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NRF2 is an important regulatory transcription factor involved in tumor immunity and tumorigenesis. In this study, we firstly identified that FKBP4/NR3C1 axis was a novel negative regulator of NRF2 in human breast cancer (BC) cells. The effect of FKBP4 appeared to be at protein level of NRF2 since it could not suppress the expression of NRF2 at mRNA level. Bioinformatics analysis and in vitro experiments further demonstrated that FKBP4 regulated NRF2 via regulating nuclear translocation of NR3C1. We then reported that naringenin, a flavonoid, widely distributed in citrus and tomato, could suppress autophagy and proliferation of BC cells through FKBP4/NR3C1/NRF2 signaling pathway in vitro and in vivo. Naringenin was also found to promote dendritic cell (DC) differentiation and maturation through FKBP4/NR3C1/NRF2 axis. Therefore, our study found that naringenin could induce inhibition of autophagy and cell proliferation in BC cells and enhance DC differentiation and maturation, at least in part, though regulation of FKBP4/NR3C1/NRF2 signaling pathway. Identification of FKBP4/NR3C1/NRF2 axis would provide insights for novel anti-tumor strategy against BC among tumor microenvironment. [ABSTRACT FROM AUTHOR]

Objectives The aim of the present study was to investigate changes in the psychological state of medical personnel in the Department of Radiotherapy during the COVID-19 epidemic. Methods Psychological state was evaluated using the Pittsburgh Sleep Quality Index (PSQI), Self-Rating Depression Scale (SDS), and Self-Rating Anxiety Scale (SAS). All three questionnaires were first completed by medical personnel on 17–18 February 2020 and were repeated every 3 months thereafter until 17–18 August. The number and intentions of patients receiving radiotherapy (RT) in our department were also collected. Results Twenty medical personnel participated in the present study. The global PSQI score recorded in August was significantly lower than that recorded in February (P = 0.045). Among the seven components of the PSQI, sleep quality (P = 0.048) and daytime dysfunction (P = 0.006) in August were significantly improved compared with February, whereas SDS and SAS did not significantly differ among the three different time points. The proportion of patients who received palliative radiotherapy was significantly higher on 18 May than on 17 February (P = 0.005). Conclusions Medical personnel in the Department of Radiotherapy experienced a significantly elevated incidence of sleeping problems during the early COVID-19 outbreak period. Multiple combinations of protective measures to avoid infection could improve sleep quality and ensure the safe delivery of RT to cancer patients. [ABSTRACT FROM AUTHOR]

Background: To evaluate the expression of programmed death‐1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) by using immunohistochemistry analysis in locoregionally advanced nasopharyngeal carcinoma (NPC) patients receiving cisplatin, fluorouracil, and docetaxel followed by concurrent chemoradiotherapy. Methods: As part of a previously reported trial, 108 patients were enrolled in this study. Results: We observed that Epstein–Barr Virus (EBV) antibody levels were associated with PD‐1 positive staining in NPC and PD‐1 positive staining was identified as an independent prognostic factor for progression‐free survival (hazard ratio 0.363, 95% confidence interval 0.134‐0.987, P = .047). By contrast, the correlation between the PD‐L1 level and hemoglobin, lactate dehydrogenase and high‐sensitivity C‐reactive protein was not identified. Moreover, high levels of PD‐L1 staining were not significantly associated with clinical outcomes. Conclusion: NPC patients with negative PD‐1 staining had a significantly reduced survival outcome. Furthermore, patients with positive PD‐1 staining had significantly higher EBV antibody levels. [ABSTRACT FROM AUTHOR]

