7 results on '"Frances Chow"'
Search Results
2. Multi-omic profiling reveals discrepant immunogenic properties and a unique tumor microenvironment among melanoma brain metastases
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Gino K. In, Jennifer R. Ribeiro, Jun Yin, Joanne Xiu, Matias A. Bustos, Fumito Ito, Frances Chow, Gabriel Zada, Lindsay Hwang, April K. S. Salama, Soo J. Park, Justin C. Moser, Sourat Darabi, Evidio Domingo-Musibay, Maria L. Ascierto, Kim Margolin, Jose Lutzky, Geoffrey T. Gibney, Michael B. Atkins, Benjamin Izar, Dave S. B. Hoon, and Ari M. VanderWalde
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Melanoma brain metastases (MBM) are clinically challenging to treat and exhibit variable responses to immune checkpoint therapies. Prior research suggests that MBM exhibit poor tumor immune responses and are enriched in oxidative phosphorylation. Here, we report results from a multi-omic analysis of a large, real-world melanoma cohort. MBM exhibited lower interferon-gamma (IFNγ) scores and T cell-inflamed scores compared to primary cutaneous melanoma (PCM) or extracranial metastases (ECM), which was independent of tumor mutational burden. Among MBM, there were fewer computationally inferred immune cell infiltrates, which correlated with lower TNF and IL12B mRNA levels. Ingenuity pathway analysis (IPA) revealed suppression of inflammatory responses and dendritic cell maturation pathways. MBM also demonstrated a higher frequency of pathogenic PTEN mutations and angiogenic signaling. Oxidative phosphorylation (OXPHOS) was enriched in MBM and negatively correlated with NK cell and B cell-associated transcriptomic signatures. Modulating metabolic or angiogenic pathways in MBM may improve responses to immunotherapy in this difficult-to-treat patient subset.
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- 2023
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3. Neoadjuvant PD-1 blockade induces T cell and cDC1 activation but fails to overcome the immunosuppressive tumor associated macrophages in recurrent glioblastoma
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Alexander H. Lee, Lu Sun, Aaron Y. Mochizuki, Jeremy G. Reynoso, Joey Orpilla, Frances Chow, Jenny C. Kienzler, Richard G. Everson, David A. Nathanson, Steven J. Bensinger, Linda M. Liau, Timothy Cloughesy, Willy Hugo, and Robert M. Prins
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Science - Abstract
Immune-checkpoint blockade has shown limited benefits in patients with glioblastoma. To understand how the composition of the tumor immune microenvironment might limit clinical responses, here the authors present a high dimensional profiling of the immune landscape in patients with glioblastoma following neoadjuvant PD-1 checkpoint blockade.
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- 2021
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4. 421 A Phase 1 and Randomized Phase 2 Clinical Trial of Selinexor and Temozolomide in Recurrent Glioblastoma Among Adults: The Product of a Successful Team Science Approach
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Frances Chow, Michael Berens, Sharon Tamir, Yosef Landesman, Christopher Walker, Mark Krailo, Steven Gore, and Jana Portnow
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Medicine - Abstract
OBJECTIVES/GOALS: Selinexor is a novel XPO1 inhibitor that blocks nuclear export, thus impairing DNA repair and causing apoptosis. Our goal was to conduct preclinical and clinical studies to test our hypothesis that selinexor’s efficacy is boosted by priming with temozolomide and is associated with a tissue biomarker. METHODS/STUDY POPULATION: We leveraged a team science approach through the NCI Cancer Therapy Evaluation Program (CTEP) to design preclinical experiments, develop a novel RNAseq analysis pipeline, and use pre-existing clinical experience to open an early phase clinical trial for recurrent glioblastoma. Team members included a CTEP medical officer, cancer biologist, pharmacist, industry scientist, translational scientist, and early career clinician scientist mentored by an expert clinician scientist. Based on preclinical results, participants in the clinical trial experimental arm will receive sequential temozolomide 150mg/m2 on days 1-5 and a starting dose of selinexor 60mg on days 8 and 15 of a 28-day cycle. Participants in the control arm will receive monotherapy temozolomide. RESULTS/ANTICIPATED RESULTS: Sequential treatment of U87 cells and intracranial xenografts had superior DNA damage (É£H2A.X, cleaved PARP) and overall survival compared to combination or single-agent (HR 0.25 [95% CI, 0.07-0.84]; p=0.01, log-rank). We used the top-scoring gene pair method to identify an RNAseq signature associated with response to selinexor. We then designed a trial for first recurrent MGMT methylated glioblastoma. Primary objectives are safety and preliminary efficacy. Secondary objectives are overall response rate, efficacy, and validation of a molecular signature. Phase 1 dose finding (n=12) will be followed by a randomized phase 2 (n=72); using proportional hazards regression, RHR 0.5 with p DISCUSSION/SIGNIFICANCE: The NCI CTEP Project Team employs team science as a framework to successfully develop multidisciplinary collaborations, build investigator trial experience, and lead the way to future research opportunities. Our trial addresses a significant unmet need to offer novel therapies and molecular biomarkers in glioblastoma.
