1.A Phase 3 Randomized Clinical Trial to Compare Efficacy and Safety between Combination Therapy and Monotherapy in Elderly Patients with Advanced Gastric Cancer (KCSG ST13-10)
Keun-Wook LEE ; Dae Young ZANG ; Min-Hee RYU ; Hye Sook HAN ; Ki Hyang KIM ; Mi-Jung KIM ; Sung Ae KOH ; Sung Sook LEE ; Dong-Hoe KOO ; Yoon Ho KO ; Byeong Seok SOHN ; Jin Won KIM ; Jin Hyun PARK ; Byung-Ho NAM ; In Sil CHOI
Cancer Research and Treatment 2023;55(4):1250-1260
Purpose:
This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy.
Materials and Methods:
Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy.
Results:
After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%.
Conclusion
Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.
2.TM4SF4 and LRRK2 Are Potential Therapeutic Targets in Lung and Breast Cancers through Outlier Analysis
Kyungsoo JUNG ; Joon-Seok CHOI ; Beom-Mo KOO ; Yu Jin KIM ; Ji-Young SONG ; Minjung SUNG ; Eun Sol CHANG ; Ka-Won NOH ; Sungbin AN ; Mi-Sook LEE ; Kyoung SONG ; Hannah LEE ; Ryong Nam KIM ; Young Kee SHIN ; Doo-Yi OH ; Yoon-La CHOI
Cancer Research and Treatment 2021;53(1):9-24
Purpose:
To find biomarkers for disease, there have been constant attempts to investigate the genes that differ from those in the disease groups. However, the values that lie outside the overall pattern of a distribution, the outliers, are frequently excluded in traditional analytical methods as they are considered to be ‘some sort of problem.’ Such outliers may have a biologic role in the disease group. Thus, this study explored new biomarker using outlier analysis, and verified the suitability of therapeutic potential of two genes (TM4SF4 and LRRK2).
Materials and Methods:
Modified Tukey’s fences outlier analysis was carried out to identify new biomarkers using the public gene expression datasets. And we verified the presence of the selected biomarkers in other clinical samples via customized gene expression panels and tissue microarrays. Moreover, a siRNA-based knockdown test was performed to evaluate the impact of the biomarkers on oncogenic phenotypes.
Results:
TM4SF4 in lung cancer and LRRK2 in breast cancer were chosen as candidates among the genes derived from the analysis. TM4SF4 and LRRK2 were overexpressed in the small number of samples with lung cancer (4.20%) and breast cancer (2.42%), respectively. Knockdown of TM4SF4 and LRRK2 suppressed the growth of lung and breast cancer cell lines. The LRRK2 overexpressing cell lines were more sensitive to LRRK2-IN-1 than the LRRK2 under-expressing cell lines
Conclusion
Our modified outlier-based analysis method has proved to rescue biomarkers previously missed or unnoticed by traditional analysis showing TM4SF4 and LRRK2 are novel target candidates for lung and breast cancer, respectively.
3.Dieckol, a Component of Ecklonia cava, Suppresses the Production of MDC/CCL22 via Down-Regulating STAT1 Pathway in Interferon-gamma Stimulated HaCaT Human Keratinocytes.
Na Jin KANG ; Dong Hwan KOO ; Gyeoung Jin KANG ; Sang Chul HAN ; Bang Won LEE ; Young Sang KOH ; Jin Won HYUN ; Nam Ho LEE ; Mi Hee KO ; Hee Kyoung KANG ; Eun Sook YOO
Biomolecules & Therapeutics 2015;23(3):238-244
Macrophage-derived chemokine, C-C motif chemokine 22 (MDC/CCL22), is one of the inflammatory chemokines that controls the movement of monocytes, monocyte-derived dendritic cells, and natural killer cells. Serum and skin MDC/CCL22 levels are elevated in atopic dermatitis, which suggests that the chemokines produced from keratinocytes are responsible for attracting inflammatory lymphocytes to the skin. A major signaling pathway in the interferon-gamma (IFN-gamma)-stimulated inflammation response involves the signal transducers and activators of transcription 1 (STAT1). In the present study, we investigated the anti-inflammatory effect of dieckol and its possible action mechanisms in the category of skin inflammation including atopic dermatitis. Dieckol inhibited MDC/CCL22 production induced by IFN-gamma (10 ng/mL) in a dose dependent manner. Dieckol (5 and 10 muM) suppressed the phosphorylation and the nuclear translocation of STAT1. These results suggest that dieckol exhibits anti-inflammatory effect via the down-regulation of STAT1 activation.
