Aberrant DNA Methylation and Epigenetic Inactivation of hMSH2 Decrease Overall Survival of Acute Lymphoblastic Leukemia Patients via Modulating Cell Cycle and Apoptosis

Wang, Cai-Xia,Wang, Xiang,Liu, Hai-Bai,Zhou, Zhi-Heng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Objective: Altered regulation of many transcription factors has been shown to play important roles in the development of leukemia. hMSH2 can modulate the activity of some important transcription factors and is known to be a regulator of hematopoietic differentiation. Herein, we investigated epigenetic regulation of hMSH2 and its influence on cell growth and overall survival of acute lymphoblastic leukemia (ALL) patients. Methods: hMSH2 promoter methylation status was assessed by COBRA and pyrosequencing in 60 ALL patients and 30 healthy volunteers. mRNA and protein expression levels of hMSH2, PCNA, CyclinD1, Bcl-2 and Bax were determined by real time PCR and Western blotting, respectively. The influence of hMSH2 on cell proliferation and survival was assessed in transient and stable expression systems. Results: mRNA and protein expression of hMSH2 and Bcl-2 was decreased, and that of PCNA, CyclinD1 and Bax was increased in ALL patients as compared to healthy volunteers (P<0.05). hMSH2 was inactivated in ALL patients through promoter hypermethylation. Furthermore, hMSH2 hypermethylation was found in relapsed ALL patients (85.7% of all cases). The median survival of patients with hMSH2 methylation was shorter than that of patients without hMSH2 methylation (log-rank test, P=0.0035). Over-expression of hMSH2 in cell lines resulted in a significant reduction in growth and induction of apoptosis. Conclusions: This study suggests that aberrant DNA methylation and epigenetic inactivation of hMSH2 play an important role in the development of ALL through altering cell growth and survival.

ppGalNAc T1 as a Potential Novel Marker for Human Bladder Cancer

Ding, Ming-Xia,Wang, Hai-Feng,Wang, Jian-Song,Zhan, Hui,Zuo, Yi-Gang,Yang, De-Lin,Liu, Jing-Yu,Wang, Wei,Ke, Chang-Xing,Yan, Ru-Ping Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Objectives: To investigate the effect of glycopeptide-preferring polypeptide GalNAc transferase 1 (ppGalNAc T1 ) targeted RNA interference (RNAi) on the growth and migration of human bladder carcinoma EJ cells in vitro and in vivo. Methods: DNA microarray assays were performed to determine ppGalNAc Ts(ppGalNAc T1-9) expression in human bladder cancer and normal bladder tissues. We transfected the EJ bladder cancer cell line with well-designed ppGalNAc T1 siRNA. Boyden chamber and Wound healing assays were used to investigate changes of shppGalNAc T1-EJ cell migration. Proliferation of shppGalNAc T1-EJ cells in vitro was assessed using [3H]-thymidine incorporation assay and soft agar colony formation assays. Subcutaneous bladder tumors in BALB/c nude mice were induced by inoculation of shppGalNAc T1-EJ cells and after inoculation diameters of tumors were measured every 5 days to determine gross tumor volumes. Results: ppGalNAc T1 mRNA in bladder cancer tissues was 11.2-fold higher than in normal bladder tissues. When ppGalNAc T1 expression in EJ cells was knocked down through transfection by pSUPER-shppGalNAc T1 vector, markedly reduced incorporation of [3H]-thymidine into DNA of EJ cells was observed at all time points compared with the empty vector transfected control cells. However, ppGalNAc T1 knockdown did not significantly inhibited cell migration (only 12.3%). Silenced ppGalNAc T1 expression significantly inhibited subcutaneous tumor growth compared with the control groups injected with empty vector transfected control cells. At the end of observation course (40 days), the inhibitory rate of cancerous growth for ppGalNAc T1 knockdown was 52.5%. Conclusion: ppGalNAc T1 might be a potential novel marker for human bladder cancer. Although ppGalNAc T1 knockdown caused no remarkable change in cell migration, silenced expression significantly inhibited proliferation and tumor growth of the bladder cancer EJ cell line.

