Original Article
Brief Report
Treatment of Ménétrier's Disease with a Monoclonal Antibody against the Epidermal Growth Factor Receptor
N Engl J Med 2000; 343:1697-1701December 7, 2000
- Article
MÉnÉtrier's disease (hypoproteinemic hypertrophic gastropathy) is a rare, acquired, premalignant disorder of the stomach.1-4 It is characterized by giant hypertrophic folds that most often involve the fundus, excess mucus secretion, decreased acid secretion (hypochlorhydria), and hypoproteinemia due to selective loss of serum proteins across the gastric mucosa.5,6 The cause of Ménétrier's disease is unknown, although infection with cytomegalovirus (CMV) in children and infection with Helicobacter pylori have been implicated.7,8 Symptoms include epigastric pain, vomiting, edema, anorexia, and weight loss. Gastric cancer has been reported at diagnosis or during follow-up in patients with hypertrophic gastropathy. Evidence of the benefits of anticholinergic drugs, acid suppression, octreotide, and eradication of H. pylori is inconsistent.2,9,10 Except in cases of CMV-associated Ménétrier's disease in children,11 spontaneous remissions are rare. Partial or total gastrectomy is generally reserved for patients with debilitating disease and for cases in which there is concern over the development of gastric cancer.12
Increased signaling of the epidermal growth factor receptor has been implicated in the pathogenesis of Ménétrier's disease.13 We recently cared for a patient with this disorder who had not had a response to drug therapy. We hypothesized that the administration of a neutralizing monoclonal antibody against the epidermal growth factor receptor might be of clinical benefit. After one day of treatment with this antibody, the patient's nausea and vomiting decreased, and after one month there was clinical and biochemical improvement, including an increase in the serum albumin concentration and a decrease in the loss of protein in the stool.
Case Report
A 48-year-old man presented with nausea, vomiting, edema up to the waist, and hypoalbuminemia in July 1998. A gastric analysis revealed the secretion of a large volume of viscous gastric juice with a pH of 7.0. An endoscopic evaluation showed enlarged gastric folds in the fundus, and snare biopsies of the fundus showed foveolar hyperplasia (an expansion of surface mucous cells) and the absence of parietal cells. The results of a carbon-13 urea breath test were normal, and the rate of basal secretion of gastric acid was 0 mmol of hydrogen in 30 minutes (as compared with the normal rate of 4.0 mmol of hydrogen per hour). Trials of prochlorperazine, promethazine, ondansetron, lansoprazole, cisapride, octreotide, and glycopyrrolate did not alleviate the patient's symptoms. He was not considered for gastrectomy, because of the risk associated with anesthesia and surgery as a result of his primary pulmonary hypertension. This condition had been diagnosed in 1993, at which time a continuous infusion of epoprostenol (prostacyclin) had been initiated. Reduction in the dose of epoprostenol did not ameliorate his symptoms.
Approval for compassionate use of a monoclonal antibody against the epidermal growth factor receptor (C225, ImClone Systems) was granted by the Food and Drug Administration and the institutional review boards of the University of Texas Southwestern Medical Center and the Vanderbilt University Medical Center, and the patient gave informed written consent for a month-long course of treatment with this antibody. Intravenous infusion was initiated at a loading dose of 490 mg per square meter of body-surface area given over a two-hour period, followed by three weekly treatments of 250 mg per square meter, each given over a two-hour period.
Results
After the initiation of treatment with antibody against the epidermal growth factor receptor, the patient's nausea and vomiting decreased immediately. An actiniform eruption with pustular lesions and erythematous papules developed across his face and chest during the first week of treatment. These lesions responded to topical clindamycin therapy.
