• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2219-2225
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• 2015

SHP1 negatively regulates the Janus kinase 2/signal transducer and activator of transcription (JAK2/STAT) signaling pathway, which is constitutively activated in myeloproliferative neoplasms (MPNs) and leukemia. Promoter hypermethylation resulting in epigenetic inactivation of SHP1 has been reported in myelomas, leukemias and other cancers. However, whether SHP1 hypermethylation occurs in MPNs, especially in Chinese patients, has remained unclear. Here, we report that aberrant hypermethylation of SHP1 was observed in several leukemic cell lines and bone marrow mononuclear cells from MPN patients. About 51 of 118 (43.2%) MPN patients including 23 of 50 (46%) polycythaemia vera patients, 20 of 50 (40%) essential thrombocythaemia and 8 of 18 (44.4%) idiopathic myelofibrosis showed hypermethylation by methylation-specific polymerase chain reaction. However, SHP1 methylation was not measured in 20 healthy volunteers. Hypermethylation of SHP1 was found in MPN patients with both positive (34/81, 42%) and negative (17/37, 45.9%) JAK2V617F mutation. The levels of SHP1 mRNA were significantly lower in hypermethylated samples than unmethylated samples, suggesting SHP1 may be epigenetically inactivated in MPN patients. Furthermore, treatment with 5-aza-2'-deoxycytidine (AZA) in K562 cells showing hypermethylation of SHP1 led to progressive demethylation of SHP1, with consequently increased reexpression of SHP1. Meanwhile, phosphorylated JAK2 and STAT3 were progressively reduced. Finally, AZA increased the expression of SHP1 in primary MPN cells with hypermethylation of SHP1. Therefore, our data suggest that epigenetic inactivation of SHP1 contributes to the constitutive activation of JAK2/STAT signaling. Restoration of SHP1 expression by AZA may contribute to clinical treatment for MPN patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.515-521
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• 2013

Purpose: To evaluate the efficacy and toxicity of induction chemotherapy followed by concurrent chemoradiotherapy (the treatment group) versus concurrent chemoradiotherapy with or without adjuvant chemotherapy (the control group) for locoregionally advanced nasopharyngeal carcinoma. Methods: The search strategy included Pubmed, Embase, the Cochrane Library, China National Knowledge Internet Web, Chinese Biomedical Database and Wanfang Database. We also searched reference lists of articles and the volumes of abstracts of scientific meetings. All randomized controlled trials were included for a meta-analysis performed with RevMan 5.1.0. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to rate the level of evidence. Results: Eleven studies were included. Risk ratios of 0.99 (95%CI 0.72-1.36), 0.37 (95%CI 0.20-0.69), 1.08 (95%CI 0.84-1.38), 0.98 (95%CI 0.75-1.27) were observed for 3 years overall survival, 3 years progression-free survival, 2 years loco-regional failure-free survival and 2 years distant metastasis failure-free survival. There were no treatment-related deaths in either group in the 11 studies. Risk ratios of 1.90 (95%CI 1.24-2.92), 2.67 (95%CI 0.64-11.1), 1.04 (95%CI 0.79-1.37), 0.98 (95%CI 0.27-3.52) were found for grade 3-4 leukopenia, grade 3-4 thrombocytopenia, grade 3-4 mucous membrane, and grade 3-4 hepatic hematologic and gastrointestinal toxicity, the most significant toxicities for patients. Conclusion: Compared with the control group, induction chemotherapy followed by concurrent chemoradiotherapy was well tolerated but could not significantly improve prognosis in terms of overall survival, loco-regional failure-free survival or distant metastasis failure-free survival.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1221-1233
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• 2016

Purpose: To investigate any potential association between wine and breast cancer risk. Materials and Methods: We quantitatively assessed associations by conducting a meta-analysis based on evidence from observational studies. In May 2014, we performed electronic searches in PubMed, EmBase and the Cochrane Library to identify studies examining the effect of wine drinking on breast cancer incidence. The relative risk (RR) or odds ratio (OR) were used to measure any such association. Results: The analysis was further stratified by confounding factors that could influence the results. A total of twenty-six studies (eight case-control and eighteen cohort studies) involving 21,149 cases were included in our meta-analysis. Our study demonstrated that wine drinking was associated with breast cancer risk. A 36% increase in breast cancer risk was observed across overall studies based on the highest versus lowest model, with a combined RR of 1.0059 (95%CI 0.97-1.05) in dose-response analysis. However, 5 g/d ethanol from wine seemed to have protective value from our non-linear model. Conclusions: Our findings indicate that wine drinking is associated with breast cancer risk in a dose-dependent manner. High consumption of wine contributes to breast cancer risk with protection exerted by low doses. Further investigations are needed for clarification.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3195-3201
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• 2015

