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Basic Pancreatic Cancer 97 Evaluation of Lentiviral Vectors for Human Pancreatic Cancer Gene Therapy G. Saraga, E. Costello, P. Ghaneh Department of Surgery, University of Liverpool, Royal Liverpool University Hospital, Liverpool, UK Aims: 1. To examine the suitability of lentiviral vectors as a gene delivery system for pancreatic cancer gene therapy. 2. To compare the efficiency of vectors based on the equine infectious anaemia virus (EIAV) and human immunodeficiency virus type-1 (HIV-1) for gene transfer to pancreatic cancer cells. Methods: Vectors (Oxford Biomedica, UK) were produced by co-transfection of 293T cells with 1. a packaging construct encoding viral structural and enzymatic proteins, 2. a transfer construct encoding the enhanced green fluorescence protein (EGFP) and 3. a plasmid expressing the vesicular stomatitis virus glycoprotein ...

Clinical Pancreatic Cancer 15 Tumor M2-Pyruvate Kinase in Patients Suffering from Pancreatic Cancer E. Coato, L. Frulloni, S. Carrara, S. Brunelli, B. Ferri, B. Calore, L. Bernardoni, K. Faitini, M. Falconi, R. Salvia, G.M. Cavestro 1 , P. Pederzoli, G. Cavallini Department of Surgical and Gastroenterological Sciences, University of Verona and 1 Department of Clinical Sciences, University of Parma, Italy Background: Tumour marker pyruvate kinase type tumour M2 has been proposed as a new specific marker for the diagnosis of pancreatic cancer . Aim of the study was to evaluate M2-PK in patients with benign, malignant and metastasic pancreatic lesions and to compare it to the reference marker Ca 19-9. Materials and Methods: We studied 54 healthy volunteers and 103 consecutive patients suffering from ...

Basic Pancreatic Cancer 112 Decreased 15-Lipoxygenase-1 (15-LOX-1) Expression in Human Pancreatic Adenocarcinoma R. Hennig, S.M. Rao, M.W. Büchler 1 , H. Friess 1 , T.E. Adrian Department of Surgery and Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA and 1 Department of Surgery, University of Heidelberg, Germany Introduction: Polyunsaturated ( -6) fats such as arachidonic and linoleic acid, are asso- ciated with an increased incidence and growth of pancreatic cancer . Cyclooxygenases and 5- and 12-lipoxygenases play key roles in promoting pancreatic cancer growth. However, nothing is known about 15-LOX-1 in pancreatic cancer . Since this enzyme metabolizes the major dietary PUFA, linoleic acid, we investigated its expression. Materials and Methods: 15-LOX-1 ...

Clinical Pancreatic Cancer 1 Heredity in Pancreatic Cancer . The Association between Asthma and Pancreatic Cancer (Preliminary Results) A. Staka 1 , A. Pukitis 1 , B. Isaksson 2 , J. Permert 2 1 Gastroenterology Center, P. Stradin Clinical University Hosp., Riga, Latvia, 2 Gastrocentrum, Huddinge University Hosp., Sweden Introduction: Pancreatic adenocarcinoma is an important cause of death from cancer throughout the developed world. Pancreatic cancer has been reported to aggregate in some families. In small studies was found that asthma and other allergies were signifi- cant risk factors as well. Material and Methods: The study is prospective population-based case-control investi- gation to establish heredity of pancreatic cancer , association ...

Clinical Pancreatic Cancer 18 New Hope for Pancreatic Cancer Patients: LY293111 in Combination with Gemcitabine R. Hennig, J. Ventura, R. Segersvärd, E. Ward, X.Z. Ding, T. Iwamura, S.M. Rao, B.D. Jovanovich, R.H. Bell Jr, T.E. Adrian Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Introduction: New drugs are desperately needed for pancreatic cancer . Leukotriene B4 receptors are up-regulated in human pancreatic cancer tissues and LTB4 stimulates pancreatic cancer growth. The LTB4 antagonist LY293111 blocks pancreatic cancer cell growth and induces apoptosis. LY293111 was tested in a fluorescent orthotopic tumor model that mimics the clinical behaviour of pancreatic adenocarcinoma and allows monitoring of tumor growth and metastases. Materials and Methods: GFP-expressing human ...

