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  Jan Zeromski / Poznań University of Medical Sciences, Poland

  Title: Pattern recognition receptors (PRRs) and cancer: are friends or foes?

  Abstract

  PRRs agents of innate (nonspecific) immunity phylogenetically old, dispersed widely in animal kingdom, in all vertebrates and in some invertebrates. They are expressed on several normal and neoplastic cell types, predominantly on cell surface but also in cell interior. The comprise of at least six families, such as Toll-like receptors (TLRs), NOD-like receptors (NLR) RIG-1 like receptors (RLRs), cGAS-STING and other, each having a number of sensors able to recognize various organic compounds. In the case of cell infection some PRRs can “see” pathogen molecules dispensable for their growth and spreading such as glycolipids, LPS, carbohydrates and other but absent in higher animals. Following their recognition complex cell biochemical events take place leading to the formation in cytoplasm transcription factors which penetrate cell nucleus and induce DNA transcription with subsequent production of several proinflammatory cytokines, up regulation of MHC antigens etc. The engagement of PRRs in cancer is multifactorial in dependence from PRR family, tumor type and its stage of progression. Toll-like receptors rather promote tumor growth, via binding ligands (agonists) on tumor cells. In contrast, RLRs and cGAS-STING sensing tumor nucleic acids are usually inhibitory. The latter have been promising in virally induced tumors. Artificial, man-made ligands of TLRs were found to inhibit tumor growth and now some o0f them are being used in anti-tumor therapy (for example, imiquimod, TLR7 ligand in skin cancer). PRRs anti-cancer therapy has some advantages and disadvantages. The former include lack of immunosuppression, relatively few unwanted effects and usually good patient’s adherence. The latter harbor potential risk of tumor promotion, relatively high cost of treatment and, so far modest number of cancers already classified to such therapy. Thus, PRRs at present day may be named a “double edge sword”, able, both, to promote and inhibit malignant growth.
  
  

  Biography

  Jan Zeromski has completed his MD and PhD from Poznan University of Medical Sciences, Poznan, Poland. He performed his postdoctoral studies at Glasgow University, Dept Immunology, Glasgow Scotland U.K. and at Stockholm University, Wenner Gren Institute, Immunology Dept., Stockholm, Sweden. His research interests include immunopathogenesis of human cancer and, in particular, the events within local tumor microenvironment. Currently, he is a retired professor at the Chair of Clinical Immunology of Poznań University of Medical Sciences, Poznań, Poland.
  
  

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  Michael W Retsky / Harvard School of Public Health, USA

  Abstract

  
  
  

  Biography

  Michael Retsky completed his PhD in experimental physics from University of Chicago in 1974. He was doing physics research at Hewlett-Packard in Colorado Springs. After a friend’ s wife was diagnosed with cancer, an informal research group began that eventually captured Retsky’ s interest more than physics. He made a career change to cancer research in 1982. He was Prof of Biology at University of Colorado and Visiting Prof at University of Texas- San Antonio. He is now on staff at HSPH and has a small business start-up focusing on late relapses. He has two patents pending.
  
  

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  Donald Lannin / Yale University, USA

  The Myth of Early Diagnosis of Breast Cancer

  Abstract

  Dr. Lannin will review the concept of early detection of breast cancer as it has evolved and been operationalized over the past four decades. He will review the principles of overdiagnosis, lead time bias, and length time bias and put the benefit of early detection in a realistic perspective. Most importantly he will show how changing knowledge about breast cancer biology is impacting not only our diagnostic and treatment algorithms but also our understanding of the limitations of early detection. He will illustrate how tumor biology has been incorporated into the latest AJCC staging manual for cancers. Many of the concepts discussed regarding breast cancer will also be applicable to other cancer types. Hopefully the talk will stimulate discussion and allow the attendees to appreciate the importance of all the biologic discoveries that will be presented at the conference.
  
  

  Biography

  Dr. Lannin did his undergraduate work at Stanford University and then received his MD and residency training in General Surgery at the University of Minnesota. For 20 years he was on the faculty of the Brody School of Medicine at East Carolina University, where he was Director of the Leo W. Jenkins Cancer Center. In 2002 he joined the faculty at Yale University School of Medicine as Professor of Surgery, and he was Director of the Yale Breast Center until 2011.
  
