Andrew Snavely, Eduardo J Pérez-Torres, Jeffrey S Weber, Sabina Sandigursky, Sujata P Thawani
OBJECTIVES: To evaluate the safety of immune checkpoint inhibitor use in patients with pre-existing neurological autoimmune diseases. METHODS: In this retrospective case-series, we examined exacerbations of underlying disease and the occurrence of immune-related adverse events in 5 patients who had been diagnosed with a neurological autoimmune disease prior to receiving immune checkpoint inhibitor therapy for advanced malignancy. RESULTS: Two patients had a prior diagnosis of myasthenia gravis, two had Guillain-Barré syndrome, and one had chronic idiopathic demyelinating polyneuropathy...
May 2, 2022: Journal of the Neurological Sciences
Juhi M Purswani, Brian Jaros, Cheongeun Oh, Sabina Sandigursky, Julie Xiao, Naamit K Gerber
BACKGROUND: Hypofractionation has historically been underutilized among breast cancer patients with connective tissue diseases given a theoretical risk for increased toxicity and their overall underrepresentation in clinical trials that established hypofractionation as standard of care. We aim to compare the rates of toxicity in patients with autoimmune connective tissue diseases treated with conventionally fractioned radiation therapy (CF-RT) and hypofractionated RT (HF-RT) including accelerated partial breast irradiation...
November 10, 2021: Practical Radiation Oncology
Salman Rafi Punekar, Rochelle Castillo, Sabina Sandigursky, Daniel Chang Cho
Immune checkpoint inhibitors (ICIs) are a class of medications targeting mostly the PD-1/PD-L1 and CTLA-4 immune pathways in the treatment of many cancers. Despite the encouraging success of ICIs, they are associated with immune-related adverse events as well as exacerbation of underlying autoimmune conditions. The treatment of these conditions often involves discontinuation of ICI in addition to the utilization of immunomodulatory agents. In this report, we discuss a case in which a patient with metastatic renal cell carcinoma experienced exacerbation of underlying paraneoplastic dermatomyositis after treatment with ICI...
October 1, 2021: Journal of Immunotherapy
Marianne Strazza, Kieran Adam, Shalom Lerrer, Johanna Straube, Sabina Sandigursky, Beatrix Ueberheide, Adam Mor
PD-1 is a critical therapeutic target in cancer immunotherapy and antibodies blocking PD-1 are approved for multiple types of malignancies. The phosphatase SHP2 is the main effector mediating PD-1 downstream signaling and accordingly attempts have been made to target this enzyme as an alternative approach to treat immunogenic tumors. Unfortunately, small molecule inhibitors of SHP2 do not work as expected, suggesting that the role of SHP2 in T cells is more complex than initially hypothesized. To better understand the perplexing role of SHP2 in T cells, we performed interactome mapping of SAP, an adapter protein that is associated with SHP2 downstream signaling...
August 2021: Inflammation
Juhi M Purswani, Cheongeun Oh, Brian Jaros, Sabina Sandigursky, Julie Xiao, Naamit K Gerber
PURPOSE: Autoimmune connective tissue disease (CTD) has historically represented a relative contraindication to breast conservation (BC) among patients with early-stage breast cancer. Controversy exists regarding the use of hypofractionated radiation therapy (RT) among patients with CTDs. We evaluated acute and late toxicity in patients with breast cancer and CTD treated with BC. METHODS AND MATERIALS: Of 1983 patients treated with BC from 2012 to 2016, we identified 91 patients with an autoimmune disease (AD)...
February 3, 2021: International Journal of Radiation Oncology, Biology, Physics
Patrick Boland, Anna C Pavlick, Jeffrey Weber, Sabina Sandigursky
In the past 10 years, immune checkpoint inhibitors (ICIs) have become an additional pillar of cancer therapy by activating the immune system to treat a number of different malignancies. Many patients receiving ICIs develop immune-related adverse events (irAEs) that mimic some features of classical autoimmune diseases. Unfortunately, patients with underlying autoimmune conditions, many of whom have an increased risk for malignancy, have been excluded from clinical trials of ICIs due to a concern that they will have an increased risk of irAEs...
