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  1. Article ; Online: Supercharging with m-nitrobenzyl alcohol and propylene carbonate: forming highly charged ions with extended, near-linear conformations.

    Going, Catherine C / Williams, Evan R

    Analytical chemistry

    2015  Volume 87, Issue 7, Page(s) 3973–3980

    Abstract: ... the collisional cross sections of the most highly charged ions of both ubiquitin and cytochrome c formed ...

    Abstract The effectiveness of the supercharging reagents m-nitrobenzyl alcohol (m-NBA) and propylene carbonate at producing highly charged protein ions in electrospray ionization is compared. Addition of 5% m-NBA or 15% propylene carbonate increases the average charge of three proteins by ∼21% or ∼23%, respectively, when these ions are formed from denaturing solutions (water/methanol/acetic acid). These results indicate that both reagents are nearly equally effective at supercharging when used at their optimum concentrations. A narrowing of the charge state distribution occurs with both reagents, although this effect is greater for propylene carbonate. Focusing the ion signal into fewer charge states has the advantage of improving sensitivity. The maximum charge state of ubiquitin formed with propylene carbonate is 21+, four charges higher than previously reported. Up to nearly 30% of all residues in a protein can be charged, and the collisional cross sections of the most highly charged ions of both ubiquitin and cytochrome c formed with these supercharging reagents were measured for the first time and found to be similar to those calculated for theoretical highly extended, linear or near-linear conformations. Under native supercharging conditions, m-NBA is significantly more effective at producing high charge states than propylene carbonate.
    MeSH term(s) Benzyl Alcohols/chemistry ; Carbonic Anhydrases/chemistry ; Carbonic Anhydrases/metabolism ; Cytochromes c/chemistry ; Ions/chemistry ; Ions/metabolism ; Propane/analogs & derivatives ; Propane/chemistry ; Protein Conformation ; Solubility ; Tandem Mass Spectrometry ; Ubiquitin/chemistry
    Chemical Substances Benzyl Alcohols ; Ions ; Ubiquitin ; propylene carbonate (8D08K3S51E) ; Cytochromes c (9007-43-6) ; Carbonic Anhydrases (EC 4.2.1.1) ; 3-nitrobenzyl alcohol (F829X990IV) ; Propane (T75W9911L6)
    Language English
    Publishing date 2015-04-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1508-8
    ISSN 1520-6882 ; 0003-2700
    ISSN (online) 1520-6882
    ISSN 0003-2700
    DOI 10.1021/acs.analchem.5b00071
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4033: Show issues Location:
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  2. Article ; Online: Real-time HD Exchange Kinetics of Proteins from Buffered Aqueous Solution with Electrothermal Supercharging and Top-Down Tandem Mass Spectrometry.

    Going, Catherine C / Xia, Zijie / Williams, Evan R

    Journal of the American Society for Mass Spectrometry

    2016  Volume 27, Issue 6, Page(s) 1019–1027

    Abstract: Electrothermal supercharging (ETS) with electrospray ionization produces highly charged protein ions from buffered aqueous solutions in which proteins have native folded structures. ETS increases the charge of ribonuclease A by 34%, whereas only a 6% ... ...

    Abstract Electrothermal supercharging (ETS) with electrospray ionization produces highly charged protein ions from buffered aqueous solutions in which proteins have native folded structures. ETS increases the charge of ribonuclease A by 34%, whereas only a 6% increase in charge occurs for a reduced-alkylated form of this protein, which is unfolded and its structure is ~66% random coil in this solution. These results indicate that protein denaturation that occurs in the ESI droplets is the primary mechanism for ETS. ETS does not affect the extent of solution-phase hydrogen-deuterium exchange (HDX) that occurs for four proteins that have significantly different structures in solution, consistent with a droplet lifetime that is considerably shorter than observable rates of HDX. Rate constants for HDX of ubiquitin are obtained with a spatial resolution of ~1.3 residues with ETS and electron transfer dissociation of the 10+ charge-state using a single capillary containing a few μL of protein solution in which HDX continuously occurs. HDX protection at individual residues with ETS HDX is similar to that with reagent supercharging HDX and with solution-phase NMR, indicating that the high spray potentials required to induce ETS do not lead to HD scrambling. Graphical Abstract ᅟ.
    MeSH term(s) Deuterium Exchange Measurement ; Kinetics ; Protein Conformation ; Proteins ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry
    Chemical Substances Proteins
    Language English
    Publishing date 2016
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1073671-2
    ISSN 1879-1123 ; 1044-0305
    ISSN (online) 1879-1123
    ISSN 1044-0305
    DOI 10.1007/s13361-016-1350-z
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    Zs.A 4618: Show issues Location:
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  3. Article ; Online: New supercharging reagents produce highly charged protein ions in native mass spectrometry.

