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Moses T. Bility,Banchob Sripa 대한기생충학열대의학회 2014 The Korean Journal of Parasitology Vol.52 No.6
Chronic Opisthorchis viverrini-induced hepatobiliary disease is associated with significant leukocyte infiltration, including activated macrophages; however, the polarization of infiltrating macrophages remains to be fully characterized. In this study, we characterized macrophage polarization and phenotype in chronic O. viverrini-induced hepatobiliary disease in humans and hamsters using gene expression and histochemical analysis. Chronic O. viverrini infection and associated hepatobiliary diseases were associated with iron loaded M2-like macrophages in both humans and hamsters. This study provides suggestive evidence that iron loaded M2-like macrophages promote hepatobiliary disease in chronic O. viverrini infection.
Differential Expression of O-glycoprotein Glycans in Cholangiocarcinoma Cell Lines
Talabnin, Krajang,Talabnin, Chutima,Ishihara, Mayumi,Azadi, Parastoo,Wongkham, Sopit,Sripa, Banchob Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.2
Protein glycosylation is the most common posttranslational modification in mammalian cells. Aberrant protein glycosylation has been reported in various diseases, including cancer. We identified and quantified the glycan structures of O-linked glycoprotein from cholangiocarcinoma (CCA) cell lines from different histological types and compared their profiles by nanospray ionization-linear ion trap mass spectrometry (NSI-$MS^n$). Five human CCA cell lines, K100, M055, M139, M213 and M214 were characterized. The results showed that the O-linked glycans of the CCA cell lines comprised tri- to hexa-saccharides with terminal galactose and sialic acids: NeuAc1Gal1GalNAc1, Gal2GlcNAc1GalNAc1, NeuAc2Gal1GalNAc1 NeuAc1Gal2GlcNAc1GalNAc1 and NeuAc2Gal2GlcNAc1GalNAc1 All five CCA cell lines showed a similar glycan pattern, but with differences in their quantities. NeuAc1Gal1GalNAc1 proved to be the most abundant structure in poorly differentiated adenocarcinoma (K100; 57.1%), moderately differentiated adenocarcinoma (M055; 42.6%) and squamous cell carcinoma (M139; 43.0%), while moderately to poorly differentiated adenocarcinoma (M214; 40.1%) and adenosquamous cell carcinoma (M213; 34.7%) appeared dominated by $NeuA_{c2}Gal_1GalNA_{c1}$. These results demonstrate differential expression of the O-linked glycans in the different histological types of CCA. All five CCA cell lines have abundant terminal sialic acid (NeuAc) O-linked glycans, suggesting an important role for sialic acid in cancer cells. Our structural analyses of glycans may provide important information regarding physiology of disease-related glycoproteins in CCA.
Clinicopathological Significance of Osteopontin in Cholangiocarcinoma Cases
Laohaviroj, Marut,Chamgramol, Yaovalux,Pairojkul, Chawalit,Mulvenna, Jason,Sripa, Banchob Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.1
Cholangiocarcinoma (CCA) is generally a rare primary liver tumor of the bile duct with extremely poor clinical outcomes due to late diagnosis. Osteopontin (OPN) is the most abundant expressed gene in intrahepatic CCA and its involvement in tumor aggressiveness suggests it could be a useful prognostic biomarker. However, the prognostic significance of OPN expression in CCA is still controversial. We therefore immunohistochemically studied OPN expression in 354 resected CCAs and correlated the results with patient clinicopathological parameters. OPN expression was separately scored according to the percentage of cancer cells or degree of stromal tissue staining and classified as low (score 0-1) and high (score 2-3). OPN expression in CCA cells was found in 177 out of 354 patients (56.5%), whereas stroma was positive in 185 out of 354 patients (52.3%). Univariate analysis with several of the aforementioned parameters revealed that stromal but not cancer cell OPN expression was significantly associated with tumor size, tumor direct invasion into normal liver parenchyma, regional lymph node metastasis and higher staging. The combination of cancer cell and stromal OPN expression demonstrated a positive trend for linkage with lymph node metastasis. Multivariate analysis identified gender, the presence of lymphatic permeation and lymph node metastasis, but not OPN expression, as independent prognostic factors. This study confirms the presence of stromal OPN expression in tumor aggressiveness but not survival in CCA patients.
Prayong, Pokpong,Mairiang, Eimorn,Pairojkul, Chawalit,Chamgramol, Yaovalux,Mairiang, Pisaln,Bhudisawasdi, Vajarabhongsa,Sripa, Banchob Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13
The cholangiocarcinoma (CCA) is a relatively rare cancer worldwide but it is highly prevalent in Thailand where the liver fluke, Opisthorchis viverrini is endemic. There are reports that interleukin 6 (IL-6) may play an important role in the pathogenesis of opisthorchiasis associated CCA. Functionally, IL-6 can act on target cells through its receptor, IL-6R, and IL-6R polymorphisms may affect the functional activity of IL-6 leading to susceptibility to cholangiocarcinogenesis. Therefore, we assessed the association of the 48892 A/C (Asp358Ala) polymorphism in exon 9 of the IL-6R gene in 79 CCA cases compared to 80 healthy controls using the PCR-RFLP technique. The results showed significant differences between CCA cases and controls in overall genotype (p=0.001) and allele frequencies (p=0.0002). Chi-square for trend test revealed a significant association between genotype and CCA susceptibility (p=0.0002). The odds ratios (ORs) for genotype were 0.283 (95% CI=0.131-0.605, AC vs. AA; p=0.0003) and 0.206 (95% CI=0.196-1.245, CC vs. AA; p=0.0416), the OR for alleles was 0.347 (95% CI=0.187-0.633, allele C vs. allele A; p=0.0002) and that for the carrier C variant was 0.272 (95% CI=0.130-0.564; p=0.0001). This study demonstrated a close association between an IL-6R polymorphism, specifically higher A allele, and cholangiocarcinoma.
