Int J Oncol
· 2026 Mar · PMID 41543185
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<p>Hypoxic tumor microenvironment (TME) is a common occurrence in the development of solid tumors, which activates hypoxia‑inducible factors (HIFs) and their downstream signaling pathways in cancer cells to facilitate tu...<p>Hypoxic tumor microenvironment (TME) is a common occurrence in the development of solid tumors, which activates hypoxia‑inducible factors (HIFs) and their downstream signaling pathways in cancer cells to facilitate tumor progression and immune escape. However, among the various immune cells that constitute innate and adaptive immune systems, HIFs have a more intricate function; moreover, different isoforms of HIFs play different functions under spatial and temporal conditions. HIFs are conducive to the adaptation of various immune cells to the hypoxic TME. The stability of HIF‑α can regulate metabolism and directly regulate the expression of immune genes. Additionally, the activation of HIF signaling may also inhibit the development of immune cells in some tumor environments, affecting the antigen recognition and killing processes to assist cancer cells in immune escape. Therefore, understanding the relationship between HIF signaling and immune cells more comprehensively may yield substantial benefits for the immunotherapy of various types of cancer. The present study reviewed the role of HIFs in immunity, including their role in T cells, B cells, macrophages, neutrophils, dendritic cells and natural killer cells. It also discussed the effectiveness of HIF targeted therapy in clinical application, the challenges associated with it and the development of a precise targeting drug delivery system. The present review may help researchers comprehend the tumor immune process in a hypoxic microenvironment. It aimed to offer novel strategies for cancer immunotherapy and prolonging the overall survival of patients.</p>.
Rauschenberg S, Orgler-Gasche E, Karakas Zeybek D
… +5 more, Regel I, Löhr JM, Öhlund D, Günther M, Aguilera Munoz L
Int J Oncol
· 2026 Mar · PMID 41543183
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<p>Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer‑related death worldwide in both men and women. While sex‑specific differences are increasingly recognized as critical determinants of heal...<p>Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer‑related death worldwide in both men and women. While sex‑specific differences are increasingly recognized as critical determinants of health and disease, particularly in oncology, they remain markedly underexplored in PDAC. Emerging evidence suggests that sex differences influence numerous aspects of PDAC, including treatment response and prognosis. This knowledge gap represents a notable barrier to the development of effective, personalized therapeutic strategies for both sexes. The present review provides a comprehensive overview of the current knowledge on sex‑based differences in PDAC, encompassing epidemiology, risk factors, chemotherapy pharmacokinetics and toxicity, prognosis, therapeutic response, immune interactions, tumor microenvironment, tumor microbiota and molecular biomarkers.</p>.
Wang J, Liang WJ, Min GT
… +3 more, Wang HP, Chen W, Yao N
Int J Oncol
· 2026 Mar · PMID 41543158
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<p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell cell migration and invasion assay data shown in Fig. 5A on p. 1895 were strikingly si...<p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell cell migration and invasion assay data shown in Fig. 5A on p. 1895 were strikingly similar to data in an article written by different authors at different research institutes that had already been accepted for publication in the journal . Owing to the fact that the contentious data in the above article had already been published prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 52: 1886‑1898, 2018; DOI: 10.3892/ijo.2018.4356]</p>.
