http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Chloroquine Exerts Anti-metastatic Activities Under Hypoxic Conditions in Cholangiocarcinoma Cells
Thongchot, Suyanee,Loilome, Watcharin,Yongvanit, Puangrat,Dokduang, Hasaya,Thanan, Raynoo,Techasen, Anchalee,Namwat, Nisana Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5
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 ($CoCl_2$)-stimulated hypoxia. We showed that chloroquine suppressed CCA cell migration under hypoxic-mimicking conditions on exposure to $100{\mu}M$ $CoCl_2$. 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-$1{\alpha}$) 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-$1{\alpha}$/VEGF/EMT which may serve as a useful additional strategy for CCA therapy.
Thanee, Malinee,Loilome, Watcharin,Techasen, Anchalee,Namwat, Nisana,Boonmars, Thidarut,Pairojkul, Chawalit,Yongvanit, Puangrat Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7
The tumor microenvironment (TME) includes numerous non-neoplastic cells such as leukocytes and fibroblasts that surround the neoplasm and influence its growth. Tumor-associated macrophages (TAMs) and cancerassociated fibroblasts (CAFs) are documented as key players in facilitating cancer appearance and progression. Alteration of the macrophage (CD68, CD163) and fibroblast (${\alpha}-SMA$, FSP-1) cells in Opisthorchis viverrini (Ov) -induced cholangiocarcinoma (CCA) was here assessed using liver tissues from an established hamster model and from 43 human cases using immunohistochemistry. We further investigated whether M2-activated TAMs influence CCA cell migration ability by wound healing assay and Western blot analysis. Macrophages and fibroblasts change their phenotypes to M2-TAMs (CD68+, CD163+) and CAFs (${\alpha}-SMA+$, FSP-1+), respectively in the early stages of carcinogenesis. Interestingly, a high density of the M2-TAMs CCA in patients is significantly associated with the presence of extrahepatic metastases (p=0.021). Similarly, CD163+ CCA cells are correlated with metastases (p=0.002), and they may be representative of an epithelial-to-mesenchymal transition (EMT) with increased metastatic activity. We further showed that M2-TAM conditioned medium can induce CCA cell migration as well as increase N-cadherin expression (mesenchymal marker). The present work revealed that significant TME changes occur at an early stage of Ov-induced carcinogenesis and that M2-TAMs are key factors contributing to CCA metastasis, possibly via EMT processes.
Thongchot, Suyanee,Yongvanit, Puangrat,Loilome, Watcharin,Seubwai, Wanchana,Phunicom, Kutcharin,Tassaneeyakul, Wichittra,Pairojkul, Chawalit,Promkotra, Wisuttiphong,Techasen, Anchalee,Namwat, Nisana Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14
Hypoxia and autophagy are known to facilitate tumor progression. We here aimed to investigate the role of hypoxia-associated autophagy in cholangiocarcinoma (CCA) survival and metastasis. Immunostaining of hypoxic-responsive proteins (HIF-$1{\alpha}$ and BNIP3) and a key regulator of autophagy (PI3KC3) were examined in CCA tissues and their expression levels were compared with clinicopathological parameters. A hypoxia mimicking condition ($CoCl_2$ treatment) was also tested regarding CCA cell functions. Our results showed that HIF-$1{\alpha}$ (66%), BNIP3 (44%) and PI3KC3 (46%) showed strong staining in human CCA tissues. Positive expression of HIF-$1{\alpha}$ (p=0.033), BNIP3 (p=0.040) and PI3KC3 (p=0.037) was significantly correlated with lymph node metastasis. HIF-$1{\alpha}$ was well associated with BNIP3 (r=0.3, p<0.01) and PI3KC3 (r=0.2, p<0.01). The survival rates of patients who were positive with HIF-$1{\alpha}$ (p=0.047) or co-expressed HIF-$1{\alpha}$ and BNIP3 (p=0.032) or HIF-$1{\alpha}$ and PI3KC3 (p=0.043) were significantly greater than in the negative groups. CCA cells treated with $CoCl_2$ showed an increase in HIF-$1{\alpha}$, BNIP3, PI3KC3 and LC3-II, with increased cell migration and pFAK levels. These data suggest that hypoxia associated autophagy enhances CCA metastasis, resulting in a poor prognosis of CCA.
