PReD-Bench/PRed-Bench huggingface dataset:
Knockdown of ISOC1 inhibits the proliferation and migration and induces the apoptosis of colon cancer cells through the AKT/GSK-3β pathway
Authors: Hanyu Bai
Bo Gao
Lianmei Zhao
Jian Cao
Feifei Wang
Guiying Wang
Meng Li
Jing Li
Xuhua Hu
Journal: Carcinogenesis (2020)
Discipline: CLINICAL MEDICINE
Keywords: ISOC1; colorectal cancer; biological function; mechanism; tumor size
Affiliations: The Second General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China., Scientific Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China., Department of General Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, China.

Abstract:  Isochorismatase domain-containing 1 (ISOC1) is a coding gene that contains an isochorismatase domain. The precise functions of ISOC1 in humans have not been clarified; however, studies have speculated that it may be involved in unknown metabolic pathways. Currently, it is reported that ISOC1 is associated with breast cancer. In this research, the aim is to investigate the critical role of ISOC1 in colorectal cancer (CRC) and to explore its biological function and mechanism in colon cancer cells. In 106 paired clinical samples, we found that the levels of ISOC1 expression were widely increased in cancer tissues compared with matched adjacent non-tumor tissues and that increased expression of ISOC1 was significantly associated with tumor size, tumor invasion, local lymph node metastasis and Tumor, Node and Metastasis (TNM) stage. Moreover, higher expression levels of ISOC1 were correlated with shorter disease-free survival in patients 2 years after surgery. In vitro, ISOC1 knockdown inhibited the proliferation and migration and induced the apoptosis of colon cancer cells, and in vivo, the xenograft tumors were also inhibited by ISOC1 silencing. We also used MTS, Transwell and cell apoptosis assays to confirm that ISOC1 plays a critical role in regulating the biological functions of colon cancer cells through the AKT/GSK-3β pathway. Additionally, the results of confocal microscopy and western blot analysis indicated that ISOC1 knockdown could promote p-STAT1 translocation to the nucleus. 

Retracted: No

PubPeer comments:
 The cells (5.0 u00d7 105 well) were used in migration assay. In paper  DUOX2 promotes the progression of colorectal cancer cells by regulating the AKT pathway and interacting with RPL3 , 1.5 u00d7 105 cells were used ? The same cell HCT116 was used. Is there any difference? ,
Evaluating the immunomodulatory responses of Ld ODC‐derived MHC Class‐II restricted peptides against VL
Authors: Manas Ranjan Dikhit
RajKishor Pandey
Avinash Kumar
Pradeep Das
Roshan Kamal Topno
Krishna Pandey
Budheswar Dehury
Sanjiva Bimal
Journal: Parasite Immunology (2020)
Discipline: IMMUNOLOGY
Keywords: Leishmania donovani; CD4+ T-cell epitopes; ODC; reverse vaccinology; visceral leishmaniasis.
Affiliations: Department of Biotechnology National Institute of Pharmaceutical Education &amp; Research Hajipur India, Division of Immunology Rajendra Memorial Research Institute of Medical Sciences Patna India, Department of Biomedical Informatics Rajendra Memorial Research Institute of Medical Sciences Patna India, Department of Bioinformatics ICMR‐RMRC Government of India Bhubaneswar India, Departmentof Clinical Medicine Rajendra Memorial Research Institute of Medical Sciences Patna India, Departmentof Epidemiology Rajendra Memorial Research Institute of Medical Sciences Patna India, Department of Molecular Biology Rajendra Memorial Research Institute of Medical Sciences Patna India

Abstract:  In a bid to develop a novel immunoprophylactic measure against visceral leishmaniasis (VL), MHC class-II-restricted epitopes of LdODC were identified by reverse vaccinology approach. Five consensus HLA-DRB1*0101-restricted epitopes were screened. The analysis revealed that the set of epitopes was presented by at least 54 diverse MHC class-II alleles. Based on in silico screening, followed by molecular dynamics simulation, population coverage analysis, and HLA cross-presentation ability, five best epitopes were evaluated. PBMCs isolated from treated VL subjects, when stimulated with synthetic peptide alone or as a cocktail of peptides, triggered a secretory IFN-γ, but not the IL-10 level. Support in this notion came from intracellular cytokine level with a considerable up-regulated IFN-γ produced by CD4+ T cells. Also, the enhanced IFN-γ seemed to be augmented with the activation of macrophages with prominent IL-12 production. Therefore, it can be concluded that the screened MHC class-II-restricted epitope hotspots derived from Leishmania ODC can trigger CD4+ T cells, which can skew macrophage functions towards protection. However, a detailed analysis can explore its potentiality as a vaccine candidate. 

Retracted: No

PubPeer comments:
 Authors used two different kind of T cell epitopes u2013 MHC class I and MHC class II u2013 in T cell stimulation assays on different patient groups. However, the FACS representative plot seems to be duplicated across publications. ![file] EDIT: Figure has wrong journal and DOI on the first panel, correct ones: Journal of Biomolecular Structure and Dynamics, doi: 10.1080 07391102.2021.1876773 In reference to: https: pubpeer.com publications 14E95236E38001A402CA9B9164671A ,
The role of DOT1L in the proliferation and prognosis of gastric cancer
Authors: Xinxin Zhang
Qingkang Wang
Xiaoying Tao
Zaozhi Song
Jun Qian
Nan Wu
Zhuoli Wei
Xue Liu
Journal: Bioscience Reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: DOT1L; EPZ5676; Gastric cancer; Prognosis.
Affiliations: Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China., Central Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China., Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China., Department of Orthopedic, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

