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Article ; Online: Differential sensing of sugars by colorimetric arrays.

Musto, Christopher J / Suslick, Kenneth S

2010 Volume 14, Issue 6, Page(s) 758–766

Abstract: While the complexes between boronic acids and diols have been studied for decades, researchers continue to design new and interesting methods to use these interactions to produce saccharide sensors that are more sensitive and selective. Herein we discuss ...

Abstract	While the complexes between boronic acids and diols have been studied for decades, researchers continue to design new and interesting methods to use these interactions to produce saccharide sensors that are more sensitive and selective. Herein we discuss how the use of pattern-based colorimetric arrays from a collection of crossreactive sensors have been developed as new differential sensing platforms for sugars and related saccharides.
MeSH term(s)	Animals ; Boronic Acids/chemistry ; Carbohydrates/analysis ; Colorimetry/methods ; Humans ; Hydrogen-Ion Concentration ; Oxidation-Reduction
Chemical Substances	Boronic Acids ; Carbohydrates
Language	English
Publishing date	2010-08-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1439176-4
ISSN	1879-0402 ; 1367-5931
ISSN (online)	1879-0402
ISSN	1367-5931
DOI	10.1016/j.cbpa.2010.07.006
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Article ; Online: Development of Solid-Phase Site-Specific Conjugation and Its Application toward Generation of Dual Labeled Antibody and Fab Drug Conjugates.

Puthenveetil, Sujiet / Musto, Sylvia / Loganzo, Frank / Tumey, L Nathan / O'Donnell, Christopher J / Graziani, Edmund

Bioconjugate chemistry

2016 Volume 27, Issue 4, Page(s) 1030–1039

Abstract: The focus of the antibody-drug conjugate (ADC) field is shifting toward development of site-specific, next-generation ADCs to address the issue of heterogeneity, metabolic instability, conjugatability, and less than ideal therapeutic index associated ... ...

Abstract	The focus of the antibody-drug conjugate (ADC) field is shifting toward development of site-specific, next-generation ADCs to address the issue of heterogeneity, metabolic instability, conjugatability, and less than ideal therapeutic index associated with the conventional (heterogeneous) ADCs. It is evident from the recent literature that the site of conjugation, the structure of the linker, and the physicochemical properties of the linker-payload all have a significant impact on the safety and efficacy of the resulting ADCs. Screening multiple linker-payloads on multiple sites of an antibody presents a combinatorial problem that necessitates high-throughput conjugation and purification methodology to identify ADCs with the best combination of site and payload. Toward this end, we developed a protein A/L-based solid-phase, site-specific conjugation and purification method that can be used to generate site-specific ADCs in a 96-well plate format. This solid-phase method has been shown to be versatile because of its compatibility with various conjugation functional handles such as maleimides, haloacetamides, copper free click substrates, and transglutaminase substrates. The application of this methodology was further expanded to generate dual labeled, site-specific antibody and Fab conjugates.
MeSH term(s)	Antibodies/chemistry ; Immunoconjugates/chemistry ; Immunoglobulin Fab Fragments/chemistry
Chemical Substances	Antibodies ; Immunoconjugates ; Immunoglobulin Fab Fragments
Language	English
Publishing date	2016-04-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1024041-x
ISSN	1520-4812 ; 1043-1802
ISSN (online)	1520-4812
ISSN	1043-1802
DOI	10.1021/acs.bioconjchem.6b00054
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Article ; Online: Novel PIKK inhibitor antibody-drug conjugates: Synthesis and anti-tumor activity.

Zhou, Dahui / Casavant, Jeffrey / Graziani, Edmund I / He, Haiyin / Janso, Jeffrey / Loganzo, Frank / Musto, Sylvia / Tumey, Nathan / O'Donnell, Christopher J / Dushin, Russell

Bioorganic & medicinal chemistry letters

2019 Volume 29, Issue 7, Page(s) 943–947

Abstract: Novel neolymphostin-based antibody-drug conjugate (ADC) precursors were synthesized either through amide couplings between both cleavable and non-cleavable linkers and neolymphostin derivatives, or through Cu(I)-catalyzed acetylene-azide click ... ...

