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Sample records for pancreatic cancer results

  1. Results of intraoperative radiotherapy for pancreatic cancers

    International Nuclear Information System (INIS)

    Okazaki, Atsushi; Shinozaki, Jun; Noda, Masanobu

    1991-01-01

    Reported are the results and observations of the authors who, from July 1986 through December 1989, have used electron beam intraoperative radiotherapy (IORT) on 20 patients with locally advanced pancreatic cancers, said number including 3 patients given a resection. In 14 of the 17 unresected patients, a chief symptom was pain, and 8 patients were given a celiac plexus block at the same time. The results and observations are given below. Life-threatening complications occurred in two patients, i.e., an insufficient pancreatojejunostomy, and a perforative peritonitis. In 12 of 13 evaluable patients, pain control was achieved for a mean period of 5 months, indicating that an IORT with celiac plexus block may be useful for palliation. In the resected patients, the mean survival time was 6 months, whereas in the unresected patients, the mean survival time was 7 months. The common cause of death in the unresected patients was a metastatic dissemination. Finally, in 3 of the 5 unresected patients, marked effects such as massive fibrosis were seen in the pancreatic tumor on autopsy. (author)

  2. Pancreatic Cancer

    Science.gov (United States)

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  3. Intraoperative radiotherapy in resected pancreatic cancer: feasibility and results

    International Nuclear Information System (INIS)

    Coquard, Regis; Ayzac, Louis; Gilly, Francois-Noeel; Romestaing, Pascale; Ardiet, Jean-Michel; Sondaz, Chrystel; Sotton, Marie-Pierre; Sentenac, Irenee; Braillon, Georges; Gerard, Jean-Pierre

    1997-01-01

    Background and purpose: To evaluate the impact of intraoperative radiotherapy (IORT) combined with postoperative external beam irradiation in patients with pancreatic cancer treated with curative surgical resection. Materials and methods: From January 1986 to April 1995 25 patients (11 male and 14 female, median age 61 years) underwent a curative resection with IORT for pancreatic adenocarcinoma. The tumour was located in the head of the pancreatic gland in 22 patients, in the body in two patients and in the tail in one patient. The pathological stage was pT1 in nine patients, pT2 in nine patients, pT3 in seven patients, pN0 in 14 patients and pN1 in 11 patients. All the patients were pM0. A pancreaticoduodenectomy was performed in 22 patients, a distal pancreatectomy was performed in two patients and a total pancreatectomy was performed in one patient. The resection was considered to be complete in 20 patients. One patient had microscopic residual disease and gross residual disease was present in four patients. IORT using electrons with a median energy of 12 MeV was performed in all the patients with doses ranging from 12 to 25 Gy. Postoperative EBRT was delivered to 20 patients (median dose 44 Gy). Concurrent chemotherapy with 5-fluorouracil was given to seven patients. Results: The overall survival was 56% at 1 year, 20% at 2 years and 10% at 5 years. Nine local failures were observed. Twelve patients developed metastases without local recurrence. Twenty patients died from tumour progression and two patients died from early post-operative complications. Three patients are still alive; two patients in complete response at 17 and 94 months and one patient with hepatic metastases at 13 months. Conclusion: IORT after complete resection combined with postoperative external beam irradiation is feasible and well tolerated in patients with pancreatic adenocarcinoma

  4. Results of diagnosis of pancreatic cancer by computed tomography (CT)

    International Nuclear Information System (INIS)

    Kimura, Kazue; Okuaki, Koji; Ito, Masami; Katakura, Toshihiko; Suzuki, Kenji

    1981-01-01

    Results of examination of pancreatic diseases, especially pancreatic cancer, conducted by CT during the past 3 years are summarized. The EMI CT Type 5000 or 5005 were used. During the 3 years from September 1976 to August 1979, a total of 1961 patients were examined by CT, and the upper abdomen was examined in 772 of these patients. In 97 patients, positive findings were obtained in the CT image of the pancreas. In 52 of these patients, the findings were confirmed operatively or by autopsy. Though cancer of the pancreas was diagnosed by CT in 30 patients, it was confirmed in 20 by surgical operation and in 1 by autopsy. Of the 9 misdiagnosed cases, 4 were cases of infiltration of the pancreas by carcinoma of the stomach or bile duct, and the other 5 were one case each of lipoma of the abdominal wall, normal pancreas, hyperplasia of Langerhans's islets of the pancreas tail, abscess between the pancreas and the posterior wall of the stomach, and choledocholithiasis. A case diagnosed by CT as cholelithiasis was a carcinoma measuring 5 x 5 x 6 cm located on the head of the pancreas, complicated by choledocholithiasis. The 22 patients with carcinoma of the pancreas were 9 with lesions less than 3.5 x 3.0 x 3.0 cm in size who could be radically operated, 6 who underwent exploratory laparotomy or autopsy, and 7 in whom operation was impossible. False negative and false positive CT results are also discussed. (author)

  5. Intraarterial Ultrasound in Pancreatic Cancer: Feasibility Study and Preliminary Results

    International Nuclear Information System (INIS)

    Larena-Avellaneda, Axel; Timm, Stephan; Kickuth, Ralph; Kenn, Werner; Steger, Ulrich; Jurowich, Christian; Germer, Christoph-Thomas

    2010-01-01

    Despite technological advances in computed tomography (CT) and magnetic resonance imaging, the involvement of the celiac or mesenteric artery in pancreatic cancer remains uncertain in many cases. Infiltration of these vessels is important in making decisions about therapy choices but often can only be definitively determined through laparotomy. Local (intraarterial) ultrasound may increase diagnostic accuracy. Using the Volcano intravascular ultrasound (IVUS) system, we applied a transfemoral method to scan the celiac and mesenteric arteries directly intraarterial. This technique was used in five patients with suspected pancreatic cancer. Technical success was achieved in all cases. In one case, a short dissection of the mesenteric artery occurred but could be managed interventionally. In tumors that did not contact with the vessels, IVUS was unable to display the tissue pathology. Our main interest was the infiltration of the arteries. In one case, infiltration was certain in the CT scan but uncertain in two patients. In the latter two cases, IVUS correctly predicted infiltration in one and freedom from tumor in the other case. In our preliminary study, IVUS correctly predicted arterial infiltration in all cases. IVUS did not provide new information when the tumor was far away from the vessel. Compared with IVUS in the portal vein, the information about the artery is more detailed, and the vessel approach is easier. These results encouraged us to design a prospective study to evaluate the sensitivity and specificity of this method.

  6. Cancer Stem Cells in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J., E-mail: christiane.bruns@med.uni-muenchen.de [Department of Surgery, Ludwig Maximilian University of Munich, Klinikum Grosshadern, Marchioninistr. 15, D-81377, Munich (Germany)

    2010-08-19

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  7. Cancer Stem Cells in Pancreatic Cancer

    Science.gov (United States)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J.

    2010-01-01

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer. PMID:24281178

  8. Cancer Stem Cells in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Karl-Walter Jauch

    2010-08-01

    Full Text Available Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs. Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  9. Pancreatic Exocrine Insufficiency in Pancreatic Cancer.

    Science.gov (United States)

    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J-Matthias

    2017-02-23

    Abstract : Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  10. PANCREATIC CANCER

    Directory of Open Access Journals (Sweden)

    Alojz Pleskovič

    2003-12-01

    Full Text Available Background. The pancreatic cancer is quite common malignant tumor of gastointestinal tract and its incidence is increasing in well developed part of the world. Despite of all advanced diagnostic methods the disease is in most cases recognised too late when the tumor is not resectable.Conclusions. Only in 20–30% of patients with pancreatic cancer surgical resection is possible, and even in this group 5year survival is very low. In the patients where the tumor is not resectable, sometimes only palliative procedures are indicated and sometimes only simptomatic therapy is possible. The average survival period in this group of patients is 12–20 months. Adjuvant chemo and radiotherapy has not shown much of benefit and the prognosis is still very bad.

  11. Current knowledge on pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Juan eIovanna

    2012-01-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer death with a median survival of 6 months and a dismal 5-year survival rate of 3-5%. The development and progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes and the deregulation of many signalling pathways. Therefore, the strategies targeting these molecules as well as their downstream signalling could be promising for the prevention and treatment of pancreatic cancer. However, although targeted therapies for pancreatic cancer have yielded encouraging results in vitro and in animal models, these findings have not been translated into improved outcomes in clinical trials. This failure is due to an incomplete understanding of the biology of pancreatic cancer and to the selection of poorly efficient or imperfectly targeted agents. In this review, we will critically present the current knowledge regarding the molecular, biochemical, clinical and therapeutic aspects of pancreatic cancer.

  12. Current Knowledge on Pancreatic Cancer

    International Nuclear Information System (INIS)

    Iovanna, Juan; Mallmann, Maria Cecilia; Gonçalves, Anthony; Turrini, Olivier; Dagorn, Jean-Charles

    2012-01-01

    Pancreatic cancer is the fourth leading cause of cancer death with a median survival of 6 months and a dismal 5-year survival rate of 3–5%. The development and progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways. Therefore, the strategies targeting these molecules as well as their downstream signaling could be promising for the prevention and treatment of pancreatic cancer. However, although targeted therapies for pancreatic cancer have yielded encouraging results in vitro and in animal models, these findings have not been translated into improved outcomes in clinical trials. This failure is due to an incomplete understanding of the biology of pancreatic cancer and to the selection of poorly efficient or imperfectly targeted agents. In this review, we will critically present the current knowledge regarding the molecular, biochemical, clinical, and therapeutic aspects of pancreatic cancer.

  13. Current Knowledge on Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Iovanna, Juan [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, Marseille (France); Mallmann, Maria Cecilia [Centre d’Investigation Clinique de Marseille, Marseille (France); Gonçalves, Anthony [Département d’Oncologie Médicale, Institut Paoli-Calmettes, Marseille (France); Turrini, Olivier [Département de Chirurgie Oncologique, Institut Paoli-Calmettes, Marseille (France); Dagorn, Jean-Charles, E-mail: juan.iovanna@inserm.fr [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, Marseille (France)

    2012-01-31

    Pancreatic cancer is the fourth leading cause of cancer death with a median survival of 6 months and a dismal 5-year survival rate of 3–5%. The development and progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways. Therefore, the strategies targeting these molecules as well as their downstream signaling could be promising for the prevention and treatment of pancreatic cancer. However, although targeted therapies for pancreatic cancer have yielded encouraging results in vitro and in animal models, these findings have not been translated into improved outcomes in clinical trials. This failure is due to an incomplete understanding of the biology of pancreatic cancer and to the selection of poorly efficient or imperfectly targeted agents. In this review, we will critically present the current knowledge regarding the molecular, biochemical, clinical, and therapeutic aspects of pancreatic cancer.

  14. Pancreatic Exocrine Insufficiency in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Miroslav Vujasinovic

    2017-02-01

    Full Text Available Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor’s metabolism (Warburg effect and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  15. Correlation of the results of radiotherapy of pancreatic cancer with different clinical factors

    Energy Technology Data Exchange (ETDEWEB)

    Barkanov, A I [Akademiya Meditsinskikh Nauk SSSR, Moscow. Onkologicheskij Nauchnyj Tsentr

    1983-01-01

    Altogether 124 patients with pancreatic cancer radiation treated at doses of 50-80 Gy. With the period of medical history from 1 to 6 months in 82.1 % of the patients, 6-12 months in 74.4 % and over 12 months in 61.9 % of the patients the mean survival time after radiotherapy was respectively 20.1, 15.5 and 14.3 months, i.e. radiotherapeutic results got worse with the increase of the period of disease. Better survival results were obtained for pancreatic head cancer (14.7 months), worse results in its total involvement (10.4 months). Optimum time between operation and irradiation depending on the degree of jaundice was 0.5-1.5 months. With concomitant pancreatitis irradiation was combined with i.v. administration of contrykal that helped to alleviate the pain syndrome. Irradiation of pancreatic cancer complicated by diabetes mellitus facilitates the course of diabetes during follow-up.

  16. Therapy of pancreatic cancer

    International Nuclear Information System (INIS)

    Takeda, Yutaka; Kitagawa, Toru; Nakamori, Shoji

    2009-01-01

    Pancreatic cancer remains one of the most difficult diseases to cure. Japan pancreas society guidelines for management of pancreatic cancer indicate therapeutic algorithm according to the clinical stage. For locally limited pancreatic cancer (cStage I, II, III in Japanese classification system), surgical resection is recommended, however prognosis is still poor. Major randomized controlled trials of resected pancreatic cancer indicates that adjuvant chemotherapy is superior to observation and gemcitabine is superior to 5-fluorouracil (FU). For locally advanced resectable pancreatic cancer (cStage IVa in Japanese classification system (JCS)), we perform neoadjuvant chemoradiotherapy. Phase I study established a recommended dose of 800 mg gemcitabine and radiation dose of 36 Gy. For locally advanced nonresectable pancreatic cancer (cStage IVa in JCS), chemoradiotherapy followed by chemotherapy is recommended. Although pancreatic cancer is chemotherapy resistant tumor, systemic chemotherapy is recommended for metastatic pancreatic cancer (cStage IVb in JCS). Single-agent gemcitabine is the standard first line agent for the treatment of advanced pancreatic cancer. Meta-analysis of chemotherapy showed possibility of survival benefit of gemcitabine combination chemotherapy over gemcitabine alone. We hope gemcitabine combination chemotherapy or molecular targeted therapy will improve prognosis of pancreatic cancer in the future. (author)

  17. [Neoadjuvant Chemotherapy Using S-1 for Pancreatic Cancer - Mid-Term Results].

    Science.gov (United States)

    Homma, Yuki; Honda, Goro; Sakamoto, Katsunori; Kurata, Masanao; Honjo, Masahiko; Hirata, Yoshihiro; Shinya, Satoshi

    2016-10-01

    Although surgical resection is the only curative strategy for pancreatic cancer, the prognosis of patients with pancreatic cancer remains poor. Recently, neoadjuvant treatment has been frequently employed as a promising treatment. Here, the mid-term results of neoadjuvant chemoradiotherapy(NACRT)using S-1, which has been performed in our hospital since 2008, are reported. Seventy-nine patients with resectable or borderline resectable pancreatic ductal adenocarcinoma, who had been intended to undergo NACRT treatment using S-1, were enrolled. The NACRT comprised radiotherapy( 1.8 Gy×28 days)and full-dose twice-daily oral S-1 given on the same days as the radiotherapy. The results of the NACRT and pancreatectomy and the patients' prognoses were evaluated. Fifty-five patients(69.6%)underwent pancreatectomy, with no case of mortality. The curative resection rate was 94.5%. Postoperative adjuvant chemotherapy was administered in 46 patients(83.6%). The 3-year survival rates of all 79 patients and 55 pancreatectomy patients were 40.1% and 50.4%, respectively. NACRT using S-1 was found to be feasible, and good mid-term outcomes were obtained. However, analysis of the long-term outcomes and comparisons with other novel anti-cancer drugs are still required.

  18. Prevention of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Stefan Kuroczycki-Saniutycz

    2017-02-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDA accounts for 95% of all pancreatic cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the lowest five-year survival rate as compared to others cancers. PDA in Poland is the fifth leading cause of death after lung, stomach, colon and breast cancer. In our paper we have analysed the newest epidemiological research, some of it controversial, to establish the best practical solution for pancreatic cancer prevention in the healthy population as well as treatment for patients already diagnosed with pancreatic cancer. We found that PDA occurs quite frequently but is usually diagnosed too late, at its advanced stage. Screening for PDA is not very well defined except in subgroups of high-risk individuals with genetic disorders or with chronic pancreatitis. We present convincing, probable, and suggestive risk factors associated with pancreatic cancer, many of which are modifiable and should be introduced and implemented in our society.

  19. Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice.

    Science.gov (United States)

    Diaz Beveridge, Robert; Alcolea, Vicent; Aparicio, Jorge; Segura, Ángel; García, Jose; Corbellas, Miguel; Fonfría, María; Giménez, Alejandra; Montalar, Joaquin

    2014-01-10

    The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.

  20. Recent Progress in Pancreatic Cancer

    Science.gov (United States)

    Wolfgang, Christopher L.; Herman, Joseph M.; Laheru, Daniel A.; Klein, Alison P.; Erdek, Michael A.; Fishman, Elliot K.; Hruban, Ralph H.

    2013-01-01

    Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in our understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer. PMID:23856911

  1. The epidemiology of pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Yadav, Dhiraj; Lowenfels, Albert B

    2013-06-01

    Acute pancreatitis is one of the most frequent gastrointestinal causes of hospital admission in the United States. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreatic cancer is associated with a high mortality rate and is one of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect the black population more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  2. The Epidemiology of Pancreatitis and Pancreatic Cancer

    Science.gov (United States)

    Yadav, Dhiraj; Lowenfels, Albert B.

    2013-01-01

    Acute pancreatitis is one of the most frequent gastrointestinal causes for hospital admission in the US. Chronic pancreatitis, although lower in incidence, significantly reduces patients’ quality of life. Pancreatic cancer has high mortality and is 1 of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect Blacks more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. PMID:23622135

  3. Pancreatic cancer

    International Nuclear Information System (INIS)

    Diamond, D.; Fisher, B.

    1975-01-01

    Diagnostic and therapeutic advances of the last 30 years have left unchanged the course and prognosis of carcinoma of the exocrine pancreas. The most important reasons for this are the anatomic location and biologic nature of the tumor. An additional factor of importance is the consistently reported 4 to 9 month delay in diagnosis, also unchanged in 30 years. Recent controversy has developed concerning the mainstay of our current surgical treatment surgical treatment, the Whipple pancreaticoduodenectomy and its modifications, and its role as the most efficacious surgical approach to this disease. It is the purpose of this paper to review and summarize the clinical characteristics of carcinoma of the exocrine pancreas and to review and reassess the standard operative approach. Cancer of the head, body, and tail of the pancreas will be considered together because they have many features in common

  4. Hypermutation in pancreatic cancer

    OpenAIRE

    Humphris, Jeremy L.; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J.; Johns, Amber L.; McKay, Skye; Chang, David K.; Miller, David K.; Pajic, Marina; Kassahn, Karin S.; Quinn, Michael C.J.; Bruxner, Timothy J.C.; Christ, Angelika N.; Harliwong, Ivon; Idrisoglu, Senel

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechan...

  5. Incidence of pancreatic cancer in Denmark

    DEFF Research Database (Denmark)

    Weble, Tanja Cruusberg; Bjerregaard, Jon Kroll; Kissmeyer, Peter

    2017-01-01

    BACKGROUND: The aim of this study was to monitor the evolution of the incidence of pancreatic cancer in Denmark over 70 years. We also compared registrations of pancreatic cancer in a nationwide population-based database, the Danish Cancer Registry, and a clinical database, the Danish Pancreatic...... Cancer Database, in 2012-2013. MATERIAL AND METHODS: Registrations of pancreatic cancer from the Danish Cancer Registry over 1943-2012 were used to calculate age-specific incidence rates per 100 000 person years by sex and age in 5-year period, weighted by the Segi World Standard Population for age...... standardization. We used absolute numbers from the Cancer Registry and the Pancreatic Cancer Database, including distribution of topography of cancers registered in 2012-2013, to compare registration in the two data sources. RESULTS: The incidence rates of pancreatic cancer among Danish men increased until 1968...

  6. Stages of Pancreatic Cancer

    Science.gov (United States)

    ... overweight. Having a personal history of diabetes or chronic pancreatitis . Having a family history of pancreatic cancer or ... have not started treatment. Five types of standard treatment are used: Surgery ... Whipple procedure : A surgical procedure in which the head of the pancreas , ...

  7. Hypermutation In Pancreatic Cancer.

    Science.gov (United States)

    Humphris, Jeremy L; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J; Johns, Amber L; McKay, Skye; Chang, David K; Miller, David K; Pajic, Marina; Kassahn, Karin S; Quinn, Michael C J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Stone, Andrew; Wilson, Peter J; Anderson, Matthew; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Mead, Ronald S; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Nagrial, Adnan M; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Rooman, Ilse; Giry-Laterriere, Marc; Samra, Jaswinder S; Kench, James G; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; McKay, Colin J; Carter, C Ross; Dickson, Euan J; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Morton, Jennifer P; Sansom, Owen J; Grützmann, Robert; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Rusev, Borislav; Corbo, Vincenzo; Salvia, Roberto; Cataldo, Ivana; Tortora, Giampaolo; Tempero, Margaret A; Hofmann, Oliver; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Gill, Anthony J; Pearson, John V; Grimmond, Sean M; Waddell, Nicola; Biankin, Andrew V

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  8. Results of a pancreatectomy with a limited venous resection for pancreatic cancer.

    Science.gov (United States)

    Illuminati, Giulio; Carboni, Fabio; Lorusso, Riccardo; D'Urso, Antonio; Ceccanei, Gianluca; Papaspyropoulos, Vassilios; Pacile, Maria Antonietta; Santoro, Eugenio

    2008-01-01

    The indications for a pancreatectomy with a partial resection of the portal or superior mesenteric vein for pancreatic cancer, when the vein is involved by the tumor, remain controversial. It can be assumed that when such involvement is not extensive, resection of the tumor and the involved venous segment, followed by venous reconstruction will extend the potential benefits of this resection to a larger number of patients. The further hypothesis of this study is that whenever involvement of the vein by the tumor does not exceed 2 cm in length, this involvement is more likely due to the location of the tumor being close to the vein rather than because of its aggressive biological behavior. Consequently, in these instances a pancreatectomy with a resection of the involved segment of portal or superior mesenteric vein for pancreatic cancer is indicated, as it will yield results that are superposable to those of a pancreatectomy for cancer without vascular involvement. Twenty-nine patients with carcinoma of the pancreas involving the portal or superior mesenteric vein over a length of 2 cm or less underwent a macroscopically curative resection of the pancreas en bloc with the involved segment of the vein. The venous reconstruction procedures included a tangential resection/lateral suture in 15 cases, a resection/end-to-end anastomosis in 11, and a resection/patch closure in 3. Postoperative mortality was 3.4%; morbidity was 21%. Local recurrence was 14%. Cumulative (standard error) survival rate was 17% (9%) at 3 years. A pancreatectomy combined with a resection of the portal or superior mesenteric vein for cancer with venous involvement not exceeding 2 cm is indicated in order to extend the potential benefits of a curative resection.

  9. Pancreatic cancer risk in hereditary pancreatitis

    Directory of Open Access Journals (Sweden)

    Frank Ulrich Weiss

    2014-02-01

    Full Text Available Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1 gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. Hereditary pancreatitis often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of hereditary pancreatitis patients to develop pancreatic cancer.

  10. Familial Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Stephen J. Lanspa

    2010-11-01

    Full Text Available Pancreatic cancer’s high mortality rate equates closely with its incidence, thereby showing the need for development of biomarkers of its increased risk and a better understanding of its genetics, so that high-risk patients can be better targeted for screening and early potential lifesaving diagnosis. Its phenotypic and genotypic heterogeneity is extensive and requires careful scrutiny of its pattern of cancer associations, such as malignant melanoma associated with pancreatic cancer, in the familial atypical multiple mole melanoma syndrome, due to the CDKN2A germline mutation. This review is designed to depict several of the hereditary pancreatic cancer syndromes with particular attention given to the clinical application of this knowledge into improved control of pancreatic cancer.

  11. The results of palliative radiation therapy in patients with unresectable advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Ryu, Mi Ryeong; Yoon, Sei Chul; Kim, Yeon Sil; Chung, Su Mi

    2006-01-01

    To evaluate the treatment results and prognostic factors of palliative radiation therapy in the patients with unresectable advanced pancreatic cancer. Thirty-seven evaluable patients with unresectable advanced pancreatic cancer who were treated by palliative radiation therapy for pain relief at the Department of Radiation Oncology, Kangnam St. Mary's hospital, the Catholic University of Korea between March 1984 and February 2005 were analysed retrospectively. There were 22 men and 15 women. Age at diagnosis ranged from 30 to 80 (median 57) years. Twelve patients (32.4%) had liver metastases and 22 patients (59.5%) had lymph node metastases. Radiation therapy was delivered to primary tumor and regional lymph nodes with 1 ∼ 2 cm margin, and total dose was 3,240 ∼ 5,580 cGy (median 5,040 cGy). Chemotherapy with radiotherapy was delivered in 30 patients (81%) with 5-FU alone (21 patients) or gemcitabine (9 patients). The follow-up period ranged from 1 to 44 months. Survival and prognostic factors were analysed using Kaplan-Meier method and log-rank test respectively. Overall mean and median survival were 11 and 8 months and 1-year survival rate was 20%. Among 33 patients who were amenable for response evaluation, 7 patients had good response and 22 patients had fail response with overall response rate of 87.9%. Mild to moderate toxicity were observed in 14 patients with nausea, vomiting, and indigestion, but severe toxicity requiring interruption of treatment were not observed. Chemotherapy didn't influence the survival and symptomatic palliation, but the group containing gemcitabine showed a tendency of longer survival (median 12 months) than 5-FU alone group (median 5.5 months) without statistical significance (ρ > 0.05). The significant prognostic factors were Karnofsky performance status and liver metastasis (ρ 0.05). Radiation therapy was effective for symptomatic palliation in the patients with unresectable advanced pancreatic cancer and would play an

  12. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection.

    Science.gov (United States)

    Gilliland, Taylor M; Villafane-Ferriol, Nicole; Shah, Kevin P; Shah, Rohan M; Tran Cao, Hop S; Massarweh, Nader N; Silberfein, Eric J; Choi, Eugene A; Hsu, Cary; McElhany, Amy L; Barakat, Omar; Fisher, William; Van Buren, George

    2017-03-07

    Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL). The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI) manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995-2016) addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC). We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1) patients with albumin 10% should postpone surgery and begin aggressive nutrition supplementation; (2) patients with albumin endocrine and exocrine pancreatic insufficiency alongside implementation of appropriate treatment to improve the patient's quality of life.

  13. Hedgehog signaling and therapeutics in pancreatic cancer.

    LENUS (Irish Health Repository)

    Kelleher, Fergal C

    2012-02-01

    OBJECTIVE: To conduct a systematic review of the role that the hedgehog signaling pathway has in pancreatic cancer tumorigenesis. METHOD: PubMed search (2000-2010) and literature based references. RESULTS: Firstly, in 2009 a genetic analysis of pancreatic cancers found that a core set of 12 cellular signaling pathways including hedgehog were genetically altered in 67-100% of cases. Secondly, in vitro and in vivo studies of treatment with cyclopamine (a naturally occurring antagonist of the hedgehog signaling pathway component; Smoothened) has shown that inhibition of hedgehog can abrogate pancreatic cancer metastasis. Thirdly, experimental evidence has demonstrated that sonic hedgehog (Shh) is correlated with desmoplasia in pancreatic cancer. This is important because targeting the Shh pathway potentially may facilitate chemotherapeutic drug delivery as pancreatic cancers tend to have a dense fibrotic stroma that extrinsically compresses the tumor vasculature leading to a hypoperfusing intratumoral circulation. It is probable that patients with locally advanced pancreatic cancer will derive the greatest benefit from treatment with Smoothened antagonists. Fourthly, it has been found that ligand dependent activation by hedgehog occurs in the tumor stromal microenvironment in pancreatic cancer, a paracrine effect on tumorigenesis. Finally, in pancreatic cancer, cells with the CD44+CD24+ESA+ immunophenotype select a population enriched for cancer initiating stem cells. Shh is increased 46-fold in CD44+CD24+ESA+ cells compared with normal pancreatic epithelial cells. Medications that destruct pancreatic cancer initiating stem cells are a potentially novel strategy in cancer treatment. CONCLUSIONS: Aberrant hedgehog signaling occurs in pancreatic cancer tumorigenesis and therapeutics that target the transmembrane receptor Smoothened abrogate hedgehog signaling and may improve the outcomes of patients with pancreatic cancer.

  14. ABO blood groups and pancreatic cancer risk and survival: Results from the PANcreatic Disease ReseArch (PANDoRA) consortium

    Czech Academy of Sciences Publication Activity Database

    Rizzato, C.; Campa, D.; Pezzilli, R.; Souček, P.; Greenhalf, W.; Capurso, G.; Talar-Wojnarowska, R.; Heller, A.; Jamroziak, K.; Khaw, K. T.; Key, T.; Bambi, F.; Landi, S.; Mohelníková-Duchoňová, B.; Vodičková, Ludmila; Buechler, M. W.; Bugert, P.; Vodička, Pavel; Neoptolemos, J. P.; Werner, J.; Hoheisel, J. D.; Bauer, A. S.; Giese, N.; Canzian, F.

    2013-01-01

    Roč. 29, č. 4 (2013), s. 1637-1644 ISSN 1021-335X Institutional support: RVO:68378041 Keywords : pancreatic cancer * genetic susceptibility * cancer risk Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.191, year: 2013

  15. Diabetes, pancreatic cancer, and metformin therapy

    Directory of Open Access Journals (Sweden)

    Jun eGong

    2014-11-01

    Full Text Available Pancreatic cancer carries a poor prognosis as most patients present with advanced disease and preferred chemotherapy regimens offer only modest effects on survival. Risk factors include smoking, obesity, heavy alcohol, and chronic pancreatitis. Pancreatic cancer has a complex relationship with diabetes, as diabetes can be both a risk factor for pancreatic cancer and a result of pancreatic cancer. Insulin, insulin-like growth factor-1 (IGF-1, and certain hormones play an important role in promoting neoplasia in diabetics. Metformin appears to reduce risk for pancreatic cancer and improve survival in diabetics with pancreatic cancer primarily by decreasing insulin/IGF signaling, disrupting mitochondrial respiration, and inhibiting the mammalian target of rapamycin (mTOR pathway. Other potential anti-tumorigenic effects of metformin include the ability to downregulate specificity protein transcription factors and associated genes, alter microRNAs, decrease cancer stem cell proliferation, and reduce DNA damage and inflammation. Here, we review the most recent knowledge on risk factors and treatment of pancreatic cancer and the relationship between diabetes, pancreatic cancer, and metformin as a potential therapy.

  16. Dual-energy perfusion-CT in recurrent pancreatic cancer. Preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Fritz, F.; Skornitzke, S.; Kauczor, H.U.; Stiller, W.; Klauss, M. [Heidelberg Univ. (Germany). Clinic of Diagnostic and Interventional Radiology; Hackert, T. [Heidelberg Univ. (Germany). Clinic of Surgery; Grenacher, L. [Diagnostik Muenchen (Germany). Diagnostic Imaging Center

    2016-06-15

    To evaluate the diagnostic performance of dual energy (DE) perfusion-CT for the differentiation between postoperative soft-tissue formation and tumor recurrence in patients after potentially curative pancreatic cancer resection. 24 patients with postoperative soft-tissue formation in the conventional regular follow-up CT acquisition after pancreatic cancer resection with curative intent were included prospectively. They were examined with a 64-row dual-source CT using a dynamic sequence of 34 DE acquisitions every 1.5 s (80 ml of iodinated contrast material, 370 mg/ml, flow rate 5 ml/s). Weighted average (linearly blended M0.5) 120 kVp-equivalent dual-energy perfusion image data sets were evaluated with a body-perfusion CT tool for estimating blood flow, permeability, and blood volume. Diagnosis was confirmed by histological study (n=4) and by regular follow-up. Final diagnosis was local recurrence of pancreatic cancer in 15 patients and unspecific postoperative tissue formation in 9 patients. The blood-flow values for recurrence tissue trended to be lower compared to postoperative tissue formation with 16.6 ml/100 ml/min and 24.7 ml/100 ml/min, respectively for weighted average 120 kVp-equivalent image data, which was not significant (n.s.) (p=0.06, significance level 0.05). Permeability- and blood-volume values were only slightly lower in recurrence tissue (n.s.). DE perfusion-CT is feasible in patients after pancreatic cancer resection and a promising functional imaging technique. As only a trend for lower perfusion values in local recurrence compared to unspecific postoperative alterations was found, the perfusion differences are not yet sufficient to differentiate between malignancy and unspecific postoperative alterations for this new technique. Further studies and technical improvements are needed to generate reliable data for this clinically highly relevant differentiation.

  17. Review of Adjuvant Radiochemotherapy for Resected Pancreatic Cancer and Results From Mayo Clinic for the 5th JUCTS Symposium

    International Nuclear Information System (INIS)

    Miller, Robert C.; Iott, Matthew J.; Corsini, Michele M.

    2009-01-01

    Purpose: To present an overview of Phase III trials in adjuvant therapy for pancreatic cancer and review outcomes at the Mayo Clinic after adjuvant radiochemotherapy (RT/CT) for resected pancreatic cancer. Methods and Materials: A literature review and a retrospective review of 472 patients who underwent an R0 resection for T1-3N0-1M0 invasive carcinoma of the pancreas from 1975 to 2005 at the Mayo Clinic, Rochester, MN. Patients with metastatic or unresectable disease at the time of surgery, positive surgical margins, or indolent tumors and those treated with intraoperative radiotherapy were excluded from the analysis. Median radiotherapy dose was 50.4Gy in 28 fractions, with 98% of patients receiving concurrent 5-fluorouracil- based chemotherapy. Results: Median follow-up was 2.7 years. Median overall survival (OS) was 1.8 years. Median OS after adjuvant RT/CT was 2.1 vs. 1.6 years for surgery alone (p = 0.001). The 2-y OS was 50% vs. 39%, and 5-y was 28% vs. 17% for patients receiving RT/CT vs. surgery alone. Univariate and multivariate analysis revealed that adverse prognostic factors were positive lymph nodes (risk ratio [RR] 1.3, p < 0.001) and high histologic grade (RR 1.2, p < 0.001). T3 tumor status was found significant on univariate analysis only (RR 1.1, p = 0.07). Conclusions: Results from recent clinical trials support the use of adjuvant chemotherapy in resected pancreatic cancer. The role of radiochemotherapy in adjuvant treatment of pancreatic cancer remains a topic of debate. Results from the Mayo Clinic suggest improved outcomes after the administration of adjuvant radiochemotherapy after a complete resection of invasive pancreatic malignancies.

  18. Ultrasonographic diagnosis of pancreatic and peripancreatic cancer

    International Nuclear Information System (INIS)

    Park, Churl Min; Kim, Ho Kyun; Yoon, Yup; Lee, Sun Wha; Kim, Soon Yong; Ahn, Chi Yul

    1982-01-01

    Seventeen cases of cancers in and adjacent to the pancreas were studied by high resolution and wide field real time ultrasonographic scanner with 3.5 MHz linear array electronically focusing transducer. The result were as follows: 1. In a total of 17 cases, 7 cases were pancreatic cancers and the rests were 3 cases of ampulla of Vaster cancer, 3 cases of distal CBD cancers, and 4 cases of metastatic cancers, respectively. 2. Pancreatic cancers were located mainly in head portion, and metastatic cancers were noted in head, tail, and retropancreatic areas. 3. The sizes of all distal CBD cancer were less than 1.8 cm, usually smaller than other tumors, and the size of metastatic cancers were variable (1-6 cm). 4. The shape, margin, contour and echogenicity of the tumors were variable. 5. Pancreatic duct showed marked dilatation in one of pancreatic cancer, and mild dilatation in one of ampulla of Vater cancer. 6. The caliber of extrahepatic duct were moderately or markedly dilated in nearly all cases except 2 cases of pancreatic body cancer. 7. The pancreatic margin is partially obliterated in pancreatic and ampulla of Vater cancers but not in distal CBD cancer. 8. Gallbladder enlargement is secondary change due to the obstruction of extrahepatic bile duct. 9. Effects on the vessels are due to not only direct mass effect but direct invasion resulting in obliteration. The most commonly involved vessels are spleno-portal junction, splenic vein and portal vein. In case of pancreatic cancer in uncinate process, the superior mesenteric vessels are displaced anteriorly. 10. Surrounding metastatic lesions were suspected in pancreatic and ampulla of Vater cancer, but not seen in distal CBD cancer. 11. Ascites were seen in only two cases of metastasis

  19. Localized Unresectable Pancreatic Cancer Treated with High Energy Neutrons and Chemotherapy at Fermilab - Preliminary Results

    Energy Technology Data Exchange (ETDEWEB)

    Saroja, K. R. [Unlisted, US, IL; Cohen, Lionel [Unlisted, US, IL; Hendrickson, Frank R. [Unlisted, US, IL; Mansell, JoAnne [Fermilab

    1990-01-01

    Between January 1985 and July 1989 a total of thirty-eight patients with locally advanced pancreatic cancer were treated with high energy neutrons at Fermilab. Twenty-one patients received only neutrons and seventeen were given chemotherapy in addition, either concurrently or subsequently following the completion of neutron irradiation. This is a retrospective study. Data were analyzed for tolerance, complications and survival. Three of the twenty-one (14%) patients who received only neutron beam therapy developed Grade ID or greater complications in the RTOG/EORTC scale. The median survival was 6.4 months. One of these patients is alive 10 months post treatment. Of seventeen patients who also received chemotherapy, five (29%) had severe complications. However, median survival was 13.5 months. Four of these seventeen patients are still alive at the time of this analysis. The preliminary results show that there is improvement in the survival of patients treated with combined neutron irradiation and chemotherapy. A pilot study to further evaluate these results in a larger group of patients is underway. Details of complications and chemotherapy regimen will be preseqted.

  20. Systemic therapy of pancreatic cancer

    International Nuclear Information System (INIS)

    Andrezalova Vochyanova, I.; Salek, T.

    2012-01-01

    Pancreatic cancer is the fourth comment cause of cancer-related death in men. Most patients with pancreatic cancer are diagnosed at advanced, non-resectable stage. Late detection, early metastases, difficult surgical approached, cancer resistant to systemic chemo and radiotherapy - all contribute to its in faust prognosis. Only about 5 % of patients will live 5 years after diagnosis. Gemcitabine - based combination treatments is the standard for advanced pancreatic cancer. The combination of fluorouracil, folinic acid, irinotecan and oxaliplatin led to median survival of 11 months. No standard second-line treatment exists for pancreatic cancer. (author)

  1. Pancreatic cancer risk in hereditary pancreatitis

    OpenAIRE

    Weiss, Frank U.

    2014-01-01

    Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1) gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic...

  2. Long-term results of concurrent radiotherapy and UFT in patients with locally advanced pancreatic cancer

    DEFF Research Database (Denmark)

    Bjerregaard, Jon K; Mortensen, Michael B; Jensen, Helle A

    2009-01-01

    BACKGROUND: Definition and treatment options for locally advanced non-resectable pancreatic cancer (LAPC) vary. Treatment options range from palliative chemotherapy to chemoradiotherapy (CRT). Several studies have shown that a number of patients become resectable after complementary treatment prior...... underwent resection, leading to a resection rate of 17%, and a median survival of 46 (23-nr) months. All 11 patients had a R0 resection. Median survival for the patients not resected was 8.8 (8-12) months. CONCLUSION: CRT with 50 Gy combined with UFT, is a well-tolerated and effective treatment for patients...

  3. Danish Pancreatic Cancer Database

    DEFF Research Database (Denmark)

    Fristrup, Claus; Detlefsen, Sönke; Palnæs Hansen, Carsten

    2016-01-01

    : Death is monitored using data from the Danish Civil Registry. This registry monitors the survival status of the Danish population, and the registration is virtually complete. All data in the database are audited by all participating institutions, with respect to baseline characteristics, key indicators......AIM OF DATABASE: The Danish Pancreatic Cancer Database aims to prospectively register the epidemiology, diagnostic workup, diagnosis, treatment, and outcome of patients with pancreatic cancer in Denmark at an institutional and national level. STUDY POPULATION: Since May 1, 2011, all patients...... with microscopically verified ductal adenocarcinoma of the pancreas have been registered in the database. As of June 30, 2014, the total number of patients registered was 2,217. All data are cross-referenced with the Danish Pathology Registry and the Danish Patient Registry to ensure the completeness of registrations...

  4. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection

    Directory of Open Access Journals (Sweden)

    Taylor M. Gilliland

    2017-03-01

    Full Text Available Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL. The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995–2016 addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC. We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1 patients with albumin < 2.5 mg/dL or weight loss > 10% should postpone surgery and begin aggressive nutrition supplementation; (2 patients with albumin < 3 mg/dL or weight loss between 5% and 10% should have nutrition supplementation prior to surgery; (3 enteral nutrition (EN should be preferred as a nutritional intervention over total parenteral nutrition (TPN postoperatively; and, (4 a multidisciplinary approach should be used to allow for early detection of symptoms of endocrine and exocrine pancreatic insufficiency alongside implementation of

  5. Immunotherapy for pancreatic cancer: present and future.

    Science.gov (United States)

    Aroldi, Francesca; Zaniboni, Alberto

    2017-06-01

    Despite the identification of some efficient drugs for the treatment of metastatic pancreatic cancer, this tumor remains one of the most lethal cancers and is characterized by a strong resistance to therapies. Pancreatic cancer has some unique features including the presence of a microenvironment filled with immunosuppressive mediators and a dense stroma, which is both a physical barrier to drug penetration and a dynamic entity involved in immune system control. Therefore, the immune system has been hypothesized to play an important role in pancreatic cancer. Thus, therapies acting on innate or adaptive immunity are being investigated. Here, we review the literature, report the most interesting results and hypothesize future treatment directions.

  6. Parenteral nutrition support for patients with pancreatic cancer. Results of a phase II study

    Directory of Open Access Journals (Sweden)

    Riess Hanno

    2010-03-01

    Full Text Available Abstract Background Cachexia is a common problem in patients (pts suffering from upper gastrointestinal cancer. In addition, most of these patients suffer from malabsorption and stenosis of the gastrointestinal tract due to their illness. Various methods of supplementary nutrition (enteral, parenteral are practised. In patients with advanced pancreatic cancer (APC, phase angle, determined by bio-electrical impedance analysis (BIA, seems to be a survival predictor. The positive influence of BIA determinate predictors by additional nutrition is currently under discussion. Methods To examine the impact of additional parenteral nutrition (APN we assessed outpatients suffering from APC and progressive cachexia. The assessment based on the BIA method. Assessment parameters were phase angle, ECM/BCM index (ratio of extracellular mass to body cell mass, and BMI (body mass index. Patients suffering from progressive weight loss in spite of additional enteral nutritional support were eligible for the study. Results Median treatment duration in 32 pts was 18 [8-35] weeks. Response evaluation showed a benefit in 27 pts (84% in at least one parameter. 14 pts (43.7% improved or stabilised in all three parameters. The median ECM/BCM index was 1.7 [1.11-3.14] at start of APN and improved down to 1.5 [1.12-3.36] during therapy. The median BMI increased from 19.7 [14.4-25.9] to 20.5 [15.4-25.0]. The median phase angle improved by 10% from 3.6 [2.3-5.1] to 3.9 [2.2-5.1]. Conclusions We demonstrated the positive impact of APN on the assessed parameters, first of all the phase angle, and we observed at least a temporary benefit or stabilisation of the nutritional status in the majority of the investigated patients. Based on these findings we are currently investigating the impact of APN on survival in a larger patient cohort. Trial registration ClinicalTrials.gov Identifier: NCT00919659

  7. Acute Pancreatitis and Pancreatic Cancer Risk: A Nationwide Matched-cohort Study in Denmark

    DEFF Research Database (Denmark)

    Kirkegård, Jakob; Cronin Fenton, Deirdre; Heide-Jørgensen, Uffe

    2018-01-01

    . Pancreatic cancer risk was expressed as hazard ratios (HRs) with 95% CIs, calculated using the Cox proportional hazards model. Cox models were stratified by age, sex, and year of pancreatitis diagnosis and adjusted for alcohol- and smoking-related conditions, and Charlson Comorbidity Index score. Results We...... included 41,669 patients diagnosed with incident acute pancreatitis and 208,340 comparison individuals. Patients with acute pancreatitis had an increased risk of pancreatic cancer compared with the age- and sex-matched general population throughout the follow-up period. The risk decreased over time......Background & Aims Acute pancreatitis may be a risk factor for pancreatic cancer. However, findings from studies on this association are conflicting. We investigated the association between acute pancreatitis and increased risk of pancreatic cancer. Methods We conducted a nationwide, population...

  8. Diagnostic Management of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dabizzi, Emanuele [Division of Gastroenterology and Hepatology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, Florida 32224 (United States); Assef, Mauricio Saab [Faculdade de Ciências Médicas da Santa Casa de São Paulo, Rua Dr. Cesário Motta Jr. #61 Cep: 01221-020, São Paulo (Brazil); Raimondo, Massimo, E-mail: raimondo.massimo@mayo.edu [Division of Gastroenterology and Hepatology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, Florida 32224 (United States)

    2011-01-31

    Pancreatic cancer is one of the most deadly solid tumors, with an overall 5-year survival rate of less than 5%. Due to a non-specific clinical presentation, it is often diagnosed at an advanced stage and is rarely amenable for curative treatment. Therefore early diagnosis and appropriate staging are still essential to define the best care and to improve patient survival. Several imaging modalities are currently available for the evaluation of pancreatic cancer. This review focuses on different techniques and discusses the diagnostic management of patients with pancreatic cancer. This review was conducted utilizing Pubmed and was limited to papers published within the last 5 years. The search key words pancreatic cancer, pancreatic adenocarcinoma, pancreatic tumors, diagnosis, radiology, imaging, nuclear imaging, endoscopy, endoscopic ultrasound and biochemical markers were used.

  9. Diagnostic Management of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Dabizzi, Emanuele; Assef, Mauricio Saab; Raimondo, Massimo

    2011-01-01

    Pancreatic cancer is one of the most deadly solid tumors, with an overall 5-year survival rate of less than 5%. Due to a non-specific clinical presentation, it is often diagnosed at an advanced stage and is rarely amenable for curative treatment. Therefore early diagnosis and appropriate staging are still essential to define the best care and to improve patient survival. Several imaging modalities are currently available for the evaluation of pancreatic cancer. This review focuses on different techniques and discusses the diagnostic management of patients with pancreatic cancer. This review was conducted utilizing Pubmed and was limited to papers published within the last 5 years. The search key words pancreatic cancer, pancreatic adenocarcinoma, pancreatic tumors, diagnosis, radiology, imaging, nuclear imaging, endoscopy, endoscopic ultrasound and biochemical markers were used

  10. Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Kirkegård, Jakob; Mortensen, Frank Viborg; Cronin-Fenton, Deirdre

    2017-09-01

    Chronic pancreatitis is a putative risk factor for pancreatic cancer. The aim of this study was to examine the magnitude and temporality of this association. We searched MEDLINE and EMBASE for observational studies investigating the association between chronic pancreatitis and pancreatic cancer. We computed overall effect estimates (EEs) with associated 95% confidence intervals (CIs) using a random-effects meta-analytic model. The EEs were stratified by length of follow-up from chronic pancreatitis diagnosis to pancreatic cancer (lag period). Robustness of the results was examined in sensitivity analyses. We identified 13 eligible studies. Pooled EEs for pancreatic cancer in patients with chronic pancreatitis were 16.16 (95% CI: 12.59-20.73) for patients diagnosed with pancreatic cancer within 2 years from their chronic pancreatitis diagnosis. The risk of pancreatic cancer in patients with chronic pancreatitis decreased when the lag period was increased to 5 years (EE: 7.90; 95% CI: 4.26-14.66) or a minimum of 9 years (EE: 3.53; 95% CI: 1.69-7.38). In conclusion, chronic pancreatitis increases the risk of pancreatic cancer, but the association diminishes with long-term follow-up. Five years after diagnosis, chronic pancreatitis patients have a nearly eight-fold increased risk of pancreatic cancer. We suggest that common practice on inducing a 2-year lag period in these studies may not be sufficient. We also recommend a close follow-up in the first years following a diagnosis of chronic pancreatitis to avoid overlooking a pancreatic cancer.

  11. Diet and Pancreatic Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Ilaria Casari

    2015-11-01

    Full Text Available Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer.

  12. Drugs Approved for Pancreatic Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for pancreatic cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  13. Current status and progress of pancreatic cancer in China.

    Science.gov (United States)

    Lin, Quan-Jun; Yang, Feng; Jin, Chen; Fu, De-Liang

    2015-07-14

    Cancer is currently one of the most important public health problems in the world. Pancreatic cancer is a fatal disease with poor prognosis. As in most other countries, the health burden of pancreatic cancer in China is increasing, with annual mortality rates almost equal to incidence rates. The increasing trend of pancreatic cancer incidence is more significant in the rural areas than in the urban areas. Annual diagnoses and deaths of pancreatic cancer in China are now beyond the number of cases in the United States. GLOBOCAN 2012 estimates that cases in China account for 19.45% (65727/337872) of all newly diagnosed pancreatic cancer and 19.27% (63662/330391) of all deaths from pancreatic cancer worldwide. The population's growing socioeconomic status contributes to the rapid increase of China's proportional contribution to global rates. Here, we present an overview of control programs for pancreatic cancer in China focusing on prevention, early diagnosis and treatment. In addition, we describe key epidemiological, demographic, and socioeconomic differences between China and developed countries. Facts including no nationwide screening program for pancreatic cancer, delay in early detection resulting in a late stage at presentation, lack of awareness of pancreatic cancer in the Chinese population, and low investment compared with other cancer types by government have led to backwardness in China's pancreatic cancer diagnosis and treatment. Finally, we suggest measures to improve health outcomes of pancreatic cancer patients in China.

  14. Pancreatic Metastasis from Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Julian Jacob

    2010-01-01

    Full Text Available The pancreas is an unusual location for metastases from other primary cancers. Rarely, pancreatic metastases from kidney or colorectal cancers have been reported. However, a variety of other cancers may also spread to the pancreas. We report an exceptional case of pancreatic metastasis from prostate cancer. Differences in management between primary and secondary pancreatic tumors make recognition of metastases to the pancreas an objective of first importance. Knowledge of unusual locations for metastatic spread will reduce diagnostic delay and lead to a timely delivery of an appropriate treatment.

  15. Assessment value of quantitative indexes of pancreatic CT perfusion scanning for malignant degree of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Jiang-Xia Lei

    2016-10-01

    Full Text Available Objective: To analyze the assessment value of the quantitative indexes of pancreatic CT perfusion scanning for malignant degree of pancreatic cancer. Methods: A total of 58 patients with space-occupying pancreatic lesions were divided into 20 patients with pancreatic cancer and 38 patients with benign pancreatic lesions after pancreatic CT perfusion. Patients with pancreatic cancer received palliative surgery, and the cancer tissue and para-carcinoma tissue specimens were collected during operation. The differences in pancreatic CT perfusion scanning parameter values and serum tumor marker levels were compared between patients with pancreatic cancer and patients with benign pancreatic lesions, mRNA expression levels of malignant molecules in pancreatic cancer tissue and para-carcinoma tissue were further determined, and the correlation between pancreatic CT perfusion scanning parameter values and malignant degree of pancreatic cancer was analyzed. Results: CT perfusion scanning BF, BV and Per values of patients with pancreatic cancer were lower than those of patients with benign pancreatic lesions; serum CA19-9, CEA, CA125 and CA242 levels were higher than those of patients with benign pancreatic lesions (P<0.05; mRNA expression levels of Bcl-2, Bcl-xL and survivin in pancreatic cancer tissue samples were higher than those in paracarcinoma tissue samples, and mRNA expression levels of P53 and Bax were lower than those in para-carcinoma tissue samples (P<0.05; CT perfusion scanning parameters BF, BV and Per values of patients with pancreatic cancer were negatively correlated with CA19-9, CEA, CA125 and CA242 levels in serum as well as mRNA expression levels of Bcl-2, Bcl-xL and survivin in pancreatic cancer tissue, and positively correlated with mRNA expression levels of P53 and Bax in pancreatic cancer tissue (P<0.05. Conclusions: Pancreatic CT perfusion scanning is a reliable way to judge the malignant degree of pancreatic cancer and plays a

  16. Patterns of Radiotherapy Practice for Pancreatic Cancer in Japan: Results of the Japanese Radiation Oncology Study Group (JROSG) Survey

    International Nuclear Information System (INIS)

    Ogawa, Kazuhiko; Ito, Yoshinori; Karasawa, Katsuyuki; Ogawa, Yoshihiro; Onishi, Hiroshi; Kazumoto, Tomoko; Shibuya, Keiko; Shibuya, Hitoshi; Okuno, Yoshishige; Nishino, Shigeo; Ogo, Etsuyo; Uchida, Nobue; Karasawa, Kumiko; Nemoto, Kenji; Nishimura, Yasumasa

    2010-01-01

    Purpose: To determine the patterns of radiotherapy practice for pancreatic cancer in Japan. Methods and Materials: A questionnaire-based national survey of radiotherapy for pancreatic cancer treated between 2000 and 2006 was conducted by the Japanese Radiation Oncology Study Group (JROSG). Detailed information on 870 patients from 34 radiation oncology institutions was accumulated. Results: The median age of all patients was 64 years (range, 36-88), and 80.2% of the patients had good performance status. More than 85% of patients had clinical Stage T3-T4 disease, and 68.9% of patients had unresectable disease at diagnosis. Concerning radiotherapy (RT), 49.8% of patients were treated with radical external beam RT (EBRT) (median dose, 50.4 Gy), 44.4% of patients were treated with intraoperative RT (median dose, 25 Gy) with or without EBRT (median dose, 45 Gy), and 5.9% of patients were treated with postoperative radiotherapy (median dose, 50 Gy). The treatment field consisted of the primary tumor (bed) only in 55.6% of the patients. Computed tomography-based treatment planning and conformal RT was used in 93.1% and 83.1% of the patients treated with EBRT, respectively. Chemotherapy was used for 691 patients (79.4%; before RT for 66 patients; during RT for 531; and after RT for 364). Gemcitabine was the most frequently used drug, followed by 5-fluorouracil. Conclusion: This study describes the general patterns of RT practice for pancreatic cancer in Japan. Most patients had advanced unresectable disease, and radical EBRT, as well as intraoperative RT with or without EBRT, was frequently used. Chemotherapy with gemcitabine was commonly used in conjunction with RT during the survey period.

  17. Synchronous Onset of Breast and Pancreatic Cancers: Results of Germline and Somatic Genetic Analysis

    Directory of Open Access Journals (Sweden)

    Michael Castro

    2016-07-01

    Full Text Available Background: Synchronous cancers have occasionally been detected at initial diagnosis among patients with breast and ovarian cancer. However, simultaneous coexistence and diagnosis of breast and pancreas cancer has not previously been reported. Case Report: Paternal transmission of a germline BRCA2 mutation to a patient who was diagnosed at age 40 with locally advanced breast and pancreas cancer is presented. Somatic genomic analysis of both cancers with next-generation DNA sequencing confirmed the germline result and reported a variety of variants of unknown significance alterations, of which two were present in both the breast and pancreas cancers. Discussion: The possibility that genomic alterations could have been responsible for modulating the phenotypic or clinical expression of this rare presentation is considered. The authors call attention to the practice of privatizing the clinicogenetic information gained from genetic testing and call for health policy that will facilitate sharing in order to advance the outcomes of patients diagnosed with hereditary cancers.

  18. General Information about Pancreatic Cancer

    Science.gov (United States)

    ... overweight. Having a personal history of diabetes or chronic pancreatitis . Having a family history of pancreatic cancer or ... have not started treatment. Five types of standard treatment are used: Surgery ... Whipple procedure : A surgical procedure in which the head of the pancreas , ...

  19. Targeting Apoptosis Signaling in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Fulda, Simone

    2011-01-01

    The ability to escape apoptosis or programmed cell death is a hallmark of human cancers, for example pancreatic cancer. This can promote tumorigenesis, since too little cell death by apoptosis disturbs tissue homeostasis. Additionally, defective apoptosis signaling is the underlying cause of failure to respond to current treatment approaches, since therapy-mediated antitumor activity requires the intactness of apoptosis signaling pathways in cancer cells. Thus, the elucidation of defects in the regulation of apoptosis in pancreatic carcinoma can result in the identification of novel targets for therapeutic interference and for exploitation for cancer drug discovery

  20. Targeting Apoptosis Signaling in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fulda, Simone [Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Komturstr. 3a, 60528 Frankfurt (Germany)

    2011-01-11

    The ability to escape apoptosis or programmed cell death is a hallmark of human cancers, for example pancreatic cancer. This can promote tumorigenesis, since too little cell death by apoptosis disturbs tissue homeostasis. Additionally, defective apoptosis signaling is the underlying cause of failure to respond to current treatment approaches, since therapy-mediated antitumor activity requires the intactness of apoptosis signaling pathways in cancer cells. Thus, the elucidation of defects in the regulation of apoptosis in pancreatic carcinoma can result in the identification of novel targets for therapeutic interference and for exploitation for cancer drug discovery.

  1. Comparison of Pancreas Juice Proteins from Cancer Versus Pancreatitis Using Quantitative Proteomic Analysis

    Science.gov (United States)

    Chen, Ru; Pan, Sheng; Cooke, Kelly; Moyes, Kara White; Bronner, Mary P.; Goodlett, David R.; Aebersold, Ruedi; Brentnall, Teresa A.

    2008-01-01

    Objectives Pancreatitis is an inflammatory condition of the pancreas. However, it often shares many molecular features with pancreatic cancer. Biomarkers present in pancreatic cancer frequently occur in the setting of pancreatitis. The efforts to develop diagnostic biomarkers for pancreatic cancer have thus been complicated by the false-positive involvement of pancreatitis. Methods In an attempt to develop protein biomarkers for pancreatic cancer, we previously use quantitative proteomics to identify and quantify the proteins from pancreatic cancer juice. Pancreatic juice is a rich source of proteins that are shed by the pancreatic ductal cells. In this study, we used a similar approach to identify and quantify proteins from pancreatitis juice. Results In total, 72 proteins were identified and quantified in the comparison of pancreatic juice from pancreatitis patients versus pooled normal control juice. Nineteen of the juice proteins were overexpressed, and 8 were underexpressed in pancreatitis juice by at least 2-fold compared with normal pancreatic juice. Of these 27 differentially expressed proteins in pancreatitis, 9 proteins were also differentially expressed in the pancreatic juice from pancreatic cancer patient. Conclusions Identification of these differentially expressed proteins from pancreatitis juice provides useful information for future study of specific pancreatitis-associated proteins and to eliminate potential false-positive biomarkers for pancreatic cancer. PMID:17198186

  2. Conventional external irradiation alone as adjuvant treatment in resectable pancreatic cancer; Results of a prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Bosset, J.F.; Pavy, J.J.; Gillet, M.; Mantuon, G.; Pelissier, E.; Schraub, S. (Centre Hospitalier Universitaire, 25 - Besancon (France))

    1992-07-01

    Between 1/85 and 1/90, 14 consecutive patients were entered into a prospective study of conventional adjuvant post-operative external beam radiotherapy after complete resection for a pancreatic adeno-carcinoma. The surgical procedure was a Whipple resection in 9 patients, a distal pancrea-tectomy in 1 patient. There were 3 T[sub 1b], 8 T[sub 2] and 3 T[sub 3] tumors (UICC 1987); nodal involvement was present in 5 cases. The radiotherapy was delivered using a 4-field box technique with a 23 x MV photon beam. All patients received a total dose of 54 Gy to the tumor bed. The mean treated volume was 900 cm[sup 3]. Acute toxicities consisted mainly of weight loss (mean: 2 kg). Two patients had a grade 2 diarrhea and 2 patients a grade 2 gastritis. Late effects were minimal and only observed in 2 patients. The overall loco-regional recurrence (LR) rate was 50%. The median disease-free survival was 12 months, and the median survival was 23 months. This post-operative conventional radiotherapy treatment gives results that are comparable to the results of GITSG-adjuvant study using a combination of split-course radiotherapy and 5-fluorouracil (5-FU). (author). 46 refs.; 1 fig.; 1 tab.

  3. Molecular biology of pancreatic cancer.

    Science.gov (United States)

    Zavoral, Miroslav; Minarikova, Petra; Zavada, Filip; Salek, Cyril; Minarik, Marek

    2011-06-28

    In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syndromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

  4. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Hamada, Shin; Masamune, Atsushi; Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa; Hamada, Hirofumi; Kobune, Masayoshi; Satoh, Kennichi; Shimosegawa, Tooru

    2012-01-01

    Highlights: ► Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. ► Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. ► Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. ► Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. ► This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called “cancer stem cells”, within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the “stemness” of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.

  5. Vitamin D and pancreatic cancer

    OpenAIRE

    Stolzenberg-Solomon, Rachael Z.

    2008-01-01

    Sun exposure has been associated with lower death rates for pancreatic cancer in ecological studies. Skin exposure to solar ultra-violet B radiation induces cutaneous production of precursors to 25-hydroxy (OH) vitamin D (D) and is considered the primary contributor to vitamin D status in most populations. Pancreatic islet and duct cells express 25-(OH) D3-1α-hydroxylase that generates the biologically active 1,25-dihydroxy(OH)2 D form. Thus, 25(OH)D concentrations could affect pancreatic fun...

  6. Childhood body mass index and risk of adult pancreatic cancer

    DEFF Research Database (Denmark)

    Nogueira, Leticia; Stolzenberg-Solomon, Rachael; Gamborg, Michael

    2017-01-01

    incident pancreatic cancer cases from 1968-2012. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regressions. Results: During 8,207,015 person-years of follow-up, 1,268 pancreatic cancer cases were diagnosed. Childhood BMI z-scores at ages 7-13 years were......Background: Excess weight in adulthood is one of the few modifiable risk factors for pancreatic cancer, and height has associations as well. This leads to question whether body weight and height in childhood are associated with adult pancreatic cancer. Objective: To examine if childhood body mass...... from 7-13 years is positively and linearly associated with adult pancreatic cancer; the higher the BMI, the higher the risk. Excess childhood BMI may be indicative of processes initiated early in life that lead to this cancer. Prevention of childhood adiposity may decrease the burden of pancreatic...

