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International
Translational and Regenerative Medicine Conference April 25-27, 2018 | Rome, Italy.

Program Schedule

  • Keynote Speaker

    Time:

    Title

    Title: Respiratory Support of the Failing Lung: from Respiratory Dialysis to Wearable Artificial Lungs

    William J Federspiel
    University of Pittsburgh, USA and the McGowan Institute of Regenerative Medicine.
    Biography
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    Biography

    William J Federspiel
    University of Pittsburgh, USA and the McGowan Institute of Regenerative Medicine.

    Dr. William J. Federspiel received his PhD in 1983 in Chemical Engineering from the University of Rochester and currently is the William Kepler Whiteford Professor of Bioengineering in the Swanson School of Engineering at the University of Pittsburgh, with a secondary appointment in Critical Care Medicine. He is a Co-Founder of Alung Technologies, a Pittsburgh based medical device company that develops respiratory assist systems, and currently serves as Head of the Scientific Advisory Board for Alung. Dr. Federspiel is an elected Fellow of the American Institute of Medical and Biological Engineering (AIMBE) and the Biomedical Engineering Society (BMES). He has over 100 research publications and book chapters and holds numerous patents related to devices and methods for respiratory assist and inflammatory modulation. He directs research in the Medical Devices Laboratory, a core laboratory of the McGowan Institute for Regenerative Medicine.



    Abstract
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    Abstract

    William J Federspiel
    University of Pittsburgh, USA and the McGowan Institute of Regenerative Medicine.

    Extracorporeal CO2 removal represents an effective treatment strategy for patients with acute and acute-on-chronic respiratory insufficiency. The technology holds the most promise as a means of avoiding intubation and mechanical ventilation in patients with an acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD), and as a means of allowing for lung protective ventilation in patients with Acute Respiratory Distress Syndrome (ARDS). Unlike oxygen supply, carbon dioxide can be removed at therapeutic levels from blood at relatively low extracorporeal blood flowrates, similar to those used in acute hemodialysis. To do so effectively, a novel integrated artificial lung and blood pump system called the Hemolung® Respiratory Assist System (RAS) has recently been developed and commercialized. The talk will describe the early design and development work leading to the Hemolung RAS, and features which distinguish it from other systems focused on CO2 removal. Key results from recent animal and human clinical trials of the Hemolung RAS will be presented, along with current work on novel enzymatic coatings and other approaches being developed in the laboratory for next generation respiratory dialysis systems. For patients requiring oxygenation in addition to CO2 removal, the Medical Devices Laboratory at the University of Pittsburgh’s McGowan Institute of Regenerative Medicine is developing wearable artificial lungs for adults and children as a bridge to lung transplant or lung recovery. Bench and animal studies of these technologies will be presented along with the vision on how the next generation of wearable artificial lungs will evolve to provide both low blood flow CO2 removal, along with higher blood flow oxygenation in an integrated platform. The challenges of spinning out technology from a university laboratory and commercializing that technology through a startup company, ALung Technologies, will also be discussed.

    Keynote Speaker

    Time:

    Title

    Title: Soluble Receptor for Advanced Glycation End Products (Srage) as Potential Biomarker for Diabetic Retinopathy and Chronic Kidney Disease

    Umah Rani Kuppusamy
    University of Malaya, Malaysia, Singapore.
    Biography
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    Biography

    Umah Rani Kuppusamy
    University of Malaya, Malaysia, Singapore.

    Professor Dr. Umah Rani Kuppusamy is the Head of the Department of Biomedical Science, Faculty of Medicine, University of Malaya. She obtained her Ph.D in Biochemistry from the National University of Singapore in 1994. Her research interest revolves around free radicals, antioxidants and oxidative stress in diseases with predominant focus on the etiology and complications of diabetes, obesity and mechanism of action of micronutrients on oxidative stress. She has more than 80 publications in ISI-ranked journals, 130 conference papers, medals and awards and several patents to her credit.



    Abstract
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    Abstract

    Umah Rani Kuppusamy
    University of Malaya, Malaysia, Singapore.

    The global prevalence of Type 2 diabetes (T2D) which often leads to dire complications has increased significantly and 17.5% of adult population in Malaysia has T2D.Receptor for advanced glycation end-products (RAGE) is a multi-ligand, cell-surface receptor, which has been widely investigated for its role in the pathogenesis of complications with or without diabetic origin. RAGE also exists as other isoforms which include soluble RAGE (sRAGE) which acts as a decoy receptor that circumvents signal transduction originating from RAGE-ligand binding. Assessment of the levels of sRAGE and oxidative indices in diabetic patients with and/or without diabetic retinopathy (DR) or chronic kidney disease (CKD) and healthy control revealed mixed results. The soluble RAGE level of the patients with DR was significantly higher than healthy controls. Both sRAGE and pentosidine (an oxidative glycation marker) were significantly correlated with diabetes duration. The sRAGE/pentosidinewas lower in patients with DR than the healthy controls. Logistic regression analysis revealed positive correlation between sRAGE/pentosidineratio and the severity of DR and thus, it could serve as a biochemical tool for monitoring the progression of DR. Diabetic patients had significantly higher sRAGE levels in the presence of CKD or DR than in the absence of complications. However, the correlation between sRAGE and renal function in non-diabetic CKD was confounded by other factors but remained highly significant in diabetic CKD even after the adjustment of the potential confounding factors thus, serving as a more convincing indicator of the latter. These findings suggest that sRAGE can serve as a potential biomarker of DR and diabetic CKD. In view of the significant correlations between sRAGE and the severity of these complications, sRAGE could also serve as a tool for monitoring the progression of these complications.

    Sessions:
    Translational Medicine Approaches in Drug Discovery & Development & Cardio-Vascular Translational Medicine

    Time:

    Title: Inhibition of Breast Cancer Bone Metastasis and Pancreatic and Colon Cancer by Synthetic Curcumin Analogs

    Mamoru Shoji
    Emory University School of Medicine, Winship Cancer Institute. Atlanta, USA.

    Biography
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    Biography

    Mamoru Shoji
    Emory University School of Medicine, Winship Cancer Institute. Atlanta, USA.

    Dr. Mamoru Shoji obtained his Medical Degree from the Hokkaido University, Japan, and completed internships at the US Naval Hospital, Yokosuka, Japan and the University of Pennsylvania in Philadelphia, residency in internal medicine at the Lahey Clinic, Boston, fellowship training in immunology at the Peter Bent Brigham and Robert Breck Brigham Hospitals (mentor, John R. David, MD), Harvard Medical School in Boston, in tumor immunology at the University of Minnesota (mentor, Charles F. Mckhann, MD from Massachusetts General Hospital) in Minneapolis, followed by fellowship in Hematology and Medical Oncology at Emory University (mentor, Charles M. Huguley, Jr, MD).



    Abstract
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    Abstract

    Mamoru Shoji
    Emory University School of Medicine, Winship Cancer Institute. Atlanta, USA.

    Curcumin (diferuloylmethane) is a β-diketone constituent of the turmeric. It is used as a spice to give a specific flavor and yellow color to curry. However, its clinical efficacy is poor because of its low solubility. He worked with professors Liotta and Snyder at the Chemistry Department to synthesize a series of novel monocarbonyl analogs of curcumin (MACs) approximately 100 analogs including EF24, EF31 and UBS109. Dr. Shojis laboratory and the NCI tested the analogs for the anticancer activity. The NCI determined the mean growth inhibitory concentration (GI-50) of EF24, curcumin and cisplatin on the NCI-60 cancer cell panel, which are 0.7 μM, 7.3 μM and 9.5 μM, respectively. MACs do not kill normal breast cells MCF-10A but kill all cancer cells tested (KB-3-1, TU212, MiaPaCa, SE-Mel-28, RPMI-7951, and MDA-MB-231 cells) at concentrations (0-20 μM) [Zhu S, Current Cancer Drug Targets, 2014]. MACs inhibit NF-κB by inhibiting IKK-α and IKK-β. UBS109 inhibited breast cancer metastasis and osteolysis by inhibiting osteoclasts precursors and osteoclasts, but promotes new bone formation by stimulating osteoblast activation. UBS109 and EF24 inhibited four pancreatic cancer cell lines 100% at less than 1.25 μM, whereas gemcitabine did not up to 20 μM . UBS109 significantly inhibited MiaPaCa-2 pancreatic cancer xenografts and colon cancer (HT-29 and HCT-116) xenografts in mice at 25 mg/kg, iv once a week better than a combination of oxaliplatin (5 mg/kg) and 5FU (30 mg/kg) iv. (234 words)

    Time:

    Title: Immune Modulating Properties of the Anti-Cancer Preparation NSC631570

    Wassil Nowciky
    Nowicky Pharma and Ukrainian Anti-Cancer Institute, Vienna, Austria.

    Biography
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    Biography

    Wassil Nowciky
    Nowicky Pharma and Ukrainian Anti-Cancer Institute, Vienna, Austria.

    Dr. WassilNowicky Dipl. Ing., Dr. techn., DDDr. h. c., Director of Nowicky Pharma and President of the Ukrainian Anti-Cancer Institute (Vienna, Austria). Has finished his study at the Radiotechnical Faculty of the Technical University of Lviv (Ukraine) with the end of 1955 with graduation to Diplomingeniueur in 1960 which title was nostrificated in Austria in 1975. Dr. WassilNowicky became the very first scientist in the development of the anticancer protonic therapy and is the inventor of the preparation against cancer with a selective effect on basis of celandine alkaloids NSC-631570. He used the factor that cancer cells are more negative charged than normal cells and invented the Celandine alkaloid with a positive charge thanks to which it accumulates in cancer cells very fast. Thus, Dr. Nowicky is invited as an Honorable Speaker to take part in many scientific international congresses and conferences in USA, Australia, Japan, UAE, Europe. Author of over 300 scientific articles dedicated to cancer research. Dr. WassilNowicky is a real member of the New York Academy of Sciences, member of the European Union for applied immunology and of the American Association for scientific progress, honorary doctor of the JankaKupala University in Hrodno, doctor honoris causa of the Open international university on complex medicine in Colombo, honorary member of the Austrian Society of a name od Albert Schweizer. He has received the award for merits of National guild of pharmasists of America. the award of Austrian Society of sanitary, hygiene and public health services and others.



    Abstract
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    Abstract

    Wassil Nowciky
    Nowicky Pharma and Ukrainian Anti-Cancer Institute, Vienna, Austria.

    Unusual for an anticancer agent NSC-631570 possesses some distinct immune properties [35, 49]. It was Prof.AndrejsLiepins of the St. Johns Memorial University, St. Johns, Canada who first pointed to this interesting fact. In the work with the C57BL/6 mice he revealed NSC-631570 to be an effective biological response modifier (BRM). After incubation with NSC-631570 the lytic activity of the splenic lymphocytes from the alloimmunised mice increased up to 48 fold (fig. 4). The immune modulating effect of NSC-631570 was studied in several studies in mice. Repeated subcutaneous injections of NSC-631570 to mice infected with the twofold LD50 of E. coli, S. aureus, or influenza virus increased the survival rate of the animals significantly. When human lymphocytes were incubated with phytohemagglutinin (PHA) and NSC-631570, increased absorption of 3H-thymidin in the cells was observed. The authors point out the strong synergetic effect of NSC-631570 and phytohemagglutinin. NCS-631570 induces immunogenic death of B16 melanoma cells and could restore antitumor activity of hypoxia-polarized macrophages. It suggests that NSC-631570 can be used for multimodal tumor therapy not only to kill the tumor cells, but also to stimulate a specific immune response to keep residual tumor (stem) cells and metastases under control. To investigate the adjuvant and immunomodulatory effects of the S.aureus cytoplasmic membrane extraction (CPM) in mono- and combined anticancer therapy outbred mice were transplanted with ascite and solid form of Ehrlich carcinoma followed by sixday course of bacterial polymer used alone or in combination with cytotoxic anticancer drug NSC-631570. To estimate adjuvant effect tumor growth dynamics were evaluated, to characterize immunomodulating effect the number of circulating mononuclear phagocytes and their hagocytic activity were analyzed by flow cytometry. Our results suggest synergistic effect of PAMP and antineoplastic drug NSC-631570, that was accompanied by positive immunomodulation. The effects of cancer-selective drug NSC-631570 (Ukrain) used alone and in combination with pathogen-associated polymers of Gram-positive (peptidoglycan, lipoteichoic acid, and cytoplasmic membrane extraction of Staphylococcus aureus) and Gram-negative (Escherichia coli lipopolysaccharide) bacteria on mouse peritoneal macrophage metabolic activity in vitro are investigated. It is shown that NSC-631570, as used alone, causes a moderate enchancement of oxidative metabolism and arginase activity of intact peritoneal macrophages. The co-modulatory effect of the preparation depends on the initial functional state of phagocytes.

