43 research outputs found
sj-pdf-1-eso-10.1177_23969873221106907 – Supplemental material for Temporal profiles of systolic blood pressure variability and neurologic outcomes after endovascular thrombectomy
No full textSupplemental material, sj-pdf-1-eso-10.1177_23969873221106907 for Temporal profiles of systolic blood pressure variability and neurologic outcomes after endovascular thrombectomy by Ayush Prasad, Jessica Kobsa, Sreeja Kodali, David Bartolome, Liza Begunova, Darko Quispe-Orozco, Mudassir Farooqui, Cynthia Zevallos, Santiago Ortega-Gutiérrez, Mohammad Anadani, Eyad Almallouhi, Alejandro M Spiotta, James A Giles, Salah G Keyrouz, Joon-Tae Kim, Ilko L Maier, Jan Liman, Marios-Nikos Psychogios, Nolwenn Riou-Comte, Sébastien Richard, Benjamin Gory, Stacey Quintero Wolfe, Patrick A Brown, Kyle M Fargen, Eva A Mistry, Hiba Fakhri, Akshitkumar Mistry, Ka-Ho Wong, Fábio A Nascimento, Peter Kan, Adam de Havenon, Kevin N Sheth and Nils H Petersen in European Stroke Journal</p
Response by Mistry et al to Letter Regarding Article, “Mechanical Thrombectomy Outcomes With and Without Intravenous Thrombolysis in Stroke Patients: A Meta-Analysis”
No full textAssessing the influence of subventricular zone contact of glioblastomas with gross total resection on patient survival
No full textConsiderations in Meta-Analyses to Understand the Value of Intravenous Thrombolysis in Current, Guideline-Based, Endovascular Practice of Stroke Treatment
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Abstract 120: Systolic Blood Pressure Trajectories 72 Hours After Mechanical Thrombectomy Are Associated With Poor Functional Outcome: A Multicenter Analysis of Individual Patient Blood Pressure Data
No full textAbstract 364: Mass cytometry of human glioblastoma characterizes more than 99 percent of cells and reveals intratumoral cell subsets defined by contrasting signaling network profiles
No full textAbstract
Background: Glioblastoma (GBM) remains largely incurable despite intense study of resected tissue. Prior studies have revealed GBM cell subsets (Patel et al., Science 2014) and have implicated subset emergence as a potential mechanism of poor outcome in other cancer types. Signaling in rare cells or a mix of cell subsets may enable therapy resistance and recurrence of GBM. For example, STAT3 RNA expression has been previously shown to correlate with poor outcome in GBM (Jahani-Asl et al., Nat Neurosci 2016 and TCGA). The complexity of GBM, combined with the interconnectedness between cancer and host cells in the microenvironment, means that a single cell biology approach is needed to comprehensively characterize patient biopsy cells and determine how protein expression, signaling, and functional capabilities impact treatment response.
Methods: We developed a novel mass cytometry approach to characterize human GBM that identified ~90-95% of tumor cells (Leelatian & Doxie et al., Cytometry B 2016). Here, we applied this approach using a newly created 35-antibody mass cytometry panel focused on basal phospho-protein signaling. The published panel of 16 identity proteins included SOX2, CD44, Nestin, PDGFRα, S100B, and NCAM. This panel was augmented to measure 10 additional proteins and 9 phospho-proteins including p-STAT3, p-EGFR, and p-NFκB. Signaling measurements were chosen to match prior single cell studies of signaling networks that stratified clinical outcomes in blood cancers (Irish et al., Cell 2004; PNAS 2010, Levine et al., Cell 2015). Between 10,000 and 250,000 viable cells were characterized for each tumor (N = 7). Tumors were collected with informed consent and in accord with the Declaration of Helsinki.
Results: This new 35-antibody mass cytometry panel positively identified &gt;99% of GBM cells. Subsets of GBM cells displayed protein expression that matched previously observed transcriptional molecular subclasses (Verhaak et al., Cancer Cell 2010 and TCGA). Strikingly, this panel revealed novel GBM cell subsets defined by contrasting basal signaling profiles. An inverse correlation was observed between baseline STAT3 phosphorylation and the abundance of CD45+ leukocytes. Additionally, similar signaling patterns were seen in cells that expressed proteins associated with distinct functions, such as proliferation and migration.
Conclusions: The correlation between low STAT3 signaling and high immune cell abundance provides evidence for the idea that an intimate relationship exists between immune cells and GBM tumor growth and survival. Moreover, single cell analysis may reveal biomarkers of treatment response and allow prediction of clinical outcomes. The abnormal signaling mechanisms observed here in some GBM cell subsets should be studied further as potential targets for novel cancer-selective combination therapies.
Citation Format: Nalin Leelatian, Justine Sinnaeve, Bret C. Mobley, Akshitkumar M. Mistry, Daniel Liu, Kyle D. Weaver, Reid C. Thompson, Lola B. Chambless, Rebecca A. Ihrie, Jonathan M. Irish. Mass cytometry of human glioblastoma characterizes more than 99 percent of cells and reveals intratumoral cell subsets defined by contrasting signaling network profiles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 364. doi:10.1158/1538-7445.AM2017-364</jats:p
Clinical prognostic value of the isocitrate dehydrogenase 1 single-nucleotide polymorphism rs11554137 in glioblastoma
No full textRecommended from our members
Subarachnoid Hemorrhage Trials: Cutting, Sliding, or Keeping mRS Scores and WFNS Grades.
No full textRigorous evidence generation with randomized controlled trials has lagged for aneurysmal subarachnoid hemorrhage (SAH) compared with other forms of acute stroke. Besides its lower incidence compared with other stroke subtypes, the presentation and outcome of patients with SAH also differ. This must be considered and adjusted for in designing pivotal randomized controlled trials of patients with SAH. Here, we show the effect of the unique expected distribution of the SAH severity at presentation (World Federation of Neurological Surgeons grade) on the outcome most used in pivotal stroke randomized controlled trials (modified Rankin Scale) and, consequently, on the sample size. Furthermore, we discuss the advantages and disadvantages of different options to analyze the outcome and control the expected distribution of the World Federation of Neurological Surgeons grades in addition to showing their effects on the sample size. Finally, we offer methods that investigators can adapt to more precisely understand the effect of common modified Rankin Scale analysis methods and trial eligibility pertaining to the World Federation of Neurological Surgeons grade in designing their large-scale SAH randomized controlled trials
Beyond the message: advantages of snapshot proteomics with single‐cell mass cytometry in solid tumors
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