Purpose: This study was aimed to identify the expression pattern of vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC) and to explore its potential correlation with the progression of NSCLC. Methods: Gene expression profile GSE39345 was downloaded from the Gene Expression Omnibus database. Twenty healthy controls and 32 NSCLC samples before chemotherapy were analyzed to identify the differentially expressed genes (DEGs). Then pathway enrichment analysis of the DEGs was performed and protein-protein interaction networks were constructed. Particularly, VEGF genes and the VEGF signaling pathway were analyzed. The sub-network was constructed followed by functional enrichment analysis. Results: Total 1666 up-regulated and 1542 down-regulated DEGs were identified. The down-regulated DEGs were mainly enriched in the pathways associated with cancer. VEGFA and VEGFB were found to be the initiating factor of VEGF signaling pathway. In addition, in the epidermal growth factor receptor (EGFR), VEGFA and VEGFB associated sub-network, kinase insert domain receptor (KDR), fibronectin 1 (FN1), transforming growth factor beta induced (TGFBI) and proliferating cell nuclear antigen (PCNA) were found to interact with at least two of the three hub genes. The DEGs in this sub-network were mainly enriched in Gene Ontology terms related to cell proliferation. Conclusion: EGFR, KDR, FN1, TGFBI and PCNA may interact with VEGFA to play important roles in NSCLC tumorigenesis. These genes and corresponding proteins may have the potential to be used as the targets for either diagnosis or treatment of patients with NSCLC. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is a disease with morbidity ranking the first of women worldwidely. In current study, 11 DE-miRNAs, consisting of four FKBP4 related DE-miRNAs and seven FKBP5 related DE-miRNAs, were screened. Four hundred and eighty two predicted lncRNAs were found for DE-miRNAs. Then, expression and prognostic results of nine of top 20 lncRNAs of BC were significantly identified. LINC00662 and LINC00963 expression were significantly associated with patients' overall survival (OS). Then, nine potential upstream transcription factors were identified in motifs of DE-miRNAs. Three hundred and twenty target genes were identified for GO annotation and KEGG pathway analysis, which were mainly enriched in cysteine-type endopeptidase activity involved in apoptotic process. Construction and analysis in PPI network showed that RAB7A was selected as a hub gene with the topest connectivity scores. Differential expression analysis of nine in top ten hub genes of BC were significantly identified. RAB7A and ARRB1 expression were significantly related with BC patients' OS. • Eleven FKBP mRNA-miRNA regulatory networks in BC by miRWalk database were established. • Twenty most frequent DE-miRNAs associated lncRNAs were screened by LncBase v.2 database. • Nine transcription factors for DE-miRNAs and corresponding motifs were predicted by miRGen v3 database. • Downstream target genes of DE-miRNAs were screened by miRWalk database and hub genes were identified. [ABSTRACT FROM AUTHOR]

Objective: To explore the advantages of dosimetry and the treatment efficiency of tangent-arc technology in deep inspiration breath-hold radiotherapy for breast cancer., Methods: Forty patients with left-sided breast cancer who were treated in our hospital from May 2020 to June 2021 were randomly selected and divided into two groups. The first group's plan was a continuous semi-arc that started at 145° ( ± 5°) and stopped at 325° ( ± 5°). The other group's plan, defined as the tangent-arc plan, had two arcs: the first arc started at 145° ( ± 5°) and stopped at 85° ( ± 5°), and the second arc started at 25° ( ± 5°) and stopped at 325° ( ± 5°). We compared the target dose, dose in organs at risk (OARs), and treatment time between the two groups., Results: The target dose was similar between the continuous semiarc and tangent-arc groups. The V 5 of the right lung was significantly different between the two groups (Dif 5.52, 95% confidence interval 1.92-9.13, t =3.10, P =0.004), with the patients in the continuous semi-arc and tangent-arc groups having lung V 5 values of (9.16 ± 1.62)%, and (3.64 ± 0.73)%, respectively. The maximum dose to the spinal cord was (1835.88 ± 222.17) cGy in the continuous semi-arc group and (599.42 ± 153.91) cGy in the tangent-arc group, yielding a significant difference between the two groups (Dif 1236.46, 95% confidence interval 689.32-1783.6, t =4.57, P <0.001). The treatment times was (311.70 ± 60.45) s for patients in the continuous semi-arc group and (254.66 ± 40.73) s for patients in the tangent-arc group, and there was a significant difference in the mean number of treatment times between the two groups (Dif 57.04, 95% confidence interval 24.05-90.03, t =3.5, P =0.001)., Conclusion: Both the continuous semi-arc and tangent-arc plans met the clinical prescription dose requirements. The OARs received less radiation with the tangent-arc plan than the continuous semi-arc plan, especially for the lung (measured as V 5 ) and the spinal cord (measured as the maximum dose). Tangent-arc plan took significantly less time than the continuous semi-arc, which can greatly improve treatment efficiency. Therefore, tangent-arc plans are superior continuous semi-arc plans for all cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Zhan, Jia, Xiong, Lin, Li, Liu, Qiu, Zhang, Ding, Fu and Chen.)

