1.Dexamethasone Inhibits Interleukin-1beta-Induced Matrix Metalloproteinase-9 Expression in Cochlear Cells.
Clinical and Experimental Otorhinolaryngology 2014;7(3):175-180
OBJECTIVES: To investigate the effect of interleukin (IL)-1beta on matrix metalloproteinase (MMP)-9 expression in cochlea and regulation of IL-1beta-mediated MMP-9 expression by dexamethasone and the molecular and signaling mechanisms involved. METHODS: House ear institute-organ of Corti 1 (HEI-OC1) cells were used and exposed to IL-1beta with/without dexamethasone. Glucocorticoid receptor antagonist, RU486, was used to see the role of dexamethasone. PD98059 (an extracellular signal-regulated kinases [ERKs] inhibitor), SB203580 (a p38 mitogen-activated protein kinases [MAPK] inhibitor), SP600125 (a c-Jun N-terminal kinase [JNK] inhibitor) were also used to see the role of MAPKs signaling pathway(s) in IL-1beta-induced MMP-9 expression in HEI-OC1 cells. Reverse transcription-polymerase chain reaction and gelatin zymography were used to measure mRNA expression level of MMP-9 and activity of MMP-9, respectively. RESULTS: Treatment with IL-1beta-induced the expression of MMP-9 in a dose- and time-dependent manner. IL-1beta (1 ng/mL)-induced MMP-9 expression was inhibited by dexamethasone. Interestingly, p38 MAPK inhibitor, SB203580, significantly inhibited IL-1beta-induced MMP-9 mRNA and MMP-9 activity. However, inhibition of JNKs and ERKs had no effect on the IL-1beta-induced MMP-9 expression. CONCLUSION: These results suggest that the pro-inflammatory cytokine IL-1beta strongly induces MMP-9 expression via activation of p38 MAPK signaling pathway in HEI-OC1 cells and the induction was inhibited by dexamethasone.
Cochlea
;
Dexamethasone*
;
Ear
;
Extracellular Signal-Regulated MAP Kinases
;
Gelatin
;
Interleukin-1beta
;
Interleukins
;
JNK Mitogen-Activated Protein Kinases
;
Matrix Metalloproteinase 9*
;
Mifepristone
;
p38 Mitogen-Activated Protein Kinases
;
Receptors, Glucocorticoid
;
RNA, Messenger
2.Synchronous Dual Primary Ovarian Carcinoma and Adnocarcinoma of the Cervix.
Sung Taeg KWON ; Jin Sung KIM ; Won Joun CHOI ; Young Taeg JOUNG ; Soon Ae LEE ; Jong Hak LEE ; Joung Hwa KIM ; Kyoung Hyuck KO ; Won Young PAIK
Korean Journal of Obstetrics and Gynecology 1997;40(12):2903-2908
No abstract available.
Adenocarcinoma
;
Cervix Uteri*
;
Cystadenocarcinoma, Mucinous
;
Female
3.Risk Factors of Portal Vein Invasion in Hepatocellular Carcinoma.
Sung Won KIM ; Young Taeg KHO ; Ki Ho KIM ; Oh Joong KWON ; Kyung Suk SUH ; Kuhn Uk LEE
Journal of the Korean Surgical Society 1999;56(6):865-871
BACKGROUND: The long-term prognosis of patients with hepatocellular carcinomas is still disappointing primarily because of intrahepatic recurrence. Among many factors, portal vein invasion is considered to be the most important risk factor leading to recurrence, and it is thought to be the direct evidence of tumor invasiveness. In clinical aspects, it seems to be more practical to determine the factors associated with portal vein invasion. METHODS: Three hundred and seventy-one patients who underwent a curative hepatic resection for hepatocellular carcinomas between 1991 and 1995 at Seoul National University Hospital were included in this study. Portal vein invasion was identified histopathologically. The prognostic factors of hepatocellular carcinoma and the risk factors linked to portal vein invasion were analyzed by both univariate and multivariate analyses. RESULTS: Portal vein invasion was detected in thirty seven patients (10%), and the 5-year overall and disease-free survival rates in this group were 39.9% and 6.5%, respectively. The 5-year overall and disease-free survival rates of patients without portal vein invasion were 60.1% and 36.8%, respectively. In multivariate analysis using Cox's proportional hazards model, portal vein invasion was proven to be the most important risk factor in both overall and disease-free survival. In a multiple stepwise logistic regression analysis, the size and the number of the tumors were strong independent predictors of portal vein invasion by a hepatocellular carcinoma. CONCLUSIONS: Intrahepatic recurrence and patient survival in cases of hepatocellular carcinomas were closely related to portal vein invasion. Patients with tumor sizes larger than 4 cm or with multiple tumors should be monitored closely for early recurrence.
