• Parasites, Hosts and Diseases
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• v.57 no.1
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• pp.49-53
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• 2019

Contaminated liver fluke egg in the environment has led to the high prevalence of human opisthorchiasis associated with cholangiocarcinoma in Southeast Asia. To find the effective lessening methods of Opisthorchis viverrini eggs in the contaminated environment, we investigated the temperature conditions for killing of these trematode eggs in vitro. Numerous O. viverrini eggs were obtained in the proximal part of uteri of adult worms from experimental hamsters. Mature eggs with miracidium were allocated by experimental groups (2 control: positive and negative and 4 treatment: 50, 60, 70, and $80^{\circ}C$) with 0.85% saline, and treated by the experimental plan. Eggs in each experimental groups were observed under the confocal microscope after stain with Propidium Iodide (PI) to evaluate the effect of temperatures. Eggs in 70 and $80^{\circ}C$ groups were all killed after over 10 min heated. Majority of eggs in $60^{\circ}C$ (10, 15, and 30 min heated), 70 and $80^{\circ}C$ (5 min heated) groups were inactivated. However in $50^{\circ}C$ group, below half of eggs were to be killed in all time lapse (10, 15 and 30 min). In order to prevent O. viverrini infection and cholangiocarcinoma, direct treatment of sewage by heating at 70 or $80^{\circ}C$ at least 10 min is essential. Therefore, treatment of O. viverrini eggs at a high temperature is a potential method for controlling egg contamination in sewage.

• Journal of Microbiology and Biotechnology
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• v.32 no.10
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• pp.1262-1274
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• 2022

Cholangiocarcinoma (CCA) is a complex and refractor type of cancer with global prevalence. Several barriers remain in CCA diagnosis, treatment, and prognosis. Therefore, exploring more biomarkers and therapeutic drugs for CCA management is necessary. CCA gene expression data was downloaded from the TCGA and GEO databases. KEGG enrichment, GO analysis, and protein-protein interaction network were used for hub gene identification. miRNA were predicted using Targetscan and validated according to several GEO databases. The relative RNA and miRNA expression levels and prognostic information were obtained from the GEPIA. The candidate drug was screened using pharmacophore-based virtual screening and validated by molecular modeling and through several in vitro studies. 301 differentially expressed genes (DEGs) were screened out. Complement and coagulation cascades-related genes (including AHSG, F2, TTR, and KNG1), and cell cycle-related genes (including CDK1, CCNB1, and KIAA0101) were considered as the hub genes in CCA progression. AHSG, F2, TTR, and KNG1 were found to be significantly decreased and the eight predicted miRNA targeting AHSG, F2, and TTR were increased in CCA patients. CDK1, CCNB1, and KIAA0101 were found to be significantly abundant in CCA patients. In addition, Molport-003-703-800, which is a compound that is derived from pharmacophores-based virtual screening, could directly bind to CDK1 and exhibited anti-tumor activity in cholangiocarcinoma cells. AHSG, F2, TTR, and KNG1 could be novel biomarkers for CCA. Molport-003-703-800 targets CDK1 and work as potential cell cycle inhibitors, thereby having potential for consideration for new chemotherapeutics for CCA.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2031-2035
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• 2015

Intra-tumoral hypoxia is an environment that promotes tumor cell migration, angiogenesis and epithelial-mesenchymal transition that accounts for a major mechanism of metastasis. Chloroquine potentially offers a new therapeutic approach with an 'old' drug for effective and safe cancer therapies, as it exerts anti-metastatic activity. We investigated the inhibitory effect of chloroquine on cholangiocarcinoma (CCA) cell migration under cobalt chloride ($CoCl_2$)-stimulated hypoxia. We showed that chloroquine suppressed CCA cell migration under hypoxic-mimicking conditions on exposure to $100{\mu}M$ $CoCl_2$. Moreover, chloroquine stabilized the protein level of prolyl hydroxylase domain proteins (PHD-2) but reduced the levels of hypoxic responsive proteins such as hypoxia-inducible factor (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF). It also suppressed epithelial mesenchymal transition (EMT) by increasing the ratio of E-cadherin to N-cadherin under hypoxic conditions. In conclusion, chloroquine can inhibit hypoxia-stimulated metastasis via HIF-$1{\alpha}$/VEGF/EMT which may serve as a useful additional strategy for CCA therapy.

• BMB Reports
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• v.49 no.11
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• pp.590-597
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• 2016

Parasitic diseases remain an unarguable public health problem worldwide. Liver fluke Clonorchis sinensis is a high risk pathogenic parasitic helminth which is endemic predominantly in Asian countries, including Korea, China, Taiwan, Vietnam, and the far eastern parts of Russia, and is still actively transmitted. According to the earlier $8^{th}$ National Survey on the Prevalence of Intestinal Parasitic Infections in 2012, C. sinensis was revealed as the parasite with highest prevalence of 1.86% in general population among all parasite species surveyed in Korea. This fluke is now classified under one of the definite Group 1 human biological agents (carcinogens) by International Agency of Research on Cancer (IARC) along with two other parasites, Opisthorchis viverrini and Schistosoma haematobium. C. sinensis infestation is mainly linked to liver and biliary disorders, especially cholangiocarcinoma (CCA). For the purposes of this mini-review, we will only focus on C. sinensis and review pathogenesis and carcinogenesis of clonorchiasis, disease condition by C. sinensis infestation, and association between C. sinensis infestation and CCA. In this presentation, we briefly consider the current scientific status for progression of CCA by heavy C. sinensis infestation from the food-borne trematode and development of CCA.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1623-1627
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• 2013

