AllDocs -> cancers

Clinical Pancreatic Cancer 23 Clinical Epidemiology of Pancreatic Neuroendocrine Tumours (PNTs): Comparison of Data from Three UK Cancer Registries (CRs) H.E. Doran 1 , R. Sutton 1 , E.M.I. Williams 2 Departments of 1 Surgery and 2 Public Health, University of Liverpool, Merseyside and Cheshire Cancer Registry, Liverpool, UK Background: We compared data from three UK CRs to determine the feasibility of a national approach to assess PNT clinical epidemiology. Methods: All PNT cases (including age, sex, treatment and survival) were identified from three CRs (West Midlands, North Western and Mersey) for 1996–2000. Results: Forty-three cases (median age 63 years, range 34–77; 23 male: 20 female) were identified from West Midlands CR (population 5.3m; 1.6per m per year) with ...

Clinical Pancreatic Cancer 12 Periampullary Gangliocytic Paraganglioma: A Report of Two Cases G.R. Fronda, D. Campra, P. De Paolis, G. Avagnina, S. Perardi 1 , M. Bernardi 2 , G. Palestro 3 7 Department of Surgery-ASO S. Giovanni Battista (Molinette)- Turin, 1 Department of Gastroenterology-ASO S. Luigi Gonzaga- Orbassano (TO), 2 I and 3 II Department of Pathology, University of Turin, Italy Introduction: Gangliocytic paraganglioma (GP) is rare tumor usually located in peri- ampullary region with uncertain histogenesis and behavior. Methods: Case 1 . 40-years-old male presented with gastrointestinal bleeding and anaemia. Upper endoscopy found an ulcerated polyps near papilla of Vater, confirmed by CT-scan and EUS. No metastases were found. Surgical excision was ...

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 was carried ...

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 5FU 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 GA and ...

Clinical Pancreatic Cancer 2 Localisation of Endocrine Pancreatic Tumours – The Role of Endoscopic and Intraoperative Ultrasound T. Winternitz, T.F. Tihanyi, M. Borsodi, J. Horányi, L. Flautner 1st Surgical Department of Medical Faculty, Semmelweis University, Budapest, Hungary Background: Although adequate pre and intraoperative localisation is remains a difficult problem associated with endocrine pancreatic tumours. Endoscopic ultrasonography (EUS) and intraoperative ultrasonography (IOUS) has shown promise for the detection of pancreatic insulomas. The aim of this study was to analyse the diagnostic power of the EUS and IOUS (LIOUS) for identification of small sized pancreatic insulinomas. Methods: We evaluated seventeen patients (15 women/2 men, mean age (44.1) with EUS and nineteen cases (6 men/13 women, mean age: 49.3) with IOUS of small sized (5–30mm) ...

Basic Pancreatic Cancer 118 Antiproliferative Efficacy of a Focused Library of Tyrosine-Kinase Inhibitors E.Z. Szabó, R. Schwab, G. Bökönyi, F. Hollósy, F. Waczek, B. Bánhegyi, B. Hegymegi-Barakonyi, B. Németh, E. Várkondi, E. Schafer, S. Radinovic, T. Gyökeres, J. Hamvas, L. Örfi, M. Idei, G. Kéri, Á. Pap MTA-TKI Peptide Biochemistry R.G., Department of Gastroenterology, MÁV Hospital, Co-operation Research Centre, Semmelweis University, Budapest, Hungary Background: Inhibition of false proliferative signals is one of the major targets of drug development, today. Tyrosine kinase enzymes (TK) are considered among the key molecular targets in this respect. Our aim was to characterise the antiproliferative effi- cacy of a focused library of compounds with known TK inhibitory potential, that are used in Quantitative Structure Relationship (QSAR) predictive models for TK ...

Clinical Pancreatic Cancer 17 Analysis of Long Term Survival After R-0 Resection for Pancreatic and Periampullary Adenocarcinoma H.G. Smeenk 1 , T.C.K. Tran 1 , W.C.J. Hop 3 , J. Jeekel 1 , H. van Dekken 2 , C.H.J. van Eijck 1 1 Department of General Surgery, 2 Department of Pathology and 3 Department of Epidemiology & Biostatistics, Erasmus Medical Centre, Rotterdam, The Netherlands Background: Numerous clinicopathological parameters have been demonstrated to predict the prognosis in patients with pancreatic carcinoma and periampullary tumours after surgical resection. Radical (R-0) resections are difficult to achieve. Factors most predictive for survival after R-0 resection (without microscopic evidence of residual ...

