Publications by authors named "Bo Jansson"

31 Publications

A Graphene-Based Glycan Biosensor for Electrochemical Label-Free Detection of a Tumor-Associated Antibody.

Sensors (Basel) 2019 Dec 9;19(24). Epub 2019 Dec 9.

Department of Glycobiotechnology, Institute of Chemistry, Slovak Academy of Sciences, Dubravska cesta 9, 845 38 Bratislava, Slovakia.

The study describes development of a glycan biosensor for detection of a tumor-associated antibody. The glycan biosensor is built on an electrochemically activated/oxidized graphene screen-printed electrode (GSPE). Oxygen functionalities were subsequently applied for covalent immobilization of human serum albumin (HSA) as a natural nanoscaffold for covalent immobilization of Thomsen-nouvelle (Tn) antigen (GalNAc--Ser/Thr) to be fully available for affinity interaction with its analyte-a tumor-associated antibody. The step by step building process of glycan biosensor development was comprehensively characterized using a battery of techniques (scanning electron microscopy, atomic force microscopy, contact angle measurements, secondary ion mass spectrometry, surface plasmon resonance, Raman and energy-dispersive X-ray spectroscopy). Results suggest that electrochemical oxidation of graphene SPE preferentially oxidizes only the surface of graphene flakes within the graphene SPE. Optimization studies revealed the following optimal parameters: activation potential of +1.5 V Ag/AgCl/3 M KCl, activation time of 60 s and concentration of HSA of 0.1 g L. Finally, the glycan biosensor was built up able to selectively and sensitively detect its analyte down to low aM concentration. The binding preference of the glycan biosensor was in an agreement with independent surface plasmon resonance analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s19245409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960651PMC
December 2019

A novel monoclonal antibody targeting carboxymethyllysine, an advanced glycation end product in atherosclerosis and pancreatic cancer.

PLoS One 2018 8;13(2):e0191872. Epub 2018 Feb 8.

Chemical Glyco-Biology Laboratory, Department of Chemistry, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.

Advanced glycation end products are formed by non-enzymatic reactions between proteins and carbohydrates, causing irreversible lysine and arginine alterations that severely affect protein structure and function. The resulting modifications induce inflammation by binding to scavenger receptors. An increase in advanced glycation end products is observed in a number of diseases e.g. atherosclerosis and cancer. Since advanced glycation end products also are present in healthy individuals, their detection and quantification are of great importance for usage as potential biomarkers. Current methods for advanced glycation end product detection are though limited and solely measure total glycation. This study describes a new epitope-mapped single chain variable fragment, D1-B2, against carboxymethyllysine, produced from a phage library that was constructed from mouse immunizations. The phage library was selected against advanced glycation end product targets using a phage display platform. Characterization of its binding pattern was performed using large synthetic glycated peptide and protein libraries displayed on microarray slides. D1-B2 showed a preference for an aspartic acid, three positions N-terminally from a carboxymethyllysine residue and also bound to a broad collection of glycated proteins. Positive immunohistochemical staining of mouse atherosclerotic plaques and of a tissue microarray of human pancreatic tumors confirmed the usability of the new scFv for advanced glycation end product detection in tissues. This study demonstrates a promising methodology for high-throughput generation of epitope-mapped monoclonal antibodies against AGE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191872PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805250PMC
March 2018

Epitope mapping of a new anti-Tn antibody detecting gastric cancer cells.

Glycobiology 2017 07;27(7):635-645

Chemical Glyco-Biology Laboratory, Department of Chemistry, University of Copenhagen, 2100 Copenhagen, Denmark.

Here, we introduce a novel scFv antibody, G2-D11, specific for two adjacent Tn-antigens (GalNAc-Ser/Thr) binding equally to three dimeric forms of the epitope, Ser-Thr, Thr-Thr and Thr-Ser. Compared to other anti-Tn reagents, the binding of G2-D11 is minimally influenced by the peptide structure, which indicates a high degree of carbohydrate epitope dominance and a low influence from the protein backbone. With a high affinity (KDapp = 1.3 × 10-8 M) and no cross-reactivity to either sialyl-Tn epitope or blood group A antigens, scFv G2-D11 is an excellent candidate for a well-defined anti-Tn-antigen reagent. Detailed immunohistochemical evaluation of tissue sections from a cohort of 80 patients with gastric carcinoma showed in all cases positive tumor cells. The observed staining was localized to the cytoplasm and in some cases to the membrane, whereas the surrounding tissue was completely negative demonstrating the usefulness of the novel Tn-antigen binding antibody.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/glycob/cwx033DOI Listing
July 2017

Optimization of the Small Glycan Presentation for Binding a Tumor-Associated Antibody: Application to the Construction of an Ultrasensitive Glycan Biosensor.

Langmuir 2017 03 8;33(11):2709-2716. Epub 2017 Mar 8.

Department of Glycobiotechnology, Institute of Chemistry, Slovak Academy of Sciences , Dubravska cesta 9, 845 38 Bratislava, Slovakia.

The main aim of the study was to optimize the interfacial presentation of a small antigen-a Tn antigen (N-acetylgalactosamine)-for binding to its analyte anti-Tn antibody. Three different methods for the interfacial display of a small glycan are compared here, including two methods based on the immobilization of the Tn antigen on a mixed self-assembled monolayer (SAM) (2D biosensor) and the third one utilizing a layer of a human serum albumin (HSA) for the immobilization of a glycan forming a 3D interface. Results showed that the 3D interface with the immobilized Tn antigen is the most effective bioreceptive surface for binding its analyte. The 3D impedimetric glycan biosensor exhibited a limit of detection of 1.4 aM, a wide linear range (6 orders of magnitude), and high assay reproducibility with an average relative standard deviation of 4%. The buildup of an interface was optimized using various techniques with the visualization of the glycans on the biosensor surface by atomic force microscopy. The study showed that the 3D biosensor is not only the most sensitive compared to other two biosensor platforms but that the Tn antigen on the 3D biosensor surface is more accessible for antibody binding with better kinetics of binding (t = 137 s, t = the time needed to attain 50% of a steady-state signal) compared to the 2D biosensor configuration with t = 354 s. The 3D glycan biosensor was finally applied for the analysis of a human serum sample spiked with an analyte.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.langmuir.6b04021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659382PMC
March 2017

A Combinatory Antibody-Antigen Microarray Assay for High-Content Screening of Single-Chain Fragment Variable Clones from Recombinant Libraries.