    Time:

    Title: Synthetic Aromatse Inhibitors in the Treatment of Estrogen Dependent Breast Cancer

    Shagufta Waseem
    American University of Ras Al Khaimah, UAE.

    Biography
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    Biography

    Shagufta Waseem
    American University of Ras Al Khaimah, UAE.

    Dr. Shagufta joined the American University of Ras Al Khaimah as an Assistant Professor of Chemistry in the School of Arts and Sciences in August 2014. Prior to joining AURAK, worked as an Adjunct Assistant Professor of Chemistry at the University of Modern Sciences, Dubai and American University of Ras Al Khaimah, UAE. Worked as a Postdoctoral Researcher Associate at the Department of Chemistry and Biochemistry, Oklahoma University, USA. She developed the noble drug delivery system for breast cancer drugs using carbon nanotubes and acquired the significant experience in nanotechnology and synthetic organic chemistry. She was appointed as a Postdoctoral Research Fellow and Visiting Scientist at Leiden/Amsterdam Centre for Drug Research (LACDR), Leiden, The Netherlands. Her research interest was In silico prediction and clinical evaluation of the cardiotoxicity of drug candidates. She was focused to identify chemical substructures as chemical alerts that interact with this hERG channel. Dr. Shagufta received a Ph.D. under the prestigious CSIR-JRF and SRF research fellowship in Chemistry from Central Drug Research Institute (CDRI)/Lucknow University, India in 2008, her PhD research work was in the field of estrogens and antiestrogens, design and synthesis of steroidal and non-steroidal tissue selective estrogen receptor modulators (SERMs) for breast cancer, 3D-QSAR CoMFA and CoMSIA studies and analysis of pharmaceutical important molecules. She has published 20 articles in peer-reviewed International journals of Royal Society of Chemistry, Elsevier, Wiley and Springer. And teaches courses such as General chemistry, Organic Chemistry, Chemistry in Everyday Life, and Spectroscopy along with laboratory courses.



    Abstract
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    Abstract

    Shagufta Waseem
    American University of Ras Al Khaimah, UAE.

    Breast cancer is the most common form of cancer present in women worldwide and is the second leading cause of death after lung cancer.1 In estrogen-dependent breast cancer, estrogen plays a significant role in the stimulation of breast cancer cell proliferation.2 Two main approaches have been developed to control or block the pathological activity of estrogens. The first approach involves the design and synthesis of estrogen receptor antagonist and inhibition of enzyme aromatase is the second approach for the development of new agents for the breast cancer treatment.3-5 Aromatase, an enzyme complex present in breast tissues, plays a substantial role in the biosynthesis of important endogenous estrogens from androgens. The source of oestrogen production in breast cancer tissues is intra-tumoral aromatase, and inhibition of aromatase may inhibit the growth stimulating effect of estrogens in breast cancer tissues. Consequently, aromatase is considered a useful therapeutic target in the treatment and prevention of estrogen-dependent breast cancer. Recently, different natural products and synthetic compounds have been rapidly developed, studied, and evaluated for aromatase inhibitory activity. Aromatase inhibitors are classified into two categories on the basis of their chemical structures, i.e., Steroidal and nonsteroidal aromatase inhibitors.6 This presentation will emphasize the potent role of synthetic steroidal and nonsteroidal aromatase inhibitors for the treatment of breast cancer.

    Time:

    Title: Therapeutic Potential of Quinazoline Derivatives as Anticancer Agents

    Irshad Ahmad
    American University of Ras Al Khaimah, UAE.

    Biography
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    Biography

    Irshad Ahmad
    American University of Ras Al Khaimah, UAE.

    Dr. Irshad Ahmad joined the American University of Ras Al Khaimah in spring 2011 as an Assistant Professor of Chemistry. He received the masters degree in chemistry from Jiwaji University in 1999. Subsequently acquired significant pharmaceutical industrial experience and developed cardio-selective beta-blocker drug molecule. He joined Central Salt and Marine Chemical Research Institute and Bhavnagar University under the sponsored project of DST and CSIR as a senior research fellow and received his PhD degree in chemistry in 2006. Subsequently, he accepted an invited scientist position in Korea Research Institute of Chemical Technology, South Korea and contributed his expertise in the field of Nanotechnology. Dr. Irshad is a recipient of prestigious European fellowships (NWO-Rubicon & FCT) and he joined Vant Hoff Institute for Molecular Sciences, University of Amsterdam, The Netherlands as a NWO Rubicon fellow (Netherlands Organization for Scientific Research, the Dutch Science Foundation), he acquired expertise in the field of supramolecular chemistry. Afterward, he moved to the Leibniz Institute for Surface Modification, Leipzig, Germany under the Deutsche Forschungsgemeinschaft Grant. Dr. Irshad developed Novel ultra-fast metathesis catalyst for the production of high quality alternating copolymers. Subsequently Dr. Irshad, joined Department of Chemistry and Biochemistry, Stephenson Life Science Research Center, University of Oklahoma, USA as a postdoctoral research associate. He developed strategies for the novel environmentally friendly reactions for the production of value added chemicals from biomass. Dr. Irshad specialized in the area of chemistry, bridging the traditional disciplines of inorganic, organic and bio-organic chemistry. He contributed US and European patent for green and clean technology development. He has published peer-reviewed international research articles in the American Chemical Society (ACS), Royal Society of Chemistry (RSC) Cambridge, Elsevier Science, Wiley, and Springer journals. He has presented his research at several scientific conferences worldwide and received awards.



    Abstract
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    Abstract

    Irshad Ahmad
    American University of Ras Al Khaimah, UAE.

    Cancer is one of the major causes of worldwide human mortality. It is estimatedthat about 1 688 780 new cancer cases will be diagnosed in2017.1A wide range of cytotoxic drugs are available on the market, and several compounds are in different phases of clinical trials.2 Many studies suggest that these cytotoxic molecules are also associated with different types of adverse side effects; therefore researchers around the globe are involved in the development of more efficient and safer anticancer drugs. The heterocycles are widely investigated bioactive moleculesand are considered important synthetic targets for thedevelopment of novel therapeutic agents.3 In recent years, quinazoline and its derivatives have been considered as a novel class of cancer chemotherapeutic agents that show promising activity against different tumors.4This presentation will comprehensively highlight the recent developments concerning the anticancer activity of quinazoline derivatives as well as offer perspectives on the development of novel quinazoline derivatives as anticancer agents in the near future.

    Time:

    Title: Inhibition of NF-Κbpathway Attenuates the Multiple Organ Dysfunction Associated with Polymicrobial Sepsis in Mice with Pre-Existing Type 2 Diabetes Mellitus (T2DM).

    Sura Al Zoubi
    Queen Mary University of London, United kingdom.

    Biography
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    Biography

    Sura Al Zoubi
    Queen Mary University of London, United kingdom.

    PhD Student at Queen Mary University of London, United kingdom.



    Abstract
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    Abstract

    Sura Al Zoubi
    Queen Mary University of London, United kingdom.

    Introduction: Patients with diabetes are at higher risk of infections and sepsis. Activation of nuclear factor-κB (NF-κB) plays a substantial role in the pathophysiology of sepsis and diabetes. Here we investigate i) the effect of pre-existing type 2 diabetes mellitus on organ dysfunction (MOD) associated with sepsis and ii) whether inhibition of NF-κB using IKK-16 or linagliptin attenuatesMOD in mice with sepsis and diabetes. Methods: Ten-week old male C57BL/6 mice received high fat(HFD) or chow diet for 12 weeks, and were subjected to caecal ligation and puncture (CLP) or sham surgery for 24 hours. At 1 hour after CLP, mice received IKK-16, linagliptin,or vehicle. Results: Administration of HFD resulted ina significant (i) impairment in glucose tolerance, (ii) (small) reduction in ejection fraction and, (iii) increase in alanine aminotransferase. HFD caused (Immunoplot analysis; heart) significant NF-κBpathway activation and expression of inducible nitric oxide synthase (iNOS). Mice on HFD subjected to CLP showed further (i) decline in EF, (ii) increase in serum ALT, and (iii) a significant renal dysfunction.Treatment of HFD-CLP mice withIKK-16 or linagliptinresulted in significant reduction of the CLP-induced i) MOD (cardiac/liver/renal), ii) NF-κBpathway activation, and iii) iNOS expression when compared to mice treated with vehicle. Conclusion: Our results show that HFD results in inflammation, cardiac dysfunction, and liver injury. Moreover, a pre-existing diabetic phenotype worsened the organ injury/dysfunction associated with CLP-sepsis. Most notably, inhibition of NF-κBreduced the organ injury/dysfunction caused by sepsis in animals with pre-existing T2DM.

    Sessions:
    Translational Therapeutics/ Novel Therapeutic Technologies

    Time:

    Title: Fetal Cells Role in Combating Adult Anemia: A Study of Cord Blood Transfusion in Adults from 1999 till Date

    Niranjan Bhattacharya
    Regenerative Medicine and Translational Science, Calcutta School of Tropical Medicine, Kolkata, India.

    Biography
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    Biography

    Niranjan Bhattacharya
    Regenerative Medicine and Translational Science, Calcutta School of Tropical Medicine, Kolkata, India.

    Holds a MD in Obst and Gynaecology, MS in General Surgery and a DSc in Developmental Immunology. His principal specializations are cell and tissue therapy. Has presented Invited lectures in several international universities and institutions. Has published widely in international and national journals on cord blood and regenerative medicine; is the co-editor of five books on the subject published by Springer. Currently, Chair Professor and Head of the Department, Regenerative Medicine and Translational Science, and Director General, first Public Cord Blood Bank in India, Calcutta School of Tropical Medicine, Kolkata. Cited among top five global cord blood influencers by BioInformant.



    Abstract
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    Abstract

    Niranjan Bhattacharya
    Regenerative Medicine and Translational Science, Calcutta School of Tropical Medicine, Kolkata, India.

    There are about 100 million births in the world annually at a conservative estimate. In India, there are over 20 million births per annum, which means that over 20 million placentas are discarded every year as waste. One of the products of the placenta is cord blood; it has immense potentials. An estimated 8,785,000 Litres of cord blood is produced globally per year if an average of 84-90 ml/placenta collection is assumed. Our group of medical scientists and clinicians transfused ABO screened and HLA matched randomized fetal blood in cases of anemia resulting from malaria, diabetes, thalassemia, leprosy, rheumatoid arthritis, tuberculosis, malignancy, AIDS, and found it not only to be safe but perhaps providing additional benefits that need further study. In parts of the world where research is ongoing, a microscopic section of cord bloods mononuclear cells (0.01% nucleated cells) is used for transplantation purposes, while the rest, i.e., 99.99% is discarded. But the discarded part has many potential uses. Cord blood is free from infection, hypoantigenic in nature, has an altered metabolic profile, is enriched with growth factors and cytokine filled plasma and has a potentially higher oxygen carrying capacity than adult blood The blood volume of a fetus at term is around 80-85 ml/kg. The placental vessel at term contains approximately 150 ml of cord blood. Cord blood contains three types of hemoglobin, HbF (major fraction), HbA (15-40%) and HbA2 (trace amounts). HbF, which is the major component, has a greater oxygen binding affinity than HbA. Our group of medical scientists and clinicians conducted over 1260 cord blood transfusions with safe outcomes in all cases, as indicated in our published studies, from 1999 till date (follow-up) in children and adults for various indications. Not a single case of immediate or delayed immunological or non immunological reaction was reported.

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    Title: Development of Epoxy-Tigliane Pharmaceuticals as Novel Therapeutics for Impaired Wound Re-Epithelialisation in Skin

    Ryan Moseley
    Cardiff University, United Kingdom.

    Biography
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    Biography

    Ryan Moseley
    Cardiff University, United Kingdom.

    Dr. Ryan Moseley is a Reader in Tissue Repair and Director of the MSc Programmein Tissue Engineering at Cardiff University, UK. Dr. Moseleys research focusses on the mechanisms underlying dermal and oral wound healing responses during health and disease; and the development of stem cell-, biomaterial- and pharmaceutical-based strategies to address impaired healing in these tissues.Dr Moseleyhas been supported by funding bodies worldwide, including the MRC, NHMRC and Wellcome Trust, culminating in numerous published papers, filed patents with industrial partners in the dermal wound healing sector (Convatec, Systagenix Wound Management, Peplin/LEO Pharma, QBiotics); and many conference prizes.



    Abstract
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    Abstract

    Ryan Moseley
    Cardiff University, United Kingdom.

