This study explored teamwork in two hospitals implementing Total Quality Management. Its objectives were to: document and describe the social process of constructing teamwork in the two hospitals and the patterns of interaction that emerged; to compare the experiences of teamwork in the hospitals to the conceptualization of teamwork prescribed by TQM and to compare the experiences of the two hospitals to each other; and to understand how teamwork is interpreted by members of TQM hospitals. A multi-site case design was used; data was collected through participant observation, interviews, and document analysis. Results suggested that quality improvement teams represent a means for creating teamwork in hospitals by providing a forum for members to understand each other's needs, work, and problems through which respect and cooperative relationships emerged. Team leaders played a key role in the construction of teamwork by managing the meaning of teamwork, guiding the work of teams, assuring equal participation and facilitating the establishment of meaningful ground rules and mutually shared objectives. Identified obstacles to teamwork included the lack of physician involvement in team efforts; managers and staff who would not cooperate with team recommendations; the time required to improve work processes; managers who attempted to control a team's work; and leaders who failed to provide clear direction and guidance. In exploring the practice of teamwork outside the boundaries of QIT's, the data revealed that barriers between departments still existed. Management efforts to forge teamwork across functional areas were fragmented. Department heads who promoted teamwork tended to be those who had been involved in QIT's. In both hospitals conflict, distrust and a lack of mutually shared objectives among senior managers was identified by middle managers as antithetical to TQM and an obstacle to building a sense of "all one team" hospital-wide. Recognizing that the hierarchical, departmental structure in hospitals prevents the construction of teamwork across departments and recognizing the ability of quality improvement teams to break down departmental barriers, this study recommends that organizational restructuring be explored for hospitals which might include the management of processes or systems vs. departments and incorporates the team structure.

Prostate cancer is the most commonly diagnosed cancer in men and nearly 30,000 patients will die this year due to complications arising from the disease. Prostate cancer patients are frequently treated with androgen deprivation therapies, but the duration of response is variable, and patients frequently progress to an incurable stage of the disease referred to as castration-resistant prostate cancer (CRPC). Second-generation AR antagonists such as enzalutamide and apalutamide are effective therapies that block androgen receptor (AR) transactivation and signaling in over 50% of CRPC patients. However, an estimated 30% of responders will develop resistance to these therapies within two years. There is another class of AR antagonists which are referred to as pan AR antagonists, that have shown to inhibit the activity of wild-type AR as well as several mutated versions of AR. Currently, there are several pan AR antagonists in preclinical development and approved for the treatment of CRPC in patients harboring pathogenic point mutations in AR. We chose four genetically distinct AR-positive prostate cancer preclinical models to generate enzalutamide, JNJ-pan-AR, or apalutamide resistant cell lines. We then performed transcriptomic and proteomic profiling on the AR antagonist sensitive and resistant cell lines to uncover molecular alterations that may be critical to the maintenance and/ or predictive biomarkers of the resistant phenotype. Global profiling uncovered significant variability in molecular alterations across the AR antagonist resistant cell lines as well as the prostate cancer preclinical models. However, we uncovered upregulation of AKR1C3 protein expression across all three AR antagonist resistant cell lines using the LNCaP and LNCaP/AR preclinical models. Further characterization of the functional significance of AKR1C3 upregulation demonstrated that AKR1C3 protein expression contributes to JNJ-pan-AR resistance. Similar findings have reported the correlation between AKR1C3 expression and changes in drug efficacy across several chemotherapeutic agents approved to CRPC treatment. Collectively the findings from this study support the rationale of AKR1C3 as a target for AR antagonist resistant prostate cancer disease progression.