1.Dioscin Decreases Breast Cancer Stem-like Cell Proliferation via Cell Cycle Arrest by Modulating p38 Mitogen-activated Protein Kinase and AKT/mTOR Signaling Pathways
Journal of Cancer Prevention 2021;26(3):183-194
Dioscin (DS), a steroidal saponin, has been shown to have anti-cancer activity by exerting antioxidant effects and inducing apoptosis. However, the anti-cancer activity of DS in breast cancer-derived stem cells is still controversial. The purpose of this study was to evaluate the effects of DS on migration, invasion, and colony formation in MDA-MB-231 and MCF-7 cell lines and the mechanism by which it inhibits proliferation of breast cancer stem-like cells after inducing differentiation into breast cancer stem cells. DS treatment significantly reduced cellular migration, invasion, and colony formation in MDA-MB-231 and MCF-7 cells. During the differentiation process that induced manifestation of breast cancer stem-like cells, DS significantly inhibited mammosphere formation in a dose-dependent manner and increased the expression of p53 and p21 in breast cancer stem-like cells, reducing the expression of cdc2 and cyclin B1 in MDA-MB-231 cells and cyclin D, cyclin E, CDK4, and CDK2 in MCF-7 cells. Interestingly, DS treatment induced G2/M and G0/G1 cell cycle arrest in the MDA-MB-231 and MCF-7 cells, respectively. DS also increased the phosphorylation of p38 and decreased the expression levels of p-AKT and p-mTOR. These results suggest that DS regulates the p38 mitogen-activated protein kinase and AKT/mTOR signaling pathways to reduce the proliferation of breast cancer stem-like cells through cell cycle arrest. Therefore, these findings suggest that DS may serve as a potential treatment candidate targeting breast cancer stem cells.
3.Dioscin Decreases Breast Cancer Stem-like Cell Proliferation via Cell Cycle Arrest by Modulating p38 Mitogen-activated Protein Kinase and AKT/mTOR Signaling Pathways
Journal of Cancer Prevention 2021;26(3):183-194
Dioscin (DS), a steroidal saponin, has been shown to have anti-cancer activity by exerting antioxidant effects and inducing apoptosis. However, the anti-cancer activity of DS in breast cancer-derived stem cells is still controversial. The purpose of this study was to evaluate the effects of DS on migration, invasion, and colony formation in MDA-MB-231 and MCF-7 cell lines and the mechanism by which it inhibits proliferation of breast cancer stem-like cells after inducing differentiation into breast cancer stem cells. DS treatment significantly reduced cellular migration, invasion, and colony formation in MDA-MB-231 and MCF-7 cells. During the differentiation process that induced manifestation of breast cancer stem-like cells, DS significantly inhibited mammosphere formation in a dose-dependent manner and increased the expression of p53 and p21 in breast cancer stem-like cells, reducing the expression of cdc2 and cyclin B1 in MDA-MB-231 cells and cyclin D, cyclin E, CDK4, and CDK2 in MCF-7 cells. Interestingly, DS treatment induced G2/M and G0/G1 cell cycle arrest in the MDA-MB-231 and MCF-7 cells, respectively. DS also increased the phosphorylation of p38 and decreased the expression levels of p-AKT and p-mTOR. These results suggest that DS regulates the p38 mitogen-activated protein kinase and AKT/mTOR signaling pathways to reduce the proliferation of breast cancer stem-like cells through cell cycle arrest. Therefore, these findings suggest that DS may serve as a potential treatment candidate targeting breast cancer stem cells.
4.Induction chemotherapy in head and neck squamous cell carcinoma of the paranasal sinus and nasal cavity: a role in organ preservation.