Abstract:  Background: Disruptor of telomeric silencing-1-like (DOT1L), a methyltransferase of H3K79, was observed to be amplified and overexpressed in certain malignancies. This work was aimed at investigating the differences in DOT1L expression and its regulatory mechanism in gastric cancer (GC) and healthy samples. Methods: Immunohistochemistry was used to detect DOT1L levels in 101 cases of GC and marching adjacent normal tissues. DOT1L was inhibited by small interfering RNA (siRNA) and EPZ5676; a targeting drug. The ability of cells to proliferate were checked by cell counting kit-8 (CCK-8) and clone formation assays, with flow cytometry for observing the cell cycle. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot revealed the gene and protein profiles. Finally, the outcome of EPZ5676 administration was checked on a murine model. Results: The expression of DOT1L is significantly increased in gastric malignant tumors that is related to the degree of differentiation, lymph node metastasis and TNM staging. DOT1L serves as an independent marker for the prognosis of overall survival (OS) with high levels implying worse prognosis. In addition, DOT1L regulates cyclin-dependent kinase (CDK) 4 (CDK4) and CDK6 through H3K79me2, which leads to a change in the cell cycle at G1, thereby affecting the proliferation of tumors in vitro and in vivo. Conclusions: This is a first clinical demonstration of the applicability of DOT1L overexpression in gastric tumors. The work is suggestive of altered proliferation of cells by DOT1L via regulating cyclins and H3K79 methylation. This indicates the role of DOT1L in the prognosis and possible medical intervention of GC. 

Retracted: No

PubPeer comments:
 Several bands in figure 3 a show a similar mark in a similar location. This suggests that these bands may be repeated. Could the authors please provide the original uncropped scan to help address this concern? *** ![file] *** Full figure ![file] , 
 April 6, 2021 The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. , 
 Another issue with Figure 3A that I didn t flag before: a band appears to have been reused. *** ![file] ,
Potential mechanisms of microRNA-129-5p in inhibiting cell processes including viability, proliferation, migration and invasiveness of glioblastoma cells U87 through targeting FNDC3B
Authors: Wusi Qiu
Yanxia Hu
Haisong Xu
Journal: Biomedicine & Pharmacotherapy (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: FNDC3B; Glioblastoma; MiR-129-5p.
Affiliations: Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, Zhejiang, PR China. Electronic address: ., Community Health Service Center of Zha Long Kou Lane, Hangzhou 310004, Zhejiang, PR China., Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, Zhejiang, PR China.

Abstract:  The purpose of our study is to clarify the effects of microRNA-129-5p (miR-129-5p) in cellular processes correlated with cancer development and progression of Glioblastoma (GBM) cell by regulating FNDC3B. MiR-129-5p and FNDC3B expression in GBM tissues and tumor adjacent tissues were tested by quantitative real-time PCR. We validated the target relationship between miR-129-5p and FNDC3B by dual luciferase reporter gene system. MTT, colony formation, flow cytometry, Transwell and wound healing assays were used to analyze cell viability, proliferation, apoptosis, invasiveness and migration. The level of FNDC3B protein expression was detected by Western Blot. MiR-129-5p was downregulated in GBM tissues and cell lines, while FNDC3B was upregulated in GBM tissues. The result of luciferase reporter gene assay demonstrated that miR-129-5p could target FNDC3B by binding to the 3' UTR. The overexpression of miR-129-5p or the inhibition of FNDC3B can both inhibit U87 cell viability, proliferation, migration and invasion, while promote cell apoptosis. Our results suggested that miR-129-5p could directly suppress FNDC3B, which might be one of potential mechanisms in inhibiting cell processes including viability, proliferation, migration and invasiveness of U87 cells. 

Retracted: No

PubPeer comments:
  Fig. 3. MiR-129-5p repressed the cell viability, proliferation and apoptosis of U87 cells by targeting FNDC3B. ... (F) The cell apoptosis measured by flow cytometry. Two plots differ only in the lower right quadrant, and are unlikely to represent separate experiments for different conditions. ![file] ,
1'-Acetoxychavicol acetate suppresses angiogenesis-mediated human prostate tumor growth by targeting VEGF-mediated Src-FAK-Rho GTPase-signaling pathway
Authors: Weijing Qu
Zhengfang Yi
Li Zhang
Li Lai
Mingyao Liu
Jing Chen
Yuanyuan Wu
Bharat B Aggarwal
Jian Zhang
Xiufeng Pang
Journal: Carcinogenesis (2011)
Discipline: CLINICAL MEDICINE
Keywords: Cancer therapeutic agents; ACA; angiogenesis; VEGF; HUVECs
Affiliations: Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. 

Abstract:  Cancer therapeutic agents that are safe, effective and affordable are urgently needed. We describe that 1'-acetoxychavicol acetate (ACA), a component of Siamese ginger (Languas galanga), can suppress prostate tumor growth by largely abrogating angiogenesis. ACA suppressed vascular endothelial growth factor (VEGF)-induced proliferation, migration, adhesion and tubulogenesis of primary cultured human umbilical vascular endothelial cells (HUVECs) in a dose-dependent manner. ACA also inhibited VEGF-induced microvessel sprouting from aortic rings ex vivo and suppressed new vasculature formation in Matrigel plugs in vivo. We further demonstrated that the mechanisms of this chavicol were to block the activation of VEGF-mediated Src kinase, focal adhesion kinase (FAK) and Rho family of small guanosine triphosphatases (GTPases) (Rac1 and Cdc42 but not RhoA) in HUVECs. Furthermore, treatment of human prostate cancer cells (PC-3) with ACA resulted in decreased cell viability and suppression of angiogenic factor production by interference with dual Src/FAK kinases. After subcutaneous administration to mice bearing human prostate cancer PC-3 xenografts, ACA (6 mg/kg/day) remarkably inhibited tumor volume and tumor weight and decreased levels of Src, CD31, VEGF and Ki-67. As indicated by immunohistochemistry and TUNEL analysis, microvessel density and cell proliferation were also dramatically suppressed in tumors from ACA-treated mice. Taken together, our findings suggest that ACA targets the Src-FAK-Rho GTPase pathway, leading to the suppression of prostate tumor angiogenesis and growth. 

