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href="https://www.academia.edu/80828408/Anti_leukemic_mechanisms_of_novel_FTY720_analogue_a_crucial_role_of_mitochondrial_stress_in_apoptosis_and_autophagy"><img alt="Research paper thumbnail of Anti-leukemic mechanisms of novel FTY720 analogue-a crucial role of mitochondrial stress in apoptosis and autophagy" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/80828408/Anti_leukemic_mechanisms_of_novel_FTY720_analogue_a_crucial_role_of_mitochondrial_stress_in_apoptosis_and_autophagy">Anti-leukemic mechanisms of novel FTY720 analogue-a crucial role of mitochondrial stress in apoptosis and autophagy</a></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828408"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828408"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828408; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80828408]").text(description); $(".js-view-count[data-work-id=80828408]").attr('title', description).tooltip(); }); });</script></span></span><span><span 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$a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828407"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828407/Antileukemic_Natural_Product_Induced_Both_Apoptotic_and_Pyroptotic_Programmed_Cell_Death_and_Differentiation_Effect"><img alt="Research paper thumbnail of Antileukemic Natural Product Induced Both Apoptotic and Pyroptotic Programmed Cell Death and Differentiation Effect" class="work-thumbnail" src="https://attachments.academia-assets.com/87079795/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828407/Antileukemic_Natural_Product_Induced_Both_Apoptotic_and_Pyroptotic_Programmed_Cell_Death_and_Differentiation_Effect">Antileukemic Natural Product Induced Both Apoptotic and Pyroptotic Programmed Cell Death and Differentiation Effect</a></div><div class="wp-workCard_item"><span>International Journal of Molecular Sciences</span><span>, 2021</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Acute myeloid leukemia (AML) is one of the most common forms of leukemia. Despite advances in the...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Acute myeloid leukemia (AML) is one of the most common forms of leukemia. Despite advances in the management of such malignancies and the progress of novel therapies, unmet medical needs still exist in AML because of several factors, including poor response to chemotherapy and high relapse rates. Ardisianone, a plant-derived natural component with an alkyl benzoquinone structure, induced apoptosis in leukemic HL-60 cells. The determination of dozens of apoptosis-related proteins showed that ardisianone upregulated death receptors and downregulated the inhibitor of apoptosis protein (IAPs). Western blotting showed that ardisianone induced a dramatic increase in tumor necrosis factor receptor 2 (TNFR2) protein expression. Ardisianone also induced downstream signaling by activating caspase-8 and -3 and degradation in Bid, a caspase-8 substrate. Furthermore, ardisianone induced degradation in DNA fragmentation factor 45 kDa (DFF45), a subunit of inhibitors of caspase-activated DNase (IC...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="0b5264e504815a23d7e2e7d0660c1cf8" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079795,"asset_id":80828407,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079795/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828407"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828407"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828407; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828406"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828406/Synthesis_distribution_analysis_and_mechanism_studies_of_N_acyl_glucosamine_bearing_oleanolic_saponins"><img alt="Research paper thumbnail of Synthesis, distribution analysis and mechanism studies of N-acyl glucosamine-bearing oleanolic saponins" class="work-thumbnail" src="https://attachments.academia-assets.com/87079879/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828406/Synthesis_distribution_analysis_and_mechanism_studies_of_N_acyl_glucosamine_bearing_oleanolic_saponins">Synthesis, distribution analysis and mechanism studies of N-acyl glucosamine-bearing oleanolic saponins</a></div><div class="wp-workCard_item"><span>Bioorganic Chemistry</span><span>, 2020</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828405"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828405/Mechanistic_Study_of_Triazole_Based_Aminodiol_Derivatives_in_Leukemic_Cells_Crosstalk_between_Mitochondrial_Stress_Involved_Apoptosis_and_Autophagy"><img alt="Research paper thumbnail of Mechanistic Study of Triazole Based Aminodiol Derivatives in Leukemic Cells—Crosstalk between Mitochondrial Stress-Involved Apoptosis and Autophagy" class="work-thumbnail" src="https://attachments.academia-assets.com/87079796/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828405/Mechanistic_Study_of_Triazole_Based_Aminodiol_Derivatives_in_Leukemic_Cells_Crosstalk_between_Mitochondrial_Stress_Involved_Apoptosis_and_Autophagy">Mechanistic Study of Triazole Based Aminodiol Derivatives in Leukemic Cells—Crosstalk between Mitochondrial Stress-Involved Apoptosis and Autophagy</a></div><div class="wp-workCard_item"><span>International Journal of Molecular Sciences</span><span>, 2020</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Various derivatives that mimic ceramide structures by introducing a triazole to connect the amino...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Various derivatives that mimic ceramide structures by introducing a triazole to connect the aminodiol moiety and long alkyl chain have been synthesized and screened for their anti-leukemia activity. SPS8 stood out among the derivatives, showing cytotoxic selectivity between leukemic cell lines and human peripheral blood mononuclear cells (about ten times). DAPI nuclear staining and H&E staining revealed DNA fragmentation under the action of SPS8. SPS8 induced an increase in intracellular Ca2+ levels and mitochondrial stress in HL-60 cells identified by the loss of mitochondrial membrane potential, transmission electron microscopy (TEM) examination, and altered expressions of Bcl-2 family proteins. SPS8 also induced autophagy through the detection of Atg5, beclin-1, and LC3 II protein expression, as well as TEM examination. Chloroquine, an autophagy inhibitor, promoted SPS8-induced apoptosis, suggesting the cytoprotective role of autophagy in hindering SPS8 from apoptosis. Furthermor...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="530002d56a274efb51d28125e474a86b" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079796,"asset_id":80828405,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079796/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828405"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828405"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828405; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828403"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/80828403/P1_084Antileukemic_activity_and_mechanism_of_ardisianone_a_crucial_role_of_mitochondrial_stress_in_apoptosis_and_necroptosis"><img alt="Research paper thumbnail of P1-084Antileukemic activity and mechanism of ardisianone-a crucial role of mitochondrial stress in apoptosis and necroptosis" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/80828403/P1_084Antileukemic_activity_and_mechanism_of_ardisianone_a_crucial_role_of_mitochondrial_stress_in_apoptosis_and_necroptosis">P1-084Antileukemic activity and mechanism of ardisianone-a crucial role of mitochondrial stress in apoptosis and necroptosis</a></div><div class="wp-workCard_item"><span>Annals of Oncology</span><span>, 2019</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background Ardisianone was reported to induce apoptosis in prostate cancer cells, but necroptosis...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background Ardisianone was reported to induce apoptosis in prostate cancer cells, but necroptosis in leukemia cell lines. It is needed to clarify whether ardisianone could cause apoptosis and necroptosis in leukemia cells and investigate its underlying mechanisms. Methods Cytotoxicity was examined using the MTT assay. Cytoflowmetric analysis of JC-1 and PI staining was used to examine mitochondrial membrane potential and cell cycle progression, respectively. Apoptosis was examined by annexin V-PI staining assay. Protein expression was detected by Western blot and apoptosis antibody array chip. Immunofluorescence staining detected necroptosis effect. Results Ardisianone inhibited cell viability in HL-60, a promyelocytic leukemia cell line, with IC50 value of 1.87 µ M in a 24h exposure. Further detection showed that ardisianone induced time- and concentration-dependent apoptosis. JC-1 staining demonstrated that ardisianone caused a profound loss of mitochondrial membrane potential. We...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828403"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828403"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828403; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80828403]").text(description); $(".js-view-count[data-work-id=80828403]").attr('title', description).tooltip(); 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</script> <div class="js-work-strip profile--work_container" data-work-id="80828402"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828402/Determination_of_synthetic_cathinone_%CE%B1_PVP_and_its_metabolite_in_urine_using_solid_phase_extraction_and_gas_chromatography_mass_spectrometry"><img alt="Research paper thumbnail of Determination of synthetic cathinone “α‐PVP” and its metabolite in urine using solid phase extraction and gas chromatography‐mass spectrometry" class="work-thumbnail" src="https://attachments.academia-assets.com/87079870/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828402/Determination_of_synthetic_cathinone_%CE%B1_PVP_and_its_metabolite_in_urine_using_solid_phase_extraction_and_gas_chromatography_mass_spectrometry">Determination of synthetic cathinone “α‐PVP” and its metabolite in urine using solid phase extraction and gas chromatography‐mass spectrometry</a></div><div class="wp-workCard_item"><span>Rapid Communications in Mass Spectrometry</span><span>, 2019</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">A toxicological challenge is that the metabolites of α-PVP exhibit amphoteric properties, which m...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">A toxicological challenge is that the metabolites of α-PVP exhibit amphoteric properties, which make them unsuitable for detection using gas chromatography-mass spectrometry (GC/MS). In the study reported, proper derivatization and sample extraction were essential for improving the sensitivity for GC/MS analysis. Methods: An automated solid-phase extraction (SPE) method has been developed and optimized. The derivatization efficiency was tested using longer reaction time and the addition of polar pyridine into a mixture of N,O-bis(trimethylsilyl) trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane. Method validation, including linearity, limit of detection, precision, accuracy, and recovery, was evaluated using automatic SPE and GC/MS. Results: The results suggested that adding pyridine to BSTFA (1:1, v/v) significantly improved derivatization efficiency and precision. After optimization, the linear range was from 25 to 1000 ng mL −1 with R 2 > 0.9950. The limit of detection was 5 ng mL −1 for α-PVP and 25 ng mL −1 for OH-α-PVP. The recovery for SPE was over 88%. The inter-day and intra-day precisions were less than 15%. A forensic sample has been found containing α-PVP (67.3 ng mL −1) and OH-α-PVP (560.2 ng mL −1). Conclusions: This study is the first to validate an auto-SPE-GC/MS method for the quantification and qualification of α-PVP and OH-α-PVP in urine. We have successfully improved the derivatization efficiency and developed a sensitive and semi-automatic approach. This approach is desirable for the detection of synthetic cathinone at trace levels in biological samples. 1 | INTRODUCTION Synthetic cathinones are compounds that mimic the effects of the classic drugs that are abused. Administration of such designer drugs increases the release of norepinephrine and dopamine. These drugs also act as inhibitors of dopamine and norepinephrine transporters, which thus reduce serotonin reuptake and, consequently, cause stimulatory effects in the central nervous system. 1-5 These drugs</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="fa4211150c56d1c98650b2ea6144b9cf" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079870,"asset_id":80828402,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079870/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828402"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828402"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828402; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828401"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828401/An_integrated_approach_to_elucidate_signaling_pathways_of_dioscin_induced_apoptosis_energy_metabolism_and_differentiation_in_acute_myeloid_leukemia"><img alt="Research paper thumbnail of An integrated approach to elucidate signaling pathways of dioscin-induced apoptosis, energy metabolism and differentiation in acute myeloid leukemia" class="work-thumbnail" src="https://attachments.academia-assets.com/87079881/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828401/An_integrated_approach_to_elucidate_signaling_pathways_of_dioscin_induced_apoptosis_energy_metabolism_and_differentiation_in_acute_myeloid_leukemia">An integrated approach to elucidate signaling pathways of dioscin-induced apoptosis, energy metabolism and differentiation in acute myeloid leukemia</a></div><div class="wp-workCard_item"><span>Naunyn-Schmiedeberg's Archives of Pharmacology</span><span>, 2018</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Although the therapeutics have improved the rates of remission and cure of acute myelogenous leuk...