• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1589-1595
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• 2014

Objective: Forkhead box C2 (FOXC2) is a member of the winged helix/forkhead box (Fox) family of transcription factors. It has been suggested to regulate tumor vasculature, growth, invasion and metastasis, although it has not been studied in cervical cancer. Here, we analyzed FOXC2 expression in cervical tissues corresponding to different stages of cervical cancer development and examined its correlation with clinicopathological characteristics. In addition, we examined the effects of targeting FOXC2 on the biological behavior of human cervical cancer cells. Methods: The expression of FOXC2 in normal human cervix, CIN I-III and cervical cancer was examined by immunohistochemistry and compared among the three groups and between cervical cancers with different pathological subtypes. Endogenous expression of FOXC2 was transiently knocked down in human Hela and SiHa cervical cells by siRNA, and cell viability and migration were examined by scratch and CCK8 assays, respectively. Results: In normal cervical tissue the frequency of positive staining was 25% (10/40 cases), with a staining intensity (PI) of $0.297{\pm}0.520$, in CIN was 65% (26/40cases), with a PI of $3.00{\pm}3.29$, and in cancer was 91.8% (68/74 cases), with a PI of $5.568 {\pm}3.449$. The frequency was 100% in adenocarcinoma (5/5 cases) and 91.3% in SCCs (63/69 cases). The FOXC2 positive expression rate was 88.5% in patients with cervical SCC stage I and 100% in stage II, showing significant differences compared with normal cervix and CIN. With age, pathologic differentiation degree and tumor size, FOXC2 expression showed no significant variation. On transient transfection of Hela and SiHa cells, FOXC2-siRNA inhibition rates were 76.2% and 75.7%; CCK8 results showed reduced proliferation and relative migration (in Hela cells from $64.5{\pm}3.16$ to $49.5{\pm}9.24$ and in SiHa cells from $60.1{\pm}3.05$ to $44.3{\pm}3.98$) (P < 0.05). Conclusion: FOXC2 gene expression increases with malignancy, especially with blood vessel hyperplasia and invasion degree. Targeted silencing was associated with reduced cell proliferation as well as invasion potential.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7639-7644
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• 2014

Background: Results from previous studies concerning the association of ERCC4 rs1800067 polymorphism with risk of cancer were inconsistent. To explore the exact relation with susceptibility, we conducted the present meta-analysis. Materials and Methods: Literature of electronic databases including PubMed, Web of Science, EMBASE, Wanfang and Chinese National Knowledge Infrastructure (CNKI) were systematically searched. ORs and their 95%CIs were used to assess the strength of associations between ERCC4 polymorphism and cancer risk. Results: There was no significant association between ERCC4 rs1800067 AA or AG genotypes and overall risk of cancer (AA vs. GG: OR=0.998, 95%CI=0.670-1.486, P=0.992; AG vs. GG: OR=0.970, 95%CI=0.888-1.061, P=0.508). A dominant genetic model also did not demonstrate significant association of (AA+AG) genotype carriers with altered risk of overall cancer (OR=0.985, 95%CI=0.909-1.068, P=0.719). In addition, no significant association was observed between A allele of ERCC4 rs1800067 A/G polymorphism and altered cancer risk compared with G allele (OR=0.952, 95%CI=0.851-1.063, P=0.381). Subgroup analysis suggested that AA genotype carriers were significantly associated with decreased risk of glioma compared with wild-type GG genotype individuals (OR=0.523, 95%CI=0.275-0.993, P=0.048). For subgroup of lung cancer, A allele of ERCC4 rs1800067 A/G polymorphism was significantly associated with decreased risk of lung cancer compared with G allele (OR=0.806, 95%CI=0.697-0.931, P=0.003). Conclusions: This meta-analysis indicated that ERCC4 rs1800067 A/G polymorphism might not be associated with risk of overall cancer. However, individuals with the AA genotype were associated with significantly reduced risk of glioma compared with wild-type GG genotype; The A allele was associated with significantly reduced risk of lung cancer compared with G allele. Future large-scale studies performed in multiple populations are warranted to confirm our results.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6715-6719
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• 2013

