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Pancreatic Neoplasms: HELP
Articles from US Dept of Health and Human Services
Based on 341 articles published since 2008
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These are the 341 published articles about Pancreatic Neoplasms that originated from US Dept of Health and Human Services during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14
1 Editorial Pancreatic Cancer Chemoprevention: Challenges and Opportunities. 2018

Mohammed, Altaf / Rao, Chinthalapally V. ·Chemopreventive Agent Development Research Group (CADRG) Division of Cancer Prevention National Cancer Institute Rockville, MD 20850, United States. · Center for Cancer Prevention and Drug Development (CCPDD) Stephenson Cancer Center, Medical Oncology University of Oklahoma Health Sciences Center Oklahoma City, OK 73104, United States. ·Curr Med Chem · Pubmed #30014794.

ABSTRACT: -- No abstract --

2 Editorial Pancreatic Cancer: Current Progress and Future Challenges. 2016

Hussain, S Perwez. ·Head Pancreatic Cancer Unit, Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institutes, NIH, Bethesda, MD 20892, USA. ·Int J Biol Sci · Pubmed #26929733.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, remains one of the highly lethal malignancies. The highly refractory nature of clinically advanced disease and lack of a reliable biomarker for early detection are major obstructions in improving patient outcome. The recent efforts, however, in understanding the pancreatic tumor biology have resulted in the recognition of novel addictions as well as vulnerabilities of tumor cells and are being assessed for their clinical potential. This special issue highlights some of the recent progress, complexity and challenges towards improving disease outcome in patients with this lethal malignancy.

3 Editorial Timely completion of scientifically rigorous cancer clinical trials: an unfulfilled priority. 2013

Doroshow, James H. ·National Cancer Institute, National Institutes of Health, Bethesda, MD. ·J Clin Oncol · Pubmed #23960175.

ABSTRACT: -- No abstract --

4 Review Gastrinomas: Medical or Surgical Treatment. 2018

Norton, Jeffrey A / Foster, Deshka S / Ito, Tetsuhide / Jensen, Robert T. ·Department of Surgery, Stanford University School of Medicine, 291 campus Drive, Stanford, CA 94305-5101, USA. · Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital, International University of Health and Welfare, 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan. · Digestive Diseases Branch, NIDDK, National Institutes of Health, Building 10, Room 9C-103, Bethesda, MD 20892-1804, USA. Electronic address: robertj@bdg10.niddk.nih.gov. ·Endocrinol Metab Clin North Am · Pubmed #30098717.

ABSTRACT: This article reviews the role of surgical and medical management in patients with Zollinger-Ellison syndrome (ZES) due to a gastrin-secreting neuroendocrine tumor (gastrinoma). It concentrates on the status at present but also briefly reviews the changes over time in treatment approaches. Generally, surgical and medical therapy are complementary today; however, in some cases, such as patients with ZES and multiple endocrine neoplasia type 1, the treatment approach remains controversial.

5 Review Imaging of pancreatic neuroendocrine tumors: recent advances, current status, and controversies. 2018

Lee, Lingaku / Ito, Tetsuhide / Jensen, Robert T. ·a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan. · b Digestive Diseases Branch , NIDDK, NIH , Bethesda , MD , USA. · c Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital International University of Health and Welfare 3-6-45 Momochihama , Sawara-Ku, Fukuoka , Japan. ·Expert Rev Anticancer Ther · Pubmed #29973077.

ABSTRACT: INTRODUCTION: Recently, there have been a number of advances in imaging pancreatic neuroendocrine tumors (panNETs), as well as other neuroendocrine tumors (NETs), which have had a profound effect on the management and treatment of these patients, but in some cases are also associated with controversies. Areas covered: These advances are the result of numerous studies attempting to better define the roles of both cross-sectional imaging, endoscopic ultrasound, with or without fine-needle aspiration, and molecular imaging in both sporadic and inherited panNET syndromes; the increased attempt to develop imaging parameters that correlate with tumor classification or have prognostic value; the rapidly increasing use of molecular imaging in these tumors and the attempt to develop imaging parameters that correlate with treatment/outcome results. Each of these areas and the associated controversies are reviewed. Expert commentary: There have been numerous advances in all aspects of the imaging of panNETs, as well as other NETs, in the last few years. The advances are leading to expanded roles of imaging in the management of these patients and the results being seen in panNETs/GI-NETs with these newer techniques are already being used in more common tumors.

