Wai-Kwan Alfred Yung, MD, Oral History Interview, May 7, 2014

Major Topics Coveted: History of Neuro-Oncology services and research at MD Anderson History of the Department of Neuro-Oncology The Brain Tumor Center: collaborative relationships and shared resources with Neuro-Oncology, Neuro-Surgery, Neuro-Pathology, neuro-imaging and other support fieldshttps://openworks.mdanderson.org/mchv_interviewsessions/1048/thumbnail.jp

Se-methylselenocysteine inhibits phosphatidylinositol 3-kinase activity of mouse mammary epithelial tumor cells in vitro

INTRODUCTION: Se-methylselenocysteine (MSC), a naturally occurring selenium compound, is a promising chemopreventive agent against in vivo and in vitro models of carcinogen-induced mouse and rat mammary tumorigenesis. We have demonstrated previously that MSC induces apoptosis after a cell growth arrest in S phase in a mouse mammary epithelial tumor cell model (TM6 cells) in vitro. The present study was designed to examine the involvement of the phosphatidylinositol 3-kinase (PI3-K) pathway in TM6 tumor model in vitro after treatment with MSC. METHODS: Synchronized TM6 cells treated with MSC and collected at different time points were examined for PI3-K activity and Akt phosphorylation along with phosphorylations of Raf, MAP kinase/ERK kinase (MEK), extracellular signal-related kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). The growth inhibition was determined with a [(3)H]thymidine incorporation assay. Immunoblotting and a kinase assay were used to examine the molecules of the survival pathway. RESULTS: PI3-K activity was inhibited by MSC followed by dephosphorylation of Akt. The phosphorylation of p38 MAPK was also downregulated after these cells were treated with MSC. In parallel experiments MSC inhibited the Raf–MEK–ERK signaling pathway. CONCLUSION: These studies suggest that MSC blocks multiple signaling pathways in mouse mammary tumor cells. MSC inhibits cell growth by inhibiting the activity of PI3-K and its downstream effector molecules in mouse mammary tumor cells in vitro

Chapter 04: A Reputation For Experimentation and the Impact of Shifting to a Division System in the Eighties

Dr. Yung connects MD Anderson\u27s reputation for radical research in the 1980s to the move to reorganize the institution by Divisions in order to foster collaboration. He sets context by noting that MD Anderson struggled with a reputation for experimenting on people as well as with limits imposed on its growth. Dr. Yung explains how in 1982 the second president, Dr. Charles LeMaistre, reorganized the institution according to a division system to foster collaboration between departments and services and created a more systematic environment for promoting clinical research. The division system also fostered a more systematic approach to patient care and more structure in services by focusing on disease type. Dr. Yung next explains that, with that administrative reorganization, many new faculty were hired to provide a platform to enhance the quality of research and research driven patient care.https://openworks.mdanderson.org/mchv_interviewchapters/1263/thumbnail.jp

Wai-Kwan Alfred Yung, MD, Oral History Interview, June 18, 2014

Major Topics Covered: History of Neuro-Oncology services and research at MD Anderson History of the Department of Neuro-Oncology The Brain Tumor Center: collaborative relationships and shared resources with Neuro-Oncology, Neuro-Surgery, Neuro-Pathology, neuro-imaging and other support fieldshttps://openworks.mdanderson.org/mchv_interviewsessions/1049/thumbnail.jp

Chapter 14: Building the Advanced Practice Nurse Program

In this chapter, Dr. Yung talks about the expansion of the Advanced Practice Nurse program once he became department chair. He first notes how important support staff are to extending clinical care and then explains why he elected to expand APNs in particular. Dr. Young says that most institutions do not have the rich resource of nurses that MD Anderson has: research nurses, APNs, clinic nurses, and in-patient nurses. He sketches the roles that the APN services in assisting patients\u27 caregivers and building quality of life for patients.https://openworks.mdanderson.org/mchv_interviewchapters/1273/thumbnail.jp

Chapter 09: The Challenges of Glioblastoma; MD Anderson\u27s Moon Shot Program; No Low-Hanging Fruit for Neuro-Oncology Research

