Day 2 :
Keynote Forum
Diana Anderson
University of Bradford, UK
Keynote: An empirical assay for assessing genomic sensitivity and for improving cancer diagnostics
Time : 08:30-08:55
Biography:
Diana Anderson holds the Established Chair in Biomedical Sciences at the University of Bradford. Her first degree is from the University of Wales and second degrees from the Faculty of Medicine, University of Manchester. She has 450+ peer-reviewed papers, 9 books, has successfully supervised 28 PhDs. She is currently supervising 6 more and is/has been a Member of Editorial Boards of 10 international journals. She is Editor in Chief of a Book Series on Toxicology for the Royal Society of Chemistry. She gives key note addresses at international meetings and is a Consultant for international organisations (WHO, NATO, TWAS, UNIDO, OECD). Her H index=54.
Abstract:
Detection tests have been developed for many cancers, but there is no single test to identify cancer in general. We have developed such an assay. In this modified patented Comet assay, we investigated peripheral lymphocytes of 208 individuals: 20 melanoma, 34 colon cancer, 4 lung cancer patients 18 suspect melanoma, 28 polyposis, 10 COPD patients and 94 healthy volunteers. The natural logarithm of the Olive tail moment was plotted for exposure to UVA through different agar depths for each of the above groups and analysed using a repeated measures regression model. Response patterns for cancer patients formed a plateau after treating with UVA where intensity varied with different agar depths. In comparison, response patterns for healthy individuals returned towards control values and for pre/suspected cancers were intermediate with less of a plateau. All cancers tested exhibited comparable responses. Analyses of Receiver Operating Characteristic curves, of mean log Olive tail moments, for all cancers plus pre/suspected-cancer versus controls gave a value for the area under the curve of 0.87; for cancer versus pre/suspected-cancer plus controls the value was 0.89; and for cancer alone versus controls alone (excluding pre/suspected-cancer), the value was 0.93. By varying the threshold for test positivity, its sensitivity or specificity can approach 100% whilst maintaining acceptable complementary measures. Evidence presented indicates that this modified assay shows promise as both a stand-alone test and as a possible adjunct to other investigative procedures, as part of detection programmes for a range of cancers.
Keynote Forum
Xiaolian Gao
University of Houston, USA
Keynote: How pancreatic cancer cell signaling proteins (CSPs) respond to tyrosine kinase inkibitor (TKIs) therapeutics - Peptide MicroArray, PepArrayTM, is a powerful molecular tool for CSP profiling
Time : 08:55-09:20
Biography:
Xiaolian Gao has expertise in Chemistry and Biotechnology Development, specifically technologies for massively parallel synthesis of peptides and oligonucleotides on microarray/biochip surfaces. Her team has since developed genomic and proteomic applications to analyze complex biological samples to address questions of biological functions of microRNA and long noncoding RNAs, enzymatic proteins and post-translational modified (PTM) proteins. The biochip technology has led to the establishment of platform of high throughput production of biomolecules and multiplex assay of biomolecules and their interactions.
Abstract:
It is well accepted that molecular profiling of cellular proteins or nucleic acids can offer answers to causes of diseases and underlined connections of pathogenic molecules, and thus, pointing out therapeutic targets. However, protein profiling, especially at the cellular level has been challenging. There is only limited choices to allow systematic investigation of cellular protein activities, such as their responses, (i.e., sensitive, or nonresponsive or resistant, to therapeutic treatment). This presentation reports peptide microarray chip (PeparrayTM) technology developed as a powerful molecular tool for proteomic profiling of Cellular Signaling Proteins (CSPs) to interrogate CSP variations in cancer cells induced by treatment of a new generation of anti-cancer therapies, i.e., tyrosine kinase therapeutics (TKIs). Peparray chips encode a large number of receptor kinase protein (RTK) phosphotyrosine (pY) motif peptides. These are probes for capturing of phosphotyrosine binding domain proteins (PPBD), the profiling thus reveal signaling network activities, which can be translated into clinic relevant information valuable for therapeutic treatments. The case studies involving cellular protein profiling of pancreatic cancer treated with three generations of small molecule tyrosine kinase (EGFR) inhibitors (TKis): Erlotinib (TarcevaTM); Afatinib (Gilotrif TM); and the 2016 FDA approved AZD9291 (TagrissoTM). Peparray™ studies revealed molecular signature profiles of cellular conditions through proteins of commonly or differentially expressed. These proteomic profiles revealed 80 signaling proteins with Erlotinib treatment and 135 signaling proteins with Afatinib treatment and 78 signaling proteins with AZD9291 treatment. The detected signaling proteins are implicated in 38-39 cancer related KEGG pathways. Such information about functional cellular proteins provided valuable molecular signature, which reflect cancer status to allow assessment of effectiveness of cancer treatment, i.e., sensitive vs. insensitive, responsive vs. resistant. Our analysis further revealed signaling pathways responsible for therapeutic resistance. Peparray proteomic and signaling pathway results thus hold clinical significance in identifying molecular markers in therapeutic treatment of cancers, and in cancer therapeutic strategy decision making. These results call for population applications for monitoring and predicting of therapeutic effectiveness, for wide spread expansion of molecular medicine as basis of precision medicine to greatly benefit human health and wellness.