PLoS One 2016 21;11(12):e0168761. Epub 2016 Dec 21.

Chemical Glyco-Biology Laboratory, Department of Chemistry, Copenhagen University, Copenhagen, Denmark.

We have developed a combinatory antibody-antigen microarray for direct screening of multiple single-chain fragment variable (scFv) clones with no need for pre-purification or enrichment before screening. The straightforward workflow allows for early selection of binders to predefined peptide and glycopeptide targets. A capture antibody is contact printed on microarray slides, side by side with the antigens of interest. A large number of scFv clones, in supernatants, are printed on top of the capture antibody and the antigen in a "spot-on-spot" print. The printed scFv clones, which bind to the capture antibody, are detected using biotinylated antigen, while the binding of scFv clones to the printed antigen is detected through a mouse anti-tag antibody. Two different analyses are thus performed on the same slide, generating two kinds of information: one on the ability of an individual scFv clone to bind to the soluble form of the antigen, which may favour selection for higher affinity rather than avidity, while the other allows the identification of large numbers of clones, simultaneously, due to the binding of scFv clones to densely presented antigens, thus providing an overall increased hit rate. The functionality of the new screening approach was illustrated through the generation of antibodies against peptides from the chaperone complex Ku70/Ku80 and the GalNAcα-serine/threonine epitope on the IgA1 alpha chain hinge region. In total, 659 scFv clones were screened with a hit rate of approximately 20%. This approach allowed the identification of functional antibodies in both cases, illustrating the usefulness and capacity of this combinatory microarray screening technique for efficient analysis and validation of antibodies at an early stage of antibody generation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168761PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5176327PMC
July 2017

Intra-tumour IgA1 is common in cancer and is correlated with poor prognosis in bladder cancer.

Heliyon 2016 Aug 16;2(8):e00143. Epub 2016 Aug 16.

Division of Oncology and Pathology, Dept. of Clinical Sciences Lund, Lund University, Lund, Sweden.

A high frequency of IgA1-positive tumour cells was found in tissue micro-arrays of oesophagus, colon, testis, lung, breast, bladder and ovarian cancer. IgA1 was observed in the cytoplasm and the plasma membrane. A correlation was found between intra-tumour IgA1 and poor overall survival in a large cohort of bladder cancer patients (n = 99, p = 0.011, log-rank test). The number of IgA1-positive tumour cells was also found to be higher in female than male bladder cancer patients. The presence of IgA1 was confirmed in formalin-fixed paraffin-embedded ovarian carcinoma samples using LC-MS/MS analysis. Uptake of IgA1 was also observed in breast cancer and melanoma cell lines when cultivated in the presence of serum from healthy individuals, indicating a possible origin of the IgA1 antibodies in cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heliyon.2016.e00143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992093PMC
August 2016

A protein deep sequencing evaluation of metastatic melanoma tissues.

PLoS One 2015 13;10(4):e0123661. Epub 2015 Apr 13.

Centre of Excellence in Biological and Medical Mass Spectrometry "CEBMMS", Biomedical Centre D13, Lund University, Lund, Sweden; Clinical Protein Science & Imaging, Biomedical Centre, Dept. of Biomedical Engineering, Lund University, Lund, Sweden; First Dept. of Surgery, Tokyo Medical University, Tokyo, Japan.

Malignant melanoma has the highest increase of incidence of malignancies in the western world. In early stages, front line therapy is surgical excision of the primary tumor. Metastatic disease has very limited possibilities for cure. Recently, several protein kinase inhibitors and immune modifiers have shown promising clinical results but drug resistance in metastasized melanoma remains a major problem. The need for routine clinical biomarkers to follow disease progression and treatment efficacy is high. The aim of the present study was to build a protein sequence database in metastatic melanoma, searching for novel, relevant biomarkers. Ten lymph node metastases (South-Swedish Malignant Melanoma Biobank) were subjected to global protein expression analysis using two proteomics approaches (with/without orthogonal fractionation). Fractionation produced higher numbers of protein identifications (4284). Combining both methods, 5326 unique proteins were identified (2641 proteins overlapping). Deep mining proteomics may contribute to the discovery of novel biomarkers for metastatic melanoma, for example dividing the samples into two metastatic melanoma "genomic subtypes", ("pigmentation" and "high immune") revealed several proteins showing differential levels of expression. In conclusion, the present study provides an initial version of a metastatic melanoma protein sequence database producing a total of more than 5000 unique protein identifications. The raw data have been deposited to the ProteomeXchange with identifiers PXD001724 and PXD001725.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123661PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395420PMC
January 2016

Cytokeratin 20 improves the detection of circulating tumor cells in patients with colorectal cancer.

Cancer Lett 2015 Mar 17;358(1):43-6. Epub 2014 Dec 17.

