PReD-Bench/PRed-Bench huggingface dataset:
Paclitaxel induces apoptosis and reduces proliferation by targeting epidermal growth factor receptor signaling pathway in oral cavity squamous cell carcinoma
Authors: N A Zhang
Ronglin Wang
Guang Li
Jing Hu
Fei Huang
Journal: Oncology Letters (2015)
Discipline: CLINICAL MEDICINE
Keywords: epidermal growth factor receptor; oral cavity squamous; paclitaxel; tea8113.

Abstract:  Oral cavity cancer is common worldwide. Furthermore, the epidermal growth factor receptor (EGFR) signaling pathway is considered to be constitutively activated in oral cancers. Paclitaxel is widely accepted as an antitumor drug as it effectively inhibits the cell cycle. This study predominantly explores the possible molecule mechanism of paclitaxel on oral cancer treatment. Cell viability was first detected using an MTT assay. Cell apoptosis was examined by Hoechst staining and flow cytometry using an annexin-V and propidium iodide kit. Specific EGFR signaling pathways were further explored through western blot analysis. Abnormal protein expression levels were determined via immunofluoresence. Additionally, the protein levels of matrix metalloproteinase (MMP)-2 and 9 were determined using ELISA. Paclitaxel significantly inhibited oral cancer cell viability in a time- and dose-dependent manner. Paclitaxel also enhanced oral cancer cell apoptosis via increased Bim and Bid protein expression. Furthermore, paclitaxel was observed to inhibit oral cancer cell proliferation through increased MMP-2 and MMP-9 protein levels. Paclitaxel inhibited the growth of the oral cancer cell line, tea8113 malignant proliferation and enhanced tea8113 cell apoptosis through inhibiting the EGFR signaling pathway. 

Retracted: No

PubPeer comments:
 Looks like lane 6 was obtained from a different blot ![file] ,
Huaier polysaccharide induces apoptosis in hepatocellular carcinoma cells through p38 MAPK
Authors: Haidong Bao
Peng Liu
Zhongyu Wang
Ke Jiang
Peng Gong
Xianbin Zhang
Long Xie
Journal: Oncology letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: Huaier polysaccharide; apoptosis; hepatocellular carcinoma; mitogen-activated protein kinase; p38 MAPK.
Affiliations: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China., Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, Liaoning 116044, P.R. China.

Abstract:  The underlying mechanism of the antitumor activity of Huaier polysaccharide (HP) remains to be explored. The present study aimed to investigate the inhibitory effect of HP on hepatocellular carcinoma (HCC) cells, and to explore the possible mechanisms of its anticancer effect. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while apoptotic nuclear changes were observed using Hoechst 33258 staining. The distribution of cell cycle and apoptosis were analyzed by flow cytometry, and western blotting was used to test the apoptotic pathways. Apoptosis and mitogen-activated protein kinase (MAPK) inhibitors were used to investigate the mechanism of apoptosis. HP triggered cell cycle arrest and apoptosis in HepG2 and Huh7 cells. Both the extrinsic and intrinsic apoptotic pathways were activated after HP treatment. Furthermore, HP enhanced the three major MAPK pathways (extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38 MAPK) and inhibited the AKT/mechanistic target of rapamycin signaling pathway in HCC cells. Notably, the inactivation of p38 MAPK impaired the HP-induced cell death. HP exerted its antitumor effect on HCC cells through the regulation of the expression of the apoptosis-related proteins B-cell lymphoma (Bcl)-2, Bcl-2-associated X protein and survivin. The present study provides evidence that HP induces apoptosis in HCC cells and demonstrated the role of p38 MAPK in HP-triggered cancer cell death. 

Retracted: No

PubPeer comments:
 In Figure 1B, one of the micrographs has been duplicated, modified (different magnification) and presented as something else. In Figure 4C, in the dot plots, discontinuities in the gating lines are seen. This is unusual, since the gating lines are supposed to be put on the dot plot, not opposite. ![file] ,
In vitro antimicrobial activity of natural toxins and animal venoms tested against Burkholderia pseudomallei
Authors: A Pachiappan
Maung M Thwin
Joseph T Weng
Vincent T K Chow
P Gopalakrishnakone
Yap E Hian
Ho Bow
R Perumal Samy
Journal: BMC Infectious Diseases (2006)
Discipline: IMMUNOLOGY
Keywords: Burkholderia pseudomallei; antimicrobial peptides; venoms; L-amino acid oxidase; phospholipase A2
Affiliations: Venom and Toxin Research Programme, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore-117597. 

Abstract:  Background: Burkholderia pseudomallei are the causative agent of melioidosis. Increasing resistance of the disease to antibiotics is a severe problem in treatment regime and has led to intensification of the search for new drugs. Antimicrobial peptides are the most ubiquitous in nature as part of the innate immune system and host defense mechanism. Methods: Here, we investigated a group of venoms (snakes, scorpions and honey bee venoms) for antimicrobial properties against two strains of Gram-negative bacteria Burkholderia pseudomallei by using disc-diffusion assay for in vitro susceptibility testing. The antibacterial activities of the venoms were compared with that of the isolated L-amino acid oxidase (LAAO) and phospholipase A2 (PLA2s) enzymes. MICs were determined using broth dilution method. Bacterial growth was assessed by measurement of optical density at the lowest dilutions (MIC 0.25 mg/ml). The cell viability was measured using tetrazolium salts (XTT) based cytotoxic assay. Results: The studied venoms showed high antimicrobial activity. The venoms of C. adamanteus, Daboia russelli russelli, A. halys, P. australis, B. candidus and P. guttata were equally as effective as Chloramphenicol and Ceftazidime (30 microg/disc). Among those tested, phospholipase A2 enzymes (crotoxin B and daboiatoxin) showed the most potent antibacterial activity against Gram-negative (TES) bacteria. Naturally occurring venom peptides and phospholipase A2 proved to possess highly potent antimicrobial activity against Burkholderia pseudomallei. The XTT-assay results showed that the cell survival decreased with increasing concentrations (0.05-10 mg/mL) of Crotalus adamanteus venom, with no effect on the cell viability evident at 0.5 mg/mL. Conclusion: This antibacterial profile of snake venoms reported herein will be useful in the search for potential antibacterial agents against drug resistant microorganisms like B. pseudomallei. 

