15 results on '"Lisa Pabst"'
Search Results
2. Further Evaluation of Functional Analysis Screening Methods in Early Autism Intervention
- Author
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Slanzi, Crystal M., Vollmer, Timothy R., Iwata, Brian A., Kronfli, Faris R., Williams, Lisa Pabst, and Perez, Brandon C.
- Abstract
A goal of some functional analysis (FA) variations is to reduce assessment time while still maintaining efficacy. This may be especially important when conducting FAs in early intervention programs, where time is a crucial commodity. To that end, we evaluated a model for using the results of the no-interaction condition as a screening for behavioral function and to guide selection of FA test conditions with 20 participants (22 assessments) aged 3 to 7 years old. We used the no-interaction condition to develop hypotheses for both automatic reinforcement and socially mediated reinforcement. The outcome of the no-interaction condition guided the selection of test conditions for the remainder of the FA. We also incorporated methods from prior FA studies (e.g., divided attention) to modify the test conditions. We obtained differentiated results in 91% of assessments, all within 70 min and, as such, extended evidence that an FA can be completed in little time without sacrificing efficacy.
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- 2022
- Full Text
- View/download PDF
3. Novel Presentation of Hemiplegic Migraine in a Patient With Cockayne Syndrome
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Jennifer Carroll, Lisa Pabst, Daniel C. Koboldt, Samuel J. Franklin, Samantha Choi, Richard K. Wilson, and Warren Lo
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Male ,Phenotype ,Developmental Neuroscience ,Neurology ,Siblings ,Migraine with Aura ,Pediatrics, Perinatology and Child Health ,Humans ,Hemiplegia ,Neurology (clinical) ,Cockayne Syndrome - Abstract
Cockayne syndrome is a rare DNA repair disorder marked by premature aging, poor growth, and intellectual disability. Neurological complications such as seizures, movement disorder, and stroke have been reported. Hemiplegic migraine has not been reported in association with Cockayne syndrome.We report a male with Cockayne syndrome due to biallelic heterozygous pathogenic variants in ERCC6 who presented repeatedly with transient focal neurological deficits and headache, which were consistent with hemiplegic migraine. Two siblings also had Cockayne syndrome and presented with similar symptoms.Our patient was originally diagnosed based on clinical suspicion and then confirmed by targeted exome analysis of genes associated with Cockayne syndrome. The family's research exome sequencing data were reanalyzed to identify variants in genes known to cause familial hemiplegic migraine. No variants in the genes known to cause familial hemiplegic migraine were identified.This is a novel association of familial hemiplegic migraine in three full siblings with Cockayne syndrome. Hemiplegic migraine has not previously been described as part of the Cockayne syndrome presentation. A separate genetic cause of familial hemiplegic migraines was not identified in an exome-based analysis of genes known to cause this condition. This report may represent an expansion of the Cockayne syndrome phenotype.
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- 2023
4. Further evaluation of functional analysis screening methods in early autism intervention
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Crystal M. Slanzi, Timothy R. Vollmer, Brian A. Iwata, Faris R. Kronfli, Lisa Pabst Williams, and Brandon C. Perez
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Motivation ,Philosophy ,Sociology and Political Science ,Child, Preschool ,Early Intervention, Educational ,Humans ,Attention ,Autistic Disorder ,Child ,Reinforcement, Psychology ,Applied Psychology - Abstract
A goal of some functional analysis (FA) variations is to reduce assessment time while still maintaining efficacy. This may be especially important when conducting FAs in early intervention programs, where time is a crucial commodity. To that end, we evaluated a model for using the results of the no-interaction condition as a screening for behavioral function and to guide selection of FA test conditions with 20 participants (22 assessments) aged 3 to 7 years old. We used the no-interaction condition to develop hypotheses for both automatic reinforcement and socially mediated reinforcement. The outcome of the no-interaction condition guided the selection of test conditions for the remainder of the FA. We also incorporated methods from prior FA studies (e.g., divided attention) to modify the test conditions. We obtained differentiated results in 91% of assessments, all within 70 min and, as such, extended evidence that an FA can be completed in little time without sacrificing efficacy.
