Scientific Program

Conference Series Ltd invites all the participants across the globe to attend International Conference on Pancreatic Disorders and Treatment Chicago, Illinois, USA.

Day 2 :

Keynote Forum

Animesh Dhar

University of Kansas Medical Center, Kansas City, Kansas

Keynote: Novel nutraceuticals GZ17-06.02 suppresses pancreatic cancer tumorigenesis and metastasis by inhibiting cancer stem cells

Time : 09:40-10:20

Conference Series Pancreas 2016 International Conference Keynote Speaker Animesh Dhar photo
Biography:

Dhar rcompleted his PhD from University of Calcutta in Physiology and did his post-doctoral training in University of Puerto Rico in Biochemistry and University of Missouri-Columbia in Pharmacology. Then, Dr. Dhar became Research Track Assistant Professor in Pharmacology, University of Columbia and then moved at University of Missouri-Kansas City School of Medicine as Associate Professor. He joined in the Department of Cancer Biology as an Associate Professor in University of Kansas Medical Center. Dr. Dhar has published more than 60 publications in the journals of international repute and about more than 10 reviews in thw area of his research

Abstract:

Purpose: Current therapeutic regimens have limited effectiveness in pancreatic adenocaricinom (PDAC). Novel therapeutic targets are needed to treat this disease. GZ17-06.02, novel nutraceutical, showed its anti-cancer properties in several cancers. We hypothesize that GZ17-06.02 will inhibit tumor progression and metastasis in PDAC.

Experimental Procedure: In this study, we have determined cell proliferation, pancosphere formation and apoptosis following treatment of different doses GZ17-06.02 in human pancreatic cancer cells. Cell cycle distribution and apoptosis were measured using flow cytometic analysis. Orthotopic pancreatic cancer model in athymic mice was developed and GZ17-06.02 was given orally for 20 days to those mice. Proliferative markers, pEGFR/pAkt and apoptotic markers, Bax/Bcl-2, were monitored following treatment with GZ17-06.02 in both in vivo and in vitro models. Metastatic markers, MMP-2 and MMP-9 were measured in metastatic tissues in orthotopic models.

Results: GZ17-06.02 inhibited proliferation of pancreatic cancer cell lines in a dose- and time-dependent manner. GZ17-06.02 induced apoptosis in both in vitro and in vivo pancreatic cancer. Moreover, the compound significantly inhibited epidermal growth factor receptor and Akt phosphorylation. Furthermore, GZ17-06.02 decreased the number and size of the pancospheres in S2-007 cells with concomitant inhibition of pancreatic cancer stem cell markers, DCLK1, Lgr5 and EpCam. The effect of GZ17-06.02 suppressed tumor growth and metastatic potential as indicative of MMP-2 and MMP-9 activity in primary and metastatic tumors.

Conclusions: GZ17-06.02 significantly inhibits pancreatic cancer stem cells, thereby suppressing tumorigenesis and metastasis in both in vitro and in vivo pancreatic cancer models.

Conference Series Pancreas 2016 International Conference Keynote Speaker Amy H. Tang photo
Biography:

Tang received a B.S. in Biophysics from Fudan University, and a Ph.D. in Biochemistry and Molecular Biology from Pennsylvania State University. She completed her postdoctoral training at UC Berkeley. Dr. Amy Tang is a Professor of Cancer Biology at Eastern Virginia Medical School. She is a lead pancreatic cancer researcher and a recipient of the national 2010 AACR-PanCAN Innovative Award. Dr. Tang and her research team have developed an innovative strategy to control and eradiacte oncogenic K-RAS-driven pancreatic cancer in preclinical and clinical settings. She has published more than 28 papers in peer-reviewed journals, and has served as an editorial board member at 6 scientfic journals.
 

Abstract:

Hyperactive K-RAS signaling is a major menace that drives aggressive cancer cell dissemination, tumor progression and systemic metastasis in human pancreatic cancer. Counteracting K-RAS hyperactivation in attempt to reverse malignant transformation and inhibit latent tumor spread is an important goal in pancreatic cancer biology. Instead of targeting an upstream signaling module such as EGFR/K-RAS/B-RAF/MEK/MAPK/ERK/AKT/mTOR, we targeted the most downstream signaling module in the K-RAS signaling pathway called the SIAH-dependent proteolytic machinery. SIAHs are the human homologs of Seven-In-Absentia (SINA), an evolutionarily conserved RING E3 ligase, an essential downstream signaling module and a critical "gatekeeper" required for proper K-RAS signal transduction. We found that inhibiting SIAH function is highly effective to abolish well-established and late-stage pancreatic tumor growth and metastasis in our pre-clinical studies. These findings demonstrate that SIAH is indeed an attractive, logical and potent anti-K-RAS therapeutic target for us to develop new and effective anticancer strategy against human pancreatic cancer. Through our work, SIAH has emerged as a new and effective drug target against oncogenic K-RAS hyperactivation in pancreatic cancer. As one of the most evolutionarily conserved signalimng components, SIAH is ideally and logically positioned to become a next-generation anti-K-RAS drug target in human pancreatic cancer. By attacking this most downstream “gatekeeper” critical for the proper oncogenic K-RAS signaling transmission, we will be in a position to halt the genesis, progression and metastasis of the deadliest forms of human pancreatic cancer in the future. We aim to translate anti-SIAH therapy to benefit our pancreatic cancer patients in the clinic

