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Alterations of Gefitinib Pharmacokinetics by Co-administration of Herbal Medications in Rats

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Chinese Journal of Integrative Medicine 2018年第6期24卷 460-466页

作者： Kwon-Yeon Weon Min Gi Kim Soyoung Shin Tae Hwan Kim Sang Hoon Joo Eunsook Ma seok Won Jeong Sun Dong Yoo Yu Seok Youn Beom Soo Shin College of Pharmacy Catholic University of Daegu School of Pharmacy Sungkyunkwan University College of Pharmacy Wonkwang University

Objective： To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib （Iressae） and the oriental medications Guipi Decoction （归脾汤, GPD, Guibi-tang in Korean） and Bawu Decoction （八物汤, BWD, Palmul-tang in Korean）. Methods： Methylceliulose （MC, control）, GPD （1,200 mg/kg）, or BWD （6,000 mg/kg） was orally administered to rats either as a single dose or multiple doses prior to gefitinib administration. To examine the effects of a single dose of the herbal medicines, gefitinib （10 mg/kg） was orally administered after 5 min or 1 h of MC or the herbal medicine pretreatments. To examine the effects of the multiple doses of the herbal medicines, gefltinib （10 mg/kg） was orally administered following 7 consecutive days of the administration of MC or each herbal medicine. The plasma concentrations of gefitinib were determined with liquid chromatography-tandem mass spectrometry assay. The plasma concentration-time profiles of gefitinib were analyzed with a noncompartmental analysis. Results： Gefitinib was rapidly absorbed and showed a mono- exponential decline with an elimination half-life of 3.7-4.1 h. The pharmacokinetics of gefitinib was not affected by GPD pretreatment. However, a significantly lower maximum plasma concentration （Crux, P〈0.05） and area under the curve （P〈0.05）, and a delayed time to reach Cmax （Tmax, P〈0.01） were observed in both single- and multiple- dose BWD-pretreated rats compared with the control rats. Conclusions： BWD and not GPD might delay and interfere with gefitinib absorption. Further evaluations of the clinical significance of these findings are needed.

关键词： herb-drug interaction pharmacokinetics gefitinib Guipi Decoction Bawu Decoction

Upconverting nanoparticle-containing erythrocyte-sized hemoglobin microgels that generate heat,oxygen and reactive oxygen species for suppressing hypoxic tumors

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Bioactive Materials 2023年第4期22卷 112-126页

作者： Hanju Kim Johyun Yoon Hwang Kyung Kim Woo Tak Lee Nguyen Thi Nguyen Xuan Thien Le Eun-Hee Lee Eun Seong Lee Kyung Taek Oh Han-Gon Choi Yu Seok Youn School of Pharmacy Sungkyunkwan University2066 Seobu-roJangan-guSuwonGyeonggi-do16419Republic of Korea College of Pharmacy Korea University2511 Sejong-roSejong30019Republic of Korea Department of Biotechnology and Department of Biomedical-Chemical Engineering the Catholic University of Korea43 Jibong-roBucheon-siGyeonggi-do14662Republic of Korea College of Pharmacy Chung-Ang University84 Heukseok-roDongjak-guSeoul06974Republic of Korea College of Pharmacy Hanyang University55Hanyangdaehak-roSangnok-guAnsan15588Republic of Korea

Inspired by erythrocytes that contain oxygen-carrying hemoglobin(Hb)and that exhibit photo-driven activity,we introduce homogenous-sized erythrocyte-like Hb microgel(μGel)systems(5-6μm)that can(i)emit heat,(ii)supply oxygen,and(iii)generate reactive oxygen species(ROS;1O2)in response to near-infrared(NIR)laser irradiation.Hb μGels consist of Hb,bovine serum albumin(BSA),chlorin e6(Ce6)and erbium@lutetium upconverting nanoparticles(UCNPs;~35 nm)that effectively convert 808 nm NIR light to 660 nm visible light.These Hb μGels are capable of releasing oxygen to help generate sufficient reactive oxygen species(^(1)O_(2))from UCNPs/Ce6 under severely hypoxic condition upon NIR stimulation for efficient photodynamic activity.Moreover,the Hb μGels emit heat and increase surface temperature due to NIR light absorption by heme(iron protoporphyrin IX)and display photothermal activity.By changing the Hb/UCNP/Ce6 ratio and controlling the amount of NIR laser irradiation,it is possible to formulate bespoke Hb μGels with either photothermal or photodynamic activity or both in the context of combined therapeutic effect.These Hb μGels effectively suppress highly hypoxic 4T1 cell spheroid growth and xenograft mice tumors in vivo.

