RETRACTED: IP1867B suppresses the insulin-like growth factor 1 receptor (IGF1R) ablating epidermal growth factor receptor inhibitor resistance in adult high grade gliomas
Authors: P A Madureira
C A Duckworth
C Simms
R Hill
M Reay
K Mihajluk
D M Pritchard
P Murray
S Nasser
A Howarth
G J Pilkington
Journal: Cancer Letters (2019)
Discipline: CLINICAL MEDICINE
Keywords: Adult high grade glioma; Drug repurposing; EGFR; IGFR1.
Affiliations: Brain Tumour Research Centre, Institute of Biomedical and Biomolecular Sciences, IBBS, University of Portsmouth, PO1 2DT, UK., Centre for Biomedical Research (CBMR), University of Algarve, Campus of Gambelas, Building 8, Room 3.4, 8005-139, Faro, Portugal., Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, L69 3GE, UK., Brain Tumour Research Centre, Institute of Biomedical and Biomolecular Sciences, IBBS, University of Portsmouth, PO1 2DT, UK. Electronic address: .

Abstract:  This article has been retracted at the request of the Editor-in-Chief due to concerns regarding the legitimacy of images and data presented in the paper. Though a corrigendum (Can. Lett. Vol. 469, 2020, pages 524-535) was previously published to address some of these concerns, this corrigendum has also been found to contain errors and therefore cannot stand. Specific concerns are listed below. The Editor and Publisher received a letter from the University of Portsmouth alerting us to an investigation into alleged research misconduct. The University concluded their investigation with external experts and determined that misconduct did take place in relation to the research involved in this paper. Upon our separate investigation, it has been determined that the paper headline relies on showing that there was considerable reduction of IGF1R, IL6R and EGFR post treatment in all cell lines. During review, it was determined that this cannot be concluded from the presented data. For example, in SEBTA-003 the EGFR levels go up and there is no difference in IGFR1. It is apparent from Fig 4d that in the SEBTA-003 cell line the EGFR level does not go down, which is stated in the Results section on page 32, it is rather going up. The data for IGFR1 are inconclusive and there are concerns regarding the blot. The general implications would be that the effects of the drug IP1867B does not seem to be the same for all tested cell lines, and this should have been discussed in detail by the authors. Additionally, in subsequent experiments (Fig. 4g and h) the SEBTA-003 cell line (no reduction of EGFR, rather increased expression) and the other 3 cell lines (reduction of EGFR) show similar responses. This is particularly evident in Fig. 4g: Two cell lines are compared, SEBTA-003 (increased EGFR expression) and UP-029 (decreased EGFR expression), both behave similarly after exposure to drugs. The corrigendum (https://doi.org/10.1016/j.canlet.2019.10.002) issue is with respect to the Supplemental Figure 6i EGFR, particularly panel IP1867B. The Corrigendum states that the left part is a cut out of the very right part. If so, the bands for IP1867B should show the same staining pattern - but they do not. Also, in the Corrigendum, there are incorrect mentions between day 14 in the Figure and day 19 in the Figure legend. All authors were informed of the retraction in advance. Drs. Pritchard and Duckworth agreed to the retraction. The corresponding author, Dr Hill, did not agree to the retraction. No response had been received from Drs. Mihajluk, Simms, Reay, Madureira, Howarth, Murray, Nasser and Pilkinton at the time of the retraction being published. 