Basic Pancreatic Cancer 113 Anti- Pancreatic Cancer Effects of Myristoleic Acid X.Z. Ding, R. Witt, W.G. Tong, X.Q. Li, H. Betts, P. Collin, T.E. Adrian Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Background: We have previously shown that certain lipid fractions of a commercial extract of the sea cucumber, Cucumaria frondosa have potent anti- pancreatic cancer activity. We have now identified myristoleic acid as an component of one extract that exhibits anticancer activity and lipoxygenase inhibitory activity. The current study was designed to characterize the effects of myristoleic acid, a monounsaturated fatty acid, in pancreatic cancer . Materials and Methods: Cellular proliferation and apoptosis were evaluated by thy- midine incorporation, TUNEL assay and annexin V binding in different cell lines. ...

Clinical Pancreatic Cancer 21 Risk Factors for Pancreatic Cancer in Patients with Chronic Pancreatitis S. Barbu, M. Cazacu IVth Surgical Clinic, University of Medicine and Pharmacy, ‘Iuliu Hatieganu’ Cluj-Napoca, Romania Introduction: Pancreatic cancer developed on chronic pancreatitis has a late diagnosis and a fatal outcome. Purpose: To find risk factors for pancreatic cancer in our patients with chronic pancre- atitis. Methods: 106 patients (87 men, 19 women) from Transilvania region were operated in our clinic (1991–2000) for intractable pain (10) and complications (96) of chronic pan- creatitis (78 alcoholic, 25 idiopathic, 3 hypertriglyceridaemic). At laparotomy, 3 males (38, 51 and 56 years old) with a follow up period of 9, 11 and 14 years, were found to have a pancreatic cancer developed on chronic pancreatitis (final ...

Basic Pancreatic Cancer 110 Nestin-Positive Cells in the Pancreas – Precursor Cell for Pancreatic Adenocarcinoma? T. Kennedy, X.Z. Ding, T.E. Adrian, R.H. Bell Jr Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Introduction: The cell type of origin for development of pancreatic adenocarcinoma is controversial. While pancreatic cancers cells behave like ductal cells, other evidence sug- gests that islet or acinar cells may be the origin. Recently, a new pancreatic cell type was characterized as a nestin-positive stem cell. These nestin-positive cells have extended proliferative capacity in culture and are capable of differentiating into multiple cell types. We hypothesize that this nestin-positive cell is the origin for pancreatic adenocarcinoma. Materials and Methods: RT-PCR was performed on RNA extracted ...

Basic Pancreatic Cancer 95 New Approaches for Molecular Diagnostic of Pancreatic Cancer V. Seibert 1 , P. von Hoegen 1 , M . Taeger 3,4 , H.-U. Schulz 3,4 , W. Halangk 3,4 , U. Kellner 2,4 1 Europroteome AG, Hennigsdorf, 2 Klinikum Minden, Minden, 3 Universitätsklinikum Magdeburg, Magdeburg, 4 Member of Europroteom’s Clinical Cancer Network, Germany Introduction: Therapy of pancreatic cancer can be improved by the detection of new targets at the tumor cell level. However, obtaining sufficient quantities of high quality tissue for analysis is methodologically difficult. Methods/Results: Here we report a procedure which allows epithelial tumor cells to be isolated selectively from ...

Clinical Pancreatic Cancer 9 The Comparison of Bypass and Palliative Resection Therapy for Pancreatic Cancer R. Strnad, J. Fronek, D. Langer, F. Belina, M. Ryska Transplant Surgery Department, IKEM, Prague, Czech Republic Pancreatic cancer is the fifth cause of cancer death in Europe. 80% of cases are locally advanced or/with distant metastases. Radical procedure is only for minority of patients. Palliative or symptomatic procedures are common. Bypassing is usually planned according to the preoperative investigations. Palliative resection is usually extorted by the peroperative or postoperatively by the definitive histology. Methods and Materials: In IKEM 4/1998–12/2002 72 patients underwent palliative surgery and 13 resection for pancreatic cancer : total pancreatectomy 3 and duo- denopancreatectomy 10 . Bypass procedure underwent 59 patients. ...

