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Article ; Online: IL-10-producing memory B regulatory cells as a novel target for HLA-G to prolong human kidney allograft survival.

Ajith, Ashwin / Mamouni, Kenza / Musa, Abu / Horuzsko, Daniel D / Gani, Imran / Mulloy, Laura L / Horuzsko, Anatolij

2023 Volume 84, Issue 8, Page(s) 366–373

Abstract: Despite the growing interest in the role of regulatory B cells (Bregs) in autoimmunity ...

Abstract	Despite the growing interest in the role of regulatory B cells (Bregs) in autoimmunity, their distinct role and function in kidney transplant outcomes remain elusive. Here, we retrospectively analyzed the proportion of Bregs, transitional Bregs (tBregs) and memory Bregs (mBregs) and their capacity to produce IL-10 in non-rejected (NR) versus rejected (RJ) kidney transplant recipients. In the NR group, we observed a significant increase in the proportion of mBregs (CD19
MeSH term(s)	Humans ; Kidney Transplantation ; HLA-G Antigens/metabolism ; Interleukin-10/metabolism ; Retrospective Studies ; B-Lymphocytes, Regulatory ; Kidney ; Allografts
Chemical Substances	HLA-G Antigens ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2023-03-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	801524-7
ISSN	1879-1166 ; 0198-8859
ISSN (online)	1879-1166
ISSN	0198-8859
DOI	10.1016/j.humimm.2023.03.003
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Article ; Online: 5-alpha reductase inhibitors (5-ARi) with or without alpha-blockers (α-B) for Benign Prostatic Hyperplasia do NOT lower the risk of incident Bladder Cancer: United States insurance claims data.

Del Giudice, Francesco / Belladelli, Federico / Glover, Frank / Basran, Satvir / Li, Shufeng / Mulloy, Evan / Pradere, Benjamin / Soria, Francesco / Krajewski, Wojciech / Nair, Rajesh / Muncey, Wade / Seranio, Nicolas / Eisenberg, Michael L

World journal of urology

2023 Volume 41, Issue 10, Page(s) 2783–2791

Abstract: ... to explore the association between 5-ARi and BCa over time. Administration of alpha-blockers (α-B) w/o 5-ARi ... with BCa was 0.8% for the 5-ARi, 1.4% for the 5-ARi + α-B, and 0.6% for the untreated BPH group of incident ... up. In addition, α-B alone had no change in BCa risk (HR 1.06, 0.86-1.30).: Conclusions: We did ...

Abstract	Background: Chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer (BCa) risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results. We sought to examine the effect of 5-ARi on new BCa diagnoses in a large US database. Methods: Men ≥ 50 y/o with a prescription for 5-ARi after BPH diagnosis were identified in the IBM® Marketscan® Research de-identified Databases between 2007 and 2016 and matched with paired controls. Incident BCa diagnoses were identified after BPH diagnosis and/or pharmacologic treatment. Multivariable regression modeling adjusting for relevant factors was implemented. Sub-group analyses by exposure risk were performed to explore the association between 5-ARi and BCa over time. Administration of alpha-blockers (α-B) w/o 5-ARi was also examined. Results: In total, n = 24,036 men on 5-ARi, n = 107,086 on 5-ARi plus alpha-blockers, and n = 894,275 without medical therapy for BPH were identified. The percentage of men diagnosed with BCa was 0.8% for the 5-ARi, 1.4% for the 5-ARi + α-B, and 0.6% for the untreated BPH group of incident BCa (adjusted hazard ratio [aHR], 0.90, 95% confidence interval [CI] 0.56 - 1.47), and 1.08, 95%CI 0.89 - 1.30, respectively). This was also true at both shorter (≤ 2 yr) and longer-term (> 2 yr) follow up. In addition, α-B alone had no change in BCa risk (HR 1.06, 0.86-1.30). Conclusions: We did not find any diminished risk of new BCa in men treated with 5-ARi (i.e., chemoprotective effect). The current report suggests that 5-ARi do not change a man's bladder cancer risk.
MeSH term(s)	Male ; Humans ; United States/epidemiology ; 5-alpha Reductase Inhibitors/therapeutic use ; Prostatic Hyperplasia/drug therapy ; Prostatic Hyperplasia/epidemiology ; Risk ; Insurance ; Urinary Bladder Neoplasms/epidemiology ; Urinary Bladder Neoplasms/drug therapy
Chemical Substances	5-alpha Reductase Inhibitors
Language	English
Publishing date	2023-08-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	380333-8
ISSN	1433-8726 ; 0724-4983
ISSN (online)	1433-8726
ISSN	0724-4983
DOI	10.1007/s00345-023-04551-4
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Article: PD-1 Inhibition Enhances Blinatumomab Response in a UCB/PDX Model of Relapsed Pediatric B-Cell Acute Lymphoblastic Leukemia.