Cholangiocarcinoma (CCA) is a major health problem and cause of death among people in Northeastern Thailand. In this prospective study 171 patients newly diagnosed with CCA by physicians in 5 tertiary hospitals in four provinces of northeastern of Thailand between February and July 2011 were followed up to January 2012. The outcome was survival time from diagnosis to death. A total of 758.4 person-months of follow-up were available. The mortality rate was 16.9 per 100 person-months (95%CI: 14.1-20.1). The median survival time among CCA patients was 4.3 months (95%CI: 3.3-5.1). Cox's proportional hazard model was used to study the independent effects of factors affecting survival time among patients. Statistically significant factors included advanced stage at diagnosis (HR: 2.5, 95%CI: 1.7-3.8), presentation with jaundice (HR: 1.7, 95%CI: 1.1-2.4) or ascites (HR: 2.8, 95%CI: 1.8-4.4), and positive serum carcinoembryonic antigen (HR: 2.3, 95%CI: 1.2-4.3). Patients who had received standard treatment had a better prognosis that those who did not (HR: 0.5, 95%CI: 0.3-0.7).

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4007-4011
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• 2012

Purpose: Retinoblastoma-interacting zinc finger gene (RIZ1) is a tumor suppressor gene which is highly inactivated by promoter hypermethylation in patients with liver fluke-related cholangiocarcinoma (CCA). Epigenetic aberration of this gene might withdraw the ability to restrain tumor cell proliferation and migration. We aimed to define the role of RIZ1 on cell proliferation and migration in CCA cell line. Materials and methods: Small interference RNA (siRNA) was used to knock down the expression of RIZ1 in a CCA-derived cell line in which cell proliferation and cell migration were performed. Results: A predominant nuclear localization of RIZ1 was observed. Reduction of RIZ1 by siRNA augmented cell proliferation and migration. Conclusion: The result suggested that RIZ1 might play a role in regulating cell proliferation and migration in CCA. Reduction of RIZ1 expression may aggravate the progression of CCA.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.281-283
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• 2016

The Cholangiocarcinoma is a. The risk of development of cholangiocarcinoma, generally a rare type of a liver tumor, increases during infection of Opisthorchiasis. For this reason the timely detection of Opisthorchiasis is important for Cholangiocarcinoma prevention. There are many studies which concern the detection of pathogenesis of Opisthorchis viverrini infection but a little known about Opisthorchis felineus. In this study we investigate a correlation of the eggs which are found in a faeces and are comparable with a serum Ig G and Ig M antibody level that were detected with ELISA test in a large group of patients. The result is showing positive correlation between evidence of the Opisthorchis felineus eggs that were found in a faeces and antibody Ig G and Ig M level in a serum. Moreover the combination of two methods can improve the Opisthorchiasis diagnostic: the serum antibody and faeces investigation of eggs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1995-1997
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• 2012

Background: Brain metastasis from cholangiocarcinoma (CCA) is a rare but fatal event. To the best of our knowledge, only few cases have been reported. Herein, we report the incident rate and a first case series of brain metastases from CCA. Methods: Between January 2006 and December 2010 5,164 patients were treated at Srinagarind hospital, Khon Kaen University; of those, 8 patients developed brain metastasis. Here we reviewed clinical data and survival times. Results: The incident rate of brain metastases from CCA was 0.15%. The median age of the patients was 60 years. Tumor subtypes were intrahepatic in 6 and hilar in 2 patients. All suffered from symptoms related to brain metastasis. Three patients were treated with whole-brain radiation therapy (WBRT), one of whom also underwent surgery. The median survival after the diagnosis of brain metastasis was 9.5 weeks (1-28 weeks). The longest survival observed in a patient in RPA class I with two brain lesions and received WBRT. Conclusion: This is a first case series of brain metastases from CCA with the incident rate of 0.15%. It is rare and associated with short survival time.

• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.770-775
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• 2006

Objectives : This study was designed to evaluate the effects of oriental treatment on cancer patients. Methods : We retrospectively analyzed the medical record of a distal cholangiocarcinoma patient who had been treated with oriental medicine for 150 days. He complained of anorexia, dyspepsia, fatigue, weight loss, constipation, abdominal discomfort and pain. etc. We prescribed him Samchulkunbi-tang and other oriental medicines, in order to treat symptoms and improve long term survival. Results and Conclusion : For 150 days, he was treated with oriental medicine and the symptoms mostly disappeared. We had a worthwhile improvement of long term survival. When it comes to therapeutic effects, it could be suggested that oriental medicine has significant effects on improving symptoms, survival and quality of lifes.

• Parasites, Hosts and Diseases
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• v.54 no.5
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• pp.679-684
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• 2016

Clonorchiasis, caused by direct contact with Clonorchis sinensis worms and their excretory-secretory products (ESPs), is associated with chronic inflammation, malignant changes in bile ducts, and even cholangiocarcinogenesis. Our previous report revealed that intracellular free radicals enzymatically generated by C. sinensis ESPs cause NF-${\kappa}B$-mediated inflammation in human cholangiocarcinoma cells (HuCCT1). Therefore, the present study was conducted to examine the role of upstream Toll-like receptors (TLRs) on the initial host innate immune responses to infection. We found that treatment of HuCCT1 cells with native ESPs induced changes in TLR mRNA levels in a time-dependent manner, concomitant with the generation of free radicals. ESP-mediated free radical generation was markedly attenuated by preincubation of the cells with TLR1-4-neutralizing antibodies, indicating that at least TLR1 through 4 participate in stimulation of the host innate immune responses. These findings indicate that free radicals triggered by ESPs are critically involved in TLR signal transduction. Continuous signaling by this pathway may function in initiating C. sinensis infection-associated inflammation cascades, a detrimental event leading to progression to more severe hepatobiliary diseases.