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Although the therapeutics have improved the rates of remission and cure of acute myelogenous leukemia (AML) in recent decades, there is still an unmet medical need for AML therapies because disease relapses are a major obstacle in patients who become refractory to salvage therapy. The development of therapeutic agents promoting both cytotoxicity and cell differentiation may provide opportunities to improve the clinical outcome. Dioscin-induced apoptosis in leukemic cells was identified through death receptor-mediated extrinsic apoptosis pathway. The formation of Bak and tBid, and loss of mitochondrial membrane potential were induced by dioscin suggesting the activation of intrinsic apoptotsis pathway. A functional analysis of transcription factors using transcription factor-DNA interaction array and IPA analysis demonstrated that dioscin induced a profound increase of protein expression of CCAAT/enhancer-binding protein α (C/EBPα), a critical factor for myeloid differentiation. Twodimensional gel electrophoresis assay confirmed the increase of C/EBPα expression. Dioscin-induced differentiation was substantiated by an increase of CD11b protein expression and the induction of differentiation toward myelomonocytic/granulocytic lineages using hematoxylin and eosin staining. Moreover, both glycolysis and gluconeogenesis pathways after two-dimensional gel electrophoresis assay and IPA network enrichment analysis were proposed to dioscin action. In conclusion, the data suggest that dioscin exerts its antileukemic effect through the upregulation of both death ligands and death receptors and a crosstalk activation of mitochondrial apoptosis pathway with the collaboration of tBid and Bak formation. In addition, proteomics approach reveals an altered metabolic signature of dioscin-treated cells and the induction of differentiation of promyelocytes to granulocytes and monocytes in which the C/EBPα plays a key role.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="2b614c520983afe01b046061e4fe38f5" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079881,"asset_id":80828401,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079881/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828401"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828401"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828401; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828400"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828400/Phosphodiesterase_Type_5_PDE5_Inhibitors_Sensitize_Topoisomerase_II_Inhibitors_in_Killing_Prostate_Cancer_Through_PDE5_Independent_Impairment_of_HR_and_NHEJ_DNA_Repair_Systems"><img alt="Research paper thumbnail of Phosphodiesterase Type 5 (PDE5) Inhibitors Sensitize Topoisomerase II Inhibitors in Killing Prostate Cancer Through PDE5-Independent Impairment of HR and NHEJ DNA Repair Systems" class="work-thumbnail" src="https://attachments.academia-assets.com/87079863/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828400/Phosphodiesterase_Type_5_PDE5_Inhibitors_Sensitize_Topoisomerase_II_Inhibitors_in_Killing_Prostate_Cancer_Through_PDE5_Independent_Impairment_of_HR_and_NHEJ_DNA_Repair_Systems">Phosphodiesterase Type 5 (PDE5) Inhibitors Sensitize Topoisomerase II Inhibitors in Killing Prostate Cancer Through PDE5-Independent Impairment of HR and NHEJ DNA Repair Systems</a></div><div class="wp-workCard_item"><span>Frontiers in Oncology</span><span>, 2019</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Human castration-resistant prostate cancer (CRPC) is a significant target of clinical research. T...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Human castration-resistant prostate cancer (CRPC) is a significant target of clinical research. The use of DNA-damaging agents has a long history in cancer chemotherapy but is limited by their toxicities. The combination with a safer drug can be a strategy in reducing dosage and toxicity while increasing anticancer activity in CRPC treatment. Phosphodiesterase type 5 (PDE5) inhibitors are used to treat erectile dysfunction through the selective inhibition of PDE5 that is responsible for cGMP degradation in the corpus cavernosum. Several studies have reported that PDE5 inhibitors display protective effect against doxorubicin-induced cardiotoxicity. The combinatory treatment of CRPC with doxorubicin and PDE5 inhibitors has been studied accordingly. The data demonstrated that sildenafil or vardenafil (two structure-related PDE5 inhibitors) but not tadalafil (structure-unrelated to sildenafil) sensitized doxorubicin-induced apoptosis in CRPC cells with deteriorating the down-regulation of anti-apoptotic Bcl-2 family members, including Bcl-xL and Mcl-1, and amplifying caspase activation. Homologous recombination (HR) and non-homologous end joining (NHEJ) DNA repair systems were inhibited in the apoptotic sensitization through detection of nuclear foci formation of Rad51 and DNA end-binding of Ku80. PDE5 knockdown to mimic the exposure to PDE5 inhibitors did not reproduce apoptotic sensitization, suggesting a PDE5-independent mechanism. Not only doxorubicin, sildenafil combined with other inhibitors of topoisomerase II but not topoisomerase I also triggered apoptotic sensitization. In conclusion, the data suggest that sildenafil and vardenafil induce PDE5-independent apoptotic sensitization to doxorubicin (or other topoisomerase II inhibitors) through impairment of both HR and NHEJ repair systems that are evident by a decrease of nuclear Rad51 levels and their foci formation in the nucleus, and an inhibition of Ku80 DNA end-binding capability. The combinatory treatment may enable an important strategy for anti-CRPC development.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="84c7ab4e4042f1b55058578fcc07b098" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079863,"asset_id":80828400,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079863/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828400"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828400"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828400; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828399"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828399/Design_synthesis_and_cytotoxic_activity_of_N_Modified_oleanolic_saponins_bearing_A_glucosamine"><img alt="Research paper thumbnail of Design, synthesis and cytotoxic activity of N-Modified oleanolic saponins bearing A glucosamine" class="work-thumbnail" src="https://attachments.academia-assets.com/87079868/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828399/Design_synthesis_and_cytotoxic_activity_of_N_Modified_oleanolic_saponins_bearing_A_glucosamine">Design, synthesis and cytotoxic activity of N-Modified oleanolic saponins bearing A glucosamine</a></div><div class="wp-workCard_item"><span>European journal of medicinal chemistry</span><span>, Jan 6, 2017</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">A series of N-acyl, N-alkoxycarbonyl, and N-alkylcarbamoyl derivatives of 2&#39;-deoxy-glucosyl b...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">A series of N-acyl, N-alkoxycarbonyl, and N-alkylcarbamoyl derivatives of 2&#39;-deoxy-glucosyl bearing oleanolic saponins were synthesized and evaluated against HL-60, PC-3, and HT29 tumor cancer cells. The SAR studies revealed that the activity increased in order of conjugation of 2&#39; -amino group with carbamate &gt; amide &gt; urea derivatives. Lengthening the alkyl chain increased the cytotoxicity, the peak activity was found to around heptyl to nonyl substitutions. 2&#39;-N-heptoxycarbonyl derivative 56 was found to be the most cytotoxic (IC50 = 0.76 μM) against HL-60 cells. Due to the interesting SARs of alkyl substitutions, we hypothesized that their location in the cell was different, and pursued a location study using 2&#39;-(4″-pentynoylamino) 2&#39;-deoxy-glucosyl OA, which suggested that these compounds distributed mainly in the cytosol.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="717d8d650a188018c62fbad0f1519c2c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079868,"asset_id":80828399,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079868/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828399"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828399"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828399; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828398"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/80828398/P1_9_56Anti_leukemic_mechanisms_of_novel_FTY720_analogue_a_crucial_role_of_mitochondrial_stress_in_apoptosis_and_autophagy"><img alt="Research paper thumbnail of P1-9-56Anti-leukemic mechanisms of novel FTY720 analogue-a crucial role of mitochondrial stress in apoptosis and autophagy" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/80828398/P1_9_56Anti_leukemic_mechanisms_of_novel_FTY720_analogue_a_crucial_role_of_mitochondrial_stress_in_apoptosis_and_autophagy">P1-9-56Anti-leukemic mechanisms of novel FTY720 analogue-a crucial role of mitochondrial stress in apoptosis and autophagy</a></div><div class="wp-workCard_item"><span>Annals of Oncology</span><span>, 2015</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828398"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828398"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828398; 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</script> <div class="js-work-strip profile--work_container" data-work-id="80828397"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828397/Non_immunosuppressive_triazole_based_small_molecule_induces_anticancer_activity_against_human_hormone_refractory_prostate_cancers_the_role_in_inhibition_of_PI3K_AKT_mTOR_and_c_Myc_signaling_pathways"><img alt="Research paper thumbnail of Non-immunosuppressive triazole-based small molecule induces anticancer activity against human hormone-refractory prostate cancers: the role in inhibition of PI3K/AKT/mTOR and c-Myc signaling pathways" class="work-thumbnail" src="https://attachments.academia-assets.com/87079869/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828397/Non_immunosuppressive_triazole_based_small_molecule_induces_anticancer_activity_against_human_hormone_refractory_prostate_cancers_the_role_in_inhibition_of_PI3K_AKT_mTOR_and_c_Myc_signaling_pathways">Non-immunosuppressive triazole-based small molecule induces anticancer activity against human hormone-refractory prostate cancers: the role in inhibition of PI3K/AKT/mTOR and c-Myc signaling pathways</a></div><div class="wp-workCard_item"><span>Oncotarget</span><span>, 2016</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">A series of triazole-based small molecules that mimic FTY720-mediated anticancer activity but min...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">A series of triazole-based small molecules that mimic FTY720-mediated anticancer activity but minimize its immunosuppressive effect have been produced. SPS-7 is the most effective derivative displaying higher activity than FTY720 in anti-proliferation against human hormone-refractory prostate cancer (HRPC). It induced G1 arrest of cell cycle and subsequent apoptosis in thymidine blockmediated synchronization model. The data were supported by a decrease of cyclin D1 expression, a dramatic increase of p21 expression and an associated decrease in RB phosphorylation. c-Myc overexpression replenished protein levels of cyclin D1 indicating that c-Myc was responsible for cell cycle regulation. PI3K/Akt/mTOR signaling pathways through p70S6K-and 4EBP1-mediated translational regulation are critical to cell proliferation and survival. SPS-7 significantly inhibited this translational pathway. Overexpression of Myr-Akt (constitutively active Akt) completely abolished SPS-7-induced inhibitory effect on mTOR/p70S6K/4EBP1 signaling and c-Myc protein expression, suggesting that PI3K/Akt serves as a key upstream regulator. SPS-7 also demonstrated substantial anti-tumor efficacy in an in vivo xenograft study using PC-3 mouse model. Notably, FTY720 but not SPS-7 induced a significant immunosuppressive effect as evidenced by depletion of marginal zone B cells, downregulation of sphingosine-1-phosphate receptors and a decrease in peripheral blood lymphocytes. In conclusion, the data suggest that SPS-7 is not an immunosuppressant while induces anticancer effect against HRPC through inhibition of Akt/mTOR/ p70S6K pathwaysthat down-regulate protein levels of both c-Myc and cyclin D1, leading to G1 arrest of cell cycle and subsequent apoptosis. The data also indicate the potential of SPS-7 since PI3K/Akt signalingis responsive for the genomic alterations in prostate cancer.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="ed0b098cc7d1d1008a4c7bc14d2e415d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079869,"asset_id":80828397,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079869/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828397"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828397"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828397; 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dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "ed0b098cc7d1d1008a4c7bc14d2e415d" } } $('.js-work-strip[data-work-id=80828397]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":80828397,"title":"Non-immunosuppressive triazole-based small molecule induces anticancer activity against human hormone-refractory prostate cancers: the role in inhibition of PI3K/AKT/mTOR and c-Myc signaling pathways","internal_url":"https://www.academia.edu/80828397/Non_immunosuppressive_triazole_based_small_molecule_induces_anticancer_activity_against_human_hormone_refractory_prostate_cancers_the_role_in_inhibition_of_PI3K_AKT_mTOR_and_c_Myc_signaling_pathways","owner_id":223033354,"coauthors_can_edit":true,"owner":{"id":223033354,"first_name":"She-Hung","middle_initials":null,"last_name":"Chan","page_name":"SheHungChan","domain_name":"independent","created_at":"2022-05-09T07:50:30.677-07:00","display_name":"She-Hung Chan","url":"https://independent.academia.edu/SheHungChan"},"attachments":[{"id":87079869,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/87079869/thumbnails/1.jpg","file_name":"92119b12984b86dafa9fbb50cca913bc8f8a.pdf","download_url":"https://www.academia.edu/attachments/87079869/download_file","bulk_download_file_name":"Non_immunosuppressive_triazole_based_sma.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/87079869/92119b12984b86dafa9fbb50cca913bc8f8a-libre.pdf?1654522739=\u0026response-content-disposition=attachment%3B+filename%3DNon_immunosuppressive_triazole_based_sma.pdf\u0026Expires=1739799212\u0026Signature=USEZGpuxeyL3ml8txkO116Auudt1Qyu0fgDC5bYOMztC5tqt4Wix8a-3Z2LKH4HAJBhQ2tFZFsRcZqPPe2H48duN30tyZRLW0elTWqPphU1x0VzjwMqssOsVypkHZOcmg~EK7rE1XcCbyXmxQY7IUQnF44PR9u1983xwS2oQZuJbvrB3H862DJN3DFHGT3RlWY952faPU2V-1zRoh7bC2Lt4i9~knW~9FLGdwMhVNONNZxpNKWx0TYflmxyn1gzlMfFySlTDw4trHo3e1cCgHjPrz4wwhL54LiXa~Vhokpiis0LJ~PMGSBgHzAHzbIMBKhNULGHNTdirF7BUgtJwWA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828396"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828396/The_effects_of_antiepileptic_drugs_on_the_growth_of_glioblastoma_cell_lines"><img alt="Research paper thumbnail of The effects of antiepileptic drugs on the growth of glioblastoma cell lines" class="work-thumbnail" src="https://attachments.academia-assets.com/87079865/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828396/The_effects_of_antiepileptic_drugs_on_the_growth_of_glioblastoma_cell_lines">The effects of antiepileptic drugs on the growth of glioblastoma cell lines</a></div><div class="wp-workCard_item"><span>Journal of Neuro-Oncology</span><span>, 2016</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">To determine the effects of antiepileptic drug compounds on glioblastoma cellular growth, we expo...