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. ,
Ku affects the ATM-dependent S phase checkpoint following ionizing radiation
Authors: Hongyan Wang
Xiang-Yang Zhou
George Iliakis
Xiang Wang
Ya Wang
Gloria C Li
David J Chen
Journal: Oncogene (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: genotoxic stress; DNA replication; S phase checkpoint; ATM-dependent pathway; ionizing irradiation
Affiliations: Department of Radiation Oncology, Kimmel Cancer Center of Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, PA 19107, USA.

Abstract:  Following exposure to genotoxic stress, proliferating cells actively slow down DNA replication through an S phase checkpoint to provide time for repair. The ATM-dependent pathway plays an important role in the S phase checkpoint response following ionizing irradiation. We report that there is a stronger S phase checkpoint response in irradiated Ku80(-/-) cells as compared with their wild-type counterparts, which has no relationship to DNA-dependent protein kinase (DNA-PK) activity but correlates with a higher ATM activity and with more ATM bound to chromatin DNA in such cells. Wortmannin, a nonspecific inhibitor of ATM, not only reduces the higher activity of ATM kinase, but also abolishes the stronger S phase checkpoint response in Ku80(-/-) cells. Furthermore, a specific ATM antisense oligonucleotide abolishes the stronger S checkpoint response in Ku80(-/-) cells and renders these cells practically indistinguishable from Ku80(+/+) cells for this endpoint. These results in aggregate indicate that the stronger S checkpoint in irradiated Ku80(-/-) cells is due to the higher ATM kinase activity. 

Retracted: No

PubPeer comments:
 The p-values given in Table 2 make no sense. Numerous values are  0.000 or  0.00 . Could the author please check and give the real p-values? Thank you. ,
CD163+CD14+ macrophages, a potential immune biomarker for malignant pleural effusion
Authors: Shengdian Wang
Qun Gao
Jing Wang
Lan Huang
Fei Wang
Yi Zhang
Bin Zhang
Li Yang
Liping Wang
Journal: Cancer Immunology Immunotherapy (2015)
Discipline: IMMUNOLOGY
Keywords: Malignant pleural effusion; CD163+CD14+ tumor-associated macrophages; biomarker; diagnosis; sensitivity
Affiliations: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan Province, China.

Abstract:  Background: Malignant pleural effusion (MPE) is a common complication caused by malignant diseases. However, subjectivity, poor sensitivity, and substantial false-negative rates of cytology assay hamper accurate MPE diagnosis. The aim of this study was to assess whether CD163+CD14+ tumor-associated macrophages (TAMs) could be used as a biomarker for enabling sensitive and specific MPE diagnosis. Methods: Pleural effusion samples and peripheral blood samples were collected from 50 MPE patients and 50 non-malignant pleural effusion (NMPE) patients, respectively. Flow cytometry was performed to analyze cell phenotypes, and RT-qPCR was used to detect cytokine expression in these monocytes and macrophages. A blinded validation study (n = 40) was subsequently performed to confirm the significance of CD163+CD14+ TAMs in MPE diagnosis. Student's t test, rank sum test, and receiver operating characteristic curve analysis were used for statistical analysis. Results: Notably, CD163+CD14+ cell frequency in MPE was remarkably higher than that in NMPE (P &lt; 0.001). In a blinded validation study, a sensitivity of 78.9 % and a specificity of 100 % were obtained with CD163+CD14+ TAMs as a MPE biomarker. In total (n = 140), by using a cutoff level of 3.65 %, CD163+CD14+ cells had a sensitivity of 81.2 % and a specificity of 100 % for MPE diagnosis. Notably, MPE diagnosis by estimating CD163+CD14+ cells in pleural effusion could be obtained one week earlier than that obtained by cytological examination. Conclusions: CD163+CD14+ macrophages could be potentially used as an immune diagnostic marker for MPE and has better assay sensitivity than that of cytological analysis. 

Retracted: No

PubPeer comments:
 Identical plots with these from another publication (PMID: 25871392). ![file] However, the ratio number (92.9% vs 96.2%) and fluorescence intensities are different in two publications. ![file] Even in the same figure, the fluorescence intensities of CD14 are different. ![file] The shapes and colors of dots are different in the upper and lower plots. It unlikely happens. ![file] The gating lines are drawn manually. ![file] , 
 In the correction, the fluorescent intensities are different between the last and descendant plots as well. The empty arrows indicate the intensities at which are gated. The solid arrows indicate the numbers where the displayed dots fall. The axis numbers are different. And it seems a large part of dots are hidden or added to display in the descendant plots. Why not display the actual gates and events straightly? ![file] ,
Effects of Chicory on Serum Uric Acid, Renal Function, and GLUT9 Expression in Hyperuricaemic Rats with Renal Injury and In Vitro Verification with Cells
Authors: Yun-Fei Bai
Zhi-Jian Lin
Yong-Nan Jin
Bing Zhang
Journal: Evidence-based Complementary and Alternative Medicine (2018)
Discipline: CLINICAL MEDICINE
Keywords: Hyperuricaemia; Chronic kidney disease; Chicory extract; Uric acid levels; Renal function
Affiliations: Department of Clinical Chinese Pharmacy, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100029, China., Department of Integrated TCM and Western Medicine, Yanbian University Hospital, Yanji 133000, China.

