Pei-Yi Chu

Show Chwan Memorial Hospital, Chang-hua Pei-pu, Taiwan, Taiwan

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Publications (48)127.9 Total impact

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    ABSTRACT: Regulatory factor X (RFX) 1 is a transcription factor that has been linked to negative regulation of tumor progression; however, its biological function and signaling cascades are unknown. Here, we performed several studies to elucidate the roles of RFX-1 in the regulation of SHP-1 in HCC cells. Overexpression of RFX-1 resulted in the activation of SHP-1 and repressed colony formation of HCC cells. In addition, by a mouse xenograft model, we demonstrated that RFX-1 overexpression also inhibited the tumor growth of HCC cells in vivo, suggesting that RFX-1 is of potential interest for small molecule targeted therapy. We also found that SC-2001, a bipyrrole molecule, induced apoptosis in HCC cells through activating RFX-1 expression. SC-2001-induced RFX-1 translocation from the cytosol to nucleus, bound to the SHP-1 promoter, and activated SHP-1 transcription. In a xenograft model, knockdown of RFX-1 reversed the anti-tumor effect of SC-2001. Notably, SC-2001 is much more potent than sorafenib, a clinically approved drug for HCC, in in vitro and in vivo assays. Our study confirmed that RFX-1 acts as a tumor suppressor in HCC and might be a new target for HCC therapy. The findings of this study also provide a new lead compound for targeted therapy via the activation of the RFX-1/SHP-1 pathway.
    Carcinogenesis 10/2014; · 5.64 Impact Factor
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    ABSTRACT: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodent model of FAS, we found that ethanol exposure (5.25g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPARγ were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms.
    Biochemical and Biophysical Research Communications 09/2014; · 2.28 Impact Factor
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    ABSTRACT: Purpose:Here, we aim to investigate the molecular mechanism of regorafenib and verify the potential druggable target for the treatment of HCC. Experimental Design:HCC cell lines (PLC5, HepG2, Hep3B, SK-Hep1, and HA59T) were used to investigate the in vitro effect of regorafenib. Phosphatase activity was analyzed in HCC cells and purified SHP-1 proteins. PLC5-bearing mice were tested the therapeutic efficiency with 20 and 40 mg/kg/day treatment of regorafenib (n ≧ 8 mice). The clinical relevance of STAT3 signaling was investigated with 142 tumor samples from different patients with HCC. Descriptive statistical analysis was used to compare the baseline characteristics of patients and the expression of p-STAT3. Results:Regorafenib inhibited STAT3-related signaling in a dose-dependent manner and was a more potent inhibitor of STAT3 than sorafenib. Regorafenib increased SHP-1 phosphatase activity in purified SHP-1 protein directly. N-SH2 domain deletion and D61A mutants mimicking open-form SHP-1 partially abolished regorafenib-induced STAT3 inhibition and apoptosis. Importantly, a higher level of expression of STAT3 was found in patients with advanced clinical stages (p=0.009) and poor differentiated tumors (p=0.035). Conclusions:Regorafenib induced significant tumor inhibition by relieving auto-inhibited N-SH2 domain of SHP-1 directly and inhibiting p-STAT3 signals. STAT3 may be suitable as a prognostic marker of HCC development, and may be a druggable target for HCC targeted therapy using regorafenib.
