Oncology reports最新文献

Despite advances in science and technology, lung cancer remains a major public health issue. The discovery of early diagnostic and prognostic markers is still needed to reduce the mortality rate of lung cancer, which is the highest among all cancer types. Aberrations in the DNA methylation system have an important role in human cancer and are promising for the development of early diagnostic and prognostic markers. The present study focused on zinc finger protein (ZNF)577, whose encoding gene was indicated to exhibit promoter hypermethylation together with 9 other genes in lung adenocarcinoma (LADC) in a previous study by our group. ZN577 is a member of the ZNG family and its functional role has so far remained elusive. LADC tissue samples surgically resected at Tokushima University Hospital (Tokushima, Japan) between April 1999 and November 2013 were collected. A total of 73 tumors and 27 paired tumor-adjacent normal tissues were examined for DNA methylation and mRNA expression of ZNF577. A total of 149 LADC tissue samples were collected and evaluated by immunohistochemistry (IHC) for the tissue expression of ZNF577. High methylation (n=27, P<0.0001) and low mRNA expression levels (n=27, P<0.031) of ZNF577 were identified in LADC tissues, and it was demonstrated that methylation levels were inversely correlated with mRNA expression levels (P=0.0116, ρ=-0.2515). Among the LADC tissues, lepidic-patterned samples had lower methylation levels of ZNF577 than other pathological types. In addition, mRNA expression levels of ZNF577 were significantly higher in females, non-smokers and stage I samples. Overall survival [P<0.0001; area under curve (AUC)=0.8658] and disease-free survival (DFS; P<0.0004; AUC=0.7232) rates were significantly higher in the ZNF577 high mRNA expression group than in the ZNF577 low mRNA expression group. Among the 149 LADC samples examined by IHC, 105 were negative and 44 were positive for the tissue expression of ZNF577. Cox regression analysis showed poorer DFS (hazard ratio: 3.917; P=0.023) in patients with lower expression of ZNF577. In conclusion, higher methylation levels of ZNF577 were observed in LADC tissues than in normal lung tissue and low mRNA expression of ZNF577 was associated with unfavorable prognosis.

Senescent cells are known to secrete proteins, including inflammatory cytokines and damage‑associated molecular patterns. This phenomenon is known as the senescence‑associated secretory phenotype (SASP). SASP in cancer stromal fibroblasts is involved in cancer growth and progression. Conversely, metformin, an antidiabetic drug, has been reported to inhibit SASP induction by inhibiting the activation of NF‑κB, a regulator of SASP. To date, at least to the best of our knowledge, there have been no reports regarding cellular senescence in fibroblasts and tumor progression via the SASP‑mediated paracrine pathway. The present study thus aimed to elucidate the induction mechanisms of SASP in radiation‑induced fibroblasts and to determine its effects on cancer progression via the paracrine pathway. Furthermore, the present study aimed to determine whether controlling SASP using metformin suppresses cancer progression. A well‑differentiated esophageal cancer cell line established by the authors' department and fibroblasts isolated and cultured from the non‑cancerous esophageal mucosa of resected esophageal cancer cases were used for the experiments. Fibroblasts were irradiated with 8 Gy radiation, and the changes in the expression of the senescence markers, SA‑β‑gal, p21, p16 and NF‑κB were evaluated using immunofluorescent staining and western blot analysis in the presence or absence of metformin treatment. The culture supernatants of irradiated fibroblasts treated with metformin and those treated without metformin were collected and added to the cancer cells to evaluate their proliferative, invasive and migratory abilities. Vimentin and E‑cadherin expression levels were also evaluated using immunofluorescent staining and western blot analysis. The expression levels of p16, p21 and NF‑κB in irradiated fibroblasts were attenuated by treatment with metformin. Supernatants collected from irradiated fibroblasts exhibited the proliferative activity of esophageal cancer cells, and the promotion of migratory and invasion abilities, which may be due to epithelial‑mesenchymal transition and changes in cell morphology. These reactions were confirmed to be suppressed by the addition of the supernatant of cultured fibroblasts pre‑treated with metformin. On the whole, the present study demonstrates that fibroblasts in the cancer stroma may be involved in tumor progression through cellular senescence.

