodynamic separations, but these are considered obsolete, at least from a commercial perspective. Laser isotope separation shows promise as a possible enrichment technique of the future but has yet to be

  5. Selective enrichment of commensal gut bacteria protects against Citrobacter rodentium-induced colitis.

    Science.gov (United States)

    Vong, Linda; Pinnell, Lee J; Määttänen, Pekka; Yeung, C William; Lurz, Eberhard; Sherman, Philip M

    2015-08-01

    The intestinal microbiota plays a key role in shaping the host immune system. Perturbation of gut microbial composition, termed dysbiosis, is associated with an increased susceptibility to intestinal pathogens and is a hallmark of a number of inflammatory, metabolic, and infectious diseases. The prospect of mining the commensal gut microbiota for bacterial strains that can impact immune function represents an attractive strategy to counteract dysbiosis and resulting disease. In this study, we show that selective enrichment of commensal gut lactobacilli protects against the murine pathogen Citrobacter rodentium, a well-characterized model of enteropathogenic and enterohemorrhagic Escherichia coli infection. The lactobacilli-enriched bacterial culture prevented the expansion of Gammaproteobacteria and Actinobacteria and was associated with improved indexes of epithelial barrier function (dextran flux), transmissible crypt hyperplasia, and tissue inflammatory cytokine levels. Moreover, cultivation of gut bacteria from Citrobacter rodentium-infected mice reveals the differential capacity of bacterial subsets to mobilize neutrophil oxidative burst and initiate the formation of weblike neutrophil extracellular traps. Our findings highlight the beneficial effects of a lactobacilli-enriched commensal gut microenvironment and, in the context of an intestinal barrier breach, the ability of neutrophils to immobilize both commensal and pathogenic bacteria.

  6. Virgin Coconut Oil (VCO Enriched with Zn as Immunostimulator for Vaginal Candidiasis Patient

    Directory of Open Access Journals (Sweden)

    HERY WINARSI

    2008-12-01

    Full Text Available Disturbance on the immune system and deficiency of Zn is two factors which often trigger vaginal candidiasis patient. The aim of the research was to study the effect of virgin coconut oil (VCO enriched with Zn to the amount of neutrophil and lymphocyte subset cells, and the level of IL-2 and IgG in vaginal candidiasis patient. Thirty women were grouped into three (ten women in each group: A, B and C, and intervened for two months. Women in A group were intervened with two tablespoon/day; those in B group were intervened with one tablespoon/day; while those in C group served as control (placebo. Blood was sampled at baseline time, one and two months after intervention. Hematological test by Micros-OT was done on a part of blood, and the plasma was used for IL-2 and IgG level tests using ELISA. The virgin coconut oil enriched with Zn maintained the number of neutrophil and NK cells, but increased Tc cells from 521 to 649 cells/mm3, increased Th cells from 1.090 to 1.380 cells/mm3. The enriched VCO also increase level of IL-2 from 0.25313 to 0.27337 pg/ml, while the IgG level changed from equivocal to negative. The recommended dosage was one tablespoon each day.

  7. Nutrient enrichment increases mortality of mangroves.

    Directory of Open Access Journals (Sweden)

    Catherine E Lovelock

    Full Text Available Nutrient enrichment of the coastal zone places intense pressure on marine communities. Previous studies have shown that growth of intertidal mangrove forests is accelerated with enhanced nutrient availability. However, nutrient enrichment favours growth of shoots relative to roots, thus enhancing growth rates but increasing vulnerability to environmental stresses that adversely affect plant water relations. Two such stresses are high salinity and low humidity, both of which require greater investment in roots to meet the demands for water by the shoots. Here we present data from a global network of sites that documents enhanced mortality of mangroves with experimental nutrient enrichment at sites where high sediment salinity was coincident with low rainfall and low humidity. Thus the benefits of increased mangrove growth in response to coastal eutrophication is offset by the costs of decreased resilience due to mortality during drought, with mortality increasing with soil water salinity along climatic gradients.

  8. Uranium enrichment management review: summary of analysis

    Energy Technology Data Exchange (ETDEWEB)

    1981-01-01

    In May 1980, the Assistant Secretary for Resource Applications within the Department of Energy requested that a group of experienced business executives be assembled to review the operation, financing, and management of the uranium enrichment enterprise as a basis for advising the Secretary of Energy. After extensive investigation, analysis, and discussion, the review group presented its findings and recommendations in a report on December 2, 1980. The following pages contain background material on which that final report was based. This report is arranged in chapters that parallel those of the uranium enrichment management review final report - chapters that contain summaries of the review group's discussion and analyses in six areas: management of operations and construction; long-range planning; marketing of enrichment services; financial management; research and development; and general management. Further information, in-depth analysis, and discussion of suggested alternative management practices are provided in five appendices.

  9. Nutrient Enrichment Increases Mortality of Mangroves

    Science.gov (United States)

    Lovelock, Catherine E.; Ball, Marilyn C.; Martin, Katherine C.; C. Feller, Ilka

    2009-01-01

    Nutrient enrichment of the coastal zone places intense pressure on marine communities. Previous studies have shown that growth of intertidal mangrove forests is accelerated with enhanced nutrient availability. However, nutrient enrichment favours growth of shoots relative to roots, thus enhancing growth rates but increasing vulnerability to environmental stresses that adversely affect plant water relations. Two such stresses are high salinity and low humidity, both of which require greater investment in roots to meet the demands for water by the shoots. Here we present data from a global network of sites that documents enhanced mortality of mangroves with experimental nutrient enrichment at sites where high sediment salinity was coincident with low rainfall and low humidity. Thus the benefits of increased mangrove growth in response to coastal eutrophication is offset by the costs of decreased resilience due to mortality during drought, with mortality increasing with soil water salinity along climatic gradients. PMID:19440554

  10. Some Observations on the Subset Simulation Related to the Wind Turbine Mechanics

    DEFF Research Database (Denmark)

    Sichani, Mahdi Teimouri; Nielsen, Søren R.K.; Thoft-Christensen, Palle

    2012-01-01

    systems. It is interesting to determine applicability of the Subset Simulation (SS) techniques, as a powerful representative of Variance Reduction Monte Carlo (VRMC) methods, on the wind turbine systems specifically with an active controller. Hence in this paper we apply and discuss these methods...... on a benchmark wind turbine model and analyze the results in view of their applicability....

  11. An actin-binding protein, CAP, is expressed in a subset of rat taste bud cells.

    Science.gov (United States)

    Ishimaru, Y; Yasuoka, A; Asano-Miyoshi, M; Abe, K; Emori, Y

    2001-02-12

    Single cell cDNA libraries were constructed from taste bud cells of rat circumvallate papillae. Using three steps of screening, including differential hybridization, sequence analyses and in situ hybridization, a clone encoding a rat homolog of yeast adenylyl cyclase-associated protein (CAP) was identified to be highly expressed in a subset of taste bud cells.

  12. Selective effects of alpha interferon on human T-lymphocyte subsets during mixed lymphocyte cultures

    DEFF Research Database (Denmark)

    Hokland, M; Hokland, P; Heron, I

    1983-01-01

    Mixed lymphocyte reaction (MLR) cultures of human lymphocyte subsets with or without the addition of physiological doses of human alpha interferon (IFN-alpha) were compared with respect to surface marker phenotypes and proliferative capacities of the responder cells. A selective depression on the T...

  13. Alterations in lymphocyte subset patterns and co-stimulatory molecules in patients with Alzheimer disease

    Institute of Scientific and Technical Information of China (English)

    XUE Shou-ru; XU Dong-hua; YANG Xin-xin; DONG Wan-li

    2009-01-01

    @@ Alzheimer disease (AD) is characterized by the presence of β-amyloid (Aβ) plaques in the brain.1 More evidence of inflammatory parameters, such as, complement factors, proinflammatory cytokines and lymphocytes has been found to be co-localized with Aβ plaques,1,2 The research in the past decades has demonstrated abnormalities of both the humoral and cellular immune responses, suggesting an association of immunological aberration and AD. The total percentage of lymphocytes was not found to be altered, whereas the alterations of T-cell function, differentiation and subset distribution have still been unresolved.3,4 A significantly decreased function of suppressor as well as helper T-cells and natural killer (NK) cells in AD patients has been observed. Studies on lymphocyte subpopulations showed conflicting results, while other studies could not find alterations in lymphocyte subset distribution. In the present study, we assume the immune system dysregulation depending on a defective immune response which also affects lymphocyte differentiation and subset distribution. We investigated T lymphocyte subset pattems and co-stimulatory molecules, as well as B lymphocytes and NK cells in peripheral blood of AD patients and age matched healthy controls.

  14. Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy.

    Science.gov (United States)

    Golubovskaya, Vita; Wu, Lijun

    2016-01-01

    This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy--a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4⁺ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh) and CD8⁺ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.); intracellular markers (FOXP3); epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic); and these differences can be modulated to improve CAR-T therapy. In addition, CD4⁺ Treg cells suppress the efficacy of CAR-T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors.

  15. The performance of tests on endogeneity of subsets of explanatory variables scanned by simulation

    NARCIS (Netherlands)

    J.F. Kiviet; M. Pleus

    2011-01-01

    Tests for classification as endogenous or predetermined of arbitrary subsets of regressors are formulated as significance tests in auxiliary IV regressions and their relationships with various more classic test procedures are examined. Simulation experiments are designed by solving the data generati

  16. Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane

    DEFF Research Database (Denmark)

    Rørvig, Sara; Østergaard, Ole; Heegaard, Niels Henrik Helweg;

    2013-01-01

    granules, SVs, and plasma membrane has been performed before. Here, we performed subcellular fractionation on freshly isolated human neutrophils by nitrogen cavitation and density centrifugation on a four-layer Percoll gradient. Granule subsets were pooled and subjected to SDS-PAGE, and gel pieces were in...

  17. T cell subsets in human airways prior to and following endobronchial administration of endotoxin

    DEFF Research Database (Denmark)

    Ronit, Andreas; Plovsing, Ronni R; Gaardbo, Julie C

    2015-01-01

    BACKGROUND AND OBJECTIVES: Bronchial instillation of lipopolysaccharide (LPS) provides a reversible model of lung inflammation that may resemble early stages of acute respiratory distress syndrome (ARDS). We investigated the distributions of T-cell subsets in the human airways and sought to deter...

  18. Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Strefford, J C; Sutton, L-A; Baliakas, P;

    2013-01-01

    Recent studies have revealed recurrent mutations of the NOTCH1, SF3B1 and BIRC3 genes in chronic lymphocytic leukemia (CLL), especially among aggressive, chemorefractory cases. Nevertheless, it is currently unknown whether their presence may differ in subsets of patients carrying stereotyped B...

  19. Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy

    Directory of Open Access Journals (Sweden)

    Vita Golubovskaya

    2016-03-01

    Full Text Available This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy––a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4+ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh and CD8+ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.; intracellular markers (FOXP3; epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic; and these differences can be modulated to improve CAR-T therapy. In addition, CD4+ Treg cells suppress the efficacy of CAR-T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors.

  20. Fluorescent activated cell sorting: an effective approach to study dendritic cell subsets in human atherosclerotic plaques.

    Science.gov (United States)

    Van Brussel, Ilse; Ammi, Rachid; Rombouts, Miche; Cools, Nathalie; Vercauteren, Sven R; De Roover, Dominique; Hendriks, Jeroen M H; Lauwers, Patrick; Van Schil, Paul E; Schrijvers, Dorien M

    2015-02-01

    Different immune cell types are present within atherosclerotic plaques. Dendritic cells (DC) are of special interest, since they are considered as the 'center of the immuniverse'. Identifying inflammatory DC subtypes within plaques is important for a better understanding of the lesion pathogenesis and pinpoints their contribution to the atherosclerotic process. We have developed a flow cytometry-based method to characterize and isolate different DC subsets (i.e. CD11b(+), Clec9A(+) and CD16(+) conventional (c)DC and CD123(+) plasmacytoid (p)DC) in human atherosclerotic plaques. We revealed a predominance of pro-inflammatory CD11b(+) DC in advanced human lesions, whereas atheroprotective Clec9A(+) DC were almost absent. CD123(+) pDC and CD16(+) DC were also detectable in plaques. Remarkably, plaques from distinct anatomical locations exhibited different cellular compositions: femoral plaques contained less CD11b(+) and Clec9A(+) DC than carotid plaques. Twice as many monocytes/macrophages were observed compared to DC. Moreover, relative amounts of T cells/B cells/NK cells were 6 times as high as DC numbers. For the first time, fluorescent activated cell sorting analysis of DC subsets in human plaques indicated a predominance of CD11b(+) cDC, in comparison with other DC subsets. Isolation of the different subsets will facilitate detailed functional analysis and may have significant implications for tailoring appropriate therapy.

  1. Tracking a Subset of Skeleton Joints: An Effective Approach towards Complex Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Muhammad Latif Anjum

    2017-01-01

    Full Text Available We present a robust algorithm for complex human activity recognition for natural human-robot interaction. The algorithm is based on tracking the position of selected joints in human skeleton. For any given activity, only a few skeleton joints are involved in performing the activity, so a subset of joints contributing the most towards the activity is selected. Our approach of tracking a subset of skeleton joints (instead of tracking the whole skeleton is computationally efficient and provides better recognition accuracy. We have developed both manual and automatic approaches for the selection of these joints. The position of the selected joints is tracked for the duration of the activity and is used to construct feature vectors for each activity. Once the feature vectors have been constructed, we use a Support Vector Machines (SVM multiclass classifier for training and testing the algorithm. The algorithm has been tested on a purposely built dataset of depth videos recorded using Kinect camera. The dataset consists of 250 videos of 10 different activities being performed by different users. Experimental results show classification accuracy of 83% when tracking all skeleton joints, 95% when using manual selection of subset joints, and 89% when using automatic selection of subset joints.

  2. The ICPC coding system in pharmacy : developing a subset, ICPC-Ph

    NARCIS (Netherlands)

    van Mil, JWF; Brenninkmeijer, R; Tromp, TFJ

    1998-01-01

    The ICPC system is a coding system developed for general medical practice, to be able to code the GP-patient encounters and other actions. Some of the codes can be easily used by community pharmacists to code complaints and diseases in pharmaceutical care practice. We developed a subset of the ICPC

  3. The acquisition of subset and superset phonotactic knowledge in a second language

    NARCIS (Netherlands)

    M. Trapman; R. Kager

    2009-01-01

    Can second language (L2) learners acquire a grammar that allows a subset of the structures allowed by their native grammar? This question is addressed here with respect to acquisition of phonotactics. On the assumption that the L2 initial state equals the native grammar's final state, learnability t

  4. Two New Types of Rings Defined by Using a Translational Invariant Fuzzy Subset

    Directory of Open Access Journals (Sweden)

    Manal Ghanem

    2010-01-01

    Full Text Available We use a translational invariant fuzzy subset of a ring to define two new types of commutative rings namely, -presimplifiable and -associate rings. We present some results of these rings. The interest of these results is that most of them are mirrors of corresponding results of presimplifiable and associate rings in classical ring theory.

  5. Mass Cytometry of the Human Mucosal Immune System Identifies Tissue- and Disease-Associated Immune Subsets.

    Science.gov (United States)

    van Unen, Vincent; Li, Na; Molendijk, Ilse; Temurhan, Mine; Höllt, Thomas; van der Meulen-de Jong, Andrea E; Verspaget, Hein W; Mearin, M Luisa; Mulder, Chris J; van Bergen, Jeroen; Lelieveldt, Boudewijn P F; Koning, Frits

    2016-05-17

    Inflammatory intestinal diseases are characterized by abnormal immune responses and affect distinct locations of the gastrointestinal tract. Although the role of several immune subsets in driving intestinal pathology has been studied, a system-wide approach that simultaneously interrogates all major lineages on a single-cell basis is lacking. We used high-dimensional mass cytometry to generate a system-wide view of the human mucosal immune system in health and disease. We distinguished 142 immune subsets and through computational applications found distinct immune subsets in peripheral blood mononuclear cells and intestinal biopsies that distinguished patients from controls. In addition, mucosal lymphoid malignancies were readily detected as well as precursors from which these likely derived. These findings indicate that an integrated high-dimensional analysis of the entire immune system can identify immune subsets associated with the pathogenesis of complex intestinal disorders. This might have implications for diagnostic procedures, immune-monitoring, and treatment of intestinal diseases and mucosal malignancies.

  6. 21 CFR 136.115 - Enriched bread, rolls, and buns.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Enriched bread, rolls, and buns. 136.115 Section... § 136.115 Enriched bread, rolls, and buns. (a) Each of the foods enriched bread, enriched rolls, and... label statement of ingredients prescribed for bread, rolls or buns by § 136.110, except that: (1)...

  7. Candidate genes for obesity-susceptibility show enriched association within a large genome-wide association study for BMI

    Science.gov (United States)

    Vimaleswaran, Karani S.; Tachmazidou, Ioanna; Zhao, Jing Hua; Hirschhorn, Joel N.; Dudbridge, Frank; Loos, Ruth J.F.

