Day 1 :
Keynote Forum
Alexander D Verin
Georgia Regents University, USA
Keynote: Extracellular purines in lung endothelial barrier regulation
Time : 09:45-10:20
Biography:
Alexander D Verin has completed his PhD from Moscow State University, Moscow Russia and Postdoctoral studies from University of Indiana, School of Medicine. Currently he is a Professor of Vascular Biology and Medicine at Vascular Biology Center and Pulmonary Division at Georgia Regents University, Augusta, GA. He has published more than 135 papers in reputed journals and serving as an Academic Editor of Cardiology and Angiology and an Editorial Board Member in several other journals in the field of pulmonary and cardiovascular research such as Cardiovascular Pharmacology, Journal of Multidisciplinary Pathology, Journal of Vascular Diagnostics, The Journal of Biopharmaceutics Sciences, Tissue Barriers, World Journal of Respirology. In addition, he served as Editorial Board Member in American Journal of Physiology (Lung) from 2006 to 2011 and was a reviewer for a number of highly regarded journals (ex. Circulation Research, Critical Care Medicine, Physiological Reviews, PNAS).
Abstract:
Endothelial cells (EC) form a semi-permeable barrier between the interior space of blood vessels and the underlying tissues. In acute lung injury (ALI) the EC barrier is weakened leading to increased permeability. The mechanisms that govern the highly clinically relevant process of increased EC permeability are under intense investigation. Little is known about the processes that determine barrier enhancement or preservation. Recently, attention has been given to the therapeutic potential of purinergic agonists in the treatment of cardiovascular and pulmonary diseases. Our data indicate that ATP and its degradation product adenosine are able to protect and restore EC barrier in vitro and in vivo. We and others show that adenosine induces rapid increases in cAMP level and activation of protein kinase A (PKA)/myosin light chain (MLC) phosphatase (MLCP) cascade and this correlates with a significant attenuation of lipopolysaccharide (LPS)-induced EC permeability. In contrast, ATP induced PKA/MLCP activation and EC barrier enhancement without increase in cAMP. We also have shown the involvement of P2Y receptors coupled to Gi2 or Gq (for ATP) and P1 A2A receptors coupled to Gs (for adenosine) in purine-induced EC barrier enhancement. In addition, we have shown that inhibition of MLCP leads to the phosphorylation of several cytoskeletal targets, which correlates with permeability increase suggesting that dephosphorylation of these proteins may be involved in the barrier-enhancing effect. Further, introduction of active MLCP subunits into the lung endothelium reduces LPS-induced lung inflammation strongly supporting the positive role of MLCP activity in EC barrier preservation against ALI in murine model. Collectively, our data strongly suggest that EC barrier preservation induced by extracellular purines is dependent upon activation of specific purinergic receptor/G-protein complexes. Further, purine-induced EC barrier preservation requires the coordinated activation of PKA signaling and MLCP activation leading to EC cytoskeletal changes.
Keynote Forum
Ahmed Al-Jumaily
Auckland University of Technology, New Zealand
Keynote: Airway Passages Narrowness and Pressure Oscillation
Time : 10:20-10:55
Biography:
Ahmed Al-Jumail did PhD and MSc from the Ohio State University and BSc from the University of Baghdad. He is a Fellow member of the ASME, and a member of 11 other international professional societies. He is the Editor of the ASME monograph series-Biomedical and Nanomedical Technologies and the Editor in Chief of the Journal of Biomedical Engineering and Technology, and has been on the editorial and refereeing boards for several international journals. He has published more than 270 papers in international journals and conference proceedings including two ASME books on Vibration and Acoustics in Biomedical Applications and a third one on CPAP devices. He has supervised more than 90 Postgraduate students in biomedical applications, vibrations, biomechanics, and electroactive polymers. During his academic career, he forged strong alliances between academia and industries; in particular in the medical devices area. His current research focuses on biomedical applications with particular interest in the application of vibration and acoustics to airways constriction therapies and artery non-invasive diagnostics.