    Dysfunctional woundrepair can cause significantly delayed re-epithelialization, leading to non-healing chronic wounds and burns. Management of chronic woundsand burnsposes significant challenges to Healthcare Services worldwide, confounded by acceptance that existing therapies are largely unsatisfactory. We are addressing such inadequacies, by evaluating the novel healing properties of epoxy-tigliane compounds, EBC-46 and EBC-211, isolated from seeds of the FontainsBlushwood Tree indigenous to Queenslands tropical rainforest. Our industrial partner, QBiotics Ltd., is developing EBC-46 as an anti-cancer drug. In addition to its anti-cancer properties, EBC-46 stimulates exceptional healing following tumour destruction, manifested as enhanced wound re-epithelialisation, closure and minimal scarring. This work describes epoxy-tigliane effects on keratinocyte wound healing responses and their underlying mechanisms of action. Immortalized humanepidermal keratinocytes (HACATs) were treated with EBC-46 or EBC-211 (0-10µg/mL). Cell cycle progression/proliferation wereassessed by FACS analysis and MTT assay. HACAT migration was assessed usingin vitro scratch wounds/Time-Lapse Microscopy.Global gene expression changes induced by epoxy-tiglianes were quantified by Microarrays, with differentially expressed genes confirmed by protein level analysis. As epoxy-tiglianes mediate responses via classical protein kinase (PKC) activation, mechanistic studies were performed with BIM-1 (pan-PKC), Gö6976 (classical-PKC) and LY317615 (PKC-βI/PKC-βII) inhibitors. Western blotting confirmed phospho-PKC activation following epoxy-tigliane treatment. Both epoxy-tiglianesinduced significant HACAT cell cycle progression and proliferation at 0.001-10µg/mL.EBC-46 (0.001-0.1µg/mL) and EBC-211 (0.001-10µg/mL) also promoted significant HACAT scratch wound closure. Epoxy-tiglianessignificantly up-regulated genefor keratins, positive cell cycle/proliferation regulatory factors and matrix metalloproteinases; and down-regulated genes for other keratins and numerous cytokines, growth factors and chemokines. Enhanced proliferative and migratory responses were significantly abrogated by BIM-1 and Gö6976, although LY317615 exhibited minimal inhibitory effects.PKC activation increased following epoxy-tigliane treatment. Such findings explain the enhanced re-epithelialization responses in epoxy-tigliane-treated skin; and provide justification for their translational development as novel therapeutics for impaired wound re-epithelialisation.

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    Title: Upstream Open Reading Frames in Rare Human Diseases and Related Therapeutics

    Ioanna A Armata
    Florida State University, USA.

    Biography
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    Biography

    Ioanna A Armata
    Florida State University, USA.

    Ioanna A. Armata obtained her Bachelors Degree, School of Biology, University of Patras, Greece. Major: Biology in 1999. In 2008 she acquired her Doctoral Degree, Mount Sinai School of Medicine. Major: Neuroscience. Masters Degree in 2001 from School of Biology, University of Patras, Greece. Major: Biologic Technology. From 2008 to 2012 she was a Research Fellow, Neurogenetics/Movement Disorders, Harvard Medical School, Massachusetts General Hospital. In 2012 worked as an Instructor, Neurogenetics/Movement Disorders, Harvard Medical School, Massachusetts General Hospital. Presently is an Assistant in Research, Biomedical Sciences Centre for Brain Repair, Florida State University. Neuroscience/Movement Disorders. She has obtained the Travel Award, 2011 Dystonia Symposium (2011) and Award for Best Poster Presentation, Hellenic Society of Neuroscience (2001). Her major Research Interests: Neuroscience-Movement Disorders, Gene Regulation, and Human polymorphisms.



    Abstract
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    Abstract

    Ioanna A Armata
    Florida State University, USA.

    Translation generally initiates at the AUG codon (cAUG) marking the beginning of the coding region of a gene. Approximately 40% of human transcripts can also initiate translation within the 5 untranslated region, at upstream AUG codons (uAUGs) which precede the cAUG. The presence of auAUG within a transcript marks the beginning of an upstream open reading frame (uORF), which represents a potentially translatable nucleotide sequence. Single nucleotide polymorphisms that disruptuAUG/uORF-mediated translation are associated with approximately 30 untreatable human diseases, such as melanoma, β-thalassemia, campomelic dysplasiaand Dopa-Responsive Dystonia (DRD). Pathogenic uAUGs/uORFscan deregulatetranslation through two distinct molecular mechanisms: i) byreducingtranslation efficiency ofnormal protein products; and ii) byencoding mutant proteins that can trigger cellular death.Utilizing a uAUG/uORFassociated with DRD, a high throughput screening assay was developed for identifying compounds that prompt the translational machinery to bypass pathogenic uAUGs. Screening of a small collection of bioactive compounds reveals that Salubrinal (SAL), - (a potent and selective inhibitor of eukaryotic initiation factor 2dephosphorylation)-, promotes overriding of pathogenic uAUGs associated with DRD, as well as with melanoma predisposition, and theVan der Woude syndrome. Evaluation of SAL against uAUGs associated with additional human diseases is required to determine if SAL is a promising therapeutic agent for the group of uAUG-associated diseases. Such therapeutic agents would satisfy an unmet medical need.

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    Title: Cell Based Regenerative Therapy in Lung Fibrosis

    Ena Ray Banerjee
    University of Calcutta, Kolkata, India.

    Biography
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    Biography

    Ena Ray Banerjee
    University of Calcutta, Kolkata, India.

    Dr.Ena Ray Banerjee is Professor of Zoology,University of Calcutta, India and leads the Translational Outcomes Research Group that focuses on Immunobiology and Regenerative Medicine, drug discovery studies and basic research, including development and validation of novel drugs (small molecules), herbal extracts (functional food), probiotics (nutraceuticals), novel antibody-mediated (camelid antibody) and cells (tissue engineering of stem cells from embryo, foetal and adult tissue) in inflammatory (asthma, colitis, fibrosis, dermatitis, arthritis etc.) and degenerative disease models. She has published extensively in premiere scientific journals and her publications are widely cited in methods volumes as well as drug discovery websites and portals.



    Abstract
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    Abstract

    Ena Ray Banerjee
    University of Calcutta, Kolkata, India.

    Background: Idiopathic Pulmonary Fibrosis is characterized by excessive matrix deposition that disrupts the normal architecture of the lung parenchyma and causes airway remodeling. It is a progressive and fatal lung disorder with high mortality rate. The current treatments provide only minimal benefits and have significant side effects, highlighting the need for novel treatment approaches to Pulmonary Fibrosis. Objective: The aim of this study was to investigate the therapeutic potential of umbilical cord derived MSC (uMSC) bleomycin induced fibrosis. Methods: A mouse model of bleomycin induced pulmonary fibrosis was used in the study. Wharton jelly derived mesenchymal stem cells were injected intravenously and inflammation, fibrosis and regeneration was examined using a series of assays such as assessment of total cell count, inflammation, hydroxyproline, cell proliferation and clonogenic potential and histology. Results: We found in an increase in the total cell count (p < 0.001) and collagen content and a decrease in clonogenic potential (p <0.01) in the lung after bleomycin treatment as compared to the control group. Interestingly, intravenous administration of umbilical cord derived MSC showed reversal of these effects by decrease in collagen content, a decrease in total inflammatory cell count (p <0.01) and increase in clonogenic potential (p < 0.05) in the lung. Upon umbilical cord derived MSC administration, reactive oxygen species and reactive nitrogen species generation in the lung decreased as compared to only bleomycin treated group. Histological study of bleomycin treated lung revealed extracellular matrix decomposition, abnormal collagen degradation and distorted lung morphology compared to control groups; stem cell treatment assisted in restoration of lung morphology. Conclusion: The present research suggests that administration of umbilical cord derived mesenchymal stem cells led to reduction in inflammation and collagen content, increased proliferative ability of the cells and restored lung morphology. Thus these cells may be used for future reference to formulate effective therapeutic protocols in managing bleomycin induced IPF.

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    Title: Protein Replacement Therapy for Mitochondrial Genetic Diseases

    Haya Lorberboum-Galski
    Institute for Medical Research Israel-Canada (IMRIC), Hebrew University of Jerusalem, Israel.

    Biography
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    Biography

    Haya Lorberboum-Galski
    Institute for Medical Research Israel-Canada (IMRIC), Hebrew University of Jerusalem, Israel.

    Lorberboum-Galski is a Full Professor at the Department of Biochemistry and Molecular Biology, Faculty of Medicine, Hebrew University of Jerusalem. After receiving her Ph.D. in Biochemistry from the Hebrew University, she became a postdoctoral fellow at the Laboratory of Molecular Biology, NCI, NIH, USA. Her main research area is Developing reagents for Targeted Human Therapy with the lately focus of mitochondrial genetic diseases. She published over 65 publications in peer-reviewed journals, review articles, edited a book on chimeric proteins and holds several patents. She served as the Head of the Department, Head of the Program for Biochemistry at the Faculty and many other committees. For the last five years she is the Chairman of the Institute for Medical Research (IMRIC) at the Faculty of Medicine, Hebrew University.



    Abstract
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    Abstract

    Haya Lorberboum-Galski
    Institute for Medical Research Israel-Canada (IMRIC), Hebrew University of Jerusalem, Israel.

    Modern medicine offers no cure for genetic mitochondrial disorders and the usual treatment is mostly palliative. We developed a novel concept for the treatment of mitochondrial disorders using Cell/Organelle-Directed Protein Replacement Therapy; the delivery of a wild type mitochondrial protein/enzyme directly to its sub-cellular location and into its natural complexes, in the form of a fusion protein. Our approach is to fuse a wild type mitochondrial protein, including the Mitochondrial Targeting Sequence (MTS), with the delivery peptide TAT [HIV-transactivator of transcription (TAT) peptide], which will lead the protein/enzyme into the cells and their mitochondria, where it will substitute for the mutated endogenous protein. We tested this novel approach using a number of mitochondrial proteins, implicated in mitochondrial human diseases: Lipoamide Dehydrogenase (LAD), C6ORF66 (ORF), Frataxin (FXN) and methylmalonyl-CoA mutase (MCM), both in vitro, in patients cells and in vivo, in mouse models. TAT-MTS-Mitochondrial fusion proteins are rapidly and efficiently internalizing into cells and their mitochondria, both in patients cells and into mice tissues, including the brain. Treatment with the new TAT-MTS-Mitochondrial fusion proteins, improves mitochondrial functions and life span in animal models. One such fusion protein TAT-MTS-LAD is now being developed for human use. The novel approach may open new inroads in management of many incurable mitochondrial diseases.

  • Sessions:
    Clinical and Translational Oncology

    Time:

    Title: FABP5-Related Signaling Pathway Used as Therapeutic Target for Castration-Resistance Prostate Cancer

    Youqiang Ke
    Liverpool University, United Kingdom.

    Biography
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    Biography

    Youqiang Ke
    Liverpool University, United Kingdom.

    Dr. Youqiang Ke finished his PhD in Leeds University and joined the Cancer & Polio Research Laboratories in Liverpool University in 1989 to work as a Postdoctoral Research Associate. In 1994, Dr. Ke got a lecturer position in the Department of Pathology in the same university and started his research work on the molecular mechanisms involved in the malignant progression of prostate cancer cells. Dr. Ke was promoted to a Senior Lecturer in 2001, a Reader in 2003 and a Full Professor in 2005. Dr. Ke is the Director of Molecular Pathology in the School of Cancer Studies, Liverpool University, United Kingdom.



    Abstract
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    Abstract

    Youqiang Ke
    Liverpool University, United Kingdom.

    Castration resistant-prostate cancer is largely impervious to feather hormonal therapy and hence the outlook for patients is grim. Here we use an approach to attach the recently discovered Achilles heel. The experimental treatments established in this study are based on the recent report that it is the FABP5-PPARγ-VEGF signalling axis, rather than the androgen receptor activated pathway, played a dominant role in promoting the malignant progression of castration resistant prostate cancer cells. Treatments have been established in nude mice by suppressing the biological activity of FABP5 using a chemical inhibitor SBFI26 and a novel bio-inhibitor, dmrFABP5. Both inhibitors significantly supressedthe proliferation, migration, invasiveness and colony formation of PC3-M cells in vitro. They also produced a highly significant suppression of both metastatic rates and average sizes of primary tumours developed from cancer cells implanted orthotopically into the prostate gland of the mouse. Strikingly, the bio-inhibitor dmrFABP5, amutated FABP5 incapable of binding to fatty acids, produced a much better suppression of both primary tumour and metastasis. Both inhibitors interfere with the FABP5-PPARγ- signalling pathway. SBFI26 can competitively bindto FABP5 and hence suppresses cellular fatty acid uptake. In contrast, dmrFABP5 can block the fatty-acid stimulation ofPPARγ and prevent it activating the down-stream regulated cancer- promoting genes. This is an entirely novel experimental approach to treating castration- resistant prostate cancer and is completely different from current treatments that are based on androgen-blockade therapy.

    Time:

    Title: Health Benefits of Date Palm Phytochemicals: Carotenoids, Polyphenols, and Phytosterols

    Shri Mohan Jain
    University of Helsinki, Finland.

