Risk Factors for Cervical Cancer in Rural Areas of Wuhan China: a Matched Case-control Study

Zhang, Bin,Zhou, Ai-Fen,Zhu, Chang-Cai,Zhang, Ling,Xiang, Bing,Chen, Zhong,Hu, Rong-Hua,Zhang, Ya-Qi,Qiu, Lin,Zhang, Yi-Ming,Xiong, Chao-Du,Du, Yu-Kai,Shi, Yu-Qin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Cervical cancer is a serious public health problem in developing countries. We investigated possible risk factors for cervical cancer in rural areas of Wuhan China using a matched case-control study with 33 women diagnosed with cervical cancer and 132 healthy women selected from the same area as matched controls. A questionnaire, which included questions about general demography conditions, environmental and genetic factors, the first sexual intercourse, first marriage age, age at first pregnancy, pregnancy first child's age, female personal health history, social psychological factors, dietary habits, smoking and alcohol status and other living habits was presented to all participants. At the same time, HPV infection of every participant was examined in laboratory testing. Results showed HPV infection (P<0.000, OR=23.4) and pregnancy first child's age (P<0.000, OR=13.1) to be risk factors for cervical cancer. Menopause (P=0.003, OR=0.073) was a protective factor against cervical cancer. However, there was no indication of associations of environmental (drinking water, insecticide, disinfectant) genetic (cancer family history), or life-style factors (smoking status, alcohol status, physical training, sleep quality), including dietary habits (intake of fruit and vegetable, meat, fried food, bean products and pickled food) or social psychological factors with cervical cancer. The results suggest that the risk of cervical cancer in Chinese rural women may be associated with HPV infection, menopause and the pregnancy first child's age.

Biocatalysis and Fermentation Technology : Secretory Expression, Functional Characterization, and Molecular Genetic Analysis of Novel Halo-Solvent-Tolerant Protease from Bacillus gibsonii

( Ai Hua Deng ),( Guo Qiang Zhang ),( Na Na Shi ),( Jie Wu ),( Fu Ping Lu ),( Ting Yi Wen ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.2

A novel protease gene from Bacillus gibsonii, aprBG, was cloned, expressed in B. subtilis, and characterized. High-level expression of aprBG was achieved in the recombinant strain when a junction was present between the promoter and the target gene. The purified recombinant enzyme exhibited similar N-terminal sequences and catalytic properties to the native enzyme, including high affinity and hydrolytic efficiency toward various substrates and a superior performance when exposed to various metal ions, surfactants, oxidants, and commercial detergents. AprBG was remarkably stable in 50% organic solvents and retained 100% activity and stability in 0-4 M NaCl, which is better than the characteristics of previously reported proteases. AprBG was most closely related to the high-alkaline proteases of the subtilisin family with a 57-68% identity. The secretion and maturation mechanism of AprBG was dependent on the enzyme activity, as analyzed by site-directed mutagenesis. Thus, when taken together, the results revealed that the halo-solvent-tolerant protease AprBG displays significant activity and stability under various extreme conditions, indicating its potential for use in many biotechnology applications.

Expression of Ang-2/Tie-2 and PI3K/AKT in Colorectal Cancer

Zhang, Ji-Hong,Wang, Li-Hua,Li, Xiang-Jun,Wang, Ai-Ping,Reng, Li-Qun,Xia, Feng-Guo,Yang, Zhi-Ping,Jiang, Jing,Wang, Xiao-Dan,Wen, Chun-Yang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Purpose: To study the expression of angiogenin-2 (Ang-2) and its receptor Tie-2 in colorectal cancer and discuss the possible mechanisms behind this process. Materials and Methods: Using the streptavidin-peroxidase (SP) immunohistochemical method, paraffin sections from 100 colorectal cancer samples and 10 samples from tumor-adjacent normal tissue (> 2 cm from the edge of the gross tumor) were tested for protein expression of Ang-2, Tie-2, PI3K, and AKT. Reverse transcription-polymerase chain reaction and Western blots were further used to measure expression of the 4 genes and proteins in 20 freshly-resected colorectal cancer samples and tumor-adjacent normal tissues. Results: In colorectal cancer tissues, the expression of the Ang-2, Tie-2, PI3K, and AKT genes and their proteins was significantly higher than in tumor-adjacent normal tissues. Protein expression in poorly-differentiated adenocarcinoma was higher than that in well and moderately differentiated adenocarcinoma. According to Duke's classification, the protein expression in Stages C and D was significantly higher than that in Stages A and B. In the group with lymphatic metastasis, the protein expression was higher than that without lymphatic metastasis. Conclusions: In colorectal cancer, the expression of the Ang-2, Tie-2, PI3K, and AKT genes and their proteins is markedly higher than those in tumor-adjacent normal tissues. No correlation was observed between protein expression and gender, location, or histologic type. Correlations did exist between protein expression and differentiation level, stage of Duke's classification, and lymphatic metastasis; in colorectal cancer tissues with lower differentiation levels, higher stages of Duke's classification, and lymphatic metastasis, the expression of all 4 proteins was higher. The study of their expression patterns and relationships with aggression and metastasis will provide a valuable experimental foundation for assessing prognosis and targeted therapy of colorectal cancer.