    Clinical cancer research : an official journal of the American Association for Cancer Research. 09/2014;
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    ABSTRACT: IntroductionTamoxifen, a selective estrogen receptor (ER) modulator, may affect cancer cell survival through mechanisms other than ER antagonism. Here, we tested the efficacy of tamoxifen in a panel of ER-negative breast cancer cell lines and examined the drug mechanism.Methods In total, five ER-negative breast cancer cell lines HCC-1937, MDA-MB-231, MDA-MB-468, MDA-MB-453 and SK-BR-3 were used for in vitro studies. Cell apoptosis was examined by flow-cytometry and western blot. Signal transduction pathways in cells were assessed by western blot. In vivo efficacy of tamoxifen was tested in xenograft nude mice.ResultsTamoxifen induced significant apoptosis in MDA-MB-231, MDA-MB-468, MDA-MB-453, SK-BR-3, but not in HCC-1937 cells. Tamoxifen-induced apoptosis was associated with inhibition of cancerous inhibitor of protein phosphatase 2A (CIP2A) and p-Akt in a dose-dependent manner. Ectopic expression of CIP2A or Akt protected MDA-MB-231 cells from tamoxifen-induced apoptosis. In addition, tamoxifen increased protein phosphatase 2A (PP2A) activity and tamoxifen-induced apoptosis was attenuated by PP2A antagonist okadaic acid in the sensitive cell lines but not in resistant HCC-1937 cells. Moreover, silencing CIP2A by siRNA sensitized HCC-1937 cells to tamoxifen-induced apoptosis. Furthermore, tamoxifen regulated CIP2A protein expression by downregulating CIP2A mRNA. Importantly, tamoxifen inhibited the in vivo growth of MDA-MB-468 xenograft tumors in association with CIP2A downregulation, whereas tamoxifen had no significant effect on CIP2A expression and anti-tumor growth in HCC-1937 tumors.Conclusions Inhibition of CIP2A determines the effects of tamoxifen-induced apoptosis in ER-negative breast cancer cells. Our data suggest a novel ¿off-target¿ mechanism of tamoxifen and suggest that CIP2A/PP2A/p-Akt signaling as a feasible anti-cancer pathway.
    Breast cancer research: BCR 09/2014; 16(5):431. · 5.87 Impact Factor
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    ABSTRACT: Dyregulation of autophagy has been reported in various human cancers including oral squamous cell carcinoma (OSCC). The objective of this study was to link expression of autophagy-related 16-like 1 (ATG16L1), a protein essential for autophagosome formation, to clinical outcome in a cohort of 90 OSCC patients. Expression level of ATG16L1 was assessed by immunohistochemistry and an immunoreactivity score (IRS), ranging from 0 to 9, was assigned to each case. The results were correlated with clinicopathological parameters and outcome of patients. Twenty-seven patients (30 %) exhibited ATG16L1 overexpression as indicated by an IRS of 9. Overexpression of ATG16L1 was significantly associated with disease stage (p = 0.001), size (p = 0.031) of the tumor, lymph node metastasis (p = 0.004), and histological grade (p = 0.038). ATG16L1 overexpression significantly affected the overall survival (p = 0.020) and time to recurrence (p = 0.031) of OSCC patients in Kaplan-Meier analysis. The present study suggested that ATG16L1 may be used as a biomarker for selecting OSCC patients with a more aggressive phenotype.
    Pathology oncology research : POR. 07/2014;
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    ABSTRACT: Interfering oncogenic STAT3 signaling is a promising anti-cancer strategy. We examined the efficacy and drug mechanism of an obatoclax analog SC-2001, a novel STAT3 inhibitor, in human breast cancer cells. Human breast cancer cell lines were used for in vitro studies. Apoptosis was examined by both flow cytometry and western blot. Signaling pathways were assessed by western blot. In vivo efficacy of SC-2001 was tested in xenograft nude mice. SC-2001 inhibited cell growth and induced apoptosis in association with downregulation of p-STAT3 (Tyr 705) in breast cancer cells. STAT3-regulated proteins, including Mcl-1, survivin, and cyclin D1, were repressed by SC-2001. Over-expression of STAT3 in MDA-MB-468 cells protected cells from SC-2001-induced apoptosis. Moreover, SC-2001 enhanced the expression of protein tyrosine phosphatase SHP-1, a negative regulator of STAT3. Furthermore, the enhanced SHP-1 expression, in conjunction with increased SHP-1 phosphatase activity, was mediated by upregulated transcription by RFX-1. Chromatin immunoprecipitation assay revealed that SC-2001 increased the binding capacity of RFX-1 to the SHP-1 promoter. Knockdown of either RFX-1 or SHP-1 reduced SC-2001-induced apoptosis, whereas ectopic expression of RFX-1 increased SHP-1 expression and enhanced the apoptotic effect of SC-2001. Importantly, SC-2001 suppressed tumor growth in association with enhanced RFX-1 and SHP-1 expression and p-STAT3 downregulation in MDA-MB-468 xenograft tumors. SC-2001 induced apoptosis in breast cancer cells, an effect that was mediated by RFX-1 upregulated SHP-1 expression and SHP-1-dependent STAT3 inactivation. Our study indicates targeting STAT3 signaling pathway may be a useful approach for the development of targeted agents for anti-breast cancer.
