Day 2 :
Keynote Forum
Choon Nam ONG
National University of Singapore, Singapore
Keynote: Plasma metabolic profiles are associated with habitual dietary patterns
Time : 09:00-09:30
Biography:
Choon Nam ONG is the Director of the NUS Environmental Research Institute (NERI) and a professor at the Saw Swee Hock School of Public Health, National University of Singapore. He has published more than 300 papers in international peer-reviewed journals with an h-index of 75, and over 17,000 citations. His main research interest is Environmental Health Sciences and teaches in Toxicology and Environment Health, and nursing a lifelong passion of all matters related to environment on health. Since 1985, he has served as a consultant to the World Health Organization (WHO) on many occasions and was involved in 12 of its Health Criteria publications.He is an editorial board member of several international journals on environment and sustainability. He is a visiting professor to several overseas universities and serves as a Scientific Advisor to the China Center of Disease Control and Prevention (CDC). He was the recipient of Astra-Zeneca American Toxicology Society Award, 2002. Dr Ong also served as an advisor to the OECD, US National Water Research Institute, and has been consulted often by international health agencies on issues related to environmental health. He has been a member of the WHO Guidelines for Drinking Water Quality Expert Panel since 2003. His research group currently focuses on the use of metabolomics as a technology platform for biomedical and environmental research.
Abstract:
Dietary factors play important roles in human metabolism and influence the status of health. So far, few human studies have been focused on how diet affects the palsma metabolome. In this study, we investigated the differences in plasma metabolic profiles between habitual high meat and seafood (HMS) eaters and low meat and seafood (LMS) eaters using mass spectrometry-based metabolomics methods, aimed to reveal the link between plasma metabolic profiles and habitual dietary intake. Plasma metabolites were profiled and compared between 83 HMS eaters and 82 LMS eaters from a healthy cohort in Singapore. A total of 49 differential metabolites were found between the two dietary groups. The difference was mainly reflected by higher concentrations of arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and AA/EPA/DHA-content phospholipids in HMS eaters than in LMS eaters, although there were also differences in levels of other metabolites, such as D-glucose, glycine, and urea. We observed strong correlations across a wide range of plasma metabolites and food variables. The strongest association was found for DHA levels with fish consumption (r = 0.535). Our study demonstrates that mass spectrometry-based metabonomics is a valid technique to dietary pattern analysis, and the findings illustrates that plasma metabolic profiles were associated with habitual diets.
Keynote Forum
Jian Zhi Hu
Pacific Northwest National Laboratory, USA
Keynote: NMR Metabolomics Studies of Mice Exposed to Ionizing Radiation
Time : 09:31-10:00
Biography:
Jian Zhi Hu received his Ph.D in 1994 and is currently a senior staff scientist and principal investigator of Pacific Norwest National Laboratory. He has published more than 170 papers in peer reviewed journals, delivered a large number of presentations, received two US R&D 100 awards and 10 US patents.
Abstract:
Ionizing radiation can be fatal to a living system and is a growing concern in the fields of medicine where diagnostic imaging techniques using X-rays are frequently used on patients, the space exploration where astronauts have a great chance of exposing to high energy space particle radiation and nuclear energy generation where an unfortunate accident may happen. In this work, NMR based metabolomics combined with multivariate data analysis are used to evaluate the metabolic changes in the C57BL/6 mice 4 and 11 days post whole body 3.0 Gy and 7.8 Gy gamma radiations, including proton irradiation, using various organs (liver, spleen, lung and heart) and blood. Principal component analysis (PCA) and orthogonal projection to latent structures analysis (OPLS) are employed for classification and identification of potential metabolite markers associated with gamma irradiation. Two different strategies for NMR spectral data reduction, i.e., spectral binning and spectral deconvolution are compared with normalization to constant sum and unit weight before multivariate data analysis. It is found that the combination of spectral deconvolution and normalization to unit weight is the best way for identifying discriminatory metabolites between the irradiation and control groups. Using this method, metabolite markers responsible for gamma radiation are identified on each organ and blood, separately. The possibility of accessingindividual organ injury due to ionizing radiation via minimally invasive blood will be discussed.