Sekiguchi N, Takahashi H, Kobayashi S
… +13 more, Sasaki K, Hasegawa S, Iwagami Y, Yamada D, Tomimaru Y, Akita H, Asaoka T, Noda T, Shimizu J, Tanaka K, Chijimatsu R, Doki Y, Eguchi H
Int J Oncol
· 2026 Mar · PMID 41543155
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<p>Circular RNAs (circRNAs) are associated with various biological features of cancer, including chemosensitivity and the structural characteristics of circRNAs indicate their potential as liquid biomarkers. Gemcitabine...<p>Circular RNAs (circRNAs) are associated with various biological features of cancer, including chemosensitivity and the structural characteristics of circRNAs indicate their potential as liquid biomarkers. Gemcitabine is a cornerstone treatment for pancreatic cancer (PC). A deeper understanding of gemcitabine sensitivity and the exploration of clinically valuable liquid biomarkers that are predictive of gemcitabine sensitivity may contribute to the development of improved‑tailored treatment strategies for PC. The aim of the present study was to identify a candidate circRNA associated with gemcitabine sensitivity, investigate its biological functions and evaluate its potential as a liquid biomarker in predicting gemcitabine sensitivity. circRNA sequencing analysis was conducted to identify candidate circRNAs and the function of a candidate circRNA in modulating gemcitabine sensitivity was investigated . Further, the potential of this circRNA in predicting gemcitabine sensitivity in patients with PC who received gemcitabine‑based neoadjuvant chemotherapy was evaluated using pre‑treatment serum samples. circ72309 was identified as the candidate circRNA and its overexpression in gemcitabine‑resistant PC cell lines increased gemcitabine‑induced apoptosis and markedly increased gemcitabine sensitivity . Furthermore, circ72309 decreased cytidine deaminase by increasing reactive oxygen species activity and increasing human equilibrative nucleoside transporter 1 expression via regulation of target miRNAs. Patients with high serum circ72309 had markedly improved progression‑free survival (PFS) and high serum circ72309 was an independent prognostic predictor of a favorable PFS in patients with PC. circ72309 affected multiple steps in the gemcitabine metabolic pathway and its overexpression resulted in markedly increased gemcitabine sensitivity. Therefore, circ72309 expression in the pre‑treatment serum samples may serve as a predictor of gemcitabine sensitivity in patients with PC.</p>.
Int J Oncol
· 2026 Mar · PMID 41508940
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Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the wound healing assay data shown in Fig. 2D, a pair of the data panels appeared to be overlappi...Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the wound healing assay data shown in Fig. 2D, a pair of the data panels appeared to be overlapping, such that the data from the same original source had apparently been used to show the results of differently performed experiments. Furthermore, concerning the immunohistochemical data shown in Fig. 7A and C, similarly, two pairs of the data panels contained overlapping data, where the results of different experiments were intended to have been portrayed. Owing to the duplications of data that were identified in this paper, the Editor of has decided that it should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 41: 599‑610, 2012; DOI: 10.3892/ijo.2012.1496].
Zhang N, Wang T, Bai B
… +5 more, Zhang X, Xu W, Chen W, Yu Y, Wang B
Int J Oncol
· 2026 Mar · PMID 41480706
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Protein tyrosine phosphatase non‑receptor 18 (PTPN18) is widely expressed in breast cancer (BC) cell lines. Additionally, high levels of PTPN18 facilitate an improved overall survival and prognosis in patients with BC. H...Protein tyrosine phosphatase non‑receptor 18 (PTPN18) is widely expressed in breast cancer (BC) cell lines. Additionally, high levels of PTPN18 facilitate an improved overall survival and prognosis in patients with BC. However, the effects and mechanisms of PTPN18 in BC remain unclear. In the present study, it was found that PTPN18 serves a tumor suppressor role in BC cells by promoting apoptosis, inhibiting proliferation and metastasis and inducing cell cycle arrest. Bioinformatics analysis showed that PTPN18 was significantly negatively correlated with the cell cycle and downregulated cyclin E expression, which was consistent with the experimental results. Subsequent co‑immunoprecipitation assay results showed that PTPN18 could bind to cyclin E and promote its degradation through the ubiquitin‑proteasome pathway. Moreover, the addition of cyclin E2 did not reduce the binding of PTPN18 to cyclin E1. In the present study, the signaling pathways involved in cell cycle regulation were further investigated and it was found that PTPN18 may regulate the expression levels of cyclin‑dependent kinase (CDK) inhibitor 1A and CDK inhibitor 1B proteins through phosphatidylinositol 3‑kinase/protein kinase B signaling pathway, which leads to cell cycle arrest and tumor inhibition in BC. Thus, analysis of the tumor suppressor mechanism of PTPN18 not only helps us to understand its biological function but also provides a theoretical basis for the development of new therapeutic strategies for BC.