April 2020: Journal for Immunotherapy of Cancer
Elizaveta Efuni, Samuel Cytryn, Patrick Boland, Timothy B Niewold, Anna Pavlick, Jeffrey Weber, Sabina Sandigursky
INTRODUCTION: Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced cancer. Rheumatoid arthritis (RA) is associated with an increased risk of malignancies; however, patients with RA have been excluded from ICI trials. In this study, we evaluated risk of toxicity after initiation of ICI treatment in RA patients. METHODS: We conducted a single-institution, medical records review analysis to assess the incidence of immune-related adverse events (irAEs) and autoimmune disease (AID) flares among patients with AIDs treated with ICIs from 2011 to 2018...
October 1, 2021: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
Daniel A Nadelman, David Orbuch, Sabina Sandigursky, Alisa N Femia
No abstract text is available yet for this article.
December 2019: JAAD Case Reports
Patrick Boland, Jacqueline Heath, Sabina Sandigursky
PURPOSE OF REVIEW: Clinical use of immune checkpoint inhibitor (ICI) therapy has revolutionized the therapeutic landscape of cancer. By activating the immune system using monoclonal anti-CTLA-4 and PD(L)-1 antibodies, remission can be induced in previously terminal cancers. However, these breakthroughs come at a price. Multiple de-novo autoimmune illnesses, termed immune-related adverse events (irAEs), have been reported with patients increasingly being referred to rheumatologists with varying diagnoses...
January 2020: Current Opinion in Rheumatology
Sabina Sandigursky, Adam Mor
PURPOSE OF REVIEW: With the advent of cancer immunotherapy and immune checkpoint inhibitors, patients with malignancies can now achieve durable remissions for conditions previously described as terminal. However, immune-related adverse events (irAEs) associated with cancer immunotherapy have become an anticipated consequence of enhanced T cell activation. Through an extensive literature review, we assess the most recent clinical and basic research data concerning immune checkpoint blockade and describe the spectrum of associated irAEs as well as their management...
September 6, 2018: Current Rheumatology Reports
Michael Peled, Anna S Tocheva, Sabina Sandigursky, Shruti Nayak, Elliot A Philips, Kim E Nichols, Marianne Strazza, Inbar Azoulay-Alfaguter, Manor Askenazi, Benjamin G Neel, Adam J Pelzek, Beatrix Ueberheide, Adam Mor
Programmed cell death-1 (PD-1) is an essential inhibitory receptor in T cells. Antibodies targeting PD-1 elicit durable clinical responses in patients with multiple tumor indications. Nevertheless, a significant proportion of patients do not respond to anti-PD-1 treatment, and a better understanding of the signaling pathways downstream of PD-1 could provide biomarkers for those whose tumors respond and new therapeutic approaches for those whose tumors do not. We used affinity purification mass spectrometry to uncover multiple proteins associated with PD-1...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
Neha Shah, Sabina Sandigursky, Adam Mor
Psoriasis is a common autoimmune disorder that affects the skin. Approximately 30% of individuals with psoriasis will develop inflammatory arthritis, often in the setting of human leukocyte antigen B27. Both forms of disease are thought to be the result of prolonged inflammation mediated by T lymphocytes, dendritic cells, and keratinocytes. While there are treatments aimed at immunomodulation, targeting T cell co-inhibitory receptors signaling pathways may provide therapeutic benefit. This review will discuss in detail four T cell co-inhibitory receptors and their potential application for the treatment of psoriasis and psoriatic arthritis...