Abstract:  Hyperuricaemia (HUA) is an independent risk factor for chronic kidney disease. Urate crystals are deposited in the kidney and can cause renal tubular interstitial fibrosis, leading to renal dysfunction. Chicory extract (hereafter referred to as chicory) clearly reduced serum uric acid levels in rats with HUA induced by 10% fructose. This is the first study to observe the effect of chicory on serum uric acid levels and renal function in rats with HUA and renal injury. In vivo studies using hyperuricaemic rats with renal injury induced by yeast and adenine demonstrated that chicory decreased serum uric acid level, and its effect of delaying the progression of kidney injury was better than that of benzbromarone. In vitro cell experiments showed that this effect is related to the inhibition of GLUT9 protein expression in renal tubules and that lowering blood uric acid concentrations is one of the factors that alleviates renal damage. The results of this study indicate that chicory can be used as an alternative for alleviating renal dysfunction in hyperuricaemia. 

Retracted: No

PubPeer comments:
 Figure 1A of Hallson et al., 2012 and Supplemental Fig. S1 of Hallson et al., 2008 used very similar images (which might implicate image duplication), although the Drosophila strains and genes analyzed differ. Could authors provide an explanation, please? ![file] ,
La-related protein 1 (LARP1) repression of TOP mRNA translation is mediated through its cap-binding domain and controlled by an adjacent regulatory region
Authors: Carson C Thoreen
Jean-Jacques Vasseur
Lucas Philippe
Françoise Debart
Journal: Nucleic Acids Research (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cell growth; gene expression; translation; mRNA; TOP motif
Affiliations: Department of Cellular and Molecular Physiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA., Department of Nucleic Acids, IBMM, Université de Montpellier, CNRS UMR 5247, ENSCM, Montpellier, France.

Abstract:  Cell growth is a complex process shaped by extensive and coordinated changes in gene expression. Among these is the tightly regulated translation of a family of growth-related mRNAs defined by a 5' terminal oligopyrimidine (TOP) motif. TOP mRNA translation is partly controlled via the eukaryotic initiation factor 4F (eIF4F), a translation factor that recognizes the mRNA 5' cap structure. Recent studies have also implicated La-related protein 1 (LARP1), which competes with eIF4F for binding to mRNA 5' ends. However, it has remained controversial whether LARP1 represses TOP mRNA translation directly and, if so, what features define its mRNA targets. Here, we show that the C-terminal half of LARP1 is necessary and sufficient to control TOP mRNA translation in cells. This fragment contains the DM15 cap-binding domain as well as an adjacent regulatory region that we identified. We further demonstrate that purified LARP1 represses TOP mRNA translation in vitro through the combined recognition of both the TOP sequence and cap structure, and that its intrinsic repressive activity and affinity for these features are subject to regulation. These results support a model whereby the translation of TOP mRNAs is controlled by a growth-regulated competition between eIF4F and LARP1 for their 5' ends. 

Retracted: No

PubPeer comments:
 Figure 3A u2013 more similar than expected ![file] , 
 This article has a Corrigendum  In Figure 3A, the authors inadvertently duplicated the input levels of two different FLAG-tagged LARP1 fragments. A new figure is provided below, and the published article has been updated. This error does not affect the results or conclusion of the article. https: academic.oup.com nar advance-article doi 10.1093 nar gkaa535 5859950 ,
Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors
Authors: Lu Zhao
Tsz Kan Fung
Nadine Martin
Jayant K Rane
Anskar Y Leung
Maria Teresa Esposito
Chi Wai Eric So
Alan Ashworth
Jesus Gil
Amanda Wilson
Journal: Nature Medicine (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Acute myeloid leukemia; oncogenic transcription factors; small-molecule inhibitors; AML1-ETO; PML-RARα
Affiliations: Leukemia and Stem Cell Biology Group, Department of Haematological Medicine, Division of Cancer Studies, King's College London, London, UK., Cell Proliferation Group, Medical Research Council Clinical Sciences Centre, Imperial College London, London, UK., Department of Medicine, The University of Hong Kong, Hong Kong, China., University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA.

Abstract:  Acute myeloid leukemia (AML) is mostly driven by oncogenic transcription factors, which have been classically viewed as intractable targets using small-molecule inhibitor approaches. Here we demonstrate that AML driven by repressive transcription factors, including AML1-ETO (encoded by the fusion oncogene RUNX1-RUNX1T1) and PML-RARα fusion oncoproteins (encoded by PML-RARA) are extremely sensitive to poly (ADP-ribose) polymerase (PARP) inhibition, in part owing to their suppressed expression of key homologous recombination (HR)-associated genes and their compromised DNA-damage response (DDR). In contrast, leukemia driven by mixed-lineage leukemia (MLL, encoded by KMT2A) fusions with dominant transactivation ability is proficient in DDR and insensitive to PARP inhibition. Intriguingly, genetic or pharmacological inhibition of an MLL downstream target, HOXA9, which activates expression of various HR-associated genes, impairs DDR and sensitizes MLL leukemia to PARP inhibitors (PARPis). Conversely, HOXA9 overexpression confers PARPi resistance to AML1-ETO and PML-RARα transformed cells. Together, these studies describe a potential utility of PARPi-induced synthetic lethality for leukemia treatment and reveal a novel molecular mechanism governing PARPi sensitivity in AML. 

