Day 1 :
Keynote Forum
Deepak Sampath
Genentech, USA
Keynote: Grim reaping the benefits of the BCL-2 selective antagonist, Venetoclax, Venclextaâ„¢ for the treatment of hematological malignancies
Time : 09:30-10:15
Biography:
Programmed cell death is governed by a complex interaction of BCL-2 (B-cell Lymphoma 2) family of pro-survival (BCL-2,BCL-XL and MCL-1) and pro-death proteins (BIM, PUMA, NOXA). BCL-2 family proteins share a common set of BCL-2 homology domains. Venetoclax (GDC-0199/ABT-199) is a first in-class BCL-2 selective antagonist that is currently approved for the treatment of Chronic Lymphocytic Leukemia. Current research efforts have focused on assessing the potential utility of venetoclax in other hematological malignancies such as multiple myeloma (MM) in which a high unmet medical need remains. In human MM cell lines (n=21) BCL-2 is expressed but sensitivity to venetoclax correlated with high BCL-2 and low BCL-XL or MCL-1 expression. MM cells that co-express BCL-2 and BCL-XL were resistant to venetoclax but sensitive to a BCL-XL selective inhibitor (A-1155463). MM xenograft models that co-expressed BCL-XL or MCL-1 with BCL-2 were also resistant to venetoclax in vivo. Resistance to venetoclax was mitigated by co-treatment with bortezomib in MM xenografts that co-expressed BCL-2 and MCL-1 due to upregulation of NOXA, a pro-apoptotic factor that neutralizes MCL-1. In contrast, xenografts that co-expressed BCL-XL and BCL-2 were more sensitive to the combination of bortezomib and BCL-XL selective inhibitor (A-1331852). Immunohistochemistry of MM patient bone marrow biopsies and aspirates (n=95) revealed high levels of BCL-2 and BCL-XL in 62% and 43% of evaluable samples, respectively. In addition to MCL-1, our data suggests that BCLXL may also be a potential resistance factor to venetoclax monotherapy and in combination with standard of care drugs such as bortezomib
Abstract:
Deepak Sampath is graduated from Washington University in St. Louis, Graduate School of Arts and Sciences earning a PhD in Molecular Cell Biology and Biomedical Sciences. Following a post-doctoral fellowship at Wyeth Research, Dr. Sampath joined the Department of Oncology at Wyeth Pharmaceuticals as Senior Scientist focusing on the discovery of orally bioavailable taxanes. Presently, Dr. Sampath is a Principal Scientist at Genentech in the Department of Translational Oncology and his lab focuses on the molecular and in vivo pharmacology of drugs that target the PI3K/Akt and BCL-2 apoptotic pathways in solid
and hematological cancers.
Keynote Forum
Hans J. Nielsen
University of Copenhagen,Denmark
Keynote: Improvements of colorectal cancer screening by development and implementation blood-based biomarker concepts
Time : 10:15:11:00
Biography:
Professor Nielsen has completed his MD (1989) and DMSc (1995) at University of Copenhagen. He has more than 25 years of experience in translational and clinical research mostly with focus on colorectal cancer, including tumor-and trauma-immunology and adverse effects to blood transfusion. He is currently head of Surgical Immunological Laboratory and PI of major studies on early detection of primary malignancy and of recurrence as well. Dr. Nielsen has published more than 250 papers in peer-reviewed journals, has been and currently is mentor of more than 30 Ph.D. and doctoral thesis students.
Abstract:
Screening concepts for colorectal cancer (CRC) are either under implementation or already implemented in most industrialized countries. The current concept is based on occult human blood in a feces test – FIT screening. Persons with a positive test are offered a subsequent colonoscopy to verify the source of occult blood. The FIT test has an excellent sensitivity of 75% at 90-95% specificity. The compliance is however, only 65%, which leads to a clinical sensitivity of < 50% (0.75 x 0.65). Long story short: >50% of those subjects with an occult bowel neoplasia in the screen relevant populations are not identified. Therefore, development and implementation of improved screening concepts is urgently needed. Once such concept appears to be based on analysis of proteomics, genomics, epigenomics and metabolomics in blood samples and statistically performing various combinations by data fusion. Results of major prospective, clinical studies with focus on subjects referred to colonoscopy due to symptoms attributable to CRC are compelling. In addition, results of retrospective studies have indicated that biomarker profiles may identify subjects at risk of developing primary intra- or extra-colonic malignancy subsequent to colonoscopy with diagnosis of clean colorectum. Collectively, such results have led to validation of the screening concept of blood-based biomarker combinations in large series of subjects undergoing FIT screening. Preliminary results have confirmed the results previously achieved in populations of symptomatic subjects.
Break: Networking and Refreshment Break 11:00-11:20 @ Foyer
- Translational Modeling of Efficacy and Safety
Clinical and Translational Oncology
Immunology and Infectious Diseases
Translational Therapeutics and Technologies
Session Introduction
Sihem Bihorel
University of Florida, USA
Title: Immunotherapy with novel tri-functional lipid nanoparticles to overcome resistance to HER2 therapy in breast cancer
Biography:
Sihem Bihorel (Ait-Oudhia) held the position of Research Assistant Professor at the State University of New York at Buffalo where she was also trained as a Post-doc and received her PhD. She utilizes quantitative systems pharmacology approaches to guide the development of new therapies and the identification of promising combination therapies as well as of novel biomarkers in oncology. She integrates quantitative systems pharmacology with PK/PD modeling and simulation to advance drug discovery and development, and leverage the understanding of drugs’ action which holds great promise to facilitate translational research. Her research is also focused on investigating how priming solid tumors with a pro-apoptotic agent then combining a subsequent large protein therapeutic and an antiagiogenic agent can defeat drug resistance and treatment failure in cancer and further enhance the efficacy of targeted anticancer agents, and translating these findings towards clinical settings.
Abstract:
Purpose: Breast cancer (BC) is the second leading cause of cancer deaths in women, and about 25% of BCs have overexpression of the HER2 receptor. Although HER2 targeted therapies have shown considerable improvement in HER2-positive BC patients outcome, treatment resistance remains a clinical challenge. Here, we sought to develop and evaluate a novel tri-functional lipid nanoparticulate (TFLP) drug delivery system that overcomes HER2 treatment resistance by dually targeting HER2 on BC cells and CD3 receptors on cytotoxic T-lymphocytes (CTLs).
Material & Methods: Anti-HER2 (Trastuzumab) and anti-CD3 (OKT-3) antibodies were conjugated to lipid nanoparticles by the micelle-transfer method, and the resulting formulation was purified by dextran gradient ultra-centrifugation. Targeted lipid nanoparticles were formulated with a fluorescent lipophilic dye, DiD, for studying receptor binding and internalization. Studies were conducted with HER2-positive BT474 cells and CD3-positive Jurkat cells using flow cytometry analyses. Doxorubicin HCl (DXR) was encapsulated in the nanoparticles by the remote-loading technique for cell-kill experiments. In vitro cell-kill studies were conducted by co-culturing BT474 as the target cells, and peripheral blood mononuclear cells as the effector cells, at varying ratios.
Results: Purified formulations were successfully characterized for conjugation by determining protein to lipid ratio. Flow cytometry analyses demonstrated successful cell binding and/or internalization of the TFLP with both the HER2 and CD3-positive cell lines.Moreover, these dual-targeted nanoparticles were able to retarget T cells to kill HER2 positive BC cells, and showed improved efficacy compared to non-targeted and plain HER2-targeted formulations in vitro.
Conclusion: A novel TFLP drug delivery system that targets HER2 receptors on tumor cells, CD3 on CTLs, and is able to slowly release DXR, was successfully developed and evaluated in vitro on HER2 overexpressing BC cells. Our findings show great promise at overcoming resistance to present HER2 targeted BC therapies, and may translate into improved anti-tumor activity clinically compared to other treatment options.
