AllDocs -> cancers

First American Gains Therapeutic Benefit From REXIN-G TM , The Leading Tumor- targeted Gene Therapy Vector For Pancreatic Cancer LOS ANGELES, California, May 11, 2004 - Epeius Biotechnologies Corporation ( www.epeiusbiotech.com ), today announced that the first American with advanced pancreatic cancer has responded favorably to Rexin-G TM , the leading tumor-targeted injectable gene therapy vector. While Epeius Biotechnologies Corporation has recently gained FDA approval to open Phase I/II clinical trials in the United States, the first American patient opted to travel to Manila, Philippines, to receive the gene therapy intervention there, where the first clinical studies using Rexin-G TM for pancreatic cancer were conducted. Over a one-month period, Rexin-G TM induced a progressive reduction in the size of his pancreatic ...

Abstract. The protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved and activated by trypsin and tryptase. The purpose of this study was to clarify the role of PAR-2 in proliferation of human pancreatic cancer cells. PAR-2 mRNA and protein expression were detected by RT-PCR and Western blotting in three cell lines, SW1990, Capan-2, and Panc-1. The PAR-2 agonist peptide, SLIGKV (25, 50 µ g/ml) and trypsin (10, 100 ng/ml) significantly increased cell proliferation. Enhancement of MAP kinase also was observed in cancer cells treated with SLIGKV and trypsin. In vivo , subcutaneous xenografted tumors showed significantly enhanced growth after treatment with SLIGKV. Tumor-associated trypsinogen (TAT) mRNA and protein expression was detected in SW1990 and Capan-2, suggesting autocrine trypsin production. PAR-2 activated by trypsin plays an important role in promoting ...

Abstract. Mitogen-activated protein kinase kinase 2 (MEK2) was detected as an invasion-metastasis related factor between highly invasive (PC-1.0) and weakly invasive (PC-1) pancreatic cancer cell lines in our previous study. On the other hand, tight junction (TJ) was found to be correlated with carcino- genesis and tumor development. In this study, the expressions and correlation of TJ transmembrane protein occludin and MEK/extracellular signal-regulated kinase (ERK) signaling pathway were analyzed to clarify the regulatory mechanism of cell dissociation in pancreatic cancer cells. Two hamster (PC-1.0 and PC-1) and human (AsPC-1 and CAPAN-2) pancreatic cancer cell lines were analyzed immunocyto- chemically with anti-occludin, phosphorylated MEK1/2 (p- MEK1/2), phosphorylated ERK1/2 (p-ERK1/2) antibodies. MEK1/2 inhibitor U0126 significantly induced the expression of occludin at the cell-cell ...

182 Cryptosporidiosis of the biliary tract mimicking pancreatic cancer in an AIDS patient Criptosporidiose do trato biliar simulando câncer do pâncreas em paciente com AIDS Lenice do Rosário de Souza 1 , Maria Aparecida M. Rodrigues 1 , José Morceli 1 Raphael Kemp and Rinaldo Poncio Mendes 1 ABSTRACT Diarrhea caused by Cryptosporidium sp is frequent in patients with AIDS, but involvement of other organs of the digestive tract is uncommon. We report a case of Cryptosporidium -associated obstruction of the biliary tract mimicking cancer of the head of the pancreas in a 43-year-old woman with AIDS. Key-words: Cryptosporidiosis. AIDS. Biliary tract. Pancreatitis. RESUMO A diarréia causada pelo Cryptosporidium sp é muito freqüente em pacientes com aids, mas o envolvimento de outros órgãos ...

Bax -Induction Gene Therapy of Pancreatic Cancer Elissa C. Pirocanac, B.S.,* Rounak Nassirpour, M.S.,* Meng Yang, M.D., Ph.D.,* , † Jinwei Wang, M.D.,† Stephanie R. Nardin, B.S.,‡ Jian Gu, M.D.,‡ Bingliang Fang, M.D.,‡ A. R. Moossa, M.D.,* Robert M. Hoffman, Ph.D.,* , † and Michael Bouvet, M.D.* * Department of Surgery, University of California at San Diego, San Diego, California 92161; † AntiCancer, Inc., San Diego, California 92111; and ‡ Department of Cardiovascular and Thoracic Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 Submitted for publication January 22, 2002; published online July 19, 2002 Background. Bax is a strong pro-apoptotic gene that induces programmed cell death when ex- pressed. Human telomerase reverse transcriptase (hTERT) is the catalytic subunit for telomerase, an enzyme found to be active ...