  

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  Denis Larrivee / Loyola University Chicago, USA

  | Integrating System Performance: The Motor Image in Autonomous Action

  Abstract

  Living systems are distinctive for their unity of action and autonomy in behavior. How these properties are integrated is unknown but in higher organisms key influences likely center on motor plans that are autonomously executed on behalf of a coded, neural self representation. This concept of self, evoked when the body is dynamically engaged in intentional action, has been traced to the notion of the motor image, a covert action sequence undertaken only mentally and so simulating a non-executed action. A critical requirement of the motor plan is that of framing motions in the context of an agent, where the body is appropriated as an origin of action emergence. Embodied, motor actions propel the consumption of free energy reserves needed to sustain organismal operation in its entirety thereby driving global integration. As a global determinant of integration free energy influences track energy use homeostatically and are motivationally agnostic with respect to goal selection suggesting a non-specific influence on integration. Numerous studies indicate, on the other hand, that the motor plan is teleologically oriented, linking the agent to an objective terminus. These studies suggest that representations of body posture are likely to be an important proxy for the global and neural self-representation in dynamic actions and are likely to be directly modified by goal specific content. Significantly, goal specific information does not appear to be contained in action identification processes of the motor plan but instead to be bound to the postural representations, where decisional acts mediate integration of motor behavior in the context of specific goals. Notable candidate influences for goal related modulation likely include egocentric coding in the posterior parietal and pre motor cortices that shape self representations to integrate goal directed motor movement. Neural correlates for behavioral integration are thus likely to include two separate and independently staged global mechanisms: a) a non-specific, bottom up influence associated with enhancing energy efficiency, and b) a goal specific, top down influence that is autonomously executed.
  
  

  Biography

  Dr. Denis Larrivee is a Visiting Scholar at the Mind and Brain Institute, University of Navarra Medical School and Loyola University Chicago and has held professorships at the Weill Cornell University Medical College, NYC, and Purdue University, Indiana. A former fellow at Yale University's Medical School he received the Association for Research in Vision and Ophthalmology's first place award for studies on photoreceptor degenerative and developmental mechanisms. He is the editor of a recently released text on Brain Computer Interfacing with InTech Publishing and an editorial board member of the journals Annals of Neurology and Neurological Sciences (USA) and EC Neurology (UK). An International Neuroethics Society Expert he is the author of more than 70 papers and book chapters in such varied journals/venues as Neurology and Neurological Sciences (USA), EC Neurology (UK), Journal of Neuroscience, Journal of Religion and Mental Health, and IEEE Explore. In 2018 he was a finalist in the international Joseph Ratzinger Expanded Reason award.
  
  

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  Sasha Shafikhani / Rush University Medical Center, USA

  | Apoptotic Compensatory Proliferation Signaling and its Implication in Tumor Biology and Cancer Therapy

  Abstract

  Apoptosis, in addition to its role in programmed cell death (PCD), has also been implicated in triggering Compensatory Proliferation Signaling (CPS) -- whereby dying cells induce proliferation in neighboring cells as a means to restore homeostasis. To date, the molecular components, the nature of signaling, and the underlying mechanism of CPS remain largely unknown. Recently, we demonstrated that Pseudomonas aeruginosa Exotoxin T (ExoT) induces potent apoptosis in a variety of highly metastatic and resistant tumor cells in vitro and in vivo. We demonstrated that ExoT induces two distinct forms of apoptosis. Through its GTPase Activating Protein (GAP) domain activity, it induces caspase-9-dependent intrinsic apoptosis, while through its ADP-ribosyl transferase (ADPRT) domain, it disrupts integrin survival, causing anoikis apoptosis. During these studies, we have discovered that a fraction of apoptotic cellsgenerate and release CrkI-containing microvesicles, in vitro and in vivo, which are capable of inducing compensatory proliferation in neighboring cancer cells upon contact by activating JNK. For the first time, we provide visual evidence of CPS and show by live videomicroscopy how CrkI-containing microvesicles are generated and how they induce proliferation in other cancer cells upon contact.Our Scanning Electron Microscopic (SEM) and Differential Interference Contrast (DIC) imaging as well as our proteomics and biochemical data indicate that ACPSVs are distinct from apoptotic bodies and exosomes.We further provide evidence that inactivating CrkI by ExoT or by mutagenesis blocks vesicle formation and inhibits CPS in apoptotic cells, thus uncoupling CPS from apoptosis. we show that these vesicles are also present in various tumors resected from human cancer patients. Given that majority of existing cancer cytotoxic therapeutics destroy tumor cells by apoptosis, CPS could significantly limit their effectiveness, contributing to the disappointing outcomes associated with therapeutic agents against cancer. Understanding the mechanism of CPS could lead to the development of novel targeted therapies that improve the effectiveness of current cancer therapies by inhibiting CPS.
  