Department of Surgery and Urology, Office for Health Care Sund, Helsingborg Hospital, SE-251 87 Helsingborg, Sweden. Electronic address:

Cytokeratin 20 (CK20) is a well-established marker for colon epithelium. Herein, we suggest that CK20 is a biomarker for detecting circulating tumor cells (CTCs) in patients with metastatic colorectal cancer. Blood specimens (7.5 mL) were collected during surgery after liver mobilization from 25 patients with colorectal cancer. The FDA approved CellSearch™ system and two panels of antibodies against cytokeratins, cytokeratin 8, 18 and 19 (CK8/18/19) and CK8/18/19/20, were used for the detection of CTCs. All the patients' samples were processed using the anti-CK8/18/19 panel. The number of detected CTCs was low, 52% of the patients lacked CTCs and 40% had ≤ 2 CTCs/7.5 mL blood. Nine of the patients' blood samples were processed with both antibody panels. The detection rate of CTCs was significantly higher using the anti-CK8/18/19/20 panel compared with the anti-CK8/18/19 panel, p-value 0.0078. Our data show that inclusion of CK20 as a biomarker efficiently improves the detection of CTCs in colorectal cancer patients. The finding in our study is of clinical importance since a new prognostic biomarker would provide an important tool in individual clinical decision-making for colorectal cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2014.12.024DOI Listing
March 2015

Analysis of alpha-synuclein in malignant melanoma - development of a SRM quantification assay.

PLoS One 2014 21;9(10):e110804. Epub 2014 Oct 21.

Centre of Excellence in Biological and Medical Mass Spectrometry, Lund University, Lund, Sweden; Clinical Protein Science & Imaging, Biomedical Center, Biomedical Engineering, Lund University, Lund, Sweden; First Department of Surgery, Tokyo Medical University, Tokyo, Japan.

Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM) assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light) versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0110804PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204935PMC
December 2015

A new look at drugs targeting malignant melanoma--an application for mass spectrometry imaging.

Proteomics 2014 Sep 18;14(17-18):1963-70. Epub 2014 Aug 18.

Department of Oncology, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden.

Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors has been highly effective for certain subsets of MM patients. Vemurafenib, a protein kinase inhibitor targeting BRAF-mutated protein, has shown significant efficacy in slowing disease progression. In this paper, we provide an overview of this new generation of targeted drugs, and demonstrate the first data on localization of PM drugs within tumor compartments. In this study, we have introduced MALDI-MS imaging to provide new information on one of the drugs currently used in the PM treatment of MM, vemurafenib. In a proof-of-concept in vitro study, MALDI-MS imaging was used to identify vemurafenib applied to metastatic lymph nodes tumors of subjects attending the regional hospital network of Southern Sweden. The paper provides evidence of BRAF overexpression in tumors isolated from MM patients and localization of the specific drug targeting BRAF, vemurafenib, using MS fragment ion signatures. Our ability to determine drug uptake at the target sites of directed therapy provides important opportunity for increasing our understanding about the mode of action of drug activity within the disease environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pmic.201300476DOI Listing
September 2014

Preclinical evaluation of (111)In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer.

Am J Nucl Med Mol Imaging 2014 7;4(4):311-23. Epub 2014 Jun 7.

Division of Urological Cancers, Department of Clinical Sciences Malmö, Lund University Sweden.

The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the (111)In-labeled human internalizing antibody, INCA-X ((111)In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of (111)In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours post-injection of labeled DTPA-INCA-X. Biodistribution of the labeled antibody showed enriched activity in tumor, spleen and liver. Animals pre-administered with DTPA-INCA-X showed increased tumor uptake and blood content of (111)In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the (111)In-labeled INCA-X antibody is internalized into prostate cancer cells and by pre-administering non-labeled DTPA-INCA-X, we were able to significantly reduce the off target binding and increase the (111)In-DTPA-INCA-X mAb uptake in PC-3, PC-3M-Lu2 and DU145 xenografts. The results are encouraging and identifying the Ku70/Ku80 antigen as a target is worth further investigation for functional imaging of prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074497PMC
July 2014

Multi-radionuclide digital autoradiography of the intra-aortic atherosclerotic plaques using a monoclonal antibody targeting oxidized low-density lipoprotein.

Am J Nucl Med Mol Imaging 2014 20;4(2):172-80. Epub 2014 Mar 20.

Department of Medical Radiation Physics, Lund University Lund, Sweden.

The aim of this study was to use multi-radionuclide autoradiography to compare the different distributions of three radiolabelled tracers in an atherosclerotic mouse model. This method, along with immunohistochemistry, was applied to investigate the intra-aortic distribution of 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG), (131)I/(125)I labeled anti-oxidized Low Density Lipoprotein (oxLDL), and non-binding control antibodies. Aortas were isolated from a total of 12 apoB-100/LDL receptor deficient mice 73 h post injection of radioiodine-labeled anti-oxLDL and control antibody and 1 h post injection of (18)F-FDG. A solid-state real-time digital autoradiography system was used to image the slide mounted aortas. Contributions from each radionuclide were separated by half-life and emission energy and the aortas were subsequently stained with Oil Red O for plaque to aorta contrast ratios. Immunohistochemical staining was performed to detect anti-oxLDL and control antibody localization. Radiolabeled anti-oxLDL showed increased total activity uptake in the aorta over control antibody and immunohistochemical analysis of plaques indicated increased binding of the specific antibody compared to control. The intra-aortic activity distribution of the anti-oxLDL antibody was however very similar to that of the control antibody although both had higher atherosclerotic plaques to aorta wall ratios than (18)F-FDG. Given the right choice of radionuclides, multi-radionuclide digital autoradiography can be employed to compare several tracers ex vivo in the same animal. The distribution of anti-oxLDL antibodies did not significantly differ from the control antibody but it did appear to have a better plaque to aorta contrast at 73 h post injection than (18)F-FDG at 1 h post injection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992210PMC
April 2014

Feasibility study on measuring selected proteins in malignant melanoma tissue by SRM quantification.

J Proteome Res 2014 Mar 17;13(3):1315-26. Epub 2014 Feb 17.

