Aneurus Inconstans, a plant scientist by background, wandered into cancer research, wide-eyed and excited like a child into a toy store. Everything he touches brings immense joy of discovery to our data integrity sleuth. Everything is beautifully fake and excitingly fraudulent.

After his recent Sicilian adventure, follow Aneurus now to the little visited aisle of Argentinian cancer research. A fairy-tale world inside a CONICET lab in Buenos Aires whose trainees move on to USA to do great science at Weill Cornell.

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Magic in cancer research: yet another case from Argentina

By Aneurus Inconstans

Cancer researcher Patricia Virginia Elizalde is principal investigator at the Instituto de Biología y Medicina Experimental (IBYME) in Buenos Aires, an institute that belongs to CONICET, the National Scientific and Technical Research Council of Argertina. IBYME was founded in 1944 by the Nobel Prize winner Bernardo Houssay and enjoys a certain reputation. Its former director, as well as former president of the whole CONICET, was Elizalde’s mentor, the late Eduardo Charreau, a bigwig of cancer research in South America. Among 52 original research articles authored by Dr Elizalde and her collaborators (many with Charreau on), 16 (a third) are now flagged on PubPeer for issues hard to explain with random errors. The rest doesn’t inspire much confidence either, but in many (too many) suspicious blots the proverbial “smoking gun” wasn’t found. None of the authors replied to any thread on PubPeer as of today.

Dr Elizalde became senior tenured scientist at IBYME in 1994 and troubles arose as early as 2001, when she was aiming to get promoted to principal scientist, which then happened in 2006. The time span of the problematic articles is 20+ years and up to the present day.

The Elizalde lab works on breast cancer, and in particular on the receptor tyrosine kinase ErbB-2/HER2. ErbB-2 overexpression is a trademark of a breast cancer subtype, namely ErbB-2-enriched (ErbB-2E). The Elizalde lab allegedly contributed to demonstrate that ErbB-2 migrates to the nucleus of ErbB-2E breast cancer cells where it binds promoters of target genes and functions as a transcription factor to promote breast cancer growth. Another line of research carried out in this lab is on triple negative breast cancer (TNBC), defined by lack of expression of both estrogen and progesterone receptors as well as ErbB-2. The Elizalde lab apparently developed a vaccination protocol based on the serial injection of breast cancer cells – whose oncoprotein Stat3 was previously blocked -that was able to inhibit TNBC growth in mice, as stated on the lab website.

Here are two problematic works from 2001, the time when data digitalization and the spread of Photoshop use came into play in each laboratory:

Balañá ME, Labriola L, Salatino M, Movsichoff F, Peters G, Charreau EH, Elizalde PV* Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insulin-like growth factor receptor in mammary tumor cells Oncogene (2001) doi: 10.1038/sj.onc.1204050 (*corresponding author)

The IGF-IR Western blot of Figure 4 is the same one published two years before in Figure 6 of Balañá et al. 1999, which allegedly shows Erb-B3 signal after immuno-precipitation. The experiment type, the treatments involved and the detected protein are all different, this is why a picture reuse due to files mislabelling seems unlikely. Was that just a mistake by the first author Maria Eugenia Balaña, now senior scientist at ICT-CONICET (Instituto de Ciencia y Tecnología César Milstein), or was instead the beginning of the history of fraudulent shortcuts taken by this lab?

More serious and not explainable by an accidental event is the patchwork of bands found in Figure 3 of the following paper, published in a Spandidos Publications (!) journal. Dr Elizalde is just a middle author here, while the first and corresponding author is María Giselle Peters, now group leader at the Instituto de Oncología Ángel H. Roffo in Buenos Aires:

Peters MG*, Vanzulli S, Elizalde PV, Charreau EH, Goin MM. Effects of antiprogestins RU486 and ZK98299 on the expression of cell cycle proteins of a medroxyprogesterone acetate (MPA)-induced murine mammary tumor Oncol Rep (2001) doi: 10.3892/or.8.2.445

Dr Peters published only 11 papers in total, and 5 are flagged in PubPeer with outrageous fabrications. A heck of a ratio. She published very fake stuff also without Elizalde actually, please have a look at Stigliano et al. 2009 or Fernandez et al. 2018 for instance, but the following one is probably the worst:

Buchanan C, Stigliano I, Garay-Malpartida HM, Rodrigues Gomes L, Puricelli L, Sogayar MC, Bal de Kier Joffé E, Peters MG* Glypican-3 reexpression regulates apoptosis in murine adenocarcinoma mammary cells modulating PI3K/Akt and p38MAPK signaling pathways Breast Cancer Res Treat (2010) doi: 10.1007/s10549-009-0362-9