    2012-01-01

    Before the advent of genome-wide association studies (GWASs), hundreds of candidate genes for obesity-susceptibility had been identified through a variety of approaches. We examined whether those obesity candidate genes are enriched for associations with body mass index (BMI) compared with non-candidate genes by using data from a large-scale GWAS. A thorough literature search identified 547 candidate genes for obesity-susceptibility based on evidence from animal studies, Mendelian syndromes, linkage studies, genetic association studies and expression studies. Genomic regions were defined to include the genes ±10 kb of flanking sequence around candidate and non-candidate genes. We used summary statistics publicly available from the discovery stage of the genome-wide meta-analysis for BMI performed by the genetic investigation of anthropometric traits consortium in 123 564 individuals. Hypergeometric, rank tail-strength and gene-set enrichment analysis tests were used to test for the enrichment of association in candidate compared with non-candidate genes. The hypergeometric test of enrichment was not significant at the 5% P-value quantile (P = 0.35), but was nominally significant at the 25% quantile (P = 0.015). The rank tail-strength and gene-set enrichment tests were nominally significant for the full set of genes and borderline significant for the subset without SNPs at P < 10−7. Taken together, the observed evidence for enrichment suggests that the candidate gene approach retains some value. However, the degree of enrichment is small despite the extensive number of candidate genes and the large sample size. Studies that focus on candidate genes have only slightly increased chances of detecting associations, and are likely to miss many true effects in non-candidate genes, at least for obesity-related traits. PMID:22791748

  8. Phosphopeptide enrichment by immobilized metal affinity chromatography

    DEFF Research Database (Denmark)

    Thingholm, Tine E.; Larsen, Martin R.

    2016-01-01

    Immobilized metal affinity chromatography (IMAC) has been the method of choice for phosphopeptide enrichment prior to mass spectrometric analysis for many years and it is still used extensively in many laboratories. Using the affinity of negatively charged phosphate groups towards positively...... charged metal ions such as Fe3+, Ga3+, Al3+, Zr4+, and Ti4+ has made it possible to enrich phosphorylated peptides from peptide samples. However, the selectivity of most of the metal ions is limited, when working with highly complex samples, e.g., whole-cell extracts, resulting in contamination from...

  9. Gene expression analysis in human breast cancer associated blood vessels.

    Directory of Open Access Journals (Sweden)

    Dylan T Jones

    Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

  10. Phenotypic, ultra-structural, and functional characterization of bovine peripheral blood dendritic cell subsets.

    Directory of Open Access Journals (Sweden)

    Janet J Sei

    Full Text Available Dendritic cells (DC are multi-functional cells that bridge the gap between innate and adaptive immune systems. In bovine, significant information is lacking on the precise identity and role of peripheral blood DC subsets. In this study, we identify and characterize bovine peripheral blood DC subsets directly ex vivo, without further in vitro manipulation. Multi-color flow cytometric analysis revealed that three DC subsets could be identified. Bovine plasmacytoid DC were phenotypically identified by a unique pattern of cell surface protein expression including CD4, exhibited an extensive endoplasmic reticulum and Golgi apparatus, efficiently internalized and degraded exogenous antigen, and were the only peripheral blood cells specialized in the production of type I IFN following activation with Toll-like receptor (TLR agonists. Conventional DC were identified by expression of a different pattern of cell surface proteins including CD11c, MHC class II, and CD80, among others, the display of extensive dendritic protrusions on their plasma membrane, expression of very high levels of MHC class II and co-stimulatory molecules, efficient internalization and degradation of exogenous antigen, and ready production of detectable levels of TNF-alpha in response to TLR activation. Our investigations also revealed a third novel DC subset that may be a precursor of conventional DC that were MHC class II+ and CD11c-. These cells exhibited a smooth plasma membrane with a rounded nucleus, produced TNF-alpha in response to TLR-activation (albeit lower than CD11c+ DC, and were the least efficient in internalization/degradation of exogenous antigen. These studies define three bovine blood DC subsets with distinct phenotypic and functional characteristics which can be analyzed during immune responses to pathogens and vaccinations of cattle.

  11. Three distinct subsets of thymic epithelial cells in rats and mice defined by novel antibodies.

    Directory of Open Access Journals (Sweden)

    Yasushi Sawanobori

    Full Text Available AIM: Thymic epithelial cells (TECs are thought to play an essential role in T cell development and have been detected mainly in mice using lectin binding and antibodies to keratins. Our aim in the present study was to create a precise map of rat TECs using antibodies to putative markers and novel monoclonal antibodies (i.e., ED 18/19/21 and anti-CD205 antibodies and compare it with a map from mouse counterparts and that of rat thymic dendritic cells. RESULTS: Rat TECs were subdivided on the basis of phenotype into three subsets; ED18+ED19+/-keratin 5 (K5+K8+CD205+ class II MHC (MHCII+ cortical TECs (cTECs, ED18+ED21-K5-K8+Ulex europaeus lectin 1 (UEA-1+CD205- medullary TECs (mTEC1s, and ED18+ED21+K5+K8dullUEA-1-CD205- medullary TECs (mTEC2s. Thymic nurse cells were defined in cytosmears as an ED18+ED19+/-K5+K8+ subset of cTECs. mTEC1s preferentially expressed MHCII, claudin-3, claudin-4, and autoimmune regulator (AIRE. Use of ED18 and ED21 antibodies revealed three subsets of TECs in mice as well. We also detected two distinct TEC-free areas in the subcapsular cortex and in the medulla. Rat dendritic cells in the cortex were MHCII+CD103+ but negative for TEC markers, including CD205. Those in the medulla were MHCII+CD103+ and CD205+ cells were found only in the TEC-free area. CONCLUSION: Both rats and mice have three TEC subsets with similar phenotypes that can be identified using known markers and new monoclonal antibodies. These findings will facilitate further analysis of TEC subsets and DCs and help to define their roles in thymic selection and in pathological states such as autoimmune disorders.

  12. SPECIFICITIES OF THE SUBSET PROFILE OF PERIPHERAL BLOOD IN PATIENTS WITH GLIOBLASTOMA: PATHOGENETIC AND CLINICAL ASSESSMENTS

    Directory of Open Access Journals (Sweden)

    V. A. Chumakov

    2006-01-01

    Full Text Available Abstract. In glioblastoma (GB, it is necessary to take into consideration GB-associated secondary immunodeficiency (SID, so-called syndrome of tumor-associated SID (STASID. Cell subsets having effector and regulatory functions, play an important role in developing STASID, and their proportions in patients with different forms of GB can be of pathogenetic importance and have clinical value for treatment and rehabilitation scheduling as well. The most pathogenically and clinically important features of cell subsets profile of peripheral blood were analyzed in patients with different clinical and morphological types of GB. The patients were divided into three groups, i.e., groups I and II were formed by patients with STASID (marked and slightly marked SID, accordingly; group III – patients with SIDTAS (tumor-associated autoimmune syndrome, associated with SID. Marked suppression of cell immunity is typical of group I - imbalance in T-lymphocytes, in a number of specific subsets, and in subsets clusters, as well as disproportions in the immunoregulatory indexes. In group II, the subset profiles of blood were slightly different from the norm. In patients with SIDTAS, activation of cell immunity was evident, forming SID with signs of autoimmune syndrome, affecting effector and regulatory chains of immunity, and influencing the severity and forecast of the disease. Specific features of the immune status in patients with GB identified can be resulted from different clinicalmorphological types of the tumor; the latter are to be considered in differential diagnostics of clinical course of GB and in scheduling of clinical-immunological efficient anti-tumor pharmacotherapy in pre- and postoperative periods.

  13. Enrichment and identification of glycoproteins in human saliva using lectin magnetic bead arrays.

    Science.gov (United States)

    Caragata, Michael; Shah, Alok K; Schulz, Benjamin L; Hill, Michelle M; Punyadeera, Chamindie

    2016-03-15

    Aberrant glycosylation of proteins is a hallmark of tumorigenesis and could provide diagnostic value in cancer detection. Human saliva is an ideal source of glycoproteins due to the relatively high proportion of glycosylated proteins in the salivary proteome. Moreover, saliva collection is noninvasive and technically straightforward, and the sample collection and storage is relatively easy. Although differential glycosylation of proteins can be indicative of disease states, identification of differential glycosylation from clinical samples is not trivial. To facilitate salivary glycoprotein biomarker discovery, we optimized a method for differential glycoprotein enrichment from human saliva based on lectin magnetic bead arrays (saLeMBA). Selected lectins from distinct reactivity groups were used in the saLeMBA platform to enrich salivary glycoproteins from healthy volunteer saliva. The technical reproducibility of saLeMBA was analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify the glycosylated proteins enriched by each lectin. Our saLeMBA platform enabled robust glycoprotein enrichment in a glycoprotein- and lectin-specific manner consistent with known protein-specific glycan profiles. We demonstrated that saLeMBA is a reliable method to enrich and detect glycoproteins present in human saliva.

  14. Oleuropein-Enriched Olive Leaf Extract Affects Calcium Dynamics and Impairs Viability of Malignant Mesothelioma Cells

    Directory of Open Access Journals (Sweden)

    Carla Marchetti

    2015-01-01

    Full Text Available Malignant mesothelioma is a poor prognosis cancer in urgent need of alternative therapies. Oleuropein, the major phenolic of olive tree (Olea europaea L., is believed to have therapeutic potentials for various diseases, including tumors. We obtained an oleuropein-enriched fraction, consisting of 60% w/w oleuropein, from olive leaves, and assessed its effects on intracellular Ca2+ and cell viability in mesothelioma cells. Effects of the oleuropein-enriched fraction on Ca2+ dynamics and cell viability were studied in the REN mesothelioma cell line, using fura-2 microspectrofluorimetry and MTT assay, respectively. Fura-2-loaded cells, transiently exposed to the oleuropein-enriched fraction, showed dose-dependent transient elevations of cytosolic Ca2+ concentration (Ca2+i. Application of standard oleuropein and hydroxytyrosol, and of the inhibitor of low-voltage T-type Ca2+ channels NNC-55-0396, suggested that the effect is mainly due to oleuropein acting through its hydroxytyrosol moiety on T-type Ca2+ channels. The oleuropein-enriched fraction and standard oleuropein displayed a significant antiproliferative effect, as measured on REN cells by MTT cell viability assay, with IC50 of 22 μg/mL oleuropein. Data suggest that our oleuropein-enriched fraction from olive leaf extract could have pharmacological application in malignant mesothelioma anticancer therapy, possibly by targeting T-type Ca2+ channels and thereby dysregulating intracellular Ca2+ dynamics.

  15. 77 FR 14838 - General Electric-Hitachi Global Laser Enrichment LLC, Commercial Laser-Based Uranium Enrichment...

    Science.gov (United States)

    2012-03-13

    ... COMMISSION General Electric-Hitachi Global Laser Enrichment LLC, Commercial Laser-Based Uranium Enrichment... applicant) to authorize construction of a laser-based uranium enrichment facility and possession and use of...-based uranium enrichment facility. Revisions to the application were submitted on March 23, 2010;...

  16. SUMO-Enriched Proteome for Drosophila Innate Immune Response

    Science.gov (United States)

    Handu, Mithila; Kaduskar, Bhagyashree; Ravindranathan, Ramya; Soory, Amarendranath; Giri, Ritika; Elango, Vijay Barathi; Gowda, Harsha; Ratnaparkhi, Girish S.

    2015-01-01

    Small ubiquitin-like modifier (SUMO) modification modulates the expression of defense genes in Drosophila, activated by the Toll/nuclear factor-κB and immune-deficient/nuclear factor-κB signaling networks. We have, however, limited understanding of the SUMO-modulated regulation of the immune response and lack information on SUMO targets in the immune system. In this study, we measured the changes to the SUMO proteome in S2 cells in response to a lipopolysaccharide challenge and identified 1619 unique proteins in SUMO-enriched lysates. A confident set of 710 proteins represents the immune-induced SUMO proteome and analysis suggests that specific protein domains, cellular pathways, and protein complexes respond to immune stress. A small subset of the confident set was validated by in-bacto SUMOylation and shown to be bona-fide SUMO targets. These include components of immune signaling pathways such as Caspar, Jra, Kay, cdc42, p38b, 14-3-3ε, as well as cellular proteins with diverse functions, many being components of protein complexes, such as prosß4, Rps10b, SmD3, Tango7, and Aats-arg. Caspar, a human FAF1 ortholog that negatively regulates immune-deficient signaling, is SUMOylated at K551 and responds to treatment with lipopolysaccharide in cultured cells. Our study is one of the first to describe SUMO proteome for the Drosophila immune response. Our data and analysis provide a global framework for the understanding of SUMO modification in the host response to pathogens. PMID:26290570

  17. Semantically enriched data for effective sensor data fusion

    Science.gov (United States)

    de Mel, Geeth; Pham, Tien; Damarla, Thyagaraju; Vasconcelos, Wamberto; Norman, Tim

    2011-06-01

    Data fusion plays a major role in assisting decision makers by providing them with an improved situational awareness so that informed decisions could be made about the events that occur in the field. This involves combining a multitude of sensor modalities such that the resulting output is better (i.e., more accurate, complete, dependable etc.) than what it would have been if the data streams (hereinafter referred to as 'feeds') from the resources are taken individually. However, these feeds lack any context-related information (e.g., detected event, event classification, relationships to other events, etc.). This hinders the fusion process and may result in creating an incorrect picture about the situation. Thus, results in false alarms, waste valuable time/resources. In this paper, we propose an approach that enriches feeds with semantic attributes so that these feeds have proper meaning. This will assist underlying applications to present analysts with correct feeds for a particular event for fusion. We argue annotated stored feeds will assist in easy retrieval of historical data that may be related to the current fusion. We use a subset of Web Ontology Language (OWL), OWL-DL to present a lightweight and efficient knowledge layer for feeds annotation and use rules to capture crucial domain concepts. We discuss a solution architecture and provide a proof-of-concept tool to evaluate the proposed approach. We discuss the importance of such an approach with a set of user cases and show how a tool like the one proposed could assist analysts, planners to make better informed decisions.

  18. Fas and Bcl-2 Expression on T Lymphocyte Subsets in the Peripheral Blood of Relapsing Patients with Condyloma Acuminatum

    Institute of Scientific and Technical Information of China (English)

    顾军; 范清源; 高春芳; 代夫; 郑茂荣

    2003-01-01

    Objective: To study the expression of Fas and Bcl-2 proteins on T lymphocyte subsets in the peripheral blood of relapsing patients with condyloma acuminatum(CA) and healthy controls.Methods: Flow cytometry (permeabization and staining procedure with conjugated antibodies) was used.Results: We observed that the expression of Fas protein on CD4+ T lymphocyte subset of CA patients was significantly higher than that of healthy controls( P<0.01 ).Conclusions: Increased expression of Fas proteinon CD4+ T lymphocyte subset may be a cause of de-creased percentage of CD4+ T lymphocyte subset. This induces the increased ratio of CD4+/CD8+.

  19. RNA Helicase DDX5 Regulates MicroRNA Expression and Contributes to Cytoskeletal Reorganization in Basal Breast Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Daojing; Huang, Jing; Hu, Zhi

    2011-11-15

    RNA helicase DDX5 (also p68) is involved in all aspects of RNA metabolism and serves as a transcriptional co-regulator, but its functional role in breast cancer remains elusive. Here, we report an integrative biology study of DDX5 in breast cancer, encompassing quantitative proteomics, global MicroRNA profiling, and detailed biochemical characterization of cell lines and human tissues. We showed that protein expression of DDX5 increased progressively from the luminal to basal breast cancer cell lines, and correlated positively with that of CD44 in the basal subtypes. Through immunohistochemistry analyses of tissue microarrays containing over 200 invasive human ductal carcinomas, we observed that DDX5 was upregulated in the majority of malignant tissues, and its expression correlated strongly with those of Ki67 and EGFR in the triple-negative tumors. We demonstrated that DDX5 regulated a subset of MicroRNAs including miR-21 and miR-182 in basal breast cancer cells. Knockdown of DDX5 resulted in reorganization of actin cytoskeleton and reduction of cellular proliferation. The effects were accompanied by upregulation of tumor suppressor PDCD4 (a known miR-21 target); as well as upregulation of cofilin and profilin, two key proteins involved in actin polymerization and cytoskeleton maintenance, as a consequence of miR-182 downregulation. Treatment with miR-182 inhibitors resulted in morphologic phenotypes resembling those induced by DDX5 knockdown. Using bioinformatics tools for pathway and network analyses, we confirmed that the network for regulation of actin cytoskeleton was predominantly enriched for the predicted downstream targets of miR-182. Our results reveal a new functional role of DDX5 in breast cancer via the DDX5→miR-182→actin cytoskeleton pathway, and suggest the potential clinical utility of DDX5 and its downstream MicroRNAs in the theranostics of breast cancer.