    Breast Cancer Research and Treatment 06/2014; · 4.47 Impact Factor
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    ABSTRACT: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma (PTCL) of follicular helper T-cell origin and is rare in Taiwan. There are overlapping features of AITL and peripheral T-cell lymphoma with a follicular growth pattern (PTCL-F). Around one fifth of PTCL-F exhibits t(5;9)(q33;q22)/ITK-SYK chromosomal translocation, which is essentially absent in AITL. We retrospectively investigated 35 cases of AITL from Taiwan with histopathology review, immunohistochemistry, in situ hybridization for Epstein-Barr virus (EBV) and fluorescence in situ hybridization (FISH) for t(5;9)(q33;q22)/ITK-SYK and correlated the results with overall survival. Twenty-six cases of not otherwise specified PTCL (PTCL-NOS) were also examined by FISH for comparison. Most AITL patients were male (69%) and elderly (median age at 67 years) with frequent bone marrow involvement (53%), high Ann Arbor stages (77%), and elevated serum lactate dehydrogenase (68%). Most cases (80%) showed a typical CD4+/CD8- phenotype and in 90% cases there were scattered EBV-positive B-cells (less than 10% cells). None of these cases showed t(5;9)(q33;q22)/ITK-SYK translocation by FISH. Gain of ITK and SYK gene was identified in 38% and 14% tumors, respectively, but both were not associated with overall survival. Performance status < 2 was associated with a better outcome but not the other clinicopathological factors. All PTCL-NOS cases were negative for ITK-SYK translocation with similar rates (38% and 12%, respectively) of gains at ITK and SYK loci as that of AITL. In this so far the largest series of AITL from Taiwan, we reported the clinicopathological features and FISH findings on ITK and SYK genes. We confirmed the absence of t(5;9)(q33;q22)/ITK-SYK translocation, which may serve as an additional differential diagnostic tool from PTCL-F when present. PTCL-NOS shared a similar pattern of ITK and SYK gains with AITL. More studies are warranted to elucidate the roles of SYK and ITK and other genes in the lymphomagenesis of AITL in Taiwan.
    International journal of clinical and experimental pathology. 01/2014; 7(9):6097-107.
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    ABSTRACT: Aim: To evaluate the expression and prognostic value of two autophagy-related (Atg) proteins, Beclin-1 and Atg5, in human oral squamous cell carcinoma (OSCC) and to correlate findings with clinical outcomes. Immunohistochemistry for Beclin-1 and Atg5 was assessed in tumor specimens from 90 patients with OSCC. Immunopositivity was semi-quantitatively scored and receiver-operating characteristic curve analysis was used to determine the cut-off positivity score. 55 (61.1%) and 52 (57.8%) cases showed positive Beclin-1 and Atg5 staining, respectively. 40 tumors (44.4%) were positive for both Beclin-1 and Atg5 expression and 23 cases (25.6%) showed absence of both proteins. Beclin-1 expression significantly correlated with tumor grade (p=0.008) and lymph node metastasis (p=0.009). The expression of Atg5 was associated with tumor grade (p=0.016), advanced clinical stage (p<0.001), large tumor size (p=0.002), and lymph node metastasis (p<0.001). A significant difference in 3-year OS (p=0.050) and TTR (p=0.049) between the patients with Beclin-1 expression and those not showing Beclin-1 expression was found whereas the difference did not reach a statistical significance for Atg5 expression. 3-year OS and TTR differed significantly between patients with dual expression and those with double-negative expression (p=0.022 and p=0.026, respectively). Dual expression of tumor Beclin-1 and Atg5 expression may be an adverse prognostic indicator for OSCC.
