Functional Annotation of the Pancreatic Cancer Genome

Summary

Principal Investigator: Steven D Leach
Abstract: DESCRIPTION (provided by applicant): The past decade has witnessed unprecedented progress in our understanding of the genetic changes underlying human pancreatic cancer. Led by a long series of important contributions by Program investigators, the genetic and epigenetic basis for pancreatic cancer has slowly been unraveled, with over 30 genetic loci now recognized to undergo mutation in this disease, and characteristic changes in gene expression reported for an even larger number of coding genes and non-coding microRNAs. However, the functional contribution of these mutations to the pancreatic cancer phenotype remains largely uninvestigated. The central Aim of this Program Project Grant is to narrow the gap between genetic and functional data, by determining the functional significance of molecular alterations identified in human pancreatic cancer. This functional annotation will be pursued by examining the impact of candidate dominant and recessive mutations, as well as characteristic changes in microRNA expression, using novel cell-, zebrafish- and mouse-based assays developed by members of our group. Four projects will be pursued: Project 1: Functional annotation of human pancreatic cancer genes in a zebrafish system (Leach);Project 2: Discovery and evaluation of prioritized mutations in human pancreatic cancer (Kern);Project 3: The Hippo signaling pathway in pancreatic cancer (Maitra);and Project 4: Functional evaluation of microRNAs in pancreatic neoplasia (Mendell). These projects will be supported by three shared Cores: Core A: Cellular and Transgenic Phenotyping Core (Huso);Core B: Zebrafish Core (Parsons), and Core C: Administrative Core (Leach). The investigators pursuing these projects are all leaders in the field of pancreatic cancer research, and have an outstanding track record of synergistic interaction. The Program also leverages many already existing resources available at Johns Hopkins, including aspects of the NCI Gl SPORE grant, core resources provided by the Johns Hopkins Comprehensive Cancer Center, and the independently funded Pancreatic Cancer Genome Project. Together, these studies will dramatically accelerate the functional annotation of the pancreatic cancer genome, setting the stage for future therapeutic applications.
Funding Period: 2009-04-15 - 2015-03-31
more information: NIH RePORT

Top Publications

  1. pmc An essential mesenchymal function for miR-143/145 in intestinal epithelial regeneration
    Raghu R Chivukula
    Medical Scientist Training Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 157:1104-16. 2014
  2. pmc Conceptual framework for cutting the pancreatic cancer fuel supply
    Anne Le
    Departments of Pathology and Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Clin Cancer Res 18:4285-90. 2012
  3. pmc Heterogeneity and targeting of pancreatic cancer stem cells
    Vesselin R Penchev
    Department of Oncology and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Clin Cancer Res 18:4277-84. 2012
  4. pmc Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver
    Shu Hao Hsu
    Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH, USA
    J Clin Invest 122:2871-83. 2012
  5. pmc Stromal galectin-1 expression is associated with long-term survival in resectable pancreatic ductal adenocarcinoma
    Ru Chen
    Department of Medicine, University of Washington, Seattle, WA, USA
    Cancer Biol Ther 13:899-907. 2012
  6. pmc miRNA biomarkers in cyst fluid augment the diagnosis and management of pancreatic cysts
    Hanno Matthaei
    Departments of Pathology, Oncology, and Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Clin Cancer Res 18:4713-24. 2012
  7. pmc MicroRNAs in stress signaling and human disease
    Joshua T Mendell
    Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Cell 148:1172-87. 2012
  8. pmc EMT and dissemination precede pancreatic tumor formation
    Andrew D Rhim
    Gastroenterology Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell 148:349-61. 2012
  9. pmc Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer
    A Hunter Shain
    Department of Pathology, Stanford University, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 109:E252-9. 2012
  10. pmc Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia
    Mitsuro Kanda
    Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Gastroenterology 142:730-733.e9. 2012

