Liver Fluke and Cholangiocarcinoma Research Center


Liver Fluke and Cholangiocarcinoma Research Center

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Boonjaraspinyo S.,Liver Fluke and Cholangiocarcinoma Research Center | Boonjaraspinyo S.,Neglected and Vector Borne Zoonosis Research Group | Juasook A.,Mahasarakham University | Boonmars T.,Neglected and Vector Borne Zoonosis Research Group | And 12 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2015

The present study was designed to investigate cholangiocarcinoma (CCA) antibodies in hamster serum. Hamster CCA cell lines were processed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A candidate biomarker was confirmed by immunoprecipitation and western blot, and was further analyzed using ELISA and sera from normal control hamsters, hamsters with opisthorchiasis and hamsters with various stages of CCA, as well as from CCA patients and healthy individuals. One candidate marker was identified as HSP90α, as indicated by a high level of anti-HSP90α in hamster CCA sera. It was found that the levels of anti-HSP90α were specifically elevated in the sera of hamsters with CCA compared with other groups and progressively increased with the clinical stage. At the cut-off point of 0.4850 on the receiver operating characteristic curve, anti-HSP90α could discriminate CCA from healthy control groups with a sensitivity of 76.2%, specificity of 71.4% and total accuracy 75.5%. In the present study, we have shown that anti-HSP90α may be a potential useful serum biomarker to discriminate CCA cases from healthy persons.

Barusrux S.,Clinical Research Laboratories | Nanok C.,Khon Kaen University | Puthisawas W.,Liver Fluke and Cholangiocarcinoma Research Center | Pairojkul C.,Liver Fluke and Cholangiocarcinoma Research Center | Poovorawan Y.,Chulalongkorn University
Asian Pacific Journal of Cancer Prevention | Year: 2012

The prevalence of HBV and HCV infection among 295 cholangiocarcinoma (CCA) patients in northeast Thailand was analyzed. Hepatitis B surface antigen (HBsAg) was detected in 8.8% (26/295 cases) and antibodies to HCV (anti-HCV) in 2.7% (8/295 cases) of CCA cases. Screening for HBV DNA was performed in 15 of 26 HBV seropositive cases and genotypes could be determined in all 15. HBV genotypes C and B were detected in 73.3% (11/15 cases) and 26.7% (4/15 cases), respectively. HCV RNA was detected in 87.5% (7/8 cases) of anti-HCV positive cases. Specifically, 57.1% (4/7 cases) were HCV genotype 1a and 42.9% (3/7 cases) were HCV genotype 3a. The prevalence of infection and genotype distribution of both HCV and HBV among CCA in northeast Thailand is comparable to that in the general population, suggesting that HCV and HBV infections are, if at all, not serious risk factors for CCA.

Aunpromma S.,Khon Kaen University | Tangkawattana P.,Khon Kaen University | Papirom P.,Khon Kaen University | Kanjampa P.,Khon Kaen University | And 5 more authors.
Parasitology International | Year: 2012

Khon Kaen, a northeastern province of Thailand, has been considered as one of the human opisthorchiasis endemic areas with continuing high prevalence. Unsuccessful eradication of the disease is probably from the culture of eating raw and undercooked fish of local residence and the parasitic persistency in animal reservoir hosts, such as cats and dogs. In cooperation with the other human opisthorchiasis control programs in an endemic area of 29 villages in Ban Haet, Ban Phai, Chonnabot and Muncha Khiri Districts, Khon Kaen, this study investigated the prevalence of Opisthorchis viverrini infection using a formalin-ether sedimentation method as the gold standard, and hematology and blood chemistry of the reservoir hosts in this endemic area. The results showed that cats had much higher prevalence (76 of 214, 35.51%) than dogs (3 of 821, 0.37%). Hematology between the infected and uninfected cats was not different. Complete blood count and biochemistry reflected some altered hepatic functions. However, only severely infected cats showed apparent clinical signs, including lethargy, diarrhea, ocular and nasal discharges. Moreover, the ultrasonogram of infected cats with very high egg per gram (> 1500 EPG) showed apparent thickening of the gall bladder wall with hyperechoicity of hepatic parenchyma. This study suggests that cat is the most important animal reservoir of human opisthorchiasis, especially in this endemic area. It is also interesting that villages with infection are mostly located in the vicinity of Chi River and two large water reservoirs (Lawa and Nong Kongkaew Lakes), but people without infection were away from Chi River, on the south of Kudkhow Lake. Further investigation on this particular geofactor is essential for effective opisthorchiasis control programs. © 2011 Elsevier Ireland Ltd.

