Pharmacokinetics of Intravitreally Injected Bevacizumab in Vitrectomized Eyes

Ahn, Jeeyun,Kim, Hyuncheol,Woo, Se Joon,Park, Ji Hyun,Park, Sunyoung,Hwang, Duck Jin,Park, Kyu Hyung Mary Ann Liebert 2013 Journal of ocular pharmacology and therapeutics Vol.29 No.7

Clinical Features and Course of Ocular Toxocariasis in Adults

Ahn, Seong Joon,Woo, Se Joon,Jin, Yan,Chang, Yoon-Seok,Kim, Tae Wan,Ahn, Jeeyun,Heo, Jang Won,Yu, Hyeong Gon,Chung, Hum,Park, Kyu Hyung,Hong, Sung Tae Public Library of Science 2014 PLoS neglected tropical diseases Vol.8 No.6

<▼1><P><B>Purpose</B></P><P>To investigate the clinical features, clinical course of granuloma, serologic findings, treatment outcome, and probable infection sources in adult patients with ocular toxocariasis (OT).</P><P><B>Methods</B></P><P>In this retrospective cohort study, we examined 101 adult patients diagnosed clinically and serologically with OT. Serial fundus photographs and spectral domain optical coherence tomography images of all the patients were reviewed. A clinic-based case-control study on pet ownership, occupation, and raw meat ingestion history was performed to investigate the possible infection sources.</P><P><B>Results</B></P><P>Among the patients diagnosed clinically and serologically with OT, 69.6% showed elevated immunoglobulin E (IgE) levels. Granuloma in OT involved all retinal layers and several vitreoretinal comorbidities were noted depending on the location of granuloma: posterior pole granuloma was associated with epiretinal membrane and retinal nerve fiber layer defects, whereas peripheral granuloma was associated with vitreous opacity. Intraocular migration of granuloma was observed in 15 of 93 patients (16.1%). Treatment with albendazole (400 mg twice a day for 2 weeks) and corticosteroids (oral prednisolone; 0.5–1 mg/kg/day) resulted in comparable outcomes to patients on corticosteroid monotherapy; however, the 6-month recurrence rate in patients treated with combined therapy (17.4%) was significantly lower than that in patients treated with corticosteroid monotherapy (54.5%, P = 0.045). Ingestion of raw cow liver (80.8%) or meat (71.2%) was significantly more common in OT patients than healthy controls.</P><P><B>Conclusions</B></P><P>Our study discusses the diagnosis, treatment, and prevention strategies for OT. Evaluation of total IgE, in addition to anti-toxocara antibody, can assist in the serologic diagnosis of OT. Combined albendazole and corticosteroid therapy may reduce intraocular inflammation and recurrence. Migrating feature of granuloma is clinically important and may further suggest the diagnosis of OT. Clinicians need to carefully examine comorbid conditions for OT. OT may be associated with ingestion of uncooked meat, especially raw cow liver, in adult patients.</P></▼1><▼2><P><B>Author Summary</B></P><P>Toxocariasis is one of America's most common neglected infections of poverty and a helminthiasis of global importance. Little is known about the epidemiologic, demographic, and clinical features of ocular toxocariasis (OT) in adult patients, and the treatment regimen for OT has not been standardized. We conducted a retrospective cohort study examining the clinical features, serologic markers, clinical course of granuloma, probable infection sources, and treatment outcome in 101 adult patients diagnosed clinically and serologically with OT. All the patients had unilateral involvement. Ninety-three (92.1%) and 78 (77.2%) of 101 adult patients had retinal granuloma and intraocular inflammation, respectively. In addition to retinal granuloma, retinal nerve fiber layer defect, epiretinal membrane, vitreous opacity, retinal detachment, macular edema, and macular hole were observed in the eyes with OT. Granuloma in OT can involve all retinal layers, and its intraocular migration was observed in 15 patients (16.1%). Among the 101 patients, 69.6% and 11.6% showed elevated immunoglobulin E levels and eosinophilia, respectively. We believe that OT may be associated with ingestion of uncooked meat, especially cow liver, in adult patients. Furthermore, we suggest that combined albendazole and corticosteroid therapy may reduce intraocular inflammation and recurrence.</P></▼2>

The 18p11.22 locus is associated with never smoker non-small cell lung cancer susceptibility in Korean populations.