6 Review Dietary patterns and risk of pancreatic cancer: a systematic review. 2017

Zheng, Jiali / Guinter, Mark A / Merchant, Anwar T / Wirth, Michael D / Zhang, Jiajia / Stolzenberg-Solomon, Rachael Z / Steck, Susan E. ·Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA. · Cancer Prevention and Control Program, University of South Carolina, Columbia, South Carolina, USA. · Connecting Health Innovations LLC, Columbia, South Carolina, USA. · Division of Cancer Epidemiology and Genetics, Nutritional Epidemiology Branch, National Cancer Institute, Rockville, Maryland, USA. ·Nutr Rev · Pubmed #29025004.

ABSTRACT: Context: Pancreatic cancer has the highest case fatality rate of all major cancers. Objective: A systematic review using PRISMA guidelines was conducted to summarize the associations between dietary patterns and risk of pancreatic cancer. Data Sources: PubMed and Web of Science databases were searched for case-control and cohort studies published up to June 15, 2016. Study Selection: Eligible studies included a dietary pattern as exposure and pancreatic cancer incidence or mortality as outcome and reported odds ratios, hazard ratios, or relative risks, along with corresponding 95%CIs. Data Extraction: Important characteristics of each study, along with the dietary assessment instrument, the component foods or nutrients included in each dietary pattern or the scoring algorithm of a priori dietary patterns, were presented. For each dietary pattern identified, the estimate of association and the 95%CI comparing the highest versus the lowest category from the model with the most covariate adjustment were reported. Results: A total of 16 studies were identified. Among the 8 studies that examined data-driven dietary patterns, significant positive associations were found between pancreatic cancer risk and the Animal Products, Starch Rich, and Western dietary patterns, with effect estimates ranging from 1.69 to 2.40. Significant inverse relationships were found between risk of pancreatic cancer and dietary patterns designated as Fruits and Vegetables, Vitamins and Fiber, and Prudent, with effect estimates ranging from 0.51 to 0.55. Eight studies of a priori dietary patterns consistently suggested that improved dietary quality was associated with reduced risk of pancreatic cancer. Conclusions: Better diet quality is associated with reduced risk of pancreatic cancer. The associations between dietary patterns and pancreatic cancer were stronger in case-control studies than in cohort studies and were stronger among men than among women.

7 Review EUS and related technologies for the diagnosis and treatment of pancreatic disease: research gaps and opportunities-Summary of a National Institute of Diabetes and Digestive and Kidney Diseases workshop. 2017

Lee, Linda S / Andersen, Dana K / Ashida, Reiko / Brugge, William R / Canto, Mimi I / Chang, Kenneth J / Chari, Suresh T / DeWitt, John / Hwang, Joo Ha / Khashab, Mouen A / Kim, Kang / Levy, Michael J / McGrath, Kevin / Park, Walter G / Singhi, Aatur / Stevens, Tyler / Thompson, Christopher C / Topazian, Mark D / Wallace, Michael B / Wani, Sachin / Waxman, Irving / Yadav, Dhiraj / Singh, Vikesh K. ·Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. · Departments of Cancer Survey and Gastrointestinal Oncology, Osaka Prefectural Hospital Organization, Osaka International Cancer Institute, Osaka, Japan. · Department of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA. · Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Comprehensive Digestive Disease Center, Department of Gastroenterology and Hepatology, University of California at Irvine Health, Orange, California, USA. · Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. · Division of Gastroenterology, Indiana University Health Medical Center, Indianapolis, Indiana, USA. · Department of Medicine, University of Washington, Seattle, Washington, USA. · Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. · Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. · Department of Medicine, Stanford University School of Medicine, Stanford, California, USA. · Department of Pathology, University of Pittsburgh Medical Center, Sewickley, Pennsylvania, USA. · Department of Gastroenterology, Cleveland Clinic, Cleveland, Ohio, USA. · Department of Gastroenterology and Hepatology, Mayo Clinic Florida, Jacksonville, Florida, USA. · Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. · Department of Medicine, The University of Chicago Comprehensive Cancer Center, University of Chicago School of Medicine, Chicago, Illinois, USA. ·Gastrointest Endosc · Pubmed #28941651.

ABSTRACT: A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to address the research gaps and opportunities in pancreatic EUS. The event occurred on July 26, 2017 in 4 sessions: (1) benign pancreatic diseases, (2) high-risk pancreatic diseases, (3) diagnostic and therapeutics, and (4) new technologies. The current state of knowledge was reviewed, with identification of numerous gaps in knowledge and research needs. Common themes included the need for large multicenter consortia of various pancreatic diseases to facilitate meaningful research of these entities; to standardize EUS features of different pancreatic disorders, the technique of sampling pancreatic lesions, and the performance of various therapeutic EUS procedures; and to identify high-risk disease early at the cellular level before macroscopic disease develops. The need for specialized tools and accessories to enable the safe and effective performance of therapeutic EUS procedures also was discussed.

