-
[show abstract]
[hide abstract]
ABSTRACT: Genomic rearrangement occasionally affects the BRCA1/2 genes in Caucasian breast cancer patients. However, the incidence of BRCA1/2 genomic rearrangement in Asians, including the Korean population, has not been well established. Here, we investigated the contribution of BRCA1/2 genomic rearrangement to high-risk breast cancer patients in this population. We screened for BRCA1/2 genomic rearrangement using multiplex ligation-dependent probe amplification for 122 high-risk breast cancer patients who tested negative for BRCA1/2 mutations. A novel deletion of exons 13-15 in BRCA1 was identified in one patient (0.8% occurrence frequency). Further analyses revealed that this c.4186-1593_4676-1465del might be the result of homologous recombination mediated by two Alu-elements: the AluY in intron 12, and an AluSp in intron 15. This result suggests that subsequent screening for BRCA1/2 genomic rearrangements should be considered in high-risk Korean breast cancer patients who test negative for BRCA1/2 mutations. BRCA1/2 genomic rearrangement, however, is likely to make only a small contribution to breast cancer in this population.
Familial Cancer 09/2009; 8(4):505-8. · 1.30 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cell death has been traditionally classified in apoptosis and necrosis. Apoptosis, known as programmed cell death, is an active form of cell death mechanism that is tightly regulated by multiple cellular signaling pathways and requires ATP for its appropriate process. Apoptotic death plays essential roles for successful development and maintenance of normal cellular homeostasis in mammalian. In contrast to apoptosis, necrosis is classically considered as a passive cell death process that occurs rather by accident in disastrous conditions, is not required for energy and eventually induces inflammation. Regardless of different characteristics between apoptosis and necrosis, it has been well defined that both are responsible for a wide range of human diseases. Glycogen storage disease type I (GSD-I) is a kind of human genetic disorders and is caused by the deficiency of a microsomal protein, glucose-6-phosphatase-α (G6Pase-α) or glucose-6-phosphate transporter (G6PT) responsible for glucose homeostasis, leading to GSD-Ia or GSD-Ib, respectively. This review summarizes cell deaths in GSD-I and mostly focuses on current knowledge of the neutrophil apoptosis in GSD-Ib based upon ER stress and redox signaling.
Molecules and Cells 09/2009; 28(3):139-48. · 2.18 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Natural cytotoxicity receptors (NCRs) are major activating receptors involved in NK cytotoxicity. NCR expression varies with the activation state of NK cells, and the expression level correlates with NK cells' natural cytotoxicity. In this study, we found that Gö6983, a PKC inhibitor, induced a remarkable increase of NCR expression on primary NK cells, but other PKC inhibitors and NK cell stimulators such as IL-2 and PMA, did not. Gö6983 increased the expression of NCR in a time- and concentration-dependent manner. Furthermore, Gö6983 strongly upregulated the surface expression of death ligands FasL and TRAIL, but not cytotoxic molecules perforin and granzyme B. Unlike two other NK stimulating molecules, IL-2, and PMA, Gö6983 did not induce NK cell proliferation. Up-regulation of NCRs and death ligands on NK cells by Gö6983 resulted in a significant enhancement of NK cytotoxicity against various cancer cell lines. Most importantly, administration of Gö6983 effectively inhibited pulmonary tumor metastasis in mice in a dose-dependent manner. These results suggest that Gö6983 functions as an NK cell activating molecule (NKAM); this NKAM is a novel anti-cancer and anti-metastasis drug candidate because it enhances NK cytotoxicity against cancer cells in vivo as well as in vitro.
Cancer Immunology and Immunotherapy 04/2009; 58(10):1691-700. · 3.70 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Secreted proteins control a multitude of biological and physiological processes in multicellular organisms such as plants. Identification of secreted proteins in reference plants like Arabidopsis and rice under normal growth conditions and adverse environmental conditions will help better understand the secretory pathways. Here, we have performed a systematic in planta and in vitro analyses of proteins secreted by rice leaves (in planta) and seed callus suspension-cultured cells (SCCs; in vitro), respectively, using a combination of biochemical and two-dimensional gel electrophoresis (2-DGE) coupled with liquid chromatography mass spectrometry analyses. Secreted proteins prepared from either leaves or SCCs medium were essentially free from contamination of intracellular proteins as judged by biochemical and Western blot analyses. 2-DGE analyses of secreted proteins collectively identified 222 protein spots with only 6 protein spots common to both in planta and in vitro derived data sets. Data were used to establish high-resolution and high-density 2-D gel reference maps for both in planta and in vitro secreted proteins. Identified proteins belonged to 11 (in planta) and 6 (in vitro) functional classes. Proteins involved in carbon metabolism (33%) and cell wall metabolism having plant defense mechanism (18%) were highly represented in the in planta secreted proteins accounting for 51% of total identified proteins, whereas proteins of cell wall metabolism having plant defense mechanism (64%) were predominant in the in vitro secreted proteins. Interestingly, secreted proteins possessing signal peptides were significantly lower in an in planta (27%) prepared secreted protein population than in vitro (76%) as predicted by SignalP prediction tool, implying the notion that plant might possess yet unidentified secretory pathway(s) in addition to the classical endoplasmic reticulum/Golgi pathway. Taken together, this systematic study provides evidence for (i) significant difference in protein population secreted in planta and in vitro suggesting both approaches are complementary, (ii) identification of many novel and previously known secreted proteins, and (iii) the presence of large number of functionally diverse proteins secreted in planta and in vitro.
Journal of Proteome Research 12/2008; 7(12):5187-210. · 5.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Secretin-stimulated magnetic resonance cholangiopancreatography (MRCP) not only facilitate the depiction of anatomic variations or morphologic changes of the pancreatic duct in the normal and diseased pancreas but also help assessing functional abnormalities of the exocrine pancreas. In this article, we illustrate findings of normal pancreas and various pancreatic diseases on magnetic resonance cholangiopancreatography after secretin stimulation.
Abdominal Imaging 10/2006; · 1.73 Impact Factor
