Cholangiocarcinoma (CCA) is a unique liver cancer subtype with an increasing incidence globally. The lack of specific symptoms and definite diagnostic markers results in a delayed diagnosis and disease progression. Systemic chemotherapy is commonly selected for advanced CCA even though its advantages remain unknown. Targeted therapy, especially anti-vascular endothelial growth factor (VEGF) therapy, is promising for CCA; however, improvements in the therapeutic regimen are necessary to overcome subsequent resistance. We demonstrated VEGF expression was higher in CCA cell lines than in other liver cancer cells. Secreted VEGFs played roles in the induction of peri- and intra-tumoral vascularization. VEGF neutralization by bevacizumab effectively reduced tumor growth, mainly through the suppression of angiogenesis; however, increases in the expression of hypoxia-inducible factor 1α (HIF1α) and HIF1α-responsive genes (such as VEGF, VEGFR1, VEGFR2, carbonic anhydrase (CA) IX and CAXII) indicated the potential for subsequent therapeutic resistance. Supplementation with a carbonic anhydrase inhibitor, acetazolamide, enhanced the anti-CCA effects of bevacizumab. Anti-angiogenesis and anti-proliferation were observed with the combination treatment. These results suggested a novel treatment strategy to overcome anti-angiogenesis resistance and the importance of "induced essentiality" in the treatment of CCA.

BackgroundTwo important helminths, Strongyloides stercoralis (an intestinal roundworm) and Opisthorchis viverrini (a liver fluke), are endemic in northeast Thailand. There have been national campaigns in place aimed at the control and eradication of soil-transmitted helminthiasis and opisthorchiasis in Thailand for several decades. However, these helminths still exist and raise concerns regarding public health. This study aimed to evaluate the current prevalence of S. stercoralis and O. viverrini infections in rural communities in northeast Thailand. The data from this study will be useful to improve strategies for future helminth prevention and control.MethodsA cross-sectional study was conducted from December 2016 to June 2017 in Mueang Khon Kaen district in Khon Kaen, Thailand. The participants were selected using a simple random sampling method. Demographic data were collected using a questionnaire. Stool samples were collected and processed using agar plate culture to determine the presence of S. stercoralis infection and an in-house formalin-ethyl acetate concentration technique to determine the presence of O. viverrini and other intestinal parasite infections (IPIs).ResultsIn total, 602 persons were enrolled. However, only 526 were analyzed for S. stercoralis and 387 for O. viverrini risk factors. The overall prevalence of S. stercoralis infection was 23.0% (95% confidence interval [95%CI]: 19.4 to 26.6). The prevalence of O. viverrini infection and IPIs other than S. stercoralis was 20.4% (95%CI: 16.5 to 24.8). The prevalence of O. viverrini infection was 19.4% (95%CI: 15.6 to 23.7). Male sex was significantly associated with S. stercoralis infection [Adjusted Odds Ratio (aOR) 4.0; 95%CI: 2.5 to 6.2; P-value < 0.001]. Males were significantly more likely to be infected with O. viverrini and other IPIs (aOR 4.1; 95%CI: 2.3 to 7.2, P-value < 0.001).ConclusionsThis study demonstrated that the updated prevalence of intestinal parasite infections is still high in rural communities in northeast Thailand, especially that of strongyloidiasis and opisthorchiasis.

Cholangiocarcinoma (CCA) is a highly metastatic tumor, and the lung is a common site of metastasis. A greater understanding of the biology of metastases is needed to improve treatment outcomes. Herein, a highly metastatic human CCA subline, KKU-213L5 from an original cell line, KKU-213 that has marginally metastatic ability, was established and characterized. KKU-213L5 was selected in vivo through the fifth serial passage of pulmonary metastasized tissues via tail-vein injection in NOD/scid/Jak3 mice. The metastatic abilities of the KKU-213L5 cells were compared with the parental line in vitro and in vivo. The expression profile of this metastatic cell line was determined using real-time PCR. KKU-213L5 cells were found to possess higher metastatic phenotypes, i.e., growth rates, stem cell surface markers (CD133), migration and invasion characteristics when compared with the parental cells. Compared to the KKU-213 cells, KKU-213L5 cells formed larger tumors in subcutaneous xenografted mice and had a >10-fold increase in lung metastases in the tail-vein injected metastatic mouse model. Mice injected intravenously with KKU-213L5 cells had a significantly shorter survival. Analysis of the expressed genes related to progression of cancer revealed significant upregulation of anterior gradient protein-2 (AGR2) and suppression of KiSS-1 in the KKU-213L5 cells. The association of these two genes with metastasis was affirmed in CCA patient tissues since increased AGR2 expression and decreased KiSS-1 expression were found in higher stage patient tumors. In conclusion, a highly metastatic human CCA cell line was established and characterized. It is plausible that the differential expression between the parental KKU-213 and highly metastatic KKU-213L5 cells may be beneficial to classify novel genes associated with metastasis. The KKU-213L5 cell line should serve as a valued device for discovering the molecular mechanisms of CCA metastasis and enabling the search for an effective therapy for the unmet clinical need in CCA.

BackgroundHuman strongyloidiasis is a chronic and persistent gastrointestinal disease caused by infection with soil-transmitted helminths of the genus Strongyloides. The aim of this research was to obtain diagnostic prevalence regarding strongyloidiasis in northeast Thailand through a hospital-based study.MethodsPatients’ demographic data and the results of stool examinations conducted using the formalin ethyl acetate concentration technique were collected from the parasitology laboratory records at Srinagarind Hospital in Khon Kaen, Thailand. The relevant information from years 2004 to 2014 was collected and descriptively analyzed.ResultsOf a total of 22,338 patients, 3889 (17.4%) had stool samples that tested positive for Strongyloides larvae. The highest prevalence was 22.8% (95% CI = 19.6–26.2%) in the year 2004. This percentage progressively decreased, reaching 11.2% (95% CI = 10.2–12.4%) in 2013 and remaining stable at 12.9% (95% CI = 11.8–14.1%) in 2014. Males (2741 cases) had double the positivity rate of females (1148 cases). The prevalence of infection was highest (25.9%; 95% CI = 24.5–27.3%) among patients that were 51–60 years of age.ConclusionsAreas endemic for strongyloidiasis should be emphasized under the national helminth control program and health education campaigns. Nationwide assessments should also be performed regarding Strongyloides infection, including risk factors, treatment, and prevention. The diagnostic laboratory data presented here identify the geographical focus of disease to be the northeastern region of the country. Further targeted surveillance using more sensitive methods will almost certainly reveal a higher individual disease burden than found in this report.

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