  20. The Complexity of Enriched Mu-Calculi

    CERN Document Server

    Bonatti, Piero A; Murano, Aniello; Vardi, Moshe Y

    2008-01-01

    The fully enriched mu-calculus is the extension of the propositional mu-calculus with inverse programs, graded modalities, and nominals. While satisfiability in several expressive fragments of the fully enriched mu-calculus is known to be decidable and ExpTime-complete, it has recently been proved that the full calculus is undecidable. In this paper, we study the fragments of the fully enriched mu-calculus that are obtained by dropping at least one of the additional constructs. We show that, in all fragments obtained in this way, satisfiability is decidable and ExpTime-complete. Thus, we identify a family of decidable logics that are maximal (and incomparable) in expressive power. Our results are obtained by introducing two new automata models, showing that their emptiness problems are ExpTime-complete, and then reducing satisfiability in the relevant logics to these problems. The automata models we introduce are two-way graded alternating parity automata over infinite trees (2GAPTs) and fully enriched automa...

  1. Phosphopeptide enrichment by immobilized metal affinity chromatography

    DEFF Research Database (Denmark)

    Thingholm, Tine E.; Larsen, Martin R.

    2016-01-01

    Immobilized metal affinity chromatography (IMAC) has been the method of choice for phosphopeptide enrichment prior to mass spectrometric analysis for many years and it is still used extensively in many laboratories. Using the affinity of negatively charged phosphate groups towards positively...

  2. Teaching Mathematical Modelling: Demonstrating Enrichment and Elaboration

    Science.gov (United States)

    Warwick, Jon

    2015-01-01

    This paper uses a series of models to illustrate one of the fundamental processes of model building--that of enrichment and elaboration. The paper describes how a problem context is given which allows a series of models to be developed from a simple initial model using a queuing theory framework. The process encourages students to think about the…

  3. Implementing the Schoolwide Enrichment Model in Brazil

    Science.gov (United States)

    de Souza Fleith, Denise; Soriano de Alencar, Eunice M. L.

    2010-01-01

    The Schoolwide Enrichment Model (SEM) has been one of the most widely used models in the education of the gifted in Brazil. It has inspired the political and pedagogical project of the Centers of Activities of High Abilities/Giftedness recently implemented in 27 Brazilian states by the Ministry of Education. In this article, our experience in…

  4. Recommendations based on semantically enriched museum collections

    NARCIS (Netherlands)

    Wang, Y.; Stash, N.; Aroyo, L.; Gorgels, P.; Rutledge, L.; Schreiber, G.

    2008-01-01

    This article presents the CHIP demonstrator1 for providing personalized access to digital museum collections. It consists of three main components: Art Recommender, Tour Wizard, and Mobile Tour Guide. Based on the semantically enriched Rijksmuseum Amsterdam2 collection, we show how Semantic Web tech

  5. The enrichment history of cosmic metals

    CERN Document Server

    Wiersma, Robert P C; Vecchia, Claudio Dalla; Booth, C M; Theuns, Tom; Aguirre, Anthony

    2010-01-01

    We use a suite of cosmological, hydrodynamical simulations to investigate the chemical enrichment history of the Universe. Specifically, we trace the origin of the metals back in time to investigate when various gas phases were enriched and by what halo masses. We find that the age of the metals decreases strongly with the density of the gas in which they end up. At least half of the metals that reside in the diffuse intergalactic medium (IGM) at redshift zero (two) were ejected from galaxies above redshift two (three). The mass of the haloes that last contained the metals increases rapidly with the gas density. More than half of the mass in intergalactic metals was ejected by haloes with total masses less than 1e11 solar masses and stellar masses less than 1e9 solar masses. The range of halo masses that contributes to the enrichment is wider for the hotter part of the IGM. By combining the `when' and `by what' aspects of the enrichment history, we show that metals residing in lower density gas were typically...

  6. Enrichment Education: Key to NCLEX Success.

    Science.gov (United States)

    Wolahan, Caryle G. Hussey; Wieczorek, Rita Reis

    1991-01-01

    A concomitant decrease in test scores and major change in the composition of the student body was dealt with by the College of Nursing at the State University of New York through the Nursing Education Success Plan. The plan addresses student preparation for the National Council Licensure Exam (NCLEX), curriculum revision, remediation/enrichment,…

  7. 21 CFR 137.165 - Enriched flour.

    Science.gov (United States)

    2010-04-01

    ... riboflavin, 24 milligrams of niacin, 0.7 milligrams of folic acid, and 20 milligrams of iron. (b) It may... calcium or wheat germ is excluded in calculating ash content. (f) All ingredients from which the food is... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Enriched flour. 137.165 Section 137.165 Food...

  8. Characterization of Plasma Membrane Proteins from Ovarian Cancer Cells Using Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    David L. Springer

    2004-01-01

    Full Text Available To determine how the repertoire of plasma membrane proteins change with disease state, specifically related to cancer, several methods for preparation of plasma membrane proteins were evaluated. Cultured cells derived from stage IV ovarian tumors were grown to 90% confluence and harvested in buffer containing CHAPS detergent. This preparation was centrifuged at low speed to remove insoluble cellular debris resulting in a crude homogenate. Glycosylated proteins in the crude homogenate were selectively enriched using lectin affinity chromatography. The crude homogenate and the lectin purified sample were prepared for mass spectrometric evaluation. The general procedure for protein identification began with trypsin digestion of protein fractions followed by separation by reversed phase liquid chromatography that was coupled directly to a conventional tandem mass spectrometer (i.e. LCQ ion trap. Mass and fragmentation data for the peptides were searched against a human proteome data base using the informatics program SEQUEST. Using this procedure 398 proteins were identified with high confidence, including receptors, membrane-associated ligands, proteases, phosphatases, as well as structural and adhesion proteins. Results indicate that lectin chromatography provides a select subset of proteins and that the number and quality of the identifications improve as does the confidence of the protein identifications for this subset. These results represent the first step in development of methods to separate and successfully identify plasma membrane proteins from advanced ovarian cancer cells. Further characterization of plasma membrane proteins will contribute to our understanding of the mechanisms underlying progression of this deadly disease and may lead to new targeted interventions as well as new biomarkers for diagnosis.

  9. Two-stage atlas subset selection in multi-atlas based image segmentation

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Tingting, E-mail: tingtingzhao@mednet.ucla.edu; Ruan, Dan, E-mail: druan@mednet.ucla.edu [The Department of Radiation Oncology, University of California, Los Angeles, California 90095 (United States)

    2015-06-15

    Purpose: Fast growing access to large databases and cloud stored data presents a unique opportunity for multi-atlas based image segmentation and also presents challenges in heterogeneous atlas quality and computation burden. This work aims to develop a novel two-stage method tailored to the special needs in the face of large atlas collection with varied quality, so that high-accuracy segmentation can be achieved with low computational cost. Methods: An atlas subset selection scheme is proposed to substitute a significant portion of the computationally expensive full-fledged registration in the conventional scheme with a low-cost alternative. More specifically, the authors introduce a two-stage atlas subset selection method. In the first stage, an augmented subset is obtained based on a low-cost registration configuration and a preliminary relevance metric; in the second stage, the subset is further narrowed down to a fusion set of desired size, based on full-fledged registration and a refined relevance metric. An inference model is developed to characterize the relationship between the preliminary and refined relevance metrics, and a proper augmented subset size is derived to ensure that the desired atlases survive the preliminary selection with high probability. Results: The performance of the proposed scheme has been assessed with cross validation based on two clinical datasets consisting of manually segmented prostate and brain magnetic resonance images, respectively. The proposed scheme demonstrates comparable end-to-end segmentation performance as the conventional single-stage selection method, but with significant computation reduction. Compared with the alternative computation reduction method, their scheme improves the mean and medium Dice similarity coefficient value from (0.74, 0.78) to (0.83, 0.85) and from (0.82, 0.84) to (0.95, 0.95) for prostate and corpus callosum segmentation, respectively, with statistical significance. Conclusions: The authors

  10. Altered Cytokine Production By Specific Human Peripheral Blood Cell Subsets Immediately Following Spaceflight

    Science.gov (United States)

    Crucian, Brian E.; Cubbage, Michael L.; Sams, Clarence F.

    1999-01-01

    In this study, we have attempted to combine standard immunological assays with the cellular resolving power of the flow cytometer to positively identify the specific cell types involved in spaceflight-induced immune alterations. We have obtained whole blood samples from 27 astronauts collected at three timepoints (L-10, R+0 and R+3) surrounding four recent space shuttle missions. The duration of these missions ranged from 10 to 18 days. Assays performed included serum/urine cortisol, comprehensive subset phenotyping, assessment of cellular activation markers and intracellular cytokine production following mitogenic stimulation. Absolute levels of peripheral granulocytes were significantly elevated following spaceflight, but the levels of circulating lymphocytes and monocytes were unchanged. Lymphocyte subset analysis demonstrated trends towards a decreased percentage of T cells and an increased percentage of B cells. Nearly all of the astronauts exhibited an increased CD4:CD8 ratio, which was dramatic in some individuals. Assessment of memory (CD45RA+) vs. naive (CD45RO+) CD4+ T cell subsets was more ambiguous, with subjects tending to group more as a flight crew. All subjects from one mission demonstrated an increased CD45RA:CD45RO ratio, while all subjects from another Mission demonstrated a decreased ratio. While no significant trend was seen in the monocyte population as defined by scatter, a decreased percentage of the CD14+ CD16+ monocyte subset was seen following spaceflight in all subjects tested. In general, most of the cellular changes described above which were assessed at R+O and compared to L-10 trended to pre-flight levels by R+3. Although no significant differences were seen in the expression of the cellular activation markers CD69 and CD25 following exposure to microgravity, significant alterations were seen in cytokine production in response to mitogenic activation for specific subsets. T cell (CD3+) production of IL-2 was significantly decreased

  11. OPTIMAL ANTENNA SUBSET SELECTION AND BLIND DETECTION APPROACH APPLIED TO ORTHOGONAL SPACE-TIME BLOCK CODING

    Institute of Scientific and Technical Information of China (English)

    Xu Hongji; Liu Ju; Gu Bo

    2007-01-01

    An approach combining optimal antenna subset selection with blind detection scheme for Orthogonal Space-Time Block Coding (OSTBC) is proposed in this paper. The optimal antenna subset selection is taken into account at transmitter and/or receiver sides, which chooses the optimal antennas to increase the diversity order of OSTBC and improve further its performance. In order to enhance the robustness of the detection used in the conventional OSTBC scheme, a blind detection scheme based on Independent Component Analysis (ICA) is exploited which can directly extract transmitted signals without channel estimation. Performance analysis shows that the proposed approach can achieve the full diversity and the flexibility of system design by using the antenna selection and the ICA based blind detection schemes.

  12. Interpretation of Fuzzy Attribute Subsets in Generalized One-Sided Concept Lattices

    Directory of Open Access Journals (Sweden)

    Peter Butka

    2013-12-01

    Full Text Available In this paper we describe possible interpretation and reduction of fuzzy attributes in GeneralizedOne-sided Concept Lattices (GOSCL. This type of concept lattices represent generalization ofFormal Concept Analysis (FCA suitable for analysis of datatables with different types of attributes. FCA as well as generalized one-sided concept lattices represent conceptual data miningmethods. With growing number of attributes the interpretation of fuzzy subsets may become unclear, hence another interpretation of this fuzzy attribute subsets can be valuable. The originalityof the presented method is based on the usage of one-sided concept lattices derived from submodels of former object-attribute model by grouping attributes with the same truth value structure.This leads to new method for attribute reduction in GOSCL environment.

  13. Analysis of Information Content in High-Spectral Resolution Sounders using Subset Selection Analysis

    Science.gov (United States)

    Velez-Reyes, Miguel; Joiner, Joanna

    1998-01-01

    In this paper, we summarize the results of the sensitivity analysis and data reduction carried out to determine the information content of AIRS and IASI channels. The analysis and data reduction was based on the use of subset selection techniques developed in the linear algebra and statistical community to study linear dependencies in high dimensional data sets. We applied the subset selection method to study dependency among channels by studying the dependency among their weighting functions. Also, we applied the technique to study the information provided by the different levels in which the atmosphere is discretized for retrievals and analysis. Results from the method correlate well with intuition in many respects and point out to possible modifications for band selection in sensor design and number and location of levels in the analysis process.

  14. Combining ordered subsets and momentum for accelerated X-ray CT image reconstruction.

    Science.gov (United States)

    Kim, Donghwan; Ramani, Sathish; Fessler, Jeffrey A

    2015-01-01

    Statistical X-ray computed tomography (CT) reconstruction can improve image quality from reduced dose scans, but requires very long computation time. Ordered subsets (OS) methods have been widely used for research in X-ray CT statistical image reconstruction (and are used in clinical PET and SPECT reconstruction). In particular, OS methods based on separable quadratic surrogates (OS-SQS) are massively parallelizable and are well suited to modern computing architectures, but the number of iterations required for convergence should be reduced for better practical use. This paper introduces OS-SQS-momentum algorithms that combine Nesterov's momentum techniques with OS-SQS methods, greatly improving convergence speed in early iterations. If the number of subsets is too large, the OS-SQS-momentum methods can be unstable, so we propose diminishing step sizes that stabilize the method while preserving the very fast convergence behavior. Experiments with simulated and real 3D CT scan data illustrate the performance of the proposed algorithms.

  15. Ordered-subset analysis of savant skills in autism for 15q11-q13.

    Science.gov (United States)

    Ma, D Q; Jaworski, J; Menold, M M; Donnelly, S; Abramson, R K; Wright, H H; Delong, G R; Gilbert, J R; Pericak-Vance, M A; Cuccaro, Michael L

    2005-05-05

    Autism is a complex disorder characterized by genetic and phenotypic heterogeneity. Analysis of phenotypically homogeneous subtypes has been used to both confirm and narrow potential autism linkage regions such as the chromosomal region 15q11-q13. Increased evidence for linkage in this region had been found in a subgroup of 21 autism families (total families = 94) stratified based on a savant skill factor (SSF) from the Autism Diagnostic Interview, Revised (ADI-R). We examined the savant phenotypic finding in our sample of 91 multiplex autism families. Using two-point parametric analysis in stratification with a cutoff point of a savant skill score of 0.16, our families failed to demonstrate linkage to 15q11-q13. In addition, ordered subset analysis (OSA) using SSF as a covariate also failed to show evidence for linkage. Our findings do not support savant skills as an informative phenotypic subset for linkage in our sample.

  16. Data Mining Techniques to Estimate Plutonium, Initial Enrichment, Burnup, and Cooling Time in Spent Fuel Assemblies

    Energy Technology Data Exchange (ETDEWEB)

    Trellue, Holly Renee [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Fugate, Michael Lynn [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Tobin, Stephen Joesph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-03-19

    The Next Generation Safeguards Initiative (NGSI), Office of Nonproliferation and Arms Control (NPAC), National Nuclear Security Administration (NNSA) of the U.S. Department of Energy (DOE) has sponsored a multi-laboratory, university, international partner collaboration to (1) detect replaced or missing pins from spent fuel assemblies (SFA) to confirm item integrity and deter diversion, (2) determine plutonium mass and related plutonium and uranium fissile mass parameters in SFAs, and (3) verify initial enrichment (IE), burnup (BU), and cooling time (CT) of facility declaration for SFAs. A wide variety of nondestructive assay (NDA) techniques were researched to achieve these goals [Veal, 2010 and Humphrey, 2012]. In addition, the project includes two related activities with facility-specific benefits: (1) determination of heat content and (2) determination of reactivity (multiplication). In this research, a subset of 11 integrated NDA techniques was researched using data mining solutions at Los Alamos National Laboratory (LANL) for their ability to achieve the above goals.

  17. Global expression profile of highly enriched cardiomyocytes derived from human embryonic stem cells.

    Science.gov (United States)

    Xu, Xiu Qin; Soo, Set Yen; Sun, William; Zweigerdt, Robert

    2009-09-01

    Human embryonic stem cells (hESC), with their ability to differentiate into cardiomyocytes in culture, hold great potential for cell replacement therapies and provide an in vitro model of human heart development. A genomewide characterization of the molecular phenotype of hESC-derived cardiomyocytes is important for their envisioned applications. We have employed a lineage selection strategy to generate a pure population of cardiomyocytes (>99%) from transgenic hESC lines. Global gene expression profiling showed that these cardiomyocytes are distinct from pluripotent and differentiated hESC cultures. Pure cardiomyocytes displayed similarities with heart tissue, but in many aspects presented an individual transcriptome pattern. A subset of 1,311 cardiac-enriched transcripts was identified, which were significantly overpresented (p human heart development.

