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Sheng Chieh Hsu

Bio: Sheng Chieh Hsu is an academic researcher from China Medical University (Taiwan). The author has contributed to research in topics: Gefitinib & Protein kinase B. The author has an hindex of 4, co-authored 4 publications receiving 320 citations.

Papers
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Journal ArticleDOI
TL;DR: Light is shed on the role of nuclear EGFR in the sensitivity of wtEGFR-expressing cancer cells to EGFR tyrosine kinase inhibitors and a putative molecular mechanism contributing to gefitinib resistance through BCRP/ABCG2 expression is deciphered.

177 citations

Journal ArticleDOI
23 Jun 2011-PLOS ONE
TL;DR: It is shown that acquired resistance of wtEGFR-expressing cancer cells to an EGFR TKI, gefitinib, is associated with elevated expression of breast cancer resistance protein (BCRP/ABCG2), which in turn leads to gefITinib efflux from cells.
Abstract: Background The sensitivity of non-small cell lung cancer (NSCLC) patients to EGFR tyrosine kinase inhibitors (TKIs) is strongly associated with activating EGFR mutations. Although not as sensitive as patients harboring these mutations, some patients with wild-type EGFR (wtEGFR) remain responsive to EGFR TKIs, suggesting that the existence of unexplored mechanisms renders most of wtEGFR-expressing cancer cells insensitive.

80 citations

Journal ArticleDOI
31 Dec 2013-PLOS ONE
TL;DR: Results suggest not only that BCRP/ABCG2 is a potential predictor for the sorafenib sensitivity in HCC, but also that blockage of B CRP/ ABCG2 may be a potential strategy to increase the response of HCC cells to sorafinib.
Abstract: The multikinase inhibitor, sorafenib (Nexavar®, BAY43-9006), which inhibits both the Raf/MEK/ERK pathway and several receptor tyrosine kinases (RTKs), has shown significantly therapeutic benefits in advanced hepatocellular carcinoma (HCC). However, not all HCC patients respond to sorafenib well and new therapeutic strategies to optimize the efficacy of sorafenib are urgently required. Overexpression of breast cancer resistance protein (BCRP/ABCG2) mediates the drug-efflux of several tyrosine kinase inhibitors (TKIs) to attenuate their efficacy. This study aimed to investigate the role of BCRP/ABCG2 in the sensitivity of HCC to sorafenib. Our data showed that BCRP/ABCG2 mediated the efflux of sorafenib. Co-treatment with a BCRP/ABCG2 inhibitor greatly augmented the cytotoxicity of sorafenib in HCC cells. Similar results were also achieved by the competitive inhibitor of BCRP/ABCG2, gefitinib, in combination with sorafenib. These results suggest not only that BCRP/ABCG2 is a potential predictor for the sorafenib sensitivity in HCC, but also that blockage of BCRP/ABCG2 may be a potential strategy to increase the response of HCC cells to sorafenib.

71 citations

Journal ArticleDOI
TL;DR: HBx is disclosed as a new inducer of IKKα nuclear transport in hepatoma cells and a potential role of nuclear IKK α in HBx‐mediated hepatocellular carcinoma (HCC) progression is provided.
Abstract: Hepatitis B virus (HBV) X protein (HBx) has been implicated in HBV-associated carcinogenesis through activation of IκB kinase (IKK)/nuclear factor kappa B (NF-κB) signaling pathway. Besides activating NF-κB in the cytoplasm, IKKα was found in the nucleus to regulate gene expression epigenetically in response to various stimuli. However, it is unknown whether nuclear IKKα plays a role in HBx-associated tumor progression. Moreover, the molecular mechanism underlying IKKα nuclear transport also remains to be elucidated. Here, we disclosed HBx as a new inducer of IKKα nuclear transport in hepatoma cells. HBx induced IKKα nuclear transport in an Akt-dependent manner. HBx-activated Akt promoted IKKα nuclear translocation via phosphorylating its threonine-23 (Thr23). In addition, IKKα ubiquitination enhanced by HBx and Akt also contributed to the IKKα accumulation in the nucleus, indicating the involvement of ubiquitination in Akt-increased IKKα nuclear transport in response to HBx. Furthermore, inhibition of IKKα nuclear translocation by mutation of its nuclear localization signal and Thr23 diminished IKKα-dependent cell migration. Taken together, our findings shed light on the molecular mechanism of IKKα nuclear translocation and provide a potential role of nuclear IKKα in HBx-mediated hepatocellular carcinoma (HCC) progression. J. Cell. Physiol. 227: 1446–1454, 2012. © 2011 Wiley Periodicals, Inc.