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">To determine the effects of antiepileptic drug compounds on glioblastoma cellular growth, we exposed glioblastoma cell lines to select antiepileptic drugs. The effects of selected antiepileptic drugs on glioblastoma cells were measured by MTT assay. For compounds showing significant inhibition, cell cycle analysis was performed. Statistical analysis was performed using SPSS. The antiepileptic compounds selected for screening included carbamazepine, ethosuximide, gabapentin, lamotrigine, levetiracetam, magnesium sulfate, oxcarbazepine, phenytoin, primidone, tiagabine, topiramate, valproic acid, and vigabatrin. Dexamethasone and temozolomide were used as a negative and positive control respectively. Our results showed temozolomide and oxcarbazepine significantly inhibited glioblastoma cell growth and reached IC 50 at therapeutic concentrations. The other antiepileptic drugs screened were unable to reach IC 50 at therapeutic concentrations. The metabolites of oxcarbazepine were also unable to reach IC 50. Dexamethasone, ethosuximide, levetiracetam, and vigabatrin showed some growth enhancement though they did not reach statistical significance. The growth enhancement effects of ethosuximide, levetiracetam, and vigabatrin found in the study may indicate that these compounds should not be used for prophylaxis or short term treatment of epilepsy in glioblastoma. While valproic acid and oxcarbazepine were effective, the required dose of valproic acid was far above that used for the treatment of epilepsy and the metabolites of oxcarbazepine failed to reach significant growth inhibition ruling out the use of oral oxcarbazepine or valproic acid as monotherapy in glioblastoma. The possibility of using these compounds as local treatment is a future area of study.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="d2130c814ec80d9bdd7a4d97c0ad8c2a" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079865,"asset_id":80828396,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079865/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828396"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828396"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828396; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80828396]").text(description); $(".js-view-count[data-work-id=80828396]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 80828396; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='80828396']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "d2130c814ec80d9bdd7a4d97c0ad8c2a" } } $('.js-work-strip[data-work-id=80828396]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":80828396,"title":"The effects of antiepileptic drugs on the growth of glioblastoma cell lines","internal_url":"https://www.academia.edu/80828396/The_effects_of_antiepileptic_drugs_on_the_growth_of_glioblastoma_cell_lines","owner_id":223033354,"coauthors_can_edit":true,"owner":{"id":223033354,"first_name":"She-Hung","middle_initials":null,"last_name":"Chan","page_name":"SheHungChan","domain_name":"independent","created_at":"2022-05-09T07:50:30.677-07:00","display_name":"She-Hung Chan","url":"https://independent.academia.edu/SheHungChan"},"attachments":[{"id":87079865,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/87079865/thumbnails/1.jpg","file_name":"pmc4835521.pdf","download_url":"https://www.academia.edu/attachments/87079865/download_file","bulk_download_file_name":"The_effects_of_antiepileptic_drugs_on_th.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/87079865/pmc4835521-libre.pdf?1654522733=\u0026response-content-disposition=attachment%3B+filename%3DThe_effects_of_antiepileptic_drugs_on_th.pdf\u0026Expires=1739799213\u0026Signature=SwoGWbjpjjENR57fvFQCuEou~S-MbvXqEdJSzpXfGz9RUj7EHAyDe4IGHOsEt0OykcKXadr3VF4AmPOguzF-LaeIvzrmsGGUI9R10Fn5ex5h~kpO3oX0CaI8jKofk1UX0d0lf3jXNa3GNLifu5rjwIOdRXwIFkrqqEFOUDcAJL2H5BnuT89o1nAuwmiIJs1aKeHf7Uaiy7i-qwwVnISn1dSkvfdN9-ohfskowXIW6bhZngwuqVy1xpXSQADRyL6JC18GDcWuo0B25GrhupbQb5SiWoiSiAmawvtE5R2MVLmhNZCwSFvMNjiVAyCpZzoJiVflmPMqfiMmpjZlTFZkCQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828395"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/80828395/Raised_Proinflammatory_Cytokine_Production_Within_Cerebrospinal_Fluid_Precedes_Fever_Onset_in_Patients_With_Neurosurgery_Associated_Bacterial_Meningitis_"><img alt="Research paper thumbnail of Raised Proinflammatory Cytokine Production Within Cerebrospinal Fluid Precedes Fever Onset in Patients With Neurosurgery-Associated Bacterial Meningitis*" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/80828395/Raised_Proinflammatory_Cytokine_Production_Within_Cerebrospinal_Fluid_Precedes_Fever_Onset_in_Patients_With_Neurosurgery_Associated_Bacterial_Meningitis_">Raised Proinflammatory Cytokine Production Within Cerebrospinal Fluid Precedes Fever Onset in Patients With Neurosurgery-Associated Bacterial Meningitis*</a></div><div class="wp-workCard_item"><span>Critical Care Medicine</span><span>, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The objective of the present study was to determine whether selective inflammatory cytokine conce...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The objective of the present study was to determine whether selective inflammatory cytokine concentrations within cerebrospinal fluid are useful markers for the differential diagnosis of aseptic and bacterial meningitis within neurosurgical patients. Prospective, open-label, observational, cohort study. Neurosurgical ICU, Chang Gung Memorial Hospital. Thirty-two consecutive neurosurgical patients who had postoperative fever following external ventricular drain insertion for the treatment of brain injury underwent serial cerebrospinal fluid cytokine analysis pre and post fever to determine the value of such markers in ascertaining the differential diagnosis of meningitis. Cerebrospinal fluid samples were collected on the day of fever onset, as well as on day 2 and 4 pre and post fever development. Tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-8, transforming growth factor-β, and procalcitonin were subsequently analyzed using enzyme-linked immunosorbent assay analysis techniques. Inflammatory marker levels were compared among febrile aseptic, bacterial, and nonmeningitis patients to determine cerebrospinal fluid inflammatory changes over time. Significant increases in cerebrospinal fluid tumor necrosis factor -α, interleukin-1β, interleukin-6, and interleukin-8 levels were observed within patients with bacterial meningitis at fever onset, which was not evident in aseptic or nonmeningitis patients. Furthermore, significant increases in cerebrospinal fluid tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8 levels were detected as early as 4 days prior to fever onset within patients with bacterial meningitis when compared with both aseptic and nonmeningitis groups. Interestingly, procalcitonin was only significantly increased in patients with bacterial meningitis on the fourth day post fever. The present study suggests that raised cerebrospinal fluid tumor necrosis factor -α, interleukin-1β, and interleukin-8 in a temporal manner may indicate early bacterial meningitis development in neurosurgical patients, enabling earlier diagnostic certainty and improved patient outcomes.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828395"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828395"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828395; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80828395]").text(description); $(".js-view-count[data-work-id=80828395]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 80828395; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='80828395']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=80828395]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":80828395,"title":"Raised Proinflammatory Cytokine Production Within Cerebrospinal Fluid Precedes Fever Onset in Patients With Neurosurgery-Associated Bacterial Meningitis*","internal_url":"https://www.academia.edu/80828395/Raised_Proinflammatory_Cytokine_Production_Within_Cerebrospinal_Fluid_Precedes_Fever_Onset_in_Patients_With_Neurosurgery_Associated_Bacterial_Meningitis_","owner_id":223033354,"coauthors_can_edit":true,"owner":{"id":223033354,"first_name":"She-Hung","middle_initials":null,"last_name":"Chan","page_name":"SheHungChan","domain_name":"independent","created_at":"2022-05-09T07:50:30.677-07:00","display_name":"She-Hung Chan","url":"https://independent.academia.edu/SheHungChan"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828394"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828394/Cytotoxic_protobassic_acid_glycosides_from_Planchonella_obovata_leaf"><img alt="Research paper thumbnail of Cytotoxic protobassic acid glycosides from Planchonella obovata leaf" class="work-thumbnail" src="https://attachments.academia-assets.com/87079864/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828394/Cytotoxic_protobassic_acid_glycosides_from_Planchonella_obovata_leaf">Cytotoxic protobassic acid glycosides from Planchonella obovata leaf</a></div><div class="wp-workCard_item"><span>Phytochemistry Letters</span><span>, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Four triterpenoid glycosides, possessing protobassic acid as common aglycon, together with 16 kno...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Four triterpenoid glycosides, possessing protobassic acid as common aglycon, together with 16 known compounds were isolated from the leaves of Planchonella obovata. They are 6b-hydroxy-conyzasaponin G (2), 3 000-Ode -b-D-apiofuranosylisoarganin F (3), isoarganin F (4), and 6b-hydroxy-conyzasaponin N (5). The structures of these glycosides were elucidated based on spectroscopic analysis, in particular using 1D TOCSY to confirm the 1 H NMR assignment of each sugar residue. The absolute configuration of each monosaccharide in the glycon part was determined by GC-FID. Compound 5, Mi-saponin A (8), and ursolic acid (10) showed moderate inhibitory activities against HL-60 leukemia cell line with the IC 50</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="dc271100afc193e4f1c6039e8cf0581f" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079864,"asset_id":80828394,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079864/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828394"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828394"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828394; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828392"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828392/ChemInform_Abstract_Asymmetric_Synthesis_of_Brevipolide_H_Through_Cyclopropanation_of_the_%CE%B1_%CE%B2_Unsaturated_Ketone"><img alt="Research paper thumbnail of ChemInform Abstract: Asymmetric Synthesis of (-)-Brevipolide H Through Cyclopropanation of the α,β-Unsaturated Ketone" class="work-thumbnail" src="https://attachments.academia-assets.com/87079859/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828392/ChemInform_Abstract_Asymmetric_Synthesis_of_Brevipolide_H_Through_Cyclopropanation_of_the_%CE%B1_%CE%B2_Unsaturated_Ketone">ChemInform Abstract: Asymmetric Synthesis of (-)-Brevipolide H Through Cyclopropanation of the α,β-Unsaturated Ketone</a></div><div class="wp-workCard_item"><span>ChemInform</span><span>, 2015</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="78b54329405a86b6c32e7a3ac2d8134b" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079859,"asset_id":80828392,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079859/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828392"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828392"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828392; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80828392]").text(description); $(".js-view-count[data-work-id=80828392]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 80828392; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='80828392']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "78b54329405a86b6c32e7a3ac2d8134b" } } $('.js-work-strip[data-work-id=80828392]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":80828392,"title":"ChemInform Abstract: Asymmetric Synthesis of (-)-Brevipolide H Through Cyclopropanation of the α,β-Unsaturated Ketone","internal_url":"https://www.academia.edu/80828392/ChemInform_Abstract_Asymmetric_Synthesis_of_Brevipolide_H_Through_Cyclopropanation_of_the_%CE%B1_%CE%B2_Unsaturated_Ketone","owner_id":223033354,"coauthors_can_edit":true,"owner":{"id":223033354,"first_name":"She-Hung","middle_initials":null,"last_name":"Chan","page_name":"SheHungChan","domain_name":"independent","created_at":"2022-05-09T07:50:30.677-07:00","display_name":"She-Hung Chan","url":"https://independent.academia.edu/SheHungChan"},"attachments":[{"id":87079859,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/87079859/thumbnails/1.jpg","file_name":"chin.19981308620220606-1-u5yekm.pdf","download_url":"https://www.academia.edu/attachments/87079859/download_file","bulk_download_file_name":"ChemInform_Abstract_Asymmetric_Synthesis.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/87079859/chin.19981308620220606-1-u5yekm-libre.pdf?1654522729=\u0026response-content-disposition=attachment%3B+filename%3DChemInform_Abstract_Asymmetric_Synthesis.pdf\u0026Expires=1739799213\u0026Signature=Knz0TASE3hgJIz4mYxdDzxSVockM6V095ZE3KeKxn3IMAIy6zRAwFxdE8fcAlVcTGx4CjNuv9BFRJ8kpzBytX3O5AmL9LJKuEiY3YmhXBFeJr9oEa8GsrvGVn3iF2alRu1GBJXHmLfAeBH~GiMvQhVXOP949aCRJeTwXlFBraI-akOFsCjjM6BHiwCufA1IiVpm7R3TwB~4G396DBP6xC6E4WLpK6KnBCDUa83Sb14eQwmmDAqi4YpCd0g08paT5jwfGhYus9cIiZfa-q~r0DXxcfqR7NVXI-rQoYhaes6bNU-jueBorHbyruaHWpr8wKiKENsoj62G9~FzDK7AXcg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828391"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828391/Medical_Record_Review_for_Faculty_Promotion_A_Cohort_Analysis"><img alt="Research paper thumbnail of Medical Record Review for Faculty Promotion: A Cohort Analysis" class="work-thumbnail" src="https://attachments.academia-assets.com/87079860/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828391/Medical_Record_Review_for_Faculty_Promotion_A_Cohort_Analysis">Medical Record Review for Faculty Promotion: A Cohort Analysis</a></div><div class="wp-workCard_item"><span>Biomedical Journal</span><span>, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background: A medical record is an important source of information regarding medical care and med...