Chemokine CCL22
;
Chemokines
;
Dendritic Cells
;
Dermatitis, Atopic
;
Down-Regulation
;
Humans
;
Inflammation
;
Interferon-gamma*
;
Keratinocytes*
;
Killer Cells, Natural
;
Lymphocytes
;
Monocytes
;
Phosphorylation
;
Skin
;
Transducers
4.Impact of immunosuppressant therapy on early recurrence of hepatocellular carcinoma after liver transplantation.
Ju Yeun LEE ; Yul Hee KIM ; Nam Joon YI ; Hyang Sook KIM ; Hye Suk LEE ; Byung Koo LEE ; Hyeyoung KIM ; Young Rok CHOI ; Geun HONG ; Kwang Woong LEE ; Kyung Suk SUH
Clinical and Molecular Hepatology 2014;20(2):192-203
BACKGROUND/AIMS: The most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated. METHODS: Ninety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 +/- 1.3 ng/mL (mean +/- SD). RESULTS: The 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P<0.05). High AFP and PIVKA-II levels, and positive 18fluoro-2-deoxy-d-glucose positron-emission tomography findings were significantly associated with 3-year recurrence (P<0.05). CONCLUSIONS: Induction therapy with basiliximab, a strong immunosuppressant, may have a negative impact with respect to early HCC recurrence (i.e., within 1 year) in high-risk patients.
Adult
;
Aged
;
Biological Markers/analysis
;
Carcinoma, Hepatocellular/mortality/pathology/*therapy
;
Female
;
Humans
;
Immunosuppressive Agents/*therapeutic use
;
Liver Neoplasms/mortality/pathology/*therapy
;
*Liver Transplantation
;
Male
;
Middle Aged
;
Neoplasm Recurrence, Local
;
Positron-Emission Tomography
;
Protein Precursors/analysis
;
Prothrombin/analysis
;
Regression Analysis
;
Risk Factors
;
Severity of Illness Index
;
Survival Rate
;
alpha-Fetoproteins/analysis
5.Effect of Peritoneal Dialysis Modality on the 1-Year Rate of Decline of Residual Renal Function.
Chan Ho KIM ; Hyung Jung OH ; Mi Jung LEE ; Young Eun KWON ; Yung Ly KIM ; Ki Heon NAM ; Kyoung Sook PARK ; Seong Yeong AN ; Kwang Il KO ; Hyang Mo KOO ; Fa Mee DOH ; Seung Hyeok HAN ; Tae Hyun YOO ; Beom Seok KIM ; Shin Wook KANG ; Kyu Hun CHOI
Yonsei Medical Journal 2014;55(1):141-148
PURPOSE: The effect of different peritoneal dialysis (PD) modalities on the decline in residual renal function (RRF) is unclear due to inconsistencies among studies. In particular, the effect of automated peritoneal dialysis (APD) modalities [continuous cyclic peritoneal dialysis (CCPD) and nightly intermittent peritoneal dialysis (NIPD)] on RRF has not been examined in a large cohort. MATERIALS AND METHODS: We conducted a single-center retrospective study to investigate the association between PD modalities and decline in RRF in 142 incident PD patients [34 on CCPD, 36 on NIPD, and 72 on continuous ambulatory peritoneal dialysis (CAPD)]. RRF was measured within 2 months from PD start and at 1 year after PD initiation. RESULTS: The RRF at 1 year after PD initiation was 1.98+/-2.20 mL/min/1.73 m2 in CCPD patients and 3.63+/-3.67 mL/min/1.73 m2 in NIPD patients, which were moderately lower than 4.23+/-3.51 mL/min/1.73 m2 in CAPD patients (p=0.064). Moreover, there was no significant difference in the 1-year rate of decline of RRF between CCPD and NIPD patients, although APD patients had a faster 1-year RRF decline rate than CAPD patients (CCPD and NIPD vs. CAPD: -45.68 and -36.69 vs. 1.17%/year, p=0.045). APD was associated with a more rapid decline in RRF in patients with end-stage renal disease undergoing PD, although multivariate analysis attenuated the significance of this finding (beta=-31.50; 95% CI, -63.61 to 0.62; p=0.052). CONCLUSION: Our results suggest that CAPD might be more helpful than APD for preserving RRF during the first year of dialysis therapy, although there was no significant difference in the 1-year rate of decline of RRF between the two APD modalities.