Sergey Suchkov
I M Sechenov First Moscow State Medical University, Russia
Title: PPPM (Predictive, Preventive and Personalized Medicine) as a novel avenue and a source of new translational tools to predict and to prevent chronic autoimmune disorders
Biography:
Sergey Suchkov was born in the City of Astrakhan, Russia, in a dynasty medical doctors, graduated from Astrakhan State Medical University and was awarded with MD.Then maintained his PhD and Doctor Degree. And later was working for Helmholtz Eye Research Institute in Moscow, Moscow Clinical Research Institute (MONIKI). Dr Suchkov was a Secretary-in-Chief of the Editorial Board, Biomedical Science, an international journal published jointly by the USSR Academy of Sciences and the Royal Society of Chemistry, UK. At present, Dr Sergey Suchkov is a Chair of Dept of Personalized Medicine, I.M.Sechenov First Moscow State Medical University, and Secretary
General, United Cultural Convention (UCC), Cambridge, UK; a member of the: New York Academy of Sciences, American Chemical Society (ACS), American Heart Association (AHA), AMEE, Dundee, UK; EPMA, Brussels, EU; PMC, Washington, DC, USA and ISPM, Tokyo, Japan.
Abstract:
Autoimmune diseases (ADs) are a family of complex heterogeneous disorders with similar underlying mechanisms characterized by immune responses against self. The link that might exert reliable control over morbidity, mortality and disabling rates and significantly optimize the cost of treatment for the latter is just Predictive, Preventive and Personalized Medicine (PPPM). And a combination of genomic and proteomic biomarkers are becoming of great significance to predict risks of the chronification. Although a single biomarker is a tangible entity that can be easily understood, aggregate measures comprised of multiple genes are also informative as the combinatorial biomarkers. The simultaneous addition of combinatorial biomarkers of autoimmune disorders to the score index panel substantially improves he risk stratification fordeath and disabling. And there is urgent clinical need to identify predictive combinatorial biomarkers for subclinical PIFAS (post-infectious autoimmune syndrome) to allow preventive/treatment strategies to be instituted early in the disease running. Thus, the need for biomarkers of newer generations, newer algorithms and software applications to support integrative data analysis and to secure the databanks becomes critical to the discovery of linkages and concordance between different data types such as genomics-, proteomics-, immunomics-, metabolomics- and clinically-rooted. PPPM is thus a model of healthcare services being tailored to the individual and dictates a construction of PPPM-based algorithms to diagnose, predict, and to prevent autoimmune conditions in time!
Khatja Batool
University of Illinois, USA
Title: High nitric oxide exposure causes Upregulation of JUN, FOS & AP1 and may play a role in cancer stem cell formation by pseudogenes expression
Time : 12:20-12:50
Biography:
Khatja Batool graduated with her Bachelor of Medicine and Bachelor of Surgery from Gulf Medical University, UAE. She started her research at UIC-Chicago, IL where she studied the effects of nitric oxide in cancer stem-cell lines. Additionally, she is a certified expert in Botulinum Toxin, Dermal Fillers and Facial reconstruction. Her distinguished efforts led her to be a part of the organizing committee at the 43rd ISOBM annual conference in Chicago, IL which was attended by Nobel laureate Dr. Ferid Murad and other well-known scientists. She has also had her works published in research journals such as Tumor Biology. Furthermore, Khatja is on the reviewer board for international journals like Tumor Biology and JCMT, Board member at Oncomarks.org and a member of professional societies like ASCO and ISOBM. She has an active interest in oncology research especially in the studies of nitric oxide and telomerase shortening in cancer stem cells.
Abstract:
Hypothesis: The high exposure causes up-regulation of JUN, FOS & AP1; genes in adapted cell lines and over expression of Pseudogenes which has metastatic potential.
Objective: When subjected to high concentration of NO, H&N tumour cell express more aggressive phenotype compared to nonexposed cell. Upon exposure these cells exhibit adaptation causing greater metastatic potential. Five H&N cell lines were adapted to high concentrations of NO. It appears that AP1, which is a transcription factor protein, composed of JUN and FOS family proteins.These proteins are responsible for various cellular process including cell differentiation, proliferation and apoptosis which up regulate these cells. MicroRNA isolation due to CeRNA add to Pseudogenes and their influence on the growth of cancer. One well studied gene is the BRAF pseudogene and its functional BRAF gene. Studies have shown that high levels of the BRAF pseudogene are directly proportional to the formation of aggressive malignancies.
Methods: This study used five human H&N cells lines (SSC-016, SSC-040, SSC-056, SSC-114, and SSC-116). Known pseudogenes were identified in each line, as well as their coding counterparts.Slow exposure of high NO was used on the cell lines to increase quantities of DETA-NONOate (NO donor). Both the parent and NO cell lines were tagged with red/green fluorescent markers and mRNA was isolated. A gene chip analysis was used to assess genome wide gene expression. Via scratch assays cell migration rates were assessed. Within these five cell lines JUN, FOS, and AP1 genes were up-regulated when exposed to high NO. Increased migration velocities was demonstrated among all three genes.
Results: The adenocarcinoma cell lines RP6-159A1.2, RP11-255N24.3, AC004490.1, LDHBP, RP11-572H4.2 were down regulated pseudogenes, and there was no up regulated pseudogenes. The squamous cell carcinomas (SCCs) had the following up regulated pseudogenes: RPL37AP1, AC138972.1, RP11-641D5.1, AC005534.6, AC022431.1, RPL26P12, and they had these down regulated pseudogenes: RP6-159A1.2, RP11-255N24.3, RBMXP1, RP11-20O23.1, RP11-551G24.2. All cell lines showing an increase in a pseudogene expression indicating an increase in the corresponding gene (with the exception of the adenocarcinoma cell lines). JUN,FOS and AP1 genes showed increased migration velocities with up- regulation compared to the parent cell lines.
Conclusions: The high concentration of CeRNA may reduce expressions of microRNA, which would then lead to high concentrations of pseudogenes (likely due to high levels of HNO). Pseudogenes, along with BRAF, in turn reduce the expression of microRNA. Therefore, the pseudogenes and BRAF take the same role as the CeRNA. This results in a feedback loop of over expression of the coding gene.Within these cell lines JUN, FOS, and AP1 genes had an increased migration velocities which demonstrated an increased tumour aggressiveness.
Sheng Wang
Guangdong Academy of Medical Sciences, China
Title: Role of PKC-E/STAT3 signaling in repeated non-invasive remote ischemic preconditioning mediated cardioprotection diabetic rats
Time : 12:50-13:20
Biography:
Sheng Wang is the Chief of Department of Anesthesiology, Guangdong General Hospital, Guangzhou, China. He completed his MD in Anesthesiology from Peking Union Medical College in 2003, and was Master of Cardiac Anesthesia of International Heart School of Italy in Massa. He is now Vice President of Committee of Chinese Society of Cardiothoracic and Vascular Anesthesiology; member of Chinese Society of Anesthesiology (CSA) Youth Committee and member of committee of China Association of Anesthesiology (CAA).
Abstract:
Background: Protein kinase C (PKC)-ε activation is a mechanism of preconditioning cardio-protection, but its role in repeated noninvasive
limb ischemic preconditioning (rNLIP) mediated cardio-protection against myocardial ischemia/reperfusion (I/R) injury in
diabetes is unknown.
Methods: Sprague–Dawley rats were induced diabetes with streptozotocin and subjected to coronary artery occlusion and reperfusion in the absence or presence of rNLIP (three cycles of 5 minutes occlusion/5 minutes reperfusion) in a hind limb daily for three days prior to inducing I/R. In vitro, cardiac H9C2 cells were cultured with normal or high glucose for 48 hours and subjected to hypoxia/re-oxygenation(H/R) with or without siRNAs of PKC-ε or signal transducers and activators of transcription 3(STAT3). Remote time hypoxia preconditioning (HPC) was achieved by three cycles of 5 minutes hypoxia followed by 5 minutes re-oxygenation 24 hours before inducing H/R.
