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Biodegradable nanocarriers for small interfering ribonucleic acid （siRNA） co-delivery strategy increase the chemosensitivity of pancreatic cancer cells to gemcitabine

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Nano Research 2017年第9期10卷 3049-3067页

作者： Chengbin Yang Kok Ken Chan Wen-Jen Lin Alana Mauluidy Soehartono Guimiao Lin Huiting Toh ho sup yoon Chih-Kuang Chen Ken-Tye Yong School of Electrical and Electronic Engineering Nanyang Technological University Singapore 639798 Singapore Polymeric Biomaterials Lab Department of Fiber and Composite Materials Feng Chia University Taichung 40724 Taiwan China Key Lab of Biomedical Engineering School of Medicine Shenzhen University Shenzhen 518060 China Division of Structural Biology & Biochemistry School of Biological Sciences Nanyang Technological University Singapore 639798Singapore Department of Genetic Engineering College of Life Sciences Kyung Hee University Yongin-si Gyeonggi-do 446701 Republic of Korea

Ribonucleic acid (RNA) interference (RNAi) therapies are promising cancer treatment modalities that can specifically target abnormal proto-oncogenes, thus improving the therapeutic effect. For the treatment of pancreatic cancer, targeting one mutant proto-oncogene by RNAi usually does not yield the desired therapeutic efficiency. Both K-ras gene mutations and Notch1 overexpression are common symptoms in pancreatic cancer patients, and play a crucial role in pancreatic cancer cell drug resistance. In this study, biodegradable charged polyester-based vectors (BCPVs) were synthesized for the co-delivery of K-ras and Notch1 small interfering ribonucleic acid (siRNA) into MiaPaCa-2 cells (pancreatic cancer cell line) to overcome drug resistance to gemcitabine (GEM), a first-line chemotherapeutic drug used in the clinic. BCPVs could effectively absorb negative siRNA to form a capsule-like structure, prevent siRNA from nuclease digestion in the serum, and promote effective siRNA cell internalization and endosomal escape. Through K-ras and Notch1 gene silencing in MiaPaCa-2 cells, BCPV-siRNAK-ras-siRNANotch1 nanocomplexes effectively reversed the epithelia-mesenchymal transition (EMT) in MiaPaCa-2 cells, thereby greatly enhancing the sensitivity of MiaPaCa-2 cells to GEM. MiaPaCa-2 cell proliferation, migration, and invasion were effectively inhibited, and cell apoptosis was also significantly enhanced by the synergistic antitumor effect of BCPV-siRNAK-ras-siRNANotch1 nanocomplexes and GEM. These results suggest that this combination RNAi therapy can be used to improve cancer cell sensitivity to chemotherapeutic drugs. Specifically, this newly developed strategy has a great potential for treating pancreatic cancer.

关键词： pancreatic cancer small interfering ribonucleic acid (siRNA) biodegradable charged polyester-based vector (BCPV) gemcitabine (GEM) epithelia-mesenchymal transition (EMT)

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Aggregation-induced emission （ALE） dye loaded polymer nanoparticles for gene silencing in pancreatic cancer and their in vitro and in vivo biocompatibility evaluation

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Nano Research 2015年第5期8卷 1563-1576页

作者： Rui Hu Chengbin Yang Yucheng Wang Guimiao Lin Wei Qin Qingling Ouyang Wing-Cheung Law Quoc Toan Nguyen ho sup yoon Xiaomei Wang Ken-Tye Yong Ben Zhong Tang School of Electrical and Electronic Engineering Nanyang Technological University Singapore 639798 Singapore The Engineering Lab of Synthetic Biology and the Key Lab of Biomedical Engineering School of Medicine Shenzhen University Shenzhen 518060 China Department of Chemistry The Hang Kong University of Science and Technology Clear Water Bay Kowloon Hang Kong China Department of Industrial and Systems Engineering The Hang Kong Polytechnic University Hung Ham Kowloon Hang Kong China Division of Structural Biology & Biochemistry School of Biological Sciences Nanyang Technological University Singapore 539798 Singapore