Wunderlich, Mark / Manning, Nicole / Sexton, Christina / O'Brien, Eric / Byerly, Luke / Stillwell, Cody / Perentesis, John P / Mulloy, James C / Mizukawa, Benjamin

Frontiers in oncology

2021 Volume 11, Page(s) 642466

Abstract: ... resulted in significant improvements in outcomes for relapsed B-cell acute lymphoblastic leukemia (B ... with patient-derived xenograft (PDX) cells derived from pediatric and adolescent/young adult (AYA) B ... overt disease within 30 days of engraftment of B-ALL. However, single agent therapy ...

Abstract	Immune therapies such as blinatumomab, CD19-directed bispecific CD3 T-cell Engager (BiTE), have resulted in significant improvements in outcomes for relapsed B-cell acute lymphoblastic leukemia (B-ALL). However, up to half of blinatumomab treated patients do not respond completely or relapse after therapy. As a result, there is a need to identify potential strategies to improve the efficacy of BiTE therapy. The anti-PD-1 antibody pembrolizumab has been shown to successfully activate T cells against a wide range of cancer types. Here, we tested the ability of umbilical cord blood (UCB) reconstituted mice to respond to blinatumomab therapy with or without concurrent pembrolizumab treatment. Humanized mice were engrafted with patient-derived xenograft (PDX) cells derived from pediatric and adolescent/young adult (AYA) B-ALL patients who had either failed to achieve remission with negative minimum residual disease (MRD negative) or experienced a relapse. Mock-treated humanized mice engrafted with PDX cells efficiently developed overt disease within 30 days of engraftment of B-ALL. However, single agent therapy with either blinatumomab or pembrolizumab reduced disease burden in engrafted mice, with some mice observed to be MRD negative after the 28-day treatment course. Combination therapy significantly improved the percentage of MRD negative mice and improved long-term survival and cure rates as compared to mice that were given blinatumomab alone. Importantly, no benefits were observed in treated mice that lacked human immune cell reconstitution. These results indicate that UCB-humanized NRGS mice develop activatable immune function, and UCB-humanized PDX leukemia models can be used in preclinical studies to evaluate specificity, efficacy, and cooperativity of immune therapies in B-ALL.
Language	English
Publishing date	2021-04-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2021.642466
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Book ; Online: Glycosaminoglycans and Proteoglycans

Mulloy, Barbara

2018

Abstract: Proteoglycans (PGs) are glycoconjugates in which a protein or peptide core is substituted with polysaccharide chains known as glycosaminoglycans (GAGs). The GAG sidechains carry a significant proportion of the functionality of PGs, interacting with many ... ...

Abstract	Proteoglycans (PGs) are glycoconjugates in which a protein or peptide core is substituted with polysaccharide chains known as glycosaminoglycans (GAGs). The GAG sidechains carry a significant proportion of the functionality of PGs, interacting with many proteins to form structural units in the extracellular matrix and to modulate the transport and signalling of small proteins acting as morphogens, growth factors and cytokines. Purified GAGs such as heparin and hyaluronan are in common use as therapeutic agents, with many more PG-based natural products, synthetic and semi-synthetic mimetics on the way; in addition, potential therapeutic strategies involving PG/GAG biosynthesis and degradation as targets are currently in development
Keywords	Therapeutics. Pharmacology
Size	1 electronic resource (XVI, 230 p.)
Publisher	MDPI - Multidisciplinary Digital Publishing Institute
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT020098833
ISBN	9783038428350 ; 9783038428367 ; 3038428353 ; 3038428361
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: HLA-G dimer targets Granzyme B pathway to prolong human renal allograft survival.

Ajith, Ashwin / Portik-Dobos, Vera / Nguyen-Lefebvre, Anh Thu / Callaway, Christine / Horuzsko, Daniel D / Kapoor, Rajan / Zayas, Carlos / Maenaka, Katsumi / Mulloy, Laura L / Horuzsko, Anatolij

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2019 Volume 33, Issue 4, Page(s) 5220–5236

Abstract: Human leukocyte antigen G (HLA-G), a nonclassic HLA class Ib molecule involved in the maintenance of maternal tolerance to semiallogeneic fetal tissues during pregnancy, has emerged as a potential therapeutic target to control allograft rejection. We ... ...