Results: In eight week diabetic rats, post-ischemic myocardial infarct size and troponin-I release were significantly higher with concomitant cardiac PKC-E overexpression, while the phosphorylation of cardioprotective proteins STAT3 (p-STAT3) and Akt (p-Akt) were lower compared to non-diabetic rats (all P<0.05). rNLIP reduced infarct size and post-ischemic troponin release in
non-diabetic and diabetic rats and moderately but significantly reduced cardiac PKC-E expression and increased cardiac p-STAT3 and p-Akt. In H9C2 cells, high glucose increased PKC-E activation and exacerbated post-H/R injury, accompanied with reducing p-STAT3 and p-Akt, which were all reversed by HPC. The above HPC protective effects were abolished by either PKC-E or STAT3 gene-knockdown.
Conclusion: rNLIP may attenuate diabetic heart I/R injury by mitigating high glucose induced PKC-E overexpression and
subsequently activating STAT3.
Break: Lunch Break 13:20-14-10 @ Redwood Restaurant
Suoqin Tang
PLA General Hospital,China
Title: Study on pharmacokinetics of siRNA-survivin nano-liposomes
Time : 14:10-14:40
Biography:
Suoqin Tang has completed his MD at the age of 23 years from The Fourth Medical University in China and postdoctoral studies from University of Southern California School of Medicine. He is chief physician and professor of Department of Pediatrics, Chinese PLA General Hospital, a famous and one of the best hospitals in China. He has published more than 65 papers both in China and overseas. He is an international member of Childrens Oncology Group(US), standing member of Chinese Pediatric Society, and editor of Chinese Journal of Pediatrics. He is doing clinical work on chemotherapy of leukemia and solid tumors, including lymphoma, neuroblastoma and PNET, his research work focus on target therapy of cancer.
Abstract:
Background: Our previous studies revealed that survivin siRNA nano particles are capable of inhibiting liver cancer, colon cancer and cervical cancer cell growth both in vitro and in vivo, yet pharmacokinetic parameters are largely unknown.
Objective: To investigate the pharmacokinetics of nano-liposomal survivin siRNA (CL01-si-survivin) and provide important basis for its biosafety evaluation.
Methods: Male BALB/c mice (aged 8 weeks) were randomly divided into 3 groups(n=8 for each group). Different doses of CL01-si-survivin were injected via the caudal vein in group A (1mg/kg), group B (3 mg/kg) and group C (6mg/kg). Blood samples (0.1ml each) were collected through eye socket vein after injection at the following time points: 0.083(5 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 7, 24, 30 and 48 hours (7 blood collections for each mouse). Real-time PCR was performed to detect the plasma concentration of CL01-si-survivin based on the standard curve, which was made via the following protocol: prepare survivin siRNA solution at the concentrations of 2.0E+07ã€2.0E+06ã€2.0E+05ã€2.0E+04ã€2.0E+03 pg/ml respectively, collect 10μl of each and another 10μl plasma from healthy male BALB/c mouse and put them together to 190 μL 0.25% Triton X-100 in PBS (TPS)（95℃ water bath），making the final concentrations of survivin siRNA as 1.0E+06ã€1.0E+05ã€1.0E+04ã€1.0E+03ã€1.0E+02 pg/mL, then run RT-PCR, taking the logarithm of the plasma survivin siRNA concentration as the independent variable, the average Ct value of each concentration level was the dependent variable, the linear regression, the regression equation and correlation coefficient of the standard curve were obtained, and the standard curve was drawn.
Results: The peak plasma concentrations in each group, reached at 15 minutes after injections, were 1042538.00, 6837099.54 and 14631333.15 pg/ml, respectively. The plasma concentration decreased significantly after 24 hours. The pharmacokinetic parameters were analyzed (table 1). The half- life of CL01-si-survivin in each group was 3.60, 2.64, 2.80 hours, respectively. The AUC (area under the curve) values were 952190.88, 6800687.79, 13803680.96 hr*pg/ml and the total drug clearance were 1050.12, 441.13, 434.67 ml/h/kg. Mean residence time (MRT) were 1.70, 1.97 and 2.10 hours respectively.
Conclusions:The RT-PCR method was successfully applied to pharmacokinetic study of CL01-si-survivin in vivo; The half- life t1/2 at three dosages were closed to 2-4h; Tmax was similar at 15minutes; Cmax and AUC were positively correlated to dosage between 1-6mg/kg; the MRT was close to 1-3 hours.
Zhengyuan Xia
The University of Hong Kong, China
Title: Ischemic preconditioning: Remote distance versus remote time
Time : 14:40-15:10
Biography:
Dr. Zhengyuan Xia is Associate Professor, Department of Anesthesiology, The University of Hong Kong, China. He received PhD in Pharmacology & Therapeutics from University of British Columbia, Canada in 2004, and M.B. (medical doctoral program) and Master of Medicine degrees respectively in 1984 and 1991 from China. He has published more than 120 research in internationally reputed journals, and serve as peer reviewer for reputed journals like The Lancet, Diabetes, and Anesthesiology , and for grants agencies like NSFC(Natural Science Foundation of China) and CIHR (Canadian Institute of Health Research), and is President-elect, China Association of Perioperative Translational Medical Research.
Abstract:
Brief ischemia and reperfusion to no vital organs, referred to as remote ischemic preconditioning(RIPC), can help the heart to withstand a prolonged ischemia during cardiac surgeries in non-diabetic patients. However, RIPC cardioprotection is reduced/diminished in diabetic patients with increased oxidative stress. Notably, recent large-scale clinical trials showed that RIPC, when induced immediately before surgery in patients anesthetized solely or primarily with propofol, an anesthetic reported to attenuate RIPC cardioprotection, is potentially detrimental evidenced as more than doubled1 or about 50% more patient death in the RIPC than in the sham-RIPC group, which is of clinical significance although the trials were not powered to detect statistically between-group differences. By contrast, RIPC applied before/during hospital admission increased myocardial salvage-index(area at risk-final infarct size)/area at risk) without increasing patient death. Experimentally, we demonstrated that repeated RIPC for three consecutively days reduced myocardial infarction in diabetic rats by activating mitochondrial STAT3, a key molecule in RIPC cardioprotection. RIPC at a remote time may allow the second-window cardioprotection to manifest to help better withstand ischemia during cardiac surgery and merits clinical trials to confirm.
Heshu S Rahman
Universiti Putra Malaysia, Malaysia
Title: nanoZER- Novel treatment for cancer
Time : 15:10-15:40
Biography:
Heshu S Rahman obtained her PhD from Universiti Putra Malaysia in 2014 in the field of Hematology and Clinical Pathology. Her thesis was granted as best PhD thesis at the Universiti Putra Malaysia for year 2014. Her research areas include the development of alternative treatments for cancers and nanoparticles development for drug delivery. The nanoZER (WO2014/123406 A1) is one of the products of her research. She is currently a Senior Lecturer at the Faculty of Veterinary Medicine, Univerisiti Putra Malaysia. She has published more than 100 journal and proceeding articles, produced 6 patents and received 10 awards including Gold, Silver and Bronze Medals.