Detail Information

Publications47

  1. pmc An essential mesenchymal function for miR-143/145 in intestinal epithelial regeneration
    Raghu R Chivukula
    Medical Scientist Training Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 157:1104-16. 2014
    ..These results provide important insights into the regulation of epithelial wound healing and argue against a cell-autonomous tumor suppressor role for miR-143/145 in colon cancer...
  2. pmc Conceptual framework for cutting the pancreatic cancer fuel supply
    Anne Le
    Departments of Pathology and Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Clin Cancer Res 18:4285-90. 2012
    ..Herein, the conceptual framework for blocking the pancreatic fuel supply is reviewed...
  3. pmc Heterogeneity and targeting of pancreatic cancer stem cells
    Vesselin R Penchev
    Department of Oncology and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Clin Cancer Res 18:4277-84. 2012
    ..In this CCR Focus article, we discuss the potential relationships between different pancreatic CSC populations and strategies to identify novel targeting approaches...
  4. pmc Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver
    Shu Hao Hsu
    Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH, USA
    J Clin Invest 122:2871-83. 2012
    ....
  5. pmc Stromal galectin-1 expression is associated with long-term survival in resectable pancreatic ductal adenocarcinoma
    Ru Chen
    Department of Medicine, University of Washington, Seattle, WA, USA
    Cancer Biol Ther 13:899-907. 2012
    ....
  6. pmc miRNA biomarkers in cyst fluid augment the diagnosis and management of pancreatic cysts
    Hanno Matthaei
    Departments of Pathology, Oncology, and Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Clin Cancer Res 18:4713-24. 2012
    ..We assessed the diagnostic benefit of using miRNAs as biomarkers in pancreatic cyst fluid, focusing on IPMNs because of their frequency and malignant potential...
  7. pmc MicroRNAs in stress signaling and human disease
    Joshua T Mendell
    Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Cell 148:1172-87. 2012
    ..These discussions further highlight the unique challenges and opportunities associated with the mechanistic dissection of miRNA functions and the development of miRNA-based therapeutics...
  8. pmc EMT and dissemination precede pancreatic tumor formation
    Andrew D Rhim
    Gastroenterology Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell 148:349-61. 2012
    ..These results provide insight into the earliest events of cellular invasion in situ and suggest that inflammation enhances cancer progression in part by facilitating EMT and entry into the circulation...
  9. pmc Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer
    A Hunter Shain
    Department of Pathology, Stanford University, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 109:E252-9. 2012
    ..Our findings reveal SWI/SNF to be a central tumor suppressive complex in pancreatic cancer...
  10. pmc Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia
    Mitsuro Kanda
    Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Gastroenterology 142:730-733.e9. 2012
    ..These findings could improve our understanding of the development and progression of these premalignant lesions...
  11. pmc The HMGA1-COX-2 axis: a key molecular pathway and potential target in pancreatic adenocarcinoma
    Joelle Hillion
    Hematology Division, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
    Pancreatology 12:372-9. 2012
    ..We previously reported that the high-mobility group A1 (HMGA1) protein is overexpressed in >90% of primary pancreatic cancers, with absent or low levels in early precursor lesions...
  12. pmc GNAS codon 201 mutations are uncommon in intraductal papillary neoplasms of the bile duct
    Hanno Matthaei
    Departments of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    HPB (Oxford) 14:677-83. 2012
    ..Intraductal papillary neoplasms of the bile ducts (IPNBs) morphologically resemble pancreatic IPMNs. This study sought to assess the mutational status of GNAS at codon 201 in IPNBs...
  13. pmc APE1/Ref-1 regulates STAT3 transcriptional activity and APE1/Ref-1-STAT3 dual-targeting effectively inhibits pancreatic cancer cell survival
    Angelo A Cardoso
    Division of Hematology Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
    PLoS ONE 7:e47462. 2012
    ....
  14. pmc Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia
    Florencia McAllister
    Department of Oncology, Johns Hopkins University, Baltimore, MD 21205, USA Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
    Cancer Cell 25:621-37. 2014
    ..Together, these studies suggest that a hematopoietic-to-epithelial IL-17 signaling axis is a potent and requisite driver of PanIN formation. ..
  15. pmc GNAS sequencing identifies IPMN-specific mutations in a subgroup of diminutive pancreatic cysts referred to as "incipient IPMNs"
    Hanno Matthaei
    Departments of Pathology Oncology Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine Ludwig Center for Cancer Genetics Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD Department of Pathology, Microbiology, Immunology, Vanderbilt University Medical Center, Nashville, TN Departments of General, Visceral, Thoracic and Vascular Surgery Prostate Cancer Research Institute of Pathology, University of Bonn, Bonn, Germany
    Am J Surg Pathol 38:360-3. 2014
    ..Additional studies in a larger cohort are needed to define the relationship of incipient IPMNs to larger IPMNs and, more importantly, to determine their clinical significance...
  16. pmc TERT promoter mutations occur early in urothelial neoplasia and are biomarkers of early disease and disease recurrence in urine
    Isaac Kinde
