AllDocs -> cancers

O1 PANCREATIC CANCER . BASIC AND CLINICAL ASPECTS 4 Real-time Quantitative PCR of Telomerase mRNA is Useful for the Differentiation of Benign and Malignant Pancreatic Disorders P. Büchler 1,2 , H. Friess 3 , M.C. Büchler 2 , O.J. Hines 2 , H.G. Beger 1 , J.R. Conejo Garcia 3 , H.A. Reber 2 , M.W. Büchler 3 Departments of Surgery, University of Ulm 1 , Germany, Los Angeles 2 , California, Bern 3 , Inselspital, Switzerland Background: The ends of chromosomes are normally capped with telomeres, which are synthesized by the ribonucleoprotein telomerase and necessary for proper DNA replication. The presence of telomerase activity in pancreatic cancer (PaCa) has been reported in up to ...

O2 GENE THERAPY 7 Enzyme-Activation Prodrug/Suicide Gene Therapy of Pancreatic Cancer using the Bacterial Purine Nucleoside Phosphorylase S. Deharvangt, A. Hajri, S. Wack, M. Aprahamian IRCAD, Laboratoire de biologie des tumeurs et de thérapie génique 1, Place de l’hôpital BP426, 67091 Strasbourg, Cedex, France Pancreatic cancer is still a disease with an extremely poor prognosis even when surgical treatment can be accomplished. Gene therapy has been suggested as a novel approach for pancreatic cancer management. The enzyme-prodrug/gene suicide strategy has gained considerable importance in clinical medicine. A major challenge in cancer gene therapy is the development of efficient system to induce tumor cell killing with a pronounced bystander effect in the in vivo use perspective. In the present work, we have constructed a recombinant vector expressing the ...

O1 PANCREATIC CANCER . BASIC AND CLINICAL ASPECTS 6 Subcellular Redistribution and Upregulation of the Cell-Adhesion Protein p120 ctn in Pancreatic Cancer J. Mayerle, H. Friess, M.W. Büchler, J. Schnekenburger, M.M. Lerch Department of Medicine B, Universität Münster, Germany and Department of Visceral Surgery, Inselspital, Universität Bern, Switzerland p120 ctn is a recently detected member of the Cadherin/Catenin family of cell adhesion proteins which mediate cell–cell contact formation. The maintenance of intact cell–cell contacts within a tumour, however, prevents the dissemination of malignant cells and several adhesion proteins are therefore now regarded as tumour suppressors. Here we have studied the role of p120 ctn in human pancreatic cancer . Snap-frozen pancreatic tissue samples from 32 patients ...

P2 CANCER . BASIC ASPECTS 70 Screening Pancreatic Juice for p53 Mutations using a Yeast Functional Assay J. Threadgold 1 , N. Howes 1 , I. Ellis 2 , I. Gilmore 1 , H. Smart 1 , M. Lombard 1 , W. Greenhalf 1 , J.P. Neoptolemos 1 Dept of Surgery 1 , University of Liverpool, UK, Dept of Clinical Genetics 2 , Alder Hey Children’s Hospital, Liverpool, UK Pancreatic cancer only represents 2–3% of total cancer cases, yet is the 4th biggest cancer killer. Pancreatic Ductal Adenocarcinoma (PDAC) is characterised by rapid metastasis and high mortality. Early surgery dramatically increases survival, however current diagnostic techniques cannot identify resectable PDAC against a background of chronic pancreatitis. ...

P2 CANCER . BASIC ASPECTS 62 Galectins are Dysregulated in Human Pancreatic Cancer A. Tempia-Caliera, H. Friess, P.O. Berberat, L. Wang, Z.W. Zhu, T. Bley, L. Frigeri*, A. Zimmermann**, M.W. Büchler Department of Visceral and Transplantation Surgery and Institute of Pathology**, University of Bern, Switzerland, The Scripps Research Institute*, La Jolla, California, USA Background: Galectins – a family of galactosidase-binding proteins – are a potentially new group of pro-metastatic genes. Galectin-1 and -3 were proposed to stimulate tumor growth and to promote cell transformation to a metastatic phenotype in several gastro- intestinal tumors. This study analyzed the expression pattern of these two members of the galectin family in pancreatic cancer , and correlates the molecular findings with the clinicopathological patient data. Patients and Methods: Galectin-1 and ...

