Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 14th Annual Conference on Translational Medicine and Oncologists Meet San Francisco, California, USA.

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Scientific Program Day 1
Scientific Program Day 2
Scientific Program Day 3

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

Conference Series Translational Medicine 2016 International Conference Keynote Speaker Deepak Sampath photo
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

Conference Series Translational Medicine 2016 International Conference Keynote Speaker Hans J. Nielsen photo
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
Speaker
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
Speaker
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

Speaker
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

Speaker
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

Speaker
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+07、2.0E+06、2.0E+05、2.0E+04、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+06、1.0E+05、1.0E+04、1.0E+03、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

Speaker
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
Speaker
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
Speaker
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.