Keynote Forum
Colleen Huber
Naturopathic Oncology Research Institute, USA
Keynote: Vitamin C and cell signaling in cancer
Time : 09:20-09:45
Biography:
Colleen Huber is a Naturopathic Medical Doctor in Tempe, Arizona. She was the Keynote Speaker at the 2015 Euro Cancer Summit, the 2016 World Congress on Cancer Therapy, and a Keynote Speaker at the 2016 World Congress on Breast Cancer. She is President of the Naturopathic Cancer Society. She is a Naturopathic Oncologist and Fellow of the Naturopathic Oncology Research Institute. She authored the largest and longest study in medical history on sugar intake in cancer patients, which was reported in media around the world in 2014.
Abstract:
Research has shown that cytokines such as interferon and interleukin, secreted by the immune system, have an inflammatory effect and play an important role in tumor angiogenesis. High dose intravenous Vitamin C (HDIVC) counteracts this. Vitamin C taken orally cannot attain sufficiently high concentrations in the bloodstream to kill cancer cells. However, intravenous use of ascorbic acid has been shown to rise to concentrations that have killed cancer cells in vivo and in vitro. Vitamin C has been shown to form collagen and to inhibit hyaluronidase leading to stronger membrane integrity and tensile strength of normal tissue, which inhibits invasion and thus metastases. Cancer patients were given HDIVC as part of a naturopathic treatment protocol in an out-patient clinical setting. Data are reported for all patients. Many patients voluntarily left our practice, against our advice, primarily for financial reasons, while still having cancer. Of the remaining patients, 175 either went into remission confirmed by imaging. 44 died while still our patients. Of the 175 who went into remission, 12 had chosen chemotherapy also while having our treatments. Stages 1, 2, 3 and early stage 4 patients at start of treatment had much better outcomes than late stage 4 patients in general. The 32 patients who complied with our dietary and treatment protocol, and still did not survive their cancers must be seen as an 8% failure rate if considered of all 379 patients, or a 15% failure rate if taken of the 210 patients who stayed to complete our treatments.
Keynote Forum
Michael D. West
BioTime, Inc., USA
Keynote: The use of pluripotency in the manufacture of advanced cell-based tissue-engineered therapeutics
Time : 09:45-10:10
Biography:
Michael D West is the Chief Executive Officer of BioTime, Inc. (NYSE-MKT: BTX) and its subsidiary AgeX Therapeutics. The companies are focused on developing therapeutic products using human embryonic stem cells. He received his PhD from Baylor College of Medicine and has focused his academic and business career on the application of developmental biology to the age-related degenerative disease. He was previously the Founder of Geron Corporation (NASDAQ: GERN), where he initiated and managed programs in telomere biology and human embryonic stems and later CEO at ACT (Ocata) (NASDAQ: OCAT) managing programs in somatic cell nuclear transfer and cell-based retinal therapeutics.
Abstract:
Human pluripotent stem cell lines display the potential to cascade through all primary germ layers and hence, almost certainly, all human somatic cell types. This pluripotency has led to the prospect of using master cell banks of pluripotent cells to generate previously rare and valuable cell types on an industrial scale. The growing need for precise genetic modifications in cell-based therapeutics (such as in applications in immunotherapy) highlights the unique advantage of pluripotency in facilitating repeated targeting events in the master cell banks followed by immortal propagation and subsequent differentiation of differentiated cell types. The demonstration that downstream embryonic progenitors can be robustly expanded clonally is leading to improved manufacturing technologies with enhanced definition of purity and identity. The maintenance of a regenerative phenotype in pluripotent stem cell-derived products as evidenced by a lack of markers of the embryonic-fetal transition (EFT), suggests these cells may have the potential to participate in scarless tissue regeneration. Lastly, the use of defined matrices to facilitate differentiation in vitro or to facilitate engraftment in vivo, provide a broad technology platform that will potentially impact numerous fields of medicine. We will provide an update on ongoing clinical trials as well as products in preclinical development.
Keynote Forum
Xiuzhi Susan Sun
Kansas State University, USA
Keynote: Advanced biomaterial PepGel - a new tool for translational research in cell therapy
Time : 10:10-10:35
Biography:
Xiuzhi Susan Sun is a distinguished Professor of Kansas State University. She is the Founder of the Biomaterials and Technology Lab at KSU. Her research interests are in biomaterials design and fabrication, particularly in protein and lipids structure and functional properties at monomers and polymer levels for environmental and medical applications, such as hydrogels, biobased adhesives, resins and coatings. She is a key Founder of the PepGel and PG Biotech companies with the purpose of improving human health through her novel biomaterial discoveries. She earned her Doctor of Philosophy from the University of Illinois Urbana-Champaign, IL.