P2 CANCER . BASIC ASPECTS 76 Metastasis-Associated Genes are Differentially Expressed in Pancreatic and Papilla of Vater Cancer and Correlate with Prognosis H. Friess, X.-Z. Guo, A.A. Tempia-Caliera, A. Zimmermann*, M.W. Büchler Department of Visceral and Transplantation Surgery, and Institute of Pathology*, University of Bern, Inselspital, Bern, Switzerland Papilla of Vater cancer has a much better prognosis than pancreatic cancer . However, it is not known whether this is due to differences in the tumor biology of the two malignancies. Since metastasis formation is a critical step in tumor progression and a negative prognostic factor, we compared the expression of two metastasis-suppressing genes (nm23-H1, KAI1) in papilla of Vater cancer and pancreatic cancer . Analysis was carried out in 9 normal and 27 papilla of Vater cancer samples and in 16 normal and 29 pancreatic ...

O1 PANCREATIC CANCER . BASIC AND CLINICAL ASPECTS 5 Aberrant Expression and Cell Cycle-Dependent Regulation of ADAM17/TACE in Pancreatic Cancer J. Ringel 1,2 , N. Moniaux 1 , M. Andrianifahanana 1 , G. Faulmann 2 , A. Choudhury 1 , M. Löhr 2 , S.K. Batra 1 Dept. of Biochemistry 1 , UNMC, Omaha, NE, USA, Dept. of Medicine IV 2 , University of Heidelberg at Mannheim, Germany Introduction: The ADAM (A Disintegrin And Metalloprotease) molecules are known for their potential to combine adhesion, proteolytic, and signaling functions. Recent findings postulate a link between ADAM molecules and cell cycle processes. Here we investigated the expression, function, and regulation of the tumor necrosis factor (TNF- ...

P2 CANCER . BASIC ASPECTS 75 Lysozyme Expression in Pancreatic Cancer – An Independent Prognostic Factor M. Ramadani, S. Gansauge, Z. Stankovic, F. Gansauge, H.G. Beger Department of General Surgery, University of Ulm, Germany Lysozyme expression constitutes one of the unspecific defence mechanisms in the gastrointestinal tract. Its broad spectrum of antibacterial activities is well documentated. To investigate the expression and distribution of lysozyme in pancreatic cancer we performed immunohistochemistry in 70 pancreatic cancer tissues and 6 normal pancreas. Western blot analysis was used to confirm immunohistochemical findings. Flourescence immunohistochemistry was used to detect lysozyme binding to the extra- cellular matrix. Serum lysozyme and TNF- levels were determined by ELISA in 40 pancreatic cancer patients and 33 age-matched healthy controls. Lysozyme serum ...

O8 PANCREATIC CANCER . FURTHER BASIC ASPECTS 29 Ectopic Cytoplasmic Expression of -Catenin Correlates with Cyclin D1 Overexpression in Pancreatic Cancer M. Ramadani, Q. Qiao, F. Gansauge, S. Gansauge, G. Leder and H.G. Beger Department of General Surgery, University of Ulm, Germany -catenin is a component of the E-cadherin–catenin cell adhesion complex. It plays also a role in the intracellular signalling and can function as an oncogene when it binds to the T cell factor 4 (Tcf4)-binding site in the promoter region of cyclin D1 and transactivates genes after translocation to the nucleus. We evaluated the expression of -catenin in relationship with cyclin D1 overexpression, tumor grade, clinicopathological parameters and patients’survival in 43 adenocarcinomas of the pancreas and in 5 normal pancreatic tissues by immunohistochemistry. We could show that, both, ...

O8 PANCREATIC CANCER . FURTHER BASIC ASPECTS 28 Differential Gene Expression Underlying the Inhibition of Cell Proliferation by Cholecystokinin-A Receptors in Human Pancreatic Cancer Cells G. Rácz 1 , C. Wenger 2 , B. Burghardt 1 , K. Barabás 1 , C.D. Logsdon 3 , T.M. Gress 2 and G. Varga 1 Institute of Experimental Medicine 1 , Hung. Acad. Sci., Budapest, Hungary, Universitätsklinikum Ulm 2 , Ulm, Germany, University of Michigan 3 , Ann Arbor, Michigan, USA Background: G-protein coupled receptors have been shown to be involved in the regulation of cell proliferation of cancer cells. Detjen et al. ( Gastroenterology 112:952–959) demonstrated that transfected cholecystokinin (CCK) receptors ...

