AllDocs -> cancers

Basic: Pancreatic Cancer 87 Expression of Cytokeratin 20 in the Blood of Patients with Disseminated Carcinoma of the Pancreas, Colon, Stomach, Parathyroid and Liver V. Lukyanchuk 1 , H. Friess 1 , J. Kleeff 1 , E. Ayuni 1 , A. Roggo 1 , S. Osinsky 2 , D. Candinas 1 Department of Visceral and Transplantation Surgery 1 , Inselspital, University of Bern, Switzerland; Depart. Modifying Agent of Cancer Therapy**, Inst. exp. Pathol. Oncol. Radiobiol 2 , Kiev, Ukraine Background: Cytokeratins are constituents of the intermediate filaments of epithelial cells that are expressed in various combinations depending on the epithelial cell type and degree of differentiation. The recently identified cytokeratin 20 (CK-20) was ...

Basic: Pancreatic Cancer 125 Progression-dependent Disturbance of Junctional Communication in Ductal Pancreatic Carcinoma Cells T. Bert, S. Hoormann, N. Auerbach, T. Iwamura, M. Kalff-Suske, B. Simon Departments of Gastroenterology and Clinical Genetics, Philipps- University Marburg, Germany Background: Therapeutic options in patients with metastasized pancreatic cancer are poor. In an effort to discover novel therapeutic targets we recently isolated multiple genes differentially expressed in metastasized pancreatic cancer cells using cDNA-representa- tional difference analysis (cDNA-RDA). Methods and Results: One of the isolated cDNA fragments revealed homology to claudin-2, a four transmembrane region protein, member of the tight junction (TJ) pro- tein family of claudins. TJ integral membrane proteins bridge adjacent cells and periph- eral cytoplasmic ...

Basic: Pancreatic Cancer 128 Molecular Analysis of DCC and Smad4 in Pancreatic Cancer : Evidence for two Independant Tumour Suppressor Genes Involved in Pancreatic Carcinogenesis C. Schleger 1 , C. Verbeke 2 , R. Hildenbrand 1 1 Institute of Pathology, University Hospital Mannheim, Germany; 2 Histopathology, St. James’s University Hospital Leeds, UK Background: Loss of chromosome 18q has been observed in about 90% of pancreatic cancer and was proposed as an early genetic event during pancreatic carcinogenesis. Three potential tumour suppressor genes, DCC, Smad4, Smad2 have been identified from this chromosomal region. Smad2 alterations are rarely seen in pancreatic cancers, but functional inactivation of Smad4 has been demonstrated for about 50% of pancre- atic tumours. Highly reduced or ...

Clinical: Pancreatic Cancer 253 Heredity in Pancreatic Cancer . The Association between Asthma and Pancreatic Cancer . A Prospective Population-Based Case-Control Study. Preliminary Results A. Pukitis 1 , B. Isaksson, J. Permert Gastroenterology Center, P. Stradin Clinical Univ. Hosp, Riga, Latvia 1 Huddinge University Hospital, Gastrocentrum, Sweden Introduction: Pancreatic adenocarcinoma is an important cause of death from cancer throughout the developed world. There are few established environmental risk factors, but exposure to tobacco and possibly a previous history of pancreatitis appear to be the most important. Pancreatic cancer has been reported to aggregate in some families (Hruban RH, 1999). In the United States pancreatic cancer has been reported to be hereditary in an estimated 10% of cases (Brentall ...

Clinical: Pancreatic Cancer 252 Familial Aggregation of Pancreatic Cancer in the Utah Population Database J. DiSario, R. Kerber, N. Omer, G. Mineau, R. Burt University of Utah Health Sciences Center, Huntsman Cancer Institute, Salt Lake City, Utah, USA Aim: To measure the degree of familial aggregation of pancreatic cancer in the Utah Population Database (UPDB). The UPDB consists of genealogical data on over one mil- lion individuals, linked to vital statistics data from the Utah Department of Health, and cancer incidence information from the Utah Cancer Registry (UCR). Methods: We identified a cohort of 241,435 individuals who were born between 1870 and 1931 and who were resident in the state of Utah between 1966 and the present. The UCR began collecting statewide cancer incidence data in 1966, so members of the cohort were followed for cancer risk ...