Retracted: No

PubPeer comments:
 Supplementary Figure 1I: more similar than expected ![file] Supplementary Figure 6D: more similar than expected ![file] , 
 I have been recently made aware of these issues. I am not corresponding author of this manuscript and neither myself nor my lab were involved in this experiment. I have brought them to the attention of the corresponding author , 
 Thank you for pointing out the issue, please see attachments below for my detailed response.![file] ![file] ![file] ![file] ,
Diversity effect of capsaicin on different types of skeletal muscle
Authors: Jiawen Wang
Qianyun Xi
Gan Zhou
Kelin Yang
Leshan Wang
Yongliang Zhang
Lina Wang
Yongxiang Li
Jiajie Sun
Qingyan Jiang
Lv Luo
Yaqiong Xu
Xiaotong Zhu
Songbo Wang
Ping Gao
Gang Shu
Journal: Molecular and Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cannabinoid receptors; Capsaicin; Muscle fiber types; TRPV1.
Affiliations: Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, 510642, Guangdong, People's Republic of China., College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, 510642, People's Republic of China., Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, 510642, Guangdong, People's Republic of China. ., College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, 510642, People's Republic of China. .

Abstract:  Capsaicin is a major pungent content in green and red peppers which are widely used as spice, and capsaicin may activate different receptors. To determine whether capsaicin has different effects on different types of skeletal muscle, we applied different concentrations (0, 0.01, and 0.02%) of capsaicin in the normal diet and conducted a four-week experiment on Sprague-Dawley rats. The fiber type composition, glucose metabolism enzyme activity, and different signaling molecules' expressions of receptors were detected. Our results suggested that capsaicin reduced the body fat deposition, while promoting the slow muscle-related gene expression and increasing the enzyme activity in the gastrocnemius and soleus muscles. However, fatty acid metabolism was significantly increased only in the soleus muscle. The study of intracellular signaling suggested that the transient receptor potential vanilloid 1 (TRPV1) and cannabinoid receptors in the soleus muscle were more sensitive to capsaicin. In conclusion, the distribution of TRPV1 and cannabinoid receptors differs in different types of muscle, and the different roles of capsaicin in different types of muscle may be related to the different degrees of activation of receptors. 

Retracted: No

PubPeer comments:
 Figures 3D, 3F, 4A, 5A, 6A, and 6C ALL use the same b-actin loading control. Altogether, these 6 panels contain 34 (!) separate blots for proteins of interest, all supported by this single loading control. Even though all the samples originate from the same conditions, it is physically impossible that the authors cut up the membrane to probe with 34 different antibodies. Ergo, these are not proper loading controls. The exact same problem occurs again in Figures 3E, 3G, 4B, 5B, 6B, and 6D, with again a single b-actin loading control used to support 34 separate blot images. This is not good scientific practice. ,
Hypermethylation of the 5′ CpG island of the p14ARF flanking exon 1β in human colorectal cancer displaying a restricted pattern of p53 overexpression concomitant with increased MDM2 expression
Authors: Roger Detry
Christine Nyiraneza
Alex Kartheuser
Christine Sempoux
Karin Dahan
Journal: Clinical Epigenetics (2012)
Discipline: CLINICAL MEDICINE
Keywords: p14ARF; tumor suppressor; p53; MDM2; colorectal cancers
Affiliations: Center for Human Genetics, Université Catholique de Louvain, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels, B-1200, Belgium. .

Abstract:  Background: It has been suggested that inactivation of p14ARF, a tumor suppressor central to regulating p53 protein stability through interaction with the MDM2 oncoprotein, abrogates p53 activity in human tumors retaining the wild-type TP53 gene. Differences in expression of tumor suppressor genes are frequently associated with cancer. We previously reported on a pattern of restricted p53 immunohistochemical overexpression significantly associated with microsatellite instability (MSI), low TP53 mutation frequency, and MDM2 overexpression in colorectal cancers (CRCs). In this study, we investigated whether p14ARF alterations could be a mechanism for disabling the p53 pathway in this subgroup of CRCs. Results: Detailed maps of the alterations in the p14ARF gene were determined in a cohort of 98 CRCs to detect both nucleotide and copy-number changes. Methylation-specific PCR combined with bisulfite sequencing was used to evaluate the prevalence and distribution of p14ARF methylation. p14ARF alterations were then correlated with MSI status, TP53 mutations, and immunohistochemical expression of p53 and MDM2. The frequency of p14ARF mutations was extremely low (1/98; 1%), whereas coexistence of methylated and unmethylated alleles in both tumors and normal colon mucosa was common (91/98; 93%). Only seven of ninety-eight tumors (7%) had a distinct pattern of methylation compared with normal colon mucosa. Evaluation of the prevalence and distribution of p14ARF promoter methylation in a region containing 27 CpG sites in 35 patients showed a range of methylated CpG sites in tumors (0 to 25 (95% CI 1 to 13) versus 0 to 17 (95% CI 0 to 2)) in adjacent colon mucosa (P = 0.004). Hypermethylation of the p14ARF promoter was significantly correlated with the restricted p53 overexpression pattern (P = 0.03), and MDM2 overexpression (P = 0.02), independently of MSI phenotype. Although no significant correlation between p14ARF methylation and TP53 mutational status was seen (P = 0.23), methylation involving the proximal CpG sites within the 5' CpG flanking exon 1β was present more frequently in tumors with restricted p53 overexpression than in those with diffuse p53 overexpression (range of methylated clones 17 to 36% (95% CI 24 to 36%) versus range 0 to 3% (95% CI 0 to 3%), P = 0. 0003). Conclusion: p14ARF epigenetic silencing may represent an important deregulating mechanism of the p53-MDM2-p14ARF pathway in CRCs exhibiting a restricted p53 overexpression pattern. 