Abstract:
Life science and biomedical advancement have been limited by the traditional 2D cell culture system. Industries and scientists are switching to 3D cell culture system with the hope of more accurately mimicking the native extracellular microenvironment for translational research leading to clinical applications. Advanced self-assembly peptide hydrogel (PepGel) technology has been recently developed in the Biomaterials and Technology Lab at Kansas State University. The peptide structure was inspired by human muscle and spider silk backbone structure that can form hydrogels at physiological conditions. The peptide can self-assemble into nanofiber networks with 5-150 nm in diameter and 50-2000 nm in pore size that are similar geometry to extracellular matrix (ECM). The hydrogel has sheer-thinning and self-healing properties. This new PepGel system has large flexibility in controlling the gel stiffness, viscoelastic behavior, and surface properties. ECM ligands can be rationally built in the backbone of the PepGel to improve cell properties as needed. PepGel is injectable and biocompatible to biological system as well as compatible with many ECM proteins and cell growth factors. Because of this, the PepGel may have multi applications in the advancement of cell therapeutics strategies for various difficult diseases. This seminar will present PepGel technology, cell studies in vitro and cell delivery in vivo, and case studies with stem cells , cancer cells, virus/antigen, and 3D cell based model for drug toxicity testing.
Keynote Forum
Magnus S. Magnusson
University of Iceland, Iceland
Keynote: T-patterns in human and neuronal interactions and on DNA: Spatio-temporal selfsimilarity and translation symmetry
Time : 10:35-10:55
Biography:
Magnus S Magnusson, PhD, Research Professor, created the T-pattern model with detection algorithms and special purpose software (THEMETM, PatternVision). He Co-directed a two-year DNA analysis project, published numerous papers and invited talks and keynotes at international conferences and at leading universities in Europe, Japan and the US within Ethology, Science of Religion, Mathematical Sciences, Neuroscience, Bioinformatics, Genetics, Proteomics and Mass Spectroscopy. He served as Deputy Director 1983-1988 in the Museum of Mankind of the National Museum of Natural History, Paris. From 1988 to 1993, he served as invited Professor at the University of Paris (V, VIII & XIII) in Psychology and Ethology (Biology of Behavior). Since 1991, he is the Founder and Director of the Human Behavior Laboratory, University of Iceland, leading a formalized network of 24 universities initiated at the University of Paris V, Sorbonne, Paris, in 1995 based on “Magnusson’s analytical model”.
Abstract:
How do cells organize their interactions in time? As a candidate for the search for answers, this talk considers a particular pattern type, called T-pattern. Originally proposed and developed for ethological analysis of human interaction, it has more recently also been applied to dynamic signaling between cells in neuronal networks in brains. The T-pattern is a self-similar hierarchical structure on a single dimension, in time or space, and can be seen as a particular recurrent statistical pseudo-fractal object characterized by statistically significant translation symmetry over all its instances. Just two occurrences may allow detection. A number of extensions to the T-pattern have been defined together constituting the T-System, all of which can be detected using the especially developed THEMETM software widely applied to interaction analysis of organisms from neurons to humans, while DNA and protein analyses are in progress. Examples of T-patterns detected in human interactions and within neuronal networks are presented. The T-pattern structure of genes in DNA and, consequently, in proteins, suggests self-similar spatio-temporal structure across wide spans of temporal and spatial scales, from nano, to neuronal, to human. The self-similarity extends to broader aspects of intra- and inter-cellular interactions as the organization of the biologically recent human mass-societies seem to reflect important aspects of social organization in Cell City as will also be exemplified.
Keynote Forum
Sasha Shafikhani
Rush University Medical Center, USA
Keynote: Discovery of apoptotic compensatory proliferation signaling and its implication in tumor biology and cancer therapy
Biography:
Sasha Shafikhani is an Associate Professor in the Department of Medicine, Division of Hematology, Oncology, and Cell therapy at Rush University Medical Center. His 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 disregulation that renders diabetic wounds vulnerable to infection.
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 cells generate 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. 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.