  7. Pancreatic Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  8. Preliminary results on the feasibility of using ultrasound to monitor intrafractional motion during radiation therapy for pancreatic cancer

    International Nuclear Information System (INIS)

    Omari, Eenas A.; Erickson, Beth; Noid, George; Li, X. Allen; Ehlers, Christopher; Quiroz, Francisco; Cooper, David T.; Lachaine, Martin

    2016-01-01

    Purpose: Substantial intrafraction organ motion during radiation therapy (RT) for pancreatic cancer is well recognized as a major limiting factor for accurate delivery of RT. The aim of this work is to determine the feasibility of monitoring the intrafractional motion of the pancreas or surrounding structures using ultrasound for RT delivery. Methods: Transabdominal ultrasound (TAUS) and 4DCT data were acquired on ten pancreatic cancer patients during radiation therapy process in a prospective study. In addition, TAUS and MRI were collected for five healthy volunteers. The portal vein (PV) and the head of the pancreas (HP) along with other structures were contoured on these images. Volume changes, distance between the HP and PV, and motion difference between the HP and PV were measured to examine whether PV can be used as a motion surrogate for HP. TAUS images were acquired and processed using a research version of the Clarity autoscan ultrasound system (CAUS). Motion monitoring was performed with the ultrasound probe mounted on an arm fixed to the couch. Video segments of the monitoring sessions were captured. Results: On TAUS, PV is better visualized than HP. The measured mean volume deviation for all patients for the HP and PV was 1.4 and 0.6 ml, respectively. The distance between the HP and PV was close to a constant with 0.22 mm mean deviation throughout the ten breathing phases. The mean of the absolute motion difference for all patients was 1.7 ± 0.8 mm in LR, 1.5 ± 0.5 mm in AP, and 2.3 ± 0.7 mm in SI, suggesting that the PV is a good surrogate for HP motion estimation. By using this surrogate, the HP motion tracking using TAUS was demonstrated. Conclusions: Large intrafractional organ motion due to respiratory and/or bowel motion is a limiting factor in administering curative radiation doses to pancreatic tumors. The authors investigate the use of real-time ultrasound to track pancreas motion. Due to the poor visibility of the pancreas head on an

  9. Preliminary results on the feasibility of using ultrasound to monitor intrafractional motion during radiation therapy for pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Omari, Eenas A.; Erickson, Beth; Noid, George; Li, X. Allen, E-mail: ali@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 (United States); Ehlers, Christopher; Quiroz, Francisco [Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 (United States); Cooper, David T.; Lachaine, Martin [Elekta Ltd., Montreal, Québec H3A 2J5 (Canada)

    2016-09-15

    Purpose: Substantial intrafraction organ motion during radiation therapy (RT) for pancreatic cancer is well recognized as a major limiting factor for accurate delivery of RT. The aim of this work is to determine the feasibility of monitoring the intrafractional motion of the pancreas or surrounding structures using ultrasound for RT delivery. Methods: Transabdominal ultrasound (TAUS) and 4DCT data were acquired on ten pancreatic cancer patients during radiation therapy process in a prospective study. In addition, TAUS and MRI were collected for five healthy volunteers. The portal vein (PV) and the head of the pancreas (HP) along with other structures were contoured on these images. Volume changes, distance between the HP and PV, and motion difference between the HP and PV were measured to examine whether PV can be used as a motion surrogate for HP. TAUS images were acquired and processed using a research version of the Clarity autoscan ultrasound system (CAUS). Motion monitoring was performed with the ultrasound probe mounted on an arm fixed to the couch. Video segments of the monitoring sessions were captured. Results: On TAUS, PV is better visualized than HP. The measured mean volume deviation for all patients for the HP and PV was 1.4 and 0.6 ml, respectively. The distance between the HP and PV was close to a constant with 0.22 mm mean deviation throughout the ten breathing phases. The mean of the absolute motion difference for all patients was 1.7 ± 0.8 mm in LR, 1.5 ± 0.5 mm in AP, and 2.3 ± 0.7 mm in SI, suggesting that the PV is a good surrogate for HP motion estimation. By using this surrogate, the HP motion tracking using TAUS was demonstrated. Conclusions: Large intrafractional organ motion due to respiratory and/or bowel motion is a limiting factor in administering curative radiation doses to pancreatic tumors. The authors investigate the use of real-time ultrasound to track pancreas motion. Due to the poor visibility of the pancreas head on an

  10. Engineered T cells for pancreatic cancer treatment

    Science.gov (United States)

    Katari, Usha L; Keirnan, Jacqueline M; Worth, Anna C; Hodges, Sally E; Leen, Ann M; Fisher, William E; Vera, Juan F

    2011-01-01

    Objective Conventional chemotherapy and radiotherapy produce marginal survival benefits in pancreatic cancer, underscoring the need for novel therapies. The aim of this study is to develop an adoptive T cell transfer approach to target tumours expressing prostate stem cell antigen (PSCA), a tumour-associated antigen that is frequently expressed by pancreatic cancer cells. Methods Expression of PSCA on cell lines and primary tumour samples was confirmed by immunohistochemistry. Healthy donor- and patient-derived T cells were isolated, activated in vitro using CD3/CD28, and transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) targeting PSCA. The ability of these cells to kill tumour cells was analysed by chromium-51 (Cr51) release. Results Prostate stem cell antigen was expressed on >70% of the primary tumour samples screened. Activated, CAR-modified T cells could be readily generated in clinically relevant numbers and were specifically able to kill PSCA-expressing pancreatic cancer cell lines with no non-specific killing of PSCA-negative target cells, thus indicating the potential efficacy and safety of this approach. Conclusions Prostate stem cell antigen is frequently expressed on pancreatic cancer cells and can be targeted for immune-mediated destruction using CAR-modified, adoptively transferred T cells. The safety and efficacy of this approach indicate that it deserves further study and may represent a promising novel treatment for patients with pancreatic cancer. PMID:21843265

  11. Environmental risk factors for chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Nitsche, Claudia; Simon, Peter; Weiss, F Ulrich; Fluhr, Gabriele; Weber, Eckhard; Gärtner, Simone; Behn, Claas O; Kraft, Matthias; Ringel, Jörg; Aghdassi, Ali; Mayerle, Julia; Lerch, Markus M

    2011-01-01

    Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke. Copyright © 2011 S. Karger AG, Basel.

  12. [Treatments for Pancreatic Cancer with Oligometastasis].

    Science.gov (United States)

    Furuse, Junji

    2017-10-01

    Pancreatic cancer, adenocarcinoma, generally rapidly progresses, and if a metastatic lesion is detected, chemotherapy is applied even in solitary metastasis. However, surgical resection for solitary metastasis have been reported to achieve long survival in some pancreatic cancer patients. In a prospective study of surgery for hepatic and lymph node oligometastasis of pancreatic cancer, long survival of 5 years or more was reported around 10%. Furthermore, longer survival and fewer rerecurrence were achieved with surgery in lung metastasis than in liver metastasis and loco-regional recurrence. Although there has been no establishment of concept or no consensus of treatment strategy for oligometastasis in pancreatic cancer, some patients with pancreatic cancer have long disease-free survival by surgery for oligometastasis. A population of pancreatic cancer patients who have benefits of surgery for oligometastasis should be identified, and it is necessary to establish treatments for oligometastasis as standard treatments in pancreatic cancer.

  13. Are meat and heme iron intake associated with pancreatic cancer? Results from the NIH-AARP Diet and Health Cohort

    Science.gov (United States)

    Taunk, Pulkit; Hecht, Eric; Stolzenberg-Solomon, Rachael

    2015-01-01

    Several studies on pancreatic cancer have reported significant positive associations for intake of red meat but null associations for heme iron. We assessed total, red, white, and processed meat intake, meat cooking methods and doneness, and heme iron and mutagen intake in relation to pancreatic cancer in the NIH-AARP Diet and Health Study cohort. 322,846 participants (187,265 men; 135,581 women) successfully completed and returned the food frequency questionnaire between 1995–1996. After a mean follow-up of 9.2 years (up to 10.17 years), 1,417 individuals (895 men, 522 women) developed exocrine pancreatic cancer. Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI), and trends were calculated using the median value of each quantile. Models incorporated age as the time metric and were adjusted for smoking history, BMI, self-reported diabetes, and energy-adjusted saturated fat. Pancreatic cancer risk significantly increased with intake of total meat (Q5 vs. Q1 HR=1.20, 95% CI 1.02–1.42, p-trend=0.03), red meat (HR=1.22, 95% CI 1.01–1.48, p-trend=0.02), high-temperature cooked meat (HR=1.21, 95% CI 1.00–1.45, p-trend=0.02), grilled/barbequed meat (HR=1.24, 95% CI 1.03–1.50, p-trend=0.007), well/very well done meat (HR=1.32, 95% CI 1.10–1.58, p-trend = 0.005), and heme iron from red meat (Q4 vs. Q1 HR=1.21, 95% CI 1.01–1.45, p-trend=0.04). When stratified by sex, these associations remained significant in men but not women except for white meat intake in women (HR = 1.33, 95% CI 1.02–1.74, p-trend = 0.04). Additional studies should confirm our findings that consuming heme iron from red meat increases pancreatic cancer risk. PMID:26666579

  14. Endoscopic Palliation for Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Mihir Bakhru

    2011-04-01

    Full Text Available Pancreatic cancer is devastating due to its poor prognosis. Patients require a multidisciplinary approach to guide available options, mostly palliative because of advanced disease at presentation. Palliation including relief of biliary obstruction, gastric outlet obstruction, and cancer-related pain has become the focus in patients whose cancer is determined to be unresectable. Endoscopic stenting for biliary obstruction is an option for drainage to avoid the complications including jaundice, pruritus, infection, liver dysfunction and eventually failure. Enteral stents can relieve gastric obstruction and allow patients to resume oral intake. Pain is difficult to treat in cancer patients and endoscopic procedures such as pancreatic stenting and celiac plexus neurolysis can provide relief. The objective of endoscopic palliation is to primarily address symptoms as well improve quality of life.

  15. New insights into pancreatic cancer biology.

    Science.gov (United States)

    Hidalgo, M

    2012-09-01

    Pancreatic cancer remains a devastating disease. Over the last few years, there have been important advances in the molecular and biological understanding of pancreatic cancer. This included understanding of the genomic complexity of the disease, the role of pancreatic cancer stem cells, the relevance of the tumor microenvironment, and the unique metabolic adaptation of pancreas cancer cells to obtain nutrients under hypoxic environment. In this paper, we review the most salient developments in these few areas.

  16. Incidence of and risk factors for developing pancreatic cancer in patients with chronic pancreatitis.

    Science.gov (United States)

    Kudo, Yujin; Kamisawa, Terumi; Anjiki, Hajime; Takuma, Kensuke; Egawa, Naoto

    2011-01-01

    Pancreatic cancer sometimes occurs during the course of chronic pancreatitis. This study aimed to identify risk factors for developing pancreatic cancer associated with chronic pancreatitis. The incidence of pancreatic cancer developing in 218 patients with chronic pancreatitis and clinical features of the chronic pancreatitis patients who developed pancreatic cancer were studied. Nine patients developed pancreatic cancer. Average period from the diagnosis of chronic pancreatitis to the diagnosis of pancreatic cancer was 9.6 years. All pancreatic cancers were diagnosed at an advanced stage. Only 2 patients had been followed-up periodically. There were no significant differences between chronic pancreatitis patients who developed pancreatic cancer and those who did not in male/female ratio (3.5 vs. 8), average age on diagnosis (65.0 vs. 56.5), alcoholic/non-alcoholic chronic pancreatitis (1.6 vs. 2.6), smoking habits (62.5% vs. 70.7%), diabetes mellitus (77.8% vs. 54.4%), and continued alcohol drinking (37.5% vs. 53.1%). Over the period examined, 4% of chronic pancreatitis patients developed pancreatic cancer. Sex ratio, onset age, etiology, smoking habits, diabetes mellitus, and continued alcohol drinking were not significant risk factors for developing pancreatic cancer in chronic pancreatitis patients. Periodic follow-up due to the possibility of pancreatic cancer is necessary in chronic pancreatitis patients.

  17. Differential diagnosis of focal pancreatitis and pancreatic cancer

    NARCIS (Netherlands)

    van Gulik, T. M.; Moojen, T. M.; van Geenen, R.; Rauws, E. A.; Obertop, H.; Gouma, D. J.

    1999-01-01

    The differentiation of focal, chronic pancreatitis (CP) and pancreatic cancer (PAC) poses a diagnostic dilemma. Both conditions may present with the same symptoms and signs. The complexity of differential diagnosis is enhanced because PAC is frequently associated with secondary inflammatory changes

  18. Pancreatic cancer stromal biology and therapy

    Science.gov (United States)

    Xie, Dacheng; Xie, Keping

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies. Significant progresses have been made in understanding of pancreatic cancer pathogenesis, including appreciation of precursor lesions or premalignant pancreatic intraepithelial neoplasia (PanINs), description of sequential transformation from normal pancreatic tissue to invasive pancreatic cancer and identification of major genetic and epigenetic events and the biological impact of those events on malignant behavior. However, the currently used therapeutic strategies targeting tumor epithelial cells, which are potent in cell culture and animal models, have not been successful in the clinic. Presumably, therapeutic resistance of pancreatic cancer is at least in part due to its drastic desmoplasis, which is a defining hallmark for and circumstantially contributes to pancreatic cancer development and progression. Improved understanding of the dynamic interaction between cancer cells and the stroma is important to better understanding pancreatic cancer biology and to designing effective intervention strategies. This review focuses on the origination, evolution and disruption of stromal molecular and cellular components in pancreatic cancer, and their biological effects on pancreatic cancer pathogenesis. PMID:26114155

  19. Pancreatic cancer clinical trials and accrual in the United States.

    Science.gov (United States)

    Hoos, William A; James, Porsha M; Rahib, Lola; Talley, Anitra W; Fleshman, Julie M; Matrisian, Lynn M

    2013-09-20

    Pancreatic cancer clinical trials open in the United States and their accrual were examined to identify opportunities to accelerate progress in the treatment of pancreatic cancer. Pancreatic cancer-specific clinical trials open in the United States in the years 2011 and 2012 were obtained from the Pancreatic Cancer Action Network database. Accrual information was obtained from trial sponsors. The portfolio of pancreatic cancer clinical trials identified by type (adenocarcinoma or neuroendocrine), phase, disease stage, and treatment approach is reported. More than half of trials for patients with pancreatic ductal adenocarcinoma applied biologic insights to new therapeutic approaches, and 38% focused on optimization of radiation or chemotherapy delivery or regimens. In 2011, pancreatic cancer trials required total enrollment of 11,786 patients. Actual accrual to 93.2% of trials was 1,804 patients, an estimated 4.57% of the patients with pancreatic cancer alive in that year. The greatest need was for patients with resectable cancer. Trials open in 2011 enrolled an average of 15% of their total target accrual. Physician recommendations greatly influenced patients' decision to enroll or not enroll onto a clinical trial. Matching to a clinical trial within a 50-mile radius and identifying trials for recurrent/refractory disease were documented as challenges for patient accrual. Overall trial enrollment indicates that pancreatic cancer trials open in 2011 would require 6.7 years on average to complete accrual. These results suggest that harmonizing patient supply and demand for clinical trials is required to accelerate progress toward improving survival in pancreatic cancer.

  20. Is Pancreatic Cancer Hereditary?

    Science.gov (United States)

    ... for BRCA2 gene mutations. We advise that people speak with a trained cancer genetics counselor before undergoing genetic ... and PALB2 gene mutations. We advise that people speak with a trained cancer genetics counselor before undergoing genetic ...

  1. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer. Results of the first prospective randomized phase II trial

    International Nuclear Information System (INIS)

    Golcher, Henriette; Merkel, Susanne; Hohenberger, Werner; Brunner, Thomas B.; Witzigmann, Helmut; Marti, Lukas; Bechstein, Wolf-Otto; Bruns, Christiane; Jungnickel, Henry; Schreiber, Stefan; Grabenbauer, Gerhard G.; Meyer, Thomas; Fietkau, Rainer

    2015-01-01

    In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging. Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS). The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48 % (A) and 52 % (B, P = 0.81) and (y)pN0 was 30 % (A) vs. 39 % (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79). This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543. (orig.) [de

  2. Laboratory diagnosis of pancreatitis and cancer of the pancreas

    International Nuclear Information System (INIS)

    Degtyareva, I.I.; Gajsenko, A.V.; Putseva, N.M.

    1989-01-01

    The content of fibrin fibrinogen splitting products (FSP), radioimmune trypsine, C-peptide and carbohydrate antigen (CA) 19-9 in the blood of 82 patients with acute pancreatitis (edematous and hemorrhagic), and chronic recurrent pancreatitis at the stage of exacerbation, 42 patients with chronic pancreatitis, 34 patients with cancer of the pancreas (stages 3-4) and 22 healthy persons were studied. Results indicate a high diagnostic value of determination FSP, trypsin and C-peptide in patients with acute pancreatitis and chronic recurring pancreatitis at the stage of exacerbation, trypsin and C-peptide in patients with chronic pancreatitis associated with severe exocrinous insufficiency of the pancreas, KA 19-9 in patients with cancer of the pancreas

  3. Biomarkers and Targeted Therapy in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Fataneh Karandish

    2016-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC constitutes 90% of pancreatic cancers. PDAC is a complex and devastating disease with only 1%–3% survival rate in five years after the second stage. Treatment of PDAC is complicated due to the tumor microenvironment, changing cell behaviors to the mesenchymal type, altered drug delivery, and drug resistance. Considering that pancreatic cancer shows early invasion and metastasis, critical research is needed to explore different aspects of the disease, such as elaboration of biomarkers, specific signaling pathways, and gene aberration. In this review, we highlight the biomarkers, the fundamental signaling pathways, and their importance in targeted drug delivery for pancreatic cancers.

  4. Biomarkers and Targeted Therapy in Pancreatic Cancer.

    Science.gov (United States)

    Karandish, Fataneh; Mallik, Sanku

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of pancreatic cancers. PDAC is a complex and devastating disease with only 1%-3% survival rate in five years after the second stage. Treatment of PDAC is complicated due to the tumor microenvironment, changing cell behaviors to the mesenchymal type, altered drug delivery, and drug resistance. Considering that pancreatic cancer shows early invasion and metastasis, critical research is needed to explore different aspects of the disease, such as elaboration of biomarkers, specific signaling pathways, and gene aberration. In this review, we highlight the biomarkers, the fundamental signaling pathways, and their importance in targeted drug delivery for pancreatic cancers.

  5. Diagnosis and treatment of pancreatic cancer. Oncology overview

    International Nuclear Information System (INIS)

    1982-09-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Radiological diagnosis of pancreatic cancer; Biopsy and cytology in the diagnosis of pancreatic cancer; Pathology and morphology of pancreatic cancer; Staging and prognosis of pancreatic cancer; Biological and immunological markers in the diagnosis of pancreatic cancer; Surgical treatment of pancreatic cancer; Drug therapy of pancreatic cancer; Radiation therapy of pancreatic cancer; Selected studies on the epidemiology of pancreatic cancer; Clinical correlates and syndromes associated with pancreatic neoplasia

  6. Ultrasound-enhanced nanotherapy of pancreatic cancer

    Science.gov (United States)

    Rapoport, N.; Nam, K.-H.; Christensen, D. A.; Kennedy, A. M.; Shea, J. E.; Scaife, C. L.

    2010-03-01

    The paper reports in vivo results of ultrasonic nanotherapy of orthotopically grown pancreatic cancer. Phase-shift paclitaxel (PTX) loaded perfluoropentane (PFP) nanoemusions combined with tumor-directed ultrasound have been used with a considerable success for tumor-targeted chemotherapy of gemcitabin (GEM)-refractory pancreatic cancer (PC). The GEM-resistant pancreatic cancer proved sensitive to treatment by a micellar PTX formulation Genexol PM (GEN) andor nanodroplet PTX formulation ndGEN. Due to increased permeability of tumor blood vessels, drug-loaded nanodroplets accumulated in the tumor via passive targeting, which was confirmed by ultrasound imaging. Nanodroplets converted into microbubbles in situ under the action of tumor-directed 1-MHz therapeutic ultrasound. The strongest therapeutic effect was observed for the combination therapy by PTX-loaded nanodroplets, GEM and ultrasound (ndGEN+GEM+ultrasound). This combination therapy resulted in a spectacular tumor regression and in some cases complete tumor resolution. Moreover, formation of metastases was dramatically decreased and ascitis generation was completely suppressed. However for all animal groups, local tumor recurrence was observed after the completion of the treatment indicating that some cancer cells survived the treatment. The recurrent tumors proved more resistant to the repeated therapy than initial tumors.

  7. Apoptosis: Targets in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Kalthoff Holger

    2003-01-01

    Full Text Available Abstract Pancreatic adenocarcinoma is characterized by poor prognosis, because of late diagnosis and lack of response to chemo- and/or radiation therapies. Resistance to apoptosis mainly causes this insensitivity to conventional therapies. Apoptosis or programmed cell death is a central regulator of tissue homeostasis. Certain genetic disturbances of apoptotic signaling pathways have been found in carcinomas leading to tumor development and progression. In the past few years, the knowledge about the complex pathways of apoptosis has strongly increased and new therapeutic approaches based on this knowledge are being developed. This review will focus on the role of apoptotic proteins contributing to pancreatic cancer development and progression and will demonstrate possible targets to influence this deadly disease.

  8. Chronic alcohol drinking: Liver and pancreatic cancer?

    Science.gov (United States)

    Zakhari, Samir

    2015-09-01

    Cancer is a multifactorial disease that results from complex interactions of numerous risk factors - genetic and environmental - over time, eventually leading to the diseased phenotypes. Thus, while epidemiological studies can point to risk factors, they cannot determine cause and effect relationships, and are unable to give biological and clinical insights into carcinogenesis. The link between any risk factor and carcinogenesis needs to be validated in experimental models. This is particularly true in epidemiological studies on alcohol consumption and its consequences. While there is no doubt that heavy alcohol consumption has devastating health effects, the inconsistencies in alcohol-related epidemiological studies and cancer suffer from possible sources of the variability in outcomes, ranging from inaccuracy of self-report of consumption to the problem of correlating cancer that started decades earlier to current or recent alcohol consumption. To further study the interactions between alcohol and cancer, the use of "Molecular Pathological Epidemiology" (MPE) advocated by Ogino et al. for dissecting the interplay between etiological factors, cellular and molecular characteristics, and disease progression in cancer is appropriate. MPE does not consider cancer as a single entity, rather it integrates analyses of epidemiological studies with the macroenvironment and molecular and microenvironment. This approach allows investigating the relationships between potential etiological agents and cancer based on molecular signatures. More research is needed to fully elucidate the link between heavy alcohol consumption and pancreatic cancer, and to further investigate the roles of acetaldehyde and FAEEs in pancreatic carcinogenesis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Evaluation of Treatment Patterns and Survival Outcomes in Elderly Pancreatic Cancer Patients: A Surveillance, Epidemiology, and End Results-Medicare Analysis.

    Science.gov (United States)

    Shaib, Walid L; Jones, Jeb S; Goodman, Michael; Sarmiento, Juan M; Maithel, Shishir K; Cardona, Kenneth; Kane, Sujata; Wu, Christina; Alese, Olatunji B; El-Rayes, Bassel F

    2018-02-14

    Management of pancreatic cancer (PC) in elderly patients is unknown; clinical trials exclude patients with comorbidities and those of extreme age. This study evaluated treatment patterns and survival outcomes in elderly PC patients using linked Surveillance, Epidemiology, and End Results (SEER) and Medicare data. Histology codes 8140, 8500, 8010, 8560, 8490, 8000, 8260, 8255, 8261, 8263, 8020, 8050, 8141, 8144, 8210, 8211, or 8262 in Medicare Parts A and B were identified. Data regarding demographic, characteristics, treatments, and vital status between 1998 and 2009 were collected from the SEER. Determinants of treatment receipt and overall survival were examined using logistic regression and Cox proportional hazards models, respectively. A total of 5,975 patients met inclusion. The majority of patients were non-Hispanic whites (85%) and female (55%). Most cases presented with locoregional stage disease (74%); 41% received only chemotherapy, 30% chemotherapy and surgery, 10% surgery alone, 3% radiation, and 16% no cancer-directed therapy. Patients with more advanced cancer, older age, and those residing in areas of poverty were more likely to receive no treatment. Among patients 66-74 years of age with locoregional disease, surgery alone (hazard ratio [HR] = 0.54; 95% confidence interval [CI]: 0.39-0.74) and surgery in combination with chemotherapy (HR = 0.69; 95% CI: 0.53-0.91) showed survival benefit as compared with the no treatment group. Among patients ≥75 years of age with locoregional disease, surgery alone (HR = 2.04; 95% CI: 0.87-4.8) or in combination with chemotherapy (HR = 1.59; 95% CI: 0.87-2.91) was not associated with better survival. Treatment modality and survival differs by age and stage. Low socioeconomic status appears to be a major barrier to the receipt of PC therapy among Medicare patients. Elderly patients with cancer are under-represented on clinical trials and usually have comorbid illnesses. The management of elderly

  10. Family history of cancer and risk of Pancreatic Cancer: A Pooled Analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

    Science.gov (United States)

    Jacobs, Eric J.; Chanock, Stephen J.; Fuchs, Charles S.; LaCroix, Andrea; McWilliams, Robert R.; Steplowski, Emily; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gross, Myron; Helzlsouer, Kathy; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Allen, Naomi E.; Amundadottir, Laufey; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Canzian, Federico; Clipp, Sandra; Dorronsoro, Miren; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Jacobs, Kevin B.; Jenab, Mazda; Kraft, Peter; Kooperberg, Charles; Lynch, Shannon M.; Sund, Malin; Mendelsohn, Julie B.; Mouw, Tracy; Newton, Christina C.; Overvad, Kim; Palli, Domenico; Peeters, Petra H.M.; Rajkovic, Aleksandar; Shu, Xiao-Ou; Thomas, Gilles; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wactawski-Wende, Jean; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne

    2010-01-01

    A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e. ovarian, breast, and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of five types of cancer (pancreas, prostate, ovarian, breast, and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe, and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling, or child was associated with increased risk of pancreatic cancer (multivariate-adjusted OR = 1.76, 95% CI 1.19–2.61). A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI 1.12–1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI 0.52–1.31), breast cancer (OR = 1.21, 95% CI 0.97–1.51), or colorectal cancer (OR = 1.17, 95% CI 0.93–1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study. PMID:20049842

  11. Surgery for chronic pancreatitis decreases the risk for pancreatic cancer: a multicenter retrospective analysis.

    Science.gov (United States)

    Ueda, Junji; Tanaka, Masao; Ohtsuka, Takao; Tokunaga, Shoji; Shimosegawa, Tooru

    2013-03-01

    Chronic pancreatitis is suggested to be one of the risk factors for the development of pancreatic cancer. The aim of this study was to confirm the high incidence of pancreatic cancer in patients with chronic pancreatitis in Japan and to determine the factors associated with the risk for pancreatic cancer in patients with chronic pancreatitis. The working group of the Research Committee of Intractable Disease supported by the Ministry of Health, Labour and Welfare of Japan carried out a nationwide survey to investigate the relationship between chronic pancreatitis and pancreatic cancer. This retrospective study included patients diagnosed with chronic pancreatitis who had had at least 2 years of follow-up. They were contacted through 22 Japanese referral centers experienced in the management of chronic pancreatitis. The standardized incidence ratio (95 CI) of pancreatic cancer was 11.8 (7.1-18.4). The incidence of pancreatic cancer was significantly lower in patients who had received surgery for chronic pancreatitis than in those who had not undergone surgery (hazard ratio estimated by Cox regression 0.11; 95% CI, 0.0014-0.80; P = .03). Patients who continued to drink alcohol after diagnosis of chronic pancreatitis showed a significantly higher incidence of pancreatic cancer than those who stopped drinking after diagnosis of chronic pancreatitis (hazard ratio, 5.07; 95% CI, 1.13-22.73; P = .03). This study confirmed that chronic pancreatitis is an important risk factor for the development of pancreatic cancer in Japan. Patients who underwent surgery for the treatment of chronic pancreatitis had significantly lower incidences of pancreatic cancer. Surgery for chronic pancreatitis may inhibit the development of pancreatic cancer in patients with chronic pancreatitis. Copyright © 2013 Mosby, Inc. All rights reserved.

  12. Management of pancreatic cancer in the elderly.

    Science.gov (United States)

    Higuera, Oliver; Ghanem, Ismael; Nasimi, Rula; Prieto, Isabel; Koren, Laura; Feliu, Jaime

    2016-01-14

    Currently, pancreatic adenocarcinoma mainly occurs after 60 years of age, and its prognosis remains poor despite modest improvements in recent decades. The aging of the population will result in a rise in the incidence of pancreatic adenocarcinoma within the next years. Thus, the management of pancreatic cancer in the elderly population is gaining increasing relevance. Older cancer patients represent a heterogeneous group with different biological, functional and psychosocial characteristics that can modify the usual management of this disease, including pharmacokinetic and pharmacodynamic changes, polypharmacy, performance status, comorbidities and organ dysfunction. However, the biological age, not the chronological age, of the patient should be the limiting factor in determining the most appropriate treatment for these patients. Unfortunately, despite the increased incidence of this pathology in older patients, there is an underrepresentation of these patients in clinical trials, and the management of older patients is thus determined by extrapolation from the results of studies performed in younger patients. In this review, the special characteristics of the elderly, the multidisciplinary management of localized and advanced ductal adenocarcinoma of the pancreas and the most recent advances in the management of this condition will be discussed, focusing on surgery, chemotherapy, radiation and palliative care.

  13. Preoperative biliary drainage for pancreatic cancer

    NARCIS (Netherlands)

    van Heek, N. T.; Busch, O. R.; van Gulik, T. M.; Gouma, D. J.

    2014-01-01

    This review is to summarize the current knowledge about preoperative biliary drainage (PBD) in patients with biliary obstruction caused by pancreatic cancer. Most patients with pancreatic carcinoma (85%) will present with obstructive jaundice. The presence of toxic substances as bilirubin and bile

  14. Epidermal Growth Factor Receptor in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Oliveira-Cunha, Melissa; Newman, William G.; Siriwardena, Ajith K.

    2011-01-01

    Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer

  15. Targeting Mcl-1 for Radiosensitization of Pancreatic Cancers

    Directory of Open Access Journals (Sweden)

    Dongping Wei

    2015-02-01

    Full Text Available In order to identify targets whose inhibition may enhance the efficacy of chemoradiation in pancreatic cancer, we previously conducted an RNAi library screen of 8,800 genes. We identified Mcl-1 (myeloid cell leukemia-1, an anti-apoptotic member of the Bcl-2 family, as a target for sensitizing pancreatic cancer cells to chemoradiation. In the present study we investigated Mcl-1 inhibition by either genetic or pharmacological approaches as a radiosensitizing strategy in pancreatic cancer cells. Mcl-1 depletion by siRNA produced significant radiosensitization in BxPC-3 and Panc-1 cells in association with Caspase-3 activation and PARP cleavage, but only minimal radiosensitization in MiaPaCa-2 cells. We next tested the ability of the recently identified, selective, small molecule inhibitor of Mcl-1, UMI77, to radiosensitize in pancreatic cancer cells. UMI77 caused dissociation of Mcl-1 from the pro-apoptotic protein Bak and produced significant radiosensitization in BxPC-3 and Panc-1 cells, but minimal radiosensitization in MiaPaCa-2 cells. Radiosensitization by UMI77 was associated with Caspase-3 activation and PARP cleavage. Importantly, UMI77 did not radiosensitize normal small intestinal cells. In contrast, ABT-737, an established inhibitor of Bcl-2, Bcl-XL, and Bcl-w, failed to radiosensitize pancreatic cancer cells suggesting the unique importance of Mcl-1 relative to other Bcl-2 family members to radiation survival in pancreatic cancer cells. Taken together, these results validate Mcl-1 as a target for radiosensitization of pancreatic cancer cells and demonstrate the ability of small molecules which bind the canonical BH3 groove of Mcl-1, causing displacement of Mcl-1 from Bak, to selectively radiosensitize pancreatic cancer cells.

  16. Association between allergies and risk of pancreatic cancer.

    Science.gov (United States)

    Cotterchio, Michelle; Lowcock, Elizabeth; Hudson, Thomas J; Greenwood, Celia; Gallinger, Steven

    2014-03-01

    Less than 10% of pancreatic cancer cases survive 5 years, yet its etiology is not well understood. Studies suggest allergies are associated with reduced pancreatic cancer risk. Our study collected additional information on allergies (including skin prick test results and differentiation of allergic/nonallergic asthma), and is the first to assess possible confounding by allergy medications. A population-based case-control study was designed to comprehensively assess the association between allergy and pancreatic cancer risk. Pancreas cancer cases were diagnosed during 2011 to 2012, and identified through the Ontario Cancer Registry (345 cases). Population-based controls were identified using random digit dialing and age/sex frequency matched to cases (1,285 controls). Questionnaires collected lifetime allergy history (type of allergy, age at onset, skin prick testing results), allergy medications, and established pancreas cancer risk factors. Logistic regression was used to estimate odd ratios and test potential confounders, including allergy medications. Hay fever was associated with a significant reduction in pancreatic cancer risk [AOR = 0.68; 95% confidence intervals (CI), 0.52-0.89], and reduction was greatest for those whose skin prick test was positive for hay fever allergens. No particular patterns were observed as regards age at onset and duration of allergy. Positive dust/mold allergy skin prick test and animal allergies were associated with a statistically significant reduced pancreatic cancer risk; AOR = 0.49; 95% CI, 0.31-0.78 and AOR = 0.68; 95% CI, 0.46-0.99, respectively. Asthma was not associated with pancreatic cancer risk. These findings support the growing body of evidence that suggests certain allergies are associated with reduced pancreatic cancer risk. ©2014 AACR.

  17. Screening Technologies for Target Identification in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Michl, Patrick, E-mail: michlp@med.uni-marburg.de; Ripka, Stefanie; Gress, Thomas; Buchholz, Malte [Department of Gastroenterology and Endocrinology, University Hospital, Philipps-University Marburg, Baldinger Strasse, D-35043 Marburg (Germany)

    2010-12-29

    Pancreatic cancer exhibits an extraordinarily high level of resistance to almost any kind of systemic therapy evaluated in clinical trials so far. Therefore, the identification of novel therapeutic targets is urgently required. High-throughput screens have emerged as an important tool to identify putative targets for diagnosis and therapy in an unbiased manner. More than a decade ago, microarray technology was introduced to identify differentially expressed genes in pancreatic cancer as compared to normal pancreas, chronic pancreatitis and other cancer types located in close proximity to the pancreas. In addition, proteomic screens have facilitated the identification of differentially secreted proteins in body fluids of pancreatic cancer patients, serving as possible biomarkers. Recently, RNA interference-based loss-of-function screens have been used to identify functionally relevant genes, whose knock-down has impact on pancreatic cancer cell viability, thereby representing potential new targets for therapeutic intervention. This review summarizes recent results of transcriptional, proteomic and functional screens in pancreatic cancer and discusses potentials and limitations of the respective technologies as well as their impact on future therapeutic developments.

  18. Screening Technologies for Target Identification in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Michl, Patrick; Ripka, Stefanie; Gress, Thomas; Buchholz, Malte

    2010-01-01

    Pancreatic cancer exhibits an extraordinarily high level of resistance to almost any kind of systemic therapy evaluated in clinical trials so far. Therefore, the identification of novel therapeutic targets is urgently required. High-throughput screens have emerged as an important tool to identify putative targets for diagnosis and therapy in an unbiased manner. More than a decade ago, microarray technology was introduced to identify differentially expressed genes in pancreatic cancer as compared to normal pancreas, chronic pancreatitis and other cancer types located in close proximity to the pancreas. In addition, proteomic screens have facilitated the identification of differentially secreted proteins in body fluids of pancreatic cancer patients, serving as possible biomarkers. Recently, RNA interference-based loss-of-function screens have been used to identify functionally relevant genes, whose knock-down has impact on pancreatic cancer cell viability, thereby representing potential new targets for therapeutic intervention. This review summarizes recent results of transcriptional, proteomic and functional screens in pancreatic cancer and discusses potentials and limitations of the respective technologies as well as their impact on future therapeutic developments

  19. Optimizing Adjuvant Therapy for Resected Pancreatic Cancer

    Science.gov (United States)

    In this clinical trial, patients with resected pancreatic head cancer will be randomly assigned to receive either gemcitabine with or without erlotinib for 5 treatment cycles. Patients who do not experience disease progression or recurrence will then be r

  20. Current radiotherapeutic approaches to pancreatic cancer

    International Nuclear Information System (INIS)

    Dobelbower, R.R. Jr.

    1981-01-01

    Adenocarcinoma of the pancreas is not a radioresistant neoplasm, as was once believed. The data now suggest that in some instances this cancer may be radiocurable. This fact seems to justify the risk of pancreatic biopsy even in the face of unresectable disease, for it is well known that many benign conditions imitate pancreatic cancer. Clinical benefit from radiation for pancreatic cancer treatment is dose related. Careful delineation of tumor margins, precision treatment planning, and precision dose delivery can minimize damage to adjacent normal tissues. Interstitial implantation and intraoperative electron beam therapy are being studied as methods of accurate dose delivery for pancreatic cancer. Fractionation studies and high LET studies are in embryonic stages. Combined modality regimens may have much to offer in terms of improved palliation and survival for patients with localized adenocarcinoma of the pancreas

  1. A diagnostic pitfall: pancreatic tuberculosis, not pancreatic cancer

    International Nuclear Information System (INIS)

    Samuel, D.O.; Mukhtar, A.A.M.; Philip, I.O.

    2013-01-01

    Abdominal tuberculosis (TB) is one of the most common forms of extra-pulmonary tuberculosis and is responsible for considerable morbidity and mortality globally. Tuberculosis can involve any part of the gastrointestinal tract from mouth to anus, the peritoneum, liver, spleen and the pancreatobiliary system. The occurrence of abdominal TB is independent of pulmonary disease in most patients, with a reported incidence of co-existing pulmonary disease varying from 6 to 38% worldwide. We report a case of pancreatic tuberculosis also involving the vertebrae, which was initially treated as a case of pancreatic cancer. (author)

  2. Pancreatic cancer: any prospects for prevention?

    OpenAIRE

    Hart, A.

    1999-01-01

    Primary prevention of pancreatic cancer and public health measures to reduce its incidence are dependent on data from epidemiological studies. Currently, the only definite risk factor is smoking, although a diet rich in fruit and vegetables may be protective. The K-ras mutation may have a role in diagnosis and screening.


Keywords: pancreatic cancer; epidemiology; risk factors; smoking; diet; alcohol

  3. Vaccine Therapy in Treating Patients With Colon, Pancreatic, or Lung Cancer

    Science.gov (United States)

    2015-04-27

    Recurrent Colon Cancer; Extensive Stage Small Cell Lung Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Limited Stage Small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage III Non-small Cell Lung Cancer; Stage I Pancreatic Cancer; Stage II Non-small Cell Lung Cancer; Stage IVB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage IVA Pancreatic Cancer

  4. Differentiation of autoimmune pancreatitis from suspected pancreatic cancer by fluorine-18 fluorodeoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Ozaki, Yayoi; Hamano, Hideaki; Oguchi, Kazuhiro

    2008-01-01

    Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely used for the diagnosis of pancreatic cancer. Because autoimmune pancreatitis is easily misdiagnosed as pancreatic cancer and can be tested for by FDG-PET analysis based on the presence of suspected pancreatic cancer, we attempted to clarify the differences in FDG-PET findings between the two conditions. We compared FDG-PET findings between 15 patients with autoimmune pancreatitis and 26 patients with pancreatic cancer. The findings were evaluated visually or semiquantitatively using the maximum standardized uptake value and the accumulation pattern of FDG. FDG uptake was found in all 15 patients with autoimmune pancreatitis, whereas it was found in 19 of 26 patients (73.1%) with pancreatic cancer. An accumulation pattern characterized by nodular shapes was significantly more frequent in pancreatic cancer, whereas a longitudinal shape indicated autoimmune pancreatitis. Heterogeneous accumulation was found in almost all cases of autoimmune pancreatitis, whereas homogeneous accumulation was found in pancreatic cancer. Significantly more cases of pancreatic cancer showed solitary localization, whereas multiple localization in the pancreas favored the presence of autoimmune pancreatitis. FDG uptake by the hilar lymph node was significantly more frequent in autoimmune pancreatitis than in pancreatic cancer, and uptake by the lachrymal gland, salivary gland, biliary duct, retroperitoneal space, and prostate were seen only in autoimmune pancreatitis. FDG-PET is a useful tool for differentiating autoimmune pancreatitis from suspected pancreatic cancer, if the accumulation pattern and extrapancreatic involvement are considered. IgG4 measurement and other current image tests can further confirm the diagnosis. (author)

  5. Risk of Pancreatic Cancer After a Primary Episode of Acute Pancreatitis.

    Science.gov (United States)

    Rijkers, Anton P; Bakker, Olaf J; Ahmed Ali, Usama; Hagenaars, Julia C J P; van Santvoort, Hjalmar C; Besselink, Marc G; Bollen, Thomas L; van Eijck, Casper H

    2017-09-01

    Acute pancreatitis may be the first manifestation of pancreatic cancer. The aim of this study was to assess the risk of pancreatic cancer after a first episode of acute pancreatitis. Between March 2004 and March 2007, all consecutive patients with a first episode of acute pancreatitis were prospectively registered. Follow-up was based on hospital records audit, radiological imaging, and patient questionnaires. Outcome was stratified based on the development of chronic pancreatitis. We included 731 patients. The median follow-up time was 55 months. Progression to chronic pancreatitis was diagnosed in 51 patients (7.0%). In this group, the incidence rate per 1000 person-years for developing pancreatic cancer was 9.0 (95% confidence interval, 2.3-35.7). In the group of 680 patients who did not develop chronic pancreatitis, the incidence rate per 1000 person-years for developing pancreatic cancer in this group was 1.1 (95% confidence interval, 0.3-3.3). Hence, the rate ratio of pancreatic cancer was almost 9 times higher in patients who developed chronic pancreatitis compared with those who did not (P = 0.049). Although a first episode of acute pancreatitis may be related to pancreatic cancer, this risk is mainly present in patients who progress to chronic pancreatitis.

  6. External beam radiotherapy for unresectable pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kagami, Yoshikazu; Nishio, Masamichi; Narimatsu, Naoto; Ogawa, Hajime; Betsuyaku, Takashi; Hirata, Kouji; Ikeda, Shigeyuki (Sapporo National Hospital (Japan). Hokkaido Cancer Center)

    1992-04-01

    Between 1980 to 1989, 24 patients with unresectable pancreatic cancer (10 with localized tumor alone and 14 with distant metastases) have been treated with external beam radiation at Sapporo National Hospital, Hokkaido Cancer Center. Response rate of pancreatic tumor treated with external beam radiation was 33.3% (7/21) with no complete response. Median survival time of the patients with localized tumor was 10 months and that of the patients with distant metastases was 3 months. Relief of pain occurred in 92.9% (12/13) of patients having pain due to pancreatic tumor and in 75% (3/4) of patients having pain due to bone metastases. Major complication was gastric ulcer which developed in 5 patients of 21 patients given stomach irradiation. We concluded that unresectable pancreatic cancer would be frequently indicated for radiotherapy. (author).

  7. Prospective assessment of the influence of pancreatic cancer resection on exocrine pancreatic function.

    Science.gov (United States)

    Sikkens, E C M; Cahen, D L; de Wit, J; Looman, C W N; van Eijck, C; Bruno, M J

    2014-01-01

    Exocrine insufficiency frequently develops in patients with pancreatic cancer owing to tumour ingrowth and pancreatic duct obstruction. Surgery might restore this function by removing the primary disease and restoring duct patency, but it may also have the opposite effect, as a result of resection of functional parenchyma and anatomical changes. This study evaluated the course of pancreatic function, before and after pancreatic resection. This prospective cohort study included patients with tumours in the pancreatic region requiring pancreatic resection in a tertiary referral centre between March 2010 and August 2012. Starting before surgery, exocrine function was determined monthly by measuring faecal elastase 1 levels (normal value over 0.200 µg per g faeces). Endocrine function, steatorrhoea-related symptoms and bodyweight were also evaluated before and after surgery. Subjects were followed from diagnosis until 6 months after surgery, or until death. Twenty-nine patients were included, 12 with pancreatic cancer, 14 with ampullary carcinoma and three with bile duct carcinoma (median tumour size 2.6 cm). Twenty-six patients underwent pancreaticoduodenectomy and three distal pancreatectomy. Thirteen patients had exocrine insufficiency at preoperative diagnosis. After a median follow-up of 6 months, this had increased to 24 patients. Diabetes was present in seven patients at diagnosis, and developed in one additional patient within 1 month after surgery. Most patients with tumours in the pancreatic region requiring pancreatic resection either had exocrine insufficiency at diagnosis or became exocrine-insufficient soon after surgical resection. © 2013 BJS Society Ltd. Published by John Wiley & Sons Ltd.

  8. Pancreatic cancer vaccine: a unique potential therapy

    Directory of Open Access Journals (Sweden)

    Cappello P

    2015-12-01

    Full Text Available Paola Cappello, Moitza Principe, Francesco Novelli Department of Molecular Biotechnologies and Health Sciences, Center for Experimental Research and Medical Studies, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy Abstract: Pancreatic ductal adenocarcinoma (PDA is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological

  9. [Non surgical treatment of pancreatic cancers].

    Science.gov (United States)

    Bleiberg, H; Gerard, B; Hendlisz, A; Jagodzinski, R

    1997-09-01

    Pancreatic cancer is a disease difficult to treat. Diagnosis is late, cancer remaining clinically unapparent even if locally advanced or metastatic. Few patients can be submitted to curative surgery. Even if resection is possible, 5-year survival varies from 0% to 18% according to series. Some data suggest that chemotherapy with or without radiotherapy could influence disease free survival but a benefit on overall survival has not been demonstrated. For locally advanced disease, the results of a trial published in 1968, showed that a combination of radiotherapy and 5-Fluorouracil (5FU) improved median survival as compared to radiotherapy alone (5.5 versus 10 months). Since then, no progress has been achieved. At the present time, survival of patients with metastatic pancreatic cancer cannot be improved. Very recently, a new agent, gemcitabine, has been compared to 5FU. Criteria for activity were based on clinical improvement analgesia consumption, performance status and weight gain. Twenty-four percent of the patients treated with gemcitabine had a clinical benefit as compared to 5% for those treated with 5FU. Other studies comparing chemotherapy to best supportive care show a significant decrease of depression and anxiety as well as an improvement in quality of life for patients being treated.

  10. Circulating 25-Hydroxyvitamin D and Risk of Pancreatic Cancer

    Science.gov (United States)

    Stolzenberg-Solomon, Rachael Z.; Jacobs, Eric J.; Arslan, Alan A.; Qi, Dai; Patel, Alpa V.; Helzlsouer, Kathy J.; Weinstein, Stephanie J.; McCullough, Marjorie L.; Purdue, Mark P.; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R.; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Albanes, Demetrius; Cai, Qiuyin; Harvey, Chinonye; Hayes, Richard; Clipp, Sandra; Horst, Ronald L.; Irish, Lonn; Koenig, Karen; Le Marchand, Loic; Kolonel, Laurence N.

    2010-01-01

    Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974–2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50–<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (≥100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered. PMID:20562185

  11. [Surgery for pancreatic cancer: Evidence-based surgical strategies].

    Science.gov (United States)

    Sánchez Cabús, Santiago; Fernández-Cruz, Laureano

    2015-01-01

    Pancreatic cancer surgery represents a challenge for surgeons due to its technical complexity, the potential complications that may appear, and ultimately because of its poor survival. The aim of this article is to summarize the scientific evidence regarding the surgical treatment of pancreatic cancer in order to help surgeons in the decision making process in the management of these patients .Here we will review such fundamental issues as the need for a biopsy before surgery, the type of pancreatic anastomosis leading to better results, and the need for placement of drains after pancreatic surgery will be discussed. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Out-FOXing Pancreatic Cancer | Center for Cancer Research

    Science.gov (United States)

    Pancreatic cancer is one of the most lethal cancer types worldwide with increasing incidence and mortality rates in the United States. Consequently, it is projected to become the second leading cause of cancer death by 2020. Poor patient outcomes are due to a combination of diagnosis at an advanced stage and a lack of effective treatments. However, a better understanding of the molecular pathways at work in pancreatic cancers may lead to the identification of novel therapeutic targets.

  13. Value of computed tomography as a screening examination of pancreatic cancer

    International Nuclear Information System (INIS)

    Honda, Hiroshi; Watanabe, Katsushi; Nishikawa, Kiyoshi

    1983-01-01

    The abdominal CT films of 50 patients were reviewed by ten radiologists to evaluate the role of CT examination in the screening of pancreatic cancer. The 50 patients consisted of 10 with pancreatic cancer, 8 with other pancreatic abnormalities, and 32 with normal pancreas. Ten radiologists were divided into two groups according to their experience in evaluating CT examinations, an experienced group and an unexperienced group, respectively. In the detectability of pancreatic abnormality, the experienced group showed a sensitivity of 72.2% and a specificity of 86.2%. The unexperienced group showed a sensitivity of 70.9% and a specificity of 72.0%. In the detectability of pancreatic cancer, the experienced group showed a sensitivity of 62.0% and a specificity of 83.4%. The unexperienced group showed a sensitivity of 66.0% and a specificity of 81.8%. In the localization of the pancreatic cancer, there was no difference between the two groups. Pancreatic abnormality can be detected with high accuracy, but diagnosis of the nature of pancreatic cancer is difficult. Experience in evaluating CT examinations elevates the detectability of pancreatic abnormality but does not elevate the detectability of pancreatic cancer. These results suggest the difficulty in diagnosis of pancreatic cancer. (author)

  14. Complex role for the immune system in initiation and progression of pancreatic cancer.

    Science.gov (United States)

    Inman, Kristin S; Francis, Amanda A; Murray, Nicole R

    2014-08-28

    The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, pancreatic cancer is characterized by an immunosuppressive environment, which is thought to promote tumor progression and invasion. Here we review the current literature describing the role of the immune response in the progressive development of pancreatic cancer, with a focus on the mechanisms that drive recruitment and activation of immune cells at the tumor site, and our current understanding of the function of the immune cell types at the tumor. Recent clinical and preclinical data are reviewed, detailing the involvement of the immune response in pancreatitis and pancreatic cancer, including the role of specific cytokines and implications for disease outcome. Acute pancreatitis is characterized by a predominantly innate immune response, while chronic pancreatitis elicits an immune response that involves both innate and adaptive immune cells, and often results in profound systemic immune-suppression. Pancreatic adenocarcinoma is characterized by marked immune dysfunction driven by immunosuppressive cell types, tumor-promoting immune cells, and defective or absent inflammatory cells. Recent studies reveal that immune cells interact with cancer stem cells and tumor stromal cells, and these interactions have an impact on development and progression of pancreatic ductal adenocarcinoma (PDAC). Finally, current PDAC therapies are reviewed and the potential for harnessing the actions of the immune response to assist in targeting pancreatic cancer using immunotherapy is discussed.

  15. Targeting pancreatic cancer with magneto-fluorescent theranostic gold nanoshells.

    Science.gov (United States)

    Chen, Wenxue; Ayala-Orozco, Ciceron; Biswal, Nrusingh C; Perez-Torres, Carlos; Bartels, Marc; Bardhan, Rizia; Stinnet, Gary; Liu, Xian-De; Ji, Baoan; Deorukhkar, Amit; Brown, Lisa V; Guha, Sushovan; Pautler, Robia G; Krishnan, Sunil; Halas, Naomi J; Joshi, Amit

    2014-01-01

    We report a magneto-fluorescent theranostic nanocomplex targeted to neutrophil gelatinase-associated lipocalin (NGAL) for imaging and therapy of pancreatic cancer. Gold nanoshells resonant at 810 nm were encapsulated in silica epilayers doped with iron oxide and the near-infrared (NIR) dye indocyanine green, resulting in theranostic gold nanoshells (TGNS), which were subsequently conjugated with antibodies targeting NGAL in AsPC-1-derived xenografts in nude mice. Anti-NGAL-conjugated TGNS specifically targeted pancreatic cancer cells in vitro and in vivo providing contrast for both NIR fluorescence and T2-weighted MRI with higher tumor contrast than can be obtained using long-circulating, but nontargeted, PEGylated nanoparticles. The nanocomplexes also enabled highly specific cancer cell death via NIR photothermal therapy in vitro. TGNS with embedded NIR and magnetic resonance contrasts can be specifically targeted to pancreatic cancer cells with expression of early disease marker NGAL, and enable molecularly targeted imaging and photothermal therapy.

  16. Survivin as a radioresistance factor in pancreatic cancer

    International Nuclear Information System (INIS)

    Asanuma, Koichi; Moriai, Ryosuke; Yajima, Tomomi; Yagihashi, Atsuhito; Yamada, Mikako; Kobayashi, Daisuke; Watanabe, Naoki

    2000-01-01

    We examined whether survivin acts as a constitutive and inducible radioresistance factor in pancreatic cancer cells. Using a quantitative TaqMan reverse transcription-polymerase chain reaction for survivin mRNA in five pancreatic cancer cell lines, we found an inverse relationship between survivin mRNA expression and radiosensitivity. PANC-1 cells, which had the highest survivin mRNA levels, were most resistant to X-irradiation; MIAPaCa-2 cells, which showed the least survivin mRNA expression, were the most sensitive to X-irradiation. Our results suggested that survivin could act as a constitutive radioresistance factor in pancreatic cancer cells. To determine whether radioresistance is enhanced by induction of survivin expression by irradiation, PANC-1 and MIAPaCa-2 cells were subjected to sublethal doses of X-irradiation followed by a lethal dose. Survivin mRNA expression was increased significantly in both PANC-1 and MIAPaCa-2 cell lines by pretreatment with a sublethal dose of X-irradiation, as was cell survival after exposure to the lethal dose. In this system, enzymatic caspase-3 activity was significantly suppressed in cells with acquired resistance. These results suggest that survivin also acts as an inducible radioresistance factor in pancreatic cancer cells. Survivin, then, appears to enhance radioresistance in pancreatic cancer cells; inhibition of survivin mRNA expression may improve the effectiveness of radiotherapy. (author)

  17. Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic growth

    International Nuclear Information System (INIS)

    Ohkura, Yu; Sasaki, Kazunari; Matsuda, Masamichi; Hashimoto, Masaji; Fujii, Takeshi; Watanabe, Goro

    2015-01-01

    Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic growth is extremely rare. Diagnosis of pancreatic cancer on preoperative imaging is difficult when the pancreatic parenchyma is compressed by a pseudocyst and becomes unclear. Despite advances in imaging techniques, accurate preoperative diagnosis of cystic lesions of the pancreas remains difficult. In this case, it was challenging to diagnose pancreatic cancer preoperatively as we could not accurately assess the pancreatic parenchyma, which had been compressed by a moderate-sized cystic lesion with extrapancreatic growth. A 63-year-old woman underwent investigations for epigastric abdominal pain. She had no history of pancreatitis. Although we suspected pancreatic ductal carcinoma with a pancreatic cyst, there was no mass lesion or low-density area suggestive of pancreatic cancer. We did not immediately suspect pancreatic cancer, as development of a moderate-sized cyst with extrapancreatic growth is extremely rare and known tumor markers were not elevated. Therefore, we initially suspected that a massive benign cyst (mucinous cyst neoplasm, serous cyst neoplasm, or intraductal papillary mucinous neoplasm) resulted in stenosis of the main pancreatic duct. We were unable to reach a definitive diagnosis prior to the operation. We had planned a pancreaticoduodenectomy to reach a definitive diagnosis. However, we could not remove the tumor because of significant invasion of the surrounding tissue (portal vein, superior mesenteric vein, etc.). The fluid content of the cyst was serous, and aspiration cytology from the pancreatic cyst was Class III (no malignancy), but the surrounding white connective tissue samples were positive for pancreatic adenocarcinoma on pathological examination during surgery. We repeated imaging (CT, MRI, endoscopic ultrasound, etc.) postoperatively, but there were neither mass lesions nor a low-density area suggestive of pancreatic cancer. In retrospect, we think

  18. Targeting senescence cells in pancreatic cancer | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Targeting senescence cells in pancreatic cancer. Cellular senescence is a programmed response to oncogenic (tumour-causing) stress that aims to halt the expansion of cells with malignant potential. It does this by stopping the proliferation of pre-cancerous lesions and recruitment of the immune system for their elimination.

  19. Occupational exposures and risk of pancreatic cancer

    International Nuclear Information System (INIS)

    Santibanez, Miguel; Vioque, Jesus; Alguacil, Juan; Hera, Manuela Garcia de la; Moreno-Osset, Eduardo; Carrato, Alfredo; Porta, Miquel; Kauppinen, Timo

    2010-01-01

    The objective was to analyze the relationship between occupation (and specific occupational exposures) and risk of exocrine pancreatic cancer (EPC). We conducted a multicenter hospital-based case-control study in Eastern Spain. We included 161 incident cases of EPC (59.6% men, 94 with histological confirmation, of whom 80% had ductal adenocarcinoma). Cases were frequency-matched with 455 controls by sex, age and province of residence. Information was elicited using structured questionnaires. Occupations were coded according to the Spanish version of the International Standard Classification of Occupations 1988. Occupational exposure to a selection of carcinogenic substances was assessed with the Finnish Job-Exposure Matrix (FINJEM). Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multiple logistic regression, adjusting for sex, age, province, education, alcohol and smoking. A higher risk of EPC was associated with having worked as 'Miners, shotfirers, stone cutters and carvers', 'Machinery mechanics and fitters', 'Building trades workers' and 'Motor vehicle drivers' in men, 'Office Clerks' in women, and 'Waiters' in both sexes. Cases with ductal adenocarcinomas were more likely to have been exposed to chlorinated hydrocarbon solvents (OR = 4.1, 95% CI: 1.1-15.2, p-trend = 0.04). We also observed significant associations with exposure to 'synthetic polymer dust exposure' and 'ionizing radiation'. Suggestive increases in risk were observed for 'pesticides', 'diesel and gasoline engine exhaust', and 'hydrocarbon solvents'. Results support the hypothesis that occupational exposure to chlorinated hydrocarbon solvents is associated with exocrine pancreatic cancer.

  20. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer. Results of the first prospective randomized phase II trial

    Energy Technology Data Exchange (ETDEWEB)

    Golcher, Henriette; Merkel, Susanne; Hohenberger, Werner [University Hospital Erlangen, Department of Surgery, Erlangen (Germany); Brunner, Thomas B. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); University Hospital Freiburg, Department of Radiation Oncology, Freiburg (Germany); Witzigmann, Helmut [University Hospital Leipzig, Department of Surgery, Leipzig (Germany); Hospital Dresden-Friedrichstadt, General Surgery, Dresden (Germany); Marti, Lukas [Hospital of Kanton St. Gallen, General Surgery, St. Gallen (Switzerland); Bechstein, Wolf-Otto [University Hospital Frankfurt, Department of Surgery, Frankfurt/Main (Germany); Bruns, Christiane [University Hospital Munich, Department of Surgery - Hospital Campus Grosshadern, Munich (Germany); University Hospital Magdeburg, Department of Surgery, Magdeburg (Germany); Jungnickel, Henry [Hospital Dresden-Friedrichstadt, General Surgery, Dresden (Germany); Schreiber, Stefan [University Hospital Leipzig, Department of Surgery, Leipzig (Germany); Grabenbauer, Gerhard G. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Hospital Coburg, Department of Radiation Oncology, Coburg (Germany); Meyer, Thomas [University Hospital Erlangen, Department of Surgery, Erlangen (Germany); Hospital Ansbach, General Surgery, Ansbach (Germany); Fietkau, Rainer [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany)

    2014-09-25

    In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging. Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS). The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48 % (A) and 52 % (B, P = 0.81) and (y)pN0 was 30 % (A) vs. 39 % (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79). This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543. (orig.) [German] Mehrere nichtrandomisierte Studien zeigten, dass eine neoadjuvante Therapie das Ueberleben bei Patienten mit Pankreaskarzinom verlaengert. Beim lokal fortgeschrittenen Rektumkarzinom gehoert die

  1. Selected medical conditions and risk of pancreatic cancer.

    Science.gov (United States)

    Olson, Sara H

    2012-01-01

    We review the current evidence for associations of several medical conditions with risk of pancreatic cancer, including allergies, pancreatitis, gall bladder disease, cholecystectomy, ulcers, gastrectomy, appendectomy, and tonsillectomy. There are consistent findings of reduced risk associated with presence of self-reported allergies, particularly hay fever but not asthma; data on other allergies are limited and inconclusive. Several studies provide evidence that patients with pancreatic cancer are more likely than comparison groups to report pancreatitis. Those studies that investigated the time between onset of pancreatitis and diagnosis of pancreatic cancer found that risk estimates declined with longer periods of time; however, increased risks were noted for long-term pancreatitis, indicating that this condition is both a risk factor and a sign of early disease. Increased risk was reported in association with cholelithiasis, but the few studies that considered time before diagnosis of cancer did not find increased risk for cholelithiasis diagnosed in the more distant past. There is weak evidence that cholecystectomy 2 or more years before cancer diagnosis is related to risk, but this is based on only a few studies. There is no consistent association between ulcers and risk, while gastrectomy may increase risk. Overall, study of these conditions, particularly those that are rare, presents methodologic challenges. Time between diagnoses is likely to be important but is not considered in most studies. Lack of adequate control in several studies for risk factors such as smoking and heavy alcohol use also makes it difficult to draw firm conclusions about these results. Copyright © 2011 Wiley Periodicals, Inc.

  2. Pancreatic cancer and depression: myth and truth

    Directory of Open Access Journals (Sweden)

    Schmid Roland M

    2010-10-01

    Full Text Available Abstract Background Various studies reported remarkable high incidence rates of depression in cancer patients compared with the general population. Pancreatic cancer is still one of the malignancies with the worst prognosis and therefore it seems quite logical that it is one of the malignancies with the highest incidence rates of major depression. However, what about the scientific background of this relationship? Is depression in patients suffering from pancreatic cancer just due to the confrontation with a life threatening disease and its somatic symptoms or is depression in this particular group of patients a feature of pancreatic cancer per se? Discussion Several studies provide evidence of depression to precede the diagnosis of pancreatic cancer and some studies even blame it for its detrimental influence on survival. The immense impact of emotional distress on quality of life of cancer patients enhances the need for its early diagnosis and adequate treatment. Knowledge about underlying pathophysiological mechanisms is required to provide the optimal therapy. Summary A review of the literature on this issue should reveal which are the facts and what is myth.

  3. Obesity adversely affects survival in pancreatic cancer patients.

    Science.gov (United States)

    McWilliams, Robert R; Matsumoto, Martha E; Burch, Patrick A; Kim, George P; Halfdanarson, Thorvardur R; de Andrade, Mariza; Reid-Lombardo, Kaye; Bamlet, William R

    2010-11-01

    Higher body-mass index (BMI) has been implicated as a risk factor for developing pancreatic cancer, but its effect on survival has not been thoroughly investigated. The authors assessed the association of BMI with survival in a sample of pancreatic cancer patients and used epidemiologic and clinical information to understand the contribution of diabetes and hyperglycemia. A survival analysis using Cox proportional hazards by usual adult BMI was performed on 1861 unselected patients with pancreatic adenocarcinoma; analyses were adjusted for covariates that included clinical stage, age, and sex. Secondary analyses incorporated self-reported diabetes and fasting blood glucose in the survival model. BMI as a continuous variable was inversely associated with survival from pancreatic adenocarcinoma (hazard ratio [HR], 1.019 for each increased unit of BMI [kg/m2], PFasting blood glucose and diabetes did not affect the results. Higher BMI is associated with decreased survival in pancreatic cancer. Although the mechanism of this association remains undetermined, diabetes and hyperglycemia do not appear to account for the observed association. Copyright © 2010 American Cancer Society.

  4. The Key Genes of Chronic Pancreatitis which Bridge Chronic Pancreatitis and Pancreatic Cancer Can be Therapeutic Targets.