- Track : 11 Metabolic Syndrome
Track : 12 Metabolomics in Precision Medicine
Chair
Robert Plumb
Imperial College London, UK
Co-Chair
Houkai Li
Shanghai University of Traditional Chinese Medicine, China
Session Introduction
Jose Castro-Perez
Waters Corp, USA
Title: Biomarker Discovery in Cardiovascular Disease and role of LC/MS
Time : 10:01-10:20
Biography:
Jose is the Director of Health Sciences Marketing. Prior to this, Jose spent part of his career as the Team Leader of Biomarkers and Translational Research at Merck, USA. He has published 62 publications and numerous scientific patent applications. He attained his BSc in Chemistry from King's College in London (UK) and subsequently received his MSc in Clinical Biochemistry and Molecular Biology from the University of Surrey (UK). He obtained his Ph.D at the University of Leiden (Netherlands) in Metabolomics and Biomarker discovery. In 2014, Jose was awarded by Thompson Reuters the prestigious Highly Sited Researcher Award.
Abstract:
Metabolomics and Lipidomics play an increasingly important role in the understanding and diagnosis of cardiovascular disease. Lipid profiling in cardiovascular disease drug discovery whether targeted or untargeted is key to provide an insight in the mechanism of action and to prove target engagement. This is particularly important in the early stages of target identification and validation. Furthermore, metabolic tracing of pathways and flux analyses plays a pivotal role because it allows for early indication of lipid target efficacy and aid in the interpretation of phenotypic differences when steady state concentration measurements are insufficient. In this presentation we will present a number of examples using UPLC/high resolution TOF MS which highlights how this technology may be applied to exploratory biomarkers of the metabolic syndrome. The examples will include; perturbation of diet, genetic knockdowns, transcriptome/lipidome relationships, metabolic tracers and metabolic flux of lipids.
Houkai Li
Shanghai University of Traditional Chinese Medicine, China
Title: Metabolomic study on the different responses to simvastatin therapy in normal and antibiotic-treated mice
Time : 10:21-10:40
Biography:
Houkai Li has completed his PhD from Shanghai Jiao Tong University and Post-doctoral studies from University of North Carolina (2011.8-2013.5) and Chinese Academy Sciences (2008.11-2011.3) respectively. He is now a Professor at Center for Traditional Chinese Medicine and Systems Biology in Shanghai University of Traditional Chinese Medicine. He has published over 25 papers in reputed journals
Abstract:
Simvastatin is a classical HMG-CoA reductase inhibitor that is widely used for reducing plasma LDL-cholesterol (LDL-c) and risk of cardiovascular disease. There are frequently interindividual variations in therapeutic efficacy of simvastatin among individuals in clinic, while the mechanisms are unclear. Previous study showed that the pre-dose variations of some gut microbial metabolites were correlated with the extent of LDL-c reduction in patients, and lovastatin, an analog of simvastatin could be metabolized by bacteria. Accordingly, we hypothesized that the interindividual variations in therapeutic efficacy of simvastatin might be associated with the variation of gut microbiota. In current study, fifty male C57BL/6J mice were divided into five groups including control (Con), high-fat/cholesterol diet (HFD), antibiotic (AB), simvastatin (ST) and simvastatin plus antibiotic (AB_ST) groups. These mice were fed with correspondingdiet for 12 weeks. Simvastatin was given orally (20 mg/kg) once a day and antibiotic was provided in drinking water during the whole experiment. We performed metabolic profiling on serum samples by using combined GC/MS and UPLC/QTOFMS metabolomic approach. First of all, we found that the disruption of gut microbiota with antibiotic significantly attenuated the hypolipidemic effect of simvastatin in mice. Then, the metabolic profiling showed a distinct separation between ST and AB_ST groups, and the subsequent analysis identified several metabolites that were differently altered between ST and AB_ST groups such as alanine, ribose-5-phosphate, alpha-monooleoylglycerol, cholesterol, PCs and some bile acids. Moreover, we found that the expression of hepatic CYP7A1, CYP7B1 and FXR proteins was differently regulated, while no difference was observed in HMG-CoA reductase between ST and AB_ST groups. These results suggested that the gut microbiota associated alteration in bile acids synthesis processfrom cholesterol might contribute to the different responses tosimvastatin in antibiotic-treated mice.
Robert Plumb
Imperial College London, UK
Title: Understanding human health and disease with LC/MS based metabolic phenotyping
Time : 11:01-11:20
Biography:
Robert Plumb is the Director of Metabolic Phenotyping and Stratified Medicine in the Waters Health Sciences Business Operations Division, based in Milford, Massachusetts. He has published over 100 papers on HPLC/MS and NMR for bioanalysis, metabolomics and metabolite identification. He is a recognized expert in the use of liquid chromatography with mass spectrometry, capillary scale LC, purifications scale LC and metabonomics, giving many invited papers at international meetings around the world. He is currently a visiting Professor in Analytical Chemistry at Kings College London, visiting Professor at Imperial College in the Dept. Surgery and Cancer and a Fellow of the Royal Society of Chemistry. In 2014 he was awarded Highly Cited Researcher by Thompson Reuters.