Carcinoma, Hepatocellular*
;
Disease-Free Survival
;
Humans
;
Logistic Models
;
Multivariate Analysis
;
Portal Vein*
;
Prognosis
;
Proportional Hazards Models
;
Recurrence
;
Risk Factors*
;
Seoul
4.Fas-induced Apoptosis in Renal Cell Carcinoma Cell Line by Interferon-gamma (IFN-gamma) Treatment.
Soo Jung YOON ; Jae Sik YOON ; Taeg Kyu KWON ; Min Ho SUH ; Won Ki BAEK ; Young Sun LEE ; Sung Joon LEE ; Jong Wook PARK
Korean Journal of Urology 2000;41(5):594-601
No abstract available.
Apoptosis*
;
Carcinoma, Renal Cell*
;
Cell Line*
;
Interferon-gamma*
5.The colchicine derivative CT20126 shows a novel microtubule-modulating activity with apoptosis.
Sung Kuk KIM ; Sang Min CHO ; Ho KIM ; Heon SEOK ; Soon Ok KIM ; Taeg Kyu KWON ; Jong Soo CHANG
Experimental & Molecular Medicine 2013;45(4):e19-
New colchicine analogs have been synthesized with the aim of developing stronger potential anticancer activities. Among the analogs, CT20126 has been previously reported to show immunosuppressive activities. Here, we report that CT20126 also shows potential anticancer effects via an unusual mechanism: the modulation of microtubule integrity and cell cycle arrest at the G2/M phase before apoptosis. When we treated COS-7 cells with CT20126 (5 muM), the normal thread-like microtubules were disrupted into tubulin dimers within 10 min and thereafter repolymerized into short, thick filaments. In contrast, cells treated with the same concentration of colchicine exhibited microtubule depolymerization after 20 min and never underwent repolymerization. Furthermore, optical density (OD) analysis (350 nm) with purified tubulin showed that CT20126 had a higher repolymerizing activity than that of Taxol, a potent microtubule-polymerizing agent. These results suggest that the effects of CT20126 on microtubule integrity differ from those of colchicine: the analog first destabilizes microtubules and then stabilizes the disrupted tubulins into short, thick polymers. Furthermore, CT20126 induced a greater level of apoptotic activity in Jurkat T cells than colchicine (assessed by G2/M arrest, caspase-3 activation and cell sorting). At 20 nM, CT20126 induced 47% apoptosis among Jurkat T cells, whereas colchicine induced only 33% apoptosis. Our results suggest that the colchicine analog CT20126 can potently induce apoptosis by disrupting microtubule integrity in a manner that differs from that of colchicine or Taxol.
Acetylation/drug effects
;
Animals
;
Apoptosis/*drug effects
;
COS Cells
;
Caspase 3/metabolism
;
Cattle
;
Cell Division/drug effects
;
Cercopithecus aethiops
;
Colchicine/*analogs & derivatives/chemistry/pharmacology
;
Enzyme Activation/drug effects
;
G2 Phase/drug effects
;
Humans
;
Jurkat Cells
;
Microtubules/*metabolism
;
Poly(ADP-ribose) Polymerases/metabolism
;
Tubulin/metabolism
;
Tubulin Modulators/chemistry/*pharmacology
6.A Case of Recurrent Subacute Necrotizing Lymphadenitis with Pancytopenia.
