Impact of pilot diesel injection timing on performance and emission characteristics of marine natural gas/diesel dual-fuel engine.

In diesel-ignited natural gas marine dual-fuel engines, the pilot diesel injection timing (PDIT) determines the premixing time and ignition moment of the combustible mixture in the cylinder. The PDIT plays a crucial role in the subsequent development of natural gas flame combustion. In this paper, four PDITs (- 8 °CA, - 6 °CA, - 4 °CA, and - 2 °CA) were studied. The results show that the advancement of PDIT increased the engine's power, thermal efficiency, and natural gas flame spread velocity, and increased NO emissions and CH4 emissions of the marine engine. The PDIT affected the ignition delay period and the rapid combustion period to a greater extent than the slow combustion period and the post combustion period. With each 2 °CA advancement of PDIT, the engine's power increased by 69.87 kW, thermal efficiency increased by 0.42%, radial flame spread velocity increased by 2 m/s, axial flame spread velocity increased by 1.7 m/s, NO emissions increased by 6.1%, and CH4 emissions increased by 3.75%.

Integrative analysis of single-cell and bulk transcriptome data reveal the significant role of macrophages in lupus nephritis.

OBJECTIVE: We attempted to identify abnormal immune cell components and signaling pathways in lupus nephritis (LN) and to identify potential therapeutic targets. METHODS: Differentially expressed genes (DEGs) between LN and normal kidney tissues were identified from bulk transcriptome data, and functional annotation was performed. The phenotypic changes in macrophages and aberrant intercellular signaling communications within immune cells were imputed from LN scRNA-seq data using trajectory analysis and verified using immunofluorescence staining. Finally, lentivirus-mediated overexpression of LGALS9, the gene encoding Galectin 9, in THP-1 cells was used to study the functional effect of this gene on monocytic cells. RESULTS: From bulk transcriptome data, a significant activation of interferon (IFN) signaling was observed, and its intensity showed a significantly positive correlation with the abundance of infiltrating macrophages in LN. Analysis of scRNA-seq data revealed 17 immune cell clusters, with macrophages showing the highest enrichment of intercellular signal communication in LN. Trajectory analysis revealed macrophages in LN undergo a phenotypic change from inflammatory patrolling macrophages to phagocytic and then to antigen-presenting macrophages, and secrete various pro-inflammatory factors and complement components. LGALS9 was found significantly upregulated in macrophages in LN, which was confirmed by the immunofluorescence assay. Gene functional study showed that LGALS9 overexpression in THP-1 cells significantly elicited pro-inflammatory activation, releasing multiple immune cell chemoattractants. CONCLUSION: Our results present an important pathophysiological role for macrophages in LN, and our preliminary results demonstrate significant pro-inflammatory effects of LGALS9 gene in LN macrophages.

Mechanism of Exosomal LncRNA PART1 in Esophageal Cancer Angiogenesis by Targeting miR-302a-3p/CDC25A Axis.

OBJECTIVE: LncRNA PART1 has been confirmed related to multiple cancer bioactivities mediated with vascular endothelial growth factor signaling. Nevertheless, the role of LncRNA PART1 in esophageal cancer induced angiogenesis remains unclear. The present work focused on assessing LncRNA PART1 effects on esophageal cancer-induced angiogenesis and exploring possible mechanisms. METHODS: Western blot and immunofluorescence were conducted for identifying EC9706 exosomes. MiR-302a-3p and LncRNA PART1 levels were assessed by real-time quantitative polymerase chain reaction. Cell Counting Kit-8, EdU, wound healing, transwell, and tubule information were adopted for detecting human umbilical vein endothelial cell viability, proliferation, migration, invasion, and tubule information, respectively. Starbase software and dual-luciferase reporter were conducted for predicting and judging the expression interrelation of LncRNA PART1 and its potential target-miR-302a-3p. The same methods were carried out for verifying the inhibiting influences of miR-302a-3p upregulation and its potential target-cell division cycle 25 A. RESULTS: LncRNA PART1 levels were upregulated and related to the overall survival of patients in esophageal cancer. EC9706-Exos accelerated human umbilical vein endothelial cell proliferation, migration, invasion, and tubule formation via LncRNA PART1. LncRNA PART1 served as a sponge of miR-302a-3p, then miR-302a-3p targeted cell division cycle 25 A, and EC9706-Exos accelerated human umbilical vein endothelial cell angiogenesis via LncRNA PART1/ miR-302a-3p/cell division cycle 25 A axis. CONCLUSION: EC9706-Exos accelerates human umbilical vein endothelial cell angiogenesis via LncRNA PART1/miR-302a-3p/ cell division cycle 25 A axis, indicating EC9706-Exos may act as a promoter of angiogenesis. Our research will contribute to clarify the mechanism of tumor angiogenesis.