Abstract:
The MRC-NIHR National Phenome Centre, Imperial College London, is the first of its kind facility. Born out of the UK Olympic Legacy its mandate is to provide “high throughput, forensic quality, metabolic phenotyping to support large scale epidemiological studies as well as basic medical research into disease understanding and patient stratification”. As global life-styles change we are seeing increasing cases of obesity, diabetes, and mental health issues. This not only affects a person’s quality of life but also places increased strain on the health-care systems to provide the right treatment whilst managing costs closely. Metabolic Phenotyping offers a valuable and unique insight into the underlying biochemistry of diseases as well as the patients individual biochemistry “phenotype’, diet, health status, age and stress. To deliver this information, the analytical data generated in processed via a variety of chemometric modelling and analysis methodologies to deliver the relevant biochemical information. These chemometric platforms employed vary from simple multivariant analysis to highly complex model based analysis and is presented in a format ready for interpretation by medics. In this presentation, we will discuss the development of LC/MS analytical platforms as well as a detailed discussion on the workflow, validation, reporting and decision making process. The presentation will cover the development and validation of the “discovery’ screening methods for polar, non polar metabolites and lipid profiling using LC/MS methodology, as well as the quantitative targeted LC/MS assays and the various compounds classes such as bile acids, amino acids, eicosanoids, and acyl cartanines will also be discussed.
Jingxin Zhou
Beijing University of Chinese Medicine, China
Title: Treatment of Natural Plants on Diabetes and Metabolic Syndrome
Time : 11:21-11:40
Biography:
Jingxin Zhou has completed MD from Beijing University of Chinese Medicine in 2014. She is a doctor in Department of Endocrinology, Dongzhimen Hospital Eastern, Beijing University of Chinese Medicine. She does research on Chinese medicine treating diabetes and metabolic sysdrome.
Abstract:
The increasing incidence of diabeties and metabolic syndrome becomes a worldwide threat to global human health. Chinese herbs and natural plants have played an important role in health maintenance for thousand years. Our study have indicated that Chinese medicine including formula, herbal extracts, and compounds mediates the glucose and lipid metabolism. We found Tang-Nai-Kang granules improve the glucose intolerance and insulin resistance by mediating fatty acid oxidation in SHR.Cg-Leprcp/NDmcr rats. Meanwhile, Guava leaf extracts significantly enhanced the insulin-related signaling to activate the insulin signaling and promoting glucose metabolism and fatty acid oxidation, lead to the improvement of insulin sensitivity in the SHRSP/ZF rats. In addition, Isoquercitrin appears to regulate AMPK activation, thereby enhancing AdipoR1 expression, suppressing SREBP-1 and FAS expressions, and resulting in the regulation of lipid accumulation in vivo.
Chia-Lin Hsu
National Yang-Ming University, Taiwan
Title: Metabolism and immunity: From a nucleic acid recycling viewpoint
Biography:
Chia-Lin Hsu received her PhD degree in Immunology from Duke University, focusing on cytokine signaling and lineage commitment in hematopoiesis. She was trained as postdoctoral research fellow at Genentech, a San Francisco-based biotechnology company. During this period, she discovered that the nucleoside equilibrium is crucial to the homeostasis of immune system, and when out-of-balance, can lead to lysosomal storage disease-like phenotypes. She then accepted the position as Senior Scientist at the Center of Innovative Therapeutics, Pfizer. She was the biology lead of a multi-centers project that aims to develop immune-modulatory therapeutics with the combined efforts from both pharmaceutical and academic laboratories. She returned to Taiwan in 2013, and now is an Assistant Professor at the Institute of Microbiology and Immunology, National Yang-Ming University.
