PE-164: Impact of Ledipasvir/Sofosbuvir on the Work Productivity of Chronic Hepatitis C Patients in Asia

( Young-suk Lim ),( Henry Lik Yuen Chan ),( Yock Young Dan ),( Mei Hsuan Lee ),( Eliza Kruger ),( Seng Tan5,Zobair M. Younossi ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: To estimate the work productivity gains associated with LDV/SOF treatment for CHC in Hong Kong, Singapore, South Korea and Taiwan. Methods: The model captures anticipated impact of LDV/SOF on productivity loss over a one-year time horizon from a societal perspective for each country. A literature review was performed to identify country- specific inputs and expert advice was solicited to verify key variables. Patients enter the model post-treatment, having achieved SVR12, or not. Absenteeism and presenteeism rates were estimated based on the Work Productivity and Activity Index-Specific Health Problem (WPAI-SHP) data collected from the Phase III ION trials (US participants only) at baseline and at 12 weeks with rates assumed to remain unchanged from baseline for patients not achieving SVR. Sensitivity analyses were performed on key variables. Results: Total Work productivity loss due to not treating CHC was highest in Taiwan at US$349M ($355 per capita) given high prevalence of HCV, followed by US$146M ($358) in Korea, US$17M ($914) in Singapore and US$11M ($351) in Hong Kong. Treatment with LDV/SOF resulted in estimated productivity gains of $138 million, $58.7 million, $6.8 million and $4.5 million in Taiwan, Korea, Singapore and Hong Kong respectively. Conclusions: CHC imposes a significant indirect economic burden. Our model demonstrates that treatment of HCV GT1 patients with LDV/SOF is likely to result in significant cost savings due to an improvement in presenteeism versus no treatment across 4 Asian countries. This indirect economic gain should be considered when assessing the benefits of treating CHC.

A curcumin-loaded polymeric micelle as a carrier of a microRNA-21 antisense-oligonucleotide for enhanced anti-tumor effects in a glioblastoma animal model

Tan, Xiaonan,Kim, Gyeungyun,Lee, Dahee,Oh, Jungju,Kim, Minkyung,Piao, Chunxian,Lee, Jaewon,Lee, Min Sang,Jeong, Ji Hoon,Lee, Minhyung The Royal Society of Chemistry 2018 Biomaterials Science Vol.6 No.2

<P>A glioblastoma is a common primary brain tumor that expresses microRNA-21 (miR-21), which inhibits the expression of pro-apoptotic genes such as phosphatase and tensin homologue (PTEN) and programmed cell death 4 (PDCD4). Therefore, an antisense-oligonucleotide against miR-21 (miR21ASO) could have therapeutic effects for glioblastomas. In this study, curcumin was loaded into deoxycholic acid-conjugated polyethylenimine (DP) micelles. The curcumin-loaded DP micelle (DP-Cur) was evaluated as a carrier for the combined delivery of curcumin and miR21ASO. Gel retardation and heparin competition assays showed that DP-Cur formed stable complexes with miR21ASO. The anti-tumor effects of the combined delivery of curcumin and miR21ASO were evaluated in C6 glioblastoma cells. <I>In vitro</I> transfection showed that DP-Cur had an miR21ASO delivery efficiency similar to that of polyethylenimine (25 kDa, PEI25k) and DP. In the C6 cells, the delivery of miR21ASO using DP-Cur effectively reduced the miR21 level. The miR21ASO/DP-Cur complex induced apoptosis more effectively than the single delivery of curcumin or miR21ASO. The therapeutic effect of the miR21ASO/DP-Cur complex was also evaluated in an intracranial glioblastoma animal model. The miR21ASO/DP-Cur complex reduced the tumor volume more effectively than single therapy of curcumin or miR21ASO. Immunohistochemistry showed that PDCD4 and PTEN were induced in the miR21ASO/DP and miR21ASO/DP-Cur complex groups. Therefore, DP-Cur is an efficient carrier of miR21ASO and the combined delivery of miR21ASO and curcumin may be useful in the development of combination therapy for glioblastoma.</P>

Anti-stress Effect of Artichoke Juice in SD Rats and ICR Mice

Blendyl Saguan Tan-Lee,Gu Young Yu,Kyungjae Kim,Shinha Han,Jeongsup Han,Geum Soon Lee,Eun Seok Kim,Choong Jae Lee,Jong Hoon Ryu,Jae Hoon Cheong 한국식품과학회 2004 Food Science and Biotechnology Vol.13 No.3

Outcomes of salvage liver transplant for recurrent hepatocellular carcinoma

Yuxin Guo,Ek-Khoon Tan,Thinesh-Lee Krishnamoorthy,Chee-Kiat Tan,Ban-Hock Tan,Thuan-Tong Tan,Ser-Yee Lee,Chung-Yip Chan,Peng-Chung Cheow,Alexander Y. F. Chung,Prema Raj Jeyaraj,Brian K. P. Goh 한국간담췌외과학회 2019 Annals of hepato-biliary-pancreatic surgery Vol.23 No.1