Abstract:
Obstructive sleep apnea (OSA), asthma and respiratory distress syndrome (RDS) are three lung diseases associated with narrowing of the airway passages which is attributed to either collapse of the upper airways, airway constriction and/or lack of surfactant generation, respectively. These ailments are the major cause of morbidity and mortality worldwide and have serious negative contributions to the quality of life. Each one of these ailments has different mechanisms and are stimulated by various physiological activities, some are biochemical while others are biophysical. Various pharmaceutical treatments are available, but very seldom without side effects. Pressurizing the lung, such as using continuous positive airway pressure (CPAP) method to reduce the airway narrowness has been an effective treatment method for some cases. This presentation elaborates on how this treatment method can be enhanced and improved using pressure oscillation (PO). Some successful cases including clinical trials, tissue testing and an animal model will be discussed to show the successful results of using PO in the treatment of OSA, asthma and RDS. While in vitro as well as in vivo experiments have demonstrated that length oscillations can reduce forces in contracted airway smooth muscles (the main driving mechanism for asthma attack), it has been proven that PO improves lung compliance, inflammatory stresses on patients and preserves surfactant function. This presentation highlights how engineering innovation can convert PO to a lung therapy and how this could be expanded further to the cell level to achieve asthma therapy. Is this an alternative and/or supplement to inhalers? Can oscillation help to reduce the use of current relaxants
Keynote Forum
Janet M Urban
Motivator Tobacco Treatment and Wellness Services, USA
Keynote: Smoking cessation: A review of the literature
Time : 11:20-11:55
Biography:
Janet M Urban is a lifelong resident of Central New York and currently resides in Nedrow. She holds an MS in Special Education and has taught for OCM BOCES for the past fifteen years. She holds certifications as a Tobacco Treatment Specialist from the Mayo Clinic Nicotine Dependence Center, Rochester, MN and as a Facilitator for the “Freedom from Smoking” program through the American Lung Association. She also holds certification as: Personal Trainer through WITS (World Instruction Training Schools), “Practical Yoga for Personal Trainers” and “Holistic Fitness Specialist” through the Academy of Holistic Fitness. She is also certified as a Work-Based Learning Coordinator through SUNY Buffalo. She provides individual consultations, customized treatment plans and group counseling smoking cessation services.
Abstract:
There is much literature on smoking cessation. As a worker in the substance abuse field it is necessary to gain insight into the facts, implications and treatments for smoking cessation. Areas to be briefly discussed in this lecture include the following highlights from my recently published book:There is a long history of tobacco use and findings in regards to tobacco use including the following time periods: “The Emerging Awareness of Tobacco’s Hazardous Effects”, “Taking Action”, and “The New Millennium”. Tobacco Dependence is a chronic Biopsychosocial disease characterized by frequent relapse. It has the same manifestation, maintenance and course that addictions have, and it has the same rationale for treatment as other chemical dependencies. Further, it has been found that there is a high morbidity rate related to tobacco use and dependence in people with co-occurring disorders including alcohol and other drug dependencies along with other serious mental disorders. There are multiple biological reasons that clients use tobacco and one proven solution is Nicotine Replacement Therapy as it is safe and has little potential for abuse. Supportive counseling such as group and individual has been shown to be successful in treatment. Various counseling models include: Psychological, Social, Integrative, The five A’s Intervention Tool, Motivational Interviewing, Stage of Change Model, Cognitive Behavior Therapy, Decisional Balance Model, Relapse Prevention Therapy, Behavior Therapy, and Cognitive Social Learning Therapy among others. Tobacco treatment plans include assessment, Integrated Program Therapy Activities and Relapse Prevention strategies. The tobacco industry targets those with mental health disorders. 