Abstract:
Cancer nanotherapy is progressing rapidly with the introduction of many innovative drug delivery systems to replace conventional therapy. Zerumbone, a natural dietary lipophilic compound with low water solubility (1.296 mg/L at 25°C) was used in this investigation. The zerumbone was loaded into nanostruc¬tured lipid carriers using a hot, high-pressure homogenization technique. The physicochemical properties of the zerumbone-loaded nanostructured lipid carriers (ZER-NLC) were determined. The ZER-NLC particles had an average size of 52.68±0.1 nm and a polydispersity index of 0.29±0.004 μm. Transmission electron microscopy showed that the particles were spherical in shape. The zeta potential of the ZER-NLC was −25.03±1.24 mV, entrapment efficiency was 99.03%, and drug loading was 7.92%. In vitro drug release of zerumbone from ZER-NLC was 46.7%, and for a pure zerumbone dispersion was 90.5% over 48 hours, following a zero equation. Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in human T-cell acute lymphoblastic leukemia (Jurkat) cells, the half maximal inhibitory concentration (IC50) of ZER-NLC was 5.64±0.38 μg/mL, and for free zerumbone was 5.39±0.43 μg/mL after 72 hours of treatment. This study strongly suggests that ZER-NLC have potential as a sustained-release drug carrier system for the treatment of leukemia. Although the antitumor activity of zerumbone (ZER) has been reported, there has been no information available on the effect of ZER-loaded nanostructured lipid carrier (NLC) (nanoZER) on murine leukemia cell. The in vitro and in vivo effects of nanoZER on murine leukemia induced with WEHI-3B cells were investigated. The results from 3-[4,5-dimethylthiazol-2-yl]-2,5-iphenyltetrazolium bromide, Hoechst 33342, Annexin V, cell cycle, and caspase activity assays showed that the growth of leukemia cells in vitro was inhibited by nanoZER. In addition, outcomes of histopa¬thology, transmission electron microscopy, and Tdt-mediated dUTP nick-end labeling analyses revealed that the number of leukemia cells in the spleen of BALB/c leukemia mice significantly decreased after 4 weeks of oral treatment with various doses of nanoZER. Western blotting and reverse-transcription quantitative polymerase chain reaction assays confirmed the anti-leukemia effects of nanoZER. In conclusion, nanoZER was shown to induce a mitochondrial-dependent apoptotic pathway in murine leukemia. Loading of ZER in NLC did not compromise the anti-cancer effect of the compound, suggesting nanoZER as a promising and effective delivery system for treatment of cancer
Reza Sanaye
Shiraz University of Medical Sciences, Iran
Title: The state of the art cancer treatment
Time : 15:40-16:10
Biography:
Abstract:
To ratchet up natural body’s immune response towards cancer, subtypes of opsonizing reagents have been infused through injection (before getting into the metastasis stage) into the micro-environment of the cancerous tumor. Such chemical agents have acted in the range of 69-82% (p<0.05) in getting the peripheral tumor cells to get prepared to receive levels of spontaneously
stimulated natural killer cells. Later on, the hooking of the natural killer cells onto the opsonized peripheral micro-environment was enhanced by both changing the flow cytology through the means of micro-fluids designed in our own high-throughput scanning labs.These were copied out multifariously [in two stages] following high energy consumption from biochips as the medium in between the simulation in silico and the actual in vitro. The process of the getting of the “eat-me” signal to the natural killer cells was enhanced by 41% (p<0.05). This was accomplished as a result of porosity grading matrix inserted by boundary-atom schemes which most probably acted in response to adjuvant radiation therapy when from 100 to 1000 molecules came out of their relatively stable biomolecular structure to elaborately dissect the cancerous micro-environment into segmental lobes with a non-boundary precision 50 Angstroms.It is to be noted that Professor Reza Sanaye’s non-conventional use of Bayesian statistics has, in some cases, caused changes in the aforesaid statistical.
Break: Networking and Refreshment Break 16:10-16:30 @ Foyer
Young Research Forum
Kholoud Alwosaibai
University of Ottawa, Canada
Title: PAX2 maintains the differentiation of mouse oviductal epithelium and inhibits the transition to a stem cell-like state
Time : 16:30-17:00
Biography:
Abstract:
Recent studies have provided evidence that the secretory cells of the fallopian tube (oviduct) are a probable origin for highgrade serous ovarian carcinoma. In addition to secretory cells, the fallopian tube epithelium consists of ciliated cells and CD44+ undifferentiated stem-like cells. Loss of PAX2 expression is recognized as an early event in epithelial transformation, but the specific role of PAX2 in this transition is unknown.The aim of this study was to define the role of PAX2 in oviduct epithelial (OVE) cells and its response to transforming growth factor β1 (TGFβ), characterizing specifically its potential involvement in regulating stem cell-like behaviors that may contribute to formation of cancer-initiating cells. Treatment of primary cultures of mouse OVE cells with TGFβ induced an epithelial-mesenchymal transition (EMT) associated with decreased expression of PAX2 and an increase in the fraction of cells expressing CD44. PAX2 knockdown in OVE cells and overexpression in ovarian epithelial cells confirmed that PAX2 inhibits stem cell characteristics and regulates the degree of epithelial differentiation of OVE cells. These results suggest that loss of PAX2, as occurs in serous tubal intraepithelial carcinomas, may shift secretory cells to a more mesenchymal phenotype associated with stemlike features.
Eugenia Belcastro
University of Pisa Medical School,Italy
Title: Oxidative stress conditions induce differential S-nitrosation of smooth muscle cell proteins by S-nitrosoglutathione (GSNO)
Time : 17:00-17:30
Biography:
Eugenia Belcastro is a PhD student under joint supervision between University of Lorraine(Faculty of Pharmacy, Ḗcole Doctoral BioSe, Nancy) and University of Siena (PhD in Genetics,Oncology and Clinical Medicine, GenOMeC) and with work station at the University of Pisa(Department of Translational Research and New Technologies in faculty of Medicine). She will complete and get the PhD in November 2016. She has already participated in several international conferences and she has published several articles in reputed journals.
Abstract:
Background & Aims: Reduced availability or depletion of nitric oxide (NO) is often involved in pathogenesis and/or progression of cardiovascular diseases, such as atherosclerosis, thrombosis, pulmonary hypertension, ischemia and arrhythmia. Several NO-related therapeutics have been developed to overcome the problem, such as e.g. organic nitrates, metal—NO complexes, nitrosamines etc., but all have relatively short half-lives and produce tolerance phenomena and oxidant stress. These drawbacks are absent in S-nitrosothiols (RSNOs), i.e. molecules in which NO is reversibly bound to SH groups, and in particular, S-nitrosoglutathione (GSNO) – the endogenous/physiological storage and transport form of NO – is under active investigation. However, the ability of GSNO to regulate NO bioavailability under oxidative stress is poorly studied. Using protein S-nitrosation (Pr-SNO), a post-translational protein modification, as a biomarker of the NO pool (1), the study aims to evaluated the capacity of GSNO to deliver NO to smooth muscle cells (SMCs) under oxidative stress. Furthermore, the implication of redox enzymes implicated in GSNO metabolism, such as gamma-glutamyl transferase (GGT) and protein disulfide isomerase (PDI), in Pr-SNO formation under oxidative stress will be assessed.
Experimental: Rat aorta embryonic SMCs (A-10 cell line) were exposed in vitro to a free radical generator, AAPH, as an oxidative stress model. Oxidative stress impact on the expression/activity of redox enzymes implicated in GSNO metabolism, as well as NO release were evaluated. The intracellular thiol redox status was also monitored in relation with the extent and distribution of GSNO-induced intracellular proteins S-nitrosation (mass spectrometry (LCMALDI) analysis).
Results: Under oxidative stress, GSNO-metabolizing enzymes were differentially modulated: GGT (activity) was in fact decreased by 3.5-fold, while PDI (expression) was increased by 1.7- fold. Oxidative stress produced the increase of extracellular GSNO-catabolism into nitrite ions as well as an increase in seric proteins S-nitrosation. Moreover, oxidative stress caused both a decrease of SH groups in cellular proteins and an efflux of intracellular GSH to the extracellular space. However, only the first phenomenon was prevented by concomitant administration of GSNO. In agreement with the increased NO release, GSNO-dependent protein S-nitrosation was approx. 2-fold increased under oxidative stress. Experiments with GGT inhibitor serine-borate complex (SBC) and PDI inhibitor bacitracin confirmed that even oxidative stress modified their activity/localization, both enzymes participated in GSNO catabolism and subsequent Pr-SNO. LCMALDI analysis revealed that the number of proteins S-nitrosated by GSNO was increased under oxidative stress (51 proteins, vs. 32 in basal condition). Compared to basal condition, oxidative stress promoted the S-nitrosation of three additional classes of proteins, implicated in cell adhesion, transfer/carrier functions and cellular transport, and in particular favored the S-nitrosation of a higher number of cytoskeletal proteins (17 vs. 8 in basal condition).
