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Involvement of PI3K and ERK1/2 pathways in hepatocyte growth factor-induced cholangiocarcinoma cell invasion

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World Journal of Gastroenterology 2010年第6期16卷 713-722页

作者： Apaporn Menakongka Tuangporn Suthiphongchai Department of Biochemistry Faculty of ScienceMahidol University

AIM:To investigate the role of hepatocyte growth factor(HGF) in cholangiocarcinoma(CCA) cell invasiveness and the mechanisms underlying such cellular responses. METHODS:Effects of HGF on cell invasion and motility were investigated in two human CCA cell lines,HuCCA-1 and KKU-M213,using Transwell in vitro *** of proteins of interest and their phosphorylated forms were determined by Western *** of E-cadherin was analyzed by immunofluorescence staining and visualized under confocal microscope. Activities of matrix degrading enzymes were determined by zymography. RESULTS:Both CCA cell lines expressed higher Met levels than the H69 immortalized cholangiocyte cell *** induced invasion and motility of the cell lines and altered E-cadherin from membrane to cytoplasm localization,but did not affect the levels of secreted matrix metalloproteinase(MMP) -2,MMP-9 andurokinase plasminogen activator,key matrix degrading enzymes involved in cell ***,HGF stimulated Akt and extracellular signal-regulated kinase(ERK) 1/2 phosphorylation but with slightly different kinetic profiles in the two cell *** of the phosphoinositide 3-kinase(PI3K) /Akt pathway by the PI3K inhibitor,LY294002,markedly suppressed HGFstimulated invasion of both CCA cell lines,and inhibition of the ERK pathway by U0126 suppressed HGF-induced invasion of the KKU-M213 cell line but had a moderate effect on HuCCA-1 cells. CONCLUSION:These data indicate that HGF promotes CCA cell invasiveness through dys-localization of E-cadherin and induction of cell motility by distinct signaling pathways depending on cell line type.

关键词： Hepatocyte growth factor Invasion Cholangiocarcinoma Phosphoinositide 3-kinase Extracellular signal-regulated kinase

High expression of ErbB2 contributes to cholangiocarcinoma cell invasion and proliferation through AKT/p70S6K

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World Journal of Gastroenterology 2010年第32期16卷 4047-4054页

作者： Warapen Treekitkarnmongkol Tuangporn Suthiphongchai Department of Biochemistry Faculty of ScienceMahidol UniversityBangkok 10400Thailand

AIM:To compare the impact of ErbB2 on cell invasion and proliferation in cholangiocarcinoma(CCA) cell ***:Level of endogenous ErbB2 expression in three CCA cell lines,namely HuCCA-1,KKU-100 and KKU-M213,was determined by real-time reversetranscriptase polymerase chain *** ErbB2 inhibitory methods,a small molecule ErbB2 kinase inhibitor(AG825) and siRNA,were used to disrupt ErbB2 function in the cell *** cell invasion,motility and proliferation under ErbB2-disrupted conditions were detected using Transwell and 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide *** addition,ErbB2 downstream effectors were investigated by Western blotting ***:Suppression of ErbB2 activity,using a specific kinase inhibitor(AG825),reduced invasion,motility and proliferation of all three CCA cell *** ability of this drug to inhibit neoplastic properties(invasion,motility and proliferation) increased concomitantly with the level of ErbB2 ***,knockdown of ErbB2 level by siRNA inhibited cell invasion and proliferation of KKU-M213,a high-ErbB2-expressing cell,better than those of the lower-ErbB2-expressing cells,HuCCA-1 and ***,both inhibitory methods indicated that there is more ErbB2-dependency for malignancy of the high-ErbB2-expressing cell,KKU-M213,than for that of low-ErbB2-expressing *** addition,interrupting ErbB2 activity decreased phosphorylation of AKT and p70S6K,but not extracellular signal-regulated kinase 1/2,in the high-ErbB2-expressing CCA cell ***:Our data indicated that high ErbB2 expression enhances CCA invasion,motility and proliferation via the AKT/p70S6K pathway,which suggests the possibility of targeting these molecules for CCA therapy.