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background: A medical record is an important source of information regarding medical care and medical record review plays an important role in the evaluation of the teaching proficiency. The study analyzed the difference between internal and external auditing when conducting medical record review for faculty promotion in a study institute. Methods: We analyzed the scores related to the medical records maintained by applicants for the faculty promotion of attending physicians during the period between 2008 and 2010 at the Chang Gung Memorial Hospital. The scores were obtained from one internal reviewer of the study institute and two external reviewers from other medical centers, and routine scores were obtained from the Committee of Medical Record 1 year before application. Pearson's correlation coefficient was used to analyze the correlation and statistical significance. Results: There were 259 applicants for faculty promotion enrolled in this study [professors (n = 33, 13%), associate professors (n = 63, 24%), assistant professors (n = 90, 35%), lecturers (n = 73, 28%)]. The scores of the external reviewers 1 and 2 were correlated with routine scores (r = 0.187, p = 0.002; r = 0.198, p = 0.001; N= 259), respectively. The correlation between external reviewers' average and ordinary scores was significant for assistant professor (r = 0.334, p = 0.001, n = 90) and professor grades (r = 0.469, p = 0.006, n = 33). However, the internal reviewer scores did not correlate with the routine scores (r = 0.073, p = 0.241, N = 259). Conclusions: The scores from external reviewers correlated more with routine scores than the scores from internal reviewers, suggesting that utilizing an external auditing system of medical records for the faculty promotion of attending physicians is quite feasible and balanced.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="400a96851f0e9cafc3fbd51346c04114" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079860,"asset_id":80828391,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079860/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828391"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828391"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828391; 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dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "400a96851f0e9cafc3fbd51346c04114" } } $('.js-work-strip[data-work-id=80828391]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":80828391,"title":"Medical Record Review for Faculty Promotion: A Cohort Analysis","internal_url":"https://www.academia.edu/80828391/Medical_Record_Review_for_Faculty_Promotion_A_Cohort_Analysis","owner_id":223033354,"coauthors_can_edit":true,"owner":{"id":223033354,"first_name":"She-Hung","middle_initials":null,"last_name":"Chan","page_name":"SheHungChan","domain_name":"independent","created_at":"2022-05-09T07:50:30.677-07:00","display_name":"She-Hung Chan","url":"https://independent.academia.edu/SheHungChan"},"attachments":[{"id":87079860,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/87079860/thumbnails/1.jpg","file_name":"BiomedJ_2015_38_5_456_151028.pdf","download_url":"https://www.academia.edu/attachments/87079860/download_file","bulk_download_file_name":"Medical_Record_Review_for_Faculty_Promot.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/87079860/BiomedJ_2015_38_5_456_151028.pdf?1738506381=\u0026response-content-disposition=attachment%3B+filename%3DMedical_Record_Review_for_Faculty_Promot.pdf\u0026Expires=1739799213\u0026Signature=cPrU82h9bYQTqubQWCHcRau9d9kA6J-AF-aIQRmqyj-RKut8bqvYOOuFTVpbb6yE34HgNVSaoOdvTlSNd1~P2KuKO1FKEtT3v0tuptYNUypPlxG-QAOEITA41xk0M9yv3IyG1OMiorYXpFaAWXH0E0yitVtvAj0j9ovHSShTMxuvP5WrlkSM92kYizEZbPlBNBEy~ZsEe7vJ0O~r5Zm8PCoAqBIh9RRt3zehqzpTQ9-2CcjWlg49SNNfOc3JJRKCh4PMAQ8gRyWArW6cm9fs5ExOvMdMC8oSmXuekLIWyPxsh7ZNrzVlXSAORyf~4yFkOWZf6OQeq3GlC4VSBQ7n8w__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828389"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/80828389/Synthesis_and_anti_cancer_activity_of_a_glycosyl_library_of_varvec_N_N_acetylglucosamine_bearing_oleanolic_acid"><img alt="Research paper thumbnail of Synthesis and anti-cancer activity of a glycosyl library of \varvec{N} N -acetylglucosamine-bearing oleanolic acid" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/80828389/Synthesis_and_anti_cancer_activity_of_a_glycosyl_library_of_varvec_N_N_acetylglucosamine_bearing_oleanolic_acid">Synthesis and anti-cancer activity of a glycosyl library of \varvec{N} N -acetylglucosamine-bearing oleanolic acid</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">N-Acetylglucosamine-bearing triterpenoid saponins (GNTS) were reported to be a unique type of sap...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">N-Acetylglucosamine-bearing triterpenoid saponins (GNTS) were reported to be a unique type of saponins with potent anti-tumor activity. In order to study the structure-activity relationship of GNTS, 24 oleanolic acid saponins with (1 --&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 3)-linked, (1 --&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 4)-linked, (1 --&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 6)-linked N-acetylglucosamine oligosaccharide residues were synthesized in a combinatorial and concise method. The cytotoxicity of these compounds toward the leukemia cell line HL-60 and the colorectal cancer cell line HT-29 could not be improved. Half maximal inhibition below 10 μM was achieved in one single case. The study revealed that the activity decreased following the order of 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 4&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 6&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; glycosyl modifications. GNTS that incorporated (D/L)-xylose and L-arabinose at positions 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; and 4&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; were more potent than those bearing other sugars.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828389"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828389"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828389; 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</script> <div class="js-work-strip profile--work_container" data-work-id="80828387"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/80828387/Asymmetric_Synthesis_of_Brevipolide_H_through_Cyclopropanation_of_the_%CE%B1_%CE%B2_Unsaturated_Ketone"><img alt="Research paper thumbnail of Asymmetric Synthesis of (−)-Brevipolide H through Cyclopropanation of the α,β-Unsaturated Ketone" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/80828387/Asymmetric_Synthesis_of_Brevipolide_H_through_Cyclopropanation_of_the_%CE%B1_%CE%B2_Unsaturated_Ketone">Asymmetric Synthesis of (−)-Brevipolide H through Cyclopropanation of the α,β-Unsaturated Ketone</a></div><div class="wp-workCard_item"><span>Organic Letters</span><span>, 2014</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Brevipolides are 5,6-dihydro-γ-pyrone derivatives, first reported in 2004 as the inhibitors of th...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Brevipolides are 5,6-dihydro-γ-pyrone derivatives, first reported in 2004 as the inhibitors of the chemokine receptor CCR5 and exhibiting cytotoxicity against cancer cells. Starting from the C2 symmetric diene-diol 2, ent-brevipolide H was synthesized for the first time in 11 steps. The anti-addition of the sulfur ylide to the α,β-unsaturated enones was developed to give the key cyclopropane moiety. The synthetic (-)-brevipolide H showed an IC50 value of 7.7 μM against PC-3 cells.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828387"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828387"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828387; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80828387]").text(description); 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</script> <div class="js-work-strip profile--work_container" data-work-id="80828386"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828386/Reevesioside_A_a_Cardenolide_Glycoside_Induces_Anticancer_Activity_against_Human_Hormone_Refractory_Prostate_Cancers_through_Suppression_of_c_myc_Expression_and_Induction_of_G1_Arrest_of_the_Cell_Cycle"><img alt="Research paper thumbnail of Reevesioside A, a Cardenolide Glycoside, Induces Anticancer Activity against Human Hormone-Refractory Prostate Cancers through Suppression of c-myc Expression and Induction of G1 Arrest of the Cell Cycle" class="work-thumbnail" src="https://attachments.academia-assets.com/87079932/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828386/Reevesioside_A_a_Cardenolide_Glycoside_Induces_Anticancer_Activity_against_Human_Hormone_Refractory_Prostate_Cancers_through_Suppression_of_c_myc_Expression_and_Induction_of_G1_Arrest_of_the_Cell_Cycle">Reevesioside A, a Cardenolide Glycoside, Induces Anticancer Activity against Human Hormone-Refractory Prostate Cancers through Suppression of c-myc Expression and Induction of G1 Arrest of the Cell Cycle</a></div><div class="wp-workCard_item"><span>PLoS ONE</span><span>, 2014</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">In the past decade, there has been a profound increase in the number of studies revealing that ca...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">In the past decade, there has been a profound increase in the number of studies revealing that cardenolide glycosides display inhibitory activity on the growth of human cancer cells. The use of potential cardenolide glycosides may be a worthwhile approach in anticancer research. Reevesioside A, a cardenolide glycoside isolated from the root of Reevesia formosana, displayed potent anti-proliferative activity against human hormone-refractory prostate cancers. A good correlation (r 2 = 0.98) between the expression of Na + /K +-ATPase a 3 subunit and anti-proliferative activity suggested the critical role of the a 3 subunit. Reevesioside A induced G1 arrest of the cell cycle and subsequent apoptosis in a thymidine block-mediated synchronization model. The data were supported by the down-regulation of several related cell cycle regulators, including cyclin D1, cyclin E and CDC25A. Reevesioside A also caused a profound decrease of RB phosphorylation, leading to an increased association between RB and E2F1 and the subsequent suppression of E2F1 activity. The protein and mRNA levels of c-myc, which can activate expression of many downstream cell cycle regulators, were dramatically inhibited by reevesioside A. Transient transfection of c-myc inhibited the down-regulation of both cyclin D1 and cyclin E protein expression to reevesioside A action, suggesting that c-myc functioned as an upstream regulator. Flow cytometric analysis of JC-1 staining demonstrated that reevesioside A also induced the significant loss of mitochondrial membrane potential. In summary, the data suggest that reevesioside A inhibits c-myc expression and downregulates the expression of CDC25A, cyclin D1 and cyclin E, leading to a profound decrease of RB phosphorylation. G1 arrest is, therefore, induced through E2F1 suppression. Consequently, reevesioside A causes mitochondrial damage and an ultimate apoptosis in human hormone-refractory prostate cancer cells.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="135a63dbd7afa8b55b04f4168019d062" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079932,"asset_id":80828386,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079932/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828386"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828386"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828386; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80828386]").text(description); $(".js-view-count[data-work-id=80828386]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 80828386; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='80828386']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "135a63dbd7afa8b55b04f4168019d062" } } $('.js-work-strip[data-work-id=80828386]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":80828386,"title":"Reevesioside A, a Cardenolide Glycoside, Induces Anticancer Activity against Human Hormone-Refractory Prostate Cancers through Suppression of c-myc Expression and Induction of G1 Arrest of the Cell Cycle","internal_url":"https://www.academia.edu/80828386/Reevesioside_A_a_Cardenolide_Glycoside_Induces_Anticancer_Activity_against_Human_Hormone_Refractory_Prostate_Cancers_through_Suppression_of_c_myc_Expression_and_Induction_of_G1_Arrest_of_the_Cell_Cycle","owner_id":223033354,"coauthors_can_edit":true,"owner":{"id":223033354,"first_name":"She-Hung","middle_initials":null,"last_name":"Chan","page_name":"SheHungChan","domain_name":"independent","created_at":"2022-05-09T07:50:30.677-07:00","display_name":"She-Hung Chan","url":"https://independent.academia.edu/SheHungChan"},"attachments":[{"id":87079932,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/87079932/thumbnails/1.jpg","file_name":"9117d147cc043b6ce4764cac1c01ac907c46.pdf","download_url":"https://www.academia.edu/attachments/87079932/download_file","bulk_download_file_name":"Reevesioside_A_a_Cardenolide_Glycoside_I.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/87079932/9117d147cc043b6ce4764cac1c01ac907c46-libre.pdf?1654522726=\u0026response-content-disposition=attachment%3B+filename%3DReevesioside_A_a_Cardenolide_Glycoside_I.pdf\u0026Expires=1739799213\u0026Signature=PRtbixjgkk2UspkWAr0t3bKxBVvOCO-1grVxXSZt8V~~oUoxn2k1jVCf5CZwbrNkDTQ8C9ZUnXdjpYxhROAIGzRV5MtVsXALW43WgBLiPTEc8cSn7Q8esv271ae48IBYtmC5pSHXNNxNVtXioqTyJgvj0SW0C5ZA6xGSDr7G~8U4BTNjWxD1z-cTzSQjtGDdo33uVU2XK1BMY2gZ6u6L0KrKi3vDOLNA0PWaxrX~aNXxL8PFv9c06PtnIj1xOrp3zr9woEl5ms--z4aO9zgZ0YRZ8TOMtBqcilQ7erA35hLkk4zlMA1i4HpGn18xh84g3cjd-Bbnq9veAXMCIs-Cbw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828385"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/80828385/Terfenadine_induces_anti_proliferative_and_apoptotic_activities_in_human_hormone_refractory_prostate_cancer_through_histamine_receptor_independent_Mcl_1_cleavage_and_Bak_up_regulation"><img alt="Research paper thumbnail of Terfenadine induces anti-proliferative and apoptotic activities in human hormone-refractory prostate cancer through histamine receptor-independent Mcl-1 cleavage and Bak up-regulation" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/80828385/Terfenadine_induces_anti_proliferative_and_apoptotic_activities_in_human_hormone_refractory_prostate_cancer_through_histamine_receptor_independent_Mcl_1_cleavage_and_Bak_up_regulation">Terfenadine induces anti-proliferative and apoptotic activities in human hormone-refractory prostate cancer through histamine receptor-independent Mcl-1 cleavage and Bak up-regulation</a></div><div class="wp-workCard_item"><span>Naunyn-Schmiedeberg's Archives of Pharmacology</span><span>, 2013</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Although the results of several studies have underscored the regulatory effect of H1-histamine re...