31 results on '"Wingren, Anette Gjörloff"'
Search Results
2. Fluorescent Molecularly Imprinted Polymer Layers against Sialic Acid on Silica-Coated Polystyrene Cores — Assessment of the Binding Behavior to Cancer Cells
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Beyer, Sarah, Kimani, Martha, Zhang, Yuecheng, Verhassel, Alejandra, Sternbæk, Louise, Wang, Tianyan, Persson, Jenny L., Härkönen, Pirkko, Johansson, Emil, Caraballo, Remi, Elofsson, Mikael, Gawlitza, Kornelia, Rurack, Knut, Ohlsson, Lars, El-Schich, Zahra, Wingren, Anette Gjörloff, and Stollenwerk, Maria M.
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sialic acid ,Cell- och molekylärbiologi ,Biochemistry and Molecular Biology ,SA conjugates ,cancer ,molecularly imprinted polymers ,imprinting ,Biokemi och molekylärbiologi ,Cell and Molecular Biology - Abstract
Sialic acid (SA) is a monosaccharide usually linked to the terminus of glycan chains on the cell surface. It plays a crucial role in many biological processes, and hypersialylation is a common feature in cancer. Lectins are widely used to analyze the cell surface expression of SA. However, these protein molecules are usually expensive and easily denatured, which calls for the development of alternative glycan-specific receptors and cell imaging technologies. In this study, SA-imprinted fluorescent core-shell molecularly imprinted polymer particles (SA-MIPs) were employed to recognize SA on the cell surface of cancer cell lines. The SA-MIPs improved suspensibility and scattering properties compared with previously used core-shell SA-MIPs. Although SA-imprinting was performed using SA without preference for the α2,3- and α2,6-SA forms, we screened the cancer cell lines analyzed using the lectins Maackia Amurensis Lectin I (MAL I, α2,3-SA) and Sambucus Nigra Lectin (SNA, α2,6-SA). Our results show that the selected cancer cell lines in this study presented a varied binding behavior with the SA-MIPs. The binding pattern of the lectins was also demonstrated. Moreover, two different pentavalent SA conjugates were used to inhibit the binding of the SA-MIPs to breast, skin, and lung cancer cell lines, demonstrating the specificity of the SA-MIPs in both flow cytometry and confocal fluorescence microscopy. We concluded that the synthesized SA-MIPs might be a powerful future tool in the diagnostic analysis of various cancer cells.
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- 2022
3. Circulating Tumor Cell Models Mimicking Metastasizing Cells In Vitro: Discrimination of Colorectal Cancer Cells and White Blood Cells Using Digital Holographic Cytometry.
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Feith, Marek, Zhang, Yuecheng, Persson, Jenny L., Balvan, Jan, El-Schich, Zahra, and Wingren, Anette Gjörloff
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COLORECTAL cancer ,MONONUCLEAR leukocytes ,CYTOMETRY ,CELL size ,METASTASIS - Abstract
Colorectal cancer (CRC) is the second most metastatic disease with the majority of cases detected in Western countries. Metastases are formed by circulating altered phenotype tumor cells causing 20% of CRC related deaths. Metastatic cells may show higher expression of surface molecules such as CD44, and changes in morphological properties are associated with increased invasiveness and poor prognosis. In this study, we intended to mimic the environment for metastasizing cells. Here, we used digital holographic cytometry (DHC) analysis to determine cellular morphological properties of three metastatic and two non-metastatic colorectal cancer cell lines to show differences in morphology between the CRC cells and peripheral blood mononuclear cells (PBMCs). By establishing differences in cell area, cell thickness, cell volume, and cell irregularity even when the CRC cells were in minority (5% out of PBMCs), DHC does discriminate between CRC cells and the PBMCs in vitro. We also analyzed the epithelial marker EpCAM and migration marker CD44 using flow cytometry and demonstrate that the CRC cell lines and PBMC cells differ in EpCAM and CD44 expression. Here, we present DHC as a new powerful tool in discriminating cells of different sizes in suspension together with a combination of biomarkers. [ABSTRACT FROM AUTHOR]
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- 2022
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4. K-RAS Associated Gene-Mutation-Based Algorithm for Prediction of Treatment Response of Patients with Subtypes of Breast Cancer and Especially Triple-Negative Cancer.
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Johnson, Heather, Ali, Amjad, Zhang, Xuhui, Wang, Tianyan, Simoulis, Athanasios, Wingren, Anette Gjörloff, and Persson, Jenny L.
