AllDocs -> cancers

Clinical: Pancreatic Cancer 265 Pancreatic Cancer Risk is Similar in Men and Women with Hereditary Pancreatitis (HP) N. Howes, M.M. Lerch, W. Greenhalf, H. Smart, M. Lombard, I. Gilmore, J. Mössner, S. Endres, J. Devière, G. Verreman, V. Lucidi, R. Charnley, C. Imrie, A. Olah, I. Ihse, A. Poll, R. Rutherford, I. Ellis, D.C. Whitcomb, J.P. Neoptolemos for the UK and Ireland Consortium of EUROPAC Departments of Surgery, Clinical and Molecular Genetics on behalf of the consortium of EUROPAC, UK Background: HP has an early age of symptom onset and is associated with a high inci- dence of complications, and has been reported to have a high life time risk of pancreatic cancer PC. The European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) was established in 1997 to investigate HP in Europe. Methods: HP was diagnosed ...

Basic: Pancreatic Cancer 122 BTEB3 and BTEB4 Expand the Repertoire of Repressors of the Carcinogen-Metabolizing CYP1A1 Gene Promoter in Pancreatic Cells J. Kaczynski, A. Conley, M.F. Zapico, J.-S. Zhang, R. Urrutia Mayo Clinic, Rochester, MN, USA Our laboratory is focused on the study of mechanisms involved in pancreatic carcino- genesis, including the analysis of specific genetic factors (mutations in oncogenes and tumor suppressors) and environmental factors (tobacco carcinogens) that may predis- pose to this disease. Studies in non- pancreatic cell populations indicate that the P450 enzyme CYP1A1 plays a significant role in the activation of carcinogens found in cig- arette smoke, an environmental factor linked to pancreatic cancer . Upon CYP1A1 acti- vation, carcinogens can form DNA adducts that promote mutations of genes important for the initiation and/or progression ...

Clinical: Pancreatic Cancer 246 Patients Affected by p53-Expressing Pancreatic Cancer Benefit from Extended Lymphatic Clearance I. Esposito 1 , M. del Chiaro 2 , D. Campani 1 , U. Boggi 2 , M. Menicagli 1 , L.E. Pollina 1 , F. Mosca 2 , G. Bevilacqua 1 Department of Oncology, Division of Pathology 1 and Surgery 2 , University of Pisa, Italy Background: Lymph node metastases occur frequently in patients undergoing ‘cura- tive’ pancreatic resection. Moreover, the aggressiveness of pancreatic cancer is related to a number of genetic alterations that contribute to rapid tumor progression. The aim of this study was to evaluate the efficacy of extended lymphatic clearance (ELC) in the treatment ...

Clinical: Pancreatic Cancer 259 The Impact of Recent Changes in Surgical Practice on Patterns of Referral in Pancreatic Surgery C. Coldham, N. Jarufe, P. McMaster, A.D. Mayer, D. Candinas, D.F. Mirza, J.A.C. Buckels, S.R. Bramhall The Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH, UK Aims: To assess the impact of treatment guidelines, Clinical Governance and changes to surgical training on referrals for pancreatic cancer . Methods: Data was collected on patients undergoing pancreatic resection for adeno- carcinoma between 1987 and 2001 and on all referrals with pancreatic cancer since September 1997. Prior to September 1997 data was collected retrospectively but since then data have been recorded prospectively on a dedicated database. Data on regional incidence was obtained from the West Midlands (WM) Cancer Intelligence Unit and individual ...

Basic: Pancreatic Cancer 94 The Influence of Genetic Manipulations of the Ras-cascade on the Expression Profile of Pancreatic Cancer Cells H. Fensterer 1 , K. Giehl 2 , M. Buchholz 1 , P. Gierschik 2 , G. Adler 1 , T.M. Gress 1 1 Department of Internal Medicine I and 2 Department of Pharmacology, University of Ulm, Germany Background: Up to 90% of all pancreatic cancers carry an activating mutation in the ras -gene. Therefore, this mutation is thought to play a crucial role in carcinogenesis. In order to improve our understanding of the impact of this alteration, we performed expres- sion profiling of PANC-1 pancreatic carcinoma cells which stably express H-Ras(S17N) as an EGFP-fusion protein. Methods: PANC-1-cells, harbouring ...

