Day 3 :
- Antimicrobial Drugs
Location: Room 1
Session Introduction
Maude Loignon
University of Montreal, Canada
Title: Some HIV protease inhibitors have also other beneficial, non-virological effects with potential therapeutic applications
Biography:
Maude Loignon has completed her MSc in 2007 and her MD in 2012. She is now a 3rd year Resident in Microbiology and Infectious Diseases at the University of Montreal, Canada. She has published 7 papers in peer-reviewed journals.
Abstract:
The introduction of HIV-protease inhibitors (PIs) in antiretroviral therapy drastically diminished the incidence, prevalence and severity of opportunistic infections. These beneficial effects are primarily due to immune reconstitution following the decrease of HIV replication. We reported that some PIs increase the RALDH’s activity and consequently augment the production of retinoic acid (RA) in vitro. We demonstrated that in vivo, PIs (as part of an optimal antiretroviral therapeutic regimen) decrease serum RA concentrations. These discrepancies of in vivo and in vitro data are due to the fact that RA synthesis and its alteration by PIs take place intracellularly. Elevated intracellular RA level increases its own catabolism and inhibits (feedback) its synthesis. Based on these and other published data we have suggested that altered RA metabolism by PIs might affect the expression of retinoid-responsive genes and retinoid-mediated signaling pathways. Several beneficial effects of PIs, such as improvements in the control of certain infections of HIV-associated nephropathy (HIVAN), Kaposi’s sarcoma, other cancers, HIV-dementia, HIV-associated colitis, etc., could be partially explained by their direct effect on RA synthesis. Moreover, therapeutic uses of synthetic retinoids have been proven efficacious in the treatment of Kaposi’s sarcoma and HIVAN and experimentally, RA is synergistic with primaquine against Pneumocystis. PIs also inhibit the aspartyl proteases of several parasites and fungi as documented by numerous publications. And finally, other effects such as inhibition of the proteasome-ubiquitin process and diminished apoptosis are now exploited for the treatment of different cancers and neurodegenerative disorders.
Bin Li
The University of Hong Kong, China
Title: Identification of miR-29c/FBXO31 as a key regulatory mechanism in esophageal cancer chemoresistance
Biography:
Bin Li has completed his PhD at the age of 30 years from University of Hong Kong, and his PhD research focused on the role of Id1 in activating PI3K/AKT signaling pathway and promoting esophageal cancer progression. He is currently a Postdoctoral research scientist, and he has established highly chemoresistant and metastatic esophageal cancer cell models. His current research interests include functional identification and characterization of novel genes/miRNAs associated with chemoresistance and metastasis, the mechanistic study and targeted therapy; identification and characterization of esophageal cancer stem cells. He has over ten peer-reviewed research papers published in reputed journals.
Abstract:
Esophageal cancer ranks as the 6th most frequent cause of cancer death in the world. Chemoresistance is a major obstacle in cancer therapy, but the mechanism remains unclear. MicroRNAs have received increasing attention as a novel and promising targets in cancer diagnosis, prognosis and treatment. Identification and experimental validation of the chemoresistance-related miRNAs in esophageal cancer are urgently needed. We have established esophageal squamous cell carcinoma (ESCC) cell line models of acquired chemoresistance to 5-FU (FR sublines). MicroRNA profiling and subsequent RT-PCR confirmation showed that miR-29c was one of the most down-regulated miRNA in FR sublines. We found that miR-29c overexpression could revert acquired chemoresistance of FR cells, and that lower miR-29c expression in ESCC was associated with poor survival of patients. FBXO31, a novel F Box protein with prognostic significance in ESCC, was amongst the upregulated mRNAs identified in the FR cells using cDNA microarray and was predicted by computational algorithms to be a target of miR-29c. Our data showed that FBXO31 increased chemoresistance of ESCC cells in vitro and in vivo, and that ectopic expression of miR-29c significantly reduced FBXO31 expression. More importantly, FBXO31 mediated the functions of miR-29c in chemoresistance of ESCC cells. In summary, this study greatly enhances our understanding of the functions of miR-29c and FBXO31 in esophageal cancer; their significance in diagnosis, prognosis and treatment warrants further investigation.
Natalia Martins
Polytechnic Institute of Braganca, Portugal
Title: Folk medicinal plant extracts as a source of biomolecules with antifungal properties against Candida species
Biography:
Natália Martins has 25 years and she is a PhD student from University of Minho since March 2013. She is graduated in Dietetics and Nutrition from Polytechnic Institute of Bragança (including a period of extra-curricular training in Brazil), in Natural Medicine from School of Alternative and Complementary Medicines of Oporto, and also attended other short courses in Traditional Medicine. She has published 7 articles in ISI and Scopus indexed journals, and presented 12 abstracts in national and international conferences/congresses.