Retracted: No

PubPeer comments:
 Identified by another reader. Both papers: https: pubpeer.com publications 909FC1FC7257C1C38065DAF4CF6AF4 https: pubpeer.com publications 9FEED0603DE857EE805FC0E043F866 *** ![file] , 
 Thanks. We have clarified the issues and made responses by the link: https: pubpeer.com publications 9FEED0603DE857EE805FC0E043F866#2 ,
Up-regulation of miR-1245 by c-myc targets BRCA2 and impairs DNA repair
Authors: Jueheng Wu
Yingjun Xie
Chanjuan Wang
Mengfeng Li
Jun Li
Chuyong Lin
Ting Dai
Zhe Ying
Zhiqiang Wu
Libing Song
Journal: Journal of Molecular Cell Biology (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: BRCA2; miR-1245; breast cancer; homologous recombination; DNA damage
Affiliations: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center,  Sun Yat-sen University, Guangzhou 510060,  China.

Abstract:  BRCA2, a clinical prognostic factor, is significantly up-regulated in mRNA level, while its protein expression is often decreased in sporadic breast cancer. However, how BRCA2 protein expressions are suppressed in these tumors remains unknown. In this study, we demonstrated that miR-1245 directly suppressed BRCA2 3'-UTR and translation, impaired homologous recombination (HR)-mediated repair, reduced DNA damage-induced Rad51 nuclear foci, and rendered cells hypersensitive to γ-irradiation (IR), ultimately inducing high chromosomal abnormalities in normal breast cells and breast cancer cells. Conversely, inhibiting miR-1245 in breast cancer cells enhanced BRCA2 levels and induced resistance to IR. Furthermore, we demonstrated that c-myc up-regulated miR-1245 expression via direct binding to the miR-1245 promoter, which led to down-regulation of BRCA2 and reduction in HR efficiency. Significantly, miR-1245 levels in primary breast tumors correlated with c-myc overexpression and BRCA2 suppression. These findings uncover a BRCA2 regulatory and signaling pathway in sporadic breast cancer and support a functionally and clinically relevant epigenetic mechanism in cancer pathogenesis. 

Retracted: No

PubPeer comments:
 WB bands in Fig. 6B potentially contain internal repetition. ![file] , 
 Dear Sir Madam, The authors thank the reader for the comment on our article. The orginal WB image has been found, which showed that it is not internal repetition. Thank you very muchuff01 Jun Li ![file] , 
 #2 Thanks very much! I feel very sorry to take the trouble to you. ,
MicroRNA‑145 inhibits proliferation and induces apoptosis in human prostate carcinoma by upregulating long non‑coding RNA GAS5
Authors: Xin Huang
Wei He
Jun Dai
Xin Xie
Chen Fang
Journal: Oncology Letters (2019)
Discipline: CLINICAL MEDICINE
Keywords: apoptosis; long non-coding RNA growth arrest specific 5; microRNA-145; proliferation; prostate carcinoma.
Affiliations: Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.

Abstract:  MicroRNA-145 (miR-145) and long non-coding RNA (lncRNA) growth arrest specific 5 (GAS5) function as tumor suppressors in prostate carcinoma. The aim of the present study was to investigate the role of miR-145 and lncRNA GAS5 in prostate carcinoma. In the present study, miR-145 and lncRNA GAS5 expression levels were demonstrated to be downregulated in tumor tissues compared with adjacent healthy tissues of patients with prostate carcinoma. miR-145 and lncRNA GAS5 expression levels were found to be positively and significantly correlated in tumor tissues, but not in adjacent healthy tissues. A follow-up study revealed that low miR-145 and lncRNA GAS5 expression levels were associated with poor survival. Overexpression of miR-145 resulted in upregulated lncRNA GAS5, whereas lncRNA GAS5 overexpression or silencing did not affect miR-145 expression. Overexpression of miR-145 and lncRNA GAS5 promoted apoptosis and inhibited cell proliferation in prostate carcinoma cell lines, whereas lncRNA GAS5 knockdown had an opposite effect. In addition, lncRNA GAS5 knockdown partially attenuated the effect of miR-145 overexpression of cancer cell proliferation and apoptosis. Therefore, miR-145 may inhibit cell proliferation and induce apoptosis in human prostate carcinoma by upregulating lncRNA GAS5. 