Abstract	Human leukocyte antigen G (HLA-G), a nonclassic HLA class Ib molecule involved in the maintenance of maternal tolerance to semiallogeneic fetal tissues during pregnancy, has emerged as a potential therapeutic target to control allograft rejection. We demonstrate here that the level of soluble HLA-G dimer was higher in a group of 90 patients with a functioning renal allograft compared with 40 patients who rejected (RJ) their transplants. The HLA-G dimer level was not affected by demographic status. One of the potential mechanisms in tissue-organ allograft rejection involves the induction of granzymes and perforin, which are the main effector molecules expressed by CD8
MeSH term(s)	Adult ; Animals ; Antigens, CD/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Concanavalin A/pharmacology ; Female ; Flow Cytometry ; Graft Rejection ; Graft Survival ; Granzymes/metabolism ; HLA-G Antigens/metabolism ; Humans ; Kidney Transplantation ; Leukocyte Immunoglobulin-like Receptor B1/antagonists & inhibitors ; Leukocyte Immunoglobulin-like Receptor B1/metabolism ; Mice ; Real-Time Polymerase Chain Reaction ; T-Lymphocytes/metabolism
Chemical Substances	Antigens, CD ; HLA-G Antigens ; LILRB1 protein, human ; Leukocyte Immunoglobulin-like Receptor B1 ; Concanavalin A (11028-71-0) ; Granzymes (EC 3.4.21.-)
Language	English
Publishing date	2019-01-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.201802017R
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Zs.A 2266: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 296: Show issues

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Article ; Online: Instructive Role of MLL-Fusion Proteins Revealed by a Model of t(4;11) Pro-B Acute Lymphoblastic Leukemia.

Lin, Shan / Luo, Roger T / Ptasinska, Anetta / Kerry, Jon / Assi, Salam A / Wunderlich, Mark / Imamura, Toshihiko / Kaberlein, Joseph J / Rayes, Ahmad / Althoff, Mark J / Anastasi, John / O'Brien, Maureen M / Meetei, Amom Ruhikanta / Milne, Thomas A / Bonifer, Constanze / Mulloy, James C / Thirman, Michael J

Cancer cell

2016 Volume 30, Issue 5, Page(s) 737–749

Abstract: The t(4;11)(q21;q23) fuses mixed-lineage leukemia (MLL) to AF4, the most common MLL-fusion partner. Here we show that MLL fused to murine Af4, highly conserved with human AF4, produces high-titer retrovirus permitting efficient transduction of human ... ...

Abstract	The t(4;11)(q21;q23) fuses mixed-lineage leukemia (MLL) to AF4, the most common MLL-fusion partner. Here we show that MLL fused to murine Af4, highly conserved with human AF4, produces high-titer retrovirus permitting efficient transduction of human CD34
MeSH term(s)	Animals ; Antigens, CD34/metabolism ; Cell Lineage ; Cell Transformation, Neoplastic/genetics ; Disease Models, Animal ; Drug Resistance, Neoplasm ; Histone-Lysine N-Methyltransferase/genetics ; Humans ; Mice ; Myeloid-Lymphoid Leukemia Protein/genetics ; Myeloid-Lymphoid Leukemia Protein/metabolism ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism ; Translocation, Genetic
Chemical Substances	Antigens, CD34 ; KMT2A protein, human ; MLL-AF4 fusion protein, human ; MLL-AF9 fusion protein, human ; Oncogene Proteins, Fusion ; Myeloid-Lymphoid Leukemia Protein (149025-06-9) ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43)
Language	English
Publishing date	2016-11-15
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2016.10.008
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Zs.A 5650: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 104: Show issues

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Article ; Online: The non-anticoagulant promise of heparin and its mimetics.

Mulloy, Barbara

Current opinion in pharmacology

2019 Volume 46, Page(s) 50–54

Abstract: Heparin, the widely used anticoagulant and antithrombotic polysaccharide, has other potential therapeutic uses that arise from its similarity to heparan sulfate. This review provides a brief overview of the most recent developments in this field, paying ... ...