Objective: To explore the incidence, clinical characteristics, diagnosis and treatment strategies, prognosis of patients with malignancy-associated hypercalcemia (MAH). Methods: The data of 115 patients with MAH who were treated at the Medical Oncology Department of Chinese PLA General Hospital from Jan., 2001 to Dec., 2010 was retrospectively reviewed. Survival analysis was performed using the Kaplan-Meier method and the Cox proportional hazard model with statistic software SPSS 18.0. Results: The patients had blood calcium levels ranging from 2.77 to 4.87 mmol/L. Except for 9 cases who died or were discharged within 5 days after admission, all other patients recovered to normal blood calcium level after treatment with bisphosphonates or intravenous hydration and diuretics; their survival after occurrence of MAH was from 1 day to 4,051 days, and the median survival time was only 50 days. In the log-rank test, the male, renal metastasis, central nervous system symptoms and hypercalcemia occurring over 140 days after cancer diagnosis were predictors of poor survival (P=0.002, P=0.046, P=0.000, P=0.009). In the COX analysis, being male, central nervous system symptoms and hypercalcemia lasting over 140 days after cancer diagnosis were independent prognostic factors for survival time (RR=2.131, P=0.027; RR=3.054, P=0.002; RR=2.403, P=0.001). According to these factors, a score system was established to predict the patient prognosis and adjust the treatment. Conclusion: Cancer patients with MAH have an extremely poor median survival. Some independent factors indicate poor prognosis, including male gender, central nervous system symptoms and hypercalcemia lasting over 140 days after cancer diagnosis. The prognostic score can serve as a reference for MAH prognosis and treatment, worthy of further investigation.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6357-6362
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• 2013

Background: The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) has been associated with acute lymphoblastic leukemia (ALL). However, results were conflicting. The aim of this study was to quantitatively summarize the evidence for the MTHFRC677T polymorphism and ALL risk. Methods: Electronic searches of PubMed and the Chinese Biomedicine database were conducted to select case-control studies containing available genotype frequencies of C677T and the odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of any association. Results: Case-control studies including 6,371 cases and 10,850 controls were identified. The meta-analysis stratified by ethnicity showed that individuals with the homozygous TT genotype had decreased risk of ALL (OR= 0.776, 95% CI: 0.687~0.877, p< 0.001) in Caucasians (OR= 0.715, 95% CI: 0.655~0.781, p= 0.000). However, results among Asians (OR=0.711, 95% CI: 0.591~1.005, p= 0.055) and others (OR=0.913, 95% CI: 0.656~1.271, p= 0. 590) did not suggest an association. A symmetric funnel plot, the Egger's test (P=0.093), and the Begg- test (P=0.072) were all suggestive of the lack of publication bias. Conclusion: This meta-analysis supports the idea that the MTHFR C677T genotype is associated with risk of ALL in Caucasians. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between the MTHFRC677T polymorphism and ALL.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6293-6299
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• 2013

Background: A number of clinicopathologic factors have been found to be associated with pathological lymph node metastasis (pLNM) in rectal cancer; however, most of them can only be identified by expensive high resolution imaging or obtained after surgical treatment. Just like the Child-Turcotte-Pugh (CTP) and the model for end-stage liver disease (MELD) scores which have been widely used in clinical practice, our study was designed to assess the pre-operative factors which could be obtained easily to predict intra-operative pLNM in rectal cancer. Methods: A cohort of 469 patients who were treated at our hospital in the period from January 2003 to June 2011, and with a pathologically hospital discharge diagnosis of rectal cancer, were included. Clinical, laboratory and pathologic parameters were analyzed. A multivariate unconditional logistic regression model, areas under the curve (AUC), the Kaplan-Meier method (log-rank test) and the Cox regression model were used. Results: Of the 469 patients, 231 were diagnosed with pLNM (49.3%). Four variables were associated with pLNM by multivariate logistic analysis, age<60 yr (OR=1.819; 95% CI, 1.231-2.687; P=0.003), presence of abdominal pain or discomfort (OR=1.637; 95% CI, 1.052-2.547; P=0.029), absence of allergic history (OR=1.879; 95% CI, 1.041-3.392; P=0.036), and direct $bilirubin{\geq}2.60{\mu}mol/L$ (OR=1.540; 95% CI, 1.054-2.250; P=0.026). The combination of all 4 variables had the highest sensitivity (98.7%) for diagnostic performance. In addition, age<60 yr and direct $bilirubin{\geq}2.60{\mu}mol/L$ were found to be associated with prognosis. Conclusion: Age, abdominal pain or discomfort, allergic history and direct bilirubin were associated with pLNM, which may be helpful for preoperative selection.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4243-4247
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• 2013