Basic Pancreatic Cancer 108 Delay of Tumour Growth in Nude Mice by Expression of Suppressor Enhancer Line (SEL1L) Gene in Pancreatic Carcinoma Cell Lines A. Bonora, S. Beghelli 1 , C. Bassi, M. Cattaneo 2 , C. Sorio 1 , I. Biunno 2 , A. Scarpa 1 , P. Pederzoli Departments of Surgical Sciences and 1 Pathology, University of Verona, 2 Institute for Biomedical Technologies (National Research Council), Milan, Italy Reduction of in vitro proliferation in SEL1L cell lines treated with dexamethasone (DEX) suggested a possible role for this gene in pancreatic carcinoma. In order to further investigate the effects of SEL1L overexpression in tumour growth, SUIT-2 cell lines transfected with pDEX.1 and SEL1L-pDEX.1 construction were used. Four ...

Basic Pancreatic Cancer 93 Detection of p16 and K-ras Mutations is Useful in Pancreatic Adenocarcinoma (PA) and Chronic Pancreatitis (CP) Differential Diagnosis R. Talar-Wojnarowska 1 , A. Gasiorowska 1 , B. Smolarz 2 , H. Romanowicz-Makowska 2 , J. Strzelczyk 3 , A. Janiak 3 , E. Malecka-Panas 1 1 Department of Digestive Tract Diseases, Medical University, Lodz, 2 Laboratory of Molecular Genetics, Department of Pathology, Institute of Polish Mother’s Memorial Hospital, Lodz and 3 Department of General Surgery and Transplantology, Medical University, Lodz, Poland The purpose of the study was to compare the prevalence of p16 and K-ras mutation in PA and CP in order to evaluate their usefulness in differential ...

Progress Review Groups Pancreatic Cancer : An Agenda for Action Report of the Pancreatic Cancer Progress Review Group February 2001 Page 2 Pancreatic Cancer : An Agenda for Action Report of the Pancreatic Cancer Progress Review Group February 2001 Page 3 From the Leadership It is a great pleasure to submit this Report of the Pancreatic Cancer Progress Review Group (PRG) to the Director and Advisory Committee to the Director of the National Cancer Institute (NCI). To accelerate progress against pancreatic cancer , the Director, NCI, requested the PRG to identify scientific priorities and needs so that the Institute can forge a national agenda for research on this disease. This report is the outcome of the PRG’s 10-month effort to carry out this charge. ...

Abstract. Pancreatic cancer is a malignant tumor with an extremely poor prognosis. The mechanisms of the aggressive growth and metastasis are not yet extensively understood. Over-expression of epidermal growth factor receptor (EGFR) was suggested to be associated with malignant transformation of pancreatic cancer . We examined EGFR expression in 77 cases of invasive ductal adenocarcinoma of the pancreas, and analyzed the relation between the EGFR expression pattern and clinicopathological factors. EGFR immunoreactivity was detected in 41.6% (32/77) of human pancreatic cancers; i.e. diffuse expression in 32.5% (25/77) and focal expression in 9.1% (7/77). The EGFR expression was associated with gender (p<0.05), histological differentiation (p<0.05) and metastatic status of TNM classification (p<0.01). The observations suggested that EGFR expression plays important roles in metastasis, ...

Laparoscopic Staging for Potentially Resectable and Locally Advanced Pancreatic Cancer Richard S. Swanson, M.D. Brigham and Women’s Hospital Harvard Medical School Page 2 Pancreatic Cancer Surgeons’ Philosophy Regarding Staging Laparoscopy • Ardent Opponents: – Pisters and Evans: • Nothing beats a good CT scan – Yeo: • It does not help the Hopkins’ algorithm • Die-hard Proponents: – It is vitally important in the management of pancreatic cancer • In-between: – Use it selectively – Don’t use it but can see why others do – Use it, but beginning to question the value Page 3 Staging Laparoscopy for Pancreatic Cancer • First suggested by Bernheim – Ann Surg 53:764, 1911 • Introduced by Cuschieri et al. – Gut 19:672, 1978 ...