Basic Pancreatic Cancer 101 Regulation of ADAM17/TACE mRNA in Human Pancreatic Cancer Cells J. Ringel 1,2 , R. Jesnowski 1 , N. Moniaux 2 , A. Choudhury 2 , S.K. Batra 2 , M. Löhr 1 1 Department of Medicine II, Mannheim Medical Faculty, University of Heidelberg, Germany, 2 Department of Biochemistry, UNMC, Omaha, Nebr., USA Background: Recently, we reported an aberrant and cell cycle-dependent expression of ADAM17/TACE in pancreatic cancer . Here we investigated the regulation of ADAM17/ TACE mRNA. Methods: The regulation was investigated in a mouse model and in vitro assays by using semi-quantitative RT-PCR. We tested whether the ADAM17/TACE mRNA expression is affected after orthotopic or subcutaneous implantation ...

Basic Pancreatic Cancer 114 Inhibition of Hypoxia Inducible Factor-1 Reduces Neoangiogenesis and VEGF Production in Pancreatic Cancer In Vivo and In Vitro P. Büchler, O.J. Hines, R. Ludwig, M. Schneider, M.W. Büchler, H. Friess, H.A. Reber Department of Surgery, University of Heidelberg, Germany, UCLA School of Medicine, University of California, Los Angeles, Calif., USA Background: Pancreatic cancer is marked by its aggressive and resistant tumor growth. Neoangiogenesis is a requirement for both local and metastatic tumor growth. In vitro low oxygen levels activate Hypoxia inducible factor-1, which upregulate vascular endothelial growth factor (VEGF). Genistein, inhibits hypoxic activation of HIF-1, thereby inhibiting tumor angiogenesis. Aim: The aims of this study were to inhibit HIF-1 activation by genistein and to analyze the effects ...

Clinical Pancreatic Cancer 25 Metastatic Involvement of Lymph Node 8a is an Independent Prognostic Factor in Pancreatic Cancer S. Connor, L. Bosonnet, H. Doran, P. Ghaneh, M.N. Hartley, N. Alexakis, F. Campbell 1 , R. Sutton, J.P. Neoptolemos Departments of Surgery and Pathology 1 , Royal Liverpool University Hospital, Liverpool, UK Introduction: Surgery offers the only chance of cure in those with pancreatic cancers. With the advent of improved radiology and laparoscopic staging the number of unnec- essary laparotomies has been reduced. Despite this a number of patients who undergo resection have undetected micrometastatic disease resulting a short disease free inter- val. Current prognostic factors are difficult to determine pre-operatively limiting their use in decision making with regard to resection. The aim of this study ...

Basic Pancreatic Cancer 115 Hypoxia, Angioinvasion and Metastasis in Pancreatic Cancer : HIF-1 as a New Regulator of uPAR Expression P. Büchler, O.J. Hines, M. Schneider, R. Ludwig, M.W. Büchler, H. Friess, H.A. Reber Department of Surgery, University of Heidelberg, Germany, UCLA School of Medicine, Los Angeles, Calif., USA Background and Aims: Angioinvasion is the rate limiting step in metastatic tumor pro- gression. Among the few proteins ultimately necessary for angioinvasion – urokinase receptor (uPAR) is one of the most important. Hypoxia-Inducible-Factor-1 (HIF-1) is found to be activated during growth of human pancreatic cancer , a tumor which grows in a microenvironment of low oxygen. It is not known whether hypoxia is contributing to metastatic progression. Therefore, in the present study, we evaluated whether HIF-1 transcriptionally controls ...

Clinical Pancreatic Cancer 7 Surgical Strategy for Pancreatic and Periampullary Cancer Z. Sledzinski, J. Kostro, M.I. Pirski, D. Zadrozny, M. Lukianski, Department of General Surgery and Transplantation, Medical University of Gdansk, Poland Introduction: Purpose of this study was to estimate curative and palliative method of treatment for pancreatic and periampullary cancer . Methods: From 1994 to 2002, 306 patients were treated for pancreatic cancer (263) and periampullary cancer (41). 159 patients had pancreatic resection. Criteria of tumor resectability was: 1. No distant metastases, 2. No neoplasmatic infiltration into vascular around the pancreas. In 120 patients pancreatic head resection was done: 94 Whipple’s and 26 Traverso-Longmire procedures were performed. 33 patients were treated with total pancreatoduodenectomy and 6 ...

