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  1. Article ; Online: Intratumoral Cancer Cell Intravasation Can Occur Independent of Invasion into the Adjacent Stroma

    Elena I. Deryugina / William B. Kiosses

    Cell Reports, Vol 19, Iss 3, Pp 601-

    2017  Volume 616

    Abstract: Summary: Intravasation, active entry of cancer cells into the circulation, is often considered to be a relatively late event in tumor development occurring after stromal invasion. Here, we provide evidence that intravasation can be initiated early during ...

    Abstract Summary: Intravasation, active entry of cancer cells into the circulation, is often considered to be a relatively late event in tumor development occurring after stromal invasion. Here, we provide evidence that intravasation can be initiated early during tumor development and proceed in parallel to or independent of tumor invasion into surrounding stroma. By applying direct and unbiased intravasation-scoring methods to two histologically distinct human cancer types in live-animal models, we demonstrate that intravasation takes place almost exclusively within the tumor core, involves intratumoral vasculature, and does not involve vasculotropic cancer cells invading tumor-adjacent stroma and migrating along tumor-converging blood vessels. Highlighting an additional role for EGFR in cancer, we find that EGFR is required for the development of an intravasation-sustaining intratumoral vasculature. Intratumoral localization of intravasation supports the notion that overt metastases in cancer patients could be initiated much earlier during cancer progression than appreciated within conventional clinical tumor staging systems. : Deryugina and Kiosses investigate the localization of intravasation within primary tumors. They find that the majority of intravasation events occur within the tumor core and not at the invasive edge within tumor outgrowths into adjacent stroma in the models examined. Mechanistically, EGFR appears to impact intratumoral intravasation by regulating development of a fully interconnected angiogenic vasculature. Keywords: cancer metastasis, cell intravasation, tumor invasion, stromal invasion, tumor cell migration, tumor angiogenesis, EGFR, animal models of cancer, mouse ear tumor model, chorioallantoic membrane model
    Keywords Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2017-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Mrp1 is involved in lipid presentation and iNKT cell activation by Streptococcus pneumoniae

    Shilpi Chandra / James Gray / William B. Kiosses / Archana Khurana / Kaori Hitomi / Catherine M. Crosby / Ashu Chawla / Zheng Fu / Meng Zhao / Natacha Veerapen / Stewart K. Richardson / Steven A. Porcelli / Gurdyal Besra / Amy R. Howell / Sonia Sharma / Bjoern Peters / Mitchell Kronenberg

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 16

    Abstract: The CD1d pathway present lipid antigens resulting in the activation of iNKT cells but the complete pathway remains to be fully elucidated. Here, Chandra et al. use an siRNA screen and identify Mrp1 as crucial for CD1d lipid presentation and activation of ...

    Abstract The CD1d pathway present lipid antigens resulting in the activation of iNKT cells but the complete pathway remains to be fully elucidated. Here, Chandra et al. use an siRNA screen and identify Mrp1 as crucial for CD1d lipid presentation and activation of iNKT in the context of Streptococcus pneumoniae infection.
    Keywords Science ; Q
    Language English
    Publishing date 2018-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Mrp1 is involved in lipid presentation and iNKT cell activation by Streptococcus pneumoniae

    Shilpi Chandra / James Gray / William B. Kiosses / Archana Khurana / Kaori Hitomi / Catherine M. Crosby / Ashu Chawla / Zheng Fu / Meng Zhao / Natacha Veerapen / Stewart K. Richardson / Steven A. Porcelli / Gurdyal Besra / Amy R. Howell / Sonia Sharma / Bjoern Peters / Mitchell Kronenberg

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 16

    Abstract: The CD1d pathway present lipid antigens resulting in the activation of iNKT cells but the complete pathway remains to be fully elucidated. Here, Chandra et al. use an siRNA screen and identify Mrp1 as crucial for CD1d lipid presentation and activation of ...

    Abstract The CD1d pathway present lipid antigens resulting in the activation of iNKT cells but the complete pathway remains to be fully elucidated. Here, Chandra et al. use an siRNA screen and identify Mrp1 as crucial for CD1d lipid presentation and activation of iNKT in the context of Streptococcus pneumoniae infection.
    Keywords Science ; Q
    Language English
    Publishing date 2018-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: A novel technique for the in vivo imaging of autoimmune diabetes development in the pancreas by two-photon microscopy.

    Ken Coppieters / Marianne M Martinic / William B Kiosses / Natalie Amirian / Matthias von Herrath

    PLoS ONE, Vol 5, Iss 12, p e

    2010  Volume 15732

    Abstract: Type 1 diabetes (T1D) is characterized by the immune-mediated destruction of beta cells in the pancreas. Little is known about the in vivo dynamic interactions between T cells and beta cells or the kinetic behavior of other immune cell subsets in the ... ...