Backgrounds/Aims: Salvage liver transplantation (SLT) is a therapeutic strategy for recurrent hepatocellular carcinoma (HCC). However, it remains controversial with compromised survival outcomes and increased perioperative morbidity compared to primary liver transplant (PLT). In the present work, we describe our institution’s experience on SLT by comparing outcomes of SLT to PLT for HCCs. Methods: Retrospective analysis was conducted for 49 transplant patients from 2006-2017. A comparative analysis was carried out between 14 SLT patients and 35 PLT patients. Results: SLT patients demonstrated significantly shorter time to recurrence than PLT patients (median=5.5 versus 23 months, p<0.001) with a trend towards increased perioperative major morbidity (42.9% versus 37%, p=0.711), inferior 5-year overall survival (61% versus 75%, p=0.345) and inferior 5-year recurrence-free survival (57% versus 72%, p=0.263). However, overall survival from the point of primary resection over a 10-year period showed no statistical difference between the 2 groups (SLT=60% versus PLT=61%, p=0.685). Conclusions: SLT is a viable treatment strategy for HCCs. However, it exhibited poorer short-term perioperative and oncologic outcomes than PLT. SLT requires better patient selection with liver donor grafts for optimization of resource allocation in this era of organ shortage. Considering the worldwide shortages in liver grafts, it is hypothesized that optimization of a salvage transplant strategy may improve resource allocation and reap optimal patient outcomes.

Colloidal templating of highly ordered gelatin methacryloyl-based hydrogel platforms for three-dimensional tissue analogues

Lee, Bae Hoon,Shirahama, Hitomi,Kim, Myung Hee,Lee, Jae Ho,Cho, Nam-Joon,Tan, Lay Poh Nature Publishing Group 2017 NPG Asia Materials Vol.9 No.7

Treatment of a Ruptured Vertebrobasilar Fusiform Aneurysm Using Pipeline Embolization Device

Lee A Tan,Roham Moftakhar,Demetrius K. Lopes 대한뇌혈관외과학회 2013 Journal of Cerebrovascular and Endovascular Neuros Vol.15 No.1

Treatment options of ruptured vertebrobasilar fusiform aneurysms (VFA) are limited and often carry significant mortality and morbidity. We report the use of Pipeline Embolization Device (PED) to successfully treat a patient with a ruptured vertebrobasilar fusiform aneurysm (VFA) who presented with subarachnoid hemorrhage (SAH). A 73 year-old man with a history of cardiac stent placement seven days earlier presented with Hunt-Hess II SAH. He was taking aspirin and clopidogrel. Computed tomography angiogram revealed a large vertebrobasilar fusiform aneurysm. Microsurgical treatment options are technically challenging and carry high risk. He underwent endovascular treatment of the ruptured VFA using overlapping PEDs. Five PEDs were placed in a telescoping fashion to reconstruct the affected portions of the left vertebral and basilar arteries. An additional 2-mm blister aneurysm in the right vertebral artery was also discovered during the conventional cerebral angiography and was treated with one additional PED. The patient remained neurologically intact after the procedure. He was continued on aspirin and clopidogrel. Follow-up magnetic resonance imaging at three months demonstrated patency of the stents without any evidence of ischemic change. Follow-up conventional cerebral angiogram at six months demonstrated thrombosis of the VFA and reconstruction of the vertebrobasilar system. The patient remained clinically well. An endovascular approach using PEDs can be a safe and effective treatment option for ruptured VFA in selected cases.

Highly potent tyrosinase inhibitor, neorauflavane from Campylotropis hirtella and inhibitory mechanism with molecular docking

Tan, Xuefei,Song, Yeong Hun,Park, Chanin,Lee, Ki-Won,Kim, Jeong Yoon,Kim, Dae Wook,Kim, Kwang Dong,Lee, Keun Woo,Curtis-Long, Marcus J.,Park, Ki Hun Pergamon 2016 Bioorganic & medicinal chemistry Vol.24 No.2

<P>Tyrosinase inhibition may be a means to alleviate not only skin hyperpigmentation but also neurodegeneration associated with Parkinson's disease. In the course of metabolite analysis from tyrosinase inhibitory methanol extract (80% inhibition at 20 mu g/ml) of Campylotropis hirtella, we isolated fourteen phenolic compounds, among which neorauflavane 3 emerged as a lead structure for tyrosinase inhibition. Neorauflavane 3 inhibited tyrosinase monophenolase activity with an IC50 of 30 nM. Thus this compound is 400-fold more active than kojic acid. It also inhibited diphenolase (IC50 = 500 nM), significantly. Another potent inhibitor 1 (IC50 = 2.9 mu M) was found to be the most abundant metabolite in C. hirtella. In kinetic studies, compounds 3 showed competitive inhibitory behavior against both monophenolase and diphenolase. It manifested simple reversible slow-binding inhibition against monophenolase with the following kinetic parameters: K-i(app) = 1.48 nM, k(3) = 0.0033 nM (1) min (1) and k(4) = 0.0049 min (1). Neorauflavane 3 efficiently reduced melanin content in B16 melanoma cells with 12.95 mu M of IC50. To develop a pharmacophore model, we explored the binding mode of neuroflavane 3 in the active site of tyrosinase. Docking results show that resorcinol motif of B-ring and methoxy group in A-ring play crucial roles in the binding the enzyme. (C) 2015 Elsevier Ltd. All rights reserved.</P>

