PReD-Bench/PRed-Bench huggingface dataset:
Species- and cell type-specific requirements for cellular transformation
Authors: Sue J Hong
Robert A Weinberg
Annapoorni Rangarajan
Annie Gifford
Journal: Cancer Cell (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: genetic changes; neoplastic transformation; signaling pathways; p53; Raf
Affiliations: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Abstract:  Recent evidence suggests that human cells require more genetic changes for neoplastic transformation than do their murine counterparts. However, a precise enumeration of these differences has never been undertaken. We have determined that perturbation of two signaling pathways-involving p53 and Raf-suffices for the tumorigenic conversion of normal murine fibroblasts, while perturbation of six pathways-involving p53, pRb, PP2A, telomerase, Raf, and Ral-GEFs-is needed for human fibroblasts. Cell type-specific differences also exist in the requirements for tumorigenic transformation: immortalized human fibroblasts require the activation of Raf and Ral-GEFs, human embryonic kidney cells require the activation of PI3K and Ral-GEFs, and human mammary epithelial cells require the activation of Raf, PI3K, and Ral-GEFs. 

Retracted: No

PubPeer comments:
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 ![file] , 
 ![file] , 
 In **Fig. 2B**, two panels overlap. these images are supposed to show fibroblasts expressing *different* mutants of the large tumor antigen of SV40 (LTK1 *vs.* LTu0394434-444): ![file] , 
 #12 Figure 2A. hFS fibroblast panels. Much more similar than expected. ![file] ,
Probiotic Lactobacillus reuteri promotes TNF-induced apoptosis in human myeloid leukemia-derived cells by modulation of NF-kappaB and MAPK signalling
Authors: Bharat B Aggarwal
Gautam Sethi
Chandra Iyer
Astrid Kosters
James Versalovic
Ajaikumar B Kunnumakkara
Journal: Cellular Microbiology (2008)
Discipline: MICROBIOLOGY
Keywords: Lactobacillus reuteri; apoptosis; NF-kappaB; cell proliferation; MAPK
Affiliations: Departments of Pathology, Baylor College of Medicine, Houston, TX, USA.

Abstract:  The molecular mechanisms of pro-apoptotic effects of human-derived Lactobacillus reuteri ATCC PTA 6475 were investigated in this study. L. reuteri secretes factors that potentiate apoptosis in myeloid leukemia-derived cells induced by tumour necrosis factor (TNF), as indicated by intracellular esterase activity, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling assays and poly (ADP-ribose) polymerase cleavage. L. reuteri downregulated nuclear factor-kappaB (NF-kappaB)-dependent gene products that mediate cell proliferation (Cox-2, cyclin D1) and cell survival (Bcl-2, Bcl-xL). L. reuteri suppressed TNF-induced NF-kappaB activation, including NF-kappaB-dependent reporter gene expression in a dose-and time-dependent manner. L. reuteri stabilized degradation of IkappaBalpha and inhibited nuclear translocation of p65 (RelA). Although phosphorylation of IkappaBalpha was not affected, subsequent polyubiquitination necessary for regulated IkappaBalpha degradation was abrogated by L. reuteri. In addition, L. reuteri promoted apoptosis by enhancing mitogen-activated protein kinase (MAPK) activities including c-Jun N-terminal kinase and p38 MAPK. In contrast, L. reuteri suppressed extracellular signal-regulated kinases 1/2 in TNF-activated myeloid cells. L. reuteri may regulate cell proliferation by promoting apoptosis of activated immune cells via inhibition of IkappaBalpha ubiquitination and enhancing pro-apoptotic MAPK signalling. An improved understanding of L. reuteri-mediated effects on apoptotic signalling pathways may facilitate development of future probiotics-based regimens for prevention of colorectal cancer and inflammatory bowel disease. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] ,
A novel hematopoietic granulin induces proliferation of goldfish (Carassius auratus L.) macrophages
Authors: Daniel R Barreda
Patrick C Hanington
Miodrag Belosevic
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Granulins; Goldfish; Macrophages; Proliferation; Cysteine repeats

Abstract:  Granulins are a group of highly conserved growth factors that have been described from a variety of organisms spanning the metazoa. In this study, goldfish granulin was one of the most commonly identified transcripts in the differential cross-screening of macrophage cDNA libraries and was preferentially expressed in proliferating macrophages. Unlike mammalian granulins, which possess 7.5 repeats of a characteristic signature of 12 cysteine residues, the goldfish granulin encoded a putative peptide possessing only 1.5 cysteine repeats. Northern blot and real-time PCR analyses indicated that goldfish granulin was expressed only in the hematopoietic tissues of the goldfish, specifically the kidney and spleen, and in activated peripheral blood mononuclear cells. We expressed granulin using a prokaryotic expression system and produced an affinity-purified rabbit anti-goldfish granulin IgG. Recombinant goldfish granulin induced a dose-dependent proliferative response of goldfish macrophages that was inversely related to the myeloid differentiation stage of the cells studied. The highest proliferative response was observed in macrophage progenitor cells and monocytes. This proliferative response of macrophages was abrogated by the addition of anti-granulin IgG. These results indicate that goldfish granulin is a growth factor that positively modulates cell proliferation at distinct junctures of macrophage differentiation. 

Retracted: No

PubPeer comments:
 There are splicing sites in the immunoblots of Figure 6C, no describing in the figure lengend. ![file] ,
The molecular mechanism of serum microRNA124b induced coronary heart disease by inducing myocardial cell senescence
Authors: Q-J Qin
Y-Q Weng
Z-M Ge
Y-N Wang
M-L Guo
Y-B Wang
L-L Guo
J Yao
X-Z Zhang
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: molecular mechanism; serum microRNA124b; coronary heart disease; myocardial cell senescence; withdrawn
Affiliations: Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China.