    Abstract Type 1 diabetes (T1D) is characterized by the immune-mediated destruction of beta cells in the pancreas. Little is known about the in vivo dynamic interactions between T cells and beta cells or the kinetic behavior of other immune cell subsets in the pancreatic islets. Utilizing multiphoton microscopy we have designed a technique that allows for the real-time visualization of diabetogenic T cells and dendritic cells in pancreatic islets in a live animal, including their interplay with beta cells and the vasculature. Using a custom designed stage, the pancreas was surgically exposed under live conditions so that imaging of islets under intact blood pressure and oxygen supply became possible. We demonstrate here that this approach allows for the tracking of diabetogenic leukocytes as well as vascularization phenotype of islets and accumulation of dendritic cells in islets during diabetes pathogenesis. This technique should be useful in mapping crucial kinetic events in T1D pathogenesis and in testing the impact of immune based interventions on T cell migration, extravasation and islet destruction.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2010-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: PTP4A1 promotes TGFβ signaling and fibrosis in systemic sclerosis

    Cristiano Sacchetti / Yunpeng Bai / Stephanie M. Stanford / Paola Di Benedetto / Paola Cipriani / Eugenio Santelli / Sonsoles Piera-Velazquez / Vladimir Chernitskiy / William B. Kiosses / Arnold Ceponis / Klaus H. Kaestner / Francesco Boin / Sergio A. Jimenez / Roberto Giacomelli / Zhong-Yin Zhang / Nunzio Bottini

    Nature Communications, Vol 8, Iss 1, Pp 1-

    2017  Volume 14

    Abstract: Although protein tyrosine kinases are being explored as antifibrotic agents for the treatment of systemic sclerosis, little is known about the function of counteractive protein tyrosine phosphatases in this context. Here, the authors show that PTP4A1 is ... ...

    Abstract Although protein tyrosine kinases are being explored as antifibrotic agents for the treatment of systemic sclerosis, little is known about the function of counteractive protein tyrosine phosphatases in this context. Here, the authors show that PTP4A1 is highly expressed by fibroblasts from patients with systemic sclerosis and promotes TGFβ activity via SRC–ERK–SMAD3 signaling.
    Keywords Science ; Q
    Language English
    Publishing date 2017-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: PTP4A1 promotes TGFβ signaling and fibrosis in systemic sclerosis

    Cristiano Sacchetti / Yunpeng Bai / Stephanie M. Stanford / Paola Di Benedetto / Paola Cipriani / Eugenio Santelli / Sonsoles Piera-Velazquez / Vladimir Chernitskiy / William B. Kiosses / Arnold Ceponis / Klaus H. Kaestner / Francesco Boin / Sergio A. Jimenez / Roberto Giacomelli / Zhong-Yin Zhang / Nunzio Bottini

    Nature Communications, Vol 8, Iss 1, Pp 1-

    2017  Volume 14

    Abstract: Although protein tyrosine kinases are being explored as antifibrotic agents for the treatment of systemic sclerosis, little is known about the function of counteractive protein tyrosine phosphatases in this context. Here, the authors show that PTP4A1 is ... ...

    Abstract Although protein tyrosine kinases are being explored as antifibrotic agents for the treatment of systemic sclerosis, little is known about the function of counteractive protein tyrosine phosphatases in this context. Here, the authors show that PTP4A1 is highly expressed by fibroblasts from patients with systemic sclerosis and promotes TGFβ activity via SRC–ERK–SMAD3 signaling.
    Keywords Science ; Q
    Language English
    Publishing date 2017-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Disruption of neuronal autophagy by infected microglia results in neurodegeneration.

    Mehrdad Alirezaei / William B Kiosses / Claudia T Flynn / Nathan R Brady / Howard S Fox

    PLoS ONE, Vol 3, Iss 8, p e

    2008  Volume 2906

    Abstract: There is compelling evidence to support the idea that autophagy has a protective function in neurons and its disruption results in neurodegenerative disorders. Neuronal damage is well-documented in the brains of HIV-infected individuals, and evidence of ... ...

    Abstract There is compelling evidence to support the idea that autophagy has a protective function in neurons and its disruption results in neurodegenerative disorders. Neuronal damage is well-documented in the brains of HIV-infected individuals, and evidence of inflammation, oxidative stress, damage to synaptic and dendritic structures, and neuronal loss are present in the brains of those with HIV-associated dementia. We investigated the role of autophagy in microglia-induced neurotoxicity in primary rodent neurons, primate and human models. We demonstrate here that products of simian immunodeficiency virus (SIV)-infected microglia inhibit neuronal autophagy, resulting in decreased neuronal survival. Quantitative analysis of autophagy vacuole numbers in rat primary neurons revealed a striking loss from the processes. Assessment of multiple biochemical markers of autophagic activity confirmed the inhibition of autophagy in neurons. Importantly, autophagy could be induced in neurons through rapamycin treatment, and such treatment conferred significant protection to neurons. Two major mediators of HIV-induced neurotoxicity, tumor necrosis factor-alpha and glutamate, had similar effects on reducing autophagy in neurons. The mRNA level of p62 was increased in the brain in SIV encephalitis and as well as in brains from individuals with HIV dementia, and abnormal neuronal p62 dot structures immunoreactivity was present and had a similar pattern with abnormal ubiquitinylated proteins. Taken together, these results identify that induction of deficits in autophagy is a significant mechanism for neurodegenerative processes that arise from glial, as opposed to neuronal, sources, and that the maintenance of autophagy may have a pivotal role in neuroprotection in the setting of HIV infection.
    Keywords Medicine ; R ; Science ; Q
    Subject code 590 ; 571
    Language English
    Publishing date 2008-08-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Elucidating the Kinetics of Expression and Immune Cell Infiltration Resulting from Plasmid Gene Delivery Enhanced by Surface Dermal Electroporation

