High Interstitial Fluid Pressure Is Associated with Low Tumour Penetration of Diagnostic Monoclonal Antibodies Applied for Molecular Imaging Purposes
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Mendeley | Further Information

{"title"=>"High interstitial fluid pressure is associated with low tumour penetration of diagnostic monoclonal antibodies applied for molecular imaging purposes", "type"=>"journal", "authors"=>[{"first_name"=>"Markus", "last_name"=>"Heine", "scopus_author_id"=>"35579500600"}, {"first_name"=>"Barbara", "last_name"=>"Freund", "scopus_author_id"=>"37060747700"}, {"first_name"=>"Peter", "last_name"=>"Nielsen", "scopus_author_id"=>"56560566300"}, {"first_name"=>"Caroline", "last_name"=>"Jung", "scopus_author_id"=>"23005041000"}, {"first_name"=>"Rudolph", "last_name"=>"Reimer", "scopus_author_id"=>"22836307100"}, {"first_name"=>"Heinrich", "last_name"=>"Hohenberg", "scopus_author_id"=>"7004084425"}, {"first_name"=>"Uwe", "last_name"=>"Zangemeister-Wittke", "scopus_author_id"=>"7003825688"}, {"first_name"=>"Hans Juergen", "last_name"=>"Wester", "scopus_author_id"=>"57197554095"}, {"first_name"=>"Georg H.", "last_name"=>"Lüers", "scopus_author_id"=>"6603811547"}, {"first_name"=>"Udo", "last_name"=>"Schumacher", "scopus_author_id"=>"7102933228"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"22590529", "sgr"=>"84860693680", "doi"=>"10.1371/journal.pone.0036258", "scopus"=>"2-s2.0-84860693680", "pui"=>"364758379", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203"}, "id"=>"edead60e-cc45-36e5-96c5-594bfce403aa", "abstract"=>"The human epithelial cell adhesion molecule (EpCAM) is highly expressed in a variety of clinical tumour entities. Although an antibody against EpCAM has successfully been used as an adjuvant therapy in colon cancer, this therapy has never gained wide-spread use. We have therefore investigated the possibilities and limitations for EpCAM as possible molecular imaging target using a panel of preclinical cancer models. Twelve human cancer cell lines representing six tumour entities were tested for their EpCAM expression by qPCR, flow cytometry analysis and immunocytochemistry. In addition, EpCAM expression was analyzed in vivo in xenograft models for tumours derived from these cells. Except for melanoma, all cell lines expressed EpCAM mRNA and protein when grown in vitro. Although they exhibited different mRNA levels, all cell lines showed similar EpCAM protein levels upon detection with monoclonal antibodies. When grown in vivo, the EpCAM expression was unaffected compared to in vitro except for the pancreatic carcinoma cell line 5072 which lost its EpCAM expression in vivo. Intravenously applied radio-labelled anti EpCAM MOC31 antibody was enriched in HT29 primary tumour xenografts indicating that EpCAM binding sites are accessible in vivo. However, bound antibody could only be immunohistochemically detected in the vicinity of perfused blood vessels. Investigation of the fine structure of the HT29 tumour blood vessels showed that they were immature and prone for higher fluid flux into the interstitial space. Consistent with this hypothesis, a higher interstitial fluid pressure of about 12 mbar was measured in the HT29 primary tumour via \"wick-in-needle\" technique which could explain the limited diffusion of the antibody into the tumour observed by immunohistochemistry.", "link"=>"http://www.mendeley.com/research/high-interstitial-fluid-pressure-associated-low-tumour-penetration-diagnostic-monoclonal-antibodies", "reader_count"=>39, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>16, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>16, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>6, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Medicine and Dentistry"=>9, "Agricultural and Biological Sciences"=>10, "Physics and Astronomy"=>2, "Chemistry"=>6}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>6}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Chemistry"=>{"Chemistry"=>6}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>1, "France"=>1, "Germany"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/641799"], "description"=>"<p>MOC31-antibody binds to HT29 tumour cells <i>in vivo</i> after i.v. injection of 10 µg MOC31mAb in tumour bearing mice, as visualized with subsequent immunostaining against MOC31-antibody (red = MOC31 positive cells) in cryostat sections of the primary tumour. Controls using 10 µg IgG1 mAb confirmed the high specificity of MOC31 binding to tumour cells <i>in vivo</i>. The specific antibody MOC31 binding to the tumour cells was restricted to areas of the tumour, which were well supplied with blood vessels. Corresponding liver sections showed the intake of both antibodies by cells of the RES system.