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DRUG efficacy ,STATISTICS ,GENETIC mutation ,CONFIDENCE intervals ,ONCOGENES ,CANCER chemotherapy ,MULTIVARIATE analysis ,MACHINE learning ,RANDOM forest algorithms ,CANCER patients ,DESCRIPTIVE statistics ,KAPLAN-Meier estimator ,PREDICTION models ,TUMOR markers ,DECISION making in clinical medicine ,PREDICTIVE validity ,LOGISTIC regression analysis ,PROGRESSION-free survival ,BREAST tumors ,ALGORITHMS ,LONGITUDINAL method ,PROPORTIONAL hazards models ,EVALUATION - Abstract
Simple Summary: Despite advances in treatment of subtypes of breast cancer, there still lacks reliable biomarkers with precision to predict treatment response at diagnosis. We used machine-learning tools and developed and validated a novel 12-Gene Algorithm as a biomarker for prediction of treatment response for breast cancer patients, especially those suffering triple-negative cancer. The 12-Gene Algorithm based on KRAS-associated gene-mutation profiles showed high accuracy at predicting the response of breast cancer patients including triple-negative subtype to first-line chemotherapy treatment in two independent patient cohorts. Our study suggests that the 12-Gene Algorithm has a potential to be used in clinical practice to improve breast cancer treatment decision-making, especially for triple-negative breast cancer patients. Purpose: There is an urgent need for developing new biomarker tools to accurately predict treatment response of breast cancer, especially the deadly triple-negative breast cancer. We aimed to develop gene-mutation-based machine learning (ML) algorithms as biomarker classifiers to predict treatment response of first-line chemotherapy with high precision. Methods: Random Forest ML was applied to screen the algorithms of various combinations of gene mutation profiles of primary tumors at diagnosis using a TCGA Cohort (n = 399) with up to 150 months follow-up as a training set and validated in a MSK Cohort (n = 807) with up to 220 months follow-up. Subtypes of breast cancer including triple-negative and luminal A (ER+, PR+ and HER2−) were also assessed. The predictive performance of the candidate algorithms as classifiers was further assessed using logistic regression, Kaplan–Meier progression-free survival (PFS) plot, and univariate/multivariate Cox proportional hazard regression analyses. Results: A novel algorithm termed the 12-Gene Algorithm based on mutation profiles of KRAS, PIK3CA, MAP3K1, MAP2K4, PTEN, TP53, CDH1, GATA3, KMT2C, ARID1A, RunX1, and ESR1, was identified. The performance of this algorithm to distinguish non-progressed (responder) vs. progressed (non-responder) to treatment in the TCGA Cohort as determined using AUC was 0.96 (95% CI 0.94–0.98). It predicted progression-free survival (PFS) with hazard ratio (HR) of 21.6 (95% CI 11.3–41.5) (p < 0.0001) in all patients. The algorithm predicted PFS in the triple-negative subgroup with HR of 19.3 (95% CI 3.7–101.3) (n = 42, p = 0.000). The 12-Gene Algorithm was validated in the MSK Cohort with a similar AUC of 0.97 (95% CI 0.96–0.98) to distinguish responder vs. non-responder patients, and had a HR of 18.6 (95% CI 4.4–79.2) to predict PFS in the triple-negative subgroup (n = 75, p < 0.0001). Conclusions: The novel 12-Gene algorithm based on multitude gene-mutation profiles identified through ML has a potential to predict breast cancer treatment response to therapies, especially in triple-negative subgroups patients, which may assist personalized therapies and reduce mortality. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Sialic Acid as a Biomarker Studied in Breast Cancer Cell Lines In Vitro Using Fluorescent Molecularly Imprinted Polymers
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El-Schich, Zahra, Zhang, Yuecheng, Göransson, Tommy, Dizeyi, Nishtman, Persson, Jenny L., Johansson, Emil, Caraballo, Remi, Elofsson, Mikael, Shinde, Sudhirkumar, Sellergren, Börje, and Wingren, Anette Gjörloff
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lcsh:T ,Cell- och molekylärbiologi ,lcsh:Technology ,Sialic acid ,lcsh:QC1-999 ,Analytical Chemistry ,lcsh:Chemistry ,Breast cancer ,breast cancer ,Epithelial cell adhesion molecule ,lcsh:Biology (General) ,lcsh:QD1-999 ,sialic acid ,lcsh:TA1-2040 ,Molecularly imprinted polymers ,Analytisk kemi ,Nanoparticles ,molecularly imprinted polymers ,nanoparticles ,epithelial cell adhesion molecule ,lcsh:Engineering (General). Civil engineering (General) ,lcsh:QH301-705.5 ,Cell and Molecular Biology ,lcsh:Physics - Abstract
Sialylations are post-translational modifications of proteins and lipids that play important roles in many cellular events, including cell-cell interactions, proliferation, and migration. Tumor cells express high levels of sialic acid (SA), which are often associated with the increased invasive potential in clinical tumors, correlating with poor prognosis. To overcome the lack of natural SA-receptors, such as antibodies and lectins with high enough specificity and sensitivity, we have used molecularly imprinted polymers (MIPs), or “plastic antibodies”, as nanoprobes. Because high expression of epithelial cell adhesion molecule (EpCAM) in primary tumors is often associated with proliferation and a more aggressive phenotype, the expression of EpCAM and CD44 was initially analyzed. The SA-MIPs were used for the detection of SA on the cell surface of breast cancer cells. Lectins that specifically bind to the a-2,3 SA and a-2,6 SA variants were used for analysis of SA expression, with both flow cytometry and confocal microscopy. Here we show a correlation of EpCAM and SA expression when using the SA-MIPs for detection of SA. We also demonstrate the binding pattern of the SA-MIPs on the breast cancer cell lines using confocal microscopy. Pre-incubation of the SA-MIPs with SA-derivatives as inhibitors could reduce the binding of the SA-MIPs to the tumor cells, indicating the specificity of the SA-MIPs. In conclusion, the SA-MIPs may be a new powerful tool in the diagnostic analysis of breast cancer cells.