PO Box 2345, Beijing 100023, China World J Gastroenterol 2004;10(6):860-863 Fax: +86-10-85381893 World Journal of Gastroenterology E-mail: wjg@wjgnet.com www.wjgnet.com Copyright © 2004 by The WJG Press ISSN 1007-9327 • BASIC RESEARCH • Effects of daidzein on estrogen-receptor-positive and negative pancreatic cancer cells in vitro Jun-Ming Guo, Bing-Xiu Xiao, De-Jian Dai, Qiong Liu, Hong-Hui Ma Jun-Ming Guo, Bing-Xiu Xiao, Qiong Liu , School of Medicine, Ningbo University, Ningbo 315211, Zhejiang Province, China De-Jian Dai, Second Affiliated Hospital of Medical College, Zhejiang University, Huangzhou 310009, Zhejiang Province, China Hong-Hui Ma , School of Life Science and Bioengineering, Ningbo University, Ningbo 315211, Zhejiang Province, China Supported by Scientific Research Fund of Zhejiang Provincial Education Department, No.20010217 ...

Schwarz, Roderich E. “Targeting TGFbeta in Pancreatic Cancer ” [We plan to test a new and unique approach to treatment of pancreatic cancer by blocking the receptor activity of TGFß, which in several different ways helps the cancer cells to grow.] Pancreatic cancer is the fourth-leading cause of cancer death for both men and women, and only 4% of people affected with it do survive 5 years. Pancreatic cancers have a high rate of genetic changes that affect the function of transforming growth factor beta (TGFß); TGFß is the main downregulator of cell growth in gland-like or duct-lining cells, from which pancreatic cancer cells are derived. The majority of these cancer cells lack one or more proteins which mediate the TGFß signal within the cell, so that its break-like effect on cell growth is lost. In addition, more than half of pancreatic cancer cells produce abnormal amounts ...

Palliative Care in Pancreatic Cancer Frank J. Brescia, MD, MA, FACP Background: Pancreatic cancer is a formidable health problem, representing the 10th most common malignancy in the United States and the 4th most common cause of all cancer deaths. The overall 5-year survival rate is 4%, making this disease a model tumor in which to address the specialized care issues of palliative medicine. Methods: General considerations in both medical decision-making and symptom management are reviewed. Treatment of patients with locally unresectable, recurrent, or metastatic disease is individualized, based on considerations that include patient age, patient wishes, family influence, insurance constraints, and geographic practice variations. Results: Success in managing progressive symptoms is needed to palliate patients with advanced pancreatic cancer . Common problems include biliary obstruction, ...

January/February 2004, Vol. 11, No. 1 50 Cancer Control Krzyzanowska MK, Weeks JC, Earle CC. Treatment of locally advanced pancreatic cancer in the real world: population-based practices and effective- ness. J Clin Oncol . 2003;21:3409-3414. This analysis supports the effectiveness of cancer - directed treatment in elderly patients with locally advanced pancreatic cancer , but use is low. Receipt of treatment is strongly correlated with non-disease–related factors, especially sociodemographic characteristics, indi- cating possible disparities in access to care. Moore MJ, Hamm J, Dancey J, et al. Comparison of gemcitabine versus the matrix metalloproteinase inhibitor BAY 12-9566 in patients with advanced or metastatic adenocarcinoma of the pancreas: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol . 2003;21: ...

Applications of Endoscopic Ultrasonography in Pancreatic Cancer Shyam Varadarajulu, MD, and Michael B. Wallace, MD, MPH Background: Accurate staging of pancreatic cancer is essential for surgical planning and for identification of locally advanced and metastatic disease that is incurable by surgery. Advances in endoscopic sonography (EUS), computed tomography (CT), and positron emission tomography have improved the accuracy of staging and reduced the number of incomplete surgical resections. Tissue acquisition is necessary in nonsurgical cases when chemoradiotherapy is considered. The complex regional anatomy of the pancreas makes cytologic diagnosis of malignancy at this region difficult without exploratory surgery. Although CT-guided fine-needle aspiration (FNA) is used for this purpose, reports of an increased risk of peritoneal dissemination of cancer cells and a false-negative ...

