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  1. AU="Wanzer, Michael Beau"
  2. AU="Szymanski, Eric S"

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  1. Article: Development of Multi-Scale X-ray Fluorescence Tomography for Examination of Nanocomposite-Treated Biological Samples.

    Chen, Si / Lastra, Ruben Omar / Paunesku, Tatjana / Antipova, Olga / Li, Luxi / Deng, Junjing / Luo, Yanqi / Wanzer, Michael Beau / Popovic, Jelena / Li, Ya / Glasco, Alexander D / Jacobsen, Chris / Vogt, Stefan / Woloschak, Gayle E

    Cancers

    2021  Volume 13, Issue 17

    Abstract: Research in cancer nanotechnology is entering its third decade, and the need to study interactions between nanomaterials and cells remains urgent. Heterogeneity of nanoparticle uptake by different cells and subcellular compartments represent the greatest ...

    Abstract Research in cancer nanotechnology is entering its third decade, and the need to study interactions between nanomaterials and cells remains urgent. Heterogeneity of nanoparticle uptake by different cells and subcellular compartments represent the greatest obstacles to a full understanding of the entire spectrum of nanomaterials' effects. In this work, we used flow cytometry to evaluate changes in cell cycle associated with non-targeted nanocomposite uptake by individual cells and cell populations. Analogous single cell and cell population changes in nanocomposite uptake were explored by X-ray fluorescence microscopy (XFM). Very few nanoparticles are visible by optical imaging without labeling, but labeling increases nanoparticle complexity and the risk of modified cellular uptake. XFM can be used to evaluate heterogeneity of nanocomposite uptake by directly imaging the metal atoms present in the metal-oxide nanocomposites under investigation. While XFM mapping has been performed iteratively in 2D with the same sample at different resolutions, this study is the first example of serial tomographic imaging at two different resolutions. A cluster of cells exposed to non-targeted nanocomposites was imaged with a micron-sized beam in 3D. Next, the sample was sectioned for immunohistochemistry as well as a high resolution "zoomed in" X-ray fluorescence (XRF) tomography with 80 nm beam spot size. Multiscale XRF tomography will revolutionize our ability to explore cell-to-cell differences in nanomaterial uptake.
    Language English
    Publishing date 2021-09-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13174497
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma.

    Poropatich, Kate / Paunesku, Tatjana / Zander, Alia / Wray, Brian / Schipma, Matthew / Dalal, Prarthana / Agulnik, Mark / Chen, Si / Lai, Barry / Antipova, Olga / Maxey, Evan / Brown, Koshonna / Wanzer, Michael Beau / Gursel, Demirkan / Fan, Hanli / Rademaker, Alfred / Woloschak, Gayle E / Mittal, Bharat B

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 16965

    Abstract: Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is biologically distinct from HPV-negative HNSCC. Outside of HPV-status, few tumor-intrinsic variables have been identified that correlate to improved survival. As part of ... ...

    Abstract Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is biologically distinct from HPV-negative HNSCC. Outside of HPV-status, few tumor-intrinsic variables have been identified that correlate to improved survival. As part of exploratory analysis into the trace elemental composition of oropharyngeal squamous cell carcinoma (OPSCC), we performed elemental quanitification by X-ray fluorescence microscopy (XFM) on a small cohort (n = 32) of patients with HPV-positive and -negative OPSCC and identified in HPV-positive cases increased zinc (Zn) concentrations in tumor tissue relative to normal tissue. Subsequent immunohistochemistry of six Zn-binding proteins-zinc-α2-glycoprotein (AZGP1), Lipocalin-1, Albumin, S100A7, S100A8 and S100A9-revealed that only AZGP1 expression significantly correlated to HPV-status (p < 0.001) and was also increased in tumor relative to normal tissue from HPV-positive OPSCC tumor samples. AZGP1 protein expression in our cohort significantly correlated to a prolonged recurrence-free survival (p = 0.029), similar to HNSCC cases from the TCGA (n = 499), where highest AZGP1 mRNA levels correlated to improved overall survival (p = 0.023). By showing for the first time that HPV-positive OPSCC patients have increased intratumoral Zn levels and AZGP1 expression, we identify possible positive prognostic biomarkers in HNSCC as well as possible mechanisms of increased sensitivity to chemoradiation in HPV-positive OPSCC.
    MeSH term(s) Calgranulin A/metabolism ; Calgranulin B/metabolism ; Female ; Humans ; Lipocalin 1/metabolism ; Male ; Middle Aged ; Oropharyngeal Neoplasms/metabolism ; Oropharyngeal Neoplasms/mortality ; Oropharyngeal Neoplasms/virology ; Papillomavirus Infections/metabolism ; S100 Calcium Binding Protein A7/metabolism ; Seminal Plasma Proteins/genetics ; Seminal Plasma Proteins/metabolism ; Spectrometry, X-Ray Emission ; Squamous Cell Carcinoma of Head and Neck/metabolism ; Squamous Cell Carcinoma of Head and Neck/mortality ; Squamous Cell Carcinoma of Head and Neck/virology ; Zinc/metabolism
    Chemical Substances Calgranulin A ; Calgranulin B ; Lipocalin 1 ; S100 Calcium Binding Protein A7 ; S100A7 protein, human ; S100A8 protein, human ; S100A9 protein, human ; Seminal Plasma Proteins ; Zn-alpha-2-glycoprotein ; Zinc (J41CSQ7QDS)
    Language English
    Publishing date 2019-11-18
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-53268-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Distribution of Iron Oxide Core-Titanium Dioxide Shell Nanoparticles in VX2 Tumor Bearing Rabbits Introduced by Two Different Delivery Modalities.

    Refaat, Tamer / West, Derek / El Achy, Samar / Parimi, Vamsi / May, Jasmine / Xin, Lun / Harris, Kathleen R / Liu, William / Wanzer, Michael Beau / Finney, Lydia / Maxey, Evan / Vogt, Stefan / Omary, Reed A / Procissi, Daniele / Larson, Andrew C / Paunesku, Tatjana / Woloschak, Gayle E

    Nanomaterials (Basel, Switzerland)

    2016  Volume 6, Issue 8

    Abstract: This work compares intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core-titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits. NPs coated with glucose and decorated ... ...

    Abstract This work compares intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core-titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits. NPs coated with glucose and decorated with a peptide sequence from cortactin were administered to animals with developed VX2 liver cancer. Two hours after NPs delivery tumors, normal liver, kidney, lung and spleen tissues were harvested and used for a series on histological and elemental analysis tests. Quantification of NPs in tissues was done both by bulk inductively coupled plasma mass spectrometry (ICP-MS) analysis and by hard X-ray fluorescence microscopy. Both IV and IC NPs injection are feasible modalities for delivering NPs to VX2 liver tumors with comparable tumor accumulation. It is possible that this is an outcome of the fact that VX2 tumors are highly vascularized and hemorrhagic, and therefore enhanced permeability and retention (EPR) plays the most significant role in accumulation of nanoparticles in tumor tissue. It is, however, interesting to note that IV delivery led to increased sequestration of NPs by spleen and normal liver tissue, while IC delivery lead to more NP positive Kupffer cells. This difference is most likely a direct outcome of blood flow dynamics. Armed with this knowledge about nanoparticle delivery, we plan to test them as radiosensitizers in the future.
    Language English
    Publishing date 2016-08-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662255-5
    ISSN 2079-4991
    ISSN 2079-4991
    DOI 10.3390/nano6080143
    Database MEDical Literature Analysis and Retrieval System OnLINE

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