AIM:To study the association between hilar cholangiocarcinoma(HC) and pre-existing medical conditions. METHODS:Three hundred and thirteen HC patients admitted to the Eastern Hepatobiliary Surgery Hospital(Shanghai,Chi...AIM:To study the association between hilar cholangiocarcinoma(HC) and pre-existing medical conditions. METHODS:Three hundred and thirteen HC patients admitted to the Eastern Hepatobiliary Surgery Hospital(Shanghai,China) in 2000-2005 and 608 healthy controls were enrolled in this study.Association between HC and pre-existing medical conditions was studied with their adjusted odds ratio(OR) calculated by logistic regression analysis. RESULTS:The prevalence of choledocholithiasis(adjusted OR=2.704,P=0.039) ,hepatolithiasis(adjusted OR=3.278,P=0.018) ,cholecystolithiasis(adjusted OR =4.499,P<0.0001) ,cholecystectomy(adjusted OR =7.012,P=0.004) ,biliary ascariasis(adjusted OR= 7.188,P=0.001) ,liver fluke(adjusted OR=10.088,P =0.042) and liver schistosomiasis(adjusted OR=9.913,P=0.001) was higher in HC patients than in healthy controls. CONCLUSION:Biliary tract stone disease(choledocho-lithiasis,hepatolithiasis,cholecystolithiasis) and parasitic liver disease(biliary ascariasis,liver fluke,liver schistosomiasis) are the risk factors for HC in Chinese population.展开更多
AIM:To investigate trefoil factor(TFF) gene copy number,mRNA and protein expression as potential biomarkers in cholangiocarcinoma(CCA).METHODS:TFF mRNA levels,gene copy number and protein expression were determined re...AIM:To investigate trefoil factor(TFF) gene copy number,mRNA and protein expression as potential biomarkers in cholangiocarcinoma(CCA).METHODS:TFF mRNA levels,gene copy number and protein expression were determined respectively by quantitative reverse transcription polymerase chain reaction(PCR),quantitative PCR and immunohistochemistry in bile duct epithelium biopsies collected from individuals with CCA,precancerous bile duct dysplasia and from disease-free controls.The functional impact of recombinant human(rh) TFF2 peptide treatment on proliferation and epidermal growth factor receptor(EGFR) /mitogenactivated protein kinase(MAPK) signaling was assessed in the CCA cell line,KMBC,by viable cell counting and immunoblotting,respectively.RESULTS:TFF1,TFF2 and TFF3 mRNA expression was significantly increased in CCA tissue compared to disease-free controls,and was unrelated to gene copy number.TFF1 immunoreactivity was strongly increased in both dysplasia and CCA,whereas TFF2 immunoreactivity was increased only in CCA compared to diseasefree controls.By contrast,TFF3 immunoreactivity was moderately decreased in dysplasia and further decreased in CCA.Kaplan-Meier analysis found no association of TFF mRNA,protein and copy number with age,gender,histological subtype,and patient survival time.Treatment of KMBC cells with rhTFF2 stimulated proliferation,triggered phosphorylation of EGFR and downstream extracellular signal related kinase(ERK),whereas co-incubation with the EGFR tyrosine kinase inhibitor,PD153035,blocked rhTFF2-dependent proliferation and EGFR/ERK responses.CONCLUSION:TFF mRNA/protein expression is indicative of CCA tumor progression,but not predictive for histological sub-type or survival time.TFF2 is mitogenic in CCA via EGFR/MAPK activation.展开更多
Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of h...Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of hepatobiliary diseases, including cholangitis, obstructive jaundice, hepatomegaly, cholecystitis and cholelithiasis. Multi-factorial etiology of cholangiocarcinoma, mechanical damage, parasite secretions, and immunopathology may enhance cholangiocarcinogenesis. Moreover, both experimental and epidemiological evidences strongly implicate liver fluke infection as the major risk factor in cholangiocarcinoma, cancer of the bile ducts. The liver fluke infection is induced by eating raw or uncooked fish products that is the tradition and popular in the northeastern and northern region, particularly in rural areas, of Thailand. The health education programs to prevent and control opisthorchiasis are still required in the high-risk areas.展开更多
AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of ...AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% ± 0.49% and 72.5% ± 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy.展开更多
