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Differentially Methylated CpG Sites (2173 Sites) in 24 Nasopharyngeal Carcinoma (NPC) Tissues and 24 Non-cancer Nasopharyngitis Biopsy Tissues (NCNBT)

Kaplan-Meier curves estimation of disease-free survival (DFS) and overall survival (OS) for patients with high or low methylation levels stratified by tumor stage or the receipt of concurrent chemotherapy.

Supplementary Table S1: Clinicopathological Characteristics of 24 NPC and 24 NCNBT Supplementary Table S2: Clinical Characteristics of Nasopharyngeal Carcinoma Patients According to Gene Methylation Panel in Training, Validation, and Independent Cohorts. Supplementary Table S3: Primer Sequences of 28 Genes and GAPDH Supplementary Table S4: Primer Used for Pyrosequencing Methylation Analysis of Candidate Genes Supplementary Table S6: Data Analysis with PubMeth and NCBI PubMed Supplementary Table S7: Correlation Analysis between Methylation of Six Genes in the Training Cohort

Representative Pyrograms of Methylation Analysis by Bisulfite Pyrosequencing.

Purpose To assess the effectiveness and toxicity of radiation dose escalation in treating local advanced nasopharyngeal carcinoma patients (LA-NPCs) who have locally and/or regionally residual lesion(s) after standard treatment. Methods and materials: From November 2011 to November 2020, 259 LA-NPCs with residual local and/or regional lesion(s) after receiving induction chemotherapy followed by concurrent chemoradiotherapy (IC + CCRT) from our hospital were included. The total dose of primary radiotherapy (RT) was 68.1-74.25 Gy (median, 70.4 Gy). The boost doses were 4.0–18.0 Gy (median, 9 Gy), 1.8-2.0 Gy/fraction. Results Five-year local relapse-free survival (LRFS), regional relapse-free survival (RRFS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), failure-free survival (FFS) and overall survival (OS) for all patients were 90.2%, 89.1%, 79.5%, 87.9%, 69.0%, 86.3%, respectively. LRRFS, DMFS, FFS, and OS in patients with age ≤ 65 versus > 65, plasma EBV-DNA ≤ 500 versus > 500, T1 − 2 versus T3 − 4, N0 − 1 versus N2 − 3, and stage III versus stage IV showed no statistically significant differences. The interval between primary RT and boost was not a prognostic factor for LRRFS, DMFS, FFS, and OS. Males had a lower 3-year FFS rate than females (72.9% vs. 83.7%, P = 0.024). LA-NPCs with locally and regionally residual lesion(s) had the worst 3-year DMFS and OS rates compared with locally or regionally residual lesion(s) (77.7% vs. 98.8% vs. 87.4%, P = 0.014; 75.9% vs. 94.5% vs. 82.4%, P = 0.002). Conclusion Boost radiation was an option for LA-NPCs with locally and/or regionally residual lesions after receiving IC + CCRT. It warrants further prospective study.

Background Platinum-based chemotherapy is the standard first-line treatment for recurrent/metastatic nasopharyngeal carcinoma (NPC); however, there is no standard regimen for those who failed first-line treatment. This study aimed to evaluate the efficacy and safety of apatinib in treating patients with recurrent/metastatic NPC who failed prior platinum-based chemotherapy. Methods Patients aged 18–65 years with recurrent/metastatic NPC were treated with apatinib at an initial dose of 500 mg once daily and continued until disease progression, patient withdrawal, or unacceptable toxic effects. The primary endpoints were clinical benefit rate (CBR) and toxicity. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results Nineteen patients were enrolled in this study. At the final follow-up, the CBR was 52.6% (95% CI: 29.8–76.2%) in the intention-to-treat population. The median PFS and OS were 3.7 (95% CI: 0.6–6.8) months and 12.9 (95% CI: 9.3–16.5) months, respectively. The most common grade 3–4 adverse events (AEs) were hand-foot syndrome [3 (15.8%)], neutropenia [2 (10.5%)], proteinuria [2 (10.5%)], oral mucosal pain [2 (10.5%)], hypertension [1 (5.3%)], hyponatremia [1 (5.3%)], artery dissection [1 (5.3%)], and nasopharyngeal hemorrhage [1 (5.3%)]. A serious AEs was reported in one patient who died of nasopharyngeal hemorrhage. Treatment with apatinib did not significantly influence patient-reported quality-of-life, except for nausea/vomiting and pain (P

Background. It is controversial and unclear how N-stage would increase the risk of incidence of hypothyroidism (HT) for patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Our study aimed to explore the correlation between cervical lymph node metastasis and the incidence of HT in NPC. Materials and Methods. A total of 206 patients with NPC treated at the Cancer Hospital of University of Chinese Academy of Sciences, and their clinical information were retrospectively collected. A series of univariate logistic regression models were performed to explore the association of clinical and lymph node indices with the development of HT. Significant features in univariate analysis were then used to construct three prediction models, for HT prediction using multivariate logistic regression based on Bayesian information criterion. Prediction performance of those models was measured by area under the receiver operating characteristic curve (AUC) using 10-fold cross-validation. Results. A total of 111 patients developed HT, and the incidence of HT in N2–3 and N0–1 patients was 58.82% and 44.29%, respectively. Compared to Model 1 (consisted of pretreatment TSH concentration, thyroid volume, and N-stage) whose AUCs were 0.801 and 0.766 in training and validation sets, with N-stage be replaced by shortest distance from thyroid, Model 2 achieved more stable AUCs of 0.824 and 0.801. While with numbers of positive lymph nodes in Level IIb additionally added, Model 3 improved its AUCs to 0.841 and 0.813. Conclusion. The shortest distance between the lymph nodes and thyroid gland and the number of lymph nodes in IIb are better predictors of radiation-induced HT than the N-stage.