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Although the results of several studies have underscored the regulatory effect of H1-histamine receptors in cell proliferation of some cancer cell types, its effect in prostate cancers remains unclear. We have therefore studied the effect of terfenadine (an H1-histamine receptor antagonist) in prostate cancer cell lines. Our data demonstrate that terfenadine was effective against PC-3 and DU-145 cells (two prostate cancer cell lines). In contrast, based on the sulforhodamine B assay, loratadine had less potency while fexofenadine and diphenhydramine had little effect. Terfenadine induced the cleavage of Mcl-1 cleavage into a pro-apoptotic 28-kDa fragment and up-regulation of Bak, resulting in the loss of mitochondrial membrane potential (ΔΨm) and the release of cytochrome c and apoptosis-inducing factor into the cytosol. The activation of caspase cascades was detected to be linked to terfenadine action. Bak up-regulation was also examined at both the transcriptional and translational levels, and Bak activation was validated based on conformational change to expose the N terminus. Terfenadine also induced an indirect-but not direct-DNA damage response through the cleavage and activation of caspase-2, phosphorylation and activation of Chk1 and Chk2 kinases, phosphorylation of RPA32 and acetylation of Histone H3; these processes were highly correlated to severe mitochondrial dysfunction and the activation of caspase cascades. In conclusion, terfenadine induced apoptotic signaling cascades against HRPCs in a sequential manner. The exposure of cells to terfenadine caused the up-regulation and activation of Bak and the cleavage of Mcl-1, leading to the loss of ΔΨm and activation of caspase cascades which further resulted in DNA damage response and cell apoptosis.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828385"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828385"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828385; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> </div><div class="profile--tab_content_container js-tab-pane tab-pane" data-section-id="15112040" id="papers"><div class="js-work-strip profile--work_container" data-work-id="80828408"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/80828408/Anti_leukemic_mechanisms_of_novel_FTY720_analogue_a_crucial_role_of_mitochondrial_stress_in_apoptosis_and_autophagy"><img alt="Research paper thumbnail of Anti-leukemic mechanisms of novel FTY720 analogue-a crucial role of mitochondrial stress in apoptosis and autophagy" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/80828408/Anti_leukemic_mechanisms_of_novel_FTY720_analogue_a_crucial_role_of_mitochondrial_stress_in_apoptosis_and_autophagy">Anti-leukemic mechanisms of novel FTY720 analogue-a crucial role of mitochondrial stress in apoptosis and autophagy</a></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828408"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828408"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828408; 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</script> <div class="js-work-strip profile--work_container" data-work-id="80828407"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828407/Antileukemic_Natural_Product_Induced_Both_Apoptotic_and_Pyroptotic_Programmed_Cell_Death_and_Differentiation_Effect"><img alt="Research paper thumbnail of Antileukemic Natural Product Induced Both Apoptotic and Pyroptotic Programmed Cell Death and Differentiation Effect" class="work-thumbnail" src="https://attachments.academia-assets.com/87079795/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828407/Antileukemic_Natural_Product_Induced_Both_Apoptotic_and_Pyroptotic_Programmed_Cell_Death_and_Differentiation_Effect">Antileukemic Natural Product Induced Both Apoptotic and Pyroptotic Programmed Cell Death and Differentiation Effect</a></div><div class="wp-workCard_item"><span>International Journal of Molecular Sciences</span><span>, 2021</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Acute myeloid leukemia (AML) is one of the most common forms of leukemia. Despite advances in the...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Acute myeloid leukemia (AML) is one of the most common forms of leukemia. Despite advances in the management of such malignancies and the progress of novel therapies, unmet medical needs still exist in AML because of several factors, including poor response to chemotherapy and high relapse rates. Ardisianone, a plant-derived natural component with an alkyl benzoquinone structure, induced apoptosis in leukemic HL-60 cells. The determination of dozens of apoptosis-related proteins showed that ardisianone upregulated death receptors and downregulated the inhibitor of apoptosis protein (IAPs). Western blotting showed that ardisianone induced a dramatic increase in tumor necrosis factor receptor 2 (TNFR2) protein expression. Ardisianone also induced downstream signaling by activating caspase-8 and -3 and degradation in Bid, a caspase-8 substrate. Furthermore, ardisianone induced degradation in DNA fragmentation factor 45 kDa (DFF45), a subunit of inhibitors of caspase-activated DNase (IC...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="0b5264e504815a23d7e2e7d0660c1cf8" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079795,"asset_id":80828407,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079795/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828407"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828407"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828407; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828406"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828406/Synthesis_distribution_analysis_and_mechanism_studies_of_N_acyl_glucosamine_bearing_oleanolic_saponins"><img alt="Research paper thumbnail of Synthesis, distribution analysis and mechanism studies of N-acyl glucosamine-bearing oleanolic saponins" class="work-thumbnail" src="https://attachments.academia-assets.com/87079879/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828406/Synthesis_distribution_analysis_and_mechanism_studies_of_N_acyl_glucosamine_bearing_oleanolic_saponins">Synthesis, distribution analysis and mechanism studies of N-acyl glucosamine-bearing oleanolic saponins</a></div><div class="wp-workCard_item"><span>Bioorganic Chemistry</span><span>, 2020</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828405"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828405/Mechanistic_Study_of_Triazole_Based_Aminodiol_Derivatives_in_Leukemic_Cells_Crosstalk_between_Mitochondrial_Stress_Involved_Apoptosis_and_Autophagy"><img alt="Research paper thumbnail of Mechanistic Study of Triazole Based Aminodiol Derivatives in Leukemic Cells—Crosstalk between Mitochondrial Stress-Involved Apoptosis and Autophagy" class="work-thumbnail" src="https://attachments.academia-assets.com/87079796/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828405/Mechanistic_Study_of_Triazole_Based_Aminodiol_Derivatives_in_Leukemic_Cells_Crosstalk_between_Mitochondrial_Stress_Involved_Apoptosis_and_Autophagy">Mechanistic Study of Triazole Based Aminodiol Derivatives in Leukemic Cells—Crosstalk between Mitochondrial Stress-Involved Apoptosis and Autophagy</a></div><div class="wp-workCard_item"><span>International Journal of Molecular Sciences</span><span>, 2020</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Various derivatives that mimic ceramide structures by introducing a triazole to connect the amino...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Various derivatives that mimic ceramide structures by introducing a triazole to connect the aminodiol moiety and long alkyl chain have been synthesized and screened for their anti-leukemia activity. SPS8 stood out among the derivatives, showing cytotoxic selectivity between leukemic cell lines and human peripheral blood mononuclear cells (about ten times). DAPI nuclear staining and H&E staining revealed DNA fragmentation under the action of SPS8. SPS8 induced an increase in intracellular Ca2+ levels and mitochondrial stress in HL-60 cells identified by the loss of mitochondrial membrane potential, transmission electron microscopy (TEM) examination, and altered expressions of Bcl-2 family proteins. SPS8 also induced autophagy through the detection of Atg5, beclin-1, and LC3 II protein expression, as well as TEM examination. Chloroquine, an autophagy inhibitor, promoted SPS8-induced apoptosis, suggesting the cytoprotective role of autophagy in hindering SPS8 from apoptosis. Furthermor...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="530002d56a274efb51d28125e474a86b" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079796,"asset_id":80828405,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079796/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828405"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828405"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828405; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828403"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/80828403/P1_084Antileukemic_activity_and_mechanism_of_ardisianone_a_crucial_role_of_mitochondrial_stress_in_apoptosis_and_necroptosis"><img alt="Research paper thumbnail of P1-084Antileukemic activity and mechanism of ardisianone-a crucial role of mitochondrial stress in apoptosis and necroptosis" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/80828403/P1_084Antileukemic_activity_and_mechanism_of_ardisianone_a_crucial_role_of_mitochondrial_stress_in_apoptosis_and_necroptosis">P1-084Antileukemic activity and mechanism of ardisianone-a crucial role of mitochondrial stress in apoptosis and necroptosis</a></div><div class="wp-workCard_item"><span>Annals of Oncology</span><span>, 2019</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background Ardisianone was reported to induce apoptosis in prostate cancer cells, but necroptosis...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background Ardisianone was reported to induce apoptosis in prostate cancer cells, but necroptosis in leukemia cell lines. It is needed to clarify whether ardisianone could cause apoptosis and necroptosis in leukemia cells and investigate its underlying mechanisms. Methods Cytotoxicity was examined using the MTT assay. Cytoflowmetric analysis of JC-1 and PI staining was used to examine mitochondrial membrane potential and cell cycle progression, respectively. Apoptosis was examined by annexin V-PI staining assay. Protein expression was detected by Western blot and apoptosis antibody array chip. Immunofluorescence staining detected necroptosis effect. Results Ardisianone inhibited cell viability in HL-60, a promyelocytic leukemia cell line, with IC50 value of 1.87 µ M in a 24h exposure. Further detection showed that ardisianone induced time- and concentration-dependent apoptosis. JC-1 staining demonstrated that ardisianone caused a profound loss of mitochondrial membrane potential. We...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828403"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828403"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828403; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80828403]").text(description); $(".js-view-count[data-work-id=80828403]").attr('title', description).tooltip(); 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</script> <div class="js-work-strip profile--work_container" data-work-id="80828402"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828402/Determination_of_synthetic_cathinone_%CE%B1_PVP_and_its_metabolite_in_urine_using_solid_phase_extraction_and_gas_chromatography_mass_spectrometry"><img alt="Research paper thumbnail of Determination of synthetic cathinone “α‐PVP” and its metabolite in urine using solid phase extraction and gas chromatography‐mass spectrometry" class="work-thumbnail" src="https://attachments.academia-assets.com/87079870/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828402/Determination_of_synthetic_cathinone_%CE%B1_PVP_and_its_metabolite_in_urine_using_solid_phase_extraction_and_gas_chromatography_mass_spectrometry">Determination of synthetic cathinone “α‐PVP” and its metabolite in urine using solid phase extraction and gas chromatography‐mass spectrometry</a></div><div class="wp-workCard_item"><span>Rapid Communications in Mass Spectrometry</span><span>, 2019</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">A toxicological challenge is that the metabolites of α-PVP exhibit amphoteric properties, which m...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">A toxicological challenge is that the metabolites of α-PVP exhibit amphoteric properties, which make them unsuitable for detection using gas chromatography-mass spectrometry (GC/MS). In the study reported, proper derivatization and sample extraction were essential for improving the sensitivity for GC/MS analysis. Methods: An automated solid-phase extraction (SPE) method has been developed and optimized. The derivatization efficiency was tested using longer reaction time and the addition of polar pyridine into a mixture of N,O-bis(trimethylsilyl) trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane. Method validation, including linearity, limit of detection, precision, accuracy, and recovery, was evaluated using automatic SPE and GC/MS. Results: The results suggested that adding pyridine to BSTFA (1:1, v/v) significantly improved derivatization efficiency and precision. After optimization, the linear range was from 25 to 1000 ng mL −1 with R 2 > 0.9950. The limit of detection was 5 ng mL −1 for α-PVP and 25 ng mL −1 for OH-α-PVP. The recovery for SPE was over 88%. The inter-day and intra-day precisions were less than 15%. A forensic sample has been found containing α-PVP (67.3 ng mL −1) and OH-α-PVP (560.2 ng mL −1). Conclusions: This study is the first to validate an auto-SPE-GC/MS method for the quantification and qualification of α-PVP and OH-α-PVP in urine. We have successfully improved the derivatization efficiency and developed a sensitive and semi-automatic approach. This approach is desirable for the detection of synthetic cathinone at trace levels in biological samples. 1 | INTRODUCTION Synthetic cathinones are compounds that mimic the effects of the classic drugs that are abused. Administration of such designer drugs increases the release of norepinephrine and dopamine. These drugs also act as inhibitors of dopamine and norepinephrine transporters, which thus reduce serotonin reuptake and, consequently, cause stimulatory effects in the central nervous system. 