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Combinatory RNA-Sequencing Analyses Reveal a Dual Mode of Gene Regulation by ADAR1 in Gastric Cancer
Cho, Charles J.,Jung, Jaeeun,Jiang, Lushang,Lee, Eun Ji,Kim, Dae-Soo,Kim, Byung Sik,Kim, Hee Sung,Jung, Hwoon-Yong,Song, Ho-June,Hwang, Sung Wook,Park, Yangsoon,Jung, Min Kyo,Pack, Chan Gi,Myung, Seun Springer-Verlag 2018 Digestive diseases and sciences Vol.63 No.7
( Charles J. Cho ),( Ho June Song ),( Gin Hyug Lee ),( Kee Don Choi ),( Yong-hee Kim ),( Jin-sook Ryu ),( Sung-bae Kim ),( Jong Hoon Kim ),( Seung-il Park ),( Hwoon-yong Jung ) 대한내과학회 2017 The Korean Journal of Internal Medicine Vol.32 No.3
Background/Aims: Approximately 30% of esophageal cancer (EC) patients cannot complete endoscopic ultrasonography (EUS) due to malignant stricture (EUS non-traversability). This study examines clinical implications of EUS non-traversability in patients with advanced locoregional squamous EC receiving preoperative chemoradiotherapy (CRT) followed by esophagectomy. Methods: We retrieved data on 89 consecutive patients with advanced locoregional squamous EC (stage II or III). Relevant clinical and tumor-specific parameters were reviewed retrospectively. Significant factors affecting survival was determined by Cox regression analysis. Results: EUS non-traversable EC was observed in 26 of 89 patients (29.2%). Median serum albumin level (3.6 g/dL vs. 3.9 g/dL, p = 0.028), tumor length (6.0 cm vs. 4.0 cm, p = 0.002), and percentage of clinical stage III disease (65.4% vs. 38.1%, p = 0.019) were significantly different between the patients with EUS non-traversable and traversable EC, respectively. Patients with EUS non-traversable EC demonstrated a significantly lower 5-year overall survival than patients with EUS traversable EC (30.8% vs. 49.3%, p = 0.023). In multivariate analysis, weight loss ≥ 10% (p = 0.033), EUS non-traversability (p = 0.003), non-response to preoperative CRT (p = 0.002), and incompletion of esophagectomy (p = 0.002) were significant negative factors of survival. Conclusions: EUS non-traversability has significant negative prognostic implications in patients with advanced locoregional squamous EC receiving preoperative CRT followed by esophagectomy.
ADAR1 and MicroRNA; A Hidden Crosstalk in Cancer
Cho, Charles J.,Myung, Seung-Jae,Chang, Suhwan MDPI 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.4
<P>The evolution of cancer cells is believed to be dependent on genetic or epigenetic alterations. However, this concept has recently been challenged by another mode of nucleotide alteration, RNA editing, which is frequently up-regulated in cancer. RNA editing is a biochemical process in which either Adenosine or Cytosine is deaminated by a group of RNA editing enzymes including ADAR (Adenosine deaminase; RNA specific) or APOBEC3B (Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 3B). The result of RNA editing is usually adenosine to inosine (A-to-I) or cytidine to uridine (C-to-U) transition, which can affect protein coding, RNA stability, splicing and microRNA-target interactions. The functional impact of these alterations is largely unclear and is a subject of extensive research. In the present review, we will specifically focus on the influence of ADARs on carcinogenesis via the regulation of microRNA processing and functioning. This follows a brief review of the current knowledge of properties of ADAR enzyme, RNA editing, and microRNA processing.</P>
Generation of Soluble Human Tumor Necrosis Factor-α Receptor 1-Fc Transgenic Pig
Cho, Bumrae,Koo, Ok Jae,Hwang, Jong-Ik,Kim, Hwajung,Lee, Eun Mi,Hurh, Sunghoon,Park, Sol Ji,Ro, Han,Yang, Jaeseok,Surh, Charles D.,d’Apice, Anthony J.,Lee, Byeong Chun,Ahn, Curie Lippincott Williams Wilkins, Inc. 2011 Transplantation Vol.92 No.2
BACKGROUND.: Acute humoral xenograft rejection (AHXR) is an important barrier to xenograft survival. Human tumor necrosis factor-α (hTNF-α) is one of the essential mediators of AHXR and induces activation of porcine endothelial cells (PECs), resulting in upregulation of major histocompatibility complex molecules, adhesion molecules, and proinflammatory chemokines. We investigated whether introduction of a soluble human tumor necrosis factor receptor I-Fc (shTNFRI-Fc) fusion gene can suppress activation of PECs and, more importantly, produced shTNFRI-Fc transgenic pigs. METHODS.: The shTNFRI-Fc gene expression vector was constructed and inserted into PECs. The inhibitory effects of shTNFRI-Fc were tested by luciferase assay, reverse-transcriptase polymerase chain reaction, and flow cytometry. A shTNFRI-Fc transgenic pig was generated by somatic cell nuclear transfer. The expression of shTNFRI-Fc in the transgenic pig was evaluated by PCR, western blot, enzyme-linked immunosorbent assay, and immunohistochemistry. The inhibitory effects of shTNFRI-Fc in the serum obtained from the transgenic pig were also tested. RESULTS.: In comparison with control green fluorescent protein, shTNFRI-Fc protein showed much stronger inhibitory effects on NF-&kgr;B activation in the HEK293-NF-&kgr;B-luciferase reporting cell line, expression of chemokines and adhesion molecules in PECs, and TNF-α-mediated cytotoxicity. We successfully generated shTNFRI-Fc transgenic pig. Sera obtained from the transgenic pig inhibited induction of chemokines, and E-selectin in PECs stimulated with Human TNF-α. CONCLUSIONS.: We have generated transgenic pigs producing shTNFRI-Fc protein that can inhibit TNF-α-mediated activation of PECs. Because TNF-α is an important mediator of xenograft rejection, the use of xenografts that can produce shTNFRI-Fc proteins de novo could be an effective approach in overcoming a considerable component of the xenograft rejection process, especially AHXR.
