Jeong Hwa Lee

Konkuk University, Sŏul, Seoul, South Korea

Are you Jeong Hwa Lee?

Claim your profile

Publications (8)36.8 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Accumulating data indicate that human epidermal growth factor receptor-2 (HER2)-positive breast cancer is a heterogeneous disease. We undertook a study to correlate lipid profiles with heterogeneous clinicopathological features of HER2-positive breast cancer. Histology-directed matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS) analyses were performed on 22 retrospective frozen tissue samples collected from patients with HER2-positive metastatic breast cancer, in order to correlate lipid profiles with clinicopathological characterisitics. Additionally, a pair of tumor and adjacent normal tissue was profiled to identify cancer-associated changes in lipid profiles. Sphingomyelin 34:1, phosphatidylcholine (PC) 32:0, and PC 34:1, and PC 36:2 were overexpressed in HER2-positive breast cancer compared to adjacent normal tissue (HER2 signature). Lipid MALDI-MS profiles were different between Ki-67-high and Ki-67-low tumors. The proliferation signature (Ki-67-high vs. Ki-67-low) and the HER2 signature (cancer vs. normal) did not significantly overlap with each other. For the first time to our knowledge, this study describes lipid profiles correlated with various clinicopathological characteristics of HER2-positive breast cancer. Lipid profiling might be helpful for the molecular characterization of this disease.
    Anticancer research 06/2013; 33(6):2467-72. · 1.71 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Microvesicles (MVs, also known as exosomes, ectosomes, microparticles) are released by various cancer cells, including lung, colorectal and prostate carcinoma cells. MVs released from tumor cells and other sources accumulate in the circulation and in pleural effusion (PE). Although recent studies have shown that MVs play multiple roles in tumor progression, the potential pathological roles of MV in pleural effusion, and their protein composition, are still unknown. In this study we report the first global proteomic analysis of highly purified MVs derived from human non-small-cell-lung-cancer (NSCLC) pleural effusion. Using nano-LC-MS/MS following 1-D SDS-PAGE separation, we identified a total of 912 MV proteins with high confidence. Three independent experiments on three patients showed that MV proteins from PE were distinct from MV obtained from other malignancies. Bioinformatics analyses of the MS data identified pathologically relevant proteins and potential diagnostic makers for NSCLC, including lung-enriched surface antigens and proteins related to EGFR signaling. These findings provide new insight into the diverse functions of MVs in cancer progression and will aid in the development of novel diagnostic tools for NSCLC.
    Proteomics 04/2013; · 4.43 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: OBJECTIVE: Blocking agents targeting cell adhesion molecules have been developed to prevent cardiovascular diseases such as atherosclerosis, whereas relatively little attention has been paid to the therapeutic potential of vascular cell adhesion molecule (VCAM)-1 as an inflammatory disease target. Two novel, fully human antibodies, H6 and 7H, against human VCAM-1 (hVCAM-1) were developed and tested to validate the hypothesis that blocking VCAM-1 ameliorates atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice. METHODS AND RESULTS: Treatment with H6 or 7H effectively inhibited VCAM-1 adhesion to inflammatory cells, and reduced RhoA activation and the production of reactive oxygen species in human umbilical cord vascular endothelial cells. As 7H showed binding affinity to both murine VCAM-1 (mVCAM-1) and hVCAM-1, the therapeutic effects of 7H in ApoE(-/-) mice were tested. After confirming specific in vivo binding activity of 7H to mVCAM-1, we showed that administering 7H resulted in significantly ameliorated plaque formation compared to administering a control antibody in ApoE(-/-) mice fed a Western diet for 12 weeks. Also, 7H treatment significantly reduced infiltration of CD45(+) cells into plaques and reduced inflammation and improved plaque stability. CONCLUSION: These results indicate that the anti-VCAM-1 antibody attenuates atherosclerosis in ApoE(-/-) mice, improves plaque inflammation and stability as well as inhibiting the adhesion of inflammatory cell, and suggest that blocking VCAM-1 with a monoclonal antibody may be an effective means of anti-atherosclerotic therapy.
    Atherosclerosis 12/2012; · 3.71 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Since the development of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, this procedure has been specifically used for analyzing proteins or high molecular weight compounds because of the interference of matrix signals in the regions of the low mass range. Recently, scientists have been using a wide range of chemical compounds as matrices that ionize small molecules in a mass spectrometer and overcome the limitations of MALDI mass spectrometry. In this study, we developed a new combination matrix of 3-hydroxycoumarin (3-HC) and 6-aza-2-thiothymine (ATT), which is capable of ionizing small molecules, including drugs and single amino acids. In addition to ionization of small molecules, the combination matrix by itself gives less signals in the low mass region and can be used for performing imaging mass spectrometry (IMS) experiments on tissues, which confirms the vacuum stability of the matrix inside a MALDI chamber. The drug donepezil was mapped in the intact tissue slices of mice simultaneously with a spatial resolution of 150 μm during IMS. IMS analysis clearly showed that intact donepezil was concentrated in the cortical region of the brain at 60 min after oral administration. Our observations and results indicate that the new combination matrix can be used for analyzing small molecules in complex samples using MALDI mass spectrometry.