Basic Pancreatic Cancer 122 Expression Profiling of Microdissected Pancreatic Ductal Carcinomas Using DNA Microarrays R. Gruetzmann 1 , I. Alldinger 1 , J. Lüttges 2 , B. Sipos 2 , G. Klöppel 2 , H.D. Saeger 1 , D. Ockert 1 , C. Pilarsky 1 1 Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University of Dresden, 2 Department of Pathology, University of Kiel, Germany Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of malignancy related death. Today it is the eighth common cancer with the lowest overall 5-year rela- tive survival rate of any tumor type. Apart from surgery there is no effective therapy, but even resected patients ...

Clinical Pancreatic Cancer 5 Quality of Life After Treatment of Pancreatic Cancer J. Kostro, M. Lukianski, Z. Sledzinski Department of General Surgery and Transplantation, Medical University of Gdansk, Poland Introduction: There is a growing interest in assessing the impact of a disease and the effect of a treatment on a patient’s life, expressed as quality of life. The purpose of the study was to investigate the impact of the operative method on the quality of life in patients operated for pancreatic cancer . Methods: 54 patients operated for pancreatic cancer were divided for 4 groups depending on type of operation. Group 1 (14 patients) – radical resection; group 2 (12 patients) – pal- liative resection; group 3 (17 patients) – bypass anastomosis and group 4 (11 patients) – only laparotomy. All patients completed the questionnaires EORTC QLQ-C30 and ...

Basic Pancreatic Cancer 105 Non-Mitochondrial NAD(P)H Oxidase Mediates Growth Factor-Induced ROS Production and Suppression of Apoptosis in Pancreatic Cancer Cells E.C. Vaquero, K.J. Nam, I. Gukovsky, S.J. Pandol, A.S. Gukovskaya VA Greater Los Angeles Healthcare System, University of California, Los Angeles, Calif., USA Background: Reactive oxygen species (ROS) generation is characteristic of cancer cells and linked to tumor progression. Aim: To determine the source of ROS induced by growth factors and its role in pancre- atic cancer cell apoptosis. Methods: Human pancreatic carcinoma MIA PaCa-2 cells were cultured without serum, with fetal bovine serum (FBS), or with insulin-like growth factor I (IGF-I). Intracellular ROS level was assessed by flow cytometry; apoptosis by DNA fragmentation; NAD(P)H oxidase activity by chemiluminescence. ...

Clinical Pancreatic Cancer 20 Familial Pancreatic Cancer (FPC): Gender, Transmission and Anticipation C.W. McFaul, I.H. Ellis, J. Earl, J. Leslie, L. Yan, N. Howes, C. Hont, R. Sibson, G. Uomo, C. Pasquale, J.P. Neoptolemos and W. Greenhalf on behalf of The European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) The Department of Surgery, The University of Liverpool, UK Background: We report on 81 families with a predisposition for pancreatic ductal adenocarcinoma (PDAC) from the EUROPAC registry. Methods: Families with PDAC in more than 2 generations are ‘FPC’ (41 families). ‘Possible’ is where PDAC is in one generation or combined ages in two genera- tions 110 (22). Ten families have multiple PDAC but also Gastric Cancer (GC). Survival analysis was carried out with all possible carriers as censored ...

Clinical Pancreatic Cancer 16 Radiotherapy and 5-FU in Irradical Resected Patients with Cancer of the Pancreas H.G. Smeenk, J. Jeekel, T.C.K. Tran, L. Incrocci, C.H.J. van Eijck Erasmus Medical Centre, Rotterdam, The Netherlands Introduction: In this study an analysis was performed in 54 patients who underwent an irradical resection (R-1 and R-2) for pancreatic cancer . Thirty-three patients were treated with chemoradiation. To evaluate the effect (survival and patterns of recurrence) of therapy, this group was compared to a group of 21 patients that did not receive chemoradiation. Methods: Radiotherapy consisted of 50 GY external upper abdomen radiation in two courses, concomitant with intravenous 5-FU 25 mg/kg/24 hours continuously on the first 4 days of each treatment course. Follow-up was performed mainly by CT-scanning and occasionally by US and was ...