Retracted: No

PubPeer comments:
 Fig 5C: ![file] Many panels share many points with panels from other papers, and appear to be based on the same data sets with slightly different gating or filtering. Grey and black boxes: Compare with panels of Figs 1F and 4G from [Zhang, Long Hu (2020)] . ![file] ![file] Here in context: ![file] ![file] ---------------------------------- Mauve box: Compare with a panel of Fig 2C from [Jiao, Liu Tian (2019)] . ![file] Here in context: ![file] ---------------------------------------------- Light green box: Please compare with Figs 5C of [Lv et al (2019)] , and 5D of [Chen et al (2019)] . ![file] Here in context: ![] ![] ---------------------------------------------------------------------------- UPDATE: Adding another panel to the pair marked with grey rectangles. At left, from Figs 2C, 5B of [Wang et al (2020)] . ![] ![] ,
Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma
Authors: G Fiaschetti
M Mittelbronn
M Nagaishi
D Castelletti
D Stearns
M Pruschy
A Schramm
A Eggert
H Ohgaki
S Zoller
C Schroeder
A Arcaro
T Shalaby
F Westermann
M A Grotzer
Journal: Oncogene (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Medulloblastoma; MYC oncogene; molecular mechanisms; MYC-target genes; BMP signaling pathway
Affiliations: Department of Oncology, University Children's Hospital, Zurich, Switzerland.

Abstract:  Medulloblastoma (MB) is the most common malignant brain tumor in children. It is known that overexpression and/or amplification of the MYC oncogene is associated with poor clinical outcome, but the molecular mechanisms and the MYC downstream effectors in MB remain still elusive. Besides contributing to elucidate how progression of MB takes place, most importantly, the identification of novel MYC-target genes will suggest novel candidates for targeted therapy in MB. A group of 209 MYC-responsive genes was obtained from a complementary DNA microarray analysis of a MB-derived cell line, following MYC overexpression and silencing. Among the MYC-responsive genes, we identified the members of the bone morphogenetic protein (BMP) signaling pathway, which have a crucial role during the development of the cerebellum. In particular, the gene BMP7 was identified as a direct target of MYC. A positive correlation between MYC and BMP7 expression was documented by analyzing two distinct sets of primary MB samples. Functional studies in vitro using a small-molecule inhibitor of the BMP/SMAD signaling pathway reproduced the effect of the small interfering RNA-mediated silencing of BMP7. Both approaches led to a block of proliferation in a panel of MB cells and to inhibition of SMAD phosphorylation. Altogether, our findings indicate that high MYC levels drive BMP7 overexpression, promoting cell survival in MB cells. This observation suggests the potential relevance of targeting the BMP/SMAD pathway as a novel therapeutic approach for the treatment of childhood MB. 

Retracted: No

PubPeer comments:
 ![file] ,
A novel small-molecule disrupts Stat3 SH2 domain–phosphotyrosine interactions and Stat3-dependent tumor processes
Authors: Wei Zhao
Patrick T Gunning
Steven Fletcher
James Turkson
Xiaolei Zhang
Peibin Yue
Journal: Biochemical Pharmacology (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: molecular modeling; phosphotyrosine; SH2 domain; Stat3; dimerization
Affiliations: University of Central Florida College of Medicine, Orlando, 32827, USA.

Abstract:  The molecular modeling of the phosphotyrosine (pTyr)-SH2 domain interaction in the Stat3:Stat3 dimerization, combined with in silico structural analysis of the Stat3 dimerization disruptor, S3I-201, has furnished a diverse set of analogs. We present evidence from in vitro biochemical and biophysical studies that the structural analog, S3I-201.1066 directly interacts with Stat3 or the SH2 domain, with an affinity (K(D)) of 2.74microM, and disrupts the binding of Stat3 to the cognate pTyr-peptide, GpYLPQTV-NH(2), with an IC(50) of 23microM. Moreover, S3I-201.1066 selectively blocks the association of Stat3 with the epidermal growth factor receptor (EGFR), and inhibits Stat3 tyrosine phosphorylation and nuclear translocation in EGF-stimulated mouse fibroblasts. In cancer cells that harbor aberrant Stat3 activity, S3I-201.1066 inhibits constitutive Stat3 DNA-binding and transcriptional activities. By contrast, S3I-201.1066 has no effect on Src activation or the EGFR-mediated activation of the Erk1/2(MAPK) pathway. S3I-201.1066 selectively suppresses the viability, survival, and malignant transformation of the human breast and pancreatic cancer lines and the v-Src-transformed mouse fibroblasts harboring persistently active Stat3. Treatment with S3I-201.1066 of malignant cells harboring aberrantly active Stat3 down-regulated the expression of c-Myc, Bcl-xL, Survivin, the matrix metalloproteinase 9, and VEGF. The in vivo administration of S3I-201.1066-induced significant antitumor response in mouse models of human breast cancer, which correlates with the inhibition of constitutively active Stat3 and the suppression of known Stat3-regulated genes. Our studies identify a novel small-molecule that binds with a high affinity to Stat3, blocks Stat3 activation and function, and thereby induces antitumor response in human breast tumor xenografts harboring persistently active Stat3. 