ImportanceMicrobiota-tumor interactions have qualified microbiota as a promising prognostic biomarker in various types of cancers. Although the nasopharynx acts as a crucial niche of the upper respiratory tract microbiome, whether the intratumoral microbiota exists and its clinical significance in nasopharyngeal carcinoma (NPC) remain uncertain.ObjectiveTo evaluate the clinical significance of intratumoral microbiota for individual prognostication in patients with NPC.Design, Setting, and ParticipantsThis retrospective cohort study included NPC biopsy samples from 2 hospitals: Sun Yat-sen University Cancer Center (Guangzhou, China) and Zhejiang Cancer Hospital (Hangzhou, China) between January 2004 and November 2016, with follow-up through November 2020. A total of 802 patients were included according to the following criteria: with histologically proven NPC, without distant metastasis at initial diagnosis, had not received antitumor treatment before biopsy sampling, aged between 18 and 70 years, with complete medical records and regular follow-up, without a history of cancer, and successfully extracted enough DNA for experiments.Main Outcomes and MeasuresThe primary end point was disease-free survival, and the secondary end points included distant metastasis–free survival and overall survival. To assess the existence and load of intratumoral microbiota in 96 patients with NPC with or without tumor relapse, 16S rRNA sequencing and quantitative polymerase chain reaction were used. The associations between intratumoral bacterial load and clinical outcome were evaluated in 241 fresh-frozen NPC samples (training cohort) and validated in paraffin-embedded NPC samples of internal (n = 233) and external (n = 232) validation cohorts. Metagenomic and transcriptome analyses were performed to ascertain the origin and underlying mechanism of intratumoral bacteria.ResultsA total of 802 patients with NPC (mean [SD] age, 46.2 [10.6] years; 594 [74.1%] male) were enrolled. Microbiota presented within NPC tumor tissues, among which Corynebacterium and Staphylococcus predominated. Patients with a high bacterial load in the training cohort had inferior rates of disease-free survival (hazard ratio [HR], 2.90; 95% CI, 1.72-4.90; P P P Conclusions and RelevanceIntratumoral bacterial load was a robust prognostic tool for patients with NPC in this cohort study, indicating potential guidance for treatment decisions in patients at different levels of risk of malignant progression.

To report long-term results of a randomized controlled trial that compared cisplatin/fluorouracil/docetaxel (TPF) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with stage III-IVB (except T3-4 N0) NPC were randomly assigned to receive IC plus CCRT (n = 241) or CCRT alone (n = 239). IC included three cycles of docetaxel (60 mg/m2 d1), cisplatin (60 mg/m2 d1), and fluorouracil (600 mg/m2 /d civ d1-5) every 3 weeks. Patients from both groups received intensity-modulated radiotherapy concurrently with three cycles of 100 mg/m2 cisplatin every 3 weeks. After a median follow-up of 71.5 months, the IC plus CCRT group showed significantly better 5-year failure-free survival (FFS, 77.4% vs. 66.4%, p = 0.019), overall survival (OS, 85.6% vs. 77.7%, p = 0.042), distant failure-free survival (88% vs. 79.8%, p = 0.030), and locoregional failure-free survival (90.7% vs. 83.8%, p = 0.044) compared to the CCRT alone group. Post hoc subgroup analyses revealed that beneficial effects on FFS were primarily observed in patients with N1, stage IVA, pretreatment lactate dehydrogenase ≥170 U/l, or pretreatment plasma Epstein-Barr virus DNA ≥6000 copies/mL. Two nomograms were further developed to predict the potential FFS and OS benefit of TPF IC. The incidence of grade 3 or 4 late toxicities was 8.8% (21/239) in the IC plus CCRT group and 9.2% (22/238) in the CCRT alone group. Long-term follow-up confirmed that TPF IC plus CCRT significantly improved survival in locoregionally advanced NPC with no marked increase in late toxicities and could be an option of treatment for these patients.

Cyclophilin D (CypD) is a mitochondrial matrix peptidyl prolidase that has been identified as a target for the treatment of acute pancreatitis. However, only a few compounds have been reported as CypD inhibitors. To discover novel CypD inhibitors, a ZINC database including 206,724 compounds was screened through 3D-QSAR pharmacophore model and molecular docking in sequence. After an in-depth analysis of the docking results obtained, ZINC161011368, ZINC664707610 and ZINC665010466 were selected for the molecular dynamics simulations and the binding free energy calculations. On this basis, ZINC161011368 was identified as having the potential of application as a novel CypD inhibitor. This study provides a basis for screening highly active CypD inhibitors for the treatment of acute pancreatitis.

Protein Kinase C ζ (PKCζ) has emerged as a promising novel drug target for the treatment of arthritis. A series of isoquinoline PKCζ inhibitors were analyzed through CoMFA, CoMSIA, homology modeling, and molecular docking to obtain insights into the structural requirements of PKCζ inhibitors. To our best knowledge, this work is the first report on 3D-QSAR modeling of PKCζ inhibitors. The constructed CoMFA (q2 = 0.578, r2 = 0.89, r2predr2pred = 0.756) and CoMSIA (q2 = 0.758, r2 = 0.983, r2pred = 0.753) models showed a good statistical robustness and a high external predictability. With a reliable template structure (4DC2), a homology model of PKCζ was built and the Ramachandran plot indicated that the above homology model was acceptable. PKCζ inhibitors were docked into the binding site of the homology model of PKCζ to get their binding mode. The structural requirements for PKCζ inhibition were highlighted in our results, which may contribute to the development of novel PKCζ inhibitors.