Keynote Forum

Arlen Myron

North shore univ hosp/hofstra college med and precision biologics, USA

Keynote: Chemotherapy vs. Specific active immunotherapy in the management of patients with recurrent pancreatic adenocarcinoma

Time : 9:00 AM

Conference Series Pancreas 2016 International Conference Keynote Speaker Arlen Myron photo
Biography:

Dr. Arlen serves as the Director of Scientific Affairs for Precision Biologics.  He is involved in a consulting capacity, providing his renowned expertise as both senior scientific and clinical advisor for product development. He was trained as a cancer surgeon at Memorial Sloan-Kettering where he remained on staff for 20 years involved in the surgery of advanced cancer problems and the immunotherapeutic approaches to managing the patients. Dr. Arlen established the Surgical Oncology Division at North Shore University Hospital, and formed a practice group (North Shore Surgical Oncology Associates). He has written two major textbooks and published over 100 journal articles related to cancer treatment and tumor Immunology.

Abstract:

Pancreatic carcinoma in of itself is a relatively lethal malignant disease process.  Even when the tumor  is small and virtually confined the the pancreatic head where the prognosis is best when compared with  body and tail lesions, the overall survival ranges from  5-10 % even following whipple resection.  Usually within the short interval of evaluaton of the lesion, nodal and or  distant mets is noted with limited survival. Multiple chemotherapeutic forms of intervention have been attempted employing combination drug therapy ie FOLFIERI as well Gemcitabine  alone and in combination with Abraxane.  These appear  offer on average a 3-5 month survival advantage over no intervention. With the discovery of those immunogenic proteins that characterize pancreatic cancer,  the opportunity for enhancement in survival using specific active immunotherapy has become a possibility  Three oncofetal proteins have now been characterized and represent post translational modifications of mutated MUC5ac, mutated CEAcam5/6  and a mutated form of A33 not previously described.  In order to sequence these immunogens for immuno- therapy, monoclonal antibodies were developed for immunopurification , structural identification and sequencing of the antigen.  On examination of the antibodies to the target immunogens,  it became evident that when immunization was initiated with partially purified protein, the improved survival was a consequence of an ADCC phenomenon and not related to cytotoxic T cell responses to the tumor. The naked MUC5ac antibody, Neo-102 has been used in FDA approved Phase 1/2 studies and is being prepared for Phase III investigation with the monoclonals alone and in combination with chemotherapy.  With the ability to radiolabel the antibodies for RT and with the possible addition of checkpoint inhibitors and those lymphokines enhancing the antitumor effects of the mAb the potential of total control of the disease becomes a possibility.

Conference Series Pancreas 2016 International Conference Keynote Speaker Christine Mehner photo
Biography:

Christine Mehner has completed her MD at the University of Witten/Herdecke, Germany and became a postdoctoral fellow at the Mayo Clinic Cancer Center, Jacksonville, FL. She has published multiple first author papers in the field of cancer research, in reputed journals that have been recognized by the Faculty of 1000 and have been featured in news and media. She has been serving as an editorial board member and constant reviewer for various journals.

Abstract:

Pancreatic ductal adenocarcinoma (PDA) arises at the convergence of genetic alterations in KRAS with a fostering microenvironment shaped by immune cell influx and fibrotic changes; identification of the earliest tumorigenic molecular mediators evokes the proverbial chicken and egg problem. Matrix metalloproteinases (MMP) are key drivers of tumor progression that  originate primarily from stromal cells activated by the developing tumor. Here, MMP3, known to be expressed in PDA, was found to be associated with expression of Rac1b, a tumorigenic splice isoform of Rac1, in all stages of pancreatic cancer. Using a large cohort of human PDA tissue biopsies specimens, both MMP3 and Rac1b are expressed in PDA cells, that the expression levels of the two markers are highly correlated, and that the subcellular distribution of Rac1b in PDA is significantly associated with patient outcome. Using transgenic mouse models, coexpression of MMP3 with activated KRAS in pancreatic acinar cells stimulates metaplasia and immune cell infiltration, priming the stromal microenvironment for early tumor development. Finally, exposure of cultured pancreatic cancer cells to recombinant MMP3 stimulates expression of Rac1b, increases cellular invasiveness, and activation of tumorigenic transcriptional profiles.

IMPLICATIONS: MMP3 acts as a coconspirator of oncogenic KRAS in pancreatic cancer tumorigenesis and progression, both through Rac1b-mediated phenotypic control of pancreatic cancer cells themselves, and by giving rise to the tumorigenic microenvironment; these findings also point to inhibition of this pathway as a potential therapeutic strategy for pancreatic cancer.