- Session Introduction
Chair
Cell signaling | Modes of Signaling & Signaling Pathways | Molecular Medicine | Protein Signaling & Neuronal Signaling | Advanced Approach in Cell Signaling | Cellular and Technological Breakthroughs
Session Introduction
Ramiro Malgor
Ohio University, USA
Title: Modulation of Wnt signaling pathway, a strategy in urothelial carcinoma progression
Biography:
Ramiro Malgor is an Associate Professor of Pathology in the Department of Biomedical Sciences at Ohio University. He graduated as MD at Universidad de la Republica in Uruguay and his first area of research was orientated to the development of novel diagnostic method for E. granulosus infected dogs. In 2005, he moved to Ohio University, where his new area of research was focused on Wnt5a and its relationship with inflammation and cancer. In last 10 years, his research has been focused on two main goals, to analyze the role of Wnt5a signaling pathway in atherosclerosis, a chronic inflammatory disease; to understand the role of Wnt5a signaling in atherosclerosis to develop novel, safe, and cost-effective strategies for treatment; and, to dissect the expression pattern of Wnt5a in urothelial carcinoma, to find a novel molecular biomarker, as well as potential new targets for diagnosis and treatment to this cancer.
Abstract:
Bladder cancer is the fourth most common cancer in men and the most common malignancy of the urinary tract. When the diagnosis is made at an early stage urothelial carcinoma (UC), the five-year survival rate is high, but when detected after local metastasis the rate is only 50%. Our group has reported a positive correlation between the expression of Wnt5a, a member of the Wnt proteins family, and histopathological grade and stage of UC and recently, the expression of major components of Wnt5a / planar cell polarity (PCP) signaling pathway in UC human tissue samples and UC cell lines. The Wnt proteins have been described in late 80’s, and are best known for their association with a number of embryonic functions with critical role in developmental biology and homeostasis of tissues. The aberrant Wnt signaling activation has been described as critical in the pathogenesis of cancer, as tumor suppressor or tumor promoter, in variety of malignancies. A publication on the Wnt family has nearly doubled since 2008 and is exponentially increasing. Recently, Wnt signaling pathways have been associated with metastatic cancer via activation of epithelial mesenchymal transition (EMT) genes transcription suggesting a potential therapeutic use by interference of these pathways. The purpose of this study is to dissect the role of Wnt5a signaling in the pathogenesis/progression of UC. Our findings support that Wnt5a-Ror2 signaling plays a role in UC with potential application as a prognostic marker but most interesting provide evidence that Wnt5a signaling may be used as an effective molecular target for novel therapeutic tools. In conclusion, the correlation between Wnt5a /Ror2 and pathological grade suggests that Wnt5a/Ror2 signaling pathway could play a role in the aggressiveness of this cancer, promoting the EMT and metastasis process. Further studies are needed to determine the underlying mechanism of Wnt5a/Ror2 action in UC for targeting the Wnt signaling pathways as potential treatment for UC, as well as their application as biomarkers for UC.
Malak Haidar
King Abdullah university of science and technology, Saudi Arabia
Title: miR-34c plays a key role in theileria-transformed macrophages and human cancer cell lines by targeting PRKAR2B
Biography:
Malak Haidar is a Post-doctoral fellow is studying host-pathogen interaction of Theileria annulata causative agent of tropical theileriosis. She is focused in examining how different autocrine loops and epigenetic landscape changes contribute to infected macrophage virulence and how their oxidative stress status impacts on pathogenicity. She did her PhD in the laboratory of Cellular Biology of Apicomplexa in CNRS, INSERM, Paris, France, supervised by Prof. Gordon Langsley.
Abstract:
MicroRNAs (miRNAs) play critical roles in regulating a wide range of cellular signaling pathways; for example, both physiological and pathological processes in cancer. Here, we report on the role of miR-34c in regulating PKA activity during in cell transformation. Theileria is an intracellular eukaryotic parasite that transforms its bovine host leukocytes into disseminating leukomas that cause a widespread disease of economic importance called tropical theileriosis. By studying this unique model of cellular transformation we identified PRKAR2B (cAMP-dependent protein kinase type II-beta regulatory subunit) as a new miR-34c target gene. Overexpression of miR-34c repressed PRKAR2B levels and consequently increased PKA activity in Theileria-transformed leukocytes promoting their virulent disseminating tumor phenotype. We also validated miR-34c repression of PRKAR2B expression using human colon cancer (HCT-116) and promyelocytic leukemia (HL-60) cells. The identification of miR-34c as a novel regulator of PKA activity could improve understanding of glucose-independent growth of many different types of cancer.
Seyedmehdi Nourashrafeddin
University of Pittsburgh School of Medicine, USA
Title: Stage-specific expression of CYP26B1 in the adult testis is responsible for pulsatile retinoic acid signaling in spermatogenesis
Biography:
Seyedmehdi Nourashrafeddin had received his PhD from Tabriz University of Medical Science, Iran, in the field of Molecular Medicine. He is currently working as an academic Research Assistant at Magee-Women’s Research Institute, University of Pittsburgh, USA. His research focuses on the molecular mechanisms that govern primate spermatogonial stem cell differentiation. His graduate school research focused on the analysis of gene expression during stem cell-based spermatogenesis in vitro. In 2005, he received his Master’s degree in the field of Immunology from Tehran University of Medical Sciences, a premier University in Iran. In addition, from 2004-2006, he worked as a Research Assistant at the Hematology-Oncology and Stem cell Transplantation Research Center in Tehran, Iran. He is proficient in all standard molecular and cellular biology techniques. He is also an employee as Research Assistant in Tehran University of Medical Science. He has published more than 6 papers in reputed journals.