// Ting Jin 1, 2, * , Qun Zhang 3, * , Feng Jiang 1, 2 , Wei-Feng Qin 1, 2 , Qi-Feng Jin 1, 2 , Cai-Neng Cao 1, 2 , Yong-Feng Piao 1, 2 , Xing-Lai Feng 1, 2 , Wei Luo 4 and Xiao-Zhong Chen 1, 2 1 Key Laboratory of Radiation Oncology in Zhejiang Province, Hangzhou, Zhejiang 310022, People’s Republic of China 2 Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, People’s Republic of China 3 Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510060, People’s Republic of China 4 Department of Radiation Oncology, Sun Yat-Sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, Guangdong 510060, People’s Republic of China * These authors contributed equally to this work Correspondence to: Xiao-Zhong Chen, email: chenxiaozhongfy@163.com Wei Luo, email: luowei2@mail.sysu.edu.cn Keywords: nasopharyngeal carcinoma, neoadjuvant chemotherapy, concurrent chemoradiation, cisplatin, docetaxel Received: March 04, 2017 Accepted: July 12, 2017 Published: October 20, 2017 ABSTRACT Objective: Compare high- vs. low-dose TPF neoadjuvant chemotherapy with chemoradiotherapy in Chinese patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Materials and Methods: Retrospective analysis of 210 stage III/IV NPC patients treated between April 1, 2012 and April 1, 2014; 138 received three cycles of high-dose TPF (H-TPF) every 3 weeks at Zhejiang Cancer Hospital and 72, three cycles of low-dose TPF (L-TPF) every 3 weeks at Sun Yat-Sen University Cancer Center. H-TPF was docetaxel (75 mg/m 2 ; 1 h infusion), cisplatin (75 mg/m 2 ; 0.5–3 h), then 5-fluorouracil (600 mg/m2/day; 4 days). L-TPF was docetaxel (60 mg/m 2 ), cisplatin (65 mg/m 2 ), then 5-fluorouracil (550 mg/m 2 /day; 5 days). All patients received chemoradiotherapy. Results: During neoadjuvant chemotherapy, treatment delays were more frequent for H-TPF than L-TPF (33.3% vs. 19.4%; P = 0.034). During chemoradiotherapy, grade III–IV anemia, thrombocytopenia and neutropenia were more common for H-TPF than L-TPF ( P < 0.001, P < 0.001, P = 0.048). Fewer patients in the H-TPF group finished two cycles of concurrent chemotherapy (81.2% vs. 100%, P < 0.001). Three-year PFS (84.5% vs. 80.6%, P = 0.484) and OS (91.1% vs. 93.5%, P = 0.542) were not significantly different between H-TPF and L-TPF. Conclusions: L-TPF neoadjuvant chemotherapy has substantially better tolerance and compliance rates and similar treatment efficacy to H-TPF neoadjuvant chemotherapy in locoregionally-advanced NPC.

// Ting Jin 1, 3, * , Kai-Xin Li 4, * , Pei-Jing Li 1, 3 , Shuang Huang 1, 3 , Xiao-Zhong Chen 1, 3 , Ming Chen 1, 3 , Qiao-Ying Hu 1, 3, * , Lei Shi 2, 3, * and Yuan-Yuan Chen 1, 3, * 1 Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, People’s Republic of China 2 Department of Radiology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, People’s Republic of China 3 Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang 310022, People’s Republic of China 4 Department of Radiation Oncology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, People’s Republic of China * These authors contributed equally to this work Correspondence to: Yuan-Yuan Chen, email: chenyy@zjcc.org.cn Qiao-Ying Hu, email: huqy@zjcc.org.cn Lei Shi, email: shilei@zjcc.org.cn Keywords: nasopharyngeal carcinoma, radiotherapy, nutrition intervention, weight loss Received: March 10, 2017 Accepted: July 12, 2017 Published: July 19, 2017 ABSTRACT Purpose: To evaluate the effectiveness of nutrition intervention during radiation for patients with locoregionally advanced (III-IVa) nasopharyngeal carcinoma (NPC). Materials and Methods: We retrospectively reviewed 117 patients with locoregionally advanced (III-IVa) NPC treated between December 2015 and March 2016 in Zhejiang Cancer Hospital. All the patients underwent radical chemo-radiotherapy. First, all the patients were divided into the nutrition intervention group and the control group, depending on whether they accepted nutrition intervention. Repeated measures were used to analyze the change of nutritional indicators before, during, and after radiation therapy and to simultaneously compare the difference in nutritional status between the two groups at the same time point. Subsequently, the 117 patients were divided into the malnourished group (weight loss > 5%) and the non-malnourished group (weight loss ≤ 5%) according to whether their weight loss was over 5% of their body weight during radiotherapy. Chi-square tests and logistic regression analysis were used to explore the influence factors for the weight loss. Results: The repeated measures showed that all indicators including weight, body mass index (BMI), albumin, pre-albumin(PA), and prognostic nutritional index (PNI) dramatically declined in both groups compared with their levels before radiation therapy (All p 0.05). Logistic regression analysis revealed grade ≥ 3 radiation-induced oral mucositis as the prognostic factor for a poor nutrition status (odds ratio, OR = 3.232, p = 0.021, confidence interval, CI [1.198, 8.820]). Besides this, patients with a decrease of >15% in pre-albumin level were more likely to be malnourished (OR = 2.442, p = 0.041, CI [1.036, 5.757]). Similar to that observed in our former analysis, we did not find that existing nutrition intervention can significantly improve nutritional status (OR = 1.217, p = 0.704, CI [0.042, 3.348]). Conclusions: Our study shows that the nutritional status of the patients gradually declined during treatment. We concluded that grade ≥ 3 radiation-induced oral mucositis would aggravate the extent of malnutrition during radiation therapy in patients with locoregionally advanced NPC. Pre-albumin level was a predictive marker for weight loss in patients with NPC. However, current nutrition intervention during radiation therapy can’t significantly reverse nutritional status.