Retracted: No

PubPeer comments:
 ![file] , 
 https: onties.com canada under-the-microscope-research-lab-promising-cancer-breakthrough-and-whistleblower-who-uncovered-false-data ,
The Reversal Effect of Sigma-1 Receptor (S1R) Agonist, SA4503, on Atrial Fibrillation After Depression and Its Underlying Mechanism
Authors: Steven Liu
Shaobo Shi
Bo Yang
Xin Liu
Chuan Qu
Linglin Wang
Jinjun Liang
Dan Hu
Cui Zhang
Tianxin Ye
Journal: Frontiers in Physiology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: atrial arrhythmia; conduction; depression; inflammation; sigma-1 receptor.
Affiliations: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Abstract:  Aim: Sigma-1 receptors have been investigated and shown to play a protective role in both depression and cardiovascular disease. SA4503, known as a σ1 receptor agonist, regulates cardiac calcium and potassium channels in rat models of depression. However, it remains unknown whether SA4503 can alleviate myocardial inflammation or conduction junctions in the atrium after exposure to chronic mild stress. Methods and results: Sprague-Dawley male rats received 28-day treatment with SA4503, simultaneously with chronic mild stress. Behavior measurements were assessed after the daily doses. Additionally, a multielectrode array assessment, electrophysiological study, immunohistochemistry analysis, histological analysis, and Western blot analysis were performed. Depression rats' hearts showed abnormal electrical activity, including disordered excitation propagation and prolonged total activation time (TAT). In addition, atrial arrhythmias (AAs), induced by burst stimulation, showed higher incidence and longer duration in the depression group compared to the control group. These changes were related to reduced conduction junctions and enhanced spatial heterogeneity. Importantly, depressed rat hearts showed greater expression of inflammatory factors (TGF-α, IL-6, and TGF-β), more collagen distribution in the extracellular matrix, and lower expression of gap junction proteins (CX40 and CX43). Furthermore, SA4503 partially mitigated the above indices in the depression group (P &lt; 0.01 for all groups). Conclusion: These findings show the effects of the σ1R agonist SA4503; it alleviates atrial myocardial inflammation and conduction junctions after chronic mild stress. SA4503 may be the promising pharmacological agent to treat depression-related AAs by increasing conduction function, improving the expression of connexin 40 and 43, and reducing cardiac myocardial inflammation. 

Retracted: No

PubPeer comments:
 Much more similar than expected after horizontal flip or contrast enhancement. Shown with boxes of the same color. ![file] , 
 ![file] ,
Anlotinib Suppresses Colorectal Cancer Proliferation and Angiogenesis via Inhibition of AKT/ERK Signaling Cascade
Authors: Shaozhi Fu
Qian Yang
Zhangqiang Xiang
Rui Hai
Saber Imani
Laichao Ni
Jing Bo Wu
Qinglian Wen
Ruilin Ding
Journal: Cancer Management and Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: angiogenesis; anlotinib; colorectal cancer; proliferation; tyrosine kinase inhibitor.
Affiliations: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People's Republic of China., Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People's Republic of China.

Abstract:  Background: Anlotinib is a highly potent multi-target tyrosine kinase inhibitor, with very good anti-tumor activity against a variety of solid tumors. However, its effect on colorectal cancer (CRC) is not yet clearly understood. The objective of this study was to investigate the anti-tumor effect and underlying mechanism of anlotinib in the pathogenesis of CRC. Materials and methods: Effects of anlotinib on CT26 cells proliferation and microvessel formation in endothelial cells were determined by MTT assay and tube formation assay. Cell migration and invasion were analyzed by using the wound healing assay and transwell assay. Cell cycle and apoptosis were detected by flow cytometry. A CRC xenograft mouse model was used for conducting in-vivo studies to verify the effect of anlotinib. The expression of Ki-67 and CD31 in the tumor tissue was detected by immunohistochemistry and protein expression was measured by Western blot. Results: In-vitro studies revealed that anlotinib inhibited the proliferation, migration, and invasion of CT26 cells and the tube formation of HUVECs in a dose-dependent manner. Anlotinib also significantly induced cell apoptosis and G2/M arrest. It effectively inhibited tumor growth and prolonged survival time in the CRC xenograft mouse model. Immunohistochemical analysis of the tumor tissue revealed that anlotinib downregulated CD31 and Ki-67 which are the biomarkers of microvessel density and proliferation. Furthermore, anlotinib was able to inhibit the activation of VEGFR-2/AKT and FGFR, PDGFRβ and their downstream signaling ERK. Conclusion: The findings of the present study suggested that anlotinib suppressed cell proliferation and angiogenesis via inhibition of AKT/ERK signaling pathway in colorectal cancer and could be a novel therapeutic strategy for treatment of CRC. 

Retracted: No

PubPeer comments:
 Could the authors review Figure 6A and comment on the light colored areas? *** Enhanced contrast ![file] ,
miR-497 and miR-302b regulate ethanol-induced neuronal cell death through BCL2 protein and cyclin D2
Authors: Sarang S Talwelkar
Aruna Shukla
Ashutosh Kumar
Ankita Pandey
Aditya B Pant
Devendra Parmar
Sanjay Yadav
Journal: Journal of Biological Chemistry (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Chronic alcoholism; brain shrinkage; cognitive defects; neuronal death; microRNAs
Affiliations: Developmental Toxicology Division, Indian Institute of Toxicology Research (CSIR-IITR), MG Marg-80, Lucknow 226001, India. 

Abstract:  In chronic alcoholism, brain shrinkage and cognitive defects because of neuronal death are well established, although the sequence of molecular events has not been fully explored yet. We explored the role of microRNAs (miRNAs) in ethanol-induced apoptosis of neuronal cells. Ethanol-sensitive miRNAs in SH-SY5Y, a human neuroblastoma cell line, were identified using real-time PCR-based TaqMan low-density arrays. Long-term exposure to ethanol (0.5% v/v for 72 h) produced a maximum increase in expression of miR-497 (474-fold) and miR-302b (322-fold). Similar to SH-SY5Y, long-term exposure to ethanol induced miR-497 and miR-302b in IMR-32, another human neuroblastoma cell line. Using in silico approaches, BCL2 and cyclin D2 (CCND2) were identified as probable target genes of these miRNAs. Cotransfection studies with 3'-UTR of these genes and miRNA mimics have demonstrated that BCL2 is a direct target of miR-497 and that CCND2 is regulated negatively by either miR-302b or miR-497. Overexpression of either miR-497 or miR-302b reduced expression of their identified target genes and increased caspase 3-mediated apoptosis of SH-SY5Y cells. However, overexpression of only miR-497 increased reactive oxygen species formation, disrupted mitochondrial membrane potential, and induced cytochrome c release (mitochondria-related events of apoptosis). Moreover, ethanol induced changes in miRNAs, and their target genes were substantially prevented by pre-exposure to GSK-3B inhibitors. In conclusion, our studies have shown that ethanol-induced neuronal apoptosis follows both the mitochondria-mediated (miR-497- and BCL2-mediated) and non-mitochondria-mediated (miR-302b- and CCND2-mediated) pathway. 