Abstract:
Background: The major physiologically active form of vitamin A, Retinoic acid (RA), plays important roles in germ cell development in both male and female. Studies of mice deficient in the RA degradation enzyme, CYP26B1, indicated that RA is responsible for meiotic initiation; however, the mechanisms underlying the pulsatile RA signaling in spermatogenesis has not been understood yet. We studied the localization and expression analysis of CYP26B1 during development of rhesus monkey testis in order to better understanding of the mechanisms of RA signaling in spermatogenesis process.
Methods: Quantitative real-time PCR (qPCR) and immunohistochemistry was performed to determine the profile expression of CYP26B1 at both mRNA and protein levels in the juvenile and adult rhesus monkey.
Results: The expression of CYP26B1 mRNA was down-regulated during the development of monkey testis. As described previously, the CYP26B1 protein was detected in the cytoplasm of undifferentiated spermatogonia in the developing testis. A rather heterogeneous pattern of the CYP26B1 protein expression was observed along the different stages of seminiferous epithelium, indicating the expression of the protein is stage specific. In adult testes, the highest level of CYP26B1 protein was found in in differentiating germ cells within seminiferous epithelial stages X-XII. The peak of CYP26B1 protein expression was coincided with the onset of meiosis and observed in preleptotene and early leptotene spermatocytes. Whereas, lowest level of CYP26B1 expression was observed in stages VI-IX of the seminiferous epithelium, where undifferentiated Type A spermatogonia divide and differentiate to Type B spermatogonia, meiosis initiates and spermiogenesis occurs.
Conclusion: Down-regulation of CYP26B1 mRNA during the development of monkey testis is consistent with initiation of meiosis in the adult testis. However, the stage-specific expression of RA degradation enzyme CYP26B1 in the seminiferous tubules of adult testis led us to suggest that it might be responsible for pulsatile RA signaling in spermatogenesis. These findings presumably support that the elevated amount of RA in the undifferentiated Type A spermatogonia during stages VI-IX of the seminiferous epithelium of the adult testis is responsible for differentiation of spermatogonia and meiosis entry.
Yiguang Lin
University of Technology Sydney, Australia
Title: FGFR1 lentivirus lung cancer cell model for anti-cancer drug discovery and the study of FGFR1 signaling pathway
Biography:
Yiguang Lin is a Medical Graduate and has completed his PhD in Pharmacology from the University of New South Wales and Post-doctoral training at Prince Henry Hospital, Australia. He was a Visiting Professor at the University of Michigan working with Dr. Peter A Ward and Yale University with Dr. Paul Lizardi. Since 2003, he has been a Tenured Faculty Member at the University of Technology Sydney. He has published widely in many reputed international journals. His research interest has long been in the area of pharmacology of anti-inflammatory drugs, anti-cancer drugs and natural compounds while he recently shifted his interest to cancer biology and medicine with a focus on liver and lung cancer.
Abstract:
Introduction & Aim: Lung cancer is the most common diagnosed cancer worldwide, with the highest cancer death rate. Prognosis of lung cancer patients is still poor despite recent advances in treatment, thus more effective methods for lung cancer management are urgently needed. Overexpression of fibroblast growth factor receptor 1 (FGFR1) is associated with high incidence and mortality in lung cancer. FGFR1 signaling is implicated in oncogenic traits such as proliferation, cell survival, angiogenesis and migration. FGFR1 and its ligand basic FGF (bFGF) are promising new therapeutic targets. This study aimed to develop a simple, effective in vitro lung-cancer cell model for cancer therapy development and to study FGFR signaling in lung cancer.
Methodology: An overexpressing FGFR1 cell line was developed by inserting lentiviral constructs encoding the FGFR1 gene into A549 human lung adenocarcinoma cells and validated by PCR, gel electrophoresis, and gene sequence. FGFR1 overexpression was characterized using a unique bFGF mAb developed in our laboratory and assayed for adhesion, invasion, migration, clonogenicity, cell cycle and apoptosis. PI3K/Akt/mTOR signaling pathway was examined by Western blots.
Results: A stable lentiviral FGFR1 A549 cell model was established with >20-fold higher expression of FGFR1 protein and mRNA compared to A549 parent. Ligand binding to FGFR1 activated the PI3K/Akt/mTOR signaling pathway increasing adhesion, invasion, migration and apoptosis. The overactive PI3K pathway, associated with negative metastatic signaling, can be effectively blocked by unique bFGF mAb. The bFGF mAb not only neutralized free bFGF but also inhibited the endogenous bFGF.