8 Review Management Options for Advanced Low or Intermediate Grade Gastroenteropancreatic Neuroendocrine Tumors: Review of Recent Literature. 2017

Neychev, Vladimir / Kebebew, Electron. ·Department of Surgery, University Hospital "Alexandrovska", Medical University, Sofia, Bulgaria. · Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ·Int J Surg Oncol · Pubmed #28593056.

ABSTRACT: Our understanding of the biology, genetics, and natural history of neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas has improved considerably in the last several decades and the spectrum of available therapeutic options is rapidly expanding. The management of patients with metastatic low or intermediate grade NETs has been revolutionized by the development of new treatment strategies such as molecular targeting therapies with everolimus and sunitinib, somatostatin analogs, tryptophan hydroxylase inhibitors, and peptide receptor radionuclide therapy that can be used alone or as a multimodal approach with or without surgery. To further define and clarify the utility, appropriateness, and the sequence of the growing list of available therapies for this patient population will require more high level evidence; however, data from well-designed randomized phase III clinical trials is rapidly accumulating that will further stimulate development of new management strategies. It is therefore important to thoroughly review emerging evidence and report major findings in frequent updates, which will expand our knowledge and contribute to a better understanding, characterization, and management of advanced NETs.

9 Review Pancreatic Cancer: "A Riddle Wrapped in a Mystery inside an Enigma". 2017

Borazanci, Erkut / Dang, Chi V / Robey, Robert W / Bates, Susan E / Chabot, John A / Von Hoff, Daniel D. ·HonorHealth, Scottsdale, Arizona and TGen, Phoenix, Arizona. Erkut.Borazanci@HonorHealth.com. · Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania. · National Institutes of Health, Bethesda, Maryland. · Columbia University Medical Center, New York, New York. · James J. Peters Bronx VA Medical Center, Bronx, New York. · HonorHealth, Scottsdale, Arizona and TGen, Phoenix, Arizona. ·Clin Cancer Res · Pubmed #28373361.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most difficult-to-treat cancers. With an increasing incidence and inability to make major progress, it represents the very definition of unmet medical need. Progress has been made in understanding the basic biology-systematic genomic sequencing has led to the recognition that PDAC is not typically a heavily mutated tumor, although there are exceptions. The most consistently mutated genes are

10 Review Advances in the diagnosis and treatment of pancreatic neuroendocrine neoplasms in Japan. 2017

Ito, Tetsuhide / Hijioka, Susumu / Masui, Toshihiko / Kasajima, Atsuko / Nakamoto, Yuji / Kobayashi, Noritoshi / Komoto, Izumi / Hijioka, Masayuki / Lee, Lingaku / Igarashi, Hisato / Jensen, Robert Thomas / Imamura, Masayuki. ·Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. itopapa@intmed3.med.kyushu-u.ac.jp. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Department of Pathology, Tohoku University Hospital, Sendai, Japan. · Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Department of Oncology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. · Department of Surgery, Kansai Electric Power Hospital, Osaka, Japan. · Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. · Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. · Neuroendocrine Tumor Center, Kansai Electric Power Hospital, Osaka, Japan. ·J Gastroenterol · Pubmed #27539256.

ABSTRACT: Several new developments have occurred in the field of pancreatic neuroendocrine neoplasm (PNEN) recently in Japan. First, the utility of chromogranin A (CgA), useful for the diagnosis and monitoring of the treatment response of neuroendocrine neoplasm (NEN), has been demonstrated in Japan. For PNEN diagnosis and treatment, grading and correct histological diagnosis according to the WHO 2010 classification is important. Regarding the histological diagnosis, the advent of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has enabled correct pathological diagnosis and suitable treatment for the affected tissue. Furthermore, EUS-FNA has also facilitates the assessment of the presence or absence of gene mutations. In addition, patients who have a well-differentiated neuroendocrine tumor (NET) showing a Ki-67 index of higher than 20 % according to the WHO 2010 classification, have also been identified, and their responses to treatment were found to be different from those of patients with poorly differentiated neuroendocrine carcinoma (NEC). Therefore, the concept of NET G3 was proposed. Additionally, somatostatin receptor type 2 is expressed in several cases of NET, and somatostatin receptor scintigraphy (

11 Review NO 2017

Wang, Jian / Hussain, S Perwez. ·Pancreatic Cancer Unit, Laboratory of Human Carcinogenesis, NIH Center for Cancer Research, National Cancer Institute , Bethesda, Maryland. ·Antioxid Redox Signal · Pubmed #27510096.