© 2001 S. Karger AG, Basel Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com 33rd European Pancreatic Club (EPC) Meeting Toulouse, France, June 13–16, 2001 Pancreatology 2001;1:129–199 O1 PANCREATIC CANCER . BASIC AND CLINICAL ASPECTS 1 CD44v10 Favors Fibronectin Adhesion and Characterizes Metastatic Pancreatic Cancer Cell Lines F. Navaglia, A.L. Stefani, M.G. Piva, P. Fogar*, E. Greco, D. Basso, N. Gallo, M. Plebani, S. Pedrazzoli* Departments of Laboratory Medicine and Medical and Surgical Science*, Padova University-Hospital, Italy Introduction: CD44 variants seem implicated in favouring metastasis. Our aims were to verify: (1) the mRNA pattern of CD44 variants in 3 primary (MIAPaCa2, PANC1, PSK1) and in 2 metastatic (CAPAN1, SUIT2) pancreatic cancer (PC) cell lines; (2) whether adhesion to hyaluronic acid (HA), ...

P2 CANCER . BASIC ASPECTS 79 A 2030 D Peptide as the Putative Pancreatic Cancer -Associated Diabetogenic Factor S. Mazza, D. Basso, A. Valerio 1 , R. Seraglia 3 , E. Greco, C.F. Zambo, N. Gallo, P. Fogar 2 , S. Pedrazzoli 2 , A. Tiengo 2 , M. Pleban Dept. of Laboratory Medicine, Clinical and Experimental Medicine 1 , and Medical and Surgical Sciences 2 , University of Padova, Research National Council 3 , Research Area, Italy Introduction: Aims were to verify: (1) whether entire and mw fractioned cell culture media conditioned (CM) by pancreatic cancer (PC) cell lines are able to alter glucose metabolism of isolated and perfused rat hepatocytes (IPRH); (2) the molecular compo- sition of control (NCM) and CM by mass spectrometry analysis ...

O3 GENETICS AND PANCREAS 12 VEGF Production in Pancreatic Cancer is Controlled by Hypoxia Inducible Factor (HIF-1) P. Büchler 1,2 , H. Friess 3 , M.C. Büchler 2 , O.J. Hines 2 , H.G. Beger 1 , M.W. Büchler 3 , H.A. Reber 2 Departments of Surgery, University of Ulm 1 , Germany, Los Angeles 2 , California, Bern 3 , Inselspital, Switzerland Background: Tumor hypoxia stimulates angiogenesis which is important in local and metastatic tumor growth. The factors which influence this process in pancreatic cancer , a highly aggressive and malignant tumor, are not known. A recently described transcription factor, hypoxia inducible factor-1 (HIF-1), appears to regulate vascular endothelial growth factor (VEGF), the key ...

P2 CANCER . BASIC ASPECTS 65 NSC-631570 Induces Apoptosis in Pancreatic Cancer Cells – An Old Highly Potent Drug against Pancreatic Cancer M. Ramadani, S. Gansauge, B. Muehling, H.G. Beger, F. Gansauge Department of General Surgery, University of Ulm, Germany Several plant-derived drugs are used in medical oncology. NSC-631570 is a semi- synthetic thiophosphoric acid compound of the alkaloid chelidonine from the plant chelidonium majus. To examine the cytostatic potential of NSC-631570 the tumor cell lines AsPC1, BxPC3, Mia PaCa 2, Jurkat and THP-1 were incubated with increasing concentrations of NSC-631570 (1 g/mL, 10 g/mL and 100 g/mL). The proliferation rate was measured by BrdU-Assay and cell cycle analysis was performed by propidium iodide staining and FACS analysis. To subspecify the mitose phases cells were stained by Giemsa. Under different culture conditions the ...

Pancreatic Cancer in the Greater Bay Area, 1988-1997 Pancreatic cancer is among the most common causes of cancer death in the United States. In the Greater Bay Area, almost 5,800 people were diagnosed with the disease during the period 1988-1997. Males had slightly higher incidence rates of pancreatic cancer compared to females (data not shown). In the San Fran- cisco Region, there was a decrease in pancreatic cancer rates from 1988 to 1997 (Figure 1, above), while in the Santa Clara Region, rates were unchanged. In the San Francisco Region, the average annual age-adjusted incidence rate of pancreatic cancer (males and females combined) was 8.5 cases per 100,000 in the period 1993-1997; the rate was not substantially different for the Santa Clara Region (8.4 per 100,000). Pancreatic cancer is a disease of advancing age. Incidence rates rose steadily after age 35 (Figure 2, above). Figure 1. ...