    Science.gov (United States)

    Li, Shuang; Li, Rui; Wang, Heping; Li, Lisha; Li, Huiyu; Li, Yulin

    2018-04-01

    An important question in systems biology is what role the underlying molecular mechanisms play in disease progression. The relationship between chronic pancreatitis and pancreatic cancer needs further exploration in a system view. We constructed the disease network based on gene expression data and protein-protein interaction. We proposed an approach to discover the underlying core network and molecular factors in the progression of pancreatic diseases, which contain stages of chronic pancreatitis and pancreatic cancer. The chronic pancreatitis and pancreatic cancer core network and key factors were revealed and then verified by gene set enrichment analysis of pathways and diseases. The key factors provide the microenvironment for tumor initiation and the change of gene expression level of key factors bridge chronic pancreatitis and pancreatic cancer. Some new candidate genes need further verification by experiments. Transcriptome profiling-based network analysis reveals the importance of chronic pancreatitis genes and pathways in pancreatic cancer development on a system level by computational method and they can be therapeutic targets.

  5. Helicobacter pylori infection, atrophic gastritis, and pancreatic cancer risk

    Science.gov (United States)

    Liu, Hong; Chen, Yue-Tong; Wang, Rui; Chen, Xin-Zu

    2017-01-01

    Abstract Background: To investigate the associations of Helicobacter pylori (Hp) infection and atrophic gastritis (AG) with pancreatic cancer risk. Methods: A literature search in PubMed was performed up to July 2017. Only prospective cohort and nested case–control studies enrolling cancer-free participants were eligible. Incident pancreatic cancer cases were ascertained during the follow-up. The risks of pancreatic cancer were compared between persons infected and noninfected with Hp, or between those with and without AG status at baseline. Odds ratios (ORs) or hazard ratios were combined. Subgroup and sensitivity analyses were performed, and publication bias was estimated. Results: Three cohort studies and 6 nested case–control studies, including 65,155 observations, were analyzed. The meta-analyses did not confirm the association between pancreatic cancer risk and Hp infection (OR = 1.09, 95% confidence interval [CI] = 0.81–1.47) or AG status (OR = 1.18, 95% CI = 0.80–1.72). However, particular subpopulations potentially had increased risks of pancreatic cancer. Cytotoxin-associated gene A (CagA)-negative strains of Hp might be a causative factor of pancreatic cancer (OR = 1.30, 95% CI = 1.05–1.62), but a sensitivity analysis by leave-one-out method did not fully warrant it (OR = 1.20, 95% CI = 0.93–1.56). In 1 nested case–control study, AG at stomach corpus in Hp-negative subpopulation might have increased risk of pancreatic cancer, but with a poor test power = 0.56. Publication biases were nonsignificant in the present meta-analysis. Conclusion: Based on current prospective epidemiologic studies, the linkage of pancreatic cancer to Hp infection or AG status was not warranted on the whole. Nevertheless, prospective studies only focusing on those specific subpopulations are further required to obtain better power. PMID:28816977

  6. Intraoperative radiotherapy in pancreatic cancer: A systematic review

    International Nuclear Information System (INIS)

    Ruano-Ravina, Alberto; Almazan Ortega, Raquel; Guedea, Ferrran

    2008-01-01

    Background and purpose: Intraoperative radiotherapy (IORT) has been considered for treatment of pancreas cancer since local recurrence rates are very high. This study assesses the efficacy and safety of IORT in pancreatic cancer. Materials and methods: We conducted a systematic review of scientific literature from January 1995 to February 2007, including Medline, Embase, ISI Web of Science and HTA (Health Technology Assessment). By applying a series of inclusion criteria, two independent reviewers selected those studies in which a minimum of 30 patients received IORT and which furnished survival results based on a minimum 3-month follow-up. Results: Fourteen papers were included, one was an IORT assessment report, 5 were cohort studies, and the remaining 8 were case series studies, 2 of which belonged to the same series. In general, these studies showed that IORT could slightly increase survival among patients with pancreatic cancer in localized stages. However, the results were not conclusively in favor of IORT in the case of pancreatic cancer in locally advanced and metastatic stages. There were no published studies that assessed quality of life. Conclusions: There is no clear evidence to indicate that IORT is more effective than other therapies in treating pancreatic cancer in locally advanced and metastatic stages

  7. Preoperative biliary drainage for pancreatic cancer.

    Science.gov (United States)

    Van Heek, N T; Busch, O R; Van Gulik, T M; Gouma, D J

    2014-04-01

    This review is to summarize the current knowledge about preoperative biliary drainage (PBD) in patients with biliary obstruction caused by pancreatic cancer. Most patients with pancreatic carcinoma (85%) will present with obstructive jaundice. The presence of toxic substances as bilirubin and bile salts, impaired liver function and altered nutritional status due to obstructive jaundice have been characterized as factors for development of complications after surgery. Whereas PBD was to yield beneficial effects in the experimental setting, conflicting results have been observed in clinical studies. The meta-analysis from relative older studies as well as more importantly a recent clinical trial showed that PBD should not be performed routinely. PBD for patients with a distal biliary obstruction is leading to more serious complications compared with early surgery. Arguments for PBD have shifted from a potential therapeutic benefit towards a logistic problem such as patients suffering from cholangitis and severe jaundice at admission or patients who need extra diagnostic tests, or delay in surgery due to a referral pattern or waiting list for surgery as well as candidates for neoadjuvant chemo(radio)therapy. If drainage is indicated in these patients it should be performed with a metal stent to reduce complications after the drainage procedure such as stent occlusion and cholangitis. Considering a change towards more neoadjuvant therapy regimes improvement of the quality of the biliary drainage concept is still important.

  8. Regular use of aspirin and pancreatic cancer risk

    Directory of Open Access Journals (Sweden)

    Mahoney Martin C

    2002-09-01

    Full Text Available Abstract Background Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs has been consistently associated with reduced risk of colorectal cancer and adenoma, and there is some evidence for a protective effect for other types of cancer. As experimental studies reveal a possible role for NSAIDs is reducing the risk of pancreatic cancer, epidemiological studies examining similar associations in human populations become more important. Methods In this hospital-based case-control study, 194 patients with pancreatic cancer were compared to 582 age and sex-matched patients with non-neoplastic conditions to examine the association between aspirin use and risk of pancreatic cancer. All participants received medical services at the Roswell Park Cancer Institute in Buffalo, NY and completed a comprehensive epidemiologic questionnaire that included information on demographics, lifestyle factors and medical history as well as frequency and duration of aspirin use. Patients using at least one tablet per week for at least six months were classified as regular aspirin users. Unconditional logistic regression was used to compute crude and adjusted odds ratios (ORs with 95% confidence intervals (CIs. Results Pancreatic cancer risk in aspirin users was not changed relative to non-users (adjusted OR = 1.00; 95% CI 0.72–1.39. No significant change in risk was found in relation to greater frequency or prolonged duration of use, in the total sample or in either gender. Conclusions These data suggest that regular aspirin use may not be associated with lower risk of pancreatic cancer.

  9. Whole genomes redefine the mutational landscape of pancreatic cancer

    OpenAIRE

    Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K.; Kassahn, Karin S.; Bailey, Peter; Johns, Amber L.; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C. J.; Robertson, Alan J.; Fadlullah, Muhammad Z. H.; Bruxner, Tim J. C.; Christ, Angelika N.

    2015-01-01

    Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (...

  10. Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Kikuta, Kazuhiro; Masamune, Atsushi; Watanabe, Takashi; Ariga, Hiroyuki; Itoh, Hiromichi; Hamada, Shin; Satoh, Kennichi; Egawa, Shinichi; Unno, Michiaki; Shimosegawa, Tooru

    2010-01-01

    Research highlights: → Recent studies have shown that pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. → Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and scattered, fibroblast-like appearance. → PSCs decreased the expression of epithelial markers but increased that of mesenchymal markers, along with increased migration. → This study suggests epithelial-mesenchymal transition as a novel mechanism by which PSCs contribute to the aggressive behavior of pancreatic cancer cells. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Because epithelial-mesenchymal transition (EMT) plays a critical role in the progression of pancreatic cancer, we hypothesized that PSCs promote EMT in pancreatic cancer cells. Panc-1 and SUIT-2 pancreatic cancer cells were indirectly co-cultured with human PSCs isolated from patients undergoing operation for pancreatic cancer. The expression of epithelial and mesenchymal markers was examined by real-time PCR and immunofluorescent staining. The migration of pancreatic cancer cells was examined by scratch and two-chamber assays. Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and a scattered, fibroblast-like appearance. The expression of E-cadherin, cytokeratin 19, and membrane-associated β-catenin was decreased, whereas vimentin and Snail (Snai-1) expression was increased more in cancer cells co-cultured with PSCs than in mono-cultured cells. The migration of pancreatic cancer cells was increased by co-culture with PSCs. The PSC-induced decrease of E-cadherin expression was not altered by treatment with anti

  11. Therapeutic management of locally unresectable pancreatic cancer

    International Nuclear Information System (INIS)

    Lombard-Bohas, C.; Saurin, J.C.; Mornex, F.

    1997-01-01

    Pancreatic cancer still have bad prognosis. At the time of diagnosis, less than 10 % of patients can undergo surgery with an overall 5-year survival rate of less than 2 %. For patients with localized pancreatic adenocarcinoma, the combination of radiation therapy and chemotherapy has been shown to control symptoms and to enhance patient survival. This treatment should be proposed to all the patients with good performance status and without icterus. Pain management should be optimized and often need morphinic and co-antalgic (anticonvulsants, steroids) consumption. The celiac plexus block with alcohol gives an excellent pain relief and should be more frequently used. (author)

  12. Common variables in European pancreatic cancer registries

    DEFF Research Database (Denmark)

    De Leede, E. M.; Sibinga Mulder, B. G.; Bastiaannet, E.

    2016-01-01

    Background Quality assurance of cancer care is of utmost importance to detect and avoid under and over treatment. Most cancer data are collected by different procedures in different countries, and are poorly comparable at an international level. EURECCA, acronym for European Registration of Cancer...... registries, as well as specific pancreatic cancer audits/registries, were invited to participate in EURECCA Pancreas. Participating countries were requested to share an overview of their collected data items. Of the received datasets, a shared items list was made which creates insight in similarities between...

  13. PTK6 promotes cancer migration and invasion in pancreatic cancer cells dependent on ERK signaling.

    Directory of Open Access Journals (Sweden)

    Hiroaki Ono

    Full Text Available Protein Tyrosine Kinase 6 (PTK6 is a non-receptor type tyrosine kinase that may be involved in some cancers. However, the biological role and expression status of PTK6 in pancreatic cancer is unknown. Therefore in this study, we evaluated the functional role of PTK6 on pancreatic cancer invasion. Five pancreatic cancer cell lines expressed PTK6 at varying levels. PTK6 expression was also observed in human pancreatic adenocarcinomas. PTK6 suppression by siRNA significantly reduced both cellular migration and invasion (0.59/0.49 fold for BxPC3, 0.61/0.62 for Panc1, 0.42/0.39 for MIAPaCa2, respectively, p<0.05 for each. In contrast, forced overexpression of PTK6 by transfection of a PTK6 expression vector in Panc1 and MIAPaCa2 cells increased cellular migration and invasion (1.57/1.67 fold for Panc1, 1.44/1.57 for MIAPaCa2, respectively, p<0.05. Silencing PTK6 reduced ERK1/2 activation, but not AKT or STAT3 activation, while PTK6 overexpression increased ERK1/2 activation. U0126, a specific inhibitor of ERK1/2, completely abolished the effect of PTK6 overexpression on cellular migration and invasion. These results suggest that PTK6 regulates cellular migration and invasion in pancreatic cancer via ERK signaling. PTK6 may be a novel therapeutic target for pancreatic cancer.

  14. RISK FACTORS FOR PANCREATIC CANCER: UNDERLYING MECHANISMS AND POTENTIAL TARGETS

    Directory of Open Access Journals (Sweden)

    Thomas eKolodecik

    2014-01-01

    Full Text Available Purpose of the review:Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer.Recent Findings:Intracellular activation of both pancreatic enzymes and the transcription factor NF-kB are important mechanisms that induce acute pancreatitis. Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogneic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16 can ultimately lead to development of pancreatic cancer. Summary:Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions.

  15. Early Detection of Sporadic Pancreatic Cancer

    Science.gov (United States)

    Kenner, Barbara J.; Chari, Suresh T.; Cleeter, Deborah F.; Go, Vay Liang W.

    2015-01-01

    Abstract Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer. PMID:25938853

  16. Pancreatic cancer surgery: past, present, and future.

    Science.gov (United States)

    Griffin, James F; Poruk, Katherine E; Wolfgang, Christopher L

    2015-08-01

    The history of pancreatic cancer surgery, though fraught with failure and setbacks, is punctuated by periods of incremental progress dependent upon the state of the art and the mettle of the surgeons daring enough to attempt it. Surgical anesthesia and the aseptic techniques developed during the latter half of the 19(th) century were instrumental in establishing a viable setting for pancreatic surgery to develop. Together, they allowed for bolder interventions and improved survival through the post-operative period. Surgical management began with palliative procedures to address biliary obstruction in advanced disease. By the turn of the century, surgical pioneers such as Alessandro Codivilla and Walther Kausch were demonstrating the technical feasibility of pancreatic head resections and applying principles learned from palliation to perform complicated anatomical reconstructions. Allen O. Whipple, the namesake of the pancreaticoduodenectomy (PD), was the first to take a systematic approach to refining the procedure. Perhaps his greatest contribution was sparking a renewed interest in the surgical management of periampullary cancers and engendering a community of surgeons who advanced the field through their collective efforts. Though the work of Whipple and his contemporaries legitimized PD as an accepted surgical option, it was the establishment of high-volume centers of excellence and a multidisciplinary approach in the later decades of the 20(th) century that made it a viable surgical option. Today, pancreatic surgeons are experimenting with minimally invasive surgical techniques, expanding indications for resection, and investigating new methods for screening and early detection. In the future, the effective management of pancreatic cancer will depend upon our ability to reliably detect the earliest cancers and precursor lesions to allow for truly curative resections.

  17. Targeting Insulin-Like Growth Factor 1 Receptor Inhibits Pancreatic Cancer Growth and Metastasis

    Science.gov (United States)

    Subramani, Ramadevi; Lopez-Valdez, Rebecca; Arumugam, Arunkumar; Nandy, Sushmita; Boopalan, Thiyagarajan; Lakshmanaswamy, Rajkumar

    2014-01-01

    Pancreatic cancer is one of the most lethal cancers. Increasing incidence and mortality indicates that there is still much lacking in detection and management of the disease. This is partly due to a lack of specific symptoms during early stages of the disease. Several growth factor receptors have been associated with pancreatic cancer. Here, we have investigated if an RNA interference approach targeted to IGF-IR could be effective and efficient against pancreatic cancer growth and metastasis. For that, we evaluated the effects of IGF-1R inhibition using small interfering RNA (siRNAs) on tumor growth and metastasis in HPAC and PANC-1 pancreatic cancer cell lines. We found that silencing IGF-1R inhibits pancreatic cancer growth and metastasis by blocking key signaling pathways such AKT/PI3K, MAPK, JAK/STAT and EMT. Silencing IGF-1R resulted in an anti-proliferative effect in PANC-1 and HPAC pancreatic cancer cell lines. Matrigel invasion, transwell migration and wound healing assays also revealed a role for IGF-1R in metastatic properties of pancreatic cancer. These results were further confirmed using Western blotting analysis of key intermediates involved in proliferation, epithelial mesenchymal transition, migration, and invasion. In addition, soft agar assays showed that silencing IGF-1R also blocks the colony forming capabilities of pancreatic cancer cells in vitro. Western blots, as well as, flow cytometric analysis revealed the induction of apoptosis in IGF-1R silenced cells. Interestingly, silencing IGF-1R also suppressed the expression of insulin receptor β. All these effects together significantly control pancreatic cancer cell growth and metastasis. To conclude, our results demonstrate the significance of IGF-1R in pancreatic cancer. PMID:24809702

  18. Circulating 25-Hydroxyvitamin D and Risk of Pancreatic Cancer

    OpenAIRE

    Stolzenberg-Solomon, Rachael Z.; Jacobs, Eric J.; Arslan, Alan A.; Qi, Dai; Patel, Alpa V.; Helzlsouer, Kathy J.; Weinstein, Stephanie J.; McCullough, Marjorie L.; Purdue, Mark P.; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R.; Yu, Kai; Zeleniuch-Jacquotte, Anne

    2010-01-01

    Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974?2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated w...

  19. Diagnosing pancreatic cancer: the role of percutaneous biopsy and CT

    International Nuclear Information System (INIS)

    Amin, Z.; Theis, B.; Russell, R.C.G.; House, C.; Novelli, M.; Lees, W.R.

    2006-01-01

    Aims: To determine the sensitivity and complications of percutaneous biopsy of pancreatic masses, and whether typical computed tomography (CT) features of adenocarcinoma can reliably predict this diagnosis. Materials and methods: A 5 year retrospective analysis of percutaneous core biopsies of pancreatic masses and their CT features was undertaken. Data were retrieved from surgical/pathology databases; medical records and CT reports and images. Results: Three hundred and three patients underwent 372 biopsies; 56 of 87 patients had repeat biopsies. Malignancy was diagnosed in 276 patients, with ductal adenocarcinoma in 259 (85%). Final sensitivity of percutaneous biopsy for diagnosing pancreatic neoplasms was 90%; for repeat biopsy it was 87%. Complications occurred in 17 (4.6%) patients, in three of whom the complications were major (1%): one abscess, one duodenal perforation, one large retroperitoneal bleed. CT features typical of ductal adenocarcinoma were: hypovascular pancreatic mass with bile and/or pancreatic duct dilatation. Atypical CT features were: isodense or hypervascular mass, calcification, non-dilated ducts, cystic change, and extensive lymphadenopathy. Defining typical CT features of adenocarcinoma as true-positives, CT had a sensitivity of 68%, specificity of 95%, positive predictive value (PPV) of 98%, and negative predictive value of 41% for diagnosing pancreatic adenocarcinoma. Conclusion: Final sensitivity of percutaneous biopsy for establishing the diagnosis was 90%. CT features typical of pancreatic adenocarcinoma had high specificity and PPV. On some occasions, especially in frail patients with co-morbidity, it might be reasonable to assume a diagnosis of pancreatic cancer if CT features are typical, and biopsy only if CT shows atypical features

  20. Diagnosing pancreatic cancer: the role of percutaneous biopsy and CT

    Energy Technology Data Exchange (ETDEWEB)

    Amin, Z.; Theis, B.; Russell, R.C.G.; House, C.; Novelli, M.; Lees, W.R

    2006-12-15

    Aims: To determine the sensitivity and complications of percutaneous biopsy of pancreatic masses, and whether typical computed tomography (CT) features of adenocarcinoma can reliably predict this diagnosis. Materials and methods: A 5 year retrospective analysis of percutaneous core biopsies of pancreatic masses and their CT features was undertaken. Data were retrieved from surgical/pathology databases; medical records and CT reports and images. Results: Three hundred and three patients underwent 372 biopsies; 56 of 87 patients had repeat biopsies. Malignancy was diagnosed in 276 patients, with ductal adenocarcinoma in 259 (85%). Final sensitivity of percutaneous biopsy for diagnosing pancreatic neoplasms was 90%; for repeat biopsy it was 87%. Complications occurred in 17 (4.6%) patients, in three of whom the complications were major (1%): one abscess, one duodenal perforation, one large retroperitoneal bleed. CT features typical of ductal adenocarcinoma were: hypovascular pancreatic mass with bile and/or pancreatic duct dilatation. Atypical CT features were: isodense or hypervascular mass, calcification, non-dilated ducts, cystic change, and extensive lymphadenopathy. Defining typical CT features of adenocarcinoma as true-positives, CT had a sensitivity of 68%, specificity of 95%, positive predictive value (PPV) of 98%, and negative predictive value of 41% for diagnosing pancreatic adenocarcinoma. Conclusion: Final sensitivity of percutaneous biopsy for establishing the diagnosis was 90%. CT features typical of pancreatic adenocarcinoma had high specificity and PPV. On some occasions, especially in frail patients with co-morbidity, it might be reasonable to assume a diagnosis of pancreatic cancer if CT features are typical, and biopsy only if CT shows atypical features.

  1. miR-146a Suppresses Invasion of Pancreatic Cancer Cells

    Science.gov (United States)

    Li, Yiwei; VandenBoom, Timothy G.; Wang, Zhiwei; Kong, Dejuan; Ali, Shadan; Philip, Philip A.; Sarkar, Fazlul H.

    2010-01-01

    The aggressive course of pancreatic cancer is believed to reflect its unusually invasive and metastatic nature, which is associated with epidermal growth factor receptor (EGFR) overexpression and NF-κB activation. MicroRNAs (miRNA) have been implicated in the regulation of various pathobiological processes in cancer, including metastasis in pancreatic cancer and in other human malignancies. In this study, we report lower expression of miR-146a in pancreatic cancer cells compared with normal human pancreatic duct epithelial cells. Reexpression of miR-146a inhibited the invasive capacity of pancreatic cancer cells with concomitant downregulation of EGFR and the NF-κB regulatory kinase interleukin 1 receptor–associated kinase 1 (IRAK-1). Cellular mechanism studies revealed crosstalk between EGFR, IRAK-1, IκBα, NF-κB, and MTA-2, a transcription factor that regulates metastasis. Treatment of pancreatic cancer cells with the natural products 3,3′-diinodolylmethane (DIM) or isoflavone, which increased miR-146a expression, caused a downregulation of EGFR, MTA-2, IRAK-1, and NF-κB, resulting in an inhibition of pancreatic cancer cell invasion. Our findings reveal DIM and isoflavone as nontoxic activators of a miRNA that can block pancreatic cancer cell invasion and metastasis, offering starting points to design novel anticancer agents. PMID:20124483

  2. Indicative findings of pancreatic cancer in prediagnostic CT

    International Nuclear Information System (INIS)

    Ahn, Sung Soo; Choi, Jin-Young; Hong, Hye-Suk; Chung, Yong Eun; Lim, Joon Seok; Kim, Myeong-Jin

    2009-01-01

    We examined 20 prediagnostic CTs from 16 patients for whom the diagnosis of pancreatic cancer was delayed until full diagnostic CT was performed. Three radiologists independently reviewed the prediagnostic CTs along with 50 CTs of control subjects, including patients without pancreatic disease (n = 38) or with chronic pancreatitis without calcification visible on CT (n=12). The reviewers recorded the presence of biliary or pancreatic ductal dilation, interruption of the pancreatic duct, distal parenchymal atrophy, contour abnormality and focal hypoattenuation. Frequency, sensitivity and specificity of the significant findings were calculated. Logistic regression analysis was performed. Findings indicative of pancreatic cancer were seen on 85% (17/20) of the prediagnostic CTs. Patients with pancreatic cancer were significantly (p<0.05) more likely to show focal hypoattenuation, pancreatic duct dilation, interruption of the pancreatic duct, and distal parenchymal atrophy, with sensitivities and specificities of 75%/84%, 50%/78%, 45%/82% and 45%/96%, respectively. Focal hypoattenuation and distal parenchymal atrophy were the independent predictors of pancreatic cancer with odds ratios of 20.92 and 11.22, respectively. In conclusion, focal hypoattenuation and pancreatic duct dilation with or without interruption, especially when accompanied by distal parenchymal atrophy, were the most useful findings for avoiding delayed diagnosis of pancreatic cancer. (orig.)

  3. Thoracoscopic Splanchnicectomy for Pain Control in Irresectable Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Alireza Tavassoli

    2013-08-01

    Full Text Available Introduction : Severepain is a major problem in patients with unresectable pancreatic cancer. The goal of this study is to evaluate the effects of Thoracoscopic Splanchnicectomy (TS on pain control in these patients suffering from unresectable pancreatic cancer. Methods:Between years 2000 to 2011, 20 patients suffering from unresectable pancreatic cancer underwent TS due to severe pain. They were studied in terms of age, sex, location of pancreas tumor, history of previous surgery, response to treatments for pain control (assessed with VAS scoring system and complications of surgery. Results:M/F = 14/6 with a mean age of 63 years. The most common tumour site was at the pancreas head (in 8 patients. The most cause of unresectability was local expansion to critical adjacent elements (in 10 patients. Surgery was performed successfully in all patients. Post-operative complication included only pleural effusion on the left side which was cured by proper treatment. There were no post-op mortalities.  15 patients had acceptable levels of pain at the end of a six month follow-up period. ConclusionTS provides good pain control, little side effects and minimal invasiveness, the technique is recommended for pain control in patients with unresectable pancreatic cancer.

  4. Knowledge discovery for pancreatic cancer using inductive logic programming.

    Science.gov (United States)

    Qiu, Yushan; Shimada, Kazuaki; Hiraoka, Nobuyoshi; Maeshiro, Kensei; Ching, Wai-Ki; Aoki-Kinoshita, Kiyoko F; Furuta, Koh

    2014-08-01

    Pancreatic cancer is a devastating disease and predicting the status of the patients becomes an important and urgent issue. The authors explore the applicability of inductive logic programming (ILP) method in the disease and show that the accumulated clinical laboratory data can be used to predict disease characteristics, and this will contribute to the selection of therapeutic modalities of pancreatic cancer. The availability of a large amount of clinical laboratory data provides clues to aid in the knowledge discovery of diseases. In predicting the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer, using the ILP model, three rules are developed that are consistent with descriptions in the literature. The rules that are identified are useful to detect the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer and therefore contributed significantly to the decision of therapeutic strategies. In addition, the proposed method is compared with the other typical classification techniques and the results further confirm the superiority and merit of the proposed method.

  5. Pancreatic Enzymes

    Science.gov (United States)

    ... Contact Us DONATE NOW GENERAL DONATION PURPLESTRIDE Pancreatic enzymes Home Facing Pancreatic Cancer Living with Pancreatic Cancer ... and see a registered dietitian. What are pancreatic enzymes? Pancreatic enzymes help break down fats, proteins and ...

  6. Inaugural Meeting of North American Pancreatic Cancer Organizations: Advancing Collaboration and Communication.

    Science.gov (United States)

    Kenner, Barbara J; Fleshman, Julie M; Goldberg, Ann E; Rothschild, Laura J

    2015-11-01

    A meeting of North American Pancreatic Cancer Organizations planned by Kenner Family Research Fund and Pancreatic Cancer Action Network was held on July 15-16, 2015, in New York City. The meeting was attended by 32 individuals from 20 nonprofit groups from the United States and Canada. The objectives of this inaugural convening were to share mission goals and initiatives, engage as leaders, cultivate potential partnerships, and increase participation in World Pancreatic Cancer Day. The program was designed to provide opportunities for informal conversations, as well as facilitated discussions to meet the stated objectives. At the conclusion of the meeting, the group agreed that enhancing collaboration and communication will result in a more unified approach within the field and will benefit individuals diagnosed with pancreatic cancer. As a first step, the group will actively collaborate to participate in World Pancreatic Cancer Day, which is planned for November 13, 2015, and seeks to raise the level of visibility about the disease globally.

  7. Targeted Alpha Therapy Approach to the Management of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Allen, Barry J.; Abbas Rizvi, Syed M.; Qu, Chang F.; Smith, Ross C.

    2011-01-01

    Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting vectors are examined. These are the C595 monoclonal antibody that targets the MUC1 antigen and the PAI2 ligand that targets the uPA receptor. The expression of the tumor-associated antigen MUC-1 and the uPA receptor on three pancreatic cancer cell lines is reported for cell clusters, human mouse xenografts and lymph node metastases, as well as for human pancreatic cancer tissues, using immuno-histochemistry, confocal microscopy and flow cytometry. The targeting vectors C595 and PAI2 were labeled with the alpha emitting radioisotope 213 Bi using the chelators cDTPA and CHX-A″ to form the alpha-conjugates (AC). Cell clusters were incubated with the AC and examined at 48 hours. Apoptosis was documented using the TUNEL assay. In vivo, the anti-proliferative effect for tumors was tested at two days post-subcutaneous cell inoculation. Mice were injected with different concentrations of AC by local or systemic administration. Changes in tumor progression were assessed by tumor size. MUC-1 and uPA are strongly expressed on CFPAC-1, PANC-1 and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The ACs can target pancreatic cells and regress cell clusters (∼100 μm diameter), causing apoptosis in some 70–90 % of cells. At two days post-cell inoculation in mice, a single local injection of 74 MBq/kg of AC causes complete inhibition of tumor growth. Systemic injections of 111, 222 and 333 MBq/kg of alpha-conjugate caused significant tumor growth delay in a dose dependent manner after 16 weeks, compared with the non-specific control at 333 MBq/kg. Cytotoxicity was assessed by the MTS and TUNEL assays. The C595 and PAI2-alpha conjugates are indicated for the treatment of micro

  8. Increased pancreatic cancer risk following radiotherapy for testicular cancer.

    Science.gov (United States)

    Hauptmann, Michael; Børge Johannesen, Tom; Gilbert, Ethel S; Stovall, Marilyn; van Leeuwen, Flora E; Rajaraman, Preetha; Smith, Susan A; Weathers, Rita E; Aleman, Berthe M P; Andersson, Michael; Curtis, Rochelle E; Dores, Graça M; Fraumeni, Joseph F; Hall, Per; Holowaty, Eric J; Joensuu, Heikki; Kaijser, Magnus; Kleinerman, Ruth A; Langmark, Frøydis; Lynch, Charles F; Pukkala, Eero; Storm, Hans H; Vaalavirta, Leila; van den Belt-Dusebout, Alexandra W; Morton, Lindsay M; Fossa, Sophie D; Travis, Lois B

    2016-09-27

    Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear. Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer patients and 145 matched controls. Chemotherapy details were recorded. Logistic regression was used to estimate odds ratios (ORs). Cumulative incidence of second primary pancreatic cancer was 1.1% at 30 years after TC diagnosis. Radiotherapy (72 (90%) cases and 115 (80%) controls) was associated with a 2.9-fold (95% confidence interval (CI) 1.0-7.8) increased risk. The OR increased linearly by 0.12 per Gy to the pancreas (P-trendcancer risk, and persists for over 20 years. These excesses, although small, should be considered when radiotherapy with exposure to the pancreas is considered for newly diagnosed patients. Additional data are needed on the role of chemotherapy.

  9. Contemporary Management of Localized Resectable Pancreatic Cancer.

    Science.gov (United States)

    Kommalapati, Anuhya; Tella, Sri Harsha; Goyal, Gaurav; Ma, Wen Wee; Mahipal, Amit

    2018-01-20

    Pancreatic cancer is the third most common cause of cancer deaths in the United States. Surgical resection with negative margins still constitutes the cornerstone of potentially curative therapy, but is possible only in 15-20% of patients at the time of initial diagnosis. Accumulating evidence suggests that the neoadjuvant approach may improve R0 resection rate in localized resectable and borderline resectable diseases, and potentially downstage locally advanced disease to achieve surgical resection, though the impact on survival is to be determined. Despite advancements in the last decade in developing effective combinational chemo-radio therapeutic options, preoperative treatment strategies, and better peri-operative care, pancreatic cancer continues to carry a dismal prognosis in the majority. Prodigious efforts are currently being made in optimizing the neoadjuvant therapy with a better toxicity profile, developing novel agents, imaging techniques, and identification of biomarkers for the disease. Advancement in our understanding of the tumor microenvironment and molecular pathology is urgently needed to facilitate the development of novel targeted and immunotherapies for this setting. In this review, we detail the current literature on contemporary management of resectable, borderline resectable and locally advanced pancreatic cancer with a focus on future directions in the field.

  10. Opium Use and Risk of Pancreatic Cancer: A Prospective Cohort Study

    Science.gov (United States)

    Moossavi, Shirin; Mohamadnejad, Mehdi; Pourshams, Akram; Poustchi, Hossein; Islami, Farhad; Sharafkhah, Maryam; Mirminachi, Babak; Nasseri-Moghaddam, Siavosh; Semnani, Shahryar; Shakeri, Ramin; Etemadi, Arash; Merat, Shahin; Khoshnia, Masoud; Dawsey, Sanford M.; Pharoah, Paul D.; Brennan, Paul; Abnet, Christian C.; Boffetta, Paolo; Kamangar, Farin; Malekzadeh, Reza

    2018-01-01

    Background We examined the association between opium consumption and pancreatic cancer incidence in a large-scale prospective cohort of the general population in Northeast of Iran. Methods A total of 50,045 adults were systematically followed-up (median of 7.4 years) and incident cases of pancreatic cancer were identified. Self-reported data on opium consumption was collected at baseline. Cumulative use (-year) was defined as number of nokhods (a local unit, approximately 0.2 g) of opium consumed per day multiplied by number of years consuming. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between opium consumption and pancreatic cancer were calculated using Cox proportional hazards regression models. Results Overall, 54 confirmed cases of pancreatic cancer were identified. Opium use of more than 81 nokhod-years (high cumulative use), compared to never use, was strongly associated with pancreatic cancer even after adjustments for multiple potential confounding factors [HR=3.01; 95% CI 1.25-7.26]. High cumulative consumption of opium was significantly associated with risk of pancreatic cancer after adjusting for cumulative dose of cigarette smoking [HR=3.56; 95% CI 1.49-8.50]. In a sensitivity analysis, we excluded participants (including 2 pancreatic cancer cases) who were recruited within the first 5 years of starting opium consumption; high cumulative use of opium was still associated with pancreatic cancer risk [HR=2.75; 95% CI 1.14-6.64]. Conclusion Our results showed a positive association between opium consumption and pancreatic cancer. Impact This is the first prospective large-scale study to show the association of opium consumption with pancreatic cancer as a risk factor. PMID:29263189

  11. Vaginal metastasis of pancreatic cancer | Benhayoune | Pan African ...

    African Journals Online (AJOL)

    Vaginal metastasis from pancreatic cancer is an extreme case and often indicates a poor prognosis. We present a case of pancreatic carcinoma with metastasis to the vagina that was discovered by vaginal bleeding. To our knowledge, this is the third case in the world of a primary pancreatic adenocarcinoma discovered of ...

  12. Pathobiological implications of MUC16 expression in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Dhanya Haridas

    Full Text Available MUC16 (CA125 belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC, the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease.

  13. Personalized RNA Medicine for Pancreatic Cancer.

    Science.gov (United States)

    Gilles, Maud-Emmanuelle; Hao, Liangliang; Huang, Ling; Rupaimoole, Rajesha; Lopez-Casas, Pedro P; Pulver, Emilia; Jeong, Jong Cheol; Muthuswamy, Senthil K; Hidalgo, Manuel; Bhatia, Sangeeta N; Slack, Frank J

    2018-04-01

    Purpose: Since drug responses vary between patients, it is crucial to develop pre-clinical or co-clinical strategies that forecast patient response. In this study, we tested whether RNA-based therapeutics were suitable for personalized medicine by using patient-derived-organoid (PDO) and patient-derived-xenograft (PDX) models. Experimental Design: We performed microRNA (miRNA) profiling of PDX samples to determine the status of miRNA deregulation in individual pancreatic ductal adenocarcinoma (PDAC) patients. To deliver personalized RNA-based-therapy targeting oncogenic miRNAs that form part of this common PDAC miRNA over-expression signature, we packaged antimiR oligonucleotides against one of these miRNAs in tumor-penetrating nanocomplexes (TPN) targeting cell surface proteins on PDAC tumors. Results: As a validation for our pre-clinical strategy, the therapeutic potential of one of our nano-drugs, TPN-21, was first shown to decrease tumor cell growth and survival in PDO avatars for individual patients, then in their PDX avatars. Conclusions: This general approach appears suitable for co-clinical validation of personalized RNA medicine and paves the way to prospectively identify patients with eligible miRNA profiles for personalized RNA-based therapy. Clin Cancer Res; 24(7); 1734-47. ©2018 AACR . ©2018 American Association for Cancer Research.

  14. Immunotherapy in pancreatic cancer: Unleash its potential through novel combinations.

    Science.gov (United States)

    Guo, Songchuan; Contratto, Merly; Miller, George; Leichman, Lawrence; Wu, Jennifer

    2017-06-10

    Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States, with poor response to current standard of care, short progression-free and overall survival. Immunotherapies that target cytotoxic T lymphocyte antigen-4, programmed cell death protein-1, and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma, renal cell carcinoma, and non-small cell lung cancer due to high numbers of somatic mutations, combined with cytotoxic T-cell responses. However, single checkpoint blockade was ineffective in pancreatic cancer, highlighting the challenges including the poor antigenicity, a dense desmoplastic stroma, and a largely immunosuppressive microenvironment. In this review, we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy, radiotherapy, and targeted therapy. These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.

  15. FDA Approves Irinotecan Liposome to Treat Pancreatic Cancer

    Science.gov (United States)

    Patients with metastatic pancreatic cancer that has progressed after receiving gemcitabine-based chemotherapy now have a new treatment option: irinotecan liposome in combination with fluorouracil and leucovorin.

  16. Early Detection of Sporadic Pancreatic Cancer

    Science.gov (United States)

    Chari, Suresh T.; Kelly, Kimberly; Hollingsworth, Michael A.; Thayer, Sarah P.; Ahlquist, David A.; Andersen, Dana K.; Batra, Surinder K.; Brentnall, Teresa A.; Canto, Marcia; Cleeter, Deborah F.; Firpo, Matthew A.; Gambhir, Sanjiv Sam; Go, Vay Liang W.; Hines, O. Joe; Kenner, Barbara J.; Klimstra, David S.; Lerch, Markus M.; Levy, Michael J.; Maitra, Anirban; Mulvihill, Sean J.; Petersen, Gloria M.; Rhim, Andrew D.; Simeone, Diane M.; Srivastava, Sudhir; Tanaka, Masao; Vinik, Aaron I.; Wong, David

    2015-01-01

    Abstract Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC. PMID:25931254

  17. Exosomes Derived From Pancreatic Stellate Cells: MicroRNA Signature and Effects on Pancreatic Cancer Cells.

    Science.gov (United States)

    Takikawa, Tetsuya; Masamune, Atsushi; Yoshida, Naoki; Hamada, Shin; Kogure, Takayuki; Shimosegawa, Tooru

    2017-01-01

    Pancreatic stellate cells (PSCs) interact with pancreatic cancer cells in the tumor microenvironment. Cell constituents including microRNAs may be exported from cells within membranous nanovesicles termed exosomes. Exosomes might play a pivotal role in intercellular communication. This study aimed to clarify the microRNA signature of PSC-derived exosomes and their effects on pancreatic cancer cells. Exosomes were prepared from the conditioned medium of immortalized human PSCs. MicroRNAs were prepared from the exosomes and their source PSCs, and the microRNA expression profiles were compared by microarray. The effects of PSC-derived exosomes on proliferation, migration, and the mRNA expression profiles were examined in pancreatic cancer cells. Pancreatic stellate cell-derived exosomes contained a variety of microRNAs including miR-21-5p. Several microRNAs such as miR-451a were enriched in exosomes compared to their source PSCs. Pancreatic stellate cell-derived exosomes stimulated the proliferation, migration and expression of mRNAs for chemokine (C - X - C motif) ligands 1 and 2 in pancreatic cancer cells. The stimulation of proliferation, migration, and chemokine gene expression by the conditioned medium of PSCs was suppressed by GW4869, an exosome inhibitor. We clarified the microRNA expression profile in PSC-derived exosomes. Pancreatic stellate cell-derived exosomes might play a role in the interactions between PSCs and pancreatic cancer cells.

  18. Platinum-Based Therapy in Adenosquamous Pancreatic Cancer: Experience at Two Institutions

    OpenAIRE

    Andre Luiz De Souza; Muhammad Wasif Saif

    2014-01-01

    Adenosquamous carcinoma of the pancreas is a rare type of pancreatic cancer. Although its molecular biology profile hasbeen shown to be similar to pancreatic ductal adenocarcinoma tumors, it has different prognostic features. There is noconsensus or guidelines to treat this tumor differently from pancreatic adenocarcinoma, but therapies based on gemcitabineand platinum chemotherapeutics such as cisplatin and oxaliplatin have been used based on results of a few case reports. Wediscuss the Abst...

  19. Kallikrein-related peptidase 7 is a potential target for the treatment of pancreatic cancer

    Science.gov (United States)

    Zheng, Jun; Zhang, Ding; Liu, Wei; Zheng, Wei Hong; Li, Xiao Song; Yao, Ru Cheng; Wang, Fangyu; Liu, Sen; Tan, Xiao

    2018-01-01

    Pancreatic cancer is one of the deadliest cancers with very poor prognosis, and the five-year survival rate of the patients is less than 5% after diagnosis. Kallikrein-related peptidases (KLKs) belong to a serine protease family with 15 members that play important roles in cellular physiological behavior and diseases. The high expression level of KLK7 in pancreatic cancer tissues is considered to be a marker for the poor prognosis of this disease. In this work, we set out to investigate whether KLK7 could be a target for the treatment of pancreatic cancer. Short hairpin RNAs (shRNAs) were designed and constructed in lentivirus to knock down KLK7 in pancreatic cancer cell line PANC-1, and the real time cellular analysis (RTCA) was used to evaluate cell proliferation, migration and invasion abilities. Small molecules inhibiting KLK7 were discovered by computer-aided drug screening and used to inhibit PANC-1 cells. Our results confirmed that KLK7 is significantly up-regulated in pancreatic cancer tissue, and knocking down or inhibiting KLK7 efficiently inhibited the proliferation, migration and invasion of pancreatic cancer cells. This study suggested that KLK7 could be a potential chemotherapy target for treatment of pancreatic cancer, which would provide us a novel strategy for the treatment of this disease. PMID:29560118

  20. Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge

    International Nuclear Information System (INIS)

    Rizwani, Wasia; Allen, Amanda E.; Trevino, Jose G.

    2015-01-01

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF), the sole ligand for c-MET (mesenchymal-epithelial transition), an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression. Inhibiting activation of c-MET in cancer cells, in combination with other approaches for reducing desmoplasia in the tumor microenvironment, might significantly improve the success of chemotherapy. Therefore, HGF makes a potent novel target for developing therapeutic strategies in combination with existing drugs for treating pancreatic adenocarcinoma. This review provides a comprehensive analysis of HGF and its promising potential as a chemotherapeutic target for pancreatic cancer

  1. Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge

    Energy Technology Data Exchange (ETDEWEB)

    Rizwani, Wasia [Department of Biochemistry, Osmania University, Hyderabad, Telangana 500007 (India); Allen, Amanda E.; Trevino, Jose G., E-mail: Jose.Trevino@surgery.ufl.edu [Department of Surgery, University of Florida, 1600 SW Archer Rd, Rm 6175, P.O. Box 100109, Gainesville, FL 32610 (United States)

    2015-09-03

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF), the sole ligand for c-MET (mesenchymal-epithelial transition), an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression. Inhibiting activation of c-MET in cancer cells, in combination with other approaches for reducing desmoplasia in the tumor microenvironment, might significantly improve the success of chemotherapy. Therefore, HGF makes a potent novel target for developing therapeutic strategies in combination with existing drugs for treating pancreatic adenocarcinoma. This review provides a comprehensive analysis of HGF and its promising potential as a chemotherapeutic target for pancreatic cancer.

  2. Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge

    Directory of Open Access Journals (Sweden)

    Wasia Rizwani

    2015-09-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF, the sole ligand for c-MET (mesenchymal-epithelial transition, an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression. Inhibiting activation of c-MET in cancer cells, in combination with other approaches for reducing desmoplasia in the tumor microenvironment, might significantly improve the success of chemotherapy. Therefore, HGF makes a potent novel target for developing therapeutic strategies in combination with existing drugs for treating pancreatic adenocarcinoma. This review provides a comprehensive analysis of HGF and its promising potential as a chemotherapeutic target for pancreatic cancer.

  3. A missing link between RON expression and oncological outcomes in resected left-sided pancreatic cancer.

    Science.gov (United States)

    Han, Dai Hoon; Kang, Chang Moo; Lee, Sung Whan; Hwang, Ho Kyoung; Lee, Woo Jung

    2017-10-01

    Alteration and activation of recepteur d'origine nantais (RON) expression is known to be associated with cancer progression and decreased survival in various types of human cancer, including pancreatic cancer. Therefore, in the present study, RON expression levels were determined in resected left-sided pancreatic cancer to evaluate the potential oncological role of RON in the clinical setting of distal pancreatic cancer. From January 2005 to December 2011, a total of 57 patients underwent radical distal pancreatectomy for left-sided pancreatic cancer. Ductal adenocarcinoma was confirmed in all patients. Among these patients, 17 patients who received preoperative neoadjuvant treatment and 7 patients without available paraffin-embedded tissue blocks were excluded from the present study. RON expression in a the pancreatic cancer cell lines ASPC-1, BxPC-3, MiaPaCa-3 and Panc-1, as well as in resected left-sided pancreatic cancer specimens was determined by Western blot analysis. RON and vascular endothelial growth factor (VEGF) overexpression in resected left-sided pancreatic cancer was also evaluated by immunohistochemistry using pre-diluted anti-RON and anti-VEGF antibodies. An association was identified between the oncological outcome and RON overexpression. Increased levels of RON expression were observed in two pancreatic cancer cell lines, AsPC-1 and BxPC-3. RON overexpression was detected in specimens from 15/33 patients (45.5%) using immunohistochemistry. No significant association was identified between RON overexpression and VEGF overexpression (25.5 vs. 87.9%; P=0.667). No significant differences in disease-free survival or disease-specific survival associated with RON overexpression were identified. Although the results of previous studies have suggested that RON is a potential target for the treatment of pancreatic cancer, in the present study no association between RON overexpression and any adverse oncological effect was identified.

  4. Concurrent chemoradiation for unresectable pancreatic cancer

    International Nuclear Information System (INIS)

    Kim, Yong Bae; Seong, Jin Sil; Song, Si Young; Park, Seung Woo; Suh, Chang Ok

    2002-01-01

    To analyze the treatment results of concurrent chemoradiation with oral 5-FU plus Gemcitabine or Paclitaxel for unresectable pancreatic cancer. The patients, who were diagnosed by imaging modalities or by explo-laparotomy were treated with concurrent chemoradiation. Radiotherapy was delivered to primary tumor and regional lymph nodes, and the total dose was 45 Gy. Patients received Gemcitabine 1,000 mg/m 2 or Paclitaxel 50 mg/m 2 weekly and oral 5-FU daily. The total number of cycles of chemotherapy ranged from 1 to 39 (median, 11 cycles). The follow-up period ranged from 6 to 36 months. Survival was analyzed using the Kaplan-Meier method. Fifty-four patients between Jan. 1999 to Nov. 2001 were included in this study. Forty-two patients who completed the planned treatment were included in this analysis. The patients' age ranged from 37 to 73 years (median, 60 years) and the male to female ratio was 30:12. Treatment was interrupted for 12 patients due to; disease progression for 6 (50%), poor performance status for 4 (33.3%), intercurrent disease for 1 (8.3%), and refusal for 1 (8.3%). Response evaluation was possible for 40 patients. One patient gained complete remission and 24 patients gained partial remission, hence the response rate was 59%. The survival rates were 46.7% and 17.0% at 1 year and 2 years, respectively with a median survival time of 12 months. Patients treated with Paclitaxel showed superior outcomes compared to those patients treated with Gemcitabine, in terms of both response rate and survival rate although this difference was not statistically significant. Grade III or IV hematologic toxicity was shown in 8 patients (19%), while grade III or IV non-hematologic toxicity was shown in 5 patients (12%). Concurrent chemoradiation with oral 5-FU and Gemcitabine or Paclitaxel improves both the response rate and survival rate in patients with unresectable pancreatic cancer. A prospective study should be investigated in order to improve both the patient

  5. Endoscopic ultrasound in the diagnosis and staging of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    J. Iglesias García

    Full Text Available Pancreatic cancer is the 5th leading cause of cancer-related death in Western countries. The 5-year survival rate is approximately 4%, without significant changes over the last 50 years. This poor survival rate and bad prognosis are associated with the diagnosis of advanced-stage disease, which precludes the only potential curative treatment - surgical resection. In this setting, the main objective in the management of pancreatic cancer is to perform an early diagnosis and a correct staging of the disease. Endoscopic ultrasonography (EUS appears to be an essential tool for the diagnosis and staging of pancreatic cancer. EUS diagnostic accuracy for detecting pancreatic tumors ranges from 85 to 100%, clearly superior to other imaging techniques. EUS accuracy for the local staging of pancreatic cancer ranges from 70 to 90%, superior or equivalent to other imaging modalities. EUS-guided fine-needle aspiration allows a cyto-histological diagnosis in nearly 90% of cases, with a very low complication rate. At present, the formal indications for EUS-guided fine-needle aspiration are the necessity of palliative treatment or whenever the possibility of neoadjuvant treatment is present. It could be also indicated to differentiate pancreatic adenocarcinoma from other pancreatic conditions, like lymphoma, metastasis, autoimmune pancreatitis or chronic pancreatitis. We can conclude that EUS is an essential tool in the management of patients with pancreatic tumors.

  6. Endoscopic ultrasound in the diagnosis and staging of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    J. Iglesias García

    2009-09-01

    Full Text Available Pancreatic cancer is the 5th leading cause of cancer-related death in Western countries. The 5-year survival rate is approximately 4%, without significant changes over the last 50 years. This poor survival rate and bad prognosis are associated with the diagnosis of advanced-stage disease, which precludes the only potential curative treatment - surgical resection. In this setting, the main objective in the management of pancreatic cancer is to perform an early diagnosis and a correct staging of the disease. Endoscopic ultrasonography (EUS appears to be an essential tool for the diagnosis and staging of pancreatic cancer. EUS diagnostic accuracy for detecting pancreatic tumors ranges from 85 to 100%, clearly superior to other imaging techniques. EUS accuracy for the local staging of pancreatic cancer ranges from 70 to 90%, superior or equivalent to other imaging modalities. EUS-guided fine-needle aspiration allows a cyto-histological diagnosis in nearly 90% of cases, with a very low complication rate. At present, the formal indications for EUS-guided fine-needle aspiration are the necessity of palliative treatment or whenever the possibility of neoadjuvant treatment is present. It could be also indicated to differentiate pancreatic adenocarcinoma from other pancreatic conditions, like lymphoma, metastasis, autoimmune pancreatitis or chronic pancreatitis. We can conclude that EUS is an essential tool in the management of patients with pancreatic tumors.

  7. Nutritional status and nutritional support before and after pancreatectomy for pancreatic cancer and chronic pancreatitis.

    Science.gov (United States)

    Karagianni, Vasiliki Th; Papalois, Apostolos E; Triantafillidis, John K

    2012-12-01

    Cachexia, malnutrition, significant weight loss, and reduction in food intake due to anorexia represent the most important pathophysiological consequences of pancreatic cancer. Pathophysiological consequences result also from pancreatectomy, the type and severity of which differ significantly and depend on the type of the operation performed. Nutritional intervention, either parenteral or enteral, needs to be seen as a method of support in pancreatic cancer patients aiming at the maintenance of the nutritional and functional status and the prevention or attenuation of cachexia. Oral nutrition could reduce complications while restoring quality of life. Enteral nutrition in the post-operative period could also reduce infective complications. The evidence for immune-enhanced feed in patients undergoing pancreaticoduodenectomy for pancreatic cancer is supported by the available clinical data. Nutritional support during the post-operative period on a cyclical basis is preferred because it is associated with low incidence of gastric stasis. Postoperative total parenteral nutrition is indicated only to those patients who are unable to be fed orally or enterally. Thus nutritional deficiency is a relatively widesoread and constant finding suggesting that we must optimise the nutritional status both before and after surgery.

  8. Selection and Outcome of Portal Vein Resection in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Nakao, Akimasa

    2010-01-01

    Pancreatic cancer has the worst prognosis of all gastrointestinal neoplasms. Five-year survival of pancreatic cancer after pancreatectomy is very low, and surgical resection is the only option to cure this dismal disease. The standard surgical procedure is pancreatoduodenectomy (PD) for pancreatic head cancer. The morbidity and especially the mortality of PD have been greatly reduced. Portal vein resection in pancreatic cancer surgery is one attempt to increase resectability and radicality, and the procedure has become safe to perform. Clinicohistopathological studies have shown that the most important indication for portal vein resection in patients with pancreatic cancer is the ability to obtain cancer-free surgical margins. Otherwise, portal vein resection is contraindicated

  9. Selection and Outcome of Portal Vein Resection in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nakao, Akimasa [Department of Surgery II, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan)

    2010-11-24

    Pancreatic cancer has the worst prognosis of all gastrointestinal neoplasms. Five-year survival of pancreatic cancer after pancreatectomy is very low, and surgical resection is the only option to cure this dismal disease. The standard surgical procedure is pancreatoduodenectomy (PD) for pancreatic head cancer. The morbidity and especially the mortality of PD have been greatly reduced. Portal vein resection in pancreatic cancer surgery is one attempt to increase resectability and radicality, and the procedure has become safe to perform. Clinicohistopathological studies have shown that the most important indication for portal vein resection in patients with pancreatic cancer is the ability to obtain cancer-free surgical margins. Otherwise, portal vein resection is contraindicated.

  10. Role of chymotrypsin C in development and progression of pancreatitis and pancreatic cancer

    Directory of Open Access Journals (Sweden)

    LIU Zejie

    2016-11-01

    Full Text Available Chymotrypsin C (CTRC is a trypsinogen synthesized by pancreatic acinar cells and secreted by pancreatic duct cells and belongs to the family of serine chymotrypsin. The main function of CTRC is to regulate the balance between activation and degradation of trypsin and maintain the structural and functional integrity of the pancreas. CTRC gene mutations can cause abnormal activation of trypsinogen and abnormal degradation of trypsin and then lead to the development of pancreatitis. The downregulation or absence of CTRC expression may be associated with the development and metastasis of pancreatic cancer. This article introduces the structure and biological function of CTRC and its mechanism of action in the development and progression of pancreatitis and pancreatic cancer.

  11. Activation Of Wild-Type Hras Suppresses The Earliest Stages Of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Jamie Weyandt

    2015-08-01

    Conclusions: Loss of wild-type Hras promotes the earliest stages of pancreatic tumorigenesis, and moreover results in more rapid progression of the disease. As such, mechanisms leading to activation of wild-type Ras proteins, including but not limited to redox-dependent reactions, may influence the development of pancreatic cancer.

  12. Diagnosis of pancreatic cancer using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET). Usefulness and limitations in clinical reality''

    International Nuclear Information System (INIS)

    Higashi, Tatsuya; Saga, Tsuneo; Ishimori, Takayoshi; Fujimoto, Koji; Doi, Ryuichiro; Imamura, Masayuki; Konishi, Junji

    2003-01-01

    The present review will provide an overview of the literature concerning the FDG PET diagnosis of pancreatic cancer and a summary from our experience of 231 cases of pancreatic lesions. FDG PET can effectively differentiate pancreatic cancer from benign lesion with high accuracy. Newly-developed PET scanners can detect small pancreatic cancers, up to 7 mm in diameter, by their high resolution, which could make a great contribution to the early detection of resectable and potentially curable pancreatic cancers. FDG PET is useful and cost-beneficial in the pre-operative staging of pancreatic cancer because an unexpected distant metastasis can be detected by whole-body PET in about 40% of the cases, which results in avoidance of unnecessary surgical procedures. FDG PET is also useful in evaluation of the treatment effect, monitoring after the operation and detection of recurrent pancreatic cancers. However, there are some drawbacks in PET diagnosis. A relatively wide overlap has been reported between semiquantitative uptake values obtained in cancers and those in inflammatory lesions. As for false-positive cases, active and chronic pancreatitis and autoimmune pancreatitis sometimes show high FDG accumulation and mimic pancreatic cancer with a shape of focal uptake. There were 8 false negative cases in the detection of pancreatic cancer by FDG PET, up to 33 mm in diameter, mainly because of their poor cellularity in cancer tissues. In addition, there are 19% of cancer cases with a decline in FDG uptake from 1 hr to 2 hr scan. FDG PET was recently applied to and was shown to be feasible in the differential diagnosis of cystic pancreatic lesions, such as intraductal papillary mucinous tumor of the pancreas. Further investigations are required to clarify the clinical value of FDG PET in predicting prognosis of the pancreatic patients. (author) 124 refs

  13. Intervention on toll-like receptors in pancreatic cancer.

    Science.gov (United States)

    Vaz, Juan; Andersson, Roland

    2014-05-21

    Pancreatic ductal adenocarcinoma (PDA) is a devastating disease with pronounced morbidity and a high mortality rate. Currently available treatments lack convincing cost-efficiency determinations and are in most cases not associated with relevant success rate. Experimental stimulation of the immune system in murine PDA models has revealed some promising results. Toll-like receptors (TLRs) are pillars of the immune system that have been linked to several forms of malignancy, including lung, breast and colon cancer. In humans, TLRs are expressed in the pancreatic cancer tissue and in several cancer cell lines, whereas they are not expressed in the normal pancreas. In the present review, we explore the current knowledge concerning the role of different TLRs associated to PDA. Even if almost all known TLRs are expressed in the pancreatic cancer microenvironment, there are only five TLRs suggested as possible therapeutic targets. Most data points at TLR2 and TLR9 as effective tumor markers and agonists could potentially be used as e.g. future adjuvant therapies. The elucidation of the role of TLR3 in PDA is only in its initial phase. The inhibition/blockage of TLR4-related pathways has shown some promising effects, but there are still many steps left before TLR4 inhibitors can be considered as possible therapeutic agents. Finally, TLR7 antagonists seem to be potential candidates for therapy. Independent of their potential in immunotherapies, all existing data indicate that TLRs are strongly involved in the pathophysiology and development of PDA.

  14. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer.

    Science.gov (United States)

    Kamerkar, Sushrut; LeBleu, Valerie S; Sugimoto, Hikaru; Yang, Sujuan; Ruivo, Carolina F; Melo, Sonia A; Lee, J Jack; Kalluri, Raghu

    2017-06-22

    The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes are extracellular vesicles generated by all cells, and are naturally present in the blood. Here we show that enhanced retention of exosomes, compared to liposomes, in the circulation of mice is likely due to CD47-mediated protection of exosomes from phagocytosis by monocytes and macrophages. Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry short interfering RNA or short hairpin RNA specific to oncogenic Kras G12D , a common mutation in pancreatic cancer. Compared to liposomes, the engineered exosomes (known as iExosomes) target oncogenic KRAS with an enhanced efficacy that is dependent on CD47, and is facilitated by macropinocytosis. Treatment with iExosomes suppressed cancer in multiple mouse models of pancreatic cancer and significantly increased overall survival. Our results demonstrate an approach for direct and specific targeting of oncogenic KRAS in tumours using iExosomes.

  15. A Case of Pancreatic Cancer in the Setting of Autoimmune Pancreatitis with Nondiagnostic Serum Markers

    Directory of Open Access Journals (Sweden)

    Manju D. Chandrasegaram

    2013-01-01

    Full Text Available Background. Autoimmune pancreatitis (AIP often mimics pancreatic cancer. The diagnosis of both conditions is difficult preoperatively let alone when they coexist. Several reports have been published describing pancreatic cancer in the setting of AIP. Case Report. The case of a 53-year-old man who presented with abdominal pain, jaundice, and radiological features of autoimmune pancreatitis, with a “sausage-shaped” pancreas and bulky pancreatic head with portal vein impingement, is presented. He had a normal serum IgG4 and only mildly elevated Ca-19.9. Initial endoscopic ultrasound-(EUS- guided fine-needle aspiration (FNA of the pancreas revealed an inflammatory sclerosing process only. A repeat EUS guided biopsy following biliary decompression demonstrated both malignancy and features of autoimmune pancreatitis. At laparotomy, a uniformly hard, bulky pancreas was found with no sonographically definable mass. A total pancreatectomy with portal vein resection and reconstruction was performed. Histology revealed adenosquamous carcinoma of the pancreatic head and autoimmune pancreatitis and squamous metaplasia in the remaining pancreas. Conclusion. This case highlights the diagnostic and management difficulties in a patient with pancreatic cancer in the setting of serum IgG4-negative, Type 2 AIP.

  16. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

    Science.gov (United States)

    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  17. Emphasis on neoadjuvant therapy for “resectable” pancreatic cancer

    Directory of Open Access Journals (Sweden)

    LIU Chang

    2015-05-01

    Full Text Available The treatment concept for pancreatic cancer is being transferred from “surgery first” to MDT model. The postoperative adjuvant treatment of pancreatic cancer can significantly improve the prognosis of patients and has become the standardized diagnostic and treatment practice; the value and significance of neoadjuvant therapy remains unclear. Limited clinical studies of “borderline resectable” pancreatic cancer have shown that neoadjuvant therapy can improve the R0 resection rate and improve the prognosis of patients, and it is recommended for clinical application. But the significance of neoadjuvant therapy in “resectable” pancreatic cancer is still controversial. There is a lack of consensus on indications, cycles, and regimens. It is necessary to carry out a series of prospective control studies to objectively evaluate the value of neoadjuvant therapy in improving the prognosis of “resectable” pancreatic cancer.

  18. Curcumin AntiCancer Studies in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte

    2016-07-01

    Full Text Available Pancreatic cancer (PC is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC.

  19. Paratesticular adenocarcinoma. Unusual presentation of metastasis of pancreatic cancer

    International Nuclear Information System (INIS)

    Ocvirk, J.; Seruga, B.

    2007-01-01

    Metastatic paratesticular adenocarcinoma from the pancreatic cancer is very rare. To our knowledge, there are less than 20 cases published in the literature. We experienced a case of paratesticular adenocarcinoma from the primary pancreatic cancer. A 42-year-old man was presented with locoregionally advanced carcinoma of the tail of the pancreas with intraoperatively found liver metastases and with a tumour in the right hemi-scrotum. Ultrasound of the scrotum revealed a paratesticular tumour. A fine needle aspiration biopsy (FNAB) confirmed a poorly differentiated adenocarcinoma and it was in concordance with the diagnosis of the primary tumour. The patient started treatment with chemotherapy with gemcitabine. Unfortunately, he progressed one month later and the treatment was discontinued. Outcome in the adenocarcinoma of the pancreas is dismal. The only possible treatment option for metastatic disease is systemic therapy but the results are disappointing, as in the present case. (author)

  20. Role of radiation therapy in patients with resectable pancreatic cancer.

    Science.gov (United States)

    Palta, Manisha; Willett, Christopher; Czito, Brian

    2011-07-01

    The 5-year overall survival of patients with pancreatic cancer is approximately 5%, with potentially resectable disease representing the curable minority. Although surgical resection remains the cornerstone of treatment, local and distant failure rates are high after complete resection, and debate continues as to the appropriate adjuvant therapy. Many oncologists advocate for adjuvant chemotherapy alone, given that high rates of systemic metastases are the primary cause of patient mortality. Others, however, view locoregional failure as a significant contributor to morbidity and mortality, thereby justifying the use of adjuvant chemoradiation. As in other gastrointestinal malignancies, neoadjuvant chemoradiotherapy offers potential advantages in resectable patients, and clinical investigation of this approach has shown promising results; however, phase III data are lacking. Further therapeutic advances and prospective trials are needed to better define the optimal role of adjuvant and neoadjuvant treatment in patients with resectable pancreatic cancer.