Abstract:  The article "The molecular mechanism of serum microRNA124b induced coronary heart disease by inducing myocardial cell senescence" by Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China, published in Eur Rev Med Pharmacol Sci 2018; 22 (7): 2070-2076 has been withdrawn. 

Retracted: No

PubPeer comments:
 This article has been retracted ,
MiR‐143‐3p suppresses cell proliferation, migration, and invasion by targeting Melanoma‐Associated Antigen A9 in laryngeal squamous cell carcinoma
Authors: Mingming Tang
Bin Jiang
Liang Han
Hongyan Qian
Xueguan Lu
Xinjiang Xu
Yingze Wei
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: invasion; laryngeal squamous cell carcinoma (LSCC); melanoma-associated antigens-A9 (MAGE-A9); miR-143-3p; migration
Affiliations: Department of Head and Neck Surgery, Nantong Tumor Hospital, Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu, China., Department of Clinical Pathology, Nantong Tumor Hospital, Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu, China., Cancer Research Center, Nantong Tumor Hospi tal, Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu, China., Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Abstract:  Previously we found that melanoma-associated antigen-A9 (MAGE-A9) was a significantly upregulated biomarker in laryngeal squamous cell carcinoma (LSCC). A high expression of MAGE-A9 indicates an unfavorable survival outcome, and the MAGE-A9 expression level is an independent prognostic factor of LSCC. To explore the mechanism of MAGE-A9 upregulation, several predicted regulatory microRNAs were screened and validated in LSCC cells. In the current study, we found that miR-143-3p (MAGE-A9 related miRNAs) expression levels correlated negatively with the MAGE-A9 protein expression in LSCC tissues. Dual-luciferase reporter assays and Western blot analysis revealed MAGE-A9 to be a direct target of miR-143-3p. Furthermore, a series of in vitro gain- and loss-of-function assays revealed that miR-143-3p inhibited LSCC cell proliferation, migration, and invasion. Also, miR-143-3p suppressed LSCC tumorigenesis in vivo. These effects were clinically relevant, as a lower expression of miR-143-3p occurred in severer clinical stages and represented poor overall survival in patients with LSCC. Taken together, these results suggest that downregulation of miR-143-3p contributes to tumor progression through upregulation of MAGE-A9. The expression level of these two key molecules maintained LSCC progression, thus, highlighting the potential of miR-143-3p as a therapeutic target for human LSCC. 

Retracted: No

PubPeer comments:
 Could the authors review Figure 2a to see if the first two images might represent to images of the same sample at different magnifications? There seem to be some areas of similarity. *** ![file] *** Closeup of areas of possible overlap ![file] ,
Inhibition of MicroRNA-381 Promotes Tumor Cell Growth and Chemoresistance in Clear-Cell Renal Cell Carcinoma
Authors: Yipeng Yu
Gang Wang
Yunhui Chan
Cheng Zhang
Daming Zhang
Zichun Wang
Wengang Jian
Changlin Wang
Xiaoxiong Wang
Journal: Medical Science Monitor (2019)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNA-381; renal cell carcinoma; ccRCC; cell proliferation; growth
Affiliations: Department of Urology, Third Ward, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland)., Department of Urology, Third Ward, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland)., Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang, China (mainland)., Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland).

Abstract:  BACKGROUND MicroRNA-381 (miR-381) is proven to be involved in many human tumors. Bioinformatics prediction suggests that miR-381 is decreased in renal cell carcinoma. However, its biological functions in clear-cell renal cell carcinoma (ccRCC) remain largely unknown. The present research aimed to evaluate miR-381 expression in renal cancer tissues and its effects on cell proliferation, growth, migration, and chemoresistance. MATERIAL AND METHODS Sixty pairs of ccRCC and the adjacent non-tumor specimens were collected during routine therapeutic surgery. Quantitative real-time PCR (qRT-PCR) assay was employed to examine miR-381 expression in the ccRCC tissues and the associated adjacent tissues (the normal tissues adjacent to tumor tissues). Cell transfection assay and Thiazolyl Blue Tetrazolium Bromide (MTT) assay were utilized to observe effects of miR-381 on the cell proliferation, growth, invasion, and chemoresistance in the Caki-1 cell line and 786-O cell line. Flow cytometry was used to assess cell apoptosis. Caki-1 cell and 786-O cell Xenograft BALB/c mouse models were established. RESULTS miR-381 expression was downregulated in ccRCC tissues in vivo and in cell lines in vitro. Downregulation of miR-381 promoted growth of cells and restrained the ccRCC cell apoptosis. Increased miR-381 combined with Ci and Pa suppressed the proliferation and enhanced the anti-tumor effects of Ci and Pa at tolerated concentrations in vitro. miR-381 inhibition promoted chemoresistance in vitro. CONCLUSIONS miR-381 levels were significantly downregulated in renal cancer tissues and miR-381 inhibition promoted tumor cell growth, migration, and chemoresistance. 