P5 CANCER . CLINICAL ASPECTS 123 Mass-Forming Pancreatitis (MFP) and Pancreatic Cancer (PC): A Diagnostic Problem L. Frulloni, C. Liani, P. Bovo, B. Vaona, B. Calore, A. Cantone, R. Turrini, G. Gasparini, S. Carrara, G. Cavallini Dept of Surgical and Gastroenterological Sciences, University of Verona, Verona, Italy Background: We postulated an immune-mediated pathogenesis for chronic pancreatitis. Among autoimmune pancreatitis, MFP is an inflammatory process that involves only partially the pancreas and may be confused by mistake with PC. Aim: of this work is to identify the clinical and radiological characteristics helpful to differentiate MFP from PC at the onset of the disease. Materials and Methods: We studied consecutively 10 patients suffering from MFP (8 males, 2 females, mean age 41.5 years, range 17–63) and 11 from PC (10 males, 1 female; mean age 61, ...

Identification of Genes With Specific Expression in Pancreatic Cancer by cDNA Representational Difference Analysis Thomas M. Gress, 1 Christine Wallrapp, 1 Marcus Frohme, 3 Friederike Müller-Pillasch, 1 Ulrike Lacher, 1 Helmut Friess, 2 Markus Büchler, 2 Guido Adler, 1 and Jörg D. Hoheisel 3 * 1 Department of Internal Medicine I, University of Ulm, Ulm, Germany 2 Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Bern, Switzerland 3 Molecular-Genetic Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany cDNA representational difference analysis (cDNA-RDA) is a polymerase-chain-reaction-coupled subtractive and kinetic enrichment procedure for the isolation ...

JOP - Journal of the Pancreas 2000; 1(4): 183-190. JOP – Journal Of the Pancreas www.joplink.net Vol.1, No. 4 November 2000 183 Subcutaneously Inoculated Cells and Implanted Pancreatic Cancer Tissue Show Different Patterns of Metastases in Syrian Golden Hamsters Cintia Yoko Morioka 1 , Seiji Saito 1 , Kouji Ohzawa 1 , Shinji Asano 2 , Yasuhide Hibino 3 , Yuji Nakada 1 , Kei-ichiro Kita 1 , Akiharu Watanabe 1 1 Third Department of Internal Medicine, 2 Molecular Genetics Research Center, and 3 First Department of Biochemistry, Toyama Medical and Pharmaceutical University. Toyama, Japan ABSTRACT Context We studied behavior of the subcutaneously implanted pancreatic tumors ...

September/October 2000, Vol.7, No.5 428 Cancer Control Treatment of Resectable and Locally Advanced Pancreatic Cancer Boris W.Kuvshinoff, MD, and Mark P.Bryer, MD Background: Pancreatic cancer is the fifth leading cause of cancer death in the United States, with an overall 5-year survival rate of less than 5%. A minority of patients are candidates for surgical resection, but most treatment strategies focus on palliative care. Methods: We discuss strategies in the diagnosis and treatment of resectable and locally advanced pancreatic cancer by reviewing available phase II and phase III trials, as well as large retrospective studies. Results: Surgical resection for pancreatic cancer is done today with an operative mortality rate below 5% and a 5-year survival rate of approximately 25%. There is evidence that chemoradiation may improve survival and quality of life ...

Endoscopic Ultrasound in the Clinical Staging and Management of Pancreatic Cancer : Its Impact on Cost of Treatment Mark E.Powis, MD, and Kenneth J.Chang, MD Background: Surgical resection for pancreatic cancer carries a 5% 5-year survival rate. Most conventional methods of imaging do not detect small pancreatic tumors and do not accurately stage pancreatic neoplasms. There is a significant impact on medical resources despite the relatively small number of patients affected. For these reasons, careful selection of patients for surgical resection is necessary. Methods: Endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) have been developed to overcome limitations of conventional staging. We address the issues of how EUS may provide cost-effective treatment in the patient with pancreatic cancer . Results: EUS produces high-resolution images of the pancreas, which can ...

Molecular Prognostic Markers in Pancreatic Cancer Domenico Coppola, MD Background: Pancreatic cancer is one of the most aggressive human tumors and is virtually incurable. Its incidence in the United States has tripled in the past 50 years. The tumor is a frequent cause of cancer death in both men and women. The current treatment options are inadequate and probably reflect the fact that the etiologic factors and the pathogenesis of pancreatic cancer are unknown. Methods: The author reviewed recent studies describing some of the molecular alterations that may play a role in pancreatic carcinogenesis. Results: Most pancreatic tumors arise in the ductal epithelium. Cytogenetic abnormalities and alterations in proliferation, oncogenes and tumor suppressor genes, cell receptors, and growth factors are described. Conclusions: Preliminary studies have implicated, among others, ...