Clinical: Pancreatic Cancer 291 Correlation of Pancreatic Head Mass Histology with Expression of alpha-1-Antitrypsin, Glutathione S- Transferase pi, and Vascular Endothelial Growth Factor S. Suthers 1 , M. Lerner 1 , J. Lees 1 , D. Brackett 1 , S. Lightfoot 2 , R. Postier 1 Departments of Surgery 1 and Pathology 2 , University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA Background: Previous cDNA array work in our laboratory demonstrated overexpres- sion of alpha-1-antitrypsin (A1AT), glutathione s-transferase pi (GSTP), and vascular endothelial growth factor (VEGF) in pancreatic adenocarcinomas. The purpose of this study was to investigate differential expression of these three proteins among histologic grades ...

Basic: Pancreatic Cancer 101 Antibody to the CCK-C Receptor Inhibits Proliferation of BxPC-3 Human Pancreatic Cancer Cells in Culture J.W. Showalter, J.P. Smith Department of Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA Background: Gastrin is a potent growth factor in human pancreatic cancer and exerts its effects through at CCK-B/gastrin-like receptor. Recently, it was demonstrated that human pancreatic cancer cells express a variant of the CCK-B receptor in which the 4th intron is not spliced but translated to form the ‘CCK-C’ receptor. The purpose of the following study was to examine whether the accelerated growth of human pancreatic cancer cells is related to the expression of the CCK-C receptor. Methods: Using a polyclonal antibody raised in chickens against a unique portion of the CCK-C receptor, the proliferation ...

Basic: Pancreatic Cancer 119 Combined Biological and Neural-network Based Selection of Apoptosis Inducing Novel Tyrosine Kinase Inhibitor Analogues on panc-1 Cells, in vitro R. Schwab, E. Schäfer, Gy. Bökönyi 1 , E. Szabó 1 , B.B. Nemeth, K. Diofalvi 1 , T. Gyökeres, L. Örfi 1 , Gy. Kéri 1 , Á. Pap Department of Gastroenterology MAV Hospital, Co-operative Research Centre, Semmelweis University 1 , Budapest, Hungary Background: Receptor Tyrosine-Kinases (RTK) have been shown to play a major role in maintaining proliferation signals in pancreatic cancer . The aim of this study was to screen a chemical library of novel TK inhibitor-analogues based on neural network- based computed pre-selection from virtual combinatorial libraries for apoptosis induc- ing efficacy ...

Basic: Pancreatic Cancer 124 Establishment and Characterization of the Multidrug Resistant Pancreatic Adenocarcinoma Cell Line SW1990/Fu J.-C. Guo, Y.-P. Zhao, L. Quan, L.-Y. Zhang, G. Chen, L.-X. Cai, Y. Zhu Dept. General surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, P R China Objective: To establish a 5-Fluorouracil (5-Fu) resistant pancreatic adenocarcinoma (PAC) cell line, and to investigate its biological characteristics and possible mechanisms of multidrug resistance in PAC chemotherapy. Materials and Methods: The PAC cell line SW1990 was selected into a multidrug resistant cell line stepwise with one of the most common drugs used in PAC chemother- apy 5-Fu for 12 months and subsequently named SW1990/Fu. The cell line was char- acterized in terms of morphology, biology, ...

Clinical: Pancreatic Cancer 299 Biologically, Pancreatic Cancer is not a Uniform Disease P.M. Pour, R.E. Brand 1 , R. Bell 2 , B. Schmied 3 , M.W. Büchler 3 UNMC Eppley Cancer Center and 1 Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA; 2 Department of Surgery, Midwestern University, Chicago, Illinois, USA; 3 Department of Surgery, University of Heidelberg, Germany Although the natural history of pancreatic ductal adenocarcinoma appears to be uniform among the population, biologically there seems to be at least three different subgroups of pancreatic cancer patients. According to our clinical and pathohistological data, around 70% of pancreatic cancer patients have impaired glucose tolerance or diabetes (Group ...