Ahn, Myung-Ju,Won, Hong-Hee,Lee, Jeeyun,Lee, Seung-Tae,Sun, Jong-Mu,Park, Yeon Hee,Ahn, Jin Seok,Kwon, O Jung,Kim, Hojoong,Shim, Young Mog,Kim, Jhingook,Kim, Kwhanmien,Kim, Yeul Hong,Park, Jae Yong,Ki Springer-Verlag 2012 HUMAN GENETICS Vol.131 No.3

<P>The proportion of never smoker non-small cell lung cancer (NSCLC) in Asia is about 30-40%. Despite the striking demographics and high prevalence of never smoker NSCLC, the exact causes still remain undetermined. Although several genome wide association (GWA) studies were conducted to find susceptibility loci for lung cancer in never smokers, no regions were replicated except for 5p15.33, suggesting locus heterogeneity and different environmental toxic effects. To identify genetic loci associated with susceptibility of lung cancer in never smokers, we performed a GWA analysis using the Affymetrix 6.0 SNP array. For discovery GWA set, we recruited 446 never smoking Korean patients with NSCLC and 497 normal subjects. We tested association of SNPs with lung cancer susceptibility using the Cochran-Armitage trend test. For validation, 39 SNPs were selected from the top 50 SNPs and five additional SNPs were selected in the DAB1 gene region which showed significant associations in the GWA analysis. The validation SNPs were genotyped in an independent sample including 434 patients and 1,000 controls. Among the 44 validation SNPs, two SNPs (rs11080466 and rs11663246) near the APCDD1, NAPG and FAM38B genes in the 18p11.22 region were replicated. P value of rs11080466 was 1.08 10(-6) in the combined sets (2.68 10(-5) in the discovery set and 2.60 10(-3) in the validation set) and odds ratio was 0.68 (0.58-0.79). We observed similar association for rs11663246. Our result suggests the 18p11.22 region as a novel lung cancer susceptibility locus in never smokers.</P>

Phase I Trial of Anti-MET Monoclonal Antibody in MET-Overexpressed Refractory Cancer

Lee, Jeeyun,Kim, Seung Tae,Park, Sungju,Lee, Sujin,Park, Se Hoon,Park, Joon Oh,Lim, Ho Yeong,Ahn, Hongmo,Bok, Haesook,Kim, Kyoung-Mee,Ahn, Myung Ju,Kang, Won Ki,Park, Young Suk Elsevier 2018 Clinical colorectal cancer Vol.17 No.2

