1.Histone Deacetylase as a Valuable Predictive Biomarker and Therapeutic Target in Immunotherapy for Non-Small Cell Lung Cancer
Hyun-Seock SHIN ; Juwhan CHOI ; Jinhwan LEE ; Sung Yong LEE
Cancer Research and Treatment 2022;54(2):458-468
Purpose:
Histone deacetylase inhibitors (HDACis) are epigenetic regulators and used clinically for hematopoietic malignancies. Recently, HDACis have received attention as a factor that modulates the immune system. In this study, the role of histone deacetylase (HDAC) expression as a predictive marker in lung cancer patients who were treated with immune checkpoint inhibitors (ICIs) and the role of HDACi and ICI combination treatment in the mouse tumor model were analyzed.
Materials and Methods:
The overall response rate (ORR) and progression-free survival (PFS) were analyzed by the expression of HDAC. In vitro assay, the mRNA and protein expression levels of cytokines and programmed death-ligand 1 (PD-L1) were analyzed after HDACi treatment. In vivo assay, TC-1 tumor-bearing mice were treated with HDACi and mouse programmed cell death 1 (PD-1) inhibitor.
Results:
The HDAC6 low expression group showed high ORR and prolonged PFS. When the selective HDAC6 inhibitor was administered to the A549 cell line, the levels of interleukin-1β and interleukin-6 decreased and the expression of PD-L1 was reduced. Mice that received both the mouse PD-1 inhibitor and pan-HDACi had a smaller tumor size than that of the mice from the control group. Moreover, mice treated with the mouse PD-1 inhibitor and pan-HDACi generated greater numbers of E7-specific CD8+ T cells.
Conclusion
HDAC6 expression can predict the prognosis of non–small cell lung cancerpatients who were treated with ICIs. Furthermore, co-treatment with HDACi and PD-1 inhibitor was shown to decrease the tumor growth rate and create a favorable tumor microenvironment for cytotoxic T lymphocytes in the TC-1 mouse model.
2.Association between Alcohol Consumption and hsCRP in Korean Adults.
Yang Hyun JO ; Eun Young CHOI ; Yoo Seock CHEONG ; Eal Whan PARK ; Jae Hun KIM
Journal of the Korean Academy of Family Medicine 2007;28(10):768-773
BACKGROUND: Cardiovascular diseases are major cause of death. In many countries, several studies reported moderate alcohol drink reduces cardiovascular diseases. High sensitivity C-reactive protein (hsCRP) is useful as a biochemical marker that can evaluate the risk of cardiovascular diseases. This study investigated the association between alcohol consumption and hsCRP. METHODS: The subjects included 769 men and 449 women who had visited a health promotion center in one university hospital from May 2006 to June 2006. They responded to self-reported questionnaire on past medical history, quantity and frequency of alcohol intake. Blood sample was taken to examine hsCRP, total cholesterol, HDL cholesterol, and triglyceride. The participants were classified into 4 groups in males and 3 groups in females by alcohol intake quantity. Using general linear model, analysis of covariance was done to evaluate the association between hsCRP and alcohol intake quantity after adjusting for smoking, body mass index, blood pressure, age, total cholesterol, HDL cholesterol, and triglycerides. RESULTS: Men who had drunk 1~4 drinks weekly had the lowest hsCRP. And a U-shaped correlation between alcohol intake quantity and hsCRP was found (P for U- shape trend test=0.059). In women, hsCRP decreased as the alcohol intake quantity increased (P for linear trend test= 0.0002). CONCLUSION: In Korean males, U-shaped relationship was found between hsCRP and alcohol intake quantity. In Korean females, inverse relationship was found between them.
Adult*
;
Alcohol Drinking*
;
Biomarkers
;
Blood Pressure
;
Body Mass Index
;
C-Reactive Protein
;
Cardiovascular Diseases
;
Cause of Death
;
Cholesterol
;
Cholesterol, HDL
;
Female
;
Health Promotion
;
Humans
;
Linear Models
;
Male
;
Smoke
;
Smoking
;
Triglycerides
;
Surveys and Questionnaires
3.Effects of BATHE Interview Protocol on Patient Satisfaction.