Aim of the study Previous results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC). Methods Patients with stage III–IVB (except T3-4N0) NPC were randomly assigned to receive CCRT plus AC or CCRT only at seven institutions in China. Patients in both groups received cisplatin 40 mg/m2 weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m2 and fluorouracil 800 mg/m2/d for 120 h every 4 weeks for three cycles. The primary end-point was failure-free survival. Results Two hundred and fifty-one patients were randomised to the CCRT plus AC group and 257 to the CCRT only group. After a median follow-up of 68.4 months, estimated 5-year failure-free survival rate was 75% in the CCRT plus AC group and 71% in the CCRT only group (hazard ratio 0.88, 95% confidence interval 0.64–1.22; p = 0.45). 66 (27%) of 249 patients in the CCRT plus AC group and 53 (21%) of 254 patients in the CCRT only group developed one or more late grade 3–4 toxicities (p = 0.14). Conclusion Adjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities. Registration number NCT00677118 .

Summary Background The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial. Methods We did an open-label, phase 3, multicentre, randomised controlled trial at ten institutions in China. Patients with previously untreated, stage III–IVB (except T3-4N0) nasopharyngeal carcinoma, aged 18–59 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1:1) to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles of 100 mg/m 2 cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m 2 on day 1), intravenous cisplatin (60 mg/m 2 on day 1), and continuous intravenous fluorouracil (600 mg/m 2 per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy. Randomisation was by a computer-generated random number code with a block size of four, stratified by treatment centre and disease stage (III or IV). Treatment allocation was not masked. The primary endpoint was failure-free survival calculated from randomisation to locoregional failure, distant failure, or death from any cause; required sample size was 476 patients (238 per group). We did efficacy analyses in our intention-to-treat population. The follow-up is ongoing; in this report, we present the 3-year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT01245959. Findings Between March 1, 2011, and Aug 22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median follow-up of 45 months (IQR 38–49), 3-year failure-free survival was 80% (95% CI 75–85) in the induction chemotherapy plus concurrent chemoradiotherapy group and 72% (66–78) in the concurrent chemoradiotherapy alone group (hazard ratio 0·68, 95% CI 0·48–0·97; p=0·034). The most common grade 3 or 4 adverse events during treatment in the 239 patients in the induction chemotherapy plus concurrent chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy alone group were neutropenia (101 [42%] vs 17 [7%]), leucopenia (98 [41%] vs 41 [17%]), and stomatitis (98 [41%] vs 84 [35%]). Interpretation Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities. Funding Shenzhen Main Luck Pharmaceuticals Inc, Sun Yat-sen University Clinical Research 5010 Program (2007037), National Science and Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10), Health & Medical Collaborative Innovation Project of Guangzhou City (201400000001), Planned Science and Technology Project of Guangdong Province (2013B020400004), and The National Key Research and Development Program of China (2016YFC0902000).

// Jin Wang 1, * , Li Li 2, * , Bai-qiang Dong 1 , Yu-jin Xu 1 , Yuan-da Zheng 1 , Zhong-wen Sun 3 , Yang Yang 1 , Yuan-Yuan Chen 1 , Xiao-zhong Chen 1 , Ming Chen 1 1 Department of Radiation Oncology, Zhejiang Key Lab of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China 2 Department of Ultrasonography, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China 3 Department of Oncology, Jining First People’s Hospital, Jining, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Yuan-Yuan Chen, e-mail: Chenyy@zjcc.org.cn Keywords: serum lactic dehydrogenase, intensity-modulated radiation therapy, nasopharyngeal carcinoma, prognostic factor, metastasis Received: January 04, 2016 Accepted: March 18, 2016 Published: March 30, 2016 ABSTRACT Purpose: To examine the function of serum lactic dehydrogenase (SLDH) level after intensity-modulated radiotherapy (IMRT) as a predictive factor for and loco-regional relapse free survival (LRFS), distant metastasis-free survival (DMFS), disease free survival (DFS), and overall survival(OS) among patients with in-situ nasopharyngeal carcinoma (NPC). Results: Compared with the normal pt-SLDH group, elevated pt-SLDH demonstrated significant lower DMFS (46 versus 66 months, hazard ratio (HR) 4.07, 95% CI 2.43–6.80, p < 0.001), DFS (46 versus 63 months, HR 2.78, 95% CI 1.70–4.53, p < 0.001), and OS (54 versus 66 months, HR 2.93, 95% CI 1.65–5.23, p < 0.001). Distant metastasis were observed in 32.8% (20/61) patients with elevated pt-SLDH, and 8% (54/678) in normal SLDH (odds ratio (OR) 6.13, 95% CI 3.35–11.18, p < 0.001). COX regression showed that pt-SLDH was an independent prognostic factors for OS (HR 2.91, 95% CI 1.57–5.41, p < 0.001), DMFS (HR 4.21, 95% CI 2.51–7.07, p < 0.001), LRFS (HR 2.53, 95% CI 1.22–5.24, p < 0.001), and DFS (HR 2.81, 95% CI 1.72–4.59, p < 0.001). Materials and Methods: The records of 739 in-situ NPC patients admitted to Zhejiang Cancer Hospital between January 2007 and May 2012 were retrospectively reviewed. The relationships between post-treatment SLDH (pt-SLDH) and LRFS, DMFS, DFS, and OS were analyzed. Conclusions: Our finding indicated that elevated pt-SLDH could be a simple available prognostic indicator for distant metastasis and survival for in-situ NPC patients.