Abstract:
Immunometabolism is a new term describing the interactions between metabolism and immunity, the biological functions that have long considered as two distinct entities. However, despite the substrate to be pathogens or nutrients, both processes work to restoring the homeostasis of the body. With modern diet, the correlation between overnutrition and chronic inflammation brings the attention to how metabolic homeostasis contribute to properly controlled immune system. It is becoming clear that immune activation can affect metabolism while metabolic changes also have profound influence on immunological functions. Nevertheless, the molecular mechanisms that connect these two systems are still unclear. For example, lysosomal storage diseases (LSDs) are a group of heterogeneous disorders caused by defects in lysosomal enzymes or transporters, resulting in accumulation of un-degraded macromolecules or metabolites. This accumulation disrupts the cell's normal functioning and gives rise to the clinical manifestations of LSDs. We found that equilibrative nucleoside transporter 3 (ENT3) is a lysosomal specific nucleoside transporter that highly expresses in macrophages. Mice lacking ENT3 developed a spontaneous and progressive macrophage-dominated histiocytosis. In the absence of ENT3, defective apoptotic cell clearance led to lysosomal nucleoside buildup, elevated intralysosomal pH, and altered macrophage function. These studies suggest a cellular and molecular basis for the development of histiocytosis in several human syndromes associated with ENT3 mutations and potentially other LSDs. Furthermore, we will discuss potential roles of ENT3 in other aspects of immune response.
- Special Session
Session Introduction
Yoshiro Fujii
Shin Kobe Dental Clinic, Kobe City, Japan
Title: Two cases of the serious dementia improved dramatically by placing denture
Time : 13:46-14:45
Biography:
Dr. Yoshiro Fujii is a director and chief dentist of Shin Kobe Dental Clinic. 1985:D.D.S. (Certified by Japanese Health Ministry).1989: He received Koide prize. Finished graduate school, Nagoya, Japan. and Ph.D (Aich Gakuin University Graduate school, Nagoya). 2000: Dr. Fujii began to run Shin Kobe Dental Clinic (Kobe, Japan). 2009: Fellow of the international college of acupuncture and electro-therapeutics (F.I.C.A.E). 2013,2014: 100 next era CEOs in Asia (Japan times). 2014: Editioriall board member of Savvy Science Publisher. 2015: Editorial board member of British Journal of Medical Research.. 2015: 100 Next-era Leaders in Asia (Japan times). He has written five published works in Japanese and two in English. He is an Authorization doctor of the Japan Bi-Digital O-Ring Test. Association and a director of the Japan Society of Dental Equipment. He published eleven international academic articles in English. 2014-15: He was a chair or co-chair three times in various international congresses.
Abstract:
Serious dementia, including Alzheimer’s disease seems intractable and progressive. The purpose of this study was to demonstrate the improvement of two cases of serious dementia by placing denture(s). The two subjects were women in their 70s. They had serious dementia and were diagnosed as having Alzheimer’s disease by a medical doctor in charge of their cases. In the first case, the subject’s symptoms included severe disorientation, impaired communication and a tendency to wander. Two weeks after a lower full denture placing, she was able to greet others. Five weeks later she was able to communicate and to read an analog clock precisely. Her improved condition continued for least three months. In the second case, the subject constantly kept her mouth open. She was in a vegetable stage; she was bedridden, hardly moved, talked or laughed. It was impossible to communicate with her. Only a few seconds after an upper full denture placement, she started to talk but it was unintelligible. Two weeks after a lower full denture placement, she could communicate smoothly, laugh and walk without help. The underlining mechanism has not yet been clarified, however, the author hypothesizes that positive signals from the oral area transferred to the brain as the positive stimulation, via the trigeminal nerve, which is the biggest of the cranial nerves.
- Track : 14 Frontiers of Metabolomics Research
Track : 16 Therapeutic Metabolomics
Track : 18 Transcriptomics & Metabolic pathways
Chair
Andrea Armirotti
Istituto Italiano di Tecnologia, Italy
Co-Chair
Horng-Mo Lee
Taipei Medical University, Taiwan
Session Introduction
Loeffler Jean Philippe
Université de Strasbourg, France
Title: Metabolomic biomarkers for amyotrophic lateral sclerosis (ALS) in patients and animal models of ALS
Time : 14:46-15:05
Biography:
Dr. Jean-Philippe Loeffler is head of the Central and Peripheral Mechanisms of Neurodegeneration Laboratory (UMRs-INSERM U1118)in Strabourg (France). He got his B Sc in Biochemistry and Physiology, M Sc in physiology and his PhD in Neurobiology at University of Strasbourg (France). After a post doctoral fellow at Dept. of Neuropharmacology, Max Plank Institute of Psychiatry, Munich, he obtained a tenure position at INSERM from 1987 to 1996 as researcher and from 1996 to present as Research Director (H index: 46).From 1994 to 2000 he was Visiting Associate professor of Molecular Neurobiology (faculty member) at the Mount Sinaï Hospital, New York, USA. Since 2001, he heads a laboratory working at the interface between fundamental and clinical research, specifically striving to understand the mechanisms underlying the processes of neuronal death in neurodegenerative diseases.