ABSTRACT: SIGNIFICANCE: Pancreatic tumors express high level of nitric oxide synthases (NOSs) in particular inducible (iNOS/NOS2) and endothelial (eNOS/NOS3) forms. However, the role of nitric oxide (NO CRITICAL ISSUES: The extremely poor prognosis in pancreatic cancer is due to the late diagnosis and lack of effective therapy in advanced disease. One of the most critical issues is to decipher the underlying mechanism of disease aggressiveness and therapeutic resistance for identifying potential therapeutic target and effective treatment. Given the evidence of a strong association between inflammation and pancreatic cancer and clinical evidence, which suggests an association between NOS2 and disease aggressiveness, it is critical to define the role of NO FUTURE DIRECTIONS: Recent preclinical and clinical evidences indicate a potential therapeutic significance of targeting NO

12 Review Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer. 2016

Hart, Phil A / Bellin, Melena D / Andersen, Dana K / Bradley, David / Cruz-Monserrate, Zobeida / Forsmark, Christopher E / Goodarzi, Mark O / Habtezion, Aida / Korc, Murray / Kudva, Yogish C / Pandol, Stephen J / Yadav, Dhiraj / Chari, Suresh T / Anonymous3191104. ·Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address: philip.hart@osumc.edu. · Division of Pediatric Endocrinology and Schulze Diabetes Institute, University of Minnesota Medical Center, Minneapolis, MN, USA. · Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. · Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University, Wexner Medical Center, Columbus, OH, USA. · Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA. · Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL, USA. · Division of Endocrinology, Diabetes, and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, USA. · Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA. · Departments of Medicine, Biochemistry, and Molecular Biology, Indiana University School of Medicine, Indiana University Simon Cancer Center, Indianapolis, IN, USA; Pancreatic Cancer Signature Center, Indiana University Simon Cancer Center, Indianapolis, IN, USA. · Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, USA. · Department of Veterans Affairs, Cedars-Sinai Medical Center, Los Angeles, CA, USA. · Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh and UPMC Medical Center, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh and UPMC Medical Center, Pittsburgh, PA, USA. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. ·Lancet Gastroenterol Hepatol · Pubmed #28404095.

ABSTRACT: Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes. It is important to note that type 3c diabetes is not a single entity; it occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia. The most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type 3c diabetes secondary to chronic pancreatitis and pancreatic ductal adenocarcinoma, and highlight several important knowledge gaps.

13 Review Molecular Imaging of Gastroenteropancreatic Neuroendocrine Tumors: Current Status and Future Directions. 2016

Deroose, Christophe M / Hindié, Elif / Kebebew, Electron / Goichot, Bernard / Pacak, Karel / Taïeb, David / Imperiale, Alessio. ·Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium. · Nuclear Medicine, Haut-Lévêque Hospital, University of Bordeaux, France. · LabEx TRAIL, University of Bordeaux, France. · Endocrine Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland. · Internal Medicine, Strasbourg University Hospitals, Strasbourg, France. · Section on Medical Neuroendocrinology, Eunice Kennedy Shriver NICHD, NIH, Bethesda, Maryland. · Nuclear Medicine, La Timone University Hospital, Aix-Marseille University, Marseille, France. · European Center for Research in Medical Imaging, Marseille, France. · INSERM UMR1068, Marseille, France. · Biophysics and Nuclear Medicine, Strasbourg University Hospitals, Strasbourg, France; and alessio.imperiale@chru-strasbourg.fr. · ICube, UMR 7357, University of Strasbourg/CNRS and FMTS, Faculty of Medicine, University of Strasbourg, Strasbourg, France. ·J Nucl Med · Pubmed #27811124.

ABSTRACT: Through diagnostic imaging and peptide receptor radionuclide therapy, nuclear medicine has earned a major role in gastroenteropancreatic neuroendocrine tumors (GEP NETs). GEP NETs are diagnosed fortuitously or on the basis of symptoms or hormonal syndrome. The functional tumor characteristics shown by radionuclide imaging allow for more accurate staging and treatment selection. Tumor grade helps determine which tracer should be selected. In the past,

14 Review Potential usefulness of apolipoprotein A2 isoforms for screening and risk stratification of pancreatic cancer. 2016

Honda, Kazufumi / Srivastava, Sudhir. ·Division of Chemotherapy & Clinical Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan. · Japan Agency for Medical Research & Development (AMED) CREST, Tokyo 100-0004, Japan. · Division of Cancer Prevention, National Cancer Institute, Rockville, MD 20852, USA. ·Biomark Med · Pubmed #27673558.

