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August 2011

Volume 141Issue 2p407-782, e1-e21

In Memoriam

  • Eugene Whitehorn Straus, MD

    • Jesse Roth,
    • Alessandra L. Szulc,
    • Jean-Pierre Raufman
    Published in issue: August 2011
    p407
    On April 2, 2011, our friend and colleague Eugene Whitehorn Straus, MD, died after a long battle with diabetes. Among many personal and professional accomplishments, the role he played in the Nobel Prize awarded to Rosalyn Yalow deserves special mention. In a May 1960 article that became one of the most-cited Journal of Clinical Investigation papers, Rosalyn S. Yalow and Solomon A. Berson introduced radioimmunoassay as a tool for measuring plasma insulin. Radioimmunoassay was extended widely, revolutionizing science and medicine.

Covering the Cover

  • Covering the Cover

    • Anson W. Lowe,
    • Richard H. Moseley
    Published online: June 27, 2011
    p408-410
    The incidence of esophageal adenocarcinoma is rising at a rate that is faster than any other cancer in the United States. Over the past 30 years, the incidence in men >65 years of age has increased by >600%. The 5-year survival rate remains at 15%. Predisposing factors for esophageal adenocarcinoma include the presence of Barrett's esophagus, in which columnar epithelia with intestinal metaplasia replaces the squamous epithelia. Barrett's esophagus increases the likelihood of developing esophageal adenocarcinoma 30-fold.

Comment From the Editor

  • One Colon Lumen but Two Organs

    • John M. Carethers
    Published online: June 27, 2011
    p411-412
    The colon is a remarkable organ in that it manages the final products of digestion after nutrient assimilation, and packages it as waste to expel. The colon has the highest bacterial load of any organ, with commensal bacteria occupying a niche that prevents noncommensal organisms from expanding, and some bacteria producing vitamins that can be utilized. It is the colon, with its local environmental influences on intrinsic stem cells and an individual's genetic background, that makes this organ the third most common site for cancer in men or women and the site with the second highest cause for cancer deaths overall.

Mentoring, Education, and Training Corner

  • Gastroenterology: A Field With Endless Career Opportunities for Physicians and Scientists

    • John Del Valle
    Published online: June 24, 2011
    p413-416
    Gastroenterology is an exciting and burgeoning field that provides an extraordinary number of career opportunities for physicians and scientists. The unique blend of intellectual and procedural-based clinical practice coupled with the excitement surrounding scientific discovery has made gastroenterology an extremely popular career option. Moreover, the financial compensation and security within the field is certainly not a deterrent. The first American Board of Internal Medicine certification in GI was in 1941 when only a total of 8 individuals certified in this subspecialty.

Editorials

  • Time to Burn? Endoscopic Ablation for Barrett's Esophagus

    • John M. Inadomi
    Published online: June 27, 2011
    p417-419
    The AIM Dysplasia Trial was a multicenter, randomized, sham-controlled trial comparing radiofrequency ablation (RFA) and endoscopic surveillance to endoscopic surveillance alone for the management of patients with Barrett's esophagus (BE) and low-grade dysplasia (LGD) or high-grade dysplasia (HGD).1 Participants undergoing active therapy could have received up to 4 RFA treatments in the first year. Outcomes were assessed by endoscopy with biopsies of any visible abnormality and 4-quadrant random biopsies every 1cm throughout the BE segment.
    Additional Online Content Available
  • Targeting Serotonin Synthesis to Treat Irritable Bowel Syndrome

    • Jan Tack,
    • Pieter Janssen,
    • Mira Wouters,
    • Guy Boeckxstaens
    Published online: June 23, 2011
    p420-422
    Serotonin (5-hydrodytryptamine; 5-HT) is an important signaling molecule in the gastrointestinal (GI) tract, where it is predominantly produced in the enterochromaffin (EC) cells in the mucosa, and also by a subpopulation of enteric neurons.1 In the brain, 5-HT is a neurotransmitter that plays a pivotal role in the regulation of mood and cognition. Animal studies revealed that 5-HT, released from EC cells and interneurons, is involved in the control of GI secretion, motility, and visceral perception.
  • The Hot Mustard Receptor's Role in Gut Motor Function