The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and gliomas remains inclusive or controversial. For better understanding of the effect of XRCC3 Thr241Met polymorphism on glioma risk, a meta-analysis was performed. All eligible studies were identified through a search of PubMed, Elsevier Science Direct, Excerpta Medica Database (Embase) and Chinese Biomedical Literature Database (CBM) before May 2013. The association between the XRCC3 Thr241Met polymorphism and gliomas risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of nine case-control studies including 3,533 cases and 4,696 controls were eventually collected. Overall, we found that XRCC3 Thr241Met polymorphism was significantly associated with the risk of gliomas (T vs. C: OR=1.10, 95%CI=1.01-1.20, P=0.034; TT vs. CC: OR=1.30, 95%CI=1.03-1.65, P=0.027; TT vs. TC/CC: OR=1.29, 95%CI=1.01-1.64, P=0.039). In the subgroup analysis based on ethnicity, the significant association was found in Asian under four models (T vs. C: OR=1.17, 95%CI=1.07-1.28, P=0.00; TT vs. CC: OR=1.79, 95%CI=1.36-2.36, P=0.00; TT vs. TC/CC: OR=1.75, 95%CI=1.32-2.32, P=0.00; TT/TC vs. CC: OR=1.11,95% CI=1.02-1.20). This meta-analysis suggested that the XRCC3 Thr241Met polymorphism is a risk factor for gliomas, especially for Asians. Considering the limited sample size and ethnicities included in the meta-analysis, further large scale and well-designed studies are needed to confirm our results.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4061-4066
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• 2013

The extranodal natural killer/T-cell lymphoma (ENKTL) shows high local or systemic failure rates when radiotherapy (RT) is taken as the primary treatment, suggesting a role for chemotherapy (CT) added to RT for this disease. However, the appropriate mode of combined modality therapy (CMT) has not been fully defined. A total of one hundred and twenty-one patients with ENKTL receiving sandwich CT with RT were reviewed between January 2003 and August 2012. The primary endpoints were the response rate, progression-free survival (PFS), overall survival (OS), and the relapse rate. After the initial CT, there were 84 (69.4%) patients in CR, 22 (18.2%) patients in PR, 9 (7.4%) patients in SD, and 6 (5%) patients in PD, respectively. At the end of RT, the CR, PR, SD, and PD rates for all patients were 90.9% (n=110), 1.7% (n=2), 4.1% (n=5), and 3.3% (n=4), respectively. After a median follow-up of 42.3 months (3.5~112.3 months), the 5-year PFS was 74.7% (95% CI 70.4%~79.0%), and 5-year OS was 77.3% (95% CI 67.9%~86.7%). Disease progression was documented in 25 (20.7%) patients. The rates of systemic failure, local failure, and regional failure were 18.2%, 5.8%, 1.7%, respectively. Twenty death events (16.5%) were observed for the entire group of patients (18 deaths related to PD). Furthermore, CR to the initial CT and low Korean Prognostic Index (KPI) can independently predict long PFS and OS. The sandwich CMT achieved an excellent outcome for localized ENKTL with acceptable toxicity. We recommend it can be applied as the optimal choice for localized ENKTL.

• Journal of Ginseng Research
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• 제42권1호
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• pp.50-56
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• 2018