  1. Nationwide prospective audit of pancreatic surgery: design, accuracy, and outcomes of the Dutch Pancreatic Cancer Audit

    NARCIS (Netherlands)

    van Rijssen, L. Bengt; Koerkamp, Bas G.; Zwart, Maurice J.; Bonsing, Bert A.; Bosscha, Koop; van Dam, Ronald M.; van Eijck, Casper H.; Gerhards, Michael F.; van der Harst, Erwin; de Hingh, Ignace H.; de Jong, Koert P.; Kazemier, Geert; Klaase, Joost; van Laarhoven, Cornelis J.; Molenaar, I. Quintus; Patijn, Gijs A.; Rupert, Coen G.; van Santvoort, Hjalmar C.; Scheepers, Joris J.; van der Schelling, George P.; Busch, Olivier R.; Besselink, Marc G.; Bollen, Thomas L.; Bruno, Marco J.; van Tienhoven, Geert-Jan; Norduyn, Arnold; Berry, David P.; Tingstedt, Bobby; Tseng, Jennifer F.; Wolfgang, Christopher L.

    2017-01-01

    Background: Auditing is an important tool to identify practice variation and 'best practices'. The Dutch Pancreatic Cancer Audit is mandatory in all 18 Dutch centers for pancreatic surgery. Methods: Performance indicators and case-mix factors were identified by a PubMed search for randomized

  2. Methylation of the SPARC gene promoter and its clinical implication in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Lv Shunli

    2010-03-01

    Full Text Available Abstract Background The secreted protein acidic and rich in cysteine (SPARC plays a pivotal role in regulating cell-matrix interactions and tumor angiogenesis, proliferation, and migration. Detection of SPARC gene methylation may be useful as a tumorigenesis marker for early detection of pancreatic cancer. Methods Methylation of the SPARC gene transcriptional regulation region (TRR was detected using bisulfite-specific (BSP PCR-based sequencing analysis in 40 cases of pancreatic cancer and the adjacent normal tissues, 6 chronic pancreatitis tissues, and 6 normal pancreatic tissues. BSP cloning-based sequencing analysis was also performed in selected cases. Clinicopathological data from the cancer patients were collected and analyzed. Results Analysis of SPARC gene TRR methylation showed two hypermethylation wave peak regions: CpG Region 1 (CpG site 1-7 and CpG Region 2 (CpG site 8-12. Pancreatic tissues have shown methylation in both regions with gradual increases from normal, chronic pancreatitis, and adjacent normal tissues to cancerous tissues. However, Methylation of CpG Region 2 was more sensitive than CpG Region 1 in pancreatic tumorigenesis. Furthermore, the methylation level of CpG Region 2 was associated with increased tumor size and exposure to the risk factors (tobacco smoke and alcohol consumption for developing pancreatic cancer. Conclusion Methylation of the SPARC gene, specifically CpG Region 2, may be an early event during pancreatic tumorigenesis and should be further evaluated as a tumorigenesis marker for early detection of pancreatic cancer.

  3. Vitamin D metabolic pathway genes and pancreatic cancer risk.

    Directory of Open Access Journals (Sweden)

    Hannah Arem

    Full Text Available Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN totaling 213 single nucleotide polymorphisms (SNPs, and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L for the most significant SNPs using a subset of cohort cases (n = 713 and controls (n = 878. The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830. Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the VDR (rs2239186, LRP2 (rs4668123, CYP24A1 (rs2762932, GC (rs2282679, and CUBN (rs1810205 genes were the top SNPs associated with pancreatic cancer (p-values 0.008-0.037, but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.

  4. Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok

    2014-01-01

    Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

  5. Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok [Seoul St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

  6. Animal models of pancreatic cancer for drug research.

    Science.gov (United States)

    Kapischke, Matthias; Pries, Alexandra

    2008-10-01

    The operative and conservative results of therapy in pancreatic ductal adenocarcinoma remain appallingly poor. This underlines the demand for further research for effective anticancer drugs. The various animal models remain the essential method for the determination of efficacy of substances during preclinical phase. Unfortunately, most of these tested substances showed a good efficacy in pancreatic carcinoma in the animal model but were not confirmed during the clinical phase. The available literature in PubMed, Medline, Ovid and secondary literature was searched regarding the available animal models for drug testing against pancreatic cancer. The models were analyzed regarding their pros and cons in anticancer drug testing. The different modifications of the orthotopic model (especially in mice) seem at present to be the best model for anticancer testing in pancreatic carcinoma. The value of genetically engineered animal model (GEM) and syngeneic models is on debate. A good selection of the model concerning the questions supposed to be clarified may improve the comparability of the results of animal experiments compared to clinical trials.

  7. CT findings of the mucin producing pancreatic cancer

    International Nuclear Information System (INIS)

    Ri, Kyoushichi; Hashimoto, Toushi; Munechika, Hirotsugu

    1992-01-01

    Mucin-producing pancreatic cancers (MPPC), which include mucinous adenocarcinoma, papillary adenocarcinoma and cystadenocarcinoma, are radiographically characterized by diffuse or localized dilatation of the main pancreatic duct due to excessive mucin production. Therefore, MPPC are occasionally difficult to distinguish from chronic pancreatitis on CT unless the primary pancreatic lesion is visualized. We compared five cases of MPPC with five cases of chronic pancreatitis with marked duct dilatation to determine differences in CT images between the two diseases. There was no significant difference between the two diseases in the nature of duct dilatation (size, extent, contour) or parenchymal changes (atrophy, enlargement, calcification, cystic lesion). However, dilatation of the intramural duct was characteristically observed in MPPC but not in chronic pancreatitis. Papillary masses in the pancreatic duct, when observed, were another finding specific to MPPC. (author)

  8. Susceptibility of ATM-deficient pancreatic cancer cells to radiation.

    Science.gov (United States)

    Ayars, Michael; Eshleman, James; Goggins, Michael

    2017-05-19

    Ataxia telangiectasia mutated (ATM) is inactivated in a significant minority of pancreatic ductal adenocarcinomas and may be predictor of treatment response. We determined if ATM deficiency renders pancreatic cancer cells more sensitive to fractionated radiation or commonly used chemotherapeutics. ATM expression was knocked down in three pancreatic cancer cell lines using ATM-targeting shRNA. Isogenic cell lines were tested for sensitivity to several chemotherapeutic agents and radiation. DNA repair kinetics were analyzed in irradiated cells using the comet assay. We find that while rendering pancreatic cancer cells ATM-deficient did not significantly change their sensitivity to several chemotherapeutics, it did render them exquisitely sensitized to radiation. Pancreatic cancer ATM status may help predict response to radiotherapy.

  9. A current perspective on stereotactic body radiation therapy for pancreatic cancer.

    Science.gov (United States)

    Hong, Julian C; Czito, Brian G; Willett, Christopher G; Palta, Manisha

    2016-01-01

    Pancreatic cancer is a formidable malignancy with poor outcomes. The majority of patients are unable to undergo resection, which remains the only potentially curative treatment option. The management of locally advanced (unresectable) pancreatic cancer is controversial; however, treatment with either chemotherapy or chemoradiation is associated with high rates of local tumor progression and metastases development, resulting in low survival rates. An emerging local modality is stereotactic body radiation therapy (SBRT), which uses image-guided, conformal, high-dose radiation. SBRT has demonstrated promising local control rates and resultant quality of life with acceptable rates of toxicity. Over the past decade, increasing clinical experience and data have supported SBRT as a local treatment modality. Nevertheless, additional research is required to further evaluate the role of SBRT and improve upon the persistently poor outcomes associated with pancreatic cancer. This review discusses the existing clinical experience and technical implementation of SBRT for pancreatic cancer and highlights the directions for ongoing and future studies.

  10. PDX-1 Is a Therapeutic Target for Pancreatic Cancer, Insulinoma and Islet Neoplasia Using a Novel RNA Interference Platform

    Science.gov (United States)

    Liu, Shi-He; Rao, Donald D.; Nemunaitis, John; Senzer, Neil; Zhou, Guisheng; Dawson, David; Gingras, Marie-Claude; Wang, Zhaohui; Gibbs, Richard; Norman, Michael; Templeton, Nancy S.; DeMayo, Francesco J.; O'Malley, Bert; Sanchez, Robbi; Fisher, William E.; Brunicardi, F. Charles

    2012-01-01

    Pancreatic and duodenal homeobox-1 (PDX-1) is a transcription factor that regulates insulin expression and islet maintenance in the adult pancreas. Our recent studies demonstrate that PDX-1 is an oncogene for pancreatic cancer and is overexpressed in pancreatic cancer. The purpose of this study was to demonstrate that PDX-1 is a therapeutic target for both hormonal symptoms and tumor volume in mouse models of pancreatic cancer, insulinoma and islet neoplasia. Immunohistochemistry of human pancreatic and islet neoplasia specimens revealed marked PDX-1 overexpression, suggesting PDX-1 as a “drugable” target within these diseases. To do so, a novel RNA interference effector platform, bifunctional shRNAPDX-1, was developed and studied in mouse and human cell lines as well as in mouse models of pancreatic cancer, insulinoma and islet neoplasia. Systemic delivery of bi-shRNAhumanPDX-1 lipoplexes resulted in marked reduction of tumor volume and improved survival in a human pancreatic cancer xenograft mouse model. bi-shRNAmousePDX-1 lipoplexes prevented death from hyperinsulinemia and hypoglycemia in an insulinoma mouse model. shRNAmousePDX-1 lipoplexes reversed hyperinsulinemia and hypoglycemia in an immune-competent mouse model of islet neoplasia. PDX-1 was overexpressed in pancreatic neuroendocrine tumors and nesidioblastosis. These data demonstrate that PDX-1 RNAi therapy controls hormonal symptoms and tumor volume in mouse models of pancreatic cancer, insulinoma and islet neoplasia, therefore, PDX-1 is a potential therapeutic target for these pancreatic diseases. PMID:22905092

  11. Multimodal treatment for unresectable pancreatic cancer

    International Nuclear Information System (INIS)

    Katayama, Kanji; Iida, Atsushi; Fujita, Takashi; Kobayashi, Taizo; Shinmoto, Syuichi; Hirose, Kazuo; Yamaguchi, Akio; Yoshida, Masanori

    1998-01-01

    In order to improve in prognosis and quality of life (QOL), the multimodal treatment for unresectable pancreatic cancers were performed. Bypass surgery was carried out for unresectable pancreatic cancer with intraoperative irradiation (IOR). After surgery, patients were treated with the combination of CDDP (25 mg) and MMC (4 mg) administration, intravenously continuous injection of 5-FU (250 mg for 24 hours), external radiation by the high voltage X-ray (1.5 Gy per irradiation, 4 times a week, and during hyperthermia 3 Gy per irradiation) and hyperthermia using the Thermotron RF-8 warmer. Six out of 13 patients received hyperthermia at over 40degC, were obtained PR, and their survival periods were 22, 21, 19, 18, 11 and 8 months and they could return to work. For all patients with pain, the symptom was abolished or reduced. The survival periods in cases of the multimodal treatment were longer than those of only bypass-surgery or of the resective cases with the curability C. The multimodal treatment combined with radiation, hyperthermia and surgery is more useful for the removal of pain and the improvement of QOL, and also expected the improvement of the prognosis than pancreatectomy. And hyperthermia has an important role on the effect of this treatment. (K.H.)

  12. Multimodal treatment for unresectable pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Katayama, Kanji; Iida, Atsushi; Fujita, Takashi; Kobayashi, Taizo; Shinmoto, Syuichi; Hirose, Kazuo; Yamaguchi, Akio; Yoshida, Masanori [Fukui Medical School, Matsuoka (Japan)

    1998-07-01

    In order to improve in prognosis and quality of life (QOL), the multimodal treatment for unresectable pancreatic cancers were performed. Bypass surgery was carried out for unresectable pancreatic cancer with intraoperative irradiation (IOR). After surgery, patients were treated with the combination of CDDP (25 mg) and MMC (4 mg) administration, intravenously continuous injection of 5-FU (250 mg for 24 hours), external radiation by the high voltage X-ray (1.5 Gy per irradiation, 4 times a week, and during hyperthermia 3 Gy per irradiation) and hyperthermia using the Thermotron RF-8 warmer. Six out of 13 patients received hyperthermia at over 40degC, were obtained PR, and their survival periods were 22, 21, 19, 18, 11 and 8 months and they could return to work. For all patients with pain, the symptom was abolished or reduced. The survival periods in cases of the multimodal treatment were longer than those of only bypass-surgery or of the resective cases with the curability C. The multimodal treatment combined with radiation, hyperthermia and surgery is more useful for the removal of pain and the improvement of QOL, and also expected the improvement of the prognosis than pancreatectomy. And hyperthermia has an important role on the effect of this treatment. (K.H.)

  13. Radiation induces invasiveness of pancreatic cancer via up-regulation of heparanase

    International Nuclear Information System (INIS)

    Lerner, I.; Bensoussan, E.; Meirovitz, A.; Elkin, M.; Vlodavsky, I.

    2013-01-01

    The full text of the publication follows. Pancreatic cancer is one of the most aggressive neoplasms with an extremely low survival rate. Because most pancreatic carcinoma patients miss the opportunity for complete surgical resection at the time of diagnosis, radiotherapy remains a major component of treatment modalities. However, pancreatic cancer often shows resistance to radiation therapy. Ionizing radiation (IR)-induced aggressiveness is emerging as one of the important mechanisms responsible for the limited benefit of radiation therapy in pancreatic cancer, but the identity of downstream effectors responsible for this effect remains poorly investigated. Here we report that IR promotes pancreatic cancer aggressiveness through up-regulation of the heparanase. Heparanase is a predominant mammalian enzyme capable of degrading heparan sulfate (HS), the main polysaccharide component of the basement membrane and other types of extracellular matrix (ECM). Cleavage of HS by heparanase leads to disassembly of ECM, enables cell invasion, releases HS-bound angiogenic and growth factors from the ECM depots, and generates bioactive HS fragments. We found that clinically relevant doses of IR augment invasive ability of pancreatic cells in vitro and in vivo via induction of heparanase. Our results indicate that the effect of IR on heparanase expression is mediated by Egr1 transcription factor. Moreover, specific inhibitor of heparanase enzymatic activity abolished IR-induced invasiveness of pancreatic carcinoma cells in vitro, while combined treatment with IR and the heparanase inhibitor, but not IR alone, attenuated ortho-topic pancreatic tumor progression in vivo. The proposed up-regulation of heparanase by IR represents a new molecular pathway through which IR may promote pancreatic tumor aggressiveness, providing explanation for the limited benefit from radiation therapy in pancreatic cancer. Our research is expected to offer a new approach to improve the efficacy of

  14. Alterations in integrin expression modulates invasion of pancreatic cancer cells.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2009-01-01

    BACKGROUND: Factors mediating the invasion of pancreatic cancer cells through the extracellular matrix (ECM) are not fully understood. METHODS: In this study, sub-populations of the human pancreatic cancer cell line, MiaPaCa-2 were established which displayed differences in invasion, adhesion, anoikis, anchorage-independent growth and integrin expression. RESULTS: Clone #3 displayed higher invasion with less adhesion, while Clone #8 was less invasive with increased adhesion to ECM proteins compared to MiaPaCa-2. Clone #8 was more sensitive to anoikis than Clone #3 and MiaPaCa-2, and displayed low colony-forming efficiency in an anchorage-independent growth assay. Integrins beta 1, alpha 5 and alpha 6 were over-expressed in Clone #8. Using small interfering RNA (siRNA), integrin beta1 knockdown in Clone #8 cells increased invasion through matrigel and fibronectin, increased motility, decreased adhesion and anoikis. Integrin alpha 5 and alpha 6 knockdown also resulted in increased motility, invasion through matrigel and decreased adhesion. CONCLUSION: Our results suggest that altered expression of integrins interacting with different extracellular matrixes may play a significant role in suppressing the aggressive invasive phenotype. Analysis of these clonal populations of MiaPaCa-2 provides a model for investigations into the invasive properties of pancreatic carcinoma.

  15. Radiosensitization effect of CMNa on hypoxic pancreatic cancer cell in vitro

    International Nuclear Information System (INIS)

    Yin Lijie; Zhang Li; Ding Tiangui; Peng Zhaoxiang; Yu Huan; Gao Yuwei

    2006-01-01

    Objective: To investigate the effects of glycodidazolum natrium (CMNa) on pancreatic cancer cells under hypoxic condition. Methods: The human pancreatic cancer Panc-1 cells were exposed to a single fraction of high-dose γ-ray radiation either with CMNa or under hypoxic condition. The percentage of dead cells was detected with a multiwell plated reader, and fluorescence intensities of propidium iodide were measured before and after digitonin treatment. The sensitizing effect of CMNa on cell killing induced by high-dose irradiation was evaluated by time and concentration dependence. The selective radiosensitive effect of CMNa on hypoxia was evaluated by flow cytometry. Results: The death rate of pancreatic cancer Panc-1 cells paralleled with the increasing concentration of CMNa under hypoxic condition after 30 gray irradiation. The selective radiosensitive effect of CMNa on hypoxia was time-dependent. Conclusions: CMNa can enhance the radiosensitivity of pancreatic cancer Pane-1 cells under hypoxic condition with high-dose irradiation. (authors)

  16. Human pancreatic cancer xenografts recapitulate key aspects of cancer cachexia.

    Science.gov (United States)

    Delitto, Daniel; Judge, Sarah M; Delitto, Andrea E; Nosacka, Rachel L; Rocha, Fernanda G; DiVita, Bayli B; Gerber, Michael H; George, Thomas J; Behrns, Kevin E; Hughes, Steven J; Wallet, Shannon M; Judge, Andrew R; Trevino, Jose G

    2017-01-03

    Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia. Specifically, human PC xenografts were generated by implantation of pancreatic cancer cells, L3.6pl and PANC-1, either in the flank or orthotopically within the pancreas. Mice bearing orthotopic xenografts demonstrated significant muscle wasting and atrophy-associated gene expression changes compared to controls. Further, despite the absence of adaptive immunity, splenic tissue from orthotopically engrafted mice demonstrated elevations in several pro-inflammatory cytokines associated with cancer cachexia, including TNFα, IL1β, IL6 and KC (murine IL8 homologue), when compared to controls. Therefore, data presented here support further investigation into the complexity of cancer cachexia in PC to identify potential targets for this debilitating syndrome.

  17. Sonic hedgehog signaling inhibition provides opportunities for targeted therapy by sulforaphane in regulating pancreatic cancer stem cell self-renewal.

    Directory of Open Access Journals (Sweden)

    Mariana Rodova

    Full Text Available Dysregulation of the sonic hedgehog (Shh signaling pathway has been associated with cancer stem cells (CSC and implicated in the initiation of pancreatic cancer. Pancreatic CSCs are rare tumor cells characterized by their ability to self-renew, and are responsible for tumor recurrence accompanied by resistance to current therapies. The lethality of these incurable, aggressive and invasive pancreatic tumors remains a daunting clinical challenge. Thus, the objective of this study was to investigate the role of Shh pathway in pancreatic cancer and to examine the molecular mechanisms by which sulforaphane (SFN, an active compound in cruciferous vegetables, inhibits self-renewal capacity of human pancreatic CSCs. Interestingly, we demonstrate here that Shh pathway is highly activated in pancreatic CSCs and plays important role in maintaining stemness by regulating the expression of stemness genes. Given the requirement for Hedgehog in pancreatic cancer, we investigated whether hedgehog blockade by SFN could target the stem cell population in pancreatic cancer. In an in vitro model, human pancreatic CSCs derived spheres were significantly inhibited on treatment with SFN, suggesting the clonogenic depletion of the CSCs. Interestingly, SFN inhibited the components of Shh pathway and Gli transcriptional activity. Interference of Shh-Gli signaling significantly blocked SFN-induced inhibitory effects demonstrating the requirement of an active pathway for the growth of pancreatic CSCs. SFN also inhibited downstream targets of Gli transcription by suppressing the expression of pluripotency maintaining factors (Nanog and Oct-4 as well as PDGFRα and Cyclin D1. Furthermore, SFN induced apoptosis by inhibition of BCL-2 and activation of caspases. Our data reveal the essential role of Shh-Gli signaling in controlling the characteristics of pancreatic CSCs. We propose that pancreatic cancer preventative effects of SFN may result from inhibition of the Shh pathway

  18. Endoscopic ultrasound in pancreatic cancer: innovative applications beyond the basics.

    Science.gov (United States)

    Yoo, Joseph; Kistler, C Andrew; Yan, Linda; Dargan, Andrew; Siddiqui, Ali A

    2016-12-01

    Endoscopic ultrasound (EUS) has become a mainstay in assisting in the diagnosis and staging of pancreatic cancer. In addition, EUS provides a modality to treat chronic pain through celiac plexus neurolysis. Currently, there is growing data and utilization of EUS in more diverse and innovative applications aimed at providing more sophisticated diagnostic, prognostic and therapeutic options for patients with pancreatic cancer. EUS delivery of chemotherapy, viral and biological vectors and fiducial markers may eventually revolutionize the way clinicians approach the care of a patient with pancreatic cancer.

  19. Targeting Cancer Stem Cells and Their Niche: Current Therapeutic Implications and Challenges in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Jiangang Zhao

    2017-01-01

    Full Text Available Cancer stem cells (CSCs have been identified as a subpopulation of stem-like cancer cells with the ability of self-renewal and differentiation in hematological malignancies and solid tumors. Pancreatic cancer is one of the most lethal cancers worldwide. CSCs are thought to be responsible for cancer initiation, progression, metastasis, chemoresistance, and recurrence in pancreatic cancer. In this review, we summarize the characteristics of pancreatic CSCs and discuss the mechanisms involved in resistance to chemotherapy, the interactions with the niche, and the potential role in cancer immunoediting. We propose that immunotherapy targeting pancreatic CSCs, in combination with targeting the niche components, may provide a novel treatment strategy to eradicate pancreatic CSCs and hence improve outcomes in pancreatic cancer.

  20. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bournet, Barbara [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome [INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Buscail, Louis, E-mail: buscail.l@chu-toulouse.fr [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Cordelier, Pierre [INSERM U1037, University Hospital Center Rangueil, Toulouse (France)

    2011-02-24

    Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer.

  1. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Bournet, Barbara; Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome; Buscail, Louis; Cordelier, Pierre

    2011-01-01

    Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer

  2. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    NARCIS (Netherlands)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Herve; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Oehlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H. M.; Molenaar, IQ; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G. J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  3. The preclinical evaluation of TIC10/ONC201 as an anti-pancreatic cancer agent.

    Science.gov (United States)

    Zhang, Qiangbo; Wang, Hong; Ran, Lin; Zhang, Zongli; Jiang, Runde

    2016-08-05

    Here we evaluated the potential anti-pancreatic cancer activity by TIC10/ONC201, a first-in-class small-molecule inducer of tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL). The in vitro results showed that TIC10 induced potent cytotoxic and cytostatic activities in several human pancreatic cancer cell lines (Panc-1, Mia-PaCa2, AsPC-1 or L3.6). TIC10 activated both extrinsic (TRAIL-caspase-8-dependent) and endogenous/mitochondrial (caspase-9-dependent) apoptosis pathways in the pancreatic cancer cells. Molecularly, we showed that TIC10 inhibited Akt-Erk activation, yet induced TRAIL expression in pancreatic cancer cells. Significantly, TIC10, at a relatively low concentration, sensitized gemcitabine-induced growth inhibition and apoptosis against pancreatic cancer cells. Further, TIC10 and gemcitabine synergistically inhibited Panc-1 xenograft growth in SCID mice. The combination treatment also significantly improved mice survival. In addition, Akt-Erk in-activation and TRAIL/cleaved-caspase-8 induction were observed in TIC10-treated Panc-1 xenografts. Together, the preclinical results of the study demonstrate the potent anti-pancreatic cancer activity by TIC10, or with gemcitabine. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Icotinib plus gemcitabine for metastatic pancreatic cancer: a case report.

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    Zhao, Jing; Shen, Hong; Hu, Han-Guang; Huang, Jian-Jin

    2015-03-21

    A large majority of patients diagnosed with pancreatic cancer have advanced metastatic disease with unresectable malignancies. Despite treatment advances, the survival benefit from chemotherapeutic regimens and targeted drugs is limited. Moreover, their application is limited in China because of high toxicity and cost. Recently, inhibitors of epidermal growth factor receptor activity have shown promise for the treatment of solid cancers when used in combination with standard therapy. However, these drugs have not been evaluated extensively for the treatment of pancreatic cancer. Here, we report the treatment of a 64-year-old male with metastatic pancreatic cancer using a novel regimen of icotinib with gemcitabine. Marked shrinkage of the mass was observed after two treatment cycles, and partial remission was achieved. The abdominal pain was relieved. The adverse effects were tolerable and treatment cost was acceptable. This is the first reported case for the treatment of advanced pancreatic cancer with icotinib plus gemcitabine and demonstrates a promising therapeutic alternative.

  5. Pancreatic adenocarcinoma upregulated factor (PAUF) confers resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNA receptor-mediated signaling

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    Kaowinn, Sirichat; Cho, Il-Rae; Moon, Jeong; Jun, Seung Won; Kim, Chang Seok [BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-736 (Korea, Republic of); Kang, Ho Young [Department of Microbiology, Pusan National University, Busan 609-736 (Korea, Republic of); Kim, Manbok [Department of Medical Science, Dankook University College of Medicine, Cheonan 330-714 (Korea, Republic of); Koh, Sang Seok [Department of Biological Sciences, Dong-A University, Busan 604-714 (Korea, Republic of); Chung, Young-Hwa, E-mail: younghc@pusan.ac.kr [BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-736 (Korea, Republic of)

    2015-04-03

    Pancreatic adenocarcinoma upregulated factor (PAUF), a novel oncogene, plays a crucial role in the development of pancreatic cancer, including its metastasis and proliferation. Therefore, PAUF-expressing pancreatic cancer cells could be important targets for oncolytic virus-mediated treatment. Panc-1 cells expressing PAUF (Panc-PAUF) showed relative resistance to parvovirus H-1 infection compared with Panc-1 cells expressing an empty vector (Panc-Vec). Of interest, expression of type I IFN-α receptor (IFNAR) was higher in Panc-PAUF cells than in Panc-Vec cells. Increased expression of IFNAR in turn increased the activation of Stat1 and Tyk2 in Panc-PAUF cells compared with that in Panc-Vec cells. Suppression of Tyk2 and Stat1, which are important downstream molecules for IFN-α signaling, sensitized pancreatic cancer cells to parvovirus H-1-mediated apoptosis. Further, constitutive suppression of PAUF sensitized Bxpc3 pancreatic cancer cells to parvovirus H-1 infection. Taken together, these results suggested that PAUF conferred resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNAR-mediated signaling. - Highlights: • PAUF confers resistance against oncolytic parvovirus H-1 infection. • PAUF enhances the expression of IFNAR in Panc-1 cells. • Increased activation of Tyk2 or Stat1 by PAUF provides resistance to parvovirus H-1-mediated apoptosis. • Constitutive inhibition of PAUF enhances parvovirus H-1-mediated oncolysis of Bxpc3 pancreatic cancer cells.

  6. Pancreatic adenocarcinoma upregulated factor (PAUF) confers resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNA receptor-mediated signaling

    International Nuclear Information System (INIS)

    Kaowinn, Sirichat; Cho, Il-Rae; Moon, Jeong; Jun, Seung Won; Kim, Chang Seok; Kang, Ho Young; Kim, Manbok; Koh, Sang Seok; Chung, Young-Hwa

    2015-01-01

    Pancreatic adenocarcinoma upregulated factor (PAUF), a novel oncogene, plays a crucial role in the development of pancreatic cancer, including its metastasis and proliferation. Therefore, PAUF-expressing pancreatic cancer cells could be important targets for oncolytic virus-mediated treatment. Panc-1 cells expressing PAUF (Panc-PAUF) showed relative resistance to parvovirus H-1 infection compared with Panc-1 cells expressing an empty vector (Panc-Vec). Of interest, expression of type I IFN-α receptor (IFNAR) was higher in Panc-PAUF cells than in Panc-Vec cells. Increased expression of IFNAR in turn increased the activation of Stat1 and Tyk2 in Panc-PAUF cells compared with that in Panc-Vec cells. Suppression of Tyk2 and Stat1, which are important downstream molecules for IFN-α signaling, sensitized pancreatic cancer cells to parvovirus H-1-mediated apoptosis. Further, constitutive suppression of PAUF sensitized Bxpc3 pancreatic cancer cells to parvovirus H-1 infection. Taken together, these results suggested that PAUF conferred resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNAR-mediated signaling. - Highlights: • PAUF confers resistance against oncolytic parvovirus H-1 infection. • PAUF enhances the expression of IFNAR in Panc-1 cells. • Increased activation of Tyk2 or Stat1 by PAUF provides resistance to parvovirus H-1-mediated apoptosis. • Constitutive inhibition of PAUF enhances parvovirus H-1-mediated oncolysis of Bxpc3 pancreatic cancer cells

  7. Gene Therapy for Pancreatic Cancer: Specificity, Issues and Hopes.

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    Rouanet, Marie; Lebrin, Marine; Gross, Fabian; Bournet, Barbara; Cordelier, Pierre; Buscail, Louis

    2017-06-08

    A recent death projection has placed pancreatic ductal adenocarcinoma as the second cause of death by cancer in 2030. The prognosis for pancreatic cancer is very poor and there is a great need for new treatments that can change this poor outcome. Developments of therapeutic innovations in combination with conventional chemotherapy are needed urgently. Among innovative treatments the gene therapy offers a promising avenue. The present review gives an overview of the general strategy of gene therapy as well as the limitations and stakes of the different experimental in vivo models, expression vectors (synthetic and viral), molecular tools (interference RNA, genome editing) and therapeutic genes (tumor suppressor genes, antiangiogenic and pro-apoptotic genes, suicide genes). The latest developments in pancreatic carcinoma gene therapy are described including gene-based tumor cell sensitization to chemotherapy, vaccination and adoptive immunotherapy (chimeric antigen receptor T-cells strategy). Nowadays, there is a specific development of oncolytic virus therapies including oncolytic adenoviruses, herpes virus, parvovirus or reovirus. A summary of all published and on-going phase-1 trials is given. Most of them associate gene therapy and chemotherapy or radiochemotherapy. The first results are encouraging for most of the trials but remain to be confirmed in phase 2 trials.

  8. Nationwide prospective audit of pancreatic surgery: design, accuracy, and outcomes of the Dutch Pancreatic Cancer Audit.

    Science.gov (United States)

    van Rijssen, L Bengt; Koerkamp, Bas G; Zwart, Maurice J; Bonsing, Bert A; Bosscha, Koop; van Dam, Ronald M; van Eijck, Casper H; Gerhards, Michael F; van der Harst, Erwin; de Hingh, Ignace H; de Jong, Koert P; Kazemier, Geert; Klaase, Joost; van Laarhoven, Cornelis J; Molenaar, I Quintus; Patijn, Gijs A; Rupert, Coen G; van Santvoort, Hjalmar C; Scheepers, Joris J; van der Schelling, George P; Busch, Olivier R; Besselink, Marc G

    2017-10-01

    Auditing is an important tool to identify practice variation and 'best practices'. The Dutch Pancreatic Cancer Audit is mandatory in all 18 Dutch centers for pancreatic surgery. Performance indicators and case-mix factors were identified by a PubMed search for randomized controlled trials (RCT's) and large series in pancreatic surgery. In addition, data dictionaries of two national audits, three institutional databases, and the Dutch national cancer registry were evaluated. Morbidity, mortality, and length of stay were analyzed of all pancreatic resections registered during the first two audit years. Case ascertainment was cross-checked with the Dutch healthcare inspectorate and key-variables validated in all centers. Sixteen RCT's and three large series were found. Sixteen indicators and 20 case-mix factors were included in the audit. During 2014-2015, 1785 pancreatic resections were registered including 1345 pancreatoduodenectomies. Overall in-hospital mortality was 3.6%. Following pancreatoduodenectomy, mortality was 4.1%, Clavien-Dindo grade ≥ III morbidity was 29.9%, median (IQR) length of stay 12 (9-18) days, and readmission rate 16.0%. In total 97.2% of >40,000 variables validated were consistent with the medical charts. The Dutch Pancreatic Cancer Audit, with high quality data, reports good outcomes of pancreatic surgery on a national level. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  9. Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).

    Science.gov (United States)

    Bonnetain, Franck; Bonsing, Bert; Conroy, Thierry; Dousseau, Adelaide; Glimelius, Bengt; Haustermans, Karin; Lacaine, François; Van Laethem, Jean Luc; Aparicio, Thomas; Aust, Daniela; Bassi, Claudio; Berger, Virginie; Chamorey, Emmanuel; Chibaudel, Benoist; Dahan, Laeticia; De Gramont, Aimery; Delpero, Jean Robert; Dervenis, Christos; Ducreux, Michel; Gal, Jocelyn; Gerber, Erich; Ghaneh, Paula; Hammel, Pascal; Hendlisz, Alain; Jooste, Valérie; Labianca, Roberto; Latouche, Aurelien; Lutz, Manfred; Macarulla, Teresa; Malka, David; Mauer, Muriel; Mitry, Emmanuel; Neoptolemos, John; Pessaux, Patrick; Sauvanet, Alain; Tabernero, Josep; Taieb, Julien; van Tienhoven, Geertjan; Gourgou-Bourgade, Sophie; Bellera, Carine; Mathoulin-Pélissier, Simone; Collette, Laurence

    2014-11-01

    Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Tissue Transglutaminase (TG2)-Induced Inflammation in Initiation, Progression, and Pathogenesis of Pancreatic Cancer

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    Mehta, Kapil, E-mail: kmehta@mdanderson.org; Han, Amy [Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 (United States); Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX 77030 (United States)

    2011-02-25

    Pancreatic cancer (PC) is among the deadliest cancers, with a median survival of six months. It is generally believed that infiltrating PC arises through the progression of early grade pancreatic intraepithelial lesions (PanINs). In one model of the disease, the K-ras mutation is an early molecular event during progression of pancreatic cancer; it is followed by the accumulation of additional genetic abnormalities. This model has been supported by animal studies in which activated K-ras and p53 mutations produced metastatic pancreatic ductal adenocarcinoma in mice. According to this model, oncogenic K-ras induces PanIN formation but fails to promote the invasive stage. However, when these mice are subjected to caerulein treatment, which induces a chronic pancreatitis-like state and inflammatory response, PanINs rapidly progress to invasive carcinoma. These results are consistent with epidemiologic studies showing that patients with chronic pancreatitis have a much higher risk of developing PC. In line with these observations, recent studies have revealed elevated expression of the pro-inflammatory protein tissue transglutaminase (TG2) in early PanINs, and its expression increases even more as the disease progresses. In this review we discuss the implications of increased TG2 expression in initiation, progression, and pathogenesis of pancreatic cancer.

  11. Gestational diabetes as a risk factor for pancreatic cancer: a prospective cohort study

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    Calderon R

    2007-08-01

    Full Text Available Abstract Background Diabetes is known to be associated with cancer of the pancreas, though there is some debate as to whether it is a cause or a consequence of the disease. We investigated the incidence of pancreatic cancer in a cohort of 37926 Israeli women followed for 28–40 years for whom information on diabetes had been collected at the time they gave birth, in 1964–1976, in Jerusalem. There were 54 cases of pancreatic cancer ascertained from the Israel Cancer Registry during follow-up. Methods We used Cox proportional hazards models to adjust for age at baseline and explore effects of other risk factors, including ethnic groups, preeclampsia, birth order and birth weight of offspring. Results We observed no cases of pancreatic cancer in the women with insulin dependent diabetes; however, there were five cases in the women with gestational diabetes. The interval between the record of diabetes in pregnancy and the diagnosis of pancreatic cancer ranged from 14–35 years. Women with a history of gestational diabetes showed a relative risk of pancreatic cancer of 7.1 (95% confidence interval, 2.8–18.0. Conclusion We conclude that gestational diabetes is strongly related to the risk of cancer of the pancreas in women in this population, and that gestational diabetes can precede cancer diagnosis by many years.

  12. Ku70 inhibits gemcitabine-induced DNA damage and pancreatic cancer cell apoptosis

    International Nuclear Information System (INIS)

    Ma, Jiali; Hui, Pingping; Meng, Wenying; Wang, Na; Xiang, Shihao

    2017-01-01

    The current study focused on the role of Ku70, a DNA-dependent protein kinase (DNA-PK) complex protein, in pancreatic cancer cell resistance to gemcitabine. In both established cell lines (Mia-PaCa-2 and PANC-1) and primary human pancreatic cancer cells, shRNA/siRNA-mediated knockdown of Ku70 significantly sensitized gemcitabine-induced cell death and proliferation inhibition. Meanwhile, gemcitabine-induced DNA damage and subsequent pancreatic cancer cell apoptosis were also potentiated with Ku70 knockdown. On the other hand, exogenous overexpression of Ku70 in Mia-PaCa-2 cells suppressed gemcitabine-induced DNA damage and subsequent cell apoptosis. In a severe combined immune deficient (SCID) mice Mia-PaCa-2 xenograft model, gemcitabine-induced anti-tumor activity was remarkably pontificated when combined with Ku70 shRNA knockdown in the xenografts. The results of this preclinical study imply that Ku70 might be a primary resistance factor of gemcitabine, and Ku70 silence could significantly chemo-sensitize gemcitabine in pancreatic cancer cells. - Highlights: • Ku70 knockdown sensitizes gemcitabine-induced killing of pancreatic cancer cells. • Ku70 knockdown facilitates gemcitabine-induced DNA damage and cell apoptosis. • Ku70 overexpression deceases gemcitabine's sensitivity in pancreatic cancer cells. • Ku70 knockdown sensitizes gemcitabine-induced anti-tumor activity in vivo.

  13. KIF20A-Mediated RNA Granule Transport System Promotes the Invasiveness of Pancreatic Cancer Cells

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    Keisuke Taniuchi

    2014-12-01

    Full Text Available Pancreatic cancers are aggressive because they are highly invasive and highly metastatic; moreover, effective treatments for aggressive pancreatic cancers are lacking. Here, we report that the motor kinesin protein KIF20A promoted the motility and invasiveness of pancreatic cancer cells through transporting the RNA-binding protein IGF2BP3 and IGF2BP3-bound transcripts toward cell protrusions along microtubules. We previously reported that IGF2BP3 and its target transcripts are assembled into cytoplasmic stress granules of pancreatic cancer cells, and that IGF2BP3 promotes the motility and invasiveness of pancreatic cancer cells through regulation of localized translation of IGF2BP3-bound transcripts in cell protrusions. We show that knockdown of KIF20A inhibited accumulation of IGF2BP3-containing stress granules in cell protrusions and suppressed local protein expression from specific IGF2BP3-bound transcripts, ARF6 and ARHGEF4, in the protrusions. Our results provide insight into the link between regulation of KIF20A-mediated trafficking of IGF2BP3-containing stress granules and modulation of the motility and invasiveness in pancreatic cancers.

  14. HIF1 Contributes to Hypoxia-Induced Pancreatic Cancer Cells Invasion via Promoting QSOX1 Expression

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    Chen-Ye Shi

    2013-08-01

    Full Text Available Background: Quiescin sulfhydryl oxidase 1 (QSOX1, which oxidizes sulfhydryl groups to form disulfide bonds in proteins, is found to be over-expressed in various pancreatic cancer cell lines and patients. QSOX1 promotes invasion of pancreatic cancer cells by activating MMP-2 and MMP-9. However, its regulatory mechanism remains largely undefined. Methods: Real-time PCR and Western blot were employed to detect the expression of QSOX1 in human pancreatic cancer cell lines under hypoxic condition. Luciferase reporter and ChIP assays were used to assess the regulation of QSOX1 by hypoxia-inducible factor 1 (HIF-1. Small interfering RNA (siRNA was applied to knock down endogenous expression of QSOX1. Matrigel-coated invasion chamber essays were conducted to detect the invasion capacity of QSOX1-depleted cells. Results: Both hypoxia and hypoxia mimicking reagent up-regulated the expression of QSOX1 in human pancreatic cancer cell lines. Knockdown of HIF-1α eliminated hypoxia induced QSOX1 expression. HIF-1α was found directly bound to two hypoxia-response elements (HRE of QSOX1 gene, both of which were required for HIF-1 induced QSOX1 expression. Moreover, QSOX1 silencing blocked hypoxia-induced pancreatic cancer cells invasion. Conclusion: QSOX1 is a direct target of HIF-1 and may contribute to hypoxia-induced pancreatic cancer cells invasion.

  15. Prognostic value of platelet-to-lymphocyte ratio in pancreatic cancer: a comprehensive meta-analysis of 17 cohort studies.

    Science.gov (United States)

    Zhou, Yongping; Cheng, Sijin; Fathy, Abdel Hamid; Qian, Haixin; Zhao, Yongzhao

    2018-01-01

    Several studies were conducted to explore the prognostic value of platelet-to-lymphocyte ratio (PLR) in pancreatic cancer and have reported contradictory results. This study aims to summarize the prognostic role of PLR in pancreatic cancer. Embase, PubMed and Cochrane Library were completely searched. The cohort studies focusing on the prognostic role of PLR in pancreatic cancer were eligible. The overall survival (OS) and progression-free survival (PFS) were analyzed. Fifteen papers containing 17 cohort studies with pancreatic cancer were identified. The results showed patients that with low PLR might have longer OS when compared to the patients with high PLR (hazard ratio=1.28, 95% CI=1.17-1.40, P analysis model, ethnicity, sample size and cut-off value. Further analyses based on the adjusted potential confounders were conducted, including CA199, neutrophil-to-lymphocyte ratio, modified Glasgow Prognostic Score, albumin, C-reactive protein, Eastern Cooperative Oncology Group, stage, tumor size, nodal involvement, tumor differentiation, margin status, age and gender, which confirmed that low PLR was a protective factor in pancreatic cancer. In addition, low PLR was significantly associated with longer PFS when compared to high PLR in pancreatic cancer (hazard ratio=1.27, 95% CI=1.03-1.57, P =0.03; I 2 =33%). In conclusion, it was found that high PLR is an unfavorable predictor of OS and PFS in patients with pancreatic cancer, and PLR is a promising prognostic biomarker for pancreatic cancer.

  16. MicroRNA-gene signaling pathways in pancreatic cancer

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    Alexandra Drakaki

    2013-10-01

    Full Text Available Pancreatic cancer is the fourth most frequent cause of cancer-related deaths and is characterized by early metastasis and pronounced resistance to chemotherapy and radiation therapy. Despite extensive esearch efforts, there is not any substantial progress regarding the identification of novel drugs against pancreatic cancer. Although the introduction of the chemotherapeutic agent gemcitabine improved clinical response, the prognosis of these patients remained extremely poor with a 5-year survival rate of 3-5%. Thus, the identification of the novel molecular pathways involved in pancreatic oncogenesis and the development of new and potent therapeutic options are highly desirable. Here, we describe how microRNAs control signaling pathways that are frequently deregulated during pancreatic oncogenesis. In addition, we provide evidence that microRNAs could be potentially used as novel pancreatic cancer therapeutics through reversal of chemotherapy and radiotherapy resistance or regulation of essential molecular pathways. Further studies should integrate the deregulated genes and microRNAs into molecular networks in order to identify the central regulators of pancreatic oncogenesis. Targeting these central regulators could lead to the development of novel targeted therapeutic approaches for pancreatic cancer patients.

  17. Expression and significance of Axin2 in pancreatic cancer cells

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    ZHANG Tao

    2016-05-01

    Full Text Available ObjectiveTo investigate the expression of Axin2 in pancreatic cancer cells, and to observe the influence of Axin2 on the proliferation, invasion, and migration of human pancreatic cancer cells (PANC-1. MethodsQuantitative real-time PCR was used to measure the expression of Axin2 in pancreatic cancer cell lines with different invasive abilities (PANC-1, Mia PaCa-2, and BxPC-3 and immortalized normal pancreatic cells (H6C7. PANC-1 cells with low expression were transfected with over-expressed Axin2 plasmid by transient transfection. MTT assay, Transwell assay, and scratch assay were used to determine the proliferation, invasion, and migration of cells transfected with over-expressed Axin2. One-way analysis of variance was used for comparison between multiple groups, and SNK-q test was used for comparison between any two groups. ResultsThe relative expression levels of Axin2 in PANC-1, BxPC-3, Mia PaCa-2, and H6C7 cells were 0.13±0.01, 0.42±0.05, 0.24±0.011, and 1.00±0.00, respectively, and PANC-1 cells had the lowest expression level of Axin2, with significant differences compared with the other cells (all P<0.05. When PANC-1 cells were transfected with over-expressed Axin2 plasmid, the cells in the over-expression group had a significant increase in the expression level of Axin2 compared with those in the blank group and the negative control group (both P<0.05. Compared with those in the non-transfection group and the blank group, PANC-1 cells in the over-expression group showed significant reductions in the proliferation, invasion, and migration abilities. ConclusionThe expression of Axin2 is down-regulated in pancreatic cancer cell lines and decreases with the increasing invasion ability, suggesting the role of tumor suppressor gene. High expression of Axin2 can reduce the proliferation, invasion, and migration abilities of PANC-1 cells.

  18. Role of respiratory-gated PET/CT for pancreatic tumors: A preliminary result

    International Nuclear Information System (INIS)

    Kasuya, Takeo; Tateishi, Ukihide; Suzuki, Kazufumi; Daisaki, Hiromitsu; Nishiyama, Yuji; Hata, Masaharu; Inoue, Tomio

    2013-01-01

    Purpose: The aim of this study is to ascertain role of respiratory-gated PET/CT for accurate diagnosis of pancreatic tumors. Materials and methods: Prior to clinical study, the phantom study was performed to evaluate the impact of respiratory motion on lesion quantification. Twenty-two patients (mean age 65 years) with pancreatic tumors were enrolled. Pathological diagnoses by surgical specimens consisted of pancreatic cancer (n = 15) and benign intraductal papillary mucinous neoplasm (IPMN, n = 7). Whole-body scan of non-respiratory-gated PET/CT was performed at first, and subsequent respiratory-gated PET/CT for one bed position was performed. All PET/CT studies were performed prior to surgery. The SUV max obtained by non-respiratory-gated PET/CT and respiratory-gated PET/CT, and percent difference in SUVmax (%SUVmax) were compared. Results: The profile curve of 5 respiratory bin image was most similar to that of static image. The third bin of 5 respiratory bin image showed highest FWHM (24.0 mm) and FWTM (32.7 mm). The mean SUVmax of pancreatic cancer was similar to that of benign IPMN on non-respiratory-gated PET/CT (p = 0.05), whereas significant difference was found between two groups on respiratory-gated PET/CT (p = 0.016). The mean %SUV of pancreatic cancer was greater than that of benign IPMN (p < 0.0001). Identification of the primary tumor in pancreatic head (n = 13, 59%) was improved by using respiratory-gated PET/CT because of minimal affection of physiological accumulation in duodenum. Conclusion: Respiratory-gated PET/CT is a feasible technique for evaluation of pancreatic tumors and allows more accurate identification of pancreatic tumors compared with non-respiratory-gated PET/CT

  19. Pancreatic Cancer: Multicenter Prospective Data Collection and Analysis by the Hungarian Pancreatic Study Group.

    Science.gov (United States)

    Lakatos, Gábor; Balázs, Anita; Kui, Balázs; Gódi, Szilárd; Szücs, Ákos; Szentesi, Andrea; Szentkereszty, Zsolt; Szmola, Richárd; Kelemen, Dezső; Papp, Róbert; Vincze, Áron; Czimmer, József; Pár, Gabriella; Bajor, Judit; Szabó, Imre; Izbéki, Ferenc; Halász, Adrienn; Leindler, László; Farkas, Gyula; Takács, Tamás; Czakó, László; Szepes, Zoltán; Hegyi, Péter; Kahán, Zsuzsanna

    2016-06-01

    Pancreatic cancer is a devastating disease with poor prognosis. There is very limited information available regarding the epidemiology and treatment strategies of pancreatic cancer in Central Europe. The purpose of the study was to prospectively collect and analyze data of pancreatic cancer in the Hungarian population. The Hungarian Pancreatic Study Group (HPSG) organized prospective, uniform data collection. Altogether 354 patients were enrolled from 14 Hungarian centers. Chronic pancreatitis was present in 3.7% of the cases, while 33.7% of the patients had diabetes. Family history for pancreatic cancer was positive in 4.8%. The most frequent presenting symptoms included pain (63.8%), weight loss (63%) and jaundice (52.5%). The reported frequency of smoking and alcohol consumption was lower than expected (28.5% and 27.4%, respectively). The majority of patients (75.6%) were diagnosed with advanced disease. Most patients (83.6%) had a primary tumor located in the pancreatic head. The histological diagnosis was ductal adenocarcinoma in 90.7% of the cases, while neuroendocrine tumor was present in 5.3%. Biliary stent implantation was performed in 166 patients, 59.2% of them received metal stents. Primary tumor resection was performed in 60 (16.9%) patients. Enteral or biliary bypass was done in 35 and 49 patients, respectively. In a multivariate Cox-regression model, smoking status and presence of gemcitabine-based chemotherapy were identified as independent predictors for overall survival. We report the first data from a large cohort of Hungarian pancreatic cancer patients. We identified smoking status and chemotherapy as independent predictors in this cohort.

  20. Surgical management of malignant bowel obstruction in recurrent pancreatic cancer

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    Hyung Sun Kim

    2017-01-01

    Discussion and conclusion: Palliative surgery improves quality of life in recurrent pancreatic cancer patients and can continue patient’s palliative management. In selected patients, palliative surgery may effective management for progress of survival and quality of life.

  1. MicroRNA-1291 targets the FOXA2-AGR2 pathway to suppress pancreatic cancer cell proliferation and tumorigenesis

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    Qiu, Jing-Xin; Kim, Edward J.; Yu, Ai-Ming

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. Better understanding of pancreatic cancer biology may help identify new oncotargets towards more effective therapies. This study investigated the mechanistic actions of microRNA-1291 (miR-1291) in the suppression of pancreatic tumorigenesis. Our data showed that miR-1291 was downregulated in a set of clinical pancreatic carcinoma specimens and human pancreatic cancer cell lines. Restoration of miR-1291 expression inhibited pancreatic cancer cell proliferation, which was associated with cell cycle arrest and enhanced apoptosis. Furthermore, miR-1291 sharply suppressed the tumorigenicity of PANC-1 cells in mouse models. A proteomic profiling study revealed 32 proteins altered over 2-fold in miR-1291-expressing PANC-1 cells that could be assembled into multiple critical pathways for cancer. Among them anterior gradient 2 (AGR2) was reduced to the greatest degree. Through computational and experimental studies we further identified that forkhead box protein A2 (FOXA2), a transcription factor governing AGR2 expression, was a direct target of miR-1291. These results connect miR-1291 to the FOXA2-AGR2 regulatory pathway in the suppression of pancreatic cancer cell proliferation and tumorigenesis, providing new insight into the development of miRNA-based therapy to combat pancreatic cancer. PMID:27322206

  2. Synergistic activity of troxacitabine (Troxatyl™ and gemcitabine in pancreatic cancer

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    Leblond Lorraine

    2007-07-01

    Full Text Available Abstract Background Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™ is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials. Methods The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For in vivo studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1 tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired t test using GraphPad prism software. Results Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth. The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of

  3. Surgery for oligometastasis of pancreatic cancer.

    Science.gov (United States)

    Lu, Fengchun; Poruk, Katherine E; Weiss, Matthew J

    2015-08-01

    The incidence of pancreatic adenocarcinoma (PDAC) has steadily increased over the past several decades. The majority of PDAC patients will present with distant metastases, limiting surgical management in this population. Hepatectomy and pulmonary metastasectomy (PM) has been well established for colorectal cancer patients with isolated, resectable hepatic or pulmonary metastatic disease. Recent advancements in effective systemic therapy for PDAC have led to the selection of certain patients where metastectomy may be potentially indicated. However, the indication for resection of oligometastases in PDAC is not well defined. This review will discuss the current literature on the surgical management of metastatic disease for PDAC with a specific focus on surgical resection for isolated hepatic and pulmonary metastases.

  4. Comprehensive Evaluation of Altered Systemic Metabolism and Pancreatic Cancer Risk

    Science.gov (United States)

    2015-10-01

    09/08/15-08/31/19 0.96 cal. mo. NIH/NCI $168,300 A prospective investigation of the oral microbiome and pancreatic cancer 1.To perform a...and BWHS. 2.To evaluate racial differences in the oral microbiome using 165 AA and 165 EA controls (from the SCCS only), and to identify any racial...risk factors for pancreatic cancer (cigarette smoking, obesity, red meat and processed meat consumption, alcohol consumption, type 2 diabetes) and oral

  5. Risk factors for pancreatic cancer and early diagnosis of pancreatic cancer

    International Nuclear Information System (INIS)

    Yamao, Kenji; Mizuno, Nobumasa; Sawaki, Akira; Shimizu, Yasuhiro; Chang, K.J.

    2008-01-01

    This paper describes the strategy for improving the poor prognosis of the pancreatic (P) cancer by its early imaging diagnosis followed by resection, based on recent findings on its high risk group. Epidemiological studies have revealed that patients with diabetes, chronic pancreatitis, intraductal papillary-mucious tumor, P cyst, familial history of P cancer, and hereditary P cancer syndrome are involved in the high risk group of P cancer. Imaging diagnosis with CT and/or endoscopic ultrasonography (EUS) followed by histological confirmation for resection can be a useful approach to improve the prognosis in those high risk, asymptomatic individuals with abnormal levels of P enzyme and tumor marker, and with US findings of P ductal dilation and cyst. The guideline 2006 for P cancer by Japan Pancreas Society shows the algorithm leading to the final diagnosis for the positive high risk group: firstly, CT and/or MRCP (MR cholangiopancreatography (CP)); or, in case of uncertainty, EUS and/or ERCP (E retrograde CP) and/or PET; and finally, cytological, histological diagnosis. The newer approach proposed recently for the group is: multi detector row (MD)-CT and EUS; then cytodiagnosis guided by ERCP and/or with fine needle aspiration by EUS, also a promising early diagnosis. As well, molecular biological approaches are supposedly useful for the future diagnosis. (R.T.)

  6. Synergistic activity of troxacitabine (Troxatyl™) and gemcitabine in pancreatic cancer

    International Nuclear Information System (INIS)

    Damaraju, Vijaya L; Bouffard, David Y; Wong, Clarence KW; Clarke, Marilyn L; Mackey, John R; Leblond, Lorraine; Cass, Carol E; Grey, Mike; Gourdeau, Henriette

    2007-01-01

    Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™) is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials. The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For in vivo studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1) tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired t test using GraphPad prism software. Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth). The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of troxacitabine when cells were exposed at equal drug

  7. Accuracy of computed tomography in determining pancreatic cancer tumor size

    International Nuclear Information System (INIS)

    Aoki, Kazunori; Okada, Shuichi; Moriyama, Noriyuki

    1994-01-01

    We compared tumor sizes determined by computed tomography (CT) with those of the resected specimens in 26 patients with pancreatic cancer in order to clarify whether or not the size of a pancreatic tumor can be accurately determined by CT. From the precontrast, postcontrast and arterial dominant phases of dynamic CT, the arterial dominant phase was found to yield the highest correlation between CT measured tumor size and that of the resected specimens (p<0.01). The correlation coefficient was, however, not high (r=0.67). CT alone may therefore be insufficient to determine tumor size in pancreatic cancer accurately. (author)

  8. Multislice CT for preoperative diagnosis of pancreatic cancer

    International Nuclear Information System (INIS)

    Horiguchi, Akihiko; Ishihara, Shin; Ito, Masahiro

    2007-01-01

    We investigated the ability of multislice (MS) CT to visualize and diagnose the progression of pancreatic cancer. With regard to local progression, good diagnosis was possible for detecting the invasion of the intrapancreatic bile duct, duodenum, portal vein, arteries and other organs, and liver metastasis. Sensitivity was high but specificity was not good for detecting the invasion of the anterior and posterior pancreatic tissue. This is thought to be because of the positive diagnosis with pancreatitis that accompanies cancer. Pancreatic plexus invasion was also thought to be a cause of the lipid elevation of the nerve plexus and decreased sensitivity accompanying pancreatitis. Identification of cancer invasion and tumor periphery changes based on concomitant pancreatitis also depends on the amount of fibrous stroma, but this will require further investigation. Factors other than the size of lymph node metastases also need to be investigated. MS-CT can provide detailed volume data in a short time and making it an essential test in diagnosing the stage of pancreatic cancer. (author)

  9. A Suspicious Pancreatic Mass in Chronic Pancreatitis: Pancreatic Actinomycosis

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    F. de Clerck

    2015-01-01

    Full Text Available Introduction. Pancreatic actinomycosis is a chronic infection of the pancreas caused by the suppurative Gram-positive bacterium Actinomyces. It has mostly been described in patients following repeated main pancreatic duct stenting in the context of chronic pancreatitis or following pancreatic surgery. This type of pancreatitis is often erroneously interpreted as pancreatic malignancy due to the specific invasive characteristics of Actinomyces. Case. A 64-year-old male with a history of chronic pancreatitis and repeated main pancreatic duct stenting presented with weight loss, fever, night sweats, and abdominal pain. CT imaging revealed a mass in the pancreatic tail, invading the surrounding tissue and resulting in splenic vein thrombosis. Resectable pancreatic cancer was suspected, and pancreatic tail resection was performed. Postoperative findings revealed pancreatic actinomycosis instead of neoplasia. Conclusion. Pancreatic actinomycosis is a rare type of infectious pancreatitis that should be included in the differential diagnosis when a pancreatic mass is discovered in a patient with chronic pancreatitis and prior main pancreatic duct stenting. Our case emphasizes the importance of pursuing a histomorphological confirmation.

  10. Knockdown of ZFR suppresses cell proliferation and invasion of human pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Xiaolan Zhao

    Full Text Available BACKGROUND: Zinc finger RNA binding protein (ZFR is involved in the regulation of growth and cancer development. However, little is known about ZFR function in pancreatic cancer. METHODS: Herein, to investigate whether ZFR is involved in tumor growth, Oncomine microarray data was firstly used to evaluate ZFR gene expression in human pancreatic tumors. Then short hairpin RNA (shRNA targeting ZFR was designed and delivered into PANC-1 pancreatic cancer cells to knock down ZFR expression. Cell viability, cell proliferation and cell cycle analysis after ZFR knockdown were determined by MTT, colony forming and FACS, respectively. In addition, cell migration and invasion were assessed using the Transwell system. RESULTS: The expression of ZFR was significantly higher in pancreatic tumors than normal pancreas tissues by Oncomine database analysis. Knockdown of ZFR by shRNA-expressing lentivirus significantly decreased the viability and invasion ability of pancreatic cancer cells. Moreover, FACS analysis showed that knockdown of ZFR in PANC-1 cells caused a significant cell cycle arrest at G0/G1 phase. Furthermore, knockdown of ZFR decreased the levels of CDK2, CDK4, CyclinA and CyclinD1 and enhanced the expression of p27, which has evidenced by qRT-PCR and Western blot analysis. CONCLUSIONS: Knockdown of ZFR might provide a novel alternative to targeted therapy of pancreatic cancer and deserves further investigation.

  11. Minimally invasive radical pancreatectomy for left-sided pancreatic cancer: Current status and future perspectives

    Science.gov (United States)

    Kang, Chang Moo; Lee, Sung Hwan; Lee, Woo Jung

    2014-01-01

    Minimally invasive distal pancreatectomy with splenectomy has been regarded as a safe and effective treatment for benign and borderline malignant pancreatic lesions. However, its application for left-sided pancreatic cancer is still being debated. The clinical evidence for radical antegrade modular pancreatosplenectomy (RAMPS)-based minimally invasive approaches for left-sided pancreatic cancer was reviewed. Potential indications and surgical concepts for minimally invasive RAMPS were suggested. Despite the limited clinical evidence for minimally invasive distal pancreatectomy in left-sided pancreatic cancer, the currently available clinical evidence supports the use of laparoscopic distal pancreatectomy under oncologic principles in well-selected left sided pancreatic cancers. A pancreas-confined tumor with an intact fascia layer between the pancreas and left adrenal gland/kidney positioned more than 1 or 2 cm away from the celiac axis is thought to constitute a good condition for the use of margin-negative minimally invasive RAMPS. The use of minimally invasive (laparoscopic or robotic) anterior RAMPS is feasible and safe for margin-negative resection in well-selected left-sided pancreatic cancer. The oncologic feasibility of the procedure remains to be determined; however, the currently available interim results indicate that even oncologic outcomes will not be inferior to those of open radical distal pancreatosplenectomy. PMID:24605031

  12. [Role of connective tissue growth factor (CTGF) in proliferation and migration of pancreatic cancer cells].

    Science.gov (United States)

    Bai, Yu-chun; Kang, Quan; Luo, Qing; Wu, Dao-qi; Ye, Wei-xia; Lin, Xue-mei; Zhao, Yong

    2011-10-01

    To explore the expression of connective tissue growth factor (CTGF) in pancreatic cancer and its influence on the proliferation and migration of cancer cells. The expression of CTGF in pancreatic cell line PANC-1 cells was analyzed by real-time PCR and in pancreatic carcinoma (50 cases) tissues by immunohistochemistry. The ability of proliferation and migration in vitro of PANC-1 cells was tested by MTT assay, scratch test and Boyden chamber test after the CTGF gene was overexpressed by Ad5-CTGF or silenced with Ad5-siCTGF transfection. CTGF was overexpressed in both pancreatic cancer cells and tissues. Overxpression of CTGF leads to increased proliferation and migration of PANC-1 cells. The CTGF-transfected PANC-1 cells showed apparent stronger proliferation ability and scratch-repair ability than that of empty vector controls. The results of Boyden chamber test showed that there were 34 cells/field (200× magnificantion) of the CTGF-transfected overexpressing cells, much more than the 11 cells/field of the empty vector control cells; and 6 cells/microscopic field of the Ad5-siCTGF-transfected silenced cells, much less than the 15 cells/field of the control cells. CTGF is overexpressed in both pancreatic cancer cells in vitro and in vivo, indicating that it may play an important role in the cell proliferation and migration in pancreatic cancer.

  13. BGLAP is expressed in pancreatic cancer cells and increases their growth and invasion

    Directory of Open Access Journals (Sweden)

    Michalski Christoph W

    2007-12-01

    Full Text Available Abstract Background Bone gamma-carboxyglutamate protein (BGLAP; osteocalcin is a small, highly conserved molecule first identified in the mineralized matrix of bone. It has been implicated in the pathophysiology of various malignancies. In this study, we analyzed the expression and role of BGLAP in the normal human pancreas, chronic pancreatitis (CP, and pancreatic ductal adenocarcinoma (PDAC using quantitative RT-PCR, immunohistochemistry, immunocytochemistry and enzyme immunoassays, as well as cell proliferation and invasion assays. Gene silencing was carried out using specific siRNA molecules. Results Compared to the normal pancreas, BGLAP mRNA and protein levels were not significantly different in CP and PDAC tissues. BGLAP was faintly present in the cytoplasm of normal acinar cells but was strongly expressed in the cytoplasm and nuclei of tubular complexes and PanIN lesions of CP and PDAC tissues. Furthermore, BGLAP expression was found in the cancer cells in PDAC tissues as well as in 4 cultured pancreatic cancer cell lines. TNFalpha reduced BGLAP mRNA and protein expression levels in pancreatic cancer cell lines. In addition, BGLAP silencing led to reduction of both cell growth and invasion in those cells. Conclusion BGLAP is expressed in pancreatic cancer cells, where it potentially increases pancreatic cancer cell growth and invasion through autocrine and/or paracrine mechanisms.