Chan Young OCK ; Bhumsuk KEAM ; Tae Min KIM ; Doo Hee HAN ; Tae Bin WON ; Se Hoon LEE ; J Hun HAH ; Tack Kyun KWON ; Dong Wan KIM ; Dong Young KIM ; Chae Seo RHEE ; Hong Gyun WU ; Myung Whun SUNG ; Dae Seog HEO
The Korean Journal of Internal Medicine 2016;31(3):570-578
BACKGROUND/AIMS: The role of induction chemotherapy (IC) for eyeball preservation has not been established in head and neck squamous cell carcinoma (HNSCC) of the paranasal sinus and nasal cavity (PNSNC). Periorbital involvement frequently leads to eyeball exenteration with a margin of safety. We evaluated the treatment outcomes, including survival and eyeball preservation, of patients who received IC for HNSCC of the PNSNC. METHODS: We reviewed 21 patients diagnosed with HNSCC of the PNSNC who were treated with IC. We analyzed response, eyeball preservation rate, and overall survival. RESULTS: Tumors were located in the paranasal sinus (n = 14) or nasal cavity (n = 7). Most patients had stage T4a (n = 10) or T4b (n = 7) disease. More than half of the patients received a chemotherapy regimen of docetaxel, fluorouracil, and cisplatin (n = 11). Thirteen patients (61.9%) achieved a partial response after IC and 15 patients (71.4%) achieved T down-staging. Among 17 patients with stage T4 disease, which confers a high risk of orbital exenteration, 14 (82.4%) achieved preservation of the involved eye. The 3-year overall survival (OS) rate of patients who achieved a partial response to IC was 84.6%. The 3-year OS rate of patients with stable disease or disease progression after IC was 25.0% (p = 0.038). CONCLUSIONS: IC could be considered for down-staging patients with advanced T-stage disease. It could also be a reasonable option for eyeball preservation in locally advanced HNSCC of the PNSNC.
Carcinoma, Squamous Cell*
;
Cisplatin
;
Disease Progression
;
Drug Therapy
;
Fluorouracil
;
Head and Neck Neoplasms
;
Head*
;
Humans
;
Induction Chemotherapy*
;
Nasal Cavity*
;
Neck*
;
Orbit
;
Orbit Evisceration
;
Organ Preservation*
;
Paranasal Sinuses
5.Ethical Issues Recognized by Critical Care Nurses in the Intensive Care Units of a Tertiary Hospital during Two Separate Periods.
Dong Won PARK ; Jae Young MOON ; Eun Yong KU ; Sun Jong KIM ; Young Mo KOO ; Ock Joo KIM ; Soon Haeng LEE ; Min Woo JO ; Chae Man LIM ; John David ARMSTRONG ; Younsuck KOH
Journal of Korean Medical Science 2015;30(4):495-501
This research aimed to investigate the changes in ethical issues in everyday clinical practice recognized by critical care nurses during two observation periods. We conducted a retrospective analysis of data obtained by prospective questionnaire surveys of nurses in the intensive care units (ICU) of a tertiary university-affiliated hospital in Seoul, Korea. Data were collected prospectively during two different periods, February 2002-January 2003 (Period 1) and August 2011-July 2012 (Period 2). Significantly fewer cases with ethical issues were reported in Period 2 than in Period 1 (89 cases [2.1%] of 4,291 ICU admissions vs. 51 [0.5%] of 9,302 ICU admissions, respectively; P < 0.001). The highest incidence of cases with identified ethical issues in both Periods occurred in MICU. The major source of ethical issues in Periods 1 and 2 was behavior-related. Among behavior-related issues, inappropriate healthcare professional behavior was predominant in both periods and mainly involved resident physicians. Ethical issue numbers regarding end-of-life (EOL) care significantly decreased in the proportion with respect to ethical issues during Period 2 (P = 0.044). In conclusion, the decreased incidence of cases with identified ethical issues in Period 2 might be associated with ethical enhancement related with EOL and improvements in the ICU care environment of the studied hospital. However, behavior-related issues involving resident physicians represent a considerable proportion of ethical issues encountered by critical care nurses. A systemic approach to solve behavior-related issues of resident physicians seems to be required to enhance an ethical environment in the studied ICU.
Critical Care Nursing/*ethics
;
Humans
;
*Intensive Care Units
;
Nurses
;
Retrospective Studies
;
Terminal Care
;
Tertiary Care Centers
6.Erdheim-Chester Disease with Hepatitis, Glomerulonephritis, Aplastic Anemia and Lung Involvement.
