Department of Pharmacy – Pharmaceutical Sciences, University of Bari, Italy
Neuroinflammation, as the earliest stage of several neurological and neurodegenerative diseases, takes please about 15-20 years before the appearance of specific neurodegenerative clinical symptoms.
Among the known mechanisms involved into the neuroinflammatory complex network, the cyclooxygenase-1 (COX-1) (predominantly localized in microglia) plays a previously unrecognized role in the neuroinflammation as demonstrated by the attenuation of the inflammatory response and neuronal loss due to the genetic ablation or pharmacological inhibition of COX-1 activity.
The lack of drugs to treat diseases involving the central nervous system (CNS) also resides into the shield exerted by the blood brain barrier (BBB) matrix. BBB has a low permeability, and the development of drugs able to penetrate through its network is one of the challenges of all scientists involved in projecting medicines having active principle ingredients targeting the CNS diseases. A commonly used strategy to overcome this drawback consists to incorporate into the pharmacological active molecule a sugar moiety (i.e. glucose or galactose), in turn capable to “carry” the entire molecule into the CNS by the GLUT-1 carrier, which is located on the membrane of the endothelial cells.
In this context, a set of novel compounds endowed with inhibitory activity with cyclooxygenase-1 and GLUT-1 substrate will be presented. Specifically, their design rationale and biological activity will particularly detailed. The work here presented is financially supported by First AIRC Grant-MFAG2015 (Project Id. 17566) “COX inhibitors in conjunction with chemotherapy to target multiple myeloma active disease”.
Biography:
Dr. Maria Grazia Perrone is a researcher of the department of pharmacy – Pharmaceutical Sciences of Bari University, Italy. After a stage at the University of Biochemical Engineering (Stuttgart-Germany), her scientific interests have been devoting to clarify the Cyclooxygenases role in inflammation as the earliest step of both neurodegenerative disorders and oncology. Author of approximately 50 scientific publications on international journals and Principal Investigator of scientific projects, among which the grant supporting my current studies [First AIRC Grant-MFAG2015 (Project Id. 17566)].
Department of Pharmacy – Pharmaceutical Sciences, University of Bari, Italy
Multiple Myeloma (MM) is an incurable malignant disease of plasma cells. PGE2 and other prostaglandins (PGs), synthesized by cyclooxygenase (COX)-mediated arachidonic acid transformation, are crucial mediators of inflammation and angiogenesis, and support the growth of several tumors. Two COX isoforms have been identified, COX-1 and COX-2. Despite considerable data concerning COX expression in solid tumors are available, their role in hematologic malignancies and in MM has been little investigated. Non-steroidal anti-inflammatory drugs (NSAIDs), mainly acting as COX inhibitors, have shown to be immunotherapeutic agents in several malignancies, including hematological tumors and MM. Some studies proven the usefulness, in the treatment of MM, of COX inhibitors like indomethacin, ibuprofen, NS-398, celecoxib endowed with a different grade of selectivity towards the inhibition of the two COX isoforms.
The pharmaceutic effect of SC-560, Mofezolac, as selective COX-1 inhibitors, Celecoxib, as a selective COX-2 inhibitor, and Aspirin, Ibuprofen with a different grade of selectivity towards COX isoforms, have been evaluated by us on cellular COX status (protein expression, and enzymatic activity) of widely used hMM cell lines (i.e., U937, RPMI-8226, HPC, ARH77).
COX-1 and COX-2 role in MM active disease, as well as the usefulness of their selective or non-selective inhibitors to be used as therapeutic agents to strength the action of the clinically used anticancer drugs (i.e., dexamethasone, bortezomib and thalidomide) will be presented. The work here presented is financially supported by First AIRC Grant-MFAG2015 (Project Id. 17566).
Biography:
Dr. Maria Laura Pati graduated cum laude in Medicinal Chemistry at the University of Bari (Italy). PhD at the University of Bari (Italy). One year as Visiting Researcher at Washington University in St. Louis (USA) working on the in vitro and in vivo efficacy of novel molecules for resistant tumors treatment. One month as Visiting Researcher at University of Vienna where she gained expertise on confocal microscopy analysis. Currently, she is granted by First AIRC Grant-MFAG2015 (Project Id. 17566) for the project “COX inhibitors in conjunction with chemotherapy to target multiple myeloma active disease”.
1Department of Pharmacy – Pharmaceutical Sciences, University of Bari, Italy
2Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Italy
Epithelial ovarian cancer (EOC) is the most lethal gynaecologic malignancy. The global EOC burden is approximately 225,000 new cases per year, with a survival rate of 30%.
