A Novel Molecular Grading Model: Combination of Ki67 and VEGF in Predicting Tumor Recurrence and Progression in Non-invasive Urothelial Bladder Cancer

Chen, Jun-Xing,Deng, Nan,Chen, Xu,Chen, Ling-Wu,Qiu, Shao-Peng,Li, Xiao-Fei,Li, Jia-Ping Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Purpose: To assess efficacy of Ki67 combined with VEGF as a molecular grading model to predict outcomes with non-muscle invasive bladder cancer (NMIBC). Materials: 72 NMIBC patients who underwent transurethral resection (TUR) followed by routine intravesical instillations were retrospectively analyzed in this study. Univariate and multivariate analyses were performed to confirm the prognostic values of the Ki67 labeling index (LI) and VEGF scoring for tumor recurrence and progression. Results: The novel molecular grading model for NMIBC contained three molecular grades including mG1 (Ki67 $LI{\leq}25%$, VEGF $scoring{\leq}8$), mG2 (Ki67 LI>25%, VEGF $scoring{\leq}8$; or Ki67 $LI{\leq}25%$, VEGF scoring > 8), and mG3 (Ki67 LI > 25%, VEGF scoring > 8), which can indicate favorable, intermediate and poor prognosis, respectively. Conclusions: The described novel molecular grading model utilizing Ki67 LI and VEGF scoring is helpful to effectively and accurately predict outcomes and optimize personal therapy.

Genetic Variants in the PI3K/PTEN/AKT/mTOR Pathway Predict Platinum-based Chemotherapy Response of Advanced Non-small Cell Lung Cancers in a Chinese Population

Xu, Jia-Li,Wang, Zhen-Wu,Hu, Ling-Min,Yin, Zhi-Qiang,Huang, Ming-De,Hu, Zhi-Bin,Shen, Hong-Bing,Shu, Yong-Qian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: The PI3K/PTEN/AKT/mTOR signaling pathway has been implicated in resistance to cisplatin. In the current study, we determined whether common genetic variations in this pathway are associated with platinum-based chemotherapy response and clinical outcome in advanced non-small cell lung cancer (NSCLC) patients. Methods: Seven common single nucleotide polymorphisms (SNPs) in core genes of this pathway were genotyped in 199 patients and analyzed for associations with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Results: Logistic regression analysis revealed an association between AKT1 rs2494752 and response to treatment. Patients carrying heterozygous AG had an increased risk of disease progression after two cycles of platinum-based chemotherapy compared to those with AA genotype (Adjusted odds ratio (OR)=2.18, 95% confidence interval (CI): 1.00-4.77, which remained significant in the stratified analyses). However, log-rank test and cox regression detected no association between these polymorphisms in the PI3K pathway genes and survival in advanced NSCLC patients. Conclusions: Our findings suggest that genetic variants in the PI3K/PTEN/AKT/mTOR pathway may predict platinum-based chemotherapy response in advanced NSCLC patients in a Chinese population.

Risk Factors for Surgical Site Infections after Liver Resec-tion (A Multivariate Analysis of 6,132 Patients)

( Li-yang Sun ),( Jiong-jie Yu ),( Ju-dong Li ),( Xin-fei Xu ),( Jia-he Wang ),( Bing Quan ),( Wen-tao Yan ),( Feng Shen ),( Chao Li ),( Lei Liang ),( Tian Yang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Surgical site infection (SSI) is a common postoperative complication and associated with an increased morbidity, hospital stay, and overall cost. The aim of the present study was to identify risk factors for SSIs after hepatic resection based on a large single-center cohort. Methods: A retrospective study was conducted of 6,132 patients who underwent liver resection without concomitant biliary reconstruction or gastrointestinal procedures between 2014 and 2016 at the largest hepatic center in China. The occurrences of SSI, classified as incisional SSI and organ/space SSI within 30 days after operation were investigated. Patient- and surgical-related risk variables were collected using standardized data collection form. A likelihood ratio forward regression model was used to assess the independent association of risk factors with SSI. Results: SSI developed in 587 patients (9.6%), including superficial/deep incisional SSI in 357 patients (5.8 %), and organ/ space SSI in 304 patients (5.0 %). Multivariate logistic regression analysis showed that obesity, diabetes mellitus, ASA score ≥ 2, liver cirrhosis, re-hepatectomy, hepatoliathiasis, and intraoperative blood transfusion were independent risk factors of overall SSI. However, incisional and organ/space SSI differed from each other with respect to risk factors. Among a variety of risk factors, hepatolithiasis, liver cirrhosis, and intraoperative blood transfusion were consistently associated with both incisional and organ/space SSI. Conclusions: SSI is a common complication after liver resection, and more caution should be taken in patients with hepatolithiasis or liver cirrhosis. Prevention strategies focusing on factors associated with SSI is necessary in order to reduce SSI after liver resection.