Conclusions & Significance: This model provides an effective and simple screening kit for anti-FGF1 drug compounds for lung cancer treatment and a tool for understanding the molecular mechanisms of the FGFR1 signaling pathway in lung cancer. Furthermore, this basic FGFR1 lentiviral toolkit is transferrable to study FGFR1 signaling in any type of cancer cell.
Heloisa Sobreiro Selistre de Araujo
Universidade Federal de São Carlos, Brazil
Title: Integrin inhibition in the tumor microenvironment
Biography:
Heloisa Sobreiro Selistre de Araujo has completed her PhD from São Paulo University in Brazil and Post-doctoral studies from Oklahoma State University, USA. She is a Full Professor of Biochemistry and Molecular Biology at Federal University of São Carlos, Brazil. She has published more than 120 papers in reputed journals and has been serving as an Editorial Board Member of several journals.
Abstract:
Tumor cell migration and invasion are critical steps in the metastatic cascade and depend on the interaction between tumor cells, the extracellular matrix (ECM) and the endothelial cells. Integrins are key receptors that link cells and ECM, acting as mechanical sensors of the cell microenvironment. Particularly, Arg-Gly-Asp (RGD)-binding integrins such as the v 3 and 5 1 integrins are of special interest in cancer progression since several well-known cancer oncogenes were identified as crucial regulators of integrin traffic and, therefore, of cell invasion and metastasis. Integrins also interact with growth factor receptors resulting in an important cross talking between intracellular signaling pathways triggered by ECM components and growth factors. Recent studies have provided evidence of distinct roles for v 3 and 5 1 integrins in the migration process, where 5 1 integrin clustering supports high matrix forces while v 3 integrin starts mechanotransduction. Therefore, v 3 and 5 1 integrins became an attractive target for pharmacological inhibition in cancer therapy and metastasis prevention. Cilengitide, the first integrin inhibitor based on the RGD motif, is currently under clinical trials in cancer patients with limited success. Efforts to achieve a better understanding of the integrin roles in cancer progression and searches for better inhibitor candidates are needed. We have used a recombinant RGD disintegrin from the Brazilian snake Bothrops alternatus to study the effects of v 3 integrin inhibitions. This protein impairs αvβ3/VEGFR2 cross talking, inhibits HUVEC proliferation, decreases migration speed, directionality and changed the migration mode of a highly invasive tumor cell line from single to collective cell migration. Our data suggest that RGD-disintegrins are interesting as lead compounds for v 3 integrin inhibition.
Zianyi Wang
Taiyuan Lingde Secondary School, China
Title: High TSTA3 expression as a candidate biomarker of poor prognosis of ESCC patients
Biography:
Zianyi Wang is a junior student of Taiyuan Lingde Secondary School. She has participated in a number of biological experiments in Shanxi Medical University due to the curiosity of biology.
Abstract:
Esophageal squamous cell carcinoma (ESCC) is the sixth most lethal cancer worldwide and the fourth most lethal cancer in China. Tissue specific transplantation antigen P35B (TSTA3) participates in the biosynthesis of GDP-L-fucose which is an important substrate involved in the biosynthesis of many glycoproteins. However, the contribution of TSTA3 to ESCC prognosis is unclear. We used immunohistochemical method to assess the expression of TSTA3 in 104 ESCC samples and paired normal esophageal epithelial tissues from ESCC specimens. The results showed that the expression of TSTA3 was statistically higher in tumors than that in normal tissues (P=0.00014) and paired adjacent normal tissues (P=0.0002). The expression of TSTA3 was associated with some clinical features of patients, such as age (P=0.017), alcohol history (P=0.007), clinical stage (P=0.010) and LN metastasis (P=0.043). Kaplan–Meier analysis and Log-rank test showed that ESCC patients with high expression levels of TSTA3 had a worse prognosis compared to the patients with low expression (P=0.048). Multivariate Cox proportional hazards regression model showed that high expression of TSTA3 could predict poor prognosis for ESCC patients independently. In conclusion, abnormal fucosylation might participate in the progress of ESCC and TSTA3 may serve as a novel biomarker for prognosis of ESCC patients.
Biography:
Kaiser Jamil is the Principle Investigator and the Head of Genetics Department, having published more than 250 papers in journals of repute and guided 34 scholars for PhD degree. During the last decade following her instincts, she has taken up several projects related to human health, for ‘War against Cancer’ she has contributed in the field of biomarkers in breast cancer, leukemia, and head and neck cancer. Her work is on SNPs of drug metabolizing genes in cancers and it has been published in peer reviewed journals, unfolding the mechanisms of several genes and other genes which network with these genes, elucidating drug-gene interactions. She has also contributed on the role of some signaling pathways such as tyrosine kinase inhibitors (TKI) and MAPK in haematological malignancies and HNC. Her research continues to unravel genotypes leading towards personalized medicine.