Identification of a novel circularized transcript of the AML1 gene

Ai Ning Xu,Xiu Hua Chen,Yan Hong Tan,Xi Ling Qi,Zhi Fang Xu,Lin Lin Zhang,Fang Gang Ren,Si Cheng Bian,Yi Chen,Hong Wei Wang 생화학분자생물학회(구 한국생화학분자생물학회) 2013 BMB Reports Vol.46 No.3

Clinicopathologic Characteristics and Prognostic Factors in Patients with Operable HER-2 Overexpressing Breast Cancer

Liu, Ai-Na,Sun, Ping,Liu, Jian-Nan,Ma, Jin-Bo,Qu, Hua-Jun,Zhu, Hua,Yu, Cai-Yan,Zhang, Liang-Ming Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Objective: To study the relationship between clinical pathologic characteristics, treatment modalities and prognostic factors in HER-2 (Human Epidermal growth factor Receptor-2) overexpressed breast carcinoma. Materials and Methods: Major clinico-pathological factors including therapeutic modalities and survival status of 371 breast cancer patients with HER2 over-expression, teated at Yantai Yuhuangding Hospital from March of 2002 to December of 2010 were retrospectively studied, with special attention focused on survival-related factors. Results: The median age of the total 371 patients in this study was 48 years at time of diagnosis, among which, the leading pathological type was infiltrating ductal carcinoma (92.5%); 62.8% presented with a primary tomor larger than 2 cm in diameter at diagnosis, 51.0% had axillary lymph node (ALN) metastases; ER (Estrogen receptor)/PR (Progesterone receptor) double negative occured in 52.8% of cases, and PCNA (proliferation cell nuclear antigen) (+++) was found in 55.1%. HER-2 overexpressed patients were usually in advanced stage when the diagnosis was made (72.8% at stages IIA~IIIC). The prognosis and survival were assessed in 259 patients with complete follow-up data. 5-year DFS (disease-free survival) and OS (overall survival) rate was 68.0% and 78.0% respectively. Univariate analysis revealed that age, tumor size, ALN metastases, LVSI (lymph-vascular space involvement), PCNA status, hormonal therapy, chemotherapy cycles, and HER-2 overexpression, correlated closely with the prognosis. ALN metastases, LVSI, PCNA status and chemotherapy cycles were independent predictors of survival. Conclusions: HER-2 overexpressed breast cancer has special clinical and pathological characteristics, with advanced clinical stages and high rate of ER/PR double negative. Lymph node metastases, LVSI, PCNA and chemotherapy cycles are independent predictors of prognosis.

Risk Assessment of Secondary Primary Malignancies in Nasopharyngeal Carcinoma: A Big-Data Intelligence Platform-Based Analysis of 6,377 Long-term Survivors from an Endemic Area Treated with Intensity-Modulated Radiation Therapy during 2003-2013

Lu-Lu Zhang,Guo-Hong Li,Yi-Yang Li,Zhen-Yu Qi,Ai-Hua Lin,Ying Sun 대한암학회 2019 Cancer Research and Treatment Vol.51 No.3

