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Dr. David Terrero
Vice Chancellor Research and Graduate Studies Minister of National Evangelical, Santo Domingo, Dominican Republic.
Pharmaceutical development and genomic aspect of a natural antineoplastic new drug
The pharmaceutical industry, in a sustained manner, for decades has been representing one of greater thrust business activities globally and the Dominican Republic is no exception. Although the growth of the Dominican pharmaceutical industry has been based in the development of traditional pharmaceutical forms with active substances released from the intellectual property protection here we present Securolide as an interesting case. The yeast Saccharomyces cerevisiae have cellular processes with really high homology to those of humans, and it has became in a rapid, inexpensive and efficient compound screening tool. The present work shows preliminary genomic aspects and the path you need to explore for the development of a new drug, whose active ingredient is under own patent. Shows also the exercise of years of a visionary company that has managed to achieve an important number of the stages to develop BIOSEC, a new drug whose active ingredient is SECUROLIDA, a novel molecule developed into the world of the antineoplastics drugs.
Dr. Frederick Williams
Professor and Chair Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
The use of zebrafish in the study of disease and drug discovery
Our research over the last decade uses the zebrafish model to study disease processes and assess how different chemicals would interrupt or change the physiological process. We have done this by studying the toxicity of drugs in our model and by creating animal models of human disease. This talk will discuss our work in both realms. The zebrafish has been lauded as a unique, powerful tool to examine development in a vertebrate animal. Fish embryo/larval models have been used for assessment of chemical effects for decades. We will examine recent published toxicity data from our laboratory on different prospective cancer chemotherapeutics. In addition, our laboratory has helped put animal models of human diseases together. We have put animal models together to study both cancer and Alzheimer’s disease in the zebrafish.
Dr. Youssef Sari
Professor and Vice Chair Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
Neuropharmacology of tobacco cigarette smoke addiction
Smoking is the world’s leading cause of preventable death among populations. Cigarette smoking increases the risk of numerous health problems, including heart diseases, stroke, atherosclerosis, and many types of cancer, such aslung, stomach and bladder cancers. Many individuals find it difficult to stop smoking because of the addictive effects of nicotine and the presence of several monoamine oxidase (MAO) inhibitors in the tobacco smoke extract. The development of novel, safe and effective medications for smoking cessation is a high public health priority. The role of mesocorticolimbic dopaminergic pathways in withdrawal symptoms and general reinforcement processes clearly suggests thedopaminergic system as a potential target for the treatment of nicotine addiction. Current FDA-approved drugs for smoking cessation therapy include bupropion as a dopamine transporter blocker as well as nicotine replacement therapy and partial agonist of α4β2 subunit of nicotinic acetylcholine receptors (nAChRs).These therapies are not usually effective for most tobacco cigarette smokeaddicts. Although dopamine and certain nAChRs are the targets for the treatment of dependence to tobacco cigarette smoke, emerging evidence suggests the important role of glutamatergic system in dependence to tobacco cigarette. Indeed, studies from our laboratory and others demonstrated that regulating glutamate homeostasis through upregulation of glial glutamate transporter 1 attenuated nicotine dependence in animal models. These suggest that targeting glutamatergic neurotransmission through different key proteins may have potential therapeutic effect in the treatment of nicotine or tobacco cigarette smoke dependence.
Dr. Amit Kumar Tiwari
Principal Investigator, Cancer & Systems Therapeutics Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
Novel technologies against drug resistant cancers.
Multidrug resistance (MDR) is a major impediment to cancer chemotherapy. MDR to current therapies, typically develop due to overexpression of ATP-binding efflux transporters, metastasis and reduced sensitivity to apoptosis, resulting in early relapse and shorter survival. We hypothesize that new opportunities to treat MDR in cancer patients could arise from the identification of compounds that are not a substrate of efflux transporters and can trigger a cell death mechanism that does not depend upon classical apoptotic pathways. In this regard, we have recently developed 2 novel technologies. First deals with the discovery of a unique, structurally constrained 4-pyridinyl probes which induce a form of non-apoptotic cell death characterized by simultaneous induction of dysregulated macropinocytosis (self-drinking) and macroautophagy (self-eating). We have defined this unique type of caspase-independent cell death ‘methuophagy’ (the neologism arises from the Greek ‘methuo’, to drink to intoxication and ‘phagy’, self-eating). Our new class of small molecular probes (4-pyridinyl moieties, BAPT analogues, patented and out-licensed) that do not involve classical apoptotic pathways, cause methuophagy by inducing the formation and accumulation of fluid-filled, heterogeneous vacuoles and autophagosomes, resulting in metabolic failure, loss of membrane integrity, and detachment of cells from the substratum. Methuophagy produces hypervacuolization and extensive autophagy without cell shrinkage, chromatin condensation, mitochondrial membrane potential alteration, or nuclear membrane damage. The second technology deals with discovery of a novel class of pyrimidin-hydrazinylidene compounds that selectively induced a unique NANI (non-apoptotic, necroptotic inducing i.e. caspase-independent programmed cell injury) cell death in specific cancer cells.The identified novel compound will be particularly beneficial for therapy of drug resistant and aggressive cancers. A contribution to adjuvant therapy is envisioned for thesenew class of drugs that kill cancer cells by inducing a non-apoptotic mechanism distinct from DNA-alkylating, apoptosis-inducing agents and receptor-targeted therapeutics. Finally, the novel probes identified will allow us to understand the biology of unique non-apoptosis-induced cell death.