Abstract:
Oral cancer is the fourth most common cancer, ranked as the sixth cause of cancer deaths. In the past few years, incidence of oral cancer was particularly high in South Asia. Oral cancer is mediated by both environmental carcinogens (including alcohol intake, tobacco consumption, and betel nut chewing) and genetic factors. Increasingly more evidence shows that miRNAs are associated with head and neck/ oral cancer, and several miRNAs have been shown to be unregulated in head and neck cancer. We have carried out studies to investigate the association of micro -RNA genetic polymorphism with the risk of oral cancer. The binding of miRNA to mRNA is critical for regulating the mRNA level and protein expression. However, this binding can be affected by single-nucleotide polymorphisms that can reside in the miRNA target site, which can either abolish existing binding sites or create illegitimate binding sites. Therefore, polymorphisms in miRNA can have a differing effect on gene and protein expression and represent another type of genetic variability that can influence the risk of certain human diseases. The increase or decrease in miRNA binding caused by the SNP variation would probably lead to a corresponding decrease or increase in protein translation. MicroRNA is a potent regulator controlling multiple biological processes including cell growth, differentiation, cell death, development and immune responses. With emerging data supporting that microRNA plays a central role in gene dysregulation in human malignancies, unraveling the microRNA genetic variations in cancer is essential and critical if we want to develop better diagnostic and prognostic system for our patients. On the other hand, gaining better insight into the regulatory mechanisms of microRNA would allow us to design therapeutic regime, which targets the disease with better outcome.
Somi Cho
Jeju National University, Korea
Title: Anticancer activities of the selected phytochemicals and their therapeutic implication in AGS gastric cancer cells
Biography:
Abstract:
Marianna Kapetanou
National Hellenic Research Foundation, Greece
Title: Regulation of proteostasis in hMSCs: Proteasome activation enhances stemness and delays senescence
Biography:
Marianna Kapetanou graduated from University of Crete, Biology Departement in 2012, having achieved a first-class honor’s degree. She obtained her PhD from University of Athens, with an excellent grade. She is currently carrying out Post-doctoral research at the National Hellenic Research Foundation (NHRF). Her excellence has been proven by the reception of the IKY-Siemens Scholarship of Excellency for PhD Studies and for Post-doctoral Research. In addition, she has published articles in reputed journals, participated in numerous conferences, has given a lecture at Seminars of NHRF and has reviewed scientific manuscripts for IUBMB Life.
Abstract:
Proteostasis is a fundamental process, essential for the majority of cellular functions. Numerous studies have demonstrated that ageing is accompanied by a failure of proteostasis, while chronic exposure to denatured or aggregated proteins contributes to the development of age-related diseases. The proteasome, being the main proteolytic cellular system, plays a pivotal role in maintaining proteostasis. Essentially, we have established a direct link between the proteasome mediated protein degradation and aging. In detail, we have revealed that senescent human mesenchymal stem cells (hMSCs) exhibit a decrease in expression of proteasome subunits, proteasome content and peptidase activities, accompanied by alterations of proteasomal complexes. Additionally, we show that senescence and the concomitant failure of proteostasis negatively affects stemness. Remarkably, the genetic activation of the proteasome through the overxpression of the catalytic β5 subunit, doubled the lifespan, induced the expression of the core pluripotency factors and enhanced the differentiation capability of hMSCs. Based on these observations, we postulated that the molecular factors and mechanisms that regulate the expression of proteasome subunits can be critical determinants of both aging and stem cell function. Shedding light on the limited data regarding the regulation of proteasome subunits’ expression and the mechanisms underlying its age-related decrease, we demontrated that the transcription factors Oct4 and FoxO1 bind at the promoter region of catalytic proteasome subunits and thus possibly regulate their expression. A firm understanding of the mechanisms regulating proteostasis in stem cells will pave the way to innovative stem cell-based interventions to improve healthspan and lifespan.
Maryam Eslami
Islamic Azad University, Iran
Title: Generation of a biologically and mechanically suitable 3D scaffold for Heart Valve
Biography:
Maryam Eslami graduated with MD (2010), PhD (2014) degrees. She has joined in Harvard Medical School (Harvard-MIT Division of Health Sciences and Technology) as a part of her PhD dissertation in the field of Heart valve. She has carried out some broad research on orthopedic fractures and has published a book and papers in this field. Her US and PCT patent achieved the rank of “Best 2008 Invention” from WIPO (World Intellectual Property Organization of the United Nations) and has received the title of "Best 2008 Women Inventor" from WIPO and 6 Gold Medals and 6 Honorary Diplomas in the Contests and Fair of the Inventors in Geneva and South Korea. International and national awards for her research were one of the fundamental achievements that she has received. She now serves as a President of Applied Biotechnology Research Institute and previously was a research Vice President of Paramedical School at Tehran Azad Medical University.
