1.p27 Cell Cycle Inhibitor and Survival in Luminal-Type Breast Cancer:Gene Ontology, Machine Learning, and Drug Screening Analysis
In Ah PARK ; Yung-Kyun NOH ; Kyueng-Whan MIN ; Dong-Hoon KIM ; Jeong-Yeon LEE ; Byoung Kwan SON ; Mi Jung KWON ; Myung-Hoon HAN ; Joon Young HUR ; Jung Soo PYO
Journal of Breast Cancer 2024;27(5):305-322
Purpose:
A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer.
Methods:
Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed.
Results:
Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs.
Conclusion
The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.
2.p27 Cell Cycle Inhibitor and Survival in Luminal-Type Breast Cancer:Gene Ontology, Machine Learning, and Drug Screening Analysis
In Ah PARK ; Yung-Kyun NOH ; Kyueng-Whan MIN ; Dong-Hoon KIM ; Jeong-Yeon LEE ; Byoung Kwan SON ; Mi Jung KWON ; Myung-Hoon HAN ; Joon Young HUR ; Jung Soo PYO
Journal of Breast Cancer 2024;27(5):305-322
Purpose:
A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer.
Methods:
Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed.
Results:
Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs.
Conclusion
The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.
3.p27 Cell Cycle Inhibitor and Survival in Luminal-Type Breast Cancer:Gene Ontology, Machine Learning, and Drug Screening Analysis
In Ah PARK ; Yung-Kyun NOH ; Kyueng-Whan MIN ; Dong-Hoon KIM ; Jeong-Yeon LEE ; Byoung Kwan SON ; Mi Jung KWON ; Myung-Hoon HAN ; Joon Young HUR ; Jung Soo PYO
Journal of Breast Cancer 2024;27(5):305-322
Purpose:
A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer.
Methods:
Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed.
Results:
Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs.
Conclusion
The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.
4.Establishment of a registry of clinical data and bioresources for rare nervous system diseases
Dayoung KIM ; Sooyoung KIM ; Jin Myoung SEOK ; Kyong Jin SHIN ; Eungseok OH ; Mi Young JEON ; Joungkyu PARK ; Hee Jin CHANG ; Jinyoung YOUN ; Jeeyoung OH ; Eunhee SOHN ; Jinse PARK ; Jin Whan CHO ; Byoung Joon KIM
Osong Public Health and Research Perspectives 2024;15(2):174-181
Rare diseases are predominantly genetic or inherited, and patients with these conditions frequently exhibit neurological symptoms. Diagnosing and treating many rare diseases is a complex challenge, and their low prevalence complicates the performance of research, which in turn hinders the advancement of therapeutic options. One strategy to address this issue is the creation of national or international registries for rare diseases, which can help researchers monitor and investigate their natural progression. In the Republic of Korea, we established a registry across 5 centers that focuses on 3 rare diseases, all of which are characterized by gait disturbances resulting from motor system dysfunction. The registry will collect clinical information and human bioresources from patients with amyotrophic lateral sclerosis, spinocerebellar ataxia, and hereditary spastic paraplegia. These resources will be stored at ICreaT and the National Biobank of Korea. Once the registry is complete, the data will be made publicly available for further research. Through this registry, our research team is dedicated to identifying genetic variants that are specific to Korean patients, uncovering biomarkers that show a strong correlation with clinical symptoms, and leveraging this information for early diagnosis and the development of treatments.
5.Comparison of Iohexol-380 and Iohexol-350 for Coronary CT Angiography: A Multicenter, Randomized, Double-Blind Phase 3 Trial.