    Biography
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    Biography

    Shri Mohan Jain
    University of Helsinki, Finland.

    He received M. Phil, 1973 and Ph.D., 1978, Jawaharlal Nehru University, New Delhi, India. He was postdoctoral fellow in Israel, and USA; visiting Professor in Japan and Italy; Technical Officer, International Atomic Energy Agency (IAEA), Vienna, Austria, 1999-2005. He is a consultant, serves on the editorial Board of several international journals; published 150 papers in peer reviewed journals, book chapters, and conference proceedings, and edited 50 books; invited speaker and acted as a Chair person in several international conferences worldwide. He was awarded Nobel Peace Prize, 2005, in commemoration the awarding to IAEA of the Nobel Peace Prize for 2005.



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    Abstract

    Shri Mohan Jain
    University of Helsinki, Finland.

    Date palm (Phoenix dactylifera L.) is widely grown in the hot arid regions, and provides nutrition, as a staple food for centuries, food security, and raw material to the food industry. Even though date fruits are rich in nutrition, minerals, sugar and phytochemicals and its global market share is extremely low. Date fruit is a rich source of sugar, nutrients and pharmaceutical secondary metabolites, and provide 3150 calories per kilogram, and contain a high percentage of carbohydrate (total sugars, 44 /88%), fat (0.2 /0.5%), 15 salts and minerals, protein (2.3 /5.6%), vitamins and a high percentage of dietary fibre (6.4 /11.5%). They contain calcium, magnesium, phosphorus, potassium, iron, zinc, copper, manganese, selenium, vitamins A, A1, B, B1, B2, B3, B5, B6, and C as well as a variety of amino acids. The seeds contain aluminum, cadmium, chloride, lead and sulphur in various proportions. Date fruits have protective property against chronic diseases, which is attributed to phytochemicals. They have antioxidant activity, cholesterol lowering properties, chemoprevention of cancer, prevention of diabetes, and cardiovascular diseases. Date fruits contain many classes of bioactive components including carotenoids, polyphenols especially phenolic acid, isoflavons, lignins, and flavonoids, tannins, and sterols. In date palm cultivars, phytosterols are in abundance in shoot tips and pollen grains, calli and somatic embryos Thin layer chromatography revealed a number of phytosterols including cholesterol, betasitosterol and stigmasterol, which are beneficial as antiinflammatory, antiatherogenicity, and anti-cancer Fresh date fruits are an excellent source of energy and remedy for alcoholic intoxication, stimulation of the uterus by regulating contractions, and treatment of constipation, However, more detailed work is needed for the identification, characterization, and quantification of phytochemicals in different date varieties at different stages of fruit ripening; systematic studies on the date health benefits and hardly recognized as a healthy food, and this aspect will be highlighted.

    Time:

    Title: Conditional BRCA2 Switch in Human Cells to Study Tumor Progression

    Jimenez Sainz Judit
    Yale School of Medicine, USA.

    Biography
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    Biography

    Jimenez Sainz Judit
    Yale School of Medicine, USA.

    Judit is a Postdoctoral Associate in the Jensen group in Therapeutic Radiology Department. Her current research involves biochemical and cellular-based approaches to prevent and unmask the initial steps in breast and ovarian cancer formation. She received her phd from Universidad de Valencia, Spain and UCL, London. She is a member of ECUSA, NYAS and WISAY and she strongly believes in supporting new generation of students in STEM.



    Abstract
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    Abstract

    Jimenez Sainz Judit
    Yale School of Medicine, USA.

    The BRCA2 (Breast Cancer Susceptibility 2) gene is a caretaker of genome integrity. Germline mutations in BRCA2 predispose to a high risk for ovarian and breast cancer. The BRCA2 protein plays an important role in repair of DNA double-strand breaks (DSBs) by homologous recombination. BRCA2 dysfunction results in genome instability including chromosome aberrations and an abnormal number of centrosomes. Centrosome amplification is a hallmark of tumors from BRCA2 mutation carriers and may be responsible for the origin of chromosome missegregation at mitosis and DNA aneuploidy found in these tumors. However, it remains an open question how BRCA2 regulates centrosome duplication and the consequences for tumor initiation and progression. Here, we present the generation of an isogenic inducible BRCA2 human cell line providing a model to study acute loss of the BRCA2 protein. We plan to measure centrosome number and how BRCA2 regulates the centrosome duplication checkpoint with the end goal of understanding tumor initiation and maintenance in BRCA2 mutation carriers.

    Time:

    Title: Expression of Cox-2,Cyclin D1 and P21 in Colorectal Cancer Patients and Their Clinicopathological and Prognostic Significances

    Ola Harb
    Zagazig University, Egypt.

    Biography
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    Biography

    Ola Harb
    Zagazig University, Egypt.

    Lecturer of Pathology, Faculty of Medicine, Zagazig University, Egypt.



    Abstract
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    Abstract

    Ola Harb
    Zagazig University, Egypt.

    Background: Cyclooxygenase-2 (COX-2), play an important role in inflammation, carcinogenesis and cell cycle alterations. It isincriminated in cancer progression by causing dysregulation of normal cell cycle control. Cyclin D1 plays a vital role in cancer cell cycle progression. The activity of cyclin D1 can be blocked by CDK inhibitors, including p21 (cyclin-dependent kinase inhibitor-1A, CDKN1A, CIP1) that plays a role in regulating cell cycle. The purpose of this study was to evaluate expression of COX-2, Cyclin D1 and P21 in colorectal cancer patients, analyze the relationship between their expression, clinicopathological criteria and the prognosis of patients. .Methods: expressions ofCox-2,Cyclin D1 and P21were evaluated in 60 paraffin blocks colorectal cancer patientsthat were followed up for 3 years. The relationship between their level of expressions and prognosis of patients was analyzed. Results:Cox-2&Cyclin D high expression was positively correlated with higher grade, advanced stage, presence of lymph node& distant metastasis and Duke stage (P=0.000). P21 high expression was negatively correlated with presence of lymph node metastases, higher grade (p=0.002), advanced stage, presence of distant metastasis and advanced Duke stage (P=0.001). We found a direct relationship between Cox-2 and Cyclin D 1, an inverse relationship between Cox-2 and P21, and an inverse relationship between Cyclin D 1 and P21 (P<0.001). Cox-2&Cyclin D1 over expression and P21 low expression were positively associated with higher incidence of tumor recurrence (P=0.04, 0.000 respectively), higher incidence of cancer specific death (p=0.002, 0.004&0.000 respectively) but no significant correlation with response to therapy with all markers. Conclusion: High levels of expression of Cox-2 &Cyclin D1are markers of poor prognosis, while high level of expression of P21is a marker of good prognosis in colon cancer patientsthese results suggest that loss of control of cell cycle checkpoints is a common occurrence in CC, and regulation in cell growth control and tumor suppression. Keywords: Cox-2, Cyclin D1, P21,colon cancer patients, immunohistochemistry, prognosis

    Time:

    Title: Prognostic Value of the Expression of Endogenous Hypoxia Associated Proteins Hypoxia Inducible Factor-1 Alpha (HIF-1α) and Carbonic Anhydrase Isoform 9 (CAIX) Expressions in Breast Carcinoma

    Ola Harb
    Zagazig University, Egypt.

    Biography
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    Biography

    Ola Harb
    Zagazig University, Egypt.

    Lecturer of Pathology, Faculty of Medicine, Zagazig University, Egypt.



    Abstract
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    Abstract

    Ola Harb
    Zagazig University, Egypt.

    Background; hypoxia has been found to be related to malignant initiation, progression, increasing the occurrence of metastasis and therapy resistance in many cancer types, which made a real need for discovering drugs that could antagonize the bad effect of hypoxia in cancer, decide which patients will have benefit from such anti-hypoxia therapy then to monitor response to therapy, especially in breast carcinoma. It is important to detect degree of hypoxia in each cancer that could be done by evaluation of the expression of hypoxia-associated protein in cancer biopsies e.g. hypoxia inducible factor-1 alpha (HIF-1α) and carbonic anhydrase IX (CAIX) and their detailed role in breast cancer is still uncertain and gives conflicting results. Aim of the work; was to evaluate HIF-1α and CAIX expressions in breast carcinoma, correlating their expressions with each other, with presence of lymph node & distant metastases, with recurrence free and overall survival rates of breast cancer patients. Methods;we evaluated HIF-1α & CAIX expressions in sections from 90 paraffin blocks of breast carcinoma using immunohistochemistry. We analyzed correlations between their levels of expressions, clinic-pathological and prognostic parameters of our patients. Results; HIF-1α and CAIX positive expression in breast carcinoma was related to advanced stage, presence of lymph node metastases,HER2 amplified and triple negative molecular subtypes(p<0.001), higher tumor grade (p= 0.001& 0.02 respectively) and negative ER (p= 0.005& 0.008 respectively) & PR (p= 0.009& 0.027 respectively) hormonal receptors, The expression of both markers was significantly positively correlated with each other (p<0.001). HIF-1α and CAIX positive expression in breast carcinoma was associated with shortened recurrence free and overall survival rates (p<0.001). Conclusion; HIF-1α and CAIX are markers of poor prognosis of breast carcinoma patients. Key words; breast carcinoma, hypoxia; HIF-1α; CAIX; immunohistochemistry; prognosis

    Time:

    Title: Tracking Tumours into Number Community? – Yes, How, And Why.

    Whyte B Bozegha
    Pioneer Developer of Numeration Science Literature.

    Biography
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    Biography

    Whyte B Bozegha
    Pioneer Developer of Numeration Science Literature.

    Whyte Bozegha is a pioneer developer of Numeration Science Literature in an ongoing personal research project. He has defined Numeration as science of number and arrangement, and found the computation of permutations and combinations of specified set(n) and selection (r) to be a purely combinatorial task in Numeration and invented Solid State Mixing Scheme, Square Kinematics Mixing Scheme, and Successive Collateral Posting Scheme, all for the production of the factorials of permutations and combinations for the first time in the long history of permutations hitherto held captive in the purported preserve of mathematics. Each of the three schemes has been used in the derivation of a 24-quadruplet genetic code from the four RNA bases A,U,G,C (Adenine, Uracil, Guanine, Cytosine) since 1991, but it is yet to be spelt because spelling experts and laboratories contacted so far from 1991 have not responded positively.



    Abstract
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    Abstract

    Whyte B Bozegha
    Pioneer Developer of Numeration Science Literature.

    Statement of the problem: Tumours are growths (of quantity) in humans with medical science literature. Isodigitals produced by pre-emptive multiplication are also growths (of quantity) in numbers with slight numeration science literature for now. The developer of inchoate numeration science literature somehow acquainted with the literature of tumours, upon encountering isodigitals would be prompted to surmise isodigitals as phenotypes (lookalikes) of tumours and be urged to explore their literatures for prospects of relationship between the two. Methodology and theoretical orientation. Tumours and isodigitals are subjected to pentadic characterization with the five parameters of identity, structure, function, operation and application for methodology. The theoretical orientation of the method is that tumours and isodigitals as growths of quantity are classic examples of quantity which is defined as the phenomenal medium of manifestation of all things, whether material or non-material. So the two can be compared and contrasted at will in the interest of science. Findings. Numeration science literature on isodigitals can borrow mode of classification of tumours from medical science literature on tumours, while medical science literature on tumours can borrow verbal formulary for the description of pattern of growth of tumours from numeration science literature on isodigitals. Conclusion and Significance. Tumours in humans and isodigitals in numbers are seen as phenotypes subsisting on manifestation of quantity. The peculiarities of one can serve as clues to the probing of the other for more light. Recommendations: The ideal of insight on quantity should be brought to bear on scientific engagements.

    Sessions:
    Pharmacology (Cancer / Clinical) & Biomedical sciences / Bioengineering & Tissue Repair and Regeneration

    Time:

    Title: Developing Patient-Specific Direct Neuronal Reprogramming for Modeling Neurodegenerative Disorders

    Janelle Drouin-Ouellet
    Lund University, Sweden.

    Biography
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    Biography

    Janelle Drouin-Ouellet
    Lund University, Sweden.

    Dr. Drouin-Ouellet has obtained her Ph.D. in Neurobiology at Laval University (Quebec City, Canada) in 2012. She is currently working at Lund University (Lund, Sweden) where she has developed a simple and efficient method for direct neuronal conversion of adult human dermal fibroblasts from patients with neurodegenerative diseases. She is now conducting research aiming at further advancing the direct neuronal reprogramming technology to provide patient specific based systems that faithfully recapitulate disease-associated phenotypes of neurodegenerative disorders in vitro.



    Abstract
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    Abstract

    Janelle Drouin-Ouellet
    Lund University, Sweden.