공은정,이정훈,정경원,Charles J. Cho,나희경,안지용,정기욱,김도훈,최기돈,송호준,이진혁,정훈용,김진호 대한소화기내시경학회 2017 Clinical Endoscopy Vol.50 No.3
Background/Aims: The detection of multifocal lesions is important for the successful management of gastric neoplasms. We investigated the characteristics of missed simultaneous lesions and the reason for the missed diagnoses. Methods: A total of 140 patients who underwent repeat endoscopy before endoscopic resection between June 2013 and June 2014 were retrospectively reviewed. We classified simultaneous lesions into three groups based on a review of earlier images: group 1, no images of the location of simultaneous lesions were taken; group 2, no corresponding lesion was evident in the previous images; and group 3, simultaneous lesions were visible in the earlier images but a biopsy was not performed. Results: Simultaneous lesions were found in 12 patients (8.6%) with 13 lesions, comprising 10 dysplasia (76.9%) and three adenocarcinoma (23.1%). Regarding the reasons for missed diagnoses, seven lesions (53.8%) were classified as group 3, five (38.5%) as group 1, and the remaining lesion (7.7%) as group 2. There were no significant differences in the characteristics of the patients with and without simultaneous lesions. Conclusions: Lesions disregarded or unnoticed during endoscopic examination were the main reason for missed diagnosis of simultaneous lesions. Endoscopists should consider the possibility of simultaneous lesions and attempt to meticulously evaluate the entire gastric mucosa.
Ji Wan Lee,Charles J. Cho,Do Hoon Kim,Ji Yong Ahn,Jeong Hoon Lee,Kee Don Choi,Ho June Song,Sook Ryun Park,Hyun Joo Lee,Hyun Joo Lee,Gin Hyug Lee,Hwoon-Yong Jung,Sung-Bae Kim,Jong Hoon Kim,Seung-Il Par 대한소화기내시경학회 2018 Clinical Endoscopy Vol.51 No.5
Background/Aims: To report the long-term survival and tumor recurrence outcomes in patients with superficial esophageal cancer(SEC) after complete non-curative endoscopic resection (ER). Methods: We retrieved ER data for 24 patients with non-curatively resected SEC. Non-curative resection was defined as the presence ofsubmucosal and/or lymphovascular invasion on ER pathology. Relevant clinical and tumor-specific parameters were reviewed. Results: The mean age of the 24 study patients was 66.3±8.3 years. Ten patients were closely followed up without treatment, while14 received additional treatment. During a mean follow-up of 59.0±33.2 months, the 3- and 5-year survival rates of all cases were90.7% and 77.6%, respectively. The 5-year overall survival rates were 72.9% in the close observation group and 82.1% in the additionaltreatment group (p=0.958). The 5-year cumulative incidences of all cases of recurrence (25.0% vs. 43.3%, p=0.388), primary ECrecurrence (10.0% vs. 16.4%, p=0.558), and metachronous EC recurrence (16.7% vs. 26.7%, p=0.667) were similar between the twogroups. Conclusions: Patients with non-curatively resected SEC showed good long-term survival outcomes. Given the similar oncologicoutcomes, close observation may be an option with appropriate caution taken for patients who are medically unfit to receive additionaltherapy
De novo formation of basal bodies in <i>Naegleria gruberi</i> : regulation by phosphorylation
Kim, Hong-Kyung,Kang, Jeong-Gu,Yumura, Shigehiko,Walsh, Charles J.,Cho, Jin Won,Lee, JooHun The Rockefeller University Press 2005 The Journal of cell biology Vol.169 No.5
<P>The de novo formation of basal bodies in <I>Naegleria gruberi</I> was preceded by the transient formation of a microtubule (MT)-nucleating complex containing γ-tubulin, pericentrin, and myosin II complex (GPM complex). The MT-nucleating activity of GPM complexes was maximal just before the formation of visible basal bodies and then rapidly decreased. The regulation of MT-nucleating activity of GPM complexes was accomplished by a transient phosphorylation of the complex. Inhibition of dephosphorylation after the formation of basal bodies resulted in the formation of multiple flagella. 2D-gel electrophoresis and Western blotting showed a parallel relationship between the MT-nucleating activity of GPM complexes and the presence of hyperphosphorylated γ-tubulin in the complexes. These data suggest that the nucleation of MTs by GPM complexes precedes the de novo formation of basal bodies and that the regulation of MT-nucleating activity of GPM complexes is essential to the regulation of basal body number.</P>