    The Analyst 10/2012; · 4.23 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Neuronal membrane phospholipids are highly affected by oxidative stress caused by ischemic injury. Thus, it is necessary to identify key lipid components that show changes during ischemia to develop an effective approach to prevent brain damage from ischemic injury. The recent development of MALDI imaging MS (MALDI IMS) makes it possible to identify phospholipids that change between damaged and normal regions directly from tissues. In this study, we conducted IMS on rat brains damaged by ischemic injury and detected various phospholipids that showed unique distributions between normal and damaged areas of the brain. Among them, we confirmed changes in phospholipids such as lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin by MALDI IMS followed by MS/MS analysis. These lipids were present in high concentrations in the brain and are important for maintenance of cellular structure as well as production of second messengers for cellular signal transduction. Our results emphasize the identification of phospholipid markers for ischemic injury and successfully identified several distinctly located phospholipids in ischemic brain tissue.
    The Journal of Lipid Research 06/2012; 53(9):1823-31. · 4.39 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: We investigated whether direct tissue matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis on lipid may assist with the histopathologic diagnosis of non-small cell lung cancers (NSCLCs). Twenty-one pairs of frozen, resected NSCLCs and adjacent normal tissue samples were initially analyzed using histology-directed, MALDI MS. 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. A lipid profile that could differentiate cancer and adjacent normal samples with a median accuracy of 92.9% was discovered. Several phospholipids including phosphatidylcholines (PC) {34:1} were overexpressed in lung cancer. Squamous cell carcinomas and adenocarcinomas were found to have different lipid profiles. Discriminatory lipids correctly classified the histology of 80.4% of independent NSCLC surgical tissue samples (41 out of 51) in validation set. MALDI MS image of 11 discriminatory lipids validated their differential expression according to the histologic type in cancer cells of bronchoscopic biopsy samples. PC {32:0} [M+Na](+) (m/z 756.68) and ST-OH {42:1} [M-H](-) (m/z 906.89) were overexpressed in adenocarcinomas. Thus, lipid profiles accurately distinguish tumor from adjacent normal tissue and classify non-small cell lung cancers according to the histologic type.
    Lung cancer (Amsterdam, Netherlands) 11/2011; 76(2):197-203. · 3.14 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Peroxiredoxin 2 (Prdx2), a thiol-specific peroxidase, has been reported to regulate proinflammatory responses, vascular remodeling, and global oxidative stress. Although Prdx2 has been proposed to retard atherosclerosis development, no direct evidence and mechanisms have been reported. We show that Prdx2 is highly expressed in endothelial and immune cells in atherosclerotic lesions and blocked the increase of endogenous H(2)O(2) by atherogenic stimulation. Deficiency of Prdx2 in apolipoprotein E-deficient (ApoE(-/-)) mice accelerated plaque formation with enhanced activation of p65, c-Jun, JNKs, and p38 mitogen-activated protein kinase; and these proatherogenic effects of Prdx2 deficiency were rescued by administration of the antioxidant ebselen. In bone marrow transplantation experiments, we found that Prdx2 has a major role in inhibiting atherogenic responses in both vascular and immune cells. Prdx2 deficiency resulted in increased expression of vascular adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemotactic protein-1, which led to increased immune cell adhesion and infiltration into the aortic intima. Compared with deficiency of glutathione peroxidase 1 or catalase, Prdx2 deficiency showed a severe predisposition to develop atherosclerosis. Prdx2 is a specific peroxidase that inhibits atherogenic responses in vascular and inflammatory cells, and specific activation of Prdx2 may be an effective means of antiatherogenic therapy.
    Circulation Research 08/2011; 109(7):739-49. · 11.86 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) has been demonstrated to be useful for molecular profiling of common solid tumors. Using recently developed MALDI matrices for lipid profiling, we evaluated whether direct tissue MALDI MS analysis on proteins and lipids may classify human breast cancer samples according to the intrinsic subtype. Thirty-four pairs of frozen, resected breast cancer and adjacent normal tissue samples were analyzed using histology-directed, MALDI MS analysis. Sinapinic acid and 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. Protein and lipid profiles distinguish cancer from adjacent normal tissue samples with the median prediction accuracy of 94.1%. Luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by permutation P values less than 0.01 for 0.632+ bootstrap cross-validated misclassification rates with all classifiers tested. Discriminatory proteins and lipids were useful for classifying tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in random test sets. Protein and lipid profiles accurately distinguish tumor from adjacent normal tissue and classify breast cancers according to the intrinsic subtype.
    BMC Cancer 01/2011; 11:465. · 3.33 Impact Factor