Abstract:
Introduction: Heart valve disease is one of the most important causes of mortality in the world. Although prosthetic valves have been widely used, prosthetic which grows with patient, maintains normal valve mechanical properties and hemodynamic flow has not been innovated. Tissue engineering offers exciting opportunity to engineer heart valves using biodegradable scaffolds and patients own cells. Heart valves are made up of spatially organized extracellular matrix (ECM) which consists of fibrous collagen and elastin and highly hydrated glycosaminoglycan. Valve interstitial cells (VICs) are the major cell types responsible for ECM remodeling in healthy valves. Elastin, proteoglycan and collagen-rich layers are the most important components of the ECM of valves. These elements due to distinct biomechanical properties to the leaflets and supporting structures
Objective: The objective of this workshop is generation of a proper 3D scaffold by mimicking heart valve structure.
Procedures: We want to show how integrated electrospun poly(glycerol sebacate) (PGS)-poly(ε-caprolactone) (PCL) microfiber scaffolds -reinforce hydrogel scaffolds for heart valve tissue engineering by use of methacrylatedhyaluronic acid (HAMA) and methacrylated gelatin (GelMA). Hyaluronic acid is selected because it plays an important role during in heart valve morphogenesis. To enhance cellular properties, denatured collagen in form of GelMA will be added to HAMA. Hypothetical of this technic is that hydrogels provide an ECM in-vivo mimicking environment and is an efficient means of encapsulating cells in desired density on the fibrous scaffolds. On the other hand, elastomeric PGS-PCL scaffolds will provide appropriate mechanical properties to otherwise weak hydrogel scaffolds. Presence of HA will promote secretion of elastin by valve interstitial cells (VICs). After teaching how to design and make this kind of composite and how to encapsulate VICs necessary biological and mechanical tests and analyzes will be taught and discussed.
Conclusions: The composite scaffold synthesis in this workshop will overcome some of the limitations of current materials use for heart valve tissue engineering. The participants will observe that the hydrogel component provides an ECM-mimicking environment and efficient means of Vic’s cell delivery to the scaffold, while the fibrous PGS-PCL mesh maintains the cells’ viability, allowing them to spread and distribute themselves within the hydrogel by providing appropriate mechanical properties to the otherwise weak hydrogel scaffolds. Furthermore, adding the hydrogel component will not adversely affect the scaffold’s mechanical properties based on the similar values of both Young's modulus and the ultimate tensile strength of the bare PGS/PCL scaffolds and the composites. The mechanical and biological advantages of this composite scaffold can motivate further studies using this technology for potential application in heart valve tissue engineering. We hopefully look forward the participants to learning more about design of heart valve scaffolds and will be motivated to generate the most useful scaffold for the patients.The following parts will be tough in this workshop: Design and synthesis of proper composite; encapsulation of VICs by composite; performance of appropriate biological and mechanical test and; analysis of results of result.
Ali Mohammad Hasan Joshaghani
Islamic Azad University, Iran
Title: Trends and limitation in hydrogel-based therapies for myocardial regeneration
Biography:
Ali Mohammad Hasan Joshaghani has completed his BS in Biomedical Engineering from Islamic Azad University and is currently an MS student in Biomedical Engineering in Islamic Azad University. He has won awards at 10th and 12th Royan International Congress on Stem Cell Biology and Technology in 2014 and 2016.
Abstract:
Struggling to expand man's life expectancy, scientists have always come across a rather remarkable obstacle damage done to cardiac tissue by myocardial infarction. Incapability of self-regeneration in myocardium causes major problems in the treatment of cardiovascular diseases. Myocardial infarction cannot be tackled effectively by existing approaches such as pharmaceutical therapy, organ transplant or implantation of medical devices; Said methods lack the efficiency expected of the modern technology, since they exert matters such as shortage of donor organs, long periods of hospitalization, rejection of the immune system, heavy operations often including high invasiveness and a high risk of degeneration. In order to regenerate damaged heart muscle, cell-based regenerative therapies and tissue engineering products have gained popularity these days. Injectable hydrogels are one of the tissue engineering products with great potential in treating heart diseases. Different kinds of hydrogels including cell-free hydrogels or those loaded with cardiac stem cells or bioactive agents are available, and previous treatments of heart diseases are now becoming less popular. Hydrogels can be injected intracoronary, epicardial or endocardial. These gels have satisfactory stiffness and viscoelasticity, most of them are biocompatible, and some are biodegradable and conductive as well; such traits encounter myocardial patches' downsides such as hypoxia, electro-provocation, patch rejection and many more. In what follows we are going to shed some light on hydrogels loaded with or carrying angiogenes drugs or cardiac stem cells and their advantages against the aforementioned methods.