We have developed aggregation-induced emission （AIE） dye loaded polymer nanoparticles with deep-red emission for siRNA delivery to pancreatic cancer cells. Two US Food and Drug Administration （FDA） approved surfactant polymers, Pluronics F127 and PEGylated phospholipid, were used to prepare the dye-loaded nanoparticle formulations and they can be used as nanovectors for gene silencing of mutant K-ras in pancreatic cancer cells. The successful transfection of siRNA by the developed nanovectors was confirmed by the fluorescent imaging and quantified through flow cytometry. Quantitative real time polymerase chain reaction （PCR） indicates that the expression of the mutant K-ras oncogene from the MiaPaCa-2 pancreatic cancer cells has been successfully suppressed. More importantly, our in vivo toxicity study has revealed that both the nanoparticle formulations are highly biocompatible in BALC/c mice. Overall, our results suggest that the AIE dye-loaded polymer nanoparticle formulations developed here are suitable for gene delivery and have high potential applications in translational medicine research.

关键词： aggregation-induced emission polymer nanoparticles gene silencing pancreatic cancer

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Indications of external radiotherapy for hepatocellular carcinoma from updated clinical guidelines: Diverse global viewpoints

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World Journal of Gastroenterology 2020年第4期26卷 393-403页

作者： Sunmin Park Won sup yoon Chai hong Rim Department of Radiation Oncology Ansan Hospital Korea University Medical College

The etiology and disease patterns of hepatocellular carcinoma(HCC)significantly vary among regions. Modern standard treatments commonly require multidisciplinary approaches, including applications of up-to date medicine and advanced procedures, and necessitate the support of socioeconomic systems. For these reasons, a number of clinical guidelines for HCC from different associations and regions have been presented. External beam radiation therapy was contraindicated for HCC until a few decades ago, but with the development of new technologies, its application has rapidly increased as selective irradiation for tumorous lesions became possible. Most of the guidelines had been opposed or indifferent to radiotherapy in the past, but several guidelines have introduced indications and recommendations for radiotherapy in their updated versions. This review will discuss the characteristics of important guidelines and their contents regarding radiotherapy and will also provide guidance to physicians who are considering applications of locoregional modalities that include radiotherapy.

关键词： Hepatocellular carcinoma Clinical guideline Radiotherapy Radiation therapy Liver neoplasm Stereotactic body radiotherapy

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A macroscopic constitutive model of shape memory alloy considering cyclic effects

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Science China(Physics,Mechanics & Astronomy) 2013年第4期56卷 755-764页

作者： ZhoU Bo yoon Sung-ho College of Pipeline and Civil Engineering China University of Petroleum School of Mechanical Engineering Kumoh National Institute of Technology

This paper presents a macroscopic constitutive model reproducing the hysteretic behaviors of the superelastic shape memory alloy (SMA) under cyclic loading. The progressive increase of residual strain with the increased cycle number in such materials is assumed to be a consequence of the progressive increase of residual stress-induced martensitic volume fraction upon the cyclic effects. The progressive decrease of phase transformation critical stresses with the increased cycle number in such materials is assumed to be a result from the progressive increase of phase transformation critical temperatures upon the cyclic effects. A cyclic evolution equation is supposed to describe the influences of cycle effects on the material properties of the SMA under cyclic loading. A phase transformation equation expressing the phase transformation behaviors of the SMA under cyclic loading is established based on the differential relationship between martensitic volume fraction and the free energy increment of phase transformation. A mechanical constitutive equation predicting the mechanical characteristics of the SMA under cyclic loading is developed on the basis of thermodynamics and continuum mechanics. The cyclic evolution equation, phase transformation equation, and mechanical constitutive equation together compose the presented macroscopic constitutive model considering cyclic effects. Results of the numerical simulations illustrate that it can well reproduce the superelastic hysteretic behaviors of the SMA under cyclic loading.

关键词： shape memory alloy cyclic effect cyclic evolution equation phase transformation equation mechanical constitutive equation

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Liver abscess and sepsis with Bacillus pantothenticus in an immunocompetent patient:A first case report

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World Journal of Gastroenterology 2009年第42期15卷 5360-5363页

作者： Jung Sik Na Tae Hyung Kim Heung Su Kim Sang Hyun Park ho sup Song Sang Woo Cha Hee Jung yoon Department of Internal Medicine Eulji University College of MedicineDaejeon 302-799South Korea

Bacillus species are aerobic,gram-positive,spore forming rods that are usually found in the soil,dust,streams,and other environmental *** for ***(***) ,most species display low virulence,and only rarely cause infections in hosts with weak or damaged immune *** are two case reports of *** as a potentially serious bacterial pathogen causing a liver abscess in an immunologically competent *** herein report a case of liver abscess and sepsis caused by *** in an immunocompetent *** now,no case of liver abscess due to *** has been reported.