  

  Biography

  Dr. Shafikhani is an Associate Professor in the Department of Medicine, Division of Hematology, Oncology, and Cell therapy at Rush University Medical Center. Dr. Shafikhani’s group is interested in understanding how the presence of tumor and infection lead to a state of immune-confusion affecting both anti-tumor and anti-bacterial immune defenses. His group is also interested in developing bacterial toxins as effective anti-cancer therapeutics. His group is also interested in innate immune dysregulation that renders diabetic wounds vulnerable to infection.
  
  

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  Katharina Pachmann / SIMFO GmbH and Transfusion Medical Laboratory Bayreuth, Germany

  | Trajectories of Circulating Tumor Cells during Diagnosis and Therapy and theImpact of Circulating Cancer Stem Cells Reflected by the Growth of Tumorspheres

  Abstract

  Tumor cells are shed into the circulation not only during growth of malignant tumors but also during diagnostic procedures such as mammography and biopsy and therapeutic actions such as preoperative chemotherapy and surgery. Inflammation due to wound healing and radiation can fuel the growth of these cells reflected by an increase in the number of the circulating tumor cells which has been shown to be highly significantly correlated to subsequent distant relapse. However, it is assumed that not all tumor cells have the capacity of dividing but that this property is restricted to few cells in a tumor called tumor stem cells or tumor initiating cells. Certain properties are ascribed to these cells such as a certain pattern of marker expression including stem cell markers. We have succeeded in growing a subpopulation from peripherally circulating tumor cells, circulating tumor stem cells, into Tumorspheres and shown that they express typical stem cell properties. In addition in some cases we were able to further grow these Tumorspheres into small tumors on chorion allantois membranes of chicken eggs. The Tumorspheres can also be tested for their sensitivity to different drugs. It can be shown that drugs which are highly effective to single circulating tumor cells are less effective in killing tumor spheres but that some drugs among them Curcuma are also effective against the cells in the Tumorspheres. This provides an additional test for drug sensitivity.
  
  

  Biography

  Prof. Dr. Katharina Pachmann is Senior Researcher at Transfusion Center Bayreuth, Germany since 2012. She is the Head of Marketing Oncology CTCs at SIMFO GmbH. She received her PhD from Institute for Hematology der GSF, München; Medical Clinic, Klinikum rechts der Isar, München; Medical Clinic, Klinikum Innenstadt der Ludwig-Maximilians Universität, München respectively. She also served as the Head of the Department of Experimental Hematology and Oncology, Friedrich Schiller-Universität Jena. She is visiting scientist at LKH Universitätsklinikum Graz Gemeinsame Einrichtung für Klinische Immunologie, Jean-Dausset Laboratorium. She has also served as a Visiting Scientist in MD Anderson Cancer Center Houston Texas Section of Molecular Hematology and Therapy from 1996-1998.
  
  

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  University of Applied Science Emden Leer, Germany / University of Applied Science Emden Leer, Germany

  | Reduction of Pathogenic, Antibiotic Resistant Bacteria by Advanced Wastewater Treatment Technologies

