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| 1 | Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines显示文摘AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemotherapeutic drugs including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), glutathione-S-transferase P1 (GSTP1), multidrug resistance protein (MDR1) and multidrug resistance-associated proteins (MRPs) were also determined.METHODS: Five human CCA cell lines (KKU-100, KKU M055, KKU-M156, KKU-M214 and KKU-OCA17) weretreated with various chemotherapeutic drugs and growth inhibition was determined by 3-(4,5-dimethylthiazol-2-yl)5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Semi-quantitative levels of gene expression were determined by a reverse transcriptase polymerase chain reaction (RT-PCR). Results of IC50 values and the ratios of gene expression were analyzed by linear regression to predict their relationship. RESULTS: Among five CCA cell lines, KKU-M055 was the most sensitive cell line towards all chemotherapeutic drugs investigated, particularly taxane derivatives with IC50 values of 0.02-3 nmol/L, whereas KKU-100 was apparently the least sensitive cell line. When compared to other chemotherapeutic agents, doxorubicin and pirarubicin showed the lowest IC50 values (<5 μmol/L) in all five CCA cell lines. Results from RT-PCR showed that TS, MRP1, MRP3 and GSTP1 were highly expressed in these five CCA cell lines while DPD and MRP2 were only moderately expressed. It should be noted that MDR1 expression was detected only in KKU-OCA17 cell lines. A strong correlation was only found between the level of MRP3 expression and the IC50 values of etoposide, doxorubicin and pirarubicin (r = 0.86-0.98, ,P<0.05). CONCLUSION: Sensitivity to chemotherapeutic agents is not associated with the histological type of CCA. Choosing of the appropriate chemotherapeutic regimen for the treatment of CCA requires knowledge of drug sensitivity. MRP3 was correlated with resistance of CCA cell lines to etoposide, doxorubicin and pirarubicin, whereas other chemotherapeutic drugs showed no association. The roleof this multidrug resistance-associated protein, MRP3, in chemotherapeutic resistance in CCA patients needs to be further investigated. | Nisana Tepsiri Liengchai Chaturat Banchob Sripa Wises Namwat Sopit Wongkham Vajarabhongsa Bhudhisawasdi Wichittra Tassaneeyakul | 2005 | World Journal of Gastroenterology2005，11，18： | 10 |
| 2 | Nitrative and oxidative DNA damage in intrahepatic cholangiocarcinoma patients in relation to tumor invasion显示文摘AIM: Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine(8-oxodG) formation has been implicated in initiation and/or promotion of inflammation-mediated carcinogenesis.The aim of this study is to clarify whether these DNA lesions participate in the progression of intrahepatic cholangiocarcinoma.METHODS: We investigated the relation of the formation of 8-nitroguanine and 8-oxodG and the expression of hypoxia-inducible factor-1α (HIF-1α) with tumor invasion in 37 patients with intra-hepatic cholangiocarcinoma.RESULTS: Immunohistochemical analyses revealed that 8-nitroguanine and 8-oxodG formation occurred to a much greater extent in cancerous tissues than in non-cancerous tissues. HIF-1α could be detected in cancerous tissues in all patients, suggesting low oxygen tension in the tumors.HIF-1α expression was correlated with inducible nitric oxide synthase (iNOS) expression (r= 0.369 and P = 0.025)and 8-oxodG formation (r = 0.398 and P = 0.015).Double immunofluorescence study revealed that iNOS and HIF-1α co-localized in cancerous tissues. Notably, the formation of 8-oxodG was correlated significantly with lymphatic invasion (r = 0.386 and P= 0.018). Moreover, 8-nitroguanine and 8-oxodG in non-cancerous tissues were associated significantly