- Published
- 2022
5. Abstract TMP20: Performing The Pediatric National Institutions Of Health Stroke Scale Over Televideo: A Pilot Study
- Author
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Lisa Pabst, Melissa G Chung, Thomas Murray, Melissa Hutchinson, Alicia Zha, and Warren D Lo
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Advanced and Specialized Nursing ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: Telestroke networks are widely used by stroke neurologists to rapidly assess adults presenting to remote facilities with suspected acute stroke. Televideo assessment of acute neurological deficits in children is potentially useful for children who live in remote areas, but has not been studied. This study tested the feasibility of assessing the pediatric National Institutes of Health stroke scale (PedNIHSS) by televideo in children. Methods: Children ages 2-17 years with and without strokes were recruited and examined in the outpatient neurology clinic. The PedNIHSS was performed on each child by separate neurologists; one by televideo and the other at the bedside. The total PedNIHSS, subscores and time to complete each exam were recorded. Intraclass correlation coefficients (ICC) were used to analyze inter-rater reliability. Results: Twenty children were recruited with an average range of 9.2 years (range 2-17 years). Six children had chronic stroke. By bedside exam, the total PedNIHSS score ranged from 0-8 with a mean of 1.65. By televideo, the PedNIHSS total score was identical to the bedside examination in 12/20 (60%) of the children and identical or within 1 point in 19/20 children (95%). All total PedNIHSS were scored higher by the bedside vs remote examiner in cases where there was a difference. There was excellent overall inter-rater reliability (ICC=0.92; 95% CI: 0.81, 0.97) for the total PedNIHSS when comparing bedside and video exams. In the subgroup of children less than 6 years of age, ICC was 0.88 (95% CI: 0.44-0.98). The PedNIHSS subscores with lowest reliability between exams were dysarthria, ataxia and sensory change. The average time to complete the bedside and remote examinations were 5 minutes and 7 minutes, respectively. Conclusions: It is feasible to perform the full PedNIHSS over televideo with reasonable accuracy and in a similar amount of time as compared to bedside evaluations. Limitations of this study include a small number of patients and overall low burden of neurologic deficits. Future studies focusing on children presenting with focal neurologic deficits in the acute care setting are needed to further determine the reliability of performing the PedNIHSS over televideo.
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- 2023
6. Pediatric Moyamoya Biomarkers: Narrowing the Knowledge Gap
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Laura L. Lehman, Matsanga Leyila Kaseka, Jeffery Stout, Alfred P. See, Lisa Pabst, Lisa R. Sun, Sahar A. Hassanein, Michaela Waak, Arastoo Vossough, Edward R. Smith, and Nomazulu Dlamini
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Stroke ,Cerebral Revascularization ,Pediatrics, Perinatology and Child Health ,Humans ,Neurology (clinical) ,Constriction, Pathologic ,Moyamoya Disease ,Child ,Biomarkers - Abstract
Moyamoya is a progressive cerebrovascular disorder that leads to stenosis of the arteries in the distal internal carotid, proximal middle cerebral and proximal anterior cerebral arteries of the circle of Willis. Typically a network of collaterals form to bypass the stenosis and maintain cerebral blood flow. As moyamoya progresses it affects the anterior circulation more commonly than posterior circulation, and cerebral blood flow becomes increasingly reliant on external carotid supply. Children with moyamoya are at increased risk for ischemic symptoms including stroke and transient ischemic attacks (TIA). In addition, cognitive decline may occur over time, even in the absence of clinical stroke. Standard of care for stroke prevention in children with symptomatic moyamoya is revascularization surgery. Treatment of children with asymptomatic moyamoya with revascularization surgery however remains more controversial. Therefore, biomarkers are needed to assist with not only diagnosis but also with determining ischemic risk and identifying best surgical candidates. In this review we will discuss the current knowledge as well as gaps in research in relation to pediatric moyamoya biomarkers including neurologic presentation, cognitive, neuroimaging, genetic and biologic biomarkers of disease severity and ischemic risk.