May 2017: Bulletin of the Hospital for Joint Diseases
Sabina Sandigursky, Gregg J Silverman, Adam Mor
Since the introduction of TNF-α inhibitors and other biologic agents, the clinical outcome for many treated rheumatoid arthritis patients has significantly improved. However, there are still a substantial proportion of patients that are intolerant, or have inadequate responses, with current agents that have become the standards of care. While the majority of these agents are designed to affect the inflammatory features of the disease, there are also agents in the clinic that instead target lymphocyte subsets (e...
August 2017: Autoimmunity Reviews
Gary P Wormser, Dustin Brisson, Dionysios Liveris, Klára Hanincová, Sabina Sandigursky, John Nowakowski, Robert B Nadelman, Sara Ludin, Ira Schwartz
BACKGROUND: Lyme disease, the most common tickborne disease in the United States, is caused exclusively by Borrelia burgdorferi sensu stricto in North America. The present study evaluated the genotypes of >400 clinical isolates of B. burgdorferi recovered from patients from suburban New York City with early Lyme disease associated with erythema migrans; it is the largest number of borrelial strains from North America ever to be investigated. METHODS: Genotyping was performed by restriction fragment-length polymorphism polymerase chain reaction analysis of the 16S-23S ribosomal RNA spacer and reverse line blot analysis of the outer surface protein C gene (ospC)...
November 1, 2008: Journal of Infectious Diseases
Dionysios Liveris, Vishwaroop Mulay, Sabina Sandigursky, Ira Schwartz
RecA is a key protein linking genetic recombination to DNA replication and repair in bacteria. Previous functional characterization of Borrelia burgdorferi RecA indicated that the protein is mainly involved in genetic recombination rather than DNA repair. Genetic recombination may play a role in B. burgdorferi persistence by generation of antigenic variation. We report here the isolation of a recA null mutant in an infectious B. burgdorferi strain. Comparison of the in vitro growth characteristics of the mutant with those of the wild-type strain under various conditions showed no significant differences...
September 2008: Infection and Immunity
Klára Hanincová, Dionysios Liveris, Sabina Sandigursky, Gary P Wormser, Ira Schwartz
Lyme borreliosis, the most commonly reported vector-borne disease in North America, is caused by the spirochete Borrelia burgdorferi. Given the extensive genetic polymorphism of B. burgdorferi, elucidation of the population genetic structure of the bacterium in clinical samples may be relevant for understanding disease pathogenesis and may have applicability for the development of diagnostic tests and vaccine preparations. In this investigation, the genetic polymorphism of the 16S-23S rRNA (rrs-rrlA) intergenic spacer and ospC was investigated at the sequence level in 127 clinical isolates obtained from patients with early Lyme borreliosis evaluated in suburban New York City...
August 2008: Applied and Environmental Microbiology
Daniel E Dykhuizen, Dustin Brisson, Sabina Sandigursky, Gary P Wormser, John Nowakowski, Robert B Nadelman, Ira Schwartz
Lineages of Borrelia burgdorferi, the bacterium that causes Lyme disease, can be characterized by distinct alleles at the outer surface protein C (ospC) locus. The lineages marked by ospC genotypes have been shown to be differentially invasive in different species of mammals, including humans; genotypes A, B, I, and K effectively disseminate to human blood and cerebrospinal fluid. In this report, we extend the sample of genotypes isolated from human blood to include genotypes N, H, C, M, and D, and rank each by their probability of disseminating from ticks to the blood of humans...
May 2008: American Journal of Tropical Medicine and Hygiene
Margarita Sandigursky, Sabina Sandigursky, Pushpalatha Sonati, Michael J Daly, William A Franklin
The extremely radiation resistant bacterium, Deinococcus radiodurans, contains a spectrum of genes that encode for multiple activities that repair DNA damage. We have cloned and expressed the product of three predicted uracil-DNA glycosylases to determine their biochemical function. DR0689 is a homologue of the Escherichia coli uracil-DNA glycosylase, the product of the ung gene; this activity is able to remove uracil from a U : G and U : A base pair in double-stranded DNA and uracil from single-stranded DNA and is inhibited by the Ugi peptide...
February 3, 2004: DNA Repair
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