  14. Design of a nanoplatform for treating pancreatic cancer

    Science.gov (United States)

    Manawadu, Harshi Chathurangi

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA. Asymptomatic early cancer stages and late diagnosis leads to very low survival rates of pancreatic cancers, compared to other cancers. Treatment options for advanced pancreatic cancer are limited to chemotherapy and/or radiation therapy, as surgical removal of the cancerous tissue becomes impossible at later stages. Therefore, there's a critical need for innovative and improved chemotherapeutic treatment of (late) pancreatic cancers. It is mandatory for successful treatment strategies to overcome the drug resistance associated with pancreatic cancers. Nanotechnology based drug formulations have been providing promising alternatives in cancer treatment due to their selective targeting and accumulation in tumor vasculature, which can be used for efficient delivery of chemotherapeutic agents to tumors and metastases. The research of my thesis is following the principle approach to high therapeutic efficacy that has been first described by Dr. Helmut Ringsdorf in 1975. However, I have extended the use of the Ringsdorf model from polymeric to nanoparticle-based drug carriers by exploring an iron / iron oxide nanoparticle based drug delivery system. A series of drug delivery systems have been synthesized by varying the total numbers and the ratio of the tumor homing peptide sequence CGKRK and the chemotherapeutic drug doxorubicin at the surfaces of Fe/Fe3O 4-nanoparticles. The cytotoxicity of these nanoformulations was tested against murine pancreatic cancer cell lines (Pan02) to assess their therapeutic capabilities for effective treatments of pancreatic cancers. Healthy mouse fibroblast cells (STO) were also tested for comparison, because an effective chemotherapeutic drug has to be selective towards cancer cells. Optimal Experimental Design methodology was applied to identify the nanoformulation with the highest therapeutic activity. A statistical analysis method known as response

  15. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

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    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  16. Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Aeson [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Kim-Fuchs, Corina [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Department of Visceral Surgery and Medicine, University Hospital Bern, Bern 3010 (Switzerland); Le, Caroline P. [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Hollande, Frédéric [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Department of Pathology, University of Melbourne, Parkville 3010 (Australia); Sloan, Erica K., E-mail: erica.sloan@monash.edu [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Cousins Center for PNI, UCLA Semel Institute, Jonsson Comprehensive Cancer Center, and UCLA AIDS Institute, University of California Los Angeles, Los Angeles, CA 90095 (United States); Peter MacCallum Cancer Centre, Division of Cancer Surgery, East Melbourne, Victoria 3002 (Australia)

    2015-07-17

    The tumor microenvironment is known to play a pivotal role in driving cancer progression and governing response to therapy. This is of significance in pancreatic cancer where the unique pancreatic tumor microenvironment, characterized by its pronounced desmoplasia and fibrosis, drives early stages of tumor progression and dissemination, and contributes to its associated low survival rates. Several molecular factors that regulate interactions between pancreatic tumors and their surrounding stroma are beginning to be identified. Yet broader physiological factors that influence these interactions remain unclear. Here, we discuss a series of preclinical and mechanistic studies that highlight the important role chronic stress plays as a physiological regulator of neural-tumor interactions in driving the progression of pancreatic cancer. These studies propose several approaches to target stress signaling via the β-adrenergic signaling pathway in order to slow pancreatic tumor growth and metastasis. They also provide evidence to support the use of β-blockers as a novel therapeutic intervention to complement current clinical strategies to improve cancer outcome in patients with pancreatic cancer.

  17. Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention

    International Nuclear Information System (INIS)

    Chang, Aeson; Kim-Fuchs, Corina; Le, Caroline P.; Hollande, Frédéric; Sloan, Erica K.

    2015-01-01

    The tumor microenvironment is known to play a pivotal role in driving cancer progression and governing response to therapy. This is of significance in pancreatic cancer where the unique pancreatic tumor microenvironment, characterized by its pronounced desmoplasia and fibrosis, drives early stages of tumor progression and dissemination, and contributes to its associated low survival rates. Several molecular factors that regulate interactions between pancreatic tumors and their surrounding stroma are beginning to be identified. Yet broader physiological factors that influence these interactions remain unclear. Here, we discuss a series of preclinical and mechanistic studies that highlight the important role chronic stress plays as a physiological regulator of neural-tumor interactions in driving the progression of pancreatic cancer. These studies propose several approaches to target stress signaling via the β-adrenergic signaling pathway in order to slow pancreatic tumor growth and metastasis. They also provide evidence to support the use of β-blockers as a novel therapeutic intervention to complement current clinical strategies to improve cancer outcome in patients with pancreatic cancer

  18. Indications and results of pancreatic stump duct occlusion after duodenopancreatectomy.

    Science.gov (United States)

    Alfieri, Sergio; Quero, Giuseppe; Rosa, Fausto; Di Miceli, Dario; Tortorelli, Antonio Pio; Doglietto, Giovanni Battista

    2016-09-01

    Severe post-operative complications after pancreaticoduodenectomy (PD) are largely due to pancreatic fistula onset. The occlusion of the main pancreatic duct using synthetic glue may prevent these complications. Aim of this study is to describe this technique and to report short- and long-term results as well as the post-operative endocrine and exocrine insufficiency. Two hundred and four patients who underwent PD with occlusion of the main pancreatic duct in a period of 15 years were retrospectively analyzed. Post-operative complications and their management were the main aim of the study with particular focus on pancreatic fistula incidence and its treatment. At 1-year follow-up endocrine and exocrine functions were analyzed. We observed a 54 % pancreatic fistula incidence, most of which (77/204 patients) were a grade A fistula with little change in medical management. Twenty-eight patients developed a grade B fistula while only 2 % of patients (5/204) developed a grade C fistula. Nine patients required re-operation, 5 of whom had a post-operative grade C fistula. Post-operative mortality was 3.4 %. At 1-year follow-up, 31 % of patients developed a post-operative diabetes while exocrine insufficiency was encountered in 88 % of patients. The occlusion of the main pancreatic duct after PD can be considered a relatively safe and easy-to-perform procedure. It should be reserved to selected patients, especially in case of soft pancreatic texture and small pancreatic duct and in elderly patients with comorbidities, in whom pancreatic fistula-related complications could be life threatening.

  19. Reduced STMN1 expression induced by RNA interference inhibits the bioactivity of pancreatic cancer cell line Panc-1.

    Science.gov (United States)

    Li, J; Hu, G H; Kong, F J; Wu, K M; He, B; Song, K; Sun, W J

    2014-01-01

    Increased expression of STMN1 has been observed in many tumor forms, but its expression and potential biological role in pancreatic cancer is still unknown. In this study, we demonstrated that STMN1 was expressed to a large extent in pancreatic cancer tissues and cell lines as compared to normal pancreatic tissues. Suppression of STMN1 expression via transfection with STMN1-specific siRNA could not only significantly inhibit the proliferation, migration and invasion ability of Panc-1 cells, but also enhance the apoptosis of Panc-1 cells. In addition, downregulation of STMN1 obviously enhanced the acetylation level of α-tubulin. All these results indicated that STMN1 plays an important role in pancreatic cancer development, and might serve as a potential therapeutic target for pancreatic cancer.

  20. A case of remnant pancreatic cancer after pancreatoduodenectomy successfully treated using chemotherapy and carbon-ion radiotherapy

    International Nuclear Information System (INIS)

    Yamamoto, Tatsuhito; Tokunou, Kazuhisa; Yamamoto, Hisato; Kamei, Ryoji; Kitamura, Yoshinori; Ando, Seiichiro

    2016-01-01

    We report a case of remnant pancreatic cancer after pancreatoduodenectomy that was successfully treated using chemotherapy and carbon-ion radiotherapy. A 68-year-old woman received SSPPD for pancreatic head cancer. Gemcitabine (GEM) was administered for a year as postoperative chemotherapy. One year 8 months after surgery, abdominal CT showed a 20 mm solid mass in the stump of the remnant pancreas and dilation of the distal pancreatic duct. FDG-PET revealed a solitary tumor without any recurrence. We diagnosed the patient with a solitary recurrence of pancreatic cancer. Chemotherapy (GEM) and carbon-ion radiotherapy were performed. After treatment, the lesion was not detected on CT or FDG-PET. Chemotherapy (GEM) and carbon-ion radiotherapy for locally advanced pancreatic cancer seems to be effective and there might result in a survival benefit. (author)

  1. Evaluation of pancreatic cancers using thallium-201 single photon emission computed tomography

    International Nuclear Information System (INIS)

    Kume, Norihiko; Suga, Kazuyoshi; Nishigauchi, Kazuya; Uchisako, Hiromichi; Sugano, Ayame; Fujita, Takeshi; Nakanishi, Takashi; Hamasaki, Tatsunori; Suzuki, Takashi

    1995-01-01

    Radionuclide study has not been frequently applied to pancreatic cancers because of the absence of suitable radiopharmaceuticals for their positive depiction. We evaluated thallium-201 chloride ( 201 T1) SPECT for the investigation of pancreatic cancers. The subjects included 24 patients with pancreatic cancer, seven with benign disorders and 10 controls. Each patient fasted prior to the examination for more than 12 hr, and 201 T1 SPECT was obtained 10 min after the injection of 148-222 MBq of 201 T1. When the boundary of tumor uptake of 201 T1 was unclear because of the adjacent physiological liver activity, subtracted SPECT using 99m Tc-phytate was performed to clarify it. 201 T1 did not accumulate in the pancreas of the controls. In contrast, of the 24 pancreatic cancers, 21 demonstrated positive uptake, for a sensitivity rate of 87.5%, and the mean tumor/liver ratio was 0.76±0.16 (range, 0.58-1.28). Abnormal uptake was also noted in three of the seven benign disorders, but with a comparatively lower lesion/liver ratio (range, 0.35-0.51). 201 T1 activity per mg tissue in the resected specimens of two patients with pancreatic cancer revealed higher activity in the tumor than in normal parenchyma. 201 T1 uptake in the five conservatively treated pancreatic cancers showed alteration similar to the serum level of tumor markers. These results suggest that 201 T1 SPECT may have clinical potential for investigating pancreatic cancers as well as for the monitoring of treatment effect. (author)

  2. External and intraoperative radiotherapy for resectable and unresectable pancreatic cancer: analysis of survival rates and complications

    International Nuclear Information System (INIS)

    Nishimura, Yasumasa; Hosotani, Ryo; Shibamoto, Yuta; Kokubo, Masaki; Kanamori, Shuichi; Sasai, Keisuke; Hiraoka, Masahiro; Ohshio, Gakuji; Imamura, Masayuki; Takahashi, Masaji; Abe, Mitsuyuki

    1997-01-01

    Purpose: Clinical results of intraoperative radiotherapy (IORT) and/or external beam radiotherapy (EBRT) for both resectable and unresectable pancreatic cancer were analyzed. Methods and Materials: Between 1980 and 1995, 332 patients with pancreatic cancer were treated with surgery and/or radiation therapy (RT). Of the 332 patients, 157 patients were treated with surgical resection of pancreatic tumor, and the remaining 175 patients had unresectable pancreatic tumors. Among the 157 patients with resected pancreatic cancer, 62 patients were not treated with RT, while 40 patients were treated with EBRT alone (mean RT dose; 46.3 Gy) and 55 patients with IORT (25.2 Gy) ± EBRT (44.0 Gy). On the other hand, among the 175 patients with unresectable pancreatic cancer, 58 patients were not treated with RT, 46 patients were treated with EBRT alone (39.2 Gy), and the remaining 71 patients with IORT (29.3 Gy) ± EBRT (41.2 Gy). Results: For 87 patients with curative resection, the median survival times (MSTs) of the no-RT, the EBRT, and the IORT ± EBRT groups were 10.4, 13.0, and 15.5 months, respectively, without significant difference. For 70 patients with non curative resection, the MSTs of the no-RT, the EBRT, and the IORT ± EBRT groups were 5.3, 8.7, and 6.5 months, respectively. When the EBRT and the IORT ± EBRT groups were combined, the survival rate was significantly higher than that of the no RT group for non curatively resected pancreatic cancers (log rank test; p = 0.028). The 2-year survival probability of the IORT ± EBRT group (16%) was higher than that of the EBRT group (0%). For unresectable pancreatic cancer, the MSTs of 52 patients without distant metastases were 6.7 months for palliative surgery alone, 7.6 months for EBRT alone, and 8.2 months for IORT ± EBRT. The survival curve of the IORT ± EBRT group was significantly better than that of the no-RT group (p 2 years) were obtained by IORT ± EBRT for non curatively resected and unresectable pancreatic

  3. Involvement of Endoplasmic Reticulum Stress in Capsaicin-Induced Apoptosis of Human Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Shengzhang Lin

    2013-01-01

    Full Text Available Capsaicin, main pungent ingredient of hot chilli peppers, has been shown to have anticarcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human pancreatic cancer cells in both in vitro and in vivo systems, as well as the possible mechanisms involved. In vitro, treatment of both the pancreatic cancer cells (PANC-1 and SW1990 with capsaicin resulted in cells growth inhibition, G0/G1 phase arrest, and apoptosis in a dose-dependent manner. Knockdown of growth arrest- and DNA damage-inducible gene 153 (GADD153, a marker of the endoplasmic-reticulum-stress- (ERS- mediated apoptosis pathway, by specific siRNA attenuated capsaicin-induced apoptosis both in PANC-1 and SW1990 cells. Moreover, in vivo studies capsaicin effectively inhibited the growth and metabolism of pancreatic cancer and prolonged the survival time of pancreatic cancer xenograft tumor-induced mice. Furthermore, capsaicin increased the expression of some key ERS markers, including glucose-regulated protein 78 (GRP78, phosphoprotein kinase-like endoplasmic reticulum kinase (phosphoPERK, and phosphoeukaryotic initiation factor-2α (phospho-eIF2α, activating transcription factor 4 (ATF4 and GADD153 in tumor tissues. In conclusion, we for the first time provide important evidence to support the involvement of ERS in the induction of apoptosis in pancreatic cancer cells by capsaicin.

  4. Nitrate in drinking water and risk of death from pancreatic cancer in Taiwan.

    Science.gov (United States)

    Yang, Chun-Yuh; Tsai, Shang-Shyue; Chiu, Hui-Fen

    2009-01-01

    The relationship between nitrate levels in drinking water and risk of pancreatic cancer development remains inconclusive. A matched case-control and nitrate ecology study was used to investigate the association between mortality attributed to pancreatic cancer and nitrate exposure from Taiwan's drinking water. All pancreatic cancer deaths of Taiwan residents from 2000 through 2006 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Data on nitrate-nitrogen (NO(3)-N) levels of drinking water throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios and confidence limits for pancreatic cancer death for those with high nitrate levels in their drinking water, as compared to the lowest tertile, were 1.03 (0.9-1.18) and 1.1 (0.96-1.27), respectively. The results of the present study show that there was no statistically significant association between the levels of nitrate in drinking water and increased risk of death from pancreatic cancer.

  5. Factors Affecting Adjuvant Therapy in Stage III Pancreatic Cancer—Analysis of the National Cancer Database

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    Mridula Krishnan

    2017-08-01

    Full Text Available Background: Adjuvant therapy after curative resection is associated with survival benefit in stage III pancreatic cancer. We analyzed the factors affecting the outcome of adjuvant therapy in stage III pancreatic cancer and compared overall survival with different modalities of adjuvant treatment. Methods: This is a retrospective study of patients with stage III pancreatic cancer listed in the National Cancer Database (NCDB who were diagnosed between 2004 and 2012. Patients were stratified based on adjuvant therapy they received. Unadjusted Kaplan-Meier and multivariable Cox regression analysis were performed. Results: We analyzed a cohort included 1731 patients who were recipients of adjuvant therapy for stage III pancreatic cancer within the limits of our database. Patients who received adjuvant chemoradiation had the longest postdiagnosis survival time, followed by patients who received adjuvant chemotherapy, and finally patients who received no adjuvant therapy. On multivariate analysis, advancing age and patients with Medicaid had worse survival, whereas Spanish origin and lower Charlson comorbidity score had better survival. Conclusions: Our study is the largest trial using the NCDB addressing the effects of adjuvant therapy specifically in stage III pancreatic cancer. Within the limits of our study, survival benefit with adjuvant therapy was more apparent with longer duration from date of diagnosis.

  6. PCA-1/ALKBH3 contributes to pancreatic cancer by supporting apoptotic resistance and angiogenesis.

    Science.gov (United States)

    Yamato, Ichiro; Sho, Masayuki; Shimada, Keiji; Hotta, Kiyohiko; Ueda, Yuko; Yasuda, Satoshi; Shigi, Naoko; Konishi, Noboru; Tsujikawa, Kazutake; Nakajima, Yoshiyuki

    2012-09-15

    The PCA-1/ALKBH3 gene implicated in DNA repair is expressed in several human malignancies but its precise contributions to cancer remain mainly unknown. In this study, we have determined its functions and clinical importance in pancreatic cancer. PCA-1/ALKBH3 functions in proliferation, apoptosis and angiogenesis were evaluated in human pancreatic cancer cells in vitro and in vivo. Further, PCA-1/ALKBH3 expression in 116 patients with pancreatic cancer was evaluated by immunohistochemistry. siRNA-mediated silencing of PCA-1/ALKBH3 expression induced apoptosis and suppressed cell proliferation. Conversely, overexpression of PCA-1/ALKBH3 increased anchorage-independent growth and invasiveness. In addition, PCA-1/ALKBH3 silencing downregulated VEGF expression and inhibited angiogenesis in vivo. Furthermore, immunohistochemical analysis showed that PCA-1/ALKBH3 expression was abundant in pancreatic cancer tissues, where it correlated with advanced tumor status, pathological stage and VEGF intensity. Importantly, patients with low positivity of PCA-1/ALKBH3 expression had improved postoperative prognosis compared with those with high positivity. Our results establish PCA-1/ALKBH3 as important gene in pancreatic cancer with potential utility as a therapeutic target in this fatal disease.

  7. Advances in the treatment of pancreatic cancer. Limitations of surgery and evaluation of new therapeutic strategies

    International Nuclear Information System (INIS)

    Yokoyama, Yukihiro; Nagino, Masato; Nimura, Yuji

    2009-01-01

    Pancreatic ductal carcinoma is one of the most dismal malignancies of the gastrointestinal system. Even after curative resection, the actual 5-year survival is only 10%-20%. Of all the treatments used against pancreatic cancer, surgery is still the only one that can achieve complete cure. Pancreatic cancer spreads easily to the adjacent tissues and distant metastasis is common. Typically, this cancer invades the retropancreatic neural tissue, duodenum, portal vein (PV), and superior mesenteric vein (SMV), or regional lymph nodes. For this reason, aggressive surgery that removes the cancerous lesion completely is recommended. Several retrospective and prospective studies have been conducted to validate the usefulness of aggressive surgery for pancreatic cancer in the past few decades. Surprisingly, the survival benefits of aggressive surgery have been denied by most randomized controlled trials (RCTs). This implies that surgery alone is not enough. Thus, adjuvant therapy, such as radiotherapy and chemotherapy, has been given in combination with surgery to improve survival. Although the benefits of radiotherapy alone are limited, the results of chemotherapy are promising. Other newly evolving molecular targeting drugs may also improve the treatment outcomes of pancreatic cancer. (author)

  8. Aberrant glycogen synthase kinase 3β in the development of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Takeo Shimasaki

    2012-01-01

    Full Text Available Development and progression of pancreatic cancer involves general metabolic disorder, local chronic inflammation, and multistep activation of distinct oncogenic molecular pathways. These pathologic processes result in a highly invasive and metastatic tumor phenotype that is a major obstacle to curative surgical intervention, infusional gemcitabine-based chemotherapy, and radiation therapy. Many clinical trials with chemical compounds and therapeutic antibodies targeting growth factors, angiogenic factors, and matrix metalloproteinases have failed to demonstrate definitive therapeutic benefits to refractory pancreatic cancer patients. Glycogen synthase kinase 3β (GSK3β, a serine/threonine protein kinase, has emerged as a therapeutic target in common chronic and progressive diseases, including cancer. Here we review accumulating evidence for a pathologic role of GSK3β in promoting tumor cell survival, proliferation, invasion, and resistance to chemotherapy and radiation in pancreatic cancer. We also discuss the putative involvement of GSK3β in mediating metabolic disorder, local inflammation, and molecular alteration leading to pancreatic cancer development. Taken together, we highlight potential therapeutic as well as preventive effects of GSK3β inhibition in pancreatic cancer.

  9. The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells

    International Nuclear Information System (INIS)

    Lou, Hai-zhou; Weng, Xiao-chuan; Pan, Hong-ming; Pan, Qin; Sun, Peng; Liu, Li-li; Chen, Bin

    2014-01-01

    Highlights: • INK-128 inhibits the survival and growth of human pancreatic cancer cells. • INK-128 induced pancreatic cancer cell apoptosis and necrosis simultaneously. • INK-128 blocks mTORC1/2 activation simultaneously in pancreatic cancer cells. • INK-128 down-regulates cyclin D1 and causes pancreatic cancer cell cycle arrest. • INK-128 significantly increases sensitivity of pancreatic cancer cells to gemcitabine. - Abstract: Pancreatic cancer has one of worst prognosis among all human malignancies around the world, the development of novel and more efficient anti-cancer agents against this disease is urgent. In the current study, we tested the potential effect of INK-128, a novel mammalian target of rapamycin (mTOR) complex 1 and 2 (mTORC1/2) dual inhibitor, against pancreatic cancer cells in vitro. Our results demonstrated that INK-128 concentration- and time-dependently inhibited the survival and growth of pancreatic cancer cells (both primary cells and transformed cells). INK-128 induced pancreatic cancer cell apoptosis and necrosis simultaneously. Further, INK-128 dramatically inhibited phosphorylation of 4E-binding protein 1 (4E-BP1), ribosomal S6 kinase 1 (S6K1) and Akt at Ser 473 in pancreatic cancer cells. Meanwhile, it downregulated cyclin D1 expression and caused cell cycle arrest. Finally, we found that a low concentration of INK-128 significantly increased the sensitivity of pancreatic cancer cells to gemcitabine. Together, our in vitro results suggest that INK-128 might be further investigated as a novel anti-cancer agent or chemo-adjuvant for pancreatic cancer treatment

  10. The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lou, Hai-zhou [Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016 (China); Weng, Xiao-chuan [Department of Anesthesiology, Hangzhou Xia-sha Hospital, Hangzhou 310018 (China); Pan, Hong-ming; Pan, Qin [Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016 (China); Sun, Peng [Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510060 (China); Liu, Li-li [Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016 (China); Chen, Bin, E-mail: chenbinhangzhou126@126.com [Department of Hepatopancreatobiliary Surgery, First People’s Hospital of Hangzhou, Hangzhou 310006 (China)

    2014-07-25

    Highlights: • INK-128 inhibits the survival and growth of human pancreatic cancer cells. • INK-128 induced pancreatic cancer cell apoptosis and necrosis simultaneously. • INK-128 blocks mTORC1/2 activation simultaneously in pancreatic cancer cells. • INK-128 down-regulates cyclin D1 and causes pancreatic cancer cell cycle arrest. • INK-128 significantly increases sensitivity of pancreatic cancer cells to gemcitabine. - Abstract: Pancreatic cancer has one of worst prognosis among all human malignancies around the world, the development of novel and more efficient anti-cancer agents against this disease is urgent. In the current study, we tested the potential effect of INK-128, a novel mammalian target of rapamycin (mTOR) complex 1 and 2 (mTORC1/2) dual inhibitor, against pancreatic cancer cells in vitro. Our results demonstrated that INK-128 concentration- and time-dependently inhibited the survival and growth of pancreatic cancer cells (both primary cells and transformed cells). INK-128 induced pancreatic cancer cell apoptosis and necrosis simultaneously. Further, INK-128 dramatically inhibited phosphorylation of 4E-binding protein 1 (4E-BP1), ribosomal S6 kinase 1 (S6K1) and Akt at Ser 473 in pancreatic cancer cells. Meanwhile, it downregulated cyclin D1 expression and caused cell cycle arrest. Finally, we found that a low concentration of INK-128 significantly increased the sensitivity of pancreatic cancer cells to gemcitabine. Together, our in vitro results suggest that INK-128 might be further investigated as a novel anti-cancer agent or chemo-adjuvant for pancreatic cancer treatment.

  11. Cardiorespiratory fitness and muscle strength in pancreatic cancer patients.

    Science.gov (United States)

    Clauss, Dorothea; Tjaden, Christine; Hackert, Thilo; Schneider, Lutz; Ulrich, Cornelia M; Wiskemann, Joachim; Steindorf, Karen

    2017-09-01

    Cancer patients frequently experience reduced physical fitness due to the disease itself as well as treatment-related side effects. However, studies on physical fitness in pancreatic cancer patients are missing. Therefore, we assessed cardiorespiratory fitness and muscle strength of pancreatic cancer patients. We included 65 pancreatic cancer patients, mostly after surgical resection. Cardiorespiratory fitness was assessed using cardiopulmonary exercise testing (CPET) and 6-min walk test (6MWT). Hand-held dynamometry was used to evaluate isometric muscle strength. Physical fitness values were compared to reference values of a healthy population. Associations between sociodemographic and clinical variables with patients' physical fitness were analyzed using multiple regression models. Cardiorespiratory fitness (VO 2 peak, 20.5 ± 6.9 ml/min/kg) was significantly lower (-24%) compared to healthy reference values. In the 6MWT pancreatic cancer patients nearly reached predicted values (555 vs. 562 m). Maximal voluntary isometric contraction (MVIC) of the upper (-4.3%) and lower extremities (-13.8%) were significantly lower compared to reference values. Overall differences were larger in men than those in women. Participating in regular exercise in the year before diagnosis was associated with greater VO 2 peak (p fitness with regard to both cardiorespiratory function and isometric muscle strength, already in the early treatment phase (median 95 days after surgical resection). Our findings underline the need to investigate exercise training in pancreatic cancer patients to counteract the loss of physical fitness.

  12. Physical activity, energy restriction, and the risk of pancreatic cancer: Prospective study in the Netherlands

    NARCIS (Netherlands)

    Heinen, M.M.; Verhage, B.A.J.; Goldbohm, R.A.; Lumey, L.H.; Brandt, P.A. van den

    2011-01-01

    Background: Because of their influence on insulin concentrations, we hypothesized that both physical activity and energy restriction may reduce the risk of pancreatic cancer. Objective: We examined the associations between physical activity, proxies for energy restriction, and pancreatic cancer

  13. Dietary fat intake and risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

    Science.gov (United States)

    Arem, Hannah; Mayne, Susan T; Sampson, Joshua; Risch, Harvey; Stolzenberg-Solomon, Rachael Z

    2013-09-01

    Epidemiologic and experimental studies suggest that dietary fat intake may affect risk of pancreatic cancer, but published results are inconsistent. We examined risk associations for specific types of dietary fat intakes and related food sources among 111,416 participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used Cox proportional hazards regression to examine associations between fat intake and pancreatic cancer risk. Over a mean 8.4 years of follow-up, 411 pancreatic cancer cases were identified. We observed an inverse association between saturated fat intake and pancreatic cancer risk (hazard ratio [HR], 0.64 comparing extreme quintiles; 95% confidence interval [CI], 0.46-0.88), but the association became weaker and nonsignificant when individuals with fewer than 4 years of follow-up were excluded to avoid possible reverse causation (HR, 0.88; 95% CI, 0.58-1.33). Total fat intake showed a similar pattern of association, whereas intakes of monounsaturated and polyunsaturated fats and fats from animal or plant sources showed no associations with risk. These results do not support the hypothesis of increased pancreatic cancer risk with higher fat consumption overall or by specific fat type or source. Dietary changes owing to undetected disease may explain the observed inverse association with saturated fat. Published by Elsevier Inc.

  14. Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

    Science.gov (United States)

    Stolzenberg-Solomon, Rachael Z; Jacobs, Eric J; Arslan, Alan A; Qi, Dai; Patel, Alpa V; Helzlsouer, Kathy J; Weinstein, Stephanie J; McCullough, Marjorie L; Purdue, Mark P; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Albanes, Demetrius; Cai, Qiuyin; Harvey, Chinonye; Hayes, Richard; Clipp, Sandra; Horst, Ronald L; Irish, Lonn; Koenig, Karen; Le Marchand, Loic; Kolonel, Laurence N

    2010-07-01

    Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974-2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50- or =100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered.

  15. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer.

    Science.gov (United States)

    Sunamura, Makoto; Duda, Dan G; Ghattas, Maivel H; Lozonschi, Lucian; Motoi, Fuyuhiko; Yamauchi, Jun-Ichiro; Matsuno, Seiki; Shibahara, Shigeki; Abraham, Nader G

    2003-01-01

    Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor angiogenesis was markedly increased in Panc-1/hHO-1 compared to mock transfected and wild type. Lectin staining and Ki-67 proliferation index confirmed these results. In addition hHO-1 stimulated in vitro tumor angiogenesis and increased endothelial cell survival. In a lung colonization model, overexpression of hHO-1 increased the occurrence of metastasis, while inhibition of HO activity by stannous mesoporphyrin completely inhibited the occurrence of metastasis. In conclusion, overexpression of HO-1 genes potentiates pancreatic cancer aggressiveness, by increasing tumor growth, angiogenesis and metastasis and that the inhibition of the HO system may be of useful benefit for the future treatment of the disease.

  16. Surgical palliation of unresectable pancreatic head cancer in elderly patients

    Science.gov (United States)

    Hwang, Sang Il; Kim, Hyung Ook; Son, Byung Ho; Yoo, Chang Hak; Kim, Hungdai; Shin, Jun Ho

    2009-01-01

    AIM: To determine if surgical biliary bypass would provide improved quality of residual life and safe palliation in elderly patients with unresectable pancreatic head cancer. METHODS: Nineteen patients, 65 years of age or older, were managed with surgical biliary bypass (Group A). These patients were compared with 19 patients under 65 years of age who were managed with surgical biliary bypass (Group B). In addition, the results for group A were compared with those obtained from 17 patients, 65 years of age or older (Group C), who received percutaneous transhepatic biliary drainage to evaluate the quality of residual life. RESULTS: Five patients (26.0%) in Group A had complications, including one intraabdominal abscess, one pulmonary atelectasis, and three wound infections. One death (5.3%) occurred on postoperative day 3. With respect to morbidity, mortality, and postoperative hospitalization, no statistically significant difference was noted between Groups A and B. The number of readmissions and the rate of recurrent jaundice were lower in Group A than in Group C, to a statistically significant degree (P = 0.019, P = 0.029, respectively). The median hospital-free survival period and the median overall survival were also significantly longer in Group A (P = 0.001 and P < 0.001, respectively). CONCLUSION: Surgical palliation does not increase the morbidity or mortality rates, but it does increase the survival rate and improve the quality of life in elderly patients with unresectable pancreatic head cancer. PMID:19248198

  17. Escin Chemosensitizes Human Pancreatic Cancer Cells and Inhibits the Nuclear Factor-kappaB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    A. Rimmon

    2013-01-01

    Full Text Available Background. There is an urgent need to develop new treatment strategies and drugs for pancreatic cancer that is highly resistant to radio-chemotherapy. Aesculus hippocastanum (the horse chestnut known in Chinese medicine as a plant with anti-inflammatory, antiedema, antianalgesic, and antipyretic activities. The main active compound of this plant is Escin (C54H84O23. Objective. To evaluate the effect of Escin alone and combined with chemotherapy on pancreatic cancer cell survival and to unravel mechanism(s of Escin anticancer activity. Methods. Cell survival was measured by XTT colorimetric assay. Synergistic effect of combined therapy was determined by CalcuSyn software. Cell cycle and induction of apoptosis were evaluated by FACS analysis. Expression of NF-κB-related proteins (p65, IκBα, and p-IκBα and cyclin D was evaluated by western blot analysis. Results. Escin decreased the survival of pancreatic cancer cells with IC50 = 10–20 M. Escin combined with gemcitabine showed only additive effect, while its combination with cisplatin resulted in a significant synergistic cytotoxic effect in Panc-1 cells. High concentrations of Escin induced apoptosis and decreased NF-κB-related proteins and cyclin D expression. Conclusions. Escin decreased pancreatic cancer cell survival, induced apoptosis, and downregulated NF-κB signaling pathway. Moreover, Escin sensitized pancreatic cancer cells to chemotherapy. Further translational research is required.

  18. MEK inhibition potentiates the activity of Hsp90 inhibitor 17-AAG against pancreatic cancer cells.

    Science.gov (United States)

    Zhang, Tao; Li, Yanyan; Zhu, Zhenkun; Gu, Mancang; Newman, Bryan; Sun, Duxin

    2010-10-04

    The Ras/Raf/MEK/ERK signaling has been implicated in uncontrolled cell proliferation and tumor progression in pancreatic cancer. The purpose of this study is to evaluate the antitumor activity of MEK inhibitor U0126 in combination with Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) in pancreatic cancer cells. Western blotting showed that 17-AAG caused a 2- to 3-fold transient activation of MEK/ERK signaling in pancreatic cancer cells. The activation sustained for 6 h before phospho-ERK (p-ERK) destabilization. The selective MEK inhibitor U0126 completely abolished 17-AAG induced ERK1/2 activation and resulted in more than 80% of phospho-ERK degradation after only 15 min treatment. Moreover, U0126 had complementary effect on 17-AAG regulated oncogenic and cell cycle related proteins. Although 17-AAG downregulated cyclin D1, cyclin E, CDK4 and CDK6, it led to cyclin A and CDK2 accumulation, which was reversed by the addition of U0126. Antiproliferation assay showed that combination of U0126 and 17-AAG resulted in synergistic cytotoxic effect. More importantly, 17-AAG alone only exhibited moderate inhibition of cell migration in vitro, while addition of U0126 dramatically enhanced the inhibitory effect by 2- to 5-fold. Taken together, these data demonstrate that MEK inhibitor U0126 potentiates the activity of Hsp90 inhibitor 17-AAG against pancreatic cancer cells. The combination of Hsp90 and MEK inhibition could provide a promising avenue for the treatment of pancreatic cancer.

  19. A current perspective on stereotactic body radiation therapy for pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Hong JC

    2016-10-01

    Full Text Available Julian C Hong, Brian G Czito, Christopher G Willett, Manisha Palta Department of Radiation Oncology, Duke University, Durham, NC, USA Abstract: Pancreatic cancer is a formidable malignancy with poor outcomes. The majority of patients are unable to undergo resection, which remains the only potentially curative treatment option. The management of locally advanced (unresectable pancreatic cancer is controversial; however, treatment with either chemotherapy or chemoradiation is associated with high rates of local tumor progression and metastases development, resulting in low survival rates. An emerging local modality is stereotactic body radiation therapy (SBRT, which uses image-guided, conformal, high-dose radiation. SBRT has demonstrated promising local control rates and resultant quality of life with acceptable rates of toxicity. Over the past decade, increasing clinical experience and data have supported SBRT as a local treatment modality. Nevertheless, additional research is required to further evaluate the role of SBRT and improve upon the persistently poor outcomes associated with pancreatic cancer. This review discusses the existing clinical experience and technical implementation of SBRT for pancreatic cancer and highlights the directions for ongoing and future studies. Keywords: pancreatic cancer, stereotactic body radiation therapy, SBRT, radiation therapy

  20. Computer-aided diagnosis of pancreatic and lung cancer

    Directory of Open Access Journals (Sweden)

    B. Luis Lancho Tofé

    2008-12-01

    Full Text Available When we talk about cancer diagnosis the most important thing is early diagnosis to prevent cancer cells from spreading. We may also consider the high cost of diagnostic tests. Our approach seeks to address both problems. It uses a software based on Bayesian networks that simulates the causeeffect relationships and gets the chance of suffering a pancreatic cancer or lung cancer. This software would support doctors and save a lot of time and resources.

  1. Ginkgo Biloba Extract Kaempferol Inhibits Cell Proliferation and Induces Apoptosis in Pancreatic Cancer Cells

    Science.gov (United States)

    Zhang, Yuqing; Chen, Aaron Y.; Li, Min; Chen, Changyi; Yao, Qizhi

    2010-01-01

    Background Kaempferol is one of the most important constituents in ginkgo flavonoids. Recent studies indicate kaempferol may have anti-tumor activities. The objective in this study was to determine the effect and mechanisms of kaempferol on pancreatic cancer cell proliferation and apoptosis. Materials and Methods Pancreatic cancer cell lines MIA PaCa-2 and Panc-1 were treated with Kampferol, and the inhibitory effects of kaempferol on pancreatic cancer cell proliferation were examined by direct cell counting, 3H-thymidine incorporation and MTS assay. Lactate dehydrogenase (LDH) release from cells was determined as an index of cytotoxicity. Apoptosis was analyzed by TUNEL assay. Results Upon the treatment with 70 μM kaempferol for 4 days, MIA PaCa-2 cell proliferation was significantly inhibited by 79% and 45.7% as determined by direct cell counting and MTS assay, respectively, compared with control cells (Pkaempferol significantly inhibited Panc-1 cell proliferation. Kaempferol treatment also significantly reduced 3H-thymidine incorporation in both MIA PaCa-2 and Panc-1 cells. Combination treatment of low concentrations of kaempferol and 5-fluorouracil (5-FU) showed an additive effect on the inhibition of MIA PaCa-2 cell proliferation. Furthermore, kaempferol had a significantly less cytotoxicity than 5-FU in normal human pancreatic ductal epithelial cells (P=0.029). In both MIA PaCa-2 and Panc-1 cells, apoptotic cell population was increased when treated with kaempferol in a concentration-dependent manner. Conclusions Ginkgo biloba extract kaempferol effectively inhibits pancreatic cancer cell proliferation and induces cancer cell apoptosis, which may sensitize pancreatic tumor cells to chemotherapy. Kaempferol may have clinical applications as adjuvant therapy in the treatment of pancreatic cancer. PMID:18570926

  2. THE FREQUENCY OF RISK FACTORS ON TRENDS OF PANCREATIC CANCER IN KOSOVO

    Science.gov (United States)

    Ramadani, Naser; Dedushi, Kreshnike; Muçaj, Sefedin; Kabashi, Serbeze; Jerliu, Naim; Hoxhaj, Astrit

    2016-01-01

    The aim: The aim of this paper is to analyze different factors that influence the trends of pancreatic cancer mortality and morbidity of patients treated at the UCCK of Kosovo. Within this study, we have evaluated pancreatic cancer risk factors, durability and lethality regarding Kosovan patients who have been diagnosed and treated within Kosovo. The study in question is that of retrospective research traversing the period of 2011-2015. Materials and methodology: This retrospective research study includes 362 patients recently diagnosed with pancreatic cancer, 2011-2015 at the University Clinical Center of Kosovo in Pristina. The main important factors included in this study are: age, sex and risk factors that altogether have considerable influence in incidence of pancreatic cancer. The imaging diagnostics are performed with the use of 2D ECHO Phillips, MSCT Sensation 64 and 6 and 1.5T MRI Symphony Siemens that are situated in the Radiologic Clinic of UCCK. The statistic data were obtained from NIPH of Kosovo and Agency of Statistics of Kosovo. Results: Out of the total number of the 362 patients diagnosed with pancreatic cancer, the mortality in all age groups was higher at male patients–61.6 % of cases (n=223) with the highest number found at 51–60 years age group. The 38.4 % (n= 139) were female patients with the highest incidence frequency at F 61–70 years age group. The F/M ratio is 1:1.6. The “plane” nicotine users were found at 34 % (n=123) while the joined, nicotine/alcohol addiction was detected at 26 % (n= 94). The 18.5% (n=67) have had established diagnose of the diabetes mellitus tip II and 9.6 % (n=35) have undergone the medical treatment of the gastroduodenal peptic ulcerations. The total number of deaths is 310 (85.6%) and there are only 52 patients (14.4%) still alive. The mortality rate of the pancreatic cancer in Kosovo was 17.2 in 100.000 residents while the morbidity rate was 2.8 in 100.000 residents. Discussion and conclusion: This

  3. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    Science.gov (United States)

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  4. Laparoscopic versus open distal pancreatectomy for pancreatic cancer

    NARCIS (Netherlands)

    Riviere, D.M.; Gurusamy, K.S.; Kooby, D.A.; Vollmer, C.M.; Besselink, M.G.; Davidson, B.R.; Laarhoven, C.J.H.M. van

    2016-01-01

    BACKGROUND: Surgical resection is currently the only treatment with the potential for long-term survival and cure of pancreatic cancer. Surgical resection is provided as distal pancreatectomy for cancers of the body and tail of the pancreas. It can be performed by laparoscopic or open surgery. In

  5. Laparoscopic versus open distal pancreatectomy for pancreatic cancer

    NARCIS (Netherlands)

    Riviere, Deniece; Gurusamy, Kurinchi Selvan; Kooby, David A.; Vollmer, Charles M.; Besselink, Marc G. H.; Davidson, Brian R.; van Laarhoven, Cornelis J. H. M.

    2016-01-01

    Surgical resection is currently the only treatment with the potential for long-term survival and cure of pancreatic cancer. Surgical resection is provided as distal pancreatectomy for cancers of the body and tail of the pancreas. It can be performed by laparoscopic or open surgery. In operations on

  6. The Genetics and Molecular Alterations of Pancreatic Cancer

    NARCIS (Netherlands)

    Wilde, R.F. de

    2015-01-01

    The prospect that pancreatic cancer will be the second most common cause of cancer death by 2030 is worrisome. Considering that the approximate 6% overall 5-year survival has not merely changed in the past decades illustrates the need to revert the bleak prognosis. Centralization of surgery

  7. Rare case of pancreatic cancer with leptomeningeal carcinomatosis

    Science.gov (United States)

    Yoo, In Kyung; Lee, Hong Sik; Kim, Chang Duk; Chun, Hoon Jai; Jeen, Yoon Tae; Keum, Bora; Kim, Eun Sun; Choi, Hyuk Soon; Lee, Jae Min; Kim, Seung Han; Nam, Seung Joo; Hyun, Jong Jin

    2015-01-01

    Leptomeningeal carcinomatosis occurs very rarely in patients with pancreatic cancer. Leptomeningeal carcinomatosis is characterized by multifocal seeding of the leptomeninges by malignant cells that originate from a solid tumor. To the best of our knowledge, brain metastasis from pancreatic cancer is extremely rare. Leptomeningeal carcinomatosis is estimated to occur in 3% to 8% of cases of solid tumors. The clinical manifestation usually involves neurological symptoms, including dizziness, headache, vomiting, nausea, and hemiparesis, symptoms similar to those of meningitis or brain tumors. Diagnostic methods for leptomeningeal carcinomatosis include brain magnetic resonance imaging and cerebrospinal fluid examination. Here, we describe a case of leptomeningeal carcinomatosis in which the primary tumor was later determined to be pancreatic cancer. Brain magnetic resonance imaging findings showed mild enhancement of the leptomeninges, and cerebrospinal fluid cytology was negative at first. However, after repeated spinal taps, atypical cells were observed on cerebrospinal fluid analysis and levels of tumor markers such as carbohydrate antigen 19-9 in cerebrospinal fluid were elevated. Abdominal computed tomography, performed to determine the presence of extracerebral tumors, revealed pancreatic cancer. Pancreatic cancer was confirmed histopathologically on examination of an endoscopic ultrasound-guided fine needle aspiration specimen. PMID:25624740

  8. Dimethylaminoparthenolide and gemcitabine: a survival study using a genetically engineered mouse model of pancreatic cancer

    International Nuclear Information System (INIS)

    Yip-Schneider, Michele T; Wu, Huangbing; Stantz, Keith; Agaram, Narasimhan; Crooks, Peter A; Schmidt, C Max

    2013-01-01

    Pancreatic cancer remains one of the deadliest cancers due to lack of early detection and absence of effective treatments. Gemcitabine, the current standard-of-care chemotherapy for pancreatic cancer, has limited clinical benefit. Treatment of pancreatic cancer cells with gemcitabine has been shown to induce the activity of the transcription factor nuclear factor-kappaB (NF-κB) which regulates the expression of genes involved in the inflammatory response and tumorigenesis. It has therefore been proposed that gemcitabine-induced NF-κB activation may result in chemoresistance. We hypothesize that NF-κB suppression by the novel inhibitor dimethylaminoparthenolide (DMAPT) may enhance the effect of gemcitabine in pancreatic cancer. The efficacy of DMAPT and gemcitabine was evaluated in a chemoprevention trial using the mutant Kras and p53-expressing LSL-Kras G12D/+ ; LSL-Trp53 R172H ; Pdx-1-Cre mouse model of pancreatic cancer. Mice were randomized to treatment groups (placebo, DMAPT [40 mg/kg/day], gemcitabine [50 mg/kg twice weekly], and the combination DMAPT/gemcitabine). Treatment was continued until mice showed signs of ill health at which time they were sacrificed. Plasma cytokine levels were determined using a Bio-Plex immunoassay. Statistical tests used included log-rank test, ANOVA with Dunnett’s post-test, Student’s t-test, and Fisher exact test. Gemcitabine or the combination DMAPT/gemcitabine significantly increased median survival and decreased the incidence and multiplicity of pancreatic adenocarcinomas. The DMAPT/gemcitabine combination also significantly decreased tumor size and the incidence of metastasis to the liver. No significant differences in the percentages of normal pancreatic ducts or premalignant pancreatic lesions were observed between the treatment groups. Pancreata in which no tumors formed were analyzed to determine the extent of pre-neoplasia; mostly normal ducts or low grade pancreatic lesions were observed, suggesting prevention

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  13. File list: Pol.Pan.50.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  16. File list: Unc.Pan.50.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: His.Pan.50.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: DNS.Pan.20.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. Systematic review on the role of serum tumor markers in the detection of recurrent pancreatic cancer.

    Science.gov (United States)

    Daamen, Lois A; Groot, Vincent P; Heerkens, Hanne D; Intven, Martijn P W; van Santvoort, Hjalmar C; Molenaar, I Quintus

    2018-04-01

    Biomarker testing can be helpful to monitor disease progression after resection of pancreatic cancer. This systematic review aims to give an overview of the literature on the diagnostic value of serum tumor markers for the detection of recurrent pancreatic cancer during follow-up. A systematic search was performed to 2 October 2017. All studies reporting on the diagnostic value of postoperatively measured serum biomarkers for the detection of pancreatic cancer recurrence were included. Data on diagnostic accuracy of tumor markers were extracted. Forest plots and pooled values of sensitivity and specificity were calculated. Four articles described test results of CA 19-9. A pooled sensitivity and specificity of respectively 0.73 (95% CI 0.66-0.80) and 0.83 (95% CI 0.73-0.91) were calculated. One article reported on CEA, showing a sensitivity of 50% and specificity of 65%. No other serum tumor markers were discussed for surveillance purposes in the current literature. Although testing of serum CA 19-9 has considerable limitations, CA 19-9 remains the most used serum tumor marker for surveillance after surgical resection of pancreatic cancer. Further studies are needed to assess the role of serum tumor marker testing in the detection of recurrent pancreatic cancer and to optimize surveillance strategies. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  20. NIK is involved in constitutive activation of the alternative NF-κB pathway and proliferation of pancreatic cancer cells

    International Nuclear Information System (INIS)

    Nishina, Takashi; Yamaguchi, Noritaka; Gohda, Jin; Semba, Kentaro; Inoue, Jun-ichiro

    2009-01-01

    Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-κB is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-κB activation. Here, we show that the alternative pathway is constitutively activated and NF-κB-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

  1. NIK is involved in constitutive activation of the alternative NF-{kappa}B pathway and proliferation of pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Nishina, Takashi [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Yamaguchi, Noritaka [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041 (Japan); Gohda, Jin [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Semba, Kentaro [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041 (Japan); Department of Life Science and Medical Bio-science, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480 (Japan); Inoue, Jun-ichiro, E-mail: jun-i@ims.u-tokyo.ac.jp [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)

    2009-10-09

    Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-{kappa}B is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-{kappa}B activation. Here, we show that the alternative pathway is constitutively activated and NF-{kappa}B-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

  2. THE FREQUENCY OF RISK FACTORS ON TRENDS OF PANCREATIC CANCER IN KOSOVO.

    Science.gov (United States)

    Ramadani, Naser; Dedushi, Kreshnike; Muçaj, Sefedin; Kabashi, Serbeze; Jerliu, Naim; Hoxhaj, Astrit

    2016-04-01

    influence the mortality and morbidity of the pancreatic cancer in Kosovo and finally, to compare these results with similar studies abroad with aim to prevent the pancreatic cancer. The analyses of the obtained statistical data shows that the nicotine addiction play important role in incidence of the pancreatic cancer as well as alcohol addiction, presence of the diseases such are diabetes mellitus tip II and gastroduodenal peptic ulcers.

  3. CT of the pancreatic body and tail in cancer of the head

    International Nuclear Information System (INIS)

    Ono, Minoru; Muranaka, Tooru; Nishitani, Hiromu; Onitsuka, Hideo; Kawanami, Takashi; Matsuura, Keiichi

    1983-01-01

    In comparison with chronic pancreatitis (27 cases), CT images of secondary changes in the pancreatic body and tail in cancer of the pancreatic head were studied in 17 cases. In cancer cases, the pancreatic duct was dilated in a rosary or linear form, and a fairly large portion of the duct was visualized in continuation in one slice. The parenchyma was uniformly atrophic. Chronic pancreatitis demonstrated various CT images. In the localized-mass-forming type, the pancreatic body and tail showed findings similar to those of cancer in some cases, but unevenness of the pancreatic parenchyma and flexion, tortuosity and discontinuity of the pancreatic duct were observed only in chronic pancreatitis. As well as improvement in CT images, the spatial relationship between the pancreatic duct and parenchyma should be studied in more detail. (Chiba, N.)

  4. The WSB1 gene is involved in pancreatic cancer progression.

    Directory of Open Access Journals (Sweden)

    Cendrine Archange

    Full Text Available BACKGROUND: Pancreatic cancer cells generate metastases because they can survive the stress imposed by the new environment of the host tissue. To mimic this process, pancreatic cancer cells which are not stressed in standard culture conditions are injected into nude mice. Because they develop xenografts, they should have developed adequate stress response. Characterizing that response might provide new strategies to interfere with pancreatic cancer metastasis. METHODOLOGY/PRINCIPAL FINDINGS: In the human pancreatic cancer cell lines Panc-1, Mia-PaCa2, Capan-1, Capan-2 and BxPC3, we used Affymetrix DNA microarrays to compare the expressions of 22.000 genes in vitro and in the corresponding xenografts. We identified 228 genes overexpressed in xenografts and characterized the implication of one of them, WSB1, in the control of apoptosis and cell proliferation. WSB1 generates 3 alternatively spliced transcripts encoding distinct protein isoforms. In xenografts and in human pancreatic tumors, global expression of WSB1 mRNA is modestly increased whereas isoform 3 is strongly overexpressed and isoforms 1 and 2 are down-regulated. Treating Mia-PaCa2 cells with stress-inducing agents induced similar changes. Whereas retrovirus-forced expression of WSB1 isoforms 1 and 2 promoted cell growth and sensitized the cells to gemcitabine- and doxorubicin-induced apoptosis, WSB1 isoform 3 expression reduced cell proliferation and enhanced resistance to apoptosis, showing that stress-induced modulation of WSB1 alternative splicing increases resistance to apoptosis of pancreatic cancer cells. CONCLUSIONS/SIGNIFICANCE: Data on WSB1 regulation support the hypothesis that activation of stress-response mechanisms helps cancer cells establishing metastases and suggest relevance to cancer development of other genes overexpressed in xenografts.

  5. Nanomedicine developments in the treatment of metastatic pancreatic cancer: focus on nanoliposomal irinotecan

    Directory of Open Access Journals (Sweden)

    Ko AH

    2016-03-01

    Full Text Available Andrew H KoDivision of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA Abstract: Nanoliposomal irinotecan (nal-IRI was originally developed using an efficient and high-loading capacity system to encapsulate irinotecan within a liposomal carrier, producing a therapeutic agent with improved biodistribution and pharmacokinetic characteristics compared to free drug. Specifically, administration of nal-IRI results in prolonged exposure of SN-38, the active metabolite of irinotecan, within tumors, while at the same time offering the advantage of less systemic toxicity than traditional irinotecan. These favorable properties of nal-IRI, confirmed in a variety of tumor xenograft models, led to its clinical evaluation in a number of disease indications for which camptothecins have proven activity, including in colorectal, gastric, and pancreatic cancers. The culmination of these clinical trials was the NAPOLI-1 (Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy trial, an international Phase III study evaluating nal-IRI both alone and in combination with 5-fluorouracil and leucovorin in patients with metastatic pancreatic adenocarcinoma following progression on gemcitabine-based chemotherapy. Positive results from NAPOLI-1 led to approval of nal-IRI (with 5-fluorouracil/leucovorin in October 2015 by the US Food and Drug Administration specifically for the treatment of metastatic pancreatic cancer in the second-line setting and beyond, a clinical context in which there had previously been no accepted standard of care. As such, nal-IRI represents an important landmark in cancer drug development, and potentially ushers in a new era where a greater number of patients with advanced pancreatic cancer can be sequenced through multiple lines of therapy translating into meaningful improvements in

  6. Pancreatic Cancer-Derived Exosomes Cause Paraneoplastic β-cell Dysfunction.

    Science.gov (United States)

    Javeed, Naureen; Sagar, Gunisha; Dutta, Shamit K; Smyrk, Thomas C; Lau, Julie S; Bhattacharya, Santanu; Truty, Mark; Petersen, Gloria M; Kaufman, Randal J; Chari, Suresh T; Mukhopadhyay, Debabrata

    2015-04-01

    Pancreatic cancer frequently causes diabetes. We recently proposed adrenomedullin as a candidate mediator of pancreatic β-cell dysfunction in pancreatic cancer. How pancreatic cancer-derived adrenomedullin reaches β cells remote from the cancer to induce β-cell dysfunction is unknown. We tested a novel hypothesis that pancreatic cancer sheds adrenomedullin-containing exosomes into circulation, which are transported to β cells and impair insulin secretion. We characterized exosomes from conditioned media of pancreatic cancer cell lines (n = 5) and portal/peripheral venous blood of patients with pancreatic cancer (n = 20). Western blot analysis showed the presence of adrenomedullin in pancreatic cancer-exosomes. We determined the effect of adrenomedullin-containing pancreatic cancer exosomes on insulin secretion from INS-1 β cells and human islets, and demonstrated the mechanism of exosome internalization into β cells. We studied the interaction between β-cell adrenomedullin receptors and adrenomedullin present in pancreatic cancer-exosomes. In addition, the effect of adrenomedullin on endoplasmic reticulum (ER) stress response genes and reactive oxygen/nitrogen species generation in β cells was shown. Exosomes were found to be the predominant extracellular vesicles secreted by pancreatic cancer into culture media and patient plasma. Pancreatic cancer-exosomes contained adrenomedullin and CA19-9, readily entered β cells through caveolin-mediated endocytosis or macropinocytosis, and inhibited insulin secretion. Adrenomedullin in pancreatic cancer exosomes interacted with its receptor on β cells. Adrenomedullin receptor blockade abrogated the inhibitory effect of exosomes on insulin secretion. β cells exposed to adrenomedullin or pancreatic cancer exosomes showed upregulation of ER stress genes and increased reactive oxygen/nitrogen species. Pancreatic cancer causes paraneoplastic β-cell dysfunction by shedding adrenomedullin(+)/CA19-9(+) exosomes into

  7. Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer

    International Nuclear Information System (INIS)

    Ramani, Vishnu C; Hennings, Leah; Haun, Randy S

    2008-01-01

    In a previous report we have demonstrated that the chymotryptic-like serine protease kallikrein 7 (KLK7/hK7) is overexpressed in pancreatic cancer. In normal skin, hK7 is thought to participate in skin desquamation by contributing in the degradation of desmosomal components, such as desmogleins. Thus, the ability of hK7 to degrade desmogleins was assessed and the effect of hK7 expression on desmoglein 2 was examined in cultured pancreatic cancer cells. The expression of Dsg1, Dsg2, and Dsg3 in pancreatic tissues was examined by immunohistochemistry and their expression in two pancreatic cancer cell lines, BxPC-3 and Panc-1, was determined by western blot analysis. The ability of hK7 to degrade Dsg1 and Dsg2 was investigated using in vitro degradation assays. BxPC-3 cells stably transfected to overexpress hK7 were used to examine the effect of hK7 on cell-surface resident Dsg2. The levels of immunoreactive Dsg1 and Dsg2 were reduced in pancreatic adenocarcinomas compared with both normal pancreatic and chronic pancreatitis tissues. Among the desmosomal proteins examined, Dsg2 exhibited robust expression on the surface of BxPC-3 cells. When hK7 was overexpressed in this cell line, there was a significant increase in the amount of soluble Dsg2 released into the culture medium compared with vector-transfected control cells. A reduction in the amount of the cell adhesion components Dsg1 and Dsg2 in pancreatic tumors suggests that loss of these desmosomal proteins may play a role in pancreatic cancer invasion. Using in vitro degradation assays, both Dsg1 and Dsg2 could be readily proteolyzed by hK7, which is overexpressed in pancreatic adenocarcinomas. The enforced expression of hK7 in BxPC-3 cells that express significant amounts of Dsg2 resulted in a marked increase in the shedding of soluble Dsg2, which is consistent with the notion that aberrant expression of hK7 in pancreatic tumors may result in diminished cell-cell adhesion and facilitate tumor cell invasion

  8. Molecular biology-based diagnosis and therapy for pancreatic cancer

    International Nuclear Information System (INIS)

    Fujita, Hayato; Ohuchida, Kenoki; Mizumoto, Kazuhiro; Tanaka, Masao

    2011-01-01

    Mainly described are author's investigations of the title subject through clinical and basic diagnosis/therapeutic approach. Based on their consideration of carcinogenesis and pathological features of pancreatic cancer (PC), analysis of expression of cancer-related genes in clinically available samples like pancreatic juice and cells biopsied can result in attaining their purposes. Desmoplasia, a pathological feature of PC, possibly induces resistance to therapy and one of strategies is probably its suppression. Targeting stem cells of the mesenchyma as well as those of PC is also a strategy in future. Authors' studies have revealed that quantitation of hTERT (coding teromerase) mRNA levels in PC cells micro-dissected from cytological specimens is an accurate molecular biological diagnostic method applicable clinically. Other cancer-related genes are also useful for the diagnosis and mucin (MUC) family genes are shown to be typical ones for differentiating the precancerous PC, PC and chronic pancreatisis. Efficacy of standard gemcitabine chemotherapy can be individualized with molecular markers concerned to metabolism of the drug like dCK. Radiotherapy/radio-chemotherapy are not so satisfactory for PC treatment now. Authors have found elevated MMP-2 expression and HGF/c-Met signal activation in irradiated PC cells, which can increase the invasive capability; and stimulation of phosphorylation and activation of c-Met/MARK in co-culture of irradiated PC cells with messenchymal cells from PC, which possibly leads to progression of malignancy of PC through their interaction, of which suppression, therefore, can be a new approach to increase the efficacy of radiotherapy. Authors are making effort to introducing adenovirus therapy in clinic; exempli gratia (e.g.), the virus carrying wild type p53, a cancer-suppressive gene, induces apoptosis of PC cells often having its mutated gene. (T.T.)

  9. The relationship between the use of statins and mortality, severity, and pancreatic cancer in Danish patients with chronic pancreatitis

    DEFF Research Database (Denmark)

    Bang, Ulrich C; Watanabe, Tomohiro; Bendtsen, Flemming

    2018-01-01

    OBJECTIVES: Chronic pancreatitis (CP) is associated with a shortened life expectancy. Statins have anti-inflammatory properties and we aimed to evaluate the association between the use of statins and the risk of death, progression of CP, and pancreatic cancer in patients with CP. PATIENTS...... AND METHODS: We carried out a nested case-cohort study and included patients with CP. We used claims of proton pump inhibitors as an active comparator. Patients with cirrhosis or cancer were excluded. We evaluated the exposure on the basis of pharmacy claims of statins. We used propensity score matching...... with a statins : nonstatins ratio of 1 : 1. RESULTS: A total of 4807 patients were eligible for propensity score matching; 33% were women and the mean (SD) age at cohort entry was 56 (10) years. During follow-up, a total of 2073 (43%) patients had died and the risk of death was significantly lower among patients...

  10. Discussion of difficult problems of early diagnosis of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    GUO Xiaozhong

    2014-08-01

    Full Text Available Pancreatic cancer is a common malignant neoplasm of the pancreas with an extremely high mortality. Currently, the early diagnosis of pancreatic cancer is still not ideal. Attention should be paid to some clinical warning symptoms, such as unexplained abdominal and back pain, jaundice, and unexpected diabetes. Additionally, the combined use of CA19-9, CEA, and other tumor markers, the attention to biochemical indicators, the detection of mutation in KAI1 or p53 gene, and the exploration of the value of miRNA in clinical diagnosis are of great significance. On the other hand, ultrasound, CT, MRCP, ERCP, PET-CT, and other imaging methods, as well as effective collection of cytology specimens, should be performed. Thus, there is hope for the early diagnosis of pancreatic cancer.

  11. The Role of Apoptosis in the Pathology of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Samm, Nicole; Werner, Kristin; Rückert, Felix; Saeger, Hans Detlev; Grützmann, Robert; Pilarsky, Christian

    2010-01-01

    Pancreatic cancer is a disease with high resistance to most common therapies and therefore has a poor prognosis, which is partly due to a lack of reaction to apoptotic stimuli. Signal transduction of such stimuli includes a death receptor-mediated extrinsic pathway as well as an intrinsic pathway linked to the mitochondria. Defects in apoptotic pathways and the deregulation of apoptotic proteins, such as Survivin, Bcl-2, Bcl-x L and Mcl-1, play decisive roles in the development of pancreatic cancer. Investigation of the molecular mechanism allowing tumors to resist apoptotic cell death would lead to an improved understanding of the physiology and the development of new molecular strategies in pancreatic cancer

  12. The Role of Apoptosis in the Pathology of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Hans Detlev Saeger

    2010-12-01

    Full Text Available Pancreatic cancer is a disease with high resistance to most common therapies and therefore has a poor prognosis, which is partly due to a lack of reaction to apoptotic stimuli. Signal transduction of such stimuli includes a death receptor-mediated extrinsic pathway as well as an intrinsic pathway linked to the mitochondria. Defects in apoptotic pathways and the deregulation of apoptotic proteins, such as Survivin, Bcl-2, Bcl-xL and Mcl-1, play decisive roles in the development of pancreatic cancer. Investigation of the molecular mechanism allowing tumors to resist apoptotic cell death would lead to an improved understanding of the physiology and the development of new molecular strategies in pancreatic cancer.