Abstract:
Amyotrophic lateral sclerosis (ALS) is the most common motor-neuron (MN) disease in adults. ALS is characterized by the degeneration of upper and lower MN and is fatal within a time frame of 2 to 5 years following diagnosis. This diagnostic rests on differential clinical diagnosis that can take a year and thus the urgent medical need for this disease is to develop a rapid and simple diagnostic test based on the use of validated biomarkers. To address this issue, we focused over the last years on the metabolic aspects of ALS. We analysed the role of hypermetabolism associated with ALS and the role of lipids, both as a source of energy supply but also as a source of biochemical signalling molecules. We recently showed that in ALS models and in ALS patients, beta oxidation is favored compared with glycolysis. This results from a loss of metabolic flexibility and could be traced down at the genetic level to the induction of pyruvate dehydrogenase (PDH) kinase (PDK)4, the main regulator of PDH in the striated muscle tissue. This effect appears to be highly specific to ALS and is found in various ALS mice models (e.g., Tg for SOD1, FUS, TDP43……) and in ALS patient biopsies. Further, using global methods (e.g., transcriptomics and metabonomics) we show that: 1) Stearoyl coenzyme desaturase 1 (SCD1), the enzyme that drives lipids (mainly C 16 and C 18) towards beta oxidation is increased in patients and could thus be responsible for the ALS associated hypermetabolism. Further, we show that SCD1 activity, estimated by ratio of unsaturated on saturated C16 is a good predictor of ALS outcome. 2) The use of UPCL/TOF-MS reveals a crucial of glucosylceramides (GlcCer) in the course of the disease. HPLC analyses showed increased amounts of GlcCer and the downstream glycosphingolipids (GSLs) in ALS mice models (SOD1 G86R) and ALS patients. These findings suggest a crucial role of GSLs in ALS. Taken together, this set of data indicates a fundamental role of lipid metabolism in ALS. This approach should help to develop reliable biomarkers that will help to validate diagnostic tools that are currently required urgently.
Woo Duck Seo
National Institute of Crop Science, Republic of Korea
Title: Comparative assessment of phenolic compounds and antioxidant properties related to the harvest times from the leaves of Korean barley (Hordeum vulgare L.) cultivars
Time : 15:06-15:25
Biography:
Woo Duck Seo has completed his PhD from Gyeongsang National University and Post-doctoral studies from Korea Institute of Radiological & Medical Sciences. His researches focus on the analyses of natural product from crop source and test of biological assay such as metabolic syndrome.
Abstract:
This research was the first to investigate changes in phenolic profiles and antioxidant capacities from the leaves of various barley cultivars through four different harvest times. Ten phenolics were characterised as hydroxycinnamic acid, orientin, isoorientin, and isovitexin derivatives using UPLC-PDA-ESI/MS and nuclear magnetic resonance (NMR), especially, lutonarin (2) and saponarin (3) were the predominant constituents (71–75%) with significant differences in cultivars and harvest times. The highest average phenolic content was found with 2671.8 mg/100g on 23 days after sowing, whereas the lowest was 1400.8 mg/100g on 56 days. The radical scavenging abilities also exhibited considerable differences in the 80% methanol extracts (40 μg/ml), depending upon the phenolic contents. Interestingly, isoorientin (5) and orientin (6) possessed potent antioxidant effects with IC50 values of 20.7±1.1 and 27.5±7.3 μM (DPPH) as well as 5.7±0.3 and 8.2±0.3 μM (ABTS), respectively. Our results may be useful information to determine the optimal harvest time (mid-April) of barley leaves.
