Two cancer researchers who hold a patent on a particular pathway that might be a target for new drugs — and one of whom leads a company that is studying those potential drugs — have retracted two related papers in the Journal of Biological Chemistry (JBC).
The notices for “Kinase suppressor of Ras signals through Thr269 of c-Raf-1” and “The kinase activity of kinase suppressor of Ras1 (KSR1) is independent of bound MEK,” which share H. Rosie Xing and Memorial Sloan-Kettering’s Richard Kolesnick as authors, say the same thing:
This article has been withdrawn by the authors.
This sort of unhelpful notice has unfortunately been par for the course for many notices at the JBC, although we have praised their efforts to add more information to some recent notices.
The first paper has been cited 49 times, according to Thomson Scientific’s Web of Knowledge, while the second has been cited 13.
One of the papers is cited by a U.S. patent Xing and Kolesnick hold, “Kinase suppressor of Ras inactivation for therapy of Ras mediated tumorigenesis.” Kolesnick is chief scientific officer of Ras Therapeutics, which licensed Ras technology from Sloan-Kettering.
We also found a Corrigendum published in 2011 of a 2003 Nature Medicine paper on which Xing and Kolesnick are first and last authors, respectively:
In the version of this article initially published, there are irregularities with the tubulin loading controls in lanes 1 through 4 and with the KSR1 bands in lanes 7 and 8 of Figure 2f. The authors have repeated the experiment and have provided a new figure panel that is now published as part of the correction notices linked to the HTML version and attached to the PDF version of the article. The original figures remain in both online versions of the article. The authors have also made a correction to Supplementary Figure 6b, which has been added to the supplementary file online. H. Rosie Xing does not agree to this correction.
Kolesnick did not respond to a request for comment. Xing seems to have been at the University of Chicago most recently, but her email bounced, and the press office did not respond to us.
Hat tip: Rolf Degen
These JBC retractions are 2 of the 4 papers by this group listed on my old website (in case anyone’s counting, that’s now 16 retractions and 47 corrections). The other 2 were the Nature Medicine paper corrected back in 2011 (the correction did not address all the issues), and this one…
PMID 21586628 Mol Cancer Ther 2011, v10, p1173
Xing is senior author, and there is apparent re-use of images between Figures 2D and 5D, as shown here… http://imgur.com/GfnCDb7
Mol Cancer Ther. 2010 Oct;9(10):2724-36. doi: 10.1158/1535-7163.MCT-10-0124. Epub 2010 Sep 28.
Pharmacologic inactivation of kinase suppressor of Ras1 sensitizes epidermal growth factor receptor and oncogenic Ras-dependent tumors to ionizing radiation treatment.
Xiao H, Zhang Q, Shen J, Bindokas V, Xing HR.
Source
Departments of Pathology, Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois 60637, USA.
PMID: 20876746
Figure 1.
http://mct.aacrjournals.org/content/9/10/2724/F1.large.jpg
Figure 1D. Blot: p-ERK2. Please compare bands in the 5 and 10 minute lanes with bands in the 60 and 90 minutes lanes respectively.
david hardman,
I have a question and a suggestion.
The question is how do you pick out these duplications? I can’t do it myself. I think I have a sensitive eye towards data, but I can never see these things until they are pointed out (and then they are obvious).
The suggestion is that I think it would be easier for people to see what you are saying if you stated what was wrong with the images rather than ‘please compare’. In other words, “…bands in the 5 and 10 minute lanes appear identical to bands in the 60 and 90 minutes lanes…” I know for myself, and I suspect for others, that it would be very helpful to just state what we should be looking for.
Dan Zabetakis November 27, 2013 at 5:23 pm
I am glad that you can see the similarity, others cannot.
1. Sent: Monday, February 25, 2013 9:34 PM
To: mct
Cc: aacr; cope_opsmanager
Subject: Mol Cancer Ther. 2010 Oct;9(10):2724-36.
Figure 1.
http://mct.aacrjournals.org/content/9/10/2724/F1.large.jpg
Figure 1D. Blot: p-ERK2. I think that the bands in the bands in the 5 and 10 minute lanes are the same as the bands in the 60 and 90 minutes lanes respectively.
Note that in the top of the right end of the bands in the 5 and 60 minute lanes there is a small light bubble.