    Anticancer research 12/2013; 33(12):5611-6. · 1.71 Impact Factor
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    ABSTRACT: Sorafenib is the first approved targeted therapeutic reagent for hepatocellular carcinoma (HCC). Here, we report that SC-60, a dimer-based sorafenib derivative, overcomes the resistance of sorafenib and shows a better anti-HCC effect in vitro and in vivo. SC-60 substantially increased SHP-1 phosphatase activity in HCC cells and purified SHP-1 proteins, suggesting that SC-60 affects SHP-1 directly. Molecular docking and truncated mutants of SHP-1 further confirmed that SC-60 interferes with the inhibitory N-SH2 domain to relieve the closed catalytic PTP domain of SHP-1. Deletion of N-SH2 domain (dN1) or point mutation (D61A) of SHP-1 abolished the effect of SC-60 on SHP-1, p-STAT3 and apoptosis. Importantly, SC-60 exhibited significant survival benefits compared to sorafenib in an HCC orthotopic model via targeting the SHP-1/STAT3-related signaling pathway. In summary, dimer derivative of sorafenib, SC-60, is a SHP-1 agonist and may be a potent reagent for HCC targeted therapy.
    Molecular Cancer Therapeutics 11/2013; · 5.60 Impact Factor
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    ABSTRACT: Endosulfine alpha (ENSA) is an endogenous ligand of sulfonylurea receptor that was reported to be associated with an ATP-dependent potassium channel that controls insulin release and the onset of type 2 diabetes. ENSA also interacts with microtubule-associated serine/threonine-protein kinase-like (MASTL) to regulate the cell cycle. Previously, we identified ENSA as a possible bivalent gene in mesenchymal stem cells (MSCs) and hypothesized its methylation might determine cellular differentiation and transformation. Because there was no link between aberrant ENSA expression and tumorigenesis, we aimed to determine if ENSA is abnormally regulated in liver cancer and plays a role in liver cancer propagation. The epigenetic states of the ENSA promoter were evaluated in different cancer cell lines and patient samples. ENSA was overexpressed in a liver cancer cell line, and its interaction with MASTL and possible tumor suppression capabilities were also determined in cultured cells and mice. Distinct ENSA promoter methylation was observed in liver cancer (n=100 pairs) and breast cancer (n=100 pairs). ENSA was predominantly hypomethylated in liver cancer but was hypermethylated in breast cancer. Overexpressed ENSA interacts with MASTL and suppresses hepatic tumor growth. We also found that ENSA is hypermethylated in CD90-expressing (CD90(+)) cells compared to CD90 non-expressing (CD90(-)) liver cancer cells. These data reveal ENSA methylation changes during hepatic tumor evolution. Overexpressed ENSA suppresses tumor growth in an established hepatic cell line whereas hypermethylated ENSA might help maintain liver cancer initiating cells.
    Biochemical and Biophysical Research Communications 11/2013; · 2.28 Impact Factor
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    ABSTRACT: Chondroitin sulfate proteoglycan 4 (CSPG4), a transmembrane proteoglycan originally identified in melanoma cells, has been reported to be expressed in breast cancer cells. This study was performed to examine the expression and significance of CSPG4 in a cohort of breast cancer patients. Immunohistochemical analysis of CSPG4 was performed on tissue microarrays constructed from tissue specimens from 240 breast cancer patients. CSPG4 staining was correlated with clinical and pathological characteristics, overall survival (OS), and disease recurrence. Contradicting to a previous report, our results showed that high CSPG4 expression was not related to triple-negative status of breast cancer patients. The Kaplan-Meier method showed that high CSPG4 expression was significantly associated with shorter time to recurrence (TTR). Patients with high CSPG4 expression had poorer OS and shorter TTR in a multivariate survival analysis after adjustment for stage, tumor grade, expression of estrogen receptor and progesterone receptor, and HER2 overexpression. This study showed that high CSPG4 expression correlates with disease recurrence and OS in breast cancers.