Going back to Elizalde’s wizardry, now come a number of articles published between 2005-2010, the time when fraud in science really became pandemic. You will admire how this group dropped all hesitations and inhibitory restraint by making up Western blots on a much larger scale. The Elizalde lab even passed peer-review in the respected journal Molecular & Cellular Biology on three occasions with massive data fabrication. Here below the first Mol Cell Biol paper, analyzed by the anonymous PubPeer commenter Fuscopannaria mediterranea, brace yourself:

Proietti C, Salatino M, Rosemblit C, Carnevale R, Pecci A, Kornblihtt AR, Molinolo AA, Frahm I, Charreau EH, Schillaci R, Elizalde PV* Progestins induce transcriptional activation of signal transducer and activator of transcription 3 (Stat3) via a Jak- and Src-dependent mechanism in breast cancer cells Mol Cell Biol (2005) doi: 10.1128/MCB.25.12.4826-4840.2005

First author Cecilia Jazmín Proietti, adjunct investigator at IBYME, co-authored 14 problematic papers with Elizalde and seems to be the right-hand woman of the boss. After all, it would have been a shame to let such a creative person slip away. Here another milestone by the magical Proietti-Elizalde duo:

Proietti CJ, Rosemblit C, Beguelin W, Rivas MA, Díaz Flaqué MC, Charreau EH, Schillaci R, Elizalde PV* Activation of Stat3 by heregulin/ErbB-2 through the co-option of progesterone receptor signaling drives breast cancer growth Mol Cell Biol (2009) doi: 10.1128/MCB.00853-08

These are just some of the problems, as figures 1B, 3D and 6C are equally entertaining (please refer to the PubPeer thread for the whole set).

Yet another one in Mol Cell Biol by Elizalde & Co.:

Béguelin W, Díaz Flaqué MC, Proietti CJ, Cayrol F, Rivas MA, Tkach M, Rosemblit C, Tocci JM, Charreau EH, Schillaci R, Elizalde PV* Progesterone receptor induces ErbB-2 nuclear translocation to promote breast cancer growth via a novel transcriptional effect: ErbB-2 function as a coactivator of Stat3 Mol Cell Biol (2010) doi: 10.1128/MCB.00012-10

The two duplicated bands of pStat3 (red boxes) are set in the middle of two blots which at first glance appear genuine. As you can see, the neighbouring bands on both sides of the red boxes are different from one blot to the other. First author Wendy Béguelin, who is also third author on the disastrous Proietti et al 2009 and boasts 7 papers flagged in PubPeer as of today, is now assistant professor at Weill Cornell Medical College in the lab of Ari Melnick. I’ll get back to this point soon.

In the next article Proietti and Béguelin joined forces again to produce some pearls of disguise:

Proietti CJ, Béguelin W, Flaqué MC, Cayrol F, Rivas MA, Tkach M, Charreau EH, Schillaci R, Elizalde PV* Novel role of signal transducer and activator of transcription 3 as a progesterone receptor coactivator in breast cancer Steroids (2011) doi: 10.1016/j.steroids.2010.12.008

The Bcl-XL mRNA gel of figure 3A and the GAPDH control blot of figure 6B (no GAPDH signal expected as it’s a ChIP) seem to be both genuine at first glance but they are not. All the remaining blots of the article are apparently unproblematic. Are they really?

The Elizalde lab, pompously named Molecular Mechanisms of Carcinogenesis and Molecular Endocrinology, includes another principal investigator (Investigadora Principal), Roxana Schillaci, who shares with Elizalde 14 out of the 16 problematic papers. The following one sees Dr Schillaci as last name and corresponding author. The article includes a countless number of blots all showing bands floating on a homogeneous and flawless background, something reminiscent of those creations produced by papermills, but this is just one aspect of my concerns:

Rivas MA, Carnevale RP, Proietti CJ, Rosemblit C, Beguelin W, Salatino M, Charreau EH, Frahm I, Sapia S, Brouckaert P, Elizalde PV, Schillaci R* TNF alpha acting on TNFR1 promotes breast cancer growth via p42/P44 MAPK, JNK, Akt and NF-kappa B-dependent pathways Exp Cell Res (2008) doi: 10.1016/j.yexcr.2007.10.005

First author Martin Alfredo Rivas (7 papers in PubPeer) is now research associate at Weill Cornell Medical College, curiously in the same lab (Ari Melnick‘s) hosting his former CONICET colleague Wendy Béguelin. From Dr Rivas’ LinkedIn profile we learn he is additionally adjunct assistant professor at John Jay College of Criminal Justice, at The City University of New York, likely involved in the teaching for the cell and molecular biology course there. An obvious joke comes to mind about that, and I won’t say more.