One day after the initiation of treatment, the concentrations of transforming growth factor α increased by a factor of approximately three in serum and gastric juice (from 16 to 44 pg per milliliter and from 64 to 201 pg per milliliter, respectively), as determined by radioimmunoassay. This increase provided evidence of effective blockade of the epidermal growth factor receptor.14
After one month of treatment, the patient's vomiting had decreased from an average of 70 episodes to just over 1 episode per week (Table 1Table 1
Clinical and Biochemical Findings in a Patient with Ménétrier's Disease before and during Treatment with a Monoclonal Antibody against the Epidermal Growth Factor Receptor.), and there was a marked improvement in the quality-of-life score. The serum albumin concentration had increased, and loss of protein through the stool had decreased. Repeated endoscopy showed enlarged gastric folds, and biopsy revealed numerous parietal cells despite persistent foveolar hyperplasia (Figure 1Figure 1
Staining of Parietal Cells in the Fundic Mucosa of a Patient with Ménétrier's Disease before and after One Month of Treatment with a Monoclonal Antibody against the Epidermal Growth Factor Receptor.). The pH of the gastric juice remained at 7.0.Protein extracts prepared from fundic-biopsy specimens obtained by gastroscopy before and after one day and one month of treatment were analyzed by Western blotting with antibodies against the epidermal growth factor receptor, mitogen-associated protein kinase, and Akt, a protein apparently involved in cell survival. There was a marked increase in the tissue content of the epidermal growth factor receptor after treatment (Figure 2AFigure 2
The Effect of a Monoclonal Antibody against the Epidermal Growth Factor Receptor (C225) on Selected Signaling Events in the Gastric Mucosa of a Patient with Ménétrier's Disease.) — a finding consistent with the reversal of receptor down-regulation after receptor blockade. In addition, there was a marked decrease in the concentration of active phosphorylated mitogen-associated protein kinase but no change in the total kinase concentration. Activation of the mitogen-associated protein kinase pathway has been linked to increased proliferation of cells.To examine this relation further, we determined the proliferative index in the fundic mucosa by immunostaining for Ki-67, a marker of actively dividing cells. The proliferative index, representing the mean number of Ki-67–positive surface mucous cells per gastric glandular unit and obtained by averaging the counts in 10 glandular units, decreased from an average of 45 (range, 20 to 65) before treatment to 5 (range, 0 to 15) in the biopsy specimen obtained one day after the initiation of treatment. At one month, the proliferative index was 18 (range, 7 to 34).
A striking finding one month after the initiation of treatment was the emergence of parietal cells. Since gastrin is a trophic factor for parietal cells, we measured serum gastrin concentrations, which increased from 82 to 425 pg per milliliter one day after the start of treatment and remained high (591 pg per milliliter) one month later. To examine the underlying molecular events, we measured the levels of fundic Akt. Total and active phosphorylated Akt increased significantly one day after the initiation of treatment, as determined by Western blot analysis (Figure 2A). This increase was correlated with increased Akt activity in the fundus (data not shown). There was no detectable immunohistochemical staining for active phosphorylated Akt in the gastric-biopsy specimens obtained one day before and one day after the initiation of treatment, but intense immunoreactivity was seen in newly emergent parietal cells after one month of treatment (Figure 2B). Akt and H+/K+–ATPase immunoreactivity colocalized within parietal cells.
After one month of treatment, the patient was evaluated for heart–lung transplantation. Unfortunately, he had cardiac arrest resulting from an anaphylactic reaction to the iodinated radiographic contrast material given during a transjugular liver biopsy, and he died suddenly. An autopsy was not performed.
Discussion
Transforming growth factor α and the epidermal growth factor receptor are produced in the stomach.18 Overproduction of transforming growth factor α in the stomach could account for several of the features of Ménétrier's disease, including decreased acid production, increased hyperplasia of surface mucous cells, oxyntic atrophy, and increased mucin production.19-22 Transgenic mice that overproduce transforming growth factor α in the stomach have many of the features of Ménétrier's disease, including foveolar hyperplasia, increased mucin content, a reduced number of parietal cells, and decreased acid production.23,24 Transforming growth factor α, however, is one of six mammalian ligands that bind to the epidermal growth factor receptor,25 and increased production of any of these ligands may contribute to Ménétrier's disease. Our previous results and the clinical and biochemical response to antibody against the epidermal growth factor receptor in this patient are evidence that increased signaling of epidermal growth factor receptor has a role in the pathogenesis of Ménétrier's disease.