To Prevent and Cure Cancer T he mission of the Arizona Cancer Center’s Pancreatic Cancer Team is to prevent and cure pancreatic cancer . This disease is the fourth leading cause of death from cancer in women and men in the United States. In the Year 2000, an estimated 28,300 new cases of pancreatic cancer will be diagnosed in the U.S., with an estimated 28,200 deaths. In Arizona alone, it is estimated that 500 people will die from pancreatic cancer this year. In response to its mission, the team has launched an all-out effort to decrease the morbidity and mortality of the disease. Under the leadership of Daniel D. Von Hoff, M.D., F.A.C.P., the team is comprised of scientists with expertise in new drug development, imaging, and pathology, along with physicians who focus on pain management and other quality of life issues, ...

Abstract. The gastrointestinal peptides gastrin and cholecysto- kinin (CCK) stimulate growth of human pancreatic cancer by a receptor-mediated process. The purpose of this study was to investigate the molecular and functional characteristics of the receptor associated with peptide-induced pancreatic cancer proliferation. Utilizing total RNA from human pancreatic cancer cells a cDNA was cloned and sequenced by RT-PCR and rapid amplification of cDNA ends methodology. The molecular characteristics of the receptor cDNA were studied by Northern analysis and protein structure by Western analysis. An antibody raised against the novel receptor was utilized to investigate the role of the CCK-C receptor on pancreatic cancer cellular growth using in vitro technology. A spliced variant of the CCK-B receptor was identified which differed from the CCK-B receptor by the presence of intron 4. Northern ...

Abstract. S-1 is a newly developed oral fluoropyrimidine derivative with demonstrated activity against several tumor types. The aim of this study was to evaluate the feasibility and efficacy of S-1 administered as a single-agent and in combination with cisplatin, for the treatment of patients with pancreatic cancer . A total of 33 patients with locally advanced or recurrent pancreatic cancer were entered into this study. Seventeen patients were treated with S-1 alone (group A), and 16 patients were treated with S-1 plus weekly cisplatin (group B). Objective tumor responses among the 15 evaluable patients in group A were 1 CR, 2 PR, 9 SD and 3 PD, and among the 14 evaluable patients in group B were 8 PR, 5 SD, and 1 PD. The overall response rates were 20.0% and 57.1% in groups A and B respectively. Seven of the 17 patients in group A with elevated CA19-9 serum concentration and 12 of the 13 patients ...

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 ...

Basic: Pancreatic Cancer 93 Clusterin Expressions and Apoptosis Resistance in Pancreatic Cancer in Human H.S. Lee, C.D. Kim, S.W. Lee, J.H. Choi, H.S. Ryu, J.H. Hyun, B.H. Min 1 , I.S. Park 2 Department of Internal Medicine, 1 Department of Pharmacology, Korea University College of Medicine, Seoul, Korea 136-705; 2 Department of Anatomy Inha University College of Medicine Incheon, Korea 402-751 Pancreatic cancer is a malignancy with an extremely poor prognosis since treatment with chemotherapeutic agents and/or irradiation has shown limited success. These poor response to chemotherapy or radiotherapy is largely due to resistance against to chemother- apy induced apoptosis of pancreatic cancer cell. Clusterin is a heterodimeric glycoprotein, which has been shown to play important roles in various biologic ...

Basic: Pancreatic Cancer 92 5-Lipoxygenase and Leukotriene B 4 Receptor are Up-regulated in Human Pancreatic Cancer and Chronic Pancreatitis R. Hennig 1 , X.-Z. Ding 1 , M.B. Schneider 2 , J. Standop 2 , H. Friess 3 , M.W. Büchler 3 , P.M. Pour 2 , T.E. Adrian 1 Department of Surgery 1 , Northwestern University Medical School, Chicago, IL, USA; Eppley Cancer Institute 2 , Omaha, NE, USA and Department of Surgery 3 , University of Heidelberg, Germany Background: High dietary fat consumption is associated with an increased incidence and growth of pancreatic cancer . We have shown that the 5-lipoxygenase (5-LOX) pathway is critical for pancreatic ...

Basic: Pancreatic Cancer 132 Pain Neurotransmitter Coregulates Human Pancreatic Cancer Growth M.W. Mueller 1 , H. Friess 1 , Z. Zhu 1 , K. Lieb 2 , M. Korc 3 , A. Zimmermann 4 , M.W. Büchler 1 Department of General Surgery 1 , University of Heidelberg, Germany; Department of Psychiatry 2 , University of Freiburg, Germany; Department of Medicine 3 , University of California, Irvine, USA; Institute of Pathology 4 , University of Bern, Switzerland Background: Nerves and nerve growth-promoting factors are altered in pancreatic can- cer and a strong interaction between pancreatic cancer and nerves exists. Recent stud- ies have demonstrated that neuropeptides and their receptors, ...