44%-80% of this population wants to quit smoking. The system of care for this population should not be limited to a single correct model or approach. Tobacco Treatment Groups include both Tobacco Awareness Groups where it is shown to the client that the relationship with the substance is the problem not the substance itself and Tobacco Recovery Groups where craving management techniques are suggested. In summary, good clinicians assess and evaluate, diagnose substance abuse and dependence, engage patients in treatment, conduct individual and group counseling, and work collaboratively with patients to formulate treatment and treat tobacco dependence.\\\\r\\\\n
- Lung and Metabolism
Lung Infections
Lung Disorders
Session Introduction
Alexander D Verin
Georgia Regents University, USA
Title: Microtubule-mediated signaling in lung endothelial barrier regulation
Time : 12:10-12:40
Biography:
Alexander D Verin has completed his PhD from Moscow State University, Moscow Russia and Postdoctoral studies from University of Indiana, School of Medicine. Currently he is a Professor of Vascular Biology and Medicine at Vascular Biology Center and Pulmonary Division at Georgia Regents University, Augusta, GA. He has published more than 135 papers in reputed journals and serving as an academic editor of Cardiology and Angiology and an Editorial Board Member in several other journals in the field of pulmonary and cardiovascular research such as Cardiovascular Pharmacology, Journal of Multidisciplinary Pathology, Journal of Vascular Diagnostics, The Journal of Biopharmaceutics Sciences, Tissue Barriers, World Journal of Respirology. In addition, he served as Editorial Board Member in American Journal of Physiology (Lung) from 2006 to 2011 and was a reviewer for a number of highly regarded journals (ex. Circulation Research, Critical Care Medicine, Physiological Reviews, PNAS).
Abstract:
The vascular endothelium (EC) acts as a semi-selective barrier between the interior space of blood vessels and underlying tissues. Disruption of the EC barrier is a prominent feature of acute lung injury (ALI). EC permeability is regulated by a balance between contractile and tethering forces and is dependent on the functional coordination of interrelated elements of the cytoskeleton, namely microfilaments (MF) and microtubules (MT). Edemagenic agents such as the serine protease thrombin induce EC barrier dysfunction primarily via MF-driven contraction. In contrast, information about the role of the MT network in EC barrier regulation is limited. Our data indicate that MT remodeling is directly involved in thrombin-induced EC barrier compromise. MT disruption by microtubule inhibitors or thrombin, significantly increases EC permeability. Conversely, stabilization of MTs by taxol attenuates thrombin-induced EC permeability increase indicating the importance of MTs in maintaining the EC barrier. Thrombin-induced EC barrier compromise involves activation of heterotrimeric G-proteins, G12 and G13, followed by activation of Rho and p38 MAPK signaling. Inhibition of this cascade attenuates the effect of thrombin on MT structure suggesting the involvement of these pathways in MT remodeling. Thrombin induces phosphorylation of several MT- and MF-associated regulatory proteins, including caldesmon, HSP-27 and tau, which are potentially responsible for thrombin-induced changes in MF and MF structure. We hypothesize that thrombin-induced activation of G12 and G13 leads to activation of Rho and p38 MAPK signaling, phosphorylation of cytoskeletal regulatory proteins, coordinated MT and MF remodeling and finally to barrier compromise.
Akiko Mammoto
Boston Children’s Hospital, USA
Title: Platelet-rich plasma extract in lung angiogenesis and regeneration
Time : 12:40-13:10
Biography:
Akiko Mammoto received her PhD from Osaka University in Japan and completed her Postdoctoral studies at Boston Children’s Hospital/Harvard Medical School. She is currently an Instructor in Vascular Biology Program at Boston Children’s Hospital. She has published more than 65 papers in high impact journals and serves as an Editorial Board Member of Scientific Reports.
