11 results on '"Panoskaltsis-Mortari, Angela"'
Search Results
2. Systemic Biological Mechanisms of Neurocognitive Dysfunction in Long-Term Survivors of Childhood Hodgkin Lymphoma.
- Author
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Williams AM, Liu W, Ehrhardt MJ, Mirzaei Salehabadi S, Panoskaltsis-Mortari A, Phillips NS, Mulrooney DA, Flerlage JE, Yasui Y, Srivastava D, Robison LL, Hudson MM, Ness KK, Sabin ND, and Krull KR
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- Humans, Female, Male, Adult, Neurocognitive Disorders etiology, Neurocognitive Disorders epidemiology, C-Reactive Protein metabolism, Neuropsychological Tests, Interleukin-6 blood, Inflammation, Middle Aged, Case-Control Studies, Child, Survivors psychology, Adolescent, Hodgkin Disease, Cancer Survivors psychology, Cancer Survivors statistics & numerical data, Oxidative Stress, Biomarkers
- Abstract
Purpose: Hodgkin lymphoma (HL) survivors experience neurocognitive impairment despite receiving no central nervous system-directed therapy, though little is known about the underlying mechanisms., Experimental Design: HL survivors (n = 197) and age-, sex- and race/ethnicity frequency-matched community controls (n = 199) underwent standardized neurocognitive testing, and serum collection. Luminex multiplex or ELISA assays measured markers of inflammation and oxidative stress. Linear regression models compared biomarker concentrations between survivors and controls and with neurocognitive outcomes, adjusting for age, sex, race, body mass index, anti-inflammatory medication, and recent infections., Results: HL survivors [mean (SD) current age 36 (8) years, 22 (8) years after diagnosis] demonstrated higher concentrations of interleukin-6 (IL6), high-sensitivity c-reactive protein (hs-CRP), oxidized low-density lipoprotein, and glutathione peroxidase (GPx), compared with controls (P's < 0.001). Among survivors, higher concentrations of IL6 were associated with worse visuomotor processing speed (P = 0.046). hs-CRP ≥3 mg/L was associated with worse attention, processing speed, memory, and executive function (P's < 0.05). Higher concentrations of malondialdehyde were associated with worse focused attention and visual processing speed (P's < 0.05). Homocysteine was associated with worse short-term recall (P = 0.008). None of these associations were statistically significant among controls. Among survivors, hs-CRP partially mediated associations between cardiovascular or endocrine conditions and visual processing speed, whereas IL6 partially mediated associations between pulmonary conditions and visuomotor processing speed., Conclusions: Neurocognitive function in long-term survivors of HL appears to be associated with inflammation and oxidative stress, both representing potential targets for future intervention trials., (©2024 American Association for Cancer Research.)
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- 2024
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3. A Modular Cytokine Analysis Method Reveals Novel Associations With Clinical Phenotypes and Identifies Sets of Co-signaling Cytokines Across Influenza Natural Infection Cohorts and Healthy Controls.
- Author
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Cohen L, Fiore-Gartland A, Randolph AG, Panoskaltsis-Mortari A, Wong SS, Ralston J, Wood T, Seeds R, Huang QS, Webby RJ, Thomas PG, and Hertz T
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- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Cluster Analysis, Cohort Studies, Cytokines genetics, Datasets as Topic, Disease Progression, Gene Expression Profiling, Humans, Infant, Middle Aged, Phenotype, Prospective Studies, Signal Transduction, Young Adult, Biomarkers metabolism, Cytokines metabolism, Influenza A virus physiology, Influenza, Human immunology
- Abstract
Cytokines and chemokines are key signaling molecules of the immune system. Recent technological advances enable measurement of multiplexed cytokine profiles in biological samples. These profiles can then be used to identify potential biomarkers of a variety of clinical phenotypes. However, testing for such associations for each cytokine separately ignores the highly context-dependent covariation in cytokine secretion and decreases statistical power to detect associations due to multiple hypothesis testing. Here we present CytoMod-a novel data-driven approach for analysis of cytokine profiles that uses unsupervised clustering and regression to identify putative functional modules of co-signaling cytokines. Each module represents a biosignature of co-signaling cytokines. We applied this approach to three independent clinical cohorts of subjects naturally infected with influenza in which cytokine profiles and clinical phenotypes were collected. We found that in two out of three cohorts, cytokine modules were significantly associated with clinical phenotypes, and in many cases these associations were stronger than the associations of the individual cytokines within them. By comparing cytokine modules across datasets, we identified cytokine "cores"-specific subsets of co-expressed cytokines that clustered together across the three cohorts. Cytokine cores were also associated with clinical phenotypes. Interestingly, most of these cores were also co-expressed in a cohort of healthy controls, suggesting that in part, patterns of cytokine co-signaling may be generalizable. CytoMod can be readily applied to any cytokine profile dataset regardless of measurement technology, increases the statistical power to detect associations with clinical phenotypes and may help shed light on the complex co-signaling networks of cytokines in both health and infection.