Our current understanding of the differentiation of fundic glandular elements suggests that the cells of the gastric gland arise from a progenitor zone located in the upper neck region of the gland. This population of progenitor cells then gives rise to two groups of cells with different life spans. Surface mucous cells with a life span of four to six days differentiate and migrate toward the lumen. In contrast, the other glandular cells (parietal cells, chief cells, and enterochromaffin-like cells) migrate basally; their predicted life spans are in excess of 60 to 100 days.26,27 In transgenic mice that overexpress transforming growth factor α in the stomach, there is a selective expansion of surface mucous cells at the expense of other cell lineages.28 Serum gastrin concentrations are inappropriately low in these mice28 and in patients with Ménétrier's disease (unpublished data), despite an alkaline gastric pH, which is a potent stimulus for gastrin secretion.29 We speculate that increased signaling of the epidermal growth factor receptor in the presence of inappropriately low serum gastrin concentrations contributes to the histologic features of Ménétrier's disease. The prompt and sustained increase in serum gastrin concentrations after the administration of antibody against epidermal growth factor receptor probably stimulates the production of parietal cells.
There is no known association between primary pulmonary hypertension and Ménétrier's disease.30,31 The long-term side effects of epoprostenol, which include nausea and vomiting, are dose-dependent and resolve with dose reduction. Our patient's gastrointestinal symptoms did not resolve after the dose of epoprostenol was decreased. There is no evidence at this time to implicate the patient's long-term epoprostenol therapy in the causation of Ménétrier's disease.
In this patient with Ménétrier's disease, systemic blockade of the epidermal growth factor receptor improved the clinical and biochemical features of the disease. Whether these results are reproducible and whether long-term treatment will be effective are not known. In the future, this treatment could be combined with inhibition of tumor necrosis factor α–converting enzyme, the enzyme that cleaves transforming growth factor α at the cell surface,32 since this combined regimen results in cooperative inhibition of the growth of mammary and colorectal cancer cells in vitro.33
Supported by grants from the National Institutes of Health (CA-46413, CA-77935, DK-48370, DK-43405, RR-00095, and RR-00633), a Veterans Affairs Merit review grant (to Dr. Goldenring), and funding from the Joseph and Mary Keller Foundation and the Peter Powell Memorial Fund (to Dr. Coffey).
We are indebted to James E. Loyd and Katherine S. Meise for their incisive comments.
Source Information
From the Departments of Medicine and Pathology, University of Texas Southwestern Medical Center, Dallas (J.S.B.); the Departments of Pathology, Medicine, and Cell Biology, Vanderbilt University School of Medicine and Nashville Veterans Affairs Medical Center, Nashville (E.C., G.T., K.W., R.J.C.); the Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa (M.S., J.E.P., J.Q.C.); and the Augusta Veterans Affairs Medical Center and Departments of Medicine, Surgery, and Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta (J.R.G.).
Address reprint requests to Dr. Coffey at CC-2201 Medical Center North, Vanderbilt University, Nashville, TN 37232, or at coffeyrj@ctrvax.vanderbilt.edu.