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- 2022
7. Pediatric Stroke and Cardiac Disease: Challenges in Recognition and Management
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Elizabeth W Mayne, Janette A Mailo, Lisa Pabst, Elizabeth Pulcine, Dana B Harrar, Michaela Waak, Mubeen F Rafay, Sahar MA Hassanein, Catherine Amlie-Lefond, and Lori C Jordan
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Stroke ,Heart Diseases ,Pediatrics, Perinatology and Child Health ,Humans ,Neurology (clinical) ,Child - Published
- 2022
8. Further evaluation of functional analysis screening methods in early autism intervention
- Author
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Slanzi, Crystal M., primary, Vollmer, Timothy R., additional, Iwata, Brian A., additional, Kronfli, Faris R., additional, Williams, Lisa Pabst, additional, and Perez, Brandon C., additional
- Published
- 2022
- Full Text
- View/download PDF
9. Abstract WP171: Incidence And Outcomes Of Pseudoaneurysm In Pediatric Patients With Blunt Cerebrovascular Injury
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Lisa Pabst, Melissa G Chung, and Eric Sribnick
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Advanced and Specialized Nursing ,cardiovascular system ,cardiovascular diseases ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine - Abstract
Objective: Pseudoaneurysm is a rare manifestation of blunt cerebrovascular injury (BCVI) in pediatric patients and carries a high risk of both ischemic stroke and rupture. There is a paucity of data regarding the incidence, prognosis and best practice in management in children. The aim of this study is to describe the history and outcomes of children with traumatic cerebrovascular pseudoaneurysm. Methods: Patients between the ages of 0 and 18 years were identified from the prospectively enrolled trauma registry at a tertiary care pediatric hospital between January 1, 2011 and July 1, 2021 who presented with head and/or neck blunt trauma, had available cerebrovascular imaging and a diagnosis consistent with BCVI. Retrospective chart review was performed to identify patients with pseudoaneurysm formation. Results: Twenty patients were identified with diagnosis of BCVI and of those, six developed pseudoaneurysm. Twelve of the fourteen other BCVIs included the internal carotid artery, while two involved vertebral arteries. All pseudoaneurysms were of the internal carotid artery. Pseudoaneurysm was diagnosed at a median interval of 5 days from initial injury (range 1 day to 6 weeks). Other BCVIs were all diagnosed within the first 2 days of hospitalization. Treatment for pseudoaneurysm included a course of antiplatelet therapy in all. Three patients were initially treated with anticoagulation with subsequent transition to antiplatelet therapy. Endovascular intervention was performed in two patients. 2 patients suffered arterial ischemic stroke. All 6 patients were living and discharged home with favorable neurologic outcomes based on Glasgow Outcome Scale with median follow-up time of 7 months. Conclusions: In this retrospective cohort, pseudoaneurysm was observed in 30% of pediatric patients with BCVI, which is higher than previously reported. Treatment of pseudoaneurysm was variable, but all patients had favorable neurologic outcomes. Compared to other forms of BCVI, pseudoaneurysm was identified following a longer period of time from initial injury. Further studies are needed to identify risk factors for pseudoaneurysm and to inform the need and timing for serial imaging in identifying pseudoaneurysms given potential treatment implications.
- Published
- 2022
10. Moyamoya syndrome in a child with Legius syndrome: Introducing a cerebral vasculopathy to the <scp> SPRED1 </scp> phenotype?
- Author
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Kristen V. Truxal, Lisa Pabst, Warren D. Lo, and Jennifer Carroll
- Subjects
0301 basic medicine ,Legius syndrome ,medicine.medical_specialty ,business.industry ,030105 genetics & heredity ,RASopathy ,medicine.disease ,Phenotype ,Dermatology ,03 medical and health sciences ,030104 developmental biology ,Genetics ,medicine ,In patient ,Neurofibromatosis ,Clinical phenotype ,business ,Vasculitis ,Genetics (clinical) - Abstract
Legius syndrome is a disorder of the RAS and mitogen-activated protein kinase (MAPK) pathway first described in 2007 by Eric Legius, et al., that has been considered a milder phenotype than reported in the RASopathy neurofibromatosis type 1 (NF1). However, with approximately 200 cases reported in the literature, the Legius syndrome phenotype remains to be fully characterized. We report a child who presented with moyamoya syndrome and who has Legius syndrome due to a pathogenic variant in SPRED1. Vascular complications such as moyamoya syndrome have been reported in NF1. However, this association has not been reported in Legius syndrome. This child's case may represent an expansion of the clinical phenotype of Legius syndrome, and further study is needed. We emphasize the importance of obtaining neuroimaging studies in patients with Legius syndrome who present with new neurologic deficits.