  • Pancreatic Enzymes and Hormones, Pancreatic Diseases and Disorders, Pancreatic Tumors and Cancers, Pancreatitis Prognosis, Pancreatic Diagnosis
Location: Hall 1
Biography:

Jose Mario F De Oliveira is an Associate Professor of Medicine in the Department of Medicine of Universidad Federal Fluminense, in the State of Rio de Janeiro, Brazil. He is also one of the Deputy Editors for Diabetes of The British Medical Journal. He has published a number of papers and served as a reviewer or author and co-author for many prestigious medical journals like “Hypertension”, “The American Journal of Hypertension”, “The Journal of the American Society of Nephrology”, “The British Medical Journal”, and the “New England Journal of Medicine”. His main interests are in the clinical research of diabetes and hypertension. He is a Certified Preventive Cardiologist, Nephrologist and Adult Intensive Care Unit Physician. Finally, he was a Post-Doctoral Clinical and Research Fellow at the Endocrinology-Hypertension-Diabetes Division of the Brigham & Women’s Hospital at Harvard Medical School, in Boston, USA and is one of the two authors of the recent electronic Diabetes e-book published and edited by The British Medical Journal for all doctors world-wide.

Abstract:

Albeit ACE-Is or ARBs have an undoubtful clinical benefit in diabetic and non-diabetic heart failure, their role as first line drug therapies in type 2 diabetics with hypertension or chronic kidney diseases have been recently put into question despite their – mild - anti-proteinuric effects, both as anti-hypertensive or as renoprotective agents specially in type 2 diabetes mellitus subjects. Angiotensin II, the main octapeptide “defence” molecule and “effector” of the renin-angiotensin-aldosterone system (RAS) has a variety of homeostatic actions in states of health and disease like regulating the salt and potassium balance for blood preesure homeostasis, keeping up the glomerular filtration rate under normal values and modulating the sympathetic nervous system, All in conditions of hypovolemia or salt depletion in order to keep our systemic – blood pressure - renal hemodynamics, and salt balance in good shape. In our Talk, we intend to show the most recent randomised clinical trial and observational evidences about how to deal with these drugs in the various clinical scenarios of diabetics, with and without chronic kidney diseases in order to keep our homeostasis in the right direction.

Speaker
Biography:

Dawn E Quelle has obtained her PhD in Biochemistry and Molecular Biology from the Pennsylvania State University. In her Post-doctoral work with Dr. Charles Sherr at St Jude Children’s Research Hospital, she studied cell cycle control and discovered the ARF tumor suppressor. She is an Associate Professor of Pharmacology at the University of Iowa and Leader of the Cancer Genes and Pathways Program in the Holden Comprehensive Cancer Center. Her research explores mechanisms of tumor suppression with a focus on the molecular and in vivo functions of ARFRABL6As binding partners, such as RABL6A, in cancer.

Abstract:

A better molecular understanding of pancreatic (neuroendocrine tumors PNETs) is needed to improve patient diagnosis and treatment. The PI3K/Akt/mTOR pathway is aberrantly activated in PNETs resulting in everolimus (mTOR inhibitor)-based therapies. However, sustained mTOR inhibition has the unintended consequence of hyper-activating Akt, thereby promoting drug resistance. Our data suggests that RABL6A, a novel oncoprotein amplified in PNETs, is a key regulator of this clinically relevant pathway. We found that RABL6A is essential for PNET cell proliferation and survival, and its loss dramatically reduces both Akt1 and Myc expression and activity. Given the central role of Akt1 and Myc in promoting tumorigenesis, we hypothesized that reinstating their activity would rescue the arrest phenotype caused by RABL6A loss. Individual restoration of Akt1 or c-Myc in –depleted PNET cells partially rescued the G1 phase arrest and induced S phase entry. This coincided with decreased expression of the cell cycle inhibitor, p27Kip1, and increased levels of CKS1B, a Myc transcriptional target that promotes p27 degradation. Notably, neither Akt nor Myc activation was sufficient to restore proliferation in the absence of RABL6A since cells became arrested in S-G2/M or died via apoptosis. Thus, controls multiple pathways essential for PNET cell cycle progression and survival. We are currently testing if RABL6A status in PNETs predicts responsiveness to clinical inhibitors of Akt, mTOR and Myc. These studies identify RABL6A as a new essential regulator of Akt1-mTOR and Myc signaling pathways, providing compelling mechanistic insight into the oncogenic function of RABL6A in PNETs.

Speaker
Biography:

Flavio Amaro Oliveira Bitar Silva has graduated from UFMG School of Medicine (Belo Horizonte - MG, Brazil) in 2006. He has finished his specialization in Surgery in 2010 (General Surgery + Trauma and Urgency Surgery). He has completed his specialization in Gastrointestinal Endoscopy in 2013, on Santa Casa de Sao Paulo (Sao Paulo - SP, Brazil), where he spent 2 more years learning Endoscopic Retrograde Colangiopancreatography (ERCP) and Endoscopic Ultrasound. He has few papers published in some of reputed journals in Endoscopy field and he is beginning his professional career.