ABSTRACT: Given the low incidence of pancreatic cancer in the general population, screening of pancreatic cancer in the general population using invasive modalities is not feasible. Combination of invasive screening with noninvasive biomarkers for pancreatic cancer and its precancerous lesions has the potential to reduce mortality due to pancreatic cancer. In this review, we focus on biomarkers found in the blood that can indicate early-stage pancreatic cancer, and we discuss current strategies for screening for pancreatic cancer. We recently identified a unique alteration in apolipoprotein A2 isoforms in pancreatic cancer and its precancerous lesions, and we describe its clinical usefulness as a potential biomarker for the early detection and risk stratification of pancreatic cancer.

15 Review Pharmacodynamic endpoints as clinical trial objectives to answer important questions in oncology drug development. 2016

Parchment, Ralph E / Doroshow, James H. ·Clinical Pharmacodynamics Program, Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, MD. · Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD. Electronic address: doroshoj@mail.nih.gov. ·Semin Oncol · Pubmed #27663483.

ABSTRACT: Analyzing the molecular interplay between malignancies and therapeutic agents is rarely a straightforward process, but we hope that this special issue of Seminars has highlighted the clinical value of such endeavors as well as the relevant theoretical and practical considerations. Here, we conclude with both an overview of the various high-value applications of clinical pharmacodynamics (PD) in developmental therapeutics and an outline of the framework for incorporating PD analyses into the design of clinical trials. Given the increasingly recognized importance of determining and administering the biologically effective dose (BED) and schedule of targeted agents, we explain how clinical PD biomarkers specific to the agent mechanism of action (MOA) can be used for the development of pharmacodynamics-guided biologically effective dosage regimens (PD-BEDR) to maximize the efficacy and minimize the toxicity of targeted therapies. In addition, we discuss how MOA-based PD biomarker analyses can be used both as patient selection diagnostic tools and for designing novel drug combinations targeting the specific mutational signature of a given malignancy. We also describe the role of PD analyses in clinical trials, including for MOA confirmation and dosage regimen optimization during phase 0 trials as well as for correlating molecular changes with clinical efficacy when establishing proof-of-concept in phase I/II trials. Finally, we outline the critical technological developments that are needed to enhance the quality and quantity of future clinical PD data collection, broaden the types of molecular questions that can be answered in the clinic, and, ultimately, improve patient outcomes.

16 Review Nanomedicine strategies to overcome the pathophysiological barriers of pancreatic cancer. 2016

Adiseshaiah, Pavan P / Crist, Rachael M / Hook, Sara S / McNeil, Scott E. ·Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA. · Office of the Director, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ·Nat Rev Clin Oncol · Pubmed #27531700.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer- related deaths. PDAC remains one of the most difficult-to-treat cancers, owing to its unique pathobiological features: a nearly impenetrable desmoplastic stroma, and hypovascular and hypoperfused tumour vessels render most treatment options largely ineffective. Progress in understanding the pathobiology and signalling pathways involved in disease progression is helping researchers to develop novel ways to fight PDAC, including improved nanotechnology-based drug-delivery platforms that have the potential to overcome the biological barriers of the disease that underlie persistent drug resistance. So-called 'nanomedicine' strategies have the potential to enable targeting of the Hedgehog-signalling pathway, the autophagy pathway, and specific RAS-mutant phenotypes, among other pathological processes of the disease. These novel therapies, alone or in combination with agents designed to disrupt the pathobiological barriers of the disease, could result in superior treatments, with increased efficacy and reduced off-target toxicities compared with the current standard-of-care regimens. By overcoming drug-delivery challenges, advances can be made in the treatment of PDAC, a disease for which limited improvement in overall survival has been achieved over the past several decades. We discuss the approaches to nanomedicine that have been pursued to date and those that are the focus of ongoing research, and outline their potential, as well as the key challenges that must be overcome.