Departments of †Oncology, ∥Surgery, and ⊥Cancer Epidemiology, Clinical Sciences, and ‡Centre of Excellence in Biological and Medical Mass Spectrometry, Lund University , 221 85 Lund, Sweden.

Currently there are no clinically recognized molecular biomarkers for malignant melanoma (MM) for either diagnosing disease stage or measuring response to therapy. The aim of this feasibility study was to develop targeted selected reaction monitoring (SRM) assays for identifying candidate protein biomarkers in metastatic melanoma tissue lysate. In a pilot study applying the SRM assay, the tissue expression of nine selected proteins [complement 3 (C3), T-cell surface glycoprotein CD3 epsilon chain E (CD3E), dermatopontin, minichromosome maintenance complex component (MCM4), premelanosome protein (PMEL), S100 calcium binding protein A8 (S100A8), S100 calcium binding protein A13 (S100A13), transgelin-2 and S100B] was quantified in a small cohort of metastatic malignant melanoma patients. The SRM assay was developed using a TSQ Vantage triple quadrupole mass spectrometer that generated highly accurate peptide quantification. Repeated injection of internal standards spiked into matrix showed relative standard deviation (RSD) from 6% to 15%. All nine target proteins were identified in tumor lysate digests spiked with heavy peptide standards. The multiplex SRM peptide assay panel was then measured and quantified on a set of frozen MM tissue samples obtained from the Malignant Melanoma Biobank collected in Lund, Sweden. All nine proteins could be accurately quantified using the new SRM assay format. This study provides preliminary data on the heterogeneity of biomarker expression within MM patients. The S100B protein, which is clinically used as the pathology identifier of MM, was identified in 9 out of 10 MM tissue lysates. The use of the targeted SRM assay provides potential advancements in the diagnosis of MM that can aid in future assessments of disease in melanoma patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/pr400876pDOI Listing
March 2014

Accessing microenvironment compartments in formalin-fixed paraffin-embedded tissues by protein expression analysis.

Bioanalysis 2013 Nov;5(21):2647-59

Clinical Protein Science & Imaging, Biomedical Center, Department of Measurement Technology & Industrial Electrical Engineering, Lund University, BMC C13, SE-221 84 Lund, Sweden.

Background: Formalin-fixed paraffin-embedded (FFPE) samples are an outstanding source of new information regarding disease evolvements. Current research on new biomarkers and diseases features has recently invested resources in FFPE-related projects.

Results: In order to initiate clinical protein-expression studies using minute amount of biological material, a workflow based on the combination of filter-assisted sample preparation with MS analysis and label-free quantification was developed. Xenograft lung tumor tissue was investigated as a model system. The workflow was optimized and characterized in terms of its reproducibility from a quantitative and qualitative point of view. We proposed a modification of the original filter-assisted sample preparation protocol to improve reproducibility and highlight its potential for the investigation of hydrophobic proteins.

Conclusions: Altogether the presented workflow allows analysis of FFPE samples with improvements in the analytical time and performance, and we show its application for lung cancer xenograft tissue samples.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4155/bio.13.222DOI Listing
November 2013

Experimental models to study drug distributions in tissue using MALDI mass spectrometry imaging.

J Proteome Res 2013 Dec 6;12(12):5626-33. Epub 2013 Nov 6.

Clinical Protein Science & Imaging, Biomedical Center, Department of Measurement Technology and Industrial Electrical Engineering, Lund University , BMC C13, SE-221 84 Lund, Sweden.

Requirements for patient safety and improved efficacy are steadily increasing in modern healthcare and are key drivers in modern drug development. New drug characterization assays are central in providing evidence of the specificity and selectivity of drugs. Meeting this need, matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) is used to study drug localization within microenvironmental tissue compartments. Thin sections of human lung tumor and rat xenograft tissues were exposed to pharmaceutical drugs by either spotting or submerging. These drugs, the epidermal growth factor receptor antagonists, erlotinib (Tarceva) and gefitinib (Iressa), and the acetylcholine receptor antagonist, tiotropium, were characterized by microenvironment localization. Intact tissue blocks were also immersed in drug solution, followed by sectioning. MALDI-MSI was then performed using a Thermo MALDI LTQ Orbitrap XL instrument to localize drug-distribution patterns. We propose three MALDI-MSI models measuring drug disposition that have been used to map the selected compounds within tissue compartments of tumors isolated from lung cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/pr400581bDOI Listing
December 2013

Primary breast cancer tumours contain high amounts of IgA1 immunoglobulin: an immunohistochemical analysis of a possible carrier of the tumour-associated Tn antigen.

PLoS One 2013 18;8(4):e61749. Epub 2013 Apr 18.

Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden.

The Tn antigen (GalNAc alpha-O-Ser/Thr) as defined by the binding of the lectin, helix pomatia agglutinin (HPA) or anti-Tn monoclonal antibodies, is known to be exposed in a majority of cancers, and it has also been shown to correlate positively with the metastatic capacity in breast carcinoma. The short O-glycan that forms the antigen is carried by a number of different proteins. One potential carrier of the Tn antigen is immunoglobulin A1 (IgA1), which we surprisingly found in tumour cells of the invasive parts of primary breast carcinoma. Conventional immunohistochemical analysis of paraffin-embedded sections from primary breast cancers showed IgA1 to be present in the cytoplasm and plasma membrane of 35 out of 36 individual primary tumours. The immunohistochemical staining of HPA and anti-Tn antibody (GOD3-2C4) did to some extent overlap with the presence of IgA1 in the tumours, but differences were seen in the percentage of stained cells and in the staining pattern in the different breast cancers analysed. Anti-Tn antibody and HPA were also shown to specifically bind to a number of possible constellations of the Tn antigen in the hinge region of IgA1. Both reagents could also detect the presence of Tn positive IgA in serum. On average 51% of the tumour cells in the individual breast cancer tumour sections showed staining for IgA1. The overall amount of staining in the invasive part of the tumour with the anti Tn antibody was 67%, and 93% with HPA. The intra-expression or uptake of IgA1 in breast cancer makes it a new potential carrier of the tumour associated and immunogenic Tn antigen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0061749PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630176PMC
December 2013

Establishing a Southern Swedish Malignant Melanoma OMICS and biobank clinical capability.