Background Clonorchiasis and opisthorchiasis,caused by the liver flukes Clonorchis sinensis and Opisthorchis viverrini respectively,represent significant neglected tropical diseases(NTDs)in Asia.The co-existence of th...Background Clonorchiasis and opisthorchiasis,caused by the liver flukes Clonorchis sinensis and Opisthorchis viverrini respectively,represent significant neglected tropical diseases(NTDs)in Asia.The co-existence of these pathogens in overlapping regions complicates effective disease control strategies.This study aimed to clarify the distribution and interaction of these diseases within Southeast Asia.Methods We systematically collated occurrence records of human clonorchiasis(n=1809)and opisthorchiasis(n=731)across the Southeast Asia countries.Utilizing species distribution models incorporating environmental and climatic data,coupled machine learning algorithms with boosted regression trees,we predicted and distinguished endemic areas for each fluke species.Machine learning techniques,including geospatial analysis,were employed to delineate the boundaries between these flukes.Results Our analysis revealed that the endemic range of C.sinensis and O.viverrini in Southeast Asia primarily spans across part of China,Vietnam,Thailand,Laos,and Cambodia.During the period from 2000 to 2018,we identified C.sinensis infections in 84 distinct locations,predominantly in southern China(Guangxi Zhuang Autonomous Region)and northern Vietnam.In a stark contrast,O.viverrini was more widely distributed,with infections documented in 721 locations across Thailand,Laos,Cambodia,and Vietnam.Critical environmental determinants were quantitatively analyzed,revealing annual mean temperatures ranging between 14 and 20°C in clonorchiasis-endemic areas and 24-30°C in opisthorchiasis regions(P<0.05).The machine learning model effectively mapped a distinct demarcation zone,demonstrating a clear separation between the endemic areas of these two liver flukes with AUC from 0.9 to1.The study in Vietnam delineates the coexistence and geographical boundaries of C.sinensis and O.viverrini,revealing distinct endemic zones and a transitional area where both liver fluke species overlap.Conclusions Our findings highlight the critical role of specific c展开更多
Background Opisthorchiid flukes,particularly Opisthorchis viverrini,Opisthorchis felineus,Clonorchis sinensis,and Metorchis spp.are the most common fish-borne zoonotic human liver flukes(hLFs).Liver fluke infections a...Background Opisthorchiid flukes,particularly Opisthorchis viverrini,Opisthorchis felineus,Clonorchis sinensis,and Metorchis spp.are the most common fish-borne zoonotic human liver flukes(hLFs).Liver fluke infections are more prevalent in resource-deprived and underprivileged areas.We herein estimated the prevalence of the metacercariae(MC)of major hLFs in common large freshwater fishes(lFWF)marketed for human consumption from some selected areas of Bangladesh along with detection of their molluscan vectors and reservoirs.Methods The current status of fish-borne zoonotic hLF infections in lFWF was investigated along with their molluscan vectors and mammalian reservoir hosts in Mymensingh and Kishoreganj in Bangladesh from July 2018-June 2022 using conventional and multiple molecular techniques,such as PCR,PCR-restriction fragment length polymorphism(RFLP),sequencing,and bioinformatic analyses.The infection rate of fishes was analyzed using the Z-test and the loads of MC were compared using the chi-squared(χ^(2))test.Results The MC of C.sinensis,Opisthorchis spp.,and Metorchis spp.were detected in 11 species of common and popular lFWF.In lFWF,the estimated prevalence was 18.7%and the mean load was 137.4±149.8 MC per 100 g of fish.The prevalence was the highest(P<0.05)in spotted snakehead fishes(Channa punctata,63.6%).The highest rate of infection(P<0.05)was observed with the MC of C.sinensis(11.8%).Metacercariae were almost equally(P>0.05)distributed between the head and body of fishes.The infection rate was slightly higher in cultured(19.6%)fishes.The MC of C.sinensis,O.felineus,O.viverrini,and Metorchis orientalis in fishes were confirmed using PCR,PCR-RFLP and bioinformatics.The cercariae of opisthorchiid(Pleurolophocercus cercariae)flukes were only recovered from Bithynia spp.(3.9%,42 out of 1089).The ova of hLFs from dogs(4.3%,5 out of 116)and cats(6.0%,6 out of 100),and adult flukes(M.orientalis)from ducks(41.1%113 out of 275)were detected.Conclusions The MC of hLFs are highly prevalent in fresh water fishe展开更多
AIM： To investigate loss of heterozygosity （LOH） and microsatellite instability （MSI） on the chromosomal region 1p36-pter in cholangiocarcinoma （CCA） patients and determine the association between microsatellit...AIM： To investigate loss of heterozygosity （LOH） and microsatellite instability （MSI） on the chromosomal region 1p36-pter in cholangiocarcinoma （CCA） patients and determine the association between microsatellite alterations and clinicopathological parameters. METHODS： Ten polymorphic microsatellite markers were determined for LOH and MSI using GS-3000 gel scan fragment autoanalyzer. RESULTS： Sixty-eight out of 90 cases （75.6%） showed LOH in one or more loci. LOH was found most frequently at DIS199 （40.0%）, DIS507 （34.6%）, DIS2845 （30.5%）, and DIS2734 （30.1%）. MSI was found in 34 of 90 cases （37.8%） at one or more loci. Fine mapping at lp36 showed two distinctive regions of common loss, which were D1S2845 and the 25.5-cM region between D1S507 and D1S2734, indicating the existence of putative tumor suppressor genes that is likely to play important roles in the development of CCA. Patients with LOH at D1S234 showed less lymphatic invasion （P = 0.017）, whereas patients with LOH at D1S2676 exhibited more lymphatic invasion than those without （P = 0.031）. LOH at D1S2845 showed a significant correlation with nerve invasion （P = 0.029）. Moreover, patients who demonstrated MSI at D1S228 showed a poor prognosis （P = 0.0026）. CONCLUSION： Allelic loss plays a major role in microsatellite alterations at chromosome lp36, which may contribute to carcinogenesis and pathogenesis of liver fluke related CCA and these alterations can be used as molecular prognostic indicators for CCA patients.展开更多
