• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.7011-7016
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• 2013

Background: The liver fluke, Opisthorchis viverrini, and the associated incidence of subsequent cholangiocarcinoma (CCA) are still a public health problem in Thailand, and praziquantel (PZQ) remains the antihelminthic drug of choice for treatment. Evidence in hamsters shows that repeated infection and PZQ treatments could increase the risk of CCA. However, the existing evidence in humans is inconclusive regarding increased risk of CCA with frequency of PZQ intake. Objectives: To investigate the relationship between number of repeated PZQ treatments and CCA in patients with O viverrini infection. Materials and Methods: The reviewed studies were searched in EMBASE, MEDLINE, ProQuest, PubMed and SCOPUS from inception to October, 2012 using prespecified keywords. The risk of bias (ROB) of included studies was independently assessed by two reviewers using a quality scale from the Newcastle-Ottawa Scale (NOS). Risk effect of PZQ was estimated as a pooled odds ratio (OR) with its 95% confidence interval (95%CI) in the random-effects model using DerSimonian and Laird's estimator. Results: Three studies involving 637 patients were included. Based on the random effects model performed in two included studies of 237 patients, the association between PZQ treatments and CCA was not statistical significant with a pooled OR of 1.8 (95%CI; 0.81 to 4.16). Conclusions: The present systematic review and meta-analysis provides inconclusive evidence of risk effect of PZQ on increasing the risk of CCA and significant methodological limitations. Further research is urgently needed to address the shortcomings found in this review, especially the requirement for histological confirmation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.5071-5076
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• 2014

Cholangiocarcinoma (CCA) is one of the aggressive cancers with a very poor prognosis. Several efforts have been made to identify and develop new agents for prevention and treatment of this deadly disease. In the present study, we examined the anticancer effect of luteolin on human CCA, KKU-M156 cells. Sulforhodamine B assays showed that luteolin had potent cytotoxicity on CCA cells with IC50 values of $10.5{\pm}5.0$ and $8.7{\pm}3.5{\mu}M$ at 24 and 48 h, respectively. Treatment with luteolin also caused a concentration-dependent decline in colony forming ability. Consistent with growth inhibitory effects, luteolin arrested cell cycle progression at the G2/M phase in a dose-dependent manner as assessed by flow cytometry analysis. Protein expression of cyclin A and Cdc25A was down-regulated after luteolin treatment, supporting the arrest of cells at the G2/M boundary. Besides evident G2/M arrest, luteolin induced apoptosis of KKU-M156 cells, demonstrated by a distinct sub-G1 apoptotic peak and fluorescent dye staining. A decrease in the level of anti-apoptotic Bcl-2 protein was implicated in luteolin-induced apoptosis. We further investigated the effect of luteolin on JAK/STAT3, which is an important pathway involved in the development of CCA. The results showed that interleukin-6 (IL-6)-induced JAK/STAT3 activation in KKU-M156 cells was suppressed by treatment with luteolin. Treatment with a specific JAK inhibitor, AG490, and luteolin diminished IL-6-stimulated CCA cell migration as assessed by wound healing assay. These data revealed anticancer activity of luteolin against CCA so the agent might have potential for CCA prevention and therapy.

• Parasites, Hosts and Diseases
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• v.60 no.4
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• pp.261-271
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• 2022

This study provides an overview of the current status of clonorchiasis and cholangiocarcinoma (CCA), and their relationship in Korea during 2012-2020. Data were obtained from the Health Insurance Review & Assessment Service of Korea. Cluster, trend, and correlation analyses were performed. Gyeongsangnam-do and Seoul had the highest average number of cases (1,026 and 4,208) and adjusted rate (306 and 424) for clonorchiasis and CCA, respectively. The most likely clusters (MLC) for clonorchiasis and CCA were Busan/Gyeongsangnam-do/Ulsan/Daegu/Gyeongsangbuk-do (Relative Risk; RR=4.55, Likelihood Ratio; LLR=9,131.115) joint cluster and Seoul (RR=2.29, LLR=7,602.472), respectively. The MLC for clonorchiasis was in the southeastern part of Korea, while that for CCA was in the southern part. Clonorchiasis showed a decreasing trend in the southeastern districts, while increased in the southwestern districts. Cities in the central region had a decreasing trend, while the western districts had an increasing trend. In most adults (30-59), infection rate of clonorchiasis showed a significant decrease until 2018, while thereafter increased, although not significant. CCA showed a sharply decreasing tendency. The incidence of clonorchiasis and CCA were positively correlated. In general, the correlation was weak (r=0.39, P<0.001), but it was strongly positive around the 4 river basins (r=0.74, P<0.001). This study might provide an analytic basis for developing an effective system against clonorchiasis and CCA.