Clin Transl Med 2013 Feb 27;2(1). Epub 2013 Feb 27.

Clinical Protein Science & Imaging, Biomedical Center, Dept, of Measurement Technology and Industrial Electrical Engineering, Lund University, BMC C13, Lund 221 84, Sweden.

Background: The objectives and goals of the Southern Swedish Malignant Melanoma (SSMM) are to develop, build and utilize cutting edge biobanks and OMICS platforms to better understand disease pathology and drug mechanisms. The SSMM research team is a truly cross-functional group with members from oncology, surgery, bioinformatics, proteomics, and genomics initiatives. Within the research team there are members who daily diagnose patients with suspect melanomas, do follow-ups on malignant melanoma patients and remove primary or metastatic lesions by surgery. This inter-disciplinary clinical patient care ensures a competence build as well as a best practice procedure where the patient benefits.

Methods: Clinical materials from patients before, during and after treatments with clinical end points are being collected. Tissue samples as well as bio-fluid samples such as blood fractions, plasma, serum and whole blood will be archived in 384-high density sample tube formats. Standardized approaches for patient selections, patient sampling, sample-processing and analysis platforms with dedicated protein assays and genomics platforms that will hold value for the research community are used. The patient biobank archives are fully automated with novel ultralow temperature biobank storage units and used as clinical resources.

Results: An IT-infrastructure using a laboratory information management system (LIMS) has been established, that is the key interface for the research teams in order to share and explore data generated within the project. The cross-site data repository in Lund forms the basis for sample processing, together with biological samples in southern Sweden, including blood fractions and tumor tissues. Clinical registries are associated with the biobank materials, including pathology reports on disease diagnosis on the malignant melanoma (MM) patients.

Conclusions: We provide data on the developments of protein profiling and targeted protein assays on isolated melanoma tumors, as well as reference blood standards that is used by the team members in the respective laboratories. These pilot data show biobank access and feasibility of performing quantitative proteomics in MM biobank repositories collected in southern Sweden. The scientific outcomes further strengthen the build of healthcare benefit in the complex challenges of malignant melanoma pathophysiology that is addressed by the novel personalized medicines entering the market.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/2001-1326-2-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599425PMC
February 2013

A new murine IgG1 anti-Tn monoclonal antibody with in vivo anti-tumor activity.

Glycobiology 2011 Aug 5;21(8):1097-107. Epub 2011 Apr 5.

Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden.

The Tn antigen (GalNAc α-O-Ser/Thr) is heterogeneously synthesized by a variety of tumors and contains an epitope defined by lectins and antibodies as a cluster of αGalNAc carbohydrates synthesized within a peptide sequence, which is rich in serine and/or threonine. The Tn antigen has been utilized as a target in vaccine experiments and also used as a biomarker for prognosis of different cancer forms. In this paper, we present a new monoclonal antibody, GOD3-2C4, with the clear hallmarks of an anti-Tn antibody. It was generated through somatic cell hybridization after immunization of a mouse with a tumor cell line and a Tn carrying mucin. The antibody recognizes synthetic Tn antigen and binds breast, colon, lung, ovarian and pancreas cancer. The GOD3-2C4 antibody has antibody-dependent cellular cytotoxicity activity against Jurkat cells in vitro, and for the first time, it can be shown that an anti-Tn antibody has a significant in vivo effect on a human cancer cell line grown as a xenograft in severe combined immunodeficiency mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/glycob/cwr048DOI Listing
August 2011

Adsorption of low-density lipoprotein, its oxidation, and subsequent binding of specific recombinant antibodies: An in situ ellipsometric study.

Biochim Biophys Acta 2011 Feb 20;1810(2):211-7. Epub 2010 Oct 20.

Faculty of Health and Society, Malmö University, 205 06 Malmö, Sweden.

Background: Low-density lipoprotein (LDL) particles accumulate in the arterial wall and become oxidized during atherogenesis, leading to the formation of atherosclerotic plaques. The major protein of the LDL particle, apolipoprotein B-100 (apoB-100), becomes fragmented during oxidation and a target for the immune system.

Methods: In this study we used in situ ellipsometry to monitor the adsorption of LDL to solid silica surfaces and the effects of oxidation on the structure of the adsorbed LDL layer. We additionally investigated the binding kinetics of two recombinant human antibodies with different specificities recognizing epitopes of apoB-100 in surface-bound native and CuCl₂-oxidized LDL (oxLDL). The latter process was studied by adsorbing LDL and then adding the antibody and CuCl₂ while continuously monitoring adsorbed amount and the thickness of the film. The molar ratios between the antibodies and surface-bound LDL and oxLDL were calculated from these data.

Results: Our results indicate that oxidation of surface-bound LDL induces swelling of the layer, accompanied by a slight desorption. We further found that both antibodies were able to recognize LDL and oxLDL in its adsorbed orientation. Quantitative information was obtained on the number of available binding sites on surface-bound LDL and oxLDL for these two antibodies.

General Significance: Using ellipsometry for real-time monitoring of adsorption, in situ oxidation of LDL and binding of specific recombinant antibodies to surface-bound LDL, will open up possibilities to map different conformations and orientations of LDL in the adsorbed state.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbagen.2010.10.006DOI Listing
February 2011

Analysis of protein expression in pure cell nuclei populations isolated from human breast cancer tissue by DNA flow cytometric sorting.