关键词： Bacillus pantothenticus, Bacillus species Immunocompetence Liver abscess and sepsis

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Photodynamic therapy prolongs metal stent patency in patients with unresectable hilar cholangiocarcinoma

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World Journal of Gastroenterology 2012年第39期18卷 5589-5594页

作者： Tae yoon Lee Young Koog Cheon Chan sup Shim Young Deok Cho Digestive Disease Center Department of Internal MedicineKonkuk University Medical CenterKonkuk University School of MedicineSeoul 143-729South Korea Institute for Digestive Research and Digestive Disease Center Soonchunhyang University College of MedicineSeoul 140-743South Korea

AIM:To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC). METhoDS:This was a retrospective analysis of patients with hilar CC referred to our institution from December, 1999 to January, 2011. Out of 232 patients, thirty-three patients with unresectable hilar CC were treated. Eighteen patients in the PDT group were treated with uncovered metal stents after one session of PDT. Fifteen patients in the control group were treated with metal stents alone. Porfimer sodium (2 mg/kg) was administered intravenously to PDT patients. Fortyeight hours later, PDT was administered using a diffusing fiber that was advanced across the tumor by either endoscopic retrograde cholangiopancreatography or percutaneous cholangiography. After performance of PDT, uncovered metal stents were inserted to ensure adequate decompression and bile drainage. Patient survival rates and cumulative stent patency were calculated using Kaplan-Meier analysis with the log-rank test. RESULTS:The PDT and control patients were comparable with respect to age, gender, health status, pretreatment bilirubin, and hilar CC stage. When compared to control, the PDT group was associated with significantly prolonged stent patency (median 244 ± 66 and 177 ± 45 d, respectively, P = 0.002) and longer patient survival (median 356 ± 213 and 230 ± 73 d, respectively, P = 0.006). Early complication rates were similar between the groups (PDT group 17%, control group 13%) and all patients were treated conservatively. Stent malfunctions occurred in 14 PDT patients (78%) and 12 control patients (80%). Of these 26 patients, twenty-two were treated endoscopically and four were treated with external drainage. CONCLUSION:Metal stenting after one session of PDT may be safe with acceptable complication rates. The PDT group was associated with a significantly longer stent patency than the control group in patients with unresectable hilar CC.

关键词： Bile duct cancer Palliative endoscopic stent-ing Photodynamic therapy Outcome

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Epidemic obesity in children and adolescents:risk factors and prevention

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Frontiers of Medicine 2018年第6期12卷 658-666页

作者： Eun Young Lee Kun-ho yoon Division of Endocrinology and Metabolism Department of Internal MedicineSeoul St.Mary's HospitalCollege of MedicineThe Catholic University of KoreaSeoul 06591Korea Institute of Catholic Ubiquitous Health Care The Catholic University of KoreaSeoul 06591Korea

The prevalence of obesity among children and adolescents (aged 2–18 years) has increased rapidly, with more than 100 million affected in 2015. Moreover, the epidemic of obesity in this population has been an important public health problem in developed and developing countries for the following reasons. Childhood and adolescent obesity tracks adulthood obesity and has been implicated in many chronic diseases, including type 2 diabetes, hypertension, and cardiovascular disease. Furthermore, childhood and adolescent obesity is linked to adulthood mortality and premature death. Although an imbalance between caloric intake and physical activity is a principal cause of childhood and adolescent obesity, environmental factors are exclusively important for development of obesity among children and adolescents. In addition to genetic and biological factors, socioenvironmental factors, including family, school, community, and national policies, can play a crucial role. The complexity of risk factors for developing obesity among children and adolescents leads to difficulty in treatment for this population. Many interventional trials for childhood and adolescent obesity have been proven ineffective. Therefore, early identification and prevention is the key to control the global epidemic of obesity. Given that the proportion of overweight children and adolescents is far greater than that of obesity, an effective prevention strategy is to focus on overweight youth, who are at high risk for developing obesity. Multifaceted, comprehensive strategies involving behavioral, psychological, and environmental risk factors must also be developed to prevent obesity among children and adolescents.