    Biochemical and Biophysical Research Communications 10/2013; · 2.28 Impact Factor
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    ABSTRACT: ATG9A is an integral membrane protein required for autophagosome formation and a membrane carrier in the autophagy pathways. The present study was designed to investigate the expression of ATG9A in oral squamous cell carcinoma (OSCC). Clinically annotated tumor specimens from 90 patients with OSCC were subjected to immunohistochemistry using an antibody against ATG9A and immunoreactivity was scored using an immunoreactivity score (IRS). Scores were compared with clinical and pathologic data to assess association with outcome. Overexpression of ATG9A was defined as an IRS of ≥9 by receiver operating characteristics curve analysis and was identified in 25 (28 %) of 90 cases. ATG9A overexpression was associated with disease recurrence and overall survival (OS) in both univariate (p = 0.030 and 0.025, respectively) and multivariate (p = 0.026 and 0.038, respectively) Cox analyses. Kaplan-Meier plots also showed that patients with ATG9A overexpression had shorter 3-year OS (p = 0.017) and time to recurrence (p = 0.021) than those with low ATG9A expression. These results suggest that the presence of ATG9A in the cytoplasm of tumor cells may be an independent biomarker for disease recurrence and survival in patients with OSCC.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 10/2013; · 2.68 Impact Factor
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    ABSTRACT: Oral squamous cell carcinoma (OSCC) is a destructive disease with very poor prognosis and no effective treatment. Autophagy is a dynamic cellular process involved in various physiological processes and diseases including cancer that degrades cytoplasmic proteins and organelles. The role of autophagy in the pathogenesis of OSCC is not yet understood. Microtubule-associated protein light chains 3 (LC3) is a reliable autophagosome markers for monitoring autophagy. In the present study, LC3 expression was determined in a cohort of 90 OSCC samples by immunohistochemistry. The results were correlated with clinical and pathological characteristics of patients. High LC3 expression (N = 57; 63.3%) correlated with stage (P < .0001), tumor size (P < .0001), and lymph node involvement (P = .0003) and with an increased risk of death (P < .0001; hazard ratio, 3.59) in a univariate analysis. In the multivariate analysis adjusted for grade, stage, and alcohol, betel, and tobacco consumption, high LC3 expression retained statistical significance with regard to survival (P = .0043; hazard ratio, 2.99). The Kaplan-Meier survival curve also showed that high LC3 expression was significantly associated with poor overall survival (P = .0001). Elevated LC3 expression, which corresponds to increased level of autophagy activity, is a frequent event and an indicator of poor prognosis in human OSCC.
    Human pathology 09/2013; · 3.03 Impact Factor
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    ABSTRACT: Signal transducers and activators of transcription 3 (STAT3) signaling is constitutively activated in various cancers including breast cancer, and has emerged as a novel potential anti-cancer target. STAT3 has been demonstrated to be a target of sorafenib, and a protein tyrosine phosphatase Src homology 2-domain containing tyrosine phosphatase 1 (SHP-1) has been demonstrated to downregulate p-STAT3 via its phosphatase activity. Here, we tested the efficacy of two sorafenib analogues, SC-1 and SC-43, in breast cancer cells and examined the drug mechanism. Breast cancer cell lines were used for in vitro studies. Cell viability was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was examined by flow cytometry and western blot. Signal transduction pathways in cells were assessed by western blot. In vivo efficacy of sorafenib, SC-1 and SC-43 were tested in xenografted nude mice. SC-1 and SC-43 induced more potent apoptosis than sorafenib, in association with downregulation of p-STAT3 and its downstream proteins cyclin D1 and survivin in a dose-dependent manner in breast cancer cell lines (HCC-1937, MDA-MB-468, MDA-MB-231, MDA-MB-453, SK-BR3, MCF-7). Overexpression of STAT3 in MDA-MB-468 cells protected cells from apoptosis induced by sorafenib, SC-1, and SC-43. Moreover, SC-1 and SC-43 upregulated SHP-1 activity to a greater extent than sorafenib as measured by in vitro phosphatase assays. Knockdown of SHP-1 by siRNA reduced apoptosis induced by SC-1 and SC-43. Importantly, SC-1 and SC-43 showed more efficacious antitumor activity and p-STAT3 downregulation than sorafenib in MDA-MB-468 xenograft tumors. Novel sorafenib analogues SC-1 and SC-43 induce apoptosis through SHP-1 dependent STAT3 inactivation and demonstrate greater potency than sorafenib in human breast cancer cells.