Note that the distribution of signal is very similar in the bands in the 10 and 90 minute lanes, including the dark spot on the upper right.
If you tilt the computer screen back to about 45 degrees you will also see that the scattered signal aound the bands in the 5 and 60 minute lanes is the same, and also the same for the bands in the 10 and 90 minute lanes.
2. On Tue, Apr 16, 2013 at 12:22 AM, McMullan, Erin wrote:
Many thanks for bringing your concern to our attention. We have evaluated the images and disagree with your assessment. We do not see evidence of image manipulation in this article.
Best regards,
Erin McMullan
Erin McMullan, Managing Editor
Cancer Epidemiology, Biomarkers & Prevention
Cancer Prevention Research
Molecular Cancer Therapeutics
American Association for Cancer Research
615 Chestnut Street
Philadelphia, PA
Remarkably cavalier response from the Managing Editor. I wonder how they evaluated the images.
Regarding your question, it is mainly a matter of training. Researchers typically apply full concentration to understand the science. They are not approaching the figures with suspicion. That requires an active change in plan. In-figure gel manipulations are quite easy to see at full resolution if the assembler is an amateur or careless. Comparing between figures and publications takes more time but the rewards are higher (in the sense that the offence is likely to be taken more seriously). Eventually, your eye becomes trained enough that you can be reading the paper in scientific mode and still be alerted to funnies.
My question is – I wonder what fraction of biomedical publications David thinks have visible figure manipulations? He obviously knows how to mine locally enriched “clusters” but I expect that he goes systematically through journals as well. (I imagine that the fingered researchers wish he would get out a bit more…)
It depends on the journal. Between about 3 and 10% of papers with western blots. Skeletal Muscle, nearer the higher end. That is based on looking through 4 or 5 journals in the last few years when the image quality has become generally better.
An interesting ratio of retractions to corrections. Keep counting….
Home on Pubpeer Mol Cancer Ther. 2010 Oct;9(10):2724-36.
https://pubpeer.com/publications/20876746
Reply to michaelhbriggs November 27, 2013 at 8:39 pm
“I wonder how they evaluated the images.” The question has been asked. No answer.
Reply to Scrutineer November 30, 2013 at 10:05 am
I find this advice helpful.
http://ori.dhhs.gov/images/ddblock/dec_vol21_no1.pdf
“Dr. Julio Turrens, who reported that he and his students found many more examples of inconsistencies when they looked at the image before reading the paper.
Journals should advise reviewers to look at the images first.”
The readers are the reviewers.
Interesting advice for figure reviewing. Probably helpful too when assessing figure design, labelling and general understandability (for the fraction of non-fraudulent ones).
Not surprised that you see => 3% figure fabrication rates but that some research fields are higher. For me the juxtaposition of natural products and western blots is the big red flag. Western blots have revealed many of the magical properties of resveratrol for ischemia and curry ingredients for cancer, for example. Even when they haven’t…
J Biol Chem. 2005 Jun 17;280(24):23262-72. Epub 2005 Apr 18.Down-regulation of ATM protein sensitizes human prostate cancer cells to radiation-induced apoptosis.Truman JP1, Gueven N, Lavin M, Leibel S, Kolesnick R, Fuks Z, Haimovitz-Friedman A.Author information1Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Figure 2. Much more similar than you would expect.
See: https://imgur.com/HLZ6shg
Cancer Biol Ther. 2009 Jan;8(1):54-63. Epub 2009 Jan 4.PKCalpha activation downregulates ATM and radio-sensitizes androgen-sensitive human prostate cancer cells in vitro and in vivo.Truman JP1, Rotenberg SA, Kang JH, Lerman G, Fuks Z, Kolesnick R, Marquez VE, Haimovitz-Friedman A.Author information1Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, Frederick, Maryland, USA.
Figure 2A. Much more similar than you would expect, although experimental conditions different.
See: https://imgur.com/xJoDcHD
FYI:
J Biol Chem. 2005 Jun 17;280(24):23262-72. Epub 2005 Apr 18.
Down-regulation of ATM protein sensitizes human prostate cancer cells to radiation-induced apoptosis.
Truman JP1, Gueven N, Lavin M, Leibel S, Kolesnick R, Fuks Z, Haimovitz-Friedman A.
Author information1Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.