Cholangiocarcinoma(CCA) is a difficult cancer to diagnose in the early stage and to treat by curative resec-tion. The incidence of CCA in the northeast of Thailand is the highest in the world. To make progress in dete...Cholangiocarcinoma(CCA) is a difficult cancer to diagnose in the early stage and to treat by curative resec-tion. The incidence of CCA in the northeast of Thailand is the highest in the world. To make progress in detecting a high risk group and in the prevention and detection of CCA, we have been analyzing the risk factors for CCA. Although liver fluke infection is known to be a risk factor, there are patients who are not infected with the liver fluke and not all people infected with the liver fluke will suffer from the disease. Therefore, it is of the utmost importance to analyze the risk factors and the mechanism to prevent the disease and also to detect the disease in its early stage to save patients' lives. Through collaboration among Thai and Japanese researchers, we analyzed the genetic and environmental determinants of risks for CCA. Also, we have been trying to develop methods to detect the disease in a non-invasive way. Without repeating findings reported in various reviews on CCA, we will first discuss the environmental and genetic determinants of the risks for CCA. Second, we will discuss the properties of CCA, including the etiological agents and the mechanism of cholangiocarcinogenesis, and finally, we will discuss future approaches to prevent and cure CCA from the standpoint of evidence-based medicine. We will discuss these points by including the data from our laboratories. We would like to emphasize the importance of the genetic data, especially whole genome approaches, to understand the properties of CCA, to find a high risk population for CCA and to develop effective preventative methods to stop the carcinogenic steps toward CCA in the near future. In addition, it is of the upmost importance to develop a non-invasive, specific and sensitive method to detect CCA in its early stage for the application of modern medical approaches to help patients with CCA.展开更多
Liver fluke is a digenetic trematode parasitizing in the hepatic ducts of humans or animals. Patients with liver fluke infection suffer from a series of hepatobiliary diseases. The prevalence of cholangiocarcinoma is ...Liver fluke is a digenetic trematode parasitizing in the hepatic ducts of humans or animals. Patients with liver fluke infection suffer from a series of hepatobiliary diseases. The prevalence of cholangiocarcinoma is significantly high in areas with high incidence of clonorchiasis. Liver fluke is an important biocarcinogenic factor in the occurrence of cholangiocarcinoma. The secretory products of the body of this parasite and long-term mechanical stimulation will induce continuous inflammation of the bile duct. Gene expression of the bile duct cells is imbalanced, leading to bile duct carcinogenesis. This paper provides a summary of recent studies on the epidemiology, clinicopathology, and molecular biology of cholangiocarcinoma induced by liver fluke infection.展开更多
AIM： To investigate the knowledge, attitude and practice （KAP） in prevention and control of liver fluke infection in northeast Thailand. METHODS： A descriptive KAP survey pertaining to liver fluke infection was ca...AIM： To investigate the knowledge, attitude and practice （KAP） in prevention and control of liver fluke infection in northeast Thailand. METHODS： A descriptive KAP survey pertaining to liver fluke infection was carried out in June 2005 to October 2006 using structured questionnaires. Data were collected by questionnaires consisting of general parameters, knowledge, attitude, practice, and a history of participation in the prevention and control of liver fluke infection. RESULTS： A total of 1077 persons who were interviewed and completed the questionnaires were enrolled in the study. The majority were females （69.5%） and many of them were 15-20 years of age （37.26%）. The questionnaires revealed that information resources on liver fluke infection included local public health volunteers （31.37%）, public health officers （18.72%）, televisions （14.38%）, local heads of sub-districts （12.31%）, doctors and nurses （9.18%）, newspaper （5.72）, intemets （5.37%）, and others （12.95%）. Fiftyfive point eleven percent of the population had a good level of liver fluke knowledge concerning the mode of disease transmission and 79.72% of the population had a good level of prevention and control knowledge with regards to defecation and consumption. The attitude and practice in liver fluke prevention and control were also at a good level with a positive awareness, participation, and satisfaction of 72.1% and 60.83% of the persons studied. However, good health behavior was found in 39.26% and 41.42% of the persons studied who had unhygienic defecation and ate raw cyprinoid＇s fish. The result also showed that 41.25% of the persons studied previously joined prevention and control campaigns. CONCLUSION： The persons studied have a high level of liver fluke knowledge and positive attitude. However, improvement is required regarding personal hygiene specifically with hygienic defecation and consumption of undercooked fish.展开更多
AIM： To determine allelic imbalance on chromosomal region 21q22-qter including trefoil factor family genes （TFF） in cholangiocarcinoma （CCA） patients and analyze the correlation between allelic imbalances and cli...AIM： To determine allelic imbalance on chromosomal region 21q22-qter including trefoil factor family genes （TFF） in cholangiocarcinoma （CCA） patients and analyze the correlation between allelic imbalances and clinicopathological parameters. METHODS： Quantitative PCR amplification was performed on four microsatellite markers and trefoil factor family genes （TFF1, TFF2, and TFF3） using a standard curve and SYBR Green I dye method. The relative copy number was determined by DNA copy number of tested locus to reference locus. The relative copy number was interpreted as deletion or amplification by comparison with normal reference range. Associations between allelic imbalance and clinicopathological parameters of CCA patients were evaluated by χ^2-tests. Kaplan-Meier method was used to analyze survival. RESULTS： The frequencies of amplification at D21S1890, D21S1893, and TFF3 were 32.5%, 30.0%, and 28.7%, respectively. Patients who had amplification at regions covering D21S1893, D21S1890, and TFF showed poor prognosis, whereas patients who had deletion showed favorable prognosis （mean： 51.7 wk vs 124.82 wk, P = 0.012）. Multivariate Cox regression analysis revealed that amplification of D21S1893, D21S1890 and TFF, blood vessel invasion, and staging were associated with poor prognosis. CONCLUSION： D21S1893-D21S1890 region may harbor candidate genes especially TFF and serine protease family, which might be involved in tumor invasion and metastasis contributing to poor survival. The amplification in this region may be used as a prognostic marker in the treatment of CCA patients.展开更多
Objective: To evaluate the effects of lead in the morphology and viability of Fasciola gigantica(F. gigantica)(giant liver fluke) isolated from infected livers of carabaos in vitro using the following concentrations o...Objective: To evaluate the effects of lead in the morphology and viability of Fasciola gigantica(F. gigantica)(giant liver fluke) isolated from infected livers of carabaos in vitro using the following concentrations of lead: 0, 100, 150 and 200 mg/L. Methods: In vitro viability and motility assay was conducted to evaluate the ef ects of lead using 1% methylene blue as the vital dye for assessment of the l ukes' viability. Results: Results indicate that F. gigantica can tolerate lead exposure as high as 200 mg/L with visible morphological variations. Upon exposure to lead, liver l ukes tend to curl and excrete black precipitates as a sign of physiological stress response. Furthermore, the lethal concentration(LC50) of lead against F. gigantica in vitro was 160 mg/L. Conclusions: In conclusion, tolerance of liver flukes to high levels of lead suggests its potential as a possible biomarker of environmental pollution.展开更多
AIM To identify the potential risk factors of cholangiocarcinoma, we determined the characteristics of cholangiocarcinoma patients among 5 different regions of Thailand. METHODS All patients diagnosed with cholangioca...AIM To identify the potential risk factors of cholangiocarcinoma, we determined the characteristics of cholangiocarcinoma patients among 5 different regions of Thailand. METHODS All patients diagnosed with cholangiocarcinoma between 2008 and 2013 were identified using the Nationwide Hospital Admission Data registry(n = 39421). Baseline characteristics, comorbidities and survival were abstracted. RESULTS The annual incidence during the study period was stable in all regions. Most patients lived in the Northeast(62.8%), followed by the North(16.9%), Central(12.3%), Bangkok(5.4%), and South(n = 2.6%) regions(P < 0.0001). Significantly more cholangiocarcinoma patients had diabetes, cirrhosis, and chronic viral hepatitis B/C infection than noncholangiocarcinoma participants(diabetes: 11.42% vs 5.28%; cirrhosis: 4.81% vs 0.92%; hepatitis B: 0.74% vs 0.12%; and hepatitis C: 0.50% vs 0.10%, P < 0.0001 for all, respectively). The overall 1-year mortality rate was 81.7%, with a stable trend over time. CONCLUSION Diabetes and chronic liver diseases may be associated with cholangiocarcinoma in the Thai population.展开更多
