Prognostic Value of Baseline and Interim Total Metabolic Tumor Volume and Total Lesion Glycolysis Measured on 18F-FDG PET-CT in Patients with Follicular Lymphoma

Jin-Hua Liang,Yun-Ping Zhang,Jun Xia,Chong-Yang Ding,Wei Wu,Li Wang,Lei Cao,Hua-Yuan Zhu,Lei Fan,Tian-Nv Li,Jian-Yong Li,Wei Xu 대한암학회 2019 Cancer Research and Treatment Vol.51 No.4

Purpose The purpose of this study was to investigate the prognostic significance of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) in patients with follicular lymphoma (FL) at baseline and mid-treatment with 18F-fluorodeoxyglucose positron emission tomography computed tomography (PET-CT) scans. Materials and Methods The study analyzed data from 48 patients with FL who were treated in Jiangsu Province Hospital and reviewed their baseline PET-CT scans. TMTV and TLG were computed by using the absolute value of 2.0, 2.5, and 3.0 thresholding method, respectively. Results Median age was 53 years, 75.0% of patients had stage III to IV disease, 43.8% had a Follicular Lymphoma International Prognostic Index 1 (FLIPI1) score of 3 to 5 and 20.8% had a FLIPI2 score of 3 to 5. Receiver operating characteristic (ROC) curve analysis showed the optimal cut-off values for TMTV3.0 and TLG3.0 were 476.4 (sensitivity, 85.7%; specificity, 78.0%; area under the curve [AUC], 0.760; p=0.003) and 2,676.9 (sensitivity, 71.4%; specificity, 78.0%; AUC, 0.760; p=0.003). On multivariable analysis, TMTV3.0 and TLG3.0 were independent predictors of both progression-free survival (PFS) (hazard ratio [HR], 5.406; 95% confidence interval [CI], 1.326 to 22.040; p=0.019 and HR, 6.502; 95% CI, 1.079 to 39.182; p=0.042) and overall survival (OS) (HR, 4.111; 95% CI, 1.125 to 15.027; p=0.033 and HR, 5.885; 95% CI, 1.014 to 34.148; p=0.049). ROC curve analysis showed the optimal cut-off values for TMTV3.0 and TLG3.0 were 66.3% (sensitivity, 85.7%; specificity, 63.4%; AUC, 0.774; p < 0.001) and 64.5% (sensitivity, 85.7%; specificity, 65.9%; AUC, 0.777; p < 0.001). Conclusion Baseline TMTV and TLG are strong predictors of PFS and OS in FL. Furthermore, interim TMTV (TMTV > 66.3%) and TLG (TLG > 64.5%) reduction are valuable tools for early treatment response assessment in FL patients.

The Prognostic Role of Circulating Epstein-Barr Virus DNA Copy Number in Angioimmunoblastic T-Cell Lymphoma Treated with Dose-Adjusted EPOCH

Jin-Hua Liang,Luo Lu,Hua-Yuan Zhu,Wang Li,Lei Fan,Jian-Yong Li,Wei Xu 대한암학회 2019 Cancer Research and Treatment Vol.51 No.1

Purpose Determine the frequency and prognostic value of circulating Epstein-Barr virus (EBV) DNA copy number in angioimmunoblastic T-cell lymphoma (AITL) patients who were treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) regimens. Materials and Methods Sixty newly-diagnosed AITL patients were retrospectively enrolled in the present study. All patients were treated with DA-EPOCH regimen. Results Twenty-two subjects (36.7%) had a EBV DNA-positive test at diagnosis. EBV DNApositive patients were associated with lower lymphocyte-monocyte ratio (p=0.024). Median followup was 40 months (range, 14 to 100 months). The overall response rate for all the 60 AITL patents were 71.7% (95% confidence interval [CI], 58.6 to 82.5) with 3-year progressivefree survival (PFS) rate of 30.9%±6.1% and overall survival (OS) rate of 60.1%±6.6%. Not only did PFS estimation differ between the EBV DNApositive and EBV DNAnegative group (hazard ratio [HR], 2.24; 95% CI, 1.15 to 4.35; p=0.006), but also worse OS was observed in the pretreatment EBV DNApositive group than in the EBV DNAnegative group (HR, 2.74; 95% CI, 1.22 to 6.19; p=0.006). EBV DNA test positivity was independent prognostic marker for both PFS (HR, 2.17; 95% CI, 1.17 to 4.00; p=0.014) and OS (HR, 3.24; 95% CI, 1.48 to 7.11; p=0.004) after adjusting International Prognostic Index and prognostic index for AITL score. Reduction in EBV copies was significantly associated with therapy-response. Conclusion Circulating EBV DNA level was an important prognostic and monitoring marker for AITL patients who treated with DA-EPOCH regimens which cannot improve outcomes for AITL patients.