Clinical: Pancreatic Cancer 260 Treatment of Advanced Pancreatic Cancer with Intra-Arterial Chemotherapy Combined with Radiotherapy (ia ChT RT) D.S. Osinsky 1 , V.A. Chorny 1 , O.G. Yugrinov 2 , V.B. Korobko 1 Department of Abdominal Oncology 1 ; Department of X-ray Surgery and Regional Chemotherapy 2 , Institute of Oncology, AMSU, Kiev, Ukraine Background: Prognosis of patients with adenocarcinoma of the pancreas is extremely poor. Pancreatic cancer is the fourth leading cause of death from cancer in industrial- ized countries, with an overall 5-year survival rate of less 5%. At the time of diagnosis more 80% of patients have locally advanced or metastatic disease. The median survival time of these patients is limited 3–6 months. Chemotherapy and ...

Clinical: Pancreatic Cancer 241 Radical or Palliative Pancreatic Cancer Surgery: What are the Costs? Å. Andrén-Sandberg, E. Vingsgård, B. Haukeland, D. Hoem Department of Surgery, Haukeland University Hospital, Bergen University, Bergen, Norway Background: For the patient with pancreatic cancer the only hope for cure is a radical resection of the tumor. Gudjonsson – frequently cited – reports 5-year survival of 0.4% in his collection of 340 papers dealing with survival rates of exocrine pancreatic cancer . Based on his figures he claims that the average excess cost for each resection is at least 150,000 $, which gives a cumulative cost per ‘successful’ resection of approximately 4.5 million $. However, the alternatives of not making any curative attempt are usually not considered. We have therefore calculated the total costs of the health care from diagnosis to ...

Basic: Pancreatic Cancer 90 Regulation of Expression from the S100A4 Promoter by BKLF and CtBP-2 C. Herbert 1 , G. Nelson 2 , R. Barraclough 2 , J.P. Neoptolemos 1 , W. Greenhalf 1 Department of Surgery, 5th Floor UCD Block, Royal Liverpool University Hospital and School of Biological Sciences, Liverpool University, UK Background: Pancreatic ductal adenocarcinoma is characterised by early metastasis. Gene therapy targeted at metastatic cancer cells would be a solution to this problem. The S100A4 protein is expressed preferentially in metastatic cells. Sequences in the pro- moter may bind to transcriptional repressors found in normal tissue, these sequences could be the basis for chimeric promoters for targeted gene therapy. Methods: Yeast tester strains (carrying sequences ...

Clinical: Pancreatic Cancer 292 Association of Prohibitin 3 UTR Single Nucleotide Polymorphism with Pancreatic Head Masses J. Lees, S. Manjeshwar, M. Lerner, J. Barton, S. Suthers, D. Brackett, R. Postier, E. Jupe Department of Surgery, University of Oklahoma Health Sciences Center; and Program in Immunobiology and Cancer , Oklahoma Medical Research Foundation; Oklahoma City, OK, USA Background: The evaluation of obstructive jaundice often results in pancreatic head resection due to the significant potential for an underlying malignancy. Although neo- plasms are often found, benign pathology such as chronic pancreatitis is also discov- ered. Although many germline and somatic mutations have been associated with pancreatic cancer , few show any promise as targets for population based screening assays or in determining prognosis. Prohibitin is a candidate tumor suppressor ...

Basic: Pancreatic Cancer 108 Gene Therapy of Experimental Pancreatic Adenocarcinoma Models Using Transcriptional Selective-promoter Targeting of E. coli Purine Nucleoside Phosphorylase Suicide Gene S. Deharvengt, S. Wack, M. Aprahamian, A. Hajri IRCAD/INSERM U375, Laboratoire de biologie des tumeurs et de thérapie génique 1, place de l’hôpital BP426, 67091 Strasbourg, Cedex, France Novel therapeutic strategies are needed against pancreatic cancer which is refractory to conventional systemic therapies. Cancer gene therapy with the transfer of suicide gene can result in sensitization of tumor cells to chemotherapy. Previously, we have developed a pro-drug/suicide gene system: 6-methylpurine deoxyribose/ E.coli purine nucleoside phosphorylase (6-MePdR)/ePNP) for digestive cancer gene therapy and we have demonstrated that ePNP gene expression inhibit efficiently ...