Retracted: No

PubPeer comments:
 Figure 2 C from Yunhui Chan et al (2019). The effect on cell apoptosis after 48-h transfection with miR-381 mimics (Caki-1) or inhibitor (786-O). ![file] Figure 3 B from Yunhui Chan et al (2019). The effect on cell apoptosis after transfected with miR-381 inhibitors (786-O) after treatment with Pa or Ci. ![file] **Two sets of duplicated results.** ,
LyGDI, a novel SHIP-interacting protein, is a negative regulator of FcγR-mediated phagocytosis
Authors: Steven E Justiniano
Jonathan P Butchar
Jianhua Yu
Richard W Burry
Timothy Eubank
Anne-Sophie Wavreille
Susheela Tridandapani
Payal Mehta
Rachel L Marsh
David Jarjoura
Michael A Caligiuri
Journal: PLoS ONE (2011)
Discipline: Multidisciplinary
Keywords: SHIP; SHIP-2; inositol phosphatases; FcγR-mediated phagocytosis; two-dimensional fluorescence difference gel electrophoresis (DIGE) analysis
Affiliations: The Ohio State Biochemistry Program, The Ohio State University, Columbus, Ohio, United States of America.

Abstract:  SHIP and SHIP-2 are inositol phosphatases that regulate FcγR-mediated phagocytosis through catalytic as well as non-catalytic mechanisms. In this study we have used two-dimensional fluorescence difference gel electrophoresis (DIGE) analysis to identify downstream signaling proteins that uniquely associate with SHIP or SHIP-2 upon FcγR clustering in human monocytes. We identified LyGDI as a binding partner of SHIP, associating inducibly with the SHIP/Grb2/Shc complex. Immunodepletion and competition experiments with recombinant SHIP domains revealed that Grb2 and the proline-rich domain of SHIP were necessary for SHIP-LyGDI association. Functional studies in primary human monocytes showed that LyGDI sequesters Rac in the cytosol, preventing it from localizing to the membrane. Consistent with this, suppression of LyGDI expression resulted in significantly enhanced FcγR-mediated phagocytosis. 

Retracted: No

PubPeer comments:
 Figure 2. * Blue boxes: the anti-pY immunoblots in Figure 2B and 2C look similar * Red boxes: the anti-SHIP immunoblots in Figure 2B and 2C look similar Could the authors please check? Maybe I am misinterpreting what was done but if I understand correctly B) and C) differ in incubation with fragments from a different antibody (FccRI antibody 32.2 in B) and FccRIIa antibody IV.3 in C). ![file] ,
Quercetin induces caspase-dependent extrinsic apoptosis through inhibition of signal transducer and activator of transcription 3 signaling in HER2-overexpressing BT-474 breast cancer cells
Authors: Seong-Gyu Ko
Han-Seok Choi
Youn Kyung Choi
Hansol Hur
Ilhwan Kim
Yong Cheol Shin
Minsoo Kim
Jin Mo Ku
Chang Hyeok Na
Jong-Kyu Woo
Hye-Sook Seo
Bo-Hyoung Jang
Journal: Oncology reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: Flavonoids; quercetin; breast cancer; proliferation; apoptosis

Abstract:  Flavonoids are assumed to exert beneficial effects in different types of cancers at high concentrations. Yet, their molecular mechanisms of action remain unknown. The present study aimed to examine the effect of quercetin on proliferation and apoptosis in HER2-expressing breast cancer cells. The anti-proliferative effects of quercetin were examined by proliferation, MTT and clonogenic survival assays. The effect of quercetin on expression of apoptotic molecules was determined by western blotting. Luciferase reporter assay was performed to measure signal transducer and activator of transcription 3 (STAT3) transcriptional activity. ELISA assay was performed to measure intracellular MMP-9 levels. Immunocytochemistry was performed to evaluate the nuclear STAT3 level. The results revealed that quercetin inhibited the proliferation of BT-474 cells in a dose- and time-dependent manner. Quercetin also inhibited clonogenic survival (anchorage-dependent and -independent) of BT-474 cells in a dose-dependent manner. These growth inhibitions were accompanied with an increase in sub-G0/G1 apoptotic populations. Quercetin induced caspase-dependent extrinsic apoptosis upregulating the levels of cleaved caspase-8 and cleaved caspase-3, and inducing the cleavage of poly(ADP‑ribose) polymerase (PARP). In contrast, quercetin did not induce apoptosis via intrinsic mitochondrial apoptosis pathway since this compound did not decrease the mitochondrial membrane potential and did not affect the levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX). Quercetin reduced the expression of phospho-JAK1 and phospho-STAT3 and decreased STAT3-dependent luciferase reporter gene activity in the BT-474 cells. Quercetin inhibited MMP-9 secretion and decreased the nuclear translocation of STAT3. Our study indicates that quercetin induces apoptosis at concentrations &gt;20 µM through inhibition of STAT3 signaling and could serve as a useful compound to prevent or treat HER2-overexpressing breast cancer. 

Retracted: No

PubPeer comments:
 ![file] Check identical tubulin in Figure 5 and Figure 6. ,
The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival
Authors: H J Zeh
K M Livesey
M T Lotze
D Tang
A Bierhaus
R Kang
A Farkas
N E Schapiro
P Loughran
Journal: Cell Death and Differentiation (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: RAGE; inflammation; tumor cell death; HMGB1; apoptosis
Affiliations: Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.