Retracted: No

PubPeer comments:
 Hard to interpret data based on western blots. In supplemental although stated, some images do not appear to be full uncropped blots. , 
 Uncropped blots in Supplemental data confirm that beta-actin controls shown in Figures 3a and 5i are at fault.![file] , 
 Panel duplication in Figure 1f![file] , 
 ![file] Looking at the supplemental data, it is possible to appreciate that beta-actin loading controls were usually not performed in the same blotting membrane as other antibodies, which may lead to errors in protein quantification. , 
 ![file] Similarly, total protein controls were not assessed in the same blot as phosphorylates proteins, which again may lead to errors in quantification. , 
 ![file] This is a serious mistake, since the same beta-actin blot was used for 2 different experiments reported in 2 different publications from the same team, this Cancer Letters article and a recent Translational Oncology article. , 
 #6  This is a serious mistake, since the same beta-actin blot was used for 2 different experiments reported in 2 different publications from the same team, this Cancer Letters article and a recent Translational Oncology article. The companion paper is [Howarth et al (2019)] . When blots have been selectively cropped and flipped horizontally, then re-presented as **original data** from quite different experiments, describing this as  a serious mistake is pushing the envelope of that word. , 
 #2 Here I am just illustrating Micropsalliota s point, that the same band has been used in Figures 3(a) and 5(i) with the lanes relabelled as if obtained in different experiments, and supplied with different lists of relative intensities. ![file] , 
 I thank Hoya (and others) for bringing these to my attention. I have already submitted an amendment notification to the journal regarding some of the concerns highlighted here. I apologise unreservedly for failing to spot the accidental microscopy duplication observed in Figure 1f, where the SEBTA-023 representative image was used twice instead of inserting the SEBTA-003 microscopy panel. I also completely agree that the beta-actin panel was duplicated between Figure 3a and Figure 5i. I do not know how this occurred, particularly because the Figure 5 (and supplemental Figure 6 where the full immunoblots are shown) files that I have, the correct, different beta-actin blot are shown. This of course does not excuse this important mistake and, as indicated here (and to the journal), needs to be corrected immediately. Sandracottus Bakewellii raises a very important comment stating that in an different publication, the same immunoblot was shown. This was immediately spotted by myself in the corrected proofs that the journal provided to me. As Hoya indicates, I immediately addressed this important issue. In regard to the general comments which relate to western blot quantification, I am in agreement with those researchers who have published comments here. In our original and revised submission, we did not conduct quantification. However, each time, both reviewers insisted on the quantification of western blots. We did this at their behest. I thank the community who raised these important issues, discussed the data and rapidly brought their concerns to my attention. Sincerely Dr. Richard Hill. , 
 2019 corrigendum. https: www.sciencedirect.com science article pii S0304383519304938?via%3Dihub In the article above, we, the authors, discovered that a single microscopy panel was inadvertently placed in Figure 1f, using the SEBTA-023 panel twice instead of the SEBTA-003 representative image. We discovered that an actin western blot loading control data associated with Figure 3a was also incorrectly placed in Figure 5i. We retrieved the original actin western blot data linked to Figure 5i and corrected this error. Neither correction alter the conclusions of the original paper; however, we sincerely apologize for any confusion that this may have caused. , 
 The full blots in the corrigendum also show EGFR IP1867B Figure versus full blots are not the same: ![file] Does this mean we will have a corrigendum to the corrigendum? , 
 Retraction to appear [1 June 2021] . ------------------------------------------ This article has been retracted at the request of the Editor-in-Chief due to concerns regarding the legitimacy of images and data presented in the paper. Though a corrigendum (Can. Lett. Vol. 469, 2020, pages 524u2013535) was previously published to address some of these concerns, this corrigendum has also been found to contain errors and therefore cannot stand. Specific concerns are listed below. The Editor and Publisher received a letter from the University of Portsmouth alerting us to an investigation into alleged research misconduct. The University concluded their investigation with external experts and determined that misconduct did take place in relation to the research involved in this paper. Upon our separate investigation, it has been determined that the paper headline relies on showing that there was considerable reduction of IGF1R, IL6R and EGFR post treatment in all cell lines. During review, it was determined that this cannot be concluded from the presented data. For example, in SEBTA-003 the EGFR levels go up and there is no difference in IGFR1. It is apparent from Fig. 4d that in the SEBTA-003 cell line the EGFR level does not go down, which is stated in the Results section on page 32, it is rather going up. The data for IGFR1 are inconclusive and there are concerns regarding the blot. The general implications would be that the effects of the drug IP1867B does not seem to be the same for all tested cell lines, and this should have been discussed in detail by the authors. Additionally, in subsequent experiments (Fig. 4g and h) the SEBTA-003 cell line (no reduction of EGFR, rather increased expression) and the other 3 cell lines (reduction of EGFR) show similar responses. This is particularly evident in Fig. 4g: Two cell lines are compared, SEBTA-003 (increased EGFR expression) and UP-029 (decreased EGFR expression), both behave similarly after exposure to drugs. The corrigendum issue is with respect to the Supplemental Figure 6i EGFR, particularly panel IP1867B. The Corrigendum states that the left part is a cut out of the very right part. If so, the bands for IP1867B should show the same staining pattern - but they do not. Also, in the Corrigendum, there are incorrect mentions between day 14 in the Figure and day 19 in the Figure legend. All authors were informed of the retraction in advance. Drs. Pritchard and Duckworth agreed to the retraction. The corresponding author, Dr Hill, did not agree to the retraction. No response had been received from Drs. Mihajluk, Simms, Reay, Madureira, Howarth, Murray, Nasser and Pilkinton at the time of the retraction being published. ,