17 Review The Role of Stromal Components in Pancreatic Cancer Progression. 2016

Xu, Mengdan / Zhou, Binhua P / Tao, Min / Liu, Jingyi / Li, Wei. ·National Cancer Institute (NCI), Frederick, MD 21702, USA. jingyi.liu@nih.gov. · Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China. liwei10@suda.edu.cn. ·Anticancer Agents Med Chem · Pubmed #27039918.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers, and is known for its extremely poor prognosis. Because of the location and composition of the organ, early symptoms cannot be visualized as easily as in other solid tumors. In the past decades, researchers have been mostly working on the genetic and epigenetic alterations of the cancer cells themselves, and therapies on pancreatic cancer cells alone have failed to significantly improve patient outcome. With the identification of abundant tumor stromal responses, the focus of pancreatic cancer research has begun to change. Increasing evidence has proved that the tumor stroma, especially the cell components (such as pancreatic stellate cells, tumor-associated macrophages, mast cells etc.) plays a key role in the development of PDAC. In this review, we discuss the interactions between cancer cells and several important cell components of the tumor stroma, as well their role in tumor growth, migration, invasion, angiogenesis and immune recognition.

18 Review Evaluation and management of pancreatic lesions in patients with von Hippel-Lindau disease. 2016

Keutgen, Xavier M / Hammel, Pascal / Choyke, Peter L / Libutti, Steven K / Jonasch, Eric / Kebebew, Electron. ·Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 4-5940, Bethesda, Maryland 20891-1201, USA. · Department of Digestive Oncology, Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 100 boulevard du Général Leclerc, 92110 Clichy, France. · Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room B3B69F, Bethesda, Maryland 20892-1088, USA. · Department of Surgery, Montefiore Medical Center, 111 East 210th Street, Bronx, New York 10467, USA. · Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA. · Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, Unit 1374, Houston, Texas 77030-3721, USA. ·Nat Rev Clin Oncol · Pubmed #27030075.

ABSTRACT: von Hippel-Lindau (VHL) disease is a heritable cancer-predisposition syndrome with multiorgan involvement. Pancreatic lesions are detected in approximately two-thirds of patients with VHL disease at some point during their lifetime. In these patients, cystic pancreatic lesions are almost exclusively benign and, unless symptomatic, do not require surgical or endoscopic intervention; however, solid pancreatic lesions can often be recognized through imaging screens, and are commonly found to be nonfunctioning pancreatic neuroendocrine tumours (pNETs) with malignant potential. The natural history of these VHL-associated pNETs is variable, and lacks clinical or imaging features that predict disease progression or metastatic potential, and generally needs to be managed more conservatively than their sporadic counterparts. Treatment options for such lesions, which range from active surveillance to surgical intervention, can nevertheless be associated with considerable morbidity and even mortality. Of note, although several guidelines have been established for the management of tumours associated with VHL syndrome, none of these have specifically focused on pancreatic lesions. Thus, we aim to characterize the types of pancreatic lesions associated with VHL disease and their natural history, to identify particular lesions that necessitate treatment, and to define what forms of treatment should be undertaken.

19 Review Immunologic approaches to cancer prevention-current status, challenges, and future perspectives. 2016

Wojtowicz, Malgorzata E / Dunn, Barbara K / Umar, Asad. ·Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: wojtowim@mail.nih.gov. · Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ·Semin Oncol · Pubmed #26970135.

ABSTRACT: The potential of the immune system to recognize and reject tumors has been investigated for more than a century. However, only recently impressive breakthroughs in cancer immunotherapy have been seen with the use of checkpoint inhibitors. The experience with various immune-based strategies in the treatment of late cancer highlighted the importance of negative impact advanced disease has on immunity. Consequently, use of immune modulation for cancer prevention rather than therapy has gained considerable attention, with many promising results seen already in preclinical and early clinical studies. Although not without challenges, these results provide much excitement and optimism that successful cancer immunoprevention could be within our reach. In this review we will discuss the current state of predominantly primary and secondary cancer immunoprevention, relevant research, potential barriers, and future directions.

20 Review Pancreatic Cancer Genetics. 2016

Amundadottir, Laufey T. ·Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ·Int J Biol Sci · Pubmed #26929738.

ABSTRACT: Although relatively rare, pancreatic tumors are highly lethal [1]. In the United States, an estimated 48,960 individuals will be diagnosed with pancreatic cancer and 40,560 will die from this disease in 2015 [1]. Globally, 337,872 new pancreatic cancer cases and 330,391 deaths were estimated in 2012 [2]. In contrast to most other cancers, mortality rates for pancreatic cancer are not improving; in the US, it is predicted to become the second leading cause of cancer related deaths by 2030 [3, 4]. The vast majority of tumors arise in the exocrine pancreas, with pancreatic ductal adenocarcinoma (PDAC) accounting for approximately 95% of tumors. Tumors arising in the endocrine pancreas (pancreatic neuroendocrine tumors) represent less than 5% of all pancreatic tumors [5]. Smoking, type 2 diabetes mellitus (T2D), obesity and pancreatitis are the most consistent epidemiological risk factors for pancreatic cancer [5]. Family history is also a risk factor for developing pancreatic cancer with odds ratios (OR) ranging from 1.7-2.3 for first-degree relatives in most studies, indicating that shared genetic factors may play a role in the etiology of this disease [6-9]. This review summarizes the current knowledge of germline pancreatic cancer risk variants with a special emphasis on common susceptibility alleles identified through Genome Wide Association Studies (GWAS).