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Samsung Advance Institute of Technology-301 (SAIT301) is a human immunoglobulin G2 antibody that can specifically target mesenchymal epithelial transition factor (c-MET). This novel antibody has higher priority over hepatocyte growth factors when binding to the Sema domain of c-MET and accelerates the internalization and degradation of c-MET, proving its powerful antitumor activities in intra- as well as extracellular areas.</P> <P><B>Materials and Methods</B></P> <P>SAIT301 was administered intravenously once every 3 weeks in c-MET overexpressed solid tumor patients, focusing on metastatic colorectal cancer (CRC) according to common clinical phase I criteria. Dose escalation was performed according to a modified Fibonacci design, following the conventional 3+3 design. The purpose of this phase I study was to assess the safety profile, to establish the recommended dose for clinical phase II studies and to assess potential anticancer activity of the compound.</P> <P><B>Results</B></P> <P>Sixteen patients with a median age of 56 (range, 39-69) years were enrolled in the study. The most common adverse events were decreased appetite (50.0%), hypophosphatemia, fatigue and dizziness (25.0%, respectively), and diarrhea, blood alkaline phosphatase increased and dyspnea (18.8%, respectively). For tumor response, no patients achieved complete response. One (9.1%) CRC patient had a partial response in the 1.23 mg/kg group, 4 (36.4%) patients achieved stable disease (2 in the 0.41 mg/kg group, 2 in the 1.23 mg/kg group, 0 in the 3.69 mg/kg group, and 1 in the 8.61 mg/kg group). Because of the increase in dose-limiting toxicities (DLTs) at 8.61 mg/kg, the 3.69 mg/kg dose was considered the maximum tolerated dose and selected for further assessment in phase II.</P> <P><B>Conclusion</B></P> <P>We successfully completed a phase I trial with MET antibody in a MET-overexpressed patient population focusing on CRC, and found that the DLTs were alkaline phosphatase elevation or hypophosphatemia. The recommended dose of SAIT301 for phase II is the dose of 3.69 mg/kg.</P>

Comparison of Optical Coherence Tomography Biomarkers between Bevacizumab Good Responders and Nonresponders Who were Switched to Dexamethasone Implant in Diabetic Macular Edema

Jeong Hyun Lee(Jeong Hyun Lee ),Joo Young Shin(Joo Young Shin),Jeeyun Ahn(Jeeyun Ahn) 대한안과학회 2023 Korean Journal of Ophthalmology Vol.37 No.2

Purpose: To compare volumetric optical coherence tomography (OCT) biomarkers in bevacizumab responsive and bevacizumabrefractory diabetic macular edema (DME) patients switched to the dexamethasone implant to ultimately identify possibleprognostic indicators. Methods: Retrospective analysis of DME patients treated with bevacizumab were done. Patients were divided into thosewho showed response to bevacizumab (bevacizumab only group) and others who were switched to the dexamethasone implantdue to lack of response to bevacizumab (switching group). Volumetric OCT biomarkers such as central macular thickness(CMT), inner and outer cystoid macular edema (CME) volume, serous retinal detachment (SRD) volume, retinal volume (CME+ SRD volume) within the 6-mm Early Treatment of Diabetic Retinopathy Study circle were calculated. OCT biomarkers werefollowed up throughout treatment. Results: Among total of 144 eyes, 113 patients were included in the bevacizumab only group and 31 patients were includedin the switching group. Compared to the bevacizumab only group, the switching group showed higher baseline CMT (558.00± 209.60 μm vs. 454.96 ± 125.88 μm, p = 0.003), larger inner CME (6.02 ± 1.43 mm3 vs. 5.12 ± 0.87 mm3, p = 0.004) and SRDvolume (0.32 ± 0.40 mm3 vs. 0.11 ± 0.09 mm3, p = 0.015) and higher proportion of patients with SRD (58.06% vs. 31.86%, p =0.008). In the switching group, CMT, inner CME and SRD volume all showed significant reduction after switching to the dexamethasoneimplant. Conclusions: DME with large SRD and inner nuclear layer edema volume may be more effectively treated with the dexamethasoneimplant than bevacizumab.

Assessment of Risk Factors Affecting Refractive Outcomes after Phacovitrectomy for Epiretinal Membrane

Yu Jin Roh(Yu Jin Roh),Joo Young Shin(Joo Young Shin),Tae Wan Kim(Tae Wan Kim),Jeeyun Ahn(Jeeyun Ahn) 대한안과학회 2023 Korean Journal of Ophthalmology Vol.37 No.1