Clinical: Pancreatic Cancer 276 Predictive Factors of Pancreatic Cancer in Patients with Chronic Pancreatitis and K-ras Gene Mutation Detected in Pancreatic Duct Brushings M. Arvanitakis 1 , J.-L. van Laethem 1 , J. Parma 2 , M. Delhaye 1 , J. Devière 1 Dept of Gastroenterology 1 and Laboratory of Genetics and Molecular Oncology 2 , ULB Erasme Hospital, Brussels, Belgium Background: Chronic pancreatitis (CP) has been shown to be a predisposing factor of pancreatic cancer (PC). The purpose of this study was to examine the prognostic sig- nificance of various factors characterizing CP and the presence of K-ras gene mutation in regard to PC development. Methods: 146 patients with CP were studied. Etiology was alcoholic CP in 109 patients ...

Clinical: Pancreatic Cancer 278 Treatment of Advanced Pancreatic Cancer Patients with Opioid Growth Factor: Phase 1 J.P. Smith 1 , M. Ahmad 1 , R. Conter 2 , H. Harvey 1 , P. McLaughlin 3 , S. Bingaman 1 , D.T. Mauger 4 , W.B. Stanley 1 , I.S. Zagon 3 Departments of Medicine 1 , Surgery 2 , Neuroscience and Anatomy 3 , and Health Evaluation Sciences 4 , Penn State University College of Medicine, Hershey, Pennsylvania, USA Background: Opioid Growth Factor (OGF) inhibits growth of human pancreatic can- cer cells in culture and as xenografted tumors to nude mice. Aim: To determine the safety and toxicity of OGF when administered to human ...

Basic: Pancreatic Cancer 83 The Angiogenesis Inhibitor IM862 Increases Survival in Pancreatic Cancer Despite Delayed Onset of Therapy H.G. Hotz, P.S. Gill 1 , R. Masood 1 , H. Graeubig, B. Hotz, H.J. Buhr Dept. of Surgery, UK Benjamin Franklin, FU Berlin, Germany and 1 Dept. of Medicine and Pathology, USC School of Medicine, Los Angeles, CA, USA Background: IM862 is a dipeptide of L-glutamyl-L-tryptophan with antiangiogenic properties and potential antitumor activity. The aim of the present study was to evalu- ate the effect of IM862 on proliferation of human pancreatic cancer (PaCa) cells in vitro and to assess the efficiency of IM862 in an orthotopic nude mouse model of human pancreatic cancer after a delayed onset of therapy. Methods: In vitro: Three human PaCa cell lines (MIAPaCa-2, undifferentiated; AsPC- ...

Clinical: Pancreatic Cancer 311 Comparison between the Disease Free Time After Surgery and the Pathological Findings in the Pancreatic Cancer T. Hatori, T. Imaizumi, N. Harada, A. Fukuda, K. Takasaki Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan Background: Pancreatic cancer is very difficult to cure even in the respectable patients. Because the rate of recurrence such as liver metastasis or retroperitoneal recurrence was very high in the patients who underwent complete removal of the tumor. This study was evaluated to examine the comparison between disease free time and pathological find- ings in the pancreatic cancer . Patients and Methods: From 1991 to 2000, a total of 71 patients who underwent com- plete removal of the tumor without any adjuvant therapy postoperatively were chosen to this study. ...

Basic: Pancreatic Cancer 106 Systematic Characterization of Pancreatic Carcinoma Cell Lines Cultured as Monolayer and Spheroid B. Sipos 1 , S. Moser 1 , V. Torok 3 , H. Kalthoff 2 , G. Klöppel 1 Departments of Pathology 1 and General Surgery 2 , University of Kiel, Germany; 2 nd Department of Pathology 3 , Semmelweis University, Hungary Background: There are a large number of stable ductal pancreatic cancer cell lines used by researchers worldwide. However, basic data about their origin and growth features are incomplete or controversial. Therefore, we classified 12 of the most commonly used pancreatic carcinoma cell lines according to their in vitro growth characteristics and dif- ferentiation. Materials and ...