Optimal resource allocation method for energy harvesting based underlay Cognitive Radio networks.

This paper proposes an optimal resource allocation method. The method is to maximize the Energy Efficiency (EE) for an Energy Harvesting (EH) enabled underlay Cognitive Radio (CR) network. First, we assumed the Secondary Users (SUs) can harvest energy from the surrounding Radio Frequency (RF) signals. Then, we modelled the EE maximisation problem as a joint time and power optimization model. Next, the optimal EH time allocation factor can be calculated. After that the optimal power allocation strategy can be obtain by the fractional programming and Lagrange multiplier method. Finally simulation results show that the proposed iterative method can be better performance advantages compared with the exhaustive method and genetic algorithm. And the EE of this system model is significantly improved compared to the EE model without considering EH.

Forecasts for the concentration of petroleum gas leakage diffusion under different liquid level heights of a sealing ring of sizeable floating roof tank.

The sealing ring of the external floating roof tank is prone to petroleum gas leakage due to material aging and oil corrosion. Petroleum gas leakage and diffusion easily accumulate above the floating deck. When it is within the explosion limit range, there will be the risk of explosion and fire. To deal with the explosion accident of storage tank caused by the concentration distribution of petroleum gas leakage for the sealing ring, and to study the influence of petroleum gas diffusion and concentration distribution after sealing ring leakage on the control area above the floating deck in the tank farm environment, this paper established numerical models of sealing ring leakage under different liquid level heights for 10 × 104 m3 external floating roof tank. Through numerical calculation, it is found that the diffusion concentration of petroleum gas is related to the wind speed, the range of the control area above the floating deck, and leakage when sealing rings leak at different liquid levels. Through dimensionless analysis, the functional relationship of gas leakage diffusion concentration distribution under different liquid level heights of external floating roof tank sealing rings is verified by numerical calculation results. The results show that the numerical results are consistent with those predicted by the formula.

Covalent and Noncovalent Complexation of Phosvitin and Gallic Acid: Effects on Protein Functionality and In Vitro Digestion Properties.

To investigate the effects of different binding modes on the structure, function, and digestive properties of the phosvitin (Pv) and gallic acid (GA) complex, Pv was covalently and noncovalently combined with different concentrations of GA (0.5, 1.5, and 2.5 mM). The structural characterization of the two Pv-GA complexes was performed by Fourier transform infrared, circular dichroism, and LC-MS/MS to investigate the covalent and noncovalent binding of Pv and GA. In addition, the microstructure of the two Pv-GA complexes was investigated by super-resolution microscopy and transmission electron microscopy. The particle size and zeta potential results showed that the addition of GA increased the particle size and the absolute potential of Pv. The determination of protein digestibility, polyphenol content, SH and S-S group levels, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and antioxidant capacity of the digests indicated that noncovalent complexes had greater antioxidant and protective effects on polyphenols. Molecular docking revealed that GA was conjugated with Pv through hydrogen bond interactions.

Mesenchymal stem cell-derived small extracellular vesicles mitigate oxidative stress-induced senescence in endothelial cells via regulation of miR-146a/Src.