    Direct conversion of adult human fibroblasts into mature and functional neurons, termed induced neurons (iNs) was achieved for the first time five years ago. This technology offers a shortcut for obtaining patient and disease specific neurons for disease modeling, drug screening and other biomedical applications. Despite their great promise, reprogramming roadblocks have prevented the generation of iNs at a sufficiently high yield from adult dermal fibroblasts, which has significantly limited the adoption of this technology. To overcome this, we have developed a new highly efficient dual promoter-based vector system that results in efficient co-delivery of the two reprogramming factors Brn2a and Ascl1 in combination with either neuron specific microRNAs or the inhibition of the RE1-silencing transcription factor (REST). Global gene expression analysis showed that while both strategies resulted in induction of a neuronal program and similar level of neural conversion, the inhibition of REST induces the expression of additional genes that are related to neuronal identity and function. Based in this, we developed an optimized one-step method to efficiently reprogram dermal fibroblasts from elderly individuals using a single vector system and demonstrate that it is possible to obtain iNs of high yield and purity from aged individuals, including Parkinsons disease patients. We are now evaluating the conversion capability of these skin fibroblasts and our preliminary results suggest that iN cells from sporadic PD patients reprogram in a similar fashion as that of healthy individuals and could thus serve as a tool to model intracellular pathological features associated with PD.

    Time:

    Title: Acute Inflammation is required for Muscle Regeneration

    Ping Hu
    Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, China.

    Biography
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    Biography

    Ping Hu
    Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, China.

    Ping Hu, Ph. D. is a Principal Investigator in Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences. She graduated from Peking University and obtained her Ph. D. degree from the joint graduate program of State University of New York, Stony Brook/Cold Spring Harbor Laboratory. She performed her postdoc research in University of California, Berkeley/Howard Hughes Medical Institute. Hu Lab is focused on the regulation of muscle stem cell functions and myogenesis, especially on the microenvironment of muscle stem cells and the epigenetic regulation of muscle stem cell functions.



    Abstract
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    Abstract

    Ping Hu
    Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, China.

    Skeletal muscle regeneration involves a series of physical responses after injury or disease, including activation of quiescent satellite cells (muscle stem cells), proliferation of satellite cells and myoblasts, differentiation of myoblasts, and formation of new myofibers. In recent years, more and more evidences suggested that inflammation plays important roles during muscle regeneration process. However, how inflammation affects muscle regeneration remains to be elusive. Here we focused on T cells mediated inflammation and found that it is a required positive regulator at early stage of skeletal muscle regeneration. Upon muscle injury, we observed large amount of T cell infiltrated at injury site. In immunodeficient mice, where the T cell infiltration is diminished while other liphocytes such as macrophage infiltration remains normal, reparation of muscle injury was dramatically delayed. To further investigate the mechanism of T cell promoting muscle regeneration, we characterized the protein profile of activated T cells. A combination of four factors was identified to be able to promote satellite cell proliferation and long term expansion dramatically in culture. The cultured expanded satellite cells continue to express muscle stem cell marker, and were able to regenerate functional myofiers in vivo. Furthermore, muscular injection of the four factor cocktail could rescue the muscle regeneration defects caused by T cell deficiency. Our results demonstrate that T cell mediated inflammation is required for muscle stem cell proliferation at early stage of post-injury regeneration.

    Time:

    Title: Papillary Thyroid Carcinoma

    Idania Teresa Mora Lopez
    Enrique Cabrera Medical Sciences University, Mexico.

    Biography
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    Biography

    Idania Teresa Mora Lopez
    Enrique Cabrera Medical Sciences University, Mexico.

    Dr. Idania Teresa Mora Lopez was born on February 10, 1967, Havana, Cuba. Graduated in Medicine on August 14, 1990, Faculty of Medicine Julio Trigo Lopez, belonging to the Medical Sciences University of Havana. She obtained her First Degree Specialist in Comprehensive General Medicine and Specialist of First and Second Degrees in Endocrinology. Diploma in Higher Medical Education. Master of Science Satisfactory Longevity. Aggregate Investigator. Presently she is Adjunct Assistant Professor of the Dr. Enrique Cabrera Medical Sciences University and the Latin American School of Medicine. She has wide publications: 15 national / international. Healthcare Center: Enrique Cabrera General Teaching Hospital.



    Abstract
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    Abstract

    Idania Teresa Mora Lopez
    Enrique Cabrera Medical Sciences University, Mexico.

    The papillary thyroid carcinoma is the most frequent endocrine neoplasia and the one with the highest presentation in thyroid carcinomas, prevalence (5-6.5%), predilection for the female sex, second to third decades of life and increase in aging, influences predisposing factors such as head and neck radiation, thyroid nodule background, representing (5-15%), family history and the association with Multiple Endocrine Neoplasia type 2, Cowden syndromes, Gardner, Garney complex or unknown etiology. Diagnosis based on questioning, specifying exposed history, physical examination, determining consistency, location of the nodule with respect to the gland, size, regional lymph nodes, supraclavicular, growth pattern and complementary studies such as ultrasound that expresses whether it is solid, hypoechoic, irregular borders, microlobulated, microcalcifications, absence of safety halo, thick and incomplete halo, determination of thyroid function with Thyroid Stimulating Hormone (TSH), Thyroglulin and Fine Needle Aspiration Cytology, which according to the Bethesda System confirms carcinoma (97-99%) and diagnosis definitive with freezing biopsy and adenomegalies if they were removed. Treatment based on total thyroidectomy, later treatment with thyroid hormones (suppressive dose), follow-up with (TSH) per month, one year Gammagraphy and thyrogluline, according to the annual follow-up results in the first 5 years and every 2 years in the following 5 years, every 5 years the rest of the life, if it detects an area in the neck, perform treatment with 131IODO assess every 6 months and repeat at the same time until there is negativity and always doing thyroglycine. Treatments such as chemotherapy and tyrosine kinase inhibitors in non-operable and advanced cases.

    Time:

    Title: Proliferation of Porcine Adipose Derived Stem Cells in Herbal Scaffolds

    Franca Nneka Alaribe
    Tshwane University of Technology, South Africa.

    Biography
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    Biography

    Franca Nneka Alaribe
    Tshwane University of Technology, South Africa.

    Dr Franca Nneka Alaribe – PhD Biomedical Sciences, University of Ferrara Italy, specializing in cellular/molecular pathology in cancer and degenerative diseases; MSc Molecular Biology/Biotechnology, Vrije University Brussels Belgium; BSc(Ed) Biology, University of Nigeria Nsukka. She is a researcher for over 10 years with high competence in biomedical research; has coordinated many research projects for NRF, THRIP, Bone South Africa and OSTA involving biomaterials; presently working on stem cells and scaffold fabrication with South African medicinal plants; published more than 12 research works and academic papers in international peer reviewed journals; founder/editorial manager of Journal of Advances in Biomedical Studies; editor of several peer reviewed journals and fellow of many scientific organisations.



    Abstract
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    Abstract

    Franca Nneka Alaribe
    Tshwane University of Technology, South Africa.

    The significance and the potentials of in vitro cell culture studies are great considering the need for more cost efficient development of new drugs, time efficient treatment of cancer patients, and an understanding of developmental biology and mechanisms of stem cell differentiation. Cells, growth factors and scaffolds are the fundamental issues for tissue engineering. If porcine derived adipose stem cells (pADSCs) can effectively proliferate and differentiate when cultured on herbal scaffolds, this makes it a potential candidate for in vivo environment with possible profound impact on therapeutic application of herbal scaffolds. This study evaluated the in vitro differentiation capacity and anti-inflammatory effect of fabricated herbal scaffolds on pADSCs. To this effect, herbal scaffolds were developed by incorporating medicinal plant extracts (Eucomisautumnalis and Pterocarpusangolensis) and natural biopolymers (Alginate and chitosan) using lyophilisation technique. A standard sterility test on the scaffolds before in vitro use showed the ultraviolet radiation with 75% (v/v) ethanol to be suitable. pADSCs cultured on the herbal scaffolds were further monitored for in vitro proliferation and differentiation using different biological, immunological and genetic techniques. The identity of pADSCs were confirmed by positive FACs analysis of mesenchymal stem cell surface markers CD44, CD90 and CD105 (≥ 85%). Their multi potency was further evaluated by trilineage differentiation of pADSCs toward adipocyte, osteocyte and chondrocyte with histology staining. Scanning electron microscope (SEM) revealed that the herbal scaffolds possess an extremely porous structure than control (non-herbal scaffold). SEM and immunofluorescence results also revealed more attachment of ells at day 7, 14 and 21 on herbal scaffolds than non-herbal scaffolds. ELISA assay with IL-6 and gene expression of collagen type 11, alkaline phosphate, osteocalcin and osteopontin with RT-PCR confirmed the anti-inflammatory nature and mRNA expression/chondrogenic nature of the pADSCs cultured with the herbal Scaffolds media. This study indicates that pADSCs would have great therapeutic potential as seeding cells for in vivo transplantation to treat various inflammatory diseases and bone injuries when co-applied with medicinal plants and biopolymers.

    Sessions:
    Stem Cells/ Regenerative Medicine

    Time:

    Title: High Throughput Characterisation of Dental Pulp Derived Stem Cells and Its Possible Application in Treatment of Traumatic Brain Injuries

    Dannie Macrin
    SRM University, Tamil Nadu, India.

    Biography
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    Biography

    Dannie Macrin
    SRM University, Tamil Nadu, India.

    DANNIE MACRIN is presently a Research Scholar in the area of Cancer Biology, Department of Genetic Engineering, Kattankulathur Campus, SRM University, India. He completed his M. Phil in Biotechnology from Bharathidasan University, India, 2008. Obtained his M.Tech during the year 2011 in Genetic Engineering from SRM University, India. And B.Tech Bioinformatics from Karunya University, India, 2009. His main research interests: Cancer cell lines and stem cells, Plant Tissue culturing and micropropagation.



    Abstract
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    Abstract

    Dannie Macrin
    SRM University, Tamil Nadu, India.

    Traumatic brain injuries (TBIs) are a major cause of disability and death worldwide. They are clinically subdivided into mild, moderate and severe forms, mild TBI (also known as concussion) accounts for 80–90% of cases. The use of stem cells for treating traumatic brain injury (TBI) or concussion presents a highly viable therapeutic strategy. In particular, using an adult mesenchymal type stem cell (MSC) as a delivery mechanism for delivering therapeutic molecules has a tremendous potential since MSCs secrete endogenous anti-inflammatory and neuro-regenerative molecules. Dental pulp stem cells show close resemblance with mesenchymal stem cells and can differentiate into adipocytes and osteoblasts. In this study, we have successfully cultured stem cells from dental pulp isolated from surgically extracted third molar with a high percentage of mesenchymal population demonstrated by expression of surface markers, CD29, CD44, CD146 and Stro1. Whole genome transcriptome sequencing revealed that DPSCs were closely related to bone marrow derived mesenchymal stem cells. We have also identified presence of many neuro-beneficial proteins expressed by dental pulp derived mesenchymal stem cells such as; Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and gonadotropin-releasing hormone 1 (GnRH1). The activity of these neuro-beneficial proteins is further increased by the presence of immune-modulating proteins such as interleukins (ILs), transforming growth factor beta 3 (TGFB3), insulin-like growth factor 2 (IGF2), intercellular adhesion molecule 3 (ICAM3). Also, DPSCs secrete a large subset of the heat shock proteins which may act as chaperones and prevent tauopathy caused by the misfolding of phosphorylated tau protein, observed both in traumatic brain injuries (TBI) and in chronic traumatic encephalopathy (CTE). We propose that these beneficial trophic factors secreted from autologous dental pulp as a potential therapy for TBIs.

    Time:

    Title: Frontiers of Induced Pluripotent Stem Cells: From Bench to Bedside

    Rosy Joshi Mukherjee
    Center for Integrative Research on Cardiovascular Aging (CIRCA), Aurora Research Institute, USA.

    Biography
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    Biography

    Rosy Joshi Mukherjee
    Center for Integrative Research on Cardiovascular Aging (CIRCA), Aurora Research Institute, USA.

    Dr. Joshi-Mukherjee developed Heart-on-µGMEA-Chip Model for cardiomyopathy using cutting-edge technology namely, induced pluripotent stem cells and multielectrode array. The model reliably predicts cardiac cell death or altered electrophysiology phenotypes such as prolongation of action potential duration and early afterdepolarizations (EADs).Presented the research at Gordon Research Conference on Cardiac Arrhythmia and Mechanisms at Ventura, CA, United States, in 2017.During postdoctoral fellowship at Johns Hopkins University Dr. Joshi-Mukherjee received T32 fellowship for developing human induced pluripotent stem cell (hiPSC) lines from patient harboring sodium channel mutations associated with long QT 3 syndrome to investigate the mechanisms contributing to arrhythmia.