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- 2021
6. Low expression of SHP-2 is associated with less favorable prostate cancer outcomes
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Tassidis, Helena, Brokken, Leon J. S., Jirström, Karin, Bjartell, Anders, Ulmert, David, Härkönen, Pirkko, and Wingren, Anette Gjörloff
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- 2013
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7. Molecularly Imprinted Polymers Exhibit Low Cytotoxic and Inflammatory Properties in Macrophages In Vitro.
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Sternbæk, Louise, Kimani, Martha, Gawlitza, Kornelia, Rurack, Knut, Janicke, Birgit, Alm, Kersti, Wingren, Anette Gjörloff, and Eriksson, Håkan
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IMPRINTED polymers ,CANCER cells ,SIALIC acids ,FLOW cytometry ,IMMUNE system ,MACROPHAGES ,CELL division - Abstract
Molecularly imprinted polymers (MIPs) against sialic acid (SA) have been developed as a detection tool to target cancer cells. Before proceeding to in vivo studies, a better knowledge of the overall effects of MIPs on the innate immune system is needed. The aim of this study thus was to exemplarily assess whether SA-MIPs lead to inflammatory and/or cytotoxic responses when administered to phagocytosing cells in the innate immune system. The response of monocytic/macrophage cell lines to two different reference particles, Alhydrogel and PLGA, was compared to their response to SA-MIPs. In vitro culture showed a cellular association of SA-MIPs and Alhydrogel, as analyzed by flow cytometry. The reference particle Alhydrogel induced secretion of IL-1β from the monocytic cell line THP-1, whereas almost no secretion was provoked for SA-MIPs. A reduced number of both THP-1 and RAW 264.7 cells were observed after incubation with SA-MIPs and this was not caused by cytotoxicity. Digital holographic cytometry showed that SA-MIP treatment affected cell division, with much fewer cells dividing. Thus, the reduced number of cells after SA-MIP treatment was not linked to SA-MIPs cytotoxicity. In conclusion, SA-MIPs have a low degree of inflammatory properties, are not cytotoxic, and can be applicable for future in vivo studies. [ABSTRACT FROM AUTHOR]
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- 2022
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8. Gene-Mutation-Based Algorithm for Prediction of Treatment Response in Colorectal Cancer Patients.
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Johnson, Heather, El-Schich, Zahra, Ali, Amjad, Zhang, Xuhui, Simoulis, Athanasios, Wingren, Anette Gjörloff, and Persson, Jenny L.
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BIOMARKERS ,DISEASE progression ,GENETIC mutation ,RANDOM forest algorithms ,MACHINE learning ,COLORECTAL cancer ,CANCER patients ,GENES ,LOGISTIC regression analysis ,PROGRESSION-free survival ,ALGORITHMS ,PROPORTIONAL hazards models - Abstract
Simple Summary: Despite the high incidence and mortality of metastatic colorectal cancer (mCRC), there are no new biomarker tools available for predicting treatment response at diagnosis. We used machine learning using gene mutations from primary tumors of patients and developed a new biomarker model termed a 7-Gene Algorithm. We showed that this algorithm can be used as a biomarker classifier to predict treatment response with better precision than the current predictive factors. The 7-Gene Algorithm showed high accuracy to predict treatment response for patients suffering mCRC. The novel 7-Gene Algorithm can be further developed as a biomarker model for improvement of personalized therapies. Purpose: Despite the high mortality of metastatic colorectal cancer (mCRC), no new biomarker tools are available for predicting treatment response. We developed gene-mutation-based algorithms as a biomarker classifier to predict treatment response with better precision than the current predictive factors. Methods: Random forest machine learning (ML) was applied to identify the candidate algorithms using the MSK Cohort (n = 471) as a training set and validated in the TCGA Cohort (n = 221). Logistic regression, progression-free survival (PFS), and univariate/multivariate Cox proportional hazard analyses were performed and the performance of the candidate algorithms was compared with the established risk parameters. Results: A novel 7-Gene Algorithm based on mutation profiles of seven KRAS-associated genes was identified. The algorithm was able to distinguish non-progressed (responder) vs. progressed (non-responder) patients with AUC of 0.97 and had predictive power for PFS with a hazard ratio (HR) of 16.9 (p < 0.001) in the MSK cohort. The predictive power of this algorithm for PFS was more pronounced in mCRC (HR = 16.9, p < 0.001, n = 388). Similarly, in the TCGA validation cohort, the algorithm had AUC of 0.98 and a significant predictive power for PFS (p < 0.001). Conclusion: The novel 7-Gene Algorithm can be further developed as a biomarker model for prediction of treatment response in mCRC patients to improve personalized therapies. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Role of the protein tyrosine phosphatase SHP-1 in Interleukin-6 regulation of prostate cancer cells
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Tassidis, Helena, Culig, Zoran, Wingren, Anette Gjörloff, and Härkönen, Pirkko
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- 2010
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10. Immunohistochemical detection of tyrosine phosphatase SHP-1 predicts outcome after radical prostatectomy for localized prostate cancer
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Tassidis, Helena, Brokken, Leon J.S., Jirström, Karin, Ehrnström, Roy, Pontén, Fredrik, Ulmert, David, Bjartell, Anders, Härkönen, Pirkko, and Wingren, Anette Gjörloff
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- 2010
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11. Gene transfer of a hybrid interleukin-1β gene to B16 mouse melanoma recruits leucocyte subsets and reduces tumour growth in vivo
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Björkdahl, Olle, Wingren, Anette Gjörloff, Hedlund, Gunnar, Ohlsson, Lennart, and Dohlsten, M.