Abstract	Novel neolymphostin-based antibody-drug conjugate (ADC) precursors were synthesized either through amide couplings between both cleavable and non-cleavable linkers and neolymphostin derivatives, or through Cu(I)-catalyzed acetylene-azide click cycloadditon between non-cleavable linkers and neolymphostin acetal derivatives. These precursors were site-specifically conjugated to cysteine mutant trastuzumab-A114C to provide neolymphostin-based ADCs. Preliminary in vitro data indicated that the corresponding ADCs were active against HER2-expressing tumor cell lines, thus providing a proof-of-concept for using neolymphostin as ADC-based anticancer agents.
MeSH term(s)	Aminoquinolines/chemical synthesis ; Aminoquinolines/pharmacology ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Humans ; Immunoconjugates/pharmacology ; Mutation ; Phosphoinositide-3 Kinase Inhibitors/chemical synthesis ; Phosphoinositide-3 Kinase Inhibitors/pharmacology ; Proof of Concept Study ; Pyrroles/chemical synthesis ; Pyrroles/pharmacology ; Trastuzumab/genetics ; Trastuzumab/pharmacology
Chemical Substances	Aminoquinolines ; Antineoplastic Agents ; Immunoconjugates ; Phosphoinositide-3 Kinase Inhibitors ; Pyrroles ; Trastuzumab (P188ANX8CK)
Language	English
Publishing date	2019-01-11
Publishing country	England
Document type	Journal Article
ZDB-ID	1063195-1
ISSN	1464-3405 ; 0960-894X
ISSN (online)	1464-3405
ISSN	0960-894X
DOI	10.1016/j.bmcl.2019.01.009
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Article ; Online: A simple and highly sensitive colorimetric detection method for gaseous formaldehyde.

Feng, Liang / Musto, Christopher J / Suslick, Kenneth S

Journal of the American Chemical Society

2010 Volume 132, Issue 12, Page(s) 4046–4047

Abstract: A colorimetric detection method using amine-functionalized polymer films doped with a pH indicator has been developed for the rapid, sensitive, and quantitative detection of gaseous formaldehyde at concentrations well below the immediately dangerous to ... ...

Abstract	A colorimetric detection method using amine-functionalized polymer films doped with a pH indicator has been developed for the rapid, sensitive, and quantitative detection of gaseous formaldehyde at concentrations well below the immediately dangerous to life or health (IDLH) limit. In 1 min, visible color changes are easily observed, even down to the permissible exposure limit (PEL) at 750 ppb. The limit of detection is below 50 ppb (7% of the PEL) after 10 min of exposure. This sensor is essentially unaffected by changes in humidity or temperature (4 to 50 degrees C) and is not sensitive to common interferents.
MeSH term(s)	Colorimetry/methods ; Formaldehyde/chemistry ; Gases ; Molecular Structure
Chemical Substances	Gases ; Formaldehyde (1HG84L3525)
Language	English
Publishing date	2010-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/ja910366p
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Article ; Online: Colorimetric detection and identification of natural and artificial sweeteners.

Musto, Christopher J / Lim, Sung H / Suslick, Kenneth S

Analytical chemistry

2010 Volume 81, Issue 15, Page(s) 6526–6533

Abstract: A disposable, low-cost colorimetric sensor array has been created by pin-printing onto a hydrophilic membrane 16 chemically responsive nanoporous pigments that are comprised of indicators immobilized in an organically modified silane (ormosil). The array ...

