6.Synergistic Antitumor Effects of Combined Treatment with HSP90 Inhibitor and PI3K/mTOR Dual Inhibitor in Cisplatin-Resistant Human Bladder Cancer Cells
Hyung Joon KIM ; Mi Kyung GONG ; Cheol Yong YOON ; Jaeku KANG ; Mijin YUN ; Nam Hoon CHO ; Sun Young RHA ; Young Deuk CHOI
Yonsei Medical Journal 2020;61(7):587-596
Purpose:
The current study aimed to investigate the synergistic antitumor effect of combined treatment with 17-DMAG (HSP90 inhibitor) and NVP-BEZ235 (PI3K/mTOR dual inhibitor) on cisplatin-resistant human bladder cancer cells.
Materials and Methods:
Human bladder cancer cells exhibiting cisplatin resistance (T24R2) were exposed to escalating doses of 17-DMAG (2.5–20 nM) with or without NVP-BEZ236 (0.5–4 μM) in combination with cisplatin. Antitumor effects were assessed by CCK-8 analysis. Based on the dose-response study, synergistic interactions between the two regimens were evaluated using clonogenic assay and combination index values. Flow cytometry and Western blot were conducted to analyze mechanisms of synergism.
Results:
Dose- and time-dependent antitumor effects for 17-DMAG were observed in both cisplatin-sensitive (T24) and cisplatin- resistant cells (T24R2). The antitumor effect of NVP-BEZ235, however, was found to be self-limiting. The combination of 17- DMAG and NVP-BEZ235 in a 1:200 fixed ratio showed a significant antitumor effect in cisplatin-resistant bladder cancer cells over a wide dose range, and clonogenic assay showed compatible results with synergy tests. Three-dimensional analysis revealed strong synergy between the two drugs with a synergy volume of 201.84 μM/mL2%. The combination therapy resulted in G1-phase cell cycle arrest and caspase-dependent apoptosis confirmed by the Western blot.
Conclusion
HSP90 inhibitor monotherapy and in combination with the PI3K/mTOR survival pathway inhibitor NVP-BEZ235 shows a synergistic antitumor effect in cisplatin-resistant bladder cancers, eliciting cell cycle arrest at the G1 phase and induction of caspase-dependent apoptotic pathway.
7.Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis.
Yu Na KIM ; So Ra CHOE ; Kyung Hwa CHO ; Do Yeun CHO ; Jaeku KANG ; Chang Gyo PARK ; Hoi Young LEE
Experimental & Molecular Medicine 2017;49(2):e296-
Hippo/YAP signaling is implicated in tumorigenesis and progression of various cancers. By inhibiting a plethora signaling cascades, resveratrol has strong anti-tumorigenic and anti-metastatic activity. In the present study, we demonstrate that resveratrol decreases the expression of YAP target genes. In addition, our data showed that resveratrol attenuates breast cancer cell invasion through the activation of Lats1 and consequent inactivation of YAP. Strikingly, we also demonstrate that resveratrol inactivates RhoA, leading to the activation of Lats1 and induction of YAP phosphorylation. Further, resveratrol in combination with other agents that inactivate RhoA or YAP showed more marked suppression of breast cancer cell invasion compared with single treatment. Collectively, these findings indicate the beneficial effects of resveratrol on breast cancer patients by suppressing the RhoA/Lats1/YAP signaling axis and subsequently inhibiting breast cancer cell invasion.