Retracted: No

PubPeer comments:
 Figure 1. Much more similar than expected. ![file] ,
ST6GalNAcII mediates the invasive properties of breast carcinoma through PI3K/Akt/NF-κB signaling pathway
Authors: Chen Liu
Dongliang Ren
Yanyan Li
Yongfu Zhao
Ning Wang
Li Jia
Yanxin Gong
Xu Zhang
Journal: IUBMB Life (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PI3K/AKt signaling; ST6GalNAcII; breast carcinoma; metastasis.
Affiliations: Department of General Surgery, Dalian Medical University, Liaoning Province, China., College of Laboratory Medicine; Dalian Medical University; Liaoning Province China, Department of General Surgery; Dalian Medical University; Liaoning Province China, Department of General Surgery; The Second Affiliated Hospital of Dalian Medical University; Liaoning Province China

Abstract:  Metastasis of tumor cells is the most deadly attribute of breast cancer patients. Aberrant sialylation is closely associated with malignant phenotype of tumor cells, including invasiveness and metastasis. The objective of this study is to clarify the possible role and mechanism of ST6GalNAcII in the metastasis process of breast carcinoma. Real-time PCR, Western blot, and immunohistochemical were used to analyze differential expression of ST6GalNAc II in breast carcinoma cell lines and tissue specimens. PI3K/AKt signaling pathway was also analyzed. The high expression level of ST6GalNAcII was corresponding to invasive phenotype of breast cancer cells both in vitro and in vivo. Further data indicated that manipulation of ST6GalNAcII gene expression led to alter the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway. Blocking the PI3K/Akt pathway resulted in reduced capacity in invasion of MDA-MB-231 cells. ST6GalNAcII elucidated the unusual properties of invasion in breast cancer cell via modulating the PI3K/AKt signaling pathway. 

Retracted: No

PubPeer comments:
 Below: Fig 3(B)  Reduced regulation of ST6GalNAcII was also shown by IHC staining in xenograft tumors derived from MDA-MB-231-ST6GalNAcII shRNA1 cells (400x) Above: Fig 3(B).  Reduced regulation of **Axl** was also shown by IHC staining in xenograft tumors derived from Axl shRNA cells (x400) , from  Axl Mediates Tumor Invasion and Chemosensitivity Through PI3K Akt Signaling Pathway and Is Transcriptionally Regulated by Slug in Breast Carcinoma [(Li et al 2014)] . Different shRNA targets seem to produce xenograft tumors differing only by a 180-deg rotation. ![] , 
 While reading two different papers from the last author, I identified striking and uncanny similarities between the data presented in Table 1 of [Miao et al. (2016) Oncol Reports] and Table 1 of [Ren et al (2014) IUBMB Life] . ![file] ![file] These data are purported to represent two different patient populations with different cancers, yet the numbers are alarmingly similar. Can the authors clarify whether these data were correctly reported? ,
MiR-186-5p upregulation inhibits proliferation, metastasis and epithelial-to-mesenchymal transition of colorectal cancer cell by targeting ZEB1
Authors: Huayu Song
Limin Xia
Chang Xu
Jinlei Li
Zhenhua Zhou
Jianhui Cai
Zhigui Zuo
Journal: Archives of Biochemistry and Biophysics (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Colorectal cancer; Epithelial mesenchymal transition; MiR-186-5p; ZEB1.
Affiliations: Department of Colorectal Surgery, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Lane, Wenzhou, Zhejiang, 325000, China., Department of Colorectal Surgery, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Lane, Wenzhou, Zhejiang, 325000, China. Electronic address: .

Abstract:  MicroRNA-186-5p (miR-186-5p) is upregulated and exhibits as a crucial oncogene in various human tumors. However, the functions and underlying mechanisms of this microRNA on colorectal cancer remain largely unknown. Here, we report that miR-186-5p share a lower expression in colorectal cancer cell lines (HT116, H29, SW620 and LoVo) than in normal colonic epithelial cell line NCM460. MiR-186-5p overexpression inhibits proliferation, metastasis and epithelial-to-mesenchymal transition (EMT) of colorectal cancer cell line LoVo. Zinc Finger E-Box Binding Homeobox 1 (ZEB1), an EMT related marker, is predicted as a target of miR-186-5p. Luciferase reporter assay, qRT-PCR and western blot analysis showed that miR-186-5p directly targeted the 3'-untranslated regions (3'UTR) of ZEB1 messenger RNA. Further functional experiments indicated that overexpression of miR-186-5p suppress the proliferation and metastasis ability of LoVo, which was consistent with the inhibitory effects by knockdown of ZEB1. Additionally, overexpression of ZEB1 could significantly reverse the miR-186-5p mimics initiated suppression impact of proliferation, metastasis and EMT on LoVo. In summary, miRNA-186-5p affects the proliferation, metastasis and EMT process of colorectal cancer cell by inhibition of ZEB1. Hence, it may serve as a promising therapeutic target for colorectal cancer. 