Basic: Pancreatic Cancer 79 Suicide Gene Therapy with HSV-TK in Pancreatic Cancer : no ‘in vivo’ Effect P. Fogar, A. Cecchetto 1 , E. Greco 2 , M. Milazzo 2 , D. Tormen 1 , D. Basso 2 , F. Navaglia 2 , C.-F. Zambon 2 , N. Gallo 2 , S. Mazza 2 , M. Plebani 2 , S. Pedrazzoli Dept. of Medical and Surgical Sciences, 1 Pathology and 2 Laboratory Medicine, University of Padova, Italy Background: Our aim was to ascertain whether gene therapy with the suicide gene thymidine kinase (TK) of the HSV and with the immunostimulatory cytokine IL-2, may exert a beneficial effect for pancreatic cancer (PC) treatment ‘in vivo’. Methods: The retroviral transduction ...

Basic: Pancreatic Cancer 133 Differential Expression of VEGF-RII Influences Prognosis, Angiogenesis and Mitogenesis in Pancreatic Cancer P. Büchler 1,2 , H. Friess 1 , J.O. Hines 2 , H.A. Reber 2 , M.W. Büchler 1 1 Department of Surgery, University of Heidelberg, Germany; 2 Department of Surgery, UCLA School of Medicine, CA, USA Background: Vascular endothelial growth factor (VEGF) and its receptors (VEGF-RI, -RII) are the most important regulators of tumor neoangiogenesis. VEGF is overex- pressed in human pancreatic cancer (PaCa), the receptors, however, were thought to be expressed by the endothelial cells only. Aim: In the present study we analyzed expression of VEGF, VEGF-RI and -II in human tissue specimens and determined their role in the growth of ...

Cancer of the Pancreas and Other Neoplasms 34 Pancreatic Cancer Registry Pancreatic Disease Multicentric Group (PDMG) Hospital Ramón y Cajal, Hospital Fundación de Alcorcón, Hospital de La Princesa, Clínica Puerta de Hierro y Hospital Príncipe de Asturias de Alcalá de Henares. Madrid, Spain Introduction: Pancreatic cancer is the fourth leading cause of cancer death. Delay on diagnosis is the main factor for the poor prognosis of the disease. Although the only potentially curative treatment is operative resection, in the last years continued improve- ments have been made in the management of pancreatic cancer in order to prolong sur- vival and improve the quality of life in these patients. Objective: To evaluate prospectively the present state of the treatment of pancreatic can- cer in our country, with the purpose of obtaining valid information to ensure the best ...

P.I.: Michael Bouvet, M.D. Title: Molecular Mechanisms of PTHrP’s Growth Regulation of Pancreatic Cancer PTHrP is an oncoprotein that regulates the growth and differentiation in virtually every cell and tissue studied. We have recently demonstrated that PTHrP is commonly expressed by pancreatic adenocarcinomas, the fourth leading cause of adult cancer deaths in the US, and in preliminary studies that PTHrP regulates tumor growth. The biological effects of PTHrP are both endocrine and intracrine, the former mediated through a cell-surface receptor and the latter through a nuclear localizing sequence (NLS). It is our Hypothesis that PTHrP mediates its growth regulatory effects in pancreatic cancer through both cell-surface receptor and nuclear localization intracrine mechanisms. Our goals are to elucidate these mechanisms by molecular biology studies and to identify the growth-influencing ...

Abstract . Radiolabeled human non-specific polyclonal immunoglobulin G (HIG), is used for the diagnosis of inflammation/infection. Focal uptake of HIG in malignant lesions has also been reported. We investigated the diagnostic value of In-111-HIG in patients with known pancreatic cancer . Fourteen consecutive patients with histologically verified pancreatic cancer were included in this prospective study. Four of them had undergone potentially curative surgery for their primary cancer . Eight patients had liver metastases. Planar and SPECT images of the abdomen were performed after administration of In-111-HIG (74-92 MBq). Scintigraphic results were compared to conventional imaging by means of CT scanning. In addition, In-111-HIG uptake was investigated in a panel of four representative human pancreatic cancer cell lines. Primary pancreatic tumors were visualized by In-111-HIG in 6 out ...