关键词： AKT Cholangiocarcinoma ErbB2 Invasion p70S6K Cell proliferation

Prognostic value of DNA alterations on chromosome 17p13.2 for intrahepatic cholangiocarcinoma

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World Journal of Gastroenterology 2007年第21期13卷 2986-2991页

作者： Ubol Chuensumran Sopit Wongkham Chawalit Pairojkul Siri Chauin Songsak Petmitr Department of Tropical Nutrition and Food Science Faculty of Tropical MedicineMahidol UniversityBangkok 10400Thailand Liver Fluke and Cholangiocarcinoma Research Center Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand

AIM:To characterize and evaluate DNA alterations among intrahepatic cholangiocarcinoma (ICC) patients. METHODS:DNA from tumor and corresponding normal tissues of 52 patients was amplified with 33 arbitrary primers. The DNA fragment that alters most frequently in ICC was cloned,sequenced,and identified by comparison with known nucleotide sequences in the genome database (***). The DNA copy numbers of the allelic alterations in cholangiocarcinoma were determined by quantitative real-time PCR and interpreted as allelic loss or DNA amplification by comparison with the reference gene. Associations between allelic imbalance and clinicopathological parameters of ICC patients were evaluated by χ2-test. The Kaplan-Meier method was used to analyze survival rates. RESULTS:From 33 primers,an altered DNA fragment (518 bp) amplified from BC17 random primer was found frequently in the tumors analyzed and mapped to chromosome 17p13.2. Sixteen of 52 (31%) cases showed DNA amplification,while 7 (13%) showed allelic loss. Interestingly,DNA amplification on chromosome 17p13.2 was associated with a good prognosis,median survival time (wk) of amp vs no amp was 44.14 vs 24.14,P=0.002; whereas allelic loss of this DNA sequence corresponded with a poor prognosis,median survival time (wk) of loss vs no loss was 18.00 vs 28.71,P=0.019). Moreover,Kaplan-Meier curves comparing the DNA alterations with survival depicted highly significant separation that the median survival time equal to DNAamplification,allelic loss,and normal was 44.14 wk,18.00 wk,and 24.29 wk,respectively (P=0.005). CONCLUSION:Alterations in the DNA sequence on chromosome 17p13.2 may be involved in cholangio-carcinogenesis,and could be used as a prognostic marker in the treatment of ICC patients.

关键词： Intrahepatic cholangiocarcinoma 17p13.2 Allelic imbalance Prognosis

Ultrasound calibration with ladder phantom at multiple depths for breast biopsy navigation system

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Theoretical & Applied Mechanics Letters 2020年第5期10卷 343-353页

作者： Jackrit Suthakorn Narucha Tanaiutchawoot Cholatip Wiratkapan Center for Biomedical and Robotics Technology(BART LAB)Department of Biomedical Engineering Faculty of EngineeringMahidol UniversitySalayaThailand Breast Diagnostic Center Division of Diagnostic RadiologyDepartment of RadiologyFaculty of MedicineRamathibodi HospitalMahidol UniversityBangkokThailand

Ultrasound guided breast biopsy navigation system with a graphical user interface and a passive robotic needle holder is developed to increase the performance and reliability of the *** calibration and tool tip calibration are required before using the system.A ladder phantom is developed to be used for ultrasound calibration in real time system with only one ultrasound image *** passive robotic needle holder structure results in an identity matrix for the makes the rotation matrix;therefore,only translation and scaling are required in the *** method can be applied to multiple ultrasound depths,which has a relationship at each depth and a relationship to the ultrasound image on the *** results show high accuracy(<1 mm.)and rapid calibration(5–10 minutes)which is suitable for a real time system like a breast biopsy navigation system based on tests with a breast phantom.

关键词： Ultrasound calibration system Ladder phantom Multi ultrasound depth Passive robotic needle holder

Thai nurses' perceptions and practices of family-centered care: The implementation gap

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International Journal of Nursing Sciences 2020年第1期7卷 74-80页

作者： Tassanee Prasopkittikun Arunrat Srichantaranit Sirisopa Chunyasing Faculty of Nursing Mahidol UniversityBangkokThailand Department of Nursing Siriraj Hospital Mahidol UniversityBangkokThailand

Objectives:This study was conducted to examine the differences between perceptions and practices of family-centered care among Thai pediatric ***:This mixed-methods study consisted of two phases,in the first phase,a descriptive comparative design using the Family-Centered Care Questionnaire-Revised(FCCQ-R)was administered to 142 pediatric nurses from a university hospital in Bangkok,*** the second phase,qualitative interviews were conducted with 16 pediatric nurses to gather complementary information regarding the major findings from the first ***:The results revealed that family strengths and individuality were rated the highest as the most important elements and the most frequent ***/professional collaboration was perceived as the least important element,while the design of the heath care delivery system was rated as the least frequent *** qualitative data revealed that the major reasons for suboptimal implementation included a common perception that family-centered care is a Western concept,nurses'weak attitudes towards their roles,and a shortage of ***:Nurses agreed that the identified elements of family-centered care were necessary but that they did not incorporate the concepts into their daily nursing practice to maintain their endorsement of the family-centered care *** study is needed to explore how family-centered care is understood and operationalized by Thai nurses and how hospital administration and environments can be modified to support this care model.