New Directions in Systemic Therapy of Pancreatic Cancer Alexander S.Rosemurgy, MD, and Francesco M.Serafini, MD Background: The aggressiveness of pancreatic adenocarcinoma makes it a deadly disease, with its incidence rate and fatality rate almost equal. Surgery represents the only means to provide cure to patients with pancreatic cancer , though the 5-year survival is less than 10%. Methods: We review the data on surgical and systemic therapies and provide more details on a newer biologically based medical approach. Results: Neoadjuvant chemotherapy protocols are confined to one or two institutions, and adjuvant chemotherapy and chemoradiation therapy protocols are far from being standardized. Chemoradiation therapy for locally advanced pancreatic cancer offers limited benefits. Protocols that include gemcitabine and 5-fluorouracil, while comparing favorably to historical ...

September/October 2000, Vol.7, No.5 452 Cancer Control Endoscopic Palliation for Inoperable Pancreatic Cancer Ananya Das, MD, and Michael V.Sivak, Jr, MD Background: The majority of patients with pancreatic cancer are not candidates for surgical resection. Palliative therapy remains the cornerstone of management of this population. Methods: We reviewed recent clinical and experimental studies on endoscopic palliative therapy of inoperable pancreatic cancer . Results: Endoscopic placement of a biliary stent is the preferred mode of palliation of obstructive jaundice in patients with pancreatic cancer . The techniques of endoscopic stent insertion are briefly described. Episodic recurrence of jaundice and cholangitis due to stent occlusion is a major drawback of biliary polyethylene stents. Self-expandable metal stents with large diameters have lower rates of stent ...

New pancreatic cancer gene identified Investigators have discovered a gene whose inactivation appears to contribute to the deadly transformation of pancreatic cells into cancer cells. Cancer of the pancreas ranks as the fifth deadliest cancer in the United States, killing more than 25,000 people a year. The newfound gene probably plays a role in about half of those deaths, says Scott E. Kern of Johns Hopkins University Medical Institutions in Baltimore. Although genes on other chromosomes have been linked to pancreatic cancer , investigators suspected that a gene on chromosome 18 was also involved: In about 90 percent of cases, pan- creatic tumor cells lack part of one of the cell’s two copies of that chromosome. “Chromosome 18 stood out as an unexplained and important player,” says Kern. To narrow the region in which a cancer gene might exist, the investigators began to deter- mine the parts of chromosome ...

A BASIC INFORMATION DESCRIPTION Uncontrolled growth of malignant cells in the pancreas. This is the 4th leading cause of cancer deaths in the U.S. The pancreas is an organ in the upper mid-abdomen that produces intestinal enzymes to help digest food and insulin to control blood sugar. Pancreas cancer affects adults ages 35-70 and men more often than women. FREQUENT SIGNS AND SYMPTOMS • Rapid, unexplained weight loss. • Pain in the back or upper abdomen that is often relieved by bending forward. • Blood clots in veins anywhere, especially the arms and legs. This is often an early sign. • Jaundice (yellow skin and eyes) from blockage of the nearby bile duct. Jaundice is usually accompanied by intense itching. • Depression. CAUSES Unknown. RISK INCREASES WITH • Chronic pancreatitis. • Diabetes mellitus. • Genetic factors: This is more ...

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Pancreatic Cancer Research at Garvan Pancreatic cancer (PC) is the fourth leading cause of cancer death in men and women in western societies including NSW, with a 5-year survival rate of less than 5% 1 . The latest Cancer Institute NSW statistics (2003) report that 580 people died of PC in NSW that year, compared to 896 dying of breast, 923 men of prostate, 1,072 of colon and 2,229 of lung cancer . The second leading group of cancer deaths is those with an unknown primary cancer site (1,256). Due to its inherent clinical characteristics, PC is likely to contribute a significantly greater proportion to these deaths than other cancers, hence the true proportion of deaths due to PC is likely to be underestimated. PC presents at an advanced stage, and as a result, only 10-20% of patients are suitable for surgical treatment at the time of presentation 1 . Chemotherapeutic agents ...