Objectives: To investigate the effects of betaine on HeLa cell growth and apoptosis and molecular mechanisms. Materials and Methods: Concentrations of 0.1, 1.0, 5.0, 20.0, 100.0 mg/ml of betaine were used to evaluate the anticancer efficacy for HeLa cells respectively, and MCF-10A was also detected as a normal diploid cell control. Results: We found that proliferation of HeLa cells was inhibited significantly upon exposure to increasing betaine levels with the MTT test (p<0.05). The percentage of S phase cells in the low dose groups (<5mg/ml) were distinctly higher than in high dose groups, and the rates of Sub-G1 phase were the opposite (p<0.01); A high concentration of betaine (>5.0mg/ml) significantly promoted the apoptosis of HeLa cells (p<0.01). SOD activities of the low dose groups were slightly higher than the control group (p<0.05) and there were obvious synchronicity and correlation among the expression of promoting apoptosis genes Bax, P53, Caspase 3 and apoptosis suppression gene Bcl-2. In response to an apoptosis-inducing stimulus, p53 and cyclin D1 could be activated with blockage of the cell cycle at G1/S or S/G2 checkpoints. Conclusions: Our data showed that betaine could promote HeLa cells proliferation in vitro at low concentrations. In contrast, high concentrations could significantly inhibit cell growth and migration, and induce apoptosis of HeLa cells through caspase 3 signaling and further promoted necrosis. This might imply that betaine exhibits tumoricidal effects and acts as a biological response modifier in cancer treatment by inducing apoptosis and cell cycle arrest in a dose and time-dependent manner.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5773-5779
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• 2014

Background: Since cervical cancer can be prevented and controlled through human papillomavirus (HPV) vaccination, it is important to train health care providers and provide them with appropriate knowledge. This study aimed to understand the level of HPV related knowledge among medical students and correlates in Southwest China in order to address any potential gap in their knowledge base. Methods: We conducted a cross-sectional survey among medical students in six selected universities across Southwest China based on a pretested questionnaire regarding HPV infection, cervical cancer, and HPV vaccines. Results: We successfully surveyed 1, 878 medical students, of whom 32.1% were males and 67.9% were females. Their mean age was 20.8 (standard deviation: 1.3) years. 91.8% of them were ethnic Han Chinese, and 43.8% were students in clinical medicine. While 76.5% had heard of HPV only 48.8% knew that the prevention of cervical cancer was possible through HPV vaccination. Only 42.9% of the male and 49.2% of the female students correctly answered over 10 out of 22 questions on HPV related knowledge. Female students appeared to know more about HPV and HPV vaccination (OR: 1.39; 95% CI: 1.11-1.75). In addition, the student knowledge improved with the grade (p<0.001). University courses were the most selected source of knowledge about HPV vaccination (66.4%). 83.6% of males and 91.4% of females were willing to have more HPV related education by experts (p<0.001). Only 10.1% of the students acknowledged that people had asked for their advice regarding HPV vaccination. Conclusions: Our survey indicates that medical students from Southwest China have poor knowledge of HPV and HPV vaccination, but are willing to receive more relevant information. Targeted education should be incorporated into school courses to inform these future health care providers and ensure success of programs for cervical cancer control and prevention.

• The Journal of Pediatrics of Korean Medicine
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• v.26 no.4
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• pp.61-70
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• 2012

Objectives: Literature Study of clinical cases with Traditional Chinese Medicine (TCM) as reference for Korean medicine based treatment of juvenile patients with Down's syndrome. Methods: 4 TCM journals with the highest impact factors were searched and selected among the journals listed in www.cnki.net. The search keywords were "蒙古症", "唐氏症(産生唐氏症)", "唐氏症候群", "先天愚型", "伸舌樣痴呆", "21三体綜合徵", "三染色体症", "Down's syndrome", and "Mongolism". Accordingly, searched papers were analyzed. Results: Total 6 studies were selected: RCT(5), case report(1). Among the RCT related studies, 2 studies tested the effect of Electroacupuncture (電鍼), 1 study tested the effect of Electroacupuncture and Pharmacopuncture (藥鍼) treatment together, and 2 studies tested the effect of Electroacupuncture and Herbal Medicines (藥物) co-treatment. In all the studies, the study groups showed significantly improved intelligence quotient (IQ) in comparison with the control groups. The case report showed improvement of cognitive ability and other clinical parameters as a result of Acupuncture (鍼) and Herbal Medicines co-treatment in juvenile patients with Down's syndrome. Conclusions: Clinical studies testing the effect of TCM for the treatment of Down's syndrome have been conducted in small scales, and all the studies showed a certain level of brain function improvement of the patients in the study groups. These results implicate that the methods in Korean medicine can be highly potential treatment options for the treatment of Down's syndrome. Conduction of accurate and well-controlled studies in large scale would be required to prove the effect of Korean medicine for the treatment of patients with Down's syndrome.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3689-3698
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• 2013