  Abstract

  Reduction or elimination of bacteria by advanced wastewater treatment technologies like ozonation in combination with adsorption onto activated carbon or slow sand filtration is a possibility for improvement of the quality of treated sewage and for reduction of the potential risk for human health and of receiving surface waters. The reduction/elimination of sewage bacteria derived from different wastewater treatment plants was determined by analyzing the concentration in a culture-based and quantitative PCR approach. The content of Escherichia coli, enterococci and staphylococci and their resistance against selected antibiotics was measured. For enterococci, single species were identified and their antibiotic resistances were determined. The influences of ozonation on viability of selected species were simulated under laboratory conditions. In comparison to the standard wastewater treatment process, ozonation plus adsorption onto activated carbon and/or sand filtration reduced the concentrations of total and antibiotic resistant E. coli, enterococci and staphylococci. However, antibiotic resistant E. coli and staphylococci apparently survived ozone treatment better than antibiotic sensitive strains. The decreased percentage of antibiotic resistant enterococci after ozonation may be the result of a different ozone sensitivity of different species. Enterococcus faecium and Enterococcus faecalis, which determined the overall resistance-level, seemed to be more sensitive for ozone than other Enterococcus-species. Overall, ozonation followed by adsorption onto activated carbon or sand filtration led to 0.8-1.1 log-units less total and antibiotic resistant E.coli, enterococci and staphylococci. Advanced wastewater treatment after common sewage treatment is an effective tool for further elimination of microorganisms from sewage before discharge in surface waters.
  
  

  Biography

  Prof. Dr. Claudia Gallert is an environmental microbiologist with research experience since 25 years in the field of wastewater and waste treatment and antibiotic resistant bacteria in aquatic environments. She has published more than 60 papers in peer-reviewed journals and she is a member of different professional groups. In 2017 she got the Scientific Award of the Federal State of Lower Saxony.
  
  

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  Mariola Sliwinska-Kowalska / Nofer Institute of Occupational Medicine, Poland

  | Applicability of the Evotion Platform for Prognosis and Prevention of Noise Induced Hearing Loss

  Abstract

  Noise exposure through the lifespan is one of the main causes of hearing loss. Although fully preventable, the incidence of noise-induced hearing loss (NIHL) is still high, reaching about 18% of overexposed industry workers. One of the main goals of the ongoing “EVOTION” project is to develop decision and simulation models for public health policy making, related to hearing loss management. Models will be based on big data analytics and executed by the EVOTION platform. The concept of prognosis and prevention of NIHL in this project is based on predictive models of temporary threshold shift (TTS) and permanent threshold shift (PTS). TTS model relies on monitoring episodes of exposure to noise/sounds of loudness, which are sufficient to induce temporary (up to 16 hours) hearing impairment. PTS model predicts the risk of hearing loss after repetitive exposures, which occur over a period of several years, as per the ISO 1999:2013 standards. TTS and PTS models are verified in the population with normal hearing and in patients with impaired hearing using hearing aids (HA). In the latter case, sound/noise monitoring refers to sound pressure levels at eardrum transferred to free field conditions, which enables personalizing prediction of TTS episodes and PTS risk associated with ambient sounds processed by the HA device. EVOTION platform will enable creation of updated public health policies regarding the prevention of NIHL.
  
  

  Biography

  
  
  

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  Josef Winter / Karlsruhe Institute of Technology, Germany

  | Microbial Growth and Biofilm Formation in Water, Groundwater and the Capillary Fringe