An Updated Meta-analysis on the Association of X-Ray Repair Cross Complementing Group 1 Codon 399 Polymorphism with Hepatocellular Carcinoma Risk

Wang, Ya-Dong,Zhai, Wen-Long,Wang, Hai-Yu,Xia, Xiang-Qun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Background: A number of studies have reported the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with susceptibility to hepatocellular carcinoma (HCC). However, the results were inconsistent and inconclusive. The aim of this study was to comprehensively explore the association of XRCC1 Arg399Gln variant with HCC risk. Materials and Methods: Systematic searches of PubMed, Elsevier, Science Direct, CNKI and Chinese Biomedical Literature Database were performed. Pooled odds ratio (OR) with 95% confidence intervals (CI) was calculated to estimate the strength of association. Results: Overall, we observed an increased HCC risk among subjects carrying XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln genotypes (OR=1.20, 95%CI: 1.05-1.38, OR=1.16, 95%CI: 1.05-1.28, and OR=1.14, 95%CI: 1.04-1.24, respectively) based on 20 studies including 3374 cases and 4633 controls. In subgroup analysis, we observed an increased risk of XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln polymorphisms for HCC in hospital-based study (OR=1.25, 95%CI: 1.03-1.51, OR=1.21, 95%CI: 1.07-1.36 and OR=1.18, 95%CI: 1.06-1.31, respectively) and in Asian population (OR=1.19, 95%CI: 1.03-1.38, OR=1.17, 95%CI: 1.04-1.30 and OR=1.14, 95%CI: 1.04-1.25, respectively). Limiting the analysis to the studies with controls in agreement with Hardy-Weinberg equilibrium (HWE), we observed an increased HCC risk among Gln/Gln, Arg/Gln and Gln/ Gln+Arg/Gln genotype carriers (OR=1.17, 95%CI: 1.05-1.29, OR=1.12, 95%CI: 1.00-1.25 and OR=1.11, 95%CI: 1.02-1.21, respectively). Conclusions: This updated meta-analysis results suggest that XRCC1 Arg399Gln variants may contribute to HCC risk. Well-designed studies with larger sample size were required to further verify our findings.

Prediction Models for Solitary Pulmonary Nodules Based on Curvelet Textural Features and Clinical Parameters

Wang, Jing-Jing,Wu, Hai-Feng,Sun, Tao,Li, Xia,Wang, Wei,Tao, Li-Xin,Huo, Da,Lv, Ping-Xin,He, Wen,Guo, Xiu-Hua Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

Lung cancer, one of the leading causes of cancer-related deaths, usually appears as solitary pulmonary nodules (SPNs) which are hard to diagnose using the naked eye. In this paper, curvelet-based textural features and clinical parameters are used with three prediction models [a multilevel model, a least absolute shrinkage and selection operator (LASSO) regression method, and a support vector machine (SVM)] to improve the diagnosis of benign and malignant SPNs. Dimensionality reduction of the original curvelet-based textural features was achieved using principal component analysis. In addition, non-conditional logistical regression was used to find clinical predictors among demographic parameters and morphological features. The results showed that, combined with 11 clinical predictors, the accuracy rates using 12 principal components were higher than those using the original curvelet-based textural features. To evaluate the models, 10-fold cross validation and back substitution were applied. The results obtained, respectively, were 0.8549 and 0.9221 for the LASSO method, 0.9443 and 0.9831 for SVM, and 0.8722 and 0.9722 for the multilevel model. All in all, it was found that using curvelet-based textural features after dimensionality reduction and using clinical predictors, the highest accuracy rate was achieved with SVM. The method may be used as an auxiliary tool to differentiate between benign and malignant SPNs in CT images.

Multiple Impairments in Male Reproduction 1 (mimr1), a Novel Male-Sterile Mutant of Arabidopsis thaliana, Shows Several Defects in Male Reproductive Development

Hai-Yan Chen,Yue-Feng Guan,Xue-Yong Huang,Yu-Ting Wu,Fen-Fei Wang,Ju-Fang Gao,Que Zhou,Zhong-Nan Yang,Jia-Yao Liu,Hong-Xia Zhang 한국식물학회 2012 Journal of Plant Biology Vol.55 No.3