with neural invasion (P = 0.042and P = 0.026, respectively). These results suggest that reciprocal activation between HIF-1α and iNOS mediates persistent DNA damage, which induces tumor invasiveness via mutations, resulting in poor prognosis.CONCLUSION: The formation of 8-nitroguanine and 8-oxodG plays an important role in multiple steps of genetic changes leading to tumor progression, including invasiveness. | Somchai Pinlaor Banchob Sripa Ning Ma Yusuke Hiraku Puangrat Yongvanit Sopit Wongkham Chawalit Pairojkul Vajarabhongsa Bhudhisawasdi Shinji Oikawa Mariko Murata Reiji Semba Shosuke Kawanishi | 2005 | World Journal of Gastroenterology2005，11，30： | 9 |
| 3 | MUC1 and MUC5AC mucin expression in liver fluke-associated intrahepatic cholangiocarcinoma显示文摘AIM: To investigate the expressions of MUC1 and MUC5AC in intrahepatic cholangiocarcinoma (ICC). Association of expressions of mucins MUC1 and MUC5AC with clinical findings, metastasis, and survival of the liver fluke-associated ICC patients was determined.METHODS: The expressions of MUC1 and MUC5AC mucins were examined by immunohistochemical staining in 87cases of histologically-proven ICC. The expressions of mucins in relationship between clinicopathological significance and prognosis of the patients were evaluated.RESULTS: Fifty-two patients (60%) exhibited both MUC1 and MUC5AC expressions, whereas 31% expressed either MUC1or MUC5AC, and 9% expressed neither. High MUC1immunoreactivity displayed a significant correlation with tumor progression as reflected by vascular invasion (P<0.001),whereas high expression of MUC5AC significantly correlated with neural invasion (P = 0.022) and advanced ICC stage (P = 0.008). Patients with high expression of MUC1 had a significantly shorter survival (P = 0.0002). According to multivariate analyses, MUC1 reactivity (P = 0.026),histological grading and stage of tumor represented the least probability of survival.CONCLUSION: MUC1 is overexpressed in liver flukeassociated cholangiocarcinoma and relates to vascular invasion and poor prognosis, whereas MUC5AC mucin is neoexpressed and relates to neural invasion and advanced ICC stage. High MUC1 expression in tumor may be useful for predicting the poor outcome of ICC patients. | Chanchai Boonla Banchob Sripa Peti Thuwajit Ubon Cha-On Anucha Puapairoj Masanao Miwa Sopit Wongkham | 2005 | World Journal of Gastroenterology2005，11，32： | 6 |
| 4 | Gene expression profiling defined pathways correlated with fibroblast cell proliferation induced by Opisthorchis viverrini excretory /secretory product显示文摘瞄准:为了调查成纤维细胞房间增长的机制,由麝后睾吸虫刺激了分泌 / 能分泌(ES ) 产品。方法:NIH-3T3,老鼠成纤维细胞房间与 O 被对待。由与成年寄生虫 co 有教养的非接触的 viverrini ES 产品。从 NIH-3T3 的全部的 RNA 对待并且与 O 未经治疗。viverrini 被提取,抄录的颠倒和有老鼠 15K 的 hybridized 互补 DNA (cDNA ) 数组。结果被 ArrayVision 版本 5 和 GeneSpring 版本 5 软件分析。在正规化以后,寄生虫的基因表示的比率对待到第 2-a 更多褶层的未经治疗的 NIH-3T3 房间在上面调整当差别表示了基因,被定义。信号转导变异基因的表达式层次被半量的基于 SYBR 的即时 RT-PCR 验证。结果:在 15,000 genes/ESTs 的一个总数之中,有确定的房间的 239 基因增长相关的功能是 2 褶层 -- 并且由 O 的 more-up-regulated。在没有到寄生产品的暴露的房间的与那些相比的 viverrini ES 产品。这些基因被分类进包括的组精力和新陈代谢,信号转导变异,蛋白质合成和翻译,矩阵和结构的蛋白质,抄写控制,房间周期和 DNA 复制。而且, serine-threonine 激酶受体,受体酷氨酸激酶和骨胶原的表情生产相关的基因由 O 是起来调整的。viverrini ES 产品。信号转导变异基因的表达式水平;pkC, pdgfr 高山哈, jak 1, eps 8,即时 RT-PCR 测量的 tgf 贝它 1i4,带和 h 地岬证实了他们的表示层次到从 cDNA 获得的那些数组。然而,仅仅 pkC 的起来调整的表示, eps 8 并且是表皮的生长因素(EGF ) 或转变生长因素贝它(TGF 贝它) 显示出的任何一个的下游的发信号分子的 tgfbeta 1i4 统计意义(P <
0.05 ) 。结论:O。viverrini ES 产品在几个功能的范畴和这些刺激基因表示的重要变化主要包括与房间增长有关的抄本。TGF 贝它和 EGF 信号转导变异小径作为 O 的可能的小径被显示。驾驶 viverrini 的房间增长。 | Chanitra Thuwajit Peti Thuwajit Kazuhiko Uchida Daoyot Daorueang Sasithorn Kaewkes Sopit Wongkham Masanao Miwa | 2006 | World Journal of Gastroenterology2006，12，22： | 5 |