  Abstract

  Soil and groundwater are naturallyinhabited by a vastvariety of prokaryotes. Itwasestimatedthat 2.5 x 1029 microorganisms live in the top 8 m of the terrestrialsubsurface and atleast 2.5 x 1030 microorganismsbelow 8 m depth, eithersuspended in the water phase or immobilizedas a biofilm on organic and mineralcompounds.Capillary fringes (CFs) form the interface between groundwater-saturated soil and the unsaturated underground and may be as thin as a few centimetres but can also span over more than one meter above the water table.Microbial life in the vadose zone (zone above permanent water saturation) requires adaptive strategies to cope with unfavorable conditions such as dryness, growth-limiting moisture content or inadequate supply of carbonaceous compounds and oxygenor other electron acceptors. Human activity may cause severe local pollution associated with surplus substrate supply, toxicity or other harmfull effects for the soil bacteria. As a consequence of the highly variable presence of water that is essential for bacterial growth and a variable supply of growth substrates, surface-attached growth and life in biofilms is an appropriate strategyfor survival. Biofilmformation in anoligotrophic, groundwater-saturated underground and in the capillary fringe (CF)above the water tableishowever a very slow process due to severe nutrientlimitation. Because of lowgroundwaterflow rates, non-motile and motilebacteriahavesufficient time to passively or activelyattach to mineralsurfacesatplaces or in the vicinity of a growth-supportingenvironment to form a stationary and permanentbiofilm. The thickness of a biofilmdepends on the continuity of nutrientsupply, the nutrientconcentration and the electron availability for aerobic, anoxic or anaerobicrespiration/fermentation. The formation of a biofilmmay cause changes in the flow behaviorof the groundwaterdue to narrowing of porediameters or changes of surfaceproperties of the overgrownsoilminerals. Bacteria in the biofilm at the surface of soil particles are surrounded by a thick layer of extracellular polymeric substances (EPS) which form a hydrogel. EPS functions as absorbant for nutrients and supplies moisture for the bacteria in the biofilm when the CF is dehydrated during long-lasting droughts with decreasing groundwater levels. Part if it may slowly be degraded when no ohter carbon sources are available. Harmless soil bacteria in biofilms of groundwater-saturated soil may mutate and get antibiotic-resistant when exposed to antibiotic resistence bacteria or antibiotic resistence genes that were found in polluted groundwater and are absorbed by EPS of biofilms.
  
  

  Biography

  Prof Dr. Josef Winter is achemist and microbiologist with researchexperienceof more than30years in the field of aerobic and anaerobicwastewater and waste treatment, soilremediation andgroundwaterpollution. He haspublished more than 100articles in peer-reviewedjournals and is amember of differentprofessionalNGOs.Since 2016 he isretiered.
  
  

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  KATM Ehsanul Huq / Hiroshima University, Japan

  | Consequence of Tuberculosis Stigma among the Bolgatanga Municipality People of Ghana

  Abstract

  Tuberculosis (TB) is the tenth leading cause of death in world-wide, especially in the developing countries and about 1.3 million people die each year. TB causes a lot of stigma among the adult population globally and makes people not to come forward because of fear of being rejected. This fear increases their chances of not being cured and leads to death. The objective of this study was to explore the experiences, perceptions and opinions about tuberculosis (TB) among the tuberculosis infected adult patients and community people who were not infected with TB. This is a qualitative study conducted in the community of Bolgatanga municipality of the upper east region of Ghana. Three focused group discussions (FGDs) were conducted from different groups: one with five TB-infected females, another with seven TB-infected males and the last one with six non-TB-infected participants. Data were analyzed using qualitative content analysis and presented in themes and sub-themes. We identified existence of stigma among the TB-infected patients and the community people. TB-infected male patients had more autonomy in decision making for getting treatment and other family matters compared to female TB patients. TB-infected women suffered more economic vulnerability and made the stigma worsening, they regarded as liabilities rather than assets. Non-TB-infected community participants didn’t support the TB patients due to fear of being infected, they became stigmatized. Our findings suggested to heighten advocacy, communication and social mobilization in the community people of Bolgatanga municipality to allay TB related stigma especially for the women.
  
  

  Biography

  KATM Ehsanul Huq is a doctoral student of Hiroshima University, Japan. He completed his masters from Uppsala University, Sweden, diploma from Swiss Tropical and Public Health Institute, Switzerland and medical graduation from Bangladesh. He worked at International Centre for Diarrhoeal Disease Research, Bangladesh (icddr, b) in different clinical researches specially vaccine trials, bioequivalence studies and drug development.
  
  

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  Yawo M Akrodou / Walden University, University of Maryland University College, United States

  | Impact of the Interactions of CYP2B6*6 and CYP2A6 Polymorphisms on the Treatment of Nicotine Dependence