Eun Ah PARK ; Whal LEE ; Doo Kyoung KANG ; Sung Jin KIM ; Young Ju KIM ; Yookyung KIM ; Yon Mi SUNG ; Soon Young SONG ; Yu Whan OH ; Hwan Seok YONG ; Heon LEE ; Eui Yong JEON ; Gong Yong JIN ; Byoung Wook CHOI ; Sang Il CHOI
Korean Journal of Radiology 2016;17(3):330-338
OBJECTIVE: This multi-center, randomized, double-blind, phase 3 trial was conducted to compare the safety and efficacy of contrast agents iohexol-380 and iohexol-350 for coronary CT angiography in healthy subjects. MATERIALS AND METHODS: Volunteers were randomized to receive 420 mgI/kg of either iohexol-350 or iohexol-380 using a flow rate of 4 mL/sec. All adverse events were recorded. Two blinded readers independently reviewed the CT images and conflicting results were resolved by a third reader. Luminal attenuations (ascending aorta, left main coronary artery, and left ventricle) in Hounsfield units (HUs) and image quality on a 4-point scale were calculated. RESULTS: A total of 225 subjects were given contrast media (115 with iohexol-380 and 110 with iohexol-350). There was no difference in number of adverse drug reactions between groups: 75 events in 56 (48.7%) of 115 subjects in the iohexol-380 group vs. 74 events in 51 (46.4%) of 110 subjects in the iohexol-350 group (p = 0.690). No severe adverse drug reactions were recorded. Neither group showed an increase in serum creatinine. Significant differences in mean density between the groups was found in the ascending aorta: 375.8 ± 71.4 HU with iohexol-380 vs. 356.3 ± 61.5 HU with iohexol-350 (p = 0.030). No significant differences in image quality scores between both groups were observed for all three anatomic evaluations (all, p > 0.05). CONCLUSION: Iohexol-380 provides improved enhancement of the ascending aorta and similar attenuation of the coronary arteries without any increase in adverse drug reactions, as compared with iohexol-350 using an identical amount of total iodine.
Angiography*
;
Aorta
;
Contrast Media
;
Coronary Vessels
;
Creatinine
;
Drug-Related Side Effects and Adverse Reactions
;
Image Enhancement
;
Iodine
;
Phenobarbital
;
Volunteers
6.Serrated Adenoma with Adenocarcinoma of Stomach Treated by Endoscopic Submucosal Dissection.
Byoung Whan PARK ; Tae Yeong LEE ; Min Sung KIM ; Jong Hyeon LEE ; Ki Soo KIM ; Jin Sook LEE
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2016;16(3):156-159
Since the first case of gastric serrated adenoma found in 2001, 35 additional cases have been reported. Among these cases, 26 cases were associated with invasive adenocarcinoma within the serrated adenoma. Gastric serrated adenoma when compared with traditional adenoma has close correlation with invasive carcinoma. Serrated colorectal polyps are classified as hyperplastic polyps, sessile serrated adenoma/polyps, and tranditional serrated adenoma (TSA) depending on histological features. Two distinct phenotypes of TSA in the colon and rectum are reported. Those are unlocked serrated crypts (US-TSA) and ectopic crypt formations (ECFs). All gastric serrated adenoma are TSA in historical aspect and ECFs on phenotype. Whereas gastric adenomas are reported with high frequency in the antrum, gastric serrated adenomas are founded in the body and cardia. We report a case of a 60-year-old woman receiving endoscopic submucosal dissection for gastric serrated adenoma with adenocarcinoma discovered during routine screening.
Adenocarcinoma*
;
Adenoma*
;
Cardia
;
Colon
;
Female
;
Humans
;
Mass Screening
;
Middle Aged
;
Phenotype
;
Polyps
;
Pyloric Antrum
;
Rectum
;
Stomach*
7.Could One-Hand Compression for a Small Child Cause Intra-abdominal Injuries?.