It is well known how the precise localization of glioblastoma multiforme (GBM) predicts the direction of tumor spread in the surrounding neuronal structures. The aim of the present review is to reveal the lateralization of GBM by evaluating the anatomical regions where it is frequently located as well as the main molecular alterations observed in different brain regions. According to the literature, the precise or most frequent lateralization of GBM has yet to be determined. However, it can be said that GBM is more frequently observed in the frontal lobe. Tractus and fascicles involved in GBM appear to be focused on the corticospinal tract, superior longitudinal I, II and III fascicles, arcuate fascicle long segment, frontal strait tract, and inferior fronto‑occipital fasciculus. Considering the anatomical features of GBM and its brain involvement, it is logical that the main brain regions involved are the frontal‑temporal‑parietal‑occipital lobes, respectively. Although tumor volumes are higher in the right hemisphere, it has been determined that the prognosis of patients diagnosed with cancer in the left hemisphere is worse, probably reflecting the anatomical distribution of some detrimental alterations such as TP53 mutations, PTEN loss, EGFR amplification, and MGMT promoter methylation. There are theories stating that the right hemisphere is less exposed to external influences in its development as it is responsible for the functions necessary for survival while tumors in the left hemisphere may be more aggressive. To shed light on specific anatomical and molecular features of GBM in different brain regions, the present review article is aimed at describing the main lateralization pathways as well as gene mutations or epigenetic modifications associated with the development of brain tumors.

Pituitary tumor‑transforming gene 1 (PTTG1), also known as securin, is a proto‑oncogene involved in the development of various cancers by promoting cell proliferation and mobility. However, its underlying biological mechanisms in oral squamous cell carcinoma (OSCC) progression remain unclear. in the present study, it was sought to elucidate the role of PTTG1 as an oncogene in OSCC progression and was attempted to unravel the underlying mechanism and impact of PTTG1 expression on cell cycle, cell death, and cellular senescence. The effect of double strand break on PTTG1 expression was investigated in OSCC growth. To identify the role of PTTG1 in OSCC growth, the cell viability and senescence was analyzed by EdU and senescence‑associated beta‑galactosidase (SA‑β‑gal) assay, respectively. To verify the DNA damage‑induced senescence of PTTG1, the chromosomal damage in OSCC was analyzed in vitro. Finally, the effect of PTTG1 on tumor growth and gene expression related to cell viability and DNA damaged‑induced senescence was investigated in vivo. PTTG1 expression was compared between OSCC and healthy patient samples (n=32) using reverse transcription‑quantitative PCR and immunohistochemistry; and it was found that PTTG1 expression was upregulated in OSCC. Small interfering RNA‑mediated knockdown of PTTG1 in two OSCC cell lines revealed that PTTG1 downregulation significantly inhibited cell proliferation and arrested the cell cycle pathway as evidenced by changes in checkpoint genes (such as cyclin D1, E and B1). PTTG1 knockdown also increased apoptosis, as evidenced by the upregulation of apoptotic genes [such as cleaved (c‑) Caspase‑7 and c‑poly (ADP‑ribose) polymerase]. Moreover, PTTG1 downregulation promoted cellular senescence, as shown by western blotting and SA‑β‑gal staining. Finally, senescence‑induced DNA damage was observed in OSCC cells, which accelerates genomic instability, through chromosomal damage analysis. Taken together, the present findings suggested that PTTG1 acts as a proto‑oncogene; regulates cell proliferation, cell cycle, cellular senescence and DNA damage in OSCC; and may serve as a novel diagnostic biomarker and potential therapeutic target for OSCC.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell invasion assay data shown in Fig. 6B on p. 940, and western blot data featured in Fig. 7B on p. 942, had already appeared in previously published articles written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, 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 satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 45: 933‑944, 2021; DOI: 10.3892/or.2020.7905].

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the western blot data shown for the MMP‑9 experiment in Fig. 4 on p. 1493 were strikingly similar to the western blots shown for the total‑Akt experiments in Fig. 6 on p. 1494. After having re‑examined their original data files, the authors realized that Fig. 6 had been inadvertently assembled incorrectly. The revised version of Fig. 6, containing the correct data for the total‑Akt experiments, is shown below. Note that the corrections made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 31: 1489‑1497, 2014; DOI: 10.3892/or.2013.2961].

