• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.719-722
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• 2016

Background: Cholangiocarcinoma (CCA) is a serious health problem in Thailand, particularly in northeastern and northern regions, but epidemiological studies are scarce and the spatial distribution of CCA remains to be determined. A database for the population at risk is required for monitoring, surveillance and organization of home health care. This study aim was to geo-visually display the distribution of CCA in northeast Thailand, using a geographic information system and Google Earth. Materials and Methods: A cross-sectional survey was carried out in 9 sub-districts and 133 villages in Chum Phuang district, Nakhon Ratchasima province during June and October 2015. Data on demography, and the population at risk for CCA were combined with the points of villages, sub-district boundaries, district boundaries, and points of hospitals in districts, then fed into a geographical information system. After the conversion, all of the data were imported into Google Earth for geo-visualization. Results: A total of 11,960 from 83,096 population were included in this study. Females and male were 52.5%, and 47.8%, the age group 41-50 years old 33.3%. Individual risk for CCA was identifed and classified by using the Korat CCA verbal screening test as low (92.8%), followed by high risk (6.74%), and no (0.49%), respectively. Gender ($X^2$-test=1143.63, p-value= 0.001), age group ($X^2$-test==211.36, p-value=0.0001), and sub-district ($X^2$-test=1471.858, p-value=0.0001) were significantly associated with CCA risk. Spatial distribution of the population at risk for CCA in Chum Phuang district was viewed with Google Earth. Geo-visual display followed Layer 1: District, Layer 2: Sub-district, Layer 3: Number of low risk in village, Layer 4: Number of high risk in village, and Layer 5: Hospital in Chum Phuang District and their related catchment areas. Conclusions: We present the first risk geo-visual display of CCA in this rural community, which is important for spatial targeting of control efforts. Risk appears to be strongly associated with gender, age group, and sub-district. Therefor, spatial distribution is suitable for the use in the further monitoring, surveillance, and home health care for CCA.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup1호
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• pp.17-23
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• 2016

The aim of this paper is to report the rate of current and ever cigarette smoking and explore correlates of current cigarette smoking among adolescents aged 13-15 in Viet Nam. This analysis was derived from GYTS survey, which comprised of 3,430 adolescents aged 13-15, conducted in 2014 in 13 cities and provinces of Viet Nam. We calculated the weighted rates of current and ever cigarette smoking and reported patterns of smoking behavior. We also performed logistic regression to explore correlates of current cigarette smoking behavior. The weighted rate of ever cigarette smoking was 9.5% (95% confidence interval (CI): 8.5 %-10.5%), in which the weighted rate among males (15.4%; 95% CI: 13.6%-17.0%) was higher than that among females (4.2%; 95% CI: 3.3%-5.1%). The weighted rate of current cigarette smoking was relatively low at 2.5% (95%CI: 2.0%-3.0%) with higher weighted rate among males (4.9%; 95% CI: 3.8%-5.9%) compared to the corresponding figure among females (0.2%; 95% CI: 0.0 %-0.5%). Current cigarette smoking was significantly higher among males than females, in students aged 15 versus 13 years old, and in students who had several or all close friends smoking and students with daily observation of smoking at school. For greater smoking reduction outcomes, we recommend that tobacco interventions for adolescents should consider targeting more male students at older ages, establish stricter adherence to school-based banning of cigarette smoking, engage both smoking and nonsmoking adolescents and empower adolescents to resist peer smoking influence as well as changing their norms or beliefs towards smoking benefits.

• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4353-4358
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• 2014

Background: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. Materials and Methods: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. Results: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. Conclusions: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of antiapoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.

• BMB Reports
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• 제51권5호
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• pp.255-260
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• 2018

Wntless/GPR177 functions as WNT ligand carrier protein and activator of $WNT/{\beta}$-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n = 184; GSE66229, n = 300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n = 909). GPR177 expression were associated with unfavorable prognosis [log-rank test, GSE15459 (P = 0.00736), GSE66229 (P = 0.0142), and Yonsei TMA (P = 0.0334)] and identified as an independent risk predictor of clinical outcomes: GSE15459 [hazard ratio (HR) 1.731 (95% confidence interval; CI; 1.103-2.715), P = 0.017], GSE66229 [HR 1.54 (95% CI, 1.10-2.151), P = 0.011], and Yonsei TMA [HR 1.254 (95% CI, 1.049-1.500), P = 0.013]. Either antibody treatment or GPR177 knockdown suppressed proliferation of GC cells and sensitized cells to apoptosis. And also inhibition of GPR177 suppresses in vitro and in vivo tumorogenesis in GC cells and inhibits $WNT/{\beta}$-catenin signaling. Finally, targeting and inhibition of GPR177 with antibody suppressed tumorigenesis in PDX model. Together, these results suggest GPR177 as a novel candidate for prognostic marker as well as a promising target for treatment of GC patients.