Benedetto Grimaldi
Istituto Italiano di Tecnologia, Italy
Title: Crosstalk between the circadian clock and cancer metabolism reveals novel anticancer strategies
Biography:
Benedetto Grimaldi, after completing his PhD in Genetics and Molecular Biology from University of Rome, La Sapienza (Italy), transitioned into a Post-doctoral fellowship under the mentorship of Prof. Sassone-Corsi (University of California, Irvine, USA), a leader in the field of circadian clock, metabolism and epigenetics. He is Senior Researcher at the “Istituto Italiano di Tecnologia (IIT)”, Italy, where he directs a laboratory of Molecular Medicine pursuing a line of research focused on the study of “clock-related pathologies”, and on the identification and evaluation of novel molecules with “clock modulator” activity for therapeutic applications
Abstract:
Despite epidemiological data indicate a close relation between circadian disruption and cancer, the suitability of a pharmacological modulation of the clock machinery as a viable approach to cancer therapy remains to be determined. We recently obtained the first evidence that the pharmacological targeting of a circadian regulator may be a suitable anticancer strategy: we revealed that the beta-variant of circadian nuclear receptor REV-ERB, REV-ERBβ, functions as an unpredicted major regulator of clock gene expression in different human tumor tissues cells, where it plays an unexpected role in sustaining cancer cell survival when the autophagy flux is compromised. These studies also identified a novel class of compounds with a dual inhibitory activity against both REV-ERBβ and autophagy, which decreased the viability of different tumor tissue cells at concentrations from 5 to 50 times lower than the singular clinically relevant autophagy inhibitor, chloroquine. The crucial position of REV-ERB proteins in the regulation of cellular metabolism suggests the provocative hypothesis in which the inhibition of both REV-ERBβ and autophagy cooperate to induce a metabolic dysfunction that is incompatible with cancer cell viability. Consistent with this view, we obtained data indicating a REV-ERBβ-mediated transcriptional regulation of cancer metabolism. Implicit in this hypothesis is the concept that the altered circadian regulation found in several tumors may be triggered by the special metabolic needs of the cancer cell. In addition, this scenario opens the possibility that REV-ERBβ inhibition may be suitable not only for combinatorial therapy with autophagy inhibitors, but also with a number of metabolic-related anticancer drugs, which identification and optimization is source of increasing effort in cancer research.
Horng-Mo Lee
Taipei Medical University, Taiwan
Title: Ferrous glycinate reverses Warburg effect and regulates cell energy metabolism via suppression of hypoxia-induced factor in human lung adenocarcinoma A549 cells
Time : 15:46-16:05
Biography:
Horng-Mo Lee graduated from School of Pharmacy in Taipei Medical University, Taipei, Taiwan. Upon graduation, he went to the U.S.A. and completed his PhD in Biochemistry at the University of Tennessee, Memphis, and postdoctoral training in St. Jude Children’s research hospital in Memphis, Tennessee. He is currently working on exploring the cancer therapeutic approaches targeting energy metabolism. He has published more than 75 articles in peer-reviewed journals. He served as the president of Central Taiwan University of Science and Technology from 2009-2015. He is now a professor in Department of Medical Technology and Biotechnology in Taipei Medical University.
Abstract:
Cancer cells are characterized with aerobic glycolysis and suppressing of mitochondrial energy metabolism (Warburg effect). In the present study, we demonstrated that treatment with ferrous glycinate reversed aerobic glycolysis, reactivated mitochondrial energy metabolism in lung adenocarcinoma A549 cells. Incubation of A549 cells with ferrous glycinate for 24h decreased expression levels of glucose transporter, Glut-1, and glycolytic enzymes including hexokinase-2, and lactate dehydrogenase A. On the other hand, treatment with ferrous glycinate reactivated oxidative phosphorylation by suppressing the expression of pyruvate dehydrogenase kinase-1 and thereby pyruvate dehydrogenase phosphorylation which subsequently increased mitochondrial membrane potential and ATP production. Treatment of A549 cells with ferrous glycinate decreased the protein levels of HIF-1 alfaunder nomoxia and hypoxia conditions. The reduction of HIF-1 alfa was reversed by pretreatment with proteosome inhibitor, or prolyl hydroxylase inhibitor. Given HIF-1 alfaplays a pivotal role in regulating cancer cell metabolism, these data suggest that ferrous glycinate may regulate energy metabolism, glycolysis in lung adenocarcinoma cells via suppression of HIF-1 alfa
Björn Riefke
Bayer Pharma AG, Germany
Title: NMR-based metabolomics analysis of 2D with 3D (Spheroids) of breast cancer cells
Time : 16:26-16:45
Biography:
Dr. Björn Riefke completed his PhD in Biology in 1994 from Heinrich-Heine-University in Duesseldorf, Germany. Since 1994 he have worked in various positions in research and development of former Schering AG and since 2006 of Bayer Pharma AG. He is head of Metabolic Profiling and Clinical Pathology Group in Toxicology and since then involved in the establishment of metabolic profiling platform supporting projects in toxicology, biomarker research and pharmacology.