Dr. Yung explains the challenges that glioblastoma presents to the researcher then sketches the work he is doing to build collaboration among the brain tumor community. He notes that Dr. Charles A. LeMaistre [Oral History Interview] started the Brain Tumor Group, now the largest in the country and the world. Dr. Yung next talks about MD Anderson\u27s Moon Shots Program, now expanding to include more than the six cancers. He talks about the structure of the Moon Shots program and evaluates the lessons learned from its early years. He notes the aim of the Program to focus on low hanging fruit that can lead quickly to treatment advances, and explains that there are no such quick remedies on the horizon for treating glioblastoma.https://openworks.mdanderson.org/mchv_interviewchapters/1268/thumbnail.jp

Chapter 05: Stepping Down as Chair of Neuro-Oncology

The recorder is started during a conversation in progress. Dr. Yung offers brief comments on his decision to step down as Chair of Neuro-oncology. (He stepped into the role as interim chair in 1999 and became permanent chair in 2002.)https://openworks.mdanderson.org/mchv_interviewchapters/1264/thumbnail.jp

Chapter 08: Brain Tumor Research: Translational Studies in Progress and the NCI Study Section

In this chapter, Dr. Yung sketches his other research activities on glioblastoma. He first talks about his activities with the NCI and other groups focused on developing clinical, translational studies of brain cancer. He talks about the challenges of setting up such studies. Dr. Yung next talks about his clinical trials with the drug, BKM 120. He explains how this study also demonstrates the difficultly of attracting attention to a small cancer and how MD Anderson can partner with drug companies.https://openworks.mdanderson.org/mchv_interviewchapters/1267/thumbnail.jp

Chapter 16: MD Anderson\u27s Horizonally-Organized Brain Tumor Center

In this chapter, Dr. Yung focuses on the Brain Tumor Center, created via the working relationships and shared resources that link sixty members from Neur-oncology, Neuro-surgery, Imaging, Neuro-pathology and other services. Dr. Yung explains that these working relationships enable neuro-focused members to get individual and multi-investigator funding, and that the SPORE grant is a triumph of the Brain Tumor Center. Dr. Yung next comments on the difficulties of formalizing the Brain Tumor Center as a self-contained unit within MD Anderson. (This discussion refers to the fact that the head of Neuro-Surgery, Dr. Raymond Sawaya, is an advocate of such independent status. Dr. Sawaya discusses this at length in his oral history interview.) Dr. Yung cites the enormous cost of running an independent Center, given the expense of the technology required. Dr. Yung says that the Brain Tumor Center will enter a new phase when a new chairman of Neuro-Oncology replaces him. He also feels that the Center currently offers a solid platform to expand immunotherapy with a new emphasis on T-cell function.https://openworks.mdanderson.org/mchv_interviewchapters/1275/thumbnail.jp

Chapter 12: Becoming Chair of Neuro-Oncology and Developing Collaborations with Neuro-Surgery

Dr. Yung explains that in 1990, Neuro-Surgery became a department and Dr. Raymond Sawaya [Oral History Interview] was recruited to head it. He describes the period of expansion that began for both departments at that time. Dr. Yung gives examples of research in Neuro-Oncology and their ties to the institution\u27s status as a comprehensive cancer center. Dr. Yung explains Dr. John Mendelsohn\u27s [Oral History Interview] continued support the combined activities of Neuro-Oncology and Neuro-Surgery, known as the Brain Tumor Program. He stresses that he and Dr. Sawaya shared a commitment to building multi-disciplinary research and care initiatives and he describes the blessing for this group that faculty work well together. HIPPA Next, Dr. Yung talks about his cancer diagnosis and treatment, and his decision to accept Dr. Mendelsohn\u27s request that he take on the role as ad interim chair. He describes his goals at the time and his continued commitment to work with Neurosurgery and related fields to develop a cohesive program in patient care and research. He talks about collaborative projects, including development of an oncolytic virus -a rare example of a successful brain tumor drug.https://openworks.mdanderson.org/mchv_interviewchapters/1271/thumbnail.jp