Dong A KIM ; Yeon Ho YOU ; Yong Chul CHO ; Seung RYU ; Jin Woong LEE ; Seung Whan KIM ; In Sool YOO ; Won Joon JEONG ; Jungsang MIN ; Ji Sook LEE ; Jin Hong MIN ; Seong Soo PARK ; Byoung Gil YOON
Journal of the Korean Society of Emergency Medicine 2014;25(4):349-355
PURPOSE: We examined the question of whether one-hand chest compression for a small child could compress intraabdominal organs. METHODS: We retrospectively examined medical charts and multidirectional computed tomography (MDCT) images obtained from children aged 1 to 18 years who presented to the hospital from March 2002 to March 2012. We measured the length of the sternum (Stotal) and the length of the lower half of the sternum (Stotal/2~X). We also measured the distance from the diaphragm to the midpoint of the sternum (Stotal/2~D) and half the width of an adult hand (Wtotal/2). Finally, we counted the number of instances at each age in which Stotal/2~X and Stotal/2~D were less than Wtotal/2. RESULTS: This study included records and MDCT images for 301 children with a mean age of 12.05+/-5.59 years. We also enrolled 47 adult rescuers (25 men, 53.2%) with a mean age of 23.20+/-2.13 years. The mean Wtotal/2 was 4.62+/-0.46 cm. All 1-year-old children had Stotal/2~X and Stotal/2~D less than Wtotal/2. Among children aged 2 years, six (60.0%) had Stotal/2~X and Stotal/2~D less than Wtotal/2. Among children aged 3 years, four (26.7%) had Stotal/2~X and Stotal/2~D less than Wtotal/2, and among those aged 4 years, two (13.3%) had Stotal/2~X and Stotal/2~D less than Wtotal/2. However, Stotal/2~X and Stotal/2~D were greater than Wtotal/2 in children aged 5 years or more. CONCLUSION: Our measurements indicate that one-hand chest compression for a small child could cause intraabdominal organ injury.
Adult
;
Cardiopulmonary Resuscitation
;
Child*
;
Diaphragm
;
Hand
;
Humans
;
Male
;
Retrospective Studies
;
Sternum
;
Thorax
8.Trends in the Incidence of Hospitalized Acute Myocardial Infarction and Stroke in Korea, 2006-2010.
Rock Bum KIM ; Byoung Gwon KIM ; Yu Mi KIM ; Jeong Wook SEO ; Young Shil LIM ; Hee Sook KIM ; Hey Jean LEE ; Ji Young MOON ; Keon Yeop KIM ; Ji Yeon SHIN ; Hyeung Keun PARK ; Jung Kook SONG ; Ki Soo PARK ; Baek Geun JEONG ; Chan Gyeong PARK ; Hee Young SHIN ; Jong Won KANG ; Gyung Jae OH ; Young Hoon LEE ; In Whan SEONG ; Weon Seob YOO ; Young Seoub HONG
Journal of Korean Medical Science 2013;28(1):16-24
This study attempted to calculate and investigate the incidence of hospitalized acute myocardial infarction (AMI) and stroke in Korea. Using the National Health Insurance claim data, we investigated patients whose main diagnostic codes included AMI or stroke during 2006 to 2010. As a result, we found out that the number of AMI hospitalized patients had decreased since 2006 and amounted to 15,893 in 2010; and that the number of those with stroke had decreased since 2006 and amounted to 73,501 in 2010. The age-standardized incidence rate of hospitalized AMI, after adjustment for readmission, was 41.6 cases per 100,000-population in 2006, and had decreased to 29.4 cases in 2010 (for trend P < 0.001). In the case of stroke was estimated at 172.8 cases per 100,000-population in 2006, and had decreased to 135.1 cases in 2010 (for trend P < 0.001). In conclusion, the age-standardized incidence rates of both hospitalized AMI and stroke in Korea had decreased continuously during 2006 to 2010. We consider this decreasing trend due to the active use of pharmaceuticals, early vascular intervention, and the national cardio-cerebrovascular disease care project as the primary and secondary prevention efforts.
Acute Disease
;
Adolescent
;
Adult
;
Age Factors
;
Aged
;
Aged, 80 and over
;
Child
;
Child, Preschool
;
Female
;
Hospitalization/*trends
;
Humans
;
Incidence
;
Infant
;
Infant, Newborn
;
Male
;
Middle Aged
;
Myocardial Infarction/*epidemiology
;
Patient Readmission
;
Republic of Korea/epidemiology
;
Sex Factors
;
Stroke/*epidemiology
;
Young Adult
9.Treatment Response and Long Term Follow-up Results of Nonspecific Interstitial Pneumonia.