Surgical Management of Early-Stage Pancreatic Cancer Emmanuel E. Zervos, MD, Alexander S. Rosemurgy, MD, Osama Al-Saif, MD, and Alan J. Durkin, MD Background: Pancreatic cancer remains a difficult disease to treat. Diagnosis at an early stage may allow curative treatment with resection. In the past, the mortality associated with surgical treatment of pancreatic carcinoma was prohibitive but mortality associated with resection is now commensurate with all other major oncologic resections. Thus, the focus of surgical management has shifted to address several issues: the diagnosis and evaluation of patients with suspected pancreatic cancer , the role of preoperative endobiliary stenting, the role of laparoscopy, the extent of resection, the role of adjuvant and neoadjuvant treatment, and the role of specialized centers in treating the disease. Methods: The current literature is reviewed ...

P.O.Box 2345, Beijing 100023,China World J Gastroenterol 2004;10(1):105-111 Fax: +86-10-85381893 World Journal of Gastroenterology E-mail: wjg@wjgnet.com www.wjgnet.com Copyright © 2004 by The WJG Press ISSN 1007-9327 • BASIC RESEARCH • Red oil A5 inhibits proliferation and induces apoptosis in pancreatic cancer cells Mi-Lian Dong, Xian-Zhong Ding, Thomas E. Adrian Mi-Lian Dong, Affiliated Taizhou Hospital, Wenzhou Medical College, Linhai 317000, Zhejiang Province, China Xian-Zhong Ding, Thomas E. Adrian, Northwestern University Medical School, Chicago, IL60611-3008, U.S.A Supported by the National Cancer Institute of USA, No. CA72712, and Special Funds for Zhejiang 151 Talent Project of China, No. 98-2095 Correspondence to: Mi-Lian Dong, Taizhou Hospital of Wenzhou Medical College, 150 Ximen Street, Linhai 317000, Zhejiang Province, ...

P.O.Box 2345, Beijing 100023,China World J Gastroenterol 2003;9(12):2759-2763 Fax: +86-10-85381893 World Journal of Gastroenterology E-mail: wjg@wjgnet.com www.wjgnet.com Copyright © 2003 by The WJG Press ISSN 1007-9327 • BASIC RESEARCH • Effects of bile acids on proliferation and ultrastructural alteration of pancreatic cancer cell lines Zheng Wu, Yi Lü, Bo Wang, Chang Liu, Zuo-Ren Wang Zheng Wu, Yi Lü, Bo Wang, Chang Liu, Zuo-Ren Wang, Department of Hepatobiliary Surgery, The First Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China Correspondence to: Yi Lü, Department of Hepatobiliary Surgery, The First Hospital of Xi’an Jiaotong University, 1 Jiankang Road, Xi’an 710061, Shaanxi Province, China. lvyi@newliver.net Telephone: +86-29-5324009 Fax: +86-29-5323626 Received: 2003-03-02 Accepted: 2003-03-28 ...

70 Application of array technology for expression profiling analyses of pancreatic cancer tissues and cells C.Wenger*, F.Müller-Pillasch*, M.Buchholz, C.Wallrapp, V.Ellenrieder, G.Adler, T.M. Gress. Department of Internal Medicine I, Universitätsklinikum Ulm, 89081 Ulm, Germany The development of new treatment modalities, diagnostic and preventive approaches for pancreatic cancer requires the understanding of the molecular mechanisms of the complex multistep process of tumourigenesis. At present mutations or alterations of gene expression have been described for a number of individual genes [1]. However, a much larger number of genes are warranted to be involved in primary and secondary processes responsible for the development of the phenotype of pancreatic cancer cells. Identification of these genes is essential as a basis for the development of new treatment or diagnostic ...

17 Genomic RDA for the identification of chromosomal aberrations in pancreatic cancer : merits and drawbacks . C. Wallrapp 1 , S. Hähnel 1 , C. Sorio 2 , A. Scarpa 2 , T.M. Gress 1 1) Department of Internal Medizin I, Universitätsklinikum Ulm, 89081 Ulm, Germany 2) Dipartimento di Patologia - Anatomia Patologica, Università di Verona, I-37134 Verona, Italy. The identification of novel tumour suppressor loci is often led by the detection of regions recurrently deleted in tumours [1]. In contrast overrepresentations of DNA, and in particular high level amplifications may lead to the identification of protooncogenes [2, 3]. Various methods are currently available for the identification of genomic imbalances. C omparative G enomic H ybridisation (CGH) is frequently used for a genome wide analysis ...