| 5 | Expression of sialyl Lewis^a relates to poor prognosis in cholangiocarcinoma显示文摘AIM: High levels of serum sialyl Lewisa (sLea) are frequently found in cholangiocarinnoma (CCA) patients and have been suggested to be a serum marker for CCA. However, the significance of this antigen in CCA is unknown. In this study,the clinical significance of sLea expression in CCA tissues and the possible role of sLea in vascular invasion in vitro were elucidated.METHODS: Expression of sLea in tumor tissues of 77patients with mass-forming CCA and 33 with periductal infiltrating CCA was determined using immunohistochemistry.The in vitro assays on adhesion and transmigration of CCA cells to human umbilical vein endothelial cells were compared between CCA cell lines with and without sLea expression.RESULTS: sLea was aberrantly expressed in 60% of CCA tumor tissues. A significant relationship was found between the frequency of sLea expression and the mass-forming type CCA (P = 0.041), well differentiated histological grading (P = 0.029), and vascular invasion (P = 0.030). Patients with positive sLea expression had a significantly poorer prognosis (21.28 wk, 95% CI = 16.75-25.81 wk) than those negative for sLea (37.30 wk, 95% CI = 27.03-47.57 wk)(P<0.001). Multivariate analysis with adjustment for all covariates showed that patients positive for sLea possessed a 2.3-fold higher risk of death than patients negative for sLea (P<0.001). The role of sLea in vascular invasion was demonstrated using in vitro adhesion and transmigration assays. KKU-M213, a human CCA cell-line with a high expression of sLea, adhered and transmigrated to IL-1β-activated endothelial cells of the human umbilical vein more than KKU-100, the line without sLea expression (P<0.001).These processes were significantly diminished when the antibodies specific to either sLea or E-selectin were added to the assays (P<0.001).CONCLUSION: This study demonstrates the clinical significance of sLea expression in vascular invasion, and an unfavorable outcome in CCA. The role of sLea in vascular invasion which may lead to poor prognosis is supported by the in vitro adhesion and transmigration studies. | Apa Juntavee Banchob Sripa Ake Pugkhem Narong Khuntikeo Sopit Wongkham | 2005 | World Journal of Gastroenterology2005，11，2： | 2 |
| 6 | Polymorphism of glutathione S -transferase Omega gene and risk of cancer显示文摘 | Sujan Babu Marahatta Phaibul Punyarit Vajarabhongsa Bhudisawasdi Anucha Paupairoj Sopit Wongkham Songsak Petmitr | 2005 | Cancer Letters2005，，2： | 1 |
| 7 | Selective activity of Streblus asper on Mutans streptococci显示文摘 | SUWIMOL T SOPIT W SUPAPORN C | 2000 | J of Ethnopharmacology2000，70，1： | 1 |
| 8 | Genetic and environmental determinants of risk for cholangiocarcinoma in Thailand显示文摘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. | Masanao Miwa Satoshi Honjo Gyokukou You Masakazu Tanaka Kazuhiko Uchida Petcharin Srivatanakul Thiravud Khuhaprema Watcharin Loilome Anchalee Techasen Chaisiri Wongkham Temduang Limpaiboon Puangrat Yongvanit Sopit Wongkham | 2014 | World Journal of Gastrointestinal Pathophysiology2014，5，4： | 1 |
| 9 | Decreased expression of galectin-3 is associated with metastatic potential of liver fluke-associated cholangiocarcinoma显示文摘 | Mutita Junking Chaisiri Wongkham Banchob Sripa Kanlayanee Sawanyawisuth Norie Araki Sopit Wongkham | 2008 | European Journal of Cancer2008，，4： | 1 |
| 10 | The dielectric response of electrostrictive (1-x)PMN-xPZT ceramics显示文摘 | Shilnikov A V Sopit A V | 1999 | JECS1999，19，： | 1 |
| 11 | Roles and Mechanisms of β-Thymosins in Cell Migration and Cancer Metastasis: An Update显示文摘 | Sirinapa Sribenja Sopit Wongkham Chaisiri Wongkham Qizhi Yao Changyi Chen | 2013 | Cancer Investigation2013，，2： | 1 |