More magic results on breast cancer research in this article from 2007:

Carnevale RP, Proietti CJ, Salatino M, Urtreger A, Peluffo G, Edwards DP, Boonyaratanakornkit V, Charreau EH, Bal de Kier Joffé E, Schillaci R, Elizalde PV* Progestin effects on breast cancer cell proliferation, proteases activation, and in vivo development of metastatic phenotype all depend on progesterone receptor capacity to activate cytoplasmic signaling pathways Mol Endocrinol (2007) doi: 10.1210/me.2006-0304

I’m not sure there’s even one single pair of adjacent bands in this article that comes from one single continuos blot. No news on what first author Romina Paula Carnevale is up to nowadays, her last publication is dated 2008 and she might have wisely chosen to leave academia.

From 2012 onwards the forgeries in Elizalde’s papers slightly descreased in number, but their seriousness remained unchanged and I speculate the group has just learnt how to build up less obviously fake blots. The next article is from 2013 and has many known names on it:

Díaz Flaqué MC, Galigniana NM, Béguelin W, Vicario R, Proietti CJ, Cordo Russo R, Rivas MA, Tkach M, Guzmán P, Roa JC, Maronna E, Pineda V, Muñoz S, Mercogliano M, Charreau EH, Yankilevich P, Schillaci R, Elizalde PV. Progesterone receptor assembly of a transcriptional complex along with activator protein 1, signal transducer and activator of transcription 3 and ErbB-2 governs breast cancer growth and predicts response to endocrine therapy Breast Cancer Res (2013) doi: 10.1186/bcr3587

Maria Celeste Díaz Flaqué (6 papers in PubPeer) is currently assistant investigator at the Instituto de Investigaciones Biomédicas (BIOMED UCA-CONICET).

The three-year period 2015-2017 was very productive for Elizalde, with six publications from her lab, three of which in Oncogene (journal IF 8.7). Five out of six of these articles are now flagged on PubPeer. Please enjoy what they managed to do with Figure 1A (!) in yet another Proietti et al. work, a figure which I believe deserves a full size presentation for the variety of camouflage techniques involved:

Proietti CJ, Izzo F, Díaz Flaqué MC, Cordo Russo R, Venturutti L, Mercogliano MF, De Martino M, Pineda V, Muñoz S, Guzmán P, Roa JC, Schillaci R, Elizalde PV* Heregulin Co-opts PR Transcriptional Action Via Stat3 Role As a Coregulator to Drive Cancer Growth Mol Endocrinol (2015) doi: 10.1210/me.2015-1170

From that busy period for the lab comes also Mercogliano et al. 2017, while here below I’ll present you the Oncogene triplet:

Co-first author (with Béguelin) Rosalia Ines Cordo Russo (7 papers in PubPeer) is currently adjunct investigator in the Elizalde lab, and the hierarchies seem consolidated: the magic wand will likely be handed down from Elizalde & Schillaci to Proietti & Cordo Russo, from one generation to the next. Abracadabra.

The next two papers, both from 2016, have the same first author:

Venturutti L, Cordo Russo RI, Rivas MA, Mercogliano MF, Izzo F, Oakley RH, Pereyra MG, De Martino M, Proietti CJ, Yankilevich P, Roa JC, Guzmán P, Cortese E, Allemand DH, Huang TH, Charreau EH, Cidlowski JA, Schillaci R, Elizalde PV* MiR-16 mediates trastuzumab and lapatinib response in ErbB-2-positive breast and gastric cancer via its novel targets CCNJ and FUBP1 Oncogene (2016) doi: 10.1038/onc.2016.151

Venturutti L, Romero LV, Urtreger AJ, Chervo MF, Cordo Russo RI, Mercogliano MF, Inurrigarro G, Pereyra MG, Proietti CJ, Izzo F, Díaz Flaqué MC, Sundblad V, Roa JC, Guzmán P, Bal de Kier Joffé ED, Charreau EH, Schillaci R*, Elizalde PV* Stat3 regulates ErbB-2 expression and co-opts ErbB-2 nuclear function to induce miR-21 expression, PDCD4 downregulation and breast cancer metastasis Oncogene (2016) doi: 10.1038/onc.2015.281

Leandro Venturutti is now group leader at the BC Cancer Research Centre in Vancouver. Astonishingly, Dr Venturutti has previously worked as research associate at Weill Cornell Medical College, exactly in the same lab where Wendy Béguelin and Matin Rivas are working today, that is to say: the Ari Melnick lab. Obviously Dr Melnick has boundless esteem for Elizalde’s work and for the way she raises her disciples, so he decided to raid IBYME of all its brightest young minds. I wonder what kind of data those people managed to produce in New York, but lots of it got published in Cell, Nature, Cancer Cell, etc, under the supervision of Ari Melnick. Actually Dr Melnick has 6 papers flagged on PubPeer as of today, however, to be fair, he is not lead author on any of them.