    Authors Affiliations The Ludwig Center for Cancer Genetics and Therapeutics, The Swim Across America Laboratory at Johns Hopkins, and The Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center Departments of Pathology, Oncology, and Urology, The Johns Hopkins Medical Institutes, Baltimore, Maryland
    Cancer Res 73:7162-7. 2013
    ..These provocative results suggest that TERT promoter mutations may offer a useful urinary biomarker for both early detection and monitoring of bladder neoplasia...
  17. pmc DCLK1 marks a morphologically distinct subpopulation of cells with stem cell properties in preinvasive pancreatic cancer
    Jennifer M Bailey
    Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland The McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
    Gastroenterology 146:245-56. 2014
    ..Using mouse models and human pancreatic cancer cell lines, we investigated whether preinvasive pancreatic neoplasia contains a subpopulation of cells with distinct morphologies and cancer stem cell-like properties...
  18. pmc "Selective cell death mediated by small conditional RNAs" is not selective
    Kalpesh Patel
    The Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD USA
    Cancer Biol Ther 14:693-6. 2013
    ..Recently the publication was retracted but without comment on the validity of the reported method. Here we provide scientific basis to consider the method impaired or invalid...
  19. pmc MicroRNA 223 is upregulated in the multistep progression of Barrett's esophagus and modulates sensitivity to chemotherapy by targeting PARP1
    Mirte Mayke Streppel
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Clin Cancer Res 19:4067-78. 2013
    ..The functional significance of these miRNAs in esophageal adenocarcinoma initiation and progression is largely unknown...
  20. pmc FAM190A deficiency creates a cell division defect
    Kalpesh Patel
    Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
    Am J Pathol 183:296-303. 2013
    ....
  21. pmc Disputed paternity: the uncertain ancestry of pancreatic ductal neoplasia
    Anirban Maitra
    Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA
    Cancer Cell 22:701-3. 2012
    ..Whereas a rare ductal subpopulation may still prove capable of neoplastic transformation, these findings refocus attention on acinar and other non-ductal cell types as initiators of this deadly neoplasm...
  22. pmc Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes
    Andrew V Biankin
    The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia
    Nature 491:399-405. 2012
    ....
  23. pmc Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways
    Jian Wu
    Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Proc Natl Acad Sci U S A 108:21188-93. 2011
    ..These results highlight the essential role of ubiquitin ligases in these neoplasms and have important implications for the diagnosis and treatment of patients with cystic tumors...
  24. pmc Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation
    Meritxell Rovira
    Department of Surgery, and McKusick Nathans Institute for Genetic Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 108:19264-9. 2011
    ..Using pharmacological approaches, we have identified and characterized two unique pathways in β-cell differentiation in the zebrafish, including down-regulation of GTP production and retinoic acid biosynthesis...
  25. pmc HMGA1 drives stem cell, inflammatory pathway, and cell cycle progression genes during lymphoid tumorigenesis
    Andrew Schuldenfrei
    Department of Medicine, Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    BMC Genomics 12:549. 2011
    ..To define the HMGA1 transcriptome, we analyzed gene expression profiles in lymphoid cells from HMGA1a transgenic mice at different stages in tumorigenesis...
  26. pmc DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors
    Yuchen Jiao
    Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 331:1199-203. 2011
    ..We also found mutations in genes in the mTOR (mammalian target of rapamycin) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors...
  27. pmc Genetic inducible fate mapping in larval zebrafish reveals origins of adult insulin-producing β-cells
    Yiyun Wang
    Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Development 138:609-17. 2011
    ..As pancreas organogenesis continues, the ventral bud derived PNCs align along the duct, remain multipotent and later in development differentiate to form secondary islets, ducts and CACs...
  28. pmc Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway
    Oliver A Kent
    Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Genes Dev 24:2754-9. 2010
    ..Additionally, KRAS and RREB1 are targets of miR-143/miR-145, revealing a feed-forward mechanism that potentiates Ras signaling...
  29. pmc The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program
    Jing Cai
    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Genes Dev 24:2383-8. 2010
    ..Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program...
  30. pmc The Axl receptor tyrosine kinase is an adverse prognostic factor and a therapeutic target in esophageal adenocarcinoma
    Alvarez Hector
    Departments of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Cancer Biol Ther 10:1009-18. 2010
    ..Axl RTK is an adverse prognostic factor in EAC. The availability of small molecule inhibitors of Axl function provides a tractable strategy for molecular therapy of established EAC...
  31. pmc Systemic administration of polymeric nanoparticle-encapsulated curcumin (NanoCurc) blocks tumor growth and metastases in preclinical models of pancreatic cancer
    Savita Bisht
    The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Mol Cancer Ther 9:2255-64. 2010