Senescent endothelial cells (ECs) could impair the integrity of the blood vessel endothelium, leading to vascular aging and a series of diseases, such as atherosclerosis, diabetes. Preventing or mitigating EC senescence might serve as a promising therapeutic paradigm for these diseases. Recent studies showed that small extracellular vesicles (sEV) have the potential to transfer bioactive molecules into recipient cells and induce phenotypic changes. Since mesenchymal stem cells (MSCs) have long been postulated as an important source cell in regenerative medicine, herein we investigated the role and mechanism of MSC-derived sEV (MSC-sEV) on EC senescence. In vitro results showed that MSC-sEV reduced senescent biomarkers, decreased senescence-associated secretory phenotype (SASP), rescued angiogenesis, migration and other dysfunctions in senescent EC induced by oxidative stress. In the In vivo natural aging and type-2 diabetes mouse wound-healing models (both of which have senescent ECs), MSC-sEV promoted wound closure and new blood vessel formation. Mechanically, miRNA microarray showed that miR-146a was highly expressed in MSC-sEV and also upregulated in EC after MSC-sEV treatment. miR-146a inhibitors abolished the stimulatory effects of MSC-sEV on senescence. Moreover, we found miR-146a could suppress Src phosphorylation and downstream targets VE-cadherin and Caveolin-1. Collectively, our data indicate that MSC-sEV mitigated endothelial cell senescence and stimulate angiogenesis through miR-146a/Src.

An Immune Cell-Based Signature Associating With EMT Phenotype Predicts Postoperative Overall Survival of ESCC.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest solid malignancies and has a poor survival rate worldwide. In this study, we aimed to establish a tumor-infiltrating immune cell-based prognosis signature (IPS) to predict patients' survival times and aid in the development of targeted therapies or immunotherapies. The abundances of 22 types of immune cells were determined by the CIBERSORT algorithm from ESCC patient gene expression data in the Gene Expression Omnibus (GEO) training set (n = 179) and The Cancer Genome Atlas (TCGA) validation set (n = 95). Then, the IPS was established by using the least absolute shrinkage and selection operator (LASSO) regression method. Kaplan-Meier analysis showed that patients with high IPS scores had significantly worse overall survival times than patients with low IPS scores in both the training set and the validation set (log-rank p = 0.001, and p = 0.050, respectively). Univariate and multivariate Cox regression analyses proved that the IPS was a robust prognostic factor for ESCC, independent of age, sex, tumor node metastasis (TNM) stage, pathology grade, and tumor location. In the mechanistic study, the epithelial-mesenchymal transition (EMT) process was identified by both gene set enrichment analysis (GSEA) and weighted correlation network analysis (WGCNA) as the underlying mechanism by which the IPS affects the prognosis of ESCC. After systematic correlation analyses, we found that M2 macrophages were the only cell type in the IPS significantly correlated with the EMT process. This relationship between M2 macrophage infiltration and the EMT phenotype was also confirmed by our preliminary immunochemistry (IHC) and multiplexed immunofluorescence study. In conclusion, we constructed an IPS that predicts the postoperative prognosis of ESCC patients and uncovered the critical role of M2 macrophages in the interplay between immune status and the EMT phenotype in ESCC.

Tumor-infiltrating plasma cells are the promising prognosis marker for esophageal squamous cell carcinoma.

BACKGROUND: There is an urgent need to improve the clinical and basic research of esophageal cancer. The purpose of this study was to explore the prognostic value of tumor-infiltrating plasma cells (TIP) on overall survival (OS) of patients with esophageal squamous cell carcinoma (ESCC). METHODS: Three independent cohorts, which include 116 consecutive cases who received radical resection of ESCC in our institution (set to be discovery set), 179 cases from public GEO database (validation GEO set) and 95 cases from TCGA (validation TCGA set), with a total of 390 cases were retrospectively enrolled in this study. RESULTS: TIP was detected by immunohistochemical staining of CD138 in the paraffin-embedded specimen after surgery in the discovery set and was validated by using an established computational algorithm in the GEO and TCGA sets. Kaplan-Meier survival analysis showed high TIP was coincidently and significantly associated with favorable OS of ESCC in discovery set (p = 0.004) and validation GEO set (p = 0.002), showed a trend of better survival in validation TCGA set (p = 0.256 for 5-year OS, p = 0.034 for 15-month OS). Univariate and multivariate Cox regression analysis, together with survival analysis of the interaction between TIP and other variables, confirmed TIP to be a significant and independent prognostic factor for OS of ESCC. The incorporation of TIP into the TNM staging system could improve the accuracy of prognosis prediction for ESCC. CONCLUSION: This study revealed that high TIP in ESCC was associated with positive regulation of adaptive immunity and anti-tumor activity.

