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Dive into the research topics where Paula Warren is active.

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Featured researches published by Paula Warren.


Science Translational Medicine | 2015

SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma

Stephanie M. Robert; Susan C. Buckingham; Susan L. Campbell; Stefanie Robel; Kenneth T. Holt; Toyin Ogunrinu-Babarinde; Paula Warren; David M. White; Meredith A. Reid; Jenny M. Eschbacher; Michael E. Berens; Adrienne C. Lahti; Louis B. Nabors; Harald Sontheimer

SLC7A11, the catalytic subunit of the cystine/glutamate antiporter, System xc− (SXC), is up-regulated in a subpopulation of patient gliomas, where it is responsible for excitotoxic glutamate release, accelerated tumor growth, and tumor-associated seizures. Seizing an opportunity to study glioma Gliomas are the most common type of malignant brain tumors, and they frequently cause seizures. A new study by Robert et al. uncovers some of the mechanisms involved in this process, showing how a specific cystine/glutamate transporter contributes to excitotoxic glutamate release, causing the death of surrounding cells and inducing seizures. The authors also showed that tumors expressing this transporter were more aggressive and grew more quickly, possibly because the destruction of surrounding normal cells allowed the tumors to expand more rapidly. These findings suggest that the expression of this cystine/glutamate transporter may be useful as a predictor of outcome and a potential therapeutic target in glioma. Glioma is the most common malignant primary brain tumor. Its rapid growth is aided by tumor-mediated glutamate release, creating peritumoral excitotoxic cell death and vacating space for tumor expansion. Glioma glutamate release may also be responsible for seizures, which complicate the clinical course for many patients and are often the presenting symptom. A hypothesized glutamate release pathway is the cystine/glutamate transporter System xc− (SXC), responsible for the cellular synthesis of glutathione (GSH). However, the relationship of SXC-mediated glutamate release, seizures, and tumor growth remains unclear. Probing expression of SLC7A11/xCT, the catalytic subunit of SXC, in patient and mouse-propagated tissues, we found that ~50% of patient tumors have elevated SLC7A11 expression. Compared with tumors lacking this transporter, in vivo propagated and intracranially implanted SLC7A11-expressing tumors grew faster, produced pronounced peritumoral glutamate excitotoxicity, induced seizures, and shortened overall survival. In agreement with animal data, increased SLC7A11 expression predicted shorter patient survival according to genomic data in the REMBRANDT (National Institutes of Health Repository for Molecular Brain Neoplasia Data) database. In a clinical pilot study, we used magnetic resonance spectroscopy to determine SXC-mediated glutamate release by measuring acute changes in glutamate after administration of the U.S. Food and Drug Administration–approved SXC inhibitor, sulfasalazine (SAS). In nine glioma patients with biopsy-confirmed SXC expression, we found that expression positively correlates with glutamate release, which is acutely inhibited with oral SAS. These data suggest that SXC is the major pathway for glutamate release from gliomas and that SLC7A11 expression predicts accelerated growth and tumor-associated seizures.


Neurocase | 2017

The use of cannabidiol for seizure management in patients with brain tumor-related epilepsy

Paula Warren; E. Martina Bebin; L. Burt Nabors; Jerzy P. Szaflarski

ABSTRACT Epilepsy, commonly encountered by patients with brain tumors, is often refractory to standard therapies. Our aim was to examine the safety and efficacy of pharmaceutical grade cannabidiol (CBD; Epidiolex; Greenwich Biosciences) in those patients with epilepsy with concomitant tumors enrolled in The University of Alabama at Birmingham CBD Program (NCT02700412 and NCT02695537). Of the three patients with refractory seizures and a history of a primary brain tumor, two had improvement in seizure frequency and all three had improvement in seizure severity. These pilot results suggest that CBD should be further studied for the treatment of brain tumor-related epilepsy.


Journal of Clinical Neuroscience | 2017

History of electromyography and nerve conduction studies: A tribute to the founding fathers

Mohamed Kazamel; Paula Warren

The early development of nerve conduction studies (NCS) and electromyography (EMG) was linked to the discovery of electricity. This relationship had been concluded by observing the effect of applying electricity to the body of an animal and discovering that nerves and muscles themselves could produce electricity. We attempt to review the historical evolution of NCS and EMG over the last three centuries by reviewing the landmark publications of Galvani, Adrian, Denny-Brown, Larrabee, and Lambert. In 1771, Galvani showed that electrical stimulation of animal muscle tissue produced contraction and, thereby, the concept of animal electricity was born. In 1929, Adrian devised a method to record a single motor unit potential by connecting concentric needle electrodes to an amplifier and a loud speaker. In 1938, Denny-Brown described the fasciculation potentials and separated them from fibrillations. Toward the end of World War II, Larrabee began measuring the compound muscle action potential in healthy and injured nerves of war victims. In 1957, Lambert and Eaton described the electrophysiologic features of a new myasthenic syndrome associated with lung carcinoma. Overall, research on this topic was previously undertaken by neurophysiologists and then later by neurologists, with Adrian most likely being the first neurologist to be involved. The field greatly benefited from the invention of equipment that was capable of amplifying small bioelectrical currents by the beginning of the 20th century. Significant scientific and technical advances were later made during and after World War II which provided a large patient population with nerve injuries to study.