The impact of comorbidity on prognosis in nasopharyngeal carcinoma (NPC) is poorly characterized.Using the Adult Comorbidity Evaluation-27 (ACE-27) system, we assessed the prognostic value of comorbidity and developed, validated and confirmed a predictive score model in a training set (n=658), internal validation set (n=658) and independent set (n=652) using area under the receiver operating curve analysis.Comorbidity was present in 40.4% of 1968 patients (mild, 30.1%; moderate, 9.1%; severe, 1.2%). Compared to an ACE-27 score ⩽1, patients with an ACE-27 score1 in the training set had shorter overall survival (OS) and disease-free survival (DFS) (both P0.001), similar results were obtained in the other sets (P0.05). In multivariate analysis, ACE-27 score was a significant independent prognostic factor for OS and DFS. The combined risk score model including ACE-27 had superior prognostic value to TNM stage alone in the internal validation set (0.70 vs. 0.66; P=0.02), independent set (0.73 vs. 0.67; P=0.002) and all patients (0.71 vs. 0.67; P0.001).Comorbidity significantly affects prognosis, especially in stages II and III, and should be incorporated into the TNM staging system for NPC. Assessment of comorbidity may improve outcome prediction and help tailor individualized treatment.

Purpose To prospectively identify the predictive value of different dosimetric parameters and also assess the predictors of acute radiation oral mucositis (ROM). Methods In accordance with the RTOG scoring criteria, ninety-two patients with locally advanced nasopharyngeal carcinoma (NPC) treated with concurrent chemoradiotherapy were evaluated for acute ROM which was defined as severe when the score ≥3. Patients’ medical records and dosimetric data exported from IMRT plan enable the authors to perform a statistical analysis for the parameters as potential predictors of severe ROM. Results Body weight loss and V30 Gy (p = 0.017 and 0.003, respectively) are related factors to severe ROM. As the receiver operating characteristics (ROC) curve shows, the threshold value of V30 for severe ROM was 73.155% (sensitivity, 0.842; specificity, 0.671), and the area under V30 Gy curves was 0.753 (p = 0.001). Conclusion New parameters were found as predictors of severe ROM using dosimetric analysis.

Despite the efficacy of gemcitabine-cisplatin (GC) regimens, the outcome of patients with metastatic nasopharyngeal carcinoma (M NPC) is poor. We conducted a phase II trial to determine the safety and efficacy of Endostar, an endogenous inhibitor of angiogenesis, in combination with GC chemotherapy. A total of 30 patients with M NPC were enrolled. The treatment regimen was a combination of gemcitabine (1,000 mg/m2) on days 1 and 8, cisplatin (80 mg/m2) on day 1, and Endostar (15 mg/day) from day 1 to day 14 of a 21-day cycle for a maximum of four cycles. The primary endpoint was progression-free survival (PFS). The median follow-up was 13.1 months (range: 2.9‐20.7 months). A total of 28 patients were evaluated. The median PFS was 19.4 months (95% CI, 13.6‐25.1 months). The 1-year PFS rate was 69.8%. The confirmed objective response rate was 85.7% (95% CI, 66.4‐95.3%), including complete response in 14 patients (50%). The 1-year overall survival rate was 90.2%. The most common grade 3/4 adverse events were neutropenia (46.4%) and thrombocytopenia (14.3%). Our results suggest that a combination of Endostar with GC chemotherapy can lead to effective tumor regression, control disease progression, and improve prognosis in M NPC. Therefore, a combined Endostar and GC regimen should be considered as a potential treatment for patients with M NPC.

The materials were extracted by 95% ethanol, and the extracting solution was isolated by kinds of chromatographic columns including polyamide, MCI, preparative MPLC, and preparative HPLC. Eight diterpenes and two sesquiterpenes were isolated from the plant. On analysis of ESI-MS and NMR spectroscopic data, the structures were established as ent-3β-hydroxy-kaur-16-en-19-al (1), 4-epi-kaurenic acid (2), mitrekaurenone (3), 7β,16α,17-trihydroxy-ent-kauran-19-oic acid (4), crotonkinin E (5), crotonkinin F (6), pterisolic acid A (7), pterisolic acid C (8), (2R)-pterosin P (9), and dehydropterosin B (10). Compounds 1-6 were obtained from Pteris for the first time, and compounds 7-10 were obtained from P. ensiformis for the first time. Compounds 5-8 showed moderate activity against HCT-116, HepG2 and BGC-823 cell lines, separately.

Twelve quinolizidine alkaloids were isolated from Sophora tonkinensis by means of silica gel, preparative MPLC, and preparative HPLC. On analysis of NMR spectroscopic data, their structures were established as 3-(4-hydroxyphenyl)-4-(3-methoxy-4-hydroxyphenyl)-3,4-dehydroquinolizidine(1), lanatine A(2), cermizines C(3), senepodines G(4), senepodines H(5), jussiaeiines A(6), jussiaeiines B(7),(+)-5α-hydroxyoxysophocarpine(8),(-)-12β-hydroxyoxysophocarpine(9),(-)-clathrotropine(10),(-)-cytisine(11), and (-)-N-methylcytisine(12), respectively. Compounds 1-7 were first isolated from Sophora L. plant. In the in vitro assays,the isolated compounds 1, 3, 6-10 exhibited potent activity against CVB3 with IC₅₀ of 6.40, 3.25, 4.66, 3.21, 0.12, 0.23 and 1.60, and with selective index values(SI=TC₅₀/IC₅₀)of 12.0, 5.6, 13.0, 15.1, 50.1, 26.2, and 23.6, respectively. Compounds 1, 3, and 7 exhibited activity against staphylococcus aureus(ATCC 29213)with MICvalues of 8.0, 3.5, 6.0 g•L⁻¹, respectively. Compounds 1, 3, 7, and 12 exhibited activity against staphylococcus aureus(ATCC 33591)with MIC values of 18.0, 7.5, 8.0, 12.0 g•L⁻¹, respectively. Compounds 2, 6, 7 exhibited activity against Escherichia coli(ATCC 25922) with MIC values of 1.0, 3.2, 0.8 g•L⁻¹.

