Choong-kun Lee

High purity ZnSe epilayers grown by atmospheric double zone metalorganic atomic layer epitaxy

Abstract ZnSe epilayers were grown on semi-insulating GaAs (100) substrates by metalorganic atomic layer epitaxy (MOALE) using dimethylzinc (DMZn) and hydrogen selenide (H 2 Se) source gases with a substrate temperature of 350°C. The MOALE system is modified from atmospheric metalorganic vapor phase epitaxy (MOVPE) by rotating susceptor to allow successive exposure to streams of gases. Also long gas inlets were introduced in the pre-heating zone of the reactor for purifying the source gases. The photoluminescence spectra of the ZnSe epilayers show dominant heavy-hole and light-hole exciton emissions for thicknesses below and above a critical thickness. The epilayer thickness was examined for the different operating cycles and was found to depend only on the number of substrate rotation cycles. These results reflect that the growth of high purity ZnSe epilayers are achieved by MOALE.

Thickness dependent properties of ZnSe on (100) GaAs grown by atomic layer epitaxy

Abstract ZnSe epilayers were grown on semi-insulating GaAs (100) substrates by ALE (atomic layer epitaxy) modified from CVD (chemical vapor deposition). The optical properties of ZnSe films depending on thickness were studied through micro-Raman and PL (photoluminescence) spectroscopy. The critical thickness was determined to be about 0.1 μm by analyzing the change in the peak shift of LO-phonon modes of ZnSe films. This is confirmed from the increase of the intensities of the deep center band in the PL spectra when the thickness exceeds 0.1 μm.

Structural properties of ZnSe on GaAs grown by atomic layer epitaxy

ZnSe epilayers were grown on GaAs (100) substrates by atomic layer epitaxy modified from chemical‐vapor deposition with thicknesses ranging from 600 to 6000 A. X‐ray‐diffraction and micro‐Raman scattering measurements were carried out to study the effects of strain in the ZnSe epilayers with different thicknesses. The increase in full width at half‐maximum of double‐crystal x‐ray rocking curves was observed for layers thicker than the critical thickness, which indicates that the crystallinity gets strongly degraded when the layers are grown over the critical thickness. The critical thickness estimated by x‐ray rocking curves is 1500 A, while that obtained by micro‐Raman scattering is 1000 A. This difference suggests that the elastic strain depends on the layer depth for ZnSe epilayers around the critical thickness.

Influence of lattice relaxation on the properties of ZnSeZnS single quantum wells by MOVPE

Abstract The growth of ZnSe ZnS single quantum well (SQW) structures was performed by atomic layer epitaxy (ALE) in an atmospheric pressure metalorganic vapour phase epitaxy (MOVPE) system. Through the photoluminescence measurement of ZnSe ZnS SQWs, we observed clear shifts of the excitons to higher energies with decreasing well width, which demonstrate effects of strain and quantum confinement. Transition energies were calculated considering (i) a simple square well potential and (ii) a parabolic potential model under the action of strain effects. From comparison of the exciton energy with the calculated transition energies, we conclude that lattice relaxation induced interdiffusion occurs as the well width becomes thicker than the critical thickness.

S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial

Purpose We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients. Materials and Methods Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2/day on days 1-14 plus docetaxel 35 mg/m2on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2/day on days 1-14 plus cisplatin 60 mg/m2on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate. Results Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment. Conclusion Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.

Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial infarction

Emerging evidence indicates that angiopoietin-2 (Angpt2), a well-recognized vascular destabilizing factor, is a biomarker of poor outcome in ischemic heart disease. However, its precise role in postischemic cardiovascular remodeling is poorly understood. Here, we show that Angpt2 plays multifaceted roles in the exacerbation of cardiac hypoxia and inflammation after myocardial ischemia. Angpt2 was highly expressed in endothelial cells at the infarct border zone after myocardial infarction (MI) or ischemia/reperfusion injury in mice. In the acute phase of MI, endothelial-derived Angpt2 antagonized Angpt1/Tie2 signaling, which was greatly involved in pericyte detachment, vascular leakage, increased adhesion molecular expression, degradation of the glycocalyx and extracellular matrix, and enhanced neutrophil infiltration and hypoxia in the infarct border area. In the chronic remodeling phase after MI, endothelial- and macrophage-derived Angpt2 continuously promoted abnormal vascular remodeling and proinflammatory macrophage polarization through integrin &agr;5&bgr;1 signaling, worsening cardiac hypoxia and inflammation. Accordingly, inhibition of Angpt2 either by gene deletion or using an anti-Angpt2 blocking antibody substantially alleviated these pathological findings and ameliorated postischemic cardiovascular remodeling. Blockade of Angpt2 thus has potential as a therapeutic option for ischemic heart failure.

A Case of von Hippel–Lindau Disease with Colorectal Adenocarcinoma, Renal Cell Carcinoma and Hemangioblastomas

von Hippel–Lindau (VHL) disease is an autosomal dominant inherited tumor syndrome associated with mutations of the VHL tumor suppressor gene located on chromosome 3p25. The loss of functional VHL protein contributes to tumorigenesis. This condition is characterized by development of benign and malignant tumors in the central nervous system (CNS) and the internal organs, including kidney, adrenal gland, and pancreas. We herein describe the case of a 74-year-old man carrying the VHL gene mutation who was affected by simultaneous colorectal adenocarcinoma, renal clear cell carcinoma, and hemangioblastomas of CNS.

Abstract B196: FGFR3 as a potential target for gastric cancer.