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- 1997
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12. An Epitope-Imprinted Biointerface with Dynamic Bioactivity for Modulating Cell-Biomaterial Interactions.
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Pan, Guoqing, Shinde, Sudhirkumar, Yeung, Sing Yee, Jakštaitė, Miglė, Li, Qianjin, Wingren, Anette Gjörloff, and Sellergren, Börje
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EPITOPES ,BIOLOGICAL interfaces ,BIOACTIVE compounds ,BIOMATERIALS ,CELL adhesion ,LIGANDS (Chemistry) - Abstract
In this study, an epitope-imprinting strategy was employed for the dynamic display of bioactive ligands on a material interface. An imprinted surface was initially designed to exhibit specific affinity towards a short peptide (i.e., the epitope). This surface was subsequently used to anchor an epitope-tagged cell-adhesive peptide ligand (RGD: Arg-Gly-Asp). Owing to reversible epitope-binding affinity, ligand presentation and thereby cell adhesion could be controlled. As compared to current strategies for the fabrication of dynamic biointerfaces, for example, through reversible covalent or host-guest interactions, such a molecularly tunable dynamic system based on a surface-imprinting process may unlock new applications in in situ cell biology, diagnostics, and regenerative medicine. [ABSTRACT FROM AUTHOR]
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- 2017
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13. Moving into a new dimension: Tracking migrating cells with digital holographic cytometry in 3D.
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Wingren, Anette Gjörloff
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- 2019
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14. Sialic Acid-Imprinted Fluorescent Core-Shell Particles for Selective Labeling of Cell Surface Glycans.
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Shinde, Sudhirkumar, El-Schich, Zahra, Malakpour, Atena, Wan, Wei, Dizeyi, Nishtman, Mohammadi, Reza, Rurack, Knut, Wingren, Anette Gjörloff, and Sellergren, Börje
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- 2015
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15. Cyclin A1 regulates the interactions between mouse haematopoietic stem and progenitor cells and their niches.
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Miftakhova, Regina, Hedblom, Andreas, Batkiewicz, Leah, Anagnosaki, Lola, Zhang, Yuan, Sjölander, Anita, Wingren, Anette Gjörloff, Wolgemuth, Debra J, and Persson, Jenny L
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- 2015
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16. EXPRESSION OF PTEN AND SHP1, INVESTIGATED FROM TISSUE MICROARRAYS IN PEDIATRIC ACUTE LYMPHOBLASTIC, LEUKEMIA.
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Gauffin, Fredrika, Diffner, Eva, Gustafsson, Bertil, Nordgren, Ann, Wingren, Anette Gjörloff, Sander, Birgitta, Persson, Jenny Liao, and Gustafsson, Britt
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LYMPHOBLASTIC leukemia in children ,APOPTOSIS ,IMMUNOHISTOCHEMISTRY ,CELL cycle ,LYMPHOPROLIFERATIVE disorders ,CLINICAL trials - Abstract
PTEN and SHP1 are tumor suppressor genes involved in the regulation of cell cycle control and apoptosis. The authors investigated the protein expression of PTEN and SHP1, by immunohistochemistry in tissue microarrays from bone marrow samples in children, diagnosed with acute lymphoblastic leukaemia and nonmalignant controls. PTEN was overexpressed in diagnostic ALL samples, while SHP1 showed a low expression. Both proteins showed a significant difference in expression compared to nonmalignant controls. The roles of PTEN and SHP1 are not well investigated in pediatric leukemia and could in the future play a role as prognostic factors. [ABSTRACT FROM AUTHOR]
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- 2009
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17. IMMUNOHISTOCHEMICAL ANALYSES OF PHOSPHATASES IN CHILDHOOD B-CELL LYMPHOMA: Lower Expression of PTEN and HePTP and Higher Number of Positive Cells for Nuclear SHP2 in B-Cell Lymphoma Cases Compared to Controls.
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Fridberg, Marie, Kjellström, Sofia, Anagnostaki, Lola, Skogvall, Ingela, Mustelin, Tomas, Wiebe, Thomas, Persson, Jenny L., Dictor, Michael, and Wingren, Anette Gjörloff
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IMMUNOHISTOCHEMISTRY ,LYMPHOMAS in children ,B cell lymphoma ,PHOSPHATASES ,CELL differentiation - Abstract
Although many pediatric B-cell lymphoma patients are being cured today, much is still unknown about the pathogenesis of this disease. Protein tyrosine phosphatases are involved in the control of survival, growth, and differentiation of cells. The authors have analyzed 26 pediatric B-cell lymphoma cases for the expression of a panel of phosphatases and report a statistically significant lower expression intensity of PTEN and HePTP and higher nuclear SHP2 expression in B-cell lymphoma cases compared to lymphoid tissue. Knowledge about the expression of key regulatory proteins in pediatric B-cell lymphomas is necessary for revealing the complex molecular background of this disease. [ABSTRACT FROM AUTHOR]
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- 2008
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18. Protein expression and cellular localization in two prognostic subgroups of diffuse large B-cell lymphoma: Higher expression of ZAP70 and PKC-β II in the non-germinal center group and poor survival in patients deficient in nuclear PTEN.