- References
References
1
Menetrier P . Des polyadénomes gastriques et de leurs rapports avec le cancer de l'estomac. Arch Physiol Norm Pathol 1888;1:32-55, 2362
Scharschmidt BF . The natural history of hypertrophic gastropathy (Menetrier's disease): report of a case with 16 year follow-up and review of 120 cases from the literature. Am J Med 1977;63:644-652
CrossRef | Web of Science | Medline3
Searcy R ,Malagelada J-R . Menetrier's disease and idiopathic hypertrophic gastropathy. Ann Intern Med 1984;100:565-570
Web of Science | Medline4
Sundt TM III ,Compton C ,Malt RA . Menetrier's disease: a trivalent gastropathy. Ann Surg 1988;208:694-701
CrossRef | Web of Science | Medline5
Jarnum S ,Jensen KB . Plasma protein turnover (albumin, transferrin, IgG, IgM) in Menetrier's disease (giant hypertrophic gastritis): evidence of non-selective protein loss. Gut 1972;13:128-137
CrossRef | Web of Science | Medline6
Wolfsen HC ,Carpenter HA ,Talley NJ . Menetrier's disease: a form of hypertrophic gastropathy or gastritis. Gastroenterology 1993;104:1310-1319
Web of Science | Medline7
Kovacs AA ,Churchill MA ,Wood D ,Mascola L ,Zaia JA . Molecular and epidemiologic evaluations of a cluster of cases of Menetrier's disease associated with cytomegalovirus. Pediatr Infect Dis J 1993;12:1011-1014
CrossRef | Web of Science | Medline8
Bayerdorffer E ,Ritter MM ,Hatz R ,Brooks W ,Ruckdeschel G ,Stolte M . Healing of protein losing hypertrophic gastropathy by eradication of Helicobacter pylori -- is Helicobacter pylori a pathogenic factor in Menetrier's disease? Gut 1994;35:701-704
CrossRef | Web of Science | Medline9
Meuwissen SG ,Ridwan BU ,Hasper HJ ,Innemee G . Hypertrophic protein-losing gastropathy: a retrospective analysis of 40 cases in the Netherlands. Scand J Gastroenterol Suppl 1992;194:1-7
CrossRef | Medline10
Yeaton P ,Frierson HF Jr . Octreotide reduces enteral protein losses in Menetrier's disease. Am J Gastroenterol 1993;88:95-98
Web of Science | Medline11
Berry E ,Ben-Dov Y ,Freund U . Spontaneous remission of protein-losing gastropathy associated with Menetrier's disease: a plea for conservative management. Arch Intern Med 1980;140:99-100
CrossRef | Web of Science | Medline12
Scott HW Jr ,Shull HJ ,Law DH IV ,Burko H ,Page DL . Surgical management of Menetrier's disease with protein-losing gastropathy. Ann Surg 1975;181:765-767
CrossRef | Web of Science | Medline13
Coffey RJ ,Romano M ,Goldenring J . Roles for transforming growth factor-α in the stomach. J Clin Gastroenterol 1995;21:Suppl 1:S36-S39
Web of Science | Medline14
Dempsey PJ ,Coffey RJ . Basolateral targeting and efficient consumption of transforming growth factor-α when expressed in Madin-Darby canine kidney cells. J Biol Chem 1994;269:16878-16889
Web of Science | Medline15
Ferrans CE ,Powers MJ . Quality of life index: development and psychometric properties. ANS Adv Nurs Sci 1985;8:15-24
Web of Science | Medline16
Strygler B ,Nicar MJ ,Santangelo WC ,Porter JL ,Fordtran JS . Alpha 1-antitrypsin excretion in stool in normal subjects and in patients with gastrointestinal disorders. Gastroenterology 1990;99:1380-1387
Web of Science | Medline17
Smolka A ,Helander HF ,Sachs G . Monoclonal antibodies against gastric H+-K+-ATPase. Am J Physiol 1983;245:G589-G596
Web of Science | Medline18