27 citations

Journal ArticleDOI
TL;DR: Results suggest that 67LR may be potentially amenable to tumor-targeted therapeutics and may mediate EGCG’s enhancement effects on nanoparticle uptake.
Abstract: Epigallocatechin gallate (EGCG), a major tea catechin, enhances cellular uptake of magnetic nanoparticles (MNPs), but the mechanism remains unclear. Since EGCG may interact with the 67-kDa laminin receptor (67LR) and epidermal growth factor receptor (EGFR), we investigate whether a receptor and its downstream signaling may mediate EGCG’s enhancement effects on nanoparticle uptake. As measured using a colorimetric iron assay, EGCG induced a concentration-dependent enhancement effect of MNP internalization by LN-229 glioma cells, which was synergistically enhanced by the application of a magnetic field. Transmission electron microscopy demonstrated that EGCG increased the number, but not the size, of internalized vesicles, whereas EGCG and the magnet synergistically increased the size of vesicles. EGCG appears to enhance particle–particle interaction and thus aggregation following a 5-min magnet application. An antibody against 67LR, knockdown of 67LR, and a 67LR peptide (amino acid 161–170 of 67LR) attenuated EGCG-induced MNP uptake by 35%, 100%, and 45%, respectively, suggesting a crucial role of 67LR in the effects of EGCG. Heparin, the 67LR-binding glycosaminoglycan, attenuated EGCG-induced MNP uptake in the absence, but not presence, of the magnet. Such enhancement effects of EGCG were attenuated by LY294002 (a phosphoinositide 3-kinase inhibitor) and Akt inhibitor, but not by agents affecting cGMP levels, suggesting potential involvement of signaling downstream of 67LR. In contrast, the antibody against EGFR exerted no effect on EGCG-enhanced internalization. These results suggest that 67LR may be potentially amenable to tumor-targeted therapeutics.

2 citations


Cited by
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Journal ArticleDOI
TL;DR: The preclinical and clinical performance of these dual-targeting approaches are described, the key mechanisms that mediate their increased efficacy and highlights areas for ongoing investigation are discussed.
Abstract: Many therapeutic agents target the ERBB family of receptor tyrosine kinases in various cancers. This Opinion article describes our latest understanding of the value of combining inhibitors directed towards an individual ERBB family member, including the molecular mechanisms of synergy and progress in clinical trials.

368 citations

Journal ArticleDOI
TL;DR: Evidence is mounting that many cancers display subpopulations of stem cells that are responsible for tumor self-renewal, and stem cells frequently manifest the "side population" phenotype characterized by expression of BCRP and other ABC transporters, which may contribute to the inherent resistance of these neoplasms and their failure to be cured.

347 citations

Journal ArticleDOI
TL;DR: The mechanisms of CSC-related therapy resistance including drug efflux by ABC transporters, activation of aldehyde dehydrogenase and developmental pathways, enhanced DNA damage response, autophagy and microenvironmental conditions are described, and possible therapeutic strategies for improving cancer treatment are discussed.

334 citations

Journal ArticleDOI
TL;DR: This review describes the most important pathways of radioresponse and several key target proteins for radiosensitization.
Abstract: During the last few decades, improvements in the planning and application of radiotherapy in combination with surgery and chemotherapy resulted in increased survival rates of tumor patients. However, the success of radiotherapy is impaired by two reasons: firstly, the radioresistance of tumor cells and, secondly, the radiation-induced damage of normal tissue cells located in the field of ionizing radiation. These limitations demand the development of drugs for either radiosensitization of tumor cells or radioprotection of normal tissue cells. In order to identify potential targets, a detailed understanding of the cellular pathways involved in radiation response is an absolute requirement. This review describes the most important pathways of radioresponse and several key target proteins for radiosensitization.

291 citations

Journal ArticleDOI
Woody Han1, Hui-Wen Lo1
TL;DR: An emerging line of research is outlined that uncovers and functionally characterizes several novel modes of EGFR signaling that take center stage in the cell nucleus, mitochondrion and other subcellular compartments and contributes to the rationale design for therapeutic strategy that overcomes tumor drug resistance.

222 citations