Summary Background The effect of the addition of adjuvant chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to assess the contribution of adjuvant chemotherapy to concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone. Methods We did an open-label phase 3 multicentre randomised controlled trial at seven institutions in China. Randomisation was by a computer-generated random number code. Patients were stratified by treatment centre and randomly assigned in blocks of four. Treatment allocation was not masked. We randomly assigned patients with non-metastatic stage III or IV (except T3–4N0) nasopharyngeal carcinoma to receive concurrent chemoradiotherapy plus adjuvant chemotherapy or concurrent chemoradiotherapy alone. Patients in both groups received 40 mg/m 2 cisplatin weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as 2·0–2·27 Gy per fraction with five daily fractions per week for 6–7 weeks to a total dose of 66 Gy or greater to the primary tumour and 60–66 Gy to the involved neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group subsequently received 80 mg/m 2 adjuvant cisplatin and 800 mg/m 2 per day fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was failure-free survival. We did efficacy analyses in our intention-to-treat population. Our trial is ongoing; in this report we present the 2 year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT00677118. Findings 251 patients were assigned to the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the concurrent chemoradiotherapy alone group. After a median follow-up of 37·8 months (range 1·3–61·0), the estimated 2 year failure-free survival rate was 86% (95% CI 81–90) in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 84% (78–88) in concurrent chemoradiotherapy only group (hazard ratio 0·74, 95% CI 0·49–1·10; p=0·13). Stomatitis was the most commonly reported grade 3 or 4 adverse event during both radiotherapy (76 of 249 patients in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 [21%] of 205 patients treated with adjuvant chemotherapy). Interpretation Adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and late toxic effects, but such regimens should not, at present, be used outside well-designed clinical trials. Funding Sun Yat-sen University Clinical Research 5010 Programme (No 2007037), Science Foundation of Key Hospital Clinical Programme of Ministry of Health PR China (No 2010–178), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2010).

Summary Background Ventricular septal defect (VSD) is the most prevalent type of congenital heart disease and is a major cause of substantial morbidity and mortality in infants. Accumulating evidence implicates genetic defects, especially in cardiac transcription factors, in the pathogenesis of VSD. However, VSD is genetically heterogeneous and the genetic determinants for VSD in most patients remain to be identified. Material/Methods A cohort of 230 unrelated patients with congenital VSD was included in the investigation. A total of 200 unrelated ethnically matched healthy individuals were recruited as controls. The entire coding region of GATA4, a gene encoding a zinc-finger transcription factor essential for normal cardiac morphogenesis, was sequenced initially in 230 unrelated VSD patients. The available relatives of the mutation carriers and 200 control subjects were subsequently genotyped for the presence of identified mutations. Results Four heterozygous missense GATA4 mutations of p.Q55R, p.G96R, p.N197S, and p.K404R were identified in 4 unrelated patients with VSD. These mutations were not detected in 200 control individuals nor described in the human SNP database. Genetic analysis of the relatives of the mutation carriers showed that in each family the mutation co-segregated with VSD. Conclusions These findings expand the mutation spectrum of GATA4 linked to VSD and provide new insight into the molecular etiology responsible for VSD, suggesting potential implications for the genetic diagnosis and gene-specific therapy for VSD.

// Yan-Yan Liu 1, 2, # , Shao-Jun Lin 3, # , Yuan-Yuan Chen 4, # , Li-Na Liu 5 , Liu-Bin Bao 5 , Lin-Quan Tang 1 , Jing-Song Ou 6 , Zhi-Gang Liu 7 , Xiao-Zhong Chen 4 , Yan Xu 4 , Jun Ma 1 , Anthony T. Chan 8 , Ming Chen 4 , Yun-Fei Xia 1 , Wan-Li Liu 1 , Yi-Xin Zeng 1 , Hai-Qiang Mai 1 , Mu-Sheng Zeng 1 , Jian-Ji Pan 3, * , Xing Zhang 1, * 1 Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China 2 Division of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 3 Department of Radiation Oncology, Fujian Provincial Cancer Hospital Affiliated to Fujian Medical University, Fuzhou, China 4 Department of Radiation Oncology, Zhejiang Cancer Hospital/Zhejiang Key Laboratory, Hangzhou, China 5 Department of Oncology, The Second Affiliated Hospital of Guangzhou Medical College, Guangzhou, China 6 Division of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China 7 Department of Radiation Oncology, Hunan Provincial Tumor Hospital, Tumor Hospital Xiangya School of Medicine of Central South University, Changsha, China 8 Partner State Key Laboratory of Oncology in South China at Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong * These authors have contributed equally and share senior authorship # These authors have contributed equally to this work Correspondence to: Xing Zhang, email: zhangxing@sysucc.org.cn Keywords: high-density lipoprotein cholesterol, nasopharyngeal carcinoma, prognosis Received: November 22, 2015 Accepted: January 19, 2016 Published: February 03, 2016 ABSTRACT Purpose: We aimed to assess the prognostic value of pretreatment high density lipoprotein cholesterol (HDL-C) levels in patients with nasopharyngeal carcinoma (NPC) and investigate the possible biological effects of these lipoproteins on NPC cells in vitro . Experimental Design: We examined the prognostic value of pretreatment HDL-C levels in 2443 patients with non-metastatic NPC from three independent institutions. The Cox proportional hazard model and log-rank test were used to analyze the correlation between HDL-C levels and overall survival (OS). Cell growth, colony formation, and apoptotic assays were used to determine the biological functions of HDL on NPC cells in vitro . All of the statistical tests were two-sided. Results: OS was decreased in patients with high pretreatment HDL-C levels compared with those with low HDL-C levels ( P < 0.05). Similarly, a decreased OS was noted in advanced stage (stage III-IV), NPC patients with high pretreatment HDL-C levels ( P < 0.01). Multivariate analyses indicated that HDL-C was an independent prognostic factor associated with shorter OS in training cohorts. These findings were confirmed in both independent validation cohorts ( P < 0.01). In vitro experiments demonstrated that HDL could increase cell proliferation, invasion, and colony formation, which were largely dependent on the expression of its receptor SR-B1. Finally, HDL could enhance chemoresistance by protecting cancer cells from apoptosis. Conclusions: Pretreatment HDL-C is a poor prognostic factor for patients with NPC. This effect may be associated with the ability of HDL to enhance proliferation, colony formation, migration, and chemoresistance in NPC cells.