Abstract:
Angiogenesis, the growth of new blood capillaries plays a key role in organ development and regeneration. Recently, we have reported that soluble platelet-rich plasma (PRP) extract which contains abundant angiopoietin-1 and multiple other angiogenic factors stimulates angiogenesis in vitro and in vivo. We have also found that PRP extract maintains endothelial cell (EC) integrity in vitro and prevents endotoxin induced pulmonary edema in a mouse lung injury model. Here we demonstrate that mouse PRP extract also accelerates EC sprouting and lung epithelial cell budding by changing the activity of the Wnt co-receptor low-density lipoprotein receptor-related protein 5 (LRP5) in vitro. PRP extract also enhances compensatory lung growth and recovery of exercise capacity after unilateral pneumonectomy in mice while Lrp5 knockdown attenuates the effects of PRP extract. Since human PRP extract is generated from autologous peripheral blood and can be frozen for long-term storage, these findings may indicate a novel treatment for various angiogenesis-related lung diseases and could potentially advance strategies for lung organ engineering.
Peisong Gao
Johns Hopkins University School of Medicine, USA
Title: Aryl hydrocarbon receptor regulates cockroach allergen induced lung inflammation through controlling the recruitment and function of mesenchymal stem cells
Time : 14:00-14:30
Biography:
Peisong Gao is currently Associate Professor of Medicine at The Johns Hopkins University School of Medicine in Baltimore, Maryland. He received his MD degree and Pulmonary Medicine Training in The Fourth Military Medical University, China. From July 1997 to January 1999, he was a Visiting Research Fellow in Oxford University. He subsequently moved to the University of Wales Swansea pursuing a PhD working in Molecular Genetics of Asthma. In 2002 he became a Postdoctoral Fellow in the Division of Allergy & Clinical Immunology at Johns Hopkins. In 2008 he was promoted to Assistant Professor. His research has been greatly recognized by several awards including the 2004 Research Excellence Award, the 2007 Interest Section Award and Outstanding Pediatric Allergy, Asthma and Immunology Award from AAAAI. His studies mainly focus on gene, environment and development of asthma. He has published more than 60 papers in reputed journals.
Abstract:
Exposure to cockroach allergen can lead to allergic sensitization and an increased risk of developing asthma. Recent studies have suggested that aryl hydrocarbon receptor (AhR) can sense not only environmental pollutants but also microbial insults. To test whether AhR can sense allergens and modulate allergic responses, we examined cockroach allergen induce AhR activation in mesenchymal stem cells (MSCs) and lung inflammation in mouse model of asthma with wild-type (WT) and AhR-deficient (AhR-/-) mice. AhR mediated MSC migration was investigated using Transwell migration assay and GFP+MSCs administration in mouse model. The role of migrated MSCs in suppressing lung inflammation and macrophage polarization was further investigated. Our studies demonstrated that AhR signaling was activated with increased expression of cyp1a1 and cyp1b1, downstream genes of AhR when MSCs were exposed to cockroach allergens. Compared to WT mice, cockroach allergen treated AhR-/- mice showed exacerbation of lung inflammation. AhR mediated allergen-induced inflammation was further validated by using the AhR agonist, 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD). Moreover, TCDD promoted CRE-induced MSCs migration while the AhR antagonist CH122319 suppresses MSCs migration in our Transwell assays. Furthermore, CRE-challenged AhR-/- mice displayed less migrated MSCs to the lungs compared to WT when GFP+MSCs were administrated intravenously. Additionally, the administration of MSCs significantly attenuated allergic inflammation which was in part rescued by TGFβ1 neutralizing antibody. Interestingly, macrophages from MSCs treated mice exhibited M2 phenotypes with increased expression of Agr-1, FIZZ-1 and Ym-1. The macrophage polarization was possibly induced by MSCs and confirmed by co-culturing MSCs with bone marrow-derived macrophages. Our findings provided evidence for a previously unidentified pathophysiological function of the AhR and suggested that AhR may be critical in modulating environmental allergen induced immune inflammation.