  Abstract

  Introduction: CYP2B6 and CYP2A6 metabolize nicotine and are involved in nicotine dependence treatment. Although evidence suggests they may interact to influence nicotine dependence treatment outcome, in terms of nicotine dependence and withdrawal syndromes and therapy types (placebo, bupropion, and NRT), the significance of their interaction in nicotine cessation has not been fully substantiated and clarified. Methods: A total of 1862 individuals, consisting of Caucasians and African Americans were studied. Nicotine dependence and withdrawal syndrome scores were evaluated using the Fagerström Test for Nicotine Dependence (FTND) and Wisconsin Inventory of Smoking Dependence Motives (WISDM) scales, respectively. Participants were required to smoke at least ten cigarettes per day and underwent specific therapy types (placebo, NRT, or bupropion) over a 2-week period, and subsequently reported their quitting status at 6 months posttreatment. Participants were also screened for SNPs CYP2A6*1A (rs1137115), *1H (rs616636070),*4A (rs28399434), *9A (rs28399443),*12A (rs28399442), and CYP2B6*6(rs3745274) for nicotine genotype analysis. Results: Gene variants were uniformly distributed in the population with p-values > 0.05 based on the chi-squared test. Logistics regression analysis showed CYP2A6*4A was most significantly associated to the odds ratio (OR) of quitting smoking in each treatment group with nicotine dependence syndrome (OR = 1.61, 95% CI 1.31-1.96), and *4A in individuals with nicotine withdrawal syndrome (OR = 1.70, 95% CI 1.15-1.95). ANOVA test also showed a strong main interaction effect between CYP2B6*6, *1A, *4A, and *12A gene variants in the bupropion group. Conclusion: CYP2A6 and CYP2B6*6 may interact to increase the likelihood of a successful outcome of nicotine dependence treatment.
  
  

  Biography

  Mr. Yawo M Akrodou has completed his PhD from Medical Walden University Indianapolis Minnesota and M Sc. In Biotechnology and Bioinformatics from University of Maryland. His research interests include genetic predisposition in disease contraction, and genes impact in disease treatment. Currently, his Executive Director for Global Health Corresponder, and specializing in Global Health Diplomacy at Seton Hall University, and Applied Epidemiology at New York University.
  
  

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  Yusef Yacouba-Issa / Pharmaligent, USA

  | The Impact of Expanding Access to Preventative Care on the Incidence of Malaria in Niamey District 3, Niger

  Abstract

  
  
  

  Biography

  
  
  

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  Li-Pin Kao /

  | Chemotherapy selection pressure elicits marked alterations sphingolipid composition in acute myelogenous leukemia cells

  Abstract

  A comprehensive understanding of the molecular mechanisms underlying chemotherapy resistance in cancer is lacking. Although recent discoveries in sphingolipid (SL) metabolism have provided insight into the role of SL’s in cancer growth, less is known about their involvement in drug resistance. To expand knowledge in this area, we investigated the effects of chemotherapy selection pressure with cytarabine (Ara-C) and daunorubicin (dnr), drugs used to treat acute myelogenous leukemia (AML), on SL composition in the AML cell lines, HL-60. HL-60 cells resistant to vincristine (VCR), widely used in treatment of liquid and solid tumors, were also characterized. Cells selected for growth in chemotherapy-containing medium (HL-60/500 nM Ara-C; HL-60/400 nM dnr) demonstrated upregulated expression and activity of glucosylceramide synthase (GCS), acid ceramidase (AC), and sphingosine kinase 1 (SPHK1). Lipidomic analysis revealed marked decreases (>50%) in levels of dhSPH (dihydrosphingosine) and a general ceramide deficit in Ara-C and dnr-selected cells. Unique to only dnr selection was a profound upswing (25-fold) in levels of sphingosine 1-phosphate (S1P) and ceramide 1-phosphate (C1P) (4-fold), the latter comprised predominantly of C16:0 species. Prominent decreases in levels of total glucosylceramides also accompanied Ara-C and dnr resistance. VCR resistance was accompanied by similar changes in the sphingolipid composition. These studies reveal that chemotherapy selection pressure induces a pro-survival SL phenotype characterized by ceramide deficits and large increases in S1P and C1P. From a strategic point, targeting SL metabolism may offer innovative approaches for modulating drug resistance.
  
  

  Biography

  Lipin Kao (Betty), a certified project manager, received her Ph.D. in Biomedical Engineering from Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia and postdoctoral studies in Cancer Biology. Her thesis focused on the mitochondrial role in human embryonic stem cells. She has extensive publications in reputed journals, covered genetic expression profile, cell biology (stem cells, and cancer cells), mitochondrial biology, cancer biology, neuroscience, toxicology, and pharmacology, and has been serving as an reviewer and an editorial board member of repute.