Estrogen Receptor α Roles in Breast Cancer Chemoresistance

Xu, Chao-Yang,Jiang, Zhi-Nong,Zhou, Ying,Li, Jia-Jia,Huang, Li-Ming Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Resistance to chemotherapy treatment, which may lead to limited efficacy of systemic therapy in breast cancer patients, is multifactorial. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to estrogen receptor ${\alpha}$, P-glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. $ER{\alpha}$ is ligand-activated transcription factor that regulates gene expression and plays a critical role in endocrine signaling. In previous preclinical and clinical studies, positive $ER{\alpha}$ expression in breast cancer cells was correlated with decreased sensitivity to chemotherapy. This article reviews current knowledge on the predictive value of $ER{\alpha}$ with regard to response to chemotherapy. Better understanding of its role may facilitate patient selection of therapeutic regimens and lead to optimal clinical outcomes.

Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

Xu, Jia-Li,Hu, Ling-Min,Huang, Ming-De,Zhao, Wan,Yin, Yong-Mei,Hu, Zhi-Bin,Ma, Hong-Xia,Shen, Hong-Bing,Shu, Yong-Qian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3

Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.

MLH1 Polymorphisms and Cancer risk: a Meta-analysis Based on 33 Case-control Studies

Xu, Jia-Li,Yin, Zhi-Qiang,Huang, Ming-De,Wang, Xie-Feng,Gao, Wen,Liu, Ling-Xiang,Wang, Rong-Sheng,Huang, Pu-Wen,Yin, Yong-Mei,Liu, Ping,Shu, Yong-Qian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3

Objective: Cumulative evidence suggests that MLH1, the key component in the mismatch pathway, plays an important role in human cancers. Two potential functional polymorphisms (-93G>A and I219V) of MLH1 have been implicated in cancer risk. The aim of this meta-analysis was to summarize the evidence for associations. Methods: Eligible studies were identified by searching the electronic literature PubMed, ScienceDirect and Embase databases for relevant reports and bibliographies. Studies were included if of case-control design investigating MLH1 polymorphisms (-93G>A and I219V) and cancer risk with sufficient raw data for analysis. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to evaluate the strength of associations. Results: Our meta-analysis from 33 published case-control studies showed the variant A allele of -93G>A polymorphism to be associated with increased risk in all genetic models (AA vs. GG: OR = 1.22, 95% CI: 1.03-1.44), especially among non-Asians (AA vs. GG: OR = 1.28, 95% CI: 1.04-1.58). For the I219V polymorphism, however, there was no main effect associated with overall cancer risk in any genetic model. Conclusions: The meta-analysis suggested that the MLH1 -93G>A polymorphism may be a biomarker of cancer susceptibility. Large sample association studies and assessment of gene-to-gene as well as gene-to-environment interactions are required to confirm these findings.

Staged Improvement in Awareness of Disease for Elderly Cancer Patients in Southern China

Li, Xing,Dong, Min,Wen, Jing-Yun,Wei, Li,Ma, Xiao-Kun,Xing, Yan-Fang,Deng, Yun,Chen, Zhan-Hong,Chen, Jie,Ruan, Dan-Yun,Lin, Ze-Xiao,Wang, Tian-Tian,Wu, Dong-Hao,Liu, Xu,Hu, Hai-Tao,Lin, Jia-Yu,Li, Zhu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: In mainland China, awareness of disease of elderly cancer patients largely relies on the patients' families. We developed a staged procedure to improve their awareness of disease. Materials and Methods: Participants were 224 elderly cancer patients from 9 leading hospitals across Southern China. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between family and patients, patient awareness of their disease and participation in medical decision-making. After first cycles of treatment, increased information of disease was given to patients with cooperation of the family. Then patient awareness of their disease and participation in medical decision-making was documented. Results: Among the 224 cancer elderly patients, 26 (11.6%) made decisions by themselves and 125 (55.8%) delegated their rights of decision-making to their family. Subordinate family members tended to play a passive role in decision-making significantly. Patients participating more in medical decision-making tended to know more about their disease. However, in contrast to the awareness of disease, patient awareness of violation of medical recommendations was reversely associated with their participation in medical decision-making. Improvement in awareness of diagnosis, stages and prognosis was achieved in about 20% elderly cancer patients. About 5% participated more actively in medical decision-making. Conclusions: Chinese elderly cancer patient awareness of disease and participation in medical decision-making is limited and relies on their family status. The staged procedure we developed to improve patient awareness of disease proved effective.