21 Review The Role of Gastrin and CCK Receptors in Pancreatic Cancer and other Malignancies. 2016

Smith, Jill P / Fonkoua, Lionel K / Moody, Terry W. ·1. Department of Medicine, Georgetown University, Washington, DC, USA. · 2. Pennsylvania State University, College of Medicine, Hershey, PA, USA. · 3. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ·Int J Biol Sci · Pubmed #26929735.

ABSTRACT: The gastrointestinal (GI) peptide gastrin is an important regulator of the release of gastric acid from the stomach parietal cells and it also plays an important role in growth of the gastrointestinal tract. It has become apparent that gastrin and its related peptide cholecystokinin (CCK) are also significantly involved with growth of GI cancers as well as other malignancies through activation of the cholecystokinin-B (CCK-B) receptor. Of interest, gastrin is expressed in the embryologic pancreas but not in the adult pancreas; however, gastrin becomes re-expressed in pancreatic cancer where it stimulates growth of this malignancy by an autocrine mechanism. Strategies to down-regulate gastrin or interfere with its interface with the CCK receptor with selective antibodies or receptor antagonists hold promise for the treatment of pancreatic cancer and other gastrin--responsive tumors.

22 Review Targeting the microenvironment of pancreatic cancer: overcoming treatment barriers and improving local immune responses. 2016

Strauss, J / Alewine, C / Figg, W D / Duffy, A. ·NCI/NIH, 9000 Rockville Pike, Bldg 10/Room 12 N-226, Bethesda, MD, 20892, USA. julius.strauss@nih.gov. · NCI/NIH, 9000 Rockville Pike, Building 37, Room 5116B, Bethesda, MD, 20892, USA. · NCI/NIH, 9000 Rockville Pike, Bldg 10/Room 5A-01, Bethesda, MD, 20892, USA. · NCI/NIH, 9000 Rockville Pike, Bldg 10/Room 12 N-226, Bethesda, MD, 20892, USA. ·Clin Transl Oncol · Pubmed #26661112.

ABSTRACT: Historically, patients diagnosed with metastatic pancreatic cancer have faced a grim prognosis. The survival benefit seen with systemic chemotherapies and even combinations thereof have been disappointing. However, growing data suggest that the microenvironment of pancreatic cancer may be contributing to this poor prognosis. This microenvironment has a dense fibrotic stroma, and is hypoxic and highly immunosuppressive, all of which pose barriers to treatment. Newer strategies looking to disrupt the fibrotic stroma, target hypoxic areas, and improve local immune responses in the tumor microenvironment are currently undergoing clinical evaluation and seem to offer great promise. In addition to these therapies, preclinical work evaluating novel cytotoxic agents including nanoparticles has also been encouraging. While much research still needs to be done, these strategies offer new hope for patients with pancreatic cancer.

23 Review Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies. 2015

Genkinger, J M / Kitahara, C M / Bernstein, L / Berrington de Gonzalez, A / Brotzman, M / Elena, J W / Giles, G G / Hartge, P / Singh, P N / Stolzenberg-Solomon, R Z / Weiderpass, E / Adami, H-O / Anderson, K E / Beane-Freeman, L E / Buring, J E / Fraser, G E / Fuchs, C S / Gapstur, S M / Gaziano, J M / Helzlsouer, K J / Lacey, J V / Linet, M S / Liu, J J / Park, Y / Peters, U / Purdue, M P / Robien, K / Schairer, C / Sesso, H D / Visvanathan, K / White, E / Wolk, A / Wolpin, B M / Zeleniuch-Jacquotte, A / Jacobs, E J. ·Department of Epidemiology, Mailman School of Public Health, Columbia University, New York Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York jg3081@columbia.edu. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda. · Division of Cancer Etiology, City of Hope National Medical Center, Duarte. · Westat, Rockville. · Division of Cancer Control and Population Sciences, National Cancer Institute, NIH, DHHS, Bethesda, USA. · Cancer Epidemiology Centre, Cancer Council of Victoria, and Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia. · Department of Epidemiology, Biostatistics and Population Medicine and The Center for Health Research, Loma Linda University School of Medicine, Loma Linda, USA. · Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø Department of Research, Cancer Registry of Norway, Oslo, Norway Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Department of Epidemiology, Harvard School of Public Health, Boston. · Division of Epidemiology and Community Health, School of Public Health, and Masonic Cancer Center, University of Minnesota, Minneapolis. · Department of Epidemiology, Harvard School of Public Health, Boston Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston. · Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston Department of Medical Oncology, Dana-Farber Cancer Institute, Boston. · Epidemiology Research Program, American Cancer Society, Atlanta. · Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston Massachusetts Veterans Epidemiology Research and Information Center, Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston. · The Prevention & Research Center, Mercy Medical Center, Baltimore Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda Division of Public Health Sciences, Washington University School of Medicine, St Louis. · Fred Hutchinson Cancer Research Center, Seattle Department of Epidemiology, University of Washington, Seattle. · Department of Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington. · Department of Epidemiology, Harvard School of Public Health, Boston Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore Department of Medical Oncology, Sidney Kimmel Cancer Center, John Hopkins School of Medicine, Baltimore, USA. · Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. · Department of Population Health and Perlmutter Cancer Center, New York University, New York, USA. ·Ann Oncol · Pubmed #26347100.

