• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2851-2857
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• 2013

Objective: REPS2 plays important roles in inhibiting cell proliferation, migration and in inducing apoptosis of cancer cells, now being identified as a useful biomarker for favorable prognosis in prostate and breast cancers. The purpose of this study was to assess REPS2 expression and to explore its role in esophageal squamous cell carcinoma (ESCC). Methods: Protein expression of REPS2 in ESCCs and adjacent non-cancerous tissues from 120 patients was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Additionally, thirty paired ESCC tissues and four ESCC cell lines and one normal human esophageal epithelial cell line were evaluated for REPS2 mRNA and protein expression levels by quantitative RT-PCR and Western blotting. Results: REPS2 mRNA and protein expression levels were down-regulated in ESCC tissues and cell lines. Low protein levels were significantly associated with primary tumour, TNM stage, lymph node metastasis and recurrence (all, P < 0.05). Survival analysis demonstrated that decreased REPS2 expression was significantly associated with shorter overall survival and disease-free survival (both, P < 0.001), especially in early stage ESCC patients. When REPS2 expression and lymph node metastasis status were combined, patients with low REPS2 expression/lymph node (+) had both poorer overall and disease-free survival than others (both, P < 0.001). Cox multivariate regression analysis further revealed REPS2 to be an independent prognostic factor for ESCC patients. Conclusions: Our findings demonstrate that downregulation of REPS2 may contribute to malignant progression of ESCC and represent a novel prognostic marker and a potential therapeutic target for ESCC patients.

• Steel and Composite Structures
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• v.30 no.6
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• pp.535-550
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• 2019

Prestressed concrete (PC) bridges using corrugated steel webbing have emerged as one of the most promising forms of steel-concrete composite bridge. However, their long-term behavior is not well understood, especially in the case of large-span bridges. In order to study the time-dependent performance, a large three-span PC bridge with corrugated steel webbing was compared to a similar conventional PC bridge to examine their respective time-dependent characteristics. In addition, a three-dimensional finite element method with step-by-step time integration that takes into account cantilever construction procedures was used to predict long-term behaviors such as deflection, stress distribution and prestressing loss. These predictions were based upon four well-established empirical creep prediction models. PC bridges with a corrugated steel web were observed to have a better long-term performance relative to conventional PC bridges. In particular, it is noted that the pre-cambering for PC bridges with a corrugated steel web could be smaller than that of conventional PC bridges. The ratio of side-to-mid span has great influence on the long-term deformation of PC bridges with a corrugated steel web, and it is suggested that the design value should be between 0.4 and 0.6. However, the different creep prediction models still showed a weak homogeneity, thus, the further experimental research and the development of health monitoring systems are required to further progress our understanding of the long-term behavior of PC bridges with corrugated steel webbing.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.175-183
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• 2021

The mitogen-activated protein kinase (MAPK) pathway controls intestinal epithelial barrier permeability by regulating tight junctions (TJs) and epithelial cells damage. Heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal epithelial barrier function, but the molecular mechanism is not yet clarified. MAPK activation and barrier permeability were studied using monolayers of Caco-2 cells treated with tissue necrosis factor α (TNF-α) transfected with FUGW-HO-1 or pLKO.1-sh-HO-1 plasmid. Intestinal mucosal barrier permeability and MAPK activation were also investigated using carbon tetrachloride (CCl4) administration with CoPP (a HO-1 inducer), ZnPP (a HO-1 inhibitor), CO releasing molecule 2 (CORM-2), or inactived-CORM-2-treated wild-type mice and mice with HO-1 deficiency in intestinal epithelial cells. TNF-α increased epithelial TJ disruption and cleaved caspase-3 expression, induced ERK, p38, and JNK phosphorylation. In addition, HO-1 blocked TNF-α-induced increase in epithelial TJs disruption, cleaved caspase-3 expression, as well as ERK, p38, and JNK phosphorylation in an HO-1-dependent manner. CoPP and CORM-2 directly ameliorated intestinal mucosal injury, attenuated TJ disruption and cleaved caspase-3 expression, and inhibited epithelial ERK, p38, and JNK phosphorylation after chronic CCl4 injection. Conversely, ZnPP completely reversed these effects. Furthermore, mice with intestinal epithelial HO-1 deficient exhibited a robust increase in mucosal TJs disruption, cleaved caspase-3 expression, and MAPKs activation as compared to the control group mice. These data demonstrated that HO-1-dependent MAPK signaling inhibition preserves the intestinal mucosal barrier integrity by abrogating TJ dysregulation and epithelial cell damage. The differential targeting of gut HO-1-MAPK axis leads to improved intestinal disease therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10329-10334
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• 2015