J Proteomics 2010 Apr 6;73(6):1111-6. Epub 2009 Dec 6.

Dept. of Oncology, Clinical Sciences, Lund University, Barngatan 2B, SE-221 85 Lund, Sweden.

In this study, cell nuclei from aneuploid breast cancer samples were sorted with respect to DNA content into pure diploid and aneuploid fractions using flow cytometry. The nuclear proteins were then separated by one-dimensional gel electrophoresis (1D-PAGE) and differences in protein expression patterns, between diploid and aneuploid nuclei from the same tumours, were compared. Using a combination of peptide finger printing and peptide identification by MALDI-TOF mass spectrometry, we identified proteins and confirmed that the proteins were of nuclear origins. The results in this study add further information to the knowledge about the breast cancer disease complexity and heterogeneity at molecular level. For some of the tumours studied different nuclei protein patterns were obtained, in the diploid respective aneuploid nuclei populations, whilst other tumours did not show these differences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jprot.2009.11.014DOI Listing
April 2010

Identification of the target for therapeutic recombinant anti-apoB-100 peptide antibodies in human atherosclerotic lesions.

Atherosclerosis 2009 Jul 30;205(1):96-100. Epub 2008 Nov 30.

Department of Clinical Sciences, Lund University, Sweden.

Purpose: Accumulation of oxidized LDL in the arterial wall is believed to play a key role in the development of atherosclerosis. Experimental studies have identified the presence of immune responses against epitopes in oxidized LDL that protects against atherosclerosis. We have produced human recombinant IgG against one of these epitopes (aldehyde-modified apoB-100 amino acids 661-680) and demonstrated that treatment with this human IgG1 2D03 antibody markedly reduces atherosclerosis in hypercholesterolemic mice.

Methods: In the present study, we screened a panel of 25 carotid plaques associated with clinical symptoms and 26 clinically silent plaques obtained at surgery for presence of the aldehyde-modified apoB-100 peptide defined by the 2D03 antibody and compared the expression of this epitope with other plaque constituents, plasma lipoproteins levels, plasma oxidized LDL and autoantibodies against apoB-100 peptides.

Results: We demonstrated that the epitope is commonly expressed in human atherosclerotic plaques and that plaques associated with clinical symptoms have an almost three-fold higher content of this epitope (8.6+/-4.9% versus 22.1+/-12.2% immunostaining of total plaque area, p<0.0005). There was also a significant association between 2D03 epitope staining and the plaque content of cholesterol esters (r=0.43, p<0.05), whereas there was no association with plasma oxidized LDL and autoantibodies against apoB-100 peptides.

Conclusions: By demonstrating the presence of the 2D03 epitope in human atherosclerotic lesions our findings support the possibility that treatment with this antibody may have beneficial effects also in humans. Furthermore, they suggest the possibility to use these or other similar antibodies for diagnostic imaging of atherosclerotic plaques in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2008.11.020DOI Listing
July 2009

Expression of Helix pomatia lectin binding glycoproteins in women with breast cancer in relationship to their blood group phenotypes.

J Proteome Res 2009 Feb;8(2):782-7

Aberrant glycosylation occurs in essentially all types of human cancers. A difference in glycopattern of proteins will result in a change of function of the proteins. The lectin from Helix pomatia (HPA) recognizes N-acetylgalactosaminylated glycoproteins and very consistent results over the increased binding of HPA in tissue sections are associated with metastasis progression and poor patient prognosis in a range of human adenocarcinomas. The induced modification of protein function after changed glycosylation is unknown, and as a part in characterizing the glycoproteins carrying the specific carbohydrates, we analyzed the major HPA binding proteins in sera from healthy women, women with primary breast cancer with no metastasis (bcmet-), and women with metastasizing breast cancer (bcmet+) using lectin affinity chromatography and lectin blotting. The binding ligands were further identified using mass spectrometry (MALDI-TOF MS) to confirm the captured glycoproteins. The major HPA binding proteins in serum were found to be IgA1, complement factor C3, von Willebrand factor (vWF), alpha-2-macroglobulin and IgM. This set of antigens is a panel of candidates for useful HPA related biomarkers in sera, but our results also emphasize the fact that the blood group phenotypes are of most importance when using the lectin HPA in recognition of cancer biomarkers in sera and plasma. The results emphasize that interpretation of an individual change in the glycosylation pattern of a specific tumor marker always needs to be analyzed in its right context. This study shows that the blood group phenotypes can have a major impact on the results when analyzing HPA lectin binding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/pr800444bDOI Listing
February 2009

Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations.

Environ Health Perspect 2008 Mar;116(3):334-9

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Background: Phthalates may pose a risk for perinatal developmental effects. An important question relates to the choice of suitable biological matrices for assessing exposure during this period.

Objectives: This study was designed to measure the concentrations of phthalate diesters or their metabolites in breast milk, blood or serum, and urine and to evaluate their suitability for assessing perinatal exposure to phthalates.

Methods: In 2001, 2-3 weeks after delivery, 42 Swedish primipara provided breast milk, blood, and urine samples at home. Special care was taken to minimize contamination with phthalates (e.g., use of a special breast milk pump, heat treatment of glassware and needles, addition of phosphoric acid).

Results: Phthalate diesters and metabolites in milk and blood or serum, if detected, were present at concentrations close to the limit of detection. By contrast, most phthalate metabolites were detectable in urine at concentrations comparable to those from the general population in the United States and in Germany. No correlations existed between urine concentrations and those found in milk or blood/serum for single phthalate metabolites. Our data are at odds with a previous study documenting frequent detection and comparatively high concentrations of phthalate metabolites in Finnish and Danish mothers' milk.