Viedma-Rodriguez R, Baiza-Gutman LA, García-Carrancá A
… +3 more, Moreno-Fierros L, Salamanca-Gómez F, Arenas-Aranda D
Int J Oncol
· 2026 Mar · PMID 41456498
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Following the publication of the above paper, a concerned reader drew to the Editor's attention that, in Fig. 6, the same data appeared to have been included in three of the flow cytometric plots featured in this figure...Following the publication of the above paper, a concerned reader drew to the Editor's attention that, in Fig. 6, the same data appeared to have been included in three of the flow cytometric plots featured in this figure (for the Non‑treated, Scrambled and SiRNAi BIK experiments). Moreover, the control β‑actin western blots in Figs. 2B, 4A and 8B appeared to be the same (although, in these cases, the lanes for the blots were labelled up identically, and so these apparent duplications may not have represented an incorrect assembly of these figures); similarly, the control blots in Fig. 7A and B were also matching. However, the control β‑actin western blots in three other figure parts (Fig. 1C and 7A/B) were also duplicated, and in this case, the numbers of lanes in the gel slices were different / the lanes were labelled differently. The authors were contacted by the Editorial Office to offer an explanation for these potential anomalies in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, the Editor of has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 43: 1777‑1786, 2013; DOI: 10.3892/ijo.2013.2127].
Int J Oncol
· 2026 Feb · PMID 41456439
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Treatment of urothelial carcinoma (UC), particularly in metastatic or cisplatin‑ineligible patients, remains challenging because of limited durable responses to conventional chemotherapy and immune checkpoint inhibitors....Treatment of urothelial carcinoma (UC), particularly in metastatic or cisplatin‑ineligible patients, remains challenging because of limited durable responses to conventional chemotherapy and immune checkpoint inhibitors. Recent advances in targeted therapies, including FGFR inhibitors (for example, erdafitinib) and antibody‑drug conjugates (ADCs) targeting Nectin‑4 (enfortumab vedotin) and HER2 (disitamab vedotin), have reshaped treatment paradigms. FGFR3 alterations, which are present in 20‑40% of patients with advanced UC, predict sensitivity to FGFR tyrosine kinase inhibitors, whereas ADCs demonstrate efficacy across biomarker‑selected and unselected populations. However, clinical implementation is complicated by resistance mechanisms, such as kinase switching, phenotypic plasticity and tumor microenvironment interactions, as well as biomarker heterogeneity. The present review synthesizes current evidence on molecularly guided therapies, contrasts resistance mechanisms between FGFR inhibitors and ADCs, and evaluates strategies to overcome therapeutic limitations. By integrating translational insights and emerging preclinical data, it was aimed to provide a roadmap for optimizing biomarker‑driven approaches, novel combinations and next‑generation agents for the treatment of UC.
Int J Oncol
· 2026 Feb · PMID 41416448
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Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, with high morbidity and mortality rates globally, ranking it among the leading causes of cancer‑related death worldwide. Despite notable adv...Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, with high morbidity and mortality rates globally, ranking it among the leading causes of cancer‑related death worldwide. Despite notable advancements in HCC treatment in recent years, high rates of recurrence and treatment resistance remain significant clinical challenges. The development of drug resistance undermines the efficacy of current therapies and leads to poor patient outcomes. However, the specific role and detailed delivery mechanism of exosomal circular RNAs (circRNAs) in mediating this treatment resistance are still largely undefined. circRNAs represent a group of non‑coding RNAs with various biological roles. An increasing number of circRNAs are abnormally expressed in HCC and participate in the malignant progression of HCC, playing a role in HCC treatment resistance. Furthermore, circRNAs can exert additional effects when packaged into exosomes. Exosomes, as signaling molecules of intercellular communication, are enriched with circRNAs, which can be packaged, secreted and transferred to target recipient tumor cells, thereby regulating the development process and drug resistance of cancer. The present comprehensive review aims to summarize how these exosomal circRNAs regulate key hallmarks of cancer in HCC and critically synthesize the current literature, elucidating how exosomal circRNAs modulate therapeutic resistance in HCC and highlighting their potential as biomarkers and therapeutic targets.
Zhao X, Zhang W, Yu X
… +6 more, Zhao X, Dai X, Chen S, Wang Y, Cheng J, Zheng W
Int J Oncol
· 2026 Feb · PMID 41416436
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The present study focused on the role of coiled‑coil domain‑containing protein 137 (CCDC137), an RNA‑binding and epigenetic protein with high expression and poor prognosis in various types of cancer. Bioinformatics analy...The present study focused on the role of coiled‑coil domain‑containing protein 137 (CCDC137), an RNA‑binding and epigenetic protein with high expression and poor prognosis in various types of cancer. Bioinformatics analysis, cellular experiments and animal models investigated the functions of CCDC137 in RNA post‑transcriptional regulation, epigenetic modification and the tumor microenvironment. The results showed that CCDC137 can bind specific mRNAs to affect physiological processes such as the cell cycle, participate in epigenetic regulation such as DNA methylation and histone modification and influence tumor immune escape by affecting the functions of tumor‑associated macrophages. Based on the multidimensional regulatory functions of CCDC137, it is expected to become a new target for cancer diagnosis and treatment and provide a theoretical basis for precision cancer therapy.