Purpose The incidence, risk factors and survival impact of secondary primary malignancies (SPMs) among survivors of nasopharyngeal carcinoma (NPC) treated with definitive intensity-modulated radiation therapy (IMRT) with or without chemotherapy are poorly characterized. Materials and Methods Consecutive patients (n=6,377) from the big-data intelligence platform at Sun Yat-sen University Cancer Center, China (in a high-incidence area) with newly diagnosed non-metastatic pathologically proven non-keratinizing undifferentiated NPC treated with IMRT±chemotherapy between January 2003 and June 2013 were retrospectively analyzed. Cumulative incidence of SPMs was calculated using the Kaplan-Meier method. Cox proportional hazards model was used to identify potential risk factors for SPMs and assess whether SPMs affect overall survival. Results Of the 6,377 patients, 189 (3.0%) suffered SPMs (median follow-up, 62 months). One-, 2-, 3-, 4-, and 5-cumulative risks of SPMs were 0.4%, 0.9%, 1.6%, 2.2%, and 2.6%, respectively. Latency from start of IMRT to SPMs diagnosis was 37 months (range, 6 to 102 months). In patients with SPMs, 14.3% suffered SPMs within 1 year post-IMRT: 1-3 years, 38.1%; 3-5 years, 33.9%; and > 5 years, 13.7%. Lung cancer was the most common SPM (50/6,377, 0.78%). Multivariate analysis demonstrated sex (male, 64% increase), age (! 50 years, 68% increase), and smoking history (41% increase) were significant risk factors for SPMs, and SPMs were associated with poorer overall survival. Conclusion This large cohort study confirms SPMs a dreadful complication for long-term survivors of NPC treated with IMRT. SPMs negatively impact overall survival in NPC. Close follow-up is recommended for older male survivors with a smoking history.

Proposal of a Pretreatment Nomogram for Predicting Local Recurrence after Intensity-Modulated Radiation Therapy in T4 Nasopharyngeal Carcinoma: A Retrospective Review of 415 Chinese Patients

Lu-Lu Zhang,Yi-Yang Li,Jiang Hu,Guan-Qun Zhou,Lei Chen,Wen-Fei Li,Ai-Hua Lin,Jun Ma,Zhen-Yu Qi,Ying Sun 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose Local relapse-free survival (LRFS) differs widely among patients with T4 category nasopharyngeal carcinoma (NPC). We aimed to build a nomogram incorporating clinicopathological information to predict LRFS in T4 NPC after definitive intensity-modulated radiation therapy (IMRT). Materials and Methods Retrospective study of 415 Chinese patients with non-metastatic T4 NPC treated with definitive IMRT with or without chemotherapy at our cancer center between October 2009 and September 2013. The nomogram for LRFS at 3 and 5 years was generated based on multivariate Cox proportional hazards regression, and validated using bootstrap resampling, assessing discriminative performance using the concordance index (C-index) and determining calibration ability via calibration curves. Results Five-year LRFS was 88.8%. We identified and incorporated four independent prognostic factors for LRFS: ethmoid sinus invasion, primary gross tumor volume, age, and pretreatment body mass index. The C-index of the nomogram for local recurrence was 0.732 (95% confidence interval, 0.726 to 0.738), indicating excellent predictive accuracy. The calibration curve revealed excellent agreement between nomogram-predicted and observed LRFS probabilities. Risk subgroups based on total point score cutoff values enabled effective discrimination of LRFS. Conclusion This pretreatment nomogram enables clinicians to accurately predict LRFS in T4 NPC after definitive IMRT, and could help to facilitate personalized patient counselling and treatment strategies.

Identification of Specific Gene Modules in Mouse Lung Tissue Exposed to Cigarette Smoke

Xing, Yong-Hua,Zhang, Jun-Ling,Lu, Lu,Li, De-Guan,Wang, Yue-Ying,Huang, Song,Li, Cheng-Cheng,Zhang, Zhu-Bo,Li, Jian-Guo,Xu, Guo-Shun,Meng, Ai-Min Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.10

Background: Exposure to cigarette may affect human health and increase risk of a wide range of diseases including pulmonary diseases, such as chronic obstructive pulmonary disease (COPD), asthma, lung fibrosis and lung cancer. However, the molecular mechanisms of pathogenesis induced by cigarettes still remain obscure even with extensive studies. With systemic view, we attempted to identify the specific gene modules that might relate to injury caused by cigarette smoke and identify hub genes for potential therapeutic targets or biomarkers from specific gene modules. Materials and Methods: The dataset GSE18344 was downloaded from the Gene Expression Omnibus (GEO) and divided into mouse cigarette smoke exposure and control groups. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to construct a gene co-expression network for each group and detected specific gene modules of cigarette smoke exposure by comparison. Results: A total of ten specific gene modules were identified only in the cigarette smoke exposure group but not in the control group. Seven hub genes were identified as well, including Fip1l1, Anp32a, Acsl4, Evl, Sdc1, Arap3 and Cd52. Conclusions: Specific gene modules may provide better understanding of molecular mechanisms, and hub genes are potential candidates of therapeutic targets that may possible improve development of novel treatment approaches.