• Environmental Analysis Health and Toxicology
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• v.22 no.4
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• pp.339-348
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• 2007

A laboratory experiment was conducted to study the characteristics of leaching of Cr, Cu, and As from chromated topper arsenate (CCA)-treated wood. The wood species tested was hemlock spruce ($10\;cm\;{\times}\;10\;cm\;{\times}\;10\;cm\;tube$). The leaching experiment was conducted over 60 days using I L of leachants whose pHs were adjusted to 2.0, 3.7, and 1.6, respectively with nitric acid, and also using lake water, according to the OECD guideline. Each leachate was analyzed for Cr and Cu using flame-AAS, and for As using vapor generation-AAS. Three metals were loathed at the highest levels at pH 2.0 but almost at similar levels at the other conditions. Cumulative quantifies over 60 days of a leaching period were in order of As>Cu>Cr. As was predicted to leach with an increase in flux over a 10 year period, while Cr and Cu fluxes were predicted to decrease with time. This result suggest that arsenic can pose a health risk to humans over a long period of time, when CCA-treated wood is used for building facilities (e.g., playgrounds, residential purposes, etc.) with which humans frequently contact.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3979-3982
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• 2016

Background: Thailand remains a primarily agricultural country and Thai farmers are heavy users of pesticides. Coincidentally the incidence of cholangio carcinoma (CCA) is high in parts of the country, but no previous study has examined any association between the two. Materials and Methods: The present matched, case-control study covered patients admitted to Srinagarind Hospital, Khon Kaen University, Thailand. The case group comprised 210 cases diagnosed with CCA and the control group 840 diagnosed with other diseases. Cases and controls were matched for sex, age within five years, and date of admission within three months. Multiple conditional logistic regression was used for the analysis. Results: After adjusting for potential confounders, pesticide use as compared with never used pesticide was not associated with CCA (ORadj=1.11, 95% CI: 0.77, 1.60) and neither was there any significant relationship between CCA and duration of pesticide use, type or number of types pesticide use. Conclusions: The current study thus found no association between pesticide use and CCA.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.299-304
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• 2014

Cholangiocarcinoma (CCA), a malignancy of biliary duct with a very poor prognosis, is the leading cause of cancer death in countries of the Mekong subregion. Liver fluke infection is the main etiological factor, but genetic variation has been recognized as also important in conferring susceptibility to CCA risk. Nuclear factor (erythroid derived 2)-like 2 (NRF2) is a key transcription factor in detoxification and antioxidant defense. Emerging evidence has demonstrated that genetic polymorphisms in the NRF2 gene may be associated with cancer development. The objectives of this study were to investigate the association of NRF2 genetic polymorphism with CCA risk and to evaluate the influence of the NRF2 genotype on survival time of affected patients. Single nucleotide polymorphisms (SNPs) of the NRF2 gene, including rs6726395: A/G, rs2886161: C/T, rs1806649: C/T, and rs10183914: C/T, were analyzed using TaqMan$^{(R)}$ SNP genotyping assays. Among 158 healthy northeastern Thai subjects, the allele frequencies were 41, 62, 94, and 92%, respectively. The correlation of NRF2 SNPs and CCA risk was analyzed in the 158 healthy subjects and 198 CCA patients, using unconditional logistic regression. The results showed that whereas the NRF2 SNPs were not associated with CCA risk (p>0.05), Kaplan-Meier analysis of 88 intrahepatic CCA patients showed median survival time with rs6726395 genotypes of GG and AA/AG to be $344{\pm}138$ (95%CI: 73-615) days and $172{\pm}37$ (95%CI: 100-244) days, respectively, (p<0.006). On multivariate Cox proportional hazard analysis, the GG genotype of rs6726395 was found to be associated with longer survival with a hazard ratio of 0.54 (95%CI: 0.31-0.94). In addition, non-papillary adenocarcinoma was associated with poor survival with a hazard ratio of 2.09 (95%CI: 1.16-3.75). The results suggest that the NRF2 rs6726395 polymorphism can be a potential prognostic biomarker for CCA patients.