Nutthasirikul N.V.,Khon Kaen University | Nutthasirikul N.V.,Liver Fluke and Cholangiocarcinoma Research Center | Hahnvajanawong C.,Liver Fluke and Cholangiocarcinoma Research Center | Techasen A.,Khon Kaen University | And 9 more authors.
International Journal of Oncology | Year: 2015

Lack of the normal p53 transactivation domain, Δ133p53 isoform exhibits anti-p53 function. Many studies report the correlation between Δ133p53 expression and poor survival in various cancers, including cholangiocarcinoma (CCA), which is a cancer of the bile ducts. CCA almost always results in short survival times. The relevance of Δ133p53 to drug resistance in CCA is not yet well understood. This study aimed to demonstrate the association between Δ133p53 and 5-fluorouracil (5-FU) resistance in CCA. Δ133p53 protein was highly expressed in CCA patients with poor outcome compared to favorable outcome but was not statistically significant. However, a significant correlation was found between normalized Δ133p53 levels and 5-FU resistance which was defined by an ex vivo histoculture drug response assay (P=0.019). Two stable 5-FU-resistant CCA cell lines, KKU-M139R (IC50 38.8 μM) and KKU-M214R (IC50 39.5 μM), were used as a model to evaluate the role of Δ133p53. Increased Δ133p53 was correlated with 5-FU in a dose-dependent manner. The transient knockdown of Δ133p53 expression can restore drug sensitivity in both resistant CCA cells with 11- to 45-fold reduction of IC50 compared to control. Upon Δ133p53 silencing, apoptotic signaling was enhanced by the upregulation of Bax and downregulation of Bcl-2. Additionally, p21 and p27 were upregulated, resulting in cell cycle arrest at G2. Inhibition of colony formation and prolong doubling time were also observed. Our findings demonstrated that chemosensitivity can be modulated via targeting of Δ133p53 suggesting the potential use of Δ133p53 as a candidate for targeting therapy in CCA.

Thongchot S.,Khon Kaen University | Thongchot S.,Liver Fluke and Cholangiocarcinoma Research Center | Loilome W.,Khon Kaen University | Loilome W.,Liver Fluke and Cholangiocarcinoma Research Center | And 10 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 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 (CoCl2)-stimulated hypoxia. We showed that chloroquine suppressed CCA cell migration under hypoxic-mimicking conditions on exposure to 100 μM CoCl2. 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-1α) 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-1α/VEGF/EMT which may serve as a useful additional strategy for CCA therapy.

Suthiwong J.,Natural Products Research Unit | Pitchuanchom S.,Lampang Rajabhat University | Wattanawongdon W.,Liver Fluke and Cholangiocarcinoma Research Center | Hahnvajanawong C.,Liver Fluke and Cholangiocarcinoma Research Center | Yenjai C.,Natural Products Research Unit
Asian Journal of Chemistry | Year: 2014

Labdanes 1-4, stigmasterol (5) and vanillin (6) were isolated from the rhizomes of Curcuma petiolata. Compounds 2-4 exhibited strong to moderate cytotoxicity against cholangiocarcinoma cell lines. Compound 3 showed strong cytotoxicity with IC50 values ranging from 5-11 μg/mL. The molecular modeling was studied using the AutoDock 4 program. The docking results reveal that 3 interacted with EGFR through the 2 H-bond at Gln767 and Met769 with binding energy of -6.89 kcal/mol.

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