Combination of Tumor Volume and Epstein-Barr Virus DNA Improved Prognostic Stratification of Stage II Nasopharyngeal Carcinoma in the Intensity Modulated Radiotherapy Era: A Large-Scale Cohort Study

Qiu-Yan Chen,Shao-Yan Guo,Lin-Quan Tang,Tong-Yu Lu,Bo-Lin Chen,Qi-Yu Zhong,Meng-Sha Zou,Qing-Nan Tang,Wen-Hui Chen,Shan-Shan Guo,Li-Ting Liu,Yang Li,Ling Guo,Hao-Yuan Mo,Rui Sun,Dong-Hua Luo,Chong Zha 대한암학회 2018 Cancer Research and Treatment Vol.50 No.3

Purpose Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors. Materials and Methods By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above. Results Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm3; EBV DNA 0 copy/mL, GTVtotal  30 cm3; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm3) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal  30 cm3). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant. Conclusion Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.

The Prognostic Value of Treatment-Related Lymphopenia in Nasopharyngeal Carcinoma Patients

Li-Ting Liu,Qiu-Yan Chen,Lin-Quan Tang,Shan-Shan Guo,Ling Guo,Hao-Yuan Mo,Ming-Yuan Chen,Chong Zhao,Xiang Guo,Chao-Nan Qian,Mu-Sheng Zeng,Jin-Xin Bei,Jing Tan,Shuai Chen,Ming-Huang Hong,Jian-Yong Shao 대한암학회 2018 Cancer Research and Treatment Vol.50 No.1

Purpose This study was conducted to evaluate the prognostic value of treatment-related lymphopenia in patients with nasopharyngeal carcinoma (NPC). Materials and Methods A total of 413 consecutive stage II-IVb NPC patients treated with concurrent chemoradiotherapy (CCRT) were enrolled. The overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared using the log-rank test. Results A minimum (mini)–absolute lymphocyte counts (ALC) of < 390 cells/μL or ALC after 3 months of CCRT (post3m-ALC) < 705 cells/μL was significantly associated with worse outcome than mini-ALC ! 390 cells/μL (OS, p=0.002; PFS, p=0.005; DMFS, p=0.004) or post3m-ALC ! 705 cells/μL (OS, p < 0.001; PFS, p < 0.001; DMFS, p=0.001). Patients with lymphopenia (mini-ALC < 390 cells/μL and post3m-ALC < 705 cells/μL) had a worse prognosis than those without lymphopenia (mini-ALC ! 390 cells/μL and post3m-ALC ! 705 cells/μL) (OS, p < 0.001; PFS, p < 0.001; DMFS, p < 0.001). Multivariate analysis revealed that post3m-ALC was an independent prognostic factor for OS (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.12 to 2.78; p=0.015), PFS (HR, 1.86; 95% CI, 1.23 to 2.82; p=0.003), and DMFS (HR, 1.87; 95% CI, 1.13 to 3.08; p=0.014). Multivariate analysis also revealed that patients with lymphopenia had a high risk of death (HR, 3.79; 95% CI, 1.75 to 8.19; p=0.001), disease progression (HR, 2.93; 95% CI, 1.59 to 5.41; p=0.001), and distant metastasis (HR, 3.89; 95% CI, 1.67 to 9.10; p=0.002). Multivariate analysis performed with time dependent Cox regression demonstrated ALC was an independent prognostic factor for OS (HR, 0.995; 95% CI, 0.991 to 0.999; p=0.025) and PFS (HR, 0.993; 95% CI, 0.988 to 0.998; p=0.006). Conclusion Treatment-related lymphopenia was a poor prognostic factor in NPC patients.