关键词： obesity children adolescents epidemiology risk factor prevention

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Unusual case of emphysematous cystitis mimicking intestinal perforation:A case report

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World Journal of Clinical Cases 2023年第28期11卷 6943-6948页

作者： Hye yoon Kang Dae-sup Lee Donghyoun Lee Department of Surgery Samsung Medical CenterSeoul 06338South Korea Department of Emergency Medicine Pusan National University Yangsan HospitalYangsan 50612South Korea Department of Surgery Jeju National University HospitalJeju National University College of MedicineJeju 63241South Korea

BACKGROUND Emphysematous cystitis(EC)is a bladder condition commonly caused by gasgenerating bacterial *** that increase the risk for developing this condition include female gender,age≥60 years,and diabetes mellitus,glycosuria,and urinary *** symptoms of EC often lack specificity,making diagnostic imaging techniques crucial for accurate identification of the *** SUMMARY This report presents an unusual case of EC that mimicked intestinal *** it was initially challenging to differentiate between intestinal perforation and EC on admission,the patient managed to avoid unnecessary surgery and made a good recovery solely through antibiotic *** Successful treatment of the patient described herein highlights the importance of accurately diagnosing EC,which can be difficult to differentiate from intestinal perforation.

关键词： Emphysematous cystitis Intestinal Bowel Perforation Bladder Case report

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New approaches to gastric cancer staging:Beyond endoscopic ultrasound,computed tomography and positron emission tomography

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World Journal of Gastroenterology 2014年第38期20卷 13783-13790页

作者： Hyuk yoon Dong ho Lee Department of Internal Medicine Seoul National University Bundang Hospital Department of Internal Medicine and Liver Research Institute Seoul National University College of Medicine

Currently, there is no single gold standard modality for staging of gastric cancer and several methods have been used complementarily in the each clinical situation. To make up for the shortcomings of conventional modalities such as endoscopic ultrasound, computed tomography and sup>18sup>F-fluoro-2-deoxyglucose positron emission tomography, numerous attempts with new approaches have been made for gastric cancer staging. For T staging, magnifying endoscopy with narrow-band was evaluated to differentiate mucosal cancer from submucosal cancer. Single/double contrast-enhanced ultrasound and diffusion-weighted magnetic resonance imaging were also tried to improve diagnostic accuracy of gastric cancer. For intraoperative staging with sentinel node mapping, indocyanine green infrared and fluorescence imaging was introduced. In addition, to detect micrometastasis, real-time reverse transcription-polymerase chain reaction system with multiple markers was studied. Staging laparoscopy using 5-aminolevulinic acid-mediated photodynamic diagnosis and percutaneous diagnostic peritoneal lavage were also evaluated. however, most studies reporting new staging methods is preliminary and further studies for validation in clinical practice are needed. In this mini-review, we discuss new progress in gastric cancer staging. Especially, we focus on new diagnostic approach to gastric cancer staging beyond the conventional modalities and briefly review the remarkable clinical results of the studies published over the past three years.

关键词： Gastric cancer Neoplasm staging Diagnostic accuracy New methods New approaches

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Purification of Astaxanthin from Laminaria japonica by Ionic Liquid-based Monolithic Cartridge

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Chemical Research in Chinese Universities 2012年第3期28卷 406-409页

作者： yoon Chang-hwan ROW Kyung-ho Department of Chemical Engineering Inha UniversityIncheon 402-751Korea

An effective and accurate method was developed for the extraction of astaxanthin from Laminariajapo- nica with subsequent separation by ionic liquid-based monolithic cartridge. The optimized extraction conditions in- cluding extraction solvent（ethanol）, extraction time（90 min） and ultrasonic power（75 W） were obtained by systema- tical investigation. Chromatographic analysis was performed on a C18 column with ultraviolet（UV） detection at 476 nm, and a solution consisting of methanol/acetonitrile/H2O/dichloromethane（83：6：6：5, volume ratio） was used as the mobile phase at a flow rate of 0.7 mL/min. After ionic liquid-based monolithic solid phase extraction, 17.82 μg/g as- taxanthin was obtained from Laminaria japonica. This ionic liquid-based monolithic cartridge exhibits high affinity and selectivity for astaxanthin, and it can be potentially used as the stationary phase of high performance liquid chromatography（HPLC）.

关键词： Laminariajaponica Astaxanthin Extraction Ionic liquid Cartridge

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