Abstract	A disposable, low-cost colorimetric sensor array has been created by pin-printing onto a hydrophilic membrane 16 chemically responsive nanoporous pigments that are comprised of indicators immobilized in an organically modified silane (ormosil). The array has been used to detect and identify 14 different natural and artificial sweeteners at millimolar concentrations, as well as commonly used individual-serving sweetener packets. The array has shown excellent reproducibility and long shelf life and has been optimized to work in the biological pH regime.
MeSH term(s)	Biosensing Techniques ; Colorimetry/instrumentation ; Colorimetry/methods ; Coloring Agents/chemistry ; Electrochemistry ; Image Processing, Computer-Assisted ; Indicators and Reagents/chemistry ; Microarray Analysis ; Principal Component Analysis ; Reproducibility of Results ; Siloxanes/chemistry ; Sweetening Agents/chemistry ; Tea/chemistry
Chemical Substances	Coloring Agents ; Indicators and Reagents ; Siloxanes ; Sweetening Agents ; Tea ; ormosil
Language	English
Publishing date	2010-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/ac901019g
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Article ; Online: Impact of severe acute respiratory syndrome coronavirus-2 infection on the outcome of primary central nervous system lymphoma treatment: A study of the International PCNSL Collaborative Group.

Steffanoni, Sara / Calimeri, Teresa / Laurenge, Alice / Fox, Christopher P / Soussain, Carole / Grommes, Christian / Tisi, Maria Chiara / Boot, Jesca / Crosbie, Nicola / Visco, Carlo / Arcaini, Luca / Chaganti, Sridhar / Sassone, Marianna C / Alencar, Alvaro / Armiento, Daniele / Romano, Ilaria / Dietrich, Jorg / Itchaki, Gilad / Bruna, Riccardo /

Fracchiolla, Nicola S / Arletti, Laura / Venditti, Adriano / Booth, Stephen / Musto, Pellegrino / Hoang Xuan, Khê / Batchelor, Tracy T / Cwynarski, Kate / Ferreri, Andrés J M

British journal of haematology

2022 Volume 199, Issue 4, Page(s) 507–519

Abstract: To optimise management of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection identifying high-risk patients and maintaining treatment dose intensity is an important issue in patients with aggressive lymphomas. In the present study, we ...

Abstract	To optimise management of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection identifying high-risk patients and maintaining treatment dose intensity is an important issue in patients with aggressive lymphomas. In the present study, we report on the presentation, management, and outcome of an international series of 91 patients with primary central nervous system lymphoma and SARS-CoV-2 infection. SARS-CoV-2 was diagnosed before/during first-line treatment in 64 patients, during follow-up in 21, and during salvage therapy in six. Among the 64 patients infected before/during first-line chemotherapy, 38 (59%) developed pneumonia and 26 (41%) did not clear the virus. Prolonged exposure to steroids before viral infection and/or treatment with high-dose cytarabine favoured pneumonia development and virus persistence and were associated with poorer survival; 81% of patients who did not clear virus died early from coronavirus disease 2019 (COVID-19). Vaccination was associated with lower pneumonia incidence and in-hospital mortality. Chemotherapy was initiated/resumed in 43 (67%) patients, more commonly among patients who did not develop pneumonia, cleared the virus, or did not receive steroids during infection. Chemotherapy resumption in patients with viral persistence should be indicated cautiously as it was associated with a poorer survival (6-month, 70% and 87%, p = 0.07). None of the 21 patients infected during follow-up died from COVID-19, requiring similar measures as infected subjects in the general population.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Central Nervous System ; Lymphoma/drug therapy
Language	English
Publishing date	2022-08-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18396
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Article ; Online: GABRA1-Related Disorders: From Genetic to Functional Pathways.

Musto, Elisa / Liao, Vivian W Y / Johannesen, Katrine M / Fenger, Christina D / Lederer, Damien / Kothur, Kavitha / Fisk, Katrina / Bennetts, Bruce / Vrielynck, Pascal / Delaby, Delphine / Ceulemans, Berten / Weckhuysen, Sarah / Sparber, Peter / Bouman, Arjan / Ardern-Holmes, Simone / Troedson, Christopher / Battaglia, Domenica I / Goel, Himanshu / Feyma, Timothy /