关键词： Hemoglobin microgel Upconversion Photothermal therapy Photodynamic therapy Hypoxic tumors Oxygen-generation

Tenofovir rescue therapy for chronic hepatitis B patients after multiple treatment failures

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World Journal of Gastroenterology 2012年第47期18卷 6996-7002页

作者： yu Jin Kim Dong Hyun Sinn Geum-youn Gwak Moon seok Choi Kwang Cheol Koh Seung Woon Paik Byung Chul Yoo Joon Hyeok Lee Department of Medicine Samsung Medical CenterSungkyunkwan University School of MedicineSeoul 135-710South Korea

AIM:To evaluate the efficacy and safety of tenofovir disoproxil fumarate(TDF) for chronic hepatitis B(CHB) patients after multiple failures.METHODS:A total of 29 CHB patients who had a suboptimal response or developed resistance to two or more previous nucleoside/nucleotide analogue(NA) treatments were included.Study subjects were treated with TDF alone(n = 13) or in combination with lamivudine(LAM,n = 12) or entecavir(ETV,n = 4) for ≥ 6 mo.Complete virologic response(CVR) was defined as an achievement of serum hepatitis B virus(HBV) DNA level ≤ 60 IU/mL by real-time polymerase chain reaction method during treatment.Safety assessment was based on serum creatinine and phosphorus level.Eleven patients had histories of LAM and adefovir dipivoxil(ADV) treatment and 18 patients were exposed to LAM,ADV,and ETV.Twenty-seven patients(93.1%) were hepatitis B e antigen(HBeAg) positive and the mean value of the baseline serum HBV DNA level was 5.5 log IU/mL ± 1.7 log IU/mL.The median treatment duration was 16 mo(range 7 to 29 mo).RESULTS:All the patients had been treated with LAM and developed genotypic and phenotypic resistance to it.Resistance to ADV was present in 7 patients and 10 subjects had a resistance to ETV.One patient had a resistance to both ADV and ETV.The cumulative probabilities of CVR at 12 and 24 mo of TDF containing treatment regimen calculated by the Kaplan Meier method were 86.2% and 96.6%,respectively.Although one patient failed to achieve CVR,serum HBV DNA level decreased by 3.9 log IU/mL from the baseline and the last serum HBV DNA level during treatment was 85 IU/mL,achieving near CVR.No patients in this study showed viral breakthrough or primary non-response during the follow-up period.The cumulative probability of HBeAg clearance in the 27 HBeAg positive patients was 7.4%,12%,and 27% at 6,12,and 18 mo of treatment,respectively.Treatment efficacy of TDF containing regimen was not statistically different according to the presence of specific HBV mutations.History of prior exposure to specific antivir

关键词：慢性乙型肝炎抢救治疗患者 DNA水平核苷酸类似物乙型肝炎病毒聚合酶链反应 HBeAg

Characterization of CD8＋CD57＋ T cells in patients wit acute myocardial infarction

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Cellular & Molecular Immunology 2015年第4期12卷 466-473页

作者： Hee Tae yu Jong-Chan youn Jino Lee Seunghyun Park Ho-seok Chi Jungsul Lee Chulhee Choi Sungha Park Donghoon Choi Jong-Won Ha Eui-Cheol Shin Laboratory of Immunology and Infectious Diseases Graduate School of Medical Science and Engineering KAIST Daejeon Republic of Korea Cardiology Division Severance Cardiovascular Hospital Yonsei University College of Medicine Seoul Republic of Korea Department of Bio and Brain Engineering KAIST Daejeon Republic of Korea ' ' The first two authors contributed equally to this article