Conclusions: Data obtained so far confirmed that oxidative stress such as those occurring in inflammation can modify the activity and/or expression of two critical enzymes in GSNO metabolism, GGT and PDI. Overall, oxidative stress induced higher levels of GSNO-dependent NO release and RSNOs formation. Protein S-nitrosation effected by GSNO under oxidative stress was more extensive, due to the involvement of additional proteins of SMCs cytoskeleton and contractile machinery. Further studies will likely elucidate the pathophysiological significance of these observations.
Md Zahid Hasan Khan
MPH Nothern University, Bangladesh
Title: Nutritional status of women of reproductive age in a selected char of rangpur district
Biography:
He is a Student Masters of Public Health degree at the age of 32 years from Northern University Bangladesh. He has published more than 10 papers in reputed journals.
Abstract:
An observational cross-sectional study was carried out at Rangpur district in Bangladesh to assess nutritional status of reproductive aged women residing in char area with a sample size 200. Face to face interview was carried out with the semi-structured questionnaire. Convenient sampling technique was used to collect data on the basis of inclusion and exclusion criteria and written consent was taken prior to interview. Nutritional status was determined according to BMI cut off value for Asian population. Descriptive as well as inferential statistics were used to present data. Mean±SD age of respondents was 34.27±8.60. More than half (67%) of the respondents were illiterate and housewife (84%). Mean±SD income of respondents was 5700.71±282.89 per month. Underweight, normal and overweight were 67%, 30% and 3% respectively. Most respondents took rice 2-3times/day. Vegetables and soyabean were taken randomly. Lentil was taken daily. Arthritis, headache, skin disease was more common. Statistical significant association was found between nutritional status and age group (p<0.05), education (p<0.05), occupation (p<0.05) and monthly income (p≤0.05). Half of the respondents suffered from underweight and most of them income was very low. Income generating capacity should be increased as well effective nutrition education programme must be instituted.
Bing Zhu
The first Affiliated Hospital of Bengbu Medical College, China
Title: Activated hepatic stellate cells promote angiogenesis via interleukin-8 in hepatocellular carcinoma
Biography:
Bing Zhu became a doctor has more than ten years, mainly engaged in general surgery department. He has completed PhD at the age of 35 years from Zhongshan University's third affiliated hospital. Currently, major directions of research are tumor angiogenesis.
Abstract:
Background: Chemokines have been recognized as important modulators of angiogenesis, and they play critical roles in the development and metastasis of hepatocellular carcinoma (HCC), although their origins and latent molecular mechanisms remain elusive. The aim of this study was to investigate how activated hepatic stellate cells (a-HSCs) promote angiogenesis in HCC.
Methods: A total of 22 HCC patients were enrolled randomly. We used immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay (ELISA) to analyse the production of interleukin-8 (IL-8) in a-HSCs derived from HCC tissues. The angiogenic effects of IL-8 in vitro and in vivo were assessed by ELISA, real-time quantitative polymerase chain reaction, capillary tube formation assay, and chick embryo chorioallantoic membrane assay.
Results: The present study showed that IL-8 was enriched predominantly in the tumour stroma of HCC tissues and was mainly derived from a-HSCs, rather than from hepatoma cells, in vivo and in vitro. Angiogenesis was most active at the invading edge, which was close to the a-HSCs. The angiogenic effect was dramatically attenuated by an IL-8 neutralizing antibody both in vitro and in vivo. Moreover, the IL-8 neutralizing antibody down-regulated Ser727-phosphorylated STAT3 levels in hepatoma cells treated with a-HSCs conditioned medium.
Conclusions: These findings reveal that a-HSCs within the stroma of HCC contribute to tumour angiogenesis via IL-8.
Veronica Robert
Clinica Las Condes,Chile
Title: Psycho-oncology: A psychosocial support and intervention model
Biography:
Veronica Robert is a Psychologyst graduated at Diego Portales University in Santiago , Chile. She has completed her postgraduate studies in Psychooncology in the same University. With a postgraduate studies also in Bioethics and Oncology Advances at Universidad de Chile She is the director of The Psychooncology Departmenten y Centro Clínico del Cáncer in Clínica Las Condes in Santiago, Chile.
Abstract:
Nowadays we face a world with a technologic environment changing and advancing constantly, which, in the oncologic scope, implies more advanced investigations and therapies, observing a constant evolution in the management and symptomatic control of the oncologic illness. This scenario implies a higher frequency of patients who suffer its consequences within a short, medium or long time limit, involving permanent adaptation processes. It was already by the mid of the past century that the Psycho-oncology subspecialty arises so as to ameliorate the pshycosocial adjustment the oncologic person has to suffer from its multiple effects. Cancer illness considers an impact that transcends not only physical shock but also an emotional process, considering the person as a whole, with personal, familiar and environmental aspects, allowing us to see this illness from a biopshychosocial view. An affective climate is generatedcreating a complex questioning and deep changes in the various contexts where the patient is set in. The fact of losing what is most important as health, with all its consequences, the person experiences the oncologic mourning. Is the way how the patient confronts the disease and his/herenvironment. The distress experience within the process of this illness ,can bring out negative effects for the patient’s health and quality of life. Moreover, the developing of psychiatric disorders are more frequent in oncologic patients than in patients who do not suffer this illness. The major vulnerability of the oncology patients to develop a psychiatric disease, is an importantissue the medical staff have to take into account., so they require special care and be aware of this patient’s emotional needs. In the present article, an interventional model is presented supported by the emotional aspects studied in the oncologic patient. Relevant aspects are presented and developed of the patient’s general evaluation , an emotional support structure and the required interventions to fulfill the aims of it.
- Biomarkers in Translational Medicine
Translational Cardiology and Vascular Medicine
Clinical Epidemiology
Immuno-Oncology
Session Introduction
Juel Chowdhury
University of Illinois, USA
Title: Exposure to high levels of Nitric Oxide (NO) showed transmembrane glycoprotein NMB (GPNMB) over expression and cadherin-1, Type-1 (CDH1) downregulation, in head and neck Squamous Cell Carcinomas (SCC)
Time : 11:35-12:05
Biography:
Juel Chowdhury began his professional education at the Gulf Medical University where he received his Bachelor of Medicine and Bachelor of Surgery. Since then, his works have led him to partner and study with Nobel laureate Dr. Ferid Murad and many well-known scientists such as Dr. Robert Winn Director of UI health. He is the founder and president of Oncomarks.org an online professional network with an open access journal for the oncologist. His innovative iGenX lab is a genetical research lab based on data-mining and data analysis of the gene-chip experiment. Editorial Board for many international journals like Tumor Biology, JCMT. JUMD, and many professional societies like ASCO and ISOBM. He was the director of ISOBM (International society of oncology and biomarkers) 2016 congress held in Chicago and also the upcoming ISOBM 2017 congress in Brazil. Expert in Botulinum Toxin and Dermal Fillers, facial reconstruction and hair transplant procedures. Faculty member of National College of Health. research interests are as follows: head & neck cancer, lung & upper aero digestive tumors, human tumor stem cells. Nitric oxide in tumor environment.
Abstract:
Hypothesis: Exposing SCC cell lines to increasing levels of NO can result in the increased expression of Transmembrane Glycoprotein NMB (GPNMB) and down regulation of Cadherin-1, Type-1 (CDH1) that contribute to the progression of metastasis.
Objective: Nitric Oxide is a free radical molecule which communicate and transmit signals throughout the body. Recent studies have shown that exposure to Nitric Oxide (NO) results in stem cell-like properties of cancer cells. Cancer metastasis is a complex process involving a number of highly regulated steps, such as, cell invasion, proliferation and migration. Overexposure of HNO levels in cells cause protein coding genes to be down regulated that play a key role in cell adhesion, cell signaling and cell communication. To study the relationship between HNO Levels and metastatic potential, High Nitric levels were presented in four H&N SCC cell lines. HNO adapted cell lines caused down regulation of CDH1 and up regulation of GPNMB in all four cell lines. One of the causes of carcinogenesis is due to abnormalities in tumor suppressor protein coding genes. In this case, CDH1 was found to be down regulated.CDH1 gene provide manuals for producing a protein that codes for Epithelial Cadherin or E-Cadherin. E-Cadherin regulate celladhesion, cell proliferation which plays an important role as tumor suppressor genes In similar studies, it was also found that cancer cells overexpress the GPNMB gene, which is believed to have a role in metastasis. GPNMB is a type I transmembrane glycoprotein protein that has been found to be up-regulated in various cancers. A key feature of GPNMB is its tripeptide (Arg-Gly-Asp) RGD motif, which is capable of integrin binding. This activity is important when it comes to the regulation of cell migration, cell adhesion, and other vital processes of metastasis.