Abstract:  Activation of the induced receptor for advanced glycation end products (RAGE) leads to initiation of NF-kappaB and MAP kinase signaling pathways, resulting in propagation and perpetuation of inflammation. RAGE-knockout animals are less susceptible to acute inflammation and carcinogen-induced tumor development. We have reported that most forms of tumor cell death result in release of the RAGE ligand, high-mobility group protein 1 (HMGB1). We now report a novel role for RAGE in the tumor cell response to stress. Targeted knockdown of RAGE in the tumor cell, leads to increased apoptosis, diminished autophagy and decreased tumor cell survival . In contrast, overexpression of RAGE is associated with enhanced autophagy, diminished apoptosis and greater tumor cell viability. RAGE limits apoptosis through a p53-dependent mitochondrial pathway. Moreover, RAGE-sustained autophagy is associated with decreased phosphorylation of mammalian target of rapamycin (mTOR) and increased Beclin-1/VPS34 autophagosome formation. These findings show that the inflammatory receptor, RAGE, has a heretofore unrecognized role in the tumor cell response to stress. Furthermore, these studies establish a direct link between inflammatory mediators in the tumor microenvironment and resistance to programmed cell death. Our data suggest that targeted inhibition of RAGE or its ligands may serve as novel targets to enhance current cancer therapies. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Indole-derived water-soluble N, O bi-dentate ligand-based mononuclear transition metal complexes: and biological screening, molecular docking and macromolecule interaction studies
Authors: Alagarraj Arunadevi
Natarajan Raman
Journal: Journal of biomolecular structure & dynamics (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: DNA interaction; Indole-derived complexes; Swiss ADME; antimicrobial activity; molecular docking
Affiliations: Research Department of Chemistry, VHNSN College, Virudhunagar, India.

Abstract:  A novel tryptophan-derived Schiff base ligand (potassium (E)-2-((4-chloro-3-nitrobenzylidene)amino)-3-(1H-indol-3-yl)propanoate) and a series of its transition metal complexes of the types [ML2] and [ML(1,10-phen)2]Cl where M = Cu(II), Co(II), Ni(II) and Zn(II) were prepared. They were analyzed by various spectral and physicochemical studies. The XRD data were also used to determine the average lattice parameters and crystalline size of the compounds. All the synthesized compounds were tested against a series of five bacterial and fungal strains. The obtained results showed that the biological activity of free ligand was increased on complexation. PASS online software predicts the various biological activities of ligand such as enzyme inhibitor, antiviral, analgesic and antituberculosis. The in silico theoretical prediction of synthesized compounds is also deliberated by Swiss ADME predictor which gives the properties of molecular hydrophobicity (log P), topological polar surface area (TPSA) and oral bioavailability score. The binding energy of the docked molecule with macromolecules 1BNA and 3EQM is also determined by using Hex 8.0 software. The ligand has the least binding energy score which signifies that the potential of binding is greater in the receptor. Moreover, the interactions of complexes with DNA have been explored by electronic absorption titration, fluorescence emission titration, viscosity measurements and gel electrophoresis. HighlightsSynthesis and characterization of novel indole-derived compounds.X-ray diffraction studies demonstrate average crystalline size of the compounds.Metal complexes act as good metallointercalators.Metal complexes show higher antimicrobial activity compared to ligand.Prediction of biological activities of the ligand by PASS online software.Drug-like nature and bioavailability of synthesized compounds predicted by Swiss ADME predictorDocking of the synthesized compounds with 1BNA and 3EQM using HEX 8.0 software.Communicated by Ramaswamy H. Sarma. 

Retracted: No

PubPeer comments:
 Could the authors comment on what appear to be some repeated features? ![file] ,
Specific targeting of Wnt/β-catenin signaling in human melanoma cells by a dietary triterpene lupeol
Authors: Rohinton S Tarapore
Mohammad Saleem
Hasan Mukhtar
Imtiaz A Siddiqui
Vaqar M Adhami
Vladimir S Spiegelman
Journal: Carcinogenesis (2010)
Discipline: CLINICAL MEDICINE
Keywords: Wnt signaling pathway; melanoma; lupeol; β-catenin; proliferation
Affiliations: Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, WI 53706, USA.

Abstract:  Wingless (Wnt) signaling pathway regulates a variety of cellular processes including proliferation, differentiation, survival, apoptosis and cell motility. Aberrant activation of Wnt/β-catenin pathway has been observed in approximately one-third of melanomas and this subset has very poor prognosis suggesting that targeting Wnt signaling could be a promising strategy against this subtype. Mel 928 and Mel 1241 melanoma cells representative of cells with constitutive activation of Wnt/β-catenin signaling pathway and Mel 1011 representative of cells that lack this pathway were treated with a dietary triterpene lupeol and its effects on growth, proliferation, β-catenin transcriptional activity and Wnt target genes were determined both in vitro and in vivo. Lupeol treatment to Mel 928 and Mel 1241 but not Mel 1011 cells resulted in a dose-dependent (i) decrease in cell viability, (ii) induction of apoptosis, (iii) decrease in colonogenic potential, (iv) decrease in β-catenin transcriptional activity and (v) decrease in the expression of Wnt target genes. Most importantly, lupeol restricted the translocation of β-catenin from the cytoplasm to the nucleus. Lupeol also decreased the growth of Mel 928 but not Mel 1011-derived tumors implanted in the athymic nude mice. The decrease in Mel 928-derived tumor growth was associated with a decrease in the expression of Wnt target genes c-myc, cyclin D1, proliferation markers proliferating cell nuclear antigen and Ki-67 and invasion marker osteopontin. We suggest that lupeol alone or as an adjuvant to current therapies could be developed as an agent for the management of human melanomas harboring constitutive Wnt/β-catenin signaling. 

Retracted: No

PubPeer comments:
 Figure 2. Much more similar than expected. https: imgur.com 6QT2NdP , 
 #1 In addition to this concern, with which I agree, there appears to be another band which has been used twice, after vertical flip. It is difficult to understand how this would occur as an error during figure assembly. *** ![file] ,
Hepatitis B virus X protein confers resistance of hepatoma cells to anoikis by up-regulating and activating p21-activated kinase 1
Authors: Lin Chen
Jianxin Gu
Yumei Wen
Linlin Sun
Shanshan Wang
Jiejie Xu
Lei Zhou
Xiaojing Yun
Haiou Liu
Journal: Gastroenterology (2012)
Discipline: CLINICAL MEDICINE
Keywords: chronic hepatitis B virus; metastatic hepatocellular carcinoma; anoikis resistance; p21-activated kinase 1; HBV replication
Affiliations: Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.