• 생명과학회지
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• 제28권4호
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• pp.488-495
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• 2018

p53 유전자는 스트레스, DNA 손상, 저산소증 및 종양 발생에 대한 세포 반응의 전사 조절에서 중요한 역할을 담당한다. 최근에 발견된 다양한 종류의 p53의 생리 활성을 생각한다면 p53이 암 조절에 관여한다는 것은 놀랄만한 일이 아니다. 인간 암의 약 50%에는 p53 유전자의 돌연변이 또는 p53을 활성화시키는 기전의 결함을 통해 p53 단백질 기능의 불활성화가 나타난다. p53 기능의 이러한 장애는 p53 의존 반응으로부터 회피를 허용함으로써 종양의 진화에 결정적인 역할을 하게 된다. 최근의 많은 연구들은 p53의 돌연변이를 대폭 감소시키거나 p53의 종양 억제 기능을 복원하기 위하여 선택적인 저분자 화합물을 동정함으로써 p53의 돌연변이를 직접 표적하는 것에 초점을 두고 있다. 이들 저분자는 좋은 약물과 유사한 특성을 유지하면서 다양한 상호작용을 효과적으로 조절해야 한다. 이 중, p53의 음성조절인자 핵심인 MDM2의 발견은 p53과 MDM2 간의 상호작용을 차단하는 새로운 저분자 억제제의 설계를 제공하였다. 저분자 화합물 중 일부는 개념 증명 연구에서 임상 시험으로 옮겨졌으며 향후 맞춤형 항암제가 추가될 전망이다. 본 리뷰에서는 야생형 p53과 돌연변이 p53의 구조적 및 기능적 중요성과 p53을 직접 표적하는 치료제 개발, p53과 MDM2 간의 상호작용을 억제하는 화합물에 대하여 검토하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7897-7907
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• 2014

Background: There is paucity of studies defining the prevalence of non-communicable disease (NCD) risk factors in Saudi Arabia despite the surging epidemic of obesity, change in dietary habits and sedentary lifestyle. Objectives: This cross-sectional study aimed to assess the prevalence of NCDs risk factors among employees at King Faisal University in Al Hassa, Saudi Arabia and to determine the possible correlates for clustering of NCDs risk factors among them. Materials and Methods: All employees were invited to participate; the World Health Organization STEPwise approach was used for data collection which consisted of a personal interview to collect socio-demographic characteristics, NCD history, tobacco use, vegetables and fruit consumption, and physical activity (PA), followed by anthropometric measurements namely weight, height and waist circumference and blood pressure measurements, subjects were finally subjected to biochemical tests with determination of fasting plasma glucose, serum triglycerides, cholesterol and high density lipoproteins. Results: Of the surveyed employees (n=691), daily current smokers accounted for 22.7%. 94.9%, 95.1% and 86% consumed < 5 servings per day of vegetables, fruits and both fruits and vegetables respectively, 73% were physically inactive, 64% were overweight or obese, 22.1% had hypertension, and 21.5% were diabetics. Elevated cholesterol levels were found in 36.6%, low high density lipoproteins in 36.8%, and elevated triglycerides in 36.1%. Only 3% had no NCD risk factors, and 57.6% had ${\geq}3$ factors. Multivariate logistic regression showed that gender (being male, adjusted odds ratio 'aOR'=1.51), aged ${\geq}50$ years (aOR=3.06), < college education (aOR=1.75), current smokers (aOR=2.37), being obese (aOR=6.96) and having a low PA level (aOR=4.59) were the significant positive predictors for clustering of NCD risk factors. Conclusions: Over fifty percent of the studied university's employees had multiple (${\geq}3$) NCD risk factors. Screening and health promotion initiatives should be launched at least targeting the modifiable factors to avert the excessive risk for cardiovascular disease, diabetes mellitus and several types of cancers.

• 전자공학회논문지SC
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• 제46권3호
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• pp.44-51
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• 2009

고 에너지 방사선을 이용하여 종양을 치료하는 과정 중 발생하는 오차를 확인하여 보다 정교한 치료를 시행하는 것은 매우 중요하다. 특히, 두경부 종양을 치료하기 위해 작은 조사면에 방사선을 집중 조사하는 정위 방사선 분할치료와 같은 특수 치료에서는 치료위치의 확인을 더욱 요구하고 있다. 작은 조사면에 고선량의 방사선을 표적체적에 집중 조사하는 정위 방사선 분할 치료법에서 치료 중심점의 정확도 검증은 매우 중요하므로 표적에 3mm 납 볼을 놓고 정위 방사선 분할 치료용 25mm 콘을 장착한 후 얻은 전자 포탈 영상으로부터 콘 원의 중심점과 볼 원의 중심점을 영상처리를 통해 서로 비교해 본 결과 1픽셀(0.76mm)의 정확도까지 얻을 수 있었다. 정위 방사선 분할 치료에 전자 포탈 영상 장치를 적용하여 치료위치오차 여부를 검증하였다. 이를 위해 첫 번째 정위 방사선 분할 치료 영상과 임의로 2mm 이동시킨 후 얻은 영상의 두개골 외곽선을 검출한 후 서로 비교해 본 결과 발생된 2mm 오차를 검증할 수 있었다. 본 논문에서는 개발된 비디오 기반 전자포탈영상장치와 정위 방사선 분할치료장치를 이용하여 실시간적으로 포탈영상을 획득할 수 있었으며 치료위치 검증을 통해 보다 정교한 방사선 치료를 할 수 있으리라 본다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3281-3285
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• 2012