While trastuzumab against HER-2 over-expression is the only approved targeted therapy against gastric cancer, it is important to find the biologically significant genetic aberrations in most of gastric cancer without HER-2 overexpression. We performed phospho-RTK (receptor tyrosine kinase) array in 25 gastric cancer cell lines, and confirmed fibroblast growth factor receptor 2 and 3 (FGFR2, 3) as one of the highly phosphorylated RTKs. Knockdown of FGFR3 with transfecting small interfering RNA (siRNA) induced the decrement of phospho-FGFR (653/654) in a time-dependent manner in cell lines with highly activated FGFR3, Hs746T and SNU-5. While cell cycle analysis and apoptosis assay showed no significant changes, invasiveness and anchorage-independent growth was inhibited after FGFR3 siRNA transfection. Modulation of downstream signaling molecules was observed by western blot after transfecting FGFR3 siRNA in Hs746T and SNU-5 cell lines in comparing with FGFR2 activated cell lines (KATO III, SNU-16) transfected with FGFR2 siRNA, since previous reports showed that FGFR2 amplification is important in gastric cancer in influencing cell proliferation and survival. Phospho-AKT was down-regulated in both FGFR2 and FGFR3 activated cell lines after specific siRNA transfection, implying that gastric cancer cells with FGFR2 or FGFR3 activation might be both dependent on PI3K-AKT-mTOR pathway. When we treated mice bearing subcutaneous SNU-5 tumor xenografts with oral FGFR inhibitor TKI-258 (70mg/kg daily), TKI-258 treated group showed anti-tumor growth and anti-angiogenic effect compared with control group. Immunohistochemistry (IHC) against FGFR3 among 116 N3 gastric cancer patient tissues showed 3+ in 62.9%, while FGFR2 positivity was only 11.2%. In summary, we identified FGFR3 harbors significant biological role in subset of gastric cancer patients as FGFR2. Further studies for validating the efficacy of FGFR inhibition in preselected subset of patients would support the proper development of FGFR inhibitor in gastric cancer. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B196. Citation Format: Choong-kun Lee, Won Suk Lee, Jeong Min Kim, Myung Eun Lee, Kyu Hyun Park, Tae Soo Kim, Hyo Song Kim, Hei-Cheul Jeung, Hyun Cheol Chung, Sun Young Rha. FGFR3 as a potential target for gastric cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B196.

Abstract C157: Identification of activated receptor tyrosine kinases in colon cancer cell lines.

Colorectal cancer (CRC) is the second most common cause of cancer-related death in the United States and increasing rapidly in Asian countries. To improve colorectal cancer treatment, relevant molecular targets need to be identified. Receptor tyrosine kinases (RTKs) are multifunctional transmembrane proteins and important mediators of the signaling cascade, determining key roles in diverse biological processes such as proliferation, growth, differentiation, and apoptosis of cells. Recent advances in understanding of cellular signaling by RTKs have brought to light the potential of RTKs as anti-cancer targets. To determine if any of these RTKs are activated in colorectal cancer, we performed phospho-receptor tyrosine kinase array and evaluated its possibility as a therapeutic target. We examined activation pattern of RTKs in 10 colon cancer cell lines using Human Phospho-RTK Antibody Proteome Profiler Array (RD 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C157.

Abstract B34: Receptor tyrosine kinases (RTKs) profiling and its role in advanced gastric cancer.

Background: Receptor tyrosine kinase (RTK) activation is the starting point of intracellular signaling cascades that control cellular process such as proliferation, differentiation, migration and survival and aberrant RTK activation may promote cancer initiation and progression. The purpose of this study was to determine the frequency and the influence of major RTKs including EGFR, HER-2, c-MET, and FGFR-2 expression on the outcomes of gastric cancer patients. Methods: Between January 2000 and December 2004, 122 patients with advanced gastric cancer in our institute were selected. All patients underwent gastrectomy and D2 lymph node dissection with a curative aim and pathologically confirmed N3 stage without distant metastasis. Formalin-fixed paraffin-embedded (FFPE) tissue specimens were examined for the expression of EGFR, HER-2, c-MET, FGFR-2 by immunohistochemistry (IHC). The score for expression was assessed by the independent pathologist with weighted histoscore method. We defined positive result as the expression of 3+ in IHC for each RTK. Results: Among 4 RTKs, c-MET expression showed highest frequency as 31 patients (25.4%) followed by FGFR-2 (13; 11.2%), HER-2 (10; 8.5%) and EGFR (6; 5.0%). The majority of samples (58.2%) were negative (wild type) for all four markers. Fourteen patients (11.5%) showed co-expression for these RTKs; one patient was quadruple positive, and the others showed double positivity for c-MET and one of 3 other markers. There were no significant correlations between each biomarker and clinic-pathologic parameters such as patient9s gender, differentiation, T stage, lymphovascular invasion, Lauren classification or the number of LN metastasis. With the follow-up period of 21.5 months (0.5–115.7), median overall survival of all patients was 20.9 months (95% CI, 15.2–26.6) and median disease-free survival (DFS) was 17.1 months (95% CI, 9.4–24.8). Based on the status of each receptor, survival outcome was only associated with c-MET over-expression; median DFS of 10.8 months in c-MET positive patients and 22.0 months in c-MET negative patients (p=0.04). Median DFS in patients with co-expression of RTKs showed poorer trend than single marker positive group and wild type group (10.8m, 15.7m, and 19.4m, respectively; p=0.27). Conclusion: We evaluated the expression pattern with four major RTKs in relatively homogenous subgroup of gastric cancer patients with pathologic N3. c-MET over-expression could be a prognostic biomarker for DFS in these patients, suggesting the significant role of c-met in gastric cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B34.