  13. Challenges of drug resistance in the management of pancreatic cancer.

    LENUS (Irish Health Repository)

    Sheikh, Rizwan

    2012-02-01

    The current treatment of choice for metastatic pancreatic cancer involves single-agent gemcitabine or a combination of gemcitabine with capecitabine or erlotinib (a tyrosine kinase inhibitor). Only 25–30% of patients respond to this treatment and patients who do respond initially ultimately exhibit disease progression. Median survival for pancreatic cancer patients has reached a plateau due to inherent and acquired resistance to these agents. Key molecular factors implicated in this resistance include: deficiencies in drug uptake, alteration of drug targets, activation of DNA repair pathways, resistance to apoptosis and the contribution of the tumor microenvironment. Moreover, for newer agents including tyrosine kinase inhibitors, overexpression of signaling proteins, mutations in kinase domains, activation of alternative pathways, mutations of genes downstream of the target and\\/or amplification of the target represent key challenges for treatment efficacy. Here we will review the contribution of known mechanisms and markers of resistance to key pancreatic cancer drug treatments.

  14. Tenascin-C induces resistance to apoptosis in pancreatic cancer cell through activation of ERK/NF-κB pathway.

    Science.gov (United States)

    Shi, Meiyan; He, Xiaodan; Wei, Wei; Wang, Juan; Zhang, Ti; Shen, Xiaohong

    2015-06-01

    processes. TNC mediated gemcitabine chemo-resistance via modulating cell apoptosis in pancreatic cancer. TNC resulted in the enrichment of pancreatic cancer cells in S-phase with a concomitant decrease in number of cells in G1 phase. The present study indicated TNC in cellular matrix induces an activation of ERK1/2/NF-κB/p65 signaling cascade and thereby mediates resistance to apoptosis in pancreatic cancer. TNC could serve as a diagnostic marker and predictor of gemcitabine response and potentially as a target for chemotherapy of pancreatic cancer.

  15. Experimental study of the intra-operative radiation therapy for pancreatic cancer

    International Nuclear Information System (INIS)

    Kodera, Taro; Matsuno, Seiki; Kobari, Masao; Akaishi, Satoshi; Sakamoto, Kiyohiko

    1988-01-01

    The radiosensitivity of pancreatic cancer, optimum dose of irradiation and the effect of 1-[4'-Hydroxy-2'-Butenoxy) Methyl]-2-Nitrosoimidaole (RK-28) on irradiation were investigated using an experimental pancreatic cancer of hamster and the following results were obtained: i) The mean lethal dose (Do) and the 50 % tumor control dose (TCD 50 ) against the pancreatic cancer were 3.5 Gy and 73.7 ± 6.9 Gy, respectively. These results indicate that the pancreatic cancer is resistant to irradiation, which could be explained by the existence of hypoxic cells consisting of 35 % of the tumor. ii) The dose of intraoperative irradiation (10 - 40 Gy) seemed to be insufficient to bring long-term anti-tumor effect and long-term survival since that dose resulted in only temporary regression of the tumor. iii) The hypoxic cell sensitizer (RK28), which is known to specifically enhance the sensitivity of hypoxic cells to irradiation, lowered TCD 50 of the pancreatic cancer to 53.8 ± 1.57 Gy. Therefore, RK-28 was effective in the treatment of the experimental pancreatic cancer (the enhancement ratio : 1.37). When combined with 30 or 40 Gy of irradiation, which is applicable to intraoperative irradiation, RK-28 induced a longer period of tumor suppression and a higher tumor regression ratio than irradiation alone. These results indicate that RK-28 significantly increases the effect of intraoperative irradiation and this combination therapy could possibly induce remarkable effect on tumor regression and long-term survival. (author)

  16. Evaluation of multimodality treatment for advanced pancreatic cancer. Special reference to intraoperative vs. external radiation therapy

    International Nuclear Information System (INIS)

    Wakasugi, Hideyuki; Funakoshi, Akihiro; Seo, Yousuke; Iguchi, Haruo; Wada, Susumu

    1999-01-01

    Intraoperative radiation therapy (IORT)+postoperative external beam radiation therapy (ERT) with chemotherapy and ERT alone with chemotherapy have been performed in our hospital for unresectable, especially locally advanced, pancreatic cancer. We compared the former method with the latter. Chemotherapy was performed together with radiation, using 5-FU, CDDP, and MMC. IORT+ERT was successful in only half of the treated patients, while ERT alone was successful in almost all of the patients. As a result, the doses of radiation were often shorter in patients treated by the former method compared to the latter method. Both methods, when completed for locally advanced pancreatic cancer (stage IVa), produced good effects on tumor markers, tumor size and pain. Furthermore, the latter method was better than the former in improving the survival time and quality of life (QOL). Therefore, ERT is a practical and useful method for patients with locally advanced pancreatic cancer. (author)

  17. Therapeutic effect of transcatheter arterial infusion chemotherapy in the treatment of advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Lin Junhua; Song Mingzhi; Zhang Yuanyuan; Xu Yiyu; Chen Jing

    2001-01-01

    Objective: To evaluate the clinical efficacy of transcatheter arterial infusion (TAI) or transcatheter arterial chemo-embolization (TACE) in the treatment of advanced pancreatic cancer. Methods: 36 cases of advanced pancreatic cancer were divided into two groups, 18 cases were treated with TAI or TACE (group A), other 18 cases were treated with systemic chemotherapy (group B). Results: The clinical benefit response rate of the group A was 55.6% (10/18) and that of the group B was 16.7%(3/18), respectively (P 0.05). Conclusions: In the transcatheter arterial infusion group, no survival advantage could be demonstrated when compared with the controls, but TAI could effectively increase clinical benefit response and improve the quality of life of advanced pancreatic cancer

  18. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    Science.gov (United States)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H.M.; Molenaar, I. Quintus; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G.J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    SUMMARY Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation and exhibit ductal- and disease stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy. PMID:25557080

  19. Simultaneous gene silencing of Bcl-2, XIAP and Survivin re-sensitizes pancreatic cancer cells towards apoptosis

    International Nuclear Information System (INIS)

    Rückert, Felix; Samm, Nicole; Lehner, Anne-Kathrin; Saeger, Hans-Detlev; Grützmann, Robert; Pilarsky, Christian

    2010-01-01

    Pancreatic ductal adenocarcinoma shows a distinct apoptosis resistance, which contributes significantly to the aggressive nature of this tumor and constrains the effectiveness of new therapeutic strategies. Apoptosis resistance is determined by the net balance of the cells pro-and anti-apoptotic 'control mechanisms'. Numerous dysregulated anti-apoptotic genes have been identified in pancreatic cancer and seem to contribute to the high anti-apoptotic buffering capacity. We aimed to compare the benefit of simultaneous gene silencing (SGS) of several candidate genes with conventional gene silencing of single genes. From literature search we identified the anti-apoptotic genes XIAP, Survivin and Bcl-2 as commonly upregulated in pancreatic cancer. We performed SGS and silencing of single candidate genes using siRNA molecules in two pancreatic cancer cell lines. Effectiveness of SGS was assessed by qRT-PCR and western blotting. Apoptosis induction was measured by flow cytometry and caspase activation. Simultaneous gene silencing reduced expression of the three target genes effectively. Compared to silencing of a single target or control, SGS of these genes resulted in a significant higher induction of apoptosis in pancreatic cancer cells. In the present study we performed a subliminal silencing of different anti-apoptotic target genes simultaneously. Compared to silencing of single target genes, SGS had a significant higher impact on apoptosis induction in pancreatic cancer cells. Thereby, we give further evidence for the concept of an anti-apoptotic buffering capacity of pancreatic cancer cells

  20. Tenascin-C enhances pancreatic cancer cell growth and motility and affects cell adhesion through activation of the integrin pathway.

    Directory of Open Access Journals (Sweden)

    Igor Paron

    Full Text Available BACKGROUND: Pancreatic cancer (PDAC is characterized by an abundant fibrous tissue rich in Tenascin-C (TNC, a large ECM glycoprotein mainly synthesized by pancreatic stellate cells (PSCs. In human pancreatic tissues, TNC expression increases in the progression from low-grade precursor lesions to invasive cancer. Aim of this study was the functional characterization of the effects of TNC on biologic relevant properties of pancreatic cancer cells. METHODS: Proliferation, migration and adhesion assays were performed on pancreatic cancer cell lines treated with TNC or grown on a TNC-rich matrix. Stable transfectants expressing the large TNC splice variant were generated to test the effects of endogenous TNC. TNC-dependent integrin signaling was investigated by immunoblotting, immunofluorescence and pharmacological inhibition. RESULTS: Endogenous TNC promoted pancreatic cancer cell growth and migration. A TNC-rich matrix also enhanced migration as well as the adhesion to the uncoated growth surface of poorly differentiated cell lines. In contrast, adhesion to fibronectin was significantly decreased in the presence of TNC. The effects of TNC on cell adhesion were paralleled by changes in the activation state of paxillin and Akt. CONCLUSION: TNC affects proliferation, migration and adhesion of poorly differentiated pancreatic cancer cell lines and might therefore play a role in PDAC spreading and metastasis in vivo.

  1. The Q705K and F359L Single-Nucleotide Polymorphisms of NOD-Like Receptor Signaling Pathway: Association with Chronic Pancreatitis, Pancreatic Cancer, and Periodontitis.

    Science.gov (United States)

    Miskiewicz, Andrzej; Szparecki, Grzegorz; Durlik, Marek; Rydzewska, Grażyna; Ziobrowski, Ireneusz; Górska, Renata

    2015-12-01

    The aim of this study was to establish the correlation between the occurrence of Q705K and F359L polymorphisms in patients diagnosed with pancreatic diseases and periodontal conditions of various degrees of severity. The above-mentioned genetic markers were assessed in patients with pancreatic cancer (n = 18) and chronic pancreatitis (n = 39) as well as in a healthy control group (n = 115). The established inclusion criteria were the following: Caucasian descent, non-smoking, and age range 20-80, with different levels of periodontitis activity according to S. Offenbacher's scale. The genotyping reactions were performed by means of an RT-PCR with the use of TaqMan(®) genotyping assay. Results of the study revealed that the state of periodontium was significantly worse in patients with chronic pancreatitis. The Q705K and F359L polymorphisms were associated with more advanced cases of periodontitis measured by clinical attachment level, whereas the Q705K was associated with intensified bleeding index. Furthermore, the F359L single-nucleotide polymorphism was significantly higher in the group with chronic pancreatitis (p periodontitis, pancreatic cancer, and chronic pancreatitis. These findings might constitute the basis for a new diagnostic and therapeutic approach.

  2. Preoperative clinical radioimmunodetection of pancreatic cancer by 111In-labeled chimeric monoclonal antibody Nd2

    International Nuclear Information System (INIS)

    Sawada, Tetsuji; Nishihara, Tamahiro; Yamamoto, Atsushi

    1999-01-01

    The present study was carried out with the purpose of evaluating the clinical usefulness of radioimmunodetection (RAID) with 111 In-labeled murine/human chimeric monoclonal antibody, Nd2 (c-Nd2) in patients with pancreatic cancer. Nineteen patients suspected to have pancreatic cancer were administered intravenously 74 MBq/2 mg 111 In-labeled c-Nd2 in 100 ml of saline containing 2% albumin over 30 min. A scintigram was obtained on the 3rd day after infusion by using single photon emission computed tomography (SPECT) imaging. Of the 14 patients finally diagnosed as having pancreatic cancer on the basis of surgical specimens or progress of disease, specific focal uptake at the site of the tumor was detected in 12 (true positive cases), representing a sensitivity of 85.7% (12/14), and liver metastasis was found in one case with metastasis. Of the 5 patients diagnosed with tumor-forming pancreatitis (TFP), 4 patients demonstrated true negative imaging, but one patient whose tumor demonstrated interesting findings in histology and immunostaining, showed false positive imaging. Of patients investigated for human anti-chimeric antibody (HACA) response, none showed HACA response, and no allergic reaction was seen in any of the patients administered c-Nd2. These results suggest that RAID with 111 In-labeled c-Nd2 is useful for differential preoperative diagnosis between invasive pancreatic cancer and TFP. (author)

  3. Qingyihuaji Formula Inhibits Pancreatic Cancer and Prolongs Survival by Downregulating Hes-1 and Hey-1

    Directory of Open Access Journals (Sweden)

    Yanli Xu

    2015-01-01

    Full Text Available The dire prognosis of pancreatic cancer has not markedly improved during past decades. The present study was carried out to explore the effect of Qingyihuaji formula (QYHJ on inhibiting pancreatic cancer and prolonging survival in related Notch signaling pathway. Proliferation of pancreatic cancer cells (SW1990 and PANC-1 was detected by MTT assay at 24, 48, and 72 h with exposure to various concentrations (0.08–50 mg/mL of QYHJ water extract. Pancreatic tumor models of nude mice were divided into three groups randomly (control, QYHJ, and gemcitabine. mRNA and protein expression of Notch target genes (Hes-1, Hey-1, Hey-2, and Hey-L in dissected tumor tissue were detected. Results showed that proliferation of SW1990 cells and PANC-1 cells was inhibited by QYHJ water extract in a dose-dependent and time-dependent manner. QYHJ effectively inhibited tumor growth and prolonged survival time in nude mice. Expression of both Hes-1 and Hey-1 was decreased significantly in QYHJ group, suggesting that Hes-1 and Hey-1 in Notch signaling pathway might be potential targets for QYHJ treatment. This research could help explain the clinical effectiveness of QYHJ and may provide advanced pancreatic cancer patients with a new therapeutic option.

  4. Is screening for pancreatic cancer in high-risk groups cost-effective?

    DEFF Research Database (Denmark)

    Jørgensen, Maiken Thyregod; Gerdes, Anne-Marie; Sørensen, Jan

    2016-01-01

    OBJECTIVE: Pancreatic cancer (PC) is the fourth leading cause of cancer death worldwide, symptoms are few and diffuse, and when the diagnosis has been made only 10-15% would benefit from resection. Surgery is the only potentially curable treatment for pancreatic cancer, and the prognosis seems to......$ per QALY. CONCLUSIONS: With a threshold value of 50,000 US$ per QALY this screening program appears to constitute a cost-effective intervention although screening of HP patients appears to be less cost-effective than FPC patients....... with Hereditary pancreatitis or with a disposition of HP and 40 first-degree relatives of patients with Familial Pancreatic Cancer (FPC) were screened for development of Pancreatic Ductal Adenocarcinoma (PDAC) with yearly endoscopic ultrasound. The cost-effectiveness of screening in comparison with no......-screening was assessed by the incremental cost-utility ratio (ICER). RESULTS: By screening the FPC group we identified 2 patients with PDAC who were treated by total pancreatectomy. One patient is still alive, while the other died after 7 months due to cardiac surgery complications. Stratified analysis of patients...

  5. Pancreatic cancer seeding of percutaneous needle tract

    Directory of Open Access Journals (Sweden)

    Qiao Zhou, MD

    2017-03-01

    Full Text Available A 65-year old African-American female presents with biliary ductal dilatation due to an obstructive pancreatic head mass. Percutaneous transhepatic cholangiogram performed and biliary drainage catheter placement for decompression of the biliary system. The patient had a Whipple procedure performed several months later. On follow up CT imaging, there was interval development and enlargement of a subcutaneous lesion by the right oblique muscles. Biopsy of this lesion revealed pancreatic adenocarcinoma from percutaneous seeding of the transhepatic needle tract.

  6. Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

    Science.gov (United States)

    2014-05-28

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

  7. Fluorodeoxyglucose positron emission tomography in pancreatic cancer: an unsolved problem

    International Nuclear Information System (INIS)

    Kato, Takashi; Fukatsu, Hiroshi; Ito, Kengo; Tadokoro, Masanori; Ota, Toyohiro; Ikeda, Mitsuru; Isomura, Takayuki; Ito, Shigeki; Nishino, Masanari; Ishigaki, Takeo

    1995-01-01

    The aim of this study was to examine the significance and problems of 2-[fluorine-18]-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in diagnosing pancreatic cancer and mass-forming pancreatitis (MFP). PET, X-ray computed tomography (CT) and magnetic resonance (MR) imaging were performed in 15 patients with pancreatic cancer and nine patients with MFP. The areas of the PET scan were determined according to the markers drawn on the patients at CT or MR imaging. Regions of interests (ROIs) were placed by reference to the CT or MR images corresponding to the PET images. Tissue metabolism was evaluated by the differential absorption ratio (DAR) at 50 min after intravenous injection of FDG [DAR = tissue tracer concentration/(injected dose/body weight). The DAR value differed significantly in pancreatic cancer (mean±SD, 4.64±1.94) and MFP (mean±SD, 2.84±2.22) (P<0.05). In one false-negative case (mucinous adenocarcinoma), the tumour contained a small number of malignant cells. In one false-positive case, lymphocytes accumulated densely in the mass in the pancreatic head. Further studies are necessary to investigate the histopathological characteristics (especially the cellularity) and other factors affecting the FDG DAR on PET images. (orig.)

  8. Problems in diagnosis and treatment of pancreatic cancer as seen in the autopsy findings

    International Nuclear Information System (INIS)

    Goseki, Norihide; Okamoto, Atsutake; Onodera, Tokio; Tabata, Ikuo; Takizawa, Toichiro; Koike, Morio; Matsuda, Tadayoshi; Kamimae, Goro

    1984-01-01

    The results obtained from a pathological study of the cancer spread, postoperative recurrence and intraoperative radiotherapy in 68 autopsy cases of pancreatic cancer were as follows: 1) The study of pancreatic cancer was conducted by classifying the cases according to the location of the cancer; uncus, head, body and tail. Difference was seen in the mode of cancer spread and also in the clinical symptoms among the pancreatic cancers in each location. Especially, it was maintained that cancer in the uncus should be treated independently from the cancer in the head. 2) There was no difference in the mode of cancer spread between postoperative recurrence or intraoperative radiotherapy cases and non-operated or non-intraoperative radiotherapy cases. Moreover, it suggested one side of difficulty of the surgical treatment, that is, all cases considered curative operation were performed through histological study of the resected specimen at operation have had retroperitoneal recurrence. 3) By histological study of autopsy cases of intraoperative radiotherapy, it was suggested that cancer cells remained or regrew in the periphery of the radiotherapy field, which is a meaningful finding for evaluating intraoperative radiotherapy in the future. (author)

  9. Low concentrations of metformin selectively inhibit CD133⁺ cell proliferation in pancreatic cancer and have anticancer action.

    Directory of Open Access Journals (Sweden)

    Shanmiao Gou

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States. The prognosis remains dismal with little advance in treatment. Metformin is a drug widely used for the treatment of type II diabetes. Recent epidemiologic data revealed that oral administration of metformin is associated with a reduced risk of pancreatic cancer, suggesting its potential as a novel drug for this disease. Many studies have demonstrated the in vitro anticancer action of metformin, but the typically used concentrations were much higher than the in vivo plasma and tissue concentrations achieved with recommended therapeutic doses of metformin, and low concentrations of metformin had little effect on the proliferation of pancreatic cancer cells. We examined the effect of low concentrations of metformin on different subpopulations of pancreatic cancer cells and found that these selectively inhibited the proliferation of CD133⁺ but not CD24⁺CD44⁺ESA⁺ cells. We also examined the effect of low concentrations of metformin on cell invasion and in vivo tumor formation, demonstrating in vitro and in vivo anticancer action. Metformin was associated with a reduction of phospho-Erk and phospho-mTOR independent of Akt and AMPK phosphorylation. CD133⁺ pancreatic cancer cells are considered to be cancer stem cells that contribute to recurrence, metastasis and resistance to adjuvant therapies in pancreatic cancer. Our results provide a basis for combination of metformin with current therapies to improve the prognosis of this disease.

  10. Low Concentrations of Metformin Selectively Inhibit CD133+ Cell Proliferation in Pancreatic Cancer and Have Anticancer Action

    Science.gov (United States)

    Li, Xiangsheng; Shi, Pengfei; Liu, Tao; Wang, Chunyou

    2013-01-01

    Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States. The prognosis remains dismal with little advance in treatment. Metformin is a drug widely used for the treatment of type II diabetes. Recent epidemiologic data revealed that oral administration of metformin is associated with a reduced risk of pancreatic cancer, suggesting its potential as a novel drug for this disease. Many studies have demonstrated the in vitro anticancer action of metformin, but the typically used concentrations were much higher than the in vivo plasma and tissue concentrations achieved with recommended therapeutic doses of metformin, and low concentrations of metformin had little effect on the proliferation of pancreatic cancer cells. We examined the effect of low concentrations of metformin on different subpopulations of pancreatic cancer cells and found that these selectively inhibited the proliferation of CD133+ but not CD24+CD44+ESA+ cells. We also examined the effect of low concentrations of metformin on cell invasion and in vivo tumor formation, demonstrating in vitro and in vivo anticancer action. Metformin was associated with a reduction of phospho-Erk and phospho-mTOR independent of Akt and AMPK phosphorylation. CD133+ pancreatic cancer cells are considered to be cancer stem cells that contribute to recurrence, metastasis and resistance to adjuvant therapies in pancreatic cancer. Our results provide a basis for combination of metformin with current therapies to improve the prognosis of this disease. PMID:23667692

  11. YAP Inhibition by Resveratrol via Activation of AMPK Enhances the Sensitivity of Pancreatic Cancer Cells to Gemcitabine

    Directory of Open Access Journals (Sweden)

    Zhengdong Jiang

    2016-09-01

    Full Text Available Resveratrol, a natural polyphenol present in most plants, inhibits the growth of numerous cancers both in vitro and in vivo. Aberrant expression of YAP has been reported to activate multiple growth-regulatory pathways and confer anti-apoptotic abilities to many cancer cells. However, the role of resveratrol in YES-activated protein (YAP expression and that of YAP in pancreatic cancer cells’ response to gemcitabine resistance remain elusive. In this study, we found that resveratrol suppressed the proliferation and cloning ability and induced the apoptosis of pancreatic cancer cells. These multiple biological effects might result from the activation of AMP-activation protein kinase (AMPK (Thr172 and, thus, the induction of YAP cytoplasmic retention, Ser127 phosphorylation, and the inhibition of YAP transcriptional activity by resveratrol. YAP silencing by siRNA or resveratrol enhanced the sensitivity of gemcitabine in pancreatic cancer cells. Taken together, these findings demonstrate that resveratrol could increase the sensitivity of pancreatic cancer cells to gemcitabine by inhibiting YAP expression. More importantly, our work reveals that resveratrol is a potential anticancer agent for the treatment of pancreatic cancer, and YAP may serve as a promising target for sensitizing pancreatic cancer cells to chemotherapy.

  12. Classification of premalignant pancreatic cancer mass-spectrometry data using decision tree ensembles

    Directory of Open Access Journals (Sweden)

    Wong G William

    2008-06-01

    Full Text Available Abstract Background Pancreatic cancer is the fourth leading cause of cancer death in the United States. Consequently, identification of clinically relevant biomarkers for the early detection of this cancer type is urgently needed. In recent years, proteomics profiling techniques combined with various data analysis methods have been successfully used to gain critical insights into processes and mechanisms underlying pathologic conditions, particularly as they relate to cancer. However, the high dimensionality of proteomics data combined with their relatively small sample sizes poses a significant challenge to current data mining methodology where many of the standard methods cannot be applied directly. Here, we propose a novel methodological framework using machine learning method, in which decision tree based classifier ensembles coupled with feature selection methods, is applied to proteomics data generated from premalignant pancreatic cancer. Results This study explores the utility of three different feature selection schemas (Student t test, Wilcoxon rank sum test and genetic algorithm to reduce the high dimensionality of a pancreatic cancer proteomic dataset. Using the top features selected from each method, we compared the prediction performances of a single decision tree algorithm C4.5 with six different decision-tree based classifier ensembles (Random forest, Stacked generalization, Bagging, Adaboost, Logitboost and Multiboost. We show that ensemble classifiers always outperform single decision tree classifier in having greater accuracies and smaller prediction errors when applied to a pancreatic cancer proteomics dataset. Conclusion In our cross validation framework, classifier ensembles generally have better classification accuracies compared to that of a single decision tree when applied to a pancreatic cancer proteomic dataset, thus suggesting its utility in future proteomics data analysis. Additionally, the use of feature selection

  13. The first report from Sapporo Tsukisamu Hospital. Chemotherapy and Chemoradiotherapy for patients with advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Yamamitsu, Susumu; Kimura, Hiromichi; Yamada, Yoshiyuki; Inui, Noriaki; Hiyama, Shigemi; Hirata, Koichi; Kimura, Yasutoshi; Koito, Kazumitsu; Shirasaka, Tetsuhiko

    2007-01-01

    The remedy, especially chemotherapy, for advanced pancreatic cancer is hardly ever successful in terms of efficacy rate and survival period, because it is virtually unable to contribute to the improvement of median survival time (MST). Thus, we devised a new intermittent dosage regimen utilizing the cell cycle difference of normal gastrointestinal (GI) tract, bone marrow cell and pancreatic cancer cell, making use of 5-FU (→S-1), cisplatin (CDDP) and paclitaxel in March 2002. Ten patients with advanced pancreatic cancer (4 in Stage IVa and 6 in Stage IVb) were treated with this new regimen. As a result, an efficacy ratio of 50.0% and a 1-year survival ratio of 60.0% were achieved. However, 2-year survival ratio of 12.0% was low, and there was no 3-year survivor. The MST was 19 months as of December 31, 2006. All of the non-hematological toxicities were under grade 2. Eight patients had hematological toxicities over grade 3 and most of them were anemia and neutropenia. Only 2 cases had thrombocytopenia. Although adverse effects related to this regimen were clinically manageable, it was difficult to improve MST of patients with advanced pancreatic cancer with chemotherapy alone including this regimen. Hence, we devised another regimen with the joint use of radiotherapy along with the same chemotherapy regimen in January 2003. Twenty patients with advanced pancreatic cancer (Stage IV) were treated with this regimen. It is presently under way, and an efficacy ratio of 35.0%, 1-year survival ratio of 86.3% and 2-year survival ratio of 64.0% were obtained by May 2005, showing that this may contribute to the extension of survival time of Stage IV pancreatic cancer patients. (author)

  14. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

    Energy Technology Data Exchange (ETDEWEB)

    Vasseur, Sophie; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L. [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, BP 915,13288 Marseille cedex 9 (France)

    2010-12-16

    Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis.

  15. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

    International Nuclear Information System (INIS)

    Vasseur, Sophie; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L.

    2010-01-01

    Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis

  16. Dual drug loaded chitosan nanoparticles-sugar--coated arsenal against pancreatic cancer.

    Science.gov (United States)

    David, Karolyn Infanta; Jaidev, Leela Raghav; Sethuraman, Swaminathan; Krishnan, Uma Maheswari

    2015-11-01

    Pancreatic cancer is an aggressive form of cancer with poor survival rates. The increased mortality due to pancreatic cancer arises due to many factors such as development of multidrug resistance, presence of cancer stem cells, development of a stromal barrier and a hypoxic environment due to hypo-perfusion. The present study aims to develop a nanocarrier for a combination of drugs that can address these multiple issues. Quercetin and 5-fluorouracil were loaded in chitosan nanoparticles, individually as well as in combination. The nanoparticles were characterized for morphology, size, zeta potential, percentage encapsulation of drugs as well as their release profiles in different media. The dual drug-loaded carrier exhibited good entrapment efficiency (quercetin 95% and 5-fluorouracil 75%) with chitosan: quercetin: 5-fluorouracil in the ratio 3:1:2. The release profiles suggest that 5-fluorouracil preferentially localized in the periphery while quercetin was located towards the core of chitosan nanoparticles. Both drugs exhibited considerable association with the chitosan matrix. The dual drug-loaded carrier system exhibited significant toxicity towards pancreatic cancer cells both in the 2D as well as in the 3D cultures. We believe that the results from these studies can open up interesting options in the treatment of pancreatic cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Identification of RegIV as a novel GLI1 target gene in human pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Feng Wang

    2011-04-01

    Full Text Available GLI1 is the key transcriptional factor in the Hedgehog signaling pathway in pancreatic cancer. RegIV is associated with regeneration, and cell growth, survival, adhesion and resistance to apoptosis. We aimed to study RegIV expression in pancreatic cancer and its relationship to GLI1.GLI1 and RegIV expression were evaluated in tumor tissue and adjacent normal tissues of pancreatic cancer patients and 5 pancreatic cancer cell lines by qRT-PCR, Western blot, and immunohistochemistry (IHC, and the correlation between them. The GLI1-shRNA lentiviral vector was constructed and transfected into PANC-1, and lentiviral vector containing the GLI1 expression sequence was constructed and transfected into BxPC-3. GLI1 and RegIV expression were evaluated by qRT-PCR and Western blot. Finally we demonstrated RegIV to be the target of GLI1 by chromatin immunoprecipitation (CHIP and electrophoretic mobility shift assays (EMSA.The results of IHC and qRT-PCR showed that RegIV and GLI1 expression was higher in pancreatic cancer tissues versus adjacent normal tissues (p<0.001. RegIV expression correlated with GLI1 expression in these tissues (R = 0.795, p<0.0001. These results were verified for protein (R = 0.939, p = 0.018 and mRNA expression (R = 0.959, p = 0.011 in 5 pancreatic cancer cell lines. RegIV mRNA and protein expression was decreased (94.7±0.3%, 84.1±0.5%; respectively when GLI1 was knocked down (82.1±3.2%, 76.7±2.2%; respectively by the RNAi technique. GLI1 overexpression in mRNA and protein level (924.5±5.3%, 362.1±3.5%; respectively induced RegIV overexpression (729.1±4.3%, 339.0±3.7%; respectively. Moreover, CHIP and EMSA assays showed GLI1 protein bound to RegIV promotor regions (GATCATCCA in pancreatic cancer cells.GLI1 promotes RegIV transcription by binding to the RegIV gene promoter in pancreatic cancer.

  18. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  19. uPAR-controlled oncolytic adenoviruses eliminate cancer stem cells in human pancreatic tumors.

    Science.gov (United States)

    Sobrevals, Luciano; Mato-Berciano, Ana; Urtasun, Nerea; Mazo, Adela; Fillat, Cristina

    2014-01-01

    Pancreatic tumors contain cancer stem cells highly resistant to chemotherapy. The identification of therapies that can eliminate this population of cells might provide with more effective treatments. In the current work we evaluated the potential of oncolytic adenoviruses to act against pancreatic cancer stem cells (PCSC). PCSC from two patient-derived xenograft models were isolated from orthotopic pancreatic tumors treated with saline, or with the chemotherapeutic agent gemcitabine. An enrichment in the number of PCSC expressing the cell surface marker CD133 and a marked enhancement on tumorsphere formation was observed in gemcitabine treated tumors. No significant increase in the CD44, CD24, and epithelial-specific antigen (ESA) positive cells was observed. Neoplastic sphere-forming cells were susceptible to adenoviral infection and exposure to oncolytic adenoviruses resulted in elevated cytotoxicity with both Adwt and the tumor specific AduPARE1A adenovirus. In vivo, intravenous administration of a single dose of AduPARE1A in human-derived pancreatic xenografts led to a remarkable anti-tumor effect. In contrast to gemcitabine AduPARE1A treatment did not result in PCSC enrichment. No enrichment on tumorspheres neither on the CD133(+) population was detected. Therefore our data provide evidences of the relevance of uPAR-controlled oncolytic adenoviruses for the elimination of pancreatic cancer stem cells. © 2013.

  20. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

    NARCIS (Netherlands)

    Klein, Alison P.; Wolpin, Brian M.; Risch, Harvey A.; Stolzenberg-Solomon, Rachael Z.; Mocci, Evelina; Zhang, Mingfeng; Canzian, Federico; Childs, Erica J.; Hoskins, Jason W.; Jermusyk, Ashley; Zhong, Jun; Chen, Fei; Albanes, Demetrius; Andreotti, Gabriella; Arslan, Alan A.; Babic, Ana; Bamlet, William R.; Beane-Freeman, Laura; Berndt, Sonja I.; Blackford, Amanda; Borges, Michael; Borgida, Ayelet; Bracci, Paige M.; Brais, Lauren; Brennan, Paul; Brenner, Hermann; Bueno-de-Mesquita, Bas; Buring, Julie; Campa, Daniele; Capurso, Gabriele; Cavestro, Giulia Martina; Chaffee, Kari G.; Chung, Charles C.; Cleary, Sean; Cotterchio, Michelle; Dijk, Frederike; Duell, Eric J.; Foretova, Lenka; Fuchs, Charles; Funel, Niccola; Gallinger, Steven; M Gaziano, J. Michael; Gazouli, Maria; Giles, Graham G.; Giovannucci, Edward; Goggins, Michael; Goodman, Gary E.; Goodman, Phyllis J.; Hackert, Thilo; Haiman, Christopher; Hartge, Patricia; Hasan, Manal; Hegyi, Peter; Helzlsouer, Kathy J.; Herman, Joseph; Holcatova, Ivana; Holly, Elizabeth A.; Hoover, Robert; Hung, Rayjean J.; Jacobs, Eric J.; Jamroziak, Krzysztof; Janout, Vladimir; Kaaks, Rudolf; Khaw, Kay-Tee; Klein, Eric A.; Kogevinas, Manolis; Kooperberg, Charles; Kulke, Matthew H.; Kupcinskas, Juozas; Kurtz, Robert J.; Laheru, Daniel; Landi, Stefano; Lawlor, Rita T.; Lee, I.-Min; Lemarchand, Loic; Lu, Lingeng; Malats, Núria; Mambrini, Andrea; Mannisto, Satu; Milne, Roger L.; Mohelníková-Duchoňová, Beatrice; Neale, Rachel E.; Neoptolemos, John P.; Oberg, Ann L.; Olson, Sara H.; Orlow, Irene; Pasquali, Claudio; Patel, Alpa V.; Peters, Ulrike; Pezzilli, Raffaele; Porta, Miquel; Real, Francisco X.; Rothman, Nathaniel; Scelo, Ghislaine; Sesso, Howard D.; Severi, Gianluca; Shu, Xiao-Ou; Silverman, Debra; Smith, Jill P.; Soucek, Pavel; Sund, Malin; Talar-Wojnarowska, Renata; Tavano, Francesca; Thornquist, Mark D.; Tobias, Geoffrey S.; van den Eeden, Stephen K.; Vashist, Yogesh; Visvanathan, Kala; Vodicka, Pavel; Wactawski-Wende, Jean; Wang, Zhaoming; Wentzensen, Nicolas; White, Emily; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Kraft, Peter; Li, Donghui; Chanock, Stephen; Obazee, Ofure; Petersen, Gloria M.; Amundadottir, Laufey T.

    2018-01-01

    In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic

  1. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

    NARCIS (Netherlands)

    Klein, Alison P; Wolpin, Brian M; Risch, Harvey A; Stolzenberg-Solomon, Rachael Z; Mocci, Evelina; Zhang, Mingfeng; Canzian, Federico; Childs, Erica J; Hoskins, Jason W; Jermusyk, Ashley; Zhong, Jun; Sund, Malin; Talar-Wojnarowska, Renata; Tavano, Francesca; Thornquist, Mark D; Tobias, Geoffrey S; Van Den Eeden, Stephen K; Vashist, Yogesh; Visvanathan, Kala; Vodicka, Pavel; Wactawski-Wende, Jean; Chen, Fei; Wang, Zhaoming; Wentzensen, Nicolas; White, Emily; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Kraft, Peter; Li, Donghui; Chanock, Stephen; Albanes, Demetrius; Obazee, Ofure; Petersen, Gloria M; Amundadottir, Laufey T; Andreotti, Gabriella; Arslan, Alan A; Babic, Ana; Bamlet, William R; Beane-Freeman, Laura; Berndt, Sonja I; Blackford, Amanda; Borges, Michael; Borgida, Ayelet; Bracci, Paige M; Brais, Lauren; Brennan, Paul; Brenner, Hermann; Bueno-de-Mesquita, Bas; Buring, Julie; Campa, Daniele; Capurso, Gabriele; Cavestro, Giulia Martina; Chaffee, Kari G; Chung, Charles C; Cleary, Sean; Cotterchio, Michelle; Dijk, Frederike; Duell, Eric J; Foretova, Lenka; Fuchs, Charles; Funel, Niccola; Gallinger, Steven; M Gaziano, J Michael; Gazouli, Maria; Giles, Graham G; Giovannucci, Edward; Goggins, Michael; Goodman, Gary E; Goodman, Phyllis J; Hackert, Thilo; Haiman, Christopher; Hartge, Patricia; Hasan, Manal; Hegyi, Peter; Helzlsouer, Kathy J; Herman, Joseph; Holcatova, Ivana; Holly, Elizabeth A; Hoover, Robert; Hung, Rayjean J; Jacobs, Eric J; Jamroziak, Krzysztof; Janout, Vladimir; Kaaks, Rudolf; Khaw, Kay-Tee; Klein, Eric A; Kogevinas, Manolis; Kooperberg, Charles; Kulke, Matthew H; Kupcinskas, Juozas; Kurtz, Robert J; Laheru, Daniel; Landi, Stefano; Lawlor, Rita T; Lee, I-Min; LeMarchand, Loic; Lu, Lingeng; Malats, Núria; Mambrini, Andrea; Mannisto, Satu; Milne, Roger L; Mohelníková-Duchoňová, Beatrice; Neale, Rachel E; Neoptolemos, John P; Oberg, Ann L; Olson, Sara H; Orlow, Irene; Pasquali, Claudio; Patel, Alpa V; Peters, Ulrike; Pezzilli, Raffaele; Porta, Miquel; Real, Francisco X; Rothman, Nathaniel; Scelo, Ghislaine; Sesso, Howard D; Severi, Gianluca; Shu, Xiao-Ou; Silverman, Debra; Smith, Jill P; Soucek, Pavel

    2018-01-01

    In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic

  2. Evaluation of Radiation Response and Gold Nanoparticle Enhancement in Drug-Resistant Pancreatic Cancer Cells

    Science.gov (United States)

    Abourabia, Assya

    literature, we hypothesize that oxaliplatin-resistant pancreatic cancer cells, PANC-1/OR, are much more resistant to radiation exposure than their drug-sensitive analogues, PANC-1 cells. We think that the acquisition of chemoresistance entails mechanisms that also impart some loss of radiation sensitivity in PANC-1/OR cells. Responsiveness of pancreatic cancer cells to the radiation was measured by clonogenic survival. The results presented in this thesis show that drug-resistant PANC- 1/OR cells survive high doses of radiation exposure better than PANC-1 cells. Moreover, the presence of gold nanoparticles decreases cell survival when combined with the X-ray radiation. In conclusion, the combination of GNP and X-rays radiation produces a slight radiosensitizing effect for pancreatic cancer cells, PANC-1, and their chemoresistance variant, and we can speculate that this is a good mean of achieving additive cytotoxic effects on pancreatic cells.

  3. Mathematical models of differential diagnostics and prognosis in chronic pancreatitis and cancer with a primary lesion of the pancreatic head

    Directory of Open Access Journals (Sweden)

    I. A. Kryvoruchko

    2017-02-01

    Methods. Analyzed the results of surgical treatment of 132 patients, including 68 - for cancer of the pancreatic head (in 46 - with jaundice and 64 - chronic pancreatitis (CP with a primary lesion of the pancreatic head (16 - with jaundice. The distribution of patients into groups was carried out with a maximum value of classification functions calculated by special formulas. Next studied indicators of endothelial dysfunction for differential diagnosis.  Results. It was defined the threshold of VEGF = 346 pg/ml, which shared the group of chronic pancreatitis or cancer of the pancreatic head, which was determined based on the Pareto criterion. This model sensitivity was 72.1% and specificity of 75% for the overall accuracy of 72.7%. Even more precision indicator was on the threshold of VEGF = 248 pg/ml, which compared groups of patients with cancer and software of the control group (125.9 pg/ml and the sensitivity was 86.8%, specificity 82.4%, and overall accuracy of 82.3%. At about the same accuracy had this test and the comparison group of patients with chronic pancreatitis and control: sensitivity 84.4% and specificity of 76.5% overall accuracy of 81.5% in the threshold VEGF of 155 pg/ml (p<0,05. To develop a prognosis of a pathological process, along with the use of diagnostic data used a method of classification trees. The model showed that the index VEGF is the criterion that discriminates for pancreas- pancreatic cancer-pancreas, but relative differences in the presence of jaundice in patients defined using S-nitrozothiol. The accuracy of the proposed method of prediction was 89%, the price of cross-checking - 82,6% (p<0,05. Pancreatoduodenal resection for Whipple was performed in 23 patients, for Traverso-Longmire - in 8, subtotal right sided pancreatectomy for Fortner - in 3, hepaticojejunostomy by Roux - in 8, duodenopreserving resection for Beger - in 6, her Bernese option - in 7, operation Frey - in 51. In 26 (19.7% patients, minimally invasive

  4. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Science.gov (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-03

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  5. Comparison of Oct4, Sox2 and Nanog Expression in Pancreatic Cancer Cell Lines and Human Pancreatic Tumor

    Directory of Open Access Journals (Sweden)

    Vahideh Assadollahi

    2015-12-01

    Full Text Available Background: Genes are involved in the control of stem cell self-renewal as a new class of molecular markers of cancer. Objectives: In this study, the expression of Oct4, Nanog and Sox2 in cell lines MIA Paca-2, PA-TU-8902 and AsPC-1 and pancreatic cancer tissue were examined. Materials and Methods: In this experimental study, cell lines, MIA Paca-2, PA-TU-8902 and AsPC-1, were cultured in DMEM (Dulbecco’s Modified Eagles Medium and RPMI-1640 (Roswell Park Memorial Institute containing FBS 10% (fetal bovine serum in a 37°C incubator containing Co2 5% and humidity 90%. Samples of tumor and non-cancer pancreatic tumor were purchased Iran tumor bank. Extraction of RNA and synthesis of cDNA was performed. Expression levels of Oct4, Nanog and Sox2 were determined using Real-time PCR. The protein expression levels of target genes in the cell lines were studied by flow cytometry and immunocytochemistry. Results: The expression rate of Oct4, Nanog and Sox2 is more in the cancer cell lines than those in the control (normal tissue samples. The protein expression levels of target genes in the cell lines were confirmed by flow cytometry and immunocytochemistry. Conclusions: The genes are involved in stem cell self-renewal as a new class of molecular markers of cancer that detected in the pancreatic cell lines. Maybe, these genes play important role in the uncontrolled proliferation of cancer cells.

  6. Role of adipocytokines and its correlation with endocrine pancreatic function in patients with pancreatic cancer.

    Science.gov (United States)

    Gąsiorowska, Anita; Talar-Wojnarowska, Renata; Kaczka, Aleksandra; Borkowska, Anna; Czupryniak, Leszek; Małecka-Panas, Ewa

    2013-01-01

    Some authors suggest that adipocytokines contribute to the induction of pancreatic carcinogenesis as well as the development of endocrine insufficiency. We evaluate the circulating concentrations of leptin, resistin and visfatin in patients with newly diagnosed pancreatic cancer (PC) and relationship between serum adipocytokines level and clinicopathological features of PC. Moreover the usefulness of those adipocytokines as possible biomarkers of endocrine pancreatic function in PC has been assessed. The pilot study group consisted of 45 individuals (mean age 65.6 ± 11.5 years, BMI 21.8 ± 3.4 kg/m(2)) with newly diagnosed PC (within last 1-3 months) and 13 healthy individuals with age, gender and BMI matched to the study group. Among PC patients 18 (40%) had recently diagnosed diabetes. Fasting plasma leptin, resistin, visfatin concentrations were determined with ELISA (R&D Systems, Phoenix Pharmaceuticals) and insulin by RIA (DakoCytomation). Patients with PC as compared to controls had significantly lower plasma leptin (40.6 ± 21.3 vs 63.2 ± 16.3 pg/mL; p pancreatic cancer are characterized with lower level of leptin. This pilot study showed significantly higher resistin concentrations in patients with PC in comparison to healthy controls, which may be helpful in PC early diagnosis. Changes in leptin and resistin level in PC are not likely related to endocrine disorders. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  7. A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Chuang, Shu-Chun; Stolzenberg-Solomon, Rachael; Ueland, Per Magne; Vollset, Stein Emil; Midttun, Oivind; Olsen, Anja; Tjonneland, Anne; Overvad, Kim; Boutron-Ruault, Marie-Christine; Morois, Sophie; Clavel-Chapelon, Francoise; Teucher, Birgit; Kaaks, Rudolf; Weikert, Cornelia; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vassiliki; Naska, Androniki; Jenab, Mazda; Slimani, Nadia; Romieu, Isabelle; Michaud, Dominique S.; Palli, Domenico; Sieri, Sabina; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Skeie, Guri; Duell, Eric J.; Rodriguez, Laudina; Molina-Montes, Esther; Maria Huerta, Jose; Larranaga, Nerea; Barricarte Gurrea, Aurelio; Johansen, Dorthe; Manjer, Jonas; Ye, Weimin; Sund, Malin; Peeters, Petra H. M.; Jeurnink, Suzanne; Wareham, Nicholas; Khaw, Kay-Tee; Crowe, Francesca; Riboli, Elio; Bueno-de-Mesquita, Bas; Vineis, Paolo

    Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5'-phosphate, riboflavin, flavin

  8. Sweet-beverage consumption and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

    Science.gov (United States)

    Navarrete-Muñoz, Eva M; Wark, Petra A; Romaguera, Dora; Bhoo-Pathy, Nirmala; Michaud, Dominique; Molina-Montes, Esther; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Katzke, Verena A; Kühn, Tilman; Steffen, Annika; Trichopoulou, Antonia; Klinaki, Eleni; Papatesta, Eleni-Maria; Masala, Giovanna; Krogh, Vittorio; Tumino, Rosario; Naccarati, Alessio; Mattiello, Amalia; Peeters, Petra H; Rylander, Charlotta; Parr, Christine L; Skeie, Guri; Weiderpass, Elisabete; Quirós, J Ramón; Duell, Eric J; Dorronsoro, Miren; Huerta, José María; Ardanaz, Eva; Wareham, Nick; Khaw, Kay-Tee; Travis, Ruth C; Key, Tim; Stepien, Magdalena; Freisling, Heinz; Riboli, Elio; Bueno-de-Mesquita, H Bas

    2016-09-01

    The consumption of sweet beverages has been associated with greater risk of type 2 diabetes and obesity, which may be involved in the development of pancreatic cancer. Therefore, it has been hypothesized that sweet beverages may increase pancreatic cancer risk as well. We examined the association between sweet-beverage consumption (including total, sugar-sweetened, and artificially sweetened soft drink and juice and nectar consumption) and pancreatic cancer risk. The study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. A total of 477,199 participants (70.2% women) with a mean age of 51 y at baseline were included, and 865 exocrine pancreatic cancers were diagnosed after a median follow-up of 11.60 y (IQR: 10.10-12.60 y). Sweet-beverage consumption was assessed with the use of validated dietary questionnaires at baseline. HRs and 95% CIs were obtained with the use of multivariable Cox regression models that were stratified by age, sex, and center and adjusted for educational level, physical activity, smoking status, and alcohol consumption. Associations with total soft-drink consumption were adjusted for juice and nectar consumption and vice versa. Total soft-drink consumption (HR per 100 g/d: 1.03; 95% CI: 0.99, 1.07), sugar-sweetened soft-drink consumption (HR per 100 g/d: 1.02; 95% CI: 0.97, 1.08), and artificially sweetened soft-drink consumption (HR per 100 g/d: 1.04; 95% CI: 0.98, 1.10) were not associated with pancreatic cancer risk. Juice and nectar consumption was inversely associated with pancreatic cancer risk (HR per 100 g/d: 0.91; 95% CI: 0.84, 0.99); this association remained statistically significant after adjustment for body size, type 2 diabetes, and energy intake. Soft-drink consumption does not seem to be associated with pancreatic cancer risk. Juice and nectar consumption might be associated with a modest decreased pancreatic cancer risk. Additional studies with specific information on juice and

  9. A role for survivin in radioresistance of pancreatic cancer cells

    International Nuclear Information System (INIS)

    Asanuma, Koichi; Kobayashi, Daisuke; Furuya, Daisuke; Tsuji, Naoki; Yagihashi, Atsuhito; Watanabe, Naoki

    2002-01-01

    Using gene-transduced pancreatic cancer cells, we examined whether survivin expression is directly involved in regulation of radiosensitivity. Ordinarily radiosensitive MIAPaCa-2 cells transduced with wild-type survivin gene (MS cells) proliferated more rapidly than cells transduced with control vector. MS cells were significantly less radiosensitive than control vector-transduced cells. Radiation-induced activity of caspase-3, but not caspase-7, was significantly inhibited in MS cells. On the other hand, transduction of a dominant-negative mutant survivin gene into radioresistant PANC-1 cells augmented radiosensitivity. Further, the radiation-induced increase in caspase-3 activity was enhanced, indicating that survivin function was truly inhibited. These results indicate that survivin expression directly down-regulates radiosensitivity. (author)

  10. Preoperative gemcitabine-based chemoradiation therapy for resectable pancreatic cancer

    International Nuclear Information System (INIS)

    Takahashi, Hidenori; Ohigashi, Hiroaki; Goto, Kunihito; Marubashi, Shigeru; Yano, Masahiko; Ishikawa, Osamu

    2013-01-01

    During the period from 2002 to 2011, a total of 240 consecutive patients with resectable pancreatic cancer received preoperative chemoradiation therapy (CRT). Among 240 patients, 201 patients underwent the subsequent pancreatectomy (resection rate: 84%). The 5-year overall survival of resected cases was 56% and the median survival of 39 unresected cases was 11 months. The 5-year locoregional recurrence rate of resected cases was 15%. The 5-year overall survival of the entire cohort (n=240) was 47%. The preoperative CRT and subsequent pancreatectomy provided a favorable surgical result, which was contributed by several characteristics of preoperative CRT: the prominent locoregional treatment effect with lower incidence of locoregional recurrence, and the discrimination between patients who are likely to benefit from subsequent surgery and those who are not. (author)

  11. Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

    International Nuclear Information System (INIS)

    Motoo, Yoshiharu; Shimasaki, Takeo; Ishigaki, Yasuhito; Nakajima, Hideo; Kawakami, Kazuyuki; Minamoto, Toshinari

    2011-01-01

    Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β) is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer). We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation

  12. Fenofibrate inhibited pancreatic cancer cells proliferation via activation of p53 mediated by upregulation of LncRNA MEG3

    International Nuclear Information System (INIS)

    Hu, Duanmin; Su, Cunjin; Jiang, Min; Shen, Yating; Shi, Aiming; Zhao, Fenglun; Chen, Ruidong; Shen, Zhu; Bao, Junjie; Tang, Wen

    2016-01-01

    There is still no suitable drug for pancreatic cancer treatment, which is one of the most aggressive human tumors. Maternally expressed gene 3 (MEG3), a LncRNA, has been suggested as a tumor suppressor in a range of human tumors. Studies found fenofibrate exerted anti-tumor roles in various human cancer cell lines. However, its role in pancreatic cancer remains unknown. The present study aimed to explore the impacts of fenofibrate on pancreatic cancer cell lines, and to investigate MEG3 role in its anti-tumor mechanisms. We used MTT assay to determine cells proliferation, genome-wide LncRNA microarray analysis to identify differently expressed LncRNAs, siRNA or pCDNA-MEG3 transfection to interfere or upregulate MEG3 expression, western blot to detect protein levels, real-time PCR to determine MEG3 level. Fenofibrate significantly inhibited proliferation of pancreatic cancer cells, increased MEG3 expression and p53 levels. Moreover, knockdown of MEG3 attenuated cytotoxicity induced by fenofibrate. Furthermore, overexpression of MEG3 induced cells death and increased p53 expression. Our results indicated fenofibrate inhibited pancreatic cancer cells proliferation via activation of p53 mediated by upregulation of MEG3. - Highlights: • We found that fenofibrate suppressed proliferation of pancreatic cancer cells. • We found fenofibrate increased LncRNA-MEG3 expression and p53 level in PANC-1 cells. • Inhibition of MEG3 expression attenuated anti-tumor effects of fenofibrate.

  13. Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Motoo, Yoshiharu, E-mail: motoo@kanazawa-med.ac.jp [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Shimasaki, Takeo [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Division of Translational & Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa (Japan); Ishigaki, Yasuhito [Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Nakajima, Hideo [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Kawakami, Kazuyuki; Minamoto, Toshinari [Division of Translational & Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa (Japan)

    2011-01-24

    Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β) is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer). We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation.

  14. Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Toshinari Minamoto

    2011-01-01

    Full Text Available Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer. We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation.

  15. Fenofibrate inhibited pancreatic cancer cells proliferation via activation of p53 mediated by upregulation of LncRNA MEG3

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Duanmin [Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou 215004 (China); Su, Cunjin [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou 215004 (China); Jiang, Min [Department of Breast Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215004 (China); Shen, Yating [Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou 215004 (China); Shi, Aiming; Zhao, Fenglun [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou 215004 (China); Chen, Ruidong [Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou 215004 (China); Shen, Zhu [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou 215004 (China); Bao, Junjie, E-mail: baojjsdfey@sina.com [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou 215004 (China); Tang, Wen, E-mail: sztangwen@163.com [Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou 215004 (China)

    2016-03-04

    There is still no suitable drug for pancreatic cancer treatment, which is one of the most aggressive human tumors. Maternally expressed gene 3 (MEG3), a LncRNA, has been suggested as a tumor suppressor in a range of human tumors. Studies found fenofibrate exerted anti-tumor roles in various human cancer cell lines. However, its role in pancreatic cancer remains unknown. The present study aimed to explore the impacts of fenofibrate on pancreatic cancer cell lines, and to investigate MEG3 role in its anti-tumor mechanisms. We used MTT assay to determine cells proliferation, genome-wide LncRNA microarray analysis to identify differently expressed LncRNAs, siRNA or pCDNA-MEG3 transfection to interfere or upregulate MEG3 expression, western blot to detect protein levels, real-time PCR to determine MEG3 level. Fenofibrate significantly inhibited proliferation of pancreatic cancer cells, increased MEG3 expression and p53 levels. Moreover, knockdown of MEG3 attenuated cytotoxicity induced by fenofibrate. Furthermore, overexpression of MEG3 induced cells death and increased p53 expression. Our results indicated fenofibrate inhibited pancreatic cancer cells proliferation via activation of p53 mediated by upregulation of MEG3. - Highlights: • We found that fenofibrate suppressed proliferation of pancreatic cancer cells. • We found fenofibrate increased LncRNA-MEG3 expression and p53 level in PANC-1 cells. • Inhibition of MEG3 expression attenuated anti-tumor effects of fenofibrate.

  16. Pancreatic cancer: Incidence, clinical profile, and frequency of ...

    African Journals Online (AJOL)

    Hana T. Al-Majed

    2012-08-09

    Aug 9, 2012 ... Diabetes has been postulated to be both a risk factor and a consequence of pancreatic cancer, ... (A.A.. El-Basmi),. Shihab@yahoo.com. (S.H. Al-Mohannadi) ..... A recent meta-analysis reported that obese people may have a ...

  17. Comprehensive Evaluation of Altered Systemic Metabolism and Pancreatic Cancer Risk

    Science.gov (United States)

    2016-10-01

    information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing...individuals provide extensive data on metabolic phenotypes, such as obesity and diabetes, and banked plasma samples for interrogation . The potential...banked plasma samples for interrogation . The potential impact of understanding the mechanisms underlying early pancreatic cancer growth is

  18. Bryostatin I inhibits growth and proliferation of pancreatic cancer ...

    African Journals Online (AJOL)

    Purpose: To evaluate the effect of bryostatin I on proliferation of pancreatic cancer cells as well as tumor growth in mice tumor xenograft model. Methods: Activation of NF-κB was evaluated by preparing nuclear material extract using nuclear extract kit (Carlsbad, CA, USA) followed by enzyme-linked immunosorbent assay ...

  19. Electroacupuncture treatment for pancreatic cancer pain: a randomized controlled trial.

    Science.gov (United States)

    Chen, Hao; Liu, Tang-Yi; Kuai, Le; Zhu, Ji; Wu, Cai-Jun; Liu, Lu-Ming

    2013-01-01

    Pancreatic cancer is often accompanied by severe abdominal or back pain. It's the first study to evaluate the analgesic effect of electroacupuncture on pancreatic cancer pain. A randomized controlled trial compared electroacupuncture with control acupuncture using the placebo needle. Sixty patients with pancreatic cancer pain were randomly assigned to the electroacupuncture group (n = 30) and the placebo control group (n = 30). Patients were treated on Jiaji (Ex-B2) points T8-T12 bilaterally for 30 min once a day for 3 days. Pain intensity was assessed with numerical rated scales (NRS) before the treatment (Baseline), after 3 treatments, and 2 days follow-up. Baseline characteristics were similar in the two groups. After 3 treatment, pain intensity on NRS decreased compared with Baseline (-1.67, 95% confidence interval [CI] -1.46 to -1.87) in the electroacupuncture group; there was little change (-0.13, 95% CI 0.08 to -0.35) in control group; the difference between two groups was statistically significant (P electroacupuncture group compared with the control group (P Electroacupuncture was an effective treatment for relieving pancreatic cancer pain. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  20. TERT gene harbors multiple variants associated with pancreatic cancer susceptibility

    Czech Academy of Sciences Publication Activity Database

    Campa, D.; Rizzato, C.; Stolzenberg-Solomon, R.; Pacetti, P.; Vodička, Pavel; Cleary, S.P.; Capurso, G.; Bueno-de-Mesquita, H. B.; Werner, J.; Gazouli, M.; Butterbach, K.; Ivanauskas, A.; Giese, N.; Petersen, G. M.; Fogar, P.; Wang, Z.; Bassi, C.; Ryska, M.; Theodoropoulos, G.E.; Kooperberg, Ch.; Li, D.; Greenhalf, W.; Pasquali, C.; Hackert, T.; Fuchs, Ch.S.; Mohelníková-Duchoňová, B.; Sperti, C.; Funel, N.; Dieffenbach, A.K.; Wareham, N.J.; Buring, J.; Holcátová, I.; Costello, E.; Zambon, C.F.; Kupcinskas, J.; Risch, H.A.; Kraft, P.; Bracci, P.M.; Pezzilli, R.; Olson, S.H.; Sesso, H. D.; Hartge, P.; Strobel, O.; Malecka-Panas, E.; Visvanathan, K.; Arslan, A. A.; Pedrazzoli, S.; Souček, P.; Gioffreda, D.; Key, T.J.; Talar-Wojnarowska, R.; Scarpa, A.; Mambrini, A.; Jacobs, E.J.; Jamroziak, K.; Klein, A.; Tavano, F.; Bambi, F.; Landi, S.; Austin, M. A.; Vodičková, Ludmila; Brenner, H.; Chanock, S. J.; Fave, G.D.; Piepoli, A.; Cantore, M.; Zheng, W.; Wolpin, B.M.; Amundadottir, L. T.; Canzian, F.

    2015-01-01

    Roč. 137, č. 9 (2015), s. 2175-2183 ISSN 0020-7136 R&D Projects: GA ČR GAP301/12/1734 Institutional support: RVO:68378041 Keywords : pancreatic cancer * polymorphisms * telomerase * susceptibility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.531, year: 2015

  1. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

    Science.gov (United States)

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M

    2012-11-15

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  2. Comparison of Plasma Tu-M2-PK and CA19-9 in Pancreatic Cancer

    DEFF Research Database (Denmark)

    Joergensen, Maiken Thyregod; Heegaard, Niels H H; Schaffalitzky de Muckadell, Ove B

    2009-01-01

    because of suspicion of pancreatic cancer. Of these, 51 patients had their conditions diagnosed as PDAC, whereas this diagnosis was ruled out in 52 after 12 months of follow-up. The performance of Tu-M2-PK was compared with that of CA19-9 using cutoff values 15 and 37 U/mL, respectively. RESULTS...

  3. Neoadjuvant Therapy in Patients with Pancreatic Cancer: A Disappointing Therapeutic Approach?

    International Nuclear Information System (INIS)

    Zimmermann, Carolin; Folprecht, Gunnar; Zips, Daniel; Pilarsky, Christian; Saeger, Hans Detlev; Grutzmann, Robert

    2011-01-01

    Pancreatic cancer is a devastating disease. It is the fourth leading cause of cancer-related death in Germany. The incidence in 2003/2004 was 16 cases per 100.000 inhabitants. Of all carcinomas, pancreatic cancer has the highest mortality rate, with one- and five-year survival rates of 25% and less than 5%, respectively, regardless of the stage at diagnosis. These low survival rates demonstrate the poor prognosis of this carcinoma. Previous therapeutic approaches including surgical resection combined with adjuvant therapy or palliative chemoradiation have not achieved satisfactory results with respect to overall survival. Therefore, it is necessary to evaluate new therapeutic approaches. Neoadjuvant therapy is an interesting therapeutic option for patients with pancreatic cancer. For selected patients with borderline or unresectable disease, neoadjuvant therapy offers the potential for tumor downstaging, increasing the probability of a margin-negative resection and decreasing the occurrence of lymph node metastasis. Currently, there is no universally accepted approach for treating patients with pancreatic cancer in the neoadjuvant setting. In this review, the most common neoadjuvant strategies will be described, compared and discussed

  4. Experimental treatment of pancreatic cancer with two novel histone deacetylase inhibitors

    Science.gov (United States)

    Haefner, Martin; Bluethner, Thilo; Niederhagen, Manuel; Moebius, Christian; Wittekind, Christian; Mossner, Joachim; Caca, Karel; Wiedmann, Marcus

    2008-01-01

    AIM: To investigate in vitro and in vivo treatment with histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 in pancreatic cancer. METHODS: Cell-growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 8 human pancreatic cancer cell lines using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, the anti-tumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral activity of the drugs was assessed by immunoblotting for p21WAF-1, acH4, cell cycle analysis, TUNEL assay, and immunohistochemistry for MIB-1. RESULTS: In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines and was associated with hyperacetylation of nucleosomal histone H4, increased expression of p21WAF-1, cell cycle arrest at G2/M-checkpoint, and increased apoptosis. In vivo, NVP-LBH589 alone significantly reduced tumor mass and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed slightly increased apoptosis and no significant reduction of cell proliferation. CONCLUSION: Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human pancreatic cancer, although the precise mechanism of in vivo drug action is not yet completely understood. Therefore, further preclinical and clinical studies for the treatment of pancreatic cancer are recommended. PMID:18595135

  5. Up-regulation of integrin β3 in radioresistant pancreatic cancer impairs adenovirus-mediated gene therapy

    International Nuclear Information System (INIS)

    Egami, Takuya; Ohuchida, Kenoki; Yasui, Takaharu; Onimaru, Manabu; Toma, Hiroki; Sato, Norihiro; Tanaka, Masao; Mizumoto, Kazuhiro; Matsumoto, Kunio

    2009-01-01

    Adenovirus-mediated gene therapy is a promising approach for the treatment of pancreatic cancer. We previously reported that radiation enhanced adenovirus-mediated gene expression in pancreatic cancer, suggesting that adenoviral gene therapy might be more effective in radioresistant pancreatic cancer cells. In the present study, we compared the transduction efficiency of adenovirus-delivered genes in radiosensitive and radioresistant cells, and investigated the underlying mechanisms. We used an adenovirus expressing the hepatocyte growth factor antagonist, NK4 (Ad-NK4), as a representative gene therapy. We established two radioresistant human pancreatic cancer cell lines using fractionated irradiation. Radiosensitive and radioresistant pancreatic cancer cells were infected with Ad-NK4, and NK4 levels in the cells were measured. In order to investigate the mechanisms responsible for the differences in the transduction efficiency between these cells, we measured expression of the genes mediating adenovirus infection and endocytosis. The results revealed that NK4 levels in radioresistant cells were significantly lower (P<0.01) than those in radiosensitive cells, although there were no significant differences in adenovirus uptake between radiosensitive cells and radioresistant cells. Integrin β3 was up-regulated and the Coxsackie virus and adenovirus receptor was down-regulated in radioresistant cells, and inhibition of integrin β3 promoted adenovirus gene transfer. These results suggest that inhibition of integrin β3 in radioresistant pancreatic cancer cells could enhance adenovirus-mediated gene therapy. (author)

  6. Dietary mutagen exposure and risk of pancreatic cancer.

    Science.gov (United States)

    Li, Donghui; Day, Rena Sue; Bondy, Melissa L; Sinha, Rashmi; Nguyen, Nga T; Evans, Douglas B; Abbruzzese, James L; Hassan, Manal M

    2007-04-01

    To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. A total of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (+/-5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P = 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (P(trend) = 0.024). A higher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. A possible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP, P(interaction) = 0.09 and 0.099, respectively. These data support the hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer.