Breast cancer is the most common and leading cause of cancer mortality among Malaysian women. Despite good survival rates, the diagnosis of cancer still invokes the feeling of stress, fear and uncertainty. Because very little is known about the experiences of Malaysian women with breast cancer, a qualitative study using semi-structured interviews to explore the lived experience of newly diagnosed breast cancer. Using a purposive sampling method, 20 Malaysian women newly diagnosed with breast cancer, including Malays (n=10) and Chinese (n=10) were recruited in two main public hospitals in Kelantan. Similarities and divergence in women's experience were identified through thematic analysis of interview transcripts. Three themes emerged from the data: uncertainty experience of the illness, transition process and fatalistic view of breast cancer. In many ways, these findings were parallel with previous studies, suggesting that the experience of breast cancer is to a certain extent similar among women newly diagnosed with breast cancer. This study adds to the sparse literature concerning the experience of illness following breast cancer diagnosis among the Malays and Chinese. More importantly, this study addressed areas that were previously lacking, specifically in depth information on breast cancer experience from a developing country with a multi-ethnic population. The results of this investigation provide preliminary information to healthcare professionals on the impact of illness and cultural influence on survivorship to plan for appropriate education and supportive programme in order to meet the needs of breast cancer women more effectively.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.291-297
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• 2014

The radioprotective effects of a single administration of kojic acid (KA) against ionizing radiation were evaluated via assessment of 30-day survival and alterations of peripheral blood parameters of adult C57BL/6 male mice. The 30-day survival rate of mice pretreated with KA (75 or 300 mg/kg body weight, KA75 or KA300) subcutaneously 27 h prior to a lethal dose (8 Gy, 153.52 cGy/min) of gamma irradiation was higher than that of mice irradiated alone (40% or 60% vs 0%). It was observed that the white blood cell (WBC) count/the red blood cell (RBC) count, haemoglobin content, haematocrit and platelet count of mice with or without KA pretreatment as exposed to a sub-lethal dose (4 Gy, 148.14 cGy/min) of gamma irradiation decreased maximally at day 4/day 8 post-irradiation. Although the initial WBC values were low in KA300 or WR-2721 (amifostine) groups, they significantly recovered to normal at day 19, whereas in the control group they did not. The results from the cytotoxicity and cell viability assays demonstrated that KA could highly protect Chinese hamster ovary (CHO) cells against ionizing radiation with low toxicity. In summary, KA provides marked radioprotective effects both in vivo and in vitro.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4327-4333
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• 2016

Purpose: To systematically review efficacyand safety of robotic gastrectomy (RG) compared with conventional laparoscopic gastrectomy (LG) for gastric carcinoma. Materials and Methods: A systematic literature search was carried out using PubMed, Cochrane Library, CBM, CNKI, WanFang, VIP and other sources like relevant references to obtain comparative studies assessing the effectiveness and safety between RG and LG published between 2013 and 2016. Then the literature was screened and the data were extracted by 2 independent reviewers. The quality of the literature was assessed, and the data analyzed using Stata/SE 14 software. Fixed effects or random effects models wereapplied according to heterogeneity. Results: A total of 12 non-randomized observational clinical studies involving 3,580 patients were included, of which 1,096 had undergone RG and 2,484 had received LG. The results of the meta-analysis showed in terms of effectiveness, RG was associated with less blood loss, less time to first flatus and greater number of harvested lymph nodes, but there were no significant differences in proximal and distal resection margins, compared with LG. In terms of efficiency, RG was associated with shorter hospital stay, but longer operative time. In terms of safety, there were no statistically significant differences in complications, mortality and conversions between RG and LG. Conclusions: RG can achieve comparable or better short-term and radical effects than LG, with respect to effectiveness, efficiency and safety in treatment of gastric carcinoma. Future studies involving RG should focus on decreasing operative time and reducing cost. Moreover, there is a need for randomized controlled trials comparing the two techniques with long-term follow-up.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.119-124
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• 2015

Background: DICER, one of the microRNA (miRNA) biogenesis proteins, is involved in the maturation of miRNAs and is implicated in cancer development and progression. The results from previous epidemiological studies on associations between DICER rs1057035 polymorphism and cancer risk were inconsistent. Thereforewe performed this meta-analysis to summarize possible associations. Materials and Methods: We searched all relevant articles on associations between DICER rs1057035 polymorphism and cancer risk from PubMed, EMBASE, Chinese Biomedical Literature and Chinese National Knowledge Infrastructure until August 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess any associations. Heterogeneity tests, sensitivity analyses and publication bias assessments were also performed in this meta-analysis. All analyses were conducted using STATA software. Results: Seven case-control studies, including 4,875 cancer cases and 7,800 controls were included in the meta-analysis. Overall, the results indicated that the C allele of DICER rs1057035 polymorphism was significantly associated with decreased cancer risk in allelic comparison, heterozygote and dominant genetic models (C vs T: OR=0.88, 95%CI 0.81-0.95, p=0.002; TC vs TT: OR=0.85, 95%CI 0.77-0.93, p=0.001; CC/TC vs TT: OR=0.86, 95%CI 0.78-0.94, p=0.001). In the subgroup analysis by ethnicity, a significantly decreased cancer risk was found in Asian but not Caucasian populations. Conclusions: The present meta-analysis suggests that the C allele of the DICER rs1057035 polymorphism probably decreases cancer risk. However, this association may be Asian-specific and the results should be treated with caution. Further well-designed studies based on larger sample sizes and group of populations are needed to validate these findings.