Ji Won PARK ; Chae Uk CHUNG ; Ji Young SHIN ; Sun Young JUNG ; Su Jin YOO ; Jeong Eun LEE ; Sung Soo JUNG ; Ju Ock KIM ; Sun Young KIM ; Hee Sun PARK
Tuberculosis and Respiratory Diseases 2009;67(4):345-350
Erdheim-Chester disease (ECD) is a proliferative non-Langerhans cell histiocytosis of multiple organs. This is a rare disease of unknown etiology with a high mortality. We present the case report of a 26-year-old man diagnosed with ECD. He was referred to our hospital with elevated levels of aminotransferases. Although the diagnosis was uncertain, the patient was lost to follow up at that time. One year later, the patient returned to the hospital with generalized edema. Although a specific bone lesion was not found, the patient was experiencing the following: glomerulonephritis, aplastic anemia, hepatitis, and lung involvement. A lung biopsy was performed: the immunohistochemical stain were positive for CD68 and negative for S-100 protein and CD1a. We diagnosed as the patient as havinf ECD. Approximately 50% of ECD cases present with extraskeletal involvement. ECD should be considered as part of the differential diagnosis when multiple organs are involved.
Adult
;
Anemia, Aplastic
;
Biopsy
;
Diagnosis, Differential
;
Edema
;
Erdheim-Chester Disease
;
Glomerulonephritis
;
Hepatitis
;
Histiocytosis
;
Humans
;
Lost to Follow-Up
;
Lung
;
Rare Diseases
;
S100 Proteins
;
Transaminases
7.Inflammatory Markers as Prognostic Factors for Patients with ARDS.
Chae Uk CHUNG ; Jae Hee HWANG ; Ji Won PARK ; Ji Young SHIN ; Sun Yuong JUNG ; Jeong Eun LEE ; Hee Sun PARK ; Sung Soo JUNG ; Ju Ock KIM ; Sun Young KIM
Tuberculosis and Respiratory Diseases 2008;65(2):99-104
BACKGROUND: Acute respiratory distress syndrome (ARDS) is ultimately an inflammatory state. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level are inflammatory markers. The aim of this study was to evaluate the value of the ESR, CRP and APACHE II score as prognostic factors for patient with ARDS. METHODS: We retrospectively analyzed the medical records of 87 ARDS patients. The predictors (APACHE II score, ESR and CRP) and outcomes (mortality and length of the total hospital stay, the ICU stay and mechanical ventilator care) were obtained from the patients' records. The patients were grouped according to survival as the Survivor and Non survivor groups. We compared the APACHE II score, the ESR and the CRP level between the survivor group and the nonsurvivor group. We evaluated the correlation between the predictors and the outcomes. The initial ESR, CRP level and APACHE II score were checked at the time of ICU admission and the second ESR and CRP level were checked 3.3+/-1.2 days after ICU admission. RESULTS: Thirty-eight (43.7%) patients remained alive and 49 (56.3%) patients died. The APACHE II score was significantly lower for the survivor group than that for the non survivor group (14.7+/-7.6 vs 19.6+/-9.1, respectively, p=0.006). The initial ESR and CRP level were not different between the survivor and non-survivor groups (ESR 64.0+/-37.8 mm/hr vs 63.3+/-36.7 mm/hr, respectively, p=0.93, CRP 15.5+/-9.6 mg/dl vs 16.3+/-8.5 mg/dl, respectively, p=0.68). The decrement of the CRP level for the survivor group was greater than that for the non survivor group (-8.23+/-10.0 mg/dl vs -1.46+/-10.1 mg/dl, respectively, p=0.003). Correlation analysis revealed the initial ESR was positively correlated with the length of the total hospital stay and the ICU stay (correlation coefficient of the total hospital days: R=0.43, p=0.001, correlation coefficient of the ICU stay: R=0.39, p=0.014). CONCLUSION: The initial APACHE II score can predict the mortality of ARDS patients, and the degree of the early CRP change can be a predictor of mortality for ARDS patients. The initial ESR has positive correlation with the ARDS patients' duration of the total hospital stay and the ICU stay.
APACHE
;
Blood Sedimentation
;
C-Reactive Protein
;
Humans
;
Length of Stay
;
Medical Records
;
Prognosis
;
Respiratory Distress Syndrome, Adult
;
Retrospective Studies
;
Survivors
;
Ventilators, Mechanical
8.Safety and Significance of Surgical Lung Biopsy for Interstitial Lung Disease.