    • L. Ashley Blackshaw,
    • Stuart M. Brierley,
    • Patrick A. Hughes,
    • Andrea M. Harrington
    Published online: June 23, 2011
    p423-427
    Receptors for the active ingredients in spices and herbs are what guide us to ingest or avoid them, but they are distributed throughout the body—not just the oral cavity. As such, they play a much wider role than in taste perception, and mediate sensations such as cold, heat, and pain, making them indispensable in our response to the environment. Research has focused on these somatosensory roles in great depth, and drugs mimicking or blocking the activity of these receptors have recently reached clinical trials for pain.
  • Rac1 Takes Center Stage in Pancreatic Cancer and Ulcerative Colitis: Quantity Matters

    • Eva Wertheimer,
    • Marcelo G. Kazanietz
    Published online: June 27, 2011
    p427-430
    The Rho GTP-binding proteins are well-established regulators of actin cytoskeleton organization and dynamics that relay signals from membrane receptors and play key roles in cell morphology, motility, mitogenicity, and survival. Rac1, an ubiquitously expressed member of this family, has been implicated widely as a pleiotropic modulator of inflammatory, oncogenic, and metastatic signaling pathways,1 Multiple oncogenic inputs signal through Rac1, including hyperactive/overexpressed tyrosine-kinase receptors and active Ras.
  • Oxaliplatin Uses JNK to Restore TRAIL Sensitivity in Cancer Cells Through Bcl-xL Inactivation

    • Joshua E. Allen,
    • Wafik S. El-Deiry
    Published online: June 22, 2011
    p430-434
    The concept of killing cancer cells without adverse effects on normal cells is a long-held ideal of cancer therapy. An epitome of such therapeutic index, TRAIL (TNF-related apoptosis-inducing ligand; Apo2L) is a protein involved in the immune surveillance of cancer that selectively induces apoptosis in cancer cells.1 This property of TRAIL has led to several clinical trials in a range of malignancies using recombinant TRAIL and TRAIL-receptor agonist antibodies.2 The sensitivity of cancer cells to TRAIL-induced apoptosis and the molecular determinants that confer this sensitivity are heterogeneous.

Clinical Challenges and Images in GI

  • A Woman Who Faints When She Eats and Drinks

    • Andrea E. Wagner,
    • David A. Katzka
    Published online: June 27, 2011
    p435
    Question: A 48-year-old woman presented with a 10-year history of intermittent liquid dysphagia that progressed to solid food dysphagia 2 years ago. Symptoms would occur several times per week, last several seconds, and resolve abruptly. Patient reported symptoms were more significant with eating and drinking quickly or ingesting large boluses. She reported 8 episodes of syncope associated with dysphagia over the past 2 years. During an episode, she would experience a sense of midsternal food sticking and lose consciousness within 5–10 seconds.
  • An Unusual Case of Peritonitis in an Intravenous Drug User

    • Neil Johns,
    • David Cooper,
    • John Terrace
    Published online: June 27, 2011
    p435
    Question: A 24-year-old man was admitted complaining of acute abdominal pain of 48 hours' duration. He also described chills, rigors, and extreme nausea. He had no significant past medical history other than active intravenous drug use. He recalled injecting heroin in his groin 48 hours before admission. He denied having ever smoked the drug. He was fully conscious, had a pulse of 138 beats per minute, blood pressure of 95/64, and temperature of 37.7°C. Positive abdominal findings were marked peritonitis and rigidity.
  • Polypoid Rectal Mass in a 21-Year-Old Woman With Hematochezia