Purpose: To investigate factors associated with refractive outcomes after phacovitrectomy for epiretinal membrane (ERM). Methods: Retrospective review of patients undergoing phacovitrectomy for ERM was done. The main outcome measure was predictive refraction error (PE), defined as observed refraction error – target refraction error, calculated by the SRK/T, Haigis, and SRK II formulae. PE was measured at postoperative 1, 3, and 6 months. Simple and multiple linear regression analysis were used to evaluate factors associated with PE. Results: A total of 53 eyes of 53 patients were included. The mean PEs at postoperative 1, 3, and 6 months were all negative, implying myopic shift in all patients regardless of the intraocular lens formula used. Haigis formula showed the least myopic shift among the three formulae (p = 0.001, Friedman test). There was no significant difference in PE depending on preoperative central macular thickness (CMT) in subgroup analysis. On stepwise multiple linear regression analysis, ERM etiology (β = 0.759, p = 0.004, SRK/T formula; β = 0.733, p = 0.008, Haigis formula; β = 0.933, p < 0.001, SRK II formula), preoperative anterior chamber depth (β = –0.662, p = 0.013, Haigis formula; β = –0.747, p = 0.003, SRK II formula), and decrease of CMT (β = –0.003, p = 0.025, SRK/T formula) were significantly associated with PE at postoperative 6 months. Conclusions: Myopic shift in PE was observed after combined phacovitrectomy for epiretinal membrane. ERM etiology, preoperative anterior chamber depth, and decrease of CMT were significantly associated with PE at postoperative 6 months. There was no difference in PE after surgery between the two groups defined by CMT (≥500 and <500 μm).

Population pharmacokinetics of CPT-11 (irinotecan) in gastric cancer patients with peritoneal seeding after its intraperitoneal administration

Ahn, Byung-Jin,Choi, Moon Ki,Park, Young Suk,Lee, Jeeyun,Park, Se Hoon,Park, Joon Oh,Lim, Ho Yeong,Kang, Won Ki,Ko, Jae-Wook,Yim, Dong-Seok Springer-Verlag 2010 European journal of clinical pharmacology Vol.66 No.12

Bridging genomics and phenomics of gastric carcinoma

Cho, Junhun,Ahn, Soomin,Son, Dae‐,Soon,Kim, Nayoung KD,Lee, Ki‐,Wook,Kim, Seungtae,Lee, Jeeyun,Park, Se Hoon,Park, Joon Oh,Kang, Won Ki,An, Ji Yeong,Choi, Min Gew,Lee, Jun‐,Ho,Sohn, Alan R. Liss, Inc 2019 International journal of cancer Vol.145 No.9

<P>Genetic alterations are the starting point leading to numerous changes in clinical and pathologic features (phenotypes) of individual cancers; however, their inter‐relationships in gastric cancers (GC) are unclear. We performed massive parallel sequencing of 381 cancer‐related genes and compared the results with clinical and pathologic findings in 330 GC. High tumor mutation burden (TMB) accounted for 11% of GC (<I>n</I> = 37) and all 19 MSI‐H GCs were high TMB. High TMB was significantly more frequent in intestinal‐type by Lauren, tumor with higher host cellular immune response, earlier AJCC stage and favorable prognosis. The most significantly mutated genes were <I>TP53</I> (54%), <I>ARID1A</I> (23%), <I>CDH1</I> (22%), <I>PIK3CA</I> (12%), <I>RNF43</I> (10%) and <I>KRAS</I> (9%). For receptor tyrosine kinases, amplifications detected by immunohistochemistry were higher than sequencing (HER2, 9.1% <I>vs</I>. 5.8%; EGFR, 11.2% <I>vs</I>. 6.1%; FGFR2, 4.6% <I>vs</I>. 3.9%, c‐MET, 3.4% <I>vs</I>. 0.9%). PTEN protein loss (22%) correlated well with underlying <I>PTEN</I> alterations while ATM loss (27%) was not significantly correlated with genetic alterations of <I>ATM</I>. p53 protein expression predicted alterations of <I>TP53</I> with high sensitivity (97.8%) and low (15.9%) specificity. The poorly cohesive histology/<I>CDH1</I>‐mutant GC subgroup showed the worst survival (<I>p</I> < 0.001). PD‐L1 expression was significantly associated with MSI‐H, MLH1 loss, ATM loss, MET positivity, higher host immune response, and genetic alterations of <I>ARID1A</I>, <I>BRD3</I>, <I>PIK3CA</I>, <I>KRAS</I>, <I>MAP3K13</I>, <I>CDH2, PTEN</I> and <I>ESR1</I>. The merged clinical, pathology and genomics of GC provide a better understanding of GC and new insights into the treatment of GC.</P>