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- 2019
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4. Amphiregulin in intestinal acute graft-versus-host disease: a possible diagnostic and prognostic aid.
- Author
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Amin K, Yaqoob U, Schultz B, Vaughn BP, Khoruts A, Howard JR, DeFor TE, Forster C, Meyer C, Gandhi I, Weisdorf DJ, Rashidi A, MacMillan ML, Blazar BR, Panoskaltsis-Mortari A, and Holtan SG
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, ErbB Receptors analysis, Female, Humans, Intestines pathology, Male, Middle Aged, Young Adult, Amphiregulin analysis, Amphiregulin biosynthesis, Biomarkers analysis, Graft vs Host Disease diagnosis, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Amphiregulin, a weak epidermal growth factor receptor agonist, is elevated, while epidermal growth factor, a strong epidermal growth factor receptor agonist, is low in the blood of patients with severe acute graft-versus-host disease. However, the tissue expression and function of these epidermal growth factor receptor ligands in acute graft-versus-host disease target organs is unknown. We compared by immunohistochemistry expression of amphiregulin and epidermal growth factor in archived, formalin-fixed, paraffin-embedded intestinal tissues of 48 patients with biopsy-proven gastrointestinal acute graft-versus-host disease to 3 groups: (1) 10 non-hematopoietic cell transplant normal controls, (2) 11 patients with newly diagnosed ulcerative colitis (ulcerative colitis), (3) 8 patients with a clinical diagnosis of acute graft-versus-host disease despite pathologically non-diagnostic biopsies, (4) and 10 cases of cytomegalovirus colitis. We used a semi-quantitative score of 0 (absent) through 3 (strong) to describe the intensity of immunohistochemical staining. We correlated serum and tissue amphiregulin and epidermal growth factor in patients with acute graft-versus-host disease. Gastrointestinal amphiregulin was significantly lower in acute graft-versus-host disease biopsies (median score 1), ulcerative colitis (median score 1.5), and cytomegalovirus colitis (median score 1) than in normal colon (median score 2, p = 0.004, p = 0.03, p = 0.009 respectively). Amphiregulin expression in was low in 74% of acute graft-versus-host disease cases with or without significant apoptosis. Patients with acute graft-versus-host disease exhibiting the pattern of high gastrointestinal amphiregulin but low serum amphiregulin (n = 14) had the best 1-year survival at 71%, but patients with high serum amphiregulin had poorer survival (<30%) regardless of gastrointestinal amphiregulin expression. Overall, our results lead to the hypothesis that amphiregulin is released into the circulation from damaged intestinal epithelium and stroma, although contributions from other cellular sources are likely. Low gastrointestinal amphiregulin expression by immunohistochemistry may be further studied for its utility in the pathologic acute graft-versus-host disease diagnosis without classic apoptotic changes.
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- 2019
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5. Association of Cerebrospinal Fluid Biomarkers of Central Nervous System Injury With Neurocognitive and Brain Imaging Outcomes in Children Receiving Chemotherapy for Acute Lymphoblastic Leukemia.