    • Rajiv Sharma,
    • Benedict Maliakkal
    Published online: June 27, 2011
    p436
    Question: A 21-year-old woman presented to the emergency room with dizziness, left lower quadrant abdominal pain, and hematochezia for 3 months. Laboratory tests showed iron-deficiency anemia. Physical examination was benign except for mild tenderness in left lower quadrant. Esophagogastroduodenoscopy was normal. Colonoscopy showed 5 × 3 cm-pedunculated, polypoid mass 15-cm from the anal verge (Figure A). Magnetic resonance imaging of the pelvis (Figure B) showed that the mass was limited to the rectum without any pelvic or ovarian connections.
  • Gastrointestinal Bleeding in a Type 1 Neurofibromatosis Patient

    • Ming-Chang Ku,
    • Chung-Ming Tsai,
    • Yeu-Sheng Tyan
    Published online: June 27, 2011
    p437
    Question: A 39-year-old woman presented to the emergency department with a 1-week history of black color stool. The patient had history of type 1 neurofibromatosis (NF-1). She was afebrile and her blood pressure was 128/90 mmHg. Physical examination revealed Café-au-lait spots (Figure A, arrow) and multiple neurofibromas (Figure B, arrow) on the skin. Tenderness at the left lower quadrant of the abdomen and tachycardia of 110 beats per minute were also noted. The laboratory values were within normal limit, except for a low hemoglobin level (5.5 g/L; normal, 12–16).

Electronic Clinical Challenges and Images in GI

  • Unexplained Anemia and Neutropenia

    • Eric H. Choi,
    • Williamson Strum
    Published online: June 27, 2011
    e1-e2
    Question: An 81-year-old man presented with fatigue and exercise intolerance. The patient's medical history was unremarkable except for mild hypertension, hyperlipidemia, and an episode 30 years earlier when the patient presented with melena related to antral ulcers, requiring numerous blood transfusions and leading to antrectomy with gastrojejunostomy (Billroth II). He has had no further episodes of overt gastrointestinal bleeding. He reported taking a daily baby aspirin, metoprolol, lovastatin, and multivitamins.
    Online Only
  • A Palpable Mass and Diarrhea

    • Maarten E. Tushuizen,
    • Merk C. van Veen,
    • Hans A.R.E. Tuynman
    Published online: June 27, 2011
    e3-e4
    Question: A 63-year-old man with a recent history of type 2 diabetes and myocardial infarction was admitted to our hospital with a 6-month history of progressive diarrhea up to 30 times a day, anorexia, weight loss, and abdominal pain. Physical examination revealed a solid, irregular but smooth surfaced mass of 20 cm in the left upper abdominal quadrant. Laboratory results, which included a full blood count, C-reactive protein, amylase, serum electrolytes, and renal and liver function tests, were all within normal limits.
    Online Only
  • An Unusual Case of Ulcerative Duodenitis

    • Jason Welch,
    • Krishna Kasturi,
    • Andrea Duchini
    Published online: June 30, 2011
    e5-e6
    Question: A 51-year-old Caucasian woman with a past medical history of gastroesophageal reflux disease presented to the emergency department with a 3-day history of worsening generalized abdominal pain, associated with nausea, non-bloody vomiting, 2–3 episodes of small volume hematochezia, and joint pains in hands and feet. Patient denied nonsteroid anti-inflammatory or aspirin use, and recent alcohol intake, before such episodes. She had a normal screening colonoscopy 1 month ago. Two weeks before presentation, she was treated with a 1-week course of cephalexin for a urinary tract infection.
    Online Only
  • A Rare Cause of Pneumoperitoneum

    • Jesús Cañete Gómez,
    • Antonio Muñoz Ortega,
    • J.M.Álamo Martínez
    Published online: June 27, 2011
    e7-e8
    Question: A 51-year-old male patient was admitted to the emergency unit with a 24-hour history of increasing abdominal pain in the right iliac fossa. On examination, the patient presents good general condition and weight loss (15 kg over the last year); he was mildly distressed and flushed. His pulse rate was 115 beats per minute, blood pressure was 115/85 mmHg, room air oxygen saturation was 95%, and his temperature was 37.2°C. His abdomen is diffusely painful, distended, and tympanitic with signs of peritoneal irritation with maximal tenderness in the right iliac fossa and associated guarding, but without other accompanying symptoms.
    Online Only
  • A Case of Punched-Out Ulcer Occurring in the Rectosigmoid Colon With Sudden Onset of Bloody Stools

