Preclinical evaluation of the Aurora kinase inhibitors AMG 900, AZD1152-HQPA, and MK-5108 on SW-872 and 93T449 human liposarcoma cells.

Liposarcoma is a malignant soft tissue tumor that originates from adipose tissue and is one of the most frequently diagnosed soft tissue sarcomas in humans. There is great interest in identifying novel chemotherapeutic options for treating liposarcoma based upon molecular alterations in the cancer cells. The Aurora kinases have been identified as promising chemotherapeutic targets based on their altered expression in many human cancers and cellular roles in mitosis and cytokinesis. In this study, we investigated the effects of an Aurora kinase A inhibitor (MK-5108), an Aurora kinase B inhibitor (AZD1152-HQPA), and a pan-Aurora kinase inhibitor (AMG 900) on undifferentiated SW-872 and well-differentiated 93T449 human liposarcoma cells. Treatment of the SW-872 and 93T449 cells with MK-5108 (0-1000 nM), AZD1152-HQPA (0-1000 nM), and AMG 900 (0-1000 nM) for 72 h resulted in a dose-dependent decrease in the total viable cell number. Based upon the EC50 values, the potency of the three Aurora kinase inhibitors in the SW-872 cells was as follows: AMG 900 (EC50 = 3.7 nM) > AZD1152-HQPA (EC50 = 43.4 nM) > MK-5108 (EC50 = 309.0 nM), while the potency in the 93T449 cells was as follows: AMG 900 (EC50 = 6.5 nM) > AZD1152-HQPA (EC50 = 74.5 nM) > MK-5108 (EC50 = 283.6 nM). The percentage of polyploidy after 72 h of drug treatment (0-1000 nM) was determined by propidium iodide staining and flow cytometric analysis. AMG 900 caused a significant increase in polyploidy starting at 25 nM in the SW-872 and 93T449 cells, and AZD1152-HQPA caused a significant increase starting at 100 nM in the SW-872 cells and 250 nM in the 93T449 cells. The Aurora kinase A inhibitor MK-5108 did not significantly increase the percentage of polyploid cells at any of the doses tested in either cell line. The expression of Aurora kinase A and B was evaluated in the SW-872 cells versus differentiated adipocytes and human mesenchymal stem cells by real-time RT-PCR and Western blot analysis. Aurora kinase A and B mRNA expression was significantly increased in the SW-872 cells versus the differentiated adipocytes and human mesenchymal stem cells. Western blot analysis revealed a ~ 48 kDa immunoreactive band for Aurora kinase A that was not present in the differentiated adipocytes or the human mesenchymal stem cells. A ~ 39 kDa immunoreactive band for Aurora kinase B was detected in the SW-872 cells, differentiated adipocytes, and human mesenchymal stem cells. A smaller immunoreactive band for Aurora kinase B was detected in the SW-872 cells but not in the differentiated adipocytes and human mesenchymal stem cells, and this may reflect the expression of a truncated splice variant of Aurora kinase B that has been associated with poor patient prognosis. The 93T449 cells demonstrated decreased expression of Aurora kinase A and B mRNA and protein compared to the SW-872 cells, and also expressed the truncated form of Aurora kinase B. The results of these in vitro studies indicate that Aurora kinase inhibitors should be further investigated as possible chemotherapeutic agents for human liposarcoma.

Professionalism in Physician Assistant, Physical Therapist, Occupational Therapist, Clinical Psychology, and Biomedical Sciences Students.

UNLABELLED: Interprofessional collaboration for healthcare requires a better understanding of the commonalities and differences in student perceptions of professionalism. METHODS: 217 students in five programs (PA 71, PT 46, OT 29, CP 12, and BMS 59) completed a 22-item survey (response rate 79.5%). A Likert scale grading from 1 (hardly ever) to 5 (always) was used to assess professional attitudes and behaviors. RESULTS: A mixed-model MANOVA, supplemented with post-hoc analyses, showed significant group by time interactions for 5 items. Sensitivity to differences and diversity of other people increased for BMS students, but decreased for PT students. Timeliness increased for BMS students, but did not change for PA students. Seeking out new learning experiences increased for BMS students, but did not change for PA or PT students. Taking a group leadership role increased for BMS students, decreased for PT students, while PA and OT students showed no change. Volunteering time to serve others decreased for OT and PA students, while BMS and BM students showed no change. CONCLUSION: It is plausible that these findings emerge from differences in program curricula and specific training objectives. The findings provide initial insight to educators on ways that attitudes and behaviors pertaining to professionalism sometimes vary among students in different health science programs.

Examining Health Care Students' Attitudes toward E-Professionalism.

Objective. To compare pharmacy, osteopathic medicine, dental medicine, and physician assistant (PA) students' perceptions of e-professionalism. Methods. A 20-item questionnaire was developed and administered to four cohorts of health care professions students early in their first professional year. The questionnaire contained 16 scenarios in which a hypothetical health care student or professional shared information or content electronically and students were asked to indicate how much they agreed that the scenario represented professional behavior. Results. Ninety-four percent of students completed the questionnaire. More female students were in the pharmacy and PA cohorts. There were statistical differences in students' perceptions of e-professionalism in five of 16 scenarios. Specific differences were most often between the osteopathic medicine students and the other cohorts. Conclusions. The health care professions students surveyed had similar perceptions of e-professionalism. Of the four cohorts, osteopathic medicine students appeared less conservative in their approach to e-professionalism than the other cohorts.