Background: To systematically summarize the association between the X-ray repair cross complementing 3 (XRCC3) gene polymorphism and oral cancer susceptibility by meta-analysis. Materials and Methods: Databases including PubMed, EMbase, CNKI, VIP and WanFang Data were searched to identify case-control studies concerning the association between an XRCC3 gene polymorphism and the risk of oral cancer from the inception to June 2014. Two reviewers independently screened the literature according to the criteria, extracted the data and assessed the quality. Then meta-analysis was performed using Stata 11.0 software. Results: Seven published case-control studies including 775 patients with oral cancer and 1922 controls were selected. Associations between the rs861539 polymorphism and overall oral cancer risk were not statistically significant in all kinds of comparison models (CT vs CC: OR=0.94, 95%CI=0.74-1.18; TT vs CC: OR=0.94, 95%CI=0.64-1.38; dominant model: OR=0.95, 95%CI=0.76-1.18; recessive model: OR=0.94, 95%CI=0.69-1.29; allele T vs C: OR=0.97, 95%CI=0.84-1.11). In the stratified analysis by ethnicity, no significant associations were found among Asians and Caucasians. On stratification by tumor type, no significant associations were found for cancer and oral premalignant lesions. Conclusions: The XRCC3 gene polymorphism was not found to be associated with the risk of oral cancer. Considering the limited quality of the included case-control studies, more high quality studies with large sample size are needed to verify the above conclusion.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6829-6835
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• 2014

Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'-deoxy-2'-${\beta}$-fluoro-4'-azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with $IC_{50}$ values of $0.2{\mu}M$ and $0.097{\mu}M$, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of ${\beta}$-catenin, the glycogen synthase kinase-3 beta (GSK-$3{\beta}$), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, ${\beta}$-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-$3{\beta}$ and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/${\beta}$-catenin signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.419-422
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• 2013

Conventional classifications of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are rather unsatisfactory because of the variation in survival within each subgroup. Molecular markers are being found able to predict patient outcome in more and more tumours. The aim of this study was to characterize the expression of the proteins cyclin D1, cyclin E and P53 in GEP-NETs and assess any prognostic impact. Tumor specimens from 68 patients with a complete follow-up were studied immunohistochemically for cyclin D1, cyclin E and P53 expression. High cyclin D1 and cyclin E immunostaining (${\geq}$ 5% positive nuclei) was found in 48 (71%) and 24 (35%) cases, and high P53 staining (${\geq}$ 10% positive nuclei) in 33 (49%). High expression of P53 was more common in gastric neuroendocrine tumors and related to malignant behavior, being associate with a worse prognosis on univariate analysis (RR=1.9, 95%CI=1.1-3.2). High expression of cyclin E was significantly associated with shorter survival in the univariate analysis (RR=2.0, 95%CI=1.2-3.6) and multivariate analysis (RR=2.1, 95%CI=1.1-4.0). We found no significant correlation between the expression of cyclin D1 and any clinicopathological variables. Our study indicated a prognostic relevance for cyclin E and P53 immunoreactivity. Cyclin E may be an independent prognostic factor from the 2010 WHO Classification which should be evaluated in further studies.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4255-4259
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• 2013