Abstract:

A young girl presented with abdominal pain and jaundice of 1 month’s duration. She had conjugated hyperbilirubinemia and negative hepatitis serology. Computed tomography showed a mass in the head of the pancreas, with foci of calcification and cystic/necrotic areas. Pancreatoblastoma and Frantz Tumor were suspected. The patient underwent a cholecystojejunal anastomosis and intraoperative biopsy of the pancreatic mass yielded inconclusive results. She was referred for endoscopic ultrasound (EUS) to reevaluate the pancreatic mass. EUS showed a solid–cystic lesion in the head of the pancreas. EUS-guided fine-needle aspiration of the pancreatic mass was performed. Cytopathologic evaluation and immunohistochemical analysis confirmed the diagnosis of peripheral primitive neuroectodermal tumor (PNET). PNET belongs to a rare group of tumors called the Ewing sarcoma family of tumors. Pancreatic PNETs are extremely rare and highly aggressive. Metastasis and recurrence are common. With modern multidisciplinary treatment, long-term survival can be achieved in 70% to 80% of patients with disease that has not metastasized. The correlation of clinical symptoms with imaging, cytopathologic, and immunohistochemical analysis is important to establish the diagnosis. An atypical rosette array of the cells, cytoplasmic neuronal secretory granules and neurofilaments, and pyknotic nuclear granules areimportant diagnostic criteria. Most tumors of the Ewing sarcoma family express high levels of a cell surface glycoprotein, CD99 [13,14]. According to a 2014 review article, 14 cases of pancreatic PNET have been reported. This is the first case of a pancreatic PNET diagnosed by EUS.

Chong Yang

Hospital of the University of Electronic Science and Technology of China

Title: The effects of hydroxyethyl starch resuscitation on the early stage of severe acute pancreatitis

Time : 12:30-12:55

Speaker
Biography:

Chong Yang has completed his PhD at the age of 28 years from Wuhan Union Hospital, Huazhong University of Science and Technology, and currently working as a surgeon in Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital. His main research subject is severe acute pancreatitis, and published more than 10 manuscripts in reputed journals and has been serving as an editorial board member of repute.

Abstract:

Objectives: This study aimed to compare the effects of hydroxyethyl starch (HES) 130/0.4 combined with crystalloid solution with those of crystalloid solution alone on inflammatory variables (IL-1, IL-6 and IL-8 and TNF-­α), immunologic variables (CD4/8+ T cells), fluid balance (FB) negative (-) rate and renal function for severe acute pancreatitis (SAP) patients.

Methods: In this retrospective study, 59 patients received 6% HES 130/0.4 combined with crystalloid solution for fluid resuscitation (HES group), and 61 patients received only crystalloid solution simultaneously (control group) after admission. The serum values of IL-1, IL-6, IL-8 and TNF-α were measured on days 1, 2, 4 and 8. The peripheral blood CD4/8+ T lymphocyte rates, serum BUN and Cr values were measured on days 1, 4 and 8. The patients with FB(-) rates were recorded from days 1 to 8.

Results: Interaction term analysis (hospital stay and fluid resuscitation methods) based on mixed-effects regression model revealed significantly lower levels of IL-1 [risk ratio (RR): -0.406, P*: 0.041] and TNF-α (RR: -1.189, P*: 0.013) in the HES group compared with control group. The curve's RR difference was not significant for IL-6,CD4/8+ T lymphocyte rate, BUN and Cr values (P*>0.05). There was a significantly higher rate of patients with FB(-) from days 4 to 8 in the HES group (P<0.05).

Conclusion: HES 130/0.4 combined with crystalloid fluid resuscitation could decrease the IL-1 and IL-8 concentration, shorten the duration of positive fluid balance, and preserve patient’s immune status and renal function during the early stage of SAP.

Ming Xiang

Huazhong University of Science and Technology, China

Title: The immune response contribution to pancreatic tumorigenesis in animal models by Reg3g treatment

Time : 13:40-14:05

Speaker
Biography:

Ming Xiang has completed her PhD from Tongji Medical College, Huazhong University of Science and Technology. She is the Vice Director of School of Pharmacy, Tongji Medical College. She is a qualified Professor with track record not only within the pathogenesis of autoimmune diseases and chronic inflammation, the mechanism of regulation and induction of antigen-specific immune tolerance by Treg and DC for the therapy of autoimmune disease, but also the mechanism of pancreatic oncogenesis. She has published more than 25 papers in reputed journals and has been serving as an Editorial Board Member of repute, obtained 2 patents, an Academic Award and hosted several NSFC projects.

Abstract:

Regenerating islet-derived protein 3, regulates a variety of important pathologic physiology processes including inflammation, cancer control and cell proliferation. RegIII and IL-6 share the same pathway to accentuate inflammation, and suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of this pathway to bear tumor suppressor function. We studied the immunological mechanisms of Reg3g for promoting the pancreatic cancer. We successfully established subcutaneous transplantation tumor model and pancreatic carcinoma in situ model in C57/BL6j mice. Firstly, we determined critical target cells of Reg3g such as dendritic cells (DC), and CD8+ T cells and CD4+ CD25+ Foxp3+ T cells (Treg); Secondly, we found that Reg3g upregulated key genes in pancreatic tissue such as STAT3, Ki67, Caspase3 gene and downregulated SOCS3 gene, which being collaborative with Th2 type cytokines inhibited tumor immune response, and promoted malignant tumor cell proliferation; Lastly, we confirmed Reg3g inhibited DC migration and phagocytosis, attenuated CD8+ T cells infiltration, decreased negative regulatory factors such as CD152 and PD-1, PD–L1, interfered interaction between CD8+ T cells and DC, inhibited CD8+ T to cells cytotoxicity tumor, and promoted pancreatic cancer formation.