Abstract:  Background &amp; aims: Patients with chronic hepatitis B virus (HBV) infection are at risk for metastatic hepatocellular carcinoma (HCC). Metastatic cancer cells develop resistance to anoikis. The serine/threonine p21-activated kinase (PAK) 1 regulates cytoskeletal dynamics and protects cells from anoikis; it also promotes virus replication. We investigated the effects of PAK1 on anoikis resistance in human hepatoma cells and in mice. Methods: We transfected human hepatoma cells with pHBV1.3 (to mimic HBV replication) or plasmids encoding different HBV proteins; we performed colony formation and anoikis assays. We knocked down levels of PAK1 and Bcl2, or inhibited their activity, in hepatoma cells and quantified anoikis and growth of tumor xenografts in nude mice; we also measured anoikis of tumor cells isolated from ascites of the mice. We performed immunohistochemical analysis of PAK1 levels in HCC samples from patients. Results: Human hepatoma cells transfected with pHBV1.3 expressing hepatitis B virus X protein (HBx) underwent anchorage-independent proliferation, were resistant to anoikis, and had higher levels of Bcl2 than nontransfected cells. Expression of HBx increased mitochondrial levels of Bcl2 and PAK1, which interacted physically. Anoikis resistance of Huh7 and SK-Hep1 cells required PAK1 activity and Bcl2. Expression of HBx promoted growth of Huh7 xenograft tumors in mice; PAK1 knockdown reduced growth of these tumors in mice and anoikis of cells isolated from these tumors. In human HCC samples, increased levels of PAK1 correlated with poor prognosis, HBV infection, and portal vein tumor thrombosis. Conclusions: The HBV protein HBx up-regulates PAK1, allows hepatoma cells to become resistant to anoikis, and promotes growth of aggressive xenograft tumors in mice. HBx induction of PAK1 might promote progression of HCC in patients with chronic HBV infection. 

Retracted: No

PubPeer comments:
 Figure 1: * Blue boxes: The pUC19 Hep3B panel looks remarkably similar to the SK-Hep1 Pol panel. ![file] , 
 Figure 1E. * Green boxes: two flow cytometry panels look remarkably similar. ![file] , 
 Figure 2C. * Cyan and pink boxes: two flow cytometry panels look remarkably similar. ![file] , 
 Figure 2E. * Purple boxes: Two panels appear to show an overlap ![file] , 
 Figure 4D. * Green boxes: Two flow cytometry panels look remarkably similar ![file] , 
 A sharp-eyed reader found some more similarities in Figure 2C. Here is an updated version. ![file] ,
Inhibition of TGF-β enhances the in vivo antitumor efficacy of EGF receptor-targeted therapy
Authors: Vui Pham
Christine H Chung
Xiaofei Chang
Rajani Ravi
Rishi Bedi
Ivan Borrello
Kimberly Noonan
Michael Considine
Elana J Fertig
Joseph A Califano
David Sidransky
Atul Bedi
Journal: Molecular Cancer Therapeutics (2012)
Discipline: CLINICAL MEDICINE
Keywords: EGF receptor; monoclonal antibodies; cetuximab; antitumor effect; in vivo
Affiliations: Head and Neck Cancer Research Division, Department of Otolaryngology-Head and Neck Surgery, 1550 Orleans Street, Johns Hopkins University School of Medicine, Cancer Research Building II, Baltimore, MD 21231, USA.

Abstract:  EGF receptor (EGFR)-targeted monoclonal antibodies (mAb), such as cetuximab, execute their antitumor effect in vivo via blockade of receptor-ligand interactions and engagement of Fcγ receptors on immune effector cells that trigger antibody-dependent cell-mediated cytotoxicity (ADCC). We show that tumors counteract the in vivo antitumor activity of anti-EGFR mAbs by increasing tumor cell-autonomous expression of TGF-β. We show that TGF-β suppresses the expression of key molecular effectors of immune cell-mediated cytotoxicity, including Apo2L/TRAIL, CD95L/FasL, granzyme B, and IFN-γ. In addition to exerting an extrinsic inhibition of the cytotoxic function of immune effectors, TGF-β-mediated activation of AKT provides an intrinsic EGFR-independent survival signal that protects tumor cells from immune cell-mediated apoptosis. Treatment of mice-bearing xenografts of human head and neck squamous cell carcinoma with cetuximab resulted in emergence of resistant tumor cells that expressed relatively higher levels of TGF-β compared with untreated tumor-bearing mice. Although treatment with cetuximab alone forced the natural selection of TGF-β-overexpressing tumor cells in nonregressing tumors, combinatorial treatment with cetuximab and a TGF-β-blocking antibody prevented the emergence of such resistant tumor cells and induced complete tumor regression. Therefore, elevated levels of TGF-β in the tumor microenvironment enable tumor cells to evade ADCC and resist the antitumor activity of cetuximab in vivo. Our results show that TGF-β is a key molecular determinant of the de novo and acquired resistance of cancers to EGFR-targeted mAbs, and provide a rationale for combinatorial targeting of TGF-β to improve anti-EGFR-specific antibody therapy of EGFR-expressing cancers. 