Ginsenoside Rb1 exerts neuroprotective effects through regulation of Lactobacillus helveticus abundance and GABA_A receptor expression

Chen, Huimin,Shen, Jiajia,Li, Haofeng,Zheng, Xiao,Kang, Dian,Xu, Yangfan,Chen, Chong,Guo, Huimin,Xie, Lin,Wang, Guangji,Liang, Yan The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.1

Background: Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure. Purpose: The present study aimed to elucidate the apparent contradiction between the pharmacokinetics and pharmacodynamics of Rb1 by studying the mechanisms underlying neuroprotective effects of Rb1 based on regulation of microflora. Methods: A pseudo germ-free (PGF) rat model was established, and neuroprotective effects of Rb1 were compared between conventional and PGF rats. The relative abundances of common probiotics were quantified to reveal the authentic probiotics that dominate in the neuroprotection of Rb1. The expressions of the gamma-aminobutyric acid (GABA) receptors, including GABAA receptors (α2, β2, and γ2) and GABAB receptors (1b and 2), in the normal, ischemia/reperfusion (I/R), and I/R+Rb1 rat hippocampus and striatum were assessed to reveal the neuroprotective mechanism of Rb1. Results: The results showed that microbiota plays a key role in neuroprotection of Rb1. The relative abundance of Lactobacillus helveticus (Lac.H) increased 15.26 fold after pretreatment with Rb1. I/R surgery induced effects on infarct size, neurological deficit score, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were prevented by colonizing the rat gastrointestinal tract with Lac.H (1 × 10⁹ CFU) by gavage 15 d before I/R surgery. Both Rb1 and Lac.H upregulated expression of GABA receptors in I/R rats. Coadministration of a GABA_A receptor antagonist significantly attenuated neuroprotective effects of Rb1 and Lac.H. Conclusion: In sum, Rb1 exerts neuroprotective effects by regulating Lac.H and GABA receptors rather than through direct distribution to the target sites.

Robust Segmentation for Low Quality Cell Images from Blood and Bone Marrow

Chen Pan,Yi Fang,Xiang-guo Yan,Chong-xun Zheng 대한전기학회 2006 International Journal of Control, Automation, and Vol.4 No.5

Biomedical image is often complex. An applied image analysis system should deal with the images which are of quite low quality and are challenging to segment. This paper presents a framework for color cell image segmentation by learning and classification online. It is a robust two-stage scheme using kernel method and watershed transform. In first stage, a two-class SVM is employed to discriminate the pixels of object from background; where the SVM is trained on the data which has been analyzed using the mean shift procedure. A real-time training strategy is also developed for SVM. In second stage, as the post-processing, local watershed transform is used to separate clustering cells. Comparison with the SSF (Scale space filter) and classical watershed-based algorithm (those are often employed for cell image segmentation) is given. Experimental results demonstrate that the new method is more accurate and robust than compared methods.

Ginsenoside Rb1 exerts neuroprotective effects through regulation of Lactobacillus helveticus abundance and GABA<SUB>A</SUB> receptor expression

Huimin Chen,Jiajia Shen,Haofeng Li,Xiao Zheng,Dian Kang,Yangfan Xu,Chong Chen,Huimin Guo,Lin Xie,Guangji Wang,Yan Liang 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.1

Background: Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure. Purpose: The present study aimed to elucidate the apparent contradiction between the pharmacokinetics and pharmacodynamics of Rb1 by studying the mechanisms underlying neuroprotective effects of Rb1 based on regulation of microflora. Methods: A pseudo germ-free (PGF) rat model was established, and neuroprotective effects of Rb1 were compared between conventional and PGF rats. The relative abundances of common probiotics were quantified to reveal the authentic probiotics that dominate in the neuroprotection of Rb1. The expressions of the gamma-aminobutyric acid (GABA) receptors, including GABAA receptors (α2, β2, and γ2) and GABAB receptors (1b and 2), in the normal, ischemia/reperfusion (I/R), and I/RþRb1 rat hippocampus and striatum were assessed to reveal the neuroprotective mechanism of Rb1. Results: The results showed that microbiota plays a key role in neuroprotection of Rb1. The relative abundance of Lactobacillus helveticus (Lac.H) increased 15.26 fold after pretreatment with Rb1. I/R surgery induced effects on infarct size, neurological deficit score, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were prevented by colonizing the rat gastrointestinal tract with Lac.H (1×10<SUP>9</SUP> CFU) by gavage 15 d before I/R surgery. Both Rb1 and Lac.H upregulated expression of GABA receptors in I/R rats. Coadministration of a GABAA receptor antagonist significantly attenuated neuroprotective effects of Rb1 and Lac.H. Conclusion: In sum, Rb1 exerts neuroprotective effects by regulating Lac.H and GABA receptors rather than through direct distribution to the target sites.