文摘AIM:To study the association between hilar cholangiocarcinoma(HC) and pre-existing medical conditions. METHODS:Three hundred and thirteen HC patients admitted to the Eastern Hepatobiliary Surgery Hospital(Shanghai,China) in 2000-2005 and 608 healthy controls were enrolled in this study.Association between HC and pre-existing medical conditions was studied with their adjusted odds ratio(OR) calculated by logistic regression analysis. RESULTS:The prevalence of choledocholithiasis(adjusted OR=2.704,P=0.039) ,hepatolithiasis(adjusted OR=3.278,P=0.018) ,cholecystolithiasis(adjusted OR =4.499,P<0.0001) ,cholecystectomy(adjusted OR =7.012,P=0.004) ,biliary ascariasis(adjusted OR= 7.188,P=0.001) ,liver fluke(adjusted OR=10.088,P =0.042) and liver schistosomiasis(adjusted OR=9.913,P=0.001) was higher in HC patients than in healthy controls. CONCLUSION:Biliary tract stone disease(choledocho-lithiasis,hepatolithiasis,cholecystolithiasis) and parasitic liver disease(biliary ascariasis,liver fluke,liver schistosomiasis) are the risk factors for HC in Chinese population.
基金Supported by The Thailand Research Fund through the Royal Golden Jubilee PhD program(grant PHD/0121/2547 code 5LKK/47/B1 to Kosriwong K and Limpaiboon T)Khon Kaen University Research Affairs(grant 48-03-1-01-03)the Centre for Research and Development of Medical Diagnostic Laboratories,Faculty of Associated Medical Sciences(No.06-01), Thailand
文摘AIM:To investigate trefoil factor(TFF) gene copy number,mRNA and protein expression as potential biomarkers in cholangiocarcinoma(CCA).METHODS:TFF mRNA levels,gene copy number and protein expression were determined respectively by quantitative reverse transcription polymerase chain reaction(PCR),quantitative PCR and immunohistochemistry in bile duct epithelium biopsies collected from individuals with CCA,precancerous bile duct dysplasia and from disease-free controls.The functional impact of recombinant human(rh) TFF2 peptide treatment on proliferation and epidermal growth factor receptor(EGFR) /mitogenactivated protein kinase(MAPK) signaling was assessed in the CCA cell line,KMBC,by viable cell counting and immunoblotting,respectively.RESULTS:TFF1,TFF2 and TFF3 mRNA expression was significantly increased in CCA tissue compared to disease-free controls,and was unrelated to gene copy number.TFF1 immunoreactivity was strongly increased in both dysplasia and CCA,whereas TFF2 immunoreactivity was increased only in CCA compared to diseasefree controls.By contrast,TFF3 immunoreactivity was moderately decreased in dysplasia and further decreased in CCA.Kaplan-Meier analysis found no association of TFF mRNA,protein and copy number with age,gender,histological subtype,and patient survival time.Treatment of KMBC cells with rhTFF2 stimulated proliferation,triggered phosphorylation of EGFR and downstream extracellular signal related kinase(ERK),whereas co-incubation with the EGFR tyrosine kinase inhibitor,PD153035,blocked rhTFF2-dependent proliferation and EGFR/ERK responses.CONCLUSION:TFF mRNA/protein expression is indicative of CCA tumor progression,but not predictive for histological sub-type or survival time.TFF2 is mitogenic in CCA via EGFR/MAPK activation.
基金the Division of Research Promotion,Ubon Rajthanee UniversityDivision of Research, College of MedicinePublic Health, Ubon Rajthanee University
文摘Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of hepatobiliary diseases, including cholangitis, obstructive jaundice, hepatomegaly, cholecystitis and cholelithiasis. Multi-factorial etiology of cholangiocarcinoma, mechanical damage, parasite secretions, and immunopathology may enhance cholangiocarcinogenesis. Moreover, both experimental and epidemiological evidences strongly implicate liver fluke infection as the major risk factor in cholangiocarcinoma, cancer of the bile ducts. The liver fluke infection is induced by eating raw or uncooked fish products that is the tradition and popular in the northeastern and northern region, particularly in rural areas, of Thailand. The health education programs to prevent and control opisthorchiasis are still required in the high-risk areas.
基金Supported by The Thailand Research Fund through The Royal Golden Jubilee PhD Program Grant No. PHD/0037/2544 for Thanasai J and Limpaiboon T and grants-in-aid from the Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Thailand, and from the Ministry of Education, Sports, Science, Culture and Technology, Japan
文摘AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% ± 0.49% and 72.5% ± 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy.