  18. Changes in lymphocyte function and subsets in dogs with naturally occurring chronic renal failure

    OpenAIRE

    Kralova, Simona; Leva, Lenka; Toman, Miroslav

    2010-01-01

    Chronic renal failure (CRF) causes immunosuppresion in humans and is thought to be one of the causes of noninfectious secondary immunosuppression in dogs. Hematological, biochemical, and immunological examinations were performed on blood samples obtained from dogs in various stages of CRF. The number of dogs with lymphopenia increased with the progression of clinical signs. All main subsets of lymphocytes were decreased, but more considerable reduction was detected in B-cells, Tc-cells, and N...

  19. The network of cytokines, receptors and transcription factors governing the development of dendritic cell subsets

    OpenAIRE

    Sathe, Priyanka; Wu, Li

    2011-01-01

    The pathways leading to the development of different dendritic cell (DC) subsets have long been unclear. In recent years, a number of precursors on the route to DC development, both under steady state and inflammatory conditions, have been described, and the nature of these pathways is becoming clearer. In addition, the development of various knockout mouse models and an in vitro system modelling DC development have revealed the role of numerous cytokines and transcription factors that influe...

  20. Feature subset selection based on mahalanobis distance: a statistical rough set method

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In order to select effective feature subsets for pattern classification, a novel statistics rough set method is presented based on generalized attribute reduction. Unlike classical reduction approaches, the objects in universe of discourse are signs of training sample sets and values of attributes are taken as statistical parameters. The binary relation and discernibility matrix for the reduction are induced by distance function. Furthermore, based on the monotony of the distance function defined by Mahalan...

  1. Defining mononuclear phagocyte subset homology across several distant warm-blooded vertebrates through comparative transcriptomics

    Directory of Open Access Journals (Sweden)

    Thien eVu Manh

    2015-06-01

    Full Text Available Mononuclear phagocytes are organized in a complex system of ontogenically and functionally-distinct subsets, that has been best described in mouse and to some extent in human. Identification of homologous mononuclear phagocyte subsets in other vertebrate species of biomedical, economic and environmental interest is needed to improve our knowledge in physiologic and physio-pathologic processes, and to design intervention strategies against a variety of diseases, including zoonotic infections.We developed a streamlined approach combining refined cell sorting and integrated comparative transcriptomics analyses which revealed conservation of the mononuclear phagocyte organization across human, mouse, sheep, pigs and, in some respect, chicken. This strategy should help democratizing the use of omics analyses for the identification and study of cell types across tissues and species. Moreover we identified conserved gene signatures that enable robust identification and universal definition of these cell types. We identified new evolutionarily conserved gene candidates and gene interaction networks for the molecular regulation of the development or functions of these cell types, as well as conserved surface candidates for refined subset phenotyping throughout species. A phylogenetic analysis revealed that orthologous genes of the conserved signatures exist in teleost fishes and apparently not in Lamprey, indicating conservation of the genetic support for mononuclear phagocyte organization throughout jawed vertebrates but likely not in agnathans. Altogether this work provides molecular clues to the definition and functions of mononuclear phagocyte subsets across vertebrates which shall be useful to rigorously identify these cells and to design universal strategies to manipulate them in many target species towards the goal to reach and maintain global health.

  2. Investigation of Combining Plant Genotypic Values and Molecular Marker Information for Constructing Core Subsets

    Institute of Scientific and Technical Information of China (English)

    Jian-Cheng Wang; Jin Hu; Ning-Ning Liu; Hai-Ming Xu; Sheng Zhang

    2006-01-01

    In the present study, a strategy was proposed for constructing plant core subsets by clusters based on the combination of continuous data for genotypic values and discrete data for molecular marker information. A mixed linear model approach was used to predict genotypic values for eliminating the environment effect.The "mixed genetic distance" was designed to solve the difficult problem of combining continuous and discrete data to construct a core subset by cluster. Four commonly used genetic distances for continuous data (Euclidean distance, standardized Euclidean distance, city block distance, and Mahalanobis distance)were used to assess the validity of the continuous data part of the mixed genetic distance; three commonly used genetic distances for discrete data (cosine distance, correlation distance, and Jaccard distance) were used to assess the validity of the discrete data part of the mixed genetic distance. A rice germplasm group with eight quantitative traits and information for 60 molecular markers was used to evaluate the validity of the new strategy. The results suggest that the validity of both parts of the mixed genetic distance are equal to or higher than the common genetic distance. The core subset constructed on the basis of a combination of data for genotypic values and molecular marker information was more representative than that constructed on the basis of data from genotypic values or molecular marker information alone. Moreover, the strategy of using combined data was able to treat dominant marker information and could combine any other continuous data and discrete data together to perform cluster to construct a plant core subset.

  3. A method for high purity sorting of rare cell subsets applied to TDC

    OpenAIRE

    2013-01-01

    TDC are a recently described subset of polyclonal αβ T-cells with dendritic cell properties. Because of their low number in peripheral immune compartments, isolation and characterization of TDC with existing purification methods is technically challenging. Here we describe a customized gating strategy and a flow cytometry-based cell sorting protocol for isolation of TDC. The protocol was developed because, despite very conservative gating for dead-cell and doublet exclusion, cells obtained wi...

  4. Predicting protein-RNA interaction amino acids using random forest based on submodularity subset selection.

    Science.gov (United States)

    Pan, Xiaoyong; Zhu, Lin; Fan, Yong-Xian; Yan, Junchi

    2014-11-13

    Protein-RNA interaction plays a very crucial role in many biological processes, such as protein synthesis, transcription and post-transcription of gene expression and pathogenesis of disease. Especially RNAs always function through binding to proteins. Identification of binding interface region is especially useful for cellular pathways analysis and drug design. In this study, we proposed a novel approach for binding sites identification in proteins, which not only integrates local features and global features from protein sequence directly, but also constructed a balanced training dataset using sub-sampling based on submodularity subset selection. Firstly we extracted local features and global features from protein sequence, such as evolution information and molecule weight. Secondly, the number of non-interaction sites is much more than interaction sites, which leads to a sample imbalance problem, and hence biased machine learning model with preference to non-interaction sites. To better resolve this problem, instead of previous randomly sub-sampling over-represented non-interaction sites, a novel sampling approach based on submodularity subset selection was employed, which can select more representative data subset. Finally random forest were trained on optimally selected training subsets to predict interaction sites. Our result showed that our proposed method is very promising for predicting protein-RNA interaction residues, it achieved an accuracy of 0.863, which is better than other state-of-the-art methods. Furthermore, it also indicated the extracted global features have very strong discriminate ability for identifying interaction residues from random forest feature importance analysis.

  5. The Search for Candidate Relevant Subsets of Variables in Complex Systems.

    Science.gov (United States)

    Villani, M; Roli, A; Filisetti, A; Fiorucci, M; Poli, I; Serra, R

    2015-01-01

    We describe a method to identify relevant subsets of variables, useful to understand the organization of a dynamical system. The variables belonging to a relevant subset should have a strong integration with the other variables of the same relevant subset, and a much weaker interaction with the other system variables. On this basis, extending previous work on neural networks, an information-theoretic measure, the dynamical cluster index, is introduced in order to identify good candidate relevant subsets. The method does not require any previous knowledge of the relationships among the system variables, but relies on observations of their values over time. We show its usefulness in several application domains, including: (i) random Boolean networks, where the whole network is made of different subnetworks with different topological relationships (independent or interacting subnetworks); (ii) leader-follower dynamics, subject to noise and fluctuations; (iii) catalytic reaction networks in a flow reactor; (iv) the MAPK signaling pathway in eukaryotes. The validity of the method has been tested in cases where the data are generated by a known dynamical model and the dynamical cluster index is applied in order to uncover significant aspects of its organization; however, it is important that it can also be applied to time series coming from field data without any reference to a model. Given that it is based on relative frequencies of sets of values, the method could be applied also to cases where the data are not ordered in time. Several indications to improve the scope and effectiveness of the dynamical cluster index to analyze the organization of complex systems are finally given.

  6. A note on fuzzy PS-ideals in PS-algebra and its level subsets

    Directory of Open Access Journals (Sweden)

    Priya Thirugapillai

    2014-03-01

    Full Text Available In this paper, a new notion, named fuzzification of PS – Algebra, which is a generalization of BCK/BCI/TM/BH/Q/d/KU-algebras, is introduced, along with PS-ideal and we have discussed some of their properties in detail. Keywords: PS-Algebra, PS-ideal, Fuzzy PS-Ideal, Level Subsets, PS-Subalgebra and Fuzzy PS-Subalgebra.

  7. Characterization of cell lines derived from breast cancers and normal mammary tissues for the study of the intrinsic molecular subtypes.

    Science.gov (United States)

    Prat, Aleix; Karginova, Olga; Parker, Joel S; Fan, Cheng; He, Xiaping; Bixby, Lisa; Harrell, J Chuck; Roman, Erick; Adamo, Barbara; Troester, Melissa; Perou, Charles M

    2013-11-01

    Five molecular subtypes (luminal A, luminal B, HER2-enriched, basal-like, and claudin-low) with clinical implications exist in breast cancer. Here, we evaluated the molecular and phenotypic relationships of (1) a large in vitro panel of human breast cancer cell lines (BCCLs), human mammary fibroblasts (HMFs), and human mammary epithelial cells (HMECs); (2) in vivo breast tumors; (3) normal breast cell subpopulations; (4) human embryonic stem cells (hESCs); and (5) bone marrow-derived mesenchymal stem cells (hMSC). First, by integrating genomic data of 337 breast tumor samples with 93 cell lines we were able to identify all the intrinsic tumor subtypes in the cell lines, except for luminal A. Secondly, we observed that the cell lines recapitulate the differentiation hierarchy detected in the normal mammary gland, with claudin-low BCCLs and HMFs cells showing a stromal phenotype, HMECs showing a mammary stem cell/bipotent progenitor phenotype, basal-like cells showing a luminal progenitor phenotype, and luminal B cell lines showing a mature luminal phenotype. Thirdly, we identified basal-like and highly migratory claudin-low subpopulations of cells within a subset of triple-negative BCCLs (SUM149PT, HCC1143, and HCC38). Interestingly, both subpopulations within SUM149PT were enriched for tumor-initiating cells, but the basal-like subpopulation grew tumors faster than the claudin-low subpopulation. Finally, claudin-low BCCLs resembled the phenotype of hMSCs, whereas hESCs cells showed an epithelial phenotype without basal or luminal differentiation. The results presented here help to improve our understanding of the wide range of breast cancer cell line models through the appropriate pairing of cell lines with relevant in vivo tumor and normal cell counterparts.

  8. Performance of sentinel lymph node biopsy in high-risk endometrial cancer

    Directory of Open Access Journals (Sweden)

    Jessie Ehrisman

    2016-08-01

    Conclusion: SLN mapping rates for high-risk cancers are slightly lower than in prior reports of lower risk cancers. The NPV of the SLN mapping alone is 92% and rises to 100% when the SLN algorithm is applied. Such results are acceptable and consistent with larger subsets of lower risk endometrial cancers.

  9. IRAK1 is a therapeutic target that drives breast cancer metastasis and resistance to paclitaxel

    DEFF Research Database (Denmark)

    Wee, Zhen Ning; Yatim, Siti Maryam J M; Kohlbauer, Vera K

    2015-01-01

    Metastatic tumour recurrence due to failed treatments remains a major challenge of breast cancer clinical management. Here we report that interleukin-1 receptor-associated kinase 1 (IRAK1) is overexpressed in a subset of breast cancers, in particular triple-negative breast cancer (TNBC), where...

  10. Effects of β4 integrin expression on microRNA patterns in breast cancer

    Directory of Open Access Journals (Sweden)

    Kristin D. Gerson

    2012-05-01

    The integrin α6β4 is defined as an adhesion receptor for laminins. Referred to as ‘β4’, this integrin plays a key role in the progression of various carcinomas through its ability to orchestrate key signal transduction events and promote cell motility. To identify novel downstream effectors of β4 function in breast cancer, microRNAs (miRNAs were examined because of their extensive links to tumorigenesis and their ability to regulate gene expression globally. Two breast carcinoma cell lines and a collection of invasive breast carcinomas with varying β4 expression were used to assess the effect of this integrin on miRNA expression. A novel miRNA microarray analysis termed quantitative Nuclease Protection Assay (qNPA revealed that β4 expression can significantly alter miRNA expression and identified two miRNA families, miR-25/32/92abc/363/363-3p/367 and miR-99ab/100, that are consistently downregulated by expression of this integrin. Analysis of published Affymetrix GeneChip data identified 54 common targets of miR-92ab and miR-99ab/100 within the subset of β4-regulated mRNAs, revealing several genes known to be key components of β4-regulated signaling cascades and effectors of cell motility. Gene ontology classification identified an enrichment in genes associated with cell migration within this population. Finally, gene set enrichment analysis of all β4-regulated mRNAs revealed an enrichment in targets belonging to distinct miRNA families, including miR-92ab and others identified by our initial array analyses. The results obtained in this study provide the first example of an integrin globally impacting miRNA expression and provide evidence that select miRNA families collectively target genes important in executing β4-mediated cell motility.

  11. Memory T cell subsets in tuberculosis: what should we be targeting?

    Science.gov (United States)

    Henao-Tamayo, Marcela; Ordway, Diane J; Orme, Ian M

    2014-09-01

    The purpose of vaccination is to establish a stable population of long lived memory T cells. In the context of tuberculosis, the BCG vaccine has been widely used for well over 60 years, but during that time its weaknesses, particularly its ineffectiveness in adults, has been increasingly recognized. In this commentary we review what is known about memory T cells, both in general and in the context of their role in expressing specific acquired resistance to tuberculosis. Current knowledge indicates that both effector memory and central memory can be generated, depending on the experimental conditions, but both in animal models and in clinical studies it is clear that effector memory T cells are the predominant subset. These issues are of importance, given the concerted effort to make new TB vaccines, not all of which may work in precisely the same manner. At the present time whether a TB vaccine would work better if it targeted one specific T cell subset rather than another is as yet completely unknown, and this is now further complicated by new evidence that suggests other subsets such as IL-17 secreting CD4 T cells and cells with stem cell-like qualities may also play important roles.

  12. Extra-thymically induced T regulatory cell subsets: the optimal target for antigen-specific immunotherapy

    Science.gov (United States)

    Verhagen, Johan; Wegner, Anja; Wraith, David C

    2015-01-01

    Antigen-specific immunotherapy aims to selectively restore tolerance to innocuous antigens in cases of autoimmune or allergic disease, without the need for general immune suppression. Although the principle of antigen-specific immunotherapy was discovered more than a century ago, its clinical application to date is limited, particularly in the control of autoimmunity. This has resulted mainly from a lack of in-depth understanding of the underlying mechanism. More recently, the differentiation of extra-thymically induced T regulatory (Treg) cell subsets has been shown to be instrumental in peripheral tolerance induction. Two main types of inducible Treg cells, interleukin-10-secreting or Foxp3+, have now been described, each with distinct characteristics and methods of therapeutic induction. It is crucial, therefore, to identify the suitability of either subset in the control of specific immune disorders. This review explores their natural function, the known mechanisms of therapeutic differentiation of either subset as well as their in vivo functionality and discusses new developments that may aid their use in antigen-specific immunotherapy, with a focus on autoimmune disease. PMID:25716063

  13. Detection of T lymphocyte subsets of children with Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Lin-Lin Wang; Qing-Wen Shan; Hai-Xing Jiang; Dinh-Binh Tran; Xue Qin; Xiang-Zhi Xie; Dan-Mei Liang

    2005-01-01

    AIM: To study the transformation of T lymphocyte subsets in children with Heliobacter pylori (H pylori) infection. METHODS: The H pylori infection status were determined by a combination of ELISA and Western blot (immunoblot) technique in 98 children and T lymphocyte subsets in peripheral blood were determined by flow cytometrical analysis.RESULTS: There were 75 children positive with H pylori infection and 23 negative in 98 children. Comparing the proportion of peripheral blood T lymphocytic subsets in children with H pylori infection and without H pylori infection, it was found that a higher proportion of CD4 T-cells in infected children (39.02±7.71 vs34.25±10.73,t = 2.246,P<0.05) and higher value of CD4 to CD8 T-cells ratio (1.51±0.52 vs 1.25, t= 2.104,P<0.05) were present, but there were not significant differences in CD3 T-cells and CD8 T-cells (73.11±10.02 vs69.49±17.08, 27.22±6.07vs 28.27±8.67, P>0.05).CONCLUSION: Th1 cell-mediated immune responses may be induced by H pylori infection in children.