• The Korean Journal of Ecology
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• v.20 no.2
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• pp.125-132
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• 1997

A study of forest vegetation in Mt. $T\v{o}kyu$ National Park was investigated by ordination technique. By TWINSPAN(Two-Way Indicator Species Analysis) method, 10 groups were recognized as follows: pinus densiflora, Quercus variabilis, Quercus serrata, Quercus mongolica-Rhododendron schlippenbachii, Quercus mongolica-Abies koreana, Quercus mongolica-Acer pseudo-sieboldi-amum, Quercus mongolica-Symplocos chinensis for. pilosa, Carpinus laxiflora, Fraxinus mandshurica and Taxus cuspidata groups. The floristic composition of these groups showed high correlation to soil moisture(r=0.831), altitude(r=0.784), topography(r=-0.722), organic matter(r=0.642), and pH(r=-0.509) among various environmental factors. According to the results of CCA(Canonical Correspondence Analysis) Pinus densiflora group and Quercus variabilis group were situated in a xeric area at a lower altitude where soil nutrients were poor compared with the other groups. Fraxinus mandshurica group was distributed throughout the valley with high soil moisture and good nutrients, Quercus serrata group and Carpinus laxiflora group were found in the low altitude region with good nutrients, Quercus mongolica group, at the high altitude region with good nutrients, and Quercus mongolica-Acer koreana and Taxus cuspidata at higher altitudes(1, 400-1600 m).

• Journal of Soil and Groundwater Environment
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• v.13 no.2
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• pp.12-20
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• 2008

This study was conducted to investigate the spatial distributions of chromated copper arsenate (CCA) metals in soils around three log structures and a sound barrier, all built with CCA-treated wood. Sixty-six surface and 35 profile soil samples were collected around the wood structures in addition to 13 background soil samples. The concentrations of chromium, copper, and arsenic in the soil samples collected in the vicinity of the structures were higher than those in the background samples, except in the case of one structure. The concentrations in the surface soils adjacent to the 3-year-old structures seemed to be higher than those in the soils adjacent to the 8-year-old ones. Although the lateral distributions of the metals varied with the structures, chromium and arsenic appeared to show concentration gradients within 20-60 cm and 40-100 cm, respectively. Copper seemed to be the least mobile, displaying concentration gradients only within 20 cm. Even though there were no explicit vertical concentration gradients for any of the metals according to the profile soil sample analysis, chromium and copper seemed to show concentration gradients only up to 5 and 10 cm, respectively, whereas arsenic showed gradients up to 35 cm. At study sites, it was evident that heavy metals leached into soil from CCA-treated wood were confined to neighboring areas both laterally and vertically, and that any plausible ecological impact may occur only within a small range.

• Korean Journal of Environment and Ecology
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• v.6 no.2
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• pp.134-146
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• 1993

A survey of the Chundong valley forest in Mt. Sobaek was conducted using 20 sample plots of 500$m^2$ size. The classification by TWINSPAN and DCA, CCA ordination techniques were applied to the study area in order to classify them into several groups based on woody plants and environmental variables. By TWINSPAN techniques, the plant community were divided into four groups. The dividing groups are Pinus densiflora community, Qurcus variabilis -Q. mongolica -P. densiflora community, Fraxinus rhynchophylla community. The successional trends of tree species by DCA ordination techniques and DBH class distribution analysis seems to be from P. densiflora through Q. mongolica. Q. variabilis to F rhynchophylla. The correlation between the score of first two axes and soil pH, soil humus, soil calcium concentration, soil magnesium concentration was significantly positive in CCA ordination. The positive correlation between the score of first two axes of F. rhynchophylla community and soil humus, soil magnesium concentration and between ones of P. densiflora community and soil pH were calculated. But there is no correlation between species and environmental variables.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3849-3856
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• 2015

Background: Cholangiocarcinoma (CCA), or bile duct cancer, is incurable with a high mortality rate due to a lack of effective early diagnosis and treatment. Identifying cytoplasmic membrane proteins of invasive CCA that facilitate cancer progression would contribute toward the development of novel tumor markers and effective chemotherapy. Materials and Methods: An invasive CCA cell line (KKU-100) was stimulated using TNF-${\alpha}$ and then biotinylated and purified for mass spectrometry analysis. Novel proteins expressed were selected and their mRNAs expression levels were determined by real-time RT-PCR. In addition, the expression of ALCAM was selected for further observation by Western blot analysis, immunofluorescent imaging, and antibody neutralization assay. Results: After comparing the proteomics profile of TNF-${\alpha}$ induced invasive with non-treated control cells, over-expression of seven novel proteins was observed in the cytoplasmic membrane of TNF-${\alpha}$ stimulated CCA cells. Among these, ALCAM is a novel candidate which showed significant higher mRNA- and protein levels. Immunofluorescent assay also supported that ALCAM was expressed on the cell membrane of the cancer, with increasing intensity associated with TNF-${\alpha}$. Conclusions: This study indicated that ALCAM may be a novel protein candidate expressed on cytoplasmic membranes of invasive CCA cells that could be used as a biomarker for development of diagnosis, prognosis, and drug or antibody-based targeted therapies in the future.