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Cheung YT, Khan RB, Liu W, Brinkman TM, Edelmann MN, Reddick WE, Pei D, Panoskaltsis-Mortari A, Srivastava D, Cheng C, Robison LL, Hudson MM, Pui CH, and Krull KR
- Subjects
- Brain pathology, Child, Female, Humans, Male, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Biomarkers cerebrospinal fluid, Brain diagnostic imaging, Neuroimaging methods, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Trauma, Nervous System diagnosis
- Abstract
Importance: Little is known about treatment-related neurotoxic mechanisms in children with acute lymphoblastic leukemia (ALL) treated with chemotherapy only., Objective: To examine concentration of cerebrospinal fluid (CSF) biomarkers of brain injury at ALL diagnosis and during cancer therapy and to evaluate associations with long-term neurocognitive and neuroimaging outcomes and relevant genetic polymorphisms., Design, Setting, and Participants: This prospective cohort study included 235 patients with ALL who received a chemotherapy-only protocol. Patients provided CSF samples after diagnosis and throughout treatment. At 5 or more years after the diagnosis, 138 (69.7%) of 198 eligible survivors participated in long-term follow-up assessments. Children were treated from June 1, 2000, through October 31, 2010. Follow-up was completed on October 21, 2014, and data were analyzed from August 1, 2015, through September 30, 2016., Exposures: Plasma concentration of high-dose intravenous methotrexate sodium and number of triple intrathecal chemotherapy injections., Main Outcomes and Measures: The CSF samples were assayed at 5 points from diagnosis to reinduction for biomarkers of myelin degradation (myelin basic protein [MBP]), neuronal damage (nerve growth factor [NGF] and total and phosphorylated tau protein), astrogliosis (glial fibrillary acidic protein [GFAP]), and neuroinflammation (chitotriosidase). DNA was genotyped for polymorphisms in drug metabolism, oxidative stress, and neurodevelopment. Leukoencephalopathy was evaluated by brain imaging. At 5 or more years after the diagnosis, survivors completed neurocognitive testing and brain imaging of white matter integrity., Results: Among the 235 patients with CSF samples (120 boys [51.1%] and 115 girls [48.9%]; mean [SD] age at diagnosis, 6.8 [4.7] years), MBP and GFAP levels were elevated at baseline and through consolidation. The number of intrathecal injections was positively correlated with NGF level increase at consolidation (r = 0.19; P = .005). Increases in GFAP (risk ratio [RR], 1.23; 95% CI, 1.09-1.40), MBP (RR, 1.06; 95% CI, 1.01-1.11), and total tau (RR, 1.76; 95% CI, 1.11-2.78) levels were associated with a higher risk for leukoencephalopathy and higher apparent diffusion coefficient in frontal lobe white matter 5 years after diagnosis (standardized estimate, 0.05; P < .001). Increase in total tau at consolidation was associated with worse attention (omissions z score estimate, -0.20; P = .04)., Conclusions and Relevance: Glial injury may be present at diagnosis of ALL. Neuronal injury was associated with intrathecal chemotherapy. The CSF biomarkers may be useful in identifying individuals at risk for worse neurologic outcomes, particularly those with genetic susceptibility to poor brain function.
- Published
- 2018
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6. Expression of and correlational patterns among neuroinflammatory, neuropeptide, and neuroendocrine molecules from cerebrospinal fluid in cerebral palsy
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Goracke-Postle, Cory J., Burkitt, Chantel C., Panoskaltsis-Mortari, Angela, Ehrhardt, Michael, Wilcox, George L., Graupman, Patrick, Partington, Michael, and Symons, Frank J.
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- 2021
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7. Circulating Angiogenic Factors Associated with Response and Survival in Patients with Acute Graft-Versus-Host Disease: Results from BMT CTN 0302 and 0802
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Holtan, Shernan G., Verneris, Michael R., Schultz, Kirk R., Newell, Laura F., Meyers, Gabrielle, He, Fiona, DeFor, Todd E., Vercellotti, Gregory M., Slungaard, Arne, MacMillan, Margaret L., Cooley, Sarah A., Blazar, Bruce R., Panoskaltsis-Mortari, Angela, and Weisdorf, Daniel J.