Background: Saponins from Panax japonicus (SPJ) are the most abundant and main active components of P. japonicus, which replaces ginseng roots in treatment for many kinds of diseases in the minority ethnic group in China. Our previous studies have demonstrated that SPJ has the effects of anti-inflammation through the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-${\kappa}B$) signaling pathways. The present study was designed to investigate whether SPJ can modulate intestinal tight junction barrier in aging rats and further to explore the potential mechanism. Methods: Aging rats had been treated with different doses (10 mg/kg, 30 mg/kg, and 60 mg/kg) of SPJ for 6 mo since they were 18 mo old. After the rats were euthanized, the colonic samples were harvested. Levels of tight junctions (claudin-1 and occludin) were determined by immunohistochemical staining. Levels of proinflammatory cytokines (interleukin-$1{\beta}$ and tumor necrosis factor-${\alpha}$) were examined by Western blot. NF-${\kappa}B$ and phosphorylation of MAPK signaling pathways were also determined by Western blot. Results: We found that SPJ increased the expression of the tight junction proteins claudin-1 and occludin in the colon of aging rats. Treatment with SPJ decreased the levels of interleukin-$1{\beta}$ and tumor necrosis factor-${\alpha}$, reduced the phosphorylation of three MAPK isoforms, and inhibited the expression of NF-${\kappa}B$ in the colon of aging rats. Conclusion: The studies demonstrated that SPJ modulates the damage of intestinal epithelial tight junction in aging rats, inhibits inflammation, and downregulates the phosphorylation of the MAPK and $NF-{\kappa}B$ signaling pathways.

• Parasites, Hosts and Diseases
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• 제55권5호
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• pp.473-480
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• 2017

Plasmodium vivax merozoite surface protein-1 (PvMSP1) gene codes for a major malaria vaccine candidate antigen. However, its polymorphic nature represents an obstacle to the design of a protective vaccine. In this study, we analyzed the genetic polymorphism and natural selection of the C-terminal 42 kDa fragment within PvMSP1 gene ($PvMSP1_{42}$) from 77 P. vivax isolates, collected from imported cases of China-Myanmar border (CMB) areas in Yunnan province and the inland cases from Anhui, Yunnan, and Zhejiang province in China during 2009-2012. Totally, 41 haplotypes were identified and 30 of them were new haplotypes. The differences between the rates of non-synonymous and synonymous mutations suggest that $PvMSP1_{42}$ has evolved under natural selection, and a high selective pressure preferentially acted on regions identified of $PvMSP1_{33}$. Our results also demonstrated that $PvMSP1_{42}$ of P. vivax isolates collected on China-Myanmar border areas display higher genetic polymorphisms than those collected from inland of China. Such results have significant implications for understanding the dynamic of the P. vivax population and may be useful information towards China malaria elimination campaign strategies.

• Asian-Australasian Journal of Animal Sciences
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• 제29권9호
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• pp.1345-1352
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• 2016

The hindgut of horses is an anaerobic fermentative chamber for a complex and dynamic microbial population, which plays a critical role in health and energy requirements. Research on the gut microbiota of Mongolian horses has not been reported until now as far as we know. Mongolian horse is a major local breed in China. We performed high-throughput sequencing of the 16S rRNA genes V4 hypervariable regions from gut fecal material to characterize the gut microbiota of Mongolian horses and compare them to the microbiota in Thoroughbred horses. Fourteen Mongolian and 19 Thoroughbred horses were used in the study. A total of 593,678 sequence reads were obtained from 33 samples analyzed, which were found to belong to 16 phyla and 75 genera. The bacterial community compositions were similar for the two breeds. Firmicutes (56% in Mongolian horses and 53% in Thoroughbred horses) and Bacteroidetes (33% and 32% respectively) were the most abundant and predominant phyla followed by Spirochaete, Verrucomicrobia, Proteobacteria, and Fibrobacteres. Of these 16 phyla, five (Synergistetes, Planctomycetes, Proteobacteria, TM7, and Chloroflexi) were significantly different (p<0.05) between the two breeds. At the genus level, Treponema was the most abundant genus (43% in Mongolian horses vs 29% in Thoroughbred horses), followed by Ruminococcus, Roseburia, Pseudobutyrivibrio, and Anaeroplasma, which were detected in higher distribution proportion in Mongolian horses than in Thoroughbred horses. In contrast, Oscillibacter, Fibrobacter, Methanocorpusculum, and Succinivibrio levels were lower in Mongolian horses. Among 75 genera, 30 genera were significantly different (p<0.05) between the two breeds. We found that the environment was one of very important factors that influenced horse gut microbiota. These findings provide novel information about the gut microbiota of Mongolian horses and a foundation for future investigations of gut bacterial factors that may influence the development and progression of gastrointestinal disease in horses.