Sudo H, Tsuji AB, Sugyo A
… +7 more, Takuwa H, Masamoto K, Tomita Y, Suzuki N, Imamura T, Koizumi M, Saga T
Int J Oncol
· 2026 Feb · PMID 41416435
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Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the bioluminescence and fluorescence images of the mouse shown in Fig. 2C and E respectively, the...Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the bioluminescence and fluorescence images of the mouse shown in Fig. 2C and E respectively, the images/positioning of the mouse appeared to be unexpectedly similar, and the authors were asked to confirm whether the images were captured at the same time, but separate results were obtained for the luminescence and fluorescence readings. Similarly, in Fig. 3A, the same mouse image (re. its appearance and positioning) appeared to be shown for the 5a‑D‑Luc cell line on Days 14 and 28, albeit with different bioluminescence. Finally, upon analyzing the data independently in the Editorial Office, it came to light that, for the phase contrast images of the MDA‑MD‑231 and 5a‑D‑Luc cell lines shown in Fig. 1A, these appeared to be the same image, but with different lighting intensities and with the 5a‑D‑Luc image rotated through 90˚. The authors were contacted by the Editorial Office to offer an explanation for these possible anomalies in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office conitnues to investigate this matter further. [International Journal of Oncology 48: 525‑532, 2016; DOI: 10.3892/ijo.2015.3300].
Int J Oncol
· 2026 Feb · PMID 41416429
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Oncolytic virotherapy has emerged as a significant advancement in cancer treatment. However, the efficacy of monotherapies is limited by tumor heterogeneity, highlighting the need for combination strategies to overcome t...Oncolytic virotherapy has emerged as a significant advancement in cancer treatment. However, the efficacy of monotherapies is limited by tumor heterogeneity, highlighting the need for combination strategies to overcome therapeutic limitations. This study provides a review of the molecular mechanisms, preclinical advancements and clinical outcomes associated with oncolytic virus (OV)‑targeted drug combinations over the past two decades, elaborating on the interaction mechanisms through which molecular targeted drugs and oncolytic viruses enhance antitumor effects. Additionally, the progress in translating OV‑based combination therapies for solid tumors into clinical practice is outlined and innovative strategies are proposed for developing novel therapeutic frameworks.
Wu G, Lu X, Wang Y
… +5 more, He H, Meng X, Xia S, Zhen K, Liu Y
Int J Oncol
· 2026 Feb · PMID 41416423
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Following the publication of the above article, a concerned reader drew to the Editor's attention that, regarding the immunohistochemical staining experiments shown in Fig. 2, the insets for the data panels 2A and B, and...Following the publication of the above article, a concerned reader drew to the Editor's attention that, regarding the immunohistochemical staining experiments shown in Fig. 2, the insets for the data panels 2A and B, and 2C and D, respectively were remarkably similar, such that these data may not have consistently been identifiable with the main images proper for these figure parts. Secondly, with the western blot data shown in Fig. 3c, the PTCH1/Huh7 and ATAD2/siRNA‑HCCLM3 protein bands were remarkably similar, such that the same data were likely to have been duplicated in the figure where different experiments were intended to have been portrayed. Finally, the two sets of flow cytometric plots shown in Fig. 2A appeared to show similar groupings of dots, which would not have been anticipated if these experiments had been performed discretely under different experimental conditions, suggesting a fundamental flaw either in the way in which these experiments were performed, or in how the results were outputted. After having conducted an internal investigation of the data in this paper, the Editor of has decided that this article should be retracted from the journal on the grounds of an overall lack of confidence in the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor sincerely apologizes to the readership for any inconvenience caused, and we thank the reader for bringing this matter to our attention. [International Journal of Oncology 45: 351‑361, 2014; DOI: 10.3892/ijo.2014.2416].