基金supported by the National Key Research and Development Program of China(No.2021YFC2300800,2021YFC2300804)the International Joint Laboratory on Tropical Diseases Control in Greater Mekong Subregion(No.21410750200)The International Development Research Centre(IDRC),Canada(No.108100-001)
文摘Background Clonorchiasis and opisthorchiasis,caused by the liver flukes Clonorchis sinensis and Opisthorchis viverrini respectively,represent significant neglected tropical diseases(NTDs)in Asia.The co-existence of these pathogens in overlapping regions complicates effective disease control strategies.This study aimed to clarify the distribution and interaction of these diseases within Southeast Asia.Methods We systematically collated occurrence records of human clonorchiasis(n=1809)and opisthorchiasis(n=731)across the Southeast Asia countries.Utilizing species distribution models incorporating environmental and climatic data,coupled machine learning algorithms with boosted regression trees,we predicted and distinguished endemic areas for each fluke species.Machine learning techniques,including geospatial analysis,were employed to delineate the boundaries between these flukes.Results Our analysis revealed that the endemic range of C.sinensis and O.viverrini in Southeast Asia primarily spans across part of China,Vietnam,Thailand,Laos,and Cambodia.During the period from 2000 to 2018,we identified C.sinensis infections in 84 distinct locations,predominantly in southern China(Guangxi Zhuang Autonomous Region)and northern Vietnam.In a stark contrast,O.viverrini was more widely distributed,with infections documented in 721 locations across Thailand,Laos,Cambodia,and Vietnam.Critical environmental determinants were quantitatively analyzed,revealing annual mean temperatures ranging between 14 and 20°C in clonorchiasis-endemic areas and 24-30°C in opisthorchiasis regions(P<0.05).The machine learning model effectively mapped a distinct demarcation zone,demonstrating a clear separation between the endemic areas of these two liver flukes with AUC from 0.9 to1.The study in Vietnam delineates the coexistence and geographical boundaries of C.sinensis and O.viverrini,revealing distinct endemic zones and a transitional area where both liver fluke species overlap.Conclusions Our findings highlight the critical role of specific c
基金funded by the Ministry of Education(MoE)and Ministry of Science and Technology(MoST),The Government of Bangladeshsupported by the JSPS Core-to-Core Program(JSJSCCB20200010).
文摘Background Opisthorchiid flukes,particularly Opisthorchis viverrini,Opisthorchis felineus,Clonorchis sinensis,and Metorchis spp.are the most common fish-borne zoonotic human liver flukes(hLFs).Liver fluke infections are more prevalent in resource-deprived and underprivileged areas.We herein estimated the prevalence of the metacercariae(MC)of major hLFs in common large freshwater fishes(lFWF)marketed for human consumption from some selected areas of Bangladesh along with detection of their molluscan vectors and reservoirs.Methods The current status of fish-borne zoonotic hLF infections in lFWF was investigated along with their molluscan vectors and mammalian reservoir hosts in Mymensingh and Kishoreganj in Bangladesh from July 2018-June 2022 using conventional and multiple molecular techniques,such as PCR,PCR-restriction fragment length polymorphism(RFLP),sequencing,and bioinformatic analyses.The infection rate of fishes was analyzed using the Z-test and the loads of MC were compared using the chi-squared(χ^(2))test.Results The MC of C.sinensis,Opisthorchis spp.,and Metorchis spp.were detected in 11 species of common and popular lFWF.In lFWF,the estimated prevalence was 18.7%and the mean load was 137.4±149.8 MC per 100 g of fish.The prevalence was the highest(P<0.05)in spotted snakehead fishes(Channa punctata,63.6%).The highest rate of infection(P<0.05)was observed with the MC of C.sinensis(11.8%).Metacercariae were almost equally(P>0.05)distributed between the head and body of fishes.The infection rate was slightly higher in cultured(19.6%)fishes.The MC of C.sinensis,O.felineus,O.viverrini,and Metorchis orientalis in fishes were confirmed using PCR,PCR-RFLP and bioinformatics.The cercariae of opisthorchiid(Pleurolophocercus cercariae)flukes were only recovered from Bithynia spp.(3.9%,42 out of 1089).The ova of hLFs from dogs(4.3%,5 out of 116)and cats(6.0%,6 out of 100),and adult flukes(M.orientalis)from ducks(41.1%113 out of 275)were detected.Conclusions The MC of hLFs are highly prevalent in fresh water fishe
基金Supported by the National Center for Genetic Engineering and Biotechnology (BIOTEC)the National Science and Technology Development Agency (NSTDA), Thailand, No. BT-B-06-MG-12-4405
文摘AIM： To investigate loss of heterozygosity （LOH） and microsatellite instability （MSI） on the chromosomal region 1p36-pter in cholangiocarcinoma （CCA） patients and determine the association between microsatellite alterations and clinicopathological parameters. METHODS： Ten polymorphic microsatellite markers were determined for LOH and MSI using GS-3000 gel scan fragment autoanalyzer. RESULTS： Sixty-eight out of 90 cases （75.6%） showed LOH in one or more loci. LOH was found most frequently at DIS199 （40.0%）, DIS507 （34.6%）, DIS2845 （30.5%）, and DIS2734 （30.1%）. MSI was found in 34 of 90 cases （37.8%） at one or more loci. Fine mapping at lp36 showed two distinctive regions of common loss, which were D1S2845 and the 25.5-cM region between D1S507 and D1S2734, indicating the existence of putative tumor suppressor genes that is likely to play important roles in the development of CCA. Patients with LOH at D1S234 showed less lymphatic invasion （P = 0.017）, whereas patients with LOH at D1S2676 exhibited more lymphatic invasion than those without （P = 0.031）. LOH at D1S2845 showed a significant correlation with nerve invasion （P = 0.029）. Moreover, patients who demonstrated MSI at D1S228 showed a poor prognosis （P = 0.0026）. CONCLUSION： Allelic loss plays a major role in microsatellite alterations at chromosome lp36, which may contribute to carcinogenesis and pathogenesis of liver fluke related CCA and these alterations can be used as molecular prognostic indicators for CCA patients.