Bo Kwon HWANG ; Jin Seok JEON ; Jae Ho BYUN ; Gyu Taeg LEE ; Jin Woo JEON ; Sung Gyu PARK ; Jong Ho WON ; Seung Ho BAICK ; Dae Sik HONG ; Hee Sook PARK
Korean Journal of Hematology 1997;32(2):318-323
We report a case of recurrent subacute necrotizing lymphadenitis with pancytopenia in 21-years-old-woman. She was admitted to our hospital 4-years interval with fever and abdominal pain. Laboratory findings of the last admission showed pancytopenia, such as WBC 700/microliter, hemoglobin 6.0mmol/L (9.7g/dL), hematocrit 28.8%, and platelet 54,000/microliter. Abdominal CT showed hepatosplenomegaly, enlarged conglomerated lymph nodes in splenic hilum, lesser sac, celiac root, and paraaortic areas. Bone marrow biopsy showed hypocellular marrow (20%) with increased number of megakaryocyte, myeloid hyperplasia, and hemophagocytic histiocytes suggesting infectious process. We performed exploratory laparotomy, and pathologic finding revealed subacute necrotizing lymphadenitis-Kikuchi disease-. She was recovered on 26th hospital day with conservative treatment.
Abdominal Pain
;
Biopsy
;
Blood Platelets
;
Bone Marrow
;
Fever
;
Hematocrit
;
Histiocytes
;
Histiocytic Necrotizing Lymphadenitis
;
Hyperplasia
;
Laparotomy
;
Lymph Nodes
;
Lymphadenitis*
;
Megakaryocytes
;
Pancytopenia*
;
Peritoneal Cavity
;
Tomography, X-Ray Computed
7.Host modulation therapy for improving the osseointegration of dental implants under bone healing-suppressed conditions: a preclinical rodent-model experiment
Young Woo SONG ; Jin-Young PARK ; Yoon-Hee KWON ; Wooyoung Eric JANG ; Sung-JinSung-Jin KIMKIM ; Jeong Taeg SEO ; Seok Jun MOON ; Ui-Won JUNG
Journal of Periodontal & Implant Science 2024;54(3):177-188
Purpose:
Placing dental implants in areas with low bone density or in conditions where bone healing is suppressed is challenging for clinicians. An experiment using a rodent model was performed with the aim of determining the efficacy of host modulation by increasing the systemic level of cholesterol sulfate (CS) using Irosustat in the context of the bone healing process around dental implants.
Methods:
In 16 ovariectomised female Sprague-Dawley rats, 2 implant fixtures were placed in the tibial bones (1 fixture on each side). At 1 week after surgery, the high-CS group (n=8) received Irosustat-mixed feed, while the control group (n=8) was fed conventionally. Block specimens were obtained at 5 weeks post-surgery for histologic analysis and the data were evaluated statistically (P<0.05).
Results:
Unlike the high-CS group, half of the specimens in the control group demonstrated severe bone resorption along with a periosteal reaction in the cortex. The mean percentages of bone-to-implant contact (21.5%) and bone density (28.1%) near the implant surface were significantly higher in the high-CS group than in the control group (P<0.05), as was the number of Haversian canals (by 5.3).
Conclusions
Host modulation by increasing the CS level may enhance the osseointegration of dental implants placed under conditions of impaired bone healing.
8.Cynaropicrin Induces Reactive Oxygen Species-Dependent Paraptosis-Like Cell Death in Human Liver Cancer Cells
Min Yeong KIM ; Hee-Jae CHA ; Su Hyun HONG ; Sung-Kwon MOON ; Taeg Kyu KWON ; Young-Chae CHANG ; Gi Young KIM ; Jin Won HYUN ; A-Young NAM ; Jung-Hyun SHIM ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):470-482
Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.
9.Cynaropicrin Induces Reactive Oxygen Species-Dependent Paraptosis-Like Cell Death in Human Liver Cancer Cells
Min Yeong KIM ; Hee-Jae CHA ; Su Hyun HONG ; Sung-Kwon MOON ; Taeg Kyu KWON ; Young-Chae CHANG ; Gi Young KIM ; Jin Won HYUN ; A-Young NAM ; Jung-Hyun SHIM ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):470-482
Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.
10.Cynaropicrin Induces Reactive Oxygen Species-Dependent Paraptosis-Like Cell Death in Human Liver Cancer Cells
Min Yeong KIM ; Hee-Jae CHA ; Su Hyun HONG ; Sung-Kwon MOON ; Taeg Kyu KWON ; Young-Chae CHANG ; Gi Young KIM ; Jin Won HYUN ; A-Young NAM ; Jung-Hyun SHIM ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):470-482
Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.