Weill Cornell is certainly not just any place. For Better Science readers may remember what kind of bogus articles its people are capable of. Illustrious examples are the Dean of Weill Cornell Augustine M.K. Choi, the director of the Cancer Center of Weill Cornell Medical College Lewis Cantley, the chair of Pathology and Laboratory Medicine Massimo Loda, and the amazing Andrew Dannenberg, who boasts 19 retractions and retired from Weill Cornell in 2021, and also the immunologists Andrea Cerutti and Paolo Casali, who worked at Weill Cornell from 1997 till 2003 and then moved elsewhere. Most of the evidence of fake dada from these guys was exposed on PubPeer by the image integrity sleuth Clare Francis.

On top of that, it’s equally funny that Weill Cornell Med College is where also Jeffrey Laurence works, the Editor-in-Chief of Translational Research since 2006, who has recently refused to investigate three papers by the mega-fraudster Javier González-Gallego (read here and here) breaking the rules of COPE guidelines. I start to believe it would be worth to comb through the research carried out by all those guys there at Weill Cornell, it could be fun.

Let’s leave the problems in New York aside for now, and go back to Buenos Aires, because troubles aren’t over with Elizalde. As said, forgeries continued up to today, so now come two papers from 2020 and 2022, both first-authored by a PhD student, Santiago Madera:

Madera S, Chervo MF, Chiauzzi VA, Pereyra MG, Venturutti L, Izzo F, Roldán Deamicis A, Guzman P, Dupont A, Roa JC, Cenciarini ME, Barchuk S, Figurelli S, Lopez Della Vecchia D, Levit C, Lebersztein G, Anfuso F, Castiglioni T, Cortese E, Ares S, Deza EG, Gercovich FG, Proietti CJ, Schillaci R, Cordo Russo RI, Elizalde PV* Nuclear PDCD4 Expression Defines a Subset of Luminal B-Like Breast Cancers with Good Prognosis Horm Cancer (2020) doi: 10.1007/s12672-020-00392-4

Madera S, Izzo F, Chervo MF, Dupont A, Chiauzzi VA, Bruni S, Petrillo E, Merin SS, De Martino M, Montero D, Levit C, Lebersztein G, Anfuso F, Roldán Deamicis A, Mercogliano MF, Proietti CJ, Schillaci R, Elizalde PV*, Cordo Russo RI* Halting ErbB-2 isoforms retrograde transport to the nucleus as a new theragnostic approach for triple-negative breast cancer Cell Death Dis (2022) doi: 10.1038/s41419-022-04855-0

The years go by, but there is always a new brood of young sorcerer’s apprentices to be initiated into the practices that have been in vogue for decades in the Elizalde lab.

Cancer research is in bad shape like the Alzheimer one, the latter being recently shaken from its foundations after the Lesné scandal. Only difference: cancer research foundations have been shaken since many years already. You may recall the cases of Stuart Aaaronson, Michael Andreev, Marina Konopleva, Alan Ashworth, Katja Lamia, Ronald Khan, Pier Paolo Pandolfi, Robert Weinberg, Anil Sood, Robert Coleman, Raghu Kalluri, Sonia Melo, Bharat Aggarwal, Stacy Blain, Joan Messagué, Michael Karin, Lufen Chang, Gökhan Hotamisligil, Umut Ozcan, Ewan Gallagher, Giuseppina Bonizzi, Roberto Gherzi, Gabriella Santoro, Carlo Croce and many, too many more.

Suddenly it comes to my mind what years ago a colleague running his own lab told me: he could not reproduce any results published in the previous 10 years by others. Here you go, mate. Hundreds, if not thousands of respected scientists working in top institutions simply fake results, and this happens in any research field. But lift your spirits up! No matter if the data behind medical protocols and oncological treatments are imaginary! Since science is long dead, we can always rely on the haruspices.

PS by LS: I wrote to Elizalde, Peters, Schillaci, Proietti and Melnick. Nobody replied.

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Update 1.09.2022

After I lodged a research misconduct notification in Elizalde’s case, the CONICET’s Vice President for Scientific Affairs Mario Pecheny informed me:

“in its meeting today, the Board of the CONICET decided to create a small scientific committee, integrated by three senior researchers, to conduct an evaluation of evidence and responsibilities, and to initiate a formal and quick investigation of the affair. “

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