基金Supported by Grant-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology Japan
文摘Cholangiocarcinoma(CCA) is a difficult cancer to diagnose in the early stage and to treat by curative resec-tion. The incidence of CCA in the northeast of Thailand is the highest in the world. To make progress in detecting a high risk group and in the prevention and detection of CCA, we have been analyzing the risk factors for CCA. Although liver fluke infection is known to be a risk factor, there are patients who are not infected with the liver fluke and not all people infected with the liver fluke will suffer from the disease. Therefore, it is of the utmost importance to analyze the risk factors and the mechanism to prevent the disease and also to detect the disease in its early stage to save patients' lives. Through collaboration among Thai and Japanese researchers, we analyzed the genetic and environmental determinants of risks for CCA. Also, we have been trying to develop methods to detect the disease in a non-invasive way. Without repeating findings reported in various reviews on CCA, we will first discuss the environmental and genetic determinants of the risks for CCA. Second, we will discuss the properties of CCA, including the etiological agents and the mechanism of cholangiocarcinogenesis, and finally, we will discuss future approaches to prevent and cure CCA from the standpoint of evidence-based medicine. We will discuss these points by including the data from our laboratories. We would like to emphasize the importance of the genetic data, especially whole genome approaches, to understand the properties of CCA, to find a high risk population for CCA and to develop effective preventative methods to stop the carcinogenic steps toward CCA in the near future. In addition, it is of the upmost importance to develop a non-invasive, specific and sensitive method to detect CCA in its early stage for the application of modern medical approaches to help patients with CCA.
文摘Liver fluke is a digenetic trematode parasitizing in the hepatic ducts of humans or animals. Patients with liver fluke infection suffer from a series of hepatobiliary diseases. The prevalence of cholangiocarcinoma is significantly high in areas with high incidence of clonorchiasis. Liver fluke is an important biocarcinogenic factor in the occurrence of cholangiocarcinoma. The secretory products of the body of this parasite and long-term mechanical stimulation will induce continuous inflammation of the bile duct. Gene expression of the bile duct cells is imbalanced, leading to bile duct carcinogenesis. This paper provides a summary of recent studies on the epidemiology, clinicopathology, and molecular biology of cholangiocarcinoma induced by liver fluke infection.
基金Supported by the Department of Research, College of Medicine and Public Healththe Division of Research Promotion, Ubon Rajathanee University, Thailand
文摘AIM： To investigate the knowledge, attitude and practice （KAP） in prevention and control of liver fluke infection in northeast Thailand. METHODS： A descriptive KAP survey pertaining to liver fluke infection was carried out in June 2005 to October 2006 using structured questionnaires. Data were collected by questionnaires consisting of general parameters, knowledge, attitude, practice, and a history of participation in the prevention and control of liver fluke infection. RESULTS： A total of 1077 persons who were interviewed and completed the questionnaires were enrolled in the study. The majority were females （69.5%） and many of them were 15-20 years of age （37.26%）. The questionnaires revealed that information resources on liver fluke infection included local public health volunteers （31.37%）, public health officers （18.72%）, televisions （14.38%）, local heads of sub-districts （12.31%）, doctors and nurses （9.18%）, newspaper （5.72）, intemets （5.37%）, and others （12.95%）. Fiftyfive point eleven percent of the population had a good level of liver fluke knowledge concerning the mode of disease transmission and 79.72% of the population had a good level of prevention and control knowledge with regards to defecation and consumption. The attitude and practice in liver fluke prevention and control were also at a good level with a positive awareness, participation, and satisfaction of 72.1% and 60.83% of the persons studied. However, good health behavior was found in 39.26% and 41.42% of the persons studied who had unhygienic defecation and ate raw cyprinoid＇s fish. The result also showed that 41.25% of the persons studied previously joined prevention and control campaigns. CONCLUSION： The persons studied have a high level of liver fluke knowledge and positive attitude. However, improvement is required regarding personal hygiene specifically with hygienic defecation and consumption of undercooked fish.