Tong-Jun Lin
Dalhousie University, Canada
Title: PTP1B is a negative regulator in the host defense against Pseudomonas aeruginosa infection
Time : 14:30-15:00
Biography:
Professor Lin’s research interests include signaling mechanisms in allergy, host defense mechanisms against bacterial infection, and immune response in cancer development. His work is interdisciplinary, collaborative and geared both to contributing to the academic literature and to developing immunological therapeutic approaches in inflammation
Abstract:
Pseudomonas aeruginosa is a major opportunistic pathogen in immune-compromised individuals. Toll-like receptors (TLRs) contribute to innate immunity against P. aeruginosa through activation of transcription factors IRF7/IRF3 and NFκB. However, mechanisms involved in the regulation of P. aeruginosa-induced TLR pathway activation remain incompletely defined. Here, we demonstrate that protein tyrosine phosphatase-1B (PTP1B) is a critical negative regulator in P. aeruginosa infection. PTP1B-deficient mice display greatly enhanced bacterial clearance which is accompanied with increased neutrophil infiltration and cytokine production. Interestingly, PTP1B-deficiency mainly up-regulates the production of IFN-stimulated response elements (ISRE)-regulated cytokines and chemokines including CCL5 (RANTES), CXCL10 (IP-10) and IFN-β production. Further studies reveal that PTP1B-deficiency leads to increased IRF7 activation. Importantly, PTP1B is physically associated with IRF7 in dendritic cells. These findings demonstrate a novel regulatory mechanism of the immune response to P. aeruginosa infection through PTP1B-IRF7 interaction. This novel PTP1B-IRF7-ISRE pathway may have broader implications in TLR-mediated innate immunity.
Daqing Ma
Imperial College London,UK
Title: Novel Strategy against Perioperative Remote Lung Injury after Renal Transplantation
Time : 15:00-15:30
Biography:
Dr. Daqing Ma is a Reader and Head of Anaesthesia Research of the Section of Anaesthetics, Pain Medicine & Intensive Care, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, and Chelsea and Westminster Hospital, London, UK. He has more than 150 publications of original articles being published in the English peer reviewed journals (e.g. PNAS, Annals of Neurology, Annals of Surgery, BMJ, JASN, Kidney International, The FASEB Journal, Critical Care Medicine, Anesthesiology and etc.) covering research fields of Anesthesiology, Pharmacology, Neuroscience, Neurology and Nephrology. He is a Fellow elect of Royal College of Anaesthetists (UK). He is a Board Member of British Journal of Anaesthesia and a council member of Anaesthetic Research Society (UK). He is an Academic Editor of PLoS One and an Associate Editor of Journal Alzheimer Disease and editorial board member of other 5 journals.
Abstract:
Remote lung injury is a common complication which has been reported previously in several pre-clinical settings. However, its clinical significance has been largely ignored. In fact, it may be the major cause of most patients following major surgery who often admit into Intensive Care Unit. Remote lung injury has been suggested to be due to putative mechanisms include the release of pro-inflammatory cytokines such as IL-1β, IL-6 and particularly TNF-α from injury organs or tissue into the systemic and pulmonary circulation and then causing pulmonary tissue injury and inflammation. However, the precise causal relationship between ischemic organ/tissue or surgical trauma and remote lung injury has not been well established and the treatment is even rather limited. Renal transplantation is inevitably associated with ischemic injury due to cold storage in transportation and histocompatibility tests. This injury can be exacerbated upon engraftment, namely ischemia-reperfusion injury, which involves a cascade of events including acute tubular necrosis, inflammation and oxidative damage to renal parenchyma and also remains as one of the most formidable obstacles in the success of renal transplantation although allograft immune-rejection is still a core cause. Recently, accumulating laboratory and clinical evidence have highlighted that acute ischemic renal injury induces remote lung injury; Likewise, early renal graft injury after transplant surgery might be also associated with the rapid development of pulmonary insufficiency. Our novel strategy that was reported recently likely has a hope to tackle this problem. This lecture will cover the mechanism of remote lung injury, its clinical manifestation and novel preventive and treating strategies which has a very high chance to be translated to bedside for the best benefit of transplant patients.