Background : Solute Carrier Family 3 Member 2 (SLC3A2) is a member of the solute carrier family that plays pivotal roles in regulation of intracellular calcium levels and transports L-type amino acids. However, there are insufficient scientific researches on the prognostic and immunological roles of SLC3A2 in breast cancer (BC) and whether everolimus regulates novel SLC3A2 related molecular mechanism in the immuno-oncology context of the tumor microenvironment (TME), therefore, we see a necessity to conduct the current in silico and biological experimental study. Methods : Using diverse online databases, we investigated the role of SLC3A2 in therapy response, clinicopathological characteristics, tumor immune infiltration, genetic alteration, methylation and single cell sequencing in BC. WB, Co-IP, cell proliferation assay, Edu staining, ROS and GSH assay and in vivo tumor xenograft assays were performed to verify FKBP1A/SLC3A2 axis in everolimus inducing ferroptosis of breast cancer. Co-cultures and IL-9 ELISA were performed to demonstrate the T lymphocyte function. Results : We demonstrated that SLC3A2 was aberrantly expressed among various BC cohorts. Our results also suggested that SLC3A2 expression was associated with chemotherapeutic outcome in BC patients. Our results further indicated that SLC3A2 was associated with tumor infiltration of cytotoxic T cell but not other immune cells among BC TME. The alterations in SLC3A2 gene had a significant correlation to relapse free survival and contributed a significant impact on BC tumor mutational burden. Finally, SLC3A2 was illustrated to be expressed in diverse BC cellular populations at single cell level, and negatively linked to angiogenesis, inflammation and quiescence, but positively correlated with other functional phenotypes. Noteworthily, everolimus (a targeted therapy drug for BC) related protein, FK506-binding protein 1A (FKBP1A) was found to bind with SLC3A2, and negatively regulated SLC3A2 expression during the processes of everolimus inducing ferroptosis of BC cells and promoting anti-proliferation of Th9 lymphocytes. Conclusions : Altogether, our study strongly implies that SLC3A2 is an immuno-oncogenic factor and FKBP1A/SLC3A2 axis would provide insights for a novel immunotherapy approach for the treatment of BC in the context of TME., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Histones are DNA-binding basic proteins found in chromosomes. After the histone translation, its amino tail undergoes various modifications, such as methylation, acetylation, phosphorylation, ubiquitination, malonylation, propionylation, butyrylation, crotonylation, and lactylation, which together constitute the "histone code." The relationship between their combination and biological function can be used as an important epigenetic marker. Methylation and demethylation of the same histone residue, acetylation and deacetylation, phosphorylation and dephosphorylation, and even methylation and acetylation between different histone residues cooperate or antagonize with each other, forming a complex network. Histone-modifying enzymes, which cause numerous histone codes, have become a hot topic in the research on cancer therapeutic targets. Therefore, a thorough understanding of the role of histone post-translational modifications (PTMs) in cell life activities is very important for preventing and treating human diseases. In this review, several most thoroughly studied and newly discovered histone PTMs are introduced. Furthermore, we focus on the histone-modifying enzymes with carcinogenic potential, their abnormal modification sites in various tumors, and multiple essential molecular regulation mechanism. Finally, we summarize the missing areas of the current research and point out the direction of future research. We hope to provide a comprehensive understanding and promote further research in this field., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Objective: In individuals with stage IB1-IIA2 cervical cancer (CC) who received postoperative radiotherapy ± chemotherapy (PORT/CRT), the interaction between sarcopenia and malnutrition remains elusive, let alone employing a nomogram model based on radiomic features of psoas extracted at the level of the third lumbar vertebra (L3). This study was set to develop a radiomics-based nomogram model to predict malnutrition as per the Patient-Generated Subjective Global Assessment (PG-SGA) for individuals with CC., Methods: In total, 120 individuals with CC underwent computed tomography (CT) scans before PORT/CRT. The radiomic features of psoas at L3 were obtained from non-enhanced CT images. Identification of the optimal features and construction of the rad-score formula were conducted utilizing the least absolute shrinkage and selection operator (LASSO) logistic regression to predict malnutrition in the training dataset (radiomic model). Identification of the major clinical factors in the clinical model was performed by means of binary logistic regression analysis. The radiomics-based nomogram was further developed by integrating radiomic signatures and clinical risk factors (combined model). The receiver operating characteristic (ROC) curves and decision curves analysis (DCA) were employed for the evaluation and comparison of the three models in terms of their predictive performance., Results: Twelve radiomic features in total were chosen, and the rad-score was determined with the help of the non-zero coefficient from LASSO regression. Multivariate analysis revealed that besides rad-score, age and Eastern Cooperative Oncology Group performance status could independently predict malnutrition. As per the data of this analysis, a nomogram prediction model was constructed. The area under the ROC curves (AUC) values of the radiomic and clinical models were 0.778 and 0.847 for the training and 0.776 and 0.776 for the validation sets, respectively. An increase in the AUC was observed up to 0.972 and 0.805 in the training and validation sets, respectively, in the combined model. DCA also confirmed the clinical benefit of the combined model., Conclusion: This radiomics-based nomogram model depicted potential for use as a marker for predicting malnutrition in stage IB1-IIA2 CC patients who underwent PORT/CRT and required further investigation with a large sample size., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, Xu, Chen, Shou, Chen, Jia, Zhang, Ding, Xiong, Wang and Song.)

TMEM173 is a pattern recognition receptor detecting cytoplasmic nucleic acids and transmits cGAS related signals that activate host innate immune responses. It has also been found to be involved in tumor immunity and tumorigenesis. In this study, we first identified that the FKBP4/NR3C1 axis was a novel negative regulator of TMEM173 in human breast cancer (BC) cells. The effect of FKBP4 appeared to be at the transcriptional level of TMEM173, because it could suppress the promoter activity of TMEM173, thereby affecting TMEM173 at mRNA and protein levels. Past studies, our bioinformatics analysis, and in vitro experiments further implied that FKBP4 regulated TMEM173 via regulating nuclear translocation of NR3C1. We then demonstrated that the FKBP4/NR3C1/TMEM173 signaling pathway could regulate autophagy and proliferation of BC cells as well as dendritic cell (DC) abundance through exosome release. Our study found an unprecedented strategy used by BC to escape from TMEM173 mediated tumor suppression. Identification of the FKBP4/NR3C1 axis as a novel TMEM173 regulator would provide insights for novel anti-tumor strategy against BC among tumor microenvironment., Competing Interests: The authors declare that they have no competing interests., (© 2022 The Author(s).)

Background: This study constructed and demonstrated a model to predict the overall survival (OS) of newly diagnosed distant metastatic cervical cancer (mCC) patients. Methods: The SEER (Surveillance, Epidemiology, and End Results) database was used to collect the eligible data, which from 2010 to 2016. Then these data were separated into training and validation cohorts (7:3) randomly. Cox regression analyses was used to identify parameters significantly correlated with OS. Harrell's Concordance index (C-index), calibration curves, and decision curve analysis (DCA) were further applied to verify the performance of this model. Results: A total of 2,091 eligible patients were enrolled and randomly split into training ( n = 1,467) and validation ( n = 624) cohorts. Multivariate analyses revealed that age, histology, T stage, tumor size, metastatic sites, local surgery, chemotherapy, and radiotherapy were independent prognostic parameters and were then used to build a nomogram for predicting 1 and 2-year OS. The C-index of training group and validation group was 0.714 and 0.707, respectively. The calibration curve demonstrated that the actual observation was in good agreement with the predicted results concluded by the nomogram model. Its clinical usefulness was further revealed by the DCAs. Based on the scores from the nomogram, a corresponding risk classification system was constructed. In the overall population, the median OS time was 23.0 months (95% confidence interval [CI], 20.5-25.5), 12.0 months (95% CI, 11.1-12.9), and 5.0 months (95% CI, 4.4-5.6), in the low-risk group, intermediate-risk group, and high-risk group, respectively. Conclusion: A novel nomogram and a risk classification system were established in this study, which purposed to predict the OS time with mCC patients. These tools could be applied to prognostic analysis and should be validated in future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yu, Huang, Zhong, Song, Xu, Jia, Hu and Shou.)

Increasing evidences have shown that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. However, the contributions of lncRNAs to colorectal cancer remain largely unknown. Here, we identify a lncRNA AFAP1-AS1 that facilitates colorectal cancer, where it is upregulated. AFAP1-AS1 expression was associated with colorectal cancer patient survival. AFAP1-AS1 knockdown inhibited cell proliferation, cell cycle, and tumorigenesis in an subcutaneous mouse xenograft model system. Further data demonstrated that AFAP1-AS1 was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of EZH2 target genes. Our findings indicate that AFAP1-AS1 is an oncogenic lncRNA that promotes tumor progression and may be a novel prognostic factor in colorectal cancer. Targeting AFAP1-AS1 might be a potential therapeutic strategy for colorectal cancer treatment., Competing Interests: None.

This study compared the efficiency and safety of definitive concurrent chemoradiotherapy (CCRT) using Paclitaxel plus Cisplatin (TP) versus S-1 plus Cisplatin (CS) in unresectable locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2009 and December 2013, 203 LAESCC patients were retrospectively reviewed. We performed a propensity score matching analysis; 41 patients treated with the CS regimen were matched 1:1 to patients who received the TP regimen. Patient- and disease-related characteristics were well-balanced between the two groups. The CS group showed significantly better treatment compliance (90.2% vs. 70.7%, P = 0.026) and less hospital stay (48 days vs 49 days, P = 0.025) over the TP group during the CCRT course. The complete response rate was comparable between the two groups (51.2% vs. 48.8%, P = 0.825). The 1- and 3-year overall survival (OS) rates in the TP group were 63.4% and 32.4% compared to 62.8% and 32.1% in the CS group, respectively (P = 0.796). The 1- and 3-year progression-free survival (PFS) rates in the TP group were 51.2% and 24.9%, compared to 53.6% and 18.9% in the CS group, respectively (P = 0.630). The incidence of severe and total neutropenia in the TP group was significantly higher compared to the CS group (P = 0.011 and 0.046, respectively). Multivariate analysis revealed that T stage and the complete response rate were strong prognostic factors associated with OS and PFS. In conclusion, both treatment regimens yielded satisfactory survival outcomes, but the CS regimen could significantly improve treatment compliance, reduce hematological toxicities and lengths of hospital stay. Future prospective studies in large cohorts are highly warranted to confirm the findings in our report.

We aimed to systematically evaluate the association between allergic conditions and the risk of Hodgkin's lymphoma (HL) and non-HL (NHL). Systematic literature searches in PubMed and Embase were conducted up to October 2015 to identify eligible studies. Either a fixed-effects model or a random-effects model was adopted to estimate overall odds ratios (ORs) according to heterogeneity across studies. Subgroup and publication bias analyses were applied. A total of 24 case-control studies and 13 cohort studies (conducted from 1987 to 2015) were included in the analysis of the risk of NHL. History of any allergic condition was inversely associated with the risk of NHL in case-control studies (OR =0.83, 95% CI 0.76-0.91), while the reduction in the risk of NHL was not observed in cohort studies (OR =1.18, 95% CI 0.98-1.42). Significant association with the risk of NHL was found for asthma, hay fever, food allergy, allergic rhinitis, and hives. In the pooled analysis of the risk of HL, 12 studies (two were cohort studies) were included. The pooled OR was 0.96 (95% CI 0.84-1.09) for case-control studies and 1.46 (95% CI 0.63-3.38) for cohort studies. For specific allergic condition, we observed a reduced risk of HL in individuals with hay fever and food allergy. In conclusion, history of any allergic condition was not significantly associated with the risk of NHL or HL. Several specific allergic conditions, including asthma, hay fever, food allergy, and allergic rhinitis, might be associated with a reduced risk of NHL, while individuals with hay fever or food allergy may have a reduced risk of HL., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: The aim of this study was to investigate the efficiency and safety of using S-1 as monotherapy and maintenance therapy combined with definitive concurrent radiotherapy for elderly patients with esophageal cancer., Patients and Methods: From January 2009 to December 2010, 68 elderly patients were included. Radiotherapy was delivered with a daily fraction of 1.8-2.0 Gy to a total radiation dose of 54.0-60.0 Gy. Preplanned concurrent S-1 (80 mg/m(2)/d) was given on days 1-14, every 3 weeks. After concurrent chemoradiotherapy, maintenance S-1 was repeated up to four cycles., Results: The median age of the enrolled patients was 76 years (range: 70-88 years), and the clinical stages were stage I (two patients), stage II (24 patients), stage III (28 patients), and stage IV (14 patients). A total of 51 (75.0%) patients finished treatment on schedule, with a median of five cycles of S-1, in which 35 (51.5%) patients achieved complete response. The median follow-up time was 42.7 months, and the median overall survival (OS) and progression-free survival (PFS) times were 25.7 months and 21.5 months, respectively. The 1-year, 3-year, and 5-year OS and PFS rates were 70.6%, 41.8%, and 25.9% and 68.1%, 32.9%, and 15.9%, respectively. Grade ≥3 neutropenia and leukopenia were found in 14 patients and 13 patients, respectively. The most common nonhematologic toxicity was esophagitis including six patients and one patient with grades 3 and 4, respectively. Multivariate analysis revealed that cycles of S-1 and complete response were strong factors for OS and PFS., Conclusion: For geriatric patients with esophageal cancer, S-1 as monotherapy and maintenance chemotherapy in combination with definitive concurrent radiation therapy yielded satisfactory survival outcomes with tolerable toxicities. More studies are highly warranted to further clarify this issue.