Ji Hyun KIM ; Yoon Na PARK ; Eal Whan PARK ; Yoo Seock CHEONG ; Eun Young CHOI
Korean Journal of Family Medicine 2012;33(6):366-371
BACKGROUND: BATHE, the acronym for background, affect, trouble, handling, and empathy, is an interview approach that can be applied in the out-patient setting whereby questions belonging to each of the 5 categories are asked in the above order. As we have been taught to believe that BATHE raises the level of patient satisfaction and the quality of medical treatment overall, this study was designed to test the validity of the claim that applying BATHE heightens patient satisfaction. METHODS: Each of the 5 doctors was assigned 10 patients (5 in the BATHE group and the other 5 in the control group) with each patient being randomly assigned to either of the groups. The control group was interviewed as usual and the BATHE group was interviewed using BATHE. Immediately after the interview, each patient anonymously filled out a patient satisfaction questionnaire. Whether the questions asked were appropriate for each category of the protocol was evaluated by the researcher through video clips taped during the interviews. RESULTS: On 7 out of 10 items on the patient satisfaction questionnaire, the BATHE group was found to experience higher level of satisfaction than the control group in a statistically significant manner. The questions asked the BATHE group were confirmed to be more appropriate for each category of the protocol except empathy than those asked the control group. CONCLUSION: As applying the BATHE approach was found to achieve higher level of patient satisfaction, we recommend using it in the out-patient setting.
Anonyms and Pseudonyms
;
Baths
;
Empathy
;
Handling (Psychology)
;
Humans
;
Outpatients
;
Patient Satisfaction
;
Surveys and Questionnaires
4.The Effect of Job Stress in Jobholders on Propensity to Anxiety.
Young Soo CHOI ; Kuk Hyun BAEK ; Sung Ook CHO ; Eun Young CHOI ; Eal Whan PARK ; Yoo Seock CHEONG ; Sun Mi YOO
Journal of the Korean Academy of Family Medicine 2004;25(3):224-232
BACKGROUND: In modern industrial society, the complexity and diversity of social structure has deeply influenced job stress, and thereby threatens mental health of jobholders more than ever. Therefore, the purpose of this study was to examine the effect of job stress in jobholders on propensity of anxiety. METHODS: Initially, 235 jobholders living in Cheonan, Asan or Seoul, from May to June 2003, were the subjects of this questionnaire. Only 233 jobholders were evaluated due to inadequate responses from two subjects. The questionnaire was made up of three contents: socio-demographic characteristic, Extended Karasek questionnaire for evaluation of job stress, and the Korean version of Goldberg anxiety scale for evaluation of anxiety. The data were analyzed by chi-square test and multiple logistic regression analysis. RESULTS: Univariate analysis of propensity to anxiety showed a statistical significance on age, monthly income and job characteristics. Moreover, in terms of multivariate analysis, in accordance with age, 40 to 49 (OR: 6.1), showed the highest odds ratio of propensity to anxiety, followed by 30 to 39 (OR: 5.2) and 10 to 29 (OR: 5.4). In job characteristics, high strain group (OR: 3.7) showed highest odds ratio, but neither low strain group nor active group revealed any statistical significance. In monthly income, there was no statistical significance. CONCLUSION: Job stress in jobholders and propensity to anxiety was positively associated; especially, the more stress jobholders got, the higher propensity to anxiety was.
Anxiety*
;
Chi-Square Distribution
;
Chungcheongnam-do
;
Logistic Models
;
Mental Health
;
Multivariate Analysis
;
Odds Ratio
;
Seoul
;
Surveys and Questionnaires
5.Evaluation of Primary Doctor's Knowledge on Target Level of Blood Pressure in Hypertensive Patients.