Basic: Pancreatic Cancer 110 Skeletal Muscle Insulin Resistance in Pancreatic Cancer Patients is Associated with Increased Expression of UCP2 and 3 B. Isaksson 1 , G.A. El-Ella 2 , U. Arnelo, J. Larsson, J. Permert 3 , T.E. Adrian 2 1 Department of Surgery, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden; 2 Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska, USA Background: A majority of pancreatic cancer (PC) patients have associated metabolic derangements, such as weight loss and glucose intolerance. The glucose metabolism is similar to type 2 diabetes with impaired postreceptor insulin signaling and decreased insulin action on glucose uptake in muscle tissue. Uncoupling proteins (UCP) 2 and 3 in ...

Clinical: Pancreatic Cancer 295 Usefulness of Laser Capture Microdissection in Microarray Analysis of Pancreatic Cancer M. Ueda 1 , Y. Miura 1 , O. Kunihiro 1 , T. Ishikawa 1 , Y. Ichikawa 1 , I. Endo 1 , H. Sekido 1 , S. Togo 1 , K. Hamada 2 , N. Inagaki 2 , H. Okabe 2 , H. Shimada 1 Department of Surgery II 1 , Yokohama City University, Yokohama, Japan Nippon Roche Research Center 2 , Kamakura, Japan Background: Pancreatic cancer is histologically characterized by highly atypical tumor cells scattering in an abundant fibrous stroma. For genetic analysis of pancreatic cancer , contamination of the stromal ...

Basic: Pancreatic Cancer 131 TGF- Signaling Pathway is not Necessarily SMAD Dependent in Pancreatic Cancer A.A. Tempia-Caliera, D. Schneider, J. Kleeff, P.O. Berberat, Z. Zhu, M. Korc 1 , H. Friess, M.W. Büchler Department of General Surgery, University of Heidelberg, Heidelberg, Germany; 1 Departments of Medicine, Biological Chemistry and Pharmacology, University of California, Irvine, California, USA Background: ig-h3 (TGFBI, keratoepithelin) is a TGF- 1-inducible gene which influences cell attachment and migration. Down-regulation of ig-h3 in transformed fibroblasts suggests its role in malignant transformation. Although TGF- is a growth inhibitor in epithelial cells, its overexpression in pancreatic cancer is associated with poor prognosis due to alterations in its intracellular Smad protein signaling pathways. In this ...

Clinical: Pancreatic Cancer 280 Overexpression and Regulation of Lymphangiogenic Growth Factor VEGF-C in Human Pancreatic Cancer J. Itakura, R.F. Tang, T. Aikawa, H. Fujii 1 , M. Korc, Y. Matsumoto Department of Surgery, Yamanashi Medical University, Japan; 1 Department of Endocrinology, University of California, Irvine, USA Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic polypeptide that has been implicated in cancer growth. In the present study we characterized VEGF-C expression and its regulation in cultured human pancreatic cancer cell lines and human pancreatic cancer tissues. VEGF-C mRNA transcripts were present in all tested cell lines. Immunoblotting also revealed the presence of VEGF-C protein in all the cell lines. To analyze what is the regulator for this VEGF-C expression in pancreatic cancer , ...

Basic: Pancreatic Cancer 78 Macrophages and Mast Cells Express Angiogenetic Factors in Pancreatic Adenocarcinoma I. Esposito 1 , D. Campani 1 , M. Menicagli 1 , U. Boggi 2 , 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: Pancreatic cancer evokes an intense desmoplastic reaction and the neo- plastic glands are embedded in a dense connective tissue populated by inflammatory cells. The aim of this study is the characterization of the inflammatory cells in pancre- atic cancer and the evaluation of their role in the production of pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and ...