  7. Dietary Mutagen Exposure and Risk of Pancreatic Cancer

    OpenAIRE

    Li, Donghui; Sue Day, Rena; Bondy, Melissa L.; Sinha, Rashmi; Nguyen, Nga T.; Evans, Douglas B.; Abbruzzese, James L.; Hassan, Manal M.

    2007-01-01

    To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. Atotal of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (±5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases tha...

  8. Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal and Pancreatic Cancer Mice.

    Science.gov (United States)

    Quirin, Kayla A; Kwon, Jason J; Alioufi, Arafat; Factora, Tricia; Temm, Constance J; Jacobsen, Max; Sandusky, George E; Shontz, Kim; Chicoine, Louis G; Clark, K Reed; Mendell, Joshua T; Korc, Murray; Kota, Janaiah

    2018-03-16

    Recombinant adeno-associated virus (rAAV)-mediated gene delivery shows promise to transduce the pancreas, but safety/efficacy in a neoplastic context is not well established. To identify an ideal AAV serotype, route, and vector dose and assess safety, we have investigated the use of three AAV serotypes (6, 8, and 9) expressing GFP in a self-complementary (sc) AAV vector under an EF1α promoter (scAAV.GFP) following systemic or retrograde pancreatic intraductal delivery. Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but gene expression did not exceed >45% with the highest dose, 5 × 10 12 viral genomes (vg). Intraductal delivery of 1 × 10 11 vg scAAV6.GFP transduced acini, ductal cells, and islet cells with >50%, ∼48%, and >80% efficiency, respectively, and >80% pancreatic transduction was achieved with 5 × 10 11 vg. In a Kras G12D -driven pancreatic cancer mouse model, intraductal delivery of scAAV6.GFP targeted acini, epithelial, and stromal cells and exhibited persistent gene expression 5 months post-delivery. In normal mice, intraductal delivery induced a transient increase in serum amylase/lipase that resolved within a day of infusion with no sustained pancreatic inflammation or fibrosis. Similarly, in PDAC mice, intraductal delivery did not increase pancreatic intraepithelial neoplasia progression/fibrosis. Our study demonstrates that scAAV6 targets the pancreas/neoplasm efficiently and safely via retrograde pancreatic intraductal delivery.

  9. Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal and Pancreatic Cancer Mice

    Directory of Open Access Journals (Sweden)

    Kayla A. Quirin

    2018-03-01

    Full Text Available Recombinant adeno-associated virus (rAAV-mediated gene delivery shows promise to transduce the pancreas, but safety/efficacy in a neoplastic context is not well established. To identify an ideal AAV serotype, route, and vector dose and assess safety, we have investigated the use of three AAV serotypes (6, 8, and 9 expressing GFP in a self-complementary (sc AAV vector under an EF1α promoter (scAAV.GFP following systemic or retrograde pancreatic intraductal delivery. Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but gene expression did not exceed >45% with the highest dose, 5 × 1012 viral genomes (vg. Intraductal delivery of 1 × 1011 vg scAAV6.GFP transduced acini, ductal cells, and islet cells with >50%, ∼48%, and >80% efficiency, respectively, and >80% pancreatic transduction was achieved with 5 × 1011 vg. In a KrasG12D-driven pancreatic cancer mouse model, intraductal delivery of scAAV6.GFP targeted acini, epithelial, and stromal cells and exhibited persistent gene expression 5 months post-delivery. In normal mice, intraductal delivery induced a transient increase in serum amylase/lipase that resolved within a day of infusion with no sustained pancreatic inflammation or fibrosis. Similarly, in PDAC mice, intraductal delivery did not increase pancreatic intraepithelial neoplasia progression/fibrosis. Our study demonstrates that scAAV6 targets the pancreas/neoplasm efficiently and safely via retrograde pancreatic intraductal delivery.

  10. Comparing human pancreatic cell secretomes by in vitro aptamer selection identifies cyclophilin B as a candidate pancreatic cancer biomarker.

    Science.gov (United States)

    Ray, Partha; Rialon-Guevara, Kristy L; Veras, Emanuela; Sullenger, Bruce A; White, Rebekah R

    2012-05-01

    Most cases of pancreatic cancer are not diagnosed until they are no longer curable with surgery. Therefore, it is critical to develop a sensitive, preferably noninvasive, method for detecting the disease at an earlier stage. In order to identify biomarkers for pancreatic cancer, we devised an in vitro positive/negative selection strategy to identify RNA ligands (aptamers) that could detect structural differences between the secretomes of pancreatic cancer and non-cancerous cells. Using this molecular recognition approach, we identified an aptamer (M9-5) that differentially bound conditioned media from cancerous and non-cancerous human pancreatic cell lines. This aptamer further discriminated between the sera of pancreatic cancer patients and healthy volunteers with high sensitivity and specificity. We utilized biochemical purification methods and mass-spectrometric analysis to identify the M9-5 target as cyclophilin B (CypB). This molecular recognition-based strategy simultaneously identified CypB as a serum biomarker and generated a new reagent to recognize it in body fluids. Moreover, this approach should be generalizable to other diseases and complementary to traditional approaches that focus on differences in expression level between samples. Finally, we suggest that the aptamer we identified has the potential to serve as a tool for the early detection of pancreatic cancer.

  11. Vitamin D and pancreas: The role of sunshine vitamin in the pathogenesis of diabetes mellitus and pancreatic cancer.

    Science.gov (United States)

    Altieri, Barbara; Grant, William B; Della Casa, Silvia; Orio, Francesco; Pontecorvi, Alfredo; Colao, Annamaria; Sarno, Gerardo; Muscogiuri, Giovanna

    2017-11-02

    Increasing evidence suggests that vitamin D exerts multiple effects beyond bone and calcium metabolism. Vitamin D seems to play a role in pancreatic disease, including type 1 and type 2 diabetes mellitus as well as pancreatic cancer. Vitamin D's immune-modulatory action suggests that it could help prevent type 1 diabetes. In type 2 diabetes, vitamin D may influence β-cell function, insulin sensitivity, and systematic inflammation-all characteristic pathways of that disease. Data from observational studies correlated vitamin D deficiency with risk of type 1 and type 2 diabetes. Prospective and ecological studies of pancreatic cancer incidence generally support a beneficial effect of higher 25-hydroxyvitamin D concentration as well as inverse correlations between UVB dose or exposure and incidence and/or mortality rate of pancreatic cancer. This review discusses the literature regarding vitamin D's role in risk of diabetes and pancreatic cancer. The results to date generally satisfy Hill's criteria for causality regarding vitamin D and incidence of these pancreatic diseases. However, large randomized, blinded, prospective studies are required to more fully evaluate the potential therapeutic role of vitamin D in preventing pancreatic diseases.

  12. Pancreatitis

    Science.gov (United States)

    ... the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is ...

  13. Dicumarol inhibition of NADPH:quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism.

    Science.gov (United States)

    Cullen, Joseph J; Hinkhouse, Marilyn M; Grady, Matthew; Gaut, Andrew W; Liu, Jingru; Zhang, Yu Ping; Weydert, Christine J Darby; Domann, Frederick E; Oberley, Larry W

    2003-09-01

    NADPH:quinone oxidoreductase (NQO(1)), a homodimeric, ubiquitous, flavoprotein, catalyzes the two-electron reduction of quinones to hydroquinones. This reaction prevents the one-electron reduction of quinones by cytochrome P450 reductase and other flavoproteins that would result in oxidative cycling with generation of superoxide (O(2)(.-)). NQO(1) gene regulation may be up-regulated in some tumors to accommodate the needs of rapidly metabolizing cells to regenerate NAD(+). We hypothesized that pancreatic cancer cells would exhibit high levels of this enzyme, and inhibiting it would suppress the malignant phenotype. Reverse transcription-PCR, Western blots, and activity assays demonstrated that NQO(1) was up-regulated in the pancreatic cancer cell lines tested but present in very low amounts in the normal human pancreas. To determine whether inhibition of NQO(1) would alter the malignant phenotype, MIA PaCa-2 pancreatic cancer cells were treated with a selective inhibitor of NQO(1), dicumarol. Dicumarol increased intracellular production of O(2)(.-), as measured by hydroethidine staining, and inhibited cell growth. Both of these effects were blunted with infection of an adenoviral vector containing the cDNA for manganese superoxide dismutase. Dicumarol also inhibited cell growth, plating efficiency, and growth in soft agar. We conclude that inhibition of NQO(1) increases intracellular O(2)(.-) production and inhibits the in vitro malignant phenotype of pancreatic cancer. These mechanisms suggest that altering the intracellular redox environment of pancreatic cancer cells may inhibit growth and delineate a potential strategy directed against pancreatic cancer.

  14. Pancreatic cancer and exposure to dietary nitrate and nitrite in the NIH-AARP Diet and Health Study.

    Science.gov (United States)

    Aschebrook-Kilfoy, Briseis; Cross, Amanda J; Stolzenberg-Solomon, Rachael Z; Schatzkin, Arthur; Hollenbeck, Albert R; Sinha, Rashmi; Ward, Mary H

    2011-08-01

    Nitrate and nitrite are precursors of N-nitroso compounds, which induce tumors of the pancreas in animals. The authors evaluated the relation of dietary nitrate and nitrite to pancreatic cancer risk in the NIH-AARP Diet and Health Study. Nitrate and nitrite intakes were assessed at baseline using a 124-item food frequency questionnaire. During approximately 10 years of follow-up between 1995 and 2006, 1,728 incident pancreatic cancer cases were identified. There was no association between total nitrate or nitrite intake and pancreatic cancer in men or women. However, men in the highest quintile of summed nitrate/nitrite intake from processed meat had a nonsignificantly elevated risk of pancreatic cancer (hazard ratio = 1.18, 95% confidence interval: 0.95, 1.47; P-trend = 0.11). The authors observed a stronger increase in risk among men for nitrate/nitrite intake from processed meat at ages 12-13 years (highest quintile vs. lowest: hazard ratio = 1.32, 95% confidence interval: 0.99, 1.76; P-trend = 0.11), though the relation did not achieve statistical significance. The authors found no associations between adult or adolescent nitrate or nitrite intake from processed meats and pancreatic cancer among women. These results provide modest evidence that processed meat sources of dietary nitrate and nitrite may be associated with pancreatic cancer among men and provide no support for the hypothesis in women.

  15. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    Science.gov (United States)

    Alejandre, Maria José; Palomino-Morales, Rogelio J.; Prados, Jose; Aránega, Antonia; Delgado, Juan R.; Irigoyen, Antonio; Martínez-Galán, Joaquina; Ortuño, Francisco M.

    2015-01-01

    The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox's proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease. PMID:26346854

  16. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Carolina Torres

    2015-01-01

    Full Text Available The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients’ outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox’s proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

  17. Radiosensitization of pancreatic cancer cells by 2',2'-difluoro-2'-deoxycytidine

    International Nuclear Information System (INIS)

    Lawrence, Theodore S.; Chang, Emily Y.; Hahn, Tina M.; Hertel, Larry W.; Shewach, Donna S.

    1996-01-01

    Purpose: We have reported that the deoxycytidine analog 2',2'-difluoro-2'-deoxycytidine (dFdCyd) is a potent radiosensitizer of HT29 human colon cancer cells probably through its effects on intracellular deoxyribonucleotide (dNTP) pools. Because dFdCyd has activity against pancreatic cancer in clinical trials, we wished to determine if dFdCyd would radiosensitize human pancreatic cancer cells. Methods and Materials: We assessed the effect of dFdCyd on radiation sensitivity of two human pancreatic cancer cell lines, Panc-1 and BxPC-3. To begin to investigate the mechanism of sensitization, we determined the effect of dFdCyd on dNTP pools and cell cycle distribution. Results: We found that dFdCyd produced radiation enhancement ratios of 1.7-1.8 under noncytotoxic conditions in both cell lines. Sensitization was not associated with intracellular levels of 2',2'-difluoro-2'-deoxycytidine triphosphate, the cytotoxic metabolite of dFdCyd, but occurred when dATP pools were depleted below the level of approximately 1 μM. Although both cell lines showed substantial cell cycle redistribution after drug treatment, the flow cytogram of the BxPC-3 cells would not, by itself, be anticipated to result in increased radiation sensitivity. Conclusions: These findings demonstrate that dFdCyd is a potent radiation sensitizer of human pancreatic cancer cells and support the development of a clinical protocol using combined dFdCyd and radiation therapy in the treatment of pancreatic cancer

  18. Pancreatic cancer in patients with chronic calcifying pancreatitis: Computed tomography findings – a retrospective analysis of 48 patients

    Energy Technology Data Exchange (ETDEWEB)

    Mohamed, Amir, E-mail: amir.med87@gmail.com [Department of Radiology, Brabois Adults Hospital, Nancy (France); Ayav, Ahmet [Department of HPB Surgery, University Hospital of Nancy (France); Belle, Arthur [Department of Hepatogastroenterologie, Brabois Adults Hospital, Nancy (France); Orry, Xavier [Department of Radiology, Brabois Adults Hospital, Nancy (France); Chevaux, Jean-Baptiste [Department of Hepatogastroenterologie, Brabois Adults Hospital, Unité Inserm U954, Nancy (France); Laurent, Valerie [Department of Radiology, Brabois Adults Hospital, Nancy (France); Laboratory IADI, INSERM u947 (France)

    2017-01-15

    Objective: Chronic calcifying pancreatitis (CCP) is a risk factor for pancreatic cancer (PC). Symptoms of PC are non-specific in patients with CCP, and diagnostic imaging can be difficult. Some studies have shown that diagnosis may take several months, leading to delays in treatment (Lin et al., 2015; Lennon et al., 2014) . The aim of this study was to describe the radiological signs of PC in patients with CCP. Methods: This retrospective, single-center study was conducted between January 2004 and December 2014. Patients with CCP who were being monitored for PC were included. Each patient diagnosed with PC was matched with two CCP controls who did not develop PC. Results: We studied 48 patients with CCP (30 men (62%) and 18 women (38%), mean age 69.4 years). Sixteen patients (with 18 tumor sites) who developed PC (1.52%) were compared with 32 controls who did not develop PC. A hypodense mass was observed in all of the patients with PC, predominantly in the pancreatic head (61.2%). No such masses were observed in the controls (p < 0.001). The average mass size was 36.3 mm, and the masses were observed to push aside the calcifications in all patients (p < 0.001). Calcifications were very abundant (>10) in 33.3% of the patients with PC and in 71.9% of the controls (p = 0.0076). The main pancreatic duct (MPD) was dilated in all of the patients with PC (average diameter 8.6 mm; homogeneous in 83.3%) and in only 46.9% of the controls (average 7.4 mm; homogeneous in 37.5%) (p > 0.05). Dilation of the intrahepatic bile ducts and common bile duct was observed in 15 (94.4%) of the patients with PC and in none of the controls (p < 0.0001). The average alcohol consumption was 1 g/day (0–5 g/day) in the PC group and 4.6 g/day (0–20 g/day) in the control group. In addition, the average smoking history was 14.25 pack-years (0–40 PY) in the PC group and 27.70 PY (0–60 PY) in the control group. Conclusion: The presence of a pancreatic mass in a patient with CCP is

  19. MiR-371-5p facilitates pancreatic cancer cell proliferation and decreases patient survival.

    Directory of Open Access Journals (Sweden)

    De He

    Full Text Available microRNAs (miRNAs play a critical role in tumorigenesis, either as a tumor suppressor or as an oncogenic miRNA, depending on different tumor types. To date, scientists have obtained a substantial amount of knowledge with regard to miRNAs in pancreatic cancer. However, the expression and function of miR-371-5p in pancreatic cancer has not been clearly elucidated. The aim of this study was to investigate the roles of miR-371-5p in pancreatic cancer and its association with the survival of patients with pancreatic cancer.The expression of miR-371-5p was examined in pancreatic duct adenocarcinoma (PDAC and their adjacent normal pancreatic tissues (ANPT or in pancreatic cancer cell lines by qRT-PCR. The association of miR-371-5p expression with overall survival was determined. The proliferation and apoptosis of SW-1990 and Panc-1 cells, transfected with miR-371-5p mimics or inhibitor, were assessed using MTT assay and flow cytometry, respectively. The tumorigenicity was evaluated via mice xenograft experiments. miR-371-5p promoter interactions were analyzed by chromatin immunoprecipitation assays (ChIP. Protein expression was analyzed by Western blot.The expression level of miR-371-5p was dramatically upregulated in clinical PDAC tissues compared with ANPT. Patients with high miR-371-5p expression had a significantly shorter survival than those with low miR-371-5p expression. The in vitro and in vivo assays showed that overexpression of miR-371-5p resulted in cell proliferation and increased tumor growth, which was associated with inhibitor of growth 1 (ING1 downregulation. Interestingly, we also found that ING1, in turn, inhibited expression of miR-371-5p in the promoter region.our study demonstrates a novel ING1-miR-371-5p regulatory feedback loop, which may have a critical role in PDAC. Thus miR-371-5p can prove to be a novel prognostic factor and therapeutic target for pancreatic cancer treatment.

  20. Vitamins in Pancreatic Cancer: A Review of Underlying Mechanisms and Future Applications12

    Science.gov (United States)

    Davis-Yadley, Ashley H; Malafa, Mokenge P

    2015-01-01

    Although there is increasing evidence that vitamins influence pancreatic adenocarcinoma biology and carcinogenesis, a comprehensive review is lacking. In this study, we performed a PubMed literature search to review the anticancer mechanisms and the preclinical and clinical studies that support the development of the bioactive vitamins A, C, D, E, and K in pancreatic cancer intervention. Preclinical studies have shown promising results for vitamin A in pancreatic cancer prevention, with clinical trials showing intriguing responses in combination with immunotherapy. For vitamin C, preclinical studies have shown slower tumor growth rates and/or increased survival when used alone or in combination with gemcitabine, with clinical trials with this combination revealing decreased primary tumor sizes and improved performance status. Preclinical studies with vitamin D analogues have shown potent antiproliferative effects and repression of migration and invasion of pancreatic cancer cells, with a clinical trial showing increased time to progression when calciferol was added to docetaxel. For vitamin E, preclinical studies have shown that δ-tocotrienol and γ-tocotrienol inhibited tumor cell growth and survival and augmented gemcitabine activity. Early-phase clinical trials with δ-tocotrienol are ongoing. Vitamin K demonstrates activation of apoptosis and inhibition of cellular growth in pancreatic tumor cells; however, there are no clinical studies available for further evaluation. Although preclinical and clinical studies are encouraging, randomized controlled trials with endpoints based on insights gained from mechanistic and preclinical studies and early-phase clinical trials are required to determine the efficacy of bioactive vitamin interventions in pancreatic cancer. PMID:26567201

  1. Pancreatic cancer stimulates pancreatic stellate cell proliferation and TIMP-1 production through the MAP kinase pathway

    International Nuclear Information System (INIS)

    Yoshida, Seiya; Yokota, Tokuyasu; Ujiki, Michael; Ding Xianzhong; Pelham, Carolyn; Adrian, Thomas E.; Talamonti, Mark S.; Bell, Richard H.; Denham, Woody

    2004-01-01

    Pancreatic adenocarcinoma is characterized by an intense desmoplastic reaction that surrounds the tumor. Pancreatic stellate cells (PSCs) are thought to be responsible for production of this extracellular matrix. When activated, PSCs have a myofibroblast phenotype and produce not only components of the extracellular matrix including collagen, fibronectin, and laminin, but also matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). Since PSCs are found in the stroma surrounding human pancreatic adenocarcinoma, we postulate that pancreatic cancer could impact PSC proliferation and TIMP-1 production. Rat PSCs were isolated and cultured. Isolated PSCs were exposed to PANC-1 conditioned medium (CM) and proliferation, activation of the mitogen-activated protein (MAP) kinase pathway, and TIMP-1 gene induction were determined. Exposure to PANC-1 CM increased PSC DNA synthesis, cell number, and TIMP-1 mRNA (real-time PCR) as well as activating the extracellular-regulated kinase (ERK) 1/2. Inhibition of ERK 1/2 phosphorylation (U0126) prevented the increases in growth and TIMP-1 expression. PANC-1 CM stimulates PSC proliferation and TIMP-1 through the MAP kinase (ERK 1/2) pathway

  2. Fast neutron irradiation for locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Smith, F.P.; Schein, P.S.; MacDonald, J.S.; Woolley, P.V.; Ornitz, R.; Rogers, C.

    1981-01-01

    Nineteen patients with locally advanced pancreatic cancer and one patient with islet cell cancer were treated with 1700-1500 neutron rad alone or in combination with 5-fluorouracil to exploit the theoretic advantages of higher linear energy of transfer, and lower oxygen enhancement ratio of neutrons. Only 5 of 14 (36%) obtained partial tumor regression. The median survival for all patients with pancreatic cancer was 6 months, which is less than that reported with 5-fluorouracil and conventional photon irradiation. Gastrointestinal toxicity was considerable; hemorhagic gastritis in five patients, colitis in two and esophagitis in one. One patient developed radiation myelitis. We therefore, caution any enthusiasm for this modality of therapy until clear evidence of a therapeutic advantage over photon therapy is demonstrated in controlled clinical trials

  3. Fast neutron irradiation for locally advanced pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Smith, F.P. (Georgetown Univ. Medical Center, Washington, DC); Schein, P.S.; MacDonald, J.S.; Woolley, P.V.; Ornitz, R.; Rogers, C.

    1981-11-01

    Nineteen patients with locally advanced pancreatic cancer and one patient with islet cell cancer were treated with 1700-1500 neutron rad alone or in combination with 5-fluorouracil to exploit the theoretic advantages of higher linear energy of transfer, and lower oxygen enhancement ratio of neutrons. Only 5 of 14 (36%) obtained partial tumor regression. The median survival for all patients with pancreatic cancer was 6 months, which is less than that reported with 5-fluorouracil and conventional photon irradiation. Gastrointestinal toxicity was considerable; hemorhagic gastritis in five patients, colitis in two and esophagitis in one. One patient developed radiation myelitis. We therefore, caution any enthusiasm for this modality of therapy until clear evidence of a therapeutic advantage over photon therapy is demonstrated in controlled clinical trials.

  4. High-Intensity Focused Ultrasound Treatment for Advanced Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Yufeng Zhou

    2014-01-01

    Full Text Available Pancreatic cancer is under high mortality but has few effective treatment modalities. High-intensity focused ultrasound (HIFU is becoming an emerging approach of noninvasively ablating solid tumor in clinics. A variety of solid tumors have been tried on thousands of patients in the last fifteen years with great success. The principle, mechanism, and clinical outcome of HIFU were introduced first. All 3022 clinical cases of HIFU treatment for the advanced pancreatic cancer alone or in combination with chemotherapy or radiotherapy in 241 published papers were reviewed and summarized for its efficacy, pain relief, clinical benefit rate, survival, Karnofsky performance scale (KPS score, changes in tumor size, occurrence of echogenicity, serum level, diagnostic assessment of outcome, and associated complications. Immune response induced by HIFU ablation may become an effective way of cancer treatment. Comments for a better outcome and current challenges of HIFU technology are also covered.

  5. Effect of Protein Hydrolysates on Pancreatic Cancer Cells

    DEFF Research Database (Denmark)

    Ossum, Carlo G.; Andersen, Lisa Lystbæk; Nielsen, Henrik Hauch

    Effect of Fish Protein Hydrolysates on Pancreatic Cancer Cells Carlo G. Ossum1, Lisa Lystbæk Andersen2, Henrik Hauch Nielsen2, Else K. Hoffmann1, and Flemming Jessen2 1University of Copenhagen, Department of Biology, Denmark, 2Technical University of Denmark (DTU), National Food Institute, Denmark...... hydrolysates obtained by enzymatic hydrolysis on cancer cell proliferation. Skin and belly flap muscle from trout were hydrolysed with the unspecific proteases Alcalase, Neutrase, or UE1 (all from Novozymes, Bagsværd, Denmark) to a hydrolysis degree of 1-15%. The hydrolysates were tested for biological...... activities affecting cell proliferation and ability to modulate caspase activity in pancreatic cancer cells COLO357 and BxPC-3 in vitro. A number of the hydrolysates showed caspase promoting activity; in particular products containing muscle tissue, i.e. belly flap, were able to stimulate caspase activity...

  6. Imaging pancreatic cancer using bioconjugated InP quantum dots.

    Science.gov (United States)

    Yong, Ken-Tye; Ding, Hong; Roy, Indrajit; Law, Wing-Cheung; Bergey, Earl J; Maitra, Anirban; Prasad, Paras N

    2009-03-24

    In this paper, we report the successful use of non-cadmium-based quantum dots (QDs) as highly efficient and nontoxic optical probes for imaging live pancreatic cancer cells. Indium phosphide (core)-zinc sulfide (shell), or InP/ZnS, QDs with high quality and bright luminescence were prepared by a hot colloidal synthesis method in nonaqueous media. The surfaces of these QDs were then functionalized with mercaptosuccinic acid to make them highly dispersible in aqueous media. Further bioconjugation with pancreatic cancer specific monoclonal antibodies, such as anticlaudin 4 and antiprostate stem cell antigen (anti-PSCA), to the functionalized InP/ZnS QDs, allowed specific in vitro targeting of pancreatic cancer cell lines (both immortalized and low passage ones). The receptor-mediated delivery of the bioconjugates was further confirmed by the observation of poor in vitro targeting in nonpancreatic cancer based cell lines which are negative for the claudin-4-receptor. These observations suggest the immense potential of InP/ZnS QDs as non-cadmium-based safe and efficient optical imaging nanoprobes in diagnostic imaging, particularly for early detection of cancer.

  7. Current options for palliative treatment in patients with pancreatic cancer.

    Science.gov (United States)

    Ridwelski, K; Meyer, F

    2001-01-01

    Palliative treatment is often the only remaining option in the management of pancreatic carcinoma, but its efficacy is poor due to low tumor sensitivity and inadequate treatment protocols. There are several options of palliative treatment with antitumor or supportive intention. Classical end points of palliative treatment are survival, tumor response, and quality of life. A decade ago, palliative chemotherapy consisted mainly of 5-fluorouracil as the standard agent in combination with either other agents and/or radiotherapy. Only the new antineoplastic drug gemcitabine, which was introduced simultaneously with the definition of novel end points of chemotherapy such as clinical benefit, allowed to achieve some progress. However, while gemcitabine monotherapy appeared to be superior to 5-fluorouracil and improved important parameters of quality of life, it could not provide a significant improvement of survival. A novel concept, therefore, is to improve this beneficial cytostatic response in pancreatic carcinoma using a gemcitabine-based protocol by combining it with antineoplastic drugs such as taxanes or platin analogs. This strategy may have the potential to improve the outcome in palliative chemotherapy of pancreatic carcinoma patients with advanced tumor growth or metastases. Best supportive care in pancreatic cancer consists of the treatment of symptoms, such as pain, jaundice, duodenal obstruction, weight loss, exocrine pancreatic insufficiency, and tumor-associated depression. Copyright 2001 S. Karger AG, Basel

  8. Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: a nested case-control study: plasma micronutrients and pancreatic cancer risk.

    Science.gov (United States)

    Jeurnink, Suzanne M; Ros, Martine M; Leenders, Max; van Duijnhoven, Franzel J B; Siersema, Peter D; Jansen, Eugene H J M; van Gils, Carla H; Bakker, Marije F; Overvad, Kim; Roswall, Nina; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Racine, Antoine; Cadeau, Claire; Grote, Verena; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vasiliki; Valanou, Elisavet; Palli, Domenico; Krogh, Vittorio; Vineis, Paolo; Tumino, Rosario; Mattiello, Amalia; Weiderpass, Elisabete; Skeie, Guri; Castaño, José María Huerta; Duell, Eric J; Barricarte, Aurelio; Molina-Montes, Esther; Argüelles, Marcial; Dorronsoro, Mire; Johansen, Dorthe; Lindkvist, Björn; Sund, Malin; Crowe, Francesca L; Khaw, Kay-Tee; Jenab, Mazda; Fedirko, Veronika; Riboli, E; Bueno-de-Mesquita, H B

    2015-03-15

    Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (α- and β-carotene, lycopene, β-cryptoxanthin, canthaxanthin, zeaxanthin and lutein), α- and γ-tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma β-carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend = 0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend = 0.06) and α-tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend = 0.08. For α- and β-carotene, lutein, sum of carotenoids and γ-tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of β-carotene, zeaxanthin and α-tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted. © 2014 UICC.

  9. Alleviating Pancreatic Cancer-Associated Pain Using Endoscopic Ultrasound-Guided Neurolysis

    Science.gov (United States)

    Takenaka, Mamoru; Kamata, Ken; Yoshikawa, Tomoe; Nakai, Atsushi; Omoto, Shunsuke; Miyata, Takeshi; Yamao, Kentaro; Imai, Hajime; Sakamoto, Hiroki; Kitano, Masayuki; Kudo, Masatoshi

    2018-01-01

    The most common symptom in patients with advanced pancreatic cancer is abdominal pain. This has traditionally been treated with nonsteroidal anti-inflammatory drugs and opioid analgesics. However, these treatments result in inadequate pain control or drug-related adverse effects in some patients. An alternative pain-relief modality is celiac plexus neurolysis, in which the celiac plexus is chemically ablated. This procedure was performed percutaneously or intraoperatively until 1996, when endoscopic ultrasound (EUS)-guided celiac plexus neurolysis was first described. In this transgastric anterior approach, a neurolytic agent is injected around the celiac trunk under EUS guidance. The procedure gained popularity as a minimally invasive approach and is currently widely used to treat pancreatic cancer-associated pain. We focus on two relatively new techniques of EUS-guided neurolysis: EUS-guided celiac ganglia neurolysis and EUS-guided broad plexus neurolysis, which have been developed to improve efficacy. Although the techniques are safe and effective in general, some serious adverse events including ischemic and infectious complications have been reported as the procedure has gained widespread popularity. We summarize reported clinical outcomes of EUS-guided neurolysis in pancreatic cancer (from the PubMed and Embase databases) with a goal of providing information useful in developing strategies for pancreatic cancer-associated pain alleviation. PMID:29462851

  10. Concurrent chemoradiotherapy with gemcitabine and cisplatin for pancreatic cancer: from the laboratory to the clinic

    International Nuclear Information System (INIS)

    Symon, Zvi; Davis, Mary; McGinn, Cornelius J.; Zalupski, Mark M.; Lawrence, Theodore S.

    2002-01-01

    Purpose: We have reported that gemcitabine and concurrent radiation is a promising therapy for patients with pancreatic cancer. We investigated whether the addition of cisplatin, which may increase the systemic efficacy of gemcitabine, would be synergistic with gemcitabine and/or radiation in human pancreatic cancer cell lines. Methods and Materials: BxPc3 and Panc-1 human pancreatic cancer cells were treated with three different schedules before radiation: (A) a sequential incubation of gemcitabine for 2 h followed by cisplatin for 2 h, (B) gemcitabine for 2 h, followed by washout of drug, replenishment of media for a 24-h incubation, followed by cisplatin for 2 h, and (C) gemcitabine for 24 h with a concurrent incubation of cisplatin for the last 2 h. Cells were assessed for clonogenic survival using a standard assay. Synergism was evaluated by the median effect analysis. Results: The schedule shown to be maximally synergistic for both cell lines was the consecutive 2-h gemcitabine, 2-h cisplatin exposure, particularly at surviving fractions of <0.5. Cisplatin did not produce radiosensitization nor did it affect gemcitabine-mediated radiosensitization. Conclusion: Cisplatin produces synergistic cytotoxicity with gemcitabine without compromising gemcitabine-mediated radiosensitization. On the basis of these laboratory and previous clinical observations, we have initiated a Phase I trial of cisplatin plus gemcitabine and radiotherapy in patients with unresectable pancreatic cancer

  11. Fasting plasma carotenoids concentrations in Crohn's and pancreatic cancer patients compared to control subjects.

    Science.gov (United States)

    Drai, J; Borel, P; Faure, H; Galabert, C; Le Moël, G; Laromiguière, M; Fayol, V

    2009-03-01

    Carotenoids are colored molecules that are widespread in the plant kingdom, but animals cannot synthesize them. Carotenes are long, apolar molecules which require fully functioning digestive processes to be absorbed properly. Hence they could be interesting markers of intestinal absorption and digestion. Indeed, only few tests are available to assess these processes and only the D-xylose tolerance test is routinely used. However D-xylose is a sugar that tests only the absorption of water-soluble compounds and it only tests duodenal absorption. In this study, we have evaluated carotenoids as markers of digestion and absorption. We compared fasting plasma carotenoids concentrations in 21 control subjects, 20 patients with Crohn's disease, and 18 patients with pancreatic cancer. Crohn's disease alters intestinal absorption while pancreatic cancer decreases pancreatic enzyme secretion thus impairing digestion. Results show that all carotenoids are significantly lower in Crohn's and cancer patients as compared to control subjects and the multifactorial analysis shows that this decrease is mostly independent of dietary intake. Interestingly, maldigestion as seen in pancreatic cancer more strongly influences plasma lutein and lycopene concentrations while malabsorption in Crohn's disease acts on other carotenoids. Thus carotenoids could be interesting alternatives for testing and following patients that are suspected of having malabsorption or maldigestion syndromes.

  12. Dynamic MR imaging of pancreatic cancer

    International Nuclear Information System (INIS)

    Akaki, Shiro; Kohno, Yoshihiro; Gohbara, Hideo

    1994-01-01

    Dynamic MRI was performed on 21 patients with pancreatic duct cell carcinoma. Turbo-FLASH or FLASH3D was performed immediately following rapid bolus injection of gadopentetate dimeglumine, and these FLASH images and conventional spin echo images were evaluated about detectability of the lesion. All images were classified into three groups of detectability of the lesion ; good, fair, and poor. On T 1 weighted image, 23% of cases were 'good' and 48% were evaluated as 'fair'. On the other hand, on dynamic MRI, 62% of cases were 'good' and 33% of cases were evaluated as 'fair'. Both T 2 weighted image and enhanced T 1 weighted image were not useful for depiction of the lesion. Direct comparison between T 1 weighted image and dynamic MRI was also done. In 55% of cases, dynamic MRI was superior to T 1 weighted image and in 40% of cases, dynamic MRI was equal to T 1 weighted image. Thus, dynamic MRI was superior to conventional spin echo images for detection of duct cell carcinoma. In 17 patients of duct cell carcinoma who underwent FLASH3D, contrast/noise ratio (CNR) was calculated before and after injection of gadopentetate dimeglumine. The absolute value of CNR became significantly larger by injection of contrast material. In nine resectable pancreatic carcinomas, two cases of INF α and two cases of medullary type were well depicted. It was concluded that dynamic MRI was useful for evaluation of pancreatic carcinoma. (author)

  13. Chronic pancreatitis: indications to surgery and remote results assessment criteria

    Directory of Open Access Journals (Sweden)

    A. V. Klimenko

    2013-06-01

    Full Text Available Present indications to surgery include intractable pain syndrome, severe dilation of the Wirsung’s duct, strictures and stones in the Wirsung’s duct, pancreatic pseudocysts, duodenal stenosis and obstructive jaundice because of “inflammatory mass” in the pancreatic head. But these absolute indications mean that in the most cases pancreatic exocrine and endocrine functions are already decompensated. Therefore it is important to produce new indications to surgical treatment of the CP in early stages. Also it is necessary to make such remote results assessment criteria that will allow to range among parenchymapreserving and resectional technics according to anatomical and functional parameters. Goal: to adjust indications to surgical treatment of the CP according to leading pathogenetic factors and develop criteria to assess remote results. Patients and methods: 122 CP patients have undergone surgery. There were 103 (84,4% men and – 19 (15,6% women, mean age - 45. Alcohol etiology of the CP was in 79 (64,8% patients, postpancreonecrotic – in 29 (23,8%, biliary – in 6 (4,9%, idiopathic – in 8 (6,6%. Wirsung’s duct diameter of 4 – 8 mm – was in 65 (53,3% patients, 8 – 12 and more – in 57 (46,7%. By Shalimov classification there were “pseudotumorous” – in 39 (31,9%, “calculouse” – in 40 (32,8%, fibrose-cystic – in 17 (13,9%, fibrose-degenerative with adjacent organs involvement and hampering of their function – in 26 (21,4% patients. All patients had pain syndrome and 79 (64,8% – exocrine and endocrine insufficiency. All patients underwent abdominal CT-scan, fecal elastase test, C-peptide, endogenic insulin, glucose, immunehystochemical investigation of biopsy samples taken from body corpus and tale simultaneously etc. Results: We have found that gastroenterologists poorly recognize “surgical” type of CP and restrain patients from being directed to surgical pancreatologists for surgical therapy. We

  14. Accelerated radiochemotherapy in pancreatic cancer is not necessarily related to a pathologic pancreatic function decline in the early period

    International Nuclear Information System (INIS)

    Horst, Eckehard; Seidel, Matthias; Micke, Oliver; Ruebe, Christian; Glashoerster, Marco; Schaefer, Ulrich; Willich, Normann A.

    2002-01-01

    Purpose: To evaluate the functional effects of ionizing radiation in patients with unresectable pancreatic cancer in the early period after accelerated radiochemotherapy (ART). Methods and Materials: To analyze the exocrine component, the amino acid consumption test and fecal elastase 1 were performed in 13 patients immediately before and 4-8 weeks after ART. Pancreatic duct morphology was evaluated before therapy. Weight loss and clinical steatorrhea were recorded. Endocrine parameters were examined according to standardized criteria. Results: The relative change of the amino acid consumption test results and the median elastase concentration was 41.2% and 56.4%, respectively. Five patients still had normal test results after ART and 5 patients developed pathologic values. The median relative weight loss of the total body weight was 7.7% ± 4.5%. No steatorrhea occurred. Of the 5 patients with normal values, 3 had a mean organ dose of 41 Gy. The endocrine function measurements remained unchanged. Conclusion: Although a nominal reduction of exocrine function parameters occurred in most patients, ART was not necessarily related to a pathologic level in the early period. Diabetes was not established. The functional impairment that was existent in the patient population presumably contributed to the weight loss. Pancreatic enzyme preparations may also play a role in maintaining an anabolic state during and after radiochemotherapy

  15. Evaluation of pancreatic cancer by multiple breath-hold dynamic contrast-enhanced magnetic resonance imaging at 3.0 T

    International Nuclear Information System (INIS)

    Yao, Xiuzhong; Zeng, Mengsu; Wang, He; Sun, Fei; Rao, Shengxiang; Ji, Yuan

    2012-01-01

    Objective: To investigate the microcirculation in pancreatic cancer by pharmacokinetic analysis of multiple breath-hold dynamic contrast-enhanced magnetic resonance imaging at 3.0 T. Materials and methods: Multiple breath-hold dynamic contrast-enhanced magnetic resonance imaging was performed in 40 healthy volunteers and 40 patients with pancreatic cancer proven by histopathology using an axial three-dimensions fat-saturated T1-weighted spoiled-gradient echo sequence at 3.0 T. A two compartment model with T1 correction was used to quantify the transfer constant, the rate constant of backflux from the extravascular extracellular space to the plasma and the extravascular extracellular space fractional volume in pancreatic cancer, obstructive pancreatitis distal to the malignant tumor, adjacent pancreatic tissue proximal to the tumor and normal pancreas. All parameters were statistically analyzed. Results: Statistical differences were noticed in both the transfer constant (p = 0.000075) and the rate constant of backflux (p = 0.006) among different tissues. Both the transfer constant and the rate constant of backflux in pancreatic cancer were statistically lower than those in normal pancreas and adjacent pancreatic tissue (p < 0.05). Both the transfer constant and the rate constant of backflux in obstructive pancreatitis were statistically lower than those in normal pancreas and adjacent pancreatic tissue (p < 0.05). The extravascular extracellular space fractional volume in pancreatic cancer was statistically lager than that in normal pancreas (p = 0.002). Conclusion: Multiple breath-hold dynamic contrast-enhanced magnetic resonance imaging offers a useful technique to evaluate the microenvironment in pancreatic cancer at 3.0 T. Compared to normal pancreas, pancreatic cancer has lower transfer constant, rate constant of backflux and larger extravascular extracellular space fractional volume.

  16. Evaluation of pancreatic cancer by multiple breath-hold dynamic contrast-enhanced magnetic resonance imaging at 3.0 T

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Xiuzhong, E-mail: yao.xiuzhong@zs-hospital.sh.cn [Department of Radiology, Zhongshan Hospital of Fudan University and Department of Medical Image, Shanghai Medical College of Fudan University, No. 138, Fenglin Road, Xuhui District, Shanghai 200032 (China); Zeng, Mengsu, E-mail: zengmengsu@gmail.com [Department of Radiology, Zhongshan Hospital of Fudan University and Department of Medical Image, Shanghai Medical College of Fudan University, No. 138, Fenglin Road, Xuhui District, Shanghai 200032 (China); Wang, He, E-mail: herry258@hotmail.com [Global Applied Science Laboratory of GE Healthcare, No. 1, Huatuo Road, Zhangjiang Hi-tech Park, Pudong District, Shanghai 201203 (China); Sun, Fei, E-mail: fei.sun@med.ge.com [Global Applied Science Laboratory of GE Healthcare, No. 1, Huatuo Road, Zhangjiang Hi-tech Park, Pudong District, Shanghai 201203 (China); Rao, Shengxiang, E-mail: rao.shengxiang@zs-hospital.sh.cn [Department of Radiology, Zhongshan Hospital of Fudan University and Department of Medical Image, Shanghai Medical College of Fudan University, No. 138, Fenglin Road, Xuhui District, Shanghai 200032 (China); Ji, Yuan, E-mail: Ji.yuan@zs-hospital.sh.cn [Department of Pathology, Zhongshan Hospital of Fudan University, No. 138, Fenglin Road, Xuhui District, Shanghai 200032 (China)

    2012-08-15

    Objective: To investigate the microcirculation in pancreatic cancer by pharmacokinetic analysis of multiple breath-hold dynamic contrast-enhanced magnetic resonance imaging at 3.0 T. Materials and methods: Multiple breath-hold dynamic contrast-enhanced magnetic resonance imaging was performed in 40 healthy volunteers and 40 patients with pancreatic cancer proven by histopathology using an axial three-dimensions fat-saturated T1-weighted spoiled-gradient echo sequence at 3.0 T. A two compartment model with T1 correction was used to quantify the transfer constant, the rate constant of backflux from the extravascular extracellular space to the plasma and the extravascular extracellular space fractional volume in pancreatic cancer, obstructive pancreatitis distal to the malignant tumor, adjacent pancreatic tissue proximal to the tumor and normal pancreas. All parameters were statistically analyzed. Results: Statistical differences were noticed in both the transfer constant (p = 0.000075) and the rate constant of backflux (p = 0.006) among different tissues. Both the transfer constant and the rate constant of backflux in pancreatic cancer were statistically lower than those in normal pancreas and adjacent pancreatic tissue (p < 0.05). Both the transfer constant and the rate constant of backflux in obstructive pancreatitis were statistically lower than those in normal pancreas and adjacent pancreatic tissue (p < 0.05). The extravascular extracellular space fractional volume in pancreatic cancer was statistically lager than that in normal pancreas (p = 0.002). Conclusion: Multiple breath-hold dynamic contrast-enhanced magnetic resonance imaging offers a useful technique to evaluate the microenvironment in pancreatic cancer at 3.0 T. Compared to normal pancreas, pancreatic cancer has lower transfer constant, rate constant of backflux and larger extravascular extracellular space fractional volume.

  17. Resveratrol-Induced Downregulation of NAF-1 Enhances the Sensitivity of Pancreatic Cancer Cells to Gemcitabine via the ROS/Nrf2 Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Liang Cheng

    2018-01-01

    Full Text Available NAF-1 (nutrient-deprivation autophagy factor-1, which is an outer mitochondrial membrane protein, is known to play important roles in calcium metabolism, antiapoptosis, and antiautophagy. Resveratrol, a natural polyphenolic compound, is considered as a potent anticancer agent. Nevertheless, the molecular mechanisms underlying the effects of resveratrol and NAF-1 and their mediation of drug resistance in pancreatic cancer remain unclear. Here, we demonstrate that resveratrol suppresses the expression of NAF-1 in pancreatic cancer cells by inducing cellular reactive oxygen species (ROS accumulation and activating Nrf2 signaling. In addition, the knockdown of NAF-1 activates apoptosis and impedes the proliferation of pancreatic cancer cells. More importantly, the targeting of NAF-1 by resveratrol can improve the sensitivity of pancreatic cancer cells to gemcitabine. These results highlight the significance of strategies that target NAF-1, which may enhance the efficacy of gemcitabine in pancreatic cancer therapy.

  18. Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis

    Directory of Open Access Journals (Sweden)

    Nelson S. Yee

    2015-03-01

    Full Text Available Our previous studies in zebrafish development have led to identification of the novel roles of the transient receptor potential melastatin-subfamily member 7 (TRPM7 ion channels in human pancreatic cancer. However, the biological significance of TRPM7 channels in pancreatic neoplasms was mostly unexplored. In this study, we determined the expression levels of TRPM7 in pancreatic tissue microarrays and correlated these measurements in pancreatic adenocarcinoma with the clinicopathological features. We also investigated the role of TRPM7 channels in pancreatic cancer cell invasion using the MatrigelTM-coated transwell assay. In normal pancreas, TRPM7 is expressed at a discernable level in the ductal cells and centroacinar cells and at a relatively high level in the islet endocrine cells. In chronic pancreatitis, pre-malignant tissues, and malignant neoplasms, there is variable expression of TRPM7. In the majority of pancreatic adenocarcinoma specimens examined, TRPM7 is expressed at either moderate-level or high-level. Anti-TRPM7 immunoreactivity in pancreatic adenocarcinoma significantly correlates with the size and stages of tumors. In human pancreatic adenocarcinoma cells in which TRPM7 is highly expressed, short hairpin RNA-mediated suppression of TRPM7 impairs cell invasion. The results demonstrate that TRPM7 channels are over-expressed in a proportion of the pre-malignant lesions and malignant tumors of the pancreas, and they are necessary for invasion by pancreatic cancer cells. We propose that TRPM7 channels play important roles in development and progression of pancreatic neoplasm, and they may be explored as clinical biomarkers and targets for its prevention and treatment.

  19. Clinical efficacy of CT-guided 125I seed implantation therapy for advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Wang Zhongmin; Lu Jian; Gong Ju; Zheng Yunfeng; Zhang Liyun; Huang Gang; Chen Kemin

    2009-01-01

    Objective: To discuss the clinical efficacy of CT-guided radioactive 125 I seed implantation treatment for unresectable pancreatic cancer. Methods: Forty patients with inoperable pancreatic cancer were enrolled in this study, including 25 males and 15 females with an median age of 69 years (38-89 years). Treatment planning system (TPS) was used to reconstruct 3-dimensional images of pancreatic tumor and to define the quantity and distribution of 125 I seeds. The radioactivity of 125 I seeds was 0.5 - 0.8 mCi / seed. The seeds were implanted into pancreatic tumor under CT guidance at intervals of 1 cm and were kept away from vessels, pancreatic duct and other adjacent important organs. The tumor matched peripheral dose (MPD) was 60-140 Gy. The median amount of implanted 125 I seeds was 36 (18-68) in number. CT scan was performed immediately after the procedure to check the quality of the seeds. In addition, 10 patients received concurrent chemotherapy with arterial infusion of gemcitabin and 5-fluororacil (5-Fu) for 3 to 4 therapeutic courses. Results: The median diameter of the tumors was 4.9 cm. The follow-up period was 2 to 28 months. After the treatment the refractory pain was significantly relieved (P 125 I seed implantation is a safe, effective and minimally-invasive brachytherapy for unresectable pancreatic cancer with reliable short-term efficacy. It has an excellent anti-pain effect. The curative results can be further improved when chemotherapy is employed together. However, its long-term efficacy needs to be observed. (authors)

  20. Whole genomes redefine the mutational landscape of pancreatic cancer.

    Science.gov (United States)

    Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K; Kassahn, Karin S; Bailey, Peter; Johns, Amber L; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C J; Robertson, Alan J; Fadlullah, Muhammad Z H; Bruxner, Tim J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Wilson, Peter J; Markham, Emma; Cloonan, Nicole; Anderson, Matthew J; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen H; Leonard, Conrad; Newell, Felicity; Poudel, Barsha; Song, Sarah; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Lee, Hong C; Jones, Marc D; Nagrial, Adnan M; Humphris, Jeremy; Chantrill, Lorraine A; Chin, Venessa; Steinmann, Angela M; Mawson, Amanda; Humphrey, Emily S; Colvin, Emily K; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Pettitt, Jessica A; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; Graham, Janet S; Niclou, Simone P; Bjerkvig, Rolf; Grützmann, Robert; Aust, Daniela; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Falconi, Massimo; Zamboni, Giuseppe; Tortora, Giampaolo; Tempero, Margaret A; Gill, Anthony J; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Pearson, John V; Biankin, Andrew V; Grimmond, Sean M

    2015-02-26

    Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.

  1. Whole genomes redefine the mutational landscape of pancreatic cancer

    Science.gov (United States)

    Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K.; Kassahn, Karin S.; Bailey, Peter; Johns, Amber L.; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C. J.; Robertson, Alan J.; Fadlullah, Muhammad Z. H.; Bruxner, Tim J. C.; Christ, Angelika N.; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Wilson, Peter J; Markham, Emma; Cloonan, Nicole; Anderson, Matthew J.; Fink, J. Lynn; Holmes, Oliver; Kazakoff, Stephen H.; Leonard, Conrad; Newell, Felicity; Poudel, Barsha; Song, Sarah; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J.; Lee, Hong C.; Jones, Marc D.; Nagrial, Adnan M.; Humphris, Jeremy; Chantrill, Lorraine A.; Chin, Venessa; Steinmann, Angela M.; Mawson, Amanda; Humphrey, Emily S.; Colvin, Emily K.; Chou, Angela; Scarlett, Christopher J.; Pinho, Andreia V.; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S.; Kench, James G.; Pettitt, Jessica A.; Merrett, Neil D.; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q.; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B.; Graham, Janet S.; Niclou, Simone P.; Bjerkvig, Rolf; Grützmann, Robert; Aust, Daniela; Hruban, Ralph H.; Maitra, Anirban; Iacobuzio-Donahue, Christine A.; Wolfgang, Christopher L.; Morgan, Richard A.; Lawlor, Rita T.; Corbo, Vincenzo; Bassi, Claudio; Falconi, Massimo; Zamboni, Giuseppe; Tortora, Giampaolo; Tempero, Margaret A.; Gill, Anthony J.; Eshleman, James R.; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A.; Pearson, John V.; Biankin, Andrew V.; Grimmond, Sean M.

    2015-01-01

    Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. PMID:25719666

  2. Exosomes derived from pancreatic cancer cells induce activation and profibrogenic activities in pancreatic stellate cells.

    Science.gov (United States)

    Masamune, Atsushi; Yoshida, Naoki; Hamada, Shin; Takikawa, Tetsuya; Nabeshima, Tatsuhide; Shimosegawa, Tooru

    2018-01-01

    Pancreatic cancer cells (PCCs) interact with pancreatic stellate cells (PSCs), which play a pivotal role in pancreatic fibrogenesis, to develop the cancer-conditioned tumor microenvironment. Exosomes are membrane-enclosed nanovesicles, and have been increasingly recognized as important mediators of cell-to-cell communications. The aim of this study was to clarify the effects of PCC-derived exosomes on cell functions in PSCs. Exosomes were isolated from the conditioned medium of Panc-1 and SUIT-2 PCCs. Human primary PSCs were treated with PCC-derived exosomes. PCC-derived exosomes stimulated the proliferation, migration, activation of ERK and Akt, the mRNA expression of α-smooth muscle actin (ACTA2) and fibrosis-related genes, and procollagen type I C-peptide production in PSCs. Ingenuity pathway analysis of the microarray data identified transforming growth factor β1 and tumor necrosis factor as top upstream regulators. PCCs increased the expression of miR-1246 and miR-1290, abundantly contained in PCC-derived exosomes, in PSCs. Overexpression of miR-1290 induced the expression of ACTA2 and fibrosis-related genes in PSCs. In conclusion, PCC-derived exosomes stimulate activation and profibrogenic activities in PSCs. Exosome-mediated interactions between PSCs and PCCs might play a role in the development of the tumor microenvironment. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Laparoscopic versus open distal pancreatectomy for pancreatic cancer.

    Science.gov (United States)

    Riviere, Deniece; Gurusamy, Kurinchi Selvan; Kooby, David A; Vollmer, Charles M; Besselink, Marc G H; Davidson, Brian R; van Laarhoven, Cornelis J H M

    2016-04-04

    (MD -2.43 days, 95% CI -3.13 to -1.73; 1068 participants; five studies; I(2) = 0%). None of the included studies reported quality of life at any point in time, recurrence within six months, time to return to normal activity and time to return to work or blood transfusion requirements. Currently, no randomised controlled trials have compared laparoscopic distal pancreatectomy versus open distal pancreatectomy for patients with pancreatic cancers. In observational studies, laparoscopic distal pancreatectomy has been associated with shorter hospital stay as compared with open distal pancreatectomy. Currently, no information is available to determine a causal association in the differences between laparoscopic versus open distal pancreatectomy. Observed differences may be a result of confounding due to laparoscopic operation on less extensive cancer and open surgery on more extensive cancer. In addition, differences in length of hospital stay are relevant only if laparoscopic and open surgery procedures are equivalent oncologically. This information is not available currently. Thus, randomised controlled trials are needed to compare laparoscopic distal pancreatectomy versus open distal pancreatectomy with at least two to three years of follow-up. Such studies should include patient-oriented outcomes such as short-term mortality and long-term mortality (at least two to three years); health-related quality of life; complications and the sequelae of complications; resection margins; measures of earlier postoperative recovery such as length of hospital stay, time to return to normal activity and time to return to work (in those who are employed); and recurrence of cancer.

  4. In vivo imaging of pancreatic tumours and liver metastases using 7 Tesla MRI in a murine orthotopic pancreatic cancer model and a liver metastases model

    Directory of Open Access Journals (Sweden)

    Hadlich Stefan

    2011-01-01

    Full Text Available Abstract Background Pancreatic cancer is the fourth leading cause of tumour death in the western world. However, appropriate tumour models are scarce. Here we present a syngeneic murine pancreatic cancer model using 7 Tesla MRI and evaluate its clinical relevance and applicability. Methods 6606PDA murine pancreatic cancer cells were orthotopically injected into the pancreatic head. Liver metastases were induced through splenic injection. Animals were analyzed by MRI three and five weeks following injection. Tumours were detected using T2-weighted high resolution sequences. Tumour volumes were determined by callipers and MRI. Liver metastases were analyzed using gadolinium-EOB-DTPA and T1-weighted 3D-Flash sequences. Tumour blood flow was measured using low molecular gadobutrol and high molecular gadolinium-DTPA. Results MRI handling and applicability was similar to human systems, resolution as low as 0.1 mm. After 5 weeks tumour volumes differed significantly (p 3+/-243 mm3 with MRI (mean 918 mm3+/-193 mm3 with MRI being more precise. Histology (n = 5 confirmed MRI tumour measurements (mean size MRI 38.5 mm2+/-22.8 mm2 versus 32.6 mm2+/-22.6 mm2 (histology, p 3+/-56.7 mm3 after 5 weeks. Lymphnodes were also easily identified. Tumour accumulation of gadobutrol was significantly (p Conclusions This model permits monitoring of tumour growth and metastasis formation in longitudinal non-invasive high-resolution MR studies including using contrast agents comparable to human pancreatic cancer. This multidisciplinary environment enables radiologists, surgeons and physicians to further improve translational research and therapies of pancreatic cancer.

  5. Nutrition Following Pancreatic Surgery

    Science.gov (United States)

    ... BACK Contact Us DONATE NOW GENERAL DONATION PURPLESTRIDE Nutrition Following Pancreatic Surgery Home Facing Pancreatic Cancer Living with Pancreatic Cancer Diet and Nutrition Nutrition Following Pancreatic Surgery Ver esta página en ...

  6. Acute Pancreatitis in Children

    Science.gov (United States)

    ... a feeding tube or an IV to prevent malnutrition and improve healing. Does my child have to ... Acute Pancreatitis in Children Chronic Pancreatitis in Children Childhood Inherited Disorders Pancreatic Cancer Pancreatic Cancer Risks and ...

  7. Retinoid Signaling in Pancreatic Cancer, Injury and Regeneration

    Science.gov (United States)

    Colvin, Emily K.; Susanto, Johana M.; Kench, James G.; Ong, Vivienna N.; Mawson, Amanda; Pinese, Mark; Chang, David K.; Rooman, Ilse; O'Toole, Sandra A.; Segara, Davendra; Musgrove, Elizabeth A.; Sutherland, Robert L.; Apte, Minoti V.; Scarlett, Christopher J.; Biankin, Andrew V.

    2011-01-01

    Background Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC). These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC. Methodology/Principal Findings We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas, pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is markedly augmented throughout the parenchyma during injury and regeneration. Both chemically induced and genetically engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a consequence, we investigated Cellular Retinoid Binding Protein 1 (CRBP1), a key regulator of retinoid signaling known to play a role in breast cancer development, as a potential therapeutic target. Loss, or significant downregulation of CRBP1 was present in 70% of human PC, and was evident in the very earliest precursor lesions (PanIN-1A). However, in vitro gain and loss of function studies and CRBP1 knockout mice suggested that loss of CRBP1 expression alone was not sufficient to induce carcinogenesis or to alter PC sensitivity to retinoid based therapies. Conclusions/Significance In conclusion, retinoid signalling appears to play a role in pancreatic regeneration and carcinogenesis, but unlike breast cancer, it is not mediated directly by CRBP1. PMID:22220202

  8. Retinoid signaling in pancreatic cancer, injury and regeneration.

    Directory of Open Access Journals (Sweden)

    Emily K Colvin

    Full Text Available BACKGROUND: Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC. These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas, pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is markedly augmented throughout the parenchyma during injury and regeneration. Both chemically induced and genetically engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a consequence, we investigated Cellular Retinoid Binding Protein 1 (CRBP1, a key regulator of retinoid signaling known to play a role in breast cancer development, as a potential therapeutic target. Loss, or significant downregulation of CRBP1 was present in 70% of human PC, and was evident in the very earliest precursor lesions (PanIN-1A. However, in vitro gain and loss of function studies and CRBP1 knockout mice suggested that loss of CRBP1 expression alone was not sufficient to induce carcinogenesis or to alter PC sensitivity to retinoid based therapies. CONCLUSIONS/SIGNIFICANCE: In conclusion, retinoid signalling appears to play a role in pancreatic regeneration and carcinogenesis, but unlike breast cancer, it is not mediated directly by CRBP1.

  9. Pan-European survey on the implementation of minimally invasive pancreatic surgery with emphasis on cancer

    NARCIS (Netherlands)

    de Rooij, Thijs; Besselink, Marc G.; Shamali, Awad; Butturini, Giovanni; Busch, Olivier R.; Edwin, Bjørn; Troisi, Roberto; Fernández-Cruz, Laureano; Dagher, Ibrahim; Bassi, Claudio; Abu Hilal, Mohammad

    2016-01-01

    Minimally invasive (MI) pancreatic surgery appears to be gaining popularity, but its implementation throughout Europe and the opinions regarding its use in pancreatic cancer patients are unknown. A 30-question survey was sent between June and December 2014 to pancreatic surgeons of the European

  10. Recent Advances in Pancreatic Cancer Surgery of Relevance to the Practicing Pathologist

    NARCIS (Netherlands)

    van Rijssen, Lennart B.; Rombouts, Steffi J. E.; Walma, Marieke S.; Vogel, Jantien A.; Tol, Johanna A.; Molenaar, Isaac Q.; van Eijck, Casper H. J.; Verheij, Joanne; van de Vijver, Marc J.; Busch, Olivier R. C.; Besselink, Marc G. H.

    2016-01-01

    Recent advances in pancreatic surgery have the potential to improve outcomes for patients with pancreatic cancer. We address 3 new, trending topics in pancreatic surgery that are of relevance to the pathologist. First, increasing awareness of the prognostic impact of intraoperatively detected

  11. Study of inter-fractional variations and adaptive radiotherapy in pancreatic cancer

    International Nuclear Information System (INIS)

    Yang Chengliang; Wang Jianhua; Li Dingjie; Mao Ronghu; Li, X. Allen

    2012-01-01

    Objective: To quantitatively characterize the inter-fractional anatomy variations and advantages of dosimetry for the adaptive radiotherapy in pancreatic cancer. Methods: A total of 226 daily CT images acquired from 10 patients with pancreatic cancer treated with image-guided radiotherapy were analyzed retrospectively. Targets and organs at risk (OARs) were delineated by the atlas-based automatic segmentation and modified by the skilled physician. Various parameters,including the center of mass (COM) distance, the maximal overlap ratio (MOR) and the Dice coefficient (DC), were used to quantify the inter-fractional organ displacement and deformation. The adaptive radiation therapy (ART) was applied to handle the daily GT images. The dose distributions parameters from the ART plan were compared with those from the repositioning plan. Results: The inter-fractional anatomy variations of pancreas head were obvious in the pancreatic cancer irradiation. The mean COM distance, MOR and DC of pancreas head after the bony or soft tissue alignment and registration was (7.8 ± 1.3)mm, (87.2 ± 8.4)% and (77.2 ±7.9)% respectively. Compared with the repositioning plan, the ART plan had better target coverage and OARs sparing. For example, the mean V 100 of PTV was improved from (93.32 ± 2.89) % for repositioning plan to (96.03 ± 1.42)% for ART plan with t =2.79, P =0.008 and the mean V 50.4 for duodenum was reduced from (43.4 ± 12.71)% for the repositioning plan to (15.6 ± 6.25)% for the ART plan with t =3.52, P=0.000. Conclusions: The ART can effectively account for the obvious inter-fractional anatomy variations in pancreatic cancer irradiation and be used to escalate the radiotherapy dose for the pancreatic cancer, which will lead to a promising higher local control rate. (authors)

  12. Outcomes and Tolerability of Chemoradiation Therapy for Pancreatic Cancer Patients Aged 75 Years or Older

    International Nuclear Information System (INIS)

    Miyamoto, David T.; Mamon, Harvey J.; Ryan, David P.