  14. Lymphocyte subsets in human immunodeficiency virus-unexposed Brazilian individuals from birth to adulthood

    Directory of Open Access Journals (Sweden)

    Maria Isabel de Moraes-Pinto

    2014-12-01

    Full Text Available Ethnic origin, genetics, gender and environmental factors have been shown to influence some immunologic indices, so that development of reference values for populations of different backgrounds may be necessary. We have determined the distribution of lymphocyte subsets in healthy Brazilian individuals from birth to adulthood. Lymphocyte subsets were determined using four-colour cytometry in a cross-sectional study of 463 human immunodeficiency virus-unexposed children and adults from birth through 49 years of age. Lymphocyte subsets varied according to age, as previously observed in other studies. However, total CD4+ T cell numbers were lower than what was described in the Pediatric AIDS Clinical Trials Group P1009 (PACTG P1009, which assessed an American population of predominantly African and Hispanic backgrounds until the 12-18 year age range, when values were comparable. Naïve percentages and absolute values of CD8+ T cells, as assessed by CD45RA expression, were also lower than the PACTG P1009 data for all analysed age ranges. CD38 expression on both CD4+ and CD8+ T cells was lower than the PACTG P1009 values, with a widening gap between the two studies at older age ranges. Different patterns of cell differentiation seem to occur in different settings and may have characteristic expression within each population.

  15. Towards Qualifiable Code Generation from a Clocked Synchronous Subset of Modelica

    Directory of Open Access Journals (Sweden)

    Bernhard Thiele

    2015-01-01

    Full Text Available So far no qualifiable automatic code generators (ACGs are available for Modelica. Hence, digital control applications can be modeled and simulated in Modelica, but require tedious additional efforts (e.g., manual reprogramming to produce qualifiable target system production code. In order to more fully leverage the potential of a model-based development (MBD process in Modelica, a qualifiable automatic code generator is needed. Typical Modelica code generation is a fairly complex process which imposes a huge development burden to any efforts of tool qualification. This work aims at mapping a Modelica subset for digital control function development to a well-understood synchronous data-flow kernel language. This kernel language allows to resort to established compilation techniques for data-flow languages which are understood enough to be accepted by certification authorities. The mapping is established by providing a translational semantics from the Modelica subset to the synchronous data-flow kernel language. However, this translation turned out to be more intricate than initially expected and has given rise to several interesting issues that require suitable design decisions regarding the mapping and the language subset.

  16. Creating a non-linear total sediment load formula using polynomial best subset regression model

    Science.gov (United States)

    Okcu, Davut; Pektas, Ali Osman; Uyumaz, Ali

    2016-08-01

    The aim of this study is to derive a new total sediment load formula which is more accurate and which has less application constraints than the well-known formulae of the literature. 5 most known stream power concept sediment formulae which are approved by ASCE are used for benchmarking on a wide range of datasets that includes both field and flume (lab) observations. The dimensionless parameters of these widely used formulae are used as inputs in a new regression approach. The new approach is called Polynomial Best subset regression (PBSR) analysis. The aim of the PBRS analysis is fitting and testing all possible combinations of the input variables and selecting the best subset. Whole the input variables with their second and third powers are included in the regression to test the possible relation between the explanatory variables and the dependent variable. While selecting the best subset a multistep approach is used that depends on significance values and also the multicollinearity degrees of inputs. The new formula is compared to others in a holdout dataset and detailed performance investigations are conducted for field and lab datasets within this holdout data. Different goodness of fit statistics are used as they represent different perspectives of the model accuracy. After the detailed comparisons are carried out we figured out the most accurate equation that is also applicable on both flume and river data. Especially, on field dataset the prediction performance of the proposed formula outperformed the benchmark formulations.

  17. The lower bound on complexity of parallel branch-and-bound algorithm for subset sum problem

    Science.gov (United States)

    Kolpakov, Roman; Posypkin, Mikhail

    2016-10-01

    The subset sum problem is a particular case of the Boolean knapsack problem where each item has the price equal to its weight. This problem can be informally stated as searching for most dense packing of a set of items into a box with limited capacity. Recently, coarse-grain parallelization approaches to Branch-and-Bound (B&B) method attracted some attention due to the growing popularity of weakly-connected distributed computing platforms. In this paper we consider one of such approaches for solving the subset sum problem. One of the processors (manager) performs some number of B&B steps on the first stage with generating some subproblems. On the second stage, the generated subproblems are sent to other processors, one subproblem per processor. The processors solve completely the received subproblems, the manager collects all the obtained solutions and chooses the optimal one. For this algorithm we formally define the parallel execution model (frontal scheme of parallelization) and the notion of the frontal scheme complexity. We study the frontal scheme complexity for a series of subset sum problems.

  18. Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults

    Directory of Open Access Journals (Sweden)

    Trautwein Christian

    2010-06-01

    Full Text Available Abstract Background Recent experimental approaches have unraveled essential migratory and functional differences of monocyte subpopulations in mice. In order to possibly translate these findings into human physiology and pathophysiology, human monocyte subsets need to be carefully revisited in health and disease. In analogy to murine studies, we hypothesized that human monocyte subsets dynamically change during ageing, potentially influencing their functionality and contributing to immunosenescence. Results Circulating monocyte subsets, surface marker and chemokine receptor expression were analyzed in 181 healthy volunteers (median age 42, range 18-88. Unlike the unaffected total leukocyte or total monocyte counts, non-classical CD14+CD16+ monocytes significantly increased with age, but displayed reduced HLA-DR and CX3CR1 surface expression in the elderly. Classical CD14++CD16- monocyte counts did not vary dependent on age. Serum MCP-1 (CCL2, but not MIP1α (CCL3, MIP1β (CCL4 or fractalkine (CX3CL1 concentrations increased with age. Monocyte-derived macrophages from old or young individuals did not differ with respect to cytokine release in vitro at steady state or upon LPS stimulation. Conclusions Our study demonstrates dynamic changes of circulating monocytes during ageing in humans. The expansion of the non-classical CD14+CD16+ subtype, alterations of surface protein and chemokine receptor expression as well as circulating monocyte-related chemokines possibly contribute to the preserved functionality of the monocyte pool throughout adulthood.

  19. PD1-Expressing T Cell Subsets Modify the Rejection Risk in Renal Transplant Patients

    Science.gov (United States)

    Pike, Rebecca; Thomas, Niclas; Workman, Sarita; Ambrose, Lyn; Guzman, David; Sivakumaran, Shivajanani; Johnson, Margaret; Thorburn, Douglas; Harber, Mark; Chain, Benny; Stauss, Hans J.

    2016-01-01

    We tested whether multi-parameter immune phenotyping before or after renal ­transplantation can predict the risk of rejection episodes. Blood samples collected before and weekly for 3 months after transplantation were analyzed by multi-parameter flow cytometry to define 52 T cell and 13 innate lymphocyte subsets in each sample, producing more than 11,000 data points that defined the immune status of the 28 patients included in this study. Principle component analysis suggested that the patients with histologically confirmed rejection episodes segregated from those without rejection. Protein death 1 (PD-1)-expressing subpopulations of regulatory and conventional T cells had the greatest influence on the principal component segregation. We constructed a statistical tool to predict rejection using a support vector machine algorithm. The algorithm correctly identified 7 out of 9 patients with rejection, and 14 out of 17 patients without rejection. The immune profile before transplantation was most accurate in determining the risk of rejection, while changes of immune parameters after transplantation were less accurate in discriminating rejection from non-rejection. The data indicate that pretransplant immune subset analysis has the potential to identify patients at risk of developing rejection episodes, and suggests that the proportion of PD1-expressing T cell subsets may be a key indicator of rejection risk. PMID:27148254

  20. VisFlow - Web-based Visualization Framework for Tabular Data with a Subset Flow Model.

    Science.gov (United States)

    Yu, Bowen; Silva, Claudio T

    2017-01-01

    Data flow systems allow the user to design a flow diagram that specifies the relations between system components which process, filter or visually present the data. Visualization systems may benefit from user-defined data flows as an analysis typically consists of rendering multiple plots on demand and performing different types of interactive queries across coordinated views. In this paper, we propose VisFlow, a web-based visualization framework for tabular data that employs a specific type of data flow model called the subset flow model. VisFlow focuses on interactive queries within the data flow, overcoming the limitation of interactivity from past computational data flow systems. In particular, VisFlow applies embedded visualizations and supports interactive selections, brushing and linking within a visualization-oriented data flow. The model requires all data transmitted by the flow to be a data item subset (i.e. groups of table rows) of some original input table, so that rendering properties can be assigned to the subset unambiguously for tracking and comparison. VisFlow features the analysis flexibility of a flow diagram, and at the same time reduces the diagram complexity and improves usability. We demonstrate the capability of VisFlow on two case studies with domain experts on real-world datasets showing that VisFlow is capable of accomplishing a considerable set of visualization and analysis tasks. The VisFlow system is available as open source on GitHub.

  1. Neurohypophysial Receptor Gene Expression by Thymic T Cell Subsets and Thymic T Cell Lymphoma Cell Lines

    Directory of Open Access Journals (Sweden)

    I. Hansenne

    2004-01-01

    transcribed in thymic epithelium, while immature T lymphocytes express functional neurohypophysial receptors. Neurohypophysial receptors belong to the G protein-linked seven-transmembrane receptor superfamily and are encoded by four distinct genes, OTR, V1R, V2R and V3R. The objective of this study was to identify the nature of neurohypophysial receptor in thymic T cell subsets purified by immunomagnetic selection, as well as in murine thymic lymphoma cell lines RL12-NP and BW5147. OTR is transcribed in all thymic T cell subsets and T cell lines, while V3R transcription is restricted to CD4+ CD8+ and CD8+ thymic cells. Neither V1R nor V2R transcripts are detected in any kind of T cells. The OTR protein was identified by immunocytochemistry on thymocytes freshly isolated from C57BL/6 mice. In murine fetal thymic organ cultures, a specific OTR antagonist does not modify the percentage of T cell subsets, but increases late T cell apoptosis further evidencing the involvement of OT/OTR signaling in the control of T cell proliferation and survival. According to these data, OTR and V3R are differentially expressed during T cell ontogeny. Moreover, the restriction of OTR transcription to T cell lines derived from thymic lymphomas may be important in the context of T cell leukemia pathogenesis and treatment.

  2. Molecular marker differences relate to developmental position and subsets of mesodiencephalic dopaminergic neurons.

    Directory of Open Access Journals (Sweden)

    Simone M Smits

    Full Text Available The development of mesodiencephalic dopaminergic (mdDA neurons located in the substantia nigra compacta (SNc and ventral tegmental area (VTA follow a number of stages marked by distinct events. After preparation of the region by signals that provide induction and patterning, several transcription factors have been identified, which are involved in specifying the neuronal fate of these cells. The specific vulnerability of SNc neurons is thought to root in these specific developmental programs. The present study examines the positions of young postmitotic mdDA neurons to relate developmental position to mdDA subset specific markers. MdDA neurons were mapped relative to the neuromeric domains (prosomeres 1-3 (P1-3, midbrain, and hindbrain as well as the longitudinal subdivisions (floor plate, basal plate, alar plate, as proposed by the prosomeric model. We found that postmitotic mdDA neurons are located mainly in the floorplate domain and very few in slightly more lateral domains. Moreover, mdDA neurons are present along a large proportion of the anterior/posterior axis extending from the midbrain to P3 in the diencephalon. The specific positions relate to some extent to the presence of specific subset markers as Ahd2. In the adult stage more of such subsets specific expressed genes are present and may represent a molecular map defining molecularly distinct groups of mdDA neurons.

  3. PIAS1-FAK Interaction Promotes the Survival and Progression of Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jerfiz D. Constanzo

    2016-05-01

    Full Text Available The sequence of genomic alterations acquired by cancer cells during tumor progression and metastasis is poorly understood. Focal adhesion kinase (FAK is a non-receptor tyrosine kinase that integrates cytoskeleton remodeling, mitogenic signaling and cell survival. FAK has previously been reported to undergo nuclear localization during cell migration, cell differentiation and apoptosis. However, the mechanism behind FAK nuclear accumulation and its contribution to tumor progression has remained elusive. We report that amplification of FAK and the SUMO E3 ligase PIAS1 gene loci frequently co-occur in non-small cell lung cancer (NSCLC cells, and that both gene products are enriched in a subset of primary NSCLCs. We demonstrate that endogenous FAK and PIAS1 proteins interact in the cytoplasm and the cell nucleus of NSCLC cells. Ectopic expression of PIAS1 promotes proteolytic cleavage of the FAK C-terminus, focal adhesion maturation and FAK nuclear localization. Silencing of PIAS1 deregulates focal adhesion turnover, increases susceptibility to apoptosis in vitro and impairs tumor xenograft formation in vivo. Nuclear FAK in turn stimulates gene transcription favoring DNA repair, cell metabolism and cytoskeleton regulation. Consistently, ablation of FAK by CRISPR/Cas9 editing, results in basal DNA damage, susceptibility to ionizing radiation and impaired oxidative phosphorylation. Our findings provide insight into a mechanism regulating FAK cytoplasm-nuclear distribution and demonstrate that FAK activity in the nucleus promotes NSCLC survival and progression by increasing cell-ECM interaction and DNA repair regulation.

  4. Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer.

    Science.gov (United States)

    Nosho, Katsuhiko; Sukawa, Yasutaka; Adachi, Yasushi; Ito, Miki; Mitsuhashi, Kei; Kurihara, Hiroyoshi; Kanno, Shinichi; Yamamoto, Itaru; Ishigami, Keisuke; Igarashi, Hisayoshi; Maruyama, Reo; Imai, Kohzoh; Yamamoto, Hiroyuki; Shinomura, Yasuhisa

    2016-01-14

    The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum (F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6% (44/511), which was lower than that in United States cohort studies (13%). Similar to the United States studies, F. nucleatum positivity in Japanese colorectal cancers was significantly associated with microsatellite instability (MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets (i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain microRNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. MicroRNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in

  5. Transposed-Letter Priming Effects with Masked Subset Primes: A Re-Examination of the "Relative Position Priming Constraint"

    Science.gov (United States)

    Stinchcombe, Eric J.; Lupker, Stephen J.; Davis, Colin J.

    2012-01-01

    Three experiments are reported investigating the role of letter order in orthographic subset priming (e.g., "grdn"-GARDEN) using both the conventional masked priming technique as well as the sandwich priming technique in a lexical decision task. In all three experiments, subset primes produced priming with the effect being considerably…

  6. Identification of a human CD8+ regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4.

    NARCIS (Netherlands)

    Joosten, S.A.; Meijgaarden, K.E. van; Savage, N.D.; Boer, T. de; Triebel, F.; Wal, A. van der; Heer, E. de; Klein, M.R.; Geluk, A.; Ottenhoff, T.H.M.

    2007-01-01

    Regulatory T cells (Treg) comprise multiple subsets and are important in controlling immunity and inflammation. However, the induction and mode of action of the various distinct Treg subsets remain ill defined, particularly in humans. Here, we describe a human CD8+ lymphocyte activation gene-3 (LAG-

  7. Porcine γδ T lymphocytes can be categorized into two functionally and developmentally distinct subsets according to expression of CD2 and level of TCR.

    Science.gov (United States)

    Stepanova, Katerina; Sinkora, Marek

    2013-03-01

    Porcine γδ T cells have two levels of TCRγδ expression. Whereas TCRγδ(med) cells are mostly CD2(+)CD8(-) and CD2(+)CD8(+), TCRγδ(hi) cells are highly enriched for CD2(-)CD8(-). This distribution is independent of bacterial colonization and it is already established in the thymus prior to export of γδ cells to the periphery. Sorting and cultivation experiments revealed that CD2(-)CD8(-) γδ cells are unable to acquire CD2 and CD8, whereas CD2(+) subsets can gain or loose CD8. There is also differential susceptibility for proliferation between CD2(+) and CD2(-) γδ cells. Although CD2(-)CD8(-) almost do not proliferate, proliferation of CD2(+)CD8(-) and CD2(+)CD8(+) is substantial. Population of CD2(-) γδ cells is also absent in CD1(+) immature thymocytes. Additionally, subpopulations of CD2(+) and CD2(-) γδ cells in the thymus differ in expression of auxiliary surface molecules such as CD25, CD45RA/RC, and MHC class II. Moreover, TCRγδ(hi) cells can generate TCRγδ(med) cells but never the opposite. The only exception is the thymus, where a few TCRγδ(med) cells can be induced to TCRγδ(hi) but only under IL-2 influence. The repertoire of TCRδ is polyclonal in all subsets, indicating that there is the same extent of diversification and equal capability of immune responses. Results collectively indicate that CD2 expression determines two lineages of γδ cells that differ in many aspects. Because CD2(-) γδ cells are missing in the blood of humans and mice but are obvious in other members of γδ-high species such as ruminants and birds, our findings support the idea that circulating CD2(-) γδ T cells are a specific lineage.

  8. Characterizing and controlling intrinsic biases of lambda exonuclease in nascent strand sequencing reveals phasing between nucleosomes and G-quadruplex motifs around a subset of human replication origins.