Clinical: Pancreatic Cancer 251 The Combined Approach of Chemo-Gene Therapy in the Treatment of Pancreatic Adenocarcinoma C.M. Halloran, P. Ghaneh, J.P. Neoptolemos, E. Costello Department of Surgery, Royal Liverpool University Hospital, Liverpool, UK Background: Pancreatic ductal adenocarcinoma is a common cause of cancer related death in Europe and the USA. This cancer has a relatively symptom free progression with patients commonly presenting with incurable disease. At present, surgery offers the only prospect of long-term survival, but is feasible in few patients (around 20%). Current adjuvant treatment achieves only a small further increase in survival. Pancreatic ductal adenocarcinoma has a typical footprint of genetic mutations, with the inactiva- tion of the tumour suppresser gene p16 INK4A being frequently encountered. Our group has previously ...

Clinical: Pancreatic Cancer 302 Willingness of Risk Taking in Patients with Pancreatic Cancer : Palliative Cytostatics and Pancreatoduodenectomy – A Questionnaire Based on Scenarios Å. Andrén-Sandberg Department of Surgery, Haukeland University Hospital, Bergen, Norway Background: Decision making for treatment of pancreatic cancer patients is often dif- ficult due to bad odds; the probability of mortality and morbidity is substantial and despite that cure or even palliation cannot be ascertained. Material and Method: Two difficult scenarios were explained to 27 senior surgeons, 21 senior gastroenterologists/oncologists, 17 junior surgeons, 11 junior gastroenterolo- gists/oncologists, 17 senior nurses, 33 junior nurses, 64 relatives to pancreatic cancer patients, 27 patients with pancreatic cancer after diagnosis but before decision of their ...

Basic: Pancreatic Cancer 126 Control of Cellular Immune Response by HLA-Class I in Human Pancreatic Cancer E. Ryschich 1 , F. Autschbach 2 , T. Noetzel 1 , M. Reidel 1 , M.W. Büchler 1 , E. Klar 1 , J. Schmidt 1 Dept. of Surgery 1 and Pathology 2 , University of Heidelberg, Im Neuenheimer Feld 120, 69120 Heidelberg, Germany Introduction: The expression of HLA class I controls the specific antigen recognition by cytotoxic CD8 T-cells. The present investigation was aimed to study the role of HLA class I in the control of lymphocyte infiltration in human pancreatic cancer . Methods: Fresh tissue samples from 31 operated patients with ductal pancreatic cancer were immediately frozen and stored in liquid ...

Basic: Pancreatic Cancer 73 Strongly Anti-Metastatic Activity Encoded by Chromosome 18 Switches to a Dormant Phenotype of Human Pancreatic Cancer Cells L.P. Lefter 1,2 , T. Furukawa 1 , M. Sunamura 2 , H. Abe 2 , K. Takeda, S. Matsuno 2 , A. Horii 1 Departments of 1 Molecular Pathology and 2 Gastrointestinal Surgery, Tohoku University School of Medicine, Sendai, Japan Considered by many to be one of the deadliest and also most studied among malignancies, pancreatic cancer is associated worldwide with the mean 5-year survival rate below 5%. Thus, acquisitions of efficiently approaches and markers able to accurately detect earliest genetic stages of pancreatic cancer should be prioritizing. A number of lines of evidence ...

Basic: Pancreatic Cancer 116 Analysis of Transcriptional Variations in Pancreatic Cancer by DNA-Microarray Technology A. Bauer 1 , G. Sposny 1 , M. Buchholz 2 , W. Boeck 2 , T.M. Gress 2 , J.D. Hoheisel 1 Division of Functional Genome Analysis 1 , Deutsches Krebsforschungszentrum, Heidelberg, Germany; Department of Internal Medicine I 2 , University of Ulm, Germany Background: The diagnosis of pancreatic carcinoma is still associated with a poor prognosis, an increasing incidence and no or only rather ineffective means of treatment. In our study, we developed and evaluated a fairly global DNA-chip for analyses of pan- creas with about 3,500 human genes known to be differentially transcribed in pancre- atic cancer cells and ...