    Going, Catherine C / Xia, Zijie / Williams, Evan R

    The Analyst

    2015  Volume 140, Issue 21, Page(s) 7184–7194

    Abstract: ... at a concentration of 2% by volume can increase the average charge of cytochrome c and myoglobin by up to 163 ... from guanidine melts of cytochrome c monitored with tryptophan fluorescence show that the supercharging reagents ...

    Abstract The effectiveness of two new supercharging reagents for producing highly charged ions by electrospray ionization (ESI) from aqueous solutions in which proteins have native structures and reactivities were investigated. In aqueous solution, 2-thiophenone and 4-hydroxymethyl-1,3-dioxolan-2-one (HD) at a concentration of 2% by volume can increase the average charge of cytochrome c and myoglobin by up to 163%, resulting in even higher charge states than those that are produced from water/methanol/acid solutions in which these proteins are denatured. The greatest extent of supercharging occurs in pure water, but these supercharging reagents are also highly effective in aqueous solutions containing 200 mM ammonium acetate buffer commonly used in native mass spectrometry (MS). These reagents are less effective supercharging reagents than m-nitrobenzyl alcohol (m-NBA) and propylene carbonate (PC) when ions are formed from water/methanol/acid. The extent to which loss of the heme group from myoglobin occurs is related to the extent of supercharging. Results from guanidine melts of cytochrome c monitored with tryptophan fluorescence show that the supercharging reagents PC, sulfolane and HD are effective chemical denaturants in solution. These results provide additional evidence for the role of protein structural changes in the electrospray droplet as the primary mechanism for supercharging with these reagents in native MS. These results also demonstrate that for at least some proteins, the formation of highly charged ions from native MS is no longer a significant barrier for obtaining structural information using conventional tandem MS methods.
    MeSH term(s) Acetates/chemistry ; Benzyl Alcohols/chemistry ; Cytochromes c/chemistry ; Indicators and Reagents/chemistry ; Ions ; Methanol/chemistry ; Myoglobin/chemistry ; Propane/analogs & derivatives ; Propane/chemistry ; Protein Conformation ; Proteins/chemistry ; Spectrometry, Mass, Electrospray Ionization ; Spectrophotometry ; Tandem Mass Spectrometry ; Thermodynamics ; Thiophenes/chemistry ; Water/chemistry
    Chemical Substances Acetates ; Benzyl Alcohols ; Indicators and Reagents ; Ions ; Myoglobin ; Proteins ; Thiophenes ; Water (059QF0KO0R) ; propylene carbonate (8D08K3S51E) ; Cytochromes c (9007-43-6) ; 3-nitrobenzyl alcohol (F829X990IV) ; ammonium acetate (RRE756S6Q2) ; Propane (T75W9911L6) ; Methanol (Y4S76JWI15) ; sulfolane (Y5L06AH4G5)
    Language English
    Publishing date 2015-11-07
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 210747-8
    ISSN 1364-5528 ; 0003-2654
    ISSN (online) 1364-5528
    ISSN 0003-2654
    DOI 10.1039/c5an01710f
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    Zs.A 2423: Show issues Location:
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  4. Article: Supercharging with m-Nitrobenzyl Alcohol and Propylene Carbonate: Forming Highly Charged Ions with Extended, Near-Linear Conformations

    Going, Catherine C / Williams Evan R

    Analytical chemistry. 2015 Apr. 07, v. 87, no. 7

    2015  

    Abstract: ... the collisional cross sections of the most highly charged ions of both ubiquitin and cytochrome c formed ...