DNA methylation, the best known epigenetic marker, can be used as a prognostic biomarker in many cancers. We examined DNA methylation status and survival in nasopharyngeal carcinoma (NPC) patients. Aberrant DNA-methylated genes in 24 NPC tissues and 24 noncancer nasopharyngitis biopsy tissues (NCNBT) were identified using Illumina 450K BeadChip. Correlations between DNA methylation and clinical outcomes were evaluated using bisulfite pyrosequencing in 454 NPC patients. Genome-wide methylation analysis demonstrated that NPC tissues had distinct DNA methylation patterns compared with NCNBT. Among all significant CpG sites, 2,173 CpG sites with β change ≥ 0.2 (1,880 hypermethylated, 293 hypomethylated) were identified (P < 0.05). A methylation gene panel comprising six hypermethylated genes was constructed with the average Z-score method. Patients in the training cohort with high methylation had poorer disease-free survival [DFS, HR, 2.26; 95% confidence interval (CI), 1.28–4.01; P, 0.005] and overall survival (OS, HR, 2.47; 95% CI, 1.30–4.71; P, 0.006) than those with low methylation. There were similar results in the validation (DFS, HR, 2.07; 95% CI, 1.17–3.67; P, 0.013; OS, HR, 1.83; 95% CI, 1.01–3.31; P, 0.046) and independent cohorts (DFS, HR, 1.94; 95% CI, 1.08–3.47; P, 0.026; OS, HR, 2.09; 95% CI, 1.10–3.98; P, 0.022). Analysis indicated that the methylation gene panel was an independent prognostic factor. Furthermore, patients with low methylation had a favorable response to concurrent chemotherapy with an improved DFS (P = 0.045) and OS (P = 0.031), whereas patients with high methylation did not benefit from concurrent chemotherapy. The six–hypermethylated gene panel was associated with poor survival in patients with NPC, demonstrating its potential usefulness as a prognostic biomarker to clinicians in NPC management. Mol Cancer Ther; 14(12); 2864–73. ©2015 AACR.

The aim of the present study was to evaluate the efficacy and safety of a neoadjuvant gemcitabine and nedaplatin chemotherapy regimen, followed by concurrent chemoradiotherapy or radiotherapy alone, in locoregionally advanced nasopharyngeal carcinoma (NPC). Eighty-six patients with stage III, IVA or IVB NPC, who received neoadjuvant chemotherapy [gemcitabine, 1,000 mg/m(2) on day 1 (d1) and d5; nedaplatin, 25 mg/m(2) on d 1-3] every 3 weeks for at least two cycles, followed by intensity-modulated radiotherapy every 3 weeks, with or without concurrent nedaplatin (25 mg/m(2), d1-3) between September 2010 and December 2013, were retrospectively analyzed. By comparing pretreatment and post-treatment MRI images, it was shown that seven patients achieved a complete response (8.5%), while 66 achieved a partial response (80.5%), following completion of neoadjuvant chemotherapy (combined response rate, 89.0%). Grade 3-4 toxicities following neoadjuvant chemotherapy included neutropenia (29.1%), leukopenia (11.6%), liver dysfunction (9.3%), thrombocytopenia (9.3%) and nausea/vomiting (8.1%). The median follow-up was 18 months (range, 5-44 months). The 2-year relapse-free survival, distant metastasis-free survival, progression-free survival and overall survival rates were 96.6, 85.4, 83.3 and 96.1%, respectively. Compared with alternative neoadjuvant chemotherapy regimens in combination with radiotherapy or concurrent chemoradiotherapy, the present gemcitabine and nedaplatin did not provide additional survival benefit and led to a higher frequency of liver dysfunction. Therefore, neoadjuvant gemcitabine and nedaplatin should be used with caution in locoregionally advanced NPC.

The seeds of Silybum marianum were extracted by hot water, and the extract was isolated by D101 macroporous resin, MCI resin, MPLC, HPLC, et al. As a result, 7 compounds including tricin 4'-O-[threo-β-guaiacyl-(7″-O-methyl)-glyceryl] ether(1), tricin 4'-O-[erythro-β-guaiacyl-(7″-O-methyl)-glyceryl] ether(2), 5'-methoxyhydnocarpin-D(3),palstatin(4),(8R,7'S,8'R)-5,5'-dimethoxy-7-oxolariciresinol 9'-O-D-xylopyranoside(5), 9-O-D-glucopyranoside(6), and(-)-haplomyrtoside(7) were isolated and identified for the first time. Compounds 1, 3, 4, and 5 exhibited activity against influenza A(H5N1)with IC₅₀ value of 0.65, 0.21, 0.32, and 0.56 μmol•L⁻¹, respectively. Compounds 1, 2, 6, and 7 exhibited cytotoxity against HepG-2 with IC₅₀ value of 0.35, 0.25, 0.53, 0.66 μmol•L⁻¹, respectively.

Thirty-five consecutive patients undergoing a third-time coronary revascularisation between 1982 and 1992 were retrospectively reviewed. These patients represented 6% (35/579) of coronary reoperations and 0.5% (35/6772) of total coronary bypass operations in the unit during that period. The indication for operation was recurrent or intractable angina due to total or partial graft failure. The mean number of grafts per patient was 2.7 (range, 1 to 5). Arterial grafts, new internal mammary arteries and inferior epigastric artery were placed in 22 patients (63%). All patients survived the early postoperative period. One patient (3%) required re-exploration for bleeding, three (9%) required intra-aortic balloon pump support, and nine (26%) had temporary postoperative atrial fibrillation. Follow-up data for 10 to 138 months (mean, 31 months) revealed a 5-year survival of 91%. Of 32 late survivors, 18 patients (57%) were free of angina. Among 14 patients (44 %) who had recurrent angina, only 1 patient (3%) had Class IV angina compared with 34% Class IV angina patients preoperatively. Third-time coronary revascularisation can be performed with good early and late clinical results.