Beauchamp RD ,Barnard JA ,McCutchen CM ,Cherner JA ,Coffey RJ Jr . Localization of transforming growth factor α and its receptor in gastric mucosal cells: implications for a regulatory role in acid secretion and mucosal renewal. J Clin Invest 1989;84:1017-1023
CrossRef | Web of Science | Medline19
Rhodes JA ,Tam JP ,Finke U , et al. Transforming growth factor alpha inhibits secretion of gastric acid. Proc Natl Acad Sci U S A 1986;83:3844-3846
CrossRef | Web of Science | Medline20
Rutten MJ ,Dempsey PJ ,Solomon TE ,Coffey RJ Jr . TGF-alpha is a potent mitogen for primary cultures of guinea pig gastric mucous epithelial cells. Am J Physiol 1993;265:G361-G369
Web of Science | Medline21
Chen MC ,Lee AT ,Soll AH . Mitogenic response of canine fundic epithelial cells in short-term culture to transforming growth factor alpha and insulinlike factor I. J Clin Invest 1991;87:1716-1723
CrossRef | Web of Science | Medline22
Romano M ,Polk WH ,Awad JA , et al. Transforming growth factor α protection against drug-induced injury to the rat gastric mucosa in vivo. J Clin Invest 1992;90:2409-2421
CrossRef | Web of Science | Medline23
Dempsey PJ ,Goldenring JR ,Soroka CJ , et al. Possible role of transforming growth factor α in the pathogenesis of Menetrier's disease: supportive evidence from humans and transgenic mice. Gastroenterology 1992;103:1950-1963
Web of Science | Medline24
Takagi H ,Jhappan C ,Sharp R ,Merlino G . Hypertrophic gastropathy resembling Menetrier's disease in transgenic mice overexpressing transforming growth factor α in the stomach. J Clin Invest 1992;90:1161-1167
CrossRef | Web of Science | Medline25
Barnard JA ,Beauchamp RD ,Russell WE ,Dubois RN ,Coffey RJ . Epidermal growth factor-related peptides and their relevance to gastrointestinal pathophysiology. Gastroenterology 1995;108:564-580
CrossRef | Web of Science | Medline26
Karam SM . Dynamics of epithelial cells in the corpus of the mouse stomach. IV. Bidirectional migration of parietal cells ending in their gradual degeneration and loss. Anat Rec 1993;236:314-332
CrossRef | Web of Science | Medline27
Gordon J ,Hermiston M . Differentiation and self-renewal in the mouse gastrointestinal epithelium. Curr Opin Cell Biol 1994;6:795-803
CrossRef | Web of Science | Medline28
Goldenring JR ,Ray GS ,Soroka CJ , et al. Overexpression of transforming growth factor-α alters differentiation of gastric cell lineages. Dig Dis Sci 1996;41:773-784
CrossRef | Web of Science | Medline29
Johnson LR . The trophic action of gastrointestinal hormones. Gastroenterology 1976;70:278-288
Web of Science | Medline30
Barst RJ ,Rubin LJ ,Long WA , et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med 1996;334:296-301
Full Text | Web of Science | Medline31
Robbins IM ,Christman BW ,Newman JH ,Matlock R ,Loyd JE . A survey of diagnostic practices and the use of epoprostenol in patients with primary pulmonary hypertension. Chest 1998;114:1269-1275
CrossRef | Web of Science | Medline32
Peschon JJ ,Slack JL ,Reddy P , et al. An essential role for ectodomain shedding in mammalian development. Science 1998;282:1281-1284
CrossRef | Web of Science | Medline33
Dong J ,Opresko LK ,Dempsey PJ ,Lauffenburger DA ,Coffey RJ ,Wiley HS . Metalloprotease-mediated ligand release regulates autocrine signaling through the epidermal growth factor receptor. Proc Natl Acad Sci U S A 1999;96:6235-6240
CrossRef | Web of Science | Medline
- Citing Articles (34)
Citing Articles
1
Peter Greaves. 2012. Digestive System. , 325-431.