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    Abstract

    Rosy Joshi Mukherjee
    Center for Integrative Research on Cardiovascular Aging (CIRCA), Aurora Research Institute, USA.

    Stem cell biology has gained tremendous interest in regenerative medicine, offering the hope of new therapies for otherwise intractable disease. Regenerative medicine involves the repair and regeneration of tissues for therapeutic purposes, such as replacing bone marrow in leukemia, cartilage in osteoarthritis or cells of the heart after a heart attack. Today advances in basic and clinical research make tissue regeneration feasible. This course is tailored for researchers with an interest in learning about current biological induced pluripotent stem research in a highly interactive setting. It aims to equip early researchers with the fundamental and cutting edge knowledge and critical understanding necessary for research in stems cells and the implications of induced pluripotent stem cell(iPSC) research for medicine and society. Participants will learn through multiple interfaces such as lectures, discussions, small group activities, and feedback from other participants. Explain the advantages and disadvantages of iPSCs as compared to embryonic stem cells. Describe various methods for creating iPSCs, including transfection methods using plasmids, retroviruses, small molecules, and adenoviruses. Discuss the advantages and disadvantages of each. We will explore basic mechanisms of how iPSC differentiate into specific tissues in response to a variety of biologic signaling molecules. We will discuss the use of such factors for in vitro tissue production. For example, bone morphogenetic proteins can be used in vitro to drive the differentiation of adult stem cells towards bone and heart. Discuss various in-vitro approaches for production of beating heart cells. We will also discuss how studies of the developmental, cellular and molecular biology of regeneration have led to the discovery of new drugswith examples from cutting-edge research. Discuss the clinical uses of iPS cells. Describe issues that must be resolved before iPS cells can safely be used in human cell-based therapy.

    Time:

    Title: Stem cells improve kidney function and remodelling in CRS type II

    Chiara Castellani
    University of Padua, Italy.

    Biography
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    Biography

    Chiara Castellani
    University of Padua, Italy.

    Chiara Castellani, Assistant Professor in Technical Sciences of Laboratory Medicine. University teaching of Cyto and histopathological diagnosis and part of courses of Pathological Anatomy. Ph.D. in Cardiovascular Pathology (2007) achieved thanks to a research on Cardiac and non-cardiac stem cells in heart transplant and cardiac hypertrophy remodelling. She completed her Specialty training in Clinical Biochemistry (March 2013). She has been visting research fellow at the Washington University in Seattle, WA (2006), where she worked under the supervisor ship of prof. Charles Murry on the heart remodeling and stem cells. Research lines: i) stem cells and cardiac remodelling; ii) stem cells and cardio renal syndrome; iii) cardiac amyloidosis; iv) cardiac allograft vasculopathy; v) exosomes and miRNA in heart and kidney transplantation The outcome of her research was presented through oral presentations and posters during many national and international meetings. She had published papers in international ISI journals and one book chapter (HI=11 and citations)



    Abstract
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    Abstract

    Chiara Castellani
    University of Padua, Italy.

    Background: we investigate the effects of human amniotic fluid stem cells (hAFS) and rat adipose tissue stromal vascular fraction GFP-positive cell (rSVC-GFP) therapy in a monocrotalinerat model of cardio-renal syndrome type II (CRSII). Methods: RHF was induced by monocrotaline (MCT) in Sprague-Dawley rats.Three weekslater, four million of hAFS orrSVC-GFPwere injected via tail vein. BNP, sCreatinine, kidney and heart NGAL and MMP9,sCytokines, kidney and heart apoptosis (TUNEL technique) were studied. Stem Cells (SC) engraftment was detected with immunofluorescence. Results: SC treated rats showed a significant reduction of serum NGAL and Creatinine (NGAL 335.6±92.60 sCrea 0.36±0.05,p= 0.01) compared to CHF rats. In both hAFS and rSVC-GFP group, kidney protein expression of NGAL was significantly lower than in CHF group (SC 2.6*106±1.2*106 vs HF 5.1*106 ± 1.5*106 A.U., p=0.0008) and similar to that to controls. In both hAFS and rSVC-GFP treated rats, we observed a substantial number of SC engrafted in the medulla and differentiated in tubular cells. Apoptosis was significantly decreased (hAFS 10.29±10.81 and rSVC-GFP 24.82±25.19 cells/mm2, p=0.05 vs CHF) and similar to controls (9.85±7.2 cell/mm2). TUNEL-positive cells were mainly located in the kidney medulla.Pro-inflammatory cytokineswere down regulated in SC-treated groups (p=0.05 vs CHF) and similar to controls. In SC treated rats, kidney and heart tissue NGAL was not complexed with MMP9 as showed in CHF groups, suggesting inhibition of MMPs activity. Conclusion: SC treatment produced improvement in kidney function in rats with CRSII. This may be the results of tubular regeneration due to SC engraftment, decrease tubular cells apoptosis and mitigation of pro-inflammatory milieu. Reduction of NGLA-MMP) complexion mainly to decrease MMPs activity with prevention of further negative heart remodeling

    Time:

    Title: Immunomodulatory Properties of Human Amnion Epithelial Cell in Support to Allogenic Transplantation without Immunosuppression

    Roberto Gramignoli
    Karolinska Institute, Sweden.

    Biography
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    Biography

    Roberto Gramignoli
    Karolinska Institute, Sweden.

    Presently is an Assistant Professor at Karolinska Institutet, Department of Laboratory Medicine Stockholm, Sweden. From May 2012 - Dec 2014 obtained PostDoc Position in Karolinska Institutet, Department of Laboratory Medicine Stockholm, Sweden. From Jul 2007 - Apr 2012 was a visiting fellow at University of Pittsburgh, Department of Pathology Pittsburgh, United States. And from Nov 2002 - May 2008 was a research fellow at Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Area della Medicina Rigenerativa (Riparazione e Sostituzione di Cellule, Organi e Tessuti) Milano, Italy. In Apr 2000 - Jul 2002 was an undergraduate student, from National Research Council, Milan, Italy.



    Abstract
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    Abstract

    Roberto Gramignoli
    Karolinska Institute, Sweden.

    Placental amnion tissue has been used for decade in clinical practice, while amnion ­derived cells has been proved successful only recently. We reported that human amnion epithelial cells (hAEC) from term placenta are not tumorigenic, have immunomodulatory and anti inflammatory properties and once transplanted differentiate into functional hepatocyte ­like cells. In preclinical studies with immune ­competent mice, hAEC engrafted and survived without administration of immunosuppressive drugs, resulting in correction of metabolic liver diseases (iMSUD and PKU) and reversal of acute liver failure. Immunogenicity of the hAEC has been confirmed on purified immune effector cells (T-­, B-­ and NK-­cells). Placental expression of non canonical HLA proteins have been identified as key regulator in maternal-­fetal immune-­toleration. Amnion characteristically lacks HLA class 2 expression, and expresses both class 1a and 1b. We measure HLA-­G and HLA-­E expression both as membrane-­bound and soluble isoforms. Recently, purinergic mediators, such ATP and NADPH, hydrolyzed by plasma membrane nucleotidases, have been identified to regulate immune cell response. High level expression of ecto-­enzymatic axis and non-­canonical HLA molecules likely play a key role in immunological tolerance and long term acceptance of the human xeno ­cell graft in immunocompetent mice. Based on their safety and the successful preclinical studies, approval was granted to begin banking of hAEC under cGMP condition at Karolinska Institutet, and to perform hAEC transplants on 10 patients with liver disease without immunosuppression.

  • Sessions:
    Poster Session

    Time:

    Title: Decoding Ca2+ Signaling in Regulation of transcription Factor Activation and Cell Cycle Progression Using Optogenetics

    Wen-Tai Chiu
    National Cheng Kung University, Taiwan.

    Biography
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    Biography

    Wen-Tai Chiu
    National Cheng Kung University, Taiwan.

    Dr. Wen-TaiChiu received the Bachelor’s, Master’s and Ph.D. degrees from National Cheng Kung University, Taiwan in 1997, 1999 and 2007, respectively. He has been a postdoctoral fellow at the University of Texas MD Anderson Cancer Center from 2008 to 2010. Prof. Chiu is currently an associate professor in the Department of Biomedical Engineering at National Cheng Kung University. His research interests lie in the area of Ca2+ signaling and molecular imaging of cancers. Much of his work has been on improving the understanding, design, and performance of Ca2+ in focal adhesion dynamics, cell migration, metastasis and chemoresistance.



    Abstract
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    Abstract

    Wen-Tai Chiu
    National Cheng Kung University, Taiwan.

    The ability of a simple ion such as Ca2+ to play an highly versatile intracellular signal results from the facility that cells have to shape Ca2+ signals in the dimensions of space, time and amplitude. Thus, spatial and temporal changes in intracellular Ca2+ concentration is important to determinate the cell fate. Optogenetics is the combination of genetics and optics tocontrol well-defined events within specific cells of living tissue in real time. Optogenetic stimulation approach that uses channelrhodopsin-2 (ChR2) related proteins has been developed for providing more precise and targeted stimulation effect on cellsin vivo and in vitro. We aimed to pose the formerly unaddressed fundamental question of how Ca2+ signals regulate transcription factor activationby manipulating intracellular Ca2+ through using optogenetic strategies. In this study, We found that (1) elevation of intracellular Ca2+ levels that correspond with the power, frequency and duty cycle of light illumination in a dose-dependent manner; (2) activation of Ca2+-dependent transcription factors is depends on Ca2+ oscillations with different frequency and amplitude; (3) cells in the various phases of the cell cycle showed different responses to Ca2+-mediated cell cycle progression. In summary, the delicate regulation and precise control of transcription factor activation and cell cycle progression can be achieved under the optogenetic platform. Parameters associated with light illumination will be optimized in the future. It will enable us to be confident in applying this advanced technique to (1) manipulate the expression patterns of genes by desire; and (2) control the growth and differentiation of cells.Such a process would be a potential platform in study ofcell development and cancer.

    Time:

    Title: L1CAM Up-Regulation in Association with P53 Over-Expression and E-Cadherin down -Regulation Can Help in Detection of Non-Endometrioid Foci, Risk Stratification, Relapse and Outcome of Endometrial Carcinoma Patients

    Ola Harb
    Zagazig University, Egypt.

    Biography
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    Biography

    Ola Harb
    Zagazig University, Egypt.

    Lecturer of Pathology, Faculty of Medicine, Zagazig University, Egypt.



    Abstract
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    Abstract

    Ola Harb
    Zagazig University, Egypt.

    Background, the recent guidelines for endometrial carcinoma (EC) management classify patients into; low-, intermediate-, high to intermediate and high-risk groups. Few numbers of patients in the category of low-risk disease were found to have relapse of the tumor that is not explained up till now. Moreover, it is essential to assess prognosis of other risk groups of EC. Also, the detection of patients that the adjuvant therapy will be more beneficial to them than other patients that will not require additional management after surgery is an essential aim of the recent researches about EC. So, recent studied has focused on detection of prognostic biomarkers that might improve risk stratification and detect which patients will need neoadjuvant chemotherapy after surgery. L1-cell adhesion molecule (L1CAM) is membrane glycoprotein member of immunoglobulin superfamily. P53 is a nuclear transcription factor and was found to be an established tumor suppressor. E-cadherin is an integral cell adhesion molecule and it is a component of adherens junction. the aim of our study to investigate the prognostic significance of L1CAM, P53 and E-cadherin expression in both early-stage, low-, intermediate-risk and high-risk EC, correlate their expression with clinicopathological criteria, tumor progression, recurrence, risk stratification of EC patients and with identification of patients that will need neoadjuvant chemotherapy after surgery. Methods: expressions ofL1CAM, P53 and E-cadherin were evaluated in 60 paraffin blocks EC patients that were followed up for 5 years. The relationship between their level of expressions, clinicopathological criteria and prognosis of patients was analyzed. Results: Positive expression of L1CAM was positively correlated with higher grade of the tumor (p = 0.043), presence of L.N metastases (p = 0.039), presence of, LVSI (p = 0.022),higher risk groups (p = 0.021), and presence of distant metastases (p=0.039). High expression of P53 was positively correlated with higher &advanced FIGO stage of the tumor, presence of L.N metastases, LVSI, higher risk groups and presence of distant metastases (p<0.001). Positive expression f E-cadherin was negatively correlated with higher grade of the tumor (p = 0.019), presence of L.N metastases (p = 0.010), presence of LVSI (p = 0.018) and presence of distant metastases (p=0.013). In multi variant analysis L1CAM expression is the most significant indicator of poor DFS & OS rates (p<0.001). We found a direct relationship between L1CAM, P53 an inverse relationship between L1CAM and E-cadherin, and an inverse relationship between P53 and E-cadherin (P<0.001). Conclusion: L1CAM & P53 over expression in addition to loss of E-cadherin expression in EC are associated with non-endometrioid subtype of EC, worse clinicopathological parameters, poor prognosis and could help in identification of patients in need for neoadjuvant chemotherapy after surgery Keywords: L1CAM, P53, E-cadherin,endometrial carcinoma, immunohistochemistry, risk stratification

    Time:

    Title: Prognostic and Predictive Values of Cell Cycle Proteins Centrosomal Protein 5 (CEPP 5) and Cyclin D1 Expression Inepithelial Ovarian Carcinoma (EOC)

    Ola Harb
    Zagazig University, Egypt.

