Risk Communication Through Health Beliefs for Preventing Opisthorchiasis-Linked Cholangiocarcinoma: A Community- Based Intervention in Multicultural Areas of Thailand.

OBJECTIVE: This research aimed to study the effects of the risk communication program through the Cambodian folk song to prevent Opisthorchiasis-linked cholangiocarcinoma (OV-CCA). METHODS: We conducted the quasi-experimental research between August and December 2017 in the Cambodian communities, one-fourth of ethnic minorities residing in multicultural areas of Sisaket Province, Thailand. The samples consisted of 94 equally people divided into experimental group and control group. The experimental group included 47 people at-risk of OV-CCA who received the program for 12 weeks, while the control group received regular services. We collected data by using a questionnaire with a reliability of 0.93. Descriptive and inferential statistics were used for data analysis. RESULTS: The study indicated that the socioeconomic information of both groups was not different. The mean scores of all issues (health beliefs, social support, and prevention behavior in the experimental group were higher than those of the control group with statistical significance. Closer inspection showed that the mean difference of the health beliefs was 55.61 points (95%CI: 52.39-57.42, p<0.001), social support was 9.09 points (95%CI: 8.12-10.05, p<0.001), and prevention behavior was 6.38 points (95%CI: 5.43-7.33, p<0.001). CONCLUSION: Through the Cambodian folk song, the risk communication program by applying the health beliefs and social support to prevent OV-CCA is beneficial for behavior modification in areas with similar cultures.

Discovering proteins for chemoprevention and chemotherapy by curcumin in liver fluke infection-induced bile duct cancer.

Modulation or prevention of protein changes during the cholangiocarcinoma (CCA) process induced by Opisthorchis viverrini (Ov) infection may become a key strategy for prevention and treatment of CCA. Monitoring of such changes could lead to discovery of protein targets for CCA treatment. Curcumin exerts anti-inflammatory and anti-CCA activities partly through its protein-modulatory ability. To support the potential use of curcumin and to discover novel target molecules for CCA treatment, we used a quantitative proteomic approach to investigate the effects of curcumin on protein changes in an Ov-induced CCA-harboring hamster model. Isobaric labelling and tandem mass spectrometry were used to compare the protein expression profiles of liver tissues from CCA hamsters with or without curcumin dietary supplementation. Among the dysregulated proteins, five were upregulated in liver tissues of CCA hamsters but markedly downregulated in the CCA hamsters supplemented with curcumin: S100A6, lumican, plastin-2, 14-3-3 zeta/delta and vimentin. Western blot and immunohistochemical analyses also showed similar expression patterns of these proteins in liver tissues of hamsters in the CCA and CCA + curcumin groups. Proteins such as clusterin and S100A10, involved in the NF-κB signaling pathway, an important signaling cascade involved in CCA genesis, were also upregulated in CCA hamsters and were then suppressed by curcumin treatment. Taken together, our results demonstrate the important changes in the proteome during the genesis of O. viverrini-induced CCA and provide an insight into the possible protein targets for prevention and treatment of this cancer.

Chemopreventive and chemotherapeutic effect of dietary supplementation of vitamin D on cholangiocarcinoma in a Chemical-Induced animal model.

Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer. Vitamin D, a pro-hormone, is getting popular due to its hormone-like functions after converted to its active form, 1α,25(OH)2D3. Here, we show that dietary supplementation with 6 IU/g of vitamin D greatly suppressed ICC initiation and progression without apparent toxicity in a chemically induced rat model. Microarray analysis of rat ICC tissues showed vitamin D supplementation modulated the expressions of several unique genes, including lipocalin 2 (Lcn2), confirmed by RT-qPCR and immunohistochemical (IHC) staining. Further, 53 of 80 human ICC specimens (66%) exhibited high LCN2 expression and LCN2 knockdown in SNU308 cells decreased cell growth and migration, suggesting LCN2 be an oncogene in human ICC. As human ICC SNU1079 cells were treated by 1α,25(OH)2D3, LCN2 expression and cell proliferation were attenuated. The downregulation of LCN2 expression was blunted when vitamin D receptor (VDR) was knocked down, implicating that the in vivo Lcn2 downregulation is a direct consequence of vitamin D supplementation Our results support the prevailing concept that vitamin D status is negatively associated with cancer incidence and mortality and suggest LCN2 may be a potential target against ICC. Further studies of application of vitamin D or its analog against ICC are warranted.

Inhibitory effect of 1α-hydroxyvitamin D3 on N-nitrosobis(2-oxopropyl)amine-induced cholangiocarcinogenesis in Syrian hamsters.

Sixty-three male 5-week-old Syrian hamsters received the carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) s.c. in 5 weekly injections (the first, 70 mg/kg body, and the remaining, 20mg/kg each). The hamsters that received BOP were given intragastric administration of 0.2 ml of medium chain triglyceride (MCT) with or without 0.04 µg of 1α-hydroxyvitamin D3 [1α(OH)D3] through a feeding tube for 12 weeks. Thus, 3 groups were assigned:Group 1;BOP alone (n＝20), Group 2;BOP＋MCT (n＝18) and Group 3;BOP＋1α(OH)D3 (n＝25). The mean body weight of Group 3 was lower than those of Groups 1 and 2 at the end of the experiment (p＜0.001,Tukey-Kramer HSD test). At the end of week 12, all surviving hamsters were put to sleep. The incidences of liver tumors were 80%, 72% and 32% in Groups 1, 2 and 3, respectively. The incidence of tumors in Group 3 was significantly lower than in Group 1 and Group 2 (p＜0.05, χ2-test). All tumors were cholangiocarcinoma. These results indicated that BOP-induced cholangiocarcinogenesis was suppressed by the supplemental administration of 1α(OH)D3.