Abstract:
Increasing rates of opportunistic fungal infections and microorganisms with drug-resistance have been observed. Candida species are the most common pathogens, considered the fourth leading cause of hematogenous infections. Thus, it is crucial to discover alternatives to the current antifungal agents. Healing properties of medicinal plants are widely recognized, but some properties and the related mechanisms of action remain unknown. Therefore, the anti-Candida potential of hydromethanolic extracts obtained from ten folk medicinal plants (Echinacea purpurea L.; Eucalyptus globulus Labill.; Foeniculum vulgare Mill.; Juglans regia L.; Matricaria recutita L.; Melissa officinalis L.; Pterospartum tridentatum L.; Rosa canina L.; Rubus ulmifolius L. and Tabebuia impetiginosa L.) was evaluated, by using disc diffusion assay and determination of minimal inhibitory concentrations by microdilution method. J. regia was the most effective, inhibiting the growth of the tested nineteen Candida strains (halo diameter varying between 9-14 mm) and causing a growth reduction of 3-5 Log(CFUs) for Candida parapsilosis and C. tropicalis, and 0.5-2.5 for C. albicans and C. glabrata. E. globulus also exhibit a significant potential, being effective against seventeen Candida strains (halo diameter ranging between 9-21 mm) and causing a growth reduction of 2-5 Log(CFUs). P. tridentatum and R. ulmifolius showed similar antifungal effects, being effective against six Candida strains (halo diameter ranging between 9-19 mm). So, as main conclusions, hydromethanolic extracts of E. globulus and J. regia could constitute promissory alternatives to the current antifungal agents, but more detailed studies are needed in order to identify the bioactive compounds and related mechanism of action.
Thomas Prince
National Cancer Institute, USA
Title: HSP90 and tyrosine kinase inhibitors: A synergistic combination for combating cancer?
Biography:
Thomas Prince research has primarily revolved around molecular chaperones and their role in cancer and disease. Raised in the Mid-South, I did graduate training in biochemistry and molecular biology at Oklahoma State University with Robert Matts. Upon graduating then began post-doctoral experience at Pacific Northwest National Laboratory with Steve Wiley studying systems biology and receptor tyrosine kinase processing. After this I travelled to Harvard Medical School to work with Stuart Calderwood on the cellular stress response in cancer. Currently I am working with Len Neckers at the National Cancer Institute focusing on HSP90 biology in cancer.
Abstract:
The merging of knowledge from genomics, cellular signal transduction and molecular evolution is producing a new paradigm of cancer analysis. Tyrosine kinases have long been understood to initiate and promote malignant cell growth. Targeting tyrosine kinases to fight cancer has been a major strategy for the pharmaceutical industry for almost 3 decades. Despite the initial success of tyrosine kinase inhibitors, the ability of cancer to evolve resistance and switch between oncogenic signals has made the effective use of tyrosine kinase inhibitors difficult. The molecular chaperone HSP90 physically supports global tyrosine kinase function while also acting as an evolutionary capacitor. The Cancer Genome Atlas has compiled a trove of data that indicates a number of cancers over-express or possess mutant tyrosine kinases that depend on HSP90 and its cohorts. Targeting HSP90 function could therefore complement tyrosine kinase inhibitors for treating cancer by inhibiting cancer evolution and preventing oncogenic switching. Based on this hypothesis our work has focused on the interplay between tyrosine kinases and the HSP90 molecular chaperone machine with the aim of developing synergistic combinations of molecular therapies to combat cancer.
- Control And Epidemiology
Location: Room 1
Session Introduction
Ntirenganya Faustin
University of Rwanda, Rwanada
Title: Equitable access to oncological services, challenge for developing countries: Experience from Rwanda
Biography:
Ntirenganya Faustin is a Consultant breast, onco-plastic, reconstructive surgeon and clinical oncologist, Lecturer of surgery and coordinator of general surgery Masters Program at the College of Medicine and Health sciences, University of Rwanda. He obtained his Doctorate of medicine at National University of Rwanda, where he did his General surgery residency before going for fellowships at University Paris XI, France. He is a member of the College of Surgeons of East, Central and Southern Africa and of Rwanda Surgical Society. He has published many papers in local, regional and international peer-reviewed journals, participated and presented papers to a good number of international conferences. Winner of 2010 ASGBI Surgical Foundation Award, 2013 Mamadi Soudavar Travelling Fellowship Award, he is engaged in global health issue, especially global surgery and strives for universal access to quality health care, including giving access to high quality cancer care services to the poor.