    Science.gov (United States)

    Foulk, Michael S; Urban, John M; Casella, Cinzia; Gerbi, Susan A

    2015-05-01

    Nascent strand sequencing (NS-seq) is used to discover DNA replication origins genome-wide, allowing identification of features for their specification. NS-seq depends on the ability of lambda exonuclease (λ-exo) to efficiently digest parental DNA while leaving RNA-primer protected nascent strands intact. We used genomics and biochemical approaches to determine if λ-exo digests all parental DNA sequences equally. We report that λ-exo does not efficiently digest G-quadruplex (G4) structures in a plasmid. Moreover, λ-exo digestion of nonreplicating genomic DNA (LexoG0) enriches GC-rich DNA and G4 motifs genome-wide. We used LexoG0 data to control for nascent strand-independent λ-exo biases in NS-seq and validated this approach at the rDNA locus. The λ-exo-controlled NS-seq peaks are not GC-rich, and only 35.5% overlap with 6.8% of all G4s, suggesting that G4s are not general determinants for origin specification but may play a role for a subset. Interestingly, we observed a periodic spacing of G4 motifs and nucleosomes around the peak summits, suggesting that G4s may position nucleosomes at this subset of origins. Finally, we demonstrate that use of Na(+) instead of K(+) in the λ-exo digestion buffer reduced the effect of G4s on λ-exo digestion and discuss ways to increase both the sensitivity and specificity of NS-seq.

  9. Challenges when developing omega-3 enriched foods

    DEFF Research Database (Denmark)

    Jacobsen, Charlotte

    2010-01-01

    the influence of important factors such as oil quality, delivery systems for omega-3 fatty acids, processing conditions, composition of the food matrix on lipid oxidation in different omega-3 enriched foods (milk, yoghurt, mayonnaise and mayonnaise-based salads, dressing, energy bar and fish paté). Moreover......Due to the polyunsaturated nature of omega-3 fatty acids, lipid oxidation is a major challenge when developing omega-3 enriched foods. In multiphase food systems, several factors can affect lipid oxidation and efficacy of antioxidants, added to prevent lipid oxidation. This review discusses......, the effect of different antioxidants (tocopherol, EDTA, lactoferrin, caffeic acid, ascorbic acid, ascorbyl palmitate, propyl gallate, gallic acid, as well as lipophilized antioxidants) is compared in different food systems....

  10. Uranium enrichment activities: the SILVA program

    Energy Technology Data Exchange (ETDEWEB)

    Guyot, J.; Cazalet, J.; Camarcat, N.; Figuet, J.

    1994-12-31

    Through its commitment to a nuclear electricity generation policy, France holds today a specific position in the uranium enrichment market thanks to the modern multinational EURODIF gaseous diffusion plant. France has, altogether, a long-term goal in developing SILVA, a laser uranium enrichment process, based on the selective photo-ionization of U-235. After reviewing the fundamentals of SILVA (the laser system with copper vapor lasers and dye lasers and the separator system), a description of the general organization of the R and D program is provided going through basic research, subsystems assessment, production demonstrations and simulations (with the LACAN code), plant design and economics. The general schedule of SILVA is outlined, leading to the possible construction of a commercial plant. 7 figs., 11 refs.

  11. Enriched model categories and diagram categories

    CERN Document Server

    Guillou, Bertrand

    2011-01-01

    We collect in one place a variety of known and folklore results in enriched model category theory and add a few new twists. One twist is a new perspective on equivariant model categories. A central theme is a general procedure for constructing a Quillen adjunction, often a Quillen equivalence, between a given V-model category and a category of diagrams in V, where V is any good enriching category. From this perspective, we rederive the result of Schwede and Shipley that reasonable stable model categories are Quillen equivalent to diagram categories of spectra (alias categories of module spectra). The general theory will be applied to G-spectra in a sequel, and for that we need quite a few technical improvements and modifications of general model categorical results. We collect those here. They are bound to have applications in a variety of other contexts.

  12. Development Issues on Linked Data Weblog Enrichment

    Science.gov (United States)

    Ruiz-Rube, Iván; Cornejo, Carlos M.; Dodero, Juan Manuel; García, Vicente M.

    In this paper, we describe the issues found during the development of LinkedBlog, a Linked Data extension for WordPress blogs. This extension enables to enrich text-based and video information contained in blog entries with RDF triples that are suitable to be stored, managed and exploited by other web-based applications. The issues have to do with the generality, usability, tracking, depth, security, trustiness and performance of the linked data enrichment process. The presented annotation approach aims at maintaining web-based contents independent from the underlying ontological model, by providing a loosely coupled RDFa-based approach in the linked data application. Finally, we detail how the performance of annotations can be improved through a semantic reasoner.

  13. Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Kern Rei Chng

    2016-06-01

    Full Text Available Cholangiocarcinoma (CCA is the primary cancer of the bile duct system. The role of bile duct tissue microbiomes in CCA tumorigenesis is unestablished. To address this, sixty primary CCA tumors and matched normals, from both liver fluke (Opisthorchis viverrini associated (OVa, n = 28 and non-O. viverrini associated (non-OVa, n = 32 cancers, were profiled using high-throughput 16S rRNA sequencing. A distinct, tissue-specific microbiome dominated by the bacterial families Dietziaceae, Pseudomonadaceae and Oxalobacteraceae was observed in bile duct tissues. Systemic perturbation of the microbiome was noted in tumor and paired normal samples (vs non-cancer normals for several bacterial families with a significant increase in Stenotrophomonas species distinguishing tumors vs paired normals. Comparison of parasite associated (OVa vs non-associated (non-OVa groups identified enrichment for specific enteric bacteria (Bifidobacteriaceae, Enterobacteriaceae and Enterococcaceae. One of the enriched families, Bifidobacteriaceae, was found to be dominant in the O. viverrini microbiome, providing a mechanistic link to the parasite. Functional analysis and comparison of CCA microbiomes revealed higher potential for producing bile acids and ammonia in OVa tissues, linking the altered microbiota to carcinogenesis. These results define how the unique microbial communities resident in the bile duct, parasitic infections and the tissue microenvironment can influence each other, and contribute to cancer.

  14. Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma.

    Science.gov (United States)

    Chng, Kern Rei; Chan, Sock Hoai; Ng, Amanda Hui Qi; Li, Chenhao; Jusakul, Apinya; Bertrand, Denis; Wilm, Andreas; Choo, Su Pin; Tan, Damien Meng Yew; Lim, Kiat Hon; Soetinko, Roy; Ong, Choon Kiat; Duda, Dan G; Dima, Simona; Popescu, Irinel; Wongkham, Chaisiri; Feng, Zhu; Yeoh, Khay Guan; Teh, Bin Tean; Yongvanit, Puangrat; Wongkham, Sopit; Bhudhisawasdi, Vajaraphongsa; Khuntikeo, Narong; Tan, Patrick; Pairojkul, Chawalit; Ngeow, Joanne; Nagarajan, Niranjan

    2016-06-01

    Cholangiocarcinoma (CCA) is the primary cancer of the bile duct system. The role of bile duct tissue microbiomes in CCA tumorigenesis is unestablished. To address this, sixty primary CCA tumors and matched normals, from both liver fluke (Opisthorchis viverrini) associated (OVa, n=28) and non-O. viverrini associated (non-OVa, n=32) cancers, were profiled using high-throughput 16S rRNA sequencing. A distinct, tissue-specific microbiome dominated by the bacterial families Dietziaceae, Pseudomonadaceae and Oxalobacteraceae was observed in bile duct tissues. Systemic perturbation of the microbiome was noted in tumor and paired normal samples (vs non-cancer normals) for several bacterial families with a significant increase in Stenotrophomonas species distinguishing tumors vs paired normals. Comparison of parasite associated (OVa) vs non-associated (non-OVa) groups identified enrichment for specific enteric bacteria (Bifidobacteriaceae, Enterobacteriaceae and Enterococcaceae). One of the enriched families, Bifidobacteriaceae, was found to be dominant in the O. viverrini microbiome, providing a mechanistic link to the parasite. Functional analysis and comparison of CCA microbiomes revealed higher potential for producing bile acids and ammonia in OVa tissues, linking the altered microbiota to carcinogenesis. These results define how the unique microbial communities resident in the bile duct, parasitic infections and the tissue microenvironment can influence each other, and contribute to cancer.

  15. 子集空间下的邻域扩张%Neighborhood Expansion in Subset Spaces

    Institute of Scientific and Technical Information of China (English)

    王轶

    2014-01-01

    子集空间逻辑是刻画知识及其在证据支持度提升时发生变化的一种具有拓扑逻辑风格的简单架构的模态认知逻辑。与关系语义学不同,子集空间逻辑的语义学借助“邻域”而非“可通达关系”来表达不确定性区间。邻域的缩小体现不确定性的减少;在认知语境下,这种不确定性的减少就表现为知识的增长。子集空间逻辑主要刻画邻域的缩小。与邻域缩小相对应的邻域扩张同样具有理论研究的价值,然而却没有在子集空间逻辑中得到刻画。本文在子集空间逻辑的框架下探讨邻域的扩张。主要成果是给出带有邻域扩张算子的子集空间逻辑,为其引入关系语义学和公理系统,并证明该系统的完全性。%Subset space logics, originating from Moss and Parikh, have been introduced and studied as a framework for reasoning about a notion of effort in epistemic logic. The semantics of subset space logic use“neighborhoods”, rather than“accessibility relations”as in Kripke semantics. A shrink of a neighborhood stands for a decrease of epistemic uncertainty, which shows an increase of knowledge. Existing work on subset space logics has focused on the shrinking of neighborhoods. Expansion of neighborhoods, on the other hand, has not received much attention in this field. In this paper we study the expansion of neighborhoods in the framework of subset space logics. The main results are a subset space logic with an operator for neighborhood expansion, a Kripke semantics for it, and its sound and complete axiomatization.

  16. Nutritional Properties of Enriched Local Complementary Flours

    Directory of Open Access Journals (Sweden)

    W.R. Compaoré

    2011-02-01

    Full Text Available This study aimed to identify the nutritional, functional, sensory and microbiological profile of experimental nutritional flours, produced with local products in Burkina Faso. The raw materials included maize (Zea mays, millet (Pennisetum glaucum and rice (Oryza sativa. Local ingredients were pulps of Adansonia digitata and Parkia biglobosa and seeds of Cucurbita maxima and Moringa oleifera. Three formula were developed, the first (F1 with maize, the second (F2 with rice and the last (F3 with millet. Each of these cereals was mixed with predetermined portions of seeds and pulps in order to obtain enriched flour. Nutritional, microbiological and functional analysis and the acceptability criteria of these enriched flours were assessed and compared to Misola (F4, the existing local complementary flour. The fat content of experimental flours were respectively in the first (F1, second (F2 and third formula (F3 15.91±0.01%, 11.82±0.02% and 17.02±0.02%. The carbohydrate range was 65.46±0.06%, 70.81±0.01% and 64.51±0.01% for F1, F2 and F3, while the energetic value is higher than recommended (453.07±0.05, 424.56±0.03 and 458.96±0.05 kcal respectively for F1, F2 and F3. Functional characteristics indicated the good viscosity (117, 119 and 121 mm/30 sec for F1, F2 and F3 least gelation (9, 6 and 7% and water absorption capacity (2, 4 and 1 g/g. Trained sensory evaluation panellists gore the enriched flour porridge a score of acceptable. These enriched flours have great potential as a weaning food in resource-poor and technologically under-developed countries.

  17. NeuroD1 mediates nicotine-induced migration and invasion via regulation of the nicotinic acetylcholine receptor subunits in a subset of neural and neuroendocrine carcinomas.

    Science.gov (United States)

    Osborne, Jihan K; Guerra, Marcy L; Gonzales, Joshua X; McMillan, Elizabeth A; Minna, John D; Cobb, Melanie H

    2014-06-01

    Cigarette smoking is a major risk factor for acquisition of small cell lung cancer (SCLC). A role has been demonstrated for the basic helix-loop-helix transcription factor NeuroD1 in the pathogenesis of neural and neuroendocrine lung cancer, including SCLC. In the present study we investigate the possible function of NeuroD1 in established tumors, as well as actions early on in pathogenesis, in response to nicotine. We demonstrate that nicotine up-regulates NeuroD1 in immortalized normal bronchial epithelial cells and a subset of undifferentiated carcinomas. Increased expression of NeuroD1 subsequently leads to regulation of expression and function of the nicotinic acetylcholine receptor subunit cluster of α3, α5, and β4. In addition, we find that coordinated expression of these subunits by NeuroD1 leads to enhanced nicotine-induced migration and invasion, likely through changes in intracellular calcium. These findings suggest that aspects of the pathogenesis of neural and neuroendocrine lung cancers may be affected by a nicotine- and NeuroD1-induced positive feedback loop.

  18. On Heavy Element Enrichment in Classical Novae

    CERN Document Server

    Alexakis, A; Heger, A; Brown, E F; Dursi, L J; Truran, J W; Rosner, R; Lamb, D Q; Timmes, F X; Fryxell, B; Zingale, M A; Ricker, P M; Olson, K

    2004-01-01

    Many classical nova ejecta are enriched in CNO and Ne. Rosner et al. recently suggested that the enrichment might originate in the resonant interaction between large-scale shear flows in the accreted H/He envelope and gravity waves at the interface between the envelope and the underlying C/O white dwarf. The shear flow amplifies the waves, which eventually form cusps and break. This wave breaking injects a spray of C/O into the superincumbent H/He. Using two-dimensional simulations, we formulate a quantitative expression for the amount of C/O that can be entrained into the H/He at saturation. The fraction of the envelope that is enriched depends on the shear velocity and density contrast between the C/O white dwarf and the H/He layer but is roughly independent of the shape of the shear profile. Using this parameterization for the mixed mass, we then perform several one-dimensional Lagrangian calculations of an accreting white dwarf envelope and consider two scenarios: that the wave breaking and mixing is driv...

  19. Enriching Earthdata by Improving Content Curation

    Science.gov (United States)

    Bagwell, R.; Wong, M. M.; Murphy, K. J.

    2014-12-01

    Since the launch of Earthdata in the later part of 2011, there has been an emphasis on improving the user experience and providing more enriched content to the user, ultimately with the focus to bring the "pixels to the people" or to ensure that a user clicks the fewest amount of times to get to the data, tools, or information which they seek. Earthdata was founded to be a single source of information for Earth Observing System Data and Information System (EOSDIS) components and services as a conglomeration between over 15 different websites. With an increased focus on access to Earth science data, the recognition is now on transforming Earthdata from a static website to one that is a dynamic, data-driven site full of enriched content.In the near future, Earthdata will have a number of components that will drive the access to the data, such as Earthdata Search, the Common Metadata Repository (CMR), and a redesign of the Earthdata website. The focus on content curation will be to leverage the use of these components to provide an enriched content environment and a better overall user experience, with an emphasis on Earthdata being "powered by EOSDIS" components and services.

  20. Enriched MU-Calculi Module Checking

    CERN Document Server

    Ferrante, Alessandro; Parente, Mimmo

    2008-01-01

    The model checking problem for open systems has been intensively studied in the literature, for both finite-state (module checking) and infinite-state (pushdown module checking) systems, with respect to Ctl and Ctl*. In this paper, we further investigate this problem with respect to the Mu-calculus enriched with nominals and graded modalities (hybrid graded Mu-calculus), in both the finite-state and infinite-state settings. Using an automata-theoretic approach, we show that hybrid graded Mu-calculus module checking is solvable in exponential time, while hybrid graded Mu-calculus pushdown module checking is solvable in double-exponential time. These results are also tight since they match the known lower bounds for Ctl. We also investigate the module checking problem with respect to the hybrid graded Mu-calculus enriched with inverse programs (Fully enriched Mu-calculus): by showing a reduction from the domino problem, we show its undecidability. We conclude with a short overview of the model checking problem ...

  1. Enriched $^{82}$Se for the LUCIFER experiment

    CERN Document Server

    Beeman, J W; Benetti, P; Cardani, L; Casali, N; Chiesa, D; Clemenza, M; Dafinei, I; Di Domizio, S; Ferroni, F; Gironi, L; Giuliani, A; Gotti, C; Laubenstein, M; Maino, M; Nagorny, S; Nisi, S; Nones, C; Orio, F; Pagnanini, L; Pattavina, L; Pessina, G; Piperno, G; Pirro, S; Previtali, E; Rusconi, C; Schäffner, K; Tomei, C; Vignati, M

    2015-01-01

    The LUCIFER project aims at deploying the first array of enriched scintillating bolometers for the investigation of neutrinoless double-beta decay of $^{82}$Se. The matrix which embeds the source is an array of ZnSe crystals, where enriched $^{82}$Se is used as decay isotope. The radiopurity of the initial components employed for manufacturing crystals, that can be operated as bolometers, is crucial for achieving a null background level in the region of interest for double-beta decay investigations. In this work, we evaluated the radioactive content in 2.5 kg of 96.3% enriched $^{82}$Se metal, measured with a high-purity germanium detector at the Gran Sasso deep underground laboratory. The limits on internal contaminations of primordial decay chain elements of $^{232}$Th, $^{238}$U and $^{235}$U are respectively: $<$61 $\\mu$Bq/kg, $<$110 $\\mu$Bq/kg and $<$74 $\\mu$Bq/kg at 90% C.L.. The extremely low-background conditions in which the measurement was carried out and the high radiopurity of the $^{82}$...