Methods: GPNMB type I transmembrane glycoprotein protein and Cadherin-1 Type-1 (CDH1) were observed in five H&N cell SCC cell lines: SCC016, SCC040, SCC056, SCC114, and SCC116 .The cell lines were subjected to increased levels of NO by DETANONOate until a maximum concentration of 600 mM was reached. RNAs were isolated from these cell lines and their respective parent cell lines. The gene level expression of these NO exposed cell lines were then compared to their individual parent cell lines using DNA microarrays. This data was further compared to a UniProt-GOA association file (Human) by a program, in order to find genes belonging to certain Gene Ontology (GO) terms. The GO term used was GO:0005178, which contains genes related to the molecular function of integrin binding.
Results: It was observed that along with GPNMB being commonly overexpressed and CDH1 genes to be down regulated, in all five SCC cell lines (SCC016, SCC040, SCC056, SCC114, SCC116) that were exposed to increased levels of NO, they also appeared to be the most consistently up-regulated genes. GPNMB contains an RGD motif in its extracellular domain region, which is recognized by many members of the integrin family. Binding of this ligand motif to integrins can lead to important cell adhesion interactions and other metastatic processes.
Conclusions: Exposure to high levels of NO is correlated with an increase in the expression levels of genes that enhance metastatic potential. NO cancer cells were found to overexpress the GPNMB gene and downregulate CDH1 gene. Down regulation of CDH1 means that the gene expression is reduced or decreased. Therefore, causing it to be increase in metastatic potential. Further study is required to understand the mechanism by which GPNMB and CDH1 contributes to the progression of metastasis. Additional studies with varying concentrations of NO and its effect on GPNMB expression may also be useful in determining the genes significance.
Ren Chongxi
Hebei Medical University, China
Title: Continuum of care should be therapeutic strategy for human metastatic colorectal cancer
Time : 12:05-12:35
Biography:
Ren Chongxi graduated from Hebei Medical University and completed his MD from QingDao University School of Medicine. He is the Director of Department of Surgical Oncology, Hebei Medical University. He has published more than 20 papers in reputed journals and has been serving as an Editorial Board Member of repute.
Abstract:
Treatment of human metastatic colorectal cancer (mCRC) remarkably changed over the past two decades. The use of novel therapies and more complex treatment strategies have contributed to progressively increase the median life expectancy of patients up to approximately 30 months. Although traditional cytotoxic chemotherapy and newly targeted therapy are now available for use in treating patients with mCRC, the optimal treatment strategy remains unknown. Currently, therapeutic strategies for mCRC patients are based on a continuum of care whereby patients are exposed throughout the course of their disease to different active drugs, the therapy is personalized according to the need for rapid response and the burden of disease and RAS status, drugs are often reintroduced if they showed activity in previous line of therapy, and extremely importantly, maintenance chemotherapy and/or intermittent therapy are considered. Here, we review available data for the use of continuum of care strategy in mCRC, and regard it as a promising treatment strategy.
Workshop
Babak Daneshfard
Shiraz University of Medical Sciences, Iran
Title: Boundary-state light emission quantums in biomolecules
Time : 12:35-13-35
Biography:
Babak Daneshfard has done his PhD from Shiraz University of Medical Sciences (SUMS). He has published more than 10 papers in reputed journals and has been serving as a Reviewer of CAM Journals. He is also an expert in Mind-Body Medicine.
Abstract:
If light is to be emitted from substance(s) through means of jumping down of an electron from a higher position to a lower energy level, as defined by modern physics mainstream phenomenon, then the collocation of an arbitrarily chosen “central” atom with its adjacent atoms would most naturally provide a hypothetical matrix for observations, and calculations to be carried out regarding how much the boundary-atom schemes can probably replace the already routine procedures in the workings of optical physics. True to the fact is that: Ordinary large-sized molecules (with from 100 to 1000 atoms) mostly have their origin in relatively stable bimolecular structures with some computational difficulties which provide some sort of continuum for studying optical links through neighboring atoms vibrations without specific recourse, for example, to yet other atoms whose gradually increasing distance to the “central” atom brings in parameters of beyond-5-Å non-boundary conditions that are normally too complicated to be brought out by eigenfunctions as eigenvalues. There are, of course, molar fractions of vibration quality atoms again to be constructurally role-playing in nearly exact determination of the amount of error arising from the actuality that biomolecular atomic regionalization gets out of the state of arbitrariness. In case this parameter were not to be detectable, adjustable (through adding on or deleting metal atoms on recipient sites on the said large molecules or: alternatively, through being in possession of optic isomers) or even removable (say, by means of picking totally different biomolecules), the clamped string of atoms considered to be in the same region should have, consequently, not provided constraints to assist in building up even the differential equations themselves.
Break: Lunch Break 13:35-14:15 @ Redwood Restaurant
Supreet Khare
University of Arizona, USA
Title: Role of immunophenotyping in the diagnosis of acute leukemias of ambiguous lineage: A new entity described in WHO 2008
Biography:
Supreet Khare has studied form Armed Forces Medical College, Pune, India. He is now the Internal Medicine Resident at University of Arizona
Abstract:
There is a rare type of acute leukemia that is difficult to classify, and which concurrently has morphologic, cytochemical and immunophenotypic characteristics of both myeloid and T- or B-lymphoid lineages. The recent WHO classification of 2008 refers to this type of entity as bilineage AL, or biphenotypic AL (BAL), and places it into a subtype of the group ‘acute leukemia of ambiguous lineage’(1,2) alongwith AL with aberrant expression. BAL represents <5% cases of acute leukemia. This study aims to analyze immunophenotypic profile of acute leukemias of ambiguous lineage and to study the prevalence in Indian scenario. Flow cytometric immunophenotyping (FCI) was performed on fresh bone marrow or blood specimens. Single-cell suspensions were incubated with combinations of monoclonal antibodies in four-color immunofluorescence. The antibodies were conjugated to fluorescein isothiocynate (FITC), phycoerythrin (PE), peridinin chlorophyll protein complex (PerCP) and allophycocyanin (APC).Antibodies used in the analysis recognized stem cell and pan-leukocyte antigens including CD45. Samples were analyzed using 4 color flow cytometry and the blast cell populations were identified by CD45 versus side scatter properties using standard staining and analytical methods. Out of 24 cases of acute leukemia in 4 months, we report 04 cases diagnosed as AML or ALL based on FAB (16%). However, on FCI these were diagnosed as BAL, bilineage AL & ALL with aberrant myeloid expression. Unlike other leukemias, BAL is a type of acute leukemia with uncommon biological and clinical features. Limited studies are available hence at least; Patients who are not responding well should be screened for ambiguous lineage using comprehensive FCI and molecular studies.
Zoheir A Damanhouri
King Abdulaziz University, Saudi Arabia
Title: Potentiation of therapeutic effect of cisplatin and protection against its nephrotoxicity by resveratrol in experimental animals
Time : 14:45-15:15
Biography:
Zoheir A Damanhouri is currently the Chairman of Pharmacology Department in the Faculty of Medicine at King Abdulaziz University, Jeddah, Saudi Arabia. He obtained his BSc degree in Biochemistry from the University of Lancaster in the United Kingdom, and his MSc and PhD in Pharmaceutical Sciences from the University of Wales. His main research focuses on various areas in pharmacology including natural products on anticancer drugs and their toxicities, implication of herbal medicine co-administration with conventional drugs and therapy also on drug metabolism in particular variability in CYP450 isozymes (and SNP’s) and their involvement in drug interactions, adverse drug effects and polymorphism. He has over 40 publications in his specialty in pharmaceutical sciences
Abstract:
Background: Cisplatin (CIS) is one of the most effective anticancer drug used in the treatment of several solid tumors. Its use is limited by its nephrotoxicity. The present study was designed to assess the role of a natural product resveratrol (RSVL) on sensitization of mammary carcinoma (Ehrlich ascites carcinoma) to the action of CIS in mice and the possible protective effect against CIS-induced nephrotoxicity in rats.