Basic: Pancreatic Cancer 99 Resveratrol Inhibits Proliferation and Induces Apoptosis in Human Pancreatic Cancer Cells X.Z. Ding, T.E. Adrian GI Oncology laboratory, Department of Surgery, Northwestern University Medical School, Chicago, IL, USA Background: Because of lack of early diagnosis and poor therapeutic responsiveness, another dimension in chemotherapeutic agents for pancreatic cancer would be extremely beneficial to control metastatic and unresectable disease. Resveratrol, a nat- ural product from grapes has been shown to be chemopreventive in carcinogen-induced skin cancer and also to inhibit proliferation of oral squamous, breast, colonic and prostate cancer cells. However, its effects on pancreatic cancer have not been reported. Methods: To evaluate the potential role of resveratrol on pancreatic cancer cell prolif- eration, two human pancreatic ...

Basic: Pancreatic Cancer 129 Tumor-Selective Augmentation of Chemotherapy Efficacy and Reduction of Toxic Side Effects by Combination of 5-FU with Adeno-Associated Virus (AAV-2) Infection S. Eisold 1 , S. Dihlmann 2 , E. Ryschich 1 , J. Schmidt 1 , E. Klar 1 , M. von Knebel Doeberitz 2 Departments of Surgery 1 and Molecular Pathology 2 , University of Heidelberg, Germany Drug resistance and toxic side effects are major limiting factors in the clinical use of anti- neoplastic chemotherapy. Due to these limitations do patients with pancreatic cancer in general not benefit from chemotherapy. The non-pathogenic adeno-associated virus type 2 (AAV-2) sensitizes human tumor cells to gamma irradiation and chemotherapeutic drugs in ...

Basic: Pancreatic Cancer 123 Expression of ADAM Molecules in Human Pancreatic Cancer Cells – Cell Cycle-Dependent Expression of ADAM9 J. Ringel 1,2 , R. Jesenofsky 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 Dept. of Biochemistry and Eppley Institute for Research in Cancer , UNMC, Omaha, NE, USA Background: ADAM (A Disintegrin And Metalloprotease) molecules are increasingly known for their unique potential to combine adhesion, proteolytic, and signaling func- tions. In addition, findings postulate a link between ADAM molecules (ADAM9; ADAM17) and cell cycle processes. Recently, we reported an aberrant and cell cycle- ...

Basic: Pancreatic Cancer 72 Human Pancreatic Renin-Angiotensin System: Its Expression and Regulation in Pancreatic Endocrine Tumour P.S. Leung 1 , K.Y. Lam 2 1 Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong and 2 Department of Pathology, School of Medicine, James Cook University, Queensland, Australia Background: Evidence for the presence of an intrinsic renin-angiotensin system (RAS) has been reported in the pancreas, which plays a role in the regulation of endocrine and exocrine functions of the pancreas. The objective of the present study is to prove the presence of an intrinsic RAS in human pancreas and to analyse the role of such RAS in pancreatic endocrine tumour (PET). Methods: Gene expression of key RAS components (angiotensinogen and angiotensin ...

Basic: Pancreatic Cancer 75 Do We Need to Inhibit Human Macrophage Metalloelastase in Pancreatic Cancer ? P. Balaz 1 , H. Friess 2 , M.W. Büchler 2 1 Department of General Surgery, Hospital Bulovka, Charles University of Prague, Czech Republic, 2 Department of Visceral and Transplantations Surgery, Inselspital, University of Berne, Switzerland Background: Human macrophage metalloelastase (HME), a member of the human matrix metalloproteinase family is expressed in macrophages, fetal chondrocytes and in certain cancer cells. HME possesses broad substrate of elastolytic activity and has a cru- cial role in the degradation of the extracellular matrix proteins. Thus, HME is involved in biological processes associated with tissue remodeling, such as vascular injury, ath- erosclerosis, angiogenesis, ...

Basic: Pancreatic Cancer 98 Biphasic Effect of 15-deoxy 12,14 -prostaglandin J2 (PGJ2) on Proliferation of Pancreatic Cancer Cells X.Z. Ding, R. Hennig, X.Q. Li, T.E. Adrian GI Oncology laboratory, Department of Surgery, Northwestern University Medical School, Chicago, IL, USA Background: Previous reports have demonstrated anti-proliferative and apoptosis- inducing effects of 15-deoxy 12,14 -prostaglandin J2 (PGJ2) on certain human cancer cell lines. It is generally believed that these biological activity of PGJ2 is dependent upon its PPAR (peroxisome proliferator-activated receptor) agonist activity. However, its direct effects on human pancreatic cancer cells are not clear. Methods: Two human pancreatic cancer cell lines, PANC-1 and MiPaCa2 were used. Cell proliferation was determined by thymidine incorporation. Apoptosis ...

