Prognostic value of gamma-interferon-inducible lysosomal thiol reductase expression in female patients diagnosed with breast cancer.

Because of the high heterogeneity of breast cancer outcome, identification of novel prognostic biomarkers is critical to improve patient stratification and guide precise treatment. We examined the prognostic value of gamma-interferon-inducible lysosomal thiol reductase (GILT) expression in a training set of 416 breast cancer patients and a validation set of 210 patients, and performed functional studies to investigate the functions and underlying mechanisms of GILT on breast cancer prognosis. Our results indicated that high GILT expression in breast cancer cells was associated with improved disease-free survival (DFS; hazard ratio [HR] = 0.189, 95% confidence interval [CI]: 0.099-0.361) and breast cancer-specific survival (BCSS; HR = 0.187, 95% CI: 0.080-0.437) of breast cancer patients both in the training set and the external validation set (HR = 0.453, 95% CI: 0.235-0.873 for DFS, HR = 0.488, 95% CI: 0.245-0.970 for BCSS). In vitro and in vivo studies showed that GILT overexpression inhibited breast cancer cells proliferation, invasion, migration and tumor formation in nude mice and increased sensitivity of breast cancer cells to standard treatment. Proteomics analysis indicated that GILT inhibited reactive oxygen species (ROS) and autophagy activation in breast cancer cells, and GILT overexpression-mediated tumor growth was further enhanced in the presence of autophagy or ROS inhibitors. Our results demonstrate that GILT expression can be effectively used to predict the prognosis and guide treatment strategies of breast cancer patients.

The predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in operable and advanced non-small-cell lung cancer.

OBJECTIVE: The incidence of brain metastases greatly varies in patients with non-small-cell lung cancer, and molecular markers are considered to predict brain metastases. Therefore, this study sought to identify the predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in non-small-cell lung cancer. METHODS: Patients who received a curable surgery for their lung cancer were screened according to our criteria. Formalin-fixed paraffin-embedded samples from the patients were examined for the expression of miRNA-328 and miRNA-378 using real-time polymerase chain reaction and the expression of N-cadherin, E-cadherin, vascular endothelial growth factor, protein kinase Cα and S100B were investigated using immunohistochemical staining. RESULTS: In total, 86 patients were screened for this study and 23 patients were diagnosed with brain metastases during the follow-up period. Comparing patients with and without brain metastases, the expression of miRNA-328 and miRNA-378 in tumor tissues were significantly different (P = 6.2 × 10(-5) and P = 2.8 × 10(-5), respectively). For the patients with brain metastases, the expression of miRNA-328 and miRNA-378 in tumor tissues compared with para-carcinoma tissues were also significantly different (P = 2.2 × 10(-5) and P = 1.6 × 10(-5), respectively). For patients with brain metastases, the association between miRNA-328 and protein kinase Cα was significant (r = 0.591, P = 0.003), but that between miRNA-378 and protein kinase Cα was not significant (r = 0.259, P = 0.232). CONCLUSIONS: The expression of miRNA-328 and miRNA-378 in tumor tissues can be used to predict brain metastases in patients with non-small-cell lung cancer. miRNA-328 might promote brain metastases by regulating the expression of protein kinase Cα. However, the mechanisms of miRNA-378 to promote brain metastases should be studied in the future.

Erythropoiesis-stimulating agents in the management of cancer patients with anemia: a meta-analysis.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are widely used in the management of anemia in cancer patients. Despite their apparent effectiveness, recent studies have suggested that ESAs could result in serious adverse events and even higher mortality. The aim of the current study was to evaluate the benefits and risks of ESAs in the management of cancer patients with anemia using a meta-analysis. METHODS: The initial literature search covered Medline, PubMed, Embase, and the Cochrane Center Register of Controlled Trials, and identified 1,569 articles. The final meta-analysis included eight randomized controlled trials (n=2,387) in cancer patients with <11 g/dL hemoglobin (Hb) at the baseline and target Hb (for stopping ESA treatment) at no more than 13 g/dL. The assessment measures included Hb response, blood transfusion rate and adverse events that included venous thromboemblism (VTE), hypertension, and on-study mortality. The results are expressed as pooled odds ratio (OR). Publication bias was assessed using funnel plot analysis. RESULTS: ESAs significantly increased the Hb concentration [OR 7.85, 95% confidence interval (CI): 5.85 to 10.53, P<0.001] and reduced the red blood cell (RBC) transfusion rate (OR 0.52, 95% CI: 0.42 to 0.65, P<0.001). ESAs did not increase the accumulated adverse events (OR 0.95, P=0.82), or the on-study mortality (OR 1.09, P=0.47). CONCLUSIONS: ESAs are not associated with increased frequency of severe adverse events in anemic cancer patients when the target Hb value is no more than 13 g/dL.

Radiation-induced NF-κB activation is involved in cochlear damage in mice via promotion of a local inflammatory response.

The radiation-induced inflammatory response is involved in radiation damage to the cochlea and causes sensorineural hearing loss (SNHL). NF-κB, as the master switch of the inflammatory response, regulates the expression of many inflammation-related genes and thus the inflammatory response. Therefore, in this study we used a mouse model to determine whether radiation-induced NF-κB activation is involved in damage to the cochlea and to investigate the underlying mechanism. Eventually, we found that NF-κB was activated after radiation of the cochleae and the activation reached a maximum at 2-6 h after radiation. And morphological analysis showed severe damage to the cochleae after radiation, but this damage was significantly ameliorated by JSH-23 (an inhibitor of NF-κB) pretreatment. Along with these morphological changes, the expression levels of proinflammatory molecules (including proinflammatory cytokines IL-6, TNF-α, COX-2 and inflammation-related proteins VCAM-1, MIP-1ß) in the cochlear tissues were significantly increased after radiation, but were significantly decreased by JSH-23 pretreatment compared to radiation alone. Therefore, these results indicated that radiation-induced NF-κB activation was involved in damage to the cochleae and resultant SNHL via its promotion of the inflammatory response mediated by overexpression of some proinflammatory molecules in cochlear tissues, and inhibition of radiation-induced NF-κB was conducive to preventing such damage.

Stathmin1 promotes lymph node metastasis in hypopharyngeal squamous cell carcinoma via regulation of HIF­1α/VEGF­A axis and MTA1 expression.

Extensive neck lymph node metastasis (LNM) is an important clinical feature of hypopharyngeal squamous cell carcinoma (HSCC). Stathmin1 (STMN1) is closely associated with LNM in numerous human cancers. In the present study, the association between STMN1 and neck LNM in HSCC and the underlying molecular mechanisms were explored. First, postoperative samples of HSCC were screened and the association between STMN1 and neck LNM in HSCC was analyzed. Then, cell functional experiments were performed to assess the potential of STMN1 to promote invasion and migration. Subsequently, the potential target genes and pathways of STMN1 were predicted using bioinformatics analysis. Finally, the obtained target genes and pathways of STMN1 were validated by reverse transcription-quantitative PCR (RT-qPCR) and western blot analyses to confirm the potential mechanisms by which STMN1 promotes LNM in HSCC. As a result, a total of 117 postoperative samples of HSCC were screened, and STMN1 was proven to be associated with neck LNM in HSCC. Further, cell functional experiments established that high expression of STMN1 could actually promote FaDu cell invasion and metastasis. Bioinformatics analysis revealed that high expression of STMN1 was associated with the activation of hypoxia inducible factor-1alpha (HIF-1α) pathway and increased expression of metastasis-associated protein 1 (MTA1). Finally, RT-qPCR and western blot analyses confirmed that STMN1 promotes the expression levels of HIF-1α/vascular endothelial growth factor (VEGF)-A and MTA1 in FaDu cell lines. In conclusion, it was found that high expression of STMN1 promoted neck LNM in HSCC and the potential mechanisms may be via regulation of the HIF-1α/VEGF-A axis and MTA1 expression.

Overexpression of microRNA-19a-3p promotes lymph node metastasis of esophageal squamous cell carcinoma via the RAC1/CDC42-PAK1 pathway.

BACKGROUND: A tendency towards extensive regional lymph node metastasis (LNM) is a typical clinical characteristic of esophageal squamous cell carcinoma (ESCC). Up-regulated microRNA (miR)-19a-3p was verified as a predictor of LNM in ESCC in previous microarray analyses, but the underlying mechanisms remain unclear. Here, in vitro experiments were performed to confirm the effect of miR-19a-3p on promoting LNM and to explore the underlying mechanisms. METHODS: KYSE-150 and TE-1 cell lines were transfected with lentiviral vectors to inhibit miR-19a-3p (LV-miR-19a-3p-inhibition), and cell proliferation, invasion, and migration were assessed. Target genes of miR-19a-3p were identified by sequencing analysis and quantitative reverse transcription PCR (qRT-PCR); Western blotting was performed to confirm targets and explore the potential mechanisms underlying the effect of miR-19a-3p on LNM. RESULTS: miR-19a-3p had no effect on ESCC cell proliferation, whereas miR-19a-3p overexpression promoted the invasion and migration of ESCC cells. qRT-PCR verification and western blot analysis showed that LV-miR-19a-3p-inhibition downregulated cell division cycle 42 (CDC42), Rac family small GTPase 1 (RAC1), and p21 activated kinase 1 (PAK1). CONCLUSIONS: Overexpression of miR-19a-3p increased the invasion and migration of ESCC cells via the RAC1/CDC42-PAK1 pathway, suggesting that this pathway mediates the effect of miR-19a-3p on promoting LNM in ESCC.

Microarray analysis of miRNA based on the regional lymph node metastasis status of esophageal squamous cell carcinoma.

BACKGROUND: Tendency toward extensive regional lymph node metastasis (LNM) is an important clinical characteristic of esophageal squamous cell carcinoma (ESCC) and differs greatly between patients. MicroRNAs (miRNAs) are involved in the invasion and metastasis of ESCC. We performed a microarray analysis of miRNAs based on LNM status to identify tumor-specific miRNAs for the prediction of LNM in ESCC. METHODS: Four pairs of ESCC tumor tissues with or without LNM were selected for microarray analysis to identify differentially expressed miRNAs, then 50 tumor tissue samples were selected to verify the differences of the screened miRNAs with quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The relations between candidate miRNAs and clinicopathologic features were analyzed to confirm tumor specificity in the prediction of LNM in ESCC. Target gene prediction using miRWalk2.0 was used to analyze the potential mechanisms of the tumor-specific miRNAs. RESULTS: The present microarray analysis identified significant differential expression in 62 miRNAs in the ESCC samples with LNM, compared to those without LNM. Of these, 19 miRNAs were selected for qRT-PCR verification, and three miRNAs were significantly upregulated in ESCC samples with LNM compared to those without LNM. The three miRNAs were not significantly associated with any other clinicopathologic features except for the TNM stage and could be regarded as tumor-specific miRNAs capable of predicting LNM in ESCC. Finally, 858 mRNAs were significantly associated with tumor-specific miRNAs and possibly involved in the regulation of LNM in ESCC. CONCLUSIONS: The present microarray analysis based on LNM status identified three tumor-specific miRNAs for predicting regional LNM in ESCC, which provides valuable clues for potential mechanism research and guarantees further investigation.

A unique radioprotective effect of resolvin E1 reduces irradiation-induced damage to the inner ear by inhibiting the inflammatory response.

BACKGROUND: In addition to the direct effects of irradiation, the induced inflammatory response may play an important role in the damage to the inner ear caused by radiotherapy for the treatment of head and neck cancers. Resolvin E1 (RvE1) has anti-inflammatory activity, acting by reducing neutrophil infiltration and proinflammatory cytokine expression. Therefore, in this study we sought to confirm whether the inflammation induced by irradiation was involved in damage to the inner ear after radiotherapy and to investigate the protective effect and underlying mechanism of RvE1 using mouse models. METHODS: A dose of RvE1 was delivered by intraperitoneal injection to mice before irradiation. Changes in the auditory brainstem response (ABR), relative balance ability, inner ear morphology and the expression levels of inflammatory factors in the inner ear were analyzed on days 7 and 14 after irradiation and compared among different experimental groups. RESULTS: Changes of ABR and relative balance ability showed the inner functions of experimental mice presented severe damage after irradiation, but the damage was significantly alleviated after RvE1 pretreatment compared to irradiation alone. Morphological analysis of the inner ear showed severe damage to the cochlea and vestibule after irradiation. In contrast, damage to the cochlea and vestibule was significantly reduced in the RvE1-pretreated group compared to that in the irradiation alone group. Along with these functional and morphological changes, the mRNA expression level of anti-inflammatory factors interleukin-2 was significantly increased, while those of proinflammatory factors interleukin-6 and tumor necrosis factor-α were significantly decreased in the inner ear of mice after RvE1 pretreatment compared to irradiation alone. CONCLUSIONS: We believe that inflammation induced by irradiation is involved in the damage to the inner ear caused by radiotherapy, and that RvE1 reduces the damage caused by irradiation to the inner ear by regulating the induced inflammatory response.

Effect of 12-month nasal continuous positive airway pressure therapy for obstructive sleep apnea on progression of chronic kidney disease.

BACKGROUND: Obstructive sleep apnea (OSA) is common among patients with chronic kidney disease (CKD). CKD may increase the risk of OSA, and OSA may increase the risk of renal injury. Nasal continuous positive airway pressure (nCPAP) is the standard treatment for OSA. However, the effect of nCPAP on the progression of CKD is unclear. METHODS: A total of 395 patients with stage 3/4 CKD were initially examined, and 269 patients (148 non-OSA cases; 79 mild OSA cases; 42 moderate/severe OSA cases) were analyzed after implementation of the exclusion criteria. The severity of OSA was determined by polysomnography (PSG). Fifty-two OSA patients (32 mild OSA cases; 20 moderate/severe OSA cases) received nCPAP treatment for 12 months. Variables associated with OSA severity and estimated glomerular filtration rate (eGFR) were evaluated before and after the 12-month nCPAP treatment. RESULTS: Among all 269 CKD patients, body mass index (BMI), and eGFR had significant associations with OSA severity. Age, BMI, apnea-hypopnea index (AHI), mean SaO2%, and SaO2 <90% monitoring time had independent associations with lower eGFR. The 12-month nCPAP treatment significantly reduced the rate of eGFR decline. Univariate and multivariate analysis indicated that age, BMI, AHI, mean SaO2%, and SaO2 <90% monitoring time were independently associated with reduced eGFR. Furthermore, nCPAP treatment significantly improved eGFR, AHI, mean SaO2, and SaO2 <90% monitoring time in patients with mild OSA, and improved systolic/diastolic blood pressure, urinary protein level, eGFR, AHI, mean SaO2, and SaO2 <90% monitoring time for patients with moderate/severe OSA. CONCLUSION: This study of patients with CKD and OSA indicated that nCPAP therapy significantly ameliorated CKD progression, especially in those with moderate/severe OSA.

Genome-wide analysis of long non-coding RNAs in esophageal squamous cell carcinoma reveals their potential role in invasion and metastasis.

BACKGROUND: A high lymphatic metastasis rate and strong local invasive ability are the key characteristics of esophageal squamous cell carcinoma (ESCC) that affect patient survival, and long non-coding RNAs (lncRNAs) may play a crucial role. We performed genome-wide analysis of lncRNAs to identify novel biomarkers associated with local invasion and lymphatic metastasis in ESCC. METHODS: Six pairs of ESCC tumor and para-tumor tissues were subjected to microarray analysis to identify differentially expressed lncRNAs, and 25 pairs of tissues samples were used to verify the effectiveness of screened lncRNAs using quantitative reverse transcription PCR. The correlations between verified lncRNAs and clinicopathological characteristics were analyzed to confirm specific lncRNAs associated with the local invasion and lymphatic metastasis of ESCC, and gene co-expression analysis was used to predict potential mechanisms. RESULTS: Microarray analysis identified 1850 lncRNAs with significant differential expression in ESCC. Of 22 lncRNAs selected for quantitative reverse transcription PCR verification, four were significantly upregulated and one was significantly downregulated in ESCC cancer compared to para-cancer tissues. ENST00000508406.1 was significantly associated with T, N, and tumor node metastasis stages, and NR_037652.1 was significantly associated with N stage. Moreover, 49 lncRNA-messenger RNA pairs were significantly associated with the two dysregulated lncRNAs and possibly involved in the regulation of local invasion and lymphatic metastasis of ESCC. CONCLUSION: The present genome-wide analysis identified two novel and tumor-specific lncRNAs for predicting ESCC local invasion and lymphatic metastasis, providing insight into the potential underlying mechanism, which warrants further investigation.

Overexpression of long noncoding RNA PEG10 promotes proliferation, invasion and metastasis of hypopharyngeal squamous cell carcinoma.

The present study aimed to investigate the impact of overexpression of long noncoding RNA PEG10 (lncRNA PEG10) on the proliferation, invasion and metastasis of hypopharyngeal squamous cell carcinoma (HSCC). Quantitative reverse transcription polymerase chain reaction was used to quantify lncRNA PEG10 expression levels in HSCC tumor tissues samples, para-carcinoma tissue samples and the HSCC FaDu cell line. Cell proliferation assays, Transwell invasion assays and wound healing assays were used to evaluate the effects of lncRNA PEG10 on FaDu cells in vitro. In 56 eligible patients, lncRNA PEG10 was expressed at higher levels in HSCC tumor tissues compared with para-carcinoma tissues, and significant associations were observed between increased tumor expression of lncRNA PEG10 and primary tumor size, lymph node status and tumor node metastasis stage. In the in vitro experimental studies, enhanced expression of lncRNA PEG10 was significantly associated with increased proliferation, invasion and metastasis of FaDu cells. lncRNA PEG10 was upregulated in HSCC, and its overexpression in HSCC cells promoted an increase in the tumorigenic activities of proliferation, invasion and migration. The potential underlying mechanisms require investigation in future studies.

Vestibular function disorders and potential mechanisms in irradiation nasopharyngeal carcinoma patients.

CONCLUSIONS: Vestibular function disorders were widespread among nasopharyngeal carcinoma (NPC) patients. The radiation doses to the inner ears were associated with the incidence of vestibular function disorders, but the correlations were mild. The inflammatory responses and possible resolution obstacles of inflammation participated in persistent vestibular function disorders after irradiation. OBJECTIVES: To investigate the incidence of vestibular function disorders in NPC patients after irradiation and potential mechanisms. METHODS: Patients who received radical intensity-modulated radiotherapy for their NPC were recruited. The serum levels of IL-6 and IL-17 were detected by ELISA method. Vestibular evoked myogenic potential (VEMP) tests were used to evaluate vestibular function and correlation analyses were used to analyze the potential mechanisms of vestibular function disorders. RESULTS: Thirty-eight patients were included. The incidences of abnormal ocular VEMP (oVEMP) and cervical VEMP (cVEMP) were 65.79% and 80.26% at the time of completion of radiotherapy, and 61.84% and 71.05% at 3 months after radiotherapy. The mean and maximum radiation doses to the inner ears were both significantly associated with abnormal oVEMP and cVEMP (p < 0.05, all), but the correlations were all mild. The serum levels of IL-6 and IL-17 were both significantly associated with abnormal oVEMP and cVEMP after irradiation (p < 0.05, all).

Predictive value of microRNAs as novel biomarkers in detection of lymphoma.

MicroRNAs (miRNAs) have attracted many attentions in lymphoma diagnostic research. The inconsistence of diagnostic performance in these existed literatures leading us to conduct this meta-analysis. In order to have a scientific and reliable study, all related articles were screened from Medline, Embase, CNKI and other databases. The sensitivity and specificity of each involved research were used to plot the summary receiver operator characteristic (SROC) curve and calculate the area under the curve (AUC). The QUADAS-2 tool was applied to estimate the quality of included studies. In addition, Deeks' funnel plot asymmetry test was performed to estimate publication bias. Overall, 14 studies from 6 articles were included to evaluate the whole test performance. The overall pooled results were as follows: sensitivity was 0.91 (95% CI: 0.83-0.95), specificity was 0.84 (95% CI: 0.75-0.90), the AUC was 0.93 (95% CI: 0.91-0.95), positive likelihood ratio-PLR was 5.5 (95% CI: 3.5-8.8), negative likelihood ratio-NLR was 0.11 (95% CI: 0.06-0.21), and diagnostic odds ratio-DOR was 50 (95% CI: 19-128). In summary, results from meta-analysis showed that miRNAs analysis might significantly increase the diagnostic accuracy of lymphoma. Further massive prospective studies still needed to validate our conclusion before clinical application.

MicroRNA­128a, BMI1 polycomb ring finger oncogene, and reactive oxygen species inhibit the growth of U­87 MG glioblastoma cells following exposure to X­ray radiation.

Radiotherapy is an important therapeutic strategy for the treatment of numerous types of malignant tumors, including glioma. However, radioresistance and anti­apoptotic mechanisms decrease the efficacy of radiotherapy in many patients with glioma. BMI1 polycomb ring finger oncogene (Bmi­1) is an oncogene associated with radioresistance in tumor cells. MicroRNA (miRNA)­128a is a brain-specific miRNA, which suppresses Bmi­1 expression. The present study investigated the effects of various radiation intensities on U­87 MG glioma cells, as well as the role of reactive oxygen species (ROS), Bmi­1, and miRNA­128a in the cellular response to radiotherapy. The response of U­87 MG cells following exposure to X­ray radiation was assessed using a cell growth curve and inhibition ratio. Cell cycle distribution and the levels of intracellular ROS were evaluated by flow cytometry. The mRNA expression levels of Bmi­1 and those of miRNA­128a in U­87 MG cells exposed to X­ray radiation were evaluated by reverse transcription­quantitative polymerase chain reaction. X­ray radiation did not decrease the number of U­87 MG cells; however, it did inhibit cellular growth in a dose­dependent manner. Following exposure to X­ray radiation for 24 h, cell cycle distribution was altered, with an increase in the number of cells in G0/G1 phase. The mRNA expression levels of Bmi­1 were downregulated in the 1 and 2 Gy groups, and upregulated in the 6 and 8 Gy groups. The expression levels of miRNA­128a were upregulated in the 1 and 2 Gy groups, and downregulated in the 8 Gy group. The levels of ROS were increased following exposure to ≥2 Gy, and treatment with N-acetyl cysteine was able to induce radioresistance. These results suggested that U­87 MG cells exhibited radioresistance. High doses of X­ray radiation increased the expression levels of Bmi­1, which may be associated with the evasion of cellular senescence. miRNA­128a and its downstream target gene Bmi­1 may have an important role in the radioresistance of U­87 MG glioma cells. In addition, ROS may be involved in the mechanisms underlying the inhibitory effects of X­ray radiation in U­87 MG cells, and the downregulation of ROS may induce radioresistance.

A systematic review of risk factors for brain metastases and value of prophylactic cranial irradiation in non-small cell lung cancer.

BACKGROUND: The incidence of brain metastases (BM) varies in patients with non-small cell lung cancer (NSCLC), calls into question the value of prophylactic cranial irradiation (PCI). It is possible that clinicopathologic characteristics are associated with the development of BM, but these have yet to be identified in detail. Thus, we conducted the present meta-analysis on risk factors for BM and the value of PCI in patients with NSCLC. METHODS: Eligible data were extracted and the risk factors for BM and the value of PCI in patients with NSCLC were analyzed by calculating the pooled odds ratio (OR). Heterogeneity was detected using Q and I-squared statistics, and publication bias was tested by funnel plots and Egger's test. RESULTS: Six randomized controlled trials with a focus on the value of PCI and 13 eligible studies with a focus on risk factors for BM were included. PCI significantly reduced the incidence of BM in patients with NSCLC (p=0.000, pooled OR=0.34, 95% confidence interval = 0.37-0.59). Compared with non-squamous cell carcinoma, squamous cell carcinoma was associated with a low incidence of BM in patients with NSCLC (p=0.000, pooled OR=0.47, 95% confidence interval =0.34- 0.65). The funnel plot and Egger's test suggested that there was no publication bias in the current meta-analysis. CONCLUSIONS: This meta-analysis provides statistical evidence that compared with non-squamous cell carcinoma, squamous cell carcinoma can be used as a predictor for BM in patients with NSCLC, and PCI might reduce the incidence of BM in patients with NSCLC, but does not provide a survival benefit.

Bmi-1 induces radioresistance by suppressing senescence in human U87 glioma cells.

Radiotherapy is the main locoregional control modality for a number of types of malignant tumors, including glioblastoma. However, radiotherapy fails to prevent recurrence in numerous patients due to the intrinsic radioresistance of cancer cells. Cell senescence is significant in tumor suppressor mechanisms and is closely associated with the radioresistance of cancer cells. Bmi-1 has been proposed to be an oncogene that can induce anti-senescence in tumor cells. The present study investigated the response of U87 glioma cells to radiation exposure and the role of Bmi-1 in the response following radiotherapy. Cell apoptosis and cell cycle distribution were assessed using flow cytometry, and a SA-ß-Gal stain was used to observe the senescence ratio of U87 cells following radiation. The expression of Bmi-1 in U87 cells exposed to different doses of radiation was evaluated by western blot analysis. X-ray radiation was found to inhibit U87 cell proliferation through the induction of senescence rather than apoptosis. Following exposure to radiation, the cell cycle distribution was dysregulated, with an increased number of cells in the G2/M phase, and the expression of Bmi-1 was upregulated, particularly when a dose of ≥6 Gy was administered. The results indicated that senescence is the main mechanism by which U87 cell growth is inhibited following radiation. In addition, Bmi-1 may be significant in increasing the radioresistance of glioma cells by enabling cell senescence.

The correlation between tumor-infiltrating Foxp3+ regulatory T cells and cyclooxygenase-2 expression and their association with recurrence in resected head and neck cancers.

The aim of this study was to investigate the correlation between tumor-infiltrating CD4+ CD25(high) Foxp3+ naturally occurring regulatory T cells (Foxp3+ nTregs) and cyclooxygenase-2 (COX-2) expression and their association with local recurrence in resected head and neck cancers. Intratumoral COX-2 and Foxp3+ nTregs expressions were retrospectively assessed using immunohistochemistry. Associations between the clinicopathological characteristics and either intratumoral COX-2 expression or number of Foxp3+ nTregs were tested using the Chi-square test. The correlation between the number of Foxp3+ nTregs and COX-2 expression was tested using Spearman's rank correlation test. Associations between recurrence-free survival (RFS) and either intratumoral COX-2 expression or number of Foxp3+ nTregs were calculated using the Kaplan-Meier method, and factors that may influence the RFS were analyzed by Cox regression. The five-year RFS for all patients was 35.09%. Patient clinicopathological characteristics had no relationship with intratumoral COX-2 expression or the number of Foxp3+ nTregs. However, a positive correlation between intratumoral COX-2 expression and the number of Foxp3+ nTregs was observed (P < 0.001). The RFS of patients with elevated COX-2 expression was significantly worse than that of patients without intratumoral COX-2 expression (P = 0.0228). The RFS of patients with tumors containing >6 Foxp3+ cells was significantly worse than that of patients with tumors containing ≤6 Foxp3+ cells (P = 0.0020). However, by Cox regression analysis, the RFS of all patients was not influenced by intratumoral COX-2 expression (P = 0.100) or the number of Foxp3+ nTregs (P = 0.071). Tumor-infiltrating CD4+ CD25(high) Foxp3+ nTregs were positively correlated with intratumoral COX-2 expression and were associated with a worse RFS in univariate analysis.