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- 저자 : Jeeyun Lee (검색결과 52 건)
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Kim, Hee Kyung,Kim, Sun Young,Lee, Su Jin,Kang, Mihyeon,Kim, Seung Tae,Jang, Jiryeon,Rath, Oliver,Schueler, Julia,Lee, Dong Woo,Park, Woong Yang,Kim, Sung Joo,Park, Se Hoon,Lee, Jeeyun Neoplasia Press 2016 Translational oncology Vol.9 No.3
<P><I>BACKGROUND:</I> Although pazopanib treatment has become the standard chemotherapy in salvage setting for metastatic sarcoma patients, most patients progress after pazopanib treatment in 4 to 6 months. After failure to pazopanib, patients have limited options for treatment. Therefore, subsequent therapy in patients who failed to pazopanib is urgently needed and the use of patient derived cells or patient derived tumors for accompanying testing with various pharmacological inhibitors could offer additional treatment options for these patients. <I>METHODS:</I> Patient derived tumor cells were collected from ascites at the time of progression to pazopanib and a 13-drug panel was tested for drug sensitivity. We confirmed the results using <I>in vitro</I> cell viability assay and immunoblot assay. We also performed the genomic profiling of PDX model. <I>RESULTS:</I> The growth of patient derived tumor cells was significantly reduced by exposure to 1.0 μM AZD2014 compared with control (control versus AZD2014, mean growth = 100.0% vs 16.04%, difference = 83.96%, 95% CI = 70.01% to 97.92%, <I>P</I> = .0435). Similarly, 1.0 μM BEZ235 profoundly inhibited tumor cell growth <I>in vitro</I> when compared to control (control versus BEZ235, mean growth = 100.0% vs 7.308%, difference = 92.69%, 95% CI = 78.87% to 106.5%, <I>P</I> < .0001). Despite the presence of CDK4 amplification in the patient-derived tumor cells, LEE011 did not considerably inhibit cell proliferation when compared with control (control vs LEE011, mean growth = 100.0% vs 80.23%, difference = 19.77%, 95% CI = 1.828% to 37.72%, <I>P</I> = .0377). The immunoblot analysis showed that BEZ235 treatment decreased pAKT, pmTOR and pERK whereas AZD2014 decreased only pmTOR. <I>CONCLUSION:</I> Taken together, upregulation of mTOR/AKT pathway in sarcoma patient derived cells was considerably inhibited by the treatment of AZD2014 and BEZ235 with downregulation of AKT pathway (greater extent for BEZ235). These molecules may be considered as treatment option in STS patient who have failed to pazopanib in the context of clinical trials.</P>
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Identification of <i>ROS1</i> rearrangement in gastric adenocarcinoma
Lee, Jeeyun,Lee, Seung Eun,Kang, So Young,Do, In‐,Gu,Lee, Sujin,Ha, Sang Yun,Cho, Jeonghee,Kang, Won Ki,Jang, Jiryeon,Ou, Sai‐,Hong Ignatius,Kim, Kyoung‐,Mee Wiley Subscription Services, Inc., A Wiley Company 2013 Cancer Vol.119 No.9
<P><B>Abstract</B></P><P><B>BACKGROUND:</B></P><P>Recently, chromosomal rearrangements involving receptor tyrosine kinases (RTKs) have been described in common epithelial malignancies, including nonsmall cell lung cancer (NSCLC), colorectal cancer, and breast cancer. One of these RTKs, c‐ros oncogene 1, receptor tyrosine kinase (ROS1), has been identified as a driver mutation in NSCLC, because its inhibition by crizotinib, an anaplastic lymphoma receptor tyrosine kinase (ALK)/met proto‐oncogene hepatocyte growth factor receptor (MET)/ROS1 inhibitor, led to significant tumor shrinkage in <I>ROS1</I>‐rearranged NSCLC. Currently, only human epidermal growth factor 2 (HER2)‐targeted therapy in combination with chemotherapy has been successful in significantly prolonging the survival of patients with advanced gastric cancer (GC). There is a need for the discovery of additional novel targets in GC.</P><P><B>METHODS:</B></P><P>Anti‐ROS1 immunohistochemistry (IHC) was used to screen 495 GC samples and was followed by simultaneous <I>ROS1</I> break‐apart fluorescence in situ hybridization (FISH) and reverse transcriptase‐polymerase chain reaction (RT‐PCR) analyses in IHC‐positive samples. Fusion partners in <I>ROS1</I>‐rearranged GC were determined by RT‐PCR. In all 495 samples, <I>HER2</I> amplification was identified with FISH, and MET expression was identified by IHC.</P><P><B>RESULTS:</B></P><P>Twenty‐three tumor samples were ROS1 IHC‐positive. Three of 23 patients were <I>ROS1</I> FISH positive, <I>HER2</I> FISH negative, and negative for MET overexpression; and 2 of those 3 patients harbored a solute carrier family 34 (sodium phosphate), member 2 (<I>SLC34A2)</I>‐<I>ROS1</I> fusion transcripts. No fusion partner was identified in the third patient. Both patients who had <I>SLC34A2</I>‐<I>ROS1</I> transcripts had poorly differentiated histology with recurrence and death within 2 years of curative surgery. ROS1 IHC‐positive status was not identified as an independent prognostic factor for overall survival.</P><P><B>CONCLUSIONS:</B></P><P>In this study, an <I>SLC34A2</I>‐<I>ROS1</I> rearrangement was identified in GC, and the results provide a rationale for investigating the clinical efficacy of ROS1 inhibitors in this unique molecular subset of GC. Cancer 2013. © 2013 American Cancer Society.</P>