Prognostic value of ESR2 expression on adjuvant chemotherapy in completely resected NSCLC.

BACKGROUND: Prognostic biomarker, which can inform the treatment outcome of adjuvant chemotherapy (ACT) after complete resection of early-stage non-small cell lung cancer (NSCLC), is urgently needed for the personalized treatment of these patients. PATIENTS AND METHODS: The prognostic value of gene expression of the estrogen receptor (ER) on the effect of ACT in completely resected NSCLC was investigated in the present study. Two independent datasets from Gene Expression Omnibus (GEO) with a total of 309 patients were included in this study. The prognostic value of ER gene expression on ACT's efficacy was evaluated by survival analysis and Cox hazards models. RESULTS: We found a consistent and significant prognostic value of ERß (ESR2) expression for ACT's efficacy in completely resected NSCLC in both of the two independent cohorts. After multivariate adjustment, a significant survival benefit of ACT was observed in patients with low expression of ESR2, with a hazard ratio (HR) of 0.19 (95%CI 0.05-0.82, p = 0.026) in the discovery cohort and an HR of 0.27 (95%CI 0.10-0.76, p = 0.012) in the validation group. No significant benefit of ACT in the subgroup of patients with high expression of ESR2 was observed, with an HR of 0.80 (95%CI 0.31-2.09, p = 0.644) in the discovery cohort and an HR of 1.05 (95%CI 0.48-2.29, p = 0.896) in the validation group. CONCLUSION: A significant survival benefit from ACT was observed in patients with low ESR2 expression. No significant survival benefit was observed in patients with high ESR2 expression. Detection of ESR2 expression in NSCLC may help personalize its treatment after complete resection.

Mesenchymal Stem Cell Therapy Using Human Umbilical Cord in a Rat Model of Autoimmune-Induced Premature Ovarian Failure.

Premature ovarian failure (POF) is one of the principal causes of female infertility, and although its causes are complex and diverse, autoimmune deficiency may be involved. Human umbilical cord mesenchymal stem cells (UCMSCs) can be used for tissue regeneration and repair. Therefore, the present study was designed to determine the role of UCMSCs in immune factor-induced POF in rats. In this study, different concentrations of UCMSCs were injected into induced POF rats. Ovarian functions were examined by evaluating the estrus cycle, follicular morphology, hormonal secretion, and the proliferation and apoptosis of granulosa cells. Our results showed that the estrus cycle of rats returned to normal and follicular development was significantly improved after transplantation of UCMSCs. In addition, serum concentrations of 17-estradiol (E2), progesterone (P4), and anti-Müllerian hormone (AMH) increased significantly with treatment. Transplantation of UCMSCs also reduced the apoptosis of granulosa cells and promoted the proliferation of granulosa cells. All of these improvements were dose dependent. Furthermore, the results of related gene expression showed that transplanted human UCMSCs upregulated the expression of Bcl-2, AMH, and FSHR in the ovary of POF rats and downregulated the expression of caspase-3. These results further validated the potential mechanisms of promoting the release of cell growth factors and enhancing tissue regeneration and provide a theoretical basis for the clinical application of stem cells in the treatment of premature ovarian failure.

Correction: Overexpression of AKR1C3 significantly enhances human prostate cancer cells resistance to radiation.

[This corrects the article DOI: 10.18632/oncotarget.10347.].

Multifunctional Gold Nanoparticles Overcome MicroRNA Regulatory Network Mediated-Multidrug Resistant Leukemia.