Adult
;
Female
;
Glomerular Filtration Rate/physiology
;
Humans
;
Kidney/pathology/physiopathology
;
Kidney Failure, Chronic/*therapy
;
Male
;
Middle Aged
;
Peritoneal Dialysis/*adverse effects
;
Retrospective Studies
6.Trends in Antibiotic Use in a Single University Hospital.
Kang Il JUN ; Hei Lim KOO ; Min Kyung KIM ; Chang Kyung KANG ; Min Jae KIM ; Shin Hye CHUN ; Jung Sook SONG ; Hyang Sook KIM ; Nam Joong KIM ; Eui Chong KIM ; Myoung Don OH
Korean Journal of Nosocomial Infection Control 2013;18(2):44-50
BACKGROUND: The aim of this study was to evaluate antibiotic consumption by adult patients at a single university hospital in Korea between 2001 and 2012. METHODS: We used the 2004 World Health Organization Anatomical Therapeutic Chemical Classification System definition of defined daily doses (DDD) per 1,000 patient-days to calculate the annual antibiotic consumption for 18 antibiotic groups. Chi-square linear-by-linear analysis was performed to evaluate antibiotic consumption trends for each group. RESULTS: Average annual antibiotic consumption during 2001-2012 was 644.6 DDD/1,000 patient-days (standard deviation, 33.3 DDD/1,000 patient-days). Although no statistically significant change was observed during the study period, consumption of first- and second-generation cephalosporins, and aminoglycosides was significantly decreased, while that of beta-lactam/beta-lactamase inhibitors, fourth-generation cephalosporins, carbapenem, glycopeptide, linezolid, colistin, and quinolone increased significantly. CONCLUSION: The total amount of prescribed antibiotics did not change, but the use of broad-spectrum antibiotics increased during the study period.
Adult
;
Aminoglycosides
;
Anti-Bacterial Agents
;
Cephalosporins
;
Classification
;
Colistin
;
Hospitals, University
;
Humans
;
Korea
;
World Health Organization
;
Linezolid
7.Clinical Safety of PMR(Palatal Muscle Resection) In Which Performed OSAS Patients.
Soo Kweon KOO ; Nam Sook MYUNG ; Jang Won CHOI ; Yang Jae KIM ; Soon Bok KWON
Journal of Rhinology 2012;19(2):101-106
BACKGROUND AND OBJECTIVES: The purpose of this study was to analyze clinical safety of PMR(Palatal Muscle Resection) in obstructive sleep apnea patients. MATERIALS AND METHODS: Fourteen Patients underwent only PMR were reviewed retrospectively. ESS(Epworth Sleepiness Scale) was analyzed after PMR surgery to assess surgical results. Visual Analogue Scale were reviewed to evaluate postoperative pain. Eustachian tube function test, voice analysis, and measurement of forced expiration power were done after two months of surgery. RESULTS: ESS were improved after PMR. There were little postoperative pain. There was no significant change is observed vowel sounds except /u/ nor postoperative nasalization in voice, Eustachian tube dysfunction and change of expiration power. CONCLUSION: PMR may be regarded clinically safe surgery in obstructive sleep apnea patient.
Eustachian Tube
;
Humans
;
Muscles
;
Pain, Postoperative
;
Palate
;
Phonation
;
Retrospective Studies
;
Sleep Apnea Syndromes
;
Sleep Apnea, Obstructive
;
Voice
8.Current Status of ADHD Treatment in Children with Epilepsy: A Retrospective, Multicenter, Cross Sectional Analysis in Korea.
So Hee EUN ; Soonhak KWON ; Young Se KWON ; Sung Koo KIM ; WonSeop KIM ; Sang Ook NAM ; Gi Youn SIM ; Baik Lin EUN ; Jun Hwa LEE ; Yun Jung HUR ; Tae Gyu HWANG ; Chan Uhung JOO ; Jung Soo KIM ; Kyeoung Sook KIM ; Sun Jun KIM
Journal of the Korean Child Neurology Society 2011;19(2):93-101
PURPOSE: The purpose of this study was to assess the current therapeutic status of attention deficit-hyperactivity disorder (ADHD) in children with epilepsy. METHODS: A cross-sectional survey of 178 patients aged 4-20 years from ten pediatric neurology clinics in eight cities in South Korea from January 2005 to July 2010 was used to assess clinical characteristics of ADHD patients with epilepsy and risk factors associated with ADHD. RESULTS: A total of 178 pediatric epileptic patients were recruited for this study. One hundred seventy-four subjects' (M:F=4:1, mean age: 12.2+/-3.3 yrs old) records were evaluated excluding four patients due to incomplete data. One hundred twenty-five of 174 patients (71.8%) had partial epilepsy and 45 had generalized epilepsy. Eighty of 112 patients showed ADHD combined type from the DSM IV. The mean prevalence rate of ADHD treatment among the epileptic patients was 1.9%. Over 45% of patients showed complete or persistent symptoms without difficulties in school life with CNS stimulants. Adverse reactions were reported in 19.8% of patients who received ADHD medication, and 18 patients discontinued ADHD medication due to severe adverse effects such as aggravated seizures (5.6%) or ADHD symptoms (3.7%). About 60% of children with ADHD and epilepsy had psychiatric comorbid disorders. CONCLUSION: The results indicate that ADHD treatment in epilepsy patients is safe and effective. However, these data also show that ADHD in pediatric epilepsy patients in Korea is under-diagnosed and under-treated.