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Lee, Su Jin,Lee, Seon Young,Lee, Weon Sup,Yoo, Jin San,Sun, Jong-Mu,Lee, Jeeyun,Park, Se Hoon,Park, Joon Oh,Ahn, Myung-Ju,Lim, Ho Yeong,Kang, Won Ki,Park, Young Suk Springer US 2017 Investigational new drugs Vol.35 No.6
<P><B>Summary</B></P><P><I>Background</I> Tanibirumab is a fully human monoclonal antibody to vascular endothelial growth factor receptor 2 (VEGFR-2). We conducted a first-in-human phase I study of tanibirumab in patients with solid tumors refractory to standard chemotherapy. Primary endpoints were evaluating safety, pharmacokinetics (PKs), estimating maximum-tolerated dose (MTD) and recommended phase II dose (RP2D). <I>Methods</I> We designed our study to escalate tanibirumab at 9 different dose levels with a 3 + 3 method and tanibirumab (1–28 mg/kg) was administered intravenously on D1, 8, 15 in 28-day courses. Dose limiting toxicities (DLTs) were only assessed during the first cycle of treatment and response evaluation was performed every 2 cycles. The effects of tanibirumab on several angiogenic factors were analyzed. <I>Results</I> From October 2011 to September 2013, a total of 26 patients with refractory solid tumors were enrolled. The median age was 58 years (range, 27–75) and 20 patients were male. The most common tumor type was colorectal cancer (<I>N</I> = 19) and seven patients had a history of previous bevacizumab treatment. As hemangioma continued to occur, the final dose level, 28 mg/kg, was not performed. DLTs were not found, and the MTD was confirmed to be 24 mg/kg. Hemangioma was observed in 16 patients (61.5%), but all were grade 1–2 and disappeared after discontinuation of the study drug. Among the 18 patients in the efficacy set, no objective response was observed, but 11 patients showed stable disease. PKs were characterized by dose-dependent linear exposure and the mean trough concentrations exceeded biologically relevant target levels at 12 mg/kg and above. Serum VEGF, soluble VEGFR-2, and PlGF increased at the 4 mg/kg dose level and above. <I>Conclusions</I> Treatment with tanibirumab showed a tolerable toxicity profile and modest clinical efficacy in patients with refractory solid tumors. A phase II trial of tanibirumab is ongoing now.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s10637-017-0463-y) contains supplementary material, which is available to authorized users.</P>
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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.
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( Jeeyun Lee ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Molecular profiling of actionable mutations in refractory cancer patients has the potential to enable “precision medicine,” inwhich individualized therapies result in improved treatment outcomes. However, its clinical benefit in practice has not been clearlydemonstrated in large cohorts with multiple cancer types.The NEXT (Next generation pErsonalized tX with mulTi-omics and preclinical model) trial is a master protocol to route participantsto different candidate drugs in trials based on clinical sequencing report. In this trial, we used a customized targeted enrichmentpanel consisting of cancer-related genes to interrogate single nucleotide variants (SNVs), insertions and deletions (Indels), copynumber variants (CNVs) and a subset of gene fusions, that were of clinical significance. In this master protocol, the responserate was assessed as the primary end point in patients who had molecularly-matched or standard therapy. Immunohistochemicalstaining was performed on MET, PTEN, EGFR, and HER2. From August 2014 through April 2015, 541 patients consented toparticipate in precision oncology clinic at a single center. Of 541 patients, 94 patients were excluded and 418 cancer patientshad sequencing data available to clinician for guidance to matched trials. The patient cohorts were gastric cancer (N = 127),colorectal cancer (N =122), pancreatic/biliary tract cancer (N=62) and sarcoma and cancer (N = 67). Of 418 patients, 159 (38.0%)patients were not treated beyond standard chemotherapy, 187 (44.7%) patients had at least one genomic variant (N=74, nomatched therapy available) and 60 (14.4%) patients were successfully routed to genome-based matched clinical trial. In thispresentation, matched trials including NEXT-1 and VIKTORY trial with collateral patient derived tumor cell screening programwill be presented.
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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>
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