    Abstract The effectiveness of the supercharging reagents m-nitrobenzyl alcohol (m-NBA) and propylene carbonate at producing highly charged protein ions in electrospray ionization is compared. Addition of 5% m-NBA or 15% propylene carbonate increases the average charge of three proteins by ∼21% or ∼23%, respectively, when these ions are formed from denaturing solutions (water/methanol/acetic acid). These results indicate that both reagents are nearly equally effective at supercharging when used at their optimum concentrations. A narrowing of the charge state distribution occurs with both reagents, although this effect is greater for propylene carbonate. Focusing the ion signal into fewer charge states has the advantage of improving sensitivity. The maximum charge state of ubiquitin formed with propylene carbonate is 21+, four charges higher than previously reported. Up to nearly 30% of all residues in a protein can be charged, and the collisional cross sections of the most highly charged ions of both ubiquitin and cytochrome c formed with these supercharging reagents were measured for the first time and found to be similar to those calculated for theoretical highly extended, linear or near-linear conformations. Under native supercharging conditions, m-NBA is significantly more effective at producing high charge states than propylene carbonate.
    Keywords acetic acid ; cytochrome c ; ionization ; ions ; methanol ; ubiquitin
    Language English
    Dates of publication 2015-0407
    Size p. 3973-3980.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 1508-8
    ISSN 1520-6882 ; 0003-2700
    ISSN (online) 1520-6882
    ISSN 0003-2700
    DOI 10.1021%2Facs.analchem.5b00071
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  5. Article ; Online: Vitamin D supplementation decreases serum 27-hydroxycholesterol in a pilot breast cancer trial.

    Going, Catherine C / Alexandrova, Ludmila / Lau, Kenneth / Yeh, Christine Y / Feldman, David / Pitteri, Sharon J

    Breast cancer research and treatment

    2017  Volume 167, Issue 3, Page(s) 797–802

    Abstract: Purpose: 27-hydroxycholesterol (27HC), an endogenous selective estrogen receptor modulator (SERM), drives the growth of estrogen receptor-positive (ER+) breast cancer. 1,25-dihydroxyvitamin D (1,25(OH): Methods: 27HC, 25-hydroxyvitamin D (25OHD), and ...

    Abstract Purpose: 27-hydroxycholesterol (27HC), an endogenous selective estrogen receptor modulator (SERM), drives the growth of estrogen receptor-positive (ER+) breast cancer. 1,25-dihydroxyvitamin D (1,25(OH)
    Methods: 27HC, 25-hydroxyvitamin D (25OHD), and 1,25(OH)
    Results: A significant increase (p = 4.3E-5) in 25OHD and a decrease (p = 1.7E-1) in 27HC was observed in high-dose versus low-dose vitamin D subjects. Excluding two statistical outliers, 25OHD and 27HC levels were inversely correlated (p = 7.0E-3).
    Conclusions: Vitamin D supplementation can decrease circulating 27HC of breast cancer patients, likely by CYP27A1 inhibition. This suggests a new and additional modality by which vitamin D can inhibit ER+ breast cancer growth, though a larger study is needed for verification.
    MeSH term(s) 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics ; Biopsy ; Breast Neoplasms/blood ; Breast Neoplasms/diet therapy ; Breast Neoplasms/pathology ; Breast Neoplasms/surgery ; Cell Line, Tumor ; Cholestanetriol 26-Monooxygenase/antagonists & inhibitors ; Cholestanetriol 26-Monooxygenase/genetics ; Dietary Supplements ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Hydroxycholesterols/blood ; Receptors, Estrogen/genetics ; Selective Estrogen Receptor Modulators/administration & dosage ; Vitamin D/administration & dosage
    Chemical Substances Hydroxycholesterols ; Receptors, Estrogen ; Selective Estrogen Receptor Modulators ; Vitamin D (1406-16-2) ; 27-hydroxycholesterol (6T2NA6P5SQ) ; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (EC 1.14.13.13) ; CYP27A1 protein, human (EC 1.14.15.15) ; Cholestanetriol 26-Monooxygenase (EC 1.14.15.15) ; CYP27B1 protein, human (EC 1.14.15.18)
    Language English
    Publishing date 2017-11-07
    Publishing country Netherlands
    Document type Clinical Trial ; Journal Article
    ZDB-ID 604563-7
    ISSN 1573-7217 ; 0167-6806
    ISSN (online) 1573-7217
    ISSN 0167-6806
    DOI 10.1007/s10549-017-4562-4
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    Zs.A 1655: Show issues Location:
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  6. Article ; Online: Quantitative Proteomic Profiling Reveals Key Pathways in the Anticancer Action of Methoxychalcone Derivatives in Triple Negative Breast Cancer.