关键词： Cognition Family-centered care Hospitals Nurses Pediatric Thailand

Detection and characterization of Chlamydophila psittaci in asymptomatic feral pigeons(Columba livia domestica) in central Thailand

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Asian Pacific Journal of Tropical Medicine 2015年第2期8卷 94-97页

作者： Ladawan Sariya Phirom Prompiram Siriporn Tangsudjai Kanaporn Poltep Tatiyanuch Chamsai Chalisa Mongkolphan Kamolphan Rattanavibul Verachai Sakdajivachareon Monitoring and Surveillance Center for Zoonotic Diseases in Wildlife and Exotic Animals Faculty of Veterinary ScienceMahidol UniversitySalayaNakhon PathomThailand 73170 Division of Veterinary Public Health Department of HealthBangkok Metropolitan AdministrationPhra NakhonBangkokThailand 10200

Objective:To detect and characterize Chlamydophila psittaci(***) in asymptomatic feral pigeons in central ***:A total 814 swabs from the trachea and cloacae of 407non-clinical feral pigeons in central Thailand were collected and tested for the presence of ***:A 10.8%of feral pigeons in the sample group were positive as determined by nested PCR primer specific to *** outer membrane protein A(orupA) gene of positive samples exhibited amino acid identity of *** ranging from 71 to 100%and were grouped in genotype ***,BF1676-56 isolate was closely related to Chlamydia avium with99%identification of the I6 S ribosomal(r) RNA ***:This is the first report on *** isolated from asymptomatic feral pigeons in Thailand,which provides knowledge for the disease status in pigeon populations in Thailand.

关键词： Chlamydophila psittaci Psittacosis ompA gene Feral pigeon

Screening of Fabry disease in patients with end-stage renal disease of unknown etiology:the first Thailand study

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The Journal of Biomedical Research 2017年第1期31卷 17-24页

作者： Objoon Trachoo Paisan Jittorntam Sarunpong Pibalyart Saowanee Kajanachumphol Norasak Suvachittanont Suthep Patputthipong Piyatida Chuengsaman Arkom Nongnuch department of medicine faculty of medicineramathibodi hospitalmahidol universityBangkok 10400Thailand center for medical genomics faculty of medicineramathibodi hospitalmahidol universityBangkok 10400Thailand graduate program in translational medicine faculty of medicineramathibodi hospitalmahidol universityBangkok 10400Thailand ramathibodi research center faculty of medicineramathibodi hospitalmahidol universityBangkok 10400Thailand department of medicine uttaradit hospitalUttaradit 53000Thailand capd service and training center banphaeo hospital(public organization)-prommitr branchBangkok 10110Thailand

We aimed to explore the prevalence of Fabry disease in Thai patients who were diagnosed with end-stage renal disease（ESRD） of an unknown *** blood samples were collected from ESRD patients for biochemical and molecular ***-galactosidase A（a-GAL A） screening was performed from dried-blood spots using *** confirmation was performed using DNA sequencing of the GLA gene.A total of 142 male and female patients were included in this *** patients（7.04%） exhibited a significant decrease in a-GAL A *** were no definitive pathogenic mutations observed in the molecular ***,four patients revealed a novel nucleotide variant at c.l-10 C〉T,which was identified as a benign variant following screening in the normal *** conclusion,the a-GAL A assay utilizing dried-blood spots revealed a significant false positive *** was no definitive Fabry disease confirmed in Thai patients diagnosed with ESRD of unknown etiology.