- Subjects
Adult ,Male ,Vascular Endothelial Growth Factor A ,Follistatin ,Adolescent ,Graft vs Host Disease ,Receptors, Cell Surface ,Article ,Angiopoietin-2 ,immune system diseases ,Antigens, CD ,hemic and lymphatic diseases ,Humans ,Transplantation, Homologous ,Child ,Aged ,Bone Marrow Transplantation ,integumentary system ,Epidermal Growth Factor ,Endoglin ,Hematopoietic Stem Cell Transplantation ,Membrane Proteins ,Middle Aged ,Survival Analysis ,surgical procedures, operative ,Treatment Outcome ,Hematologic Neoplasms ,Acute Disease ,Female ,Biomarkers - Abstract
Circulating angiogenic factors (AF) reflect tissue healing capacity, although some AF can also contribute to inflammation and are indicative of endothelial dysfunction. The AF milieu in acute graft-versus-host disease (aGVHD) has not been broadly characterized. We hypothesized that patients with abundant AF involved in repair/regeneration versus those mediating damage/inflammation would have improved outcomes. Circulating AF known predominantly for repair/regeneration (epidermal growth factor [EGF], fibroblast growth factor-1 and -2, heparin binding-EGF-like growth factor, and vascular endothelial growth factor-A [VEGF-A], -C, and -D) and for damage/inflammation (angiopoietin-2, endothelin-1, soluble endoglin [sEng], follistatin [FS], leptin, and placental growth factor [PlGF]) were measured in a discovery set of hematopoietic cell recipients with grade III and IV aGVHD and compared with controls, then validated in 2 aGVHD cohorts enrolled in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) trials 0302 (n = 105, serum) and 0802 (n = 158, plasma) versus controls without aGVHD (n = 53, serum). Levels of EGF and VEGF-A were lower than in controls at the onset of aGVHD in both trials and higher with complete response to first-line aGVHD therapy in CTN 0802. FS and PlGF were elevated in aGVHD measured in either serum or plasma. At day 28 after initial aGVHD therapy, elevated FS was an independent negative prognostic factor for survival in both cohorts (hazard ratio, 9.3 in CTN 0302; 2.8 in CTN 0802). These data suggest that circulating AF are associated with clinical outcomes after aGVHD and, thus, may contribute to both pathogenesis and recovery.
- Published
- 2015
8. Effect of Oral and Vaginal Hormonal Contraceptives on Inflammatory Blood Biomarkers.
- Author
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Divani, Afshin A., Luo, Xianghua, Datta, Yvonne H., Flaherty, James D., and Panoskaltsis-Mortari, Angela
- Subjects
VAGINAL contraceptives ,INFLAMMATION ,BIOMARKERS ,BLOOD testing ,C-reactive protein ,CYTOKINES - Abstract
The use of combined hormonal contraceptives has been reported to increase the level of C-reactive protein (CRP). We assessed the effect of hormonal contraceptive use on inflammatory cytokines including CRP, monocyte chemotactic protein-1, soluble tumor necrosis factor (sTNF), interleukin-6 (IL-6), and soluble CD40 ligand. We used 79 female subjects (19 to 30 years old) who were combined oral contraceptives users (n=29), combined vaginal contraceptive users (n=20), and nonusers (n=30) with CRP values of ≤1 (n=46) or ≥3 (n=33). Information on medical history, physical activities, and dietary and sleeping habits were collected. Both oral and vaginal contraceptive users had higher levels of CRP (P<0.0001), compared to nonusers. Only oral contraceptive users exhibited elevated sCD40L (P<0.01). When comparing the groups with CRP ≤ 1 and CRP ≥ 3, levels of IL-6 and sTNF-RI were positively correlated with CRP among oral contraceptive users. We did not observe the same elevation for other inflammatory biomarkers for the CRP ≥ 3 group among vaginal contraceptive users. The clear cause of elevation in CRP level due to the use of different hormonal contraceptive formulations and methods is not well understood. Longitudinal studies with larger sample size are required to better assess the true cause of CRP elevation among hormonal contraceptive users. [ABSTRACT FROM AUTHOR]
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- 2015
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9. Can Biomarkers Differentiate Pain and No Pain Subgroups of Nonverbal Children with Cerebral Palsy? A Preliminary Investigation Based on Noninvasive Saliva Sampling.