    Biography
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    Biography

    Ola Harb
    Zagazig University, Egypt.

    Lecturer of pathology, Faculty of Medicine, Zagazig university, Egypt.



    Abstract
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    Abstract

    Ola Harb
    Zagazig University, Egypt.

    Background; Disturbances in the expressions of centrosomal proteins (CEPs) and regulatory proteins that control G1-Sphase transition, like cyclins could participate in dysregulation of cell cycle control that has been incriminated in the pathogenesis of several malignancies. Centrosomal protein 55 (CEP55) has an important role in participation in the final stage of cell division, and cell cycle progression. CEP55 and Cyclin D1 expressions were detected in several tumors but their prognostic and predictive roles in epithelial ovarian carcinoma (EOC) are still studied. Aim of the study was to explore tissue expressions of CEPP55 and Cyclin D 1 in EOC correlating their expression with pathological, clinical and prognostic parameters. Methods: CEP55& Cyclin D1 expressions were evaluated in tissue biopsies that are retrieved from 60 cases of epithelial ovarian carcinoma using immunohistochemistry, patients that were followed up for 3 years. The relationship between their level of expressions and degree of differentiation, spread of the tumor, disease recurrence, response to therapy and survival were studied. Results: CEP55 expression in EOC was positively correlated with loss of differentiation of the tumor, presence of L.N (p<0.001), and distant metastases (p=0.012) & advanced stage of the tumor (p=0.007), cyclin D1 expression in EOC was positively correlated with loss of differentiation & advanced stage of the tumor, presence of L.N (p<0.001), and distant metastases (p=0.009). CEPP 55& Cyclin D1 were positively correlated with each other. Low CEPP 55& Cyclin D1 expressions were strongly correlated with optimal surgical eradication of the tumor, increased 3-year overall survival (OS) and low incidence of tumor recurrence after therapy (P <0.001). Conclusion: High levels of expression of CEPP 55& Cyclin D1and are markers of poor prognosis in EOC patients. Keywords: CEP55, Cyclin D1 epithelial ovarian carcinoma, immunohistochemistry; prognosis

    Time:

    Title: The Pharmacological Ascorbate as Adjuvant Cancer Therapy

    Nina Mikirova
    Director of research, Riordan Clinic, Wichita, KS, USA.

    Biography
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    Biography

    Nina Mikirova
    Director of research, Riordan Clinic, Wichita, KS, USA.

    Dr. Mikirova is director of research at the Riordan Clinic. After 15 years as the senior researcher at the Institute of Bio-Medical Problems in Russia, she joined the Riordan Clinic in 1997. Her efforts have included in vitro studies, animal studies, pharmacokinetic analyses, and clinical studies. She has published numerous articles including more than 50 in the area of the translational cancer medicine and 50 articles in the field of bio-medical aspects of radiation. Her areas of research focus include: effect of high dosage intravenous vitamin C on inflammation, cytokines, angiogenesis, gene expression and viral infection; potential of using high dose IVC alone or as the adjuvant therapy to treat cancer; and energy metabolism and functioning of mitochondria in cancer and normal cells.



    Abstract
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    Abstract

    Nina Mikirova
    Director of research, Riordan Clinic, Wichita, KS, USA.

    The use of ascorbate in oncology has long been passionately debated. Vitamin C has been shown to protect against oxidant injury at physiological concentrations and has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at pharmacological levels. We presented the summary of our and other researchers’ studies that has included in vitro and animal experiments, pharmacokinetic analyses, clinical trials and analysesof the effect of ascorbic acid in monotherapy and as adjuvant of conventional therapy in the treatment of cancer patients. The rationales for using high-dose ascorbate infusions to treat cancer can be summarized as follows: high dose vitamin C is preferentially toxic to cancer cells, inhibits angiogenesis, improves patient well-being, decreases the markers of inflammation and tumor growth and reduces the side effects of chemotherapy. Clinical studies are ongoing in pancreatic cancer, ovarian cancer, prostate cancer and several types of other cancers. Ascorbate has the advantage of being low-toxic, which is now well documented by more than 10 clinical trials. Its efficacy has been demonstrated in preclinical and clinical trials when paired with standard radiation and chemotherapy regimens. Clinical studies of chemotherapy with vitamin C demonstrated that intravenous vitamin C (IVC) does not interfere with anti-tumor effects of chemotherapy. IVC may improve time to relapse, enhance reductions in tumor mass and improve survival in combination with chemotherapy. IVC treatment improves quality of life, physical function, and toxicities associated with chemotherapy. The mechanisms underlying the preferential toxicity of vitamin C in cancer cells are not well understood. Several mechanisms are proposed that include the alterations of redox balance and cell metabolism, downregulation of several gene expressions that are involved in cancer proliferation, survival and angiogenesis, boosting immune system, strengthening the collagen structure, and inhibition of hyaluronidase. Available data provide a solid scientific rationale for the continued investigation of parenteral ascorbate as a chemotherapeutic agent.

    Sessions:
    Scaffold in Regenerative Medicine & Advances in Stem Cells and Regenerative Medicine & Nanofibers/ Nanomedicine in Regenerative Medicine

    Time:

    Title: Development of a 3D Cell Culture Model Based on Biocompatible Polymeric Scaffolds Engineered with Human Mesenchymal Stromal Cells (Mscs) for Skin, Cartilage and Bone Regenerative Therapy

    Russo Domenico
    University of Brescia, Italy.

    Biography
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    Biography

    Russo Domenico
    University of Brescia, Italy.

    Professor Russo Domenico obtained (1982) M.D. (Summa cum Laude), University of Bologna School of Medicine, Italy. In (1985-1989) he was a Post-PhD Researcher, Institute of Hematology “L. and A. Serŕgnoli”, University of Bologna, Italy. In (1991-1993) gained Fellowship in Hematology, University of Paris, France. In (1990-2001) he became Assistant Professor in Division of Hematology, University of Udine, Italy. In 2001 Professor Associate, Head of Chair of Hematology, University of Brescia, Italy. And from 2004-present is the Head of Unit of Blood Diseases and Stem Cells Transplantation, Spedali Civili of Brescia, Italy. Also in (2011) is a Full Professor, Head of Chair of Hematology at University of Brescia, Italy. His area of interest - Prognosis and therapy of Chronic Myeloid Leukemia, Therapy of acute leukemias, lymphomas and myeloma, Stem cell biology and transplantation. Is the author of more than 180 peer reviewed scientific papers, Speaker in many National and International Congress.



    Abstract
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    Abstract

    Russo Domenico
    University of Brescia, Italy.

    Regenerative medicine aims to restore normal function by repairing or replacing damaged cells and tissues in patients. The efficacy and the success of regenerative medicine depends on many factors including the manner by which the cells are organized in the new tissue that must be able to mimic the structure and function of the original one. Current treatments for articular cartilage damage, bone defects and skin lesions are quite challenging and they show limited repair and regeneration following injury. This project aims at developing an innovative 3D cell culture model composed of Mesenchymal Stromal Cells (MSCs) and biocompatible, safe, resorbable, polymeric scaffolds for studying the mechanisms involved in tissue repair and treatment of chronic skin conditions, cartilage defects and bone lesions. For this purpose, hydrogel-forming polymers scaffolds of natural origin were firstly characterized for their mechanical and morphological properties, stability and degradability. Secondly, MSCs were seeded on these scaffolds and optimal culture conditions for MSCs expansion were defined. Preliminary results suggest that hydrogel scaffolds seem to be an optimal model to host MSCs. Currently, we are exploring the effects of scaffolds on modulating MSCs behaviour, in particular in the matter of how scaffolds can affect MSCs proliferation and differentiation. Moreover, efforts are being made to implement this 3D culture system with autonomous sensors in order to have an objective way to monitor tissue restoration. This project will provide new useful insights to define novel innovative therapeutic approaches, thus making this research translatable within the clinical scenario.

    Time:

    Title: RGTA Based Matrix Therapy in Regenerative Medicine: An Example of Translational Medicine from Concept to Curing Patients

    Denis Barritault
    President of OTR3, France.

    Biography
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    Biography

    Denis Barritault
    President of OTR3, France.

    Denis Barritault graduated in Physics, completed his PhD in biochemistry in Paris University. Post doctoral in molecular immunology at Pasteur Institute and NYU as NIH Fogarty Fellow he joined INSERM unit in Paris as developmental biologist. He made the first description and patents of FGF extracted from retina in 1979 and 82 as skin and cornea healing agent, became full professor at Paris-Est University in 1985, founded and directed a CNRS Laboratory on cell and tissue regeneration until 2003. He is now President of OTR3, Emeritus professor, honorary director of CRRET laboratory, a CNRS unit and author in over 200 publications and 30 patents



    Abstract
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    Abstract

    Denis Barritault
    President of OTR3, France.

    The importance of extracellular matrix (ECM) integrity in maintaining normal tissue function is highlighted by numerous pathologies and situations of acute and chronic injury associated with dysregulation or destruction of ECM components. Heparan sulfate (HS) is a key component of The ECM, where it fulfils important functions associated with tissue homeostasis. Its degradation following tissue injury disrupts this delicate equilibrium and may impair the wound Healing process: ReGeneraTing Agents (RGTA®s) are polysaccharides specifically designed to replace degraded HS in injured tissues. The unique properties of RGTA® (resistance to degradation, binding and protection of ECM structural and signalling proteins, like HS) permit the reconstruction of the ECM, restoring both structural and biochemical functions to this essential substrate, and facilitating the processes of tissue Repair and regeneration: Furthermore, combined with cell therapy, RGTA® will participate in the regeneration process by providing a niche for cell homing. Several polymers have been tailored for specific tissues. Here, we review 25 years of academic and company research surrounding this HS mimic, supporting the mode of action, pre-clinical studies and therapeutic efficacy of RGTA® in the clinic. With over 50 000 patients treated for the first two products on the market, for skin and cornea injury, with randomized controlled trials supporting the first pilot studies and with a pipeline for several RGTA® based product and an example of translational research from academy to industry

    Time:

    Title: Advances and Challenges in the Therapeutic Use of Perinatal Stem Cells to Treat Degenerative Diseases

    G Rasul Chaudhry
    Oakland University, USA.

    Biography
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    Biography

    G Rasul Chaudhry
    Oakland University, USA.

    G. Rasul Chaudhry, Ph.D., Professor of Molecular Biology and Co-Director, Oakland University William Beaumont Institute for Stem Cell and Regenerative Medicine, Oakland University, USA. Professor Chaudhry’s research focuses on the molecular regulation of genes involved in stemness, potency, and differentiation of embryonic, adult and perinatal stem cells. He is also interested in tissue bioengineering, mechanisms of diseases processes, public cord banking, stem cell-based therapeutic applications, biomaterials, toxicology, and drug discovery. Dr. Chaudhrys research has been funded by organizations such as National Science Foundation, USDA, USEPA, Beaumont Health, St. John Providence hospital, Michigan Head and Spine Institute. He published numerous original and review papers on a wide variety of research problems and recently on stem cells. He serves as a reviewer or member on the editorial board of various journals as well as on advisory review panels of national and international funding agencies.



    Abstract
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    Abstract

    G Rasul Chaudhry
    Oakland University, USA.

    Perinatal tissues are non-invasive, primitive and abundant sources of stem cells (SCs) that have increasingly gained attention since they do not pose any ethical or moral concerns. Current methods to isolate SCs from these perinatal sources yield low amounts of cells with variable proliferation potential. We have investigated the properties of SCs isolated from cord blood (CB), discrete regions of umbilical cord (UC) such as cord lining (CL), Wharton’s jelly (WJ), and cord-placenta junction (CPJ), chorion (CH) and fetal placenta (FP). CB had predominantly two types of SCs, adherent mesenchymal stromal/stem cells (MSCs), and non-adherent hematopoietic stem cells (HSCs). HSCs were CD 34+ and were negative for MSC surface markers. The isolated cells from all other sources were adherent MSCs. All MSCs had fibroblastoid morphology and were CD29+, CD44+, CD73+, CD90+ and CD105+ similar to that of the bone marrow (BM) derived MSCs. We then investigated the therapeutic potential of MSCs to treat degenerative diseases such as degenerative disc disease (DDD) and retinal degenerative disease (RDD) using animal models. MSCs and their chondrogenic derivatives significantly improved the histology, cellularity, extracellular matrix protein, and in water and glycosaminoglycan contents in IVDs recipient of chondroprogenitors (CPCs) or NP-like cells (NPCs). The transplanted cells were functionally active as they expressed human genes and proteins, SOX9, ACAN, COL2, FOXF1, KRT19, PAX6, CA12 and COMP implicated in NP biosynthesis. These studies suggested involvement of TGFβ1 pathway in regulating NP regeneration. Therapeutic potential of UC-MSCs to treat DDD and other degenerative diseases as well as the challenges and new opportunities will be discussed in the presentation.