ABSTRACT: BACKGROUND: Body mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk. DESIGN: We conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood (ages 18-21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. RESULTS: Higher waist-to-hip ratio (HR = 1.09, 95% CI 1.02-1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00-1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11-1.25 per 5 kg/m(2)), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m(2), HR = 1.36, 95% CI 1.20-1.55 for BMI 25.0 < 27.5 kg/m(2), HR = 1.48, 95% CI 1.20-1.84 for BMI 27.5 to <30 kg/m(2), HR = 1.43, 95% CI 1.11-1.85 for BMI ≥30 kg/m(2)). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01-1.10 per 5 kg/m(2)). CONCLUSIONS: Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.

24 Review Epidemiology and Inherited Predisposition for Sporadic Pancreatic Adenocarcinoma. 2015

Stolzenberg-Solomon, Rachael Z / Amundadottir, Laufey T. ·Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Room 6E420, Rockville, MD 20850, USA. Electronic address: rs221z@nih.gov. · Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 8717 Grovemont Circle, Bethesda, MD 20892, USA. Electronic address: amundadottirl@mail.nih.gov. ·Hematol Oncol Clin North Am · Pubmed #26226901.

ABSTRACT: Given the changing demographics of Western populations, the numbers of pancreatic cancer cases are projected to increase during the next decade. Diabetes, recent cigarette smoking, and excess body weight are the cancer's most consistent risk factors. The search for common and rare germline variants that influence risk of pancreatic cancer through genome-wide association studies and high-throughput-sequencing-based studies is underway and holds the promise of increasing the knowledge of variants and genes that play a role in inherited susceptibility of this disease. Research reported in this review has advanced the understanding of pancreatic cancer.

25 Review Early detection of sporadic pancreatic cancer: summative review. 2015

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. ·From the *Department of Medicine, Mayo Clinic, Rochester, MN; †Department of Biomedical Engineering, University of Virginia, Charlottesville, VA; Departments of ‡Biochemistry and Molecular Biology, §Pathology and Microbiology, and ∥Surgery, Fred & Pamela Buffett Cancer Center, University of Nebraska, Omaha, NE; ¶Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD; #Division of Gastroenterology, University of Washington, Seattle, WA; **Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD; ††Sawgrass Leadership Institute, Ponte Vedra Beach, FL; ‡‡Department of Surgery, University of Utah, Salt Lake City, UT; §§Department of Radiology, Stanford University School of Medicine, Stanford; ∥∥Department of Medicine, David Geffen School of Medicine, and ¶¶General Surgery, University of California Los Angeles, Los Angeles, CA; ##Kenner Family Research Fund; ***Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY; †††Department of Internal Medicine, University of Greifswald, Greifswald, Germany; ‡‡‡Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX; §§§Department of Health Sciences Research, Mayo Clinic, Rochester, MN; ∥∥∥Gastroenterology Division, Department of Internal Medicine and Comprehensive Cancer Center, and ¶¶¶Department of Surgery, School of Medicine, University of Michigan, Ann Arbor, MI; ###Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD; ****Departments of Surgery and Oncology, Kyushu University, Fukuoka, Japan; ††††Department of Medicine, Eastern Virginia Medical School, Norfolk, VA; and ‡‡‡‡Division of Oral Biology and Medicine, CLA School of Dentistry, Jonnson Comprehensive Cancer Center, University of California Los Angeles, L ·Pancreas · Pubmed #25931254.

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.

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