    Breast cancer research: BCR 08/2013; 15(4):R63. · 5.87 Impact Factor
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    ABSTRACT: Sorafenib is the first approved targeted therapeutic reagent for hepatocellular carcinoma (HCC). Here, we report that Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1) is a major target of sorafenib and generates a series of sorafenib derivatives to search for potent SHP-1 agonists that may act as better anti-HCC agents than sorafenib. Sorafenib increases SHP-1 activity by direct interaction and impairs the association between the N-SH2 domain and the catalytic protein tyrosine phosphatase domain of SHP-1. Deletion of the N-SH2 domain (dN1) or point mutation (D61A) of SHP-1 abolished the effect of sorafenib on SHP-1, phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and apoptosis, suggesting that sorafenib may affect SHP-1 by triggering a conformational switch relieving its autoinhibition. Molecular docking of SHP-1/sorafenib complex confirmed our findings in HCC cells. Furthermore, novel sorafenib derivatives SC-43 and SC-40 displayed more-potent anti-HCC activity than sorafenib, as measured by enhanced SHP-1 activity, inhibition of p-STAT3, and induction of apoptosis. SC-43 induced substantial apoptosis in sorafenib-resistant cells and showed better survival benefits than sorafenib in orthotopic HCC tumors. Conclusion: In this study, we identified SHP-1 as a major target of sorafenib. SC-43 and SC-40, potent SHP-1 agonists, showed better anti-HCC effects than sorafenib in vitro and in vivo. Further clinical investigation is warranted. (Hepatology 2013;).
    Hepatology 08/2013; · 12.00 Impact Factor
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    ABSTRACT: In previous research, we found α-enolase to be inversely correlated with progression-free and overall survival in lung cancer patients and detected α-enolase on the surface of lung cancer cells. Based on these findings, we hypothesized that surface α-enolase has a significant role in cancer metastasis and tested this hypothesis in the current study. We found that α-enolase was co-immunoprecipitated with urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, and plasminogen in lung cancer cells and interacted with these proteins in a cell-free dot blotting assay, which can be interrupted by α-enolase-specific antibody. α-Enolase in lung cancer cells co-localized with these proteins and was present at the site of pericellular degradation of extracellular matrix components. Treatment with antibody against α-enolase in vitro suppressed cell-associated plasminogen and matrix metalloproteinase activation, collagen and gelatin degradation, and cell invasion. Examination of the effect of treatment with shRNA plasmids revealed that down regulation of α-enolase decreases extracellular matrix degradation by and the invasion capacity of lung cancer cells. Adoptive transfer of α-enolase-specific antibody to mice resulted in accumulation of antibody in subcutaneous tumor and inhibited the formation of tumor metastasis in lung and bone. This study demonstrated that surface α-enolase promotes extracellular matrix degradation and invasion of cancer cells and that targeting surface α-enolase is a promising approach to suppress tumor metastasis.
    PLoS ONE 07/2013; 8(7):e69354. · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND: Autophagy is a self-catabolic mechanism that degrades unnecessary cellular components through lysosomal enzymes. Beclin-1, an autophagy-related protein, establishes the first connection between autophagy and tumorigenesis. The purpose of this study is to assess the Beclin-1 expression pattern and to determine its prognostic significance in patients with malignant canine mammary tumor (CMT).