Sajida Qureshi

Dow University of Health Sciences, Pakistan

Title: Stented pancreaticoduodenectomy: Does it lead to decreased pancreatic fistula rates??

Time : 14:05-14:30

Speaker
Biography:

Sajida Qureshi is a Professor of Surgery from Dow University of Health Sciences. She has graduated from Dow Medical College Karachi Pakistan in 1996, Fellow of College of Physicians and Surgeons Pakistan, 2002 and Fellow of Royal College of Surgeons, Ireland 2003. She has indexed 22 publications in various journals. She was the Supervisor of Post-graduate training in Surgery in Pakistan. She is a reviewer of two journals in Pakistan. She has her special interest in Cancer Surgery.

Abstract:

Introduction: Pancreaticoduodenectomy (Whipple procedure) is a treatment of choice for patients with resectable carcinoma head of pancreas, lower cholangiocarcinoma, duodenal and ampullary and periampullary carcinomas. One of the much-dreaded complications of pancreaticoduodenectomy is pancreatic anastomotic leak leading to the pancreatic fistula formation, which can lead to septicemia and resultant complications leading to death of the patient. Stenting the pancreaticoenteric anastomosis has been postulated as reducing the pancreatic anastomotic leak and fistula rates up until now there is no convincing evidence supporting this fact.

Objective: To compare clinically relevant pancreatic fistula rates in patients with stinted versus non-stinted pancreaticojejunostomy.

Material & Methods: The study was conducted at Surgical Unit of 4 civil hospitals in Karachi, Pakistan, over a period of six years from September 2009 to August 2015. A total of 102 patients presenting to the unit with diagnosis of periampullary carcinoma, carcinoma head of pancreas, duodenal carcinoma involving the second part, and lower cholangiocarcinomas resectable on CT scan were included in the study. The primary study end point was pancreatic fistula or leakage, defined as amylase rich fluid (amylase concentration >3 times the upper limit of normal serum amylase level) collected from the peripancreatic drains on day 1, 3 and 7 post operatively which persisted beyond five days.

Results: A total of 102 patients were included in the study. Male to female ratio was (72:30). Mean age of the study population was 52.68 years, SD 11.6 (range 30-80 years) 53 patients had Pd stent (51.9%) while 49 did not have stented pancreaticojejunostomy (48%). Anastomotic leak was seen in 36 patients (35%). 37.7% patients with pancreatic stent and 32.6% patients without stent had a leak (p value 0.371).

Conclusion: There was no statistically significant difference in the pancreatic fistula rates between stinted and non-stinted anastomosis. We conclude that stinted pancreaticojejunostomies do not lead to decreased pancreatic fistula rates.

Jose Mario F De Oliveira

Universidad Federal Fluminense, Brazil

Title: The meanings of the

Time : 14:30-14:55

Biography:

Jose Mario F De Oliveira is an Associate Professor of Medicine in the Department of Medicine of Universidad Federal Fluminense, in the State of Rio de Janeiro, Brazil. He is also one of the Deputy Editors for Diabetes of The British Medical Journal. He has published a number of papers and served as a reviewer or author and co-author for many prestigious medical journals like “Hypertension”, “The American Journal of Hypertension”, “The Journal of the American Society of Nephrology”, “The British Medical Journal”, and the “New England Journal of Medicine”. His main interests are in the clinical research of diabetes and hypertension. He is a Certified Preventive Cardiologist, Nephrologist and Adult Intensive Care Unit Physician. Finally, he was a Post-Doctoral Clinical and Research Fellow at the Endocrinology-Hypertension-Diabetes Division of the Brigham & Women’s Hospital at Harvard Medical School, in Boston, USA and is one of the two authors of the recent electronic Diabetes e-book published and edited by The British Medical Journal for all doctors world-wide.

Abstract:

Since the published results of the UKPDS, the reduction of HbA1c levels has been the universal and even more than that, ubiquitous paradigm in clinical guidelines, in older times for macrovascular diabetic complications and in more recent times for microvascular diabetic complications. This overconfidence in the reliability of “safe” HbA1c levels, unfortunately, has increased over the last decades the frequency of severe hypoglycemic episodes, a high speed delivery onto the market of unsafe new anti-diabetic drugs, forgetting about the endponts that mostly matter to the diabetic patient survival and quality of life based on each days shorter and biased clinical trials. The purposes of this talk will be to explain for the audience; the concepts of a soft, a hard and a surrogate outcome in the clinical spectrum of diabetes and their clinical relevance to treatment and prognosis.