Methods: The percent survival of female tumor bearing mice was used for determination the cytotoxic activity of CIS in the presence or the absence of RSVL. Uptake and cell cycle effect, serum creatinine (CREA), blood urea nitrogen (BUN), reduced glutathione (GSH) and histopathological examination of kidney tissues after CIS and/or RSVL therapy were also investigated in mice and rats.
Results: RSVL increased the intracellular level of CIS in EAC cells. CIS at a dose of 5 mg/kg increased the mean survival time of female tumor bearing mice to 25 days compared with 17 days for tumor-bearing control mice. Administration of RSVL at a dose of 25 mg/kg simultaneously with CIS increased the mean survival time to 48 days with 60% survival of the tumor-bearing animals. Cell cycle analysis of tumor cells showed that CIS treatment decreases the proliferation index of tumor cells while in presence of RSVL there were more significant inhibitions. Moreover, There was more increase in the percentage cells in sub-G1 phase 24 and 48 hours after treatment with CIS+RSVL compared with CIS alone (33% and 36% respectively). CIS treatment caused increase in level of creatinine and blood urea with significant decrease in the GSH level in rats. While, in the presence of RSVL, level of creatinine and blood urea restored to control level.
Conclusion: This study suggests that RSVL could increase the cytotoxic activity of CIS and protect against its nephrotoxicity.
David Stejskal
Agel Training and Research Institute, Czech Republic
Title: Laboratory diagnostics in oncology
Biography:
Prof. David Stejskal MBA has completed his Ph.D at the age of 33 years from Palacký University and postdoctoral studies from Charles University, School of Medicine, Czech Republic. He is the head of Department of Laboratory Medicine Central Moravian Hospital Trust, Czech Republic. This is the branch of Agel Training and Research Institute. He has published more than 170 papers in reputed journals and serving as an editorial board member of repute journals.
Abstract:
- Breast Cancer
Surgical Oncology
World Cancer Market
Session Introduction
Marina A Guvakova
University of Pennsylvania, USA
Title: The quest for biomarkers of earliest signs of invasive breast cancer
Biography:
Marina A Guvakova completed her PhD in Cell Biology at Russian Academy of Sciences and Post-doctoral training at Columbia and Thomas Jefferson University, USA.She is an Assistant Professor at University of Pennsylvania Perelman School of Medicine and a Senior Research Investigator in Department of Surgery. She is an author of 20+ papers, recipient of New Investigator Award from Endocrine Society, Breast Cancer Research Award from DoD BCRP and Gordon Research Conferences Awards. She serves as a Reviewer for several journals, Editorial Board Member of ISRN Endocrinology and a CDMRP peer-review panel member.
Abstract:
Background: A subset of patients with ductal carcinoma in situ (DCIS) will develop invasive breast cancer (IBC). To date, there are no predictive biomarkers for identifying this subset with worse prognosis because progressive cancers in situ (CIS) are essentially indistinguishable histologically from those with favorable outcomes.We hypothesized that the measurable parameters discriminating CIS from CIS with concurrent microinvasion may serve as early diagnostic biomarkers (BM) of cancer progression.
Methods: Using a novel imaging-based method, we measured the relative expression levels of proteins implicated in cancer progression- the insulin-like growth factor I receptor (IGF-IR), Ras-related protein 1 (Rap1), and Vav2 oncoprotein. Protein profiles were compared in 42 histologically normal mammary samples, 71 CIS (35 without/36 with invasion either on diagnostic biopsy or final surgical excision), and 98 IBC of known estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status.
Results: The levels of the IGF-IR and Rap1 protein expression were significantly elevated in ER-positive (ER+/PR+/-/HER2–) DCIS relative to normal epithelium (P<0.0001). The IGF-IR protein expression was also significantly up regulated in HER2-positive (ER+/-/PR+/-/HER2+) DCIS relative to normal epithelium (P=0.0002). IGF-IR and Rap1 protein expression levels were similar among DCIS patients without or with concurrent invasion. Vav2 upregulation in DCIS relative to normal group was not associated with steroid hormone receptor and HER2 status, but was associated with the presence of concurrent invasion. DCIS with high Vav2 were more than twice as likely to progress to invasive cancers as DCIS with low Vav2 (odds ratio, 2.42; 95% CI, 1.26-4-65; P=0.008). Furthermore, a receiver operating characteristic curve analysis revealed moderate ability of Vav2 protein expression measurements in DCIS to predict the existence of invasion concurrent with DCIS (area under the curve, 0.71; 95% CI, 0.59-0.84).
Conclusions: Our novel findings hold promise for utilizing Vav2 as a predictive BM for differentiating progressive from nonprogressive DCIS.
Mary Mok
Texas Tech University Health Sciences Center, USA
Title: Bilateral orbital myeloid sarcoma preceding Acute Myeloid Leukemia in an adult: Case report and review of the literature
Biography:
Mary Mok has completed Medical School from Universidad de Oriente, Venezuela. Currently She is an Internal Medicine PGY-2 at Texas Tech University in Odessa, Texas
Abstract:
Acute myeloid leukemia is typically a disease of the older population and presents mostly in the fifth decade of life. Myeloid sarcoma is a rare initial presentation of acute myeloid leukemia. Previously, it has only been documented in children and younger
patients. We present an unusual case of retro-orbital myeloid sarcoma as an initial presentation of acute myeloid leukemia in a 43 year old male with rearrangement of chromosome 11q23 involving MLL gene. Our case is unique as the cytogenetics involved differs from those previously documented in literature and their impact on the prognosis has not been previously studied. Here we highlight the dilemmas faced in diagnosing this rare variant of acute myeloid leukemia.
Break: Networking and Refreshment Break 11:15-11:35 @ Foyer
Babak Daneshfard
Shiraz University of Medical Sciences, Iran
Title: Negation of negation: social psychology and mathematics meeting face to face
Biography:
Babak Daneshfard has done his PhD from Shiraz University of Medical Sciences (SUMS). He has published more than 10 papers in reputed journals and has been serving as a Reviewer of CAM Journals. He is also an expert in Mind-Body Medicine.
Abstract:
The application of open-ended classifications within the context of philosophy of science would treacherously lead researchers in the field of humanities and logics into abrupt transcendentalism. As a result, there comes on the scene thought of nontranscendental instrumentality by which genealogy of trans-cendence from Kant downwards would not include the procedural judgment by which the void of any void could possibly be defined. In cases where a psychoanalytic void proves to be some position itself qualifying various transcendental desires, then reconstructive methodology is felt to be necessitated to turn us away philosophically from such positions as Sartre or Michel Foucault to one’s more similar to those of Spinoza or Gilles Deleuze.As Lacan asseverates :“Sublimate as much as you like; you have to pay for it with something. And this something is called jouissance. I have to pay for that mystical operation with a pound of flesh.” Transference from the void of asymptoticality and/or tangentiality in not only severe neurotic cases, but also among psychoses appears to be the result of this very quasilogical turn of surrender to negation as personal denoting voids would lead to social-symbolic non-orders. Even the mathesis of negatory negation does not necessarily mean that lines of flight are part and parcel of any freedom from abstract void. This spells that transcendentalism is non-competent in laying its claim to avert the formalism through which logical formalism has to undergo.
Babak Daneshfard
Shiraz University of Medical Sciences, Iran
Title: Negation of negation: social psychology and mathematics meeting face to face
Biography:
Babak Daneshfard has done his PhD from Shiraz University of Medical Sciences (SUMS). He has published more than 10 papers in reputed journals and has been serving as a Reviewer of CAM Journals. He is also an expert in Mind-Body Medicine.