| 12 | CA ‐S27: A novel Lewis a associated carbohydrate epitope is diagnostic and prognostic for cholangiocarcinoma显示文摘 | Atit Silsirivanit Norie Araki Chaisiri Wongkham Kulthida Vaeteewoottacharn Chawalit Pairojkul Kazuhiko Kuwahara Yoshiki Narimatsu Hiromichi Sawaki Hisashi Narimatsu Seiji Okada Nobuo Sakaguchi Sopit Wongkham | 2013 | Cancer Sci2013，，10： | 1 |
| 13 | Prognostic value of DNA alterations on chromosome 17p13.2 for intrahepatic cholangiocarcinoma显示文摘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 (www.ncbi.nlm.nih.gov). 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. | Ubol Chuensumran Sopit Wongkham Chawalit Pairojkul Siri Chauin Songsak Petmitr | 2007 | World Journal of Gastroenterology2007，13，21： | 0 |
| 14 | γ-aminobutyric acid B2 receptor:A potential therapeutic target for cholangiocarcinoma in patients with diabetes mellitus显示文摘BACKGROUND The association between diabetes mellitus(DM)and the increased risk and progression of cholangiocarcinoma(CCA)has been reported with unclear underlying mechanisms.Previous studies showed thatγ-aminobutyric acid(GABA)B2 receptor(GABBR2)was upregulated in CCA cells cultured in high glucose(HG)conditions.Roles of GABA receptors in CCA progression have also been studied,but their association with DM and hyperglycemia in CCA remains unclarified.AIM To investigate the effects of hyperglycemia on GABBR2 expression and the potential use of GABBR2 as a CCA therapeutic target.METHODS CCA cells,KKU-055 and KKU-213A,were cultured in Dulbecco Modified Eagle’s Medium supplemented with 5.6 mmol/L(normal glucose,NG)or 25 mmol/L(HG)glucose and assigned as NG and HG cells,respectively.GABBR2 expression in NG and HG cells was investigated using real-time quantitative polymerase chain reaction and western blot.Expression and localization of GABBR2 in CCA cells were determined using immunocytofluorescence.GABBR2 expression in tumor tissues from CCA patients with and without DM was studied using immunohistochemistry,and the correlations of GABBR2 with the clinicopathological characteristics of patients were analyzed using univariate analysis.Effects of baclofen,a GABA-B receptor agonist,on CCA cell proliferation and clonogenicity were tested using the MTT and clonogenic assays.Phospho-kinases arrays were used to screen the affected signaling pathways after baclofen treatment,and the candidate signaling molecules were validated using the public transcriptomic data and western blot.RESULTS GABBR2 expression in CCA cells was induced by HG in a dose-and time-dependent manner.CCA tissues from patients with DM and hyperglycemia also showed a significantly higher GABBR2 expression compared with tumor tissues from those with euglycemia(P<0.01).High GABBR2 expression was significantly associated with a poorer non-papillary histological subtype but with smaller sizes of CCA tumors(P<0.05).HG cells of both tested CCA cell lines were more sensitive to baclofen treatment.Baclofen significantly suppressed the proliferation and clonogenicity of CCA cells in both NG and HG conditions(P<0.05).Phospho-kinase arrays suggested glycogen synthase kinase 3(GSK3),β-catenin,and the signal transducer and activator of transcription 3(STAT3)as candidate signaling molecules under the regulation of GABBR2,which were verified in NG and HG cells of the individual CCA cell lines.Cyclin D1 and c-Myc,the common downstream targets of GSK3/β-catenin and STAT3 involving cell proliferation,were accordingly downregulated after baclofen treatment.CONCLUSION GABBR2 is upregulated by HG and holds a promising role as a therapeutic target for CCA regardless of the glucose condition. | Charupong Saengboonmee Supannika Sorin Sakkarn Sangkhamanon Surang Chomphoo Somsiri Indramanee Wunchana Seubwai Kanyarat Thithuan Ching-Feng Chiu Seiji Okada Marie-Claude Gingras Sopit Wongkham | 2023 | World Journal of Gastroenterology2023，29，28： | 0 |
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