Retracted: No

PubPeer comments:
 Figure 4 appears to have some image duplications ![file] ![file] ,
Regulation of Angiogenic Factors by HDM2 in Renal Cell Carcinoma
Authors: Margaret Ashcroft
Veronica A Carroll
Journal: Cancer Research (2008)
Discipline: CLINICAL MEDICINE
Keywords: oncogene; HDM2; hypoxia inducible factor; HIF; VHL-defective renal carcinoma cells

Abstract:  The oncogene HDM2 has been implicated in the regulation of the transcription factor, hypoxia inducible factor (HIF). We show in von Hippel-Lindau (VHL)-defective renal carcinoma cells that express constitutively high levels of HIF-1 alpha and HIF-2 alpha that down-regulation of HDM2 by siRNA leads to decreased levels of both HIF-1 alpha and HIF-2 alpha protein levels. However, we show a differential regulation of HDM2 on the HIF angiogenic targets, vascular endothelial growth factor (VEGF), plasminogen activator inhibitor-1 (PAI-1), and endothelin-1 (ET-1): siRNA to HDM2 leads to increased expression of VEGF and PAI-1 proteins but decreased levels of ET-1. We show that HDM2-mediated regulation of these proteins is independent of VHL and p53 but dependent on a novel action of HDM2. Ablation of HDM2 leads to phosphorylation of extracellular-regulated kinase (ERK)1/2 in renal carcinoma cells. We show that regulation of these angiogenic factors is dependent on ERK1/2 phosphorylation, which can be reversed by addition of the MAP/ERK1/2 kinase inhibitors PD98059 and PD184352. This study identifies a novel role for the HDM2 oncoprotein in the regulation of angiogenic factors in renal cell carcinoma. 

Retracted: No

PubPeer comments:
 Figures 1B 3A, and 5A. Much more similar than you would expect. ![Image] , 
 Figures 1A and 1B seem to be redundant. https: imgur.com CGMNi9L ,
Characterization of a novel mechanism of genomic instability involving the SEI1/SET/NM23H1 pathway in esophageal cancers
Authors: Shu-Peng Chen
Yan Li
Yanru Qin
Li Fu
Wen Deng
Chunyu Zhang
Liang Hu
Xin-Yuan Guan
Chang-Jun Nie
Wei-Hua Jia
Hai-Bo Liu
Ting-Ting Zeng
Leilei Chen
Dan Xie
Journal: Cancer Research (2010)
Discipline: CLINICAL MEDICINE
Keywords: 19q amplification; SEI1; genomic instability; tumorigenic ability; micronuclei formation
Affiliations: State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.

Abstract:  Amplification of 19q is a frequent genetic alteration in many solid tumors, and SEI1 is a candidate oncogene within the amplified region. Our previous study found that the oncogenic function of SEI1 was associated with chromosome instability. In this study, we report a novel mechanism of genomic instability involving the SEI1-SET-NM23H1 pathway. Overexpression of SEI1 was observed in 57 of 100 of esophageal squamous cell carcinoma cases. Functional study showed that SEI1 had strong tumorigenic ability, and overexpression of SEI1 could induce the genomic instability by increasing micronuclei formation and reducing the number of chromosomes. Further study found that SEI1 was able to upregulate SET expression and subsequently promote the translocation of a small amount of NM23H1 from the cytoplasm to the nucleus. Nuclear NM23H1 can induce DNA damage through its DNA nick activity. Unlike CTL attack, only a small amount of NM23H1 translocated into the nucleus (&lt;10%) induced by the overexpression of SEI1. Further study found that the small amount of NM23H1 only induced minor DNA damage and subsequently increased genomic instability, rather than inducing irreparable DNA damage and initiating apoptosis by CTL attack. Sister chromatid exchange experiment found that the translocation of small amount of NM23H1 into the nucleus induced by the overexpressions of SEI1/SET could increase the frequency of sister chromatid exchange. In addition, overexpression of SEI1 was associated with poor prognosis of esophageal squamous cell carcinoma. Taken together, these findings define a novel mechanism of genomic instability and malignant progression in esophageal cancers, a deadly disease of increasing incidence in developed countries. 

Retracted: No

PubPeer comments:
 Fig. 1A and Fig. 3C. Two WB bands appear more similar than expected. ![file] ,
Bioinformatics and functional analyses of key genes in smoking‑associated lung adenocarcinoma
Authors: Dajie Zhou
Xiaoli Ma
Yujie Zhang
Xiaowei Chen
Jing Wang
Duanrui Liu
Yanfei Jia
Yilin Sun
Journal: Oncology Letters (2019)
Discipline: CLINICAL MEDICINE
Keywords: bioinformatics analysis; differentially expressed genes; lung adenocarcinoma; prognostic value; smoking.
Affiliations: Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China, College of Science, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China, Department of Medical Laboratory, Weifang Medical University, Weifang, Shandong 261053, P.R. China