CrossRef2
R. Fiori, L. Velari, L. Vito, F. Della Gatta, M. Bianchi, L. Capurso, G. Simonetti. (2011) Ménétrier’s disease diagnosed by enteroclysis CT: a case report and review of the literature. Abdominal Imaging 36:6, 689-693
CrossRef3
Jong Min Hwang, Gwang Ha Kim, Won Jin Kim, Hee Sun Lee, Hye Won Lee, Dong Yup Ryu, Geun Am Song, Do Yun Park. (2011) A Case of Menetrier's Disease Showing Mucus Bridge Observed during Endoscopy. The Korean Journal of Gastroenterology 57:3, 184
CrossRef4
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CrossRef6
Jae-Kwang Lim, Yun-Jin Jang, Min-Kyu Jung, Hun Kyu Ryeom, Gab-Chul Kim, Junghyun Bae. (2010) Ménétrier disease manifested by polyposis in the gastric antrum and coexisting with gastritis cystica profunda. Gastrointestinal Endoscopy 72:5, 1098-1100
CrossRef7
Willemijn A. Van Dop, Gijs R. Van Den Brink. (2010) Sonic Hedgehog: A Link Between Inflammation, Gastric Atrophy, and Acid Suppression?. Gastroenterology 138:2, 426-429
CrossRef8
S. Köklü, M. Arhan, A. Tas, M. Kurt, N. Turhan, A. Ulker. (2009) An unusual association of Ménétrier’s disease and colon cancer. Acta Endoscopica 39:6, 434-436
CrossRef9
S. C. Nalle, J. R. Turner. (2009) Menetrier's Disease Therapy: Rebooting Mucosal Signaling. Science Translational Medicine 1:8, 8ps10-8ps10
CrossRef10
W. H. Fiske, J. Tanksley, K. T. Nam, J. R. Goldenring, R. J. C. Slebos, D. C. Liebler, A. M. Abtahi, B. La Fleur, G. D. Ayers, C. D. Lind, M. K. Washington, R. J. Coffey. (2009) Efficacy of Cetuximab in the Treatment of Menetrier's Disease. Science Translational Medicine 1:8, 8ra18-8ra18
CrossRef11
Michael Rothenberg, Reetesh Pai, Kevin Stuart. (2009) Successful Use of Octreotide to Treat Ménétrier’s Disease: A Rare Cause of Abdominal Pain, Weight Loss, Edema, and Hypoalbuminemia. Digestive Diseases and Sciences 54:7, 1403-1407
CrossRef12
JERROLD R. TURNER, ROBERT D. ODZE. 2009. Polyps of the Stomach. , 415-445.
CrossRef13
Tae Il Kim. (2009) Menetrier's Disease Accompanied with Adenocarcinoma. The Korean Journal of Gastroenterology 53:5, 271
CrossRef14
P Mathew, P F Thall, S Wen, C Bucana, D Jones, E Horne, W K Oh, M J Morris, Y-C Lee, C J Logothetis, S-H Lin, I J Fidler. (2008) Dynamic change in phosphorylated platelet-derived growth factor receptor in peripheral blood leukocytes following docetaxel therapy predicts progression-free and overall survival in prostate cancer. British Journal of Cancer 99:9, 1426-1432
CrossRef15
Nagib Toubia, Mitchell L. Schubert. (2008) Menetrier’s disease. Current Treatment Options in Gastroenterology 11:2, 103-108
CrossRef16
Guilherme F Ritt, Priscila S Braga, Almir G Bitencourt, Cristiana B Oliveira, Luciano E Fonseca-Júnior, Cristiana M Nascimento-Carvalho. (2008) Case 2: Abdominal discomfort and generalized oedema in a 6-year-old boy. Acta Paediatrica 97:2, 252-254
CrossRef17
I. Hatemi, E. Caglar, D. Aksoy, S. Goksel, A. Dobrucali. (2008) Menetrier's disease coexisting with ulcerative colitis and sclerosing cholangitis. Digestive and Liver Disease 40:1, 78-79
CrossRef18
José Manuel Ramia, Eloy Sancho, Óscar Lozano, José María Santos, Fernando Domínguez. (2007) Enfermedad de Ménétrier y cáncer gástrico. Cirugía Española 81:3, 153-154
CrossRef19
Caroline Sanchez, Fred Brody, Edward Pucci, Showkat Bashir. (2007) Laparoscopic Total Gastrectomy for Ménétrier's Disease. Journal of Laparoendoscopic & Advanced Surgical Techniques 17:1, 32-35