基金Supported by the Research Grants from Khon Kaen University, No. 48-03-1-01-03 the Center for Research and Development in Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, No 06-01
文摘AIM： To determine allelic imbalance on chromosomal region 21q22-qter including trefoil factor family genes （TFF） in cholangiocarcinoma （CCA） patients and analyze the correlation between allelic imbalances and clinicopathological parameters. METHODS： Quantitative PCR amplification was performed on four microsatellite markers and trefoil factor family genes （TFF1, TFF2, and TFF3） using a standard curve and SYBR Green I dye method. The relative copy number was determined by DNA copy number of tested locus to reference locus. The relative copy number was interpreted as deletion or amplification by comparison with normal reference range. Associations between allelic imbalance and clinicopathological parameters of CCA patients were evaluated by χ^2-tests. Kaplan-Meier method was used to analyze survival. RESULTS： The frequencies of amplification at D21S1890, D21S1893, and TFF3 were 32.5%, 30.0%, and 28.7%, respectively. Patients who had amplification at regions covering D21S1893, D21S1890, and TFF showed poor prognosis, whereas patients who had deletion showed favorable prognosis （mean： 51.7 wk vs 124.82 wk, P = 0.012）. Multivariate Cox regression analysis revealed that amplification of D21S1893, D21S1890 and TFF, blood vessel invasion, and staging were associated with poor prognosis. CONCLUSION： D21S1893-D21S1890 region may harbor candidate genes especially TFF and serine protease family, which might be involved in tumor invasion and metastasis contributing to poor survival. The amplification in this region may be used as a prognostic marker in the treatment of CCA patients.
文摘Objective: To evaluate the effects of lead in the morphology and viability of Fasciola gigantica(F. gigantica)(giant liver fluke) isolated from infected livers of carabaos in vitro using the following concentrations of lead: 0, 100, 150 and 200 mg/L. Methods: In vitro viability and motility assay was conducted to evaluate the ef ects of lead using 1% methylene blue as the vital dye for assessment of the l ukes' viability. Results: Results indicate that F. gigantica can tolerate lead exposure as high as 200 mg/L with visible morphological variations. Upon exposure to lead, liver l ukes tend to curl and excrete black precipitates as a sign of physiological stress response. Furthermore, the lethal concentration(LC50) of lead against F. gigantica in vitro was 160 mg/L. Conclusions: In conclusion, tolerance of liver flukes to high levels of lead suggests its potential as a possible biomarker of environmental pollution.
基金Supported by Gastroenterological Association of Thailand(GAT)the Division of Gastroenterology,Department of Medicine,Chulalongkorn Universitythe Department of Medicine,Faculty of Medicine,Chulalongkorn University,Bangkok,Thailand
文摘AIM To identify the potential risk factors of cholangiocarcinoma, we determined the characteristics of cholangiocarcinoma patients among 5 different regions of Thailand. METHODS All patients diagnosed with cholangiocarcinoma between 2008 and 2013 were identified using the Nationwide Hospital Admission Data registry(n = 39421). Baseline characteristics, comorbidities and survival were abstracted. RESULTS The annual incidence during the study period was stable in all regions. Most patients lived in the Northeast(62.8%), followed by the North(16.9%), Central(12.3%), Bangkok(5.4%), and South(n = 2.6%) regions(P < 0.0001). Significantly more cholangiocarcinoma patients had diabetes, cirrhosis, and chronic viral hepatitis B/C infection than noncholangiocarcinoma participants(diabetes: 11.42% vs 5.28%; cirrhosis: 4.81% vs 0.92%; hepatitis B: 0.74% vs 0.12%; and hepatitis C: 0.50% vs 0.10%, P < 0.0001 for all, respectively). The overall 1-year mortality rate was 81.7%, with a stable trend over time. CONCLUSION Diabetes and chronic liver diseases may be associated with cholangiocarcinoma in the Thai population.
