Christine M. Fisher

United States Food and Drug Administration

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Ann M. Knolhoff

Center for Food Safety and Applied Nutrition

Jon R. Sobus

Environmental Protection Agency

Antony Williams

Research Triangle Park Foundation

Scott A. McLuckey

Purdue University West Lafayette

Susan Genualdi

Center for Food Safety and Applied Nutrition

Lowri DeJager

United States Food and Drug Administration

Allison L. Phillips

Duke University

Andrew D. McEachran

Agilent Technologies (United States)

Katherine T. Peter

Center for Urban Waters

Brian Ng

Florida International University

Cooperative Institutions

United States Food and Drug Administration

Center for Food Safety and Applied Nutrition

Cancer Institute (WIA)

Environmental Protection Agency

University of Colorado Denver

Cleveland Clinic

University Hospitals Seidman Cancer Center

Research Triangle Park Foundation

University of Colorado Anschutz Medical Campus

Purdue University West Lafayette

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Novel methods for manipulating ion types in the solution and gas phases for the structural analysis of biomolecules using Mass Spectrometry

Christine M. Fisher

Biomolecule

Ion-mobility spectrometry

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Data from Combination of Trastuzumab Emtansine and Stereotactic Radiosurgery Results in High Rates of Clinically Significant Radionecrosis and Dysregulation of Aquaporin-4

Priscilla K. Stumpf Diana M. Cittelly Tyler P. Robin Julie A. Carlson Kelly Stuhr

<div>AbstractPurpose:Patients with human EGFR2-positive (HER2+) breast cancer have a high incidence of brain metastases, and trastuzumab emtansine (T-DM1) is often employed. Stereotactic radiosurgery (SRS) is frequently utilized, and case series report increased toxicity with combination SRS and T-DM1. We provide an update of our experience of T-DM1 and SRS evaluating risk of clinically significant radionecrosis (CSRN) and propose a mechanism for this toxicity.Experimental Design:Patients with breast cancer who were ≤45 years regardless of HER2 status or had HER2+ disease regardless of age and underwent SRS for brain metastases were included. Rates of CSRN, SRS data, and details of T-DM1 administration were recorded. Proliferation and astrocytic swelling studies were performed to elucidate mechanisms of toxicity.Results:A total of 45 patients were identified; 66.7% were HER2+, and 60.0% were ≤ 45 years old. Of the entire cohort, 10 patients (22.2%) developed CSRN, 9 of whom received T-DM1. CSRN was observed in 39.1% of patients who received T-DM1 versus 4.5% of patients who did not. Receipt of T-DM1 was associated with a 13.5-fold (P = 0.02) increase in CSRN. Mechanistically, T-DM1 targeted reactive astrocytes and increased radiation-induced cytotoxicity and astrocytic swelling via upregulation of Aquaporin-4 (Aqp4).Conclusions:The strong correlation between development of CSRN after SRS and T-DM1 warrants prospective studies controlling for variations in timing of T-DM1 and radiation dosing to further stratify risk of CSRN and mitigate toxicity. Until such studies are completed, we advise caution in the combination of SRS and T-DM1.</div>

Trastuzumab emtansine

10.1158/1078-0432.c.6527591

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Online and Offline Prioritization of Chemicals of Interest in Suspect Screening and Non-targeted Screening with High-Resolution Mass Spectrometry

Analytical Chemistry (2024)

Drew Szabo Travis M. Falconer Christine M. Fisher Ted Heise Allison L. Phillips

Recent advances in high-resolution mass spectrometry (HRMS) have enabled the detection of thousands of chemicals from a single sample, while computational methods have improved the identification and quantification of these chemicals in the absence of reference standards typically required in targeted analysis. However, to determine the presence of chemicals of interest that may pose an overall impact on ecological and human health, prioritization strategies must be used to effectively and efficiently highlight chemicals for further investigation. Prioritization can be based on a chemical's physicochemical properties, structure, exposure, and toxicity, in addition to its regulatory status. This Perspective aims to provide a framework for the strategies used for chemical prioritization that can be implemented to facilitate high-quality research and communication of results. These strategies are categorized as either "online" or "offline" prioritization techniques. Online prioritization techniques trigger the isolation and fragmentation of ions from the low-energy mass spectra in real time, with user-defined parameters. Offline prioritization techniques, in contrast, highlight chemicals of interest after the data has been acquired; detected features can be filtered and ranked based on the relative abundance or the predicted structure, toxicity, and concentration imputed from the tandem mass spectrum (MS

Prioritization

Identification

Fragmentation

10.1021/acs.analchem.3c05705

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Citations (7)

Vulvar Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology

Journal of the National Comprehensive Cancer Network (2016)

Wui‐Jin Koh Benjamin E. Greer Nadeem R. Abu‐Rustum Susana M. Campos Kathleen R. Cho

Vulvar cancer is a rare gynecologic malignancy. Ninety percent of vulvar cancers are predominantly squamous cell carcinomas (SCCs), which can arise through human papilloma virus (HPV)–dependent and HPV-independent pathways. The NCCN Vulvar Cancer panel is an interdisciplinary group of representatives from NCCN Member Institutions consisting of specialists in gynecological oncology, medical oncology, radiation oncology, and pathology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vulvar Cancer provide an evidence- and consensus-based approach for the management of patients with vulvar SCC. This manuscript discusses the recommendations outlined in the NCCN Guidelines for diagnosis, staging, treatment, and follow-up.