Association of Lipoprotein-Associated Phospholipase A_2 with Characteristics of Vulnerable Coronary Atherosclerotic Plaques

Yu-Sheng Liu,Qing-Hua Lu,Xiao-Bo Hu,Hong-Zhuan Li,Wei-Dong Jiang,Xin Wang,Hao Lin,Ai-Qiong Qin,Yong-Mei Wang,Tong Zhao,Zhao-Qiang Dong,Mei Zhang 연세대학교의과대학 2011 Yonsei medical journal Vol.52 No.6

Purpose: Lipoprotein-associated phospholipase A2 (Lp-PLA_2) is an inflammatory enzyme expressed in atherosclerotic plaques. We investigated the association of circulating Lp-PLA_2 with characteristics of vulnerable coronary atherosclerotic plaques. Materials and Methods: We recruited 113 patients with either unstable angina (UA, n=59) and stable angina (SA, n=54) by coronary angiography. Thirty-six healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate the characteristics of coronary atherosclerotic plaque, and serum Lp-PLA2 concentration was measured as well. Results: Lp-PLA_2 concentration was significantly higher in both UA and SA patients [(396±36) μg/L and (321±39) μg/L, respectively]compared with the controls [(127±49) μg/L, p<0.01], and higher in UA than SA group. IVUS findings showed that remodeling index (RI) (0.91±0.15 vs. 0.85±0.11, p=0.005) and eccentricity index (EI) (0.73±0.16 vs. 0.65±0.22, p=0.039) were larger in UA than in SA group, and fibrous caps were thicker in SA than UA group [(0.91±0.23) mm vs. (0.63±0.21) mm, p=0.032]. Moreover, Lp-PLA_2 correlated positively with EI (r=0.439, p<0.01) and RI (r=0.592, p<0.05) in UA group. There was an inverse relationship between Lp-PLA_2 and fibrous cap thickness in both UA (r=-0.587, p<0.001) and SA (r=-0.318, p<0.05) groups. The independent risk factors in UA group were Lp-PLA_2 (OR=1.055, 95% CI: 1.03-1.08, p=0.013), LDL-cholesterol (OR=0.032, 95% CI: 0.00-0.05, p=0.041) and fibrous cap thickness (OR=0.008, 95% CI: 0.00-0.45, p=0.019). Lp-PLA_2 was strongly associated with both EI and fibrous cap thickness in both groups. Conclusion: Serum level of Lp-PLA_2 is associated with both eccentricity index and fibrous cap thickness in both UA and SA groups. Elevated levels of circulating Lp-PLA_2 might to be a strong risk factor and more serious for unstable angina than stable angina.

Neutropenia during the First Cycle of Induction Chemotherapy Is Prognostic for Poor Survival in Locoregionally Advanced Nasopharyngeal Carcinoma: A Real-World Study in an Endemic Area

Cheng Xu,Shi-Ping Yang,Yuan Zhang,Ling-Long Tang,Guan-Qun Zhou,Xu Liu,Yan-Ping Mao,Rui Guo,Wen-Fei Li,Lei Chen,Ai-Hua Lin,Ying Sun,Jun Ma 대한암학회 2018 Cancer Research and Treatment Vol.50 No.3

Purpose The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and Methods Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil after IC-1, all patients were categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1–induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin). Univariate/multivariate analyses were performed to investigate the effect of IC-1–induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLRmin on OS/DFS. Results Grade 1-2/grade 3-4 neutropenia were associated with poorer OS/DFS than no neutropenia (all p < 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel–cisplatin–5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin–5-fluorouracil (PF) (PF and docetaxel– cisplatin [TP]; all p < 0.05). Neutropenia, two/three myelosuppression events, and high post-NLRmin ( 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1–induced neutropenia, two/three myelosuppression events, and post-NLRmin  1.33 were validated as negative predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant effect. Conclusion Occurrence of neutropenia, number of myelosuppression events, and high post-NLRmin during PF/TP IC-1 have prognostic value for poor survival in LANPC.