Yu Jin LEE ; Mi Kyong JOUNG ; Chae Uk CHUNG ; Ji Won PARK ; Ji Young SHIN ; Sun Young JUNG ; Jeong Eun LEE ; Hee Sun PARK ; Sung Soo JUNG ; Ju Ock KIM ; Sun Young KIM
Tuberculosis and Respiratory Diseases 2007;63(1):59-66
BACKGROUND: Surgical lung biopsy is required to establish the etiology and stage of interstitial lung disease(ILD). and this procedure can be safe and meaningful for making clinical decisions. We wanted to determine the safety of surgical lung biopsy(SLB) in patients with interstitial lung disease(ILD). METHODS: We conducted a retrospective review of 40 patients with suspected ILD and they underwent surgical lung biopsy from January 2001 to June 2006 at Chungnam University Hospital. We analyzed retrospectively according to their age, gender, pulmonary function, chest tube duration, the arterial blood gases, the procedural technique, and the requirement for supplemental oxygen and mechanical ventilation(MV) at the time of SLB. RESULTS: The mean age of the patients was 56.4+/-16.13 years(range: 21 to 77 years). Overall, the 30-day and 90-day mortality rates were 15% and 20%, respectively. The predictors of perioperative mortality were either the need for mechanical ventilation(MV) at the time of SLB or the need for supplemental oxygen prior to undergoing SLB. Among the 32 patients who were 90-day survivors, the proportion of those patients using the oxygen supplement was 28.1% (n=9). All 8 patients who were 90-day non-survivors used oxygen supplement (p=0.000). The use of the MV was 12.5% (n=4) in the 90-day survivors (n=32) and 62.5% (n=5) in the 90-day non-survivors (n=8); there was a significant difference between the 90-day survivors and non-survivors (p=0.000). CONCLUSION: Patients who require MV and supplemental oxygen are associated with an increased risk for death following SLB.
Biopsy*
;
Chest Tubes
;
Chungcheongnam-do
;
Gases
;
Humans
;
Lung Diseases, Interstitial*
;
Lung*
;
Mortality
;
Oxygen
;
Retrospective Studies
;
Survivors
9.Comparison of Clinical Features between Idiopathic Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.
Hyun Kuk KIM ; Joo Ock NA ; Jong Joon AHN ; Yong Bum PARK ; Jae Min LIM ; Sang Bum HONG ; Yeon Mok OH ; Tae Sun SHIM ; Chae Man LIM ; Younsuck KOH ; Woo Sung KIM ; Dong Soon KIM ; Won Dong KIM ; Sang Do LEE
Tuberculosis and Respiratory Diseases 2005;59(2):170-178
BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are rare but significantly imperative in inducing chronic pulmonary hypertension. Clinically, it is difficult to distinguish between IPAH and CTEPH. However, the treatment of pulmonary hypertension is different depending on the disease. The present study was performed to analyze the similarities and differences in clinical features between IPAH and CTEPH. METHODS: During a nine-year period, thirty-three patients with IPAH and twenty-two patients with CTEPH were enrolled. Symptoms, physical findings, chest radiograph, electrocardiograph, pulmonary function test, echocardiograph, perfusion lung scan, right heart catheterization results were analyzed between both the groups. RESULTS: The median age of IPAH group was 33 (6~70) years that was lower than that (52(27~80) years) of CTEPH group. Amongst the IPAH patients, there was female predominance (76 %) and there was no sex difference between the patients with CTEPH. Both the groups exhibited similarity in the results of chest radiograph, electrocardiograph, pulmonary function test, and echocardiograph. In the perfusion lung scan, all IPAH patients exhibited findings with normal (28%) or low probability (72%) of pulmonary embolism and all CTEPH patients exhibited findings with high probability of pulmonary embolism. CONCLUSION: Although IPAH and CTEPH bear similarities in terms of symptoms, physical signs and general investigation results, there were differences in age distribution, sex predominance and results of perfusion lung scan.