  2. Inhomogeneous chemical enrichment in the Galactic Halo

    Science.gov (United States)

    Kobayashi, Chiaki

    2016-08-01

    In a galaxy, chemical enrichment takes place in an inhomogeneous fashion, and the Galactic Halo is one of the places where the inhomogeneous effects are imprinted and can be constrained from observations. I show this using my chemodynamical simulations of Milky Way type galaxies. The scatter in the elemental abundances originate from radial migration, merging/accretion of satellite galaxies, local variation of star formation and chemical enrichment, and intrinsic variation of nucleosynthesis yields. In the simulated galaxies, there is no strong age-metallicity relation. This means that the most metal-poor stars are not always the oldest stars, and can be formed in chemically unevolved clouds at later times. The long-lifetime sources of chemical enrichment such as asymptotic giant branch stars or neutron star mergers can contribute at low metallicities. The intrinsic variation of yields are important in the early Universe or metal-poor systems such as in the Galactic halo. The carbon enhancement of extremely metal-poor (EMP) stars can be best explained by faint supernovae, the low [α/Fe] ratios in some EMP stars naturally arise from low-mass (~ 13 - 15M ⊙) supernovae, and finally, the [α/Fe] knee in dwarf spheroidal galaxies can be produced by subclasses of Type Ia supernovae such as SN 2002cx-like objects and sub-Chandrasekhar mass explosions.

  3. Supply of enriched uranium for research reactors

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, H. [NUKEM GmbH, Alzenau (Germany)

    1997-08-01

    Since the RERTR-meeting In Newport/USA in 1990 the author delivered a series of papers in connection with the fuel cycle for research reactors dealing with its front-end. In these papers the author underlined the need for unified specifications for enriched uranium metal suitable for the production of fuel elements and made proposals with regard to the re-use of in Europe reprocessed highly enriched uranium. With regard to the fuel cycle of research reactors the research reactor community was since 1989 more concentrating on the problems of its back-end since the USA stopped the acceptance of spent research reactor fuel on December 31, 1988. Now, since it is apparent that these back-end problem have been solved by AEA`s ability to reprocess and the preparedness of the USA to again accept physically spent research reactor fuel the author is focusing with this paper again on the front-end of the fuel cycle on the question whether there is at all a safe supply of low and high enriched uranium for research reactors in the future.

  4. A Resolution of the Paradox of Enrichment

    Science.gov (United States)

    Feng, Z. C.; Li, Y. Charles

    2015-06-01

    The paradox of enrichment was observed by Rosenzweig [1971] in a class of predator-prey models. Two of the parameters in the models are crucial for the paradox. These two parameters are the prey's carrying capacity and prey's half-saturation for predation. Intuitively, increasing the carrying capacity due to enrichment of the prey's environment should lead to a more stable predator-prey system. Analytically, it turns out that increasing the carrying capacity always leads to an unstable predator-prey system that is susceptible to extinction from environmental random perturbations. This is the so-called paradox of enrichment. Our resolution here rests upon a closer investigation on a dimensionless number H formed from the carrying capacity and the prey's half-saturation. By recasting the models into dimensionless forms, the models are in fact governed by a few dimensionless numbers including H. The effects of the two parameters: carrying capacity and half-saturation are incorporated into the number H. In fact, increasing the carrying capacity is equivalent (i.e. has the same effect on H) to decreasing the half-saturation which implies more aggressive predation. Since there is no paradox between more aggressive predation and instability of the predator-prey system, the paradox of enrichment is resolved. The so-called instability of the predator-prey system is characterized by the existence of a stable limit cycle in the phase plane, which gets closer and closer to the predator axis and prey axis. Due to random environmental perturbations, this can lead to extinction. We also further explore spatially dependent models for which the phase space is infinite-dimensional. The spatially independent limit cycle which is generated by a Hopf bifurcation from an unstable steady state, is linearly stable in the infinite-dimensional phase space. Numerical simulations indicate that the basin of attraction of the limit cycle is riddled. This shows that spatial perturbations can

  5. Selenium enrichment of broccoli: interactions between selenium and secondary plant compounds.

    Science.gov (United States)

    Finley, John W; Sigrid-Keck, Anna; Robbins, Rebecca J; Hintze, Korry J

    2005-05-01

    Multiple components of broccoli, such as sulforaphane (Sf) and phenolic acids, may inhibit cancer. Additionally, broccoli can accumulate selenium (Se), and Se has been demonstrated to reduce the risk of cancer. Studies were conducted to determine whether enhancement of broccoli with Se would produce a plant with superior health benefits. Although increasing the concentration of Se in broccoli from 800 microg/g resulted in inhibition of colon cancer in rats, it also decreased the Sf content by >80% and inhibited production of most phenolic acids. The inclusion of Se-enriched broccoli in the diet of rats induced the activity of the selenoprotein thioredoxin reductase beyond the maximum activity induced by Se alone. These results emphasize the complex interactions of bioactive chemicals in a food; attempts to maximize one component may affect accumulation of another, and consumption of high amounts of multiple bioactive compounds may result in unexpected metabolic interactions within the body.

  6. NCR1 Expression Identifies Canine Natural Killer Cell Subsets with Phenotypic Similarity to Human Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Jennifer Ann Foltz

    2016-11-01

    Full Text Available Canines spontaneously develop many cancers similar to humans - including osteosarcoma, leukemia, and lymphoma - offering the opportunity to study immune therapies in a genetically heterogeneous and immunocompetent environment. However, a lack of antibodies recognizing canine NK cell markers has resulted in suboptimal characterization and unknown purity of NK cell products, hindering the development of canine models of NK cell adoptive immunotherapy. To this end, we generated a novel antibody to canine NCR1 (NKp46, the putative species-wide marker of NK cells, enabling purification of NK cells for further characterization. We demonstrate that CD3-/NKp46+ cells in healthy and osteosarcoma-bearing canines have phenotypic similarity to human CD3-/NKp46+ NK cells, expressing mRNA for CD16 and the natural cytotoxicity receptors NKp30, NKp44, and NKp80. Functionally, we demonstrate with the calcein release assay that canine CD3-/NKp46+ cells kill canine tumor cell lines without prior sensitization and secrete IFN-γ, TNF-α, IL-8, IL-10, and GM-CSF as measured by Luminex. Like human NK cells, CD3-/NKp46+ cells expand rapidly on feeder cells expressing 4-1BBL and membrane-bound IL-21 (median= 20,283-fold in 21 days. Further, we identify a minor Null population (CD3-/CD21-/CD14-/NKp46- with reduced cytotoxicity against osteosarcoma cells, but similar cytokine secretion as CD3-/NKp46+ cells. Null cells in canines and humans have reduced expression of NKG2D, NKp44, and CD16 compared to NKp46+ NK cells, and can be induced to express NKp46 with further expansion on feeder cells. In conclusion, we have identified and characterized canine NK cells, including an NKp46- subset of canine and human NK cells, using a novel anti-canine NKp46 antibody, and report robust ex vivo expansion of canine NK cells sufficient for adoptive immunotherapy.

  7. Canine Mammary Cancer Stem Cells are Radio- and Chemo- Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype

    Directory of Open Access Journals (Sweden)

    David J. Argyle

    2011-03-01

    Full Text Available Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelial to mesenchymal transition (EMT has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype. Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGFβ and that these cells have an increased ability to form tumorspheres. Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology.

  8. Colon cancer

    Science.gov (United States)

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma ... In the United States, colorectal cancer is one of the leading causes of deaths due to cancer. Early diagnosis can often lead to a complete cure. Almost ...

  9. 21 CFR 139.122 - Enriched nonfat milk macaroni products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Enriched nonfat milk macaroni products. 139.122... Macaroni and Noodle Products § 139.122 Enriched nonfat milk macaroni products. (a) Each of the enriched macaroni products made with nonfat milk for which a definition and standard of identity is prescribed...

  10. 78 FR 75579 - Low Enriched Uranium From France

    Science.gov (United States)

    2013-12-12

    ... COMMISSION Low Enriched Uranium From France Determination On the basis of the record \\1\\ developed in the... antidumping duty order on low enriched uranium from France would be likely to lead to continuation or...), entitled Low Enriched Uranium from France: Investigation No. 731-TA-909 (Second Review). By order of...

  11. 31 CFR 540.308 - Low Enriched Uranium (LEU).

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Low Enriched Uranium (LEU). 540.308... OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY HIGHLY ENRICHED URANIUM (HEU) AGREEMENT ASSETS CONTROL REGULATIONS General Definitions § 540.308 Low Enriched Uranium (LEU). The term low...

  12. 31 CFR 540.306 - Highly Enriched Uranium (HEU).

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Highly Enriched Uranium (HEU). 540...) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY HIGHLY ENRICHED URANIUM (HEU) AGREEMENT ASSETS CONTROL REGULATIONS General Definitions § 540.306 Highly Enriched Uranium (HEU). The term...

  13. 21 CFR 866.2330 - Enriched culture medium.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Enriched culture medium. 866.2330 Section 866.2330...) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2330 Enriched culture medium. (a) Identification. An enriched culture medium is a device that consists primarily of liquid...

  14. Aberrant overexpression of an epithelial marker, 14-3-3σ, in a subset of hematological malignancies

    Directory of Open Access Journals (Sweden)

    Nakamura Yukari

    2007-11-01

    Full Text Available Abstract Background 14-3-3σ is a p53-mediated cell-cycle inhibitor in epithelial cells. The expression of 14-3-3σ is frequently altered in cancers of epithelial origin associated with altered DNA methylation. Since its involvement in a non-epithelial tumor is unknown, we examined 14-3-3σ expression in patients with haematological malignancies. Methods We analyzed 41 hematopoietic cell lines and 129 patients with a variety of hematological malignancies for 14-3-3σ expression with real-time RT-PCR. We also examined protein levels by Western blot analysis and DNA methylation status of the 14-3-3σ gene by methylation-specific PCR analysis of bisulfite-treated DNA. In addition, mutations of p53 gene were identified by RT-PCR-SSCP analysis and the expression levels of 14-3-3σ were compared with those of other cell-cycle inhibitor genes, CDKN2A and ARF. Results The expression levels of 14-3-3σ mRNA in almost all cell lines were low and comparable to those in normal hematopoietic cells except for 2 B-cell lines. On the contrary, 14-3-3σ mRNA was aberrantly overexpressed frequently in mature lymphoid malignancies (30 of 93, 32.3% and rarely in acute leukemia (3 of 35, 8.6%. 14-3-3σ protein was readily detectable and roughly reflected the mRNA level. In contrast to epithelial tumors, methylation status of the 14-3-3σ gene was not associated with expression in hematological malignancies. Mutations of p53 were identified in 12 patients and associated with lower expression of 14-3-3σ. The expression levels of 14-3-3σ, CDKN2A and ARF were not correlated with but rather reciprocal to one another, suggesting that simultaneous overexpression of any two of them is incompatible with tumor growth. Conclusion 14-3-3σ, an epithelial cell marker, was overexpressed significantly in a subset of mature lymphoid malignancies. This is the first report of aberrant 14-3-3σ expression in non-epithelial tumors in vivo. Since the significance of 14-3-3

  15. Aberrant overexpression of an epithelial marker, 14-3-3σ, in a subset of hematological malignancies

    Science.gov (United States)

    Motokura, Toru; Nakamura, Yukari; Sato, Hiroyuki

    2007-01-01

    Background 14-3-3σ is a p53-mediated cell-cycle inhibitor in epithelial cells. The expression of 14-3-3σ is frequently altered in cancers of epithelial origin associated with altered DNA methylation. Since its involvement in a non-epithelial tumor is unknown, we examined 14-3-3σ expression in patients with haematological malignancies. Methods We analyzed 41 hematopoietic cell lines and 129 patients with a variety of hematological malignancies for 14-3-3σ expression with real-time RT-PCR. We also examined protein levels by Western blot analysis and DNA methylation status of the 14-3-3σ gene by methylation-specific PCR analysis of bisulfite-treated DNA. In addition, mutations of p53 gene were identified by RT-PCR-SSCP analysis and the expression levels of 14-3-3σ were compared with those of other cell-cycle inhibitor genes, CDKN2A and ARF. Results The expression levels of 14-3-3σ mRNA in almost all cell lines were low and comparable to those in normal hematopoietic cells except for 2 B-cell lines. On the contrary, 14-3-3σ mRNA was aberrantly overexpressed frequently in mature lymphoid malignancies (30 of 93, 32.3%) and rarely in acute leukemia (3 of 35, 8.6%). 14-3-3σ protein was readily detectable and roughly reflected the mRNA level. In contrast to epithelial tumors, methylation status of the 14-3-3σ gene was not associated with expression in hematological malignancies. Mutations of p53 were identified in 12 patients and associated with lower expression of 14-3-3σ. The expression levels of 14-3-3σ, CDKN2A and ARF were not correlated with but rather reciprocal to one another, suggesting that simultaneous overexpression of any two of them is incompatible with tumor growth. Conclusion 14-3-3σ, an epithelial cell marker, was overexpressed significantly in a subset of mature lymphoid malignancies. This is the first report of aberrant 14-3-3σ expression in non-epithelial tumors in vivo. Since the significance of 14-3-3σ overexpression is unknown even in

  16. Occupational exposure to diesel engine exhaust and alterations in lymphocyte subsets

    NARCIS (Netherlands)

    Lan, Qing; Vermeulen, Roel; Dai, Yufei; Ren, Dianzhi; Hu, Wei; Duan, Huawei; Niu, Yong; Xu, Jun; Fu, Wei; Meliefste, Kees; Zhou, Baosen; Yang, Jufang; Ye, Meng; Jia, Xiaowei; Meng, Tao; Bin, Ping; Kim, Christopher; Bassig, Bryan A; Hosgood, H Dean; Silverman, Debra; Zheng, Yuxin; Rothman, Nathaniel

    2015-01-01

    BACKGROUND: The International Agency for Research on Cancer recently classified diesel engine exhaust (DEE) as a Group I carcinogen based largely on its association with lung cancer. However, the exposure-response relationship is still a subject of debate and the underlying mechanism by which DEE ca

  17. Perturbations of Monocyte Subsets and Their Association with T Helper Cell Differentiation in Acute and Chronic HIV-1-Infected Patients

    Science.gov (United States)

    Chen, Peng; Su, Bin; Zhang, Tong; Zhu, Xiaojing; Xia, Wei; Fu, Yan; Zhao, Guoxian; Xia, Huan; Dai, Lili; Sun, Lijun; Liu, Lifeng; Wu, Hao

    2017-01-01

    Monocytes have been recently subdivided into three subsets: classical (CD14++CD16−), intermediate (CD14++CD16+), and non-classical (CD14+CD16++) subsets, but phenotypic and functional abnormalities of the three monocyte subsets in HIV-1 infection have not been fully characterized, especially in acute HIV-1 infection (AHI). In the study, we explored the dynamic changes of monocyte subsets and their surface markers, and the association between monocyte subsets and the IFN-γ, interleukin (IL)-4, IL-17, and TNF-α producing CD4+ T cells in acute and chronic HIV-1-infected patients. We found that, in the acute HIV-1-infected individuals, the frequency of the intermediate CD14++CD16+ monocyte subsets, the CD163 density and HLA-DR density on intermediate CD14++CD16+ monocytes, and plasma soluble form of CD163 (sCD163) were significantly higher than that in healthy controls. Intermediate CD14++CD16+ monocyte subsets and their HLA-DR expression levels were inversely correlated with the CD4+ T cell counts, and the intermediate CD14++CD16+ monocytes were positively correlated with plasma sCD163. In contrast to the non-classical CD14+CD16++ and classical CD14++CD16− monocyte subsets, the frequency of the intermediate CD14++CD16+ monocytes was positively associated with the frequency of IFN-γ and IL-4 producing CD4+ T cells in HIV-1-infected patients. Taken together, our observations provide new insight into the roles of the monocyte subsets in HIV pathogenesis, particularly during AHI, and our findings may be helpful for the treatment of HIV-related immune activation.

  18. slan/M-DC8+ cells constitute a distinct subset of dendritic cells in human tonsils.

