- Email: [email protected]
104. Aberrant Expression of Zinc Transporter ZIP4 (SLC39A4) Significantly Contributes to Human Pancreatic Cancer Pathogenesis and Progression
224 ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS culture periods. EP1013 therapy significantly decreased the time to normoglycemia following human islet transplantation into diabetic, immundeficient recipient mice, with 70% of the EP1013-treated animals achieving euglycemia with only 150-300 human islet equivalents versus 0% of the controls. This represents an 80-90% reduction in human islet mass required to restore normoglycemia in mice, which typically require ⬎1500 islet equivalents to achieve the same reversal rate. Conclusion: Our data suggests that EP1013 therapy will reduce the islet mass required in clinical islet transplantation, perhaps to a level that would routinely allow for insulin independence following single donor infusion. This strategy has the potential to greatly enhance the availability of islet transplantation for patients with type 1 diabetes. 104. ABERRANT EXPRESSION OF ZINC TRANSPORTER ZIP4 (SLC39A4) SIGNIFICANTLY CONTRIBUTES TO HUMAN PANCREATIC CANCER PATHOGENESIS AND PROGRESSION. Min Li1, Yuqing Zhang1, Uddalak Bharadwaj1, Xinwen Wang1, Hao Wang1, Sheng Zhang1, Juan Liuzzi2, Robert Cousins2, William Fisher1, F Charles Brunicardi1, Craig D. Logsdon8, Changyi Chen1, Qizhi Yao1; 1Baylor College of Medicine, Houston, TX; 2University of Florida, Gainesville, FL; 8 UT MD Andeson Cancer Center, Houston, TX Introduction: Recent studies indicate a possible correlation of zinc levels with risk of cancers; however, the role of zinc and zinc transporters in cancer progression is unknown. For the first time, we have recently observed that a dietary zinc transporter, ZIP4 (SLC39A4), was overexpressed in human pancreatic cancer. We hypothesize that ZIP4 upregulation may contribute to the pancreatic cancer progression. The objective of this study was to determine the roles and mechanisms of ZIP4 in human pancreatic cancer cell proliferation in vitro and pancreatic cancer progression in vivo. Methods: The expression of ZIP4 in human pancreatic cancer cell lines, normal human pancreatic ductal epithelium (HPDE), and clinical specimens of human pancreatic adenocarcinoma was determined by real-time RT-PCR, western blot, and immunohistochemistry. ZIP4 stable overexpression was established in the pancreatic cancer cell line MIA PaCa-2 using retrovirus vectors. In vitro cell proliferation was performed by MTS assay. In vivo tumor growth was performed in the nude mouse models of subcutaneous and orthotopic xenograft. Zinc uptake was determined by inductively coupled plasma mass spectrometry (ICPMS). Results: ZIP4 was substantially overexpressed in 16 of 17 (94%) clinical pancreatic adenocarcinoma specimens compared with their surrounding normal tissues, and ZIP4 mRNA levels were significantly higher in human pancreatic cancer cells than in HPDE cells (p⬍0.05). Overexpression of ZIP4 in MIA PaCa-2 cells increased tumor cell proliferation by 2-fold, and increased tumor volume by 13-fold in the nude mouse model of subcutaneous xenograft, compared with the vector control cell line (p⬍0.05). Overexpression of ZIP4 not only increased the primary tumor weight (7.2-fold) in the orthotopic nude mouse model, but also increased the incidence of peritoneal dissemination and ascites in the mice. Overexpression of ZIP4 also accumulated more zinc in both pancreatic cancer cells, and xenograft tumors. Conclusions: ZIP4 is overexpressed in human pancreatic cancer, and contributes to tumor progression by accumulation of intracellular zinc and stimulation of cell proliferation. Thus, overexpression of ZIP4 is considered a new malignant factor for pancreatic cancer progression. Consequently, targeting ZIP4 may become a new strategy to treat pancreatic cancer.
ORAL SESSION: THU 2/14 7:30 AM EDUCATION II/FOREIGN SOCIETY PAPERS 105. AN INTEGRATED FIRST YEAR SURGICAL SKILLS TRAINING CURRICULUM ENHANCES STUDENTS’ SKILLS AND IMPROVES INTEREST IN SURGERY. Harras Zaid1, Derek Ward1, Amanda Sammann1, Kim Topp1,
Frank Tendick1, John Maa2; 1University of California, San Francisco, School of Medicine, San Francisco, CA; 2University of California, San Francisco, Department of Surgery, San Francisco, CA Introduction: Reports from the Institute of Medicine have emphasized the pivotal role of pre-clinical education in enhancing the quality of patient care and promoting patient safety. Implementing early exposure to surgical skills training and surgical mentors in medical school has been rising in importance, and is a priority set forth by the 2004 Blue Ribbon committee report on undergraduate surgical education. Importantly, early exposure to tasks such as basic suturing, combined with positive surgical role models, could enhance skills retention, increase confidence, and improve patient care. Objective: The Departments of Surgery and Anatomy at the UCSF School of Medicine developed a novel curriculum to teach suturing in the first year of medical school and to provide students with exposure to potential surgical mentors in the classroom environment. We subsequently assessed the efficacy of this intervention as a teaching tool for basic surgical skills and also addressed changes in student perceptions regarding careers in surgery. Methods: A needs assessment of rising fourth year UCSF medical students with no formal pre-clinical training in surgical skills was performed. Respondents identified a need for earlier skills exposure which guided the development of a first year curriculum emphasizing basic suturing. These teaching sessions were based in the anatomy lab and were staffed by surgeon volunteers, with instruction being standardized with a teacher handbook. Groups of six students rotated through a suturing station in the anatomy lab where 30 minutes of dedicated teaching, feedback, and practice was provided. An online module supplemented the in-class instruction, and materials were provided after the sessions for students to practice. Students completed a survey asking about their experience. Results: 56 rising fourth year medical students completed the needs assessment survey. Over 75% agreed or strongly agreed that it would have been helpful to have had pre-clinical training in the following areas: identifying and handling tools, knot tying, and suturing. After implementation of the new skills curriculum, 90 first year students out of 144 (62.5%) responded to the survey. Respondents agreed or strongly agreed that the suturing session was enjoyable (97%); they gained valuable skills (88%); and they would recommend the suturing exercise for future students (97%). Furthermore, 33% of respondents stated their level of interest in surgery increased following the exercise; among reasons listed for this change was positive interaction with the surgeon instructors (18 respondents) and enjoyment of the suturing exercise (22 respondents). Qualitative data praised the suturing exercise (“one of the first true hand-on experiences” in medical school) and instructors specifically (“it was so helpful to have them in lab”). Conclusions: A needs-driven training intervention can be built into the framework of a current medical curriculum with minimal investment and without detracting from anatomy instruction. This intervention required successful collaboration at many levels, particularly between the School of Medicine and Department of Surgery. Perhaps most importantly, students received early exposure to surgical mentors and skills training, which may translate into enhanced confidence on the wards and increased interest in surgical careers. 106. UNIFORM MASTERY OF BASIC LAPAROSCOPY USING AN INTEGