Correlation between hippocampal radiation doses and psychological condition for patients with stage T1-2 nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: The study aimed to investigate the correlation between radiation doses to the hippocampi and the psychological status of patients with stage T1-2 nasopharyngeal carcinoma (NPC) undergoing intensity modulated radiotherapy (IMRT) and recommend proper hippocampal dose limits for preserving patients' psychological well-being. MATERIALS AND METHODS: A retrospective study was conducted involving 152 newly diagnosed NPC patients. The patients' psychological status was assessed using the Hospital Anxiety and Depression Scale (HADS) before and after radiotherapy. The hippocampi were manually delineated on treatment planning images, and dosimetric parameters were obtained from dose-volume histograms. Logistic regression analysis was performed to identify influential dosimetric factors associated with anxiety and depression. RESULTS: The results showed that several dosimetric parameters to the hippocampi were significantly associated with anxiety but not depression. The optimal cut-off value for the independent predictor of anxiety was determined as D40 to hippocampi > 1500 cGy. Patients with D40 to hippocampi > 1500 cGy showed a higher probability for anxiety after radiotherapy. CONCLUSION: This study provides insights into the relationship between radiation doses to the hippocampi and the psychological status of stage T1-2 NPC patients undergoing IMRT. It suggests the importance of hippocampal protection for preserving patients' psychological well-being. Further studies are needed to validate these results.

Farrerol exhibits inhibitory effects on lung adenocarcinoma cells by activating the mitochondrial apoptotic pathway.

Farrerol is an herbal compound extracted from rhododendron. Here, our study is to investigate biological effects of farrerol on lung adenocarcinoma (LAC) cells. Human LAC cell lines and xenograft mouse model were utilized to define the effects of farrerol on tumor growth. Our findings indicated that farrerol significantly reduced LAC cell viability as well as the colony-forming capacity. Flow cytometry analysis demonstrated that farrerol contributed to cell apoptosis and G0/G1 phase cell cycle arrest. Mechanistically, farrerol treatment upregulated proapoptotic molecules (Bak, Bid, cleaved caspase-3 and cleaved caspase-9) and senescence markers (p16 and p2), but downregulated antiapoptosis genes (Bcl-2 and Bcl-XL) and cell cycle-associated genes (CyclinD1 and CDK4); meanwhile, the phosphorylation of retinoblastoma (Rb) protein was attenuated upon pretreatment of LAC cells with farrerol in comparison to untreated control. Further studies indicated that farrerol elevated reactive oxygen species levels, activating mitochondrial apoptotic pathway and causing cell apoptosis. However, exposure to farrerol did not result in significant apoptosis in normal lung epithelial cells, suggesting a tumor-specific effect of farrerol on LAC cells. In animal model, farrerol showed a significant inhibitory effect on LAC xenograft tumor growth. And gene expressions in tumor tissues, as mentioned above, were in line with the in vitro results. Taken together, these results suggested that farrerol caused LAC cell apoptosis by activating mitochondrial apoptotic pathway, whereas farrerol treatment had no notable effect on normal lung epithelial cells. Farrerol might be an effective therapeutic drug for LAC.

LINC01578 affects the radiation resistance of lung cancer cells through regulating microRNA-216b-5p/TBL1XR1 axis.

Radiation resistance largely limits the survival of patients with non-small-cell lung cancer (NSCLC). To understand the mechanism underlying radiation resistance, we explored the influence of LINC01578 in radiation-resistant NSCLC cells. LINC01578, miR-216b-5p and Transducin (beta)-like 1 X-linked receptor 1 (TBL1XR1) expression was evaluated in patients with NSCLC, and their correlation with patients' prognosis was examined. Radiation-resistant NSCLC cell line (A549-RR) was induced and treated with oligonucleotide or plasmid transfection, and cell biological functions were captured. The interplay between LINC01578, miR-216b-5p and TBL1XR1 was clarified. NSCLC patients showed high LINC01578 and TBL1XR1 expression, and low miR-216b-5p expression, which was correlated to shorter patients' prognosis, respectively. LINC01578 or TBL1XR1 deficiency or miR-216b-5p elevation suppressed the functional activities of A549-RR cells. LINC01578 suppression elevated miR-216b-5p expression, consequently leading to the down-regulation of TBL1XR1. miR-216b-5p silencing or TBL1XR1 overexpression compromised LINC01578 knockdown's effects on radiation resistance of A549-RR cells. In brief, LINC01578 suppresses miR-216b-5p and enhances TBL1XR1 expression, thus to promote biological functions of radiation-resistant NSCLC cells.

Treatment outcomes of induction chemotherapy combined with intensity-modulated radiotherapy and adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma in Southeast China.

ABSTRACT: Induction chemotherapy (IC) and adjuvant chemotherapy (AC) are used to enhance tumor locoregional control and support early treatment for distant metastases. However, optimum combinatorial treatment of these chemoradiotherapy regimens with radiotherapy in curing locoregionally advanced nasopharyngeal carcinoma (NPC) remains unclear. Here, we evaluate the efficacy and therapeutic outcome of a combinatorial treatment strategy involving IC, intensity-modulated radiotherapy (IMRT), and AC, by retrospectively analyzing 243 NPC patients who were treated by IC followed by IMRT and AC. The rates of 3-/5-year local-regional control rate, distant failure-free rate (DFFR), progression-free survival (PFS), and overall survival (OS) were 93.3%/90.3%, 84.2%/79.4%, 79.6%/74.4%, and 84.0%/72.6%, respectively. The 3-/5-year OS rates of patients in stage III or IVA were 91.5%/75.1% and 86.5%/56.5%, respectively. Combination cisplatin with paclitaxel showed no significance in OS as compared to cisplatin plus 5-fluorouracil (P-value = .17). Total four-cycle IC and AC was significantly beneficious versus three-cycle in DFFR (P-value = .04), as well as total 6 chemotherapy cycles compared to 4 in DFFR and PFS (P-value = .03 and P-value = .01, respectively). All survival indicators were adversely affected by T-category, while N-category could only predict DFFR and PFS. Radiation dosage represented as a second prognostic factor for local control. We propose that IC combined with IMRT and AC for locoregionally advanced NPC shows effective treatment outcomes.

Effect of tumor and normal lung volumes on the lung volume-dose parameters of IMRT in non-small-cell lung cancer.

OBJECTIVES: To explore the effect of tumor and normal lung volumes on lung volume-dose parameters in patients with non-small-cell lung cancer (NSCLC) who had undergone intensity-modulated radiation therapy (IMRT). METHODS: The clinical data of 208 patients with NSCLC who underwent radical IMRT between June 2014 and June 2018 were retrospectively analyzed. A regression model curve was used to evaluate the effect of tumor and normal lung volumes on normal lung relative volumes receiving greater than 5 and 20 Gy (V5, V20), on mean lung dose (MLD), and on absolute volumes spared from greater than 5 and 20 Gy (AVS5, AVS20). RESULTS: The V5, V20, and MLD of the bilateral lung were fitted to a quadratic equation curve with the change in tumor volume, which increased initially and then decreased when the tumor volume increased. The V5, V20, and MLD of the lung reached their apex when the tumor volumes were 288.07, 341.69, and 326.83 cm3, respectively. AVS5 and AVS20 decreased in a logarithmic curve with an increase in tumor volume. The V5, V20, and MLD of the small normal lung volume group were all significantly higher than those of the large normal lung volume group (p<0.001, p=0.004, p=0.002). However, the AVS5 and AVS20 of the small normal lung volume group were all significantly lower than those of the large normal lung volume group (p<0.001). CONCLUSION: The effects of tumor volume and normal lung volume on dose-volume parameters should be considered. AVS5 is an important supplementary dose limitation parameter for patients whose tumor volume exceeds a certain boundary value (approximately 300 cm3).

Effect of tumor and normal lung volumes on the lung volume-dose parameters of IMRT in non-small-cell lung cancer

OBJECTIVES: To explore the effect of tumor and normal lung volumes on lung volume-dose parameters in patients with non-small-cell lung cancer (NSCLC) who had undergone intensity-modulated radiation therapy (IMRT). METHODS: The clinical data of 208 patients with NSCLC who underwent radical IMRT between June 2014 and June 2018 were retrospectively analyzed. A regression model curve was used to evaluate the effect of tumor and normal lung volumes on normal lung relative volumes receiving greater than 5 and 20 Gy (V5, V20), on mean lung dose (MLD), and on absolute volumes spared from greater than 5 and 20 Gy (AVS5, AVS20). RESULTS: The V5, V20, and MLD of the bilateral lung were fitted to a quadratic equation curve with the change in tumor volume, which increased initially and then decreased when the tumor volume increased. The V5, V20, and MLD of the lung reached their apex when the tumor volumes were 288.07, 341.69, and 326.83 cm3, respectively. AVS5 and AVS20 decreased in a logarithmic curve with an increase in tumor volume. The V5, V20, and MLD of the small normal lung volume group were all significantly higher than those of the large normal lung volume group (p<0.001, p=0.004, p=0.002). However, the AVS5 and AVS20 of the small normal lung volume group were all significantly lower than those of the large normal lung volume group (p<0.001). CONCLUSION: The effects of tumor volume and normal lung volume on dose-volume parameters should be considered. AVS5 is an important supplementary dose limitation parameter for patients whose tumor volume exceeds a certain boundary value (approximately 300 cm3).

Applicability of the Nutrition Risk Screening 2002 Combined with a Patient-Generated Subjective Global Assessment in Patients with Nasopharyngeal Carcinoma.

PURPOSE: This study aims to explore the applicability of the Nutrition Risk Screening 2002 (NRS2002) tool in screening nutritional risk and the Patient-Generated Subjective Global Assessment (PG-SGA) in determining nutrition status in nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: NRS2002 and PG-SGA were simultaneously applied to evaluate the nutritional status of NPC patients before induction chemotherapy, as well as before and after radiotherapy. The PG-SGA results were considered golden standard in evaluating nutrition status, and the ROC curve value and Youden index were applied to analyze NRS2002 effectiveness in screening nutritional risk. RESULTS: A total of 102 NPC patients were included in this study. Patients with an NRS2002 score <3 and PG-SGA score ≥4 accounted for 5.3% (5/95), 19.6% (18/92) and 94.8% (36/38) at the time before induction chemotherapy, before radiotherapy and at the end of radiotherapy, respectively. The cut-off values of NRS2002 scores all <2 corresponded to the maximum Youden index at the three procedural times. And the area under curve (AUC) were 0.598 (P = 0.390), 0.665 (P = 0.015) and 0.940 (P = 0.034), respectively. At the end of radiotherapy, NRS2002 scores of <3 and <2 were used as cut-off values for nutritional risk screening, respectively. Additionally, the malnutrition-missed detection rates were 36.0% and 12.0% (χ 2 = 15.789; P <0.001). DISCUSSION: NRS2002 nutritional risk screening combined with the PG-SGA nutritional assessment has certain applicability in NPC. NRS2002 score ≥2 can be considered as a new cut-off point for nutritional assessment.

Long noncoding RNA LINC00630 promotes radio-resistance by regulating BEX1 gene methylation in colorectal cancer cells.

This study aimed to analyze the relation between long noncoding RNA (lncRNA) LINCE00630 and radio-resistance and elucidate the underlying mechanism. Relative expression of LINC00630, BEX1, and DNMT3B in colorectal cancer (CRC) cells and clinical samples was determined by real-time PCR. Prognosis in respect of LINC00630 expression was analyzed by Kaplan-Meier survival curve. LINC00630 and BEX1 were specifically silenced by shRNAs. Cell viability and growth were analyzed by MTT and clonogenic assays, respectively. Cell apoptosis was measure by both caspase-3 activity and flow cytometry. Association between EZH2 with LINC00630 and BEX1 promoter was determined by RNA immunoprecipitation and chromatin immunoprecipitation. BEX1 and DNMT3B proteins were quantified by Western blot. We demonstrated the elevated LINC00630 correlated with radio-resistance and poorer prognosis in CRC. Knockdown of LINC00630 significantly improved the sensitivity of CRC cells to irradiation. Mechanistically, LINC00630 in complex with EZH2 negatively regulated BEX1 through promoter DNA methylation. BEX1 silencing greatly restored the cell viability and suppressed cell apoptosis, which were elicited by LINC00630 deficiency in response to irradiation. Our data uncovered the contribution of elevated LINC00630 to radio-resistance in CRC, which was predominately mediated by epigenetically repressed BEX1.

The efficacy and toxicity of induction chemotherapy plus concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: A meta-analysis of randomized controlled trials.

BACKGROUND: A systemic review and meta-analysis of randomized controlled trials (RCTs) was performed to compare the efficacy, toxicity and safety of concurrent chemoradiotherapy (CCRT) with or without induction chemotherapy (IC) for locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS: Research searching was performed in Web of Science, PubMed, The Cochrane Library, Embase, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Chongqing VIP Database for Chinese Technical Periodicals and Wanfang Database. RCTs including patients diagnosed with locoregionally advanced NPC without metastasis and randomly treated with IC plus CCRT and CCRT alone were included. Survival and outcome data were extracted and meta-analysis was performed using the Revman 5.3.0 software. RESULTS: Ten RCTs (2280 patients) were selected and used for pooled meta-analysis. In comparison with CCRT, IC plus CCRT treatment significantly improved the overall survival (OS; HR = 0.70, 95%CI 0.56-0.87, P = .002), progression-free survival (PFS; HR = 0.75, 95%CI 0.65-0.87, P < .0001), distant metastasis failure-free survival (DMFS; HR = 0.71, 95%CI 0.58-0.85, P = .0003) and loco-regional failure-free survival (LFES; HR = 0.72, 95%CI 0.59-0.88, P = .002) of patients with locoregionally advanced NPC. Patients treated with IC and CCRT had higher incidence of grade 3-4 leucopenia and thrombocytopenia than patients treated with CCRT alone (P < .0001). No significant difference in other grade 3-4 adverse events and radiation toxicity was observed between the two groups. IC combined with CCRT improved the survival of patients with locoregionally advanced NPC. CONCLUSIONS: Combined IC and CCRT therapy was an efficacy treatment regimen for locoregionally advanced NPC.

Apocynin protects retina cells from ultraviolet radiation damage via inducing sirtuin 1.

Direct exposure to Ultraviolet (UV) radiation causes progressive damages in retinal cells, which is one of the hypothetical mechanisms underlying age-related retinopathy or macular degeneration. The protective effects of Apocynin against UV damages were firstly tested in retinal pigment epithelium cells (RPEs) and retinal ganglion cells (RGCs). Subsequently the beneficial effect of Apocynin on mouse retinas against light damage were examined. Next, microarray profiling was used to identify the genes regulated by Apocynin in both RPEs and RGCs. A candidate gene was isolated for functional characterisation by knock-down study. Apocynin was shown to inhibit cell death, reduce oxidative stress and deoxyribonucleic acid damages in both RPEs and RGCs challenged with UV. Intravitreal application of Apocynin also improved retinal dysfunction caused by light damage. Sirtuin 1 (SIRT1) was identified as induced by Apocynin by microarray study. The induction was confirmed by realtime-PCR and western blotting. Knocking down SIRT1 antagonised the protective effect of Apocynin against UV damages in both RPEs and RGCs. Apocynin is a novel agent that shows both in vitro and in vivo efficacies against UV radiation induced retina damages. SIRT1 pathway is implicated in UV radiation protection of Apocynin in retinal cells.

LKB1 promotes radioresistance in esophageal cancer cells exposed to radiation, by suppression of apoptosis and activation of autophagy via the AMPK pathway.

Liver kinase B (LKB) 1 acts as a tumor suppressor in a broad spectrum of human cancers, and is important in chemoradiotherapy treatment of various tumor types. However, the potential function of LKB1 in esophageal cancer radiotherapy remains to be elucidated. The aim of the present study was to investigate the role of LKB1 in radiosensitivity of esophageal cancer in vivo and in vitro, and to explore its molecular mechanism. Eca­109 cells transfected with LKB1 overexpression plasmid were xenografted into nude mice and subjected to irradiation and it was observed that the tumor volume was significantly increased in LKB1­overexpressed tumors compared with that of the control tumors. The in vitro study revealed that LKB1 overexpression led to the radioresistance of Eca­109 cells, as determined by MTT and colony formation assays. Furthermore, it was demonstrated that LKB1 overexpression inhibited apoptosis and activated autophagy of Eca­109 cells following radiation treatment, as determined by flow cytometry and western blot analyses. AMP­activated protein kinase (AMPK) inhibition attenuated LKB1­induced radioresistance of Eca­109 cells. To the best of our knowledge, the present study, for the first time, confirmed that LKB1 induces radioresistance of esophageal cancer cells to irradiation via suppression of apoptosis and activation of autophagy, and AMPK mediates this function of LKB1 in esophageal cancer radiotherapy. These findings suggest that LKB1 may act as a novel target in the future, to maximize the efficiency of esophageal cancer radiotherapy.

Pretreatment hematologic markers as prognostic factors in patients with nasopharyngeal carcinoma: A systematic review and meta-analysis.

BACKGROUND: Pretreatment hematologic parameters of the inflammatory response, including lymphocyte, neutrophil, and platelet counts, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio, have emerged as prognostic factors for patients with cancer. This systematic review and meta-analysis aimed to summarize the association between the hematologic markers and prognosis of nasopharyngeal carcinoma (NPC). METHODS: A systematic search of PubMed, Google Scholar, MEDLINE, EMBASE, Web of Science, and the Cochrane Library was conducted up to April 2016. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and synthesized to examine prognostic outcomes including cancer-specific survival (CSS), overall survival (OS), progression-free survival (PFS), distant metastasis-free survival, and local relapse-free survival (LRFS). RESULTS: Fourteen studies comprising 11,651 NPC patients were ultimately included, and all eligible studies were conducted in East Asia. The OS, CSS, PFS, distant metastasis-free survival, and LRFS risks differed among patients according to hematologic marker levels. All of the parameters were associated with prognostic outcomes in patients with NPC. NLR and lymphocyte counts were most commonly reported. A high NLR was significantly associated with poor NPC prognosis (pooled HR 1.42, 95% CI 1.21-1.67 for CSS; pooled HR 1.77, 95% CI 1.41-2.23 for OS; pooled HR 1.67, 95% CI 1.36-2.06 for PFS; pooled HR 1.64, 95% CI 1.15-2.34 for LRFS). High lymphocyte count indicated favorable NPC prognosis (pooled HR 0.72, 95% CI 0.64-0.81 for OS; pooled HR 0.71, 95% CI 0.56-0.91 for PFS). CONCLUSIONS: Meta-analysis indicated that NLR and lymphocyte counts could be prognostic predictors in NPC for East Asian population. Patients with a high NLR or low lymphocyte count had poor prognosis. However, due to the limitation of included population, the conclusion was limited to East Asian patients only.

[Construction of recombinant lentiviral vector of Tie2-RNAi and its influence on malignant melanoma cells in vitro].

OBJECTIVE: To construct lentivector carrying Tie2-Small interfering RNA (SiRNA), so as to study its influence on malignant melanoma cells. METHODS: Recombinant plasmid pSilencer 1.0-U6-Tie2-siRNA and plasmid pNL-EGFP were digested with XbaI, ligated a target lentiviral transfer plasmid of pNL-EGFP-U6-Tie2-I or pNL-EGFP-U6-Tie2-II, and then the electrophoresis clones was sequenced. Plasmids of pNL-EGFP-U6-Tie2-I and pNL-EGFP-U6-Tie2-II were constructed and combined with pVSVG and pHelper, respectively, to constitute lentiviral vector system of three plasmids. The Lentiviral vector system was transfected into 293T cell to produce pNL-EGFP-U6-Tie2- I and pNL-EGFP-U6-Tie2-II lentivirus. Then the supernatant was collected to determine the titer. Malignant melanoma cells were infected by both lentiviruses and identified by Realtime RT-PCR to assess inhibitory efficiency. RESULTS: The recombinant lentiviral vectors of Tie2-RNAi were constructed successfully which were analyzed with restriction enzyme digestion and identified by sequencing. And the titer of lentiviral vector was 8.8 x 10(3)/ml, which was determined by 293T cell. The results of Realtime RT-PCR demonstrated that the lentiviral vectors of Tie2-RNAi could infect malignant melanoma cells and inhibit the expression of Tie2 genes in malignant melanoma cells (P<0.01). There was no significant difference in the expression level (P>0.05) between the two lentiviral vectors of Tie2-RNAi. CONCLUSIONS: Lentivector carrying Tie2-SiRNA can be constructed successfully and inhibit the expression of Tie2 gene in vitro significantly. The study will supply the theory basis for the further research on the inhibition of tumor growth in vivo.