Retracted: No

PubPeer comments:
 ![file] ,
Increased circulating β-adrenergic receptor autoantibodies are associated with smoking-related emphysema
Authors: Yi-Wei Zhang
Ming Xu
Bei-Bei Liu
Yuan Zhang
Bei He
You-Yi Zhang
Yi-Peng Du
Jia-Yi Hu
Journal: Scientific Reports (2017)
Discipline: Multidisciplinary
Keywords: Smoking; Chronic obstructive pulmonary disease (COPD); Emphysema; Immune responses; Autoantibodies
Affiliations: Department of Respiratory Medicine, Peking University Third Hospital, Beijing, China., Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; Beijing Key Laboratory of cardiovascular Receptors Research, Beijing, China.

Abstract:  Smoking is a dominant risk factor for chronic obstructive pulmonary disease (COPD) and emphysema, but not every smoker develops emphysema. Immune responses in smokers vary. Some autoantibodies have been shown to contribute to the development of emphysema in smokers. β2-adrenergic receptors (β2-ARs) are important targets in COPD therapy. β2-adrenergic receptor autoantibodies (β2-AAbs), which may directly affect β2-ARs, were shown to be increased in rats with passive-smoking-induced emphysema in our current preliminary studies. Using cigarette-smoke exposure (CS-exposure) and active-immune (via injections of β2-AR second extracellular loop peptides) rat models, we found that CS-exposed rats showed higher serum β2-AAb levels than control rats before alveolar airspaces became enlarged. Active-immune rats showed increased serum β2-AAb levels, and exhibited alveolar airspace destruction. CS-exposed-active-immune treated rats showed more extensive alveolar airspace destruction than rats undergoing CS-exposure alone. In our current clinical studies, we showed that plasma β2-AAb levels were positively correlated with the RV/TLC (residual volume/total lung capacity) ratio (r = 0.455, p &lt; 0.001) and RV%pred (residual volume/residual volume predicted percentage, r = 0.454, p &lt; 0.001) in 50 smokers; smokers with higher plasma β2-AAb levels exhibited worse alveolar airspace destruction. We suggest that increased circulating β2-AAbs are associated with smoking-related emphysema. 

Retracted: No

PubPeer comments:
 Figures 1C and 2C appear to include a repeated image representing different conditions. See green boxes. *** ![file] , 
 #1 Update: received this note from journalu2019s Deputy Editor. I am writing to update you on the issues you raised concerning u201cIncreased circulating u03b22-adrenergic receptor autoantibodies are associated with smoking-related emphysemau201d Having spoken to the authors, and seen the raw data, it seems this was a genuine mistake, and the incorrect image was used for figure 2C. I am working with the authors to publish a correction to address this. ,
RETRACTED ARTICLE: LC Method Development and Validation for the Determination of Ropivacaine Hydrochloride in Bulk Drug and Pharmaceutical Formulations
Authors: Chigurupati, Sridevi
Appala, Raju Nemela
Selvarajan, Kesavanarayanan Krishnan
Khaw, Chu How
Teoh, Chun Foo
Batumanathan, Livyashry
Mohammad, Jahidul Islam
Journal: Pharmaceutical Chemistry Journal (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: liquid chromatography; ropivacaine hydrochloride; assay; gradient elution; C8 column

Abstract: Asimple liquid chromatography method has been developed for the assay of ropivacaine hydrochloride in raw material and final products. The chromatographic separation employs gradient elution using C8 column, mobile phase consisting of solvent [A] (monobasic phosphate buffer adjusted to pH 2.5) and solvent [B] (acetonitrile) delivered at a flow rate of 1.0 mL/min. The analytes were detected at 220 nm and peak purity was examined using a photodiode array detector. The proposed method was validated to demonstrate its selectivity, accuracy, precision, robustness, and linearity within a given range. The limits of detection and quantitation were 0.1 and 0.5 g/mL, respectively. The specificity of the method was investigated under various stress conditions, including hydrolysis, heat, oxidation, and photolysis. Stress testing showed degradants, which were well separated from the parent compound proving the stability and indicating capacity of the method.

Retracted: Yes

PubPeer comments:
 Retraction, March 2022, found here: https: link.springer.com article 10.1007 s11094-022-02592-4  The Editor-in-Chief has retracted this article at the request of the authors. After publication, the authors became aware that they did not have ownership of the presented data. ,
GATA3 is downregulated in osteosarcoma and facilitates EMT as well as migration through regulation of slug
Authors: Wentao Xue
Linjie Ma
Xianghai Ma
Journal: OncoTargets and Therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: GATA3; epithelial–mesenchymal transition; migration; osteosarcoma; proliferation.
Affiliations: Department of Orthopedics, Yidu Central Hospital of Weifang City, Qingzhou 262500, People's Republic of China., Department of Orthopedics, People's Hospital of Juxian, Juxian, Shandong 276500, People's Republic of China, .