Ginsenoside Rb1 exerts neuroprotective effects through regulation of Lactobacillus helveticus abundance and GABAA receptor expression

Huimin Chen,Jiajia Shen,Haofeng Li,Xiao Zheng,Dian Kang,Yangfan Xu,Chong Chen,Huimin Guo,Lin Xie,Guangji Wang,Yan Liang 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.1

Background: Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exertsexcellent neuroprotective effects even though it has low intracephalic exposure. Purpose: The present study aimed to elucidate the apparent contradiction between the pharmacokineticsand pharmacodynamics of Rb1 by studying the mechanisms underlying neuroprotective effects ofRb1 based on regulation of microflora. Methods: A pseudo germ-free (PGF) rat model was established, and neuroprotective effects of Rb1 werecompared between conventional and PGF rats. The relative abundances of common probiotics werequantified to reveal the authentic probiotics that dominate in the neuroprotection of Rb1. The expressionsof the gamma-aminobutyric acid (GABA) receptors, including GABAA receptors (a2, b2, and g2) andGABAB receptors (1b and 2), in the normal, ischemia/reperfusion (I/R), and I/RþRb1 rat hippocampus andstriatum were assessed to reveal the neuroprotective mechanism of Rb1. Results: The results showed that microbiota plays a key role in neuroprotection of Rb1. The relativeabundance of Lactobacillus helveticus (Lac.H) increased 15.26 fold after pretreatment with Rb1. I/R surgeryinduced effects on infarct size, neurological deficit score, and proinflammatory cytokines (IL-1b, IL-6, andTNF-a) were prevented by colonizing the rat gastrointestinal tract with Lac.H (1 109 CFU) by gavage 15d before I/R surgery. Both Rb1 and Lac.H upregulated expression of GABA receptors in I/R rats. Coadministrationof a GABAA receptor antagonist significantly attenuated neuroprotective effects of Rb1 and Lac.H. Conclusion: In sum, Rb1 exerts neuroprotective effects by regulating Lac.H and GABA receptors ratherthan through direct distribution to the target sites.

Long-term Survivals, Toxicities and the Role of Chemotherapy in Early-Stage Nasopharyngeal Carcinoma Patients Treated with Intensity-modulated Radiation Therapy: A Retrospective Study with 15-year Follow-up

Lin Wang,Jingjing Miao,Huageng Huang,Boyu Chen,Xiao Xiao,Manyi Zhu,Yingshan Liang,Weiwei Xiao,Shaomin Huang,Yinglin Peng,Xiaowu Deng,Xing Lv,Weixiong Xia,Yanqun Xiang,Xiang Guo,Fei Han,Chong Zhao 대한암학회 2022 Cancer Research and Treatment Vol.54 No.1

Purpose This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients. Materials and Methods Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010. Results With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group. Conclusion Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.

Galectin-9 Acts as a Prognostic Factor with Antimetastatic Potential in Hepatocellular Carcinoma

Zhang, Zhao-Yang,Dong, Jia-Hong,Chen, Yong-Wei,Wang, Xian-Qiang,Li, Chong-Hui,Wang, Jian,Wang, Guo-Qiang,Li, Hai-Lin,Wang, Xue-Dong Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Considerable research has been conducted concerning galectin-9 and carcinomas, but little information is available about any relation with the hepatocellular carcinoma. In this study, we employed a small interfering RNA (siRNA) targeting galectin-9 to down-regulate the expression in HepG2 cells. As a result, after galectin-9 expression was reduced, cell aggregation was suppressed, while other behaviour such as the proliferation, adhesion and invasion to ECM, cell-endothelial adhesion and transendothelial invasion of the cells were markedly enhanced. When tumors of 200 patients with hepatocellular carcinoma were tested for galectin-9 expression by immunohistochemistry, binding levels demonstrated intimate correlations with the histopathologic grade, lymph node metastasis, vascular invasion and intrahepatic metastasis (P<0.05). Moreover, survival analysis indicated that patients with galectin-9 expression had much longer survival time than those with negative lesions, and the Log-rank test indicated that this difference was statistical significant (P<0.0001). The Cox proportional hazards model suggested that negative galectin-9 expression in hepatocellular carcinoma represented a significant risk factor for patient survival. We propose that galectin-9 might be a new prognostic factor with antimetastatic potential in patients with hepatocellular carcinoma.