Clinical: Pancreatic Cancer 264 Characterisation of Familial Pancreatic Cancer kindreds on the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) I. Ellis 2 , W. Greenhalf 1 , N. Howes 1 , A. Poll 2 , G. Uomo 3 , C. Pasquale 4 , J.P. Neoptolemos 1 on behalf of EUROPAC 1 Department of Surgery, Royal Liverpool University Hospital and 2 Alder Hey Children’s Hospital, Eaton Road, Liverpool, Liverpool, UK. Dept. Gastroenterology, Cardarelli Hospital, Napoli 3 , Inst. di Semeiotica Chirurgica, University of Padova 4 , Italy Background: In 10% of cases of pancreatic cancer there is a familial background to the disease. Mutated genes ...

Basic: Pancreatic Cancer 104 Autonomous Parvovirus H1-mediated Combination Suicide and Cytokine Gene Therapy for Pancreatic Adenocarcinoma A. Hajri, S. Wack, C. Dinsart 1 , J.J. Cornelis 1 , J. Rommelaere 1 , M. Aprahamian INSERM U375: IRCAD-Strasbourg, France and 1 DKFZ-Heidelberg, Germany Background: The autonomous rodent parvoviruses MVMp (Minute Virus of mice) and H1 present many characteristics of attractive candidates for cancer gene therapy. They have a strong oncotropism due to their preferential expression in tumors and an oncolytic activity mediated by the non-structural protein (NS1). However, these par- voviruses are not enough potent by themselves to destroy the solid tumor cell mass. In cancer therapy, the local presence of cytokines in tumors can activate an immune ...

Basic: Pancreatic Cancer 135 In Vitro Reconstruction of Pancreatic Duct-Like Epithelia from A818-6 Adenocarcinoma Cells: Investigation of CD95 and FAP-1 Expression B. Winterhoff, M-L. Kruse 1 , H. Kalthoff Department of General and Thoracic Surgery Molecular Oncology Research Group, University of Kiel, 1 Dept. of Medicine University of Kiel Lab. f. Molecular Gastroenterology, Kiel, Germany Background and Aims: The A818-6 differentiation system from monolayer growth of pancreatic cancer cells towards single layer epithelium in hollow sphere-organisation (Lehnert et al., J Cell Biol 2001) provides a new means to investigate CD95-induced apoptosis in pancreatic cancer . Resistance towards CD95-induced cell death in Panc 89 adenocarcinoma cells appears to be mediated by expression of FAP-1 (FAS-associated phosphatase 1) which was ...

Basic: Pancreatic Cancer 107 Concerted Deregulations of Multiple Apoptosis- Controlling Genes in Pancreatic Carcinoma Cells A. Trauzold 1 , S. Schmiedel 1 , C. Tams 1 , S. Oestern 1 , A. Arlt 2 , C. Röder 1 , H. Ungefroren 1 , H. Kalthoff 1,2 1 Molecular Oncology, Clinic for General Surgery; 2 Laboratory of Molecular Gastroenterology, 1st Dept. of Medicine, Christian- Albrechts-University, Kiel, Germany Background: Pancreatic adenocarcinoma is one of the most aggressive human tumours with extremely poor prognosis. Among the mechanisms that contribute to tumour pro- gression and failure of chemotherapy is the marked resistance to apoptosis. Materials and Methods: For Western Blot analysis 30 g total ...

Clinical: Pancreatic Cancer 300 Is There any Stage I Disease of the Pancreas? P.M. Pour, R.E. Brand, W. Kimura, R. Bell UNMC Eppley Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA, Department of Surgery, University of Tokyo, Japan and Department of Surgery, Midwestern University, Chicago, USA The natural history of pancreatic cancer makes it one of the most malignant human dis- eases. The unknown etiology, lack of early symptoms, explosive outcome, short survival and resistance to therapy are consistent markers of this cancer . Although surgery has been shown that sole effective therapeutic approach, the inevitable tendency for recur- rence even after the curative surgery has remained a mystery. Ironically, reasons for this recurrence, which leads to ultimate death of the patients within a few years after the sur- gery, have not been a focus of research. ...