Abstract:  Background: GATA3 functions as a tumor suppressor and has been observed in multiple types of cancer, but the effects and mechanisms of GATA3 in osteosarcoma (OS) are not yet known. Methods: The GATA3 expression in OS cells and tissues were detected using quantitative reverse-transcription PCR and Western blotting assay. CCK-8 assay, colony formation assay, wound healing assay as well as transwell assay, were performed to determine the effects of GATA3 on cell proliferation, migration and invasion. ChIP and qChIP as well as luciferase assay were performed whether GATA3 transcriptionally regulated slug expression. Results: GATA3 was downregulated in OS cells and tissues. The GATA3 expression was closely associated with tumor size as well as metastasis. GATA3 significantly suppressed OS cells proliferation, migration and invasion. EMT-associated transcript factor, slug, was transcriptionally inhibited by GATA3, thereby regulation of EMT in OS. Conclusion: GATA3 serves as a tumor suppressor in OS and suppresses the progression and metastasis of OS through regulation of slug. 

Retracted: No

PubPeer comments:
 The colony forming assays are all ostensibly independent experiments, yet it seems the two siGATA3 images are simply the same image, moved along the x-axis. Did the authors accidentally upload the wrong image? And, more importantly, why are the authors not showing the entire wells for this assay (but cropping the images circularly as to pretend the entirety of the well is shown)? ![file] ,
Arctiin Inhibits Cervical Cancer Cell Migration and Invasion through Suppression of S100A4 Expression via PI3K/Akt Pathway
Authors: Min-Chieh Hsin
Po-Hui Wang
Pei-Ni Chen
Shun-Fa Yang
Chung-Yuan Lee
Yi-Hsuan Hsiao
Chiao-Wen Lin
Journal: Pharmaceutics (2022)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: S100A4; arctiin; cervical cancer; migration.
Affiliations: Department of Obstetrics and Gynecology, Chiayi Chang Gung Memorial Hospital, Chiayi 613, Taiwan., Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan., Institute of Oral Sciences, Chung Shan Medical University, Taichung 402, Taiwan., School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.

Abstract:  Arctiin, a lignan glycoside, is isolated from Arctium lappa L. The anticancer effects of arctiin have been demonstrated in several studies. However, no research has been conducted on the anti-migration effect of arctiin in cervical cancer cells. The present study examined the effects of arctiin on cervical cancer cells and investigated the possible molecular mechanism. We demonstrated that arctiin exhibited low cytotoxicity and significantly inhibited cell migration and invasion in human cervical cancer cells. The S100A4 protein expression and mRNA levels were significantly reduced in HeLa and SiHa cells with arctiin treatment. Furthermore, silencing S100A4 by using small interfering RNA reduced cell migration, while overexpression of S100A4 mitigated the migration inhibition imposed by arctiin in cervical cancer cells. Western blotting revealed that arctiin significantly reduced phosphoinositide 3-kinase (PI3K) and phosphorylation of Akt in cervical cancer cells. Moreover, selective Akt induction by an Akt activator, SC-79, reverted cervical cancer cell migration and S100A4 protein expression, which were reduced in response to arctiin. Taken together, these results suggest that arctiin inhibits cervical cancer cell migration and invasion through suppression of S100A4 and the PI3K/Akt pathway. 

Retracted: No

PubPeer comments:
 Figure 3G seems to have a repeated band. Could the authors please help me understand? *** ![file] ,
Self-assembled nanoscale coordination polymers with trigger release properties for effective anticancer therapy
Authors: Christopher Poon
Wenbin Lin
Chunbai He
Demin Liu
Kuangda Lu
Journal: Nature Communications (2014)
Discipline: Multidisciplinary
Keywords: Nanoscale coordination polymers; drug delivery systems; zinc bisphosphonate; cisplatin prodrug; oxaliplatin prodrug
Affiliations: Department of Chemistry, University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.

Abstract:  Nanoscale coordination polymers (NCPs) are self-assembled from metal ions and organic bridging ligands, and can overcome many drawbacks of existing drug delivery systems by virtue of tunable compositions, sizes and shapes, high drug loadings, ease of surface modification and intrinsic biodegradability. Here we report the self-assembly of zinc bisphosphonate NCPs that carry 48 ± 3 wt% cisplatin prodrug and 45 ± 5 wt% oxaliplatin prodrug. In vivo pharmacokinetic studies in mice show minimal uptake of pegylated NCPs by the mononuclear phagocyte system and excellent blood circulation half-lives of 16.4 ± 2.9 and 12.0 ± 3.9 h for the NCPs carrying cisplatin and oxaliplatin, respectively. In all tumour xenograft models evaluated, including CT26 colon cancer, H460 lung cancer and AsPC-1 pancreatic cancer, pegylated NCPs show superior potency and efficacy compared with free drugs. As the first example of using NCPs as nanotherapeutics with enhanced antitumour activities, this study establishes NCPs as a promising drug delivery platform for cancer therapy. 