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Fridberg, Marie, Servin, Anna, Anagnostaki, Lola, Linderoth, Johan, Berglund, Mattias, Söderberg, Ola, Enblad, Gunilla, Rosén, Anders, Mustelin, Tomas, Jerkeman, Mats, Persson, Jenny L., and Wingren, Anette Gjörloff
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LYMPHOMAS ,B cell lymphoma ,PHOSPHATASES ,GERMINAL centers ,PROTEIN kinase C - Abstract
Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) show varying responses to conventional therapy, and this might be contributed to the differentiation stage of the tumor B-cells. The aim of the current study was to evaluate a panel of kinases (ZAP70, PKC-β I and II and phosphorylated PKB/Akt) and phosphatases (PTEN, SHP1 and SHP2) known to be frequently deregulated in lymphoid malignancies. De novo DLBCL cases were divided into two subgroups, the germinal center (GC) group (14/28) and the non-germinal center (non-GC) or activated B-cell (ABC) group (14/28). ZAP70 and PKC-β II were expressed in a significantly higher percentage of tumor cells in the clinically more aggressive non-GC group compared with the prognostically favourable GC group. Also, the subcellular localization of PKC-β I and II differed in DLBCL cells, with the PKC-β I isoform being expressed in both the cytoplasm and nucleus, while PKC-β II was found exclusively in the cytoplasm. Loss of nuclear PTEN correlated with poor survival in cases from both subgroups. In addition, five cell lines of DLBCL origin were analyzed for protein expression and for mRNA levels of PTEN and SHP1. For the first time, we show that ZAP70 is expressed in a higher percentage of tumor cells in the aggressive non-GC subgroup of DLBCL and that PKC-β I and II are differently distributed in the two prognostic subgroups of de novo DLBCL. [ABSTRACT FROM AUTHOR]
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- 2007
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19. Establishment of a cell line from a chemotherapy resistant diffuse large B-cell lymphoma.
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Berglund, Mattias, Thunberg, Ulf, Fridberg, Marie, Wingren, Anette Gjörloff, Gullbo, Joachim, Leuchowius, Karl-Johan, Amini, Rose-Marie, Lagercrantz, Svetlana, Horvat, Andrea, Enblad, Gunilla, and Söderberg, Ola
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LETTERS to the editor ,LYMPHOMAS - Abstract
A letter to the editor is presented that discusses a study which establishes and characterizes a cell line from a patient with diffuse large B-cell lymphomas (DLBCL) that showed multi-drug resistance.
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- 2007
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20. Inside Back Cover: An Epitope-Imprinted Biointerface with Dynamic Bioactivity for Modulating Cell-Biomaterial Interactions (Angew. Chem. Int. Ed. 50/2017).
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Pan, Guoqing, Shinde, Sudhirkumar, Yeung, Sing Yee, Jakštaitė, Miglė, Li, Qianjin, Wingren, Anette Gjörloff, and Sellergren, Börje
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EPITOPES ,BIOLOGICAL interfaces ,BIOMATERIALS - Abstract
Molecularly imprinted synthetic receptors are approaching the perfection of natural receptors! In their Communication on page 15959, G. Pan, B. Sellergren, and co‐workers report an epitope imprinting strategy for reversible anchoring of the cell‐adhesive peptide RGD to give controllable cell‐adhesion behavior. [ABSTRACT FROM AUTHOR]
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- 2017
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21. Innenrücktitelbild: An Epitope-Imprinted Biointerface with Dynamic Bioactivity for Modulating Cell-Biomaterial Interactions (Angew. Chem. 50/2017).
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Pan, Guoqing, Shinde, Sudhirkumar, Yeung, Sing Yee, Jakštaitė, Miglė, Li, Qianjin, Wingren, Anette Gjörloff, and Sellergren, Börje
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Molekular geprägte synthetische Rezeptoren erreichen die Perfektion natürlicher Rezeptoren! In ihrer Zuschrift auf S. 16175 berichten G. Pan, B. Sellergren und Mitarbeiter über eine Methode der Epitop‐Prägung zur reversiblen Verankerung des Zelladhäsionspeptids RGD und demonstrieren damit ein steuerbares Zelladhäsionsverhalten. [ABSTRACT FROM AUTHOR]
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- 2017
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22. α1-Antitrypsin inhibits Moraxella catarrhalis MID protein-induced tonsillar B cell proliferation and IL-6 release
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Hadzic, Radinka, Nita, Izabela, Tassidis, Helena, Riesbeck, Kristian, Wingren, Anette Gjörloff, and Janciauskiene, Sabina
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B cells , *CELL proliferation , *LYMPHOID tissue , *LYMPHOCYTES - Abstract
Abstract: α1-Antitrypsin (AAT) is a major circulating and tissues inhibitor of serine proteinases implicated in the regulation of inflammation and host defence. There is now increasing evidence that AAT may also exhibit anti-inflammatory activities independent of its protease inhibitor function. This study was undertaken to investigate the effects of native (inhibitory) and polymerized (non-inhibitory) forms of AAT on MID (Moraxella IgD binding protein)-induced human tonsillar B cell activation in vitro. We found that 0.5μg/ml MID induces B cell proliferation and stimulates IL-6 release (p <0.001) relative to non-stimulated controls. Both native and polymerized AAT (0.5mg/ml) inhibited MID-stimulated B cell proliferation in a similar manner (by 70%, p <0.001), whereas MID-induced IL-6 release was more strongly suppressed by polymerized (9.9-fold, p <0.001) as compared to native AAT (2.8-fold, p <0.01). Electrophoretic analysis of cell culture media did not indicate any interaction between AAT and MID, and flow cytometry data showed no competition for the same receptor. The effects of AATs were observed whether added together with MID or 2h after MID-addition to cell cultures. Thus, our data demonstrate that AAT inhibits MID-induced B cell activation in vitro that is unrelated to its protease inhibitory activity and is not dependent on MID binding to the cell surface. [Copyright &y& Elsevier]
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- 2006
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23. Reversible Self-Assembled Monolayers with Tunable Surface Dynamics for Controlling Cell Adhesion Behavior.