</p>", "links"=>[], "tags"=>["detection", "ht29"], "article_id"=>312288, "categories"=>["Physiology", "Cancer"], "users"=>["Markus Heine", "Barbara Freund", "Peter Nielsen", "Caroline Jung", "Rudolph Reimer", "Heinrich Hohenberg", "Uwe Zangemeister-Wittke", "Hans-Juergen Wester", "Georg H. Lüers", "Udo Schumacher"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036258.g005", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_EpCAM_in_vivo_detection_of_HT29_tumour_/312288", "title"=>"EpCAM <i>in vivo</i> detection of HT29 tumour.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:28:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/642035"], "description"=>"<p>(A) Unequal distribution of the blood vasculature (red) of a whole HT29 tumour vibratome slice (stitched of ×10 objective lens images). (B) Magnification of the boxed area in A, showing immature blood vessels (projection of a z series with z step size of 2.85 µm over 215 µm with ×10 objective lens). (C) Three-dimensional view of a section of B (z series with z step size of 1.4 µm over 140 µm with ×40 objective lens) showing the irregular structure of blood vessels. All tissues were viewed by confocal fluorescence microscopy (Nikon A1R confocal microscope with plan apo ×10/0.45 numerical aperture (NA) or plan fluo oil ×40/1.3 NA objective lens and with the laser excitation wavelength of 561 nm and the emission of 595). Scale bars: 2000 µm for A, 200 µm for B.</p>", "links"=>[], "tags"=>["ht29", "xenografted", "tumours", "visualized", "dii"], "article_id"=>312510, "categories"=>["Physiology", "Cancer"], "users"=>["Markus Heine", "Barbara Freund", "Peter Nielsen", "Caroline Jung", "Rudolph Reimer", "Heinrich Hohenberg", "Uwe Zangemeister-Wittke", "Hans-Juergen Wester", "Georg H. Lüers", "Udo Schumacher"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036258.g007", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vasculature_of_HT29_xenografted_tumours_visualized_by_DiI_labelling_/312510", "title"=>"Vasculature of HT29 xenografted tumours visualized by DiI labelling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:29:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/642197"], "description"=>"<p>Note that the highest EpCAM expression both <i>in vitro</i> and <i>in vivo</i> was observed in the cell lines 5061, LNCAP, PC3, HT29, and Caco2. The intensity (plus signs) and extent (percent) of the positive areas of 5 histological sections were determined by visual inspection of 3 independent observers.</p>", "links"=>[], "tags"=>["epcam", "lines"], "article_id"=>312684, "categories"=>["Physiology", "Cancer"], "users"=>["Markus Heine", "Barbara Freund", "Peter Nielsen", "Caroline Jung", "Rudolph Reimer", "Heinrich Hohenberg", "Uwe Zangemeister-Wittke", "Hans-Juergen Wester", "Georg H. Lüers", "Udo Schumacher"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036258.t001", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_in_vitro_and_in_vivo_EpCAM_expression_of_all_cell_lines_by_different_methods_/312684", "title"=>"Summary of <i>in vitro</i> and <i>in vivo</i> EpCAM expression of all cell lines by different methods.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 05:30:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/641393"], "description"=>"<p>5061, LNCAP, PC3, T47D, HT29, and Caco2 cells showed <i>in vitro</i> and <i>in vivo</i> strong binding of MOC31 by all cells. In contrast, MCF7, OH-1, SW480 and particularly 5072 cells showed strong MOC31 <i>in vitro</i> binding, but little or no binding <i>in vivo</i>. MEWO and FemX-1 cells showed no MOC31 binding in vitro and in vivo. (red = MOC31 binding).</p>", "links"=>[], "tags"=>["physiology", "oncology"], "article_id"=>311879, "categories"=>["Physiology", "Cancer"], "users"=>["Markus Heine", "Barbara Freund", "Peter Nielsen", "Caroline Jung", "Rudolph Reimer", "Heinrich Hohenberg", "Uwe Zangemeister-Wittke", "Hans-Juergen Wester", "Georg H. Lüers", "Udo Schumacher"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036258.g002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_EpCAM_protein_expression_pattern_in_vivo_and_in_vitro_/311879", "title"=>"EpCAM protein expression pattern <i>in vivo</i> and <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:26:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/641616"], "description"=>"<p>HT29 colon carcinoma (a) grown at the subcutaneous injection site above muscles (b) appear hyper-intense in two-dimensional turbo spin-echo (TSE) sequence (MR images in axial orientation).</p>", "links"=>[], "tags"=>["ht29"], "article_id"=>312104, "categories"=>["Physiology", "Cancer"], "users"=>["Markus Heine", "Barbara Freund", "Peter Nielsen", "Caroline Jung", "Rudolph Reimer", "Heinrich Hohenberg", "Uwe Zangemeister-Wittke", "Hans-Juergen Wester", "Georg H. Lüers", "Udo Schumacher"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036258.g003", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MRI_of_HT29_xenograft_/312104", "title"=>"MRI of HT29 xenograft.