Langstraat, Carrie

BACKGROUND: Learning objectives for gynecologic oncology (GO) fellowships have been created, however a standard curriculum does not exist. There is interest amongst program directors to develop a standardized curriculum with online teaching tools. This study was conducted to determine the learning needs of GO fellows and to assess the use of web-based teaching in this group of learners. METHODS: An 18 minute teaching module on surgical management of vulvar cancer was created and validated by experts. The module was then emailed to fellows with a pre and post-module survey. The survey assessed the learners needs, the learners knowledge and the usefulness of the module. RESULTS: One hundred ninety GO fellows were surveyed, 72 (38%) responses were received. Most participants were in their second year of clinical fellowship (42%). The majority of GO fellowships have a weekly teaching conference with faculty participation. Resources utilized by fellows for learning are textbooks and journal articles, with all responders ranking these as their first or second preferred resource. The teaching module was an effective teaching tool as demonstrated by improved scores across the four content based questions. The webinar was well received by the fellows, with 92% saying they liked this teaching tool and 46/48 (96%) felt that they would view additional presentations if provided. In addition 45/49 (92%) felt that this type of teaching filled a need in GO fellowship. DISCUSSION: Many GO fellowships utilize faculty directed teaching conferences. This online teaching tool improved fellow knowledge and additional modules would be well received in this population of learners.

Abstract Objective: Mullerian inhibiting substance type II receptor (MISRII) is a tissue-specific target for therapy in gynecologic cancers. MISRII plays a specialized role in regression of the mullerian tracts embryologically. Analogous to other TGF-β family members, ligand (MIS) binding to the type II receptor leads to a heteromeric complex with type I receptors, downstream Smad signaling, cell cycle arrest and regression. We previously published that the majority of epithelial ovarian cancers (EOC) and endometrial cancers (EC) express MISRII in a tissue specific manner. The purpose of these studies was to investigate the biologic significance of MISRII expression in EOC. Methods: For in vitro studies, we developed both chimeric and endogenous cell models to study MISRII. Chimeric MIS type I and II receptors were created by fusing the ligand binding domain of GM-CSF (α or β subunit) to the transmembrane and cytoplasmic domains of the type I/II receptor; these receptors were stably transfected into Ovcar8 cells. The chimera system allows specific signaling of the receptor complex and the ability to separately analyze candidate type I receptors. The endogenous cell model was created in SKOV3 (MISRII- EOC cell line) by stably expressing full-length MISRII. Growth inhibition was assessed by colony formation in soft agar in response to receptor activation and cisplatin. A BRE-luciferase reporter construct was used to measure Smad 1/5 activation after exposure to MIS. FACS analysis was used to assess cell cycle progression. Results: In the chimeric model, receptor activation resulted in up to 60% inhibition of colony formation (dependent on which candidate type I receptor was targeted). Additionally, receptor activation sensitized cells to the effects of cisplatin (1μM) with nearly 4-fold inhibition of colony formation. In the endogenous MISRII expressing EOC cell model, functional signaling was first confirmed using a BRE-luciferase reporter assay to document induction of Smad activation after exposure to rhMIS (3.2 relative light units increase after 20nM MIS). This model was then assessed for cell cycle progression in the presence of MIS. We observed a strong G1 arrest (62% vs. 43% untreated) after 15h exposure to 25nM MIS in cells expressing the receptor with no change in the MIS- parental cell line. These in vitro data are consistent with our survival results in EOC demonstrating a significantly improved overall survival (p=0.04) in MISRII expressing cancers. Conclusions: The majority of gynecologic cancers express MISRII. Our in vitro studies demonstrate that receptor activation results in cell cycle arrest, reduced colony formation, and sensitization to cisplatin. Confirming this in vitro data is the observation that EOC expressing MISRII have improved response to therapy and longer survival. Together, these results support further targeting of the MISRII pathway as an anticancer strategy in gynecologic malignancy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1586.