    • Tsutomu Mizoshita,
    • Satoshi Tanida,
    • Takashi Joh
    Published online: July 01, 2011
    e9-e10
    Question: A 60-year-old man was referred with sudden onset of bloody stools accompanied by lower abdominal pain. Laboratory investigations at symptom onset demonstrated hemoglobin had decreased to 9.2 g/dL and platelet cell count had decreased to 93 × 103/μL, with abnormal values as follows: erythrocyte sedimentation rate, 80 mm/h; C-reactive protein, 2.25 mg/dL (normal, ≤0.30); albumin, 2.4 g/dL (normal, 4.0–5.0); aspartate aminotransferase, 74 U/L (normal, 13–33); and lactate dehydrogenase, 372 U/L (normal, 119–229).
    Online Only
  • Unusual Cause of Upper Gastrointestinal Bleeding

    • Ko–Chin Chen,
    • Hsu–Heng Yen,
    • Yang–Yuan Chen
    Published online: June 27, 2011
    e11-e12
    Question: A 58-year-old woman visited the emergency department because of tarry stool passage for a month. Her medical history was significant for hypertension and diabetes. She took no nonsteroidal anti-inflammatory drugs or aspirin. An upper endoscopy was performed (Figure A) and subsequent endoscopic ultrasound was performed for the lesions found (Figure B, C, D).
    Online Only

Reviews and Perspectives

    Mini-Reviews and Perspectives

    • The Importance of the Gastrointestinal Tract in the Control of Bone Mass Accrual

      • Gerard Karsenty,
      • Michael D. Gershon
      Published online: June 20, 2011
      p439-442
      One of the least anticipated and less heralded outcomes of mouse genetics has been to rediscover whole organism physiology. Among the many unexpected findings that it has brought to our attention has been the realization that gut-derived serotonin is a hormone-inhibiting bone formation. The importance of this discovery presented in this review is 2-fold. First, it provides a molecular explanation for 2 human genetic diseases—osteoporosis, pseudoglioma, and high bone mass syndrome; second, it suggests a novel and anabolic way to treat osteoporosis.

    Imaging and Advanced Technology

    • Angle-Resolved Low Coherence Interferometry for Detection of Dysplasia in Barrett's Esophagus

      • Adam Wax,
      • Neil G. Terry,
      • Evan S. Dellon,
      • Nicholas J. Shaheen
      Published online: June 20, 2011
      p443-447.e2
      Barrett's esophagus (BE) is a metaplastic change of the esophagus which is associated with an increased risk of esophageal adenocarcinoma (EAC).1 The incidence of this cancer has risen dramatically in the United States in the last 40 years,2 and the prognosis for subjects presenting with symptomatic EAC is dismal, with fewer than 15% surviving 5 years.3 For this reason, strategies aimed at prevention figure prominently in societal guidelines for the care of BE.4
      Online ExtraAdditional Online Content Available

    Reviews in Basic and Clinical Gastroenterology and Hepatology

    • Notch: Architect, Landscaper, and Guardian of the Intestine

      • Marc Vooijs,
      • Zhenyi Liu,
      • Raphael Kopan
      Published online: June 13, 2011
      p448-459
      In the past decade, enormous progress has been made in understanding the role of stem cells in physiologic tissue renewal and in pathologic processes such as cancer. These findings have shed light on the identity and biological properties of such cells and the intrinsic and extrinsic signals that balance stem cell self-renewal with differentiation. With its astonishing self-renewal capacity, the intestinal epithelium has provided a unique model to study stem cell biology, lineage specification, and cancer.