Conclusions: Concentrations of phthalate metabolites in urine are more informative than those in milk or serum. Furthermore, collection of milk or blood may be associated with discomfort and potential technical problems such as contamination (unless oxidative metabolites are measured). Although urine is a suitable matrix for health-related phthalate monitoring, urinary concentrations in nursing mothers cannot be used to estimate exposure to phthalates through milk ingestion by breast-fed infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1289/ehp.10788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265037PMC
March 2008

Recombinant antibodies to an oxidized low-density lipoprotein epitope induce rapid regression of atherosclerosis in apobec-1(-/-)/low-density lipoprotein receptor(-/-) mice.

J Am Coll Cardiol 2007 Dec 26;50(24):2313-8. Epub 2007 Nov 26.

Department of Clinical Sciences, Malmö University Hospital, Lund University, Malmö, Sweden.

Objectives: The present study tested the hypothesis that treatment with human recombinant immunoglobulin G1 (IgG1) antibodies against a specific oxidized low-density lipoprotein (oxLDL) epitope will induce regression of existing atherosclerotic lesions in LDL receptor-deficient mice expressing apolipoprotein B-100 (apoB-100) (Apobec-1(-/-)/LDLR(-/-)).

Background: Oxidized LDL plays an essential role in the pathogenesis of atherosclerosis. We previously showed that an antibody against oxLDL reduces progression of atherosclerosis in mice.

Methods: Apobec-1(-/-)/LDLR(-/-) mice were fed a high-fat diet until they were 24 weeks and were subsequently transferred to chow. Starting at 25 weeks, mice were given 3 weekly injections of either of 2 recombinant human IgG1 antibodies (IEI-E3 or 2D03) against a malondialdehyde-modified apoB-100 peptide sequence.

Results: At 25 weeks, atherosclerotic lesions covered 10.3 +/- 3.7% of the descending aorta. Transfer to chow diet resulted in a modest regression of atherosclerosis over a 5-week period (8.28 +/- 4.36%; p = NS). Antibody treatment induced additional regression of atherosclerosis by 50% (2D03; p = 0.001) and 36% (IEI-E3; p = 0.004) compared with control IgG1. The 2D03 treatment also reduced plaque inflammation, enhanced plaque expression of the adenosine triphosphate-binding cassette transporter A1, and inhibited expression of monocyte chemoattractant protein-1 in cultured monocytes.

Conclusions: Human IgG1 against a specific oxLDL epitope can induce rapid and substantial regression of atherosclerotic lesions, possibly by stimulating lipid efflux and inhibiting macrophage recruitment. These recombinant human antibodies could represent a novel strategy for rapid regression/stabilization of atherosclerotic lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2007.07.081DOI Listing
December 2007

Design of recombinant antibody microarrays for serum protein profiling: targeting of complement proteins.

J Proteome Res 2007 Sep 16;6(9):3527-36. Epub 2007 Aug 16.

Department of Immunotechnology, BMC D13, Lund University, SE-221 84 Lund, Sweden.

Antibody-based microarrays is a novel technology with great promise for high-throughput proteomics. The process of designing high-performing arrays has, however, turned out to be challenging. Here, we have designed the next generation of a human recombinant scFv antibody microarray platform for protein expression profiling of nonfractionated biotinylated human plasma and serum proteomes. The setup, based on black polymer Maxisorb slides interfaced with a fluorescent-based read-out system, was found to provide specific, sensitive (subpicomolar (pM) range) and reproducible means for protein profiling. Further, a chip-to-chip normalization protocol critical for comparing data generated on different chips was devised. Finally, the microarray data were found to correlate well with clinical laboratory data obtained using conventional methods, as demonstrated for a set of medium abundant (micromolar (microM) to nanomolar (nM) range) protein analytes in serum and plasma samples derived from healthy and complement-deficient individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/pr070204fDOI Listing
September 2007

Oxidized LDL antibodies in treatment and risk assessment of atherosclerosis and associated cardiovascular disease.

Curr Pharm Des 2007 ;13(10):1021-30

Department of Clinical Sciences, CRC Entrance 72;91:12, Malmö University Hospital, S-20502 Malmö, Sweden.

Immune responses against oxidized forms of LDL play a critical role in activation and regulation of the inflammatory process that characterizes all stages of atherosclerosis. In humans oxidized LDL is targeted by both IgM and IgG autoantibodies. Immunization of hypercholesterolemic animals with oxidized LDL has been shown to inhibit atherosclerosis demonstrating that at least some of these immune responses have a protective effect. The identification of the structures in oxidized LDL that are responsible for activation of immunity has made it possible to develop novel therapeutic approaches for treatment of atherosclerosis based on active (vaccines) and passive (antibodies) immunization. Studies performed in atherosclerosis-prone mice demonstrate that both peptide-based vaccines and recombinant IgG targeting epitopes in oxidized LDL significantly reduce atherosclerosis. There is also evidence antibodies against oxidized LDL could also be used for imaging atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/138161207780487557DOI Listing
May 2007

Inhibition of injury-induced arterial remodelling and carotid atherosclerosis by recombinant human antibodies against aldehyde-modified apoB-100.

Atherosclerosis 2007 Feb 4;190(2):298-305. Epub 2006 May 4.

Department of Experimental Medical Science, Lund University, BMC, C12, SE-22184 Lund, Sweden.

Objective: The immune system plays an important regulatory role in the development of atherosclerotic plaques and neointima formation following various types of angioplasty. In the present study we investigated the effect of antibodies against aldehyde-modified apolipoprotein B-100 (apoB-100), a component of oxidized LDL, on atherosclerosis and response to arterial injury in mice.

Methods: The ability of a high affinity human recombinant antibody (2D03), specific for malondialdehyde-modified apoB-100, to influence formation of atherosclerosis as well as remodelling and neointima formation after a collar-induced injury of the carotid artery was studied in LDL receptor(-/-) mice over-expressing human apoB-100.