    ..NanoCurc is a promising new formulation that is able to overcome a major impediment for the clinical translation of curcumin to cancer patients by improving systemic bioavailability, and by extension, therapeutic efficacy...
  32. pmc Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression
    Anne Le
    Division of Hematology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 107:2037-42. 2010
    ....
  33. pmc A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells
    Oliver A Kent
    The McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine Baltimore, MD, USA
    Cancer Biol Ther 8:2013-24. 2009
    ....
  34. pmc FAM190A rearrangements provide a multitude of individualized tumor signatures and neo-antigens in cancer
    Francesca Scrimieri
    Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore MD 21287, USA
    Oncotarget 2:69-75. 2011
    ..In addition to its potential oncogenic role, the in-frame deletions predict the formation of cancer-specific FAM190A peptide sequences (neo-antigens) with potential diagnostic and therapeutic usefulness...
  35. pmc Inactivation of Brca2 cooperates with Trp53(R172H) to induce invasive pancreatic ductal adenocarcinomas in mice: a mouse model of familial pancreatic cancer
    Georg Feldmann
    University of Bonn, Center of Integrated Oncology Cologne Bonn, Bonn, Germany
    Cancer Biol Ther 11:959-68. 2011
    ..Loss of Brca2 function predisposes the exocrine pancreas to profound DNA damage, and the frequency of invasive neoplasia is accentuated by the concomitant deregulation of p53...
  36. pmc Restitution of tumor suppressor microRNAs using a systemic nanovector inhibits pancreatic cancer growth in mice
    Dipankar Pramanik
    The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Mol Cancer Ther 10:1470-80. 2011
    ..The nanovector is a platform with potential broad applicability in systemic miRNA delivery to cancer cells...
  37. pmc Ectopic overexpression of Sonic Hedgehog (Shh) induces stromal expansion and metaplasia in the adult murine pancreas
    Volker Fendrich
    Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Neoplasia 13:923-30. 2011
    ..This autochthonous model serves as a platform for studying epithelial stromal interactions in pancreatic carcinogenesis...
  38. pmc Molecular determinants of retinoic acid sensitivity in pancreatic cancer
    Sonal Gupta
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Clin Cancer Res 18:280-9. 2012
    ..To identify a predictive molecular "signature" for sensitivity to retinoic acid in pancreatic cancer...
  39. pmc Somatic mutations in the chromatin remodeling gene ARID1A occur in several tumor types
    Sian Jones
    Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland, USA
    Hum Mutat 33:100-3. 2012
    ..These findings suggest that the aberrant chromatin remodeling consequent to ARID1A inactivation contributes to a variety of different types of neoplasms...
  40. pmc Screening pancreatic oncogenes in zebrafish using the Gal4/UAS system
    Shu Liu
    Department of Surgery and McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Methods Cell Biol 105:367-81. 2011
    ..We also describe techniques used to identify and characterize pancreatic tumors in adult transgenic fish...
  41. pmc Loss of expression of the SWI/SNF chromatin remodeling subunit BRG1/SMARCA4 is frequently observed in intraductal papillary mucinous neoplasms of the pancreas
    Marco Dal Molin
    Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, MD 21231, USA
    Hum Pathol 43:585-91. 2012
    ..We did not observe correlation between Brg1 expression and IPMN subtype or with location of the cyst. We provide first evidence that Brg1 expression is lost in noninvasive cystic precursor lesions of pancreatic adenocarcinoma...
  42. pmc Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development
    Jian Wu
    Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Sci Transl Med 3:92ra66. 2011
    ..In addition to defining a new pathway for pancreatic neoplasia, these data suggest that GNAS mutations can inform the diagnosis and management of patients with cystic pancreatic lesions...
  43. pmc Altered telomeres in tumors with ATRX and DAXX mutations
    Christopher M Heaphy
    Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
    Science 333:425. 2011
    ..ATRX mutations also correlate with abnormal telomeres in tumors of the central nervous system. These data suggest that an alternative telomere maintenance function may operate in human tumors with alterations in the ATRX or DAXX genes...
  44. pmc Impact of APE1/Ref-1 redox inhibition on pancreatic tumor growth
    Melissa L Fishel
    Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University of School of Medicine, 980 W Walnut, R3 548, Indianapolis, IN 46202, USA
    Mol Cancer Ther 10:1698-708. 2011
    ..These data indicate that E3330, inhibitor of APE1/Ref-1, has potential in pancreatic cancer and clinical investigation of APE1/Ref-1 molecular target is warranted...
  45. pmc A polymeric nanoparticle formulation of curcumin (NanoCurc™) ameliorates CCl4-induced hepatic injury and fibrosis through reduction of pro-inflammatory cytokines and stellate cell activation
    Savita Bisht
    Department of Pathology, Division of GI and Liver Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Lab Invest 91:1383-95. 2011
    ..Finally, we show that NanoCurc™ directly induces stellate cell apoptosis in vitro. Our results suggest that NanoCurc™ might be an effective therapy for patients with chronic liver disease...
  46. pmc Epigenetic silencing of MicroRNA miR-107 regulates cyclin-dependent kinase 6 expression in pancreatic cancer
    Kwang Hyuck Lee
    Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Pancreatology 9:293-301. 2009
    ....