Masanobu Kishikawa
Fukuoka City Hospital, Japan
Title: Re-evaluation of paper bag rebreathing for hyperventilation syndrome
Time : 15:55-16:25
Biography:
Masanobu Kishikaw is a renowned personality in the related field of Hyper Ventilation Syndrome. He is currently working at Fukuoka city Hospital in Japan. He has published several research papers and recently working on paper bag rebreathing for hyperventilation syndrome.
Abstract:
Background: Paper Bag Rebreathing（PBR）as a treatment for Hyper Ventilation Syndrome（HVS）had not recommended since 1990 by the risk of hypoxic exposure. The risk, however, might be preventable by the administration of oxygen in the paper bag. Objectives: To confirm the safety and effectiveness of PBR with administration of oxygen for HVS. Materials & Methods: Four healthy adult volunteers were examined with monitoring end-tidal carbon dioxide (EtCO2) by capnometer accompanied by nasal cannula, and with monitoring SpO2 attached on the finger. The examinees were forced to continuehyper ventilation with respiratory rate of 30/minute, and we started PBR therapy with 2 l/minute of oxygen in the vinyl bag of 3 l attached to the examinees’ mouth and nose when the EtCO2 revealed down to 20 mmHg. The examinees continued hyper ventilation with respiratory rate of 30/minute even after PBR started, and their symptoms such as numbness and lightheadedness were observed every 30 seconds. Result: EtCO2 gradually elevated just after PBR start. Symptoms of numbness and lightheadedness disappeared in 2 minutes after start of PBR when EtCO2 elevated to above 27 mmHg. EtCO2 increased to 40 mmHg within 5 minutes and SpO2 was kept above 99% in all examinees. Conclusion: PBR with administration of oxygen is thought to be safe and effective treatment for HVS.
Marioara Simon
Romanian Pulmonology Society, Romania
Title: Interventional pulmonology in the management of benign tracheal stenosis BTS
Time : 16:25-16:55
Biography:
Marioara Simon has FCCP, MD, PhD degrees in Pulmonology, Bronchologist and Allergologist. She is the Head of Bronchology and Interventional Pulmonology Department, University Hospital Cluj-Napoca, Romania. She is the President of the Romanian Bronchology Section of the Romanian Pulmonology Society and on Board of WABIP as regent, on Board of EABIP as delegate from Romania. She has a strong interest in the diagnosis and endoscopic therapy of lung cancer. She has participated in EABIP, ERS and WABIP Congresses with presentations and posters and has organized and participated in many bronchological workshops. She has published books (Chronic Interstitial Fibrotic Pneumopathies, Bronchoscopist’s Guide) and more than 130 scientific articles and oral presentations, the majority in the diagnostic bronchoscopy and interventional pulmonology field.
Abstract:
Interventional pulmonology (IP) provides comprehensive care to patients with structural airway disorders. Tracheal stenosis is a potentially life-threatening condition. With the development of interventional pulmonology field in the last 20 years, definitive management of tracheal stenosis using minimally invasive endoscopic methods became a possibility. Benign airway stenoses are frequently seen by the interventional pulmonologist. Endoscopic treatment had been shown to be useful, especially in patients who are deemed high risk and too unwell for reconstructive surgery. Many endoscopic therapeutic interventions can be offered: Balloon dilatation, rigid bronchoscopy dilatation, laser or electrosurgery resection and placement of airway stents. We have retrospectively analyzed a series of 21 patients who were referred to our department between 2013-2014 for evaluation and management of symptomatic BTS. The most common condition was post-intubation stenosis that develops after prolonged endotracheal intubation. Symptoms varied according to the severity of the stenosis, being the most frequent different degrees of dyspnea, cough and retained secretions. The endoscopic modalities used were: Balloon and rigid bronchoscopy dilatation and radial incisions with electrosurgery knife. A stent was placed in two patients. Complications were minor and mostly included restenosis. Over a median follow-up of 30 months, the overall success rate was 85.7%, only three patients being referred to surgery. Thus it can be concluded that Tracheobronchial stenoses can be difficult to treat, and patients benefit from a multidisciplinary approach; every case should be discussed within a team of dedicated physicians, including a pulmonary interventionist, an otorhinolaryngologist, and a surgeon, in order to offer the best available solution.