    Going, Catherine C / Tailor, Dhanir / Kumar, Vineet / Birk, Alisha M / Pandrala, Mallesh / Rice, Meghan A / Stoyanova, Tanya / Malhotra, Sanjay / Pitteri, Sharon J

    Journal of proteome research

    2018  Volume 17, Issue 10, Page(s) 3574–3585

    Abstract: Triple negative breast cancer is an aggressive, heterogeneous disease with high recurrence and metastasis rates even with modern chemotherapy regimens and thus is in need of new therapeutics. Here, three novel synthetic analogues of chalcones, plant- ... ...

    Abstract Triple negative breast cancer is an aggressive, heterogeneous disease with high recurrence and metastasis rates even with modern chemotherapy regimens and thus is in need of new therapeutics. Here, three novel synthetic analogues of chalcones, plant-based molecules that have demonstrated potency against a wide variety of cancers, were investigated as potential therapeutics for triple negative breast cancer. These compounds exhibit IC
    MeSH term(s) Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Line ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Chalcone/chemistry ; Chalcone/pharmacology ; Female ; G1 Phase Cell Cycle Checkpoints/drug effects ; Humans ; Metabolic Networks and Pathways/drug effects ; Proteomics/methods ; Triple Negative Breast Neoplasms/metabolism ; Triple Negative Breast Neoplasms/pathology
    Chemical Substances Antineoplastic Agents ; Chalcone (5S5A2Q39HX)
    Language English
    Publishing date 2018-09-20
    Publishing country United States
    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 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.8b00636
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    Zs.A 6189: Show issues Location:
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  7. Article ; Online: Y box binding protein 1 inhibition as a targeted therapy for ovarian cancer.

    Tailor, Dhanir / Resendez, Angel / Garcia-Marques, Fernando Jose / Pandrala, Mallesh / Going, Catherine C / Bermudez, Abel / Kumar, Vineet / Rafat, Marjan / Nambiar, Dhanya K / Honkala, Alexander / Le, Quynh-Thu / Sledge, George W / Graves, Edward / Pitteri, Sharon J / Malhotra, Sanjay V

    Cell chemical biology

    2021  Volume 28, Issue 8, Page(s) 1206–1220.e6

    Abstract: Y box binding protein 1 (YB-1) is a multifunctional protein associated with tumor progression and the emergence of treatment resistance (TR). Here, we report an azopodophyllotoxin small molecule, SU056, that potently inhibits tumor growth and progression ...

    Abstract Y box binding protein 1 (YB-1) is a multifunctional protein associated with tumor progression and the emergence of treatment resistance (TR). Here, we report an azopodophyllotoxin small molecule, SU056, that potently inhibits tumor growth and progression via YB-1 inhibition. This YB-1 inhibitor inhibits cell proliferation, resistance to apoptosis in ovarian cancer (OC) cells, and arrests in the G1 phase. Inhibitor treatment leads to enrichment of proteins associated with apoptosis and RNA degradation pathways while downregulating spliceosome pathway. In vivo, SU056 independently restrains OC progression and exerts a synergistic effect with paclitaxel to further reduce disease progression with no observable liver toxicity. Moreover, in vitro mechanistic studies showed delayed disease progression via inhibition of drug efflux and multidrug resistance 1, and significantly lower neurotoxicity as compared with etoposide. These data suggest that YB-1 inhibition may be an effective strategy to reduce OC progression, antagonize TR, and decrease patient mortality.
    MeSH term(s) Aged ; Animals ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Line ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drug Screening Assays, Antitumor ; Female ; Humans ; Middle Aged ; Molecular Structure ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Rats ; Y-Box-Binding Protein 1/analysis ; Y-Box-Binding Protein 1/antagonists & inhibitors ; Y-Box-Binding Protein 1/metabolism
    Chemical Substances Antineoplastic Agents ; Y-Box-Binding Protein 1 ; YBX1 protein, human
    Language English
    Publishing date 2021-03-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2451-9448
    ISSN (online) 2451-9448
    DOI 10.1016/j.chembiol.2021.02.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: SU086, an inhibitor of HSP90, impairs glycolysis and represents a treatment strategy for advanced prostate cancer.