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- 2023
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5. The abscopal effect: systematic review in patients with brain and spine metastases
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Dhiraj J Pangal, Benjamin Yarovinsky, Tyler Cardinal, David J Cote, Jacob Ruzevick, Frank J Attenello, Eric L Chang, Jason Ye, Josh Neman, Frances Chow, and Gabriel Zada
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General Medicine - Abstract
Background The abscopal effect is a rare phenomenon whereby local radiation induces a proposed immune-mediated anti-tumor effect at distant sites. Given the growing use of immunotherapies and systemic immune checkpoint inhibitors in neuro-oncologic practice, we aimed to review prior studies pertaining to this phenomenon in the context of tumor shrinkage both within the central nervous system as well as distant disease sites. Methods A systematic review in accordance with the PRISMA guidelines was conducted to identify all studies which assessed the abscopal effect in patients with treated metastatic cancer to the brain and/or spine. Articles were included if they reported the abscopal effect in patients (case studies) or if the abscopal effect was explicitly analyzed in case series with cohorts of patients with metastatic brain or spine tumors. Laboratory investigations and clinical trials investigating new therapies were excluded. Results Twenty reports met inclusion criteria [16 case reports, 4 case series (n = 160), total n = 174]. Case reports of the abscopal effect were in relation to the following cancers: melanoma (6 patients), breast cancer (3), lung adenocarcinoma (2), non-small-cell lung cancer (2), hepatocellular carcinoma (1), and renal cell carcinoma (1). Eleven patients had irradiation to the brain and 2 to the spine. Patients undergoing whole brain radiotherapy (6) had an average dose of 33.6 Gy over 8–15 fractions, and those undergoing stereotactic radiosurgery (5) had an average dose of 21.5 Gy over 1–5 fractions. One patient had radiation to the body and an intracranial abscopal effect was observed. Most common sites of extracranial tumor reduction were lung and lymph nodes. Ten case studies (57%) showed complete resolution of extra-CNS tumor burden. Median progression-free survival was 13 months following radiation. Four papers investigated incidence of abscopal effects in patients with metastatic melanoma to the brain who received immune checkpoint inhibitor therapy (n = 160); two papers found an abscopal effect in 35% and 52% of patients (n = 16, 21 respectively), and two papers found no evidence of abscopal effects (n = 61, 62). Conclusions Abscopal effects can occur following radiotherapy in patients with brain or spine metastases and is thought to be a result of increased anti-tumor immunity. The potential for immune checkpoint inhibitor therapy to be used in combination with radiotherapy to induce an abscopal effect is an area of active investigation.
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- 2022
6. Modulating glioblastoma chemotherapy response: Evaluating long non-coding RNA effects on DNA damage response, glioma stem cell function, and hypoxic processes
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Edith Yuan, Kristie Liu, Justin Lee, Kathleen Tsung, Frances Chow, and Frank J Attenello
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Oncology ,Surgery ,Neurology (clinical) - Abstract
Glioblastoma (GBM) is the most common and aggressive primary adult brain tumor, with an estimated annual incidence of 17 000 new cases in the United States. Current treatments for GBM include chemotherapy, surgical resection, radiation therapy, and antiangiogenic therapy. However, despite the various therapeutic options, the 5-year survival rate remains at a dismal 5%. Temozolomide (TMZ) is the first-line chemotherapy drug for GBM; however, poor TMZ response is one of the main contributors to the dismal prognosis. Long non-coding RNAs (lncRNAs) are nonprotein coding transcripts greater than 200 nucleotides that have been implicated to mediate various GBM pathologies, including chemoresistance. In this review, we aim to frame the TMZ response in GBM via exploration of the lncRNAs mediating three major mechanisms of TMZ resistance: (1) regulation of the DNA damage response, (2) maintenance of glioma stem cell identity, and (3) exploitation of hypoxia-associated responses.
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- 2022
7. Treatment at Safety-Net Hospitals Is Associated with Delays in Coil Embolization in Patients with Subarachnoid Hemorrhage
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Daniel A. Donoho, Arun P. Amar, Ian A. Buchanan, Frances Chow, William J. Mack, Arati Patel, Frank J. Attenello, and Li Ding
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Adult ,Male ,medicine.medical_specialty ,Multivariate analysis ,Subarachnoid hemorrhage ,Databases, Factual ,medicine.medical_treatment ,Psychological intervention ,Article ,Time-to-Treatment ,03 medical and health sciences ,0302 clinical medicine ,Aneurysm ,medicine ,Humans ,030212 general & internal medicine ,Healthcare Disparities ,Aged ,Coil embolization ,Medically Uninsured ,Endovascular coiling ,Medicaid ,business.industry ,Endovascular Procedures ,Middle Aged ,Subarachnoid Hemorrhage ,medicine.disease ,Embolization, Therapeutic ,United States ,Quartile ,Multivariate Analysis ,Emergency medicine ,Female ,Surgery ,Neurology (clinical) ,business ,Safety-net Providers ,030217 neurology & neurosurgery - Abstract
INTRODUCTION: Successful endovascular management of aneurysmal subarachnoid hemorrhage (aSAH) requires timely access to significant resources. Prior studies suggest an association between time to treatment and patient outcome. Patients treated at safety- net hospitals are thought to be particularly vulnerable to disparities in access to interventions that require substantial technological resources. We hypothesize that patients treated at safety-net hospitals are at greater risk for delayed access to endovascular treatment. MATERIALS AND METHODS: Adults undergoing endovascular coiling procedures between 2002–2011 in the Nationwide Inpatient Sample were included. Hospitals in the quartile with the highest proportion of Medicaid or uninsured patients were defined as safety-net hospitals. A multivariable model including patient and hospital-level factors was constructed to permit analysis of delays in endovascular treatment (defined as time to treatment greater than 3 days). RESULTS: Analysis included 7,109 discharges of patients with aSAH undergoing endovascular coil embolization procedures from 2002–2011. The median time to coil embolization in all patients was 1 day; 10.1% of patients waited more than three days until treatment. In multivariable analysis, patients treated at safety-net hospitals were more likely to have a prolonged time to coil embolization (OR 1.32, p
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- 2018
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