A duplicated figure has resulted in an expression of concern for a paper in the American Journal of Pathology on a treatment for ocular neovascularization, which causes vision loss.
According to the notice, the corresponding author, David Shima, now at University College London, brought his concern to the journal. He called it a “genuine error” and stated that all the findings had been reproduced.
Unfortunately, Shima claimed the original data are missing, because the institution that owned the information — Eyetech Research Center — has “since gone through several acquisitions.”
Ocular neovascularization occurs when growth signals in the eye stimulate the creation of many new blood vessels. Over time these blood vessels break, causing bleeding and scarring that limits vision. This is called “wet” macular degeneration.
The scientists found that giving patients drugs to limit two different growth factors at the same time is more effective than one at stopping the progression of AMD. This combination method is in stage three clinical trials, though with different drugs than the authors used here.
The paper, published in 2006, has been cited 130 times, according to Thomson Scientific’s Web of Knowledge. Here’s the EoC for “Inhibition of Platelet-Derived Growth Factor B Signaling Enhances the Efficacy of Anti-Vascular Endothelial Growth Factor Therapy in Multiple Models of Ocular Neovascularization”:
It has been brought to our attention that Figure 10B of “Inhibition of Platelet-Derived Growth Factor B Signaling Enhances the Efficacy of Anti-Vascular Endothelial Growth Factor Therapy in Multiple Models of Ocular Neovascularization,” by Nobuo Jo, Carolina Mailhos, Meihua Ju, Eunice Cheung, John Bradley, Kazuaki Nishijima, Gregory S. Robinson, Anthony P. Adamis, and David T. Shima (Volume 168, pages 2036–2053 of the June 2006 issue of The American Journal of Pathology) contains data errors, specifically the duplication of fluorescent images between the Prevention (A) and Regression (B) data points. The matter was reviewed by the journal’s Editors.
Corresponding author Dr. Shima brought this matter to the attention of the Editors. Dr. Shima states that “this was a genuine error, and we are confident in the actual quantitative data presented in the figure. Not only have other investigators reproduced combination data[1], we also presented in the article another experiment performed in a distinct set of studies using Gleevec (imatinib) as the PDGF (platelet-derived growth factor) antagonist. Finally, the combination therapy approach has been validated in a Phase 2b proof-of-concept study in neovascular AMD (age-related macular degeneration) patients and is currently in Phase 3 clinical trial (https://clinicaltrials.gov/ct2/home, accession number NCT01940900).”
The authors report that they no longer have access to the original data, which was held by their employer Eyetech Research Center (Lexington, MA); Eyetech Research Center has since gone through several acquisitions.
Reference
1 A. Dong, C. Seidel, D. Snell, S. Ekawardhani, J.K. Ahlskog, M. Baumann, J. Shen, T. Iwase, J. Tian, R. Stevens, S.F. Hackett, M.T. Stumpp, P.A. Campochiaro
Antagonism of PDGF-BB suppresses subretinal neovascularization and enhances the effects of blocking VEGF-A Angiogenesis, 17 (2014), pp. 553–562
The notice had been paywalled on Science Direct, but after we reached out to the journal, they made it publicly available and sent us this note:
It is the policy of the Journal that all Corrections, Retractions, and Notes of Concern be freely available. We apologize for the error on the Science Direct platform and have asked the Publisher to release it for free access. The Note of Concern is freely available at http://ajp.amjpathol.org/
article/S0002-9440%2814% 2900680-4/fulltext and can be viewed there until the Science Direct site is updated.
So, if we set aside the reasons, and ignore the issue of bias caused by the term “genuine”, can we safely assume that a duplicated figure and no data will lead – at minimum – to an EoC in all (or any?) Elsevier journals? Thus, if we should find a duplicated figure in any Elsevier journal, may we reference this case in a bid to make the editors issue, at least, an EoC for similar cases? Is a duplicated figure equivalent to a duplicated data set, or a duplicated table? Perhaps Elsevier could offer a detailed explanation at RW? By not applying the same rule uniformly across all of its journals, the problem of inconsistency in publishing ethics by this publisher may begin to be focused.
I must admit that I found that the description of this EoC a bit confusing. The statement “The scientists found that giving patients drugs to limit two different growth factors at the same time is more effective than one at stopping the progression of AMD. This combination method is in stage three clinical trials, though with different drugs than the authors used here” seems to be a bit out of context. It implies that the data in the article comes from a clinical trial when it comes from animal models.
There is also a scientific error in the following statement “Dr. Shima states that “this was a genuine error, and we are confident in the actual quantitative data presented in the figure. Not only have other investigators reproduced combination data, we also presented in the article another experiment performed in a distinct set of studies using Gleevec (imatinib) as the PDGF (platelet-derived growth factor) antagonist.” Gleevec is not a PDGF antagonist. It is a PDGF RECEPTOR antagonist.