- Published
- 2020
11. Pyruvate uptake is increased in highly invasive ovarian cancer cells under anoikis conditions for anaplerosis, mitochondrial function, and migration
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Lisa Pabst, Nadège Bellance, Christine Caneba, Lifeng Yang, and Deepak Nagrath
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medicine.medical_specialty ,Physiology ,Cell Survival ,Endocrinology, Diabetes and Metabolism ,Citric Acid Cycle ,Oxidative phosphorylation ,Biology ,Oxidative Phosphorylation ,Extracellular matrix ,Adenosine Triphosphate ,Oxygen Consumption ,Cancer stem cell ,Cell Movement ,Physiology (medical) ,Internal medicine ,Cell Line, Tumor ,Pyruvic Acid ,medicine ,Humans ,Anoikis ,Neoplasm Invasiveness ,Protein Footprinting ,Amino Acids ,Ovarian Neoplasms ,Wound Healing ,Neovascularization, Pathologic ,medicine.disease ,Warburg effect ,Culture Media ,Mitochondria ,Kinetics ,Endocrinology ,Cell culture ,Cancer cell ,Female ,Indicators and Reagents ,Ovarian cancer ,Energy Metabolism - Abstract
Anoikis resistance, or the ability for cells to live detached from the extracellular matrix, is a property of epithelial cancers. The “Warburg effect,” or the preference of cancer cells for glycolysis for their energy production even in the presence of oxygen, has been shown to be evident in various tumors. Since a cancer cell's metastatic ability depends on microenvironmental conditions (nutrients, stromal cells, and vascularization) and is highly variable for different organs, their cellular metabolic fluxes and nutrient demand may show considerable differences. Moreover, a cancer cell's metastatic ability, which is dependent on the stage of cancer, may further create metabolic alterations depending on its microenvironment. Although recent studies have aimed to elucidate cancer cell metabolism under detached conditions, the nutrient demand and metabolic activity of cancer cells under nonadherent conditions remain poorly understood. Additionally, less is known about metabolic alterations in ovarian cancer cells with varying invasive capability under anoikis conditions. We hypothesized that the metabolism of highly invasive ovarian cancer cells in detachment would differ from less invasive ovarian cancer cells and that ovarian cancer cells will have altered metabolism in detached vs. attached conditions. To assess these metabolic differences, we integrated a secretomics-based metabolic footprinting (MFP) approach with mitochondrial bioenergetics. Interestingly, MFP revealed higher pyruvate uptake and oxygen consumption in more invasive ovarian cancer cells than their less invasive counterparts. Furthermore, ATP production was higher in more invasive vs. less invasive ovarian cancer cells in detachment. We found that pyruvate has an effect on highly invasive ovarian cancer cells' migration ability. Our results are the first to demonstrate that higher mitochondrial activity is related to higher ovarian cancer invasiveness under detached conditions. Importantly, our results bring insights regarding the metabolism of cancer cells under nonadherent conditions and could lead to the development of therapies for modulating cancer cell invasiveness.
- Published
- 2012
12. Oncosecretomics coupled to bioenergetics identifies α-amino adipic acid, isoleucine and GABA as potential biomarkers of cancer: Differential expression of c-Myc, Oct1 and KLF4 coordinates metabolic changes
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Deepak Nagrath, Nadège Bellance, Lisa Pabst, Genevara Allen, and Rodrigue Rossignol
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Bioenergetics ,Cellular respiration ,Biophysics ,Kruppel-Like Transcription Factors ,Oxidative phosphorylation ,Biology ,Biochemistry ,Kruppel-Like Factor 4 ,Mice ,Proto-Oncogene Proteins c-myb ,Neoplasms ,Biomarkers, Tumor ,Animals ,Metabolomics ,Glycolysis ,Reverse Warburg effect ,Isoleucine ,Cells, Cultured ,gamma-Aminobutyric Acid ,Metabolism ,Cell Biology ,Secretomics ,Warburg effect ,Cell biology ,Rats ,Cancer cell ,Energy Metabolism ,2-Aminoadipic Acid ,Octamer Transcription Factor-1 - Abstract
Bioenergetic profiling of tumors is a new challenge of cancer research and medicine as therapies are currently being developed. Meanwhile, methodological means must be proposed to gather information on tumor metabolism in order to adapt these potential therapies to the bioenergetic specificities of tumors. Studies performed on tumors and cancer cell lines have shown that cancer cells bioenergetics is highly variable. This profile changes with microenvironmental conditions (eg. substrate availability), the oncogenes activated (and the tumor suppressors inactivated) and the interaction with the stroma (i.e. reverse Warburg effect). Here, we assessed the power of metabolic footprinting (MFP) to unravel the bioenergetics and associated anabolic changes induced by three oncogenes, c-Myc, KLF4 and Oct1. The MFP approach provides a quantitative analysis of the metabolites secreted and consumed by cancer cells. We used ultra performance liquid chromatography for quantifying the amino acid uptake and secretion. To investigate the potential oncogene-mediated alterations in mitochondrial metabolism, we measured oxygen consumption rate and ATP production as well as the glucose uptake and lactate release. Our findings show that c-Myc deficiency initiates the Warburg effect along with a reduction of mitochondrial respiration. KLF4 deficiency also stimulated glycolysis, albeit without cellular respiration impairment. In contrast, Oct1 deficiency reduced glycolysis and enhanced oxidative phosphorylation efficiency. MFP revealed that c-Myc, KLF4 and Oct1 altered amino acid metabolism with specific patterns. We identified isoleucine, α-aminoadipic acid and GABA (γ-aminoisobutyric acid) as biomarkers related. Our findings establish the impact of Oct1, KLF4 and c-Myc on cancer bioenergetics and evidence a link between oncosecretomics and cellular bioenergetics profile.