Basic: Pancreatic Cancer 112 Suppression of Malignant Potential by Chromosome 18 or Chromosome 12 Transfer in Pancreatic Cancer Cell Lines M. Sunamura, L.P. Lefter, T. Furukawa, D.G. Duda, T. Yokoyama, L. Sun, S. Matsuno, A. Horii Departments of 1 Gastroenterological Surgery and 2 Molecular Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan Background: Previous studies have demonstrated that adenovirus-mediated induction of SMAD4/MADH4 did not suppress in vitro growth in pancreatic ductal carcinoma cells with completely inactivated SMAD4/MADH4 . Moreover, cytogenetic, allelotype, and somatic cell hybrid studies on the others human cancers have suggested that the long arm of chromosome 18 may carry a tumor suppressor gene(s) besides SMAD4/MADH4 that plays a role in the early stage of carcinogenesis. ...

Clinical: Pancreatic Cancer 309 Treatment of Pancreatic Cancer by Targeting the HER2/NEU Pathway 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: The proto-oncogene Her2/neu is overexpressed in 50–70% of pancreatic cancer (PaCa) specimens. Conventional treatment using chemotherapy and radiation has only little effect in PaCa. Recently a humanized anti-HER2/neu antibody (Herceptin™, Genentech) has proven clinical activity in breast cancer , where HER/2neu is upregulated in only 30% of patients. Aim: The aims of this study were to evaluate Herceptin™ therapy as a possible novel treatment modality in pancreatic ...

Clinical: Pancreatic Cancer 307 Pathways of Care for Patients with Pancreatic Cancer : The Primary Care-Specialist Interface in Contemporary Practice I.T. Virlos, W. Boswell, H.P.P. Siriwardana, R.F. McCloy, A.K. Siriwardena HPB unit, Manchester Royal Infirmary, UK Introduction: Evidence of improved outcome after surgery for pancreatic cancer in high-volume tertiary centres has led to governmental guidance for better co-ordination and delivery of care. This study examines pathways of care for pancreatic cancer in order to delineate patterns of referral and access to specialists. Methods: Structured questionnaires were sent to family practitioners (GPs), gastroen- terologists and gastrointestinal surgeons (including general and specialist HPB sur- geons) practising within the Greater Manchester and Cheshire network (a major conurbation with a population ...

Clinical: Pancreatic Cancer 284 A New Therapeutic Approach for Pancreatic Cancer by Gene Therapy: In Vivo Gene Transfer of Somatostatine Receptor SST2 F. Vernejoul, N. Benali, P. Faure, D. Calise, G. Tiraby, L. Pradayrol, C. Susini, L. Buscail INSERM U531, Institut Louis Bugnard IFR31, Centre Hospitalier Universitaire Rangueil and Cayla Company [G.T] 31400 Toulouse, France Background: Our previous studies conducted in pancreatic cancer model established in nude mice and in hamsters revealed that somatostatin receptor SST2 gene expression induced both an antioncogenic and a local antitumor bystander effects in vivo. We thus proposed a new approach of gene therapy for pancreatic carcinoma based on SST2 gene transfer. Methods: In the present study, in vivo gene transfer of SST2 was investigated in two transplantable models of primary and metastatic ...

Clinical: Pancreatic Cancer 242 Little Correlation between Surgical Load and Results of Pancreatoduodenectomy in Low Volume Surgery Hospital P.L. Bäckman 1 , P. Maisonneuve 2 , J. Axelson 3 , Å. Andrén-Sandberg 4 1 Department of Surgery, Lund University Hospital, Lund, Sweden, 2 European Institute of Oncology, Milano, Italy, 3 Department of Surgery, Malmö University Hospital, Malmö, Sweden, and 4 Queen Silvia’s Hospital for Children, Sahlgrenska University Hospital, Gotheburg, Sweden Background: It has been shown that the results of pancreatoduodenectomies are sig- nificantly better in hospitals and departments of surgery with a high volume of pancre- atectomies. We have investigate the results for an unselected population in a sparsely populated ...