Bakhtiari, Somayeh / Tjoa, Linda / Boxill, Martin / Demina, Nina / Shchagina, Olga / Dadali, Elena / Kruer, Michael / Cantalupo, Gaetano / Contaldo, Ilaria / Polster, Tilman / Isidor, Bertrand / Bova, Stefania M / Fazeli, Walid / Wouters, Leen / Miranda, Maria J / Darra, Francesca / Pede, Elisa / Le Duc, Diana / Jamra, Rami Abou / Küry, Sébastien / Proietti, Jacopo / McSweeney, Niamh / Brokamp, Elly / Andrews, Peter Ian / Gouray Garcia, Marie / Chebib, Mary / Møller, Rikke S / Ahring, Philip K / Gardella, Elena

Annals of neurology

2023

Abstract: Objective: Variants in GABRA1 have been associated with a broad epilepsy spectrum, ranging from genetic generalized epilepsies to developmental and epileptic encephalopathies. However, our understanding of what determines the phenotype severity and best ...

Abstract	Objective: Variants in GABRA1 have been associated with a broad epilepsy spectrum, ranging from genetic generalized epilepsies to developmental and epileptic encephalopathies. However, our understanding of what determines the phenotype severity and best treatment options remains inadequate. We therefore aimed to analyze the electroclinical features and the functional effects of GABRA1 variants to establish genotype-phenotype correlations. Methods: Genetic and electroclinical data of 27 individuals (22 unrelated and 2 families) harboring 20 different GABRA1 variants were collected and accompanied by functional analysis of 19 variants. Results: Individuals in this cohort could be assigned into different clinical subgroups based on the functional effect of their variant and its structural position within the GABRA1 subunit. A homogenous phenotype with mild cognitive impairment and infantile onset epilepsy (focal seizures, fever sensitivity, and electroencephalographic posterior epileptiform discharges) was described for variants in the extracellular domain and the small transmembrane loops. These variants displayed loss-of-function (LoF) effects, and the patients generally had a favorable outcome. A more severe phenotype was associated with variants in the pore-forming transmembrane helices. These variants displayed either gain-of-function (GoF) or LoF effects. GoF variants were associated with severe early onset neurodevelopmental disorders, including early infantile developmental and epileptic encephalopathy. Interpretation: Our data expand the genetic and phenotypic spectrum of GABRA1 epilepsies and permit delineation of specific subphenotypes for LoF and GoF variants, through the heterogeneity of phenotypes and variants. Generally, variants in the transmembrane helices cause more severe phenotypes, in particular GoF variants. These findings establish the basis for a better understanding of the pathomechanism and a precision medicine approach in GABRA1-related disorders. Further studies in larger populations are needed to provide a conclusive genotype-phenotype correlation. ANN NEUROL 2023.
Language	English
Publishing date	2023-08-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	80362-5
ISSN	1531-8249 ; 0364-5134
ISSN (online)	1531-8249
ISSN	0364-5134
DOI	10.1002/ana.26774
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Article ; Online: Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate.

Puthenveetil, Sujiet / He, Haiyin / Loganzo, Frank / Musto, Sylvia / Teske, Jesse / Green, Michael / Tan, Xingzhi / Hosselet, Christine / Lucas, Judy / Tumey, L Nathan / Sapra, Puja / Subramanyam, Chakrapani / O'Donnell, Christopher J / Graziani, Edmund I

PloS one

2017 Volume 12, Issue 5, Page(s) e0178452

Abstract: Antibody drug conjugates (ADCs) are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads ... ...

Abstract	Antibody drug conjugates (ADCs) are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads beyond the mictotubule inhibitors and DNA damaging agents has led us to the recent discovery of an mRNA splicing inhibitor, thailanstatin, as a potent ADC payload. In our previous work, we observed that the potency of this payload was uniquely tied to the method of conjugation, with lysine conjugates showing much superior potency as compared to cysteine conjugates. However, the ADC field is rapidly shifting towards site-specific ADCs due to their advantages in manufacturability, characterization and safety. In this work we report the identification of a highly efficacious site-specific thailanstatin ADC. The site of conjugation played a critical role on both the in vitro and in vivo potency of these ADCs. During the course of this study, we developed a novel methodology of loading a single site with multiple payloads using an in situ generated multi-drug carrying peptidic linker that allowed us to rapidly screen for optimal conjugation sites. Using this methodology, we were able to identify a double-cysteine mutant ADC delivering four-loaded thailanstatin that was very efficacious in a gastric cancer xenograft model at 3mg/kg and was also shown to be efficacious against T-DM1 resistant and MDR1 overexpressing tumor cell lines.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Drug Carriers ; Drug Screening Assays, Antitumor ; Humans ; Immunoconjugates/chemistry ; Peptides/chemistry ; Pyrans/chemistry ; Pyrans/pharmacology
Chemical Substances	Antineoplastic Agents ; Drug Carriers ; Immunoconjugates ; Peptides ; Pyrans
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0178452
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Article ; Online: A colorimetric sensor array for identification of toxic gases below permissible exposure limits.