Zhaohui Xua

Shanghai University of Traditional Chinese Medicine, China

Title: The antidiabetic activity and mechanism of total lignans from Fructus Arctii in KKAy mice

Time : 15:20-16:20

Biography:

Zhaohui Xua has received his PhD in Pharmacognosy in 2000 and Fructus Arctii is the object of his Doctoral research topic. He has committed his research to the treatment of Fructus Arctii in type 2 diabetes for over 20 years. He has published nearly 20 papers on the anti-diabetic activity of Fructus Arctii. He has made a useful exploration of the material basis and mechanism of the anti-diabetic activity of Fructus Arctii.

Abstract:

Research Background: Fructus Arctii, called “Niubangzi” in China (Great burdock achene in English), is a well-known Chinese materia medica. It is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and was included in the Chinese pharmacopoeia for its traditional therapeutic actions.

Aim of the study: To study antidiabetic activity and mechanism of total lignans from Fructus Arctii (TLFA) in KKAy mice, a spontaneous type 2 diabetic animal model.

Materials & Methods: TLFA was extracted from Fructus Arctii and purified as described previously. Male KKAy mice and C57BL/6J mice were used in this study, KKAy mice were gavaged once daily with either solvents (0.3% CMC-Na), TLFA (250 mg/kg), TLFA (125 mg/kg) or Metformin (200 mg/kg) for 11 weeks. Besides common evaluation indexes of antidiabetic activity such as blood glucose level, body weight, oral glucose tolerance test (OGTT), glycated hemoglobin, as well as lipid metabolism parameters in mice serum was analyzed. Histopathological examination of the pancreas, white adipose tissue, liver and skeletal muscle was performed by optical microscope. The gene expressions of protein tyrosine phosphatase 1B (PTP1B), leptin, adiponectin and glucose transporter type 4 (GLUT4) were determined by real-time PCR. The protein levels of the above molecules and PPAR-γ, ACC, p-ACC, AKT, phospho-Akt (p-Akt), AMPK, p-AMPK, insR and GSK3β were measured by Western blot.

Results: TLFA demonstrated significant hypoglycemic activity in KKAy mice and showed potential to inhibit weight gain. The

results of real-time PCR and Western blot showed that TLFA downregulated leptin, PTP1B while it upregulated adiponectin and GLUT4 (p<0.05). The protein level of AMPK, p-AMPK, GLUT4 and insR was also increased while the protein level of ACC, p-Akt, Akt was decreased (p< 0.05).

Conclusion: The results of this study indicate that TLFA has significant antidiabetic potential in KKAy mice. And this potential could be associated with activation of AMPK, insR and GLUT4 pathways and upregulated gene expression of adiponectin and GLUT4, with downregulation of Akt pathway and downregulated gene expression of leptin and PTP1B. It has a great potential to be further developed as a novel therapeutic agent for diabetes in humans.

Speaker
Biography:

Flávio Amaro has graduated from UFMG School of Medicine (Belo Horizonte - MG, Brazil) in 2006. He has finished his specialization on surgery in 2010 (General Surgery + Trauma and Urgency Surgery). He has completed his specialization in Gastrointestinal Endoscopy in 2013, on Santa Casa de São Paulo (São Paulo - SP, Brazil), where he spent 2 more years learning Endoscopic Retrograde Colangiopancreatography (ERCP) and Endoscopic Ultrasound. He has few papers published in some of reputed journals in endoscopy field and he is beginning his professional career

Abstract:

A young girl presented with abdominal pain and jaundice of 1 month’s duration. She had conjugated hyperbilirubinemia and negative hepatitis serology. Computed tomography showed a mass in the head of the pancreas, with foci of calcification and cystic/necrotic areas. Pancreatoblastoma and Frantz Tumor were suspected. The patient underwent a cholecystojejunal anastomosis, and intraoperative biopsy of the pancreatic mass yielded inconclusive results. She was referred for endoscopic ultrasound (EUS) to re-evaluate the pancreatic mass. EUS showed a solid–cystic lesion in the head of the pancreas. EUS-guided fine-needle aspiration of the pancreatic mass was performed. Cytopathologic evaluation and immunohistochemical analysis confirmed the diagnosis of peripheral primitive neuroectodermal tumor (PNET).

PNET belongs to a rare group of tumors called the Ewing sarcoma family of tumors. Pancreatic PNETs are extremely rare and highly aggressive. Metastasis and recurrence are common. With modern multidisciplinary treatment, long-term survival can be achieved in 70% to 80 % of patients with disease that has not metastasized.

The correlation of clinical symptoms with imaging, cytopathologic, and immunohistochemical analysis is important to establish the diagnosis. An atypical rosette array of the cells, cytoplasmic neuronal secretory granules and neurofilaments, and pyknotic nuclear granules are important diagnostic criteria. Most tumors of the Ewing sarcoma family express high levels of a cell surface glycoprotein, CD99 [13, 14].

According to a 2014 review article, 14 cases of pancreatic PNET have been reported. This is the first case of a pancreatic PNET diagnosed by EUS. 