    BMC Veterinary Research 04/2013; 9(1):75. · 1.86 Impact Factor
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    ABSTRACT: Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue tumor of uncertain histogenesis, occurring predominantly in deep soft tissues of the extremities. Typically, OFMT presents in adults on the extremities or trunk, as a deep soft tissue mass. Less appreciated is the fact that OFMT may also present as a mass in the superficial subcutis or dermis. We herein report a female who presented with an asymptomatic subcutaneous nodule on the left thigh for 3 years, and who was diagnosed as having typical ossifying fibromyxoid tumor, by unique histopathologic and immunohistochemical studies. Most reported cases have pursued a benign clinical course. However, recent literature emphasized the existence of morphologically atypical and clinically malignant cases of OFMTs. Pathologic criteria for malignancy have been proposed, and reclassification of these tumors as tumors of intermediate malignancy, raise our attention while coping with OFMT clinically.
    Dermatologica Sinica 03/2013; 31(1):32–34. · 0.22 Impact Factor
  • Dermatologica Sinica 03/2013; 31(1):43–44. · 0.22 Impact Factor
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    ABSTRACT: BRCA1-associated breast cancers are associated with particular features such as early onset, poor histological differentiation, and hormone receptor negativity. Previous studies conducted in Taiwanese population showed that the mutation of BRCA1 gene does not play a significant role in the occurrence of breast cancer. The present study explored methylation of BRCA1 promoter and its relationship to clinical features and outcome in Taiwanese breast cancer patients. Tumor specimens from a cohort of 139 early-stage breast cancer patients were obtained during surgery before adjuvant treatment for DNA extraction. Methylation of BRCA1 promoter region was determined by methylation-specific PCR and the results were related to clinical features and outcome of patients using statistical analysis. Methylation of the BRCA1 promoter was detected in 78 (56%) of the 139 tumors. Chi-square analysis indicated that BRCA1 promoter methylation correlated significantly with triple-negative (ER-/PR-/HER2-) status of breast cancer patients (p = 0.041). The Kaplan-Meier method showed that BRCA1 promoter methylation was significantly associated with poor overall survival (p = 0.026) and disease-free survival (p = 0.001). Multivariate analysis which incorporated variables of patients' age, tumor size, grade, and lymph node metastasis revealed that BRCA1 promoter methylation was associated with overall survival (p = 0.27; hazard ratio, 16.38) and disease-free survival (p = 0.003; hazard ratio, 12.19). Our findings underscore the clinical relevance of the methylation of BRCA1 promoter in Taiwanese patients with early-stage breast cancer.
    PLoS ONE 01/2013; 8(2):e56256. · 3.53 Impact Factor

Publication Stats

141 Citations
127.90 Total Impact Points

Institutions

  • 2014
    • Show Chwan Memorial Hospital
      Chang-hua Pei-pu, Taiwan, Taiwan
  • 2011–2014
    • San Martín de Porres
      General San Martín, Mendoza, Argentina
    • National Chung Cheng University
      • Institute of Molecular Biology
      Chia-i-hsien, Taiwan, Taiwan
    • National Taiwan University
      • Department of Bio-Industrial Mechatronics Engineering
      Taipei, Taipei, Taiwan
  • 2012–2013
    • National Taiwan University Hospital
      T’ai-pei, Taipei, Taiwan
    • National Yang Ming University
      • Institute of Biopharmaceutical Science
      Taipei, Taipei, Taiwan
    • Kaohsiung Medical University
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2010–2012
    • Changhua Christian Hospital
      Chang-hua Pei-pu, Taiwan, Taiwan
    • China Medical University (ROC)
      臺中市, Taiwan, Taiwan
  • 2008
    • National Taipei University of Technology
      T’ai-pei, Taipei, Taiwan