Atrial secretion of ANP is suppressed in renovascular hypertension: shifting of ANP secretion from atria to the left ventricle

Tan, Rui,Ahn, You Mee,Kim, Hye Yoom,Lee, Yun Jung,Cho, Kyung Woo,Kang, Dae Gill,Lee, Ho Sub American Physiological Society 2018 American journal of physiology, Heart and circulat Vol.315 No.3

<P> In the present study, the change in secretion of atrial natriuretic peptide (ANP) from the atria was defined in hypertension accompanied by ventricular hypertrophy and increased synthesis of ANP. To identify the change of the secretion and mechanisms involved, experiments were performed in isolated perfused beating atria from sham-operated normotensive and renovascular hypertensive rats. Expression of ANP, natriuretic peptide receptor (NPR)-C, components of the renin-angiotensin system, and muscarinic signaling pathway was measured in cardiac tissues. Basal levels of ANP secretion and acetylcholine (ACh)- and stretch-induced activation of ANP secretion were suppressed in the atria from hypertensive compared with normotensive rats. ACh increased ANP secretion via M2 muscarinic ACh receptor-ACh-sensitive K<SUP>+</SUP> channel signaling. In hypertensive rats, ANP concentration increased in the left ventricle but decreased in the right ventricle. The atrial concentration of ANP was not changed in hypertensive compared with normotensive rats. ANP mRNA expression was accentuated in the left ventricle but suppressed in the other cardiac chambers in the hearts of hypertensive rats. NPR-C expression was inversely related to ANP mRNA levels. Angiotensin II type 1 receptor (AT1R) expression was accentuated in the cardiac chambers from hypertensive rats compared with normotensive rats, whereas angiotensin II type 2 receptor, M2 muscarinic receptor, and Kir3.4 channels were suppressed. AT1R blockade with losartan reversed the change observed in hypertensive rats. The present findings indicate that renovascular hypertension shifts the major site of ANP secretion and synthesis from the atria to the left ventricle through modulation of the expression of ANP, NPR-C, AT1R, and the M2 muscarinic signaling pathway. </P><P> NEW & NOTEWORTHY Renovascular hypertension suppresses the atrial secretion of ANP and shifts the major site of the regulation of ANP secretion and synthesis from atria to the hypertrophied left ventricle possibly via modulation of the expression of ANP, natriuretic peptide receptor-C, angiotensin II subtype 1 receptor, and M2 muscarinic signaling pathway. </P>

Cervical Angina

Lee A. Tan 대한척추신경외과학회 2020 Neurospine Vol.17 No.4

Biomechanical Analysis of 3-Level Anterior Cervical Discectomy and Fusion Under Physiologic Loads Using a Finite Element Model

Lee A. Tan,Narayan Yoganandan,Hoon Choi,Yuvaraj Purushothaman,Davidson Jebaseelan,Aju Bosco 대한척추신경외과학회 2022 Neurospine Vol.19 No.2

Objective: Pseudarthrosis and adjacent segment degeneration (ASD) are 2 common complications after multilevel anterior cervical discectomy and fusion (ACDF). We aim to identify the potential biomechanical factors contributing to pseudarthrosis and ASD following 3-level ACDF using a cervical spine finite element model (FEM). Methods: A validated cervical spine FEM from C2 to C7 was used to study the biomechanical factors in cervical spine intervention. The FEM model was used to simulate a 3-level ACDF with intervertebral spacers and anterior cervical plating with screw fixation from C4 to C7. The model was then constrained at the inferior nodes of the T1 vertebra, and physiological loads were applied at the top vertebra. The pure moment load of 2 Nm was applied in flexion, extension, and lateral bending. A follower axial force of 75 N was applied to reproduce the weight of the cranium and muscle force, was applied using standard procedures. The motion-controlled hybrid protocol was utilized to comprehend the adjustments in the spinal biomechanics. Results: Our cervical spine FEM demonstrated that the cranial adjacent level (C3–4) had significantly more increase in range of motion (ROM) (+90.38%) compared to the caudal adjacent level at C7–T1 (+70.18%) after C4–7 ACDF, indicating that the cranial adjacent level has more compensatory increase in ROM than the caudal adjacent level, potentially predisposing it to earlier ASD. Within the C4–7 ACDF construct, the C6–7 level had the least robust fixation during fixation compared to C4–5 and C5–6, as reflected by the smallest reduction in ROM compared to intact spine (-71.30% vs. -76.36% and -77.05%, respectively), which potentially predisposes the C6–7 level to higher risk of pseudarthrosis. Conclusion: Biomechanical analysis of C4–7 ACDF construct using a validated cervical spine FEM indicated that the C3–4 has more compensatory increase in ROM compared to C7–T1, and C6–7 has the least robust fixation under physiological loads. These findings can help spine surgeons to predicate the areas with higher risks of pseudarthrosis and ASD, and thus developing corresponding strategies to mitigate these risks and provide appropriate preoperative counseling to patients.