Dae Hyun SUNG ; Ki Bo LIM ; Yang Hyun CHO ; Eun Young CHOI ; Eal Whan PARK ; Yoo Seock JUNG ; Jae Hun KIM
Journal of the Korean Academy of Family Medicine 2005;26(8):464-469
BACKGROUND: The purpose of this study was to find out whether primary physicians know the new guidelines (JNC VII) of target BP (blood pressure) and whether they educate their patients properly or not. METHODS: We made calls to local clinicians (family medicine (FM), internal medicine (IM), oriental medicine (OM)) under the disguise of the patient's caretaker and asked them the target BP for patients with hypertension without any cardiovascular disease and those with hypertension and DM (diabetes mellitus). We categorized the participants according to sex, age and departments. RESULTS: Out of the 145 clinics, 88 clinics responded (28 clinicians of FM, 30 clinicians of IM, 30 clinicians of OM). Questions on systolic target BP for patients with hypertension without cardiovascular disease, 87 clinicians answered. Among them, 64 clinicians (73.6%) answered correctly to the target BP (< or =140 mmHg), in the order of FM, IM, and OM. Questions on the diastolic pressure (< or =90 mmHg), 78 clinicians answered and all of them answered correctly. On the question of the target BP for the patients and hypertension and DM, 55 clinicians (63.2%) answered correctly to the systolic target BP (< or =130 mmHg) in the order of IM, FM, and OM. Only 19 clinicians (32.4%) answered correctly to the diastolic target BP (< or =90 mmHg) in the order of FM, IM, and OM. CONCLUSION: The clinicians have given less correct answers on the target BP in the patients and hypertension and DM than those with only essential hypertension. In conclusion, local clinicians should be fully aware of the target BP in patients with hypertension associated with cardiovascular disease or other complications. Also they should educate their patients properly.
Blood Pressure*
;
Cardiovascular Diseases
;
Humans
;
Hypertension
;
Internal Medicine
;
Medicine, East Asian Traditional
6.Individualized Tumor Response Testing for Prediction of Response to Paclitaxel and Cisplatin Chemotherapy in Patients with Advanced Gastric Cancer.
Jee Hyun KIM ; Keun Wook LEE ; Yeul Hong KIM ; Kyung Hee LEE ; Do Youn OH ; Joonhee KIM ; Sung Hyun YANG ; Seock Ah IM ; Sung Ho CHOI ; Yung Jue BANG
Journal of Korean Medical Science 2010;25(5):684-690
The purpose of our study was to determine the most accurate analytic method to define in vitro chemosensitivity, using clinical response as reference standard in prospective clinical trial, and to assess accuracy of adenosine triphosphate-based chemotherapy response assay (ATP-CRA). Forty-eight patients with chemo-naive, histologically confirmed, locally advanced or metastatic gastric cancer were enrolled for the study and were treated with combination chemotherapy of paclitaxel 175 mg/m2 and cisplatin 75 mg/m2 for maximum of six cycles after obtaining specimen for ATP-CRA. We performed the receiver operator characteristic curve analysis using patient responses by WHO criteria and ATP-CRA results to define the method with the highest accuracy. Median progression free survival was 4.2 months (95% confidence interval [CI]: 3.4-5.0) and median overall survival was 11.8 months (95% CI: 9.7-13.8) for all enrolled patients. Chemosensitivity index method yielded highest accuracy of 77.8% by ROC curve analysis, and the specificity, sensitivity, positive and negative predictive values were 95.7%, 46.2%, 85.7%, and 75.9%. In vitro chemosensitive group showed higher response rate (85.7% vs. 24.1%) (P=0.005) compared to chemoresistant group. ATP-CRA could predict clinical response to paclitaxel and cisplatin chemotherapy with high accuracy in advanced gastric cancer patients. Our study supports the use of ATP-CRA in further validation studies.