Original Research

    Clinical-Alimentary Tract

    Clinical-Liver

    Clinical-Pancreas

    • Pregabalin Reduces Pain in Patients With Chronic Pancreatitis in a Randomized, Controlled Trial

      • Søren Schou Olesen,
      • Stefan A.W. Bouwense,
      • Oliver H.G. Wilder–Smith,
      • Harry van Goor,
      • Asbjørn Mohr Drewes
      Published online: April 15, 2011
      p536-543
      Pain is a disabling symptom for patients with chronic pancreatitis (CP) and difficult to treat. Evidence from basic science and human studies indicates that pain processing by the central nervous system is abnormal and resembles that observed in patients with neuropathic pain disorders. We investigated whether agents used to treat patients with neuropathic pain are effective in CP.

    Basic and Translational-Alimentary Tract

    • Neuronal Plasticity in the Cingulate Cortex of Rats Following Esophageal Acid Exposure in Early Life

      • Banani Banerjee,
      • Bidyut K. Medda,
      • Jamie Schmidt,
      • Ivan M. Lang,
      • Jyoti N. Sengupta,
      • Reza Shaker
      Published online: April 29, 2011
      p544-552
      The cingulate cortex has been reported to be involved in processing pain of esophageal origin. However, little is known about molecular changes and cortical activation that arise from early-life esophageal acid reflux. Excitatory neurotransmission via activation of the N-methyl-d-aspartate (NMDA) receptor and its interaction with postsynaptic density protein 95 (PSD-95) at the synapse appear to mediate neuronal development and plasticity. We investigated the effect of early-life esophageal acid exposure on NMDA receptor subunits and PSD-95 expression in the developing cingulate cortex.
    • β-Catenin and p120 Mediate PPARδ-Dependent Proliferation Induced by Helicobacter pylori in Human and Rodent Epithelia

      • Toni A. Nagy,
      • Lydia E. Wroblewski,
      • Dingzhi Wang,
      • ...
      • Pelayo Correa,
      • Timothy L. Cover,
      • Richard M. Peek Jr
      Published online: June 27, 2011
      p553-564
      Colonization of gastric mucosa by Helicobacter pylori leads to epithelial hyperproliferation, which increases the risk for gastric adenocarcinoma. One H pylori virulence locus associated with cancer risk, cag, encodes a secretion system that transports effectors into host cells and leads to aberrant activation of β-catenin and p120-catenin (p120). Peroxisome proliferator-activated receptor (PPAR)δ is a ligand-activated transcription factor that affects oncogenesis in conjunction with β-catenin. We used a carcinogenic H pylori strain to define the role of microbial virulence constituents and PPARδ in regulating epithelial responses that mediate development of adenocarcinoma.
      Additional Online Content Available
    • Transient Receptor Potential Ankyrin 1 Is Expressed by Inhibitory Motoneurons of the Mouse Intestine

      • Daniel P. Poole,
      • Juan Carlos Pelayo,
      • Fiore Cattaruzza,
      • ...
      • John B. Furness,
      • Eileen F. Grady,
      • Nigel W. Bunnett
      Published online: May 05, 2011
      p565-575.e4
      Transient receptor potential ankyrin (TRPA) 1, an excitatory ion channel expressed by sensory neurons, mediates somatic and visceral pain in response to direct activation or noxious mechanical stimulation. Although the intestine is routinely exposed to irritant alimentary compounds and inflammatory mediators that activate TRPA1, there is no direct evidence for functional TRPA1 receptors on enteric neurons, and the effects of TRPA1 activation on intestinal function have not been determined. We characterized expression of TRPA1 by enteric neurons and determined its involvement in the control of intestinal contractility and transit.
      Online ExtraEditorial Accompanies ArticleAdditional Online Content Available
    • Expression Level of Hand2 Affects Specification of Enteric Neurons and Gastrointestinal Function in Mice

      • Fabien D'Autréaux,
      • Kara G. Margolis,
      • Jane Roberts,
      • ...
      • Peter Cserjesi,
      • Wanda Setlick,
      • Michael D. Gershon
      Published online: May 09, 2011
      p576-587.e6
      Hand2 is a basic helix-loop-helix transcription factor required for terminal differentiation of enteric neurons. We studied Hand2 haploinsufficient mice, to determine whether reduced expression of Hand2 allows sufficient enteric neurogenesis for survival, but not for development of a normal enteric nervous system (ENS).
      Online ExtraAdditional Online Content Available
    • Enteric Neuronal Density Contributes to the Severity of Intestinal Inflammation