Resistance to chemotherapy and molecularly targeted therapies is a major problem in current leukemia treatments. Here, we investigated cross-talk between the miR-221 network and P-glycoprotein (P-gp) in doxorubicin-induced drug resistance of leukemia cells. Multifunctional gold nanoparticles were designed and synthesized to co-deliver three anticancer agents, AS1411, doxorubicin and anti-221, for improving leukemia treatment efficacy. These nanoparticles significantly inhibited the proliferation and clonogenic potential, and induced apoptosis of drug-resistant leukemia cells. The decreased growth of drug-resistant cells induced by these nanoparticles was associated with marked downregulation of miR-221 and DNMT1, leading to restored p27kip1 and p15ink4b tumor suppressor expression, as well as miR-221-mediated reduction of P-gp expression. Finally, primary blasts derived from leukemia patients experiencing chemoresistant relapse that were exposed to these nanoparticles were sensitized to doxorubicin, as evidenced by suppression of leukemic cell growth and a significant reduction of the doxorubicin IC50 value. Our findings provide proof of concept that this novel drug delivery system can precisely reverse the multidrug resistant leukemia phenotype based on preclinical models of leukemia, providing the framework for future clinical trials aimed at overcoming drug resistance and improving patient outcome.

Inhibition of LOXL2 Enhances the Radiosensitivity of Castration-Resistant Prostate Cancer Cells Associated with the Reversal of the EMT Process.

INTRODUCTION: Radiotherapy is the mainstay in the treatment of prostate cancer. However, significant radioresistance of castration-resistant prostate cancer (CRPC) cells constitutes a main obstacle in the treatment of this disease. By using bioinformatic data mining methods, LOXL2 was found to be upregulated in both androgen-independent prostate cancer cell lines and radioresistant tumor samples collected from patients with prostate cancer. We speculate that LOXL2 may play an important role in the radioresistance of CRPC cells. METHODS: The effect of LOXL2 knockdown on the radiosensitivity of androgen-independent prostate cancer cells lines was measured by the clonogenic assay and xenograft tumor experiments under in vitro and in vivo conditions, respectively. In studies on the mechanism, we focused on the EMT phenotype changes and cell apoptosis changes induced by LOXL2 knockdown in DU145 cells. The protein levels of three EMT biomarkers, namely, E-cadherin, vimentin, and N-cadherin, were measured by western blotting and immunohistochemical staining. Cell apoptosis after irradiation was measured by flow cytometry and caspase-3 activity assay. Salvage experiment was also conducted to confirm the possible role of EMT in the radiosensitization effect of LOXL2 knockdown in CRPC cells. RESULTS: LOXL2 knockdown in CRPC cells enhanced cellular radiosensitivity under both in vitro and in vivo conditions. A significant reversal of EMT was observed in LOXL2-silenced DU145 cells. Cell apoptosis after irradiation was significantly enhanced by LOXL2 knockdown in DU145 cells. Results from the salvage experiment confirmed the key role of EMT process reversal in the radiosensitization effect of LOXL2 knockdown in DU145 cells. CONCLUSIONS: LOXL2 plays an important role in the development of cellular radioresistance in CRPC cells. Targeting LOXL2 may be a rational avenue to overcome radioresistance in CRPC cells. A LOXL2-targeting strategy for CRPC treatment warrants detailed investigation in the future.

Facile surface functionalization of upconversion nanoparticles with phosphoryl pillar[5]arenes for controlled cargo release and cell imaging.

Upon surface functionalization and stabilization of ß-NaYF4:Yb/Er upconversion nanoparticles (UCNPs) with phosphoryl pillar[5]arenes (PP5) via a facile ligand exchange method, we constructed a new hybrid material (PP5-UCNPs) with good water dispersibility especially in a physiological environment and superior capability of controlled cargo release and cell imaging.

Cordyceps sinensis Promotes the Growth of Prostate Cancer Cells.

BACKGROUND: This study aims to test whether Cordyceps sinensis (CS), the most expensive Asian nutrient supplement might stimulate growth of prostate cancer cells. METHODS: Impact of CS on growth of prostate cancer was determined in vivo and in vitro. RESULTS: Firstly, the serum testosterone level was significantly elevated in mice fed CS. Prostate glands were significantly enlarged (weight index 0.53 ± 0.04 mg/g vs. 0.31 ± 0.04 mg/g, P = 0.006). Furthermore, cell viability was increased twofold in the androgen-responsive prostate cancer cell line (VCaP) after CS treatment. This promoting effect disappeared after bicalutamide was added. In addition, serum prostate-specific antigen (PSA) in mice bearing VCaP xenografts was significantly elevated (0.66 ± 0.04 ng/ml vs. 0.26 ± 0.06 ng/ml, P < 0.001) after treatment with CS. Finally, VCaP tumors in mice treated with CS grew much faster (479.2 ± 78.74 mm3 vs. 283 ± 58.97 mm3, P = 0.074). However, the above promoting effects of CS were not observed in parallel studies using the PC-3 cell line which lacks AR expression. CONCLUSIONS: These results suggest that CS promotes growth of prostate cancer cells by increasing production of testosterone and stimulating the AR-dependent pathway. Additional studies are required to see whether CS is safely consumed by patients with prostate cancer.