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Symons, Frank J., ElGhazi, Issam, Reilly, Brian G., Barney, Chantel C., Hanson, Leah, Panoskaltsis-Mortari, Angela, Armitage, Ian M., and Wilcox, George L.
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PAIN diagnosis ,BIOMARKERS ,CHILDREN with cerebral palsy ,CYTOKINES ,HORMONES ,MAGNETIC resonance imaging ,RESEARCH funding ,SALIVA ,STATISTICS ,DATA analysis ,DATA analysis software ,DESCRIPTIVE statistics - Abstract
Objective. Assessing and treating pain in nonverbal children with developmental disabilities are a clinical challenge. Current assessment approaches rely on clinical impression and behavioral rating scales completed by proxy report. Given the growing health relevance of the salivary metabolome, we undertook a translational-oriented feasibility study using proton nuclear magnetic resonance (NMR) spectroscopy and neuropeptide/cytokine/hormone detection to compare a set of salivary biomarkers relevant to nociception. Design. Within-group observational design. Setting. Tertiary pediatric rehabilitation hospital. Subjects. Ten nonverbal pediatric patients with cerebral palsy with and without pain. Methods. Unstimulated (passively collected) saliva was collected using oral swabs followed by perchloric acid extraction and analyzed on a Bruker Avance 700 MHz NMR spectrometer. We also measured salivary levels of several cytokines, chemokines, hormones, and neuropeptides. Results. Partial least squares discriminant analysis showed separation of those children with/without pain for a number of different biomarkers. The majority of the salivary metabolite, neuropeptide, cytokine, and hormone levels were higher in children with pain vs no pain. Conclusions. The ease of collection and noninvasive manner in which the samples were collected and analyzed support the possibility of the regular predictive use of this novel biomarker-monitoring method in clinical practice. [ABSTRACT FROM AUTHOR]
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- 2015
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10. Interferon-Regulated Chemokines as Biomarkers of Systemic Lupus Erythematosus Disease Activity.
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Bauer, Jason W., Petri, Michelle, Batliwalla, Franak M., Koeuth, Thearith, Wilson, Joseph, Slattery, Catherine, Panoskaltsis-Mortari, Angela, Gregersen, Peter K., Behrens, Timothy W., and Baechler, Emily C.
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SYSTEMIC lupus erythematosus ,BIOMARKERS ,INTERFERONS ,CHEMOKINES ,LUPUS erythematosus - Abstract
The article presents a study on systemic lupus erythematosus (SLE) disease and interferon (IFN) regulated chemokines as its biomarker. It states that SLE is an autoimmune disease from irregular flares of disease activity and permanent damage of organ systems. It adds that serum chemokine levels with lupus activity acts as a better biomarker of SLE when it increases at the time of SLE flare. It concludes that the assessment of the disease may be improved by measuring serum chemokine levels.
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- 2009
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11. 74 - Follistatin and Endoglin: Potential Biomarkers of Endothelial Damage and Non-Relapse Mortality after Myeloablative Allogeneic Hematopoietic Cell Transplantation in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0402.
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Newell, Laura F., Defor, Todd E., Cutler, Corey S., Verneris, Michael R., Blazar, Bruce R., Antin, Joseph H., Howard, Alan, Wu, Juan (Maggie), MacMillan, Margaret L., Panoskaltsis-Mortari, Angela, Weisdorf, Daniel J., and Holtan, Shernan
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- *
FOLLISTATIN , *ENDOTHELIUM diseases , *HEMATOPOIETIC stem cell transplantation , *COMPLICATIONS from organ transplantation , *BIOMARKERS , *CLINICAL trials - Published
- 2017
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