Yothaisong, Supak,Thanee, Malinee,Namwat, Nisana,Yongvanit, Puangrat,Boonmars, Thidarut,Puapairoj, Anucha,Loilome, Watcharin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23
Opisthorchis viverrini (Ov) infection is the major etiological factor for cholangiocarcinoma (CCA), especially in northeast Thailand. We have previously reported significant involvement of PI3K/AKT/PTEN and $Wnt/{\beta}$-catenin in human CCA tissues. The present study, therefore, examined the expression and activation of PI3K/AKT/PTEN and $Wnt/{\beta}$-catenin signaling components during Ov-induced cholangiocarcinogenesis in a hamster animal model. Hamsters were divided into two groups; non-treated and Ov plus NDMA treated. The results of immunohistochemical staining showed an upregulation of PI3K/AKT signaling as determined by elevated expression of the $p85{\alpha}$-regulatory and $p110{\alpha}$-catalytic subunits of PI3K as well as increased expression and activation of AKT during cholangiocarcinogenesis. Interestingly, the staining intensity of activated AKT (p-AKT) increased in the apical regions of the bile ducts and strong staining was detected where the liver fluke resides. Moreover, PTEN, a negative regulator of PI3K/AKT, was suppressed by decreased expression and increased phosphorylation during cholangiocarcinogenesis. We also detected upregulation of $Wnt/{\beta}$-catenin signaling as determined by increased positive staining of Wnt3, Wnt3a, Wnt5a, Wnt7b and ${\beta}$-catenin, corresponded with the period of cholangiocarcinogenesis. Furthermore, nuclear staining of ${\beta}$-catenin was observed in CCA tissues. Our results suggest the liver fluke infection causes chronic inflammatory conditions which lead to upregulation of the PI3K/AKT and $Wnt/{\beta}$-catenin signaling pathways which may drive CCA carcinogenesis. These results provide useful information for drug development, prevention and treatment of CCA.
A Promising Serum Autoantibody Marker, Anti-Heat Shock Protein 90α, for Cholangiocarcinoma
Boonjaraspinyo, Sirintip,Juasook, Amornrat,Boonmars, Thidarut,Aukkanimart, Ratchadawan,Silsirivanit, Atit,Loilome, Watcharin,Sriraj, Pranee,Wu, Zhiliang,Ratanasuwan, Panaratana Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14
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 $HSP90{\alpha}$, as indicated by a high level of anti-$HSP90{\alpha}$ in hamster CCA sera. It was found that the levels of anti-$HSP90{\alpha}$ 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-$HSP90{\alpha}$ 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-$HSP90{\alpha}$ may be a potential useful serum biomarker to discriminate CCA cases from healthy persons.
Khenjanta, Chakkaphan,Thanan, Raynoo,Jusakul, Apinya,Techasen, Anchalee,Jamnongkan, Wassana,Namwat, Nisana,Loilome, Watcharin,Pairojkul, Chawalit,Yongvanit, Puangrat Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23
Cytochrome P450 (CYP) enzymes are a large family of constitutive and inducible mono-oxygenase enzymes that play a central role in the oxidative metabolism of both xenobiotic and endogenous compounds. Several CYPs are involved in metabolism of oxysterols, which are cholesterol oxidation products whose expression may be dysregulated in inflammation-related diseases including cancer. This study focused on CYP39A1, which can metabolize 24-hydroxycholesterol (24-OH) that plays important roles in the inflammatory response and oxidative stress. We aimed to investigate the expression status of CYP39A1 and its transcription factor (RUNX2) in relation to clinical significance in cholangiocarcinoma (CCAs) and to determine whether 24-OH could induce oxidative stress in CCA cell lines. Immunohistochemistry showed that 70% and 30% of CCA patients had low and high expression of CYP39A1, respectively. Low expression of CYP39A1 demonstrated a significant correlation with metastasis. Our results also revealed that the expression of RUNX2 had a positive correlation with CYP39A1. Low expression of both CYP39A1 (70%) and RUNX2 (37%) was significantly related with poor prognosis of CCA patients. Interestingly, oxidized alpha-1 antitrypsin (ox-A1AT), an oxidative stress marker, was significantly increased in CCA tissues in which CYP39A1 and RUNX2 were down regulated. Additionally, immunocytochemistry showed that 24-OH could induce ox-A1AT in CCA cell lines. In conclusion, our study revealed putative roles of the CYP39A1 enzyme in prognostic determination of CCAs.