Breast Neoplasms*
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Breast*
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Carcinogenesis
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Humans
;
Phosphorylation
8.The Effect of Recorded Video Monitoring on Students' Self Reflection of Patient–Physician Interaction
Misun JU ; Jiyeong HWANG ; Jaemyung KIM ; Jaeku KANG
Korean Medical Education Review 2017;19(2):83-89
The aim of this study is to examine the effect of recorded video monitoring on students' self-reflection after completing their clinical performance examination. Taking into account the particular cases involved in the examination, the present study utilized history-taking, physical examination, and patient education as bases for evaluating information-establishment ability, and asking, listening, understanding, explaining, and connectedness as the bases for evaluating patient-physician interaction ability. Student self-monitoring through recorded video feedback was carried out three days after completion of their clinical performance examination. Students self-evaluated their performance with a 10-point scale before and after self-monitoring. The results of this study show that students have a general tendency to lower their own self-evaluation scores after self-monitoring. Although there was not a statistically significant change of interrelationship in the information-establishment ability evaluation, there was a meaningful change of interrelationship in the patient-physician interaction ability evaluation after self-monitoring; specifically, in the case of acute lower abdominal pain, a high correlation was found (r=0.31, p=0.02) between the evaluation scores of standardized patients and students related to patient-physician interaction ability. This implies that self-monitoring enables the students to acquire a reflective viewpoint from which to evaluate their own performance. Therefore, it can be said that self-monitoring through recorded video feedback is a valuable method for students to use in reviewing their performance in patient-physician interactions.
Abdominal Pain
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Diagnostic Self Evaluation
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Humans
;
Methods
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Patient Education as Topic
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Patient Simulation
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Physical Examination
;
Physician-Patient Relations
;
Self-Assessment
9.Effects of Self-esteem and Academic Stress on Depression in Korean Students in Health Care Professions.
Jaeku KANG ; Yu Kyung KO ; Hye Kyung LEE ; Kyung Hee KANG ; Yera HUR ; Keum Ho LEE
Journal of Korean Academy of Psychiatric and Mental Health Nursing 2013;22(1):56-64
PURPOSE: The purposes of this study were to identify factors affecting depression in college students and the correlation of depression with self-esteem and academic stress, and to identify differences among student self-esteem, academic stress, and general characteristics and the relationship of these variables to depression. METHODS: The study was done in April 2011 with 852 students in health-related majors (medicine, nursing science, and dental hygiene) of a medical college in Korea. A self-rating survey containing 10 items from the Rosenberg Self-esteem Scale, 20 items from the Self-rating Depression Scale, and 22 items on academic stress was used. Data were analyzed using descriptive statistics, t-tests, one-way ANOVA, and logistic regression. RESULTS: Medical students' scores for self-esteem were significantly higher than dental hygiene students, but for academic stress scores, the result was the opposite. Logistic regression showed that self-esteem, academic stress, academic major and satisfaction with it (positive affect), and home income level (negative affect) significantly affected the level of depression. CONCLUSION: Designing and implementing realistic programs tailored to students' academic majors to enhance their self-esteem and provide practical knowledge in dealing with academic stress will help these students obtain a healthier school life emotionally as well as academically.
Delivery of Health Care
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Depression
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Humans
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Korea
;
Logistic Models
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Oral Hygiene
10.How to Get Students Actively Involved in Course Development: An Experience in Developing and Implementing a Mentoring Program for Medical Students.
Junhwan KIM ; Keumho LEE ; Won Min HWANG ; Jaeku KANG
Korean Journal of Medical Education 2013;25(2):157-165
PURPOSE: This study aims to explore development of a student-centered mentoring program and assess satisfaction about the course in order to improve system of the course on the basis of our implementation experience. METHODS: The course was designed for 58 third-year medical students in 2012. A student council acted as the core management team. We evaluate assessment about the course with a 50-item questionnaire administered on a 5-point Likert scale using SPSS version 20.0, and a short-answer form asked students, faculty, and lecturers for their opinions on the course. RESULTS: Students felt that 'Attitude on health care policies (28.6%)' was the most useful lecture. The 'Meeting with a patient' session was useful for developing students' abilities to empathize and communicate with other people (81.1%). The 50.9% of students were very satisfied with the course, as well as with the form of the course (49.2%). CONCLUSION: A bold action that medical educators can take is to get students involved from the outset of the curriculum development. Allowing students to become actively involved in developing the program is an effective means of hearing them and providing a more meaningful learning experience.
Curriculum
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Delivery of Health Care
;
Hearing
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Humans
;
Learning
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Mentors
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Students, Medical
;
Surveys and Questionnaires

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