Abstract:
Cancer represents a significant and rising burden of disease and a serious public health issue and outcomes are worse in Low and Middle Income Countries (LMICs). The United Nations conference in 2011 highlighted the importance of addressing health and health infrastructure needs to treat non communicable diseases including cancer in developing world. Rwanda Ministry of Health (MOH) has prioritized addressing this disease burden through approaches including standardization and expansion of access to quality cancer services. It is in that framework that, in partnership with Partners in Health (PIH), Butaro Cancer Centre of excellence has been created in 2012, in rural Rwanda. The vision was to create, strengthen and sustain high quality oncology services with equitable access to all cancer patients. Parallel to that, the MOH has integrated cancer services in all levels of the health system, from the community, passing by health centers, district hospitals to referral hospitals. These services include awareness, early detection and screening, diagnosis and treatment. Key challenges are related to sustainability of services especially chemotherapy, access to radiotherapy as currently it is not available in the country due to a few number of cancer specialists and poverty. In addition, awareness is still low and patients are present often at advanced stages. Providers are not well-prepared to communicate and deal with the complexities of cancer care. Distance and constraints of the medical care system also can impede to the accessibility of care. In conclusion, equitable access to cancers services is still a big challenge for developing countries including Rwanda. A wide range of actions are still needed to effectively prevent, diagnose, treat and control the many, often advanced forms of cancer seen in that part of the world.
Deependra Singh
Finnish Cancer Registry, Finland
Title: Screen detected symptoms of breast cancer and its relation with program performance indicators in Finland
Biography:
Deependra Singh has completed his MPH at the age of 24 years and Doctoral training in epidemiology from University of Tampere. He is currently working as a researcher in Finnish Cancer Registry, Helsinki. He is also a Doctoral student in epidemiology at School of Health Sciences, University of Tampere since 2014. He is currently running a project funded by Finnish Cancer Organization on ‘Screen detected symptoms of breast cancer and its relation with screening program performance in Finland’, as a program leader. The initial results from the project have been published in a high profile international journal.
Abstract:
A key component of breast cancer screening program is the collection of data on symptoms at the time of screening visit. In many cases, however, the data are not subsequently analyzed for relationships between symptoms and screening program performance. It is a unique study that analyzes the role of symptoms and its relation with screening program performance in a longitudinal outlook. The screening dataset consists of the total number of visits (4.5 million screening visits) made by screening age women since the start of the program and followed for more than 20 years (until 2012). Key symptom variables- lump, retraction, secretion were analyzed for their role with program performance indicators- Cancer detection rate, attendance rate, recall rate, etc. in a longitudinal outlook. Various innovative methodological approach are used to better fit the screening data of a repeated (women invited every two years) mammography screening program. Marginal and conditional probability models were developed to calculate the cumulative probability of any or first false positives and cancer detection in those who reported symptoms compared to those with no symptoms. The result shows a promising role that symptoms can contribute to a population-based screening program in addition to mammography screening. The implication of the results can be more favorable in a setting, with no repeated screening program at a population level, where clinical breast examination (CBE) is feasible provided that adequate diagnostic services are available.
- Development of New Antibiotics
Location: Room 1
Session Introduction
Juan Bueno
Anadolu University, Turkey
Title: Anti-biofilm drug discovery new topics in antimicrobial adjuvants for antibiotic improvement
Biography:
Juan Bueno is MD with Master’s degree in Microbiology, with expertise in design and implementation of antimicrobial platforms to evaluate natural products. He has more than 25 papers in this field and two book chapters. He is a Reviewer of Journal of Microbial & Biochemical Technology and Journal of Pharmacy and Pharmacology. Currently he is working as a a visiting scientist at Pharmacy School in Anadolu University in Eskisehir, Turkey.