Gynecologic oncology

Clinical Oncology

Clinical Practice

Radiation oncology

10.6004/jnccn.2017.0008

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Citations (162)

Strategies for generating peptide radical cations via ion/ion reactions

Journal of Mass Spectrometry (2015)

Joshua D. Gilbert Christine M. Fisher Jiexun Bu Boone M. Prentice James G. Redwine

Several approaches for the generation of peptide radical cations using ion/ion reactions coupled with either collision induced dissociation (CID) or ultraviolet photo dissociation (UVPD) are described here. Ion/ion reactions are used to generate electrostatic or covalent complexes comprised of a peptide and a radical reagent. The radical site of the reagent can be generated multiple ways. Reagents containing a carbon–iodine (C―I) bond are subjected to UVPD with 266‐nm photons, which selectively cleaves the C―I bond homolytically. Alternatively, reagents containing azo functionalities are collisionally activated to yield radical sites on either side of the azo group. Both of these methods generate an initial radical site on the reagent, which then abstracts a hydrogen from the peptide while the peptide and reagent are held together by either electrostatic interactions or a covalent linkage. These methods are demonstrated via ion/ion reactions between the model peptide RARARAA (doubly protonated) and various distonic anionic radical reagents. The radical site abstracts a hydrogen atom from the peptide, while the charge site abstracts a proton. The net result is the conversion of a doubly protonated peptide to a peptide radical cation. The peptide radical cations have been fragmented via CID and the resulting product ion mass spectra are compared to the control CID spectrum of the singly protonated, even‐electron species. This work is then extended to bradykinin, a more broadly studied peptide, for comparison with other radical peptide generation methods. The work presented here provides novel methods for generating peptide radical cations in the gas phase through ion/ion reaction complexes that do not require modification of the peptide in solution or generation of non‐covalent complexes in the electrospray process. Copyright © 2015 John Wiley & Sons, Ltd.

Radical ion

10.1002/jms.3548

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Citations (9)

Standardizing non-targeted analysis reporting to advance exposure science and environmental epidemiology

Journal of Exposure Science & Environmental Epidemiology (2023)

Allison L. Phillips Katherine T. Peter Jon R. Sobus Christine M. Fisher Carlos A. Manzano

Environmental epidemiology

Exposure Assessment

10.1038/s41370-022-00490-1

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Citations (6)

Exploring chemical space in non-targeted analysis: a proposed ChemSpace tool

Analytical and Bioanalytical Chemistry (2022)

Gabrielle P. Black Charles Lowe Tarun Anumol Jessica Bade Kristin Favela

Chemical space

Sample (material)

Identification

10.1007/s00216-022-04434-4

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Citations (42)

Supplementary Data from Combination of Trastuzumab Emtansine and Stereotactic Radiosurgery Results in High Rates of Clinically Significant Radionecrosis and Dysregulation of Aquaporin-4

Priscilla K. Stumpf Diana M. Cittelly Tyler P. Robin Julie A. Carlson Kelly Stuhr

Chemotherapy effects on astrocytes

Trastuzumab emtansine

10.1158/1078-0432.22470503.v1

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Citations (0)

Supplementary Data from Combination of Trastuzumab Emtansine and Stereotactic Radiosurgery Results in High Rates of Clinically Significant Radionecrosis and Dysregulation of Aquaporin-4

Priscilla K. Stumpf Diana M. Cittelly Tyler P. Robin Julie A. Carlson Kelly Stuhr

Chemotherapy effects on astrocytes

Trastuzumab emtansine

10.1158/1078-0432.22470503

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Citations (0)

Communicating with Stakeholders to Identify High-Impact Research Directions for Non-Targeted Analysis

Analytical Chemistry (2025)

Sara L. Nason James McCord Yong-Lai Feng Jon R. Sobus Christine M. Fisher

Non-targeted analysis (NTA) using high-resolution mass spectrometry without defined chemical targets has the potential to expand and improve chemical monitoring in many fields. Despite rapid advancements within the research community, NTA methods and data remain underutilized by many potential beneficiaries. To better understand barriers toward widespread adoption, the Best Practices for Non-Targeted Analysis (BP4NTA) working group conducted focus group meetings and follow-up surveys with scientists (n = 61) from various sectors (e.g., drinking water utilities, epidemiologists, n = 9) where NTA is expected to provide future value. Meeting participants included producers and end-users of NTA data with a wide range of familiarity with NTA methods and outputs. Discussions focused on identifying specific barriers that limit adoption and on setting NTA product development priorities. Stated priorities fell into four major categories: 1) education and training materials; 2) QA/QC frameworks and study design guidance; 3) accessible compound databases and libraries; and 4) NTA data linkages with chemical fate and toxicity information. Based on participant feedback, this manuscript proposes research directions, such as standardization of training materials, that BP4NTA and other institutions can pursue to expand NTA use in various application scenarios and decision contexts.

10.1021/acs.analchem.4c04801

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Citations (1)