Age Distribution
;
Cardiac Catheterization
;
Cardiac Catheters
;
Diagnosis, Differential
;
Electrocardiography
;
Female
;
Humans
;
Hypertension*
;
Hypertension, Pulmonary*
;
Lung
;
Perfusion
;
Pulmonary Embolism
;
Radiography, Thoracic
;
Respiratory Function Tests
;
Sex Characteristics
10.A Comparison of Tiotropium 18microgram, Once Daily and Ipratropium 40microgram, 4 Times Daily in a Double-Blind, Double-Dummy, Efficacy and Safety Study in Adults with Chronic Obstructive Pulmonary Disease.
Seung Joon KIM ; Myung Sook KIM ; Sang Haak LEE ; Young Kyoon KIM ; Hwa Sik MOON ; Sung Hak PARK ; Sang Yeub LEE ; Kwang Ho IN ; Chang Youl LEE ; Young Sam KIM ; Hyung Jung KIM ; Chul Min AHN ; Sung Kyu KIM ; Kyung Rok KIM ; Seung Ick CHA ; Tae Hoon JUNG ; Mi Ok KIM ; Sung Soo PARK ; Cheon Woong CHOI ; Jee Hong YOO ; Hong Mo KANG ; Won Jung KOH ; Hyoung Suk HAM ; Eun Hae KANG ; O Jung KWON ; Yang Deok LEE ; Heung Bum LEE ; Yong Chul LEE ; Yang Keun RHEE ; Won Hyuk SHIN ; Sung Yeon KWON ; Woo Jin KIM ; Chul Gyu YOO ; Young Whan KIM ; Young Soo SHIM ; Sung Koo HAN ; Hye Kyung PARK ; Yun Seong KIM ; Min Ki LEE ; Soon Kew PARK ; Mi Hye KIM ; Won Yeon LEE ; Suk Joong YONG ; Kye Chul SHIN ; Byoung Whui CHOI ; Yeon Mok OH ; Chae Man LIM ; Sang Do LEE ; Woo Sung KIM ; Dong Soon KIM ; Sung Soo JUNG ; Ju Ock KIM ; Young Chun KO ; Young Chul KIM ; Nam Soo YOO
Tuberculosis and Respiratory Diseases 2005;58(5):498-506
BACKGROUND: This study compared the bronchodilator efficacy and safety of tiotropium inhalation capsules (18microgram once daily) with a ipratropium metered dose inhaler (2 puffs of 20microgram q.i.d.) in patients with chronic obstructive pulmonary disease (COPD). METHOD: After the initial screening assessment and a two-week run-in period, patients received either tiotropium 18microgram once daily or ipratropium 40microgram four times daily over a period of 4 weeks in a double blind, double dummy, parallel group study. The outcome measures were the lung function, the daily records of the peak expiratory flow rate (PEFR), the patients' questionnaire, and the use of concomitant salbutamol. The forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC) were measured 5 minutes before inhalation, and 0.5, 1, 2 and 3 hours after inhaling the study drug on days 0, 14 and 28. RESULT: In 16 centers, 134 patients with a mean (SD) age of 66 (7) years and a predicted FEV1 of 42 (12)% were analyzed. The trough FEV1 response was significantly higher in the tiotropium group than in the ipratropium group after a four-week treatment period. The weekly mean morning PEFR of the tiotropium group was consistently higher than that of the ipratropium group during the 4-week treatment period with differences ranging from 12.52 to 13.88 l/min, which were statistically significant. Tiotropium was well tolerated by the COPD patients during the 4-week treatment period and had a similar safety profile to ipratropium. CONCLUSION: This study shows that tiotropium administrated once daily has a superior bronchodilator effect with a similar safety profile in treating COPD patients compared with ipratropium, inhaled four times daily.
Adult*
;
Albuterol
;
Bronchodilator Agents
;
Capsules
;
Forced Expiratory Volume
;
Humans
;
Inhalation
;
Ipratropium*
;
Lung
;
Mass Screening
;
Metered Dose Inhalers
;
Outcome Assessment (Health Care)
;
Peak Expiratory Flow Rate
;
Pulmonary Disease, Chronic Obstructive*
;
Surveys and Questionnaires
;
Vital Capacity
;
Tiotropium Bromide

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