Retracted: No

PubPeer comments:
 The two bands in Fig. 3E are identical but indicate different proteins. Could the authors please check? ![file] ,
Ectopic brain tissue in a neonate
Authors: Jeffrey P Blount
David R Kelly
Keith Georgeson
W Jerry Oakes
John C Wellons 3rd
R Shane Tubbs
Journal: Pediatric neurosurgery (2003)
Discipline: CLINICAL MEDICINE
Keywords: 2-week-old male; cystic mass; left cervical; face region; central nervous tissue
Affiliations: Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Ala., USA. 

Abstract:  We report a 2-week-old male with a large cystic mass in the left cervical and face region. No connection to the brain or spinal cord was discernable either at operation or on imaging. Histological study of this mass revealed central nervous tissue including neuroglia, ependymal cells, non-neuroblastic neurons, pigmented retinal epithelium, and choroid plexus. This case represents the rare ectopic 'brain'. We review this case as well as the literature concerning these unusual masses. 

Retracted: No

PubPeer comments:
 This case report is really based on bad histology ![file] This structure could be choroid plexus but I am not convinced since the authors do not use any markers. I don t see glial tissue. Surrounding tissue is made of elongated cells resembling connective tissue much more than glial tissue. ![file] The cells pointed by the arrow seem too prismatic for ependymal cells. It s impossible to be certain that the cell pointed by curved arrow is glial. An immunomarking experiment would be much more appropriate. ![file] Histology is really bad in this case and it s impossible to be certain that this is a cell containing neuromelanin. In conclusion, I am far from being convinced by this case report. ,
Ribosome association and stability of the nascent polypeptide-associated complex is dependent upon its own ubiquitination
Authors: Fabrice P A David
Martine A Collart
Olesya O Panasenko
Journal: Genetics (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ubiquitination; nascent polypeptide-associated complex (NAC); EGD; lysines residues; alpha-subunit
Affiliations: Swiss Institute for Bioinformatics, University of Geneva, 1211 Geneva 4, Switzerland.

Abstract:  In this work we addressed the role of ubiquitination in the function of the nascent polypeptide-associated complex (NAC), named EGD in the yeast Saccharomyces cerevisiae. To this end, we first identified the lysines residues required for ubiquitination of EGD/NAC. While simultaneous mutation of many lysines in the alpha-subunit of NAC (Egd2p) was required to abolish its ubiquitination, for the beta-subunit of NAC (Egd1p), mutation of K29 and K30 was sufficient. We determined that the ubiquitination of the two EGD subunits was coordinated, occurring during growth first on Egd1p and then on Egd2p. Egd2p was ubiquitinated earlier during growth if Egd1p could not be ubiquitinated. The use of mutants revealed the importance of EGD ubiqutination for its ribosome association and stability. Finally, our study demonstrated an interaction of EGD/NAC with the proteasome and revealed the importance of the Not4p E3 ligase, responsible for EGD/NAC ubiquitination, in this association. 

Retracted: No

PubPeer comments:
 Figure 2B: Several lanes or parts of lanes appear to look similar to each other. Arrows of the same color point out sets of lanes that look similar. Image made darker to bring out more details. ![file] ,
Proof of Principle for a T Lymphocyte Intrinsic Function of Coronin 1A
Authors: Natascha Hermann-Kleiter
Victoria Klepsch
Gottfried Baier
Kerstin Siegmund
Journal: Journal of Biological Chemistry (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: animal model; autoimmunity; cell signaling; immunodeficiency; lymphocyte.
Affiliations: From the Department for Pharmacology and Genetics, Medical University Innsbruck, Peter Mayr Strasse 1a, AT-6020 Innsbruck, Austria ., From the Department for Pharmacology and Genetics, Medical University Innsbruck, Peter Mayr Strasse 1a, AT-6020 Innsbruck, Austria.

Abstract:  Coronins are evolutionarily conserved proteins that were originally identified as modulators of actin-dependent processes. Studies analyzing complete Coronin 1a knock-out mice have shown that this molecule is an important regulator of naive T cell homeostasis and it has been linked to immune deficiencies as well as autoimmune disorders. Nevertheless, because Coronin 1A is strongly expressed in all leukocyte subsets, it is not conclusive whether or not this phenotype is attributed to a T cell-intrinsic function of Coronin 1A. To address this research question, we have generated a T cell-specific Coronin 1a knock-out mouse (Coro1afl/fl × Cd4[Cre]). Deletion of Coronin 1A specifically in T cells led to a strong reduction in T cell number and a shift toward the effector/memory phenotype in peripheral lymphoid organs when compared with Cd4[Cre] mice expressing wild-type Coronin 1A. In contrast to peripheral lymphoid tissue, thymocyte number and subsets were not affected by the deletion of Coronin 1a Furthermore, T cell-specific Coronin 1a knock-out mice were largely resistant to the induction of autoimmunity when tested in the myelin oligoglycoprotein-induced EAE mouse model of multiple sclerosis. Thus, the phenotype of T cell-specific Coronin 1a deletion resembles the phenotype observed with conventional (whole body) Coronin 1a knock-out mice. In summary, our findings provide formal proof of the predominant T cell-intrinsic role of Coronin 1A. 

Retracted: No

PubPeer comments:
 The flow cytometry dot plots in red boxes appear to look similar in Fig 2B. ![file] ,
MicroRNA-374b accelerates the development of lung cancer through downregulating PTEN expression via activating PI3K/Akt pathway
Authors: Y Han
D Zeng
X-Q Cao
F-C Xu
J Li
Z Zhou
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: microRNA-374b; lung cancer; PTEN; PI3K/Akt pathway; qRT-PCR
Affiliations: Department of Thoracic Surgery, Qianshan hospital, Anshan, China. .