Clinical Pancreatic Cancer 19 ESPAC-1: Final Results of a European, Randomised Controlled Trial to Assess the Roles of Adjuvant Chemotherapy and Adjuvant Chemoradiation in Resectable Pancreatic Cancer J.P. Neoptolemos 1 , D.D. Stocken 2 , H. Friess 3 , J.A. Dunn 2 , C. Bassi 4 , H.G. Beger 5 , L. Fernandez-Cruz 6 , C. Dervernis 7 , F. Lacaine 8 , M.W. Büchler 3 on behalf of the ESPAC group 1 Royal Liverpool University Hospital, 2 Cancer Research UK Clinical Trials Unit, Birmingham, UK, 3 University of Heidelberg, Germany, 4 University of Verona, Italy, 5 Ulm University Hospital of Surgery, ...

Web Immagini Gruppi Directory News Novità! Ricerca avanzata Preferenze Cerca nel Web Cerca solo le pagine in Inglese Spiacenti, nessun contenuto associato a questo URL Web La ricerca di - cache:qsZ1NEqq5VAJ:www.pancreasweb.com/Abstracts/pdf/0001637.pdf allintitle: pancreatic cancer filetype:pdf OR filetype:doc OR filetype:ppt OR filetype:xls OR filetype:rtf - non ha prodotto risultati in nessun documento. Suggerimenti: - Assicurarsi che tutte le parole siano state digitate correttamente. - Provare con parole chiave diverse. - Provare con parole chiave più generiche. - Provare con un numero minore di parole chiave. ...

Clinical Pancreatic Cancer 8 Results of Treatment of Pancreatic Cancer P. Árkosy 1 , L. Sasi Szabó 1 , Z.S. Szentkereszty 1 , J. Szántó 2 , C. András 2 , P. Sápy 1 1 2nd Deptartment of Surgery and 2 Department of Clinical Oncology, Debrecen Medical University, Hungary Introduction: Authors evaluate the results of the different types of surgical procedures in the treatment of pancreatic cancer , to examine the postoperative complications and perioperative mortality. Authors evaluate the survival rate and the results of the postop- erative adjuvant chemotherapy on the basis of regular control examinations and QLQ. Methods: Between 1991 and 2001, 326 operations were performed for pancreatic - and periampullary tumors. There were ...

Web Immagini Gruppi Directory News Novità! Ricerca avanzata Preferenze Cerca nel Web Cerca solo le pagine in Inglese Spiacenti, nessun contenuto associato a questo URL Web La ricerca di - cache:nTqDjz6S_VcJ:www.pancreasweb.com/Abstracts/pdf/0001544.pdf allintitle: pancreatic cancer filetype:pdf OR filetype:doc OR filetype:ppt OR filetype:xls OR filetype:rtf - non ha prodotto risultati in nessun documento. Suggerimenti: - Assicurarsi che tutte le parole siano state digitate correttamente. - Provare con parole chiave diverse. - Provare con parole chiave più generiche. - Provare con un numero minore di parole chiave. ...

Basic Pancreatic Cancer 98 Islet Amyloid Peptide (IAPP) Accelerates Weight-Loss and Depletion of Body Fat in the Rat B. Isaksson, F. Wang, M. Olsson, J. Permert, U. Arnelo Department of Surgery, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden Background: The metabolic and cachectic effects of elevated circulating levels of IAPP, that are observed in a majority of pancreatic cancer patients, are still unclear. The effect of S.C. IAPP on food intake (FI) and body weight (BW) were investigated in a pair- feeding experiment in the rat. Methods: Circulating IAPP, insulin, leptin, glucose, lactate, FFA, glycerol, triglycerides and BUN were determined. Glucogen, protein and DNA contents in muscle and liver were measured. Epididymal fat mass, UCP2 mRNA in fat and muscle and 3-0-methylglucose transport in isolated muscle were investigated. ...