Basic: Pancreatic Cancer 103 Laser-Capture Microdissection (LCM) and Quantitative RT-PCR Analysis of the Expression of Neurotrophins and their Receptors in Pancreatic Cancer Reveals Potential Paracrine and Autocrine Functions K. Ketterer 1 , H. Friess 2 , M.W. Büchler 2 , M. Korc 1 1 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Biological Chemistry and Pharmacology, University of California, Irvine, CA, USA; 2 Department of General Surgery, University of Heidelberg, Germany Background: Neurotrophins (NTs) can stimulate cell proliferation and differentiation in various cell types and have been shown to play a role in certain human cancers. Using northern blot analysis and in situ hybridization, we have previously reported that NGF and its receptor ...

Basic: Pancreatic Cancer 71 Functional Characterization of Claudin-4 in Pancreatic Cancer Cells C. Barth 1 , P. Michl 1 , M. Buchholz 1 , M. Rolke 1 , M. Löhr 2 , G. Adler 1 , T.M. Gress 1 1 Department of Internal Medicine I, University Medical Center, University of Ulm, Robert-Koch-Str.8, 89081 Ulm, 2 Department of Medicine IV, Medical Faculty Mannheim, University of Heidelberg, Germany Background: Claudin-4, a member of the claudin-multigene family and constituent of tight junctions, has been described as a receptor for the cytotoxic Clostridium perfrin- gens enterotoxin (CPE). Previously, we found claudin-4 to be overexpressed in pancre- atic cancer and described an acute dose-dependent cytotoxic effect of CPE on ...

Clinical: Pancreatic Cancer 256 Incidence of Pancreatic and Extra- Pancreatic Cancers in the Families of Patients with Pancreatic Adenocarcinoma: Results of Prospective Survey A.M.M. Audibert, P. Rufat, F. Maire, D. O’Toole, P. Hammel, O. Hentic, P. Lévy, P.R. Philippe Fédération Médico-Chirurgicale d’Hépato-Gastroentérologie, Hôpital Beaujon, Clichy, 92118, France The incidence of pancreatic adenocarcinoma in on the increase in industrialised coun- tries. The prognosis remains very poor as approximately only 3% of patients are alive at 5 years. The cause of such cancer is still unknown. Few studies have addressed the possibility of familial transmission in pancreatic adenocarcinoma. Aim: To investigate the possibility of familial transmission of pancreatic cancer , as sug- gested in the rare reported series, and also to explore the potential association ...

Clinical: Pancreatic Cancer 273 PPAR Agonist may be Valuable for the Treatment of Pancreatic Cancer R. Hennig 1 , X.-Z. Ding 1 , H. Friess 2 , M.W. Büchler 2 , T.E. Adrian 1 Departments of Surgery 1 , Northwestern University School of Medicine, Chicago, Il, USA and University of Heidelberg 2 , Heidelberg, Germany Background: Previous studies have shown that activation of the peroxisome prolifera- tor-activated receptor gamma (PPAR ) inhibits pancreatic cancer cell proliferation and causes apoptosis. Furthermore, PPAR is up-regulated in pancreatic carcinoma cells, based on immunohistochemically results. Because of our research in the field of 5-lipoxygenase (5-LOX) and pancreatic cancer as well as the recently published connec- tions between ...

Basic: Pancreatic Cancer 82 Lack of Heparan Sulfate Deposition in the Extracellular Matrix and Basement Membrane Correlates with Heparanase-1 Expression in Pancreatic Cancer R.M. Quiros 1 , A.W. Kim 1 , E.F. Hollinger 1 , P. Gattuso 2 , R.A. Prinz 1 , X. Xu 1 Departments of 1 General Surgery and 2 Pathology Rush Presbyterian-St. Luke’s Medical Center, Chicago, IL 60612, USA Background: Heparanase-1 (HPR1) is an endoglycosidase that degrades the side chains of heparan sulfate proteoglycan (HSPG), a main component of the extracellular matrix (ECM) and basement membrane (BM). HPR1 is not expressed in normal epithelial cells but can be detected in some gastrointestinal malignancies, including oral, esophageal, and colon cancers. ...