Green Tea Consumption May Be Associated with Cardiovascular Disease Risk and Nonalcoholic Fatty Liver Disease in Type 2 Diabetics: A Cross-Sectional Study in Southeast China

Huan-Huan Yang,Hui Zhou,Wan-Zhan Zhu,Cai-Long Chen,Guo-Chong Chen,Lu-Gang Yu,Li-qiang Qin 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.10

Dietary factors play a crucial role in the management of type 2 diabetes mellitus (T2DM) by reducing cardiovascular disease (CVD) risk. Therefore, we aimed to examine the associations between habitual green tea consumption and risk factors of CVD among T2DM patients. A total of 1013 patients with T2DM were included in a community-based cross-sectional study. Data on dietary habits, including tea consumption, were collected using a food frequency questionnaire. A multivariable logistic regression model was used to analyze the associations. In men, as compared with nongreen tea drinkers, odds ratios (ORs) (95% confidence interval [CI]) of nonalcoholic fatty liver disease (NAFLD) were 2.06 (95% CI, 1.20–3.55) for those with green tea consumption of once per day and 2.45 (95% CI, 1.31–4.58) for more than or equal to twice per day (P-trend = .004); ORs (95% CI) of general obesity were 2.19 (95% CI, 1.02–4.68) and 2.70 (95% CI, 1.18–6.21), respectively (P-trend = .021); whereas no such association was found in women. Sensitivity analysis according to self-awareness of their T2DM status revealed that the positive association between green tea consumption and general obesity was not reliable. Higher intake of green tea was still positively associated with NAFLD, but it only persisted in participants aged ≥52 years or the lower dietary quality subgroup in further analyses. Our findings suggest that tea consumption was associated with an increased risk of NAFLD among male T2DM patients aged 52 years or older, and those with lower dietary quality, which needs to be confirmed in future prospective studies.

Induction Chemotherapy Plus Concurrent Chemoradiotherapy versus Concurrent Chemoradiotherapy Alone in Locoregionally Advanced Nasopharyngeal Carcinoma in Children and Adolescents: A Matched Cohort Analysis

Yang Li,Lin-Quan Tang,Li-Ting Liu,Shan-Shan Guo,Yu-Jing Liang,Xue-Song Sun,Qing-Nan Tang,Jin-Xin Bei,Jing Tan,Shuai Chen,Jun Ma,Chong Zhao,Qiu-Yan Chen,Hai-Qiang Mai 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose The purpose of this study was to evaluate the long-term clinical outcome and toxicity of induction chemotherapy (IC) followed by concomitant chemoradiotherapy (CCRT) compared with CCRT alone for the treatment of children and adolescent locoregionally advanced nasopharyngeal carcinoma (LACANPC). Materials and Methods A total of 194 locoregionally advanced nasopharyngeal carcinoma patients younger than 21 years who received CCRT with or without IC before were included in the study population. Overall survival (OS) rate, progression-free survival (PFS) rate, locoregional recurrence-free survival (LRFS) rate, and distant metastasis-free survival (DMFS) rate were assessed by the Kaplan-Meier method and a log-rank test. Treatment toxicities were clarified and compared between two groups. Results One hundred and thiry of 194 patients received IC+CCRT. Patients who were younger and with more advanced TNM stage were more likely to receive IC+CCRT and intensive modulated radiotherapy. The addition of IC before CCRT failed to improve survival significantly. The matched analysis identified 43 well-balanced patients in both two groups. With a median follow-up of 51.5 months, no differences were found between the IC+CCRT group and the CCRT group in 5-year OS (83.7% vs. 74.6%, p=0.153), PFS (79.2% vs. 73.4%, p=0.355), LRFS (97.7% vs. 88.2%, p=0.083), and DMFS (81.6% vs. 81.6%, p=0.860). N3 was an independent prognostic factor predicting poorer OS, PFS, and DMFS. The addition of IC was associated with increased rates of grade 3 to 4 neutropenia. Conclusion This study failed to demonstrate that adding IC before CCRT could provide a significant additional survival benefit for LACANPC patients. Further investigations are warranted.