Yoram Oron

Tel Aviv University Sackler Faculty of Medicine, Israel

Title: Is PAI-1 good or bad? - Knockdown of PAI-1 in PANC-1 human pancreatic adenocarcinoma and in vitro invasiveness

Time : 10:05-10:30

Speaker
Biography:

Yoram Oron has completed his PhD from Hebrew University, Jerusalem and postdoctoral studies from University of Virginia School of Medicine. He taught physiology and pharmacology at Tel Aviv University (TAU) and served, among other functions, as Department Chair, and TAU Director of International Academic Relations. His career included Visiting Associate Professorship at Cornell Medical School and numerous periods as Visiting Scientist at NIDDK, NIH. He has published more than 110 papers in reputed journals and has served as an editorial board member of several journals. Although still actively in research, he is currently a TAU Professor Emeritus

Abstract:

It is generally accepted that overexpression of Plaminogen Activator Inhibitor 1 (PAI-1) correlates with worse prognosis and more invasive phenotype of many cancers, including Pancreatic Adenocarcinoma (PAC).  We down-regulated PAI-1 expression in PANC-1 cells via shRNA knockdown (KD).  The down-regulated variant (PD-PANC) exhibited neural morphological traits vs. cuboidal morphology of WT PANC-1s or vector-transfected cells. RT-PCR demonstrated that KD of PAI-1 leads to decreased expression of mesenchymal markers transcripts concurrently with increased expression of epithelial and neural transcripts, suggesting partial mesenchymal-to-epithelial transition. Importantly, PD-PANC1s expressed markedly more E-cadherin in a larger proportion of cells, whereas TUBB3 was expressed predominantly in cells with neural morphology. Yet, despite this apparent more epithelial phenotype, PD-PANC-1s exhibited more invasive behavior in vitro. Although the invading cells expressed more PAI-1 and less E-cadherin transcripts than non-invaders, it could not explain the observed increase in invasiveness . Using fluorescent supravital staining in a mixed vector/PD-PANC-1 population, we demonstrated that cells that down-regulated PAI-1 created environment promoting invasion of the few cells expressing high PAI-1 level. We previously reported that PD-PANCs exhibit higher uPA activity and continuously convert plasminogen to plasmin, which have been shown to activate matrix matalloproteinases. Indeed, inclusion of plasminogen enhanced invasion of PD-PANC-1s. In conclusion, our results suggest that fine balancing of different activities rather than extensive ablation of the “offending” PAI-1 protein  maybe a better strategy in maintaining a less aggressive PAC phenotype.

Speaker
Biography:

Manash Ranjan Sahoo completed his Masters degree in surgery in the year 1994 from Utkal University and followed it up with Fellowship in Surgical Gastroenterology in 1999 from Sri Ramachandra Medical College & Research Institute(Deemed University),Dr.Sahoo was invited to present his work in SAGES conference in Baltimore,USA in 2013 & was a plenary presenter in IHPBA World Congress in 2014 in Seoul,South Korea.He is an Associate Professor in S.C.B Medical College in Odisha,India & he he has 41 Pubmed indexed publications to his credit & he is the chief coordinator of Advanced Laparoscopic Surgery Training Programme in his Institution

Abstract:

AIM: Aim of  this  study  is  to  evaluate  the feasibility  of  Laparoscopic Roux-en-Y Cystojejunostomy using Suture  for pseudocyst  of  tail  of  pancreas. 

MATERIALS AND METHODS: This  is  a  retrospective  study  of  13  patients   of   pseudocyst  of  tail  of  pancreas  from   April  2007  to  November  2013. Age  of  the  patients  including  both  male  and  female  ranged  from   15  to  64  years. All  patients  were  subjected  to  Laparoscopic Roux-en-Y Cystojejunostomy using nonabsorbable suture.These  patients  were  followed  for  a  period  of  18  months  assessing  first  bowel movement, duration  of  surgery, hospital  stay, anastomosis  leak, recurrence  and  morbidity.

RESULT: Duration  of  surgery  was  156.6 ± 10.4  minutes. Postoperatively, the  mean  time  for  the  first  bowel  movement  was  36 hrs . Mean  hospital  stay  was  six (range: 5-7)  days. There  were  no  anastomosis leaks  in  any  patient. There  were  no  recurrences. Morbidity  was  comparable  to  any  other  laparoscopic  surgery.

CONCLUSION: We conclude that Laparoscopic Roux-en-Y Cystojejunostomy using Suture  for  pseudocyst  of  tail  of  pancreas  is  a  safe, effective,compliant  and  feasible  procedure.

Speaker
Biography:

Daria Dranka-Bojarowska  graduated Silesian University School of Medicine in 2000. She is assistant in The Department of Gastrointestinal Surgery, Medical University of Silesia –a leader center of pancreatic surgery in Poland. She has completed her PhD in 2014 from Silesian University School of Medicine, She is author more than 20 medical articules and conferences abstracts. She has published 7 papers in reputed journals.