      • Kara Gross Margolis,
      • Korey Stevanovic,
      • Nima Karamooz,
      • ...
      • Virginia Saurman,
      • Alcmene Chalazonitis,
      • Michael David Gershon
      Published online: April 29, 2011
      p588-598.e2
      Enteric neurons have been reported to be increased in inflamed regions of the bowel in patients with inflammatory bowel disease or intestinal neurogangliomatosis. It is impossible to determine whether this hyperinnervation predates intestinal inflammation, results from it, or contributes to its severity in humans, so we studied this process in mice.
      Online ExtraAdditional Online Content Available
    • The Intestinal Microbiota Affect Central Levels of Brain-Derived Neurotropic Factor and Behavior in Mice

      • Premysl Bercik,
      • Emmanuel Denou,
      • Josh Collins,
      • ...
      • Kathy D. McCoy,
      • Elena F. Verdu,
      • Stephen M. Collins
      Published online: May 02, 2011
      p599-609.e3
      Alterations in the microbial composition of the gastrointestinal tract (dysbiosis) are believed to contribute to inflammatory and functional bowel disorders and psychiatric comorbidities. We examined whether the intestinal microbiota affects behavior and brain biochemistry in mice.
      Online ExtraAdditional Online Content Available
    • Tolerance to Ingested Deamidated Gliadin in Mice is Maintained by Splenic, Type 1 Regulatory T Cells

      • M. Fleur Du Pré,
      • Anne E. Kozijn,
      • Lisette A. van Berkel,
      • ...
      • Ludvig M. Sollid,
      • Lars Fugger,
      • Janneke N. Samsom
      Published online: April 29, 2011
      p610-620.e2
      Patients with celiac disease have permanent intolerance to gluten. Because of the high frequency of this disorder (approximately 1 in 100 individuals), we investigated whether oral tolerance to gluten differs from that to other food proteins.
      Online ExtraAdditional Online Content Available
    • The Epithelia-Specific Membrane Trafficking Factor AP-1B Controls Gut Immune Homeostasis in Mice

      • Daisuke Takahashi,
      • Koji Hase,
      • Shunsuke Kimura,
      • ...
      • Osamu Yokosuka,
      • Satoshi Waguri,
      • Hiroshi Ohno
      Published online: May 06, 2011
      p621-632
      Epithelial cells that cover the intestinal mucosal surface maintain immune homeostasis and tolerance in the gastrointestinal tract. However, little is known about the molecular mechanisms that regulate epithelial immune functions. Epithelial cells are distinct in that they are highly polarized; this polarity is, at least in part, established by the epithelium-specific polarized sorting factor adaptor protein (AP)-1B. We investigated the role of AP-1B–mediated protein sorting in the maintenance of gastrointestinal immune homeostasis.
      Additional Online Content Available
    • Single Nucleotide Polymorphisms That Increase Expression of the Guanosine Triphosphatase RAC1 Are Associated With Ulcerative Colitis

      • Aleixo M. Muise,
      • Thomas Walters,
      • Wei Xu,
      • ...
      • Michael Glogauer,
      • Mark S. Silverberg,
      • John H. Brumell
      Published online: May 05, 2011
      p633-641
      RAC1 is a guanosine triphosphatase that has an evolutionarily conserved role in coordinating immune defenses, from plants to mammals. Chronic inflammatory bowel diseases are associated with dysregulation of immune defenses. We studied the role of RAC1 in inflammatory bowel diseases using human genetic and functional studies and animal models of colitis.
      Editorial Accompanies this ArticleAdditional Online Content Available
    • Mycobacterium bovis Bacillus Calmette-Guérin Killed by Extended Freeze-Drying Reduces Colitis in Mice