Methyl jasmonate enhances the radiation sensitivity of esophageal carcinoma cells by inhibiting the 11-ketoprostaglandin reductase activity of AKR1C3.

PURPOSE: In our previous study, we found that AKR1C3 was a radioresistance gene in KY170R cells. Downregulating the expression of AKR1C3 could enhance the radiosensitivity of esophageal carcinoma cells. In this study, we investigated whether methyl jasmonate (MeJ), an inhibitor of Aldo-keto reductase family1 member C3 (AKR1C3), could overcome radiation resistance in AKR1C3 highly expressed cells. PATIENTS AND METHODS: We used clone formation assays to detect radiosensitivity effects. Flow cytometry assays were used to detect reactive oxygen species (ROS) accumulation and apoptosis. Enzyme linked immunosorbent assays (ELISAs) were used to detect the concentrations of prostaglandin F2 (PGF2) and prostaglandin D2 (PGD2) in the cells after incubation with MeJ. Western blotting was used to detect AKR1C3 and peroxisome proliferator-activated receptor gamma (PPARγ) expression. RESULTS: We found that AKR1C3 was highly expressed in radioresistant esophageal carcinoma cells. MeJ inhibited the expression of AKR1C3 and enhanced the radiation sensitivity of esophageal carcinoma cells expressing high levels of AKR1C3 (P<0.05). MeJ could inhibit the 11-ketoprostaglandin reductase activity of AKR1C3 in a dose-dependent manner in KY170R cells. Incubation of KY170R cells with 200 µmol/L of MeJ for 24 h reduced the expression of PGF2 by roughly 30% (P<0.05). The PPAR pathway inhibitor GW9662 prevented the radiation sensitivity enhancement imparted by MeJ. After adding GW9662, there were no significant differences between the radiation sensitivities of MeJ-treated and -untreated KY170R cells (P>0.05). The radiation sensitivity effect of MeJ also depended upon the generation of ROS in KY170R cells; 48 h after irradiation, ROS levels in the MeJ group was twofold higher than in the untreated KY170R cells (P<0.05). The ROS scavenger, N-acetyl cysteine, could reverse the radiosensitivity effects of MeJ (P>0.05). CONCLUSION: Our results indicate that MeJ can increase the radiation sensitivity of AKR1C3-overexpressing KY170R cells by inhibiting the 11-ketoprostaglandin reductase activity of AKR1C3 and increasing cellular ROS levels.

Targeting epigenetic pathway with gold nanoparticles for acute myeloid leukemia therapy.

Leukemia remains a fatal disease for most patients and novel therapeutic strategies are urgently needed. Aberrant DNA methylation is an epigenetic modification that is important in the initiation and progression of leukemia. Here, we demonstrated NCL/miR-221/NFκB/DNMT1 axis as a new molecular pathway promoting aggressive acute myeloid leukemia (AML) leukemogenesis and successfully designed and prepared a nuclear localization signal (NLS) peptide-targeted gold nanoparticles with co-loaded anti-221 and AS1411 (NPsN-AS1411/a221), which can specifically target NCL/miR-221/NFκB/DNMT1 signaling pathway in AML. NPsN-AS1411/a221 synergistically abrogate endogenous miR-221 promoting cancerous growth by inhibiting the expression of p27Kip1 suppressor gene, as well as effectively deregulate the DNMT1 expression through NFκB signaling which led to a reduction of global DNA methylation and the restoration of tumor suppressor p15INK4B via its promoter DNA hypomethylation. Functionally, NPsN-AS1411/a221 remarkably blockage leukemia proliferation and clonogenic potential in NCL/miR-221/NFκB/DNMT1 positive AML cell lines. More importantly, NPsN-AS1411/a221 cooperatively extend the overall survival, lower the white blood cells, reverse splenomegaly, inhibit blasts in bone marrow and metastatic to lung in a preclinical AML animal model. Altogether, our studies provide a proof of concept for multiple-functional drug delivery system that based on the specific gene network involved in tumor growth, and highlight the clinical potential of NCL/miR-221/NFκB/DNMT1-targeted AML nanotherapy.