    2010-01-01

    Purpose: To review the outcomes and tolerability of full-dose chemoradiation in elderly patients aged 75 years or older with localized pancreatic cancer. Methods and Materials: We retrospectively reviewed patients aged 75 years or older with nonmetastatic pancreatic cancer treated with chemoradiation therapy at two institutions from 2002 to 2007. Patients were analyzed for treatment toxicity, local recurrences, distant metastases, and survival. Results: A total of 42 patients with a median age of 78 years (range, 75-90 years) who received chemoradiation therapy for pancreatic cancer were identified. Of the patients, 24 had locally advanced disease treated with definitive chemoradiation, and 18 had disease treated with surgery and chemoradiation. Before chemoradiotherapy, the mean Eastern Cooperative Oncology Group performance status was 1.0 ± 0.8, and the mean 6-month weight loss was 5.3 ± 3.8 kg. The mean radiation dose delivered was 48.1 ± 9.2 Gy. All patients received fluoropyrimidine-based chemotherapy concurrently with radiotherapy. In all, 8 patients (19%) were hospitalized, 7 (17%) had an emergency room visit, 15 (36%) required a radiation treatment break, 3 (7%) required a chemotherapy break, 9 (21%) did not complete therapy, and 22 (49%) had at least one of these adverse events. The most common toxicities were nausea, pain, and failure to thrive. Median overall survival was 8.6 months (95% confidence interval, 7.2-13.1) in patients who received definitive chemoradiation therapy and 20.6 months (95% confidence interval, 9.5-∞) in patients who underwent resection and chemoradiation therapy. Conclusions: In this dataset of very elderly patients with pancreatic cancer and good Eastern Cooperative Oncology Group performance status, outcomes after chemoradiotherapy were similar to those among historic controls for patients with locally advanced and resected pancreatic cancer, although many patients experienced substantial treatment-related toxicity.

  13. Differences in serum concentrations of organochlorine compounds by occupational social class in pancreatic cancer

    International Nuclear Information System (INIS)

    Porta, Miquel; Bosch de Basea, Magda; Benavides, Fernando G.; Lopez, Tomas; Fernandez, Esteve; Marco, Esther; Alguacil, Juan; Grimalt, Joan O.; Puigdomenech, Elisa

    2008-01-01

    Background: The relationships between social factors and body concentrations of environmental chemical agents are unknown in many human populations. Some chemical compounds may play an etiopathogenic role in pancreatic cancer. Objective: To analyze the relationships between occupational social class and serum concentrations of seven selected organochlorine compounds (OCs) in exocrine pancreatic cancer: dichlorodiphenyltrichloroethane (p,p'-DDT), dichlorodiphenyldichloroethene (p,p'-DDE), 3 polychlorinated biphenyls (PCBs), hexachlorobenzene, and β-hexachlorocyclohexane. Methods: Incident cases of exocrine pancreatic cancer were prospectively identified, and interviewed face-to-face during hospital admission (n=135). Serum concentrations of OCs were analyzed by high-resolution gas chromatography with electron-capture detection. Social class was classified according to occupation. Results: Multivariate-adjusted concentrations of all seven compounds were higher in occupational social classes IV-V (the less affluent) than in classes I-II; they were higher as well in class III than in classes I-II for four compounds. Concentrations of six OCs were higher in manual workers than in non-manual workers (p<0.05 for PCBs). Social class explained statistically between 3.7% and 5.7% of the variability in concentrations of PCBs, and 2% or less variability in the other OCs. Conclusions: Concentrations of most OCs were higher in the less affluent occupational social classes. In pancreatic cancer the putative causal role of these persistent organic pollutants may not be independent of social class. There is a need to integrate evidence on the contribution of different social processes and environmental chemical exposures to the etiology of pancreatic and other cancers

  14. Selective tumor irradiation without normal tissue exposure in non-resectable pancreatic cancer

    International Nuclear Information System (INIS)

    Order, S.E.; Siegel, J.A.; Lustig, R.A.; Principato, L.S.; Zeiger, L.; Lang, P.; Wallner, P.E.

    1996-01-01

    Purpose: To determine the maximum dose of colloidal 32 P that may be interstitially infused in non-resectable pancreatic cancer prior to external radiation [60 Gy + 5FU]. Materials and Methods: Forty-seven patients with non-resectable pancreatic cancer with and without metastasis entered a dose escalation Phase I study beginning at a specific activity of 4 mCi. Under CT guidance the center of the pancreatic tumor was localized by computer the distance and angle from a grid on the abdomen to the center of the tumor mass determined. Three drugs were infused: 4 mg Decadron - 10 minute delay; 2.5 million particles of macroaggregated albumin [MAA]; and with final dose escalation two infusions of 30 mCi colloidal chromic phosphate 32 P [3.5 ml] followed by a needle cleansing dose of .25 ml of macroaggregated albumin. Bremsstrahlung scans on three separate days determined tumor localization and radiation dose. One week later infusional brachytherapy was repeated, that is Decadron, MAA, colloidal 32 P, followed by three additional bremsstrahlung scans. Two weeks later a course of 60 Gy external radiation was initiated with four doses of 5FU [500 mg] administered with every other radiation treatment day. Toxicity was recorded using RTOG cooperative group criteria. CA19-9 and CEA were used as biomarkers to evaluate tumor progression or remission in conjunction with CT scans and clinical course. Results: Completion of the Phase I study was limited, not by toxicity, but by the volume of colloidal 32 P that could be infused into the stroma of the tumor, i.e. 3.5 ml containing 30 mCi. No significant (grade 3-4) toxicity occurred in patients with pancreatic cancer only. Patients without metastasis had reduction and, in some cases, elimination of CA19-9, etc. The median survival in 28 patients within the Phase I non-resectable pancreas cancer study without metastasis was one year in 19 patients; with metastasis was 6.9 months. The two infusions of 30 mCi 32 P ordinarily yields a

  15. Pancreatic cancer screening employing noncontrast magnetic resonance imaging combined with ultrasonography

    International Nuclear Information System (INIS)

    Kuroki-Suzuki, Seiko; Nagashima, Chieko; Machida, Minoru; Muramatsu, Yukio; Moriyama, Noriyuki; Kuroki, Yoshifumi; Nasu, Katsuhiro

    2011-01-01

    We have conducted an initial evaluation on the potential of combining noncontrast magnetic resonance imaging (MRI) and ultrasonography (US) to screen for pancreatic cancer. An independent ethics committee approved this study. A total of 2511 patients who underwent US were enrolled. Among them, noncontrast MRI was performed in patients in whom the entire pancreas was difficult to depict or in those with US-suspected pancreatic lesions. In total, using 1.5-T MRI, T1- and T2-weighted imaging, magnetic resonance cholangiopancreatography, and diffusion-weighted imaging, we acquired a variety of images. The efficacy of US and MRI in screening for pancreatic lesions, including pancreatic cancer, was evaluated. Of 2511 patients, 184 underwent MRI, and the pancreas was demonstrated in all of them. Among the 2511, five pancreatic cancers were detected by MRI combined with US (detection rate 0.20%). Of the five pancreatic cancers, three were detected by US (detection rate 0.12%) and two by MRI. Four of the five pancreatic cancers were resectable. By combining noncontrast MRI with US, pancreatic cancer can be detected with high accuracy. Other pancreatic lesions that require follow-up, including intraductal papillary mucinous neoplasms, can also be detected. Thus, pancreatic cancer screening with a combination of US and MRI is suggested. (author)

  16. Development of the PANVAC-VF vaccine for pancreatic cancer.

    Science.gov (United States)

    Petrulio, Christian A; Kaufman, Howard L

    2006-02-01

    PANVAC-VF is a vaccine regimen composed of a priming dose of recombinant vaccinia virus and booster doses of recombinant fowlpox virus expressing carcinoembryonic antigen, mucin-1 and a triad of costimulatory molecules (TRICOM), which include B7.1, intercellular adhesion molecule-1 and leukocyte function-associated antigen-3. Vaccination is administered by subcutaneous injection followed by 4 days of local recombinant adjuvant granulocyte-macrophage colony-stimulating factor at the vaccination site. The vaccine has been developed for patients with advanced pancreatic cancer and has now entered a randomized Phase III clinical trial. This review will describe the background of recombinant poxvirus technology for tumor vaccine development, detail the key preclinical studies supporting the regimen, review the clinical trials supporting the current Phase III study, and highlight the key challenges and future obstacles to successful implementation of PANVAC-VF for pancreatic cancer.

  17. Hybrid kappa\\lambda antibody is a new serological marker to diagnose autoimmune pancreatitis and differentiate it from pancreatic cancer.

    Science.gov (United States)

    Hao, Mingju; Li, Wenli; Yi, Lang; Yu, Songlin; Fan, Gaowei; Lu, Tian; Yang, Xin; Wang, Guojing; Zhang, Dong; Ding, Jiansheng; Zhang, Kuo; Zhang, Rui; Lin, Guigao; Han, Yanxi; Wang, Lunan; Li, Jinming

    2016-06-08

    The only generally accepted serological marker currently used for the diagnosis of autoimmune pancreatitis (AIP) is IgG4. Our aim was mainly to determine whether hybrid κ\\λ antibody can help to diagnose AIP and to differentiate it from pancreatic cancer. We established an enzyme-linked immunosorbent assay (ELISA) system to measure the levels of hybrid κ\\λ antibodies in human sera. Sera were obtained from 338 patients, including 61 with AIP, 74 with pancreatic cancer, 50 with acute pancreatitis, 40 with ordinary chronic pancreatitis, 15 with miscellaneous pancreatic diseases, and 98 with normal pancreas. Our study showed levels of hybrid κ\\λ antibodies in the AIP group were significantly higher than in the non-AIP group (P < 0.001). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of AIP were 80.3%, 91%, 66.2% and 95.5% respectively. Furthermore, the combined measurement of serum hybrid κ\\λ antibody and IgG4 tended to increase the sensitivity although the difference was not statistically significant (90.2% vs. 78.7%, P = 0.08), compared to measurement of IgG4 alone. Our findings suggest that hybrid κ\\λ antibody could be a new serological marker to diagnose AIP and differentiate it from pancreatic cancer.

  18. GSK3β and β-Catenin Modulate Radiation Cytotoxicity in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Richard L. Watson

    2010-05-01

    Full Text Available BACKGROUND: Knowledge of factors and mechanisms contributing to the inherent radioresistance of pancreatic cancer may improve cancer treatment. Irradiation inhibits glycogen synthase kinase 3β (GSK3β by phosphorylation at serine 9. In turn, release of cytosolic membrane β-catenin with subsequent nuclear translocation promotes survival. Both GSK3β and β-catenin have been implicated in cancer cell proliferation and resistance to death. METHODS: We investigated pancreatic cancer cell survival after radiation in vitro and in vivo, with a particular focus on the role of the function of the GSK3β/β-catenin axis. RESULTS: Lithium chloride, RNAi-medicated silencing of GSK3β, or the expression of a kinase dead mutant GSK3β resulted in radioresistance of Panc1 and BxPC3 pancreatic cancer cells. Conversely, ectopic expression of a constitutively active form of GSK3β resulted in radiosensitization of Panc1 cells. GSK3β silencing increased radiation-induced β-catenin target gene expression asmeasured by studies of AXIN2 and LEF1 transcript levels. Western blot analysis of total and phosphorylated levels of GSK3β and β-catenin showed that GSK3β inhibition resulted in stabilization of β-catenin. Xenografts of both BxPC3 and Panc1 with targeted silencing of GSK3β exhibited radioresistance in vivo. Silencing of β-catenin resulted in radiosensitization, whereas a nondegradable β-catenin construct induced radioresistance. CONCLUSIONS: These data support the hypothesis that GSK3β modulates the cellular response to radiation in a β-catenin-dependent mechanism. Further understanding of this pathway may enhance the development of clinical trials combining drugs inhibiting β-catenin activation with radiation and chemotherapy in locally advanced pancreatic cancer.

  19. The role of pancreatic cancer-derived exosomes in cancer progress and their potential application as biomarkers.

    Science.gov (United States)

    Jin, H; Wu, Y; Tan, X

    2017-08-01

    Pancreatic cancer is one of the most deadly cancers, with dismal prognosis due to its poor early detection rate and high metastatic rate. Thus, elucidation of the molecular mechanisms accounting for its metastasis and discovery of competent biomarkers is required. Exosomes are multivesicular body-derived small extracellular vesicles released by various cell types that serve as important message carriers during intercellular communication. They are also known to play critical roles during cancer-genesis, cancer-related immune reactions, and metastasis. They also possess promising potential as novel biomarkers for cancer early detection. Therefore, extensive studies on pancreatic cancer-derived exosomes are currently being performed because they hold the promising potential of elevating the overall survival rate of patients with pancreatic cancer. In the present review, we focus on the role of exosomes in pancreatic cancer-related immune reactions, metastasis, and complications, and on their potential application as pancreatic cancer biomarkers.

  20. Natural Products as Adjunctive Treatment for Pancreatic Cancer: Recent Trends and Advancements

    Directory of Open Access Journals (Sweden)

    Qingxi Yue

    2017-01-01

    Full Text Available Pancreatic cancer is a type of common malignant tumors with high occurrence in the world. Most patients presented in clinic had pancreatic cancer at advanced stages. Furthermore, chemotherapy or radiotherapy had very limited success in treating pancreatic cancer. Complementary and alternative medicines, such as natural products/herbal medicines, represent exciting adjunctive therapies. In this review, we summarize the recent advances of using natural products/herbal medicines, such as Chinese herbal medicine, in combination with conventional chemotherapeutic agents to treat pancreatic cancer in preclinical and clinical trials.

  1. Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

    International Nuclear Information System (INIS)

    Ji, S.Q.; Cao, J.; Zhang, Q.Y.; Li, Y.Y.; Yan, Y.Q.; Yu, F.X.

    2013-01-01

    To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis

  2. Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Ji, S.Q.; Cao, J. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Zhang, Q.Y.; Li, Y.Y. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China); Yan, Y.Q. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Yu, F.X. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China)

    2013-09-27

    To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis.

  3. CHOLECYSTOKININ RECEPTOR ANTAGONIST HALTS PROGRESSION OF PANCREATIC CANCER PRECURSOR LESIONS AND FIBROSIS IN MICE

    Science.gov (United States)

    Smith, Jill P.; Cooper, Timothy K.; McGovern, Christopher O.; Gilius, Evan L.; Zhong, Qing; Liao, Jiangang; Molinolo, Alfredo A.; Gutkind, J. Silvio; Matters, Gail L.

    2014-01-01

    Objectives Exogenous administration of cholecystokinin (CCK) induces hypertrophy and hyperplasia of the pancreas with an increase in DNA content. We hypothesized that endogenous CCK is involved with the malignant progression of pancreatic intraepithelial neoplasia (PanIN) lesions and the fibrosis associated with pancreatic cancer. Methods The presence of CCK receptors in early PanIN lesions was examined by immunohistochemistry in mouse and human pancreas. Pdx1-Cre/LSL-KrasG12D transgenic mice were randomized to receive either untreated drinking water or water supplemented with a CCK-receptor antagonist (proglumide, 0.1mg/ml). Pancreas from mice were removed and examined histologically for number and grade of PanINs after 1, 2 or 4 months of antagonist therapy. Results Both CCK-A and CCK-B receptors were identified in early stage PanINs from mouse and human pancreas. The grade of PanIN lesions was reversed and progression to advanced lesions arrested in mice treated with proglumide compared to controls (p=0.004). Furthermore, pancreatic fibrosis was significantly reduced in antagonist-treated animals compared to vehicle (pitalic>0.001). Conclusions These findings demonstrate that endogenous CCK is in part responsible for the development and progression of pancreatic cancer. Use of CCK-receptor antagonists may have a role in cancer prophylaxis in high risk subjects, and may reduce fibrosis in the microenvironment. PMID:25058882

  4. Molecular analysis of precursor lesions in familial pancreatic cancer.

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    Tatjana Crnogorac-Jurcevic

    Full Text Available With less than a 5% survival rate pancreatic adenocarcinoma (PDAC is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical.We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses.Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive/therapeutic targets for both familial and sporadic

  5. Transcatheter embolization of celiac artery pseudoaneurysm following pancreatico-duodenectomy for pancreatic cancer. A case report

    International Nuclear Information System (INIS)

    Mori, K.; Yoshioka, H.; Kuramochi, M.; Saida, Y.; Itai, Y.; Murata, S.; Michishita, N.; Oda, T.

    1998-01-01

    A case of transcatheter embolization of a celiac artery pseudoaneurysm in a 70-year-old man is reported. The pseudoaneurysm was considered to be the result of pancreatic anastomotic leakage and an intra-abdominal abscess following pancreaticoduodenectomy with irradiation of 66 Gy for pancreatic carcinoma. To avoid recanalization of the pseudoaneurysm due to retrograde blood flow, first all branches of the celiac artery were embolized with metallic coils, and then the celiac trunk was also occluded. Hepatic arterial flow was preserved by the right hepatic artery arising from the superior mesenteric artery. After the procedure, the patient had no noticeable complications associated with the embolization nor any recurrence of the pancreatic cancer, and he achieved a 2-year survival. (orig.)

  6. Transcatheter embolization of celiac artery pseudoaneurysm following pancreatico-duodenectomy for pancreatic cancer. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Mori, K.; Yoshioka, H.; Kuramochi, M.; Saida, Y.; Itai, Y. [Dept. of Radiology, Tsukuba Univ. Hospital (Japan); Murata, S. [Dept. of Diagnostic Radiology, Univ. Hospital, Malmoe (Sweden); Michishita, N. [Dept. of Radiology, Tsuchiura Kyodo Hospital (Japan); Oda, T. [Dept. of Surgery, Tsukuba Univ. Hospital (Japan)

    1998-11-01

    A case of transcatheter embolization of a celiac artery pseudoaneurysm in a 70-year-old man is reported. The pseudoaneurysm was considered to be the result of pancreatic anastomotic leakage and an intra-abdominal abscess following pancreaticoduodenectomy with irradiation of 66 Gy for pancreatic carcinoma. To avoid recanalization of the pseudoaneurysm due to retrograde blood flow, first all branches of the celiac artery were embolized with metallic coils, and then the celiac trunk was also occluded. Hepatic arterial flow was preserved by the right hepatic artery arising from the superior mesenteric artery. After the procedure, the patient had no noticeable complications associated with the embolization nor any recurrence of the pancreatic cancer, and he achieved a 2-year survival. (orig.)

  7. Cachexia and pancreatic cancer: Are there treatment options?

    Science.gov (United States)

    Mueller, Tara C; Burmeister, Marc A; Bachmann, Jeannine; Martignoni, Marc E

    2014-01-01

    Cachexia is frequently described in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with reduced survival and quality of life. Unfortunately, the therapeutic options of this multi-factorial and complex syndrome are limited. This is due to the fact that, despite extensive preclinical and clinical research, the underlying pathological mechanisms leading to PDAC-associated cachexia are still not fully understood. Furthermore, there is still a lack of consensus on the definition of cachexia, which complicates the standardization of diagnosis and treatment as well as the analysis of the current literature. In order to provide an efficient therapy for cachexia, an early and reliable diagnosis and consistent monitoring is required, which can be challenging especially in obese patients. Although many substances have been tested in clinical and preclinical settings, so far none of them have been proven to have a long-term effect in ameliorating cancer-associated cachexia. However, recent studies have demonstrated that multidimensional therapeutic modalities are able to alleviate pancreatic cancer-associated cachexia and ultimately improve patients’ outcome. In this current review, we propose a stepwise and pragmatic approach to facilitate and standardize the treatment of cachexia in pancreatic cancer patients. This strategy consists of nutritional, dietary, pharmacological, physical and psychological methods. PMID:25071331

  8. Pancreatic Cancer: What the Oncologist Can Offer for Palliation

    Directory of Open Access Journals (Sweden)

    Malcolm J Moore

    2002-01-01

    Full Text Available Because pancreatic cancer has a poor survival rate and only 20% of patients present with potentially resectable disease, a key goal of therapy is to provide palliation. The poor medical condition of many patients interferes with their ability to tolerate traditional chemotherapy. Recently, however, a nucleoside analogue, gemcitabine, has been developed. This drug is more effective than 5-fluorouracil (5-FU, can be used in patients who fail to respond to 5-FU and has only modest toxicity. Combination therapies including gemcitabine and other agents are being tested. Local radiotherapy seems to provide pain relief, but gastrointestinal toxicity is significant. The effect of combined modality therapy (5-FU with radiotherapy on survival is unclear, and it does not prevent local disease progression. Some novel biological agents, including angiogenesis inhibitors, matrix metalloproteinase inhibitors, antisense compounds, inhibitors of cell signalling such as epidermal growth factor and vascular endothelial growth factor, and inhibitors of oncogene activation, are undergoing phase II and III trials in patients with pancreatic cancer. Among the most promising are farnesyl protein transferase inhibitors, which modulate K-ras function. Such an approach is promising for the treatment of pancreatic cancer because this tumour frequently exhibits mutation of the ras gene.

  9. HIF-2α dictates the susceptibility of pancreatic cancer cells to TRAIL by regulating survivin expression

    Science.gov (United States)

    Harashima, Nanae; Takenaga, Keizo; Akimoto, Miho; Harada, Mamoru

    2017-01-01

    Cancer cells develop resistance to therapy by adapting to hypoxic microenvironments, and hypoxia-inducible factors (HIFs) play crucial roles in this process. We investigated the roles of HIF-1α and HIF-2α in cancer cell death induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) using human pancreatic cancer cell lines. siRNA-mediated knockdown of HIF-2α, but not HIF-1α, increased susceptibility of two pancreatic cancer cell lines, Panc-1 and AsPC-1, to TRAIL in vitro under normoxic and hypoxic conditions. The enhanced sensitivity to TRAIL was also observed in vivo. This in vitro increased TRAIL sensitivity was observed in other three pancreatic cancer cell lines. An array assay of apoptosis-related proteins showed that knockdown of HIF-2α decreased survivin expression. Additionally, survivin promoter activity was decreased in HIF-2α knockdown Panc-1 cells and HIF-2α bound to the hypoxia-responsive element in the survivin promoter region. Conversely, forced expression of the survivin gene in HIF-2α shRNA-expressing Panc-1 cells increased resistance to TRAIL. In a xenograft mouse model, the survivin suppressant YM155 sensitized Panc-1 cells to TRAIL. Collectively, our results indicate that HIF-2α dictates the susceptibility of human pancreatic cancer cell lines, Panc-1 and AsPC-1, to TRAIL by regulating survivin expression transcriptionally, and that survivin could be a promising target to augment the therapeutic efficacy of death receptor-targeting anti-cancer therapy. PMID:28476028

  10. [Relationship between the expression of beta-cat, cyclin D1 and c-myc and the occurance and biological behavior of pancreatic cancer].

    Science.gov (United States)

    Li, Yu-jun; Ji, Xiang-rui

    2003-06-01

    To study the relationship between the abnormal expression of beta-catenin (beta-cat) and the high expressions of cyclin D1 and c-myc and the occurance, proliferation, infiltration, metastasis and prognosis of pancreatic cancer, and to provide rational basis for the clinical diagnosis and treatment. Immunohistochemical PicTure trade mark was used to examine the expressions of beta-cat, cyclin D1 and c-myc in 47 cases of the cancerous tissue of pancreas, 12 cases of the pancreatic intraepithelial neoplasia and 10 cases of normal tissue of pancreas, respectively. Pancreatic cancer proliferation cell nuclear antigen (PCNA) was also tested as the index of the extent of proliferation of the pancreatic cancer. beta-cat was expressed normally in the 10 cases of the normal pancreatic tissue, while cyclin D1 and c-myc were negative. The expression rates of beta-cat, cyclin D1 and c-myc in the tissues of the pancreatic intraepithelial neoplasia and the pancreatic cancer had no significant difference [6/12 and 68.1% (32/47), 6/12 and 74.5% (35/47), 5/12 and 70.2% (33/47) respectively;P values were all more than 0.05]. The abnormal expression rate of beta-cat was significantly correlated to the metastasis of the pancreatic cancer and the one-year survival rate (both P 0.05). The expression rate of cyclin D1 was correlated with the proliferation of the pancreatic cancer and the extent of differentiation (both P 0.05). The expression rate of c-myc was not correlated with the size, the extent of proliferation, infiltration, metastasis, or one-year survival rate (both P > 0.05), but closely with the proliferation activity of the cancerous tissue of pancreas (P < 0.05). The abnormal expression of beta-cat and the high expressions of cyclin D1 and c-myc had a parallel relationship with the pancreatic intraepithelial neoplasia and pancreatic cancer (both P < 0.05, gamma = 1.000, 0.845, 0.437, 0.452). The abnormal expression of beta-cat activates cyclin D1 and c-myc, and results in the

  11. Microencapsulated tumor assay: Evaluation of the nude mouse model of pancreatic cancer

    Science.gov (United States)

    Ma, Ming-Zhe; Cheng, Dong-Feng; Ye, Jin-Hua; Zhou, Yong; Wang, Jia-Xiang; Shi, Min-Min; Han, Bao-San; Peng, Cheng-Hong

    2012-01-01

    AIM: To establish a more stable and accurate nude mouse model of pancreatic cancer using cancer cell microencapsulation. METHODS: The assay is based on microencapsulation technology, wherein human tumor cells are encapsulated in small microcapsules (approximately 420 μm in diameter) constructed of semipermeable membranes. We implemented two kinds of subcutaneous implantation models in nude mice using the injection of single tumor cells and encapsulated pancreatic tumor cells. The size of subcutaneously implanted tumors was observed on a weekly basis using two methods, and growth curves were generated from these data. The growth and metastasis of orthotopically injected single tumor cells and encapsulated pancreatic tumor cells were evaluated at four and eight weeks postimplantation by positron emission tomography-computed tomography scan and necropsy. The pancreatic tumor samples obtained from each method were then sent for pathological examination. We evaluated differences in the rates of tumor incidence and the presence of metastasis and variations in tumor volume and tumor weight in the cancer microcapsules vs single-cell suspensions. RESULTS: Sequential in vitro observations of the microcapsules showed that the cancer cells in microcapsules proliferated well and formed spheroids at days 4 to 6. Further in vitro culture resulted in bursting of the membrane of the microcapsules and cells deviated outward and continued to grow in flasks. The optimum injection time was found to be 5 d after tumor encapsulation. In the subcutaneous implantation model, there were no significant differences in terms of tumor volume between the encapsulated pancreatic tumor cells and cells alone and rate of tumor incidence. There was a significant difference in the rate of successful implantation between the cancer cell microencapsulation group and the single tumor-cell suspension group (100% vs 71.43%, respectively, P = 0.0489) in the orthotropic implantation model. The former method

  12. Mediterranean diet and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition cohort

    NARCIS (Netherlands)

    Molina-Montes, Esther; Sánchez, María José; Buckland, Genevieve; Bueno-de-Mesquita, H. Bas; Weiderpass, Elisabete; Amiano, Pilar; Wark, Petra A.; Kühn, Tilman; Katzke, Verena; Huerta, José María; Ardanaz, Eva; Quirós, José Ramón; Affret, Aurélie; His, Mathilde; Boutron-Ruault, Marie Christine; Peeters, Petra H.; Ye, Weimin; Sund, Malin; Boeing, Heiner; Iqbal, Khalid; Ohlsson, Bodil; Sonestedt, Emily; Tjønneland, Anne; Petersen, Kristina EN; Travis, Ruth C.; Skeie, Guri; Agnoli, Claudia; Panico, Salvatore; Palli, Domenico; Tumino, Rosario; Sacerdote, Carlotta; Freisling, Heinz; Huybrechts, Inge; Overvad, Kim; Trichopoulou, Antonia; Bamia, Christina; Vasilopoulou, Effie; Wareham, Nick; Khaw, Kay Tee; Cross, Amanda J.; Ward, Heather A.; Riboli, Elio; Duell, Eric J.

    2017-01-01

    Background:The Mediterranean diet (MD) has been proposed as a means for cancer prevention, but little evidence has been accrued regarding its potential to prevent pancreatic cancer. We investigated the association between the adherence to the MD and pancreatic cancer risk within the European

  13. Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

    NARCIS (Netherlands)

    Molina-Montes, Esther; Sánchez, María José; Zamora-Ros, Raul; Bueno-de-Mesquita, H. Bas; Wark, Petra A.; Obon-Santacana, Mireia; Kühn, Tilman; Katzke, Verena; Travis, Ruth C.; Ye, Weimin; Sund, Malin; Naccarati, Alessio; Mattiello, Amalia; Krogh, Vittorio; Martorana, Caterina; Masala, Giovanna; Amiano, Pilar; Huerta, José María; Barricarte, Aurelio; Quirós, José Ramón; Weiderpass, Elisabete; Angell Åsli, Lene; Skeie, Guri; Ericson, Ulrika; Sonestedt, Emily; Peeters, Petra H.; Romieu, Isabelle; Scalbert, Augustin; Overvad, Kim; Clemens, Matthias; Boeing, Heiner; Trichopoulou, Antonia; Peppa, Eleni; Vidalis, Pavlos; Khaw, Kay Tee; Wareham, Nick; Olsen, Anja; Tjønneland, Anne; Boutroun-Rualt, Marie Christine; Clavel-Chapelon, Françoise; Cross, Amanda J.; Lu, Yunxia; Riboli, Elio; Duell, Eric J.

    2016-01-01

    Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the

  14. Pegaspargase Induced Hypertriglyceridemia Resulting in Severe Fatal Pancreatitis

    Directory of Open Access Journals (Sweden)

    Neil Vyas

    2015-01-01

    Full Text Available Pegaspargase is used to treat acute lymphocytic leukemia (ALL. Pegaspargase definitely has its benefits in treating ALL; however we cannot lose sight of one of its very rare but potentially deadly complications, acute pancreatitis. Clinicians should monitor triglycerides while the patient is on treatment with Pegaspargase and suspect acute pancreatitis if the patient develops abdominal pain. If pancreatitis occurs, therapy should be stopped immediately and not reinstituted. For patients with hypertriglyceridemia without pancreatitis, discontinuation of therapy should be considered.

  15. MRI-based tumor motion characterization and gating schemes for radiation therapy of pancreatic cancer

    International Nuclear Information System (INIS)

    Heerkens, Hanne D.; Vulpen, Marco van; Berg, Cornelis A.T. van den; Tijssen, Rob H.N.; Crijns, Sjoerd P.M.; Molenaar, Izaak Q.; Santvoort, Hjalmar C. van; Reerink, Onne; Meijer, Gert J.

    2014-01-01

    Background and purpose: To characterize pancreatic tumor motion and to develop a gating scheme for radiotherapy in pancreatic cancer. Materials and methods: Two cine MRIs of 60 s each were performed in fifteen pancreatic cancer patients, one in sagittal direction and one in coronal direction. A Minimum Output Sum of Squared Error (MOSSE) adaptive correlation filter was used to quantify tumor motion in craniocaudal, lateral and anteroposterior directions. To develop a gating scheme, stability of the breathing phases was examined and a gating window assessment was created, incorporating tumor motion, treatment time and motion margins. Results: The largest tumor motion was found in craniocaudal direction, with an average peak-to-peak amplitude of 15 mm (range 6–34 mm). Amplitude of the tumor in the anteroposterior direction was on average 5 mm (range 1–13 mm). The least motion was seen in lateral direction (average 3 mm, range 2–5 mm). The end exhale position was the most stable position in the breathing cycle and tumors spent more time closer to the end exhale position than to the end inhale position. On average, a margin of 25% of the maximum craniocaudal breathing amplitude was needed to achieve full target coverage with a duty cycle of 50%. When reducing the duty cycle to 50%, a margin of 5 mm was sufficient to cover the target in 11 out of 15 patients. Conclusion: Gated delivery for radiotherapy of pancreatic cancer is best performed around the end exhale position as this is the most stable position in the breathing cycle. Considerable margin reduction can be established at moderate duty cycles, yielding acceptable treatment efficiency. However, motion patterns and amplitude do substantially differ between individual patients. Therefore, individual treatment strategies should be considered for radiotherapy in pancreatic cancer

  16. Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial.

    Science.gov (United States)

    Chantrill, Lorraine A; Nagrial, Adnan M; Watson, Clare; Johns, Amber L; Martyn-Smith, Mona; Simpson, Skye; Mead, Scott; Jones, Marc D; Samra, Jaswinder S; Gill, Anthony J; Watson, Nicole; Chin, Venessa T; Humphris, Jeremy L; Chou, Angela; Brown, Belinda; Morey, Adrienne; Pajic, Marina; Grimmond, Sean M; Chang, David K; Thomas, David; Sebastian, Lucille; Sjoquist, Katrin; Yip, Sonia; Pavlakis, Nick; Asghari, Ray; Harvey, Sandra; Grimison, Peter; Simes, John; Biankin, Andrew V

    2015-05-01

    Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices of the International Cancer Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets of patients with aberrations in their tumor genome that could be targeted with currently available therapies. The pilot stage of the IMPaCT trial assessed the feasibility of acquiring suitable tumor specimens for molecular analysis and returning high-quality actionable genomic data within a clinically acceptable timeframe. We screened for three molecular targets: HER2 amplification; KRAS wild-type; and mutations in DNA damage repair pathways (BRCA1, BRCA2, PALB2, ATM). Tumor biopsy and archived tumor samples were collected from 93 patients and 76 were screened. To date 22 candidate cases have been identified: 14 KRAS wild-type, 5 cases of HER2 amplification, 2 mutations in BRCA2, and 1 ATM mutation. Median time from consent to the return of validated results was 21.5 days. An inability to obtain a biopsy or insufficient tumor content in the available specimen were common reasons for patient exclusion from molecular analysis while deteriorating performance status prohibited a number of patients from proceeding in the study. Documenting the feasibility of acquiring and screening biospecimens for actionable molecular targets in real time will aid other groups embarking on similar trials. Key elements include the need to better prescreen patients, screen more patients, and offer more attractive clinical trial options. ©2015 American Association for Cancer Research.

  17. Analysis of PALB2 gene in BRCA1/BRCA2 negative Spanish hereditary breast/ovarian cancer families with pancreatic cancer cases.

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    Ana Blanco

    Full Text Available BACKGROUND: The PALB2 gene, also known as FANCN, forms a bond and co-localizes with BRCA2 in DNA repair. Germline mutations in PALB2 have been identified in approximately 1% of familial breast cancer and 3-4% of familial pancreatic cancer. The goal of this study was to determine the prevalence of PALB2 mutations in a population of BRCA1/BRCA2 negative breast cancer patients selected from either a personal or family history of pancreatic cancer. METHODS: 132 non-BRCA1/BRCA2 breast/ovarian cancer families with at least one pancreatic cancer case were included in the study. PALB2 mutational analysis was performed by direct sequencing of all coding exons and intron/exon boundaries, as well as multiplex ligation-dependent probe amplification. RESULTS: Two PALB2 truncating mutations, the c.1653T>A (p.Tyr551Stop previously reported, and c.3362del (p.Gly1121ValfsX3 which is a novel frameshift mutation, were identified. Moreover, several PALB2 variants were detected; some of them were predicted as pathological by bioinformatic analysis. Considering truncating mutations, the prevalence rate of our population of BRCA1/2-negative breast cancer patients with pancreatic cancer is 1.5%. CONCLUSIONS: The prevalence rate of PALB2 mutations in non-BRCA1/BRCA2 breast/ovarian cancer families, selected from either a personal or family pancreatic cancer history, is similar to that previously described for unselected breast/ovarian cancer families. Future research directed towards identifying other gene(s involved in the development of breast/pancreatic cancer families is required.

  18. Circulating Microvesicles from Pancreatic Cancer Accelerate the Migration and Proliferation of PANC-1 Cells.

    Science.gov (United States)

    An, Mingrui; Zhu, Jianhui; Wu, Jing; Cuneo, Kyle C; Lubman, David M

    2018-04-06

    Circulating microvesicles are able to mediate long-distance cell-cell communications. It is essential to understand how microvesicles from pancreatic cancer act on other cells in the body. In this work, serum-derived microvesicles were isolated from 10 patients with locally advanced pancreatic cancer and healthy controls. Using Cell Transwell and WST-1 reagents, we found that microvesicles from pancreatic cancer accelerated migration and proliferation of PANC-1 cells. Meanwhile, the proliferation of these cancer-microvesicle-treated cells (CMTCs) was affected less by 10 μM of gemcitabine relative to healthy microvesicle-treated cells (HMTCs). Next, we optimized the filter-aided sample preparation method to increase the recovery of protein samples and then applied it to the quantification of the proteome of CMTCs and HMTCs. The peptides were labeled and analyzed by liquid chromatography-tandem mass spectrometry. In total, 4102 proteins were identified, where 35 proteins were up-regulated with 27 down-regulated in CMTCs. We verified the quantitative results of three key proteins CD44, PPP2R1A, and TP53 by Western blot. The Ingenuity Pathway Analysis revealed pathways that cancer microvesicles might participate in to promote cell migration and proliferation. These findings may provide novel clues of treatment for tumorigenesis and metastasis.

  19. Inhibition of Cell Survival by Curcumin Is Associated with Downregulation of Cell Division Cycle 20 (Cdc20) in Pancreatic Cancer Cells.

    Science.gov (United States)

    Zhang, Yu; Xue, Ying-Bo; Li, Hang; Qiu, Dong; Wang, Zhi-Wei; Tan, Shi-Sheng

    2017-02-04

    Pancreatic cancer is one of the most aggressive human tumors in the United States. Curcumin, a polyphenol derived from the Curcuma longa plant, has been reported to exert its antitumor activity in pancreatic cancer. However, the molecular mechanisms of curcumin-mediated tumor suppressive function have not been fully elucidated. In the current study, we explore whether curcumin exhibits its anti-cancer function through inhibition of oncoprotein cell division cycle 20 (Cdc20) in pancreatic cancer cells. We found that curcumin inhibited cell growth, enhanced apoptosis, induced cell cycle arrest and retarded cell invasion in pancreatic cancer cells. Moreover, we observed that curcumin significantly inhibited the expression of Cdc20 in pancreatic cancer cells. Furthermore, our results demonstrated that overexpression of Cdc20 enhanced cell proliferation and invasion, and abrogated the cytotoxic effects induced by curcumin in pancreatic cancer cells. Consistently, downregulation of Cdc20 promoted curcumin-mediated anti-tumor activity. Therefore, our findings indicated that inhibition of Cdc20 by curcumin could be useful for the treatment of pancreatic cancer patients.

  20. Molecular biology of pancreatic cancer: how useful is it in clinical practice?

    Science.gov (United States)

    Sakorafas, George H; Smyrniotis, Vasileios

    2012-07-10

    During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Reports about clinical implications of molecular biology in patients with pancreatic cancer were retrieved from PubMed. These reports were selected on the basis of their clinical relevance, and the data of their publication (preferentially within the last 5 years). Emphasis was placed on reports investigating diagnostic, prognostic, and therapeutic implications. Molecular biology can be used to identify individuals at high-risk for pancreatic cancer development. Intensive surveillance is indicated in these patients to detect pancreatic neoplasia ideally at a preinvasive stage, when curative resection is still possible. Molecular biology can also be used in the diagnosis of pancreatic cancer, with molecular analysis on samples of biologic material, such as serum or plasma, duodenal fluid or preferentially pure pancreatic juice, pancreatic cells or tissue, and stools. Molecular indices have also prognostic significance. Finally, molecular biology may have therapeutic implications by using various therapeutic approaches, such as antiangiogenic factors, purine synthesis inhibitors, matrix metalloproteinase inhibitors, factors modulating tumor-stroma interaction, inactivation of the hedgehog pathway, gene therapy, oncolytic viral therapy, immunotherapy (both passive as well as active) etc. Molecular biology may have important clinical implications in patients with pancreatic cancer and represents one of the most active areas on cancer research. Hopefully clinical applications of molecular biology in pancreatic cancer will expand in the future, improving the

  1. Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Patrick; Das, Prajnan; Pinnix, Chelsea C.; Beddar, Sam; Briere, Tina; Pham, Mary; Krishnan, Sunil; Delclos, Marc E. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher H., E-mail: ccrane@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-03-01

    Purpose: Improving local control is critical to improving survival and quality of life for patients with locally advanced unresectable pancreatic cancer (LAPC). However, previous attempts at radiation dose escalation have been limited by duodenal toxicity. In order to guide future studies, we analyzed the clinical and dosimetric factors associated with duodenal toxicity in patients undergoing fractionated chemoradiation for LAPC. Methods and Materials: Medical records and treatment plans of 106 patients with LAPC who were treated with chemoradiation between July 2005 and June 2010 at our institution were reviewed. All patients received neoadjuvant and concurrent chemotherapy. Seventy-eight patients were treated with conventional radiation to 50.4 Gy in 28 fractions; 28 patients received dose-escalated radiation therapy (range, 57.5-75.4 Gy in 28-39 fractions). Treatment-related toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to assess prognostic influence of clinical, pathologic, and treatment-related factors by using Kaplan-Meier and Cox regression methods. Results: Twenty patients had treatment-related duodenal toxicity events, such as duodenal inflammation, ulceration, and bleeding. Four patients had grade 1 events, 8 had grade 2, 6 had grade 3, 1 had grade 4, and 1 had grade 5. On univariate analysis, a toxicity grade ≥2 was associated with tumor location, low platelet count, an absolute volume (cm{sup 3}) receiving a dose of at least 55 Gy (V{sub 55} {sub Gy} > 1 cm{sup 3}), and a maximum point dose >60 Gy. Of these factors, only V{sub 55} {sub Gy} ≥1 cm{sup 3} was associated with duodenal toxicity on multivariate analysis (hazard ratio, 6.7; range, 2.0-18.8; P=.002). Conclusions: This study demonstrates that a duodenal V{sub 55} {sub Gy} >1 cm{sup 3} is an important dosimetric predictor of grade 2 or greater duodenal toxicity and establishes it as a

  2. Serum Metabolomic Profiles for Human Pancreatic Cancer Discrimination

    Directory of Open Access Journals (Sweden)

    Takao Itoi

    2017-04-01

    Full Text Available This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC from malignant diseases, such as biliary tract cancer (BTC, intraductal papillary mucinous carcinoma (IPMC, and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples (n = 41 of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples (n = 140. Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups (p < 0.05; Steel–Dwass test. Four multiple logistic regression models (MLR were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC of 0.970 (95% confidential interval (CI, 0.946–0.994, p < 0.0001. Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650–1.01, p = 0.0020 with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA, carbohydrate antigen 19-9 (CA19-9, pancreatic cancer-associated antigen (DUPAN2 and s-pancreas-1 antigen (SPAN1. Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases.

  3. Contemporary Management of Borderline Resectable and Locally Advanced Unresectable Pancreatic Cancer.

    Science.gov (United States)

    Shaib, Walid L; Ip, Andrew; Cardona, Kenneth; Alese, Olatunji B; Maithel, Shishir K; Kooby, David; Landry, Jerome; El-Rayes, Bassel F

    2016-02-01

    Adenocarcinoma of the pancreas remains a highly lethal disease, with less than 5% survival at 5 years. Borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC) account for approximately 30% of newly diagnosed cases of PC. The objective of BRPC therapy is to downstage the tumor to allow resection; the objective of LAPC therapy is to control disease and improve survival. There is no consensus on the definitions of BRPC and LAPC, which leads to major limitations in designing clinical trials and evaluating their results. A multimodality approach is always needed to ensure proper utilization and timing of chemotherapy, radiation, and surgery in the management of this disease. Combination chemotherapy regimens (5-fluorouracil, leucovorin, irinotecan, oxaliplatin, and gemcitabine [FOLFIRINOX] and gemcitabine/nab-paclitaxel) have improved overall survival in metastatic disease. The role of combination chemotherapy regimens in BRPC and LAPC is an area of active investigation. There is no consensus on the dose, modality, and role of radiation therapy in the treatment of BRPC and LAPC. This article reviews the literature and highlights the areas of controversy regarding management of BRPC and LAPC. Pancreatic cancer is one of the worst cancers with regard to survival, even at early stages of the disease. This review evaluates all the evidence for the stages in which the cancer is not primarily resectable with surgery, known as borderline resectable or locally advanced unresectable. Recently, advancements in radiation techniques and use of better combination chemotherapies have improved survival and tolerance. There is no consensus on description of stages or treatment sequences (chemotherapy, chemoradiation, radiation), nor on the best chemotherapy regimen. The evidence behind the treatment paradigm for these stages of pancreatic cancer is summarized. ©AlphaMed Press.

  4. Endogenous glutamine decrease is associated with pancreatic cancer progression.

    Science.gov (United States)

    Roux, Cecilia; Riganti, Chiara; Borgogno, Sammy Ferri; Curto, Roberta; Curcio, Claudia; Catanzaro, Valeria; Digilio, Giuseppe; Padovan, Sergio; Puccinelli, Maria Paola; Isabello, Monica; Aime, Silvio; Cappello, Paola; Novelli, Francesco

    2017-11-10

    Pancreatic ductal adenocarcinoma (PDAC) is becoming the second leading cause of cancer-related death in the Western world. The mortality is very high, which emphasizes the need to identify biomarkers for early detection. As glutamine metabolism alteration is a feature of PDAC, its in vivo evaluation may provide a useful tool for biomarker identification. Our aim was to identify a handy method to evaluate blood glutamine consumption in mouse models of PDAC. We quantified the in vitro glutamine uptake by Mass Spectrometry (MS) in tumor cell supernatants and showed that it was higher in PDAC compared to non-PDAC tumor and pancreatic control human cells. The increased glutamine uptake was paralleled by higher activity of most glutamine pathway-related enzymes supporting nucleotide and ATP production. Free glutamine blood levels were evaluated in orthotopic and spontaneous mouse models of PDAC and other pancreatic-related disorders by High-Performance Liquid Chromatography (HPLC) and/or MS. Notably we observed a reduction of blood glutamine as much as the tumor progressed from pancreatic intraepithelial lesions to invasive PDAC, but was not related to chronic pancreatitis-associated inflammation or diabetes. In parallel the increased levels of branched-chain amino acids (BCAA) were observed. By contrast blood glutamine levels were stable in non-tumor bearing mice. These findings demonstrated that glutamine uptake is measurable both in vitro and in vivo . The higher in vitro avidity of PDAC cells corresponded to a lower blood glutamine level as soon as the tumor mass grew. The reduction in circulating glutamine represents a novel tool exploitable to implement other diagnostic or prognostic PDAC biomarkers.

  5. Management of advanced pancreatic cancer in daily clinical practice.

    Science.gov (United States)

    Giuliani, Jacopo; Piacentini, Paolo; Bonetti, Andrea

    2016-01-01

    The aim of this outcome study was to evaluate the management of advanced pancreatic cancer in a real-world clinical practice; few such experiences have been reported in the literature. A retrospective analysis was performed of all consecutive patients with advanced pancreatic ductal adenocarcinoma followed at our medical oncology unit between January 2003 and December 2013. We evaluated 78 patients, mostly with metastatic disease (64.1%). Median follow-up was 10.77 months, by which time 74 patients (94.9%) had died. Median overall survival was 8.29 months. Median age was 67 years. In univariate analysis, pain at onset (p = 0.020), ECOG performance status (p<0.001), stage (p = 0.047), first-line chemotherapy (p<0.001), second-line chemotherapy (p<0.001) and weight loss at diagnosis (p = 0.029) were factors that had an impact on overall survival. In multivariate analysis, the presence of pain at onset (p = 0.043), stage (p = 0.003) and second-line chemotherapy (p = 0.004) were confirmed as independent prognostic factors. Our data, derived from daily clinical practice, confirmed advanced pancreatic cancer as an aggressive malignant disease with a very short expected survival. Second-line treatment seems to provide an advantage in terms of overall survival in patients who showed a partial response as their best response to first-line treatment.

  6. A novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growth and overcomes gemcitabine resistance.

    Science.gov (United States)

    Lee, Hee Seung; Park, Soo Been; Kim, Sun A; Kwon, Sool Ki; Cha, Hyunju; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Song, Si Young

    2017-01-30

    Pancreatic cancer is predominantly lethal, and is primarily treated using gemcitabine, with increasing resistance. Therefore, novel agents that increase tumor sensitivity to gemcitabine are needed. Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents, since HDAC plays an important role in cancer initiation and progression. We evaluated the antitumor effect of a novel HDAC inhibitor, CG200745, combined with gemcitabine/erlotinib on pancreatic cancer cells and gemcitabine-resistant pancreatic cancer cells. Three pancreatic cancer-cell lines were used to evaluate the antitumor effect of CG200745 combined with gemcitabine/erlotinib. CG200745 induced the expression of apoptotic proteins (PARP and caspase-3) and increased the levels of acetylated histone H3. CG200745 with gemcitabine/erlotinib showed significant growth inhibition and synergistic antitumor effects in vitro. In vivo, gemcitabine/erlotinib and CG200745 reduced tumor size up to 50%. CG200745 enhanced the sensitivity of gemcitabine-resistant pancreatic cancer cells to gemcitabine, and decreased the level of ATP-binding cassette-transporter genes, especially multidrug resistance protein 3 (MRP3) and MRP4. The novel HDAC inhibitor, CG200745, with gemcitabine/erlotinib had a synergistic anti-tumor effect on pancreatic cancer cells. CG200745 significantly improved pancreatic cancer sensitivity to gemcitabine, with a prominent antitumor effect on gemcitabine-resistant pancreatic cancer cells. Therefore, improved clinical outcome is expected in the future.

  7. Downregulation of tight junction-associated MARVEL protein marvelD3 during epithelial-mesenchymal transition in human pancreatic cancer cells.

    Science.gov (United States)

    Kojima, Takashi; Takasawa, Akira; Kyuno, Daisuke; Ito, Tatsuya; Yamaguchi, Hiroshi; Hirata, Koichi; Tsujiwaki, Mitsuhiro; Murata, Masaki; Tanaka, Satoshi; Sawada, Norimasa

    2011-10-01

    The novel tight junction protein marvelD3 contains a conserved MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain like occludin and tricellulin. However, little is yet known about the detailed role and regulation of marvelD3 in normal epithelial cells and cancer cells, including pancreatic cancer. In the present study, we investigated marvelD3 expression in well and poorly differentiated human pancreatic cancer cell lines and normal pancreatic duct epithelial cells in which the hTERT gene was introduced into human pancreatic duct epithelial cells in primary culture, and the changes of marvelD3 during Snail-induced epithelial-mesenchymal transition (EMT) under hypoxia, TGF-β treatment and knockdown of FOXA2 in well differentiated pancreatic cancer HPAC cells. MarvelD3 was transcriptionally downregulated in poorly differentiated pancreatic cancer cells and during Snail-induced EMT of pancreatic cancer cells in which Snail was highly expressed and the fence function downregulated, whereas it was maintained in well differentiated human pancreatic cancer cells and normal pancreatic duct epithelial cells. Depletion of marvelD3 by siRNAs in HPAC cells resulted in downregulation of barrier functions indicated as a decrease in transepithelial electric resistance and an increase of permeability to fluorescent dextran tracers, whereas it did not affect fence function of tight junctions. In conclusion, marvelD3 is transcriptionally downregulated in Snail-induced EMT during the progression for the pancreatic cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Extracorporeal shock wave lithotripsy on pancreatic duck stones in patients with chronic pancreatitis: evaluation of therapeutic results with CT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Moon Gyu [Asan Medical Center, Seoul (Korea, Republic of); Lee, Yong Suk [Gunpo Medical Center, Gunpo (Korea, Republic of)

    2003-03-01

    To demonstrate by CT scanning the effect of extracorporeal shock wave lithotripsy (ESWL) on pancreatic duct stones in patients with chronic pancreatitis. Pancreatic duct stones in 11 patients with chronic pancreatitis were subject to ESWL using an electrohydraulic lithotripter. Endoscopic stone removal using a basket had failed in ten patients, and in one, endoscopy was impossible due to a previous Whipple's operation. CT scans obtained before and after ESWL were evaluated by two radiologists: the longest and shortest diameters of the target stone were measured, and according to the degree of fragmentation, determined by comparing the area of the stone before and after ESWL, a grade (1-5) was assigned. In each case, the pre- and post- treatment diameter of the main pancreatic duct, measured at the pancreatic body, was also compared. Disintegration of the target stone was achieved in all patients: grade 1 (over 75% of the area remained, compared with that of the initial stone) was assigned in two patients; grade 2 (51-75% of the original area) in one; grade 3 (26-50%) in four; grade 4 (under 25%) in two; and grade 5 (complete clearance of the target stone) in two. The mean area decreased from 175 mm{sup 2} to 69 mm{sup 2} after ESWL (p<0.05); a decrease of more than 50% was observed in eight patients (73%). The mean diameter of the main pancreatic duct decreased from 7.36 to 4.81 mm (p<0.05). No severe adverse effects or complications were noted, and all patients showed clinical improvement. Follow-up studies indicated that pancreatic duct stones recurred in three patients. ESWL can cause the fragmentation of pancreatic duct stones without significant complications, and should be considered where endoscopic stone removal has failed. CT is a suitable non-invasive and accurate tool for evaluating the therapeutic results of ESWL.

  9. Extracorporeal shock wave lithotripsy on pancreatic duck stones in patients with chronic pancreatitis: evaluation of therapeutic results with CT

    International Nuclear Information System (INIS)

    Lee, Moon Gyu; Lee, Yong Suk

    2003-01-01

    To demonstrate by CT scanning the effect of extracorporeal shock wave lithotripsy (ESWL) on pancreatic duct stones in patients with chronic pancreatitis. Pancreatic duct stones in 11 patients with chronic pancreatitis were subject to ESWL using an electrohydraulic lithotripter. Endoscopic stone removal using a basket had failed in ten patients, and in one, endoscopy was impossible due to a previous Whipple's operation. CT scans obtained before and after ESWL were evaluated by two radiologists: the longest and shortest diameters of the target stone were measured, and according to the degree of fragmentation, determined by comparing the area of the stone before and after ESWL, a grade (1-5) was assigned. In each case, the pre- and post- treatment diameter of the main pancreatic duct, measured at the pancreatic body, was also compared. Disintegration of the target stone was achieved in all patients: grade 1 (over 75% of the area remained, compared with that of the initial stone) was assigned in two patients; grade 2 (51-75% of the original area) in one; grade 3 (26-50%) in four; grade 4 (under 25%) in two; and grade 5 (complete clearance of the target stone) in two. The mean area decreased from 175 mm 2 to 69 mm 2 after ESWL (p<0.05); a decrease of more than 50% was observed in eight patients (73%). The mean diameter of the main pancreatic duct decreased from 7.36 to 4.81 mm (p<0.05). No severe adverse effects or complications were noted, and all patients showed clinical improvement. Follow-up studies indicated that pancreatic duct stones recurred in three patients. ESWL can cause the fragmentation of pancreatic duct stones without significant complications, and should be considered where endoscopic stone removal has failed. CT is a suitable non-invasive and accurate tool for evaluating the therapeutic results of ESWL

  10. Fasting cycles potentiate the efficacy of gemcitabine treatment in in vitro and in vivo pancreatic cancer models

    Science.gov (United States)

    Mazza, Tommaso; Panebianco, Concetta; Saracino, Chiara; Pereira, Stephen P.; Graziano, Paolo; Pazienza, Valerio

    2015-01-01

    Background/aims Pancreatic cancer (PC) is ranked as the fourth leading cause of cancer-related deaths worldwide. Despite recent advances in treatment options, a modest impact on the outcome of the disease is observed so far. Short-term fasting cycles have been shown to potentiate the efficacy of chemotherapy against glioma. The aim of this study was to assess the effect of fasting cycles on the efficacy of gemcitabine, a standard treatment for PC patients, in vitro and in an in vivo pancreatic cancer mouse xenograft model. Materials and Methods BxPC-3, MiaPaca-2 and Panc-1 cells were cultured in standard and fasting mimicking culturing condition to evaluate the effects of gemcitabine. Pancreatic cancer xenograft mice were subjected to 24h starvation prior to gemcitabine injection to assess the tumor volume and weight as compared to mice fed ad libitum. Results Fasted pancreatic cancer cells showed increased levels of equilibrative nucleoside transporter (hENT1), the transporter of gemcitabine across the cell membrane, and decreased ribonucleotide reductase M1 (RRM1) levels as compared to those cultured in standard medium. Gemcitabine was more effective in inducing cell death on fasted cells as compared to controls. Consistently, xenograft pancreatic cancer mice subjected to fasting cycles prior to gemcitabine injection displayed a decrease of more than 40% in tumor growth. Conclusion Fasting cycles enhance gemcitabine effect in vitro and in the in vivo PC xenograft mouse model. These results suggest that restrictive dietary interventions could enhance the efficacy of existing cancer treatments in pancreatic cancer patients. PMID:26176887

  11. Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility.

    Science.gov (United States)

    Sada, Masafumi; Ohuchida, Kenoki; Horioka, Kohei; Okumura, Takashi; Moriyama, Taiki; Miyasaka, Yoshihiro; Ohtsuka, Takao; Mizumoto, Kazuhiro; Oda, Yoshinao; Nakamura, Masafumi

    2016-03-28

    Desmoplasia and hypoxia in pancreatic cancer mutually affect each other and create a tumor-supportive microenvironment. Here, we show that microenvironment remodeling by hypoxic pancreatic stellate cells (PSCs) promotes cancer cell motility through alteration of extracellular matrix (ECM) fiber architecture. Three-dimensional (3-D) matrices derived from PSCs under hypoxia exhibited highly organized parallel-patterned matrix fibers compared with 3-D matrices derived from PSCs under normoxia, and promoted cancer cell motility by inducing directional migration of cancer cells due to the parallel fiber architecture. Microarray analysis revealed that procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) in PSCs was the gene that potentially regulates ECM fiber architecture under hypoxia. Stromal PLOD2 expression in surgical specimens of pancreatic cancer was confirmed by immunohistochemistry. RNA interference-mediated knockdown of PLOD2 in PSCs blocked parallel fiber architecture of 3-D matrices, leading to decreased directional migration of cancer cells within the matrices. In conclusion, these findings indicate that hypoxia-induced PLOD2 expression in PSCs creates a permissive microenvironment for migration of cancer cells through architectural regulation of stromal ECM in pancreatic cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Functional annotation of rare gene aberration drivers of pancreatic cancer | Office of Cancer Genomics

    Science.gov (United States)

    As we enter the era of precision medicine, characterization of cancer genomes will directly influence therapeutic decisions in the clinic. Here we describe a platform enabling functionalization of rare gene mutations through their high-throughput construction, molecular barcoding and delivery to cancer models for in vivo tumour driver screens. We apply these technologies to identify oncogenic drivers of pancreatic ductal adenocarcinoma (PDAC).

  13. Chinese herb derived-Rocaglamide A is a potent inhibitor of pancreatic cancer cells

    OpenAIRE

    Wang, Baochun; Li, Yixiong; Tan, Fengbo; Xiao, Zhanxiang

    2016-01-01

    Pancreatic cancer ranks No.1 in mortality rate worldwide. This study aims to identify the novel anti-pancreatic cancer drugs. Human pancreatic carcinoma cell lines were purchased from ATCC. CPE-based screening assay was used to examine the cell viability. Patient derived tumor xenografts in SCID mice was established. The Caspase-3 and 7 activities were measured using the Caspase Glo 3/7 Assay kit. Soft agar colony formation assay was used to evaluate the colony formation. Wound healing assay ...

  14. Molecular Biology of Pancreatic Cancer: How Useful Is It in Clinical Practice?

    OpenAIRE

    George H Sakorafas; Vasileios Smyrniotis

    2012-01-01

    Context During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. Objective To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Methods Reports about clinical implications of molecular bio...

  15. Targeting of Pancreatic Cancer with Magneto-Fluorescent Theranostic Gold Nanoshells

    Science.gov (United States)

    Chen, Wenxue; Ayala-Orozco, Ciceron; Biswal, Nrusingh C.; Perez-Torres, Carlos; Bartels, Marc; Bardhan, Rizia; Stinnet, Gary; Liu, Xian-De; Ji, Baoan; Deorukhkar, Amit; Brown, Lisa V.; Guha, Sushovan; Pautler, Robia G.; Krishnan, Sunil; Halas, Naomi J; Joshi, Amit

    2014-01-01

    Aim We report a magneto-fluorescent theranostic nanocomplex targeted to neutrophil gelatinase associated lipocalin (NGAL) for imaging and therapy of pancreatic cancer. Materials and Methods Gold nanoshells resonant at 810 nm were encapsulated in silica epilayers doped with iron oxide and the NIR dye ICG, resulting in theranostic gold nanoshells (TGNS), which were subsequently conjugated with antibodies targeting NGAL in AsPC-1-derived xenografts in nude mice. Results AntiNGAL-conjugated TGNS specifically targeted pancreatic cancer cells in vitro and in vivo providing contrast for both NIR fluorescence and T2 weighted MR imaging with higher tumor contrast than can be obtained using long-circulating but non-targeted PEGylated nanoparticles. The nanocomplexes also enabled highly specific cancer cell death via NIR photothermal therapy in vitro. Conclusions Theranostic gold nanoshells with embedded NIR and MR contrasts can be specifically targeted to pancreatic cancer cells with expression of early disease marker NGAL, and enable molecularly targeted imaging and photothermal therapy. PMID:24063415

  16. Robotic Whipple Procedure for Pancreatic Cancer: The Moffitt Cancer Center Pathway.

    Science.gov (United States)

    Rashid, Omar M; Mullinax, John E; Pimiento, Jose M; Meredith, Kenneth L; Malafa, Mokenge P

    2015-07-01

    Resection of malignancies in the head and uncinate process of the pancreas (Whipple procedure) using a robotic approach is emerging as a surgical option. Although several case series of the robotic Whipple procedure have been reported, detailed descriptions of operative techniques and a clear pathway for adopting this technology are lacking. We present a focused review of the procedure as it applies to pancreatic cancer and describe our clinical pathway for the robotic Whipple procedure used in pancreatic cancer and review the outcomes of our early experience. A systematic review of the literature is provided, focusing on the indications, variations in surgical techniques, complications, and oncological results of the robotic Whipple procedure. A clinical pathway has been defined for preoperative training of surgeons, the requirements for hospital privileges, patient selection, and surgical techniques for the robotic Whipple procedure. The robotic technique for managing malignant lesions of the pancreas head is safe when following