Abstract:
Findings in 2D tumor cell models only partly translate to experimental outcome in vivo. Chemotherapy strategies target proliferating cells adjacent to blood vessels with sufficient supply of oxygen and nutrients. In poorly vascularized regions of the tumor cells adapt to survive and are resistant to chemotherapy. 3D Spheroids of tumor cells resemble characteristics of invasive tumors and are an intersting model to target the inner core of tumors. We used NMR-based metabolomics to study the metabolic differences of T47D breast cancer cells cultivated in 2D and 3D conditions. Additionally tumor spheroids were treated with compounds targeting the inner core of the spheroids. After 48 h incubation cells were quenched and harvested with a ice-cold MeOH/Chloroform/H2O mixture. The freeze dryed sample extracts were reconstituted in phophate-buffered saline and high-resolution 1H-NMR spectra were measured with a 600 MHz Bruker Biospin equipped with a cryo-probe and sample jet system. Baseline and peak shift corrected spectra were divided into 0.04 ppm buckets and integrated. Multivariate data analysis was performed on bucketed spectra to identify difference between 2D and 3 D control conditions. Afterwards metabolites were annotated using the Chenomx Profiler software. Metabolite differences showed signatures indicative for glucose deprivation in spheroids accompanied with limited capacity to perfom synthesis and cell division to maintain cell hemostasis and resulting in tumor dormancy. Studied compounds targeting the specific inner core region of tumor spheroids resemble metabolic profiles similar to inhibitors of mitochondrial respiration like Antimycin A or Oligomycin.
Dilson Ferreira da Luz
Plastic Clinic Dilson Luz, Brazil
Title: Progressive tunnelizations in neck face lift detachment: Fat grafts as complement
Biography:
Graduated in medicine in 1969, performing plastic surgery since 1975. Presents this original technique for cutaneous detachment in Face Lift for 16 years. Having held dozens of lectures at conferences in Brazil and abroad. Publications in various journals. In 2009 he published the book Technical Dilson Luz, Tunelizações Progressive in the Face Lift. In 2013 published Technical Dilson Luz, Tunelizaciones Progresivas. In 2014, he published the chapter Progressive Tunnelizations in Neck Face Lift Detachment in necklift book, author Malcolm Paul. Member and Specialist of the Brazilian Society of Plastic Surgery and a member of the International Society Aesthetic Plastic Surgery.
Abstract:
The author describe 12 years experienced in the application of a new and simple method of facial cutaneous detachment using specially designed bi-faceted rigid steel wands called “Dilson Luz Vascular Dilation Wands®”. These wands considerably reduce the bleeding during face-lift surgery, reducing both postoperative hematomas as well as the risk of facial nerve injury. This technique "PROGRESSIVES TUNNELIZATIONS" involves stretching the blood vessels to the point of rupture by inserting progressively larger “wands.” At the point of rupture, a spontaneous coagulation within the vascular extremities occurs. This is due to a significant blood platelet migration induced by the stimulation from the rupture of the vascular intima. The wands vary in dimension from 1.5 to 20 mm and the larger were used for cutaneous facial complete detachment, and the more fine to perform tunnels. A method which we found to result in minimal bleeding across the detached surface as well as an excellent perfusion of the over lying skin. With this new technique, we have obtained improved cutaneous detachment, reduced postoperative swelling, edema and ecchymosis; prophylaxis of facial nerve damage and/or late postoperative hematoma formation. The fat grafts with active platelets always perform the face lift.
Biography:
Simon D Lytton has completed his PhD at the age of 34 years from Hebrew University-Jerusalem and postdoctoral studies from Karolinska Institute Sweden and NIH Bethedsda Maryland USA. He is private consultant of SeraDiaLogistics, focused on immunology medical research and diagnostics. He has published more than 30 papers in reputed journals and has been serving as a consultant for the VG Test device 3QBD CEO Mr. Moshe Golan
Abstract:
Purpose A new CE-marked portable desktop ion mobility spectrometer (VGTest) was used for detection of malodorous biogenic amines indicative of bacterial vaginosis (BV). This study aimed to assess the performance of this testing method for the first time in a routine ambulatory care clinic and to determine the relative levels of biogenic amines in vaginal fluid of BV. Methods Vaginal and cervical swabs (n = 57) were surveyed for infections. Cases of BV (n = 18) confirmed positive according to ‘‘Amsel’’ criteria and normal controls (n = 39) showing no infection under clinical examination and testing negative in wet mount microscopy were included in the IMS analysis. Results The trimethylamine (TMA) content in vaginal fluid of the BV-positive cases, AUCTMA/AUCTotal [mean 0.215 (range 0.15–0.35)] was significantly higher than normal controls [mean 0.06 (range 0.048–0.07)] p .0001. The putrescine (1,4-diaminobutane, PUT) and cadaverine (1,5-diaminopentane, CAD) of BV-positive cases were above controls at borderline significance. The AUCTMA/AUCTotal ratios correlated neither with AUCPUT/ AUCTotal nor AUCCAD/AUCTotal among BV-positive patients. In contrast, among normal controls all the biogenic amines were at a low level and the linear regression analysis revealed striking positive correlations of AUCTMA/AUCTotal with AUCPUT/AUCTotal (p .05) and AUCCAD/AUCTotal (p .001). The test shows 83 % sensitivity and 92 % specificity at a cut-off of AUCTMA/ AUCTotal = 0.112 and AUC of receiver operator characteristic = 0.915 (0.81–0.97, 95 % CI). Conclusions VGTest-IMS is accurate and feasible for point-of-care testing of BV in the ambulatory care setting. Further evaluations are in progress to assess the utility of VGTest-IMS for differential diagnosis of candidosis, non-BV infection and common inflammatory conditions.