We have characterized a new male-sterile mutant in Arabidopsis that exhibits conditional sterility but has restored fertility when drought-stressed. This mutant,multiple impairments in male reproduction 1 (mimr1),shows pleiotropic defects in both vegetative and reproductive development. Examination with dissecting and scanning electron microscopes revealed that its pollen grains are not effectively released from the anther locule after dehiscence, and anther differentiation is defective. Growth of the style and stamen filaments are also abnormal. Histological analysis demonstrated that these phenomena are due not only to a noticeably reduced extension of the stamen but also greater elongation of the pistil. Genetic analysis indicated that mimr1 is a single locus recessive nuclear mutant. The mutation can be mapped to a locus strongly linked to a 1200-kb region on Chromosome 3. Meta-analysis of expression patterning presented several candidate genes in that region. No mutants with similar phenotypes have previously been reported, suggesting that mimr1 is a novel male-sterile locus. Characterization of MIMR1 will provide further insights into the molecular basis for the development of plant reproductive organs.

Silencing of Twist Expression by RNA Interference Suppresses Epithelial-mesenchymal Transition, Invasion, and Metastasis of Ovarian Cancer

Wang, Wen-Shuang,Yang, Xing-Sheng,Xia, Min,Jiang, Hai-Yang,Hou, Jian-Qing Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.9

Purpose: This study aimed to explore the role of the Twist gene in the epithelial-mesenchymal transition of ovarian cancer. Methods: An RNA interference plasmid expressing a small interfering RNA (siRNA)-targeting Twist (Twist siRNA vector) was designed, constructed, and transfected into the human ovarian cancer cell line A2780. Transfection efficiency was assessed under a fluorescence microscope. Changes in the expression of Twist mRNA in A2780 after transfection with the pGenesil Twist shRNA plasmid were analyzed through RT-PCR. MTT assays and adhesion experiments were applied to determine changes in proliferation and adhesion ability of A2870 after transfection with the Twist shRNA plasmid. Changes in the expression of the E-cadherin and N-cadherin proteins in A2780 after transfection with the Twist shRNA plasmid were analyzed using Western blotting. Result: The restructuring plasmid pGenesil-Twist shRNA was constructed successfully. After 48 h of culture, 80% of the cells expressed high-intensity GFP fluorescence and stability. The expression of Twist decreased significantly after the transfection of the Twist shRNA plasmid (P<0.05). Proliferation of the transfected Twist shRNA cells showed no difference with that of the A2780-nontransfection or A2780-si-control groups (P>0.05) but the adhesion ability of A2780 decreased dramatically (P<0.05). Expression of the E-cadherin protein increased, whereas that of the N-cadherin protein decreased compared with that in the A2780-nontransfection or A2780-si-control groups (P<0.05). Conclusion: Twist is essential for epithelial-mesenchymal transition, invasion, and metastasis of ovarian cancer.

Effects of Preemptive Analgesia with Parecoxib Sodium on Haemodynamics and Plasma Stress Hormones in Surgical Patients with Thyroid Carcinoma

Wang, Lian-Dong,Gao, Xia,Li, Jun-Ying,Yu, Hong-Yan,Su, Hai-Wen,Liu, Lian-Zhong,Qi, Jun Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Background: To investigate the effects of preemptive analgesia with parecoxib sodium on haemodynamics and plasma stress hormones in surgical patients with thyroid carcinoma. Materials and Methods: Fifty-seven patients with thyroid carcinoma who underwent thyroidectomy selectively in Laiwu Hospital Affiliated to Taishan Medical University and Binzhou People's Hospital were selected and randomly divided into three groups, 19 cases in each group. The control group was intravenously injected 0.9% sodium chloride injection before anesthesia induction; trial group I was intravenously injected with parecoxib sodium 20 min before anesthesia induction; based on trial group I, trial group II was injected with parecoxib sodium again 12 h after surgery. The levels of plasma norepinephrine (NE), cortisol (Cor) and blood glucose before, 12 and 24 h after surgery and changes of haemodynamics before surgery, at the end of surgery and 12, 24 and 48 h after surgery were compared in the three groups. Besides, visual analogue scale (VAS) scores were recorded 4, 8, 12 and 24 h after surgery. Results: 12 and 24 h after surgery, the levels of plasma NE and Cor in three groups rose dramatically (P<0.05 or (P<0.01); The levels of plasma NE and Cor in trial groups I and II were evidently lower than in control group (P<0.05 or P<0.01), and those in trial group II slightly lower than in trial group I. 12 h after surgery, the heart rates (HR) and systolic pressures (SBP) in trial groups I and II increased obviously by comparison to surgery before (P<0.05 or P<0.01), but gradually returned to the preoperative level. HR, SBP and diastolic pressures (DBP) in trial groups I and II at the end of surgery and 12 h after surgery were all lower than in the control group, and significant differences were present (P<0.05 or (P<0.01). At 4, 8, 12 and 24 h after surgery, VAS scores in trial groups I and II were markedly lower than in the control group (P<0.05 or (P<0.01), the scores in trial group II being the lowest. Conclusions: Combined application of parecoxib sodium for preemptive analgesia before anesthesia and after surgery can effectively reduce the levels of plasma stress hormones and improve analgesic effects in surgical patients with thyroid carcinoma, and without conspicuous impact on haemodynamics.