Int J Oncol
· 2026 Feb · PMID 41384305
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Radiotherapy is an important treatment for tumors; however, some patients exhibit poor sensitivity to radiation, leading to unsatisfactory outcomes. mTOR regulates critical processes such as cell proliferation, autophagy...Radiotherapy is an important treatment for tumors; however, some patients exhibit poor sensitivity to radiation, leading to unsatisfactory outcomes. mTOR regulates critical processes such as cell proliferation, autophagy and DNA repair, serving a central role in tumor biology. Moreover, mTOR inhibitors have shown potential to enhance radiotherapy effectiveness and address radiation resistance. Although drug resistance and side effects limit their clinical use, combining therapies and optimizing treatment plans could improve results. The present review summarizes how mTOR signaling contributes to radiation resistance in lung cancer, as well as the underlying molecular mechanisms. Understanding these pathways may aid the development of new combination therapies to improve treatment options for patients with lung cancer.
Int J Oncol
· 2026 Feb · PMID 41384285
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Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the tumor images shown in Fig. 4A on p. 1180 were unexpectedly similar, albeit the images appeare...Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the tumor images shown in Fig. 4A on p. 1180 were unexpectedly similar, albeit the images appeared to have been horizontally stretched where they reappeared in the figure, under situations where different experiments were intended to have been shown. Owing to the anomalies identified in this figure, the Editor of has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 45: 1175‑1183, 2014; DOI: 10.3892/ijo.2014.2498].
Xu H, Si Q, Song Y
… +4 more, Sun S, Wei X, Long H, Wang X
Int J Oncol
· 2026 Feb · PMID 41347841
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Cancer stem cells (CSCs), a small subpopulation of cancer cells that exhibit stem‑like properties, possess the ability to differentiate and self‑renew. These capabilities enable CSCs to act as tumor‑initiating cells, dri...Cancer stem cells (CSCs), a small subpopulation of cancer cells that exhibit stem‑like properties, possess the ability to differentiate and self‑renew. These capabilities enable CSCs to act as tumor‑initiating cells, driving tumorigenesis and proliferation, leading to major clinical challenges. Specifically, CSCs play a crucial role in metastasis, recurrence and drug resistance, thereby leading to complications in therapeutic responses. The plasticity of CSCs leads to heterogeneity, allowing them to adopt diverse phenotypes in response to intrinsic genetic factors or extrinsic environmental cues. This adaptability may serve as a mechanism for CSCs to thrive in the tumor microenvironment (TME) and promote tumor progression. The present article aimed to review the multifaceted nature of CSCs, examining their functional diversity, biomarkers and interactions with the TME. Through elucidating the mechanisms that underlie this heterogeneity, researchers aim to develop targeted therapeutic interventions against CSCs, thereby enhancing the efficacy of cancer treatments and improving patient outcomes.
Gao J, Mcconnell MJ, Yu B
… +7 more, Li J, Balko JM, Black EP, Johnson JO, Lloyd MC, Altiok S, Haura EB
Int J Oncol
· 2026 Feb · PMID 41347839
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Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the Bcl‑2 protein bands shown for the HCC827 cell line in the western blots in Fig. 3A on p. 342 were unexpe...Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the Bcl‑2 protein bands shown for the HCC827 cell line in the western blots in Fig. 3A on p. 342 were unexpectedly similar to the Akt protein bands shown for the A549 cell line in Fig. 3B. In addition, the Bcl‑2 protein bands shown for the H358 and HCC827 cell lines (the left‑hand and middle gels) possibly contained a pair of mutually overlapping protein bands, and the β‑actin control bands featured in the left‑hand and middle lanes of Fig. 3A for the H358 and HCC827 cell lines, and the β‑actin control bands featured in the middle and right‑hand lanes for the H358 and HCC827 cell lines in Fig. 1C on p. 340, were similarly more similar than might have been expected. The authors were contacted by the Editorial Office to offer an explanation for this possible anomaly in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Oncology 35: 337‑345, 2009; DOI: 10.3892/ijo_00000345].