Ji Yeon LEE ; Sang Man JIN ; Byoung Jun LEE ; Doo Hyun CHUNG ; Bo Gun JANG ; Heae Surng PARK ; Sang Min LEE ; Jae Joon YIM ; Seok Chul YANG ; Chul Gyu YOO ; Sung Koo HAN ; Young Soo SHIM ; Young Whan KIM
Journal of Korean Medical Science 2012;27(6):661-667
The purpose of this study was to investigate the long-term clinical course of non-specific interstitial pneumonia (NSIP) and to determine which factors are associated with a response to steroid therapy and relapse. Thirty-five patients with pathologically proven NSIP were included. Clinical, radiological, and laboratory data were reviewed retrospectively. The male-to-female ratio was 7:28 (median age, 52 yr). Thirty (86%) patients responded to steroid therapy, and the median follow-up was 55.2 months (range, 15.9-102.0 months). Five patients (14%) showed sustained disease progression and three died despite treatment. In the five with sustained disease progression, NSIP was associated with various systemic conditions, and the seropositivity of fluorescent antinuclear antibody was significantly associated with a poor response to steroids (P = 0.028). The rate of relapse was 25%, but all relapsed patients improved after re-treatment. The initial dose of steroids was significantly low in the relapse group (P = 0.020). In conclusion, progression is associated with various systemic conditions in patients who show progression. A low dose of initial steroids is significantly associated with relapse.
Adult
;
Aged
;
Antibodies, Antinuclear/blood
;
Female
;
Follow-Up Studies
;
Humans
;
Idiopathic Interstitial Pneumonias/drug therapy/pathology
;
Lung Diseases, Interstitial/*drug therapy/mortality/pathology
;
Male
;
Middle Aged
;
Prognosis
;
Recurrence
;
Retrospective Studies
;
Steroids/*therapeutic use
10.Efficacy and Safety of Paliperidone Extended Release in Schizophrenia Patients Requiring a Switch in Antipsychotic Medication by Switching Previous Antipsychotics to Paliperidone Extended Release.
Young Seon MOON ; Kyoung Sae NA ; Chul Eung KIM ; Yong Sik KIM ; Jin Sang YOON ; Yong Min AHN ; Hee Yeon JUNG ; Bum Hee YU ; Yang Whan JEON ; Sang Kyu LEE ; Jeong Ho SEOK ; Byoung Joo HAM ; Doo Byung PARK ; Hyun KIM ; Byung Wook LEE ; Chang Hyung HONG ; Jong Woo KIM ; Jin Hee HAN
Korean Journal of Psychopharmacology 2012;23(3):97-106
OBJECTIVE: This study aimed to evaluate the clinical efficacy, safety, and tolerability of paliperidone extended release (ER) in patients with schizophrenia by switching previous antipsychotics to paliperidone ER. METHODS: An open-label, 24 weeks, prospective, non-comparative, multi-center study evaluated total 387 patients with schizophrenia requiring a switch in antipsychotic medication due to suboptimal efficacy, intolerability, and non-compliance. Patients were switched to flexible-dose trial of paliperidone ER (3-12 mg/day). Efficacy was measured by Krawiecka Scale, Clinical Global Impression-Schizophrenia-Severity (CGI-SCH-S), Clinical Global Impression-Schizophrenia-Improvement (CGI-SCH-I), sleep visual analog scale (VAS), and Personal and Social Performance Scale (PSP). Safety assessments included adverse events (AEs), evaluation of extrapyramidal symptoms (EPS) using the Drug Induced Extrapyramidal Symptoms Scale (DIEPSS), and laboratory tests. RESULTS: Data from a total of 321 subjects who took the paliperidone ER and had at least one follow-up assessment without a major protocol violation were analyzed. Switching to paliperidone ER led to a significant improvement in the Krawiecka, CGI-SCH-S, CGI-SCH-I, PSP, and DIEPSS scales. However, serum prolactin levels and metabolic parameters including body weight and waist circumference were significantly increased. Insomnia was the most common adverse event. CONCLUSION: This study suggested that patients with schizophrenia who showed insufficient response or intolerance to other previous antipsychotics can be switched to paliperidone ER, with efficacy, safety, and tolerability.
Antipsychotic Agents
;
Body Weight
;
Follow-Up Studies
;
Humans
;
Isoxazoles
;
Prolactin
;
Prospective Studies
;
Pyrimidines
;
Schizophrenia
;
Sleep Initiation and Maintenance Disorders
;
Waist Circumference
;
Weights and Measures

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