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- 2012
13. Abstract 1272: Role of c-Myc, Oct1 and KLF4 in cell metabolism: Involvement of pluripotency factors in metabolic remodeling during tumorigenesis
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Lisa Pabst, Thasni Karedath, Christine Caneba, Syed Asad, Nadège Bellance, and Deepak Nagrath
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Cancer Research ,Cell type ,Glutaminolysis ,Biology ,medicine.disease_cause ,Embryonic stem cell ,Warburg effect ,Cell biology ,Oncology ,Biochemistry ,KLF4 ,Cancer cell ,medicine ,Carcinogenesis ,Transcription factor - Abstract
Embryonic stem cells have the ability to give rise to different cell types and also the self reniewal capacity. Those features are essentially controlled by pluripotency factors which maintain cells into an undifferentiated state. Cancer cells are distinguished from normal cells by a dedifferentiation process in which the expression of pluripotency factors can be increased. c-Myc, Oct4 and KLF4 are pluripotency transcription factors. Oct-1, homologue of Oct-4, have been recently revealed to be pro-tumorigenic and his expression, such as c-Myc, is increased in various cancers. In this study, we investigated the role of this transcription factors into the cell metabolism. The role of the oncogene MYC on tumor cell metabolism has been largely studied. In cancer cells, c-Myc induces the expression of genes involved in glycolysis and glutaminolysis. However, the entire metabolic changes induced by c-Myc have not yet been elucidated. Furthermore, little is known about the role of Oct-1 and KLF4 in cancer metabolism. We have used the metabolic footprinting approach in order to characterize the Oct-1, c-Myc and KLF4 deficient cells and to identify the induced consecutive metabolic remodeling. Because of the variability of mutations observed in cancer cells, we investigated the effects induced by Oct-1, KLF4 and c-Myc deficiencies in mouse and rat embryonic fibroblasts by using UPLC (Ultra performance liquid chromatography). The uptake and release of metabolites was quantified by providing different substrates (glutamine or fatty acid). The glucose consumption and the lactate production which defined as the Warburg effect was measured. The mitochondrial function was investigated by oxygen consumption rate measurement. We found that the metabolites produced by Oct-1, KLF4 and c-Myc deficient cells seems to present a signature which can explain there over-expression in tumors. Our results suggest that embryonic stem cells related pluripotency transcription factors are implicated into the metabolic remodeling of cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1272. doi:10.1158/1538-7445.AM2011-1272
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- 2011
14. Abstract 45: Role of microenvironment on alterations in cancer metabolism using metabolic profiling
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Deepak Nagrath, Nadège Bellance, Prabha Ramakrishnan, Lisa Pabst, Thasni Karedath, and Alona Bozhchenko
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Cancer Research ,Matrigel ,Metabolic network ,Metabolism ,Biology ,Cell biology ,Extracellular matrix ,medicine.anatomical_structure ,Oncology ,Biochemistry ,Metabolic flux analysis ,Cancer cell ,medicine ,Fibroblast ,Intracellular - Abstract
Endothelial, fibroblast cells, and extracellular matrix play a major role in progression, growth and spread of cancers. The extent to which each plays a role in metabolic adaptations in cancer metabolism is unknown. Because of the unique signature of metabolites in endothelial and fibroblasts when compared with epithelial cancer cell metabolism, metabolic profiling is an ideal approach to study induced metabolic changes in cancer cells during cocultures with fibroblasts and endothelia cells. Additionally, interaction of extracellular matrix with cancer cells has been shown to play a key role in cancer invasion and dissemination. In current work, we study the role of microenvironment (various cell types and extracellular matrix proteins) on alterations and adaptations of cancer metabolism. Metabolic profiling of various cancer cells (lung, prostate, breast, and ovarian) in coculture with fibroblasts and endothelial cells was done using metabolic flux analysis in various extracellular matrix environments (collagen coating, collagen gel, and matrigel). Metabolic flux analysis (MFA) refers to a methodology whereby intracellular fluxes (i.e. conversion rates of metabolites through individual reactions) are calculated using a stoichiometric model for the major intracellular reactions and applying mass balances around intracellular metabolites. MFA is a powerful approach for understanding and comparing different metabolic states, and offer insights into the functional capabilities of a metabolic