The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx

Hai-Xia Li,Yan Ma,Yu-Xiao Yan,Xin-Ke Zhai,Meng-Yu Xin,Tian Wang,Dong-Cao Xu,Yu-Tong Song,Chun-Dong Song,Cheng-Xue Pan 고려인삼학회 2023 Journal of Ginseng Research Vol.47 No.6

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important rolein store-operated Ca2þ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protectionagainst myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributesto intracellular Ca2þ ([Ca2þ]i) accumulation in cardiomyocytes. The purified extract of steamed Panaxginseng (EPG) attenuated [Ca2þ]i overload against MI injury. Thus, the aim of this study was to investigatethe possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca2þ]i against MI injury in neonatalrat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca2þ]i concentration were analyzedin cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosiswere evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels ofcaveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH,cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protectedcardiomyocytes by inhibiting Ca2þ influx. And, EPG significantly relieved myocardial infarct size, cardiacapoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE viaincreasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotectionof EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury viaincreasing p-caveolin-1 to negatively regulate SOCE/[Ca2þ]i.

Correlation Between Auto-antibodies to Survivin and MUC1 Variable Number Tandem Repeats in Colorectal Cancer

Wang, Yu-Qian,Zhang, Hai-Hong,Liu, Chen-Lu,Xia, Qiu,Wu, Hui,Yu, Xiang-Hui,Kong, Wei Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Aim: The aim of this study was to investigate the frequency and correlation between auto-antibodies to survivin and MUC1 variable number tandem repeats (VNTR) in colorectal cancer (CRC), which can provide valuable information for the design of immunotherapeutic vaccines for this disease. Methods: Enzyme-linked immunosorbent assays (ELISA) were used to examine the level of auto-antibodies against survivin and MUC1 VNTR in the serum of 135 CRC patients and 95 healthy volunteers. Results: Using mean absorbance + 2 standard deviations (SD) of the healthy samples as a cut-off value, the positive rates of survivin and MUC1 VNTR auto-antibodies in CRC were 31.1% and 18.5%, respectively. Altogether, the survivin and MUC1 VNTR positive samples accounted for 36.3% of the CRC patients, and 7.4% were positive for both. Conclusion: A significant positive correlation was found between levels of specific antibodies against survivin and MUC1 VNTR in the serum of CRC patients (r = 0.3652, P < 0.0001), suggesting that vaccines against both targets would elicit immune responses more effectively.

Lignan Constituents from Chloranthus japonicus Sieb

Hai-xue Kuang,Yong-gang Xia,Bing-you Yang,Qiu-hong Wang,Shao-wa Lü 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.3

A new coumarinolignan glucoside named yinxiancaoside C, along with five known benzofuran lignans, have been isolated from the whole plant of Chloranthus japonicus Sieb. The structures of compounds 1-6 were elucidated by chemical and spectroscopic methods including 1DNMR, 2D-NMR, ESI-MS and HR-ESI-MS. Five known benzofuran lignans were firstly discovered in the Chloranthaceae. In addition, the cytotoxic activity of the isolated compounds against human hepatoma (Hepg-2), ovarian carcinoma (OV420), and breast cancer (MCF-7) cells was investigated by MTT method.