Background: Soft tissue sarcomas (STS) are a heterogeneous group of tumors, and approximately 40-50% of patients with STS develop metastatic disease. The median overall survival of those patients was 12 months and their 5-year survival rate was 8%. Therefore, study on more effective treatment, especially the targeting therapies, is urgently needed. Objective: To evaluate the efficacy and safety of Endostar$^{(R)}$ combined with chemotherapy in patients with advanced STS. Methods: A retrospective case-series study was conducted in Cancer Institute of PLA, Xinqiao Hospital. A total of 71 patients suffering from advanced STS (IIB - IV) were included, of whom 49 cases treated with chemotherapy alone were defined as the control group and the rest 22 cases treated with the traditional chemotherapy combined with Endostar$^{(R)}$ were defined as the test group. The short-term therapeutic effects including objective response rate (ORR), disease control rate (DCR) and safety were evaluated in the two groups. In the follow-up, progression-free survival (PFS) and overall survival (OS) were also observed. Results: In the test and control groups, the ORR was 18.2% and 12.2%, respectively (P=0.767), and the DCR was 86.4% and 61.2%, respectively (P=0.034). The median time to progression in the test and control groups was 120 days and 70 days with significant difference (P = 0.017), while the median overall survival was 452 days and 286 days without significant difference (P=0.503). The one-year survival rate in the test group and control group was 56.2% and 35.4%, respectively, while the two-year survival rate was 30.2% and 26.5%, respectively. No significant difference in the side effects was found between the two groups. Conclusions: Endostar$^{(R)}$ combined with chemotherapy resulted in a higher DCR and longer PFS in the patients with advanced STS, and the toxicity was tolerable.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2369-2378
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• 2012

Objectives: To assess knowledge of HPV and attitudes towards HPV vaccination among the general female population, government officials, and healthcare providers in China to assist the development of an effective national HPV vaccination program. Methods: A cross-sectional epidemiologic survey was conducted across 21 urban and rural sites in China using a short questionnaire. 763 government officials, 760 healthcare providers, and 11,681 women aged 15-59 years were included in the final analysis. Data were analyzed using standard descriptive statistics and logistic regression. Results: Knowledge of HPV among the general female population was low; only 24% had heard of HPV. Less than 20% of healthcare providers recognized sexually na$\ddot{i}$ve women as the most appropriate population for HPV vaccination. There was high acceptance of the HPV vaccine for all categories of respondents. Only 6% of women were willing to pay more than US $300 for the vaccine. Conclusions: Aggressive education is necessary to increase knowledge of HPV and its vaccine. Further proof of vaccine safety and efficacy and government subsidies combined with increased awareness could facilitate development and implementation of HPV vaccination in China.

• BMB Reports
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• v.46 no.8
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• pp.422-427
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• 2013

Although BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cell (MSCs), the molecular mechanism involved remains to be fully elucidated. Here, we explore the possible involvement and detail role of JNKs (c-Jun N-terminal kinases) in BMP9-induced osteogenic differentiation of MSCs. It was found that BMP9 stimulated the activation of JNKs in MSCs. BMP9-induced osteogenic differentiation of MSCs was dramatically inhibited by JNKs inhibitor SP600125. Moreover, BMP9-activated Smads signaling was decreased by SP600125 treatment in MSCs. The effects of inhibitor are reproduced with adenoviruses expressing siRNA targeted JNKs. Taken together, our results revealed that JNKs was activated in BMP9-induced osteogenic differentiation of MSCs. What is most noteworthy, however, is that inhibition of JNKs activity resulted in reduction of BMP9-induced osteogenic differentiation of MSCs, implying that activation of JNKs is essential for BMP9 osteoinductive activity.

• The korean journal of orthodontics
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• v.40 no.5
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• pp.349-357
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• 2010

Objective: The purpose of this study was to evaluate the dentoskeletal and soft tissue profile changes after extraction of two lower first or second premolars in "borderline" adult skeletal Class III cases. Methods: Twenty-eight patients with "borderline" skeletal Class III malocclusion were studied. All of them were treated by extraction of two lower first or second premolars. Lateral cephalometric radiographs taken at the start and end of treatment were analysed. Twenty-five cephalometric variables were calculated and paired $t$-tests were performed. Results: After treatment, no significant changes were noted in the skeletal parameters ($p{\geq}0.05$). Regarding the dental parameters, the L1-MP angle decreased by $8.1^{\circ}$, the U1-L1 angle increased by $7.7^{\circ}$ ($p$ < 0.01), the overjet distance increased by 5.7 mm ($p$ < 0.01), the L1-NB angle decreased by $7.3^{\circ}$ and the L1-NB distance decreased by 4.8 mm ($p$ < 0.01). The soft tissue parameters of Li-E, Li-H and Li-RL2 distance decreased by 3.2 mm, 3.4 mm and 4.1 mm respectively ($p$ < 0.01). Conclusions: Orthodontic camouflage treatment by extraction of two lower first or second premolars provides a viable treatment alternative for "borderline" skeletal Class III cases to achieve a good occlusal relationship.