Synergistic Antitumor Effects of Combined Treatment with HSP90 Inhibitor and PI3K/mTOR Dual Inhibitor in Cisplatin-Resistant Human Bladder Cancer Cells

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.

Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis

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.

The Effect of Recorded Video Monitoring on Students' Self Reflection of Patient–Physician Interaction / 의학교육논단

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.

Effects of Self-esteem and Academic Stress on Depression in Korean Students in Health Care Professions / 정신간호학회지

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.

How to Get Students Actively Involved in Course Development: An Experience in Developing and Implementing a Mentoring Program for Medical Students / 한국의학교육

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.

Mental Health and Coping Strategies among Medical Students / 한국의학교육

PURPOSE: Recently, concern of the college students' mental health has increased due to their continuous psychologic problems such as suicidal attempt. This study aimed to examine the correlation among depression, stress, self-esteem, and coping strategies of the medical students and also according to the academic year. METHODS: The subject was 384 medical students of K medical school in Korea. Self-rating depression scale, stress scale, self-esteem scale was used for the survey, and academic stress and coping strategies of the students were asked. Frequency analysis, one-way ANOVA, t-test, correlation analysis was carried out. RESULTS: Third year students were under most stress (F=5.67, p=0.000) and had the most students who were moderately (22.9%) and mildly depressed (6.3%). Stress form academic studies and grade was also the highest in third year students. For English fluency, freshmen students scored the top. Academic career stress and school culture stress were higher for year 3, 4, 5, 6 than year 1, 2 students. Differences of the coping strategies by academic year was significant in emotional display. Students who showed high level of depression and stress, also students with low self-esteem used emotional display as their major coping strategy. CONCLUSION: Depending on their academic year medical students' level of depression and stress was different, and they did not use a variety of coping strategies. Therefore, a program which can give a diverse access to variety of coping strategies to relieve students' stress should be developed taking their characteristics of academic year into consideration.

Quantitative PCR for Etiologic Diagnosis of Methicillin-Resistant Staphylococcus aureus Pneumonia in Intensive Care Unit / 결핵및호흡기질환

BACKGROUND: Ventilator-associated pneumonia (VAP) requires prompt and appropriate treatment. Since methicillin-resistant Staphylococcus aureus (MRSA) is a frequent pathogen in VAP, rapid identification of it, is pivotal. Our aim was to evaluate the utility of quantitative polymerase chain reaction (qPCR) as a useful method for etiologic diagnoses of MRSA pneumonia. METHODS: We performed qPCR for mecA, S. aureus-specific femA-SA, and S. epidermidis-specific femA-SE genes from bronchoalveolar lavage or bronchial washing samples obtained from clinically-suspected VAP. Molecular identification of MRSA was based on the presence of the mecA and femA-SA gene, with the absence of the femA-SE gene. To compensate for the experimental and clinical conditions, we spiked an internal control in the course of DNA extraction. We estimated number of colony-forming units per mL (CFU/mL) of MRSA samples through a standard curve of a serially-diluted reference MRSA strain. We compared the threshold cycle (Ct) value with the microbiologic results of MRSA. RESULTS: We obtained the mecA gene standard curve, which showed the detection limit of the mecA gene to be 100 fg, which corresponds to a copy number of 30. We chose cut-off Ct values of 27.94 (equivalent to 1x10(4) CFU/mL) and 21.78 (equivalent to 1x10(5) CFU/mL). The sensitivity and specificity of our assay were 88.9% and 88.9% respectively, when compared with quantitative cultures. CONCLUSION: Our results were valuable for diagnosing and identifying pathogens involved in VAP. We believe our modified qPCR is an appropriate tool for the rapid diagnosis of clinical pathogens regarding patients in the intensive care unit.