- Special Session 2
Session Introduction
Ashkan Emadi
University of Maryland School of Medicine, USA
Title: Translational Research in Targeting Glucose or Glutamine Dependency in Solid and Hematologic Neoplasms
Biography:
Dr. Emadi received his M.D. at Tehran University of Medical Sciences and his Ph.D. in Organic Chemistry at the Illinois Institute of Technology. He developed novel methodologies for the regiospecific synthesis of multiple naphthoquinone derivatives related to the natural product conocurvone, and was granted “Highest Standards of Academic Achievement Award”. Following completion of his Ph.D., he completed his internship and residency in Internal Medicine at the University of Kentucky and the University of Cincinnati, respectively. Subsequently, Dr. Emadi was trained in Hematology and Medical Oncology Fellowship Program at Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center. Dr. Emadi joined the University of Maryland Marlene and Stewart Greenebaum Cancer Center as an Associate Professor of Medicine, Pharmacology and Experimental Therapeutics at the University of Maryland School Of Medicine and serves as Director of the ACGME-accredited Hematology and Oncology Fellowship Program. He previously served as medical officer at the Division of Hematology Products (DHP), United States Food and Drug Administration (FDA), and as visiting scientist at Division of Adult Hematology, Department of Internal Medicine, School of Medicine, Johns Hopkins University. Dr. Emadi has experience and in-depth understanding of the multiple aspects of cancer drug development including basic organic chemistry and molecular synthesis, in vitro and in vivo studies, and all phases of clinical trials as well as regulatory science.
Abstract:
Before the recruitment of new blood vessels, proliferation of cancer cells in a three dimensional multi-cellular cluster is limited by diffusion of oxygen and nutrients, such that a phase of metabolic adaptation must be endured. Transcription factors such as hypoxia inducible factors (HIFs) are overexpressed in many neoplastic cells and induce genes, such as lactate dehydrogenase A (LDHA) and pyruvate dehydrogenase kinase 1 (PDK1), which permit hypoxic metabolic adaptation. Glucose, which is the main energy source for normal and tumor cells, is taken up and converted by glycolysis to two molecules of pyruvate. The dramatic increase in glucose uptake by tumors provides a means to detect cancers and follow response to therapy by PET scanning. When oxygen is available, pyruvate converted to acetyl-CoA by pyruvate dehydrogenase in the mitochondrion and further metabolized through tricarboxylic acid cycle. When oxygen is limited, HIF-1 induces virtually all glycolytic enzyme genes and PDK1, which inhibits PDH and diminishes mitochondrial acetyl-CoA production and respiration. Through this adaptation, hypoxic cells switch initially to anaerobic glycolysis that catalyzes the final conversion of pyruvate to lactate via LDHA. Later on, due to genetic alterations, even under non-hypoxic conditions, neoplastic cells utilize aerobic glycolysis phenomenon. Small molecule inhibitors against different enzymes in the glucose metabolism are already available making the potential for clinical translation the more likely. Glutamine is the most abundant amino acid in the intracellular compartment as well as human plasma. Glutamine is involved in the generation of non-essential amino acids for protein synthesis as well as nitrogen supply for purine and pyrimidine synthesis. Glutamine also stimulates the mammalian target of rapamycin complex 1 (mTORC1) and its deprivation inhibits mTORC1 and causes apoptosis of many neoplastic cells. After entering the cell through a special transporter, glutamine can be converted to glutamic acid by removal of its amide group, a reaction catalyzed by glutaminase enzymes. Subsequently, glutamic acid can be converted to α-ketoglutarate (αKG), either by transamination or by oxidation processes. Perturbation of different aspects of glutamine metabolism for treatment of solid and neoplastic malignancies is currently being tested in clinical trials. These fundamental metabolic differences between the cancers and normal tissues will be discussed for therapeutic applications.