Aneknan, Ploypailin,Kukongviriyapan, Veerapol,Prawan, Auemduan,Kongpetch, Sarinya,Sripa, Banchob,Senggunprai, Laddawan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12
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.
The Carcinogenic Liver Fluke Opisthorchis viverrini is a Reservoir for Species of Helicobacter
Deenonpoe, Raksawan,Chomvarin, Chariya,Pairojkul, Chawalit,Chamgramol, Yaowalux,Loukas, Alex,Brindley, Paul J,Sripa, Banchob Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5
There has been a strong, positive correlation between opisthorchiasis-associated cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human infection with Opisthorchis viverrini was utilized to further investigate relationships of apparent co-infections with O. viverrini and H. pylori. A total of 150 hamsters were assigned to five groups: i) Control hamsters not infected with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue, colorectal feces and O. viverrini worms were collected and the presence of species of Helicobacter determined by PCR-based approaches. In addition, O. viverrini worms were cultured in vitro with and without ABx for four weeks, after which the presence of Helicobacter spp. was determined. In situ localization of H. pylori and Helicobacter-like species was performed using a combination of histochemistry and immunohistochemistry. The prevalence of H. pylori infection in O. viverrini-infected hamsters was significantly higher than that of O. viverrini-uninfected hamsters ($p{\leq}0.001$). Interestingly, O. viverrini-infected hamsters treated with ABx and PZQ (to remove the flukes) had a significantly lower frequency of H. pylori than either O. viverr-iniinfected hamsters treated only with ABx or O. viverrini-infected hamsters, respectively ($p{\leq}0.001$). Quantitative RT-PCR strongly confirmed the correlation between intensity H. pylori infection and the presence of liver fluke infection. In vitro, H. pylori could be detected in the O. viverrini worms cultured with ABx over four weeks. In situ localization revealed H. pylori and other Helicobacter-like bacteria in worm gut. The findings indicate that the liver fluke O. viverrini in the biliary tree of the hamsters harbors H. pylori and Helicobacter-like bacteria. Accordingly, the association between O. viverrini and H. pylori may be an obligatory mutualism.
Kaewpitoon, Natthawut,Kaewpitoon, Soraya J.,Ueng-Arporn, Naporn,Rujirakul, Ratana,Churproong, Seekaow,Matrakool, Likit,Auiwatanagul, Suprakrit,Sripa, Banchob Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4
Background: Opisthorchis viverrini infection is a serious public-health problem in Southeast Asia. It is associated with a number of hepatobiliary diseases and the evidence strongly indicates that liver fluke infection is the etiology of cholangiocarcinoma. Objectives: This study aimed to investigate Opisthorchis viverrini metacercarial infection in cyprinoid fish collected from 32 districts of Nakhon Ratchasima province, Northeastern Thailand during one year period from February 2010 to February 2011. Methods: A cross-sectional study was conducted, data being collected with pepsin-HCl digestion and stereomicroscope, respectively. Analysis was performed using SPSS Windows Version 12.0. Results: A total of 640 Cyprinidae family fish including 5 species were collected from different study sites, and investigated for O. viverrini metacercariae. The infection rate was 12.3% (79/640), predominantly in Cyclocheilichthys armatus, C. repasson, Puntioplites proctzysron, Hampala macrolepitota and Hampala dispar, respectively. The prevalence of O. viverrini metaceria in Nakhon Ratchasima area was 78.1%, predominantly in Sida and KiaKham Thale So. Conclusion: This findings stress that natural fish species in rural communities are still a source of O viverrini infection and put local people at risk, therefore public awareness and prevention campaigns are urgently required.
Kaewpitoon, Soraya J.,Rujirakul, Ratana,Ueng-Arporn, Naporn,Matrakool, Likit,Namwichaisirikul, Niwatchai,Churproong, Seekaow,Wongkaewpothong, Patcharaporn,Nimkuntod, Porntip,Sripa, Banchob,Kaewpitoon, Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.9
Background: Opisthorchis viverrini infection is a serious public-health problem in Southeast Asia. It is associated with a number of hepatobiliary diseases and the evidence strongly indicates that liver fluke infection is the etiology of cholangiocarcinoma. Objectives: This study aimed to determine Opisthorchis viverrini infection in elderly people in Surin province, Northeastern Thailand. Methods: A community-based cross-sectional survey was conducted among 333 elderly in 17 districts of Surin province, during one year period from January to December 2011. O. viverrini infection was determined using Kato's Thick Smear technique and socio-demographic were collected using predesigned semi-structured questionnaires, respectively. Results: A total of 333 elderly including 116 males and 217 females were selected from different study sites. Overall intestinal parasitic infection was 16.2%, predominantly in O. viverrini (9.91%) and followed by Strongyloides stercolaris (4.80%) and hookworm (1.50%), respectively. The O. viverrini infection was found higher in males (13.8%) than females (7.83%), and frequently in elderly 60-70 year old with 14.2%. Chi-square testing indicated that education and occupation were significantly associated with O. viverrini infection (P value = 0.02). The distribution of O. viverrini infection was found in 11 districts which was covered 64.7% of the studies areas. The highest prevalence was found in Thatum with 39.1%, and followed by Sangkha (24.0%), Buachet (21.1%), Samrong Thap (19.1%), Si Narong (15.0%), and Ratanaburi (13.3%) districts. Conclusion: This findings stress that O viverrini is still a problem in Thailand. We confirmed, for the first time, the high endemicity of human O. viverrini infections in elderly in Surin province of Thailand, underlying the fact that mass treatment and health education are urgently required.