Clinical: Pancreatic Cancer 240 Outcome for Resection for Tumors of the Head of the Pancreas Y. Kawarada Ueno Municipal Hospital, Ueno-City, Mie, Japan Background: A pancreatic registry study in regard to lymph node dissection showed that D2 or greater dissection had been performed for carcinoma of the head of the pan- creas at almost all of the institutions in Japan. Materials and Methods: Examination of outcome according to extent of lymph node dissection of patients who underwent resection of invasive ductal carcinoma of the head of the pancreas in our department revealed a significantly higher cumulative survival rate after D2 dissection than after D1 resection. However, since 1994 we have been selecting a procedure that emphasizes QOL in addition to curability and performing lymph node dissections that are exactly halfway between D1 and d2:D1 resection, ...

Clinical: Pancreatic Cancer 312 Clinical Trial of the Dendritic Cell-based Immunotherapy Combined with Irradiation Against Pancreatic Cancer H. Shimamura 1,2 , M. Sunamura 1 , H. Abe 1 , Y. Saitoh 1 , A. Harada 1 , F. Motoi 1 , S. Egawa 1 , K. Shibuya 1 , K. Takeda 1 , S. Matsuno 1 Department of HBP Surgery 1 , Tohoku University, Sendai, Japan; Department of Surgery 2 , Sendai National Hospital, Sendai, Japan Background and Aim: Dendritic cell (DC) is a potent antigen presenting cell which can govern immune system, and immunotherapy using DC is now in the spotlight. To apply DC to pancreatic cancer therapy, we examined and showed that DC could phagocytize ...

Basic: Pancreatic Cancer 102 Expression Signatures of Metastasis-Associated Genes in Pancreatic Cancer Cells and Gastrointestinal Tumors M. Buchholz 1 , H. Fensterer 1 , P. Michl 1 , W. Böck 1 , T. Iwamura 4 , G. Leder 2 , H. Allgayer 3 , G. Adler 1 , T.M. Gress 1 1 Dept. Internal Med. I, and 2 Dept. General Surgery, University of Ulm, Germany; 3 Dept. Surgery, University of Munich, Germany; 4 Dept. Surgery I, Miyazaki Medical College, Miyazaki, Japan Background: In order to identify genes influencing the metastatic potential of tumor cells, we have performed expression profile analyses of two subclones of the pancreatic cancer cell line SUIT-2 ...

Basic: Pancreatic Cancer 86 Identification of a New Susceptibility Locus for Autosomal Dominant Pancreatic Cancer R.H. Pfützer 2 , M.A. Eberle 1 , K.L. Pogue-Geile 2 , M.P. Bronner 1 , D. Crispin 1 , M.B. Kimmey 1 , R.H. Duerr 2 , L. Kruglyak 1 , D.C. Whitcomb 2 , T.A. Brentnall 1 1 University of Washington, Seattle, WA, 2 University of Pittsburgh, Pittsburgh, PA, USA Background: Pancreatic cancer is the fifth leading cause of cancer death in the US. Among other factors, there is growing evidence for genetic susceptibility factors. Several familial pancreatic cancer syndromes have been described. We have recently reported a large family with a characteristic ...

Clinical: Pancreatic Cancer 288 Synergistic in vitro Activity of Gamma-linolenic Acid and Cytotoxic Drugs Against Pancreatic Adenocarcinoma Cell Lines P.A. Whitehouse, A. Cooper, C.D. Johnson Department of Surgery, Southampton General Hospital, Southampton, UK Background: Gamma-linolenic acid (GLA) has growth inhibitory effects on pancreatic cancer cell lines both in vitro and in vivo, at doses non-toxic to non- cancer cells. In pan- creatic cancer , chemotherapeutic agents have only limited activity, with toxic side effects. Interactions between GLA and cytotoxic drugs have not been investigated; any synergy might improve the therapeutic ratio of these agents. Aim: To investigate possible interactions of GLA with 5-fluorouracil (5FU) or Gemcitabine against pancreatic cancer cell lines in vitro. Methods: Two pancreatic cancer cell lines (MIA ...