With respect to the duplication, it wasn’t just a simple duplication but a duplication with a slightly different magnification. That difference in magnification might be reflected in the graph below the images.
Now I have looked at the Note of Concern closely it seems that I have a concern about the quality of the Note of Concern.
My web broswer lost the superscripted 1 after the word “data”. Sorry about that.
In addition, the statement “Finally, the combination therapy approach has been validated in a Phase 2b proof-of-concept study in neovascular AMD (age-related macular degeneration) patients” doesn’t have a citation. This seems to refer to Fovista (based on the CT.gov entry). I don’t think that the Fovista Phase 2b data have been published yet but I might be wrong.
Am J Pathol. 2002 Dec;161(6):2229-40.
Constitutive nuclear factor-kappaB activity is crucial for human retinoblastoma cell viability.
Poulaki V1, Mitsiades CS, Joussen AM, Lappas A, Kirchhof B, Mitsiades N.
Author information
1Retina Research and Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 325 Cambridge Street, Boston, MA 02114, USA.
Figure 3.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1850903/figure/f3/
Please see: https://pubpeer.com/publications/12466137
http://i.imgur.com/POtsT34.jpg
A 2015 note of concern has been published for this paper.
http://ajp.amjpathol.org/article/S0002-9440(15)00193-5/fulltext
Penultimate author of paper which is topic of post, AP Adamis.
J Clin Invest. 2002 Mar;109(6):805-15.
Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1alpha and VEGF.
Poulaki V1, Qin W, Joussen AM, Hurlbut P, Wiegand SJ, Rudge J, Yancopoulos GD, Adamis AP.
Author information
1Laboratory of Surgical Research, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Please see: https://pubpeer.com/publications/11901189
Especially:
Figure 1.
http://i.imgur.com/QVQG3ca.jpg
and figure 4a.
http://i.imgur.com/MIVDsps.jpg
Ppenultimate author of paper which is topic of post, AP Adamis.
Am J Pathol. 2004 Aug;165(2):457-69.
Insulin-like growth factor-I plays a pathogenetic role in diabetic retinopathy.
Poulaki V1, Joussen AM, Mitsiades N, Mitsiades CS, Iliaki EF, Adamis AP.
Author information
1Retina Research Institute, Massachusetts Eye and Ear Infirmary, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Please see: https://pubpeer.com/publications/15277220
http://i.imgur.com/mMCDJnU.jpg
Am J Pathol. 2004 Aug;165(2):457-69.
There’s more. See the pink.
Figure 4A.
http://i.imgur.com/uOqgLDM.jpg
Invest Ophthalmol Vis Sci. 2003 May;44(5):2184-91.
Contribution of TNF-alpha to leukocyte adhesion, vascular leakage, and apoptotic cell death in endotoxin-induced uveitis in vivo.
Koizumi K1, Poulaki V, Doehmen S, Welsandt G, Radetzky S, Lappas A, Kociok N, Kirchhof B, Joussen AM.
Author information
1Department of Vitreoretinal Surgery, Center for Ophthalmology, and Center for Molecular Medicine, University of Cologne, Cologne, Germany.
https://pubpeer.com/publications/12714660
Figure 8A.
http://i.imgur.com/4qUiWrK.jpg
Mol Vis. 2009 Jul 25;15:1418-28.
TNF-alpha mediated apoptosis plays an important role in the development of early diabetic retinopathy and long-term histopathological alterations.
Joussen AM1, Doehmen S, Le ML, Koizumi K, Radetzky S, Krohne TU, Poulaki V, Semkova I, Kociok N.
Author information
1Department of Ophthalmology, Heinrich Heine University, Duesseldorf, Germany.
https://pubpeer.com/publications/B4E26E4DFBD539DA7E9F9B755327A2#fb24898
Please compare 30 KD control band figure 6A Mol Vis 15,1418
with 30 KD anti-TNF band figure 8A Invest Ophthalmol Vis Sci 44,2184.
http://i.imgur.com/mhwiAOE.jpg
For reference.
Invest Ophthalmol Vis Sci 44,2184.
https://pubpeer.com/publications/12714660
Hi fernando pessoa, I am consider reporting this story for the German audience, would you like to get in touch?
leonid(Dot)schneider(At)gmail(Dot)com
FASEB J. 2007 Jul;21(9):2113-23. Epub 2007 Mar 30.
Inhibition of Hsp90 attenuates inflammation in endotoxin-induced uveitis.
Poulaki V1, Iliaki E, Mitsiades N, Mitsiades CS, Paulus YN, Bula DV, Gragoudas ES, Miller JW.
Author information
1Angiogenesis/Laser Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles St., Boston, MA 02114, USA.
Please see: https://pubpeer.com/publications/17400913
and http://i.imgur.com/fjkE5o3.jpg
Nat Med. 1999 May;5(5):495-502.
Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188.