Retracted: No

PubPeer comments:
 This paper has features suggestive of [what elsewhere has been labeled as  Papermill #2 ] , characterised by stylised geometrical WBs that are reduced to black blobs on a featureless grey background, reminiscent of a Miro painting: ![file] ...and by a small repertoire of recurring flow cytometry plots, ![file] slightly modified by artisanal stippling on each of their occurrences. ![] Other examples are listed in a Google document. https: docs.google.com spreadsheets d 1qBqQMXgzxoBd5bTbqdMuapGheupE5bdIopypju417NM edit?usp=sharing , 
 Retracted [6 August 2021] . ---------------------------- *Cancer Biotherapy and Radiopharmaceuticals* officially retracts the paper entitled, u201cTargeted Regulation of miR-26a on PTEN to Affect Proliferation and Apoptosis of Prostate Cancer Cells Cancer Biotherapy and Radiopharmaceuticalsu201d by Weilu Li, Yongjun Jiang, Xia Wu, and Fucun Yang (Cancer Biother Radiopharm 2019;34(7):480-485; doi: 10.1089 cbr.2018.2664) due to the discovery that the paper was submitted from a paper mill which is a violation of the journal s standard protocols and is considered an infraction against the rigorous standards of scientific publishing. The Editor and Publisher of *Cancer Biotherapy and Radiopharmaceuticals* are committed to preserving the scientific literature and the community it serves and does not tolerate any violations of scientific misconduct. ,
Propofol inhibits invasion and enhances paclitaxel- induced apoptosis in ovarian cancer cells through the suppression of the transcription factor slug
Authors: L-H Mu
X-H Niu
M-Y Zhang
P Wang
Q-H Du
J Chen
Journal: European review for medical and pharmacological sciences (2013)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Propofol; ovarian cancer cells; invasion; chemosensitization; paclitaxel
Affiliations: Department of Anesthesiology, Shandong University, Jinan, Shandong Province, China.

Abstract:  Background and aim: Propofol is one of the most commonly used intravenous anaesthetic agents during cancer resection surgery. It has recently found that propofol has the effect to inhibit cancer cell migration and invasion and sensitize cancer cells to chemotherapy. However, the role of the propofol on the ovarian cancer cells is unknown. In the present study, we explored the effect of propofol on invasion and chemosensitization of ovarian cancer cells to paclitaxel. Materials and methods: The paclitaxel sensitivity of ovarian cancer cell lines HO-8910PM, H0-8910, SKOV-3, OVCAR-3, COC1 and ES-2 were determined by MTT assays. The Slug levels in the cell lines and the effects of propofol on Slug levels in the cell lines were determined by western blot assays. The effect of propofol on invasion, migration and paclitaxel-induced ovarian cancer apoptosis was determined by Boyden chamber assays, cell MTT, TUNEL assays. Results: The results showed that the cell lines COC1, H0-8910 and ES-2 were sensitive, whereas HO-8910PM, OVCAR-3, SKOV-3, were resistant to paclitaxel. Significant correlation was observed between basal Slug levels and paclitaxel sensitivity. Paclitaxel treatment increased Slug levels. Treatment with propofol induced apoptosis and increased paclitaxel killing of all paclitaxel-sensitive and -resistant ovarian cancer cells followed by significant decrease in the Slug levels. Treatment with propofol inhibits invasion and migration. Conclusions: These data suggest a new mechanism by which the propofol inhibits invasion and metastasis,enhances paclitaxel-induced ovarian cancer cell apoptosis through suppression of Slug. 

Retracted: No

PubPeer comments:
 Figures 2 and 3. * Red boxes: Two b-actin panels appear to show a 4-lane overlap. ![file] , 
 ![file] ![file] Dear Prof Bik, Thanks again for your comment! , 
 Corrected [November 2021] . ------------------------------------------- The authors found some mistakes in the article. The Publisher apologizes for any inconvenience this may cause. The correct version of Figure 2 is reproduced below. - The band of u03b2-actin in Figure 2 was an inadvertent wrong use due to an error in figure preparation. The authors confirm that the correction does not affect the discussion and conclusions of the original article. ![file] , 
 I am still puzzled by Fig 3, in which a single beta-Actin band serves as loading control for six different Slug bands that were necessarily obtained in separate experiments (each requiring its own loading control). ![] ,
Functional significance of Wnt inhibitory factor-1 gene in kidney cancer
Authors: Ken Kawamoto
Kazumori Kawakami
Nobuyuki Kikuno
Hiroshi Hirata
Rajvir Dahiya
Masayuki Nakagawa
Yuichiro Tanaka
Soichiro Yamamura
Shahana Majid
Hideki Enokida
Sharanjot Saini
Journal: Cancer Research (2009)
Discipline: CLINICAL MEDICINE
Keywords: Wnt inhibitory factor-1; tumor suppressor; renal cell carcinoma; apoptosis; promoter methylation
Affiliations: Department of Urology, Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, California 94121, USA.

Abstract:  Wnt inhibitory factor-1 (WIF-1) has been identified as one of the secreted antagonists that bind Wnt protein. WIF-1 has been described as a tumor suppressor in various types of cancer. However, the molecular function of WIF-1 gene has never been examined in human renal cell carcinoma (RCC). Therefore, we hypothesized that WIF-1 functions as a tumor suppressor gene and overexpression of this gene may induce apoptosis and inhibit tumor growth in RCC cells. Immunohistochemistry and real-time reverse transcription-PCR revealed that WIF-1 was significantly downregulated in RCC samples and RCC cell lines, respectively. Bisulfite sequencing of the WIF-1 promoter region in RCC cell lines showed it to be densely methylated, whereas there was no methylation of WIF-1 promoter in normal kidney. Significant inhibition of cell growth and colony formation in WIF-1-transfected cells compared with controls were observed. WIF-1 transfection significantly induced apoptosis and suppressed in vivo tumor growth. Also, Wnt signaling activity and beta-catenin expression were reduced by WIF-1 transfection. In conclusion, this is the first report documenting that the WIF-1 is downregulated by promoter methylation and functions as a tumor suppressor gene by inducing apoptosis in RCC cells. 

Retracted: No

PubPeer comments:
 Figure 1A. Much more similar than expected. https: imgur.com X2emwHQ , 
 As mentioned in the  Materials and Methods section of both papers, we used the same tissue array - Biomax (KD481) tissue array. These are commercially available tissue arrays used by several scientists. Therefore, the same tissue array was used in both papers but with different antibodies. ,