1-5 These drugs</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="fa4211150c56d1c98650b2ea6144b9cf" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079870,"asset_id":80828402,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079870/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828402"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828402"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828402; 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dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "fa4211150c56d1c98650b2ea6144b9cf" } } $('.js-work-strip[data-work-id=80828402]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":80828402,"title":"Determination of synthetic cathinone “α‐PVP” and its metabolite in urine using solid phase extraction and gas chromatography‐mass spectrometry","internal_url":"https://www.academia.edu/80828402/Determination_of_synthetic_cathinone_%CE%B1_PVP_and_its_metabolite_in_urine_using_solid_phase_extraction_and_gas_chromatography_mass_spectrometry","owner_id":223033354,"coauthors_can_edit":true,"owner":{"id":223033354,"first_name":"She-Hung","middle_initials":null,"last_name":"Chan","page_name":"SheHungChan","domain_name":"independent","created_at":"2022-05-09T07:50:30.677-07:00","display_name":"She-Hung Chan","url":"https://independent.academia.edu/SheHungChan"},"attachments":[{"id":87079870,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/87079870/thumbnails/1.jpg","file_name":"rcm.pdf","download_url":"https://www.academia.edu/attachments/87079870/download_file","bulk_download_file_name":"Determination_of_synthetic_cathinone__P.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/87079870/rcm-libre.pdf?1654522738=\u0026response-content-disposition=attachment%3B+filename%3DDetermination_of_synthetic_cathinone__P.pdf\u0026Expires=1739799209\u0026Signature=VbhzHuFCImEmXNmEk0gDZIycgXLaVYXqV62xCV4vASazSpGXFWJqCHYPzSIdddP8qC7c9tqlXMpJi6e8C12hvSMh9opTFDsFnyqW5vs06VFXrWb4d3vhX20F6FltvNDa7PZpsKt0OJGWCnQCPZl4wW6ug~cfRHNaVWcJhYz22ib-gkaEoYyOq1ImmB-SfLgmLJOreF7xMo~yYiOWQ27O9iTQ~o~drZQ97dyQ3UEFG3Ep6eexKhc6hKU1YeYA5O68luSik6luD53Hbb7nOyGtnhNfcqG3MS7sB-ndyB~lT~KGN4p6h0vlAXlyUXbHBdLFe8OTFz-BKjPbdNFZNcrEDQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828401"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828401/An_integrated_approach_to_elucidate_signaling_pathways_of_dioscin_induced_apoptosis_energy_metabolism_and_differentiation_in_acute_myeloid_leukemia"><img alt="Research paper thumbnail of An integrated approach to elucidate signaling pathways of dioscin-induced apoptosis, energy metabolism and differentiation in acute myeloid leukemia" class="work-thumbnail" src="https://attachments.academia-assets.com/87079881/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828401/An_integrated_approach_to_elucidate_signaling_pathways_of_dioscin_induced_apoptosis_energy_metabolism_and_differentiation_in_acute_myeloid_leukemia">An integrated approach to elucidate signaling pathways of dioscin-induced apoptosis, energy metabolism and differentiation in acute myeloid leukemia</a></div><div class="wp-workCard_item"><span>Naunyn-Schmiedeberg's Archives of Pharmacology</span><span>, 2018</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Although the therapeutics have improved the rates of remission and cure of acute myelogenous leuk...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Although the therapeutics have improved the rates of remission and cure of acute myelogenous leukemia (AML) in recent decades, there is still an unmet medical need for AML therapies because disease relapses are a major obstacle in patients who become refractory to salvage therapy. The development of therapeutic agents promoting both cytotoxicity and cell differentiation may provide opportunities to improve the clinical outcome. Dioscin-induced apoptosis in leukemic cells was identified through death receptor-mediated extrinsic apoptosis pathway. The formation of Bak and tBid, and loss of mitochondrial membrane potential were induced by dioscin suggesting the activation of intrinsic apoptotsis pathway. A functional analysis of transcription factors using transcription factor-DNA interaction array and IPA analysis demonstrated that dioscin induced a profound increase of protein expression of CCAAT/enhancer-binding protein α (C/EBPα), a critical factor for myeloid differentiation. Twodimensional gel electrophoresis assay confirmed the increase of C/EBPα expression. Dioscin-induced differentiation was substantiated by an increase of CD11b protein expression and the induction of differentiation toward myelomonocytic/granulocytic lineages using hematoxylin and eosin staining. Moreover, both glycolysis and gluconeogenesis pathways after two-dimensional gel electrophoresis assay and IPA network enrichment analysis were proposed to dioscin action. In conclusion, the data suggest that dioscin exerts its antileukemic effect through the upregulation of both death ligands and death receptors and a crosstalk activation of mitochondrial apoptosis pathway with the collaboration of tBid and Bak formation. In addition, proteomics approach reveals an altered metabolic signature of dioscin-treated cells and the induction of differentiation of promyelocytes to granulocytes and monocytes in which the C/EBPα plays a key role.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="2b614c520983afe01b046061e4fe38f5" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079881,"asset_id":80828401,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079881/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828401"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828401"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828401; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828400"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828400/Phosphodiesterase_Type_5_PDE5_Inhibitors_Sensitize_Topoisomerase_II_Inhibitors_in_Killing_Prostate_Cancer_Through_PDE5_Independent_Impairment_of_HR_and_NHEJ_DNA_Repair_Systems"><img alt="Research paper thumbnail of Phosphodiesterase Type 5 (PDE5) Inhibitors Sensitize Topoisomerase II Inhibitors in Killing Prostate Cancer Through PDE5-Independent Impairment of HR and NHEJ DNA Repair Systems" class="work-thumbnail" src="https://attachments.academia-assets.com/87079863/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828400/Phosphodiesterase_Type_5_PDE5_Inhibitors_Sensitize_Topoisomerase_II_Inhibitors_in_Killing_Prostate_Cancer_Through_PDE5_Independent_Impairment_of_HR_and_NHEJ_DNA_Repair_Systems">Phosphodiesterase Type 5 (PDE5) Inhibitors Sensitize Topoisomerase II Inhibitors in Killing Prostate Cancer Through PDE5-Independent Impairment of HR and NHEJ DNA Repair Systems</a></div><div class="wp-workCard_item"><span>Frontiers in Oncology</span><span>, 2019</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Human castration-resistant prostate cancer (CRPC) is a significant target of clinical research. T...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Human castration-resistant prostate cancer (CRPC) is a significant target of clinical research. The use of DNA-damaging agents has a long history in cancer chemotherapy but is limited by their toxicities. The combination with a safer drug can be a strategy in reducing dosage and toxicity while increasing anticancer activity in CRPC treatment. Phosphodiesterase type 5 (PDE5) inhibitors are used to treat erectile dysfunction through the selective inhibition of PDE5 that is responsible for cGMP degradation in the corpus cavernosum. Several studies have reported that PDE5 inhibitors display protective effect against doxorubicin-induced cardiotoxicity. The combinatory treatment of CRPC with doxorubicin and PDE5 inhibitors has been studied accordingly. The data demonstrated that sildenafil or vardenafil (two structure-related PDE5 inhibitors) but not tadalafil (structure-unrelated to sildenafil) sensitized doxorubicin-induced apoptosis in CRPC cells with deteriorating the down-regulation of anti-apoptotic Bcl-2 family members, including Bcl-xL and Mcl-1, and amplifying caspase activation. Homologous recombination (HR) and non-homologous end joining (NHEJ) DNA repair systems were inhibited in the apoptotic sensitization through detection of nuclear foci formation of Rad51 and DNA end-binding of Ku80. PDE5 knockdown to mimic the exposure to PDE5 inhibitors did not reproduce apoptotic sensitization, suggesting a PDE5-independent mechanism. Not only doxorubicin, sildenafil combined with other inhibitors of topoisomerase II but not topoisomerase I also triggered apoptotic sensitization. In conclusion, the data suggest that sildenafil and vardenafil induce PDE5-independent apoptotic sensitization to doxorubicin (or other topoisomerase II inhibitors) through impairment of both HR and NHEJ repair systems that are evident by a decrease of nuclear Rad51 levels and their foci formation in the nucleus, and an inhibition of Ku80 DNA end-binding capability. The combinatory treatment may enable an important strategy for anti-CRPC development.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="84c7ab4e4042f1b55058578fcc07b098" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079863,"asset_id":80828400,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079863/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828400"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828400"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828400; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828399"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828399/Design_synthesis_and_cytotoxic_activity_of_N_Modified_oleanolic_saponins_bearing_A_glucosamine"><img alt="Research paper thumbnail of Design, synthesis and cytotoxic activity of N-Modified oleanolic saponins bearing A glucosamine" class="work-thumbnail" src="https://attachments.academia-assets.com/87079868/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828399/Design_synthesis_and_cytotoxic_activity_of_N_Modified_oleanolic_saponins_bearing_A_glucosamine">Design, synthesis and cytotoxic activity of N-Modified oleanolic saponins bearing A glucosamine</a></div><div class="wp-workCard_item"><span>European journal of medicinal chemistry</span><span>, Jan 6, 2017</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">A series of N-acyl, N-alkoxycarbonyl, and N-alkylcarbamoyl derivatives of 2&#39;-deoxy-glucosyl b...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">A series of N-acyl, N-alkoxycarbonyl, and N-alkylcarbamoyl derivatives of 2&#39;-deoxy-glucosyl bearing oleanolic saponins were synthesized and evaluated against HL-60, PC-3, and HT29 tumor cancer cells. The SAR studies revealed that the activity increased in order of conjugation of 2&#39; -amino group with carbamate &gt; amide &gt; urea derivatives. Lengthening the alkyl chain increased the cytotoxicity, the peak activity was found to around heptyl to nonyl substitutions. 2&#39;-N-heptoxycarbonyl derivative 56 was found to be the most cytotoxic (IC50 = 0.76 μM) against HL-60 cells. Due to the interesting SARs of alkyl substitutions, we hypothesized that their location in the cell was different, and pursued a location study using 2&#39;-(4″-pentynoylamino) 2&#39;-deoxy-glucosyl OA, which suggested that these compounds distributed mainly in the cytosol.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="717d8d650a188018c62fbad0f1519c2c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079868,"asset_id":80828399,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079868/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828399"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828399"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828399; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828398"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/80828398/P1_9_56Anti_leukemic_mechanisms_of_novel_FTY720_analogue_a_crucial_role_of_mitochondrial_stress_in_apoptosis_and_autophagy"><img alt="Research paper thumbnail of P1-9-56Anti-leukemic mechanisms of novel FTY720 analogue-a crucial role of mitochondrial stress in apoptosis and autophagy" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/80828398/P1_9_56Anti_leukemic_mechanisms_of_novel_FTY720_analogue_a_crucial_role_of_mitochondrial_stress_in_apoptosis_and_autophagy">P1-9-56Anti-leukemic mechanisms of novel FTY720 analogue-a crucial role of mitochondrial stress in apoptosis and autophagy</a></div><div class="wp-workCard_item"><span>Annals of Oncology</span><span>, 2015</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828398"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828398"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828398; 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</script> <div class="js-work-strip profile--work_container" data-work-id="80828397"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828397/Non_immunosuppressive_triazole_based_small_molecule_induces_anticancer_activity_against_human_hormone_refractory_prostate_cancers_the_role_in_inhibition_of_PI3K_AKT_mTOR_and_c_Myc_signaling_pathways"><img alt="Research paper thumbnail of Non-immunosuppressive triazole-based small molecule induces anticancer activity against human hormone-refractory prostate cancers: the role in inhibition of PI3K/AKT/mTOR and c-Myc signaling pathways" class="work-thumbnail" src="https://attachments.academia-assets.com/87079869/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828397/Non_immunosuppressive_triazole_based_small_molecule_induces_anticancer_activity_against_human_hormone_refractory_prostate_cancers_the_role_in_inhibition_of_PI3K_AKT_mTOR_and_c_Myc_signaling_pathways">Non-immunosuppressive triazole-based small molecule induces anticancer activity against human hormone-refractory prostate cancers: the role in inhibition of PI3K/AKT/mTOR and c-Myc signaling pathways</a></div><div class="wp-workCard_item"><span>Oncotarget</span><span>, 2016</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">A series of triazole-based small molecules that mimic FTY720-mediated anticancer activity but min...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">A series of triazole-based small molecules that mimic FTY720-mediated anticancer activity but minimize its immunosuppressive effect have been produced. SPS-7 is the most effective derivative displaying higher activity than FTY720 in anti-proliferation against human hormone-refractory prostate cancer (HRPC). It induced G1 arrest of cell cycle and subsequent apoptosis in thymidine blockmediated synchronization model. The data were supported by a decrease of cyclin D1 expression, a dramatic increase of p21 expression and an associated decrease in RB phosphorylation. c-Myc overexpression replenished protein levels of cyclin D1 indicating that c-Myc was responsible for cell cycle regulation. PI3K/Akt/mTOR signaling pathways through p70S6K-and 4EBP1-mediated translational regulation are critical to cell proliferation and survival. SPS-7 significantly inhibited this translational pathway. Overexpression of Myr-Akt (constitutively active Akt) completely abolished SPS-7-induced inhibitory effect on mTOR/p70S6K/4EBP1 signaling and c-Myc protein expression, suggesting that PI3K/Akt serves as a key upstream regulator. SPS-7 also demonstrated substantial anti-tumor efficacy in an in vivo xenograft study using PC-3 mouse model. Notably, FTY720 but not SPS-7 induced a significant immunosuppressive effect as evidenced by depletion of marginal zone B cells, downregulation of sphingosine-1-phosphate receptors and a decrease in peripheral blood lymphocytes. In conclusion, the data suggest that SPS-7 is not an immunosuppressant while induces anticancer effect against HRPC through inhibition of Akt/mTOR/ p70S6K pathwaysthat down-regulate protein levels of both c-Myc and cyclin D1, leading to G1 arrest of cell cycle and subsequent apoptosis. The data also indicate the potential of SPS-7 since PI3K/Akt signalingis responsive for the genomic alterations in prostate cancer.