Transabdominal noninvasive acquisition of stable and accurate fetal heart electrical signal: a preliminary human study for development of wearable device for surveillance based on fetal heart signal

( Ki Hoon Ahn ),( Minjeong Kim ),( Ji-hoon Kang ),( Jeeyun Lee ),( Eunjin Jung ),( Soojung Jo ),( Nack Hwan Kim ),( Jinwoo Park ),( Byeong-kwon Ju ),( Min-chul Park ) 대한산부인과학회 2018 대한산부인과학회 학술대회 Vol.104 No.-

Objective: Until now the stability and accuracy of the extracted fetal heart signals were not qualified for realization. In this study, a novel algorithm to obtain the stable and accurate fetal heart electric signals was investigated. Methods: This study was approved by the Institutional Review Board of Korea University Anam Hospital (2017AN0825). The inclusion criteria were normal singleton pregnant women over 19 years old between 20 and 24 weeks of gestation at the first visit. All women signed a informed consent form. Exclusion criteria were women who have an allergy to electric signal sensor and any neuropsychiatric disorders or epilepsies. Study participants visited three times before delivery and fetal heart signals were obtained using Biopac MP150 (Biopac Systems Inc, Goleta, CA, USA). Obstetric and neonatal outcomes were recorded. The algorithm was applied to our fetal ECG data. Results: For this preliminary study, three women were included for analyses. The mean age was 30 years old and the mean body mass index was 24.0 kg/m2. Two women were nulliparous and the other one woman was para 1. For all women, the fetal heart signals were clearer as the gestational age increased. The fetal heart electric signals were successfully obtained from all three women with stability and accuracy. Compared with reference dataset using physionet, our novel algorithm showed a higher detection rate of normal fetal heart signals (80% vs 40%). All pregnant women delivered babies by cesarean section for failure to progress or cephalopelvic disproportion at term and had no complications during pregnancy and in postpartum period. Conclusion: This study showed that our novel algorithm has a high stability and accuracy to acquire the fetal heart electric signals. This detection rate is considered enough to proceed to apply a prototype device for larger clinical study. Hereafter, the establishment of a protocol to differentiate abnormal fetal conditions and its application through clinical studies will be our next step. Acknowledgements: This research was supported by KUMC and KIST Institutional Program (Project No. K1722561).

Erlotinib Monotherapy for Stage IIIB/IV Non-small Cell Lung Cancer: A Multicenter Trial by the Korean Cancer Study Group

Uhm, Ji Eun,Park, Byeong-Bae,Ahn, Myung-Ju,Lee, Jeeyun,Ahn, Jin Seok,Kim, Sang We,Kim, Heung-Tae,Lee, Jong Seog,Kang, Jin Hyung,Cho, Jae Yong,Song, Hong Suk,Park, Se Hoon,Sohn, Chang Hak,Shin, Sang Wo Elsevier 2009 Journal of thoracic oncology Vol.4 No.9

<P>Erlotinib (Tarceva, OSI Pharmaceuticals, Melville, NY) is an oral, epidermal growth factor receptor tyrosine kinase inhibitor that has antitumor activity and good tolerability in non-small cell lung cancer (NSCLC). In particular, higher response rates have been reported in Asian patients than in Western patients. The aim of this study conducted by the Korean Cancer Study Group was to evaluate the efficacy and tolerability of erlotinib monotherapy as a palliative treatment for advanced NSCLC patients in Korea.</P>