Adenosine Triphosphate/*analysis
;
Adult
;
Aged
;
Antineoplastic Agents, Phytogenic/administration & dosage
;
Antineoplastic Combined Chemotherapy Protocols/*administration & dosage
;
Cisplatin/administration & dosage
;
Drug Screening Assays, Antitumor/*methods
;
Female
;
Humans
;
Korea
;
Male
;
Middle Aged
;
Outcome Assessment (Health Care)/methods
;
Paclitaxel/administration & dosage
;
Reproducibility of Results
;
Sensitivity and Specificity
;
Stomach Neoplasms/*diagnosis/*drug therapy/metabolism
;
Treatment Outcome
7.Residents' Expectation of Family Medicine-Specific Training Program and Its Current State.
Yong Jun KIM ; Eal Whan PARK ; Yoo Seock CHEONG ; Eun Young CHOI ; Kuk Hyun BAEK ; Hwa Yoen SUNG ; Hong Yeon LEE ; Ji Hyun KIM
Korean Journal of Family Medicine 2011;32(7):390-398
BACKGROUND: The family medicine residency program consists mainly of clinical rotations in other specialties and the family medicine-specific training. We conducted this study to investigate how family medicine residents evaluated their training program that include family-oriented medicine, clinical preventive medicine, behavioral science and research in primary care. METHODS: In 2009, third-year residents of 129 training hospitals in Korea were surveyed to investigate the current state and their expectation of the residency program. The contents of questionnaires included training periods, conferences, procedures, interview techniques, outpatient and inpatient consultations, and written thesis. RESULTS: Total 133 out of 142 residents (93.7%) responded that 3 years of training is ideal or pertinent. Residents responded that the types of conference that they need most are journal review (81%), staff lecture (73.2%), and clinical topic review (73.2%), in that order. Procedures and interview techniques that the residents want to learn most were gastroscopy (72.5%), abdominal ultrasonography (65.2%), and pain management (46.4%). Hospitals where family medicine residents do not see hospitalized patients or patients in the outpatient clinic were 7.9% and 6.5%, respectively, whereas hospitals that maintain continuous family medicine outpatient clinics were only 40.8%. Education in outpatient clinic and articlewriting seminars was done less frequently in the secondary hospitals than in the tertiary hospitals. CONCLUSION: Evaluation and quality improvement of family medicine training program as well as specialty rotations should be considered in order to foster better family physicians. The efforts have to be made to minimize the difference in quality of each family medicine residency program.
Ambulatory Care Facilities
;
Behavioral Sciences
;
Clinical Medicine
;
Congresses as Topic
;
Family Practice
;
Gastroscopy
;
Humans
;
Inpatients
;
Internship and Residency
;
Korea
;
Outpatients
;
Pain Management
;
Physicians, Family
;
Preventive Medicine
;
Quality Improvement
;
Referral and Consultation
8.A Case Report of Breast Cancer with Extensive Pulmonary Lymphovascular Tumor Emboli.
Yaewon YANG ; Younak CHOI ; Seung Hoon BEOM ; Jin Won KIM ; Yoon Kyung JOEN ; Nam Joong KIM ; Joo Hyun KIM ; Seock Ah IM ; Kyung Hun LEE
Journal of Breast Cancer 2012;15(1):128-132
We describe a patient with breast cancer who relapsed with an extensive pulmonary lymphovascular tumor embolism. A 38-year-old female, who previously received neoadjuvant chemotherapy and curative resection of breast cancer, underwent adjuvant chemotherapy and was referred to the emergency room because of sudden-onset pleuritic chest pain lasting for 10 days. Despite a trial of empirical antibiotics, the chest pain and the extent of consolidative lung lesion on chest radiographs rapidly aggravated. We performed an open lung biopsy to confirm the etiology. The histopathological review revealed a hemorrhagic infarction caused by lymphovascular tumor emboli from a metastatic breast carcinoma. Palliative first-line chemotherapy was administered, consisting of ixabepilone and capecitabine, and the lung lesion improved markedly.
Adult
;
Anti-Bacterial Agents
;
Biopsy
;
Breast
;
Breast Neoplasms
;
Chemotherapy, Adjuvant
;
Chest Pain
;
Deoxycytidine
;
Emergencies
;
Epothilones
;
Female
;
Fluorouracil
;
Humans
;
Infarction
;
Lung
;
Neoplastic Cells, Circulating
;
Thorax
;
Capecitabine
9.Is Primary Care of Family Medicine better in Quality than that of Other Specialties?.