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Yeung SY, Sergeeva Y, Pan G, Mittler S, Ederth T, Dam T, Jönsson P, El-Schich Z, Wingren AG, Tillo A, Hsiung Mattisson S, Holmqvist B, Stollenwerk MM, and Sellergren B
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- Amidines, Cell Adhesion physiology, Ethylene Glycol chemistry, HEPES, Keto Acids, Oligopeptides, Sulfhydryl Compounds, Surface Properties, Biocompatible Materials pharmacology, Gold pharmacology
- Abstract
Cells adhering onto surfaces sense and respond to chemical and physical surface features. The control over cell adhesion behavior influences cell migration, proliferation, and differentiation, which are important considerations in biomaterial design for cell culture, tissue engineering, and regenerative medicine. Here, we report on a supramolecular-based approach to prepare reversible self-assembled monolayers (rSAMs) with tunable lateral mobility and dynamic control over surface composition to regulate cell adhesion behavior. These layers were prepared by incubating oxoacid-terminated thiol SAMs on gold in a pH 8 HEPES buffer solution containing different mole fractions of ω-(ethylene glycol)
2-4 - and ω-(GRGDS)-, α-benzamidino bolaamphiphiles. Cell shape and morphology were influenced by the strength of the interactions between the amidine-functionalized amphiphiles and the oxoacid of the underlying SAMs. Dynamic control over surface composition, achieved by the addition of inert filler amphiphiles to the RGD-functionalized rSAMs, reversed the cell adhesion process. In summary, rSAMs featuring mobile bioactive ligands offer unique capabilities to influence and control cell adhesion behavior, suggesting a broad use in biomaterial design, tissue engineering, and regenerative medicine.- Published
- 2022
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24. FcγRIIIa receptor interacts with androgen receptor and PIP5K1α to promote growth and metastasis of prostate cancer.
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Larsson PF, Karlsson R, Sarwar M, Miftakhova R, Wang T, Syed Khaja AS, Semenas J, Chen S, Hedblom A, Ali A, Ekström-Holka K, Simoulis A, Kumar A, Wingren AG, Robinson B, Nyunt Wai S, Mongan NP, Heery DM, Öhlund D, Grundström T, Ødum N, and Persson JL
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- Animals, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Humans, Male, Mice, Signal Transduction, Phosphotransferases (Alcohol Group Acceptor) metabolism, Prostatic Neoplasms pathology, Receptors, Androgen metabolism, Receptors, IgG metabolism
- Abstract
Low-affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa) is a cell surface protein that belongs to a family of Fc receptors that facilitate the protective function of the immune system against pathogens. However, the role of FcγRIIIa in prostate cancer (PCa) progression remained unknown. In this study, we found that FcγRIIIa expression was present in PCa cells and its level was significantly higher in metastatic lesions than in primary tumors from the PCa cohort (P = 0.006). PCa patients with an elevated level of FcγRIIIa expression had poorer biochemical recurrence (BCR)-free survival compared with those with lower FcγRIIIa expression, suggesting that FcγRIIIa is of clinical importance in PCa. We demonstrated that overexpression of FcγRIIIa increased the proliferative ability of PCa cell line C4-2 cells, which was accompanied by the upregulation of androgen receptor (AR) and phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), which are the key players in controlling PCa progression. Conversely, targeted inhibition of FcγRIIIa via siRNA-mediated knockdown or using its inhibitory antibody suppressed growth of xenograft PC-3 and PC-3M prostate tumors and reduced distant metastasis in xenograft mouse models. We further showed that elevated expression of AR enhanced FcγRIIIa expression, whereas inhibition of AR activity using enzalutamide led to a significant downregulation of FcγRIIIa protein expression. Similarly, inhibition of PIP5K1α decreased FcγRIIIa expression in PCa cells. FcγRIIIa physically interacted with PIP5K1α and AR via formation of protein-protein complexes, suggesting that FcγRIIIa is functionally associated with AR and PIP5K1α in PCa cells. Our study identified FcγRIIIa as an important factor in promoting PCa growth and invasion. Further, the elevated activation of FcγRIII and AR and PIP5K1α pathways may cooperatively promote PCa growth and invasion. Thus, FcγRIIIa may serve as a potential new target for improved treatment of metastatic and castration-resistant PCa., (© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
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- 2022
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25. Fluorescent Molecularly Imprinted Polymer Layers against Sialic Acid on Silica-Coated Polystyrene Cores-Assessment of the Binding Behavior to Cancer Cells.