Yang L, Shu T, Liang Y
… +5 more, Gu W, Wang C, Song X, Fan C, Wang W
Int J Oncol
· 2026 Feb · PMID 41347835
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Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, for the MTT assay experiments shown in Fig. 2A on p. 1655, the GDC‑0152/ANGPTL2 panel appeared to overlap w...Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, for the MTT assay experiments shown in Fig. 2A on p. 1655, the GDC‑0152/ANGPTL2 panel appeared to overlap with the ANGPTL2 panel, albeit the panel had been rotated through 180°; moreover, the magnification of the right‑hand panel was very different, creating an impression that the ANGPTL2 panel showed more cells. Upon analyzing the data independently in the Editorial Office, it came to light that that certain of the flow cytometric data in Fig. 2B and the nuclear staining experiments in Fig. 2C were strikingly similar to data in other articles written by different authors at different research institutes that had already been accepted for publication elsewhere. Owing to the fact that the contentious data in the above article had already been published prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 46: 1651‑1658, 2015; DOI: 10.3892/ijo.2015.2872].
Wang F, Xu X, Guan B
… +7 more, Li X, Yuan J, Guan W, Chen J, Fang J, Lu Q, Xu G
Int J Oncol
· 2026 Feb · PMID 41347829
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Ovarian cancer (OC) is the most lethal disease in women. Resistance to paclitaxel (PTX) is the main cause of treatment failure in patients with OC. The STAT1 protein is a transcription factor implicated in a variety of c...Ovarian cancer (OC) is the most lethal disease in women. Resistance to paclitaxel (PTX) is the main cause of treatment failure in patients with OC. The STAT1 protein is a transcription factor implicated in a variety of cellular processes. The present study explored the function and regulatory mechanism of STAT1 in the reversal of PTX resistance and . The OC cell lines SK‑OV‑3 and OVCAR‑3 and their counterpart PTX‑resistant OC cell lines SK3R‑PTX and OV3R‑PTX were applied. The Tet‑On STAT1‑overexpression plasmids were constructed using the technique of the Tet‑On gene expression system and were packaged by lentivirus. RNA and protein were detected by reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis, respectively. OC cell mRNA‑sequencing and subsequent RT‑qPCR verification revealed that STAT1 expression was downregulated in PTX‑resistant cells compared with their sensitive counterparts (P<0.01), except for STAT1β expression in SK3R cells (P>0.05). Cell viability was assessed using a CCK‑8 assay and PTX sensitivity was detected based on their IC values. Overexpression of STAT1 sensitized PTX responses and decreased the tumor volume in xenograft mice. Bioinformatics analysis indicated that STAT1 had favorable effects on the overall survival of patients with OC. Apoptotic cells were detected using flow cytometry. STAT1α overexpression increased the percentage of apoptotic cells to 53.20±0.92 and 36.74±0.77% in OV3R‑PTX and A2780‑PTX cells, respectively, after 1 µM PTX treatment for 24 h. Mechanistically, overexpression of STAT1, especially STAT1α, confirmed by western blot and immunofluorescence staining, induced apoptosis by increasing apoptotic molecules such as Fas cell surface death receptor (FAS) and caspase‑8 (CASP8), which was abolished in the presence of a caspase blocker (Z‑VAD‑FMK). Furthermore, the dual‑luciferase assay confirmed that STAT1 directly bound to the promoter regions of the FAS and CASP8 genes. Thus, the present data demonstrated that STAT1 was a key mediator of the PTX chemotherapy response. Low STAT1 expression was a marker of PTX resistance, whereas overexpression of STAT1 sensitized OC cells to PTX and promoted apoptosis via the FAS/CASP8 signaling pathway. These findings may provide a potential therapeutic strategy to reverse PTX resistance in OC patients by targeting STAT1.
Int J Oncol
· 2026 Feb · PMID 41347822
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Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, for the transfection experiments shown in Fig. 3 on p. 760, two pairs of data panels showed a surprisingly high...Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, for the transfection experiments shown in Fig. 3 on p. 760, two pairs of data panels showed a surprisingly high level of similarity, such that the data appeared to have been derived from the same original sources where the results from differently performed experiments were intended to have been shown. The authors responded to the reader's concern by providing replacement data for Fig. 3; however, upon performing an independent analysis of the data in this paper in the Editorial Office, it was also noted that western blot data were overlapping in Fig. 4, and for the cell invasion assay experiments shown in Fig. 5, Fig. 5A and B were also found to contain overlapping data, albeit the level of brightness of the images differed. Owing to the large number of duplications of data, and other potential anomalies, that were identified in this paper, the Editor of has decided that it should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these additional concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 46: 757-763, 2015; DOI: 10.3892/ijo.2014.2748].