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="ed0b098cc7d1d1008a4c7bc14d2e415d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079869,"asset_id":80828397,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079869/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828397"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828397"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828397; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80828397]").text(description); $(".js-view-count[data-work-id=80828397]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 80828397; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='80828397']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828396"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828396/The_effects_of_antiepileptic_drugs_on_the_growth_of_glioblastoma_cell_lines"><img alt="Research paper thumbnail of The effects of antiepileptic drugs on the growth of glioblastoma cell lines" class="work-thumbnail" src="https://attachments.academia-assets.com/87079865/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828396/The_effects_of_antiepileptic_drugs_on_the_growth_of_glioblastoma_cell_lines">The effects of antiepileptic drugs on the growth of glioblastoma cell lines</a></div><div class="wp-workCard_item"><span>Journal of Neuro-Oncology</span><span>, 2016</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">To determine the effects of antiepileptic drug compounds on glioblastoma cellular growth, we expo...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">To determine the effects of antiepileptic drug compounds on glioblastoma cellular growth, we exposed glioblastoma cell lines to select antiepileptic drugs. The effects of selected antiepileptic drugs on glioblastoma cells were measured by MTT assay. For compounds showing significant inhibition, cell cycle analysis was performed. Statistical analysis was performed using SPSS. The antiepileptic compounds selected for screening included carbamazepine, ethosuximide, gabapentin, lamotrigine, levetiracetam, magnesium sulfate, oxcarbazepine, phenytoin, primidone, tiagabine, topiramate, valproic acid, and vigabatrin. Dexamethasone and temozolomide were used as a negative and positive control respectively. Our results showed temozolomide and oxcarbazepine significantly inhibited glioblastoma cell growth and reached IC 50 at therapeutic concentrations. The other antiepileptic drugs screened were unable to reach IC 50 at therapeutic concentrations. The metabolites of oxcarbazepine were also unable to reach IC 50. Dexamethasone, ethosuximide, levetiracetam, and vigabatrin showed some growth enhancement though they did not reach statistical significance. The growth enhancement effects of ethosuximide, levetiracetam, and vigabatrin found in the study may indicate that these compounds should not be used for prophylaxis or short term treatment of epilepsy in glioblastoma. While valproic acid and oxcarbazepine were effective, the required dose of valproic acid was far above that used for the treatment of epilepsy and the metabolites of oxcarbazepine failed to reach significant growth inhibition ruling out the use of oral oxcarbazepine or valproic acid as monotherapy in glioblastoma. The possibility of using these compounds as local treatment is a future area of study.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="d2130c814ec80d9bdd7a4d97c0ad8c2a" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079865,"asset_id":80828396,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079865/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828396"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828396"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828396; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80828396]").text(description); $(".js-view-count[data-work-id=80828396]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 80828396; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='80828396']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "d2130c814ec80d9bdd7a4d97c0ad8c2a" } } $('.js-work-strip[data-work-id=80828396]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":80828396,"title":"The effects of antiepileptic drugs on the growth of glioblastoma cell lines","internal_url":"https://www.academia.edu/80828396/The_effects_of_antiepileptic_drugs_on_the_growth_of_glioblastoma_cell_lines","owner_id":223033354,"coauthors_can_edit":true,"owner":{"id":223033354,"first_name":"She-Hung","middle_initials":null,"last_name":"Chan","page_name":"SheHungChan","domain_name":"independent","created_at":"2022-05-09T07:50:30.677-07:00","display_name":"She-Hung Chan","url":"https://independent.academia.edu/SheHungChan"},"attachments":[{"id":87079865,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/87079865/thumbnails/1.jpg","file_name":"pmc4835521.pdf","download_url":"https://www.academia.edu/attachments/87079865/download_file","bulk_download_file_name":"The_effects_of_antiepileptic_drugs_on_th.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/87079865/pmc4835521-libre.pdf?1654522733=\u0026response-content-disposition=attachment%3B+filename%3DThe_effects_of_antiepileptic_drugs_on_th.pdf\u0026Expires=1739799213\u0026Signature=SwoGWbjpjjENR57fvFQCuEou~S-MbvXqEdJSzpXfGz9RUj7EHAyDe4IGHOsEt0OykcKXadr3VF4AmPOguzF-LaeIvzrmsGGUI9R10Fn5ex5h~kpO3oX0CaI8jKofk1UX0d0lf3jXNa3GNLifu5rjwIOdRXwIFkrqqEFOUDcAJL2H5BnuT89o1nAuwmiIJs1aKeHf7Uaiy7i-qwwVnISn1dSkvfdN9-ohfskowXIW6bhZngwuqVy1xpXSQADRyL6JC18GDcWuo0B25GrhupbQb5SiWoiSiAmawvtE5R2MVLmhNZCwSFvMNjiVAyCpZzoJiVflmPMqfiMmpjZlTFZkCQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828395"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/80828395/Raised_Proinflammatory_Cytokine_Production_Within_Cerebrospinal_Fluid_Precedes_Fever_Onset_in_Patients_With_Neurosurgery_Associated_Bacterial_Meningitis_"><img alt="Research paper thumbnail of Raised Proinflammatory Cytokine Production Within Cerebrospinal Fluid Precedes Fever Onset in Patients With Neurosurgery-Associated Bacterial Meningitis*" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/80828395/Raised_Proinflammatory_Cytokine_Production_Within_Cerebrospinal_Fluid_Precedes_Fever_Onset_in_Patients_With_Neurosurgery_Associated_Bacterial_Meningitis_">Raised Proinflammatory Cytokine Production Within Cerebrospinal Fluid Precedes Fever Onset in Patients With Neurosurgery-Associated Bacterial Meningitis*</a></div><div class="wp-workCard_item"><span>Critical Care Medicine</span><span>, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The objective of the present study was to determine whether selective inflammatory cytokine conce...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The objective of the present study was to determine whether selective inflammatory cytokine concentrations within cerebrospinal fluid are useful markers for the differential diagnosis of aseptic and bacterial meningitis within neurosurgical patients. Prospective, open-label, observational, cohort study. Neurosurgical ICU, Chang Gung Memorial Hospital. Thirty-two consecutive neurosurgical patients who had postoperative fever following external ventricular drain insertion for the treatment of brain injury underwent serial cerebrospinal fluid cytokine analysis pre and post fever to determine the value of such markers in ascertaining the differential diagnosis of meningitis. Cerebrospinal fluid samples were collected on the day of fever onset, as well as on day 2 and 4 pre and post fever development. Tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-8, transforming growth factor-β, and procalcitonin were subsequently analyzed using enzyme-linked immunosorbent assay analysis techniques. Inflammatory marker levels were compared among febrile aseptic, bacterial, and nonmeningitis patients to determine cerebrospinal fluid inflammatory changes over time. Significant increases in cerebrospinal fluid tumor necrosis factor -α, interleukin-1β, interleukin-6, and interleukin-8 levels were observed within patients with bacterial meningitis at fever onset, which was not evident in aseptic or nonmeningitis patients. Furthermore, significant increases in cerebrospinal fluid tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8 levels were detected as early as 4 days prior to fever onset within patients with bacterial meningitis when compared with both aseptic and nonmeningitis groups. Interestingly, procalcitonin was only significantly increased in patients with bacterial meningitis on the fourth day post fever. The present study suggests that raised cerebrospinal fluid tumor necrosis factor -α, interleukin-1β, and interleukin-8 in a temporal manner may indicate early bacterial meningitis development in neurosurgical patients, enabling earlier diagnostic certainty and improved patient outcomes.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828395"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828395"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828395; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80828395]").text(description); $(".js-view-count[data-work-id=80828395]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 80828395; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='80828395']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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} }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828394"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828394/Cytotoxic_protobassic_acid_glycosides_from_Planchonella_obovata_leaf"><img alt="Research paper thumbnail of Cytotoxic protobassic acid glycosides from Planchonella obovata leaf" class="work-thumbnail" src="https://attachments.academia-assets.com/87079864/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828394/Cytotoxic_protobassic_acid_glycosides_from_Planchonella_obovata_leaf">Cytotoxic protobassic acid glycosides from Planchonella obovata leaf</a></div><div class="wp-workCard_item"><span>Phytochemistry Letters</span><span>, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Four triterpenoid glycosides, possessing protobassic acid as common aglycon, together with 16 kno...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Four triterpenoid glycosides, possessing protobassic acid as common aglycon, together with 16 known compounds were isolated from the leaves of Planchonella obovata. They are 6b-hydroxy-conyzasaponin G (2), 3 000-Ode -b-D-apiofuranosylisoarganin F (3), isoarganin F (4), and 6b-hydroxy-conyzasaponin N (5). The structures of these glycosides were elucidated based on spectroscopic analysis, in particular using 1D TOCSY to confirm the 1 H NMR assignment of each sugar residue. The absolute configuration of each monosaccharide in the glycon part was determined by GC-FID. Compound 5, Mi-saponin A (8), and ursolic acid (10) showed moderate inhibitory activities against HL-60 leukemia cell line with the IC 50</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="dc271100afc193e4f1c6039e8cf0581f" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079864,"asset_id":80828394,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079864/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828394"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828394"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828394; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80828394]").text(description); $(".js-view-count[data-work-id=80828394]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 80828394; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='80828394']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828392"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828392/ChemInform_Abstract_Asymmetric_Synthesis_of_Brevipolide_H_Through_Cyclopropanation_of_the_%CE%B1_%CE%B2_Unsaturated_Ketone"><img alt="Research paper thumbnail of ChemInform Abstract: Asymmetric Synthesis of (-)-Brevipolide H Through Cyclopropanation of the α,β-Unsaturated Ketone" class="work-thumbnail" src="https://attachments.academia-assets.com/87079859/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828392/ChemInform_Abstract_Asymmetric_Synthesis_of_Brevipolide_H_Through_Cyclopropanation_of_the_%CE%B1_%CE%B2_Unsaturated_Ketone">ChemInform Abstract: Asymmetric Synthesis of (-)-Brevipolide H Through Cyclopropanation of the α,β-Unsaturated Ketone</a></div><div class="wp-workCard_item"><span>ChemInform</span><span>, 2015</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="78b54329405a86b6c32e7a3ac2d8134b" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079859,"asset_id":80828392,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079859/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828392"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828392"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828392; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80828392]").text(description); $(".js-view-count[data-work-id=80828392]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 80828392; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='80828392']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "78b54329405a86b6c32e7a3ac2d8134b" } } $('.js-work-strip[data-work-id=80828392]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":80828392,"title":"ChemInform Abstract: Asymmetric Synthesis of (-)-Brevipolide H Through Cyclopropanation of the α,β-Unsaturated Ketone","internal_url":"https://www.academia.edu/80828392/ChemInform_Abstract_Asymmetric_Synthesis_of_Brevipolide_H_Through_Cyclopropanation_of_the_%CE%B1_%CE%B2_Unsaturated_Ketone","owner_id":223033354,"coauthors_can_edit":true,"owner":{"id":223033354,"first_name":"She-Hung","middle_initials":null,"last_name":"Chan","page_name":"SheHungChan","domain_name":"independent","created_at":"2022-05-09T07:50:30.677-07:00","display_name":"She-Hung Chan","url":"https://independent.academia.edu/SheHungChan"},"attachments":[{"id":87079859,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/87079859/thumbnails/1.jpg","file_name":"chin.19981308620220606-1-u5yekm.pdf","download_url":"https://www.academia.edu/attachments/87079859/download_file","bulk_download_file_name":"ChemInform_Abstract_Asymmetric_Synthesis.