Prognostic value of chemotherapy in addition to concurrent chemoradiotherapy in T3-4N0-1 nasopharyngeal carcinoma: a propensity score matching study.

PURPOSE: The objective of this study is to evaluate the contribution of induction (IC) or adjuvant (AC) chemotherapy additional to concurrent chemoradiotherapy (CCRT) for patients with T3-4N0-1 nasopharyngeal carcinoma (NPC) in the era of intensity-modulate radiotherapy (IMRT). METHOD AND MATERIALS: We retrospectively reviewed the data on 685 patients with newly diagnosed T3-4N0-1 NPC. Propensity score matching (PSM) method was used to match patients. Survival outcomes between different groups were calculated by Kaplan-Meier method and compared using log-rank test. Cox proportional hazard model was adopted to establish independent prognostic factors. RESULTS: In total, 236 pairs were selected from the primary cohort. Univariate analysis revealed 3-year overall survival (OS) (90.8% vs. 90.3%, P = 0.820), distant failure-free survival (DFFS) (87.3% vs. 89.4%, P = 0.896) and locoregional failure-free survival (LRFFS) (95.4% vs. 93.0%, P = 0.311) rates were comparable between CCRT plus IC/AC and CCRT alone groups. Multivariate analysis found that treatment group was not an independent prognostic factors for OS (HR, 0.964; 95% CI, 0.620-1.499; P = 0.869), DFFS (HR, 1.036; 95% CI, 0.626-1.714; P = 0.890) and LRFFS (HR, 0.670; 95% CI, 0.338-1.327; P = 0.250). Further subgroup analysis according to overall stage also obtained similar results. CONCLUSION: Patients with T3-4N0-1 NPC receiving CCRT could not benefit from additional induction or adjuvant chemotherapy in the era of IMRT.

Comparing the efficacy of induction-concurrent with concurrent-adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma: a propensity score matching analysis.

PURPOSE: This study aimed to compare the efficacy of induction-concurrent (IC-CCRT) with concurrent-adjuvant (CCRT-AC) chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated by intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Data on 834 patients with newly diagnosed, non-metastatic stage III-IVA (except T3N0) NPC receiving either IC-CCRT or CCRT-AC between July, 2004 and December, 2014 were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance prognostic factors and match patients. Survival outcomes of matched patients between IC-CCRT and CCRT-AC were compared. RESULTS: The median follow-up duration is 45.2 months (range, 1.07-145.4 months). Overall, 309 pairs were selected by PSM. Univariate analysis revealed the CCRT-AC group achieved significantly higher 3-year DFS (83.9% vs. 78.7 %; P = 0.014) and OS (87.6% vs. 87.0%; P = 0.031). Multivariate analysis also identified treatment group (IC-CCRT vs. CCRT-AC) as an independent prognostic factor for 3-year DFS (HR, 1.546; 95% CI, 1.113-2.149; P = 0.009) and OS (HR, 1.487; 95% CI, 1.035-2.136; P = 0.032). Subgroup analysis revealed IC-CCRT was a protective factor for DMFS (HR, 0.145; 95% CI, 0.043-0.488; P = 0.002) in stage III disease; however, it could adversely affected DFS (HR, 2.009; 95% CI, 1.316-3.065; P = 0.001), OS (HR, 1.671; 95% CI, 1.060-2.636; P = 0.027) and DMFS (HR, 1.986; 95% CI, 1.155-3.416; P = 0.013) in stage IVA disease. CONCLUSIONS: CCRT-AC may be a more effective treatment modality in patients with stage IVA NPC disease, while IC-CCRT was superior in stage III disease.