Abstract:  Objective: To elucidate whether microRNA-374b could participate in the development of lung cancer (LC) through downregulating PTEN (gene of phosphate and tensin homolog deleted on chromosome ten) expression via activating PI3K/Akt pathway. Patients and methods: Expression levels of microRNA-374b and PTEN in LC tissues and adjacent normal tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Moreover, the expression level of microRNA-374b in LC cell lines was detected as well. The microRNA-374b inhibitor was constructed and transfected to downregulate microRNA-374b expression in A549 and H358 cells. The regulatory effects of microRNA-374b on migratory and proliferative capacities of LC cells were explored by wound healing and cell counting kit-8 (CCK-8) assay, respectively. After co-transfection of microRNA-374b inhibitor and si-PTEN in LC cells, expression levels of PTEN/PI3K/Akt were determined by qRT-PCR and Western blot. Results: QRT-PCR results showed that microRNA-374b expression was higher, while PTEN expression was lower in LC tissues than adjacent tissues. Identically, microRNA-374b was also highly expressed in LC cell lines. PTEN expression was negatively correlated with microRNA-374b expression in LC. The downregulation of microRNA-374b in A549 and H358 cells inhibited their migratory and proliferative potentials. Subsequently, we verified that microRNA-374b could bind to PTEN through dual-luciferase reporter gene assay. MicroRNA-374b could inhibit PTEN expression and activate the PI3K/Akt pathway. Furthermore, PTEN knockdown enhanced migratory and proliferative abilities of LC cells, which were attenuated by co-transfection of microRNA-374b inhibitor. Conclusions: MicroRNA-374b promotes the development of LC by downregulating PTEN expression through activating PI3K/Akt pathway. 

Retracted: No

PubPeer comments:
 Fig 4A.  Wound healing results showed that PTEN knockdown enhanced migratory ability, which was reversed by co-transfection of si-PTEN and miR-374b inhibitor . Some overlaps are marked. ![file] , 
 Fig 2  A, PTEN expression was remarkably downregulated in lung cancer tissues compared with adjacent tissues. B, PTEN expression was negatively correlated to miR-374b expression (R=-0.88, p 0.01). The authors cannot be serious. ![file] ,
Effect of electromagnetic radiation on redox status, acetylcholine esterase activity and cellular damage contributing to the diminution of the brain working memory in rats
Authors: Samta Sharma
Sangeeta Shukla
Journal: Journal of Chemical Neuroanatomy (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Electromagnetic radiations; Oxidative damage; Spatial memory; genotoxicity.
Affiliations: Reproductive Biology and Toxicology Laboratory, UNESCO Satellite center of Trace Element Research & School of Studies in Zoology, Jiwaji University, Gwalior, M.P., India. Electronic address: ., Reproductive Biology and Toxicology Laboratory, UNESCO Satellite center of Trace Element Research & School of Studies in Zoology, Jiwaji University, Gwalior, M.P., India.

Abstract:  Behavioral impairments are the most pragmatic outcome of long-term mobile uses but the underlying causes are still poorly understood. Therefore, the Aim of the present study to determine the possible mechanism of mobile induced behavioral alterations by observing redox status, cholinesterase activity, cellular, genotoxic damage and cognitive alterations in rat hippocampus. This study was carried out on 24 male Wistar rats, randomly divided into four groups (n = 6 in each group): group I consisted of sham-exposed (control) rats, group II-IV consisted of rats exposed to microwave radiation (900 MHz) at different time duration 1 h, 2 h, and 4 h respectively for 90 days. After 90 days of exposure, rats were assessing learning ability by using T-Maze. A significantly increased level of malondialdehyde (MDA) with concomitantly depleted levels of superoxide dismutase (SOD), catalase (CAT) and redox enzymes (GSH, GPX, GR, GST, G-6PDH) indicated an exposure of mobile emitted EMR induced oxidative stress by the depleted redox status of brain cells. The depletion in the acetylcholinesterase (AChE) level reveals altered neurotransmission in brain cells. Resultant cellular degeneration was also observed in the radiation-exposed hippocampus. Conclusively, the present study revealed that microwave radiation induces oxidative stress, depleted redox status, and causes DNA damage with the subsequent reduction in working memory in a time-dependent manner. This study provides insight over the associative reciprocity between redox status, cellular degeneration and reduced cholinergic activity, which presumably leads to the behavioral alterations following mobile emitted electromagnetic radiation. 

Retracted: No

PubPeer comments:
 ![file] Figure 8. Image D is identical to image A but darker, despite the two images representing different treatments (A - no exposure, D - 1hr exposure). , 
 #1 ![file] ,
Parthenolide Augments the Chemosensitivity of Non-small-Cell Lung Cancer to Cisplatin via the PI3K/AKT Signaling Pathway
Authors: Yan Zhang
Xiao-Zhong Liao
Bin Ke
Shi-Qing Nie
Zi-Rui He
Lin Shi
Li-Mei Wu
Wen-Hui Chen
Jian-Fu Zhao
Journal: Frontiers in Cell and Developmental Biology (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: DDP; NSCLC; PI3K/Akt pathway; PTL; combination
Affiliations: Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou, China., Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China., Department of Traditional Chinese Medicine, Cancer Center of Sun Yat-sen University, Guangzhou, China., Department of Traditional Chinese Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Abstract:  The mortality rate of non-small-cell lung cancer (NSCLC) remains high worldwide. Although cisplatin-based chemotherapy may greatly enhance patient prognosis, chemotherapy resistance remains an obstacle to curing patients with NSCLC. Therefore, overcoming drug resistance is the main route to successful treatment, and combinatorial strategies may have considerable clinical value in this effort. In this study, we observed that both parthenolide (PTL) and cisplatin (DDP) inhibited the growth of NSCLC cells in a dose- and time-dependent manner. The combination of PTL and DDP presented a synergistic inhibitory effect on NSCLC at a ratio of 50:1. The combination of PTL and DDP synergistically inhibited cell migration and invasion, inhibited cell cycle progression, and induced apoptosis of A549 and PC9 cells. Bioinformatics and network pharmacology analysis indicated that PTL may primarily affect the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. After treatment with PTL and DDP either alone or in combination, Western blot analysis revealed that the proteins levels of Bax and cleaved Caspase-3 were upregulated, while p-PI3K, p-Akt, Caspase-3, and Bcl-2 proteins were downregulated. Among these alterations, the combination of PTL and DDP was found to exhibit the most significant effects. PTL might therefore be considered as a new option for combination therapy of NSCLC. 

