| 1. |
- Stanezai, S., et al.
(författare)
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Higher intensity of Low Molecular Weight Protein Tyrosine Phosphatase/ ACP-1 in survivors of patients diagnosed with Diffuse Large B Cell Lymphoma (DLBCL) compared to non-survivors
- 2016
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Ingår i: Austin Biology. - : Austin Publishing. ; 1:2
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Tidskriftsartikel (refereegranskat)abstract
- Adult Diffuse Large B Cell Lymphoma (DLBCL) is a heterogeneous form of hematopoietic cancer and difficult to treat. In order to find a better diagnostic indication for the disease, we analyzed Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) that in humans is encoded by the ACP1 gene. LMWPTP is an enzyme shown to counteract Protein Tyrosine Kinases (PTK) and was suggested to be a negative growth factor regulator. However, the 18 kDa PTP can also have a positive effect on cell growth and proliferation, indicating a controversial role in the tumorigenic process. LMWPTP exists in different isoforms which are electrophoretically, kinetically and immunologically distinct. We have studied two subgroups of DLBCL consisting of a Germinal Center B cell like (GCB) and a non-Germinal Center B cell like (non-GCB) group. The two subgroups have been defined by gene-expressing profiling and are associated with differential outcome. The expression levels of LMWPTP protein was compared and showed significant differences between the GCB and non- GCB subgroups (p=0.012). Interestingly, when the samples were divided into survivors and non-survivors, and thereafter analyzed for LMWPTP expression, the samples from patients with a higher survival rate showed increased staining intensity, whereas the samples from patients with lower intensity of LMWPTP did not survive the disease (p=0.001). In conclusion, we have shown that DLBCL patients with worse outcome express LMWPTP with a lower intensity, suggesting a tumor suppressor role for this form of the enzyme.
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| 2. |
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| 3. |
- Delfani, Payam, et al.
(författare)
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ZAP70 (zeta-chain (TCR) associated protein kinase 70kDa)
- 2015
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Ingår i: Atlas of Genetics and Cytogenetics in Oncology and Haematology. - : The Atlas of Genetics and Cytogenetics in Oncology and Haematology. - 1768-3262.
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Forskningsöversikt (refereegranskat)abstract
- Review on ZAP70, with data on DNA, on the protein encoded, and where the gene is implicated.
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| 4. |
- El-Schich, Zahra, et al.
(författare)
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Different expression levels of glycans on leukemic cells-a novel screening method with molecularly imprinted polymers (MIP) targeting sialic acid
- 2016
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Ingår i: Tumor Biology. - : Springer. - 1010-4283 .- 1423-0380. ; 10:37, s. 13763-13768
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Tidskriftsartikel (refereegranskat)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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| 5. |
- El-Schich, Zahra, et al.
(författare)
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Holography : The Usefulness of Digital Holographic Microscopy for Clinical Diagnostics
- 2017
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Ingår i: Holographic Materials and Optical Systems. - : INTECH. - 9789535130383 ; , s. 319-333
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Digital holographic (DH) microscopy is a digital high-resolution holographic imaging technique with the capacity of quantification of cellular conditions without any staining or labeling of cells. The unique measurable parameters are the cell number, cell area, thickness, and volume, which can be coupled to proliferation, migration, cell cycle analysis, viability, and cell death. The technique is cell friendly, fast and simple to use and has unique imaging capabilities for time-lapse investigations on both the single cell and the cell-population levels. The interest for analyzing specifically cell volume changes with DH microscopy, resulting from cytotoxic treatments, drug response, or apoptosis events has recently increased in popularity. We and others have used DH microscopy showing that the technique has the sensitivity to distinguish between different cells and treatments. Recently, DH microscopy has been used for cellular diagnosis in the clinic, providing support for using the concept of DH, e.g., screening of malaria infection of red blood cells (RBC), cervix cancer screening, and sperm quality. Because of its quick and label-free sample handling, DH microscopy will be an important tool in the future for personalized medicine investigations, determining the optimal therapeutic concentration for both different cancer types and individual treatments.
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| 6. |
- El-Schich, Zahra, et al.
(författare)
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Induction of morphological changes in death-induced cancer cells monitored by holographic microscopy
- 2015
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Ingår i: Journal of Structural Biology. - : Elsevier. - 1047-8477 .- 1095-8657. ; 189:3, s. 207-212
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Tidskriftsartikel (refereegranskat)abstract
- We are using the label-free technique of holographic microscopy to analyze cellular parameters including cell number, confluence, cellular volume and area directly in the cell culture environment. We show that death-induced cells can be distinguished from untreated counterparts by the use of holographic microscopy, and we demonstrate its capability for cell death assessment. Morphological analysis of two representative cell lines (L929 and DU145) was performed in the culture flasks without any prior cell detachment. The two cell lines were treated with the anti-tumour agent etoposide for one to three days. Measurements by holographic microscopy showed significant differences in average cell number, confluence, volume and area when comparing etoposide-treated with untreated cells. The cell volume of the treated cell lines was initially increased at early time-points. By time, cells decreased in volume, especially when treated with high doses of etoposide. In conclusion, we have shown that holographic microscopy allows label-free and completely non-invasive morphological measurements of cell growth, viability and death. Future applications could include real-time monitoring of these holographic microscopy parameters in cells in response to clinically relevant compounds.
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| 7. |
- El-Schich, Zahra, et al.