- Author
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Beyer S, Kimani M, Zhang Y, Verhassel A, Sternbæk L, Wang T, Persson JL, Härkönen P, Johansson E, Caraballo R, Elofsson M, Gawlitza K, Rurack K, Ohlsson L, El-Schich Z, Wingren AG, and Stollenwerk MM
- Abstract
Sialic acid (SA) is a monosaccharide usually linked to the terminus of glycan chains on the cell surface. It plays a crucial role in many biological processes, and hypersialylation is a common feature in cancer. Lectins are widely used to analyze the cell surface expression of SA. However, these protein molecules are usually expensive and easily denatured, which calls for the development of alternative glycan-specific receptors and cell imaging technologies. In this study, SA-imprinted fluorescent core-shell molecularly imprinted polymer particles (SA-MIPs) were employed to recognize SA on the cell surface of cancer cell lines. The SA-MIPs improved suspensibility and scattering properties compared with previously used core-shell SA-MIPs. Although SA-imprinting was performed using SA without preference for the α2,3- and α2,6-SA forms, we screened the cancer cell lines analyzed using the lectins Maackia Amurensis Lectin I (MAL I, α2,3-SA) and Sambucus Nigra Lectin (SNA, α2,6-SA). Our results show that the selected cancer cell lines in this study presented a varied binding behavior with the SA-MIPs. The binding pattern of the lectins was also demonstrated. Moreover, two different pentavalent SA conjugates were used to inhibit the binding of the SA-MIPs to breast, skin, and lung cancer cell lines, demonstrating the specificity of the SA-MIPs in both flow cytometry and confocal fluorescence microscopy. We concluded that the synthesized SA-MIPs might be a powerful future tool in the diagnostic analysis of various cancer cells.
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- 2022
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26. Molecularly imprinted polymers in biological applications.
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El-Schich Z, Zhang Y, Feith M, Beyer S, Sternbæk L, Ohlsson L, Stollenwerk M, and Wingren AG
- Subjects
- Animals, Biomarkers analysis, Drug Delivery Systems, Molecularly Imprinted Polymers chemical synthesis, Neoplasms pathology, Polymerization, Molecularly Imprinted Polymers chemistry
- Abstract
Molecularly imprinted polymers (MIPs) are currently widely used and further developed for biological applications. The MIP synthesis procedure is a key process, and a wide variety of protocols exist. The templates that are used for imprinting vary from the smallest glycosylated glycan structures or even amino acids to whole proteins or bacteria. The low cost, quick preparation, stability and reproducibility have been highlighted as advantages of MIPs. The biological applications utilizing MIPs discussed here include enzyme-linked assays, sensors, in vivo applications, drug delivery, cancer diagnostics and more. Indeed, there are numerous examples of how MIPs can be used as recognition elements similar to natural antibodies.
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- 2020
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27. An Epitope-Imprinted Biointerface with Dynamic Bioactivity for Modulating Cell-Biomaterial Interactions.
- Author
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Pan G, Shinde S, Yeung SY, Jakštaitė M, Li Q, Wingren AG, and Sellergren B
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- 3T3 Cells, Animals, Cell Communication, Ligands, Mice, Molecular Structure, Surface Properties, Biocompatible Materials chemistry, Epitopes chemistry, Fibroblasts chemistry, Molecular Imprinting, Oligopeptides chemistry
- Abstract
In this study, an epitope-imprinting strategy was employed for the dynamic display of bioactive ligands on a material interface. An imprinted surface was initially designed to exhibit specific affinity towards a short peptide (i.e., the epitope). This surface was subsequently used to anchor an epitope-tagged cell-adhesive peptide ligand (RGD: Arg-Gly-Asp). Owing to reversible epitope-binding affinity, ligand presentation and thereby cell adhesion could be controlled. As compared to current strategies for the fabrication of dynamic biointerfaces, for example, through reversible covalent or host-guest interactions, such a molecularly tunable dynamic system based on a surface-imprinting process may unlock new applications in in situ cell biology, diagnostics, and regenerative medicine., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
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- 2017
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28. Different expression levels of glycans on leukemic cells-a novel screening method with molecularly imprinted polymers (MIP) targeting sialic acid.
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El-Schich Z, Abdullah M, Shinde S, Dizeyi N, Rosén A, Sellergren B, and Wingren AG
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- Fluorescence, Humans, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Tumor Cells, Cultured, Cell Membrane metabolism, High-Throughput Screening Assays methods, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Molecular Imprinting, N-Acetylneuraminic Acid chemistry, Polymers chemistry, Polysaccharides metabolism
- Abstract
Sialic acid (SA) is normally expressed on the cell membranes and is located at the terminal position of the sugar chains. SA plays an important role for regulation of the innate immunity, function as markers of the cells and can be recognized by a variety of receptors. Interestingly, the level of SA expression is increased on metastatic cancer cells. The availability of specific antibodies against SA is limited and, therefore, biomarker tools for detection of SA are lacking. We have recently presented a novel method for specific fluorescence labeling of SA molecular imprinted polymers (MIP). Here, we have performed an extended screening of SA expression by using SA-MIP and included four different chronic lymphocytic leukemia (CLL) cell lines, conveniently analyzed by flow cytometry and fluorescence microscopy. SA expression was detected in four cell lines at different levels, and the SA expression were verified with lectin-FITC. These results show that SA-MIP can be used as a plastic antibody for detection of SA using both flow cytometry and fluorescence microscopy. We suggest that SA-MIP can be used for screening of different tumor cells of various stages, including CLL cells.
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- 2016
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29. Interfacing antibody-based microarrays and digital holography enables label-free detection for loss of cell volume.