EBV-miR-BHRF1-1 Targets p53 Gene: Potential Role in Epstein-Barr Virus Associated Chronic Lymphocytic Leukemia

Dan-Min Xu,Yi-Lin Kong,Li Wang,Hua-Yuan Zhu,Jia-Zhu Wu,Yi Xia,Yue Li,Shu-Chao Qin,Lei Fan,Jian-Yong Li,Jin-Hua Liang,Wei Xu 대한암학회 2020 Cancer Research and Treatment Vol.52 No.2

Purpose The purpose of this study was to investigate the prognostic impact of Epstein-Barr virus (EBV)–microRNA (miRNA, miR)-BHRF1-1 with chronic lymphocytic leukemia (CLL) as well as role of EBV-miR-BHRF1-1 in p53 gene. Materials and Methods Quantitative reverse transcription–polymerase chain reaction and western blotting were used to quantify EBV-miR-BHRF1-1 and p53 expression in cultured CLL. Results p53 aberration was associated with the higher expression level of EBV-miR-BHRF1-1 (p < 0.001) which was also an independent prognostic marker for overall survival (p=0.028; hazard ratio, 5.335; 95% confidence interval, 1.193 to 23.846) in 97 newly-diagnosed CLL patients after adjusted with International Prognostic Index for patients with CLL. We identified EBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressed luciferase reporter activity by specific interaction with the seed region within the p53 3- untranslated region. Discordance of p53 messenger RNA and protein expression was associated with high EBV-miR-BHRF1-1 levels in CLL patients and cell lines. EBV-miR-BHRF1- 1 inhibition upregulated p53 protein expression, induced cell cycle arrest and apoptosis and decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53 protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferation in cell lines. Conclusion This study supported the role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our results support the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLL with p53 gene aberration.

공기분위기 하에서 열처리된 고입체 규칙성 폴리아크릴로니트릴의 XRD에 환화반응 속도 연구

Zhi Xian Xu,Jing Xu,Liang Hua Xu,Yong Qiang Dai,Li Wei Xue,Ri Guang Jin 한국고분자학회 2008 폴리머 Vol.32 No.2

Associations of Plasma Glucagon Levels with Estimated Glomerular Filtration Rate, Albuminuria and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus

Hua-Xing Huang,Liang-Lan Shen,Hai-Yan Huang,Li-Hua Zhao,Feng Xu,Dong-Mei Zhang,Xiu-Lin Zhang,Tong Chen,Xue-Qin Wang,Yan Xie,Jian-Bin Su 대한당뇨병학회 2021 Diabetes and Metabolism Journal Vol.45 No.6

Background: Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients.Methods: Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUCgla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR <60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g who presented with diabetic retinopathy were identified as having DKD.Results: Of the 2,436 recruited patients, fasting glucagon was correlated with eGFR and UACR (r=–0.112 and r=0.157, respectively; P<0.001), and AUCgla was also correlated with eGFR and UACR (r=–0.267 and r=0.234, respectively; P<0.001). Moreover, 31.7% (n=771) presented with DKD; the prevalence of DKD was 27.3%, 27.6%, 32.5%, and 39.2% in the first (Q1), second (Q2), third (Q3), and fourth quartile (Q4) of fasting glucagon, respectively; and the corresponding prevalence for AUCgla was 25.9%, 22.7%, 33.7%, and 44.4%, respectively. Furthermore, after adjusting for other clinical covariates, the adjusted odds ratios (ORs; 95% confidence intervals) for DKD in Q2, Q3, and Q4 versus Q1 of fasting glucagon were 0.946 (0.697 to 1.284), 1.209 (0.895 to 1.634), and 1.521 (1.129 to 2.049), respectively; the corresponding ORs of AUCgla were 0.825 (0.611 to 1.114), 1.323 (0.989 to 1.769), and 2.066 (1.546 to 2.760), respectively. Additionally, when we restricted our analysis in patients with glycosylated hemoglobin <7.0% (n=471), we found fasting glucagon and AUCgla were still independently associated with DKD.Conclusion: Both increased fasting and postchallenge glucagon levels were independently associated with DKD in T2DM patients.