network. The power of this approach is that it takes into account a large set of measurements as well as the complex inter-dependence among the various pathways due to the sharing of a common pool of co-factors such as NADH, NADPH, thus providing a more complete and integrated picture of the metabolic state than isolated measurements relevant to a few pathways. Our findings using quantification of 82 metabolites pertaining to central carbon and nitrogen metabolism provided clues as to which pathways relevant to glycolysis, the pentose phosphate pathway, the TCA and urea cycles, lipid cycle, and amino acid and nucleotide metabolisms, may be altered by endothelial and fibroblasts in cancer cells, resulting in identification of dominant factors which regulate cancer cell metabolism. During extracellular matrix cultures, amino acid supplementation, irrespective of extracellular matrix type, induced dramatic changes. Amino acid supplementation also significantly increased the TCA cycle flux at the level of citrate synthase and oxidized 96% to 97% of the fatty acid-derived acetyl-CoA to CO2. The information we gain elucidates the critical role of microenvironment and nutritional supplementation in cancer metabolism and allows development of therapeutics for modulating the communication between cancer and its microenvironment to prevent cancer invasion and dissemination. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 45.
- Published
- 2010
15. Abstract 5092: Metabolomic profiling of Oct-1 and c-myc deficient cells to obtain clinical and biological insights into tumorigenicity
- Author
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Lisa Pabst, Prabha Ramakrishnan, Deepak Nagrath, Thasni Karedath, Nadège Bellance, and Alona Bozhchenko
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Cancer Research ,Oncology ,Biochemistry ,Systems biology ,Metabolic flux analysis ,Cancer cell ,Extracellular ,Metabolic network ,Stem cell ,Biology ,Transcription factor ,Intracellular - Abstract
Oct-1 and C-myc have recently been shown to be pro-tumorigenic and their expression is increased in various cancers. Despite recent surge in understanding the role of pluripotency related transcription factors of stem cells in tumorigenicity, little is understood of the role of pluripotency factors oct-1, c-myc, and oct-1 in cancer metabolism. We have used metabolic profiling of oct-1 and c-myc deficient and overexpressed cells to characterize intermediary metabolism and identify the critical nutrients in cancer metabolism. Cancer cell metabolism was investigated using systems biology tools such as metabolic flux analysis (MFA) to reveal intracellular ES cell metabolic flux distribution. Metabolic flux analysis (MFA) refers to a methodology whereby intracellular fluxes (i.e. conversion rates of metabolites through individual reactions) are calculated using a stoichiometric model for the major intracellular reactions and applying mass balances around intracellular metabolites. MFA is a powerful approach for understanding and comparing different metabolic states, and offer insights into the functional capabilities of a metabolic network. The power of this approach is that it takes into account a large set of measurements as well as the complex inter-dependence among the various pathways due to the sharing of a common pool of co-factors such as NADH, NADPH, thus providing a more complete and integrated picture of the metabolic state than isolated measurements relevant to a few pathways. Given that the turnover rate of intracellular metabolites is very fast compared to the time scale of perturbations imparted on the cells, we can assume a “pseudo-steady-state” whereby intracellular levels of metabolites do not change significantly. Under these conditions, the intracellular fluxes are linearly related to measured rates of uptake and release of extracellular metabolites. Since, the metabolites produced by oct-1 and c-myc deficient cells present a unique signature which is different from the metabolic profile of oct-1 and c-myc over expressed cells, we hypothesized that metabolic profiling based approach could lead to understanding of the role of these factors in cancer metabolism. The developed strategy first revealed pathways that were down regulated in the c-myc and oct-1 deficient cells. Second, the obtained optimal flux solutions were used to guide the up-regulation of various pathways and hence, determining the appropriate nutrient and hormonal supplements necessary for loss of oncogenic transformations. Combined biological and clinical studies using metabolic profiling of oct-1 and c-myc deficient and overexpressed cells is likely to have a major impact on the development of therapeutics targeting metabolism in cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5092.
- Published
- 2010
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