Feng, Liang / Musto, Christopher J / Kemling, Jonathan W / Lim, Sung H / Suslick, Kenneth S

Chemical communications (Cambridge, England)

2010 Volume 46, Issue 12, Page(s) 2037–2039

Abstract: A colorimetric sensor array has been developed for the rapid and sensitive detection of 20 toxic industrial chemicals (TICs) at their PELs (permissible exposure limits). The color changes in an array of chemically responsive nanoporous pigments provide ... ...

Abstract	A colorimetric sensor array has been developed for the rapid and sensitive detection of 20 toxic industrial chemicals (TICs) at their PELs (permissible exposure limits). The color changes in an array of chemically responsive nanoporous pigments provide facile identification of the TICs with an error rate below 0.7%.
MeSH term(s)	Colorimetry/instrumentation ; Gases/analysis ; Limit of Detection
Chemical Substances	Gases
Language	English
Publishing date	2010-03-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1472881-3
ISSN	1364-548X ; 1359-7345 ; 0009-241X
ISSN (online)	1364-548X
ISSN	1359-7345 ; 0009-241X
DOI	10.1039/b926848k
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Article ; Online: Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN).

Leukemia

2023 Volume 37, Issue 6, Page(s) 1175–1185

Abstract: In the post-pandemic COVID-19 period, human activities have returned to normal and COVID-19 cases are usually mild. However, patients with multiple myeloma (MM) present an increased risk for breakthrough infections and severe COVID-19 outcomes, including ...

Abstract	In the post-pandemic COVID-19 period, human activities have returned to normal and COVID-19 cases are usually mild. However, patients with multiple myeloma (MM) present an increased risk for breakthrough infections and severe COVID-19 outcomes, including hospitalization and death. The European Myeloma Network has provided an expert consensus to guide patient management in this era. Vaccination with variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4/5 strains, is essential as novel strains emerge and become dominant in the community. Boosters should be administered every 6-12 months after the last vaccine shot or documented COVID-19 infection (hybrid immunity). Booster shots seem to overcome the negative effect of anti-CD38 monoclonal antibodies on humoral responses; however, anti-BCMA treatment remains an adverse predictive factor for humoral immune response. Evaluation of the immune response after vaccination may identify a particularly vulnerable subset of patients who may need additional boosters, prophylactic therapies and prevention measures. Pre-exposure prophylaxis with tixagevimab/cilgavimab is not effective against the new dominant variants and thus is no longer recommended. Oral antivirals (nirmatrelvir/ritonavir and molnupiravir) and remdesivir are effective against Omicron subvariants BA.2.12.1, BA.4, BA.5, BQ.1.1 and/or XBB.1.5 and should be administered in MM patients at the time of a positive COVID-19 test or within 5 days post symptoms onset. Convalescent plasma seems to have low value in the post-pandemic era. Prevention measures during SARS-CoV-2 outbreaks, including mask wearing and avoiding crowded places, seem prudent to continue for MM patients.
MeSH term(s)	Humans ; COVID-19/epidemiology ; Multiple Myeloma/therapy ; SARS-CoV-2 ; COVID-19 Serotherapy ; Consensus ; Pandemics ; Antibodies, Neutralizing
Chemical Substances	Antibodies, Neutralizing
Language	English
Publishing date	2023-05-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-023-01920-1
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