关键词： Fabry disease end-stage renal disease(ESRD) Alpha-galactosidase A(α-GAL A)

Single dose dexamethasone prophylaxis of postembolisation syndrome after chemoembolisation in hepatocellular carcinoma patient:A randomised,double-blind,placebo-controlled study

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World Journal of Clinical Cases 2021年第30期9卷 9059-9069页

作者： Panot Sainamthip Chutcharn Kongphanich Naiyarat Prasongsook Sakkarin Chirapongsathorn Department of Pharmacology Chulalongkorn UniversityBangkok 10330Thailand Department of Radiology Phramongkutklao College of MedicineBangkok 10400Thailand Division of Medical Oncology Department of MedicinePhramongkutklao College of MedicineBangkok 10400Thailand Division of Gastroenterology and Hepatology Department of MedicinePhramongkutklao College of MedicineJatujak 10900Thailand

BACKGROUND Even in the immuno-oncology era,transcatheter arterial chemoembolisation(TACE)is the most effective way to treat intermediate stage hepatocellular carcinoma(HCC).Postembolisation syndrome(PES)is the most common side effect from TACE and there is still no standard prevention *** To evaluate the efficacy of single dose intravenous dexamethasone regimen to prevent PES after TACE among patients with *** This study enrolled patients with HCC who had eligible indication for TACE without macrovascular invasion/extrahepatic *** were randomly assigned to either an intravenous single dose of dexamethasone 8 mg or placebo one hour before *** primary outcome was a negative result of PES at 48 h after TACE,which was defined as score<2 of Southwest Oncology Group toxicity coding criteria using fever,nausea,vomiting and pain to *** the secondary end point was duration of admission between two *** One hundred patients were randomly assigned 1:*** intention-to-treat analysis,49 patients were randomly assigned to the dexamethasone and 51 to the placebo *** groups were similar for baseline *** negative PES rate was significantly higher in the dexamethasone group than in the placebo group(63.3%vs 29.4%;P=0.005).Mean Southwest Oncology Group toxicity coding PES was 2.14(95%CI:1.41-2.8)vs 3.71(95%CI:2.97-4.45)between the dexamethasone and placebo groups,*** incidence of fever was significantly lower in dexamethasone group with P<0.001,pain,nausea and vomiting were also lower in the dexamethasone group compared with the placebo group(P=0.16,P=0.11,and P=0.49).The dexamethasone regimen was generally well tolerated by patients with HCC patients including those with hepatitis B virus infection and well-controlled diabetes *** Single dose dexamethasone was effective at preventing PES among patients with HCC treated with *** study showed no adverse events

关键词： Hepatocellular carcinoma Chemoembolization Dexamethasone Double blind method Prevention Postembolization syndrome

Influence of chemical penetration enhancers on skin permeability of ellagic acid-loaded niosomes

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Asian Journal of Pharmaceutical Sciences 2013年第2期8卷 110-117页

作者： Varaporn Buraphacheep Junyaprasert Pratyawadee Singhsa Anchalee Jintapattanakit Excellent Center of Innovative Drug Delivery and Nanomedicine Department of PharmacyFaculty of PharmacyMahidol UniversityRajathaveeBangkok 10400Thailand

This study aimed to develop niosomes of ellagic acid(EA),a potent antioxidant phytochemical substance,for dermal delivery and to investigate the influence of chemical penetration enhancers on the physicochemical properties of EA-loaded *** EA niosomes were prepared by reverse phase evaporation method using Span 60,Tween 60 and cholesterol as vesicle forming agents and Solulan C24 as a steric *** glycol 400(PEG)was used as a solubilizer while dimethylsulfoxide(DMSO)or Nmethyl-2-pyrrolidone(NMP)was used as a skin penetration *** was found that the mean particle sizes of EA-loaded niosomes were in the range of 312e402 nm with PI values of lower than *** niosomes were determined to be spherical multilamellar vesicles as observed by transmission electron microscope and optical *** niosomes were stable after 4 months storage at 4*** vitro skin permeation through human epidermis revealed that the skin enhancers affected the penetration of EA from the niosomes at 24 *** DMSO niosomes showed the highest EA amount in epidermis;whereas the NMP niosomes had the highest EA amount in the acceptor ***,the skin distribution by confocal laser scanning microscopy showed the high fluorescence intensity of the DMSO niosomes and NMP niosomes at a penetration depth of between 30e90 mm(the epidermis layer)and 90e120 mm(the dermis layer)under the skin,*** the results,it can be concluded that the DMSO niosomes are suitable for epidermis delivery of EA while the NMP niosomes can be used for dermis delivery of EA.

关键词： Ellagic acid Niosomes Chemical penetration enhancer Skin permeation Dermal delivery