Results: The antibody recognized epitopes present in mouse plasma and reduced the plasma level of oxidized LDL by 34%. Antibody treatment inhibited injury-induced restrictive vascular remodelling but did not influence the size of the neointima. Atherosclerosis in the uninjured contra lateral carotid artery was determined by computerized image analysis and the mean plaque area in animals given control IgG1 was 7608+/-10,336 micro m(2). In contrast, essentially no plaques were present in animals treated with the 2D03 antibody (397+/-235 micro m(2), P<0.01 versus control IgG1).

Conclusions: Treatment with antibodies against aldehyde-modified apoB-100 dramatically reduces atherosclerosis and inhibits restrictive vascular remodelling in mice expressing human apoB-100.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2006.03.032DOI Listing
February 2007

Transiently binding antibody fragments against Lewis x and sialyl-Lewis x.

J Immunol Methods 2006 May 24;312(1-2):20-6. Epub 2006 Mar 24.

Department of Chemistry and Biomedical Sciences, University of Kalmar, SE-391 82 Kalmar, Sweden.

Biomolecular recognition is often characterised by low affinity where many weak interactions work either alone or in concert, resulting in an inherent dynamic situation. For example the well-studied weak binding of cell-cell interactions is predominantly based on a range of carbohydrates that interact with numerous (protein) ligands. Finding appropriate binders to these carbohydrate structures may pave the way for new analytical strategies based on low affinity, and recombinant antibody technology is a promising approach to the development of such reagents. We have in the present study characterised two low affinity human single chain antibody fragments (scFv) by surface plasmon resonance for use in such applications. The two clones, LeX1 and sLeX10, had been selected from a naive phage display library against Lewis x (Le(x)) and sialyl Le(x) (sLe(x)), respectively. Both LeX1 and sLeX10 showed low affinity, with K(D) values of 3.5+/-0.7 x 10(-5) M for Le(x) and 2.6+/-0.7 x 10(-5) M for sLe(x), respectively. Kinetic studies revealed the scFvs to be associated with fast dissociation rates, with Kd values higher than 0.1 s(-1) for both LeX1 and sLeX10. Apart from the Lewis structures Le(x) and sLe(x), we investigated the conformational isomers Lewis a and sialyl-Lewis a together with the monosaccharide units of the Lewis structures, and both scFvs showed high specificity for their respective carbohydrate. Taking these observations together we have demonstrated that scFv with fast reaction kinetics and low affinity have the necessary characteristics for further development as specific tools in analytical strategies, e.g. differentiation of cells based on the various configurations of carbohydrate epitopes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jim.2006.02.010DOI Listing
May 2006

OxLDL-IgG immune complexes induce survival of human monocytes.

Arterioscler Thromb Vasc Biol 2006 Mar 22;26(3):576-83. Epub 2005 Dec 22.

Wihuri Research Institute, Helsinki, Finland.

Objective: Immune complexes containing oxidatively modified low-density lipoprotein (oxLDL) particles are deposited in human atherosclerotic lesions during atherogenesis. Here we studied whether OxLDL-IgG immune complexes (OxLDL-IgG ICs) affect survival of human monocytes.

Methods And Results: As demonstrated by light microscopy, and analysis of cell proliferation, caspase-3 activity, and DNA fragmentation, OxLDL-IgG ICs promoted survival of cultured human monocytes by decreasing their spontaneous apoptosis. OxLDL-IgG ICs induced a concentration-dependent production of the major monocyte growth factor, monocyte colony-stimulating factor (M-CSF), by the monocytes, but its inhibition was without effect on OxLDL-IgG IC-induced monocyte survival. Rather, OxLDL-IgG ICs induced rapid phosphorylation of Akt, suggesting a direct anti-apoptotic effect mediated by cross-linking of Fcgamma receptors. Experiments with receptor blocking antibodies revealed that the OxLDL-IgG IC-induced monocyte survival was mediated by Fcgamma receptor I.

Conclusions: The results show that OxLDL-IgG ICs promote survival of monocytes by cross-linking Fcgamma receptor I and activating Akt-dependent survival signaling. The results reveal a novel mechanism by which an immune reaction toward oxLDL can play a role in the accumulation of macrophages in human atherosclerotic lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/01.ATV.0000201041.14438.8dDOI Listing
March 2006

Temporal trend studies on tetra- and pentabrominated diphenyl ethers and hexabromocyclododecane in guillemot egg from the Baltic Sea.

Environ Sci Technol 2003 Dec;37(24):5496-501

Laboratory for Analytical Environmental Chemistry, Institute of Applied Environmental Research, Stockholm University, SE-106 91 Stockholm, Sweden.

Guillemot eggs from the Baltic Sea, sampled between 1969 and 2001, were analyzed for tetra- and pentabromodiphenyl ethers (2,2',4,4'-tetraBDE (BDE-47), 2,2',4,4',5-pentaBDE (BDE-99), and 2,2',4,4',6-pentaBDE (BDE-100)), and hexabromocyclododecane (HBCD). This temporal trend study indicates that the concentrations of the polybrominated diphenyl ether compounds increased from the 1970s to the 1980s, peaking around the mid- to the late-1980s. These peaks are then followed by a rapid decrease in concentrations during the rest of the study period, with the concentrations of the major BDE congener below 100 ng/g lipid weight at the end of the period. This corresponds to less than 10% of its peak values. The concentrations of HBCD show a different pattern over time. After a peak in the middle of the 1970s followed by a decrease, the concentrations increased during the latter part of the 1980s. During the recent 10-yr period no significant change has occurred, and the annual mean concentrations are more or less stable at a higher level as compared to the beginning of the study period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/es0300766DOI Listing
December 2003
-->