    Time:

    Title: A New Polylipoic Acid-Based Nano-Platform for Heart Diseases Treatment

    Chiara Castellani
    University of Padua, Italy.

    Biography
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    Biography

    Chiara Castellani
    University of Padua, Italy.

    Chiara Castellani, Assistant Professor in Technical Sciences of Laboratory Medicine. University teaching of Cyto and histopathological diagnosis and part of courses of Pathological Anatomy. Ph.D. in Cardiovascular Pathology (2007) achieved thanks to a research on Cardiac and non-cardiac stem cells in heart transplant and cardiac hypertrophy remodelling. She completed her Specialty training in Clinical Biochemistry (March 2013). She has been visting research fellow at the Washington University in Seattle, WA (2006), where she worked under the supervisor ship of prof. Charles Murry on the heart remodeling and stem cells. Research lines: i) stem cells and cardiac remodelling; ii) stem cells and cardio renal syndrome; iii) cardiac amyloidosis; iv) cardiac allograft vasculopathy; v) exosomes and miRNA in heart and kidney transplantation The outcome of her research was presented through oral presentations and posters during many national and international meetings. She had published papers in international ISI journals and one book chapter (HI=11 and citations)



    Abstract
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    Abstract

    Chiara Castellani
    University of Padua, Italy.

    Nanomedicine, that is the application of nanotechnologies to medicine, attracts an enormous interest. The aim of this study is to evaluate the safety, feasibility and biocompatibility of a new polylipoic acid-based nano-platform (NPs) for heart diseases treatment. Material and Methods: The lipoic acid polymerization reaction developed by Matile et al. has been used to create highly cross-linked polymeric nanoparticles. Dimeric and trimeric derivatives of lipoic acid with different spacers have been synthesized and used to produce surfactant stabilized nanoemulsions. Thiol-initiated polymerization of the microemulsions have been lead to the formation of a highly reticulated polymeric nanostructure. Loading of active molecules (such as rhodamine) has been obtained either by entrapment or by copolymerization of appropriate lipoic acid derivatives in the nanoparticle matrix. HeLa cells, Raw 264.7 cells, purified human leukocytes and human monocyte-derived. Macrophages were incubated with different concentrations of nanoparticles (up to 200 µg/ml) for 24h hours, the vitality was assessed by MTS assay and the association of NPs to the cells was assessed by cytofluorimetry. Red blood cells, purified by buffy coats of healthy donors, were incubated for 24h with different concentrations of nanoparticles (up to 200 µg/ml) and then the possible lysis of the red blood cells has been monitored by the release of hemoglobin measured at 540 nm. 18 male health Sprague-Dawley rats were injected with 10mg/Kg of NPs via vein tail. 7 male health rats were taken as controls. Rats were sacrificed 1hour, 3 hour, 24 hours 3 and 7 days after NPs injection and blood and organs were collected. Section of 2mm of lung, heart, liver, kidney and spleen were analyzed by Alliance 2.7 3D software to identify and quantify NPs-rhodamine conjugated. NPs localization in tissues was identify by confocal microscopy. Results: We found that in vitro this new polylipoic acid-based nano-platform didn’t exert any toxicity towards all the different cell types we used, even at high concentrations (200 µg/ml); NPs associate at low levels to all the tested cells, but they are captured by human macrophages at high levels. Moreover, NPs didn’t induce red blood cell lysis.. In vivo, NPs fluorescence was identify immediately after injection in the heart. Moreover the heart was able to retain the NPs until 7 days after injection. The heart demonstrated to have a low clearance of NPs. Liver and kidney showed NPs fluorescence clearance at 3h after injection. Confocal microscopy showed that NPs are localize in the interstitium of organs and in the endothelial cells. NPs did not show any toxicity in the rats. Conclusion: Heart is able to retain NPs injected in blood flow for up to 7 days without evident negative side effects. These preliminary data suggest that this new nano-platform formulation could be used to target heart diseases and for therapeutic drug delivery.

    Sessions:
    Cancer Research and Regenerative Medicine & Cell & Gene therapy

    Time:

    Title: Treatment of Diabetes and Obesity with CRISPR-Mediated Genome Editing In Epidermal Progenitor Cells

    Xiaoyang Wu
    The University of Chicago, USA.

    Biography
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    Biography

    Xiaoyang Wu
    The University of Chicago, USA.

    Xiaoyang Wu received his PhD in 2000-2006 from Cornell University. He was a post doctorate fellow from Rockefeller University, in 2006-2011. From 2011-present, is an Assistant Professor at University of Chicago, USA.



    Abstract
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    Abstract

    Xiaoyang Wu
    The University of Chicago, USA.

    Somatic gene therapy with current genome editing technology provides a promising therapeutic approach for treatment of a variety of otherwise terminal or severely disabling diseases. The human skin is a tempting target for genetic engineering as it is the biggest and most accessible organ in our body. Moreover, skin epidermal stem/progenitor cells are easy to obtain and expand in vitro, and extraordinary advances have been made in the development of epidermal autograft or tissue-engineered skin equivalents for permanent skin regeneration in clinics. In this report, by combining CRISPR-mediated genome editing with epidermal progenitor cell platform, we develop skin graft with controllable release of GLP1 (glucagon-like peptide-1), a critical incretin that regulates blood glucose homeostasis, and demonstrate its therapeutic effect in vivo by reducing glycemic excursions in diet-induced obese and diabetic mice. Taken together, our study lays the essential groundwork for development of long-lasting and safe gene therapy approach for combating obesity and diabetes, and unravels the clinical potential for genome editing in skin epidermal progenitor cells.

    Time:

    Title: Development of Processing Strategies and Novel Hardware for Cell Therapy Production Processing

    Farlan Veraitch
    University College London, United kingdom

    Biography
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    Biography

    Farlan Veraitch
    University College London, United kingdom

    Farlan Veraitch gained his Ph.D. from the University of Birminham where his research focused on the optimisation of mammalian cell culture processes. He then moved to UCL where he worked as a Post Doctoral Research Assistant on the automation of embryonic stem cell processing. Since gaining his lectureship, and subsequent senior lectureship, Farlan has helped to establish the UCL's Cell Therapy Bioprocessing programme which has been applying ultra scale-down, bioprocess modelling and a whole bioprocess vision to the development of robust stem cell production processes.



    Abstract
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    Abstract

    Farlan Veraitch
    University College London, United kingdom

    Farlans talk will focus on the development of robust, reproducible and cost effective production processes in the emerging field of cell therapy. His team are establishing novel processing technologies which will underpin the commercialisation of these types of products. Their work uses a whole bioprocessing and ultra scale-down methodologies pioneered at UCL to ensure that new production process are considered as whole rather than individual operations in isolation. Farlans group are developing new methods for the majority of steps involved in the production of cellular therapies. Current projects include the application of bioprocessing methodologies to (i) the expansion of stem cells, (ii) their directed differentiation into regenerative populations, (iii) the non-destructive dissociation of differentiated cellular aggregates into single cell suspensions, (iv) purification techniques for positive selection and (v) point-of-care processing which includes cryopreservation, shipping, thawing, washing and presentation of the final therapy ready for administration.

    Time:

    Title: Potential Anti-Colon Cancer Effect of LTC4 through the Induction of 15-PGDH

    Shakti Ranjan Satapathy
    Lund University, Sweden.

    Biography
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    Biography

    Shakti Ranjan Satapathy
    Lund University, Sweden.

    Shakti Ranjan Satapathy is a postdoctoral researcher at Department of Translational Medicine, Lund University, Sweden where he studies the role of Cysteinyl leukotriene receptors in metastasis of colon cancer. He started his postdoctoral research at Purdue University, USA where he studied the role of novel kinases as potential therapeutic targets for prostate cancer and Alzheimer’s disease. He had received his PhD in Cancer nanotechnology in 2015 from KIIT University, India. Apart from his curiosity in life sciences, he is very fond of physics and world history. He is committed to advance our understanding about cancer and making the world a better place.



    Abstract
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    Abstract

    Shakti Ranjan Satapathy
    Lund University, Sweden.

    Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Cyclooxygenase-2, having a key role in the biosynthesis of prostaglandin E2 (PGE2), is often up-regulated in CRC. PGE2 induces angiogenesis and tumor cell survival, proliferation and migration. The tumor suppressor 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a key enzyme in PGE2 catabolism, converting it into its inactive metabolite 15-keto-PGE2 and is often down-regulated in cancer. Interestingly enough, CRC patients expressing high levels of Cysteinyl leukotriene receptor 2 (CysLTR2) have good prognosis and therefore, we investigated a potential link between CysLTR2-signaling and the tumor suppressor 15-PGDH in colon cancer cells. We observed a significant up-regulation of 15-PGDH after LTC4 treatment, the ligand for CysLTR2, in colon cancer cells, on both mRNA and protein levels, which could be reduced by a CysLTR2 antagonist or a JNK inhibitor. LTC4 induced 15-PGDH promoter activity via JNK/AP-1 phosphorylation. Furthermore, we also observed that LTC4 via CysLTR2/JNK-signaling pathway increased the expression of the differentiation markers sucrose isomaltase and mucin-2 in colon cancer cells. Restoration of 15-PGDH expression through CysLTR2-signaling promotes differentiation of colon cancer cells, indicating an anti-tumor effect of CysLTR2-signaling.

    Time:

    Title: Identification of T-Complex Protein 1 as a Novel Regulator of the Store-Operated Calcium Channel Orai1 Abundance at the Plasma Membrane

    Rawad Hodeify
    American University of Ras Al Khaimah, UAE.

    Biography
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    Biography

    Rawad Hodeify
    American University of Ras Al Khaimah, UAE.

    Dr. Rawad Hodeify earned his Ph.D. in Interdisciplinary Biomedical Sciences from the University of Arkansas for Medical Sciences, USA, in 2011, and M.S. in Biology from American University of Beirut, Lebanon. He received research training as postdoctoral fellow in Internal Medicine department at University of Arkansas for Medical Sciences and Weill Cornell Medicine before recently joining American University of Ras Al Khaimah as an Assistant Professor of Medical Biotechnology. His research work is focused on regulation of calcium signaling pathways during cellular development and differentiation and dissecting the crosstalk between cycle cell proteins and cell death pathways in kidney injury.



    Abstract
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    Abstract

    Rawad Hodeify
    American University of Ras Al Khaimah, UAE.

    Intracellular calcium (Ca2+) is a key signaling molecule. Store operated calcium entry (SOCE) is a fundamental Ca2+ influx pathway at cell membrane activated in response to intracellular Ca2+ store depletion. The SOCE machinery consists of ER-localized Ca2+ sensor, STIM1, and a Ca2+ selective channel at plasma membrane (PM), Orai1. At steady state, 40% of the total Orai1 protein pool localizes to PM while Orai1 cycles rapidly between PM and intracellular compartments. We discovered that a significant population of intracellular Orai1 pool localizes to a novel sub-PM vesicular compartment. Store depletion results in significant enrichment at PM. To identify Orai1-interacting proteins enriched in sub-PM vesicular compartment, we followed a quantitative proteomic analysis approach. TCP-1 (T -complex protein 1) was identified to be associated with Orai1 in sub-PM vesicular compartment. To functionally assess the role of TCP -1 in Orai1 sub-cellular localization, we knocked down TCP-1 in stable YFP-HA-tagged Orai1 CHO cells using RNA interference. Our data showed significant increase in surface Orai1 upon TCP-1 knockdown. Furthermore, we generated a mutant Orai1 in which the TCP-1-binding homologous region in the intracellular loop was scrambled. This mutant showed decrease binding to TCP-1, and 30% increase in surface Orai1. More importantly, the scrambled Orai1 mutant, when co-expressed with STIM1, showed faster TG-induced puncta formation, increased decay time after ATP-induced SOCE, and faster SOCE-dependent NFAT1 translocation. In summary, using an unbiased proteomics approach we successfully identified TCP-1 as a novel regulator of Orai1 abundance at PM. Disruption of TCP-1-Orai1 binding resulted in higher plasma membrane residence, faster puncta formation, and faster SOCE development. TCP-1, therefore, plays a key role in Orai1 residence at PM and controlling SOCE and intracellular Ca2+. These results demonstrate that TCP-1 is a novel regulator of Orai1 PM residence and activity, and introduce new directions for design of novel therapeutic strategies targeting SOCE.

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