Abstract . Adenosine triphosphate (ATP) has been shown to be an inhibitory or a stimulatory agent for cell growth in various types of cells. Here, we studied the effects of extra- cellular ATP on two pancreatic cancer cell lines, PK-1 and YAPC established by us. In both cell lines, ATP inhibited cell growth in a time- and dose-dependent manner, whereas the same doses of ATP stimulated DNA synthesis. Flow cytometric analysis of the cells incubated with or without ATP demonstrated the ATP-induced striking increase in cells at S-phase. The same analysis showed also the increase in sub- G 0 /G 1 population in the same analysis and the electro- phoretic pattern of DNA showed the occurrence of ATP- induced cell disintegration likely to be apoptosis. We suggest that extracellular ATP is cytotoxic for pancreatic cancer cells because of its induction of cell cycle arrest ...

QUESTIONS Choose the single best answer for each question. 1. Approximately how many cases of pancreatic ade- nocarcinoma occur in the United States annually? A) 30,000 B) 50,000 C) 75,000 D) 90,000 E) 150,000 2. Which of the following statements regarding pan- creatic adenocarcinoma is INCORRECT? A) Survival beyond 2 years following diagnosis is uncommon B) The majority of affected patients have surgical- ly resectable tumors C) The majority of tumors arise in the head of the pancreas D) The median age of affected patients is 60 to 70 years E) The most frequent presentation of the disease is painless obstructive jaundice 3. A previously healthy 65-year-old man with painless obstructive jaundice visits his physician. As part of his work-up, the patient undergoes a computed tomographic (CT) scan of the abdomen. Results show that the ...

JOP - Journal of the Pancreas 2000; 1(2):19-23. JOP – Journal Of the Pancreas www.joplink.net Vol.1, No. 2 July 2000 19 Cytokines and Exocrine Pancreatic Cancer : Is There a Link? Daniela Basso, Mario Plebani Department of Laboratory Medicine, University Hospital of Padua, Italy At the beginning of the third millennium, the prognosis for patients with pancreatic cancer is still extremely poor, with a five-year survival of less than 1% [1] in spite of the availability of sophisticated diagnostic and treatment aids which have, in recent years, significantly modified the prognosis for many patients with solid tumors other than those of pancreatic origin. The failure to improve upon the therapeutical approach for this type of tumor is probably due to the biological behavior of pancreatic cancer cells which acquire several molecular and biochemical ...

O1 PANCREATIC CANCER . BASIC AND CLINICAL ASPECTS 3 Lifestyle Factors and Pancreatic Cancer Risk: A Cohort Study from the Swedish Twin Registry Bengt Isaksson 1 , Fredrik Jonsson 2 , Nancy L Pedersen 3 , Jörgen Larsson 1 , Maria Feychting 2 , Johan Permert 1 Department of Surgery 1 , Karolinska Institutet at Huddinge University Hospital, Institute of Environmental Medicine 2 , Department of Medical Epidemiology 3 , Karolinska Institutet, Stockholm, Sweden Background & Aims: The relationship between lifestyle factors and pancreatic cancer remains unclear. Case-control studies have been inconclusive, and prospective data are scarce. Our aim was to examine the associations of smoking, alcohol and coffee ...

O1 PANCREATIC CANCER . BASIC AND CLINICAL ASPECTS 2 MUC4 mRNA in Peripheral Blood Mononuclear Cells as a Potential Tumor Marker for Pancreatic Cancer G. Faulmann 1,2 , J. Ringel 1,2 , R. Brand 1 , N. Moniaux 1 , S.R. Tarantolo 1 , S.S. Joshi 1 , S.K. Batra 1 , M. Löhr 2 Dept. of Biochemistry and Eppley Cancer Center 1 , UNMC, Omaha, NE, USA, Medical Faculty Mannheim 2 , University of Heidelberg, Germany Background: Despite improvements in diagnostic techniques and increasing knowledge regarding genetic alterations and serum-based tumor markers, the diagnosis of pancreatic cancer remains a pressing clinical problem. New specific diagnostic tools, therefore, are necessary. Pancreatic tumor ...