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell cell invasion assay data shown in Fig. 2B on p. 42 and the immunofluorescence data shown in Fig. 4D on p. 44 were strikingly similar to data appearing in other articles written by different authors at different research institutes that were submitted to different journals at around the same time. Moreover, a further investigation of this paper undertaken by the Editorial Office identified a large number of overlapping data panels comparing the Transwell cell migration and invasion assay data and the scratch‑wound assay data both within and between Figs. 2 and 3, where data which were intended to have shown the results from differently performed experiments had apparently been derived from the same original source, including an overlapping section of data within the 'MEG3+mimic' panel in Fig. 3G that would be difficult to attribute to pure chance. Owing to the fact that the contentious data in the above article had already been submitted for publication at around the same time as its submission to Oncology Reports, and given an overall lack of confidence in the presented data, 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. [Oncology Reports 40: 39‑48, 2018; DOI: 10.3892/or.2018.6424].

Zinc finger protein 180 (ZNF180) is a multifunctional protein that interacts with nucleic acids and regulates various cellular processes; however, the function of ZNF180 in colorectal cancer (CRC) remains unclear. The present study investigated the role and function of ZNF180 in CRC, and aimed to reveal the underlying molecular mechanism. The results revealed that ZNF180 was downregulated in CRC tissues and was associated with a good prognosis in patients with CRC. Additionally, the expression of ZNF180 was downregulated by methylation in CRC. In vivo and in vitro experiments revealed that ZNF180 overexpression was functionally associated with the inhibition of cell proliferation and the induction of apoptosis. Mechanistically, chromatin immunoprecipitation‑PCR and luciferase assays demonstrated that ZNF180 markedly regulated the transcriptional activity of methyltransferase 14, N6‑adenosine‑methyltransferase non‑catalytic subunit (METTL14) by directly binding to and activating its promoter region. Simultaneous overexpression of ZNF180 and knockdown of METTL14 indicated that the reduction of METTL14 could suppress the effects of ZNF180 on the induction of apoptosis. Clinically, the present study observed a significant positive correlation between ZNF180 and METTL14 expression levels, and low expression of ZNF180 and METTL14 predicted a poor prognosis in CRC. Overall, these findings revealed a novel mechanism by which the ZNF180/METTL14 axis may modulate apoptosis and cell proliferation in CRC. This evidence suggests that this axis may serve as a prognostic biomarker and therapeutic target in patients with CRC.

Non‑small cell lung cancer (NSCLC) is a highly prevalent lung malignancy characterized by insidious onset, rapid progression and advanced stage at the time of diagnosis, making radical surgery impossible. Sirtuin (SIRT) is a histone deacetylase that relies on NAD+ for its function, regulating the aging process through modifications in protein activity and stability. It is intricately linked to various processes, including glycolipid metabolism, inflammation, lifespan regulation, tumor formation and stress response. An increasing number of studies indicate that SIRTs significantly contribute to the progression of NSCLC by regulating pathophysiological processes such as energy metabolism, autophagy and apoptosis in tumor cells through the deacetylation of histones or non‑histone proteins. The present review elaborates on the roles of different SIRTs and their mechanisms in NSCLC, while also summarizing novel therapeutic agents based on SIRTs. It aims to present new ideas and a theoretical basis for NSCLC treatment.

Following the publication of this article, an interested reader drew to the authors' attention that, for the cell migration assay data shown in Fig. 3C on p. 1287, the '2.5 μg/ml' and '5.0 μg/ml' panels appeared to be overlapping, such that these data were apparently derived from the same original source where they were intended to show the results from differently performed experiments. Upon asking the authors to provide an explanation, after having referred back to their original data, the authors realized that they had made an inadvertent error in assembling this figure. The revised version of Fig. 3, now showing the correct data for the '5.0 μg/ml' experiment, is shown on the next page. Note that the error made in assembling the data in Fig. 3 did not greatly affect either the results or the conclusions reported in this paper, and all the authors agree to the publication of this corrigendum. The authors regret that this error went unnoticed prior to the publication of their article, and are grateful to the Editor of Oncology Reports for granting them this opportunity to publish a corrigendum. They also apologize to the readership for any inconvenience caused. [Oncology Reports 33: 1284‑1290, 2015; DOI: 10.3892/or.2014.3682].