Retracted: Yes

PubPeer comments:
 Fig 11c, image duplicated. In fact, A-C indicate overlaps, indicating same image. Could authors post source files for A-C, uncropped and unedited images? ![file] ![file] ,
Deletion of leptin signaling in vagal afferent neurons results in hyperphagia and obesity
Authors: Charlotte C Ronveaux
Guillaume de Lartigue
Helen E Raybould
Journal: Molecular Metabolism (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: High fat diet; Hyperphagy; Leptin; Meal pattern; Obesity
Affiliations: Department of Anatomy, Physiology and Cell Biology, UC Davis School of Veterinary Medicine, 1 Shields Ave, Davis, CA 95616, USA.

Abstract:  The vagal afferent pathway senses hormones released from the gut in response to nutritional cues and relays these signals to the brain. We tested the hypothesis that leptin resistance in vagal afferent neurons (VAN) is responsible for the onset of hyperphagia by developing a novel conditional knockout mouse to delete leptin receptor selectively in sensory neurons (Nav1.8/LepR (fl/fl) mice). Chow fed Nav1.8/LepR (fl/fl) mice weighed significantly more and had increased adiposity compared with wildtype mice. Cumulative food intake, meal size, and meal duration in the dark phase were increased in Nav1.8/LepR (fl/fl) mice; energy expenditure was unaltered. Reduced satiation in Nav1.8/LepR (fl/fl) mice is in part due to reduced sensitivity of VAN to CCK and the subsequent loss of VAN plasticity. Crucially Nav1.8/LepR (l/fl) mice did not gain further weight in response to a high fat diet. We conclude that disruption of leptin signaling in VAN is sufficient and necessary to promote hyperphagia and obesity. 

Retracted: No

PubPeer comments:
 Data in figure 7 are intriguing. How could WT HFD mice gain 15 g of body weight (fig 7B), but only have 5g of total body fat (fig 7D)? ,
Early-Life Adversity Induces Epigenetically Regulated Changes in Hippocampal Dopaminergic Molecular Pathways
Authors: K Rether
Katharina Braun
Jana C Köhler
A Lesse
S Guara Ciurana
J Bock
N Gröger
J Fegert
Journal: Molecular neurobiology (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: DARPP-32; Depression; Dopamine receptor 1; Histone modification; Resilience.
Affiliations: Department of Zoology/Developmental Neurobiology, Institute of Biology, Otto von Guericke University Magdeburg, Leipziger Straße 44, Bldg. 91, 39120, Magdeburg, Germany., PG "Epigenetics and Structural Plasticity", Institute of Biology, Otto von Guericke University Magdeburg, Magdeburg, Germany., Klinik für Kinder- und Jugendpsychiatrie/Psychotherapie, Universitätsklinikum Ulm, Ulm, Germany., Center for Behavioral Brain Sciences, Magdeburg, Germany., Department of Zoology/Developmental Neurobiology, Institute of Biology, Otto von Guericke University Magdeburg, Leipziger Straße 44, Bldg. 91, 39120, Magdeburg, Germany. ., Center for Behavioral Brain Sciences, Magdeburg, Germany. .

Abstract:  Early-life adversity (ELA) represents a major risk factor for the development of behavioral dysfunctions and mental disorders later in life. On the other hand, dependent on type, time point, and duration, ELA exposure can also induce adaptations, which result in better stress coping and resilience later in life. Guided by the hypothesis that chronic exposure to ELA results in dysfunctional brain and behavior, whereas short exposure to ELA may result in resilience, the behavioral and neurobiological consequences of long-term separation stress (LTSS) and short-term separation stress (STSS) were compared in a mouse model for ELA. In line with our hypothesis, we found that LTSS induced depressive-like behavior, whereas STSS reduced depressive-like behavioral symptoms. We then tested the hypothesis that the opposite behavioral outcomes of the two stress paradigms may be mediated by functional, epigenetically regulated changes of dopaminergic modulation in the hippocampal formation. We found that STSS exposure elevated dopamine receptor D1 (DRD1) gene expression and decreased gene expression of its downstream modulator DARPP-32 (32-kDa dopamine- and cAMP-regulated phosphoprotein), which was paralleled by decreased H3 acetylation at its gene promoter region. In contrast, LTSS elevated DARPP-32 gene expression, which was not paralleled by changes in histone acetylation and DRD1 gene expression. These findings indicate that short- and long-term neonatal exposure to ELA induces changes in dopaminergic molecular pathways, some of which are epigenetically regulated and which either alleviate or aggravate depressive-like symptoms later in life. 

Retracted: No

PubPeer comments:
 The paper report quantitative changes in histone acetylation in tissue samples using Western blots in Fig. 2a c apparently in a range of 10-20%. This rather mild effect and can only be detected with high quality blots. Unfortunately, no original WB data are shown in the paper and the quality of the measurements cannot be judged by the reader. ![file] ,