Abstract	Heparin, the widely used anticoagulant and antithrombotic polysaccharide, has other potential therapeutic uses that arise from its similarity to heparan sulfate. This review provides a brief overview of the most recent developments in this field, paying particular respect to pulmonary and respiratory pharmacology. It has often been said that heparin, with its mimetics and derivatives, shows great promise in the treatment of inflammatory, infectious, and malignant conditions. Difficulties are encountered, however, in translating this promise into worthwhile treatment strategies for patients in some conditions. Several clinical trials of low molecular weight heparins as adjuvant therapy to standard treatment of lung cancers have recently provided no evidence to support the supposed beneficial effects of low molecular weight heparin.
MeSH term(s)	Animals ; Anticoagulants/therapeutic use ; Heparin/analogs & derivatives ; Heparin/therapeutic use ; Humans ; Lung Diseases/drug therapy
Chemical Substances	Anticoagulants ; Heparin (9005-49-6)
Language	English
Publishing date	2019-04-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2037057-X
ISSN	1471-4973 ; 1471-4892
ISSN (online)	1471-4973
ISSN	1471-4892
DOI	10.1016/j.coph.2019.03.009
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Article: Heparin, Heparan Sulphate and Sepsis: Potential New Options for Treatment.

Hogwood, John / Gray, Elaine / Mulloy, Barbara

Pharmaceuticals (Basel, Switzerland)

2023 Volume 16, Issue 2

Abstract: Sepsis is a life-threatening hyperreaction to infection in which excessive inflammatory and immune responses cause damage to host tissues and organs. The glycosaminoglycan heparan sulphate (HS) is a major component of the cell surface glycocalyx. Cell ... ...

Abstract	Sepsis is a life-threatening hyperreaction to infection in which excessive inflammatory and immune responses cause damage to host tissues and organs. The glycosaminoglycan heparan sulphate (HS) is a major component of the cell surface glycocalyx. Cell surface HS modulates several of the mechanisms involved in sepsis such as pathogen interactions with the host cell and neutrophil recruitment and is a target for the pro-inflammatory enzyme heparanase. Heparin, a close structural relative of HS, is used in medicine as a powerful anticoagulant and antithrombotic. Many studies have shown that heparin can influence the course of sepsis-related processes as a result of its structural similarity to HS, including its strong negative charge. The anticoagulant activity of heparin, however, limits its potential in treatment of inflammatory conditions by introducing the risk of bleeding and other adverse side-effects. As the anticoagulant potency of heparin is largely determined by a single well-defined structural feature, it has been possible to develop heparin derivatives and mimetic compounds with reduced anticoagulant activity. Such heparin mimetics may have potential for use as therapeutic agents in the context of sepsis.
Language	English
Publishing date	2023-02-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph16020271
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Article ; Online: Chromatographic Molecular Weight Measurements for Heparin , Its Fragments and Fractions, and Other Glycosaminoglycans.

Mulloy, Barbara / Hogwood, John

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2303, Page(s) 227–240

Abstract: Glycosaminoglycan samples are usually polydisperse, consisting of molecules with differing length and differing sequence. Methods for measuring the molecular weight of heparin have been developed to assure the quality and consistency of heparin products ... ...

Abstract	Glycosaminoglycan samples are usually polydisperse, consisting of molecules with differing length and differing sequence. Methods for measuring the molecular weight of heparin have been developed to assure the quality and consistency of heparin products for medicinal use, and these methods can be applied in other laboratory contexts. In the method described here, high-performance gel permeation chromatography is calibrated using appropriate heparin molecular weight markers or a single broad standard calibrant and used to characterize the molecular weight distribution of polydisperse samples or the peak molecular weight of monodisperse, or approximately monodisperse, heparin fractions. The same technology can be adapted for use with other glycosaminoglycans.
MeSH term(s)	Chromatography, Gel ; Glycosaminoglycans ; Hematologic Tests ; Heparin/chemistry ; Heparitin Sulfate ; Molecular Weight
Chemical Substances	Glycosaminoglycans ; Heparin (9005-49-6) ; Heparitin Sulfate (9050-30-0)
Language	English
Publishing date	2021-10-08
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1398-6_18
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Article ; Online: Nuclear Magnetic Resonance Methods in Structural Characterization of Glycosaminoglycans.

Pomin, Vitor H / Mulloy, Barbara

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2303, Page(s) 183–207

Abstract: Glycosaminoglycans (GAGs) are sulfated glycans of complex structure and multiple biological actions. They are composed of disaccharide repeating units of alternating uronic acid/galactose and hexosamine. Sulfation patterns are an additional structural ... ...

Abstract	Glycosaminoglycans (GAGs) are sulfated glycans of complex structure and multiple biological actions. They are composed of disaccharide repeating units of alternating uronic acid/galactose and hexosamine. Sulfation patterns are an additional structural variation of these polymers. Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful analytical techniques employed in structural analysis of GAGs. 1D and 2D NMR spectra, both homonuclear
MeSH term(s)	Glycosaminoglycans ; Magnetic Resonance Spectroscopy
Chemical Substances	Glycosaminoglycans
Language	English
Publishing date	2021-10-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1398-6_16
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