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El-Schich Z, Nilsson E, Gerdtsson AS, Wingren C, and Wingren AG
- Abstract
Background: We introduce the combination of digital holographic microscopy (DHM) and antibody microarrays as a powerful tool to measure morphological changes in specifically antibody-captured cells. The aim of the study was to develop DHM for analysis of cell death of etoposide-treated suspension cells., Results/methodology: We demonstrate that the cell number, mean area, thickness and volume were noninvasively measured by using DHM. The cell number was stable over time, but the two cell lines showed changes of cell area and cell irregularity after treatment. The cell volume in etoposide-treated cells was decreased, whereas untreated cells showed stable volume., Conclusion: Our results provide proof of concept for using DHM combined with antibody-based microarray technology for detecting morphological changes in captured cells., Competing Interests: Financial & competing interests disclosureThe authors would like to thank Malmö University, the Crafoord foundation, the Swedish Research Council (VR-NT) and The Cancer Foundation at Malmö University Hospital for support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.
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- 2015
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30. Protein expression and cellular localization in two prognostic subgroups of diffuse large B-cell lymphoma: higher expression of ZAP70 and PKC-beta II in the non-germinal center group and poor survival in patients deficient in nuclear PTEN.
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Fridberg M, Servin A, Anagnostaki L, Linderoth J, Berglund M, Söderberg O, Enblad G, Rosén A, Mustelin T, Jerkeman M, Persson JL, and Wingren AG
- Subjects
- Aged, Diagnosis-Related Groups, Female, Humans, Lymphoma, Large B-Cell, Diffuse classification, Lymphoma, Large B-Cell, Diffuse metabolism, Lymphoma, Large B-Cell, Diffuse mortality, Male, Prognosis, Protein Isoforms metabolism, Protein Kinase C beta, Survival Analysis, Tissue Array Analysis, Tissue Distribution, Tumor Cells, Cultured, Cell Nucleus metabolism, Germinal Center metabolism, Lymphoma, Large B-Cell, Diffuse diagnosis, PTEN Phosphohydrolase metabolism, Protein Kinase C metabolism, ZAP-70 Protein-Tyrosine Kinase metabolism
- Abstract
Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) show varying responses to conventional therapy, and this might be contributed to the differentiation stage of the tumor B-cells. The aim of the current study was to evaluate a panel of kinases (ZAP70, PKC-beta I and II and phosphorylated PKB/Akt) and phosphatases (PTEN, SHP1 and SHP2) known to be frequently deregulated in lymphoid malignancies. De novo DLBCL cases were divided into two subgroups, the germinal center (GC) group (14/28) and the non-germinal center (non-GC) or activated B-cell (ABC) group (14/28). ZAP70 and PKC-beta II were expressed in a significantly higher percentage of tumor cells in the clinically more aggressive non-GC group compared with the prognostically favourable GC group. Also, the subcellular localization of PKC-beta I and II differed in DLBCL cells, with the PKC-beta I isoform being expressed in both the cytoplasm and nucleus, while PKC-beta II was found exclusively in the cytoplasm. Loss of nuclear PTEN correlated with poor survival in cases from both subgroups. In addition, five cell lines of DLBCL origin were analyzed for protein expression and for mRNA levels of PTEN and SHP1. For the first time, we show that ZAP70 is expressed in a higher percentage of tumor cells in the aggressive non-GC subgroup of DLBCL and that PKC-beta I and II are differently distributed in the two prognostic subgroups of de novo DLBCL.
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- 2007
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31. Alpha1-antitrypsin inhibits Moraxella catarrhalis MID protein-induced tonsillar B cell proliferation and IL-6 release.
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Hadzic R, Nita I, Tassidis H, Riesbeck K, Wingren AG, and Janciauskiene S
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- Dose-Response Relationship, Drug, Humans, Interleukin-6 biosynthesis, Interleukin-6 metabolism, Palatine Tonsil cytology, Adhesins, Bacterial immunology, Adhesins, Bacterial pharmacology, B-Lymphocytes immunology, Cell Proliferation drug effects, Palatine Tonsil immunology, alpha 1-Antitrypsin pharmacology
- Abstract
Alpha1-antitrypsin (AAT) is a major circulating and tissues inhibitor of serine proteinases implicated in the regulation of inflammation and host defence. There is now increasing evidence that AAT may also exhibit anti-inflammatory activities independent of its protease inhibitor function. This study was undertaken to investigate the effects of native (inhibitory) and polymerized (non-inhibitory) forms of AAT on MID (Moraxella IgD binding protein)-induced human tonsillar B cell activation in vitro. We found that 0.5 microg/ml MID induces B cell proliferation and stimulates IL-6 release (p<0.001) relative to non-stimulated controls. Both native and polymerized AAT (0.5 mg/ml) inhibited MID-stimulated B cell proliferation in a similar manner (by 70%, p<0.001), whereas MID-induced IL-6 release was more strongly suppressed by polymerized (9.9-fold, p<0.001) as compared to native AAT (2.8-fold, p<0.01). Electrophoretic analysis of cell culture media did not indicate any interaction between AAT and MID, and flow cytometry data showed no competition for the same receptor. The effects of AATs were observed whether added together with MID or 2h after MID-addition to cell cultures. Thus, our data demonstrate that AAT inhibits MID-induced B cell activation in vitro that is unrelated to its protease inhibitory activity and is not dependent on MID binding to the cell surface.
- Published
- 2006
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