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/87079859/chin.19981308620220606-1-u5yekm-libre.pdf?1654522729=\u0026response-content-disposition=attachment%3B+filename%3DChemInform_Abstract_Asymmetric_Synthesis.pdf\u0026Expires=1739799213\u0026Signature=Knz0TASE3hgJIz4mYxdDzxSVockM6V095ZE3KeKxn3IMAIy6zRAwFxdE8fcAlVcTGx4CjNuv9BFRJ8kpzBytX3O5AmL9LJKuEiY3YmhXBFeJr9oEa8GsrvGVn3iF2alRu1GBJXHmLfAeBH~GiMvQhVXOP949aCRJeTwXlFBraI-akOFsCjjM6BHiwCufA1IiVpm7R3TwB~4G396DBP6xC6E4WLpK6KnBCDUa83Sb14eQwmmDAqi4YpCd0g08paT5jwfGhYus9cIiZfa-q~r0DXxcfqR7NVXI-rQoYhaes6bNU-jueBorHbyruaHWpr8wKiKENsoj62G9~FzDK7AXcg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828391"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828391/Medical_Record_Review_for_Faculty_Promotion_A_Cohort_Analysis"><img alt="Research paper thumbnail of Medical Record Review for Faculty Promotion: A Cohort Analysis" class="work-thumbnail" src="https://attachments.academia-assets.com/87079860/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828391/Medical_Record_Review_for_Faculty_Promotion_A_Cohort_Analysis">Medical Record Review for Faculty Promotion: A Cohort Analysis</a></div><div class="wp-workCard_item"><span>Biomedical Journal</span><span>, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background: A medical record is an important source of information regarding medical care and med...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background: A medical record is an important source of information regarding medical care and medical record review plays an important role in the evaluation of the teaching proficiency. The study analyzed the difference between internal and external auditing when conducting medical record review for faculty promotion in a study institute. Methods: We analyzed the scores related to the medical records maintained by applicants for the faculty promotion of attending physicians during the period between 2008 and 2010 at the Chang Gung Memorial Hospital. The scores were obtained from one internal reviewer of the study institute and two external reviewers from other medical centers, and routine scores were obtained from the Committee of Medical Record 1 year before application. Pearson's correlation coefficient was used to analyze the correlation and statistical significance. Results: There were 259 applicants for faculty promotion enrolled in this study [professors (n = 33, 13%), associate professors (n = 63, 24%), assistant professors (n = 90, 35%), lecturers (n = 73, 28%)]. The scores of the external reviewers 1 and 2 were correlated with routine scores (r = 0.187, p = 0.002; r = 0.198, p = 0.001; N= 259), respectively. The correlation between external reviewers' average and ordinary scores was significant for assistant professor (r = 0.334, p = 0.001, n = 90) and professor grades (r = 0.469, p = 0.006, n = 33). However, the internal reviewer scores did not correlate with the routine scores (r = 0.073, p = 0.241, N = 259). Conclusions: The scores from external reviewers correlated more with routine scores than the scores from internal reviewers, suggesting that utilizing an external auditing system of medical records for the faculty promotion of attending physicians is quite feasible and balanced.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="400a96851f0e9cafc3fbd51346c04114" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079860,"asset_id":80828391,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079860/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828391"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828391"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828391; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828389"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/80828389/Synthesis_and_anti_cancer_activity_of_a_glycosyl_library_of_varvec_N_N_acetylglucosamine_bearing_oleanolic_acid"><img alt="Research paper thumbnail of Synthesis and anti-cancer activity of a glycosyl library of \varvec{N} N -acetylglucosamine-bearing oleanolic acid" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/80828389/Synthesis_and_anti_cancer_activity_of_a_glycosyl_library_of_varvec_N_N_acetylglucosamine_bearing_oleanolic_acid">Synthesis and anti-cancer activity of a glycosyl library of \varvec{N} N -acetylglucosamine-bearing oleanolic acid</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">N-Acetylglucosamine-bearing triterpenoid saponins (GNTS) were reported to be a unique type of sap...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">N-Acetylglucosamine-bearing triterpenoid saponins (GNTS) were reported to be a unique type of saponins with potent anti-tumor activity. In order to study the structure-activity relationship of GNTS, 24 oleanolic acid saponins with (1 --&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 3)-linked, (1 --&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 4)-linked, (1 --&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 6)-linked N-acetylglucosamine oligosaccharide residues were synthesized in a combinatorial and concise method. The cytotoxicity of these compounds toward the leukemia cell line HL-60 and the colorectal cancer cell line HT-29 could not be improved. Half maximal inhibition below 10 μM was achieved in one single case. The study revealed that the activity decreased following the order of 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 4&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 6&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; glycosyl modifications. GNTS that incorporated (D/L)-xylose and L-arabinose at positions 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; and 4&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; were more potent than those bearing other sugars.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828389"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828389"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828389; 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</script> <div class="js-work-strip profile--work_container" data-work-id="80828387"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/80828387/Asymmetric_Synthesis_of_Brevipolide_H_through_Cyclopropanation_of_the_%CE%B1_%CE%B2_Unsaturated_Ketone"><img alt="Research paper thumbnail of Asymmetric Synthesis of (−)-Brevipolide H through Cyclopropanation of the α,β-Unsaturated Ketone" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/80828387/Asymmetric_Synthesis_of_Brevipolide_H_through_Cyclopropanation_of_the_%CE%B1_%CE%B2_Unsaturated_Ketone">Asymmetric Synthesis of (−)-Brevipolide H through Cyclopropanation of the α,β-Unsaturated Ketone</a></div><div class="wp-workCard_item"><span>Organic Letters</span><span>, 2014</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Brevipolides are 5,6-dihydro-γ-pyrone derivatives, first reported in 2004 as the inhibitors of th...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Brevipolides are 5,6-dihydro-γ-pyrone derivatives, first reported in 2004 as the inhibitors of the chemokine receptor CCR5 and exhibiting cytotoxicity against cancer cells. Starting from the C2 symmetric diene-diol 2, ent-brevipolide H was synthesized for the first time in 11 steps. The anti-addition of the sulfur ylide to the α,β-unsaturated enones was developed to give the key cyclopropane moiety. The synthetic (-)-brevipolide H showed an IC50 value of 7.7 μM against PC-3 cells.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828387"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828387"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828387; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80828387]").text(description); 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</script> <div class="js-work-strip profile--work_container" data-work-id="80828386"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80828386/Reevesioside_A_a_Cardenolide_Glycoside_Induces_Anticancer_Activity_against_Human_Hormone_Refractory_Prostate_Cancers_through_Suppression_of_c_myc_Expression_and_Induction_of_G1_Arrest_of_the_Cell_Cycle"><img alt="Research paper thumbnail of Reevesioside A, a Cardenolide Glycoside, Induces Anticancer Activity against Human Hormone-Refractory Prostate Cancers through Suppression of c-myc Expression and Induction of G1 Arrest of the Cell Cycle" class="work-thumbnail" src="https://attachments.academia-assets.com/87079932/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80828386/Reevesioside_A_a_Cardenolide_Glycoside_Induces_Anticancer_Activity_against_Human_Hormone_Refractory_Prostate_Cancers_through_Suppression_of_c_myc_Expression_and_Induction_of_G1_Arrest_of_the_Cell_Cycle">Reevesioside A, a Cardenolide Glycoside, Induces Anticancer Activity against Human Hormone-Refractory Prostate Cancers through Suppression of c-myc Expression and Induction of G1 Arrest of the Cell Cycle</a></div><div class="wp-workCard_item"><span>PLoS ONE</span><span>, 2014</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">In the past decade, there has been a profound increase in the number of studies revealing that ca...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">In the past decade, there has been a profound increase in the number of studies revealing that cardenolide glycosides display inhibitory activity on the growth of human cancer cells. The use of potential cardenolide glycosides may be a worthwhile approach in anticancer research. Reevesioside A, a cardenolide glycoside isolated from the root of Reevesia formosana, displayed potent anti-proliferative activity against human hormone-refractory prostate cancers. A good correlation (r 2 = 0.98) between the expression of Na + /K +-ATPase a 3 subunit and anti-proliferative activity suggested the critical role of the a 3 subunit. Reevesioside A induced G1 arrest of the cell cycle and subsequent apoptosis in a thymidine block-mediated synchronization model. The data were supported by the down-regulation of several related cell cycle regulators, including cyclin D1, cyclin E and CDC25A. Reevesioside A also caused a profound decrease of RB phosphorylation, leading to an increased association between RB and E2F1 and the subsequent suppression of E2F1 activity. The protein and mRNA levels of c-myc, which can activate expression of many downstream cell cycle regulators, were dramatically inhibited by reevesioside A. Transient transfection of c-myc inhibited the down-regulation of both cyclin D1 and cyclin E protein expression to reevesioside A action, suggesting that c-myc functioned as an upstream regulator. Flow cytometric analysis of JC-1 staining demonstrated that reevesioside A also induced the significant loss of mitochondrial membrane potential. In summary, the data suggest that reevesioside A inhibits c-myc expression and downregulates the expression of CDC25A, cyclin D1 and cyclin E, leading to a profound decrease of RB phosphorylation. G1 arrest is, therefore, induced through E2F1 suppression. Consequently, reevesioside A causes mitochondrial damage and an ultimate apoptosis in human hormone-refractory prostate cancer cells.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="135a63dbd7afa8b55b04f4168019d062" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":87079932,"asset_id":80828386,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/87079932/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828386"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828386"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828386; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80828385"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/80828385/Terfenadine_induces_anti_proliferative_and_apoptotic_activities_in_human_hormone_refractory_prostate_cancer_through_histamine_receptor_independent_Mcl_1_cleavage_and_Bak_up_regulation"><img alt="Research paper thumbnail of Terfenadine induces anti-proliferative and apoptotic activities in human hormone-refractory prostate cancer through histamine receptor-independent Mcl-1 cleavage and Bak up-regulation" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/80828385/Terfenadine_induces_anti_proliferative_and_apoptotic_activities_in_human_hormone_refractory_prostate_cancer_through_histamine_receptor_independent_Mcl_1_cleavage_and_Bak_up_regulation">Terfenadine induces anti-proliferative and apoptotic activities in human hormone-refractory prostate cancer through histamine receptor-independent Mcl-1 cleavage and Bak up-regulation</a></div><div class="wp-workCard_item"><span>Naunyn-Schmiedeberg's Archives of Pharmacology</span><span>, 2013</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Although the results of several studies have underscored the regulatory effect of H1-histamine re...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Although the results of several studies have underscored the regulatory effect of H1-histamine receptors in cell proliferation of some cancer cell types, its effect in prostate cancers remains unclear. We have therefore studied the effect of terfenadine (an H1-histamine receptor antagonist) in prostate cancer cell lines. Our data demonstrate that terfenadine was effective against PC-3 and DU-145 cells (two prostate cancer cell lines). In contrast, based on the sulforhodamine B assay, loratadine had less potency while fexofenadine and diphenhydramine had little effect. Terfenadine induced the cleavage of Mcl-1 cleavage into a pro-apoptotic 28-kDa fragment and up-regulation of Bak, resulting in the loss of mitochondrial membrane potential (ΔΨm) and the release of cytochrome c and apoptosis-inducing factor into the cytosol. The activation of caspase cascades was detected to be linked to terfenadine action. Bak up-regulation was also examined at both the transcriptional and translational levels, and Bak activation was validated based on conformational change to expose the N terminus. Terfenadine also induced an indirect-but not direct-DNA damage response through the cleavage and activation of caspase-2, phosphorylation and activation of Chk1 and Chk2 kinases, phosphorylation of RPA32 and acetylation of Histone H3; these processes were highly correlated to severe mitochondrial dysfunction and the activation of caspase cascades. In conclusion, terfenadine induced apoptotic signaling cascades against HRPCs in a sequential manner. The exposure of cells to terfenadine caused the up-regulation and activation of Bak and the cleavage of Mcl-1, leading to the loss of ΔΨm and activation of caspase cascades which further resulted in DNA damage response and cell apoptosis.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80828385"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80828385"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80828385; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); 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