Ventricular septal defect (VSD) is the most prevalent type of congenital heart disease and a major cause for the significantly increased morbidity and mortality among infants. Aggregating evidence indicates that genetic defects are involved in the pathogenesis of congenital VSD. Nevertheless, VSD is genetically heterogeneous, and the genetic determinants for VSD in the majority of patients remain to be identified. In this study, the entire coding region of GATA4, a gene encoding a zinc finger transcription factor essential for normal cardiac morphogenesis, was sequenced in 160 unrelated patients with VSD. The available relatives of the index patient harboring the identified mutation and 200 unrelated control individuals were subsequently genotyped. The disease-causing potential of a sequence alteration was evaluated by MutationTaster, and the functional effect of the mutation was characterized using a luciferase reporter assay system. As a result, a novel heterozygous GATA4 variation, p.R43W, was identified in a proband with VSD, that was absent in control subjects. Genetic analysis of the family members of the variation carrier showed that the substitution co-segregated with VSD. The p.R43W variant was predicted to be a pathogenic mutation, and the functional analysis demonstrated that the GATA4 R43W mutant protein resulted in significantly decreased transcriptional activity compared with its wild-type counterpart. The findings expand the mutational spectrum of GATA4 linked to VSD and provide more insight into the molecular mechanism of VSD.

As a quantitative analysis tool in the research field of Social Science. Social Network Analyses has been more and more applied to the field of education these years. The thesis takes e-portfolio website as learning and assessing platform. Summed up the data of the learning and Process Assessment, and analyzed it by the angel of InDegree, OutDegree and Betweenness, etc. Finally, compared the student's score which have the extreme value of Betweenness and analyzed the relationship between student's score and the value of Betweenness.

Ventricular septal defect (VSD) is the most common type of cardiovascular developmental anomaly and is an important risk factor for the substantially increased morbidity and mortality in newborns. Aggregating evidence implicates genetic defects in the pathogenesis of congenital VSD. However, VSD is genetically heterogeneous and the genetic determinants for VSD in most patients remain to be identified. In this study, the whole coding region of the GATA4 gene, which encodes a zinc-finger transcription factor pivotal to cardiogenesis, was initially sequenced in 210 unrelated patients with VSD. The relatives of the index patient carrying the identified mutation and 200 unrelated ethnically-matched healthy individuals used as controls were subsequently genotyped. The functional effect of the mutant GATA4 was characterized in contrast to its wild-type counterpart using a luciferase reporter assay system. A novel heterozygous GATA4 mutation, p.G296R, was identified in a family with VSD inherited as an autosomal dominant trait. Absent in 200 control individuals, the mutation co-segregated with VSD in the family with 100% penetrance and was completely conserved evolutionarily across species. Functional analysis displayed that the p.G296R mutation of GATA4 was associated with a decreased transcriptional activity. The findings expand the spectrum of mutations in GATA4 linked to VSD and provide more insight into the molecular mechanism involved in VSD. The results of the present study imply the potential implications in the genetic diagnosis and gene-specific therapy of this common malformation in infancy.

Atrial septal defect (ASD) is a common cardiovascular malformation and an important contributor to substantial morbidity and mortality. Increasing evidence demonstrates that mutated NKX2-5, a gene encoding a homeobox transcription factor crucial to cardiogenesis, is a significant genetic determinant for congenital ASD. Nevertheless, the genetic basis for ASD in a majority of ASD patients remains largely unknown. In the current study, the entire coding region of NKX2-5 was sequenced initially for 58 unrelated probands with familial ASD. The relatives of the probands harboring identified mutations and 200 unrelated control individuals were subsequently genotyped. Three novel heterozygous NKX2-5 mutations (p.P43GfsX59, p.C46 W, and p.S179F) were identified respectively in three families with autosomal dominantly inherited ASD. These mutations, absent in 200 control individuals, cosegregated with ASD in the families that had complete penetrance. The findings expand the spectrum of mutations in NKX2-5 linked to ASD and contribute to genetic counseling, clinical interventions, and prenatal prevention of ASD for individuals with genetic susceptibility.

Aim of this paper was to explore the trend and characteristics of cancer incidence in 11 areas (5 cities and 6 counties) in China.Data from cancer registries during 1988 to 2002 collected from the 11 cancer registry points were used to analyze the trends and characteristics of cancer incidence rates.There were 695 050 newly developed cancer cases in this study. The crude rate of incidence and the world age-adjusted incidence were 215.50/10(5) and 170.97/10(5) respectively. The leading cancer sites were lung, stomach, liver, esophagus, breast, colon, rectum, pancreas, bladder and leukemia. The sixteen key cancers accounted for 85.56% of all the cancer cases. The crude incidence rate of all cancers had been significantly increased from 1988 to 2002. Among them, prostate (185.48%) ranked the fastest growing one followed by cancers of the gallbladder, breast, colon, ovarian, lymphoma, bladder, pancreas, rectum, lung, leukemia and liver. The one that had reduced the most was cervix uteri (17.00%), followed by esophagus, stomach and nasopharynx.Crude cancer incidence rate increased in the 11 areas in China from 1988 to 2002. The ranking of pancreas cancer, bladder cancer and leukemia came into the top ten. Even though the incidence rates of prostate and gallbladder cancer were relative low but had a fast increase. The results of this study provided a scientific base for the development of a better strategy on cancer prevention and control in China.