Molecular characterization and functional analysis of two trehalose transporter genes in the cabbage beetle, Colaphellus bowringi

Li Jia-Xu,Cao Zhen,Guo Shuang,Tian Zhong,Liu Wen,Zhu Fen,Wang Xiao-Ping 한국응용곤충학회 2020 Journal of Asia-Pacific Entomology Vol.23 No.3

The trehalose, major blood sugar in insects, enhances stress resistance of diapausing individuals in adverse environment and provides an energy source for reproduction. Trehalose transporters (TRETs) play an important role in transport of trehalose from trehalose-producing tissues, e.g. fat body, to trehalose-consuming tissues. Although studies have shown that trehalose contributes to diapause and reproduction, the function of TRETs in these processes remains unclear. In this work, we cloned two TRET genes, TRET1a and TRET1b, from the cabbage beetle Colaphellus bowringi, which is capable of entering reproductive diapause under long-day conditions. We also analyzed the expression profiles of these two genes and investigated their potential roles in diapause and reproduction. The results suggested that both TRET1a and TRET1b belong to sugar-transporter and major facilitator superfamilies. Interestingly, TRET1a was highly expressed in the fat bodies of diapause-destined (DD) females but TRET1b was predominantly expressed in the ovaries of non-diapause-destined (NDD) females. Hormonal induction indicated that juvenile hormone induced TRET1b but repressed TRET1a at transcriptional levels. Methoprene-tolerant and Krüppel homolog 1 mediated the JH-suppressed TRET1a expression but were not involved in the regulation of TRET1b expression by JH. RNAi of TRET1a in DD females elevated the trehalose content in the fat bodies and suppressed the expression of a couple of genes related to stress resistance, which is a critical diapause trait. Knockdown of TRET1b in NDD females reduced the trehalose content in the ovaries but had no apparent effect on the ovary development and yolk deposition. These data suggest that TRET1a and TRET1b could regulate the trehalose content in specific tissues and may play potential roles in reproductive diapause in the females of C. bowringi. Introduction Diapause is a survival strategy for many insects in adapting to adverse environmental conditions (Tauber and Tauber, 1976; Tougeron, 2019). Diapause is a dynamic successive process that consists of diapause induction, preparation, initiation, maintenance, termination, and post-diapause quiescence (Kostal, 2006). Insects accumulate enormous nutrients such as sugars and lipids to enter diapause during diapause preparation phase (Hahn and Denlinger, 2007, 2011). The trehalose is the major hemolymph sugar in insects. The sugar not only provides source of energy but also protects proteins and cellular membranes from dehydration, desiccation, heat, cold, and oxidation (Elbein et al., 2003; Li et al., 2002; Richards et al., 2002; Wyatt and Kalf, 1957; Yancey, 2005; Zhu et al., 2008). Therefore, trehalose can play roles in reproduction and diapause by mediating energy supply and stress tolerance, respectively (Kamei et al., 2011; Lu et al., 2019; Xu et al., 2009).

Expression of Endogenous Hypoxia Markers in Vulvar Squamous Cell Carcinoma

Li, Yu-Zhu,Li, Shu-Ling,Li, Xia,Wang, Li-Jie,Wang, Jiu-Ling,Xu, Jia-Wen,Wu, Zhi-Hong,Gong, Li,Zhang, Xiao-Dan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

Objective: To investigate the expression of endogenous hypoxia-related markers identified as being involved in vulvar squamous cell carcinoma (VSCC). Methods: We performed immunohistochemical staining of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), glucose transporter-1 (GLUT-1), carbonic anhydrase 9 (CA-9) and vascular endothelial growth factor (VEGF), on tissue sections of 25 VSCC patients, 10 vulvar intraepithelial neoplasia (VIN) patients and 12 healthy controls. Results: HIF-$1{\alpha}$ expression was found in all sections, with no significant difference between controls, VIN and VSCC sections (all P<0.05). Glut-1 expression was found in 25% of control, 90% of VIN and 100% of VSCC sections. A significant difference between control and VIN or VSCC was observed (all P<0.05), while no difference was found between VIN and VSCC sections (P>0.05). CA-9 expression was negative in control sections, but it was found in 30% of VIN sections and 52% of VSCC sections with strong staining. Similarly, CA-9 expression also showed obvious differences between controls and VIN or VSCC sections (all P<0.05). However, there was no significant difference between VIN and VSCC (P>0.05). There were only 25% of control sections with weak VEGF expression, while strong staining was found in about 60% of VIN sections and 25% of VSCC sections (all P<0.05). In addition, a difference was also found between VIN and VSCC sections (P<0.05). Conclusion: Expression of endogenous hypoxia markers (HIF-$1{\alpha}$, GLUT-1, CA-9 and VEGF) might be involved in the malignant progression of VSCC.

Mutations in the GyrA Subunit of DNA Gyrase and the ParC Subunit of Topoisomerase IV in Clinical Strains of Fluoroquinolone-Resistant Shigella in Anhui, China

Li-Fen Hu,Jia-Bin Li,Ying Ye,Xu Li 한국미생물학회 2007 The journal of microbiology Vol.45 No.2

In this research 26 Shigella isolates were examined by PCR and direct nucleotide sequencing for genetic alterations in the quinolone-resistance determining regions (QRDRs). We tested for the presence of qnr genes by PCR in 91 strains, but no qnr genes were found. The results did show, however, some novel mutations at codon 83 of gyrA (Ser→Ile) and codon 64 of parC (Ala64→Cys, Ala64→Asp), which were related to fluroquinolone resistance.