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Lee C.-H.,China Medical University at Taichung
Applied Microbiology and Biotechnology | Year: 2012

One of the primary limitations of cancer therapy is lack of selectivity of therapeutic agents to tumor cells. Current efforts are focused on discovering and developing anticancer agents that selectively target only tumor cells and spare normal cells to improve the therapeutic index. The use of preferentially replicating bacteria as an oncolytic agent is one of the innovative approaches for the treatment of cancer. This is based on the observation that some obligate or facultative anaerobic bacteria are capable of multiplying selectively in tumors and inhibiting their growth. Meanwhile, bacteria have been demonstrated to colonize and destroy tumor, and have emerged as biological gene vectors to tumor microenvironment. To improve the efficacy and safety of the bacterial therapy, a further understanding of bacteria between with immune system is required. Furthermore, we want to evaluate how bacterial infection facilitates the "bystander effect" of chemotherapeutic agent and assess if it can be used for additional antitumor effect when combined with chemotherapy. This study may not only evaluate therapeutic efficacy of bacteria for the treatment of cancer but also elucidate the mechanisms underlying antitumor activities mediated by bacteria, which involve host immune responses and the cellular molecular responses. © 2011 Springer-Verlag.


Leung Y.-M.,China Medical University at Taichung
Pharmacology and Therapeutics | Year: 2012

Voltage-gated K + (Kv) channels serve multiple functions. Besides the most well known function of controlling membrane excitability, they may also play roles in cell death and differentiation. Pharmacological activators and inhibitors of Kv channels therefore offer potential therapeutic treatments for a variety of diseases. Inhibition of Kv channels by classical blockers such as tetraethylammonium and 4-aminopyridine, and toxin peptides such as scorpion toxins, are believed to result from a direct intervention or occlusion of the K + permeation pathway. During prolonged depolarization, most Kv channels undergo a process called slow or C-type inactivation, by which the selectivity filter destabilizes and thus limits K + flux. Increasing amount of evidence shows that there are certain compounds which inhibit Kv currents not by directly obstructing the K + conduction pathway, but by accelerating or intensifying selectivity filter destabilization once the channels open. This mode of block represents an alternative mechanism of Kv channel inhibition. Indeed, some of the classical Kv channel blockers are to some extent, or in certain circumstances, involved in hastening slow inactivation. This review begins with a brief description of structure-functions of Kv channels, and then discusses the multiple mechanisms of Kv channel inhibition by classical blockers and how certain compounds inhibit Kv channels by accelerating C-type inactivation. The pharmacological and therapeutic potentials of these C-type inactivation-dependent Kv channel inhibitors are discussed. © 2011 Elsevier Inc. © 2011 Elsevier Inc. All rights reserved.


Chen J.-L.,China Medical University at Taichung
Journal of Chromatography A | Year: 2010

Prepared multi-wall carbon nanotube (MWNT) materials, including untreated MWNT, HNO3-treated MWNT and HNO3-HCl-treated MWNT were covalently attached onto a silica-hydride-modified capillary by hydrosilation, using the abundant double bonds between the pentagon carbons in the MWNT structure. These MWNT-incorporated capillaries were characterized by SEM, ATR-IR and electroosmotic flow (EOF) measurements in phosphate buffers with a pH range of 3.7-9.3 and in the mixtures of acetonitrile modifier. The untreated capillary was assumed to carry some carboxylate groups formed on the non-acid-treated MWNTs, as it had higher EOF values than the hydride capillary. As the MWNTs were treated with HNO3 and HCl solutions, the capillaries had increasingly higher EOF values. To examine the existence of an electrochromatography mechanism in the modified capillaries, a mixture of nucleosides and thymine was probed to check the velocity factor and retention factor. In addition to the π-π interaction between the probe solutes and the MWNT immobilized stationary phases; a reversed-phase mechanism could contribute to the chromatographic retention. For acidic tetracyclines, increasing the loadability of MWNTs resulted in a high retention factor and improved the separation resolution. © 2009 Elsevier B.V. All rights reserved.


Chien S.H.-L.,China Medical University at Taichung
Journal of Vision | Year: 2011

A non-specific "top-heavy" configuration bias has been proposed to explain neonatal face preference (F. Simion, E. Valenza, V. Macchi Cassia, C. Turati, & C. Umiltà, 2002). Using an eye tracker (Tobii T60), we investigated whether the top-heavy bias is still present in 3- to 5.5-month-old infants and in adults as a comparison group. Each infant and adult viewed three classes of stimuli: simple geometric patterns, face-like figures, and photographs of faces. Using area of interest analyses on fixation duration, we computed a top-heavy bias index (a number between -1 and 1) for each individual. Our results showed that the indices for the geometric and face-like patterns were about zero in infants, indicating no consistent bias for the "top-heavy" configuration. In adults, the indices for the geometric and face-like patterns were also close to zero except for the T-shaped figure and the ones that had higher rating on facedness. Moreover, the indices for photographs of faces were positive in both infants and adults, indicating significant preferences for upright natural faces over inverted ones. Taken together, we found no evidence for the top-heavy configuration bias in both infants and adults. The absence of top-heavy bias plus a clear preference for photographed upright faces in infants seem to suggest an early cognitive specialization process toward face representation. © ARVO.


Chiou S.-M.,China Medical University at Taichung
Clinical Neurology and Neurosurgery | Year: 2013

Purpose: To evaluate the impact of gamma knife radiosurgery (GKRS) alone on the survival of brain metastasis patients. Methods: Fifty patients, 17 men and 33 women, with 169 metastatic tumors were retrospectively reviewed. Before therapy, their mean Karnofsky Performance Score was 78. The majority of their primary cancers stemmed from the lung (56%). Thirty-five patients harbored multiple tumors. The mean tumor volume was 3.7 ml. The mean margin dose was 16 Gy. The mean/median clinical follow-up period was 37/25 weeks. Results: The overall image-proven tumor control rate was 76%, and the median tumor progression-free period was 26 weeks after radiosurgery. The survival rate of the patients was 58% and 30% at 6 and 12 months, respectively, and the overall median post-radiosurgery survival time was 38 weeks. Both uni- and multi-variate Cox analyses demonstrated that patients with KPS ≧ 80 or who were in Recursive Partitioning Analysis Class I survived significantly longer (p < 0.05). Conclusions: Patients treated with GKRS alone can prolong their median lifespan by a range of 6-10 months if they are in a good pre-GKRS functional state. © 2012 Elsevier B.V.

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