Aged
;
Attention Deficit Disorder with Hyperactivity
;
Child
;
Cross-Sectional Studies
;
Epilepsies, Partial
;
Epilepsy
;
Epilepsy, Generalized
;
Humans
;
Korea
;
Neurology
;
Prevalence
;
Republic of Korea
;
Retrospective Studies
;
Risk Factors
;
Seizures
9.A Case of Bronchiectasis with Elevated Serum CA 125 Level.
Bong Chul SHIN ; Tae Hyoung KOO ; Sang Ock KIM ; Hsing Chien TER ; Soo Jung UM ; Soo Keol LEE ; Choonhee SON ; Ki Nam KIM ; Ki Nam LEE ; Mee Sook ROH ; Pil Jo CHOI
Tuberculosis and Respiratory Diseases 2009;66(6):467-470
Serum CA 125 is the most useful marker for monitoring patients with epithelial ovarian cancer. However, it can be elevated above normal level in a variety of conditions other than ovarian cancer such as endometriosis, pelvic inflammation disease, and other malignant or nonmalignant disorders, including pulmonary diseases. Recently, we experienced a case of bronchiectasis in which the serum CA 125 level was elevated, changing with the patient's condition. There was no evidence of underlying malignant disease on positron emission tomography or on gynecologic examination, including transvaginal ultrasonography. During follow-up for 14 months, we could not find any clue of malignant disease that could have been the cause of the elevated levels of serum CA 125. Elevated serum CA 125 level should be interpreted carefully according to the patient's clinical condition. In addition, our case suggests that CA 125 may be used as a surrogate marker for acute inflammatory status for chronic pulmonary diseases.
Biomarkers
;
Bronchiectasis
;
CA-125 Antigen
;
Endometriosis
;
Female
;
Follow-Up Studies
;
Humans
;
Inflammation
;
Lung Diseases
;
Neoplasms, Glandular and Epithelial
;
Ovarian Neoplasms
;
Positron-Emission Tomography
10.An Acoustic and Radiologic Study on Voice Change after Uvulopalatopharyngoplasty (UPPP).
Nam Sook MYUNG ; Soo Kweon KOO ; Cheol Woo HAN ; Hyung Joo LEE ; Bum Seok PARK ; Soon Bok KWON
Korean Journal of Otolaryngology - Head and Neck Surgery 2009;52(1):46-50
BACKGROUND AND OBJECTIVES: Many people have been concerned about the voice change after uvulopalatopharyngoplasty (UPPP). A number of studies reported acoustic changes after UPPP. However, there have not been any reports regarding the association of anatomic changes and acoustic results after UPPP. The purpose of this study is to analyze changes of the voice and changes in the vocal tract after UPPP and to evaluate whether the anatomical changes of vocal tract have an effect on the voice change or not. SUBJECTS AND METHOD: By using computerized speech laboratory (CSL), we analyzed fourteen UPPP cases on the formant frequencies of six vowels (/a/, /i/, /u/, /o/, /e/) and three nasal consonants (/eom/, /eoung/, /kin/). By using MR image, we analyzed the changes of vocal tract four weeks after UPPP with preoperative findings in one case. RESULTS: In acoustic analysis, the second formant frequencies of /i/ and /u/ phonation were significantly reduced postoperatively compared to those of preoperative status. In imaging study of /i/ and /u/, the soft palate were contracted along with the widening of the oropharynx and the tongue was shifted toward posterior pharyngeal wall to compensate. CONCLUSION: UPPP reduced the second formant of /i/ and /u/, which did not result in serious voice change.
Acoustics
;
Contracts
;
Oropharynx
;
Palate
;
Palate, Soft
;
Phonation
;
Sleep Apnea, Obstructive
;
Tongue
;
Voice

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