CrossRef20
Juanita L. Merchant. (2007) Tales from the crypts: regulatory peptides and cytokines in gastrointestinal homeostasis and disease. Journal of Clinical Investigation 117:1, 6-12
CrossRef21
Robert J. Coffey, Mary Kay Washington, Christopher L. Corless, Michael C. Heinrich. (2007) Ménétrier disease and gastrointestinal stromal tumors: hyperproliferative disorders of the stomach. Journal of Clinical Investigation 117:1, 70-80
CrossRef22
Stephen H. Settle, Kay Washington, Christopher Lind, Scott Itzkowitz, W. Haley Fiske, J. Steven Burdick, W. Gray Jerome, Margaret Ray, Wilfred Weinstein, Robert J. Coffey. (2005) Chronic Treatment of Ménétrier’s Disease With Erbitux: Clinical Efficacy and Insight Into Pathophysiology. Clinical Gastroenterology and Hepatology 3:7, 654-659
CrossRef23
Sachiyo Nomura, Stephen H. Settle, Charles M. Leys, Anna L. Means, Richard M. Peek, Steven D. Leach, Christopher V. Wright, Robert J. Coffey, James R. Goldenring. (2005) Evidence for Repatterning of the Gastric Fundic Epithelium Associated With Ménétrier’s Disease and TGFα Overexpression. Gastroenterology 128:5, 1292-1305
CrossRef24
Ian L.P. Beales. (2004) Gastrin and interleukin-1β stimulate growth factor secretion from cultured rabbit gastric parietal cells. Life Sciences 75:25, 2983-2995
CrossRef25
Vinzenz Stepan, Nonthalee Pausawasdi, Saravanan Ramamoorthy, Andrea Todisco. (2004) The Akt and MAPK signal-transduction pathways regulate growth factor actions in isolated gastric parietal cells. Gastroenterology 127:4, 1150-1161
CrossRef26
Anastasia E. Konstantinidou, George Morphopoulos, Penelope Korkolopoulou, Christos Eftychiadis, Eleftheria Stamokosta, Angeliki Saetta, Emmanuel Agapitos. (2004) Menetrier Disease of Early Infancy: A Separate Entity?. Journal of Pediatric Gastroenterology and Nutrition 39:2, 177-182
CrossRef27
J. Steven Burdick, Stephen H. Settle, Robert J. Coffey. 2004. Ménétrier's Disease. , 645-646.
CrossRef28
Takeshi Aihara, Teruaki Fujishita, Keiko Kanatani, Kazuharu Furutani, Eiji Nakamura, Makoto M Taketo, Minoru Matsui, Duan Chen, Susumu Okabe. (2003) Impaired gastric secretion and lack of trophic responses to hypergastrinemia in M3 muscarinic receptor knockout mice. Gastroenterology 125:6, 1774-1784
CrossRef29
V Hoffer, Y Finkelstein, J Balter, M Feinmesser, BZ Garty. (2003) Ganciclovir treatment in Ménétrier's disease. Acta Paediatrica 92:8, 983-985
CrossRef30
Cathy McNeill Dykes. (2003) Ménétrier’s Disease. Gastroenterology Nursing 26:1, 3-6
CrossRef31
Toshiki Ogawa, Kazuhiko Maeda, Shunsuke Tonai, Takashi Kobayashi, Takeshi Watanabe, Susumu Okabe. (2003) Utilization of Knockout Mice to Examine the Potential Role of Gastric Histamine H2-Receptors in Menetrier's Disease. Journal of Pharmacological Sciences 91:1, 61-70
CrossRef32
Wilfred M. Weinstein. (2001) Emerging gastritides. Current Gastroenterology Reports 3:6, 523-527
CrossRef33
K.J. Busam, P. Capodieci, R. Motzer, T. Kiehn, D. Phelan, A.C. Halpern. (2001) Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. British Journal of Dermatology 144:6, 1169-1176
CrossRef34
John Barnard. (2001) Epidermal growth factor receptor blockade: an emerging therapeutic modality in gastroenterology. Gastroenterology 120:7, 1872-1874
CrossRef