Kuk Hyun BAEK ; Eal Whan PARK ; Nam Eui HONG ; Jun Woo JO ; Eun Young CHOI ; Yoo Seock JUNG
Journal of the Korean Academy of Family Medicine 2005;26(7):404-411
BACKGROUND: The purpose of this study was to assess the quality of primary care by patient-completed questionnaire, and to investigate whether the results of the assessment were different among the specialties of doctors (especially family medicine) and according to the existence of a family doctor. METHODS: The questionnaire, which covers 7 components of primary care (accessibility, continuity, accountability, comprehensiveness, integration, sustained partnership with patients, whole person orientation), was administered to the applicants of health screening center of a university hospital, and factory workers in Cheonan, and residents living in Seoul. Statistic analysis was performed through the collected samples. RESULTS: Total of 574 subjects were analyzed. The mean score (%) of each component of the total sample was as follows; accessibility 45.8, continuity 47.8, comprehensiveness 22.5, accountability 55.5, integration 41.8, sustained partnership with patients 48.9, and whole person orientation 31.8. The mean score (%) of all components were 42.0. Doctors were classified into internists, general surgeons, family physicians, general physicians, and others. Family physicians had the best score in accessibility (P=0.01). The mean score of all components of family physicians was better than that of internists and the other specialties (P<0.05). The respondents who had a family doctor was 129 (22.5%). The mean score of each component was higher than those without a family doctor (P<0.05). CONCLUSION: Family physicians are providing high quality primary care compared to internists and other specialists. Patients who have a family doctor are provided with higher quality primary care than those who do not. Especially, comprehensiveness and whole person orientation need to be improved.
Chungcheongnam-do
;
Surveys and Questionnaires
;
Humans
;
Mass Screening
;
Physicians, Family
;
Primary Health Care*
;
Seoul
;
Social Responsibility
;
Specialization
10.Knowledge and Attitude of Family Medicine Residents Towards Evidence-based Medicine.
Sung Ook JO ; Yang Hyun JO ; Eal Whan PARK ; Eun Young CHOI ; Jae Hun KIM ; Yoo Seock CHEONG
Journal of the Korean Academy of Family Medicine 2006;27(12):975-981
BACKGROUND: As medical informations are expanded, searching for useful information has become ever more important. Presently, teaching EBM (evidence-based medicine) is emphasiged. The purpose of this study was to survey family medicine residents' knowledge and utilization of EBM. Also, we investigated whether teaching EBM increased the knowledge and use of EBM in family medicine residents. METHODS: In July 2005, we sent a questionnaire to family medicine residents in Korea and received 260 answers. The questionnaire concerned education, attitude, utilization and knowledge of EBM. We analyzed the relationship of the level of knowledge and utilization of EBM in practice by using chi-square test. RESULTS: The family medicine residents who hed experienced learning EBM was 61%. Almost half of them were educated during their family medicine training programs (42.2%). Among the total, 33.6% of the respondents had an experience to attend EBM journal club. As for the knowledge of EBM, 59.8% of respondents knew the concept of what is EBM, 36.5% understood PICO question structure, and 28.5% knew how to calculate the NNT value. In the residents who had experienced EBM learning, the level of knowledge (P<0.001), the frequency of utilization (P<0.001), and the intention to use EBM in their practice were higher than in those who had not yet experienced EBM learning. CONCLUSION: Although family medicine residents usually learn EBM in medical school and resident training program, education and utilization of EBM were not organized enough. As can be seen in this study, it is necessary to make an effective education program in medical schools and resident training programs to increase the knowledge and utilization of EBM education.
Surveys and Questionnaires
;
Education
;
Education, Medical
;
Evidence-Based Medicine*
;
Humans
;
Intention
;
Internship and Residency
;
Korea
;
Learning
;
Schools, Medical