β3GnT8 Regulates Laryngeal Carcinoma Cell Proliferation Via Targeting MMPs/TIMPs and TGF-β1

Hua, Dong,Qin, Fang,Shen, Li,Jiang, Zhi,Zou, Shi-Tao,Xu, Lan,Cheng, Zhi-Hong,Wu, Shi-Liang Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Previous evidence showed ${\beta}1$, 3-N-acetylglucosaminyltransferase 8 (${\beta}3GnT8$), which can extend polylactosamine on N-glycans, to be highly expressed in some cancer cell lines and tissues, indicating roles in tumorigenesis. However, so far, the function of ${\beta}3GnT8$ in laryngeal carcinoma has not been characterized. To test any contribution, Hep-2 cells were stably transfected with sense or interference vectors to establish cell lines that overexpressed or were deficient in ${\beta}3GnT8$. Here we showed that cell proliferation was increased in ${\beta}3GnT8$ overexpressed cells but decreased in ${\beta}3GnT8$ knockdown cells using MTT. Furthermore, we demonstrated that change in ${\beta}3GnT8$ expression had significant effects on tumor growth in nude mice.We further provided data suggesting that overexpression of ${\beta}3GnT8$ enhanced the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) at both the mRNA and protein levels, associated with shedding of tissue inhibitors of metalloproteinase TIMP-2. In addition, it caused increased production of transforming growth factor beta 1 (TGF-${\beta}1$), whereas ${\beta}3GnT8$ gene knockdown caused the reverse effect. The results may indicate a novel mechanism by which effects of ${\beta}3GnT8$ in regulating cellular proliferation are mediated, at least in partvia targeting MMPs/TIMPs and TGF-${\beta}1$ in laryngeal carcinoma Hep-2 cells. The finding may lay a foundation for further investigations into the ${\beta}3GnT8$ as a potential target for therapy of laryngeal carcinoma.

Identification of Serum MicroRNA-21 as a Biomarker for Early Detection and Prognosis in Human Epithelial Ovarian Cancer

Xu, Yun-Zhao,Xi, Qing-Hua,Ge, Wen-Liang,Zhang, Xiao-Qian Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2

Recent investigations have confirmed up-regulation of serum miR-21 and its diagnostic and prognostic value in several human malignancies. In this study, we examined serum miR-21 levels in epithelial ovarian cancer (EOC) patients, and explored its association with clinicopathological factors and prognosis. The results showed significantly higher serum miR-21 levels in EOC patients than in healthy controls. In addition, increased serum miR-21 expression was correlated with advanced FIGO stage, high tumor grade, and shortened overall survival. These findings indicate that serum miR-21 may serve as a novel diagnostic and prognostic marker, and be used as a therapeutic target for the treatment of EOC.

MicroRNA-155 Expression has Prognostic Value in Patients with Non-small Cell Lung Cancer and Digestive System Carcinomas

Xu, Tong-Peng,Zhu, Can-Hong,Zhang, Jian,Xia, Rui,Wu, Feng-Lei,Han, Liang,Shen, Hua,Liu, Ling-Xiang,Shu, Yong-Qian Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Objective: Published data have shown that microRNAs (miRNAs) could play a potential role as diagnostic and prognostic indicators in cancers. Data for the predictive value of microRNA-155 are inconclusive. The aim of the present analysis was therefore to evaluate the role of miR-155 in prognosis for patients with a variety of carcinomas. Methods: Relevant studies were identified by searching PubMed and EMBASE. Data were extracted from studies comparing overall survival (OS), recurrence-free survival (RFS) or cancer-specific survival (CSS) in patients with carcinoma with higher miR-155 expression and those with lower levels. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of miR-155 for clinical outcome were calculated. Results: A total of 15 studies were included. The pooled hazard ratio (HR) for OS of higher miR-155 expression in cancerous tissue was 1.89 (95% CI: 1.20-2.99, P=0.006), which could markedly predict poorer survival in general cancer. For RFS/CSS, elevated miR-155 was also associated with poor prognosis of cancer (HR=1.50, 95% CI: 1.10-2.05, P=0.01). On subgroup analysis, the pooled HR for OS in non-small cell lung cancer (NSCLC) was 2.09 (95% CI: 0.68-6.41, P > 0.05), but for RFS/CSS was 1.28 (95% CI: 1.05-1.55, P=0.015), with statistical significance; the pooled HRs for OS and RFS/CSS in digestive system neoplasms were 3.04 (95% CI: 1.48-6.24, P=0.003) and 2.61 (95% CI: 1.98-3.42, P<0.05), respectively. Conclusions: The results indicated that the miR-155 expression level plays a prognostic role in patients with cancer, especially NSCLCs and digestive system carcinomas.