Basic Pancreatic Cancer 116 Gene Therapy for Pancreas Cancer with a Genetically Engineered Tumour Suppressor MTBP N. Eardley, N. Vlatkovic, M.T. Boyd University of Liverpool, UK Background: Whilst studying the regulation and function of MDM2 we discovered a novel MDM2 binding protein with potent tumour cell inhibitory properties that we named MTBP (Boyd et al. JBC 2000). We have since discovered that ectopic expression of this gene inhibits pancreatic cancer cell growth comparably to p53. We have now developed a truncated form of the protein that lacks a negative regulatory element and which has enhanced tumour cell growth inhibitory activity. Methods: Full length MTBP and deletion mutants of MTBP expressed from a CMV promoter in a eukaryotic expression vector were tested for their ability to inhibit colony formation in a variety of tumour cell lines including ...

Basic Pancreatic Cancer 94 EVITON – A New DNA-based Substance in a Preclinical Model of Pancreatic Carcinoma J. Tepel, M.L. Kruse, C. March, O. Dagvadorj, B. Kremer, H. Kalthoff Clinic for Thoracic Surgery and General Surgery, University Clinic of Schleswig-Holstein, Campus Kiel Background: New therapeutic strategies are needed for irresectable pancreatic carcinoma as well as for the reduction of high rates of local recurrence after curative resection. Therefore we tested a 5 3 -terminal modified oligodesoxynucleotide (ON) with a novel sequence (EVITON) in a preclinical model of pancreatic carcinoma. Material and Methods: Cell proliferation was measured by colorimetric tests (XTT) and 3H-thymidine incorporation assays. Induction of apoptosis was studied by FACS analysis. Cellular uptake was analysed using confocal laser scanning microscopy. In vivo testing ...

Clinical Pancreatic Cancer 6 Pancreatogastrostomy as a Method of Fistula Prevention After Pancreatoduodenectomy J. Kostro, D. Zadrozny, M.I. Pirski, M. Lukianski, Z. Sledzinski Department of General Surgery and Transplantation, Medical University of Gdansk, Poland Introduction: Pancreatic resection can be performed with great safety. Pancreato- jejunostomy remains the most frequently used reconstruction technique for the pancre- atic stump after pancreatoduodenectomy. Pancreatogastrostomy, has been known as an alternative method of reconstruction for almost 50 years. In published reports the leak- age rate for this method of anastomosis is less than 4%. The purpose of this study was to evaluate the pancreatogastrostomy as a method of fistula prevention. Methods: From 1994 to 2002, in 120 patients pancreatic head resection was performed due to pancreatic ...

Basic Pancreatic Cancer 117 Hsp90 Inhibition Sensitises Pancreatic Cancer Cells to Chemotherapeutic Agents C.J. Magee, M. Burkitt, D.I. O’Connor, J. Evans, P. Cornford, D. Spiller, M. White, F. Campbell, J.P. Neoptolemos, W. Greenhalf The Department of Surgery, The University of Liverpool, UK Background: The novel anticancer therapeutics 17AAG and Geldanamycin (GA), target the chaperone protein Hsp90. Hsp90 holds client proteins in an inactive state before release or targeted destruction, thus maintaining a constant pool of protein ready for activation. Methods: Apoptosis was induced using 5 FU or TPA and measured by caspase-3/9 cleavage and increase in sub-G1 cells. Tissue, cell-lines were examined using immuno- histochemistry, immunofluorescence and Westerns. Viability was measured using MTT and Trypan Blue exclusion. Results: Combination of ...

Clinical Pancreatic Cancer 22 Twenty Year Experience of Pancreatic Neuroendocrine Tumours (PNTs) at Royal Liverpool and Broadgreen University Hospitals Trust (RLBUHT) H.E. Doran 1 , F. Campbell 4 , L. Bosonnet 1 , C. Garvey 5 , W. Fraser 3 , M. Lombard 6 , J. Vora 7 , P. Ghaneh 1 , M. Hartley 1 , J.P. Neoptolemos 1 , E.M.I. Williams 2 , R. Sutton 1 Departments of 1 Surgery, 2 Public Health and 3 Clinical Chemistry, University of Liverpool, Merseyside and Cheshire Cancer Registry, Departments of 4 Pathology, 5 Radiology, 6 Gastroenterology and ...