Apoptosis of human cholangiocarcinoma cell lines induced by ß-escin through mitochondrial caspase-dependent pathway.

The study aimed to evaluate the effects of ß-escin on human cholangiocarcinoma cell lines (QBC939, Sk-ChA-1 and MZ-ChA-1) and to explore its mechanisms. Cell growth, cell cycle and apoptosis were investigated, respectively, by MTT assay, single PI and FITC/PI double-staining flow cytometry, and fluorescence microscopy. The protein expression was determined by western blotting. The study revealed that ß-escin inhibited cholangiocarcinoma cell growth in a dose- and time-dependent manner, and the cell cycle of QBC939 and Sk-ChA-1 cells was arrested in the G2/M phase, and MZ-ChA-1 cells in G1 phase. Apoptosis of the three cholangiocarcinoma cell lines induced by ß-escin was associated with the collapse of the mitochondrial membrane potential and the activation of caspase-3. The apoptotic effect of ß-escin was suppressed by pancaspase inhibitor z-VAD-fmk. Molecular dissection revealed that the antiapoptotic protein bcl-2 was down-regulated after cholangiocarcinoma cell lines were treated with ß-escin, while the protein levels of bax and p53 were unchanged. Apoptosis was accompanied by an increase in reactive oxygen species (ROS). These results suggest that ß-escin induces apoptosis of cholangiocarcinoma cells through an intrinsic mitochondrial caspase-dependent pathway, and the increase in the bax/bcl-2 ratio and ROS may play important roles in ß-escin-induced apoptosis of cholangiocarcinoma cells.

Chemopreventative effect of hochu-ekki-to (TJ-41) on chemically induced biliary carcinogenesis in hamsters.

BACKGROUND: Bilioenterostomy is a common surgical technique that is widely used. Recently, clinical studies have revealed that biliary carcinomas can occur after bilioenterostomy. The present study was designed to evaluate whether hochu-ekki-to (TJ-41), a Japanese herbal drug, could prevent chemically induced biliary carcinomas in bilioenterostomized hamsters. MATERIALS AND METHODS: Syrian golden hamsters were subjected to choledochojejunostomy and then received subcutaneous injections of N-nitrosobis(2-oxopropyl) amine every 2 weeks at a dose of 10 mg/kg. N-nitrosobis(2-oxopropyl) amine administration was started 4 weeks after surgery. The animals were simultaneously p.o. administered TJ-41 in water every day at a dose of 1000 mg/kg (TJ-41 group). The control hamsters were administered water alone. The hamsters were sacrificed 22 weeks after surgery, and the development of biliary carcinomas, the presence and degree of cholangitis, and the cell kinetic status of the biliary epithelium were evaluated histologically. RESULTS: Intrahepatic bile duct carcinomas developed in 15/17 (88%) hamsters in the control group and in only 8/17 (47%) hamsters in the TJ-41 group (P < 0.05). The degree of cholangitis was not different between the two groups. However, the proliferating cell nuclear antigen labeling index of the biliary epithelium in the TJ-41 group (6.46%) was significantly lower than the controls (9.67%) (P < 0.05). These findings indicated that TJ-41 reduced accelerated biliary epithelial cell kinetics after bilioenterostomy, resulting in the prevention of carcinogenesis. CONCLUSION: TJ-41 has a preventive effect on chemically induced carcinoma of the biliary tract after bilioenterostomy.

The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase.

Water-soluble ingredients of the herbal medicine sho-saiko-to dose-dependently inhibited the proliferation of a human hepatocellular carcinoma cell line (KIM-1) and a cholangiocarcinoma cell line (KMC-1). Fifty % effective doses on day 3 of exposure to sho-saiko-to were 353.5 +/- 32.4 micrograms/ml for KIM-1 and 236.3 +/- 26.5 micrograms/ml for KMC-1. However, almost no suppressive effects were detected in normal human peripheral blood lymphocytes or normal rat hepatocytes. Sho-saiko-to suppressed the proliferation of the carcinoma cell lines significantly more strongly than did each of its major ingredients, i.e., saikosaponin a, c, and d, ginsenoside Rb1 and Rg1, glycyrrhizin, baicalin, baicalein, and wogonin, or another herbal medicine, juzen-taiho-to (P < 0.05 or 0.005). Because such ingredients are barely soluble in water, there could be synergistic or additive effects of the ingredients in sho-saiko-to. Morphological, DNA, and cell cycle analyses revealed two possible modes of action of sho-saiko-to to suppress the proliferation of carcinoma cells; (a) it induces apoptosis in the early period of exposure and (b) it induces arrest at the G0/G1 phase in the late period of exposure.