Abstract. It has been reported that vascular endothelial growth factor (VEGF) is a potent angiogenic factor that also has the ability to increase vascular permeability. VEGF plays an important role in the development of malignant ascites in various cancers. Gemcitabine has been prescribed for patients with inoperable human pancreatic ductal carcinoma as a first- line chemotherapy. However, the response rates of patients with malignant ascites who were undergoing systemic chemotherapy were extremely limited. In the present study, we investigated the role of VEGF and the effects of gemcitabine on malignant ascites of human pancreatic ductal carcinoma. As an in vitro assay, the human pancreatic cancer cell line (SUIT-2) was incubated in DMEM supplemented with serially diluted concentrations of gemcitabine for 24 h. The expression levels of VEGF in culture media were assayed using an enzyme-linked ...

Basic Pancreatic Cancer 109 Identification of Protein Markers for Pancreatic Ductal Adenocarcinoma Cells C.C. Thompson 1 , A.R. Shekouh 1 , F. Campbell 2 , D. Vimalachandran 1 , W. Prime 4 , C.S. Herrington 4 , S.R. Pennington 3 , J.P. Neoptolemos 1 , E. Costello 1 Departments of Surgery 1 , Pathology 2 , Human Anatomy and Cell Biology 3 , Cancer Tissue Bank Research Centre 4 , University of Liverpool, UK Introduction: Pancreatic ductal adenocarcinoma (PDAC) is usually advanced when diagnosed and often unresectable. Reliable and specific biochemical markers that allow early detection of PDAC could improve prognosis. Our strategy ...

Abstract. Trypsinogen/trypsin is one of the major serine proteases and is produced by pancreatic acinar cells. Tumor- associated trypsinogen (TAT) has been reported to be produced by several cancer cell lines. The biological roles and activation mechanisms of both TAT and pancreatic acinar trypsinogen (PAT) have not been elucidated in the context of cancer extension, in particular at the stage of invasion and metastasis. In this study, we investigate the roles played by PAT and TAT in pancreatic cancer invasion. In addition, we determined their mechanisms of activation and identified a trypsinogen activity-stimulating factor (TASF) produced by pancreatic cancer cells. TAT expression and high TAT activity were associated with high invasive and liver metastatic potential in SW1990 and CAPAN-2 cells. Moreover, a trypsinogen activating effect and activity prolonging effect was observed ...

Abstract . Over 90% of human pancreatic cancers harbor an activating point mutation in the K-ras gene at codon 12. However, it is not clear whether all downstream K-ras are activated and which downstream contributes to the cell survival and proliferation of pancreatic cancer cells. MEK kinase 1 (MEKK1)-c-Jun N-terminal kinase (JNK)-c-Jun pathway has an important role in cell proliferation, survival and apoptosis in various cells. We previously demonstrated that the dominant negative form of MEKK1 (DN-MEKK) inhibits the survival of human pancreatic cancer cell lines. In this study we investigated whether JNK-c-Jun, the down- stream pathway of DN-MEKK, affects the survival of human pancreatic cancer cell lines. Colony formation assays indicated that c-Jun failed to inhibit the survival of pancreatic cancer cells, whereas c-Jun remarkably inhibited the cell survival of non- pancreatic ...

By Russell G. Postier, M.D. John A. Schilling Professor and Chairman, Department of Surgery Pancreatic cancer is a dismal disease. Two years ago, 32,300 people in the U.S. were diagnosed with pancreatic cancer and 30,000 died. Fewer than 4 percent of patients diagnosed survive long-term. It is the fourth most common cause of cancer death in the United States. In 2001, a Progress Review Group (PRG) submitted a detailed analysis of the state of the disease to the National Cancer Institute (NCI). It was the feeling of this PRG that there had been little real progress made in pancreatic cancer understanding or treatment and that an increased awareness and funding on the part of the NCI was necessary if any real improvements were to be made. At OU Physicians, we are building a substantial clinical program for patients with pancreatic ...

Gene Therapy for Pancreatic Cancer Using an Adenovirus Vector Encoding Soluble flt-1 Vascular Endothelial Growth Factor Receptor *Tohru Hoshida, †Makoto Sunamura, †Dan G. Duda, †Shinichi Egawa, *Shukichi Miyazaki, *Ryuzaburo Shineha, §Hirofumi Hamada, ‡Haruo Ohtani, *Susumu Satomi, and †Seiki Matsuno Divisions of *Advanced Science and Technology, †Gastroenterological Surgery, and ‡Histopathology, Tohoku University Graduate School of Medicine, Sendai, Japan; and §Department of Molecular Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan Introduction: Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis. The soluble form of flt-1 VEGF receptor inhibits VEGF activity in a dominant-negative manner. Aim: This study demonstrated the regional tumor sup- pression effect of adenovirus-mediated soluble flt-1 in human pan- creatic cancer cells. ...