Peter Carmeliet1, Yin-Shan Ng2, Dieter Nuyens1, Gregor Theilmeier1, Koen Brusselmans1, Ivo Cornelissen1, Elisabeth Ehler3, Vijay V. Kakkar4, Ingeborg Stalmans1, Virginie Mattot1, Jean-Claude Perriard3, Mieke Dewerchin1, Willem Flameng5, Andras Nagy6, Florea Lupu4, Lieve Moons1, Désiré Collen1, Patricia A. D’Amore2 & David T. Shima2, 7
1 The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven , Leuven, B-3000, Belgium
2 Schepens Eye Research Institute, Harvard Medical School , Boston, Massachusetts 02115, USA
3 Institute for Cell Biology, Swiss Federal Institute of Technology, Zürich, CH-8093, Switzerland
4 Vascular Biology Laboratory, Weston Experimental Research Center, Thrombosis Research Institute, London SW3 6LR , UK
5 Laboratory of Experimental Cardiac Surgery, KU Leuven, Leuven, B-3000, Belgium
6 Samuel Lunenfeld Institute, Mount Sinai Hospital, Toronto, ON M5 1X5, Canada
7 Cell Biology, Imperial Cancer Research Fund, London WC2A 3PX, UK
Please see:
https://pubpeer.com/publications/4BED94B956B79DEAE38C6799022E6A#fb25112
Figure 2k.
http://i.imgur.com/zsRGNDO.jpg
Figure 3g.
http://i.imgur.com/c6me8Aj.jpg
EMBO Mol Med. 2012 Sep;4(9):980-91. doi: 10.1002/emmm.201101084. Epub 2012 Aug 20.
2 comments on PubPeer
β-Secretase (BACE1) inhibition causes retinal pathology by vascular dysregulation and accumulation of age pigment.
Jun Cai1,†, Xiaoping Qi1,†, Norbert Kociok2, Sergej Skosyrski2, Alonso Emilio1, Qing Ruan1, Song Han3, Li Liu4, Zhijuan Chen1, Catherine Bowes Rickman5, Todd Golde6, Maria B. Grant4, Paul Saftig7, Lutgarde Serneels8,9, Bart de Strooper8,9, Antonia M. Joussen2 and Michael E. Boulton ([email protected]) *,1
1Department of Anatomy & Cell Biology, University of Florida, Gainesville, FL, USA
2Department of Ophthalmology, Charité Universitätsmedizin Berlin, Berlin, Germany
3Department of Surgery, University of Florida, Gainesville, FL, USA
4Department of Pharmacology & Therapeutics, University of Florida, Gainesville, FL, USA
5Department of Ophthalmology & of Cell Biology, Duke University Medical Center, Durham, NC, USA
6Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA
7Biochemical Institute, Christian‐Albrecht’s University, Kiel, Germany
8Center for Human Genetics and Leuven Institute for Neurodegenerative Diseases (LIND), KU Leuven, Leuven, Belgium
9VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
Please see Pubpeer comments.
https://pubpeer.com/publications/5CBF05BEBE80EDE91A70B48DF3358F
Invest Ophthalmol Vis Sci. 2003 Dec;44(12):5182-8.
Latanoprost stimulates secretion of matrix metalloproteinases in tenon fibroblasts both in vitro and in vivo.
Mietz H1, Esser JM, Welsandt G, Kociok N, Hueber A, Joussen A, Esser P, Krieglstein GK.
Author information
1Department of Ophthalmology, University of Cologne, 50924 Koeln, Germany.
Please see Pubpeer comments.
https://pubpeer.com/publications/14638715
Exp Eye Res. 2010 Feb;90(2):244-53. doi: 10.1016/j.exer.2009.10.012. Epub 2009 Oct 28.
Retinal localization of the glutamate receptor GluR2 and GluR2-regulating proteins in diabetic rats.
Semkova I1, Huemmeke M, Ho MS, Merkl B, Abari E, Paulsson M, Joussen AM, Plomann M.
Author information
1Department of Ophthalmology, University of Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany.
https://pubpeer.com/publications/79F9C96BFFC8C414CD19020B7AB37E#fb25238
http://i.imgur.com/9IKUtzz.jpg
Am J Pathol. 2002 May;160(5):1683-93.
Suppression of diabetic retinopathy with angiopoietin-1.
Joussen AM1, Poulaki V, Tsujikawa A, Qin W, Qaum T, Xu Q, Moromizato Y, Bursell SE, Wiegand SJ, Rudge J, Ioffe E, Yancopoulos GD, Adamis AP.
Author information
1Laboratory for Surgical Research, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Please see Pubpeer comment:
https://pubpeer.com/publications/3CF916E5F93F1A99EA8B2B6241456D#fb25824
http://ajp.amjpathol.org/cms/attachment/2000643919/2001376442/gr1_lrg.jpg
http://imgur.com/GP4TiyA