Objectives: To evaluate the clinicopathologic correlation and prognostic value of HPV18 DNA viral load in patients with early-stage cervical neuroendocrine carcinoma (NECA). Methods: Formalin-fixed, paraffin-embedded tissue of cervical NECA patients with known HPV18 infection and clinicopathologic data including follow-up results were collected. The HPV18 DNA load was assessed with quantitative PCR targeting the HPV18 E6E7 region. Results: Twenty-one patients with early-stage (IB-IIA) cervical NECA were identified. HPV18 DNA viral load ranged from 0.83 to 55,174 copies/cell (median 5.90). Disease progression, observed in 10 cases (48%), was not significantly associated with any clinicopathologic variables. However, the group of patients with progressive disease tended to have a higher rate of pelvic lymph node metastasis (50% versus 9%, p=0.063) and a lower median value of HPV18 DNA viral load (4.37 versus 8.17 copies/cell, p=0.198) compared to the non-recurrent group. When stratified by a cut-off viral load value of 5.00 copies/cell, the group of patients with viral load ${\leq}5.00$ copies/cell had a significantly shorter disease-free survival than the group with viral load >5.00 copies/cell (p=0.028). The group with a lower viral load also tended to have a higher rate of disease progression (75% versus 31%, p=0.080). No significant difference in the other clinicopathologic variables between the lower and higher viral load groups was identified. Conclusion: HPV18 DNA viral load may have a prognostic value in patients with early-stage NECA of the cervix. A low viral load may be predictive of shortened disease-free survival in these patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3773-3778
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• 2014

Background: The study was aimed to evaluate the prevalence and genotype distribution of HPV infection in vulvar squamous cell carcinoma (SCC) in northern Thailand and the clinicopathological difference with regard to HPV infection status. Materials and Methods: Formalin-fixed paraffin-embedded tissue samples of vulvar SCC diagnosed between January 2006 and December 2012 were collected. HPV infection was detected by nested polymerase chain reaction (PCR) with primers MY09/11 and GP5+/6+. HPV genotyping was performed using the Linear Array Genotyping Test, followed by type-specific PCR targeting the E6/E7 region of HPV16/18/52 if the Linear Array test was negative. The histologic slides of vulvar lesions and the medical records were reviewed. Results: There were 47 cases of vulvar SCC included in the study (mean patient age $57.9{\pm}13.2$ years). HPV infection was detected in 29 cases (62%), all of which had single HPV infections. HPV16 accounted for 23 (49%). The patients with HPV-positive SCC had a significantly younger mean age than those with HPV-negative tumors (52.7 years vs 66.2 years, p<0.001). There was no significant difference in tumor stage distribution with regard to the status of HPV infection. The presence of vulvar intraepithelial neoplasia (VIN) of usual type (basaloid or warty) was significantly more frequent in HPV-positive cases compared with HPV-negative cases (62% vs 6%, p<0.001), whereas differentiated-type VIN was more common in HPV-negative cases (24% vs 0%, p=0.019). Conclusions: HPV infection was detected in 62% of vulvar SCC in northern Thailand. HPV16 was the predominant genotype similar to the data reported from other regions. HPV-positive SCC occurred in younger patients compared with HPV-negative SCC, and was associated with usual-type VIN. Vaccination against HPV16/18 may potentially prevent almost one half of vulvar SCC in northern Thailand.

• 공업화학
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• 제27권6호
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• pp.599-605
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• 2016

최근 효과적인 암 치료 방법으로 광역학치료(photodynamic therapy)와 광열치료(photothermal therapy)가 주목받고 있다. 본 연구에서는 광열치료에 필요한 광열인자로써의 역할을 할 수 있는 골드 나노로드(AuNR)를 합성하고, 그 표면에 광역학치료를 위한 광증감제(photosensitizer)를 결합하였다. 즉, 골드 나노로드를 체내에 오래 머무르도록 하기 위해 PEG(polyethylene glycol) 및 효과적인 암 표적지향성을 위해 FA (folic acid) 리간드를 도입하였고, FA-PEG와 poly-${\beta}$-benzyl-L-aspartate (PBLA)로 이루어진 블록 공중합체를 3,4-dihydroxy hydrocinnamic acid (HCA) linker를 사용하여 골드 나노로드의 표면개질을 하였다. 또한 $AgNO_3$의 feeding ratio 변화를 통해 다양한 aspect ratio를 갖는 골드 나노로드를 합성하였고, UV-visible spectrophotometer, $^1H$-NMR, XPS, TEM 분석을 통해 FA-PEG-$P(Asp)_{50}$-HCA-AuNR100의 물리 화학적 특성과 morphology를 분석하였고, 성공적인 표면 개질을 확인할 수 있었다. 골드 나노로드의 표면 개질을 통한 생체 적합성 약물전달체의 합성은 효과적인 암 진단 및 다양한 광역학/광열치료 분야에 응용이 될 수 있을 것으로 기대된다.