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:27:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/642123"], "description"=>"<p>(A) Typical pressure recording of a HT29 tumour. After adjusting the pressure at 0 mbar and insertion of the needle (arrow a) in the tumour the pressure increased and decreased rapidly and reaches a stable value of 16 mbar. To test the fluid communication between pressure sensor and needle the tubing is compressed with a screw clamp (arrow b) which results in a sharp increase of the pressure, then an exponential decrease, followed by another period of stabilization before decompressing the tubing (arrow c) which produces a rapid decrease and an exponential increase. (B) Measurement of 6 different HT29 tumours showed a mean IFP of 11.9 (+/−4) mbar.</p>", "links"=>[], "tags"=>["ht29", "xenograft"], "article_id"=>312610, "categories"=>["Physiology", "Cancer"], "users"=>["Markus Heine", "Barbara Freund", "Peter Nielsen", "Caroline Jung", "Rudolph Reimer", "Heinrich Hohenberg", "Uwe Zangemeister-Wittke", "Hans-Juergen Wester", "Georg H. Lüers", "Udo Schumacher"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036258.g008", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IFP_measurements_of_HT29_xenograft_tumours_/312610", "title"=>"IFP measurements of HT29 xenograft tumours.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:30:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/641128"], "description"=>"<p>(A) The mRNA of the malignant cell lines 5061, 5072 (pancreatic cancer), LNCAP, PC3 (prostate cancer), FemX-1, MEWO (melanoma), T47D, MCF7 (breast cancer), HT29 (colon cancer) and OH-1 (small cell lung cancer) were relatively quantified by qPCR, using GAPDH for normalization. 5072, LNCAP, PC3, T47D, MCF7, Caco2 and HT29 showed high expression levels of EpCAM mRNA. (B) EpCAM could be detected by Western blot analysis of HT29 cell lysate with a specific binding to antibody MOC31. Beta-actin was used as loading control. (C) EpCAM could positively be detected by flow cytometry analysis with MOC31 on all cancer cell lines, except of FemX-1 and MEWO. Isotype controls are shown as dotted lines.</p>", "links"=>[], "tags"=>["malignant"], "article_id"=>311608, "categories"=>["Physiology", "Cancer"], "users"=>["Markus Heine", "Barbara Freund", "Peter Nielsen", "Caroline Jung", "Rudolph Reimer", "Heinrich Hohenberg", "Uwe Zangemeister-Wittke", "Hans-Juergen Wester", "Georg H. Lüers", "Udo Schumacher"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036258.g001", "stats"=>{"downloads"=>3, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_EpCAM_expression_of_human_malignant_cells_/311608", "title"=>"EpCAM expression of human malignant cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:25:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/641923"], "description"=>"<p>Evans Blue-Albumin complex positive areas (blue) are recognizable at blood vessels in vital tumour tissue (b), to a higher degree at well perfused areas at the margin of the tumour (a) and in the transition between vital tumour tissue and necrosis (c).</p>", "links"=>[], "tags"=>["blue-albumin", "vibratome", "sections", "ht29"], "article_id"=>312403, "categories"=>["Physiology", "Cancer"], "users"=>["Markus Heine", "Barbara Freund", "Peter Nielsen", "Caroline Jung", "Rudolph Reimer", "Heinrich Hohenberg", "Uwe Zangemeister-Wittke", "Hans-Juergen Wester", "Georg H. Lüers", "Udo Schumacher"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036258.g006", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evans_Blue_Albumin_complex_distribution_in_vibratome_sections_of_HT29_carcinoma_/312403", "title"=>"Evans Blue-Albumin complex distribution in vibratome sections of HT29 carcinoma.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:29:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/641708"], "description"=>"<p>[125I]-Labelled specific anti EpCAM MOC31 and non-specific [125I]-labelled IgG1 antibody were used for EpCAM <i>in vivo</i> binding in HT29 carcinoma bearing SCID mice. There is a significant difference between specific and control antibody by HT29 carcinoma, but except for spleen and blood not in other organs (two-way ANOVA, P<0.001, n = 3). Standard deviations are indicated by bars.</p>", "links"=>[], "tags"=>["physiology", "oncology"], "article_id"=>312191, "categories"=>["Physiology", "Cancer"], "users"=>["Markus Heine", "Barbara Freund", "Peter Nielsen", "Caroline Jung", "Rudolph Reimer", "Heinrich Hohenberg", "Uwe Zangemeister-Wittke", "Hans-Juergen Wester", "Georg H. Lüers", "Udo Schumacher"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036258.g004", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_EpCAM_in_vivo_binding_/312191", "title"=>"EpCAM <i>in vivo</i> binding.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:28:14"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
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  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
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Relative Metric

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