    Science.gov (United States)

    Micheletti, Alessandra; Finotti, Giulia; Calzetti, Federica; Lonardi, Silvia; Zoratti, Elisa; Bugatti, Mattia; Stefini, Stefania; Vermi, William; Cassatella, Marco A

    2016-01-05

    Human blood dendritic cells (DCs) include three main distinct subsets, namely the CD1c+ and CD141+ myeloid DCs (mDCs) and the CD303+ plasmacytoid DCs (pDCs). More recently, a population of slan/M-DC8+ cells, also known as "slanDCs", has been described in blood and detected even in inflamed secondary lymphoid organs and non-lymphoid tissues. Nevertheless, hallmarks of slan/M-DC8+ cells in tissues are poorly defined. Herein, we report a detailed characterization of the phenotype and function of slan/M-DC8+ cells present in human tonsils. We found that tonsil slan/M-DC8+ cells represent a unique DC cell population, distinct from their circulating counterpart and also from all other tonsil DC and monocyte/macrophage subsets. Phenotypically, slan/M-DC8+ cells in tonsils display a CD11c+HLA-DR+CD14+CD11bdim/negCD16dim/negCX3CR1dim/neg marker repertoire, while functionally they exhibit an efficient antigen presentation capacity and a constitutive secretion of TNFα. Notably, such DC phenotype and functions are substantially reproduced by culturing blood slan/M-DC8+ cells in tonsil-derived conditioned medium (TDCM), further supporting the hypothesis of a full DC-like differentiation program occurring within the tonsil microenvironment. Taken together, our data suggest that blood slan/M-DC8+ cells are immediate precursors of a previously unrecognizedcompetent DC subset in tonsils, and pave the way for further characterization of slan/M-DC8+ cells in other tissues.

  19. Impacts of parturition and body condition score on glucose uptake capacity of bovine monocyte subsets.

    Science.gov (United States)

    Eger, Melanie; Hussen, Jamal; Drong, Caroline; Meyer, Ulrich; von Soosten, Dirk; Frahm, Jana; Daenicke, Sven; Breves, Gerhard; Schuberth, Hans-Joachim

    2015-07-15

    The peripartal period of dairy cows is associated with a higher incidence of infectious diseases like mastitis or metritis, particularly in high-yielding animals. The onset of lactation induces a negative energy balance and a shift of glucose distribution toward the udder. Glucose is used as primary fuel by monocytes which give rise to macrophages, key cells in the defense against pathogens. The aim of this study was to analyze whether animals with high or low body condition score (BCS) differ in composition and glucose uptake capacities of bovine monocyte subsets. Blood samples were taken from 27 dairy cows starting 42 days before parturition until day 56 after parturition. The cows were allocated to two groups according to their BCS. A feeding regime was applied, in which the BCS high group received higher amounts of concentrate before parturition and concentrate feeding was more restricted in the BCS high group after parturition compared with the BCS low group, to promote postpartal lipolysis and enhance negative energy balance in the BCS high group. Blood cell counts of classical (cM), intermediate (intM) and nonclassical monocytes (ncM) were increased at day 7 after calving. In the BCS low group intM numbers were significantly higher compared to the BCS high group at day 7 after parturition. Within the BCS low group cows suffering from mastitis or metritis showed significantly higher numbers of cM, intM and ncM at day 7 after parturition. Classical monocytes and intM showed similar glucose uptake capacities while values for ncM were significantly lower. Compared with antepartal capacities and irrespective of BCS and postpartal mastitis or metritis, glucose uptake of all monocyte subsets decreased after parturition. In conclusion, whereas glucose uptake capacity of bovine monocyte subsets is altered by parturition, it is not linked to the energy supply of the animals or to postpartal infectious diseases.

  20. Comparative expression profiling of distinct T cell subsets undergoing oxidative stress.

    Directory of Open Access Journals (Sweden)

    Rudolf Lichtenfels

    Full Text Available The clinical outcome of adoptive T cell transfer-based immunotherapies is often limited due to different escape mechanisms established by tumors in order to evade the hosts' immune system. The establishment of an immunosuppressive micromilieu by tumor cells along with distinct subsets of tumor-infiltrating lymphocytes is often associated with oxidative stress that can affect antigen-specific memory/effector cytotoxic T cells thereby substantially reducing their frequency and functional activation. Therefore, protection of tumor-reactive cytotoxic T lymphocytes from oxidative stress may enhance the anti-tumor-directed immune response. In order to better define the key pathways/proteins involved in the response to oxidative stress a comparative 2-DE-based proteome analysis of naïve CD45RA(+ and their memory/effector CD45RO(+ T cell counterparts in the presence and absence of low dose hydrogen peroxide (H(2O(2 was performed in this pilot study. Based on the profiling data of these T cell subpopulations under the various conditions, a series of differentially expressed spots were defined, members thereof identified by mass spectrometry and subsequently classified according to their cellular function and localization. Representative targets responding to oxidative stress including proteins involved in signaling pathways, in regulating the cellular redox status as well as in shaping/maintaining the structural cell integrity were independently verified at the transcript and protein level under the same conditions in both T cell subsets. In conclusion the resulting profiling data describe complex, oxidative stress-induced, but not strictly concordant changes within the respective expression profiles of CD45RA(+ and CD45RO(+ T cells. Some of the differentially expressed genes/proteins might be further exploited as potential targets toward modulating the redox capacity of the distinct lymphocyte subsets thereby providing the basis for further studies

  1. Effect of T cell subset and inflammatory cytokine levels on prognosis in patients with pulmonary tuberculosis

    Institute of Scientific and Technical Information of China (English)

    Cheng-Zhou Wu; Yan-Qiao Wu

    2016-01-01

    Objective:To explore the effect of T cell subset and inflammatory cytokine levels on the prognosis in patients with pulmonary tuberculosis.Methods:A total of 72 patients confirmed with pulmonary tuberculosis who were admitted in our hospital from February, 2013 to February, 2015 were included in the study and served as the experiment group, among which 58 cases had active tuberculosis, and 14 cases had static tuberculosis; while 50 healthy individuals who came for physical examinations were served as the control group. The sputum bacteria before treatment and 6 months after treatment in the two groups were detected. The sputum negative conversion rate was recorded. The absorption of pulmonary lesions and the closure of tuberculosis cavity were examined. The immune cell function of T cell subset was detected again.Results: The peripheral blood CD3, CD4, CD8, and CD4/CD8 levels in the experiment group were significantly lower than those in the control group, especially for the active tuberculosis patients (P<0.01). The peripheral blood CD4/CD8 levels in the static tuberculosis patients was lower than that in the control group, but was significantly higher than that in active tuberculosis patients (P<0.01). The serum IL-1, IL-6, and TNF-α levels in the experiment group were significantly higher than those in the control group, especially for the active tuberculosis patients (P<0.01).Conclusions:The cell subsets and inflammatory cytokines play an important role in patients with pulmonary tuberculosis, whose dynamic change can effectively display the immune function and severity degree, which is of great value in estimating the condition and assessing the prognosis; therefore, it deserves to be further explored in the clinic.

  2. Inferences about nested subsets structure when not all species are detected

    Science.gov (United States)

    Cam, E.; Nichols, J.D.; Hines, J.E.; Sauer, J.R.

    2000-01-01

    Comparisons of species composition among ecological communities of different size have often provided evidence that the species in communities with lower species richness form nested subsets of the species in larger communities. In the vast majority of studies, the question of nested subsets has been addressed using information on presence-absence, where a '0' is interpreted as the absence of a given species from a given location. Most of the methodological discussion in earlier studies investigating nestedness concerns the approach to generation of model-based matrices. However, it is most likely that in many situations investigators cannot detect all the species present in the location sampled. The possibility that zeros in incidence matrices reflect nondetection rather than absence of species has not been considered in studies addressing nested subsets, even though the position of zeros in these matrices forms the basis of earlier inference methods. These sampling artifacts are likely to lead to erroneous conclusions about both variation over space in species richness and the degree of similarity of the various locations. Here we propose an approach to investigation of nestedness, based on statistical inference methods explicitly incorporating species detection probability, that take into account the probabilistic nature of the sampling process. We use presence-absence data collected under Pollock?s robust capture-recapture design, and resort to an estimator of species richness originally developed for closed populations to assess the proportion of species shared by different locations. We develop testable predictions corresponding to the null hypothesis of a nonnested pattern, and an alternative hypothesis of perfect nestedness. We also present an index for assessing the degree of nestedness of a system of ecological communities. We illustrate our approach using avian data from the North American Breeding Bird Survey collected in Florida Keys.

  3. Characterizing primary human microglia: A comparative study with myeloid subsets and culture models.

    Science.gov (United States)

    Melief, J; Sneeboer, M A M; Litjens, M; Ormel, P R; Palmen, S J M C; Huitinga, I; Kahn, R S; Hol, E M; de Witte, L D

    2016-11-01

    The biology of microglia has become subject to intense study, as they are widely recognized as crucial determinants of normal and pathologic brain functioning. While they are well studied in animal models, it is still strongly debated what specifies most accurately the phenotype and functioning of microglia in the human brain. In this study, we therefore isolated microglia from postmortem human brain tissue of corpus callosum (CC) and frontal cortex (CTX). The cells were phenotyped for a panel of typical microglia markers and genes involved in myeloid cell biology. Furthermore, their response to pro- and anti-inflammatory stimuli was assessed. The microglia were compared to key human myeloid cell subsets, including monocytes, monocyte-derived macrophages and monocyte-derived dendritic cells, and several commonly used microglial cell models. Protein and mRNA expression profiles partly differed between microglia isolated from CC and frontal cortex and were clearly distinct from other myeloid subsets. Microglia responded to both pro- (LPS or poly I:C) and anti-inflammatory (IL-4 or dexamethasone) stimuli. Interestingly, pro-inflammatory responses differed between microglia and monocyte-derived macrophages, as the former responded more strongly to poly I:C and the latter more strongly to LPS. Furthermore, we defined a large phenotypic discrepancy between primary human microglia and currently used microglial cell models and cell lines. In conclusion, we further delineated the unique and specific features that discriminate human microglia from other myeloid subsets, and we show that currently used cellular models only partly reflect the phenotype of primary human microglia. GLIA 2016;64:1857-1868.

  4. Lymphocyte subsets, dendritic cells and cytokine profiles in mice with melanoma treated with Uncaria tomentosa

    OpenAIRE

    Lozada-Requena, Iván; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú. EMINDES SAC (empresa de investigación y desarrollo en cáncer). Lima, Perú.; Núñez, César; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú. EMINDES SAC (empresa de investigación y desarrollo en cáncer). Lima, Perú.; Alvárez, Yubell; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú.; Kahn, Laura; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú.; Aguilar, José; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú.

    2015-01-01

    Objectives. To evaluate the immunomodulatory effect on lymphocyte subsets, dendritic cells (DC), Th1 / Th2 / Th17 and inflammatory cytokines on systemic level and/or in the tumor microenvironment of mice with or without melanoma. Materials and methods: Peripheral blood and/or primary tumors samples were obtained of mice with B16 melanoma treated or not with a hydroalcoholic extract of Uncaria tomentosa (UT) with 5.03% of pentacyclic oxindole alkaloids (UT-POA) obtained from the bark of the pl...

  5. Axial psoriatic arthritis: an intriguing clinical entity or a subset of an intriguing disease?

    Science.gov (United States)

    Lubrano, Ennio; Spadaro, Antonio

    2012-07-01

    This article summarizes the state of the art of axial involvement in psoriatic arthritis (axial PsA). The definition and measurement of axial disease in PsA still remain problematic, and this, in turn, could affect the best approach of recognition and treatment of this intriguing subset of the psoriatic disease. Axial PsA has been studied over the last few years looking at the difference in function and radiological finding compared to ankylosing spondylitis (AS), trying to differentiate it from a coincidental AS with psoriasis. Finally, this review has described the diagnosis and treatment of axial PsA reporting the data obtained from the literature.

  6. The multiple roles of monocyte subsets in steady state and inflammation.

    Science.gov (United States)

    Robbins, Clinton S; Swirski, Filip K

    2010-08-01

    Monocytes participate importantly in immunity. Produced in the bone marrow and released into the blood, they circulate in blood or reside in a spleen reservoir before entering tissue and giving rise to macrophages or dendritic cells. Monocytes are more than transitional cells that adapt to a particular tissue environment indiscriminately. Accumulating evidence now indicates that monocytes are heterogeneous in several species and are themselves predetermined for particular function in the steady state and inflammation. Future therapeutics may harness this heterogeneity to target harmful functions while sparing those that are beneficial. Here, we review recent advances on the ontogeny and function of monocytes and their subsets in humans and mice.

  7. On hyperbolicity and tautness modulo an analytic subset of Hartogs domains

    CERN Document Server

    Thai, Do Duc; Van Trao, Nguyen; Duc, Mai Anh

    2011-01-01

    Let $X$ be a complex space and $H$ a positive homogeneous plurisubharmonic function $H$ on $X\\times\\C^m$. Consider the Hartogs-type domain $\\Omega_{H}(X):=\\{(z,w)\\in X\\times \\C^m:H(z,w)<1 \\}$. Let $S$ be an analytic subset of $X$. We give necessary and sufficient conditions for hyperbolicity and tautness modulo $S\\times \\C^m$ of $\\Omega_{H}(X)$, with the obvious corollaries for the special case of Hartogs domains.

  8. Inflammation-Induced Changes in Circulating T-Cell Subsets and Cytokine Production During Human Endotoxemia

    DEFF Research Database (Denmark)

    Ronit, Andreas; Plovsing, Ronni R; Gaardbo, Julie C;

    2016-01-01

    -γ in response to phytohaemagglutinin but did not affect TLR4 expression on Tregs. No changes in the absolute count or frequency of BALF T cells were observed. Systemic inflammation is associated with lymphopenia, a relative increase in the frequency of anti-inflammatory Tregs, and a functional impairment of T......Observational clinical studies suggest the initial phase of sepsis may involve impaired cellular immunity. In the present study, we investigated temporal changes in T-cell subsets and T-cell cytokine production during human endotoxemia. Endotoxin (Escherichia coli lipopolysaccharide 4 ng...

  9. Comparison of some biased estimation methods (including ordinary subset regression) in the linear model

    Science.gov (United States)

    Sidik, S. M.

    1975-01-01

    Ridge, Marquardt's generalized inverse, shrunken, and principal components estimators are discussed in terms of the objectives of point estimation of parameters, estimation of the predictive regression function, and hypothesis testing. It is found that as the normal equations approach singularity, more consideration must be given to estimable functions of the parameters as opposed to estimation of the full parameter vector; that biased estimators all introduce constraints on the parameter space; that adoption of mean squared error as a criterion of goodness should be independent of the degree of singularity; and that ordinary least-squares subset regression is the best overall method.

  10. Generalized Contraction and Invariant Approximation Results on Nonconvex Subsets of Normed Spaces

    Directory of Open Access Journals (Sweden)

    Mujahid Abbas

    2014-01-01

    Full Text Available Wardowski (2012 introduced a new type of contractive mapping and proved a fixed point result in complete metric spaces as a generalization of Banach contraction principle. In this paper, we introduce a notion of generalized F-contraction mappings which is used to prove a fixed point result for generalized nonexpansive mappings on star-shaped subsets of normed linear spaces. Some theorems on invariant approximations in normed linear spaces are also deduced. Our results extend, unify, and generalize comparable results in the literature.

  11. Relationship between Various Chinese Medicine Types and T-cell Subsets in Patients with Ulcerative Colitis

    Institute of Scientific and Technical Information of China (English)

    常廷民; 李秀敏; 赵习德

    2009-01-01

    Objective:To investigate the relationship between various Chinese medicine(CM) types and T-cell subsets(CD4~+ and CD8~+) in the colonic mucous membranes of patients with ulcerative colitis(UC).Methods: Fifty UC patients were enrolled,after differentiation into four types by CM syndromes,i.e.,the internal heat-damp accumulation type(IHDA),the qi-stagnancy with blood stasis type(QSBS),the Pi(脾)-Shen(肾) yang-deficiency type(PSYD) and the yin-blood deficiency type(YBD).From every patient,3-5 pieces of intest...

  12. A weakly monotonic backward induction algorithm on finite bounded subsets of vector lattices

    Science.gov (United States)

    Dragut, A. B.

    2004-03-01

    We present a new efficient and robust backward induction algorithm, which is weakly monotonic, working on bounded subsets without holes of lattices. We prove all its properties, give examples of applications, and illustrate its behavior, comparing it with the natural extension of the unidimensional algorithm presented in Puterman (Markov Decision Processes: Discrete Stochastic Dynamic Programming, Wiley, New York, 1994), in the sense of Topkis (Frontiers of Economic Research Series, Princeton University Press, Princeton, NJ, 1998) and White (Recent Developments in Markov Decision Processes, Academic Press, New York, 1980, 261) and showing, also experimentally, that it is much more efficient.

  13. Ontogeny and characterization of blood leukocyte subsets and serum proteins in piglets before and after weaning

    DEFF Research Database (Denmark)

    Juul-Madsen, H.R.; Jensen, K.H.; Nielsen, Jens;

    2010-01-01

    Existing knowledge about the development of the porcine immune system was extended by phenotypic characterization of leukocyte subsets and with assessment of Mannan-Binding Lectin (MBL) and immunoglobulin concentrations in peripheral blood of healthy piglets. Single-color and/or double-color flow...... parameters seem to be affected at the time of weaning which took place at 45 weeks of age. Using principal component analysis, all analyzed variables - except one were grouped into 8 factors with distinct developmental profiles. Several of these factors revealed an apparent suppression, a steady state...

  14. Testing over-representation of observations in subsets of a DEA technology