Although T cells are known to be involved in the pathogenesis of coronary artery disease, it is unclear which subpopulation of T cells contributes to pathogenesis in acute myocardial infarction （MI）. We studied the immunological characteristics and clinical impact of CD8＋CD57＋ T cells in acute MI patients. The frequency of CD57＋ cells among CD8＋ T cells was examined in peripheral blood sampled the morning after acute MI events. Interestingly, the frequency of CD57＋ cells in the CD8＋ T-cell population correlated with cardiovascular mortality 6 months after acute MI. The immunological characteristics of CD8＋CD57＋ T cells were elucidated by surface immunophenotyping, intracellular cytokine staining and flow cytometry. Immunophenotyping revealed that the CD8＋CD57＋ T cells were activated, senescent T cells with pro-inflammatory and tissue homing properties. Because a high frequency of CD8＋CD57＋ T cells is associated with short-term cardiovascular mortality in acute MI patients, this specific subset of CD8＋ T cells might contribute to acute coronary events via their pro-inflammatory and high cytotoxic capacities. Identification of a pathogenic CD8＋ T-cell subset expressing CD57 may offer opportunities for the evaluation and management of acute MI.

关键词： acute myocardial infarction CD8＋CD57＋ T cells immunosenescence

Boerhaave's syndrome during bowel preparation with polyethylene glycol in a patient with postpolypectomy bleeding

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World Journal of Gastrointestinal Endoscopy 2013年第5期5卷 270-272页

作者： Ji-youn yu Seung-Kyoung Kim Eun-Chul Jang Ju-Ok Yeom Sun-young Kim young-seok Cho Division of Gastroenterology Department of Internal MedicineUijeongbu St.Hospitalthe Catholic University of Korea College of MedicineUijeongbu 480-717South Korea

Boerhaave's syndrome is spontaneous rupture of the esophagus,a rare condition with high mortality that occurs most often after forceful vomiting.Polyethylene glycol(PEG) solution is the most common preparation used for colonoscopy.Since large volumes have to be ingested,PEG may induce severe vomiting or retching.However,Boerhaave's syndrome has rarely been reported as a potential problem related to PEG solution.We report a case of spontaneous esophageal rupture due to violent vomiting during bowel preparation with PEG solution in a patient with postpolypectomy bleeding.

关键词： Esophageal perforation Colonoscopy Polyethylene glycols

Oncologic efficacy of gonadotropin-releasing hormone agonist in hormone receptor-positive very young breast cancer patients treated with neoadjuvant chemotherapy

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世界临床病例杂志 2023年第27期11卷 6398-6406页

作者： Hee Jun Choi Jun Ho Lee Chang Shin Jung Jai Min Ryu Byung Joo Chae Se Kyung Lee Jong Han yu seok Won Kim seok Jin Nam Jeong Eon Lee youn Joo Jung Hyun yul Kim Department of Surgery Samsung Changwon HospitalSungkyunkwan University School of MedicineChangwon 51353South Korea Division of Breast Surgery Department of SurgerySamsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351South Korea Department of Surgery Pusan National University Yangsan HospitalPusan National University School of MedicineGyeongnam 50612South Korea