      • Micheline Lagranderie,
      • Christoph Kluge,
      • Helene Kiefer–Biasizzo,
      • ...
      • Antonio Bandeira,
      • Herve Bercovier,
      • Gilles Marchal
      Published online: May 16, 2011
      p642-652.e4
      Mycobacterium bovis Bacillus Calmette-Guérin (BCG), killed by extended freeze-drying (EFD), induces secretion of interleukin-10 and reduces lung inflammation in a mouse model of asthma. We investigated the effects of EFD BCG in mouse models of inflammatory bowel disease.
      Online ExtraAdditional Online Content Available
    • Antigen-Presenting Cell Production of IL-10 Inhibits T-Helper 1 and 17 Cell Responses and Suppresses Colitis in Mice

      • Bo Liu,
      • Susan L. Tonkonogy,
      • R. Balfour Sartor
      Published online: May 02, 2011
      p653-662.e4
      Mice that are deficient in interleukin (IL)-10 develop colitis, mediated by T-helper (Th)1 and Th17 cells, and IL-10–producing regulatory T (Treg) cells suppress colitis, implicating IL-10 in maintaining mucosal homeostasis. We assessed the relative importance of immunoregulatory IL-10 derived from T cells or from antigen presenting cells (APCs) in development of intestinal inflammation.
      Online ExtraAdditional Online Content Available
    • Oxaliplatin Sensitizes Human Colon Cancer Cells to TRAIL Through JNK-Dependent Phosphorylation of Bcl-xL

      • Zineb El Fajoui,
      • Florent Toscano,
      • Guillaume Jacquemin,
      • ...
      • Jean–Yves Scoazec,
      • Olivier Micheau,
      • Jean–Christophe Saurin
      Published online: May 02, 2011
      p663-673
      Oxaliplatin sensitizes drug-resistant colon cancer cell lines to tumor necrosis factor–related apoptosis inducing ligand (TRAIL), a death receptor ligand that is selective for cancer cells. We investigated the molecular mechanisms by which oxaliplatin sensitizes cancer cells to TRAIL-induced apoptosis.
      Editorial Accompanies ArticleAdditional Online Content Available

    Basic and Translational-Liver

    Basic and Translational-Pancreas

    • Early Requirement of Rac1 in a Mouse Model of Pancreatic Cancer

      • Irina Heid,
      • Clara Lubeseder–Martellato,
      • Bence Sipos,
      • ...
      • Marina Lesina,
      • Roland M. Schmid,
      • Jens T. Siveke
      Published online: May 02, 2011
      p719-730.e7
      Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease without effective chemopreventive or therapeutic approaches. Although the role of oncogenic Kras in initiating development of PDAC is well established, downstream targets of aberrant Ras signaling are poorly understood. Acinar-ductal metaplasia (ADM) appears to be an important prerequisite for development of pancreatic intraepithelial neoplasia (PanIN), a common precursor to PDAC. RAS-related C3 botulinum substrate 1 (Rac1), which controls actin reorganization, can be activated by Ras, is up-regulated in several human cancers, and is required for cerulein-induced morphologic changes in acini.
      Online ExtraEditorial Accompanies ArticleAdditional Online Content Available
    • Lineage Tracing Evidence for Transdifferentiation of Acinar to Duct Cells and Plasticity of Human Pancreas

      • Isabelle Houbracken,
      • Evelien de Waele,
      • Jessy Lardon,
      • ...
      • Harry Heimberg,
      • Ilse Rooman,
      • Luc Bouwens
      Published online: May 05, 2011
      p731-741.e4
      Animal studies have indicated that pancreatic exocrine acinar cells have phenotypic plasticity. In rodents, acinar cells can differentiate into ductal precursors that can be converted to pancreatic ductal adenocarcinoma or insulin-producing endocrine cells. However, little is known about human acinar cell plasticity. We developed nongenetic and genetic lineage tracing methods to study the fate of human acinar cells in culture.
      Online ExtraAdditional Online Content Available

Continuing Medical Education (CME) Activities

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