(författare)
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Interfacing antibody-based microarrays and digital holography enables label-free detection for loss of cell volume
- 2015
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Ingår i: Future Science OA. - : Future Science Group. - 2056-5623. ; 1:3
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Tidskriftsartikel (refereegranskat)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. Result/Methodology: We demonstrate that the cell number, mean area, thickness, and volume were non-invasively 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. Conclusions: Our results provide proof of concept for using DHM combined with antibody-based microarray technology for detecting morphological changes in captured cells.
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| 8. |
- El-Schich, Zahra
(författare)
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Novel imaging technology and tools for biomarker detection in cancer
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer is a leading cause of death worldwide. Normally the balance betweencell growth and cell death is strongly controlled. Chronic lymphocytic leukemiais an indolent disease that has a highly variable clinical course and is the mostcommon hematological malignancy amongst adults in the Western countries.The protein tyrosine phosphatase SHP-1 is a key regulator that controls theintracellular phosphotyrosine level in lymphocytes by inhibiting the B cell receptorsignals. We have compared the expression and activity of SHP-1 inchronic lymphocytic leukemia cells from lymph nodes with matched peripheralblood samples. The expression levels of SHP-1 were higher in peripheral blood,but the phosphatase activity in lymph nodes and peripheral blood did not differsignificantly. All cells in the body normally present glycans on the cell surface,which are involved in cellular communication and in processes like cell differentiation,proliferation and infection, including protecting the cells from invadersand in cell-cell contacts. Sialic acid occurs on the terminal end of glycans,and the frequency of sialic acid expression is increased on metastatic cancer cellsand overexpression controls tumor cell growth and cell differentiation. Theavailability of specific antibodies against sialic acid is limited. We have beenscreening sialic acid on cancer cells by using a molecular imprinting polymertechnique. Our results show that sialic acid is expressed on chronic lymphocyticleukemia cell lines at different levels at the plasma membrane. Higher expressionof sialic acid in the more aggressive chronic lymphocytic leukemia cell lineswas observed. To analyze morphological changes of death cells, digital holographicmicroscopy was used. Digital holographic microscopy is an approachfor label-free non-invasive 3D imaging of cultured cells. We have analyzed celldeath of adherent cancer cells using digital holographic microscopy and developedit to analyze suspension cells by combining this technique with antibodybased microassays. Digital holographic microscopy can be used for cell-deathinduced cell analysis of both adherent cells and suspension cells. This thesistakes us one step further in cancer research as regards developing techniques forscreening circulating cancer cells in blood as well as for individualized treatmentof cancer patients.
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| 9. |
- El-Schich, Zahra, et al.
(författare)
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Quantitative Phase Imaging for Label-Free Analysis of Cancer Cells-Focus on Digital Holographic Microscopy
- 2018
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Ingår i: Applied Sciences. - : MDPI. - 2076-3417. ; 8:7
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Forskningsöversikt (refereegranskat)abstract
- To understand complex biological processes, scientists must gain insight into the function of individual living cells. In contrast to the imaging of fixed cells, where a single snapshot of the cell’s life is retrieved, live-cell imaging allows investigation of the dynamic processes underlying the function and morphology of cells. Label-free imaging of living cells is advantageous since it is used without fluorescent probes and maintains an appropriate environment for cellular behavior, otherwise leading to phototoxicity and photo bleaching. Quantitative phase imaging (QPI) is an ideal method for studying live cell dynamics by providing data from noninvasive monitoring over arbitrary time scales. The effect of drugs on migration, proliferation, and apoptosis of cancer cells are emerging fields suitable for QPI analysis. In this review, we provide a current insight into QPI applied to cancer research.
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| 10. |
- Mölder, Anna Leida, et al.
(författare)
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Supervised classification of etoposide-treated in vitro adherent cells based on noninvasive imaging morphology
- 2017
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Ingår i: Journal of Medical Imaging. - : SPIE - International Society for Optical Engineering. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Single-cell studies using noninvasive imaging is a challenging, yet appealing way to study cellular characteristics over extended periods of time, for instance to follow cell interactions and the behavior of different cell types within the same sample. In some cases, e.g., transplantation culturing, real-time cellular monitoring, stem cell studies, in vivo studies, and embryo growth studies, it is also crucial to keep the sample intact and invasive imaging using fluorophores or dyes is not an option. Computerized methods are needed to improve throughput of image-based analysis and for use with noninvasive microscopy such methods are poorly developed. By combining a set of well-documented image analysis and classification tools with noninvasive microscopy, we demonstrate the ability for long-term image-based analysis of morphological changes in single cells as induced by a toxin, and show how these changes can be used to indicate changes in biological function. In this study, adherent cell cultures of DU-145 treated with low-concentration (LC) etoposide were imaged during 3 days. Single cells were identified by image segmentation and subsequently classified on image features, extracted for each cell. In parallel with image analysis, an MTS assay was performed to allow comparison between metabolic activity and morphological changes after long-term low-level drug response. Results show a decrease in proliferation rate for LC etoposide, accompanied by changes in cell morphology, primarily leading to an increase in cell area and textural changes. It is shown that changes detected by image analysis are already visible on day 1 for [Formula: see text] etoposide, whereas effects on MTS and viability are detected only on day 3 for [Formula: see text] etoposide concentration, leading to the conclusion that the morphological changes observed occur before and at lower concentrations than a reduction in cell metabolic activity or viability. Three classifiers are compared and we report a best case sensitivity of 88% and specificity of 94% for classification of cells as treated/untreated.
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