BACKGROUND Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis.AIM To evaluate the outcomes of young hormone receptor(HR)-positive patients with breast cancer treated with neoadjuvant chemotherapy(NAC),and the oncologic efficacy of gonadotropin-releasing hormone(GnRH)agonists.METHODS This retrospective study involved a prospectively enrolled cohort.We included patients diagnosed with invasive breast cancer who were treated with NAC followed by curative surgery at the Samsung Medical Center and Samsung Changwon Hospital between January 2006 and December 2017.Among patients with HR-positive and human epidermal grow factor 2(HER2)-negative breast cancer,we analyzed the characteristics and oncology outcomes between the patients equal to or younger than 35 years and the patients older than 35 years.RESULTS Among 431 patients with NAC and HR-positive/HER2-negative breast cancer,78 were 35 years old or younger,and 353 patients were older than 35 years.The median follow-up was 71.0 months.There was no statistically significant difference in disease free survival(DFS,P=0.565)and overall survival(P=0.820)between the patients equal to or younger than 35 years and the patients older than 35 years.The two groups differed in that the GnRH agonist was used more frequently in the group of patients equal to or younger than 35 years than in the other group(52.4%vs 11.2%,Pyounger than 35 years,patients treated with the GnRH agonist had better DFS(P=0.037).CONCLUSION Administration of GnRH agonists might improve the DFS rate of HR-positive/HER2-negative breast cancer in the equal to or younger than 35 years group of patients with NAC.

关键词： Gonadotropin-releasing hormone Agonist young Breast Cancer

Colonic lipoma covered by hyperplastic epithelium: Case report

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World Journal of Clinical Cases 2013年第3期1卷 124-127页

作者： Ju-Ok Yeom Sun-young Kim Eun-Chul Jang Ji-youn yu Eun Deok Chang young-seok Cho Division of Gastroenterology Department of Internal MedicineUijeongbu St. Mary’s Hospitalthe Catholic University of Korea College of MedicineUijeongbu 480-717South Korea Departement of Cilinical Pathology Uijeong-bu St. Mary’s Hospitalthe Catholic University of Korea College of MedicineUijeongbu 480-717South Korea

Colonic lipomas are submucosal nonepithelial tumors covered by intact or eroded mucosa. In rare cases, alterations in the mucosa covering a lipoma include hyperplasia, adenoma, atrophy, ulceration, and necrosis. Here, we report a case of a colonic lipoma covered by hyperplastic epithelium in a 68-year-old woman. Based on the colonoscopy findings, a snare polypectomy was performed for a presumptive diagnosis of an epithelial lesion; however, the histological examination revealed a colonic submucosal lipoma with overlying hyperplastic epithelium.

关键词： Lipoma Colonic lipomas Hyperplastic Colonoscopy

Diagnosis of gastric epithelial neoplasia:Dilemma for Korean pathologists

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World Journal of Gastroenterology 2011年第21期17卷 2602-2610页

作者： Joon Mee Kim Mee-Yon Cho Jin Hee Sohn Dae young Kang Cheol Keun Park Woo Ho Kim So-young Jin Kyoung Mee Kim Hee Kyung Chang Eunsil yu Eun Sun Jung Mee Soo Chang Jong Eun Joo Mee Joo youn Wha Kim Do youn Park yun Kyung Kang Sun Hoo Park Hye Seung Han young Bae Kim Ho Sung Park Yang seok Chae Kye Won Kwon Hee Jin Chang The Gastrointestinal Pathology Study Group of Korean Society of Pathologists Department of Pathology Inha University Hospital Department of Pathology Yonsei University Wonju College of Medicine Wonju Christian Hospital Department of Pathology Sungkyunkwan University School of MedicineKangbuk Samsung Medical Center Department of Pathology Chungnam National University College of Medicine Department of Pathology Sungkyunkwan University School of MedicineSamsung Medical Center Department of Pathology Seoul National University College of Medicine Department of Pathology Soonchunhyang University Hospital Department of Pathology Kosin University College of Medicine Department of Pathology University of Ulsan College of MedicineAsan Medical Center Department of Pathology The Catholic University of KoreaSeoul St.Mary's Hospital Department of Pathology Seoul National University Boramae Hospital Department of Pathology Eulji General Hospital Department of Pathology Inje University Ilsan Paik Hospital Department of Pathology Kyunghee University College of Medicine Department of Pathology Pusan National University College of Medicine Department of Pathology Inje University Seoul Paik Hospital Department of Pathology Korea Cancer Center Hospital Department of Pathology Konkuk University Medical Center Department of Pathology Ajou University School of Medicine Department of Pathology Chonbuk National University Medical School Department of Pathology Korea University College of Medicine Department of Pathology Bundang Jesaeng Hospital Department of Pathology National Cancer Center The Korean Society of Pathologists 4FThe Korean Medical Association BuildingSeoul 140-721South Korea