Abstract:
Biofilm is considered as a microbial structure, composed of cells incrusted in a polymeric matrix which is attached in an inert or living surface. Biofilm matrix is an impermeable barrier that increases the resistance to biocides and drugs, because attached cells embedded in biofilm are 1000-fold more resistant to antimicrobials than planktonic free-floating cells. In this way it is believed that this mechanism of resistance is responsible for around 100,000 nosocomial lethal infections per year in the United States. In fact, the antibiotic treatment has been evaluated using planktonically-grown bacteria and not polymicrobial biofilms and their associations; complicating the administration of an effective therapy and cure. Because the biofilm pattern contributes to increasing microbial resistance, it is an imperative necessity to develop new drugs and biocides with the ability to destroy the cells cells within the biofilm structure. An important approach is the standardization of in vitro screening assays to evaluate activity, drug susceptibility testing as well as antimicrobial combinations with clinical correlation. For implementing this drug discovery platform, it is necessary to control several variables including, microbial species to be employed, biofilm growth conditions, and the best method for quantification of the microorganisms is included in the biofilms, with the end to obtain new compounds for attack chronic infections. The aim of this lecture is to give a rational approach for to implement antibiofilm drug discovery screening platforms, looking for new adjuvants to improve the current antimicrobial therapy.
Luis RodrÃguez-Borlado
Coretherapix SLU, Spain
Title: Challenges in I+D development of an advanced medicine product
Biography:
Luis RodrÃguez-Borlado has a PhD in Biochemistry and Molecular Biology from the University Autónoma of Madrid with the study of molecular bases of immune system development. After developing a scientific career in academic laboratories in Spain and The Netherlands developing high-throughput screenings to identify new therapeutic cancer targets, he joined Coretherapix in 2008 (a company belonging to the Genetrix group). At Coretherapix he has been responsible for designing the cell characterization and pre-clinical studies enabling the filing of the IMPD corresponding to Coretherapix’s first cell candidate product, a task he has led in his role of Scientific Director.
Abstract:
Advanced therapy medicinal products are new medical products based on genes, cells or tissues. These advanced therapies herald revolutionary treatments of a number of diseases or injuries, such as ischemic heart disease, Alzheimer's, cancer or immune-deficiencies. They have huge potential for patients and industry but they also present challenges that need to be properly addressed to be able to translate these therapies to the clinic. Marketing authorization of ATMPs requires, as for all medicinal products, that the applicant demonstrates that the product is consistently manufactured to a predefined quality, and that it is safe and efficacious in patients. Moreover, the use of a live material incorporates new challenges to the process related with bioequivalence between different cellular batches and the development of potency assays. After an AMI, the loss of contractile tissue drives to a degenerative process and finally to a chronic heart failure. There are no efficient therapies besides the organ transplantation and the scarcity of donors, the cost of the treatment and the side effects associated have limited the application of this therapy. Cell therapy has rose as an alternative for the treatment of this pathology but to be clinical effective it needs to be affordable, to produce a robust regenerative response and to be reproducible and equivalent between the different GMP produced batches. Coretherapix has initiated a clinical trial using allogeneic cardiac stem cells for the treatment of the acute myocardial infarction.
Nazim Serdar Turhal
Anadolu Medical Center, Turkey
Title: A proposal for more affordable biologicals in developing countries
Biography:
Nazim Serdar Turhal had his training in Internal Medicine in Griffin Hospital at Yale University Affiliated Program until 1992. He was trained in Hematology, Oncology and Bone Marrow Transplantation at Mount Sinai School of Medicine Hospital until 1997. He then worked at Marmara University in Istanbul until 2014 and as Professor of Medicine since 2006. He recently relocated to Anadolu Medical Center as a Senior Oncology Staff. He has over 130 publications and over 1000 citations. He is board certified in Medical Oncology until 2016 by European School of Medical Oncology and until 2017 by American Board of Internal Medicine.
Abstract:
The information on the efficacy of newer agents is spreading rapidly on internet era. It is increasingly difficult in a democratic society to say “no†for a particular treatment for patients no matter how expensive it is. The bureaucracy is showing many obstacles in registration, marketing authorization, licensing steps of these new agents in many developing countries with limited resources. These obstacles may emerge in many forms. These measures are justifiable under budget pressures but instead of complicating the authorization process and testing the patience of both the industry and the patients who are waiting for the approval, I propose forming an advisory board similar to FDA and EMEA for the developing countries and simplifying the approval process under one authority which will be practical for the industry too. The industry will finance this board with application fees and the board then can use its influence on bringing down the price of these molecules in representing countries and justify the lower prices with commitment to substantial contribution to phase I-III trials in these particular countries. A correlative link can be established in between the contribution and the price. Difficulties of this will be: 1) Agreeing upon who will represent a particular country (politicians, physicians, clinicians and pharmacologists); 2) Getting together in harmony; 3) Agreeing upon representation; 4) Administrative power; 5) Convincing the industry. It may be difficult and painstakingly slow process but certainly worth trying!