    Rice, Meghan A / Kumar, Vineet / Tailor, Dhanir / Garcia-Marques, Fernando Jose / Hsu, En-Chi / Liu, Shiqin / Bermudez, Abel / Kanchustambham, Vijayalakshmi / Shankar, Vishnu / Inde, Zintis / Alabi, Busola Ruth / Muruganantham, Arvind / Shen, Michelle / Pandrala, Mallesh / Nolley, Rosalie / Aslan, Merve / Ghoochani, Ali / Agarwal, Arushi / Buckup, Mark /
    Kumar, Manoj / Going, Catherine C / Peehl, Donna M / Dixon, Scott J / Zare, Richard N / Brooks, James D / Pitteri, Sharon J / Malhotra, Sanjay V / Stoyanova, Tanya

    Cell reports. Medicine

    2022  Volume 3, Issue 2, Page(s) 100502

    Abstract: Among men, prostate cancer is the second leading cause of cancer-associated mortality, with advanced disease remaining a major clinical challenge. We describe a small molecule, SU086, as a therapeutic strategy for advanced prostate cancer. We demonstrate ...

    Abstract Among men, prostate cancer is the second leading cause of cancer-associated mortality, with advanced disease remaining a major clinical challenge. We describe a small molecule, SU086, as a therapeutic strategy for advanced prostate cancer. We demonstrate that SU086 inhibits the growth of prostate cancer cells
    MeSH term(s) Cell Proliferation ; Glycolysis ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; Male ; Prostatic Neoplasms/drug therapy ; Proteomics
    Chemical Substances HSP90 Heat-Shock Proteins
    Language English
    Publishing date 2022-02-02
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2666-3791
    ISSN (online) 2666-3791
    DOI 10.1016/j.xcrm.2021.100502
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Novel Aza-podophyllotoxin derivative induces oxidative phosphorylation and cell death via AMPK activation in triple-negative breast cancer.

    Tailor, Dhanir / Going, Catherine C / Resendez, Angel / Kumar, Vineet / Nambiar, Dhanya K / Li, Yang / Dheeraj, Arpit / LaGory, Edward Lewis / Ghoochani, Ali / Birk, Alisha M / Stoyanova, Tanya / Ye, Jiangbin / Giaccia, Amato J / Le, Quynh-Thu / Singh, Rana P / Sledge, George W / Pitteri, Sharon J / Malhotra, Sanjay V

    British journal of cancer

    2020  Volume 124, Issue 3, Page(s) 604–615

    Abstract: Background: To circumvent Warburg effect, several clinical trials for different cancers are utilising a combinatorial approach using metabolic reprogramming and chemotherapeutic agents including metformin. The majority of these metabolic interventions ... ...