The histopathological diagnosis of gastric mucosal biopsy and endoscopic mucosal resection/endoscopic submucosal dissection specimens is important,but the diagnostic criteria,terminology,and grading system are not the same in the East and West.A structurally invasive focus is necessary to diagnose carcinoma for most Western pathologists,but Japanese pathologists make a diagnosis of cancer based on severe dysplastic cytologic atypia irrespective of the presence of invasion.Although the Vienna classification was introduced to reduce diagnostic discrepancies,it has been difficult to adopt due to different concepts for gastric epithelial neoplastic lesions.Korean pathologists experience much difficulty making a diagnosis because we are influenced by Japanese pathologists as well as Western medicine.Japan is geographically close to Korea,and academic exchanges are active.Additionally,Korean doctors are familiar with Western style medical terminology.As a result,the terminology,definitions,and diagnostic criteria for gastric intraepithelial neoplasia are very heterogeneous in Korea.To solve this problem,the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists has made an effort and has suggested guidelines for differential diagnosis:(1) a diagnosis of carcinoma is based on invasion;(2) the most important characteristic of low grade dysplasia is the architectural pattern such as regular distribution of crypts without severe branching,budding,or marked glandular crowding;(3) if nuclear pseudostratification occupies more than the basal half of the cryptal cells in three or more adjacent crypts,the lesion is considered high grade dysplasia;(4) if severe cytologic atypia is present,careful inspection for invasive foci is necessary,because the risk for invasion is very high;and(5) other structural or nuclear atypia should be evaluated to make a final decision such as cribriform pattern,papillae,ridges,vesicular nuclei,high nuclear/cytoplasmic ratio,loss of nuclear polarity,thick and irregular nuclear

关键词：病理诊断粘膜上皮理学家胃粘膜韩国学术交流活动发育不良细胞学

Mesenchymal stem cells ameliorate B-cell-mediated immune responses and increase IL-10-expressing regulatory B cells in an EBI3-dependent manner

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Cellular & Molecular Immunology 2017年第11期14卷 895-908页

作者： Kyung-Ah Cho Jun-Kyu Lee yu-Hee Kim Minhwa Park So-youn Woo Kyung-Ha Ryu Department of Microbiology School of MedicineEwha Womans UniversitySeoul 07985Republic of Korea Department of Pediatrics School of MedicineEwha Womans UniversitySeoul 07985Republic of Korea

Effector B cells are central contributors to the development of autoimmune disease by activating autoreactive T cells,producing pro-inflammatory cytokines and organizing ectopic lymphoid tissue.Conversely,IL-10-producing regulatory B(Breg)cells have pivotal roles in maintaining immunological tolerance and restraining excessive inflammation in autoinflammatory disease.Thus,regulating the equilibrium between antibody-producing effector B cells and Breg cells is critical for the treatment of autoimmune disease.In this study,we investigated the effect of human palatine tonsil-derived mesenchymal stem cells(T-MSCs)on estradiol(E2)-induced B-cell responses in vivo and in vitro.Transplantation of T-MSC into E2-treated mice alleviated B-cell-mediated immune responses and increased the population of IL-10-producing Breg cells.T-MSCs regulated the B-cell populations by producing Epstein–Barr virus(EBV)-induced 3(EBI3),one of the two subunits of IL-35 that is the well-known inducer of Breg cells.We demonstrate a critical role of EBI3(IL-35)in vitro by depleting EBI3 in T-MSCs and by adding exogenous IL-35 to the culture system.Taken together,our data suggest that IL-35-secreting MSCs may become an attractive therapeutic to treat B-cell-mediated autoimmune diseases via expanding Breg cells.

关键词： autoimmune disease B cells IL-35 mesenchymal stem cells