Dynamic characteristics and experimental study on a wind turbine gearbox

Liang Xu,Caichao Zhu,Hua iju Liu,Guo Chen,Wei Long 대한기계학회 2019 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.33 No.1

A gearbox is part of the transmission chain of wind turbine, which can increase rotational speed and reduce torque. Dynamic characteristics of the gearbox directly influence the vibration and the service life of the wind turbine system. In this paper, dynamic behaviors of a megawatt level wind turbine gearbox are studied theoretically and experimentally by dividing the gearbox into a transmission sub-system and a body sub-system. The transmission sub-system, i.e., the gear-shaft-bearing sub-system, is coupled with the gearbox body using bearings which are simulated as mass-less springs. The theoretical study applies a finite element model for the gearbox, where the internal excitations are caused by time-varying stiffness, transmission errors and mesh impacts. The time-varying wind load is considered as the external excitation, collected by a remote real-time online test and transformed into load spectrums through the rain-flow counting method. With boundary conditions and working conditions being defined in the finite element model, the natural characteristic analysis and the dynamic response analysis are conducted. Results show that the operating frequencies of the gearbox are far away from the main natural frequencies of the system, thus avoiding resonances. The main vibration components of the gearbox are with meshing frequencies of the second and third gear stage and their multiplication counterparts. Moreover, the greatest vibration occurs at the bearing housing of the high-speed shaft with the root-mean-square value of its vibration speed less than 3.5 mm/s. A test rig is developed and the experimental vibration conditions are monitored by acceleration sensors. The experimental results are in accordance well with the theoretical results. In this way, the theoretical model is validated. The methodology reported in this paper can provide valuable guidance for practical industrial engineers.

Induction Chemotherapy Followed by Concurrent Chemoradiotherapy Versus Concurrent Chemoradiotherapy with or without Adjuvant Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma: Meta-analysis of 1,096 Patients from 11 Randomized Controlled

Liang, Zhong-Guo,Zhu, Xiao-Dong,Tan, Ai-Hua,Jiang, Yan-Ming,Qu, Song,Su, Fang,Xu, Guo-Zeng Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Purpose: To evaluate the efficacy and toxicity of induction chemotherapy followed by concurrent chemoradiotherapy (the treatment group) versus concurrent chemoradiotherapy with or without adjuvant chemotherapy (the control group) for locoregionally advanced nasopharyngeal carcinoma. Methods: The search strategy included Pubmed, Embase, the Cochrane Library, China National Knowledge Internet Web, Chinese Biomedical Database and Wanfang Database. We also searched reference lists of articles and the volumes of abstracts of scientific meetings. All randomized controlled trials were included for a meta-analysis performed with RevMan 5.1.0. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to rate the level of evidence. Results: Eleven studies were included. Risk ratios of 0.99 (95%CI 0.72-1.36), 0.37 (95%CI 0.20-0.69), 1.08 (95%CI 0.84-1.38), 0.98 (95%CI 0.75-1.27) were observed for 3 years overall survival, 3 years progression-free survival, 2 years loco-regional failure-free survival and 2 years distant metastasis failure-free survival. There were no treatment-related deaths in either group in the 11 studies. Risk ratios of 1.90 (95%CI 1.24-2.92), 2.67 (95%CI 0.64-11.1), 1.04 (95%CI 0.79-1.37), 0.98 (95%CI 0.27-3.52) were found for grade 3-4 leukopenia, grade 3-4 thrombocytopenia, grade 3-4 mucous membrane, and grade 3-4 hepatic hematologic and gastrointestinal toxicity, the most significant toxicities for patients. Conclusion: Compared with the control group, induction chemotherapy followed by concurrent chemoradiotherapy was well tolerated but could not significantly improve prognosis in terms of overall survival, loco-regional failure-free survival or distant metastasis failure-free survival.