    Abstract Background: To circumvent Warburg effect, several clinical trials for different cancers are utilising a combinatorial approach using metabolic reprogramming and chemotherapeutic agents including metformin. The majority of these metabolic interventions work via indirectly activating AMP-activated protein kinase (AMPK) to alter cellular metabolism in favour of oxidative phosphorylation over aerobic glycolysis. The effect of these drugs is dependent on glycaemic and insulin conditions.  Therefore, development of small molecules, which can activate AMPK, irrespective of the energy state, may be a better approach for triple-negative breast cancer (TNBC) treatment.
    Methods: Therapeutic effect of SU212 on TNBC cells was examined using in vitro and in vivo models.
    Results: We developed and characterised the efficacy of novel AMPK activator (SU212) that selectively induces oxidative phosphorylation and decreases glycolysis in TNBC cells, while not affecting these pathways in normal cells.   SU212 accomplished this metabolic reprogramming by activating AMPK independent of energy stress and irrespective of the glycaemic/insulin state. This leads to mitotic phase arrest and apoptosis in TNBC cells. In vivo, SU212 inhibits tumour growth, cancer progression and metastasis.
    Conclusions: SU212 directly activates AMPK in TNBC cells, but does not hamper glucose metabolism in normal cells. Our study provides compelling preclinical data for further development of SU212 for the treatment of TNBC.
    MeSH term(s) AMP-Activated Protein Kinases/metabolism ; Animals ; Antineoplastic Agents, Phytogenic/pharmacology ; Apoptosis ; Cell Death ; Cell Line, Tumor ; Cell Survival ; Enzyme Activation/drug effects ; Female ; Glucose/metabolism ; Glycolysis/drug effects ; Humans ; Lactic Acid/metabolism ; Lipogenesis/drug effects ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Proteins/metabolism ; Oxidative Phosphorylation/drug effects ; Podophyllotoxin/analogs & derivatives ; Random Allocation ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/metabolism ; Triple Negative Breast Neoplasms/pathology ; Warburg Effect, Oncologic
    Chemical Substances Antineoplastic Agents, Phytogenic ; Neoplasm Proteins ; Lactic Acid (33X04XA5AT) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Glucose (IY9XDZ35W2) ; Podophyllotoxin (L36H50F353)
    Language English
    Publishing date 2020-11-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-020-01137-4
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  10. Article ; Online: Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

    Rostami, Kamran / Ensari, Arzu / Marsh, Michael N / Srivastava, Amitabh / Villanacci, Vincenzo / Carroccio, Antonio / Asadzadeh Aghdaei, Hamid / Bai, Julio C / Bassotti, Gabrio / Becheanu, Gabriel / Bell, Phoenix / Di Bella, Camillo / Bozzola, Anna Maria / Cadei, Moris / Casella, Giovanni / Catassi, Carlo / Ciacci, Carolina / Apostol Ciobanu, Delia Gabriela / Cross, Simon S /
    Danciu, Mihai / Das, Prasenjit / Del Sordo, Rachele / Drage, Michael / Elli, Luca / Fasano, Alessio / Florena, Ada Maria / Fusco, Nicola / Going, James J / Guandalini, Stefano / Hagen, Catherine E / Hayman, David T S / Ishaq, Sauid / Jericho, Hilary / Johncilla, Melanie / Johnson, Matt / Kaukinen, Katri / Levene, Adam / Liptrot, Sarah / Lu, Laura / Makharia, Govind K / Mathews, Sherly / Mazzarella, Giuseppe / Maxim, Roxana / La Win Myint, Khun / Mohaghegh-Shalmani, Hamid / Moradi, Afshin / Mulder, Chris J J / Ray, Ronnie / Ricci, Chiara / Rostami-Nejad, Mohammad / Sapone, Anna / Sanders, David S / Taavela, Juha / Volta, Umberto / Walker, Marjorie / Derakhshan, Mohammad

    Nutrients

    2022  Volume 14, Issue 12

    Abstract: Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac ...

    Abstract Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.
    MeSH term(s) Biopsy ; Celiac Disease ; Diet, Gluten-Free ; Duodenum/pathology ; Glutens/adverse effects ; Humans ; Intestinal Mucosa
    Chemical Substances Glutens (8002-80-0)
    Language English
    Publishing date 2022-06-15
    Publishing country Switzerland
    Document type Journal Article ; Multicenter Study
    ZDB-ID 2518386-2
    ISSN 2072-6643 ; 2072-6643
    ISSN (online) 2072-6643
    ISSN 2072-6643
    DOI 10.3390/nu14122487
    Database MEDical Literature Analysis and Retrieval System OnLINE

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