Abstract:

The aim of this study was a comparative analysis of the concentrations in serum of adipocytokines: adiponectin and leptin and CA 19-9 in patients with pancreatic cancer (PC), chronic pancreatitis (CP) and control group (CG). The study was performed in a group of 90 patients. The serum samples were taken from patients and the concentration of adiponectin, leptin, CA 19-9 and CEA were evaluated. The revealed concentrations levels of the adiponectin were significantly higher in the PC serum samples compared to the CP and CG. There was no significant correlation between increased adiponectin concentration and body fat mass in the PC group. The concentration of leptin was significantly lower in CP serum samples compared to PC and CG. The concentration of leptin was similar in the PC and CG. The concentration of leptin was mainly dependent on body fat mass and fat distribution. Additionally, measurement of waist circumference and body composition was recorded using bioelectrical impedance analysis. Significantly higher concentration levels of adiponectin in the PC group, independent of body fat mass, may play a potential role as a new tumor marker in PC and might be useful in the differential diagnosis between PC and CP. Author perform further investigation to validate this statement. To our knowledge, this was the first study evaluating not only BMI but also the content and distribution of body fat in patients with PC and CP.

  • Workshop

Session Introduction

Zhaohui Xua

Shanghai University of Traditional Chinese Medicine, China

Title: The antidiabetic activity and mechanism of total lignans from Fructus Arctii in KKAy mice
Biography:

Zhaohui Xua has received his PhD in Pharmacognosy in 2000 and Fructus Arctii is the object of his Doctoral research topic. He has committed his research to the treatment of Fructus Arctii in type 2 diabetes for over 20 years. He has published nearly 20 papers on the anti-diabetic activity of Fructus Arctii. He has made a useful exploration of the material basis and mechanism of the anti-diabetic activity of Fructus Arctii.

Abstract:

Research Background: Fructus Arctii, called “Niubangzi” in China (Great burdock achene in English), is a well-known Chinese materia medica. It is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and was included in the Chinese pharmacopoeia for its traditional therapeutic actions.

Aim of the study: To study antidiabetic activity and mechanism of total lignans from Fructus Arctii (TLFA) in KKAy mice, a spontaneous type 2 diabetic animal model.

Materials & Methods: TLFA was extracted from Fructus Arctii and purified as described previously. Male KKAy mice and C57BL/6J mice were used in this study, KKAy mice were gavaged once daily with either solvents (0.3% CMC-Na), TLFA (250 mg/kg), TLFA (125 mg/kg) or Metformin (200 mg/kg) for 11 weeks. Besides common evaluation indexes of antidiabetic activity such as blood glucose level, body weight, oral glucose tolerance test (OGTT), glycated hemoglobin, as well as lipid metabolism parameters in mice serum was analyzed. Histopathological examination of the pancreas, white adipose tissue, liver and skeletal muscle was performed by optical microscope. The gene expressions of protein tyrosine phosphatase 1B (PTP1B), leptin, adiponectin and glucose transporter type 4 (GLUT4) were determined by real-time PCR. The protein levels of the above molecules and PPAR-γ, ACC, p-ACC, AKT, phospho-Akt (p-Akt), AMPK, p-AMPK, insR and GSK3β were measured by Western blot.

Results: TLFA demonstrated significant hypoglycemic activity in KKAy mice and showed potential to inhibit weight gain. The

results of real-time PCR and Western blot showed that TLFA downregulated leptin, PTP1B while it upregulated adiponectin and GLUT4 (p<0.05). The protein level of AMPK, p-AMPK, GLUT4 and insR was also increased while the protein level of ACC, p-Akt, Akt was decreased (p< 0.05).

Conclusion: The results of this study indicate that TLFA has significant antidiabetic potential in KKAy mice. And this potential could be associated with activation of AMPK, insR and GLUT4 pathways and upregulated gene expression of adiponectin and GLUT4, with downregulation of Akt pathway and downregulated gene expression of leptin and PTP1B. It has a great potential to be further developed as a novel therapeutic agent for diabetes in humans.

Speaker
Biography:

Daria Dranka-Bojarowska  graduated Silesian University School of Medicine in 2000. She is assistant in The Department of Gastrointestinal Surgery, Medical University of Silesia –a leader center of pancreatic surgery in Poland. She has completed her PhD in 2014 from Silesian University School of Medicine, She is author more than 20 medical articules and conferences abstracts. She has published 7 papers in reputed journals.

Abstract:

The aim of this study was a comparative analysis of the concentrations in serum of adipocytokines: adiponectin and leptin and CA 19-9 in patients with pancreatic cancer (PC), chronic pancreatitis (CP) and control group (CG). The study was performed in a group of 90 patients. The serum samples were taken from patients and the concentration of adiponectin, leptin, CA 19-9 and CEA were evaluated. The revealed concentrations levels of the adiponectin were significantly higher in the PC serum samples compared to the CP and CG. There was no significant correlation between increased adiponectin concentration and body fat mass in the PC group. The concentration of leptin was significantly lower in CP serum samples compared to PC and CG. The concentration of leptin was similar in the PC and CG. The concentration of leptin was mainly dependent on body fat mass and fat distribution. Additionally, measurement of waist circumference and body composition was recorded using bioelectrical impedance analysis. Significantly higher concentration levels of adiponectin in the PC group, independent of body fat mass, may play a potential role as a new tumor marker in PC and might be useful in the differential diagnosis between PC and CP. Author perform further investigation to validate this statement. To our knowledge, this was the first study evaluating not only BMI but also the content and distribution of body fat in patients with PC and CP.