Jane Yu
University of Cincinnati College of Medicine, USA
Title: Dysregulation of prostaglandin metabolism and action in the progression of lymphangioleiomyomatosis
Time : 16:55-17:25
Biography:
Jane Yu has completed her PhD from the Graduate School and University Center of the City University of New York and Postdoctoral training from Fox Chase Cancer Center. She was an Assistant Professor of Medicine at the Brigham and Women’s Hospital-Harvard Medical School. She is an Associate Professor at the Pulmonary Critical Care and Sleep Medicine at University of Cincinnati College of Medicine. Her research focuses are to study mechanisms through tumor suppressor proteins hamartin (TSC1) and tuberin (TSC2) regulate cellular metabolism and cell survival, identify potential biomarkers for tuberous sclerosis complex (TSC) and rare pulmonary disease lymphangioleiomyomatosis (LAM), establish preclinical models for TSC and LAM for translational research, perform bioinformatics and network analyses, conduct high-throughput drug screens, and develop pathway targeted therapies for TSC, LAM and cancers. She has published more than 30 papers in reputed journals.
Abstract:
Lymphangioleiomyomatosis (LAM) is a female predominant and devastating pulmonary disease, characterized by diffusely infiltrated smooth muscle like cells that carry mutations in the tuberous sclerosis complex (TSC) genes. TSC1, TSC2 and TBC1D7 interact and inhibit the mammalian target of rapamycin complex 1 (mTORC1). The reasons that LAM exclusively affects women and how TSC1 or TSC2 deficiency contributes to the pathogenesis of LAM are not yet fully understood. We previously discovered that estrogen promotes the survival and lung metastases of tuberin-deficient. Recently, we reported that estrogen and mTORC2 coordinate to enhance prostaglandin biosynthesis and tumorigenesis in LAM. Prostaglandins are lipid mediators that participate in tumor survival, growth, invasion, and inflammation. Phospholipase A2 (PLA2), Cyclooxygenase-2 (COX-2) and prostacyclin synthase (PTGIS) are critical enzymes responsible for the production of prostaglandins. Prostaglandin receptors (EPs) mediate the biological function of prostaglandins. We performed bioinformatics analysis of public expression arrays and found a rapamycin-insensitive upregulation of prostaglandin biosynthesis genes including PLA2, COX-2, PTGIS, and EP3, in TSC2-deficient LAM patient-derived cells compared to TSC2-addback cells. We validated the enhanced expression of PLA2, COX-2, PTGIS and EP3 in TSC2-deficient cells using real-time RT-PCR, immunoblotting and immunohistochemistry in cell cultures, preclinical models and clinical samples. Interestingly, PGE2 specifically stimulated the growth of TSC2-deficient LAM patient-derived cells compared to TSC2-addback cells. Importantly, treatment of TSC2-deficient LAM patient-derived cells with inhibitors specific to PLA2 COX-2, or EP3 resulted in dose-dependent reduction of cells growth. Our data documents that loss of TSC2 leads to the aberrant expression and accumulation of prostaglandin biosynthesis regulators, thereby enhancing prostaglandin production and promoting TSC2-deficient cell growth and tumor development. Our data supports the potential application of prostaglandin metabolites as biomarkers of disease severity and the development of prostaglandin biosynthesis inhibitors as alternative therapeutic options for LAM patients and in other gender-specific diseases.