EOC is hallmarked by a high degree of heterogeneity. This heterogeneity is apparent in tumor histopathology such as serous, mucinous, endometrioid and clear cell histotypes. The high-grade serous ovarian cancer (HGSOC) accounts for approximately 70% of all ovarian carcinoma.
Patients with HGSOC show diverse clinical outcomes and usually low survival rates (LSRs), even after thesame or very similar treatment regimens. This LSR would also be ascribed to the diagnosis usually made in advanced stage, because no or specific symptoms are related to EOC onset and progression. Early diagnosis determines the patient overall survival. Currently, CA 125 and HE4 are used as early stage EOC biomarkers. Unfortunately, they are not EOC specific and have a poor diagnostic rate, so that the EOC biomarker research is still a challenge.
In this presentation, we will show a comparison between the transcriptome profiles of hundreds of HGSOCs and normal tissues, obtained from RNAseq experiments and reported in big data portals. Our analysis resulted in a panel of tenths of genes that are strongly over-expressed in cancer tissues and might be novel candidates as cancer biomarkers. The expression of our selected genes was further tested on a different cohort of patients by comparing matched cancer and normal tissues by the nano-string technology to validate a panel of biomarkers suitable for a very precocious EOC diagnosis.
This project is granted by First AIRC Grant-MFAG2015 (Project Id. 17566).
Biography:
Dr. Antonio Scilimati graduated cum laude in Chemistry at the University of Bari (Bari, Italy). PhD at the University of Wisconsin (Madison, USA). Four years as a Qualified Person at MerckSerono plant producing recombinant drugs. Currently, he is an Associate Professor of Medicinal Chemistry at the University of Bari. His scientific interest focus the “pharmaceutical sciences”, targeting the cyclooxygenase (COX)-1 as a novel theranostic biomarker in oncology and neuroinflammation.
1Department of Mechanical Engineering, Technical University of Denmark, Denmark
Wear problems of bearing materials for prosthetic articu Hepatoprotective Properties of the Salt-Like lar joints, such as total hip arthroplasty (THA) or total knee arthroplasty (TKA), have long been recognized as a major cause of degradation and failure of the implants. Thus, improvement of anti-wear properties of implant materials is a key requirement to improve lifetime of prosthetic with superior anti-wear properties. The present study proposes to solve this problem by administering external lubricants to prosthetic articular joints. This approach is primarily based upon recent development of various lubricant additives that improve anti-wear properties even in aqueous environment. With an aim to reduce the wear of ultrahigh molecular weight polyethylene (UHMWPE), external lubricants were formulated by dissolving commercial amphiphilic copolymers in aqueous buffer solution. Tribological studies have shown that the tested copolymers displayed immediate reduction effects in the coefficient friction upon injection for the sliding contacts between CoCrMo pin and UHMWPE disk in calf serum as model synovial fluid. For in-vitro cytotoxicity tests, cell morphology and standard MTT assay on murine fibroblast and osteoblast showed a positive result. Near future studies pursue to investigate the impact on wear properties of UHWMPE and extended biocompatibility. Ultimately, it is the aim to develop drugs in the form of pre-filled syringe to improve lifetime and biocompatibility of prosthetic articular joints.
Biography:
Dr. Seunghwan Lee completed PhD in physical chemistry in 2000(University of Houston), then worked in the field of biotribologyand biomimetic lubrication at ETHZ, Switzerland until 2008. Since 2009, he has been leading a research group focusing on biotribology of mucin, mucus, orthopaedic implants, and antifouling properties at the Department of Mechanical Engineering, DTU, Denmark.
University of Louisville, USA
Individual patient differences in drug responsiveness are well recognized by health care professionals. Understanding the basis for these differences is of major clinical and economic importance because of the high frequency of both therapeutic failure and adverse reactions to drugs. Patients may receive inadequate or suboptimal benefit and/or suffer adverse effects from drug treatment. In this presentation, we highlight pharmacogenetic/pharmacogenomic principles and provide illustrative examples where these principles can be applied to optimize therapeutic benefit and minimize adverse effects.
Biography:
Dr. Hein serves as Peter K. Knoefel Endowed Chair of Pharmacology, Professor and Chairman of the Department of Pharmacology & Toxicology, and Distinguished University Scholar at the University of Louisville (USA). His research program includes studies of the molecular epidemiology of cancer susceptibility, pharmacogenetics, genomics, personalized medicine, and functional genomics. He has coauthored over 240 peer-reviewed journal articles and book chapters, 75 published gene sequences, and over 600 abstracts. The publications have over 13, 000 citations with an h-index 58. He has served as principal investigator/co-investigator/mentor on over 75 research grants and contracts totaling over $50 million dollars.
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