Psycho-oncology | 2018

Participation and interest in support services among family caregivers of older adults with cancer

J. Nicholas Dionne-Odom; Allison J. Applebaum; Katherine Ornstein; Andres Azuero; Paula Warren; Richard A. Taylor; Gabrielle Betty Rocque; Elizabeth Kvale; Wendy Demark-Wahnefried; Maria Pisu; Edward E. Partridge; Michelle Y. Martin; Marie Bakitas

The purpose of this study was to describe distressed and underprepared family caregivers use of and interest in formal support services (eg, professional counseling, education, organizational assistance).


Neuro-oncology | 2018

Hospice care, cancer-directed therapy, and Medicare expenditures among older patients dying with malignant brain tumors

Laura Dover; Caleb Dulaney; Courtney P. Williams; John B. Fiveash; Bradford E Jackson; Paula Warren; Elizabeth Kvale; D Hunter Boggs; Gabrielle Betty Rocque

Background End-of-life care for older adults with malignant brain tumors is poorly understood. The purpose of this study is to quantify end-of-life utilization of hospice care, cancer-directed therapy, and associated Medicare expenditures among older adults with malignant brain tumors. Methods This retrospective cohort study included deceased Medicare beneficiaries age ≥65 with primary malignant brain tumor (PMBT) or secondary MBT (SMBT) receiving care within a southeastern cancer community network including academic and community hospitals from 2012-2015. Utilization of hospice and cancer-directed therapy and total Medicare expenditures in the last 30 days of life were calculated using generalized linear and mixed effect models, respectively. Results Late (1-3 days prior to death) or no hospice care was received by 24% of PMBT (n = 383) and 32% of SMBT (n = 940) patients. SMBT patients received late hospice care more frequently than PMBT patients (10% vs 5%, P = 0.002). Cancer-directed therapy was administered to 18% of patients with PMBT versus 25% with SMBT (P = 0.003). Nonwhite race, male sex, and receipt of any hospital-based care in the final 30 days of life were associated with increased risk of late or no hospice care. The average decrease in Medicare expenditures associated with hospice utilization for patients with PMBT was


International Journal of Surgical Pathology | 2016

Primary Sellar Rhabdomyosarcoma Arising in Association With a Pituitary Adenoma.

Virginia E. Duncan; L. Burt Nabors; Paula Warren; Robert M. Conry; Christopher D. Willey; Arie Perry; Kristen O. Riley; James R. Hackney

-12,138 (95% CI:


Journal of Neuro-oncology | 2015

Prolonged treatment with bevacizumab is associated with brain atrophy: a pilot study in patients with high-grade gliomas.

Asim K. Bag; Hyunki Kim; Yi Gao; Mark S. Bolding; Paula Warren; Hassan M. Fathallah-Shaykh; Demet Gurler; James M. Markert; John B. Fiveash; T. Beasley; Ayaz Khawaja; Gregory K. Friedman; Philip R. Chapman; Louis B. Nabors; Xiaosi Han

-18,065 to


JAMA Oncology | 2017

Hospital-Based End-of-Life Care and Costs for Older Patients With Malignant Brain Tumors

Laura Dover; Caleb Dulaney; John B. Fiveash; Courtney P. Williams; Bradford Jackson; Paula Warren; Gabrielle Betty Rocque

-6210) and with SMBT was


Archive | 2018

Central Nervous System and Peripheral Nerves

D. Ryan Ormond; Alexandros Bouras; Michael K. Moore; Matthew Gary; Paula Warren; Roshan S. Prabhu; Kathleen M. Egan; Srikant Rangaraju; Christina L. Appin; Constantinos G. Hadjipanayis; Burt Nabors; Alfredo Voloschin; Jeffrey J. Olson

-1,508 (95% CI:


Journal of Clinical Oncology | 2017

Factors associated with participating in formal support services among family caregivers of older adults with poor-prognosis cancers.

J. Nicholas Dionne-Odom; Allison J. Applebaum; Katherine Ornstein; Andres Azuero; Paula Warren; Richard A. Taylor; Gabrielle B. Rocque; Elizabeth Kvale; Wendy Demark-Wahnefried; Maria Pisu; Edward E. Partridge; Michelle Y. Martin; Marie Bakitas

-3,613 to

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John B. Fiveash

University of Alabama at Birmingham

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Louis B. Nabors

University of Alabama at Birmingham

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Caleb Dulaney

University of Alabama at Birmingham

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Courtney P. Williams

University of Alabama at Birmingham

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Elizabeth Kvale

University of Alabama at Birmingham

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Gabrielle Betty Rocque

University of Alabama at Birmingham

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Laura Dover

University of Alabama at Birmingham

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Allison J. Applebaum

Memorial Sloan Kettering Cancer Center

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Andres Azuero

University of Alabama at Birmingham

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Arie Perry

University of California

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