    Kate E. Broderick / Niranjan Y. Sardesai / Trevor R. F. Smith / William B. Kiosses / Christine L. Knott / Gleb Kichaev / Dinah H. Amante / Janess M. Mendoza

    Vaccines, Vol 1, Iss 3, Pp 384-

    2013  Volume 397

    Abstract: The skin is an attractive tissue for vaccination in a clinical setting due to the accessibility of the target, the ease of monitoring and most importantly the immune competent nature of the dermal tissue. While skin electroporation offers an exciting and ...

    Abstract The skin is an attractive tissue for vaccination in a clinical setting due to the accessibility of the target, the ease of monitoring and most importantly the immune competent nature of the dermal tissue. While skin electroporation offers an exciting and novel future methodology for the delivery of DNA vaccines in the clinic, little is known about the actual mechanism of the approach and the elucidation of the resulting immune responses. To further understand the mechanism of this platform, the expression kinetics and localization of a reporter plasmid delivered via a surface dermal electroporation (SEP) device as well as the effect that this treatment would have on the resident immune cells in that tissue was investigated. Initially a time course (day 0 to day 21) of enhanced gene delivery with electroporation (EP) was performed to observe the localization of green fluorescent protein (GFP) expression and the kinetics of its appearance as well as clearance. Using gross imaging, GFP expression was not detected on the surface of the skin until 8 h post treatment. However, histological analysis by fluorescent microscopy revealed GFP positive cells as early as 1 h after plasmid delivery and electroporation. Peak GFP expression was observed at 24 h and the expression was maintained in skin for up to seven days. Using an antibody specific for a keratinocyte cell surface marker, reporter gene positive keratinocytes in the epidermis were identified. H&E staining of treated skin sections demonstrated an influx of monocytes and granulocytes at the EP site starting at 4 h and persisting up to day 14 post treatment. Immunological staining revealed a significant migration of lymphocytic cells to the EP site, congregating around cells expressing the delivered antigen. In conclusion, this study provides insights into the expression kinetics following EP enhanced DNA delivery targeting the dermal space. These findings may have implications in the future to design efficient DNA vaccination strategies for the clinic.
    Keywords intradermal ; DNA vaccine ; electroporation ; kinetics ; infiltration ; Medicine ; R
    Subject code 616
    Language English
    Publishing date 2013-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: The Plasminogen Receptor, Plg-RKT, and Macrophage Function

    Lindsey A. Miles / Shahrzad Lighvani / Nagyung Baik / Nicholas M. Andronicos / Emily I. Chen / Caitlin M. Parmer / Sophia Khaldoyanidi / Jenna E. Diggs / William B. Kiosses / Mark P. Kamps / John R. Yates / Robert J. Parmer

    Journal of Biomedicine and Biotechnology, Vol

    2012  Volume 2012

    Abstract: When plasminogen binds to cells its activation to plasmin is markedly enhanced compared to the reaction in solution. Thus, cells become armed with the broad spectrum proteolytic activity of plasmin. Cell-surface plasmin plays a key role in macrophage ... ...

    Abstract When plasminogen binds to cells its activation to plasmin is markedly enhanced compared to the reaction in solution. Thus, cells become armed with the broad spectrum proteolytic activity of plasmin. Cell-surface plasmin plays a key role in macrophage recruitment during the inflammatory response. Proteins exposing basic residues on the cell surface promote plasminogen activation on eukaryotic cells. We have used a proteomics approach combining targeted proteolysis with carboxypeptidase B and multidimensional protein identification technology, MudPIT, and a monocyte progenitor cell line to identify a novel transmembrane protein, the plasminogen receptor, Plg-RKT. Plg-RKT exposes a C-terminal lysine on the cell surface in an orientation to bind plasminogen and promote plasminogen activation. Here we review the characteristics of this new protein, with regard to membrane topology, conservation of sequence across species, the role of its C-terminus in plasminogen binding, its function in plasminogen activation, cell migration, and its role in macrophage recruitment in the inflammatory response.
    Keywords Biotechnology ; TP248.13-248.65 ; Medicine ; R
    Subject code 571
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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