Abstract:
The application of open-ended classifications within the context of philosophy of science would treacherously lead researchers in the field of humanities and logics into abrupt transcendentalism. As a result, there comes on the scene thought of nontranscendental instrumentality by which genealogy of trans-cendence from Kant downwards would not include the procedural judgment by which the void of any void could possibly be defined. In cases where a psychoanalytic void proves to be some position itself qualifying various transcendental desires, then reconstructive methodology is felt to be necessitated to turn us away philosophically from such positions as Sartre or Michel Foucault to one’s more similar to those of Spinoza or Gilles Deleuze.As Lacan asseverates :“Sublimate as much as you like; you have to pay for it with something. And this something is called jouissance. I have to pay for that mystical operation with a pound of flesh.” Transference from the void of asymptoticality and/or tangentiality in not only severe neurotic cases, but also among psychoses appears to be the result of this very quasilogical turn of surrender to negation as personal denoting voids would lead to social-symbolic non-orders. Even the mathesis of negatory negation does not necessarily mean that lines of flight are part and parcel of any freedom from abstract void. This spells that transcendentalism is non-competent in laying its claim to avert the formalism through which logical formalism has to undergo.
Video Presentations
Nikola Radovic
University Hospital Dubrava, Croatia
Title: Surgical treatment of neuroendocrine carcinoma of the bladder
Biography:
Nikola Radovic has become a Urology Specialist in 1990. He graduated from School of Medicine, University of Zagreb, where he has also obtained his Master’s degree in 1991 and PhD in 2005. In 1994, he successfully qualified the Statutory Examination in Medical Profession at Medical University of Innsbruck in Austria. Currently, he works at Urology department of University Hospital Centre Zagreb. He had several publications in reputed clinical journals. For his humanitarian work, he was honored twice by Croatian Red Cross.
Abstract:
In urinary bladder, tumors with neuroendocrine differentiation account for less than 1% of primary malignances. Apart from low grade “typical” and intermediate grade “atypical” carcinoids which usually have a bit more favorable outcome for the patient, depending on whether or not there are distant metastases present, small cell neuroendocrine carcinomas (SCNEC) and large cell neuroendocrine carcinomas (LCNEC) are both extremely aggressive and have very poor prognosis. SCNEC is the most common with roughly 500 cases diagnosed annually, while carcinoids and LCNEC are far less common, as there are approximately 20 cases of each type recorded worldwide. Although carcinoids are slowly growing tumors, the final outcome of treatment would primarily depend on disease stage. SCNEC and LCNEC behave similarly, but because of their rarity most effective therapeutic strategies are still largely unknown. In a way LCNEC and SCNEC can be regarded as a systemic disease as micro-metastases may be present in clinically localized disease, so bladder-sparing protocols have a serious drawback because there is a high probability of residual or recurrentcarcinoma occurrence in the preserved bladder. Radical surgery currently seems to be the best option for patients with localized disease, and in combination with other therapeutic modalities it may provide long-term control. However, in approximately 50% of cases, distant metastases are already present at the time of diagnosis and in those patients surgery has limited power to improve the outcome. Also, advanced age along with other multiple co-morbidities typically contribute to poor survival.
Renata Dobrila-Dintinjana
Clinical Hospital Center Rijeka, Croatia
Title: The role of erythropoietin and erythropoietin receptors in gastrointestinal cancers
Biography:
Working as Head of Medical Oncology dpt in Clinic for Radiotherapy and Oncology, Clinical Hospital Centre Rijeka and Professor of Internal Medicine on School of Medicine, University of Rijeka, Croatia.Master of science acchieved in 1987, Specialist of Internal medicine 1995, PhD 1999, Assistant Professor 2003, Medical Oncologist subspecialization 2005 and Professor 2009. During education and careear development participated in numerous international courses, including Zagreb, Boston, Miami, New York, Chicago. In the same time participated as international speaker on Postgraduate courses related to oncology, chemotherapy and pain management in Moscow, Hong Kong, Athens, Tokyo, Rovingno and as International Invited speaker in Vienna, Chicago, Moscow, Bucharest, Philadelphia, Athenes, Sarajevo, Bangkok, Fuzhou, Seoul. All together more than 50 participations that covered various aspects of research and management of oncologic patients. Results of work presented in over 50 international publications and 10 books and books chapters. Involved in several projects sponsored by Croatian Ministry of Health. Member of numerous International and National organizations, including IASGO, MASCC, ASCO, ESMO, EACR. Member of Croatian Medical Oncology Society Executive Committee and Vicepresident of Croatian Oncology Foundation.
Abstract:
Anemia is an independent negative prognostic factor for survival in patients with malignant diseases. Pathophysiology of anemia in patients with malignant disease is multifactorial and anemia has effects on tumor hypoxia and is enhancing resistance to antitumor therapy .Erythropoietin (Epo) is a glycoprotein hormone that binds to cells with erythropoietin receptor, thus leading to its activation and stimulation of erythropoiesis.The mature form of Erythropoietin receptor (EpoR) is transferred to the surface of the cells where it becomes available to Epo that binds to it. Epo signaling is initiated by binding of Epo molecule to EpoR that forms a homodimer resulting in activation of two Janus kinase 2 (JAK2), (tyrosine kinase molecules). Epo is pleiotropic hormone with angiogenic and
neurotrophic functions and thus EpoR can act not only on erythroid progenitors but even in endothelial cells, epicardium and pericardium, kidney, pancreas, placenta, and in certain regions of the brain. Tissue hypoxia is the main stimulus of Epo production . Regulation of Epo expression is controlled by several DNA sequences. In a smaller part Epo is excreted through the kidneys and liver. Cancer cells and vascular endothelial cells express EpoR. EpoR is activated by Epo in the systemic circulation, which may be endogenous or synthetic origin. Synthetic forms of Epo are often used in clinical practice in patients with malignant diseases, with the aim of increasing the level of hemoglobin, decreasing the frequency of red blood cell transfusions and improving the quality of life (QoL). There are concerns about possibility that Epo can stimulate the proliferation of tumor cells in vitro but recombinant Epo administered in “in vitro” conditions in different tumor cell lines did not lead to growth stimulation, even in cases where the cell lines expressed EpoR. Additional concerns arise that Epo can act as an angiogenic and, in general, as a cell growth factor. Synthetic forms of Epo can stimulate physiological or pathological angiogenesis and can stimulate EpoR expression in tumor and vascular endothelial cells leading to tumor growth and angiogenesis.In colorectal cancer Epo and EpoR expressions are statistically higher in adenocarcinomas versus mucinous carcinomas and in moderately (G2) versus poorly differentiated (G3)tumors . Overexpression of HIF-1α (Hypoxia Induced Factor) was an independent risk factor for recurrence after curative resection of metastatic CRC. In gastric carcinoma angiogenic potential of Epo is similar to that of VEGF and also, microvessel density in tumor tissue was significantly higher in patients with high Epo or EpoR expression, compared to the patients with low EPO or EpoR expression. The most interesting finding (with no explanation) was that the expression of EpoR was age dependent - it was increased in older age. Hepatocellular carcinoma (HCC) promotes erythrocytosis and is associated with increased levels of Epo. Poorly differentiated HCC has a higher degree of vascularity compared to well-differentiated HCC and tumor progression in HCC is associated with angiogenesis and increase in microvascular density is followed by worse prognosis.Pancreatic Ductal Adenocarcinoma (PDAC) is extremely aggressive tumor and is associated with a high rate of malignancy. Ectopic non-malignant sources of Epo ( hepatocytes and capillaries) are potential sources of additional secretion of Epo and high levels of endogenous Epo is an independent negative prognostic factor for survival in patients with PDAC .Several randomized trials of ESAs in patients who have cancer have recently reported inferior outcomes in tumor progression or survival, raising appropriate concerns about the safety of these agents in oncology. Although the preponderance of the data suggests that EPO/EpoR alter survival large well-controlled trials addressing this issue are still needed.
Break: Lunch Break 13:05-14:00 @ Redwood Restaurant