Abstract. We investigated the effects of the farnesyl transferase inhibitor (FTI) manumycin and the MEK inhibitor PD98059 on growth of human pancreatic cancer , with mutant (SUIT2) or wild-type (BxPC-3) K-ras, xenografted into nude mice. Tumor growth was not reduced by either of the agents at a dose of 3 mg/kg without irradiation. Growth of SUIT2 irradiated at 15 Gy or 30 Gy was reduced by manumycin and PD98059: at 15 Gy, tumor volume doubling time (TVDT) increased from 18.6 ± 3.8 to 36.3 ± 14.2 days with PD98059 (p<0.05); at 30 Gy, TVDT increased from 32.8 ± 6.8 to 70.5 ± 10.5 days and 70.7 ± 1.5 days, respectively. Manumycin tended to reduce growth of BxPC-3, but the difference in TVDT was not statistically significant. PD98059 significantly increased the TVDT of BxPC-3 at 30 Gy from 34.4 ± 18 to 62.6 ± 9.8 at 30 Gy. The present results suggest that Ras signaling pathways are potential targets ...

doi:10.1016/j.ijrobp.2003.11.019 CLINICAL INVESTIGATION Pancreas INTENSITY-MODULATED RADIOTHERAPY (IMRT) AND CONCURRENT CAPECITABINE FOR PANCREATIC CANCER E DGAR B EN -J OSEF , M.D.,* A NTHONY F. S HIELDS , M.D., P H .D., † U LKA V AISHAMPAYAN , M.D., † V AINUTIS V AITKEVICIUS , M.D., † B ASIL F. E L -R AYES , M.D., † P ATRICK M C D ERMOTT , P H .D.,* J AY B URMEISTER , P H .D.,* T ODD B OSSENBERGER , R.T.T., C.M.D.,* AND P HILIP A. ...

This issue is dedicated to Healthy Diet issues V Editor: Zviad Kirtava; Deputy Editor: Kakha Paposhvili, Information support: Maka Kobaladze, Helen Phagava; Design: David Meskhishvili National Information Learning Centre (NILC) , Tbilisi, Georgia, 2002 NILC should be mentioned in case of reprints or references of the provided materials! Internet Medical Digest #5-6 (83-84) 01.05.2002 Fatty diet ups pancreatic cancer risk in smokers NEW YORK (Reuters Health) - Male smo kers who consume diets rich in saturated fat may be at increased risk of pancreatic cancer , researchers report. Their study findings suggest that dietary changes can help to lower the risk of pancreatic cancer , a disease in which fewer than 5% of patients live for 5 years after diagnosis. Until the tumor grows large, there are no symptoms, and the cancer usually spreads to the ...

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 pancreatic cancer ...

Clinical Pancreatic Cancer 10 Delayed Gastric Emptying after Pancreaticoduodenectomy is Associated with Post- Operative Pancreatic or Splenic Complications S. Räty, J. Sand, I. Nordback Department of Surgery, Tampere University Hospital, Finland Background: Although hospital mortality after pancreaticoduodenectomy is minimal the morbidity is not. The most common single complication is delayed gastric empty- ing. The aim of this study was to analyse the possible association of delayed gastric emptying and post-operative pancreatic complications after pancreaticoduodenectomy. Patients and Methods: 20 consecutive patients undergoing pylorus preserving pancre- aticoduodenectomy were included – 13 females and 7 males (62 [range 30–80] years): 8 pancreatic cancer , 3 bile duct cancer , 2 ampullary cancer , 1 duodenal cancer , 1 carci- noid tumour, 1 insulinoma, ...

Basic Pancreatic Cancer 100 Invasion System of Pancreatic Cancer : Enhancement of Integrin Expression by Glial Cell Line-Derived Neurotrophic Factor (GDNF) H. Funahashi, H. Sawai, M. Yamamoto, Y. Okada, T. Hayakawa, M. Tanaka, T. Manabe First Department of Surgery, Nagoya City Unversity Medical School, Nagoya, Japan Introduction: The factor and the mechanism that determine the metastatic and invasive behavior of pancreatic tumor cells are incompletely understood. Methods: The expression of integrin subunits and the alteration of their expression by GDNF were examined by flow-cytometric analysis and cellular enzyme-linked assay in pancreatic cancer cell lines. Adhesion and invasion assays of cancer cells to ECM proteins were performed. Results: Pancreatic cancer cell lines were all found to express the RET and GFR -1 receptor for GDNF. ...

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 tumor. 94 ...