Abstract:  Smoking is one of the most important factors associated with the development of lung cancer. However, the signaling pathways and driver genes in smoking-associated lung adenocarcinoma remain unknown. The present study analyzed 433 samples of smoking-associated lung adenocarcinoma and 75 samples of non-smoking lung adenocarcinoma from the Cancer Genome Atlas database. Gene Ontology (GO) analysis was performed using the Database for Annotation, Visualization and Integrated Discovery and the ggplot2 R/Bioconductor package. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using the R packages RSQLite and org.Hs.eg.db. Multivariate Cox regression analysis was performed to screen factors associated with patient survival. Kaplan-Meier and receiver operating characteristic curves were used to analyze the potential clinical significance of the identified biomarkers as molecular prognostic markers for the five-year overall survival time. A total of 373 differentially expressed genes (DEGs; |log2-fold change|≥2.0 and P&lt;0.01) were identified, of which 71 were downregulated and 302 were upregulated. These DEGs were associated with 28 significant GO functions and 11 significant KEGG pathways (false discovery rate &lt;0.05). Two hundred thirty-eight proteins were associated with the 373 differentially expressed genes, and a protein-protein interaction network was constructed. Multivariate regression analysis revealed that 7 mRNAs, cytochrome P450 family 17 subfamily A member 1, PKHD1 like 1, retinoid isomerohydrolase RPE65, neurotensin receptor 1, fetuin B, insulin-like growth factor binding protein 1 and glucose-6-phosphatase catalytic subunit, significantly distinguished between non-smoking and smoking-associated adenocarcinomas. Kaplan-Meier analysis demonstrated that patients in the 7 mRNAs-high-risk group had a significantly worse prognosis than those of the low-risk group. The data obtained in the current study suggested that these genes may serve as potential novel prognostic biomarkers of smoking-associated lung adenocarcinoma. 

Retracted: No

PubPeer comments:
 With such a ROCK curve, I would not trust anything in this paper. ![file] ,
Inverse regulation of cyclin B1 by c-Myc and p53 and induction of tetraploidy by cyclin B1 overexpression
Authors: K Katula
X Y Yin
N S Datta
L Grove
M W Long
E V Prochownik
Journal: Cancer Research (2001)
Discipline: CLINICAL MEDICINE
Keywords: mitotic spindle inhibitors; c-Myc oncoprotein; tetraploidy; DNA synthesis; p53 tumor suppressor
Affiliations: Section of Hematology/Oncology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.

Abstract:  We have shown previously that mitotic spindle inhibitors allow the c-Myconcoprotein to uncouple mitosis from DNA synthesis, resulting in the acquisition of tetraploidy. This can also occur in the absence of spindle inhibition if c-Myc deregulation is combined with inactivation of the p53 tumor suppressor. Under these conditions, cyclin B1 protein is induced but retains its normal cell cycle regulation. We now show that the cyclin B1 promoter is directly but oppositely regulated by c-Myc and p53. Enforced expression of cyclin B1 also induces tetraploidy, either after mitotic spindle inhibition or in the absence of such inhibition if cyclin B1 is coexpressed with c-Myc. Cyclin B1 represents a new class of c-Myc target genes that is also regulated by p53. It is also the first identified downstream effector of c-Myc able to produce the chromosomal instability that characterizes virtually all tumor cells. 

Retracted: No

PubPeer comments:
 Figures 1C and 1D. Much more similar and different than expected. https: imgur.com t9TcLPV , 
 Figures 1 and 5. Much more similar than expected. https: imgur.com 1bstFAM ,
MicroRNA-203 restrains epithelial–mesenchymal transition, invasion and migration of papillary thyroid cancer by downregulating AKT3
Authors: Anmin You
Xingyi Li
Bin You
Liwu Fu
Yongjiao Li
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AKT; MicroRNA-203; epithelial–mesenchymal transition; invasion; migration
Affiliations: Department of Nuclear Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, China.

Abstract:  MicroRNAs (miRNAs) have been reported to serve pivotal roles in the regulation of papillary thyroid cancer (PTC) development; thus, the aim of this study is to identify the impact of miR-203 and AKT3 on the epithelial-mesenchymal transition (EMT), migration and invasion of PTC. MiR-203 and AKT3 expression in PTC tissues and cells were tested. TPC-1 cells and K1 cells were screened for follow-up experiments. Apoptosis-related proteins (Bcl-2 and Bax), EMT-related proteins (Vimentin and E-cadherin), proliferation-associated proteins (Ki67 and CDK4), invasion- and migration-related protein (MMP-2 and MMP-9) were verified. The effects of upregulated miR-203 and downregulated AKT3 on the biological characteristics of PTC cells in each group were detected via the gain- and loss-of-function assays. The targeting relationship between miR-203 and AKT3 was verified.MiR-203 expression declined and AKT3 heightened in PTC tissues and cells. Upregulated miR-203 and downregulated AKT3 reduced the tumor volume and weight, suppressed cell migration, colony formation, proliferation, invasion, proliferation-associated proteins (Ki67 and CDK4), invasion- and migration-related protein (MMP-2 and MMP-9) and promoted cell apoptosis, raised E-cadherin and decreased Vimentin protein expression in TPC-1 cells. On the contrary, the K1 cells with the downregulated miR-203 or upregulated AKT3 exhibited an opposite result. This study suggests that upregulated miR-203 suppresses EMT, invasion, proliferation and migration as well as induces apoptosis of PTC cells via downregulated AKT3. 

Retracted: No

PubPeer comments:
 Fig 1  (a) HE staining of thyroid tissue in the control group and the PTC group. (b) Immunohistochemical staining of AKT3 expression . Boxes, and concerns, are mine. ![image] , 
 Fig 6a, e. ![file] These supposed flow-cytometry plots for cell-cycle percentages appear to be hand-drawn, with the wobbly overhanging  raw data , and the lack of any effort to match the sum of the red and hatched humps (G0 G1, S, G2 M templates) to that putative raw data. , 
 Fig 8a,d. ![file] Various organic shapes have been cut out from their backgrounds and projected onto a gray background, with unknown scale. They may well be xenograft tumors, but they have no scientific value and very little persuasive power when they are presented like this. ,
Dietary glutamine supplementation prevents mucosal injury and modulates intestinal epithelial restitution following ischemia-reperfusion injury in the rat
Authors: Arnold G Coran
Eitan Shiloni
Michael Lurie
Habib Helou
Kamal Khateeb
Jorge G Mogilner
Igor Sukhotnik
Journal: Digestive Diseases and Sciences (2007)
Discipline: CLINICAL MEDICINE
Keywords: glutamine supplementation; intestinal ischemia-reperfusion injury; rat; mucosal damage; enterocyte proliferation
Affiliations: Department of Pediatric Surgery B, Bnai Zion Medical Center, Haifa, Israel. 

Abstract:  The aim of the present study was to evaluate the preventive effect of a 2-day oral glutamine supplementation against intestinal ischemia-reperfusion (IR) injury in a rat. Male Sprague-Dawley rats were divided into four experimental groups: sham rats underwent laparotomy, sham-GLU rats underwent laparotomy and were treaded with enteral glutamine (GLU) given in drinking water (2%) 48 hr before and following operation, IR rats underwent occlusion of both the superior mesenteric artery and the portal vein for 30 min followed by 24 hr of reperfusion, and IR-GLU rats were treated with enteral glutamine 48 hr before and following IR. Intestinal mucosal damage (Park's injury score), mucosal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 hr following IR. Sham-GLU rats demonstrated a lower rate of cell apoptosis in jejunum and ileum compared to sham animals. IR-GLU animals demonstrated a greater jejunal and ileal bowel and mucosal weight, mucosal DNA, villous height and crypt depth, and enterocyte proliferation index in ileum and a lower injury score grade in jejunum compared to IR-nontreated rats. In conclusion, pretreatment with oral glutamine prevents mucosal injury and improves intestinal recovery following IR injury in the rat. 

Retracted: No

PubPeer comments:
 This paper is part of a set of at least 3 papers that appear to share microscopy images. All papers list Igor Sukhotnik as an author. Boxes of the same color highlight areas in microscopy panels that look similar. Could the authors please clarify if these are all representing the same experiments, over a period of 12 years? * Sukhotnik I et al., Pediatr Surg Int (2007) 23:473u2013478, DOI: 10.1007 s00383-006-1863-9 * Sukhotnik I et al., Dig Dis Sci (2007) 52:1497u20131504, DOI: 10.1007 s10620-006-9629-8 * Benu2010Shahar Y et al., Pediatric Surgery International (2019), DOI: 10.1007 s00383-018-4406-2 ![file] ,
Loss of PTEN facilitates HIF-1-mediated gene expression
Authors: E Chen
D Stokoe
A J Giaccia
A R Gottschalk
F Kaper
C Schindler
W Zundel
D Haas-Kogan
A Koong
R S Johnson
A B Jefferson
H E Ryan
Journal: Genes & development (2000)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PTEN; glioblastoma; apoptosis; DNA synthesis; angiogenic gene expression
Affiliations: Mayer Cancer Biology Research Laboratory, Department of Radiation Oncology, Stanford University, Stanford, California 94305-5468 USA.

Abstract:  In glioblastoma-derived cell lines, PTEN does not significantly alter apoptotic sensitivity or cause complete inhibition of DNA synthesis. However, in these cell lines PTEN regulates hypoxia- and IGF-1-induced angiogenic gene expression by regulating Akt activation of HIF-1 activity. Restoration of wild-type PTEN to glioblastoma cell lines lacking functional PTEN ablates hypoxia and IGF-1 induction of HIF-1-regulated genes. In addition, Akt activation leads to HIF-1alpha stabilization, whereas PTEN attenuates hypoxia-mediated HIF-1alpha stabilization. We propose that loss of PTEN during malignant progression contributes to tumor expansion through the deregulation of Akt activity and HIF-1-regulated gene expression. 

Retracted: No

PubPeer comments:
 Figure 1A. Splicing in some panels, but not in others. ![file] , 
 Figure 3B. Splicing in some panels, but not in others. ![file] , 
 Figure 4C. Splicing in 2 panels, but not in the 3rd panel. ![file] , 
 #3 We are sorry that we no longer have the original raw data. In general, splices in some panels may occur due to random reasons. As you can see, we had to check multiple proteins with different MW. These samples had to be analyzed on different SDS-PAGE gels according to their MW. For proteins with similar MW, we generally did not do stripe, followed by re-probe with other antibodies, because the background was too high. For the ones that had splices, they were probably loaded either in the wrong order or we had other samples in between (i.e. samples treated for extra time window), which we decided to cut out . The adjustment of the final order could result in splices. Other reasons, i.e. due to gel transfer issues, which generated bubbles on certain bands, we had to run particular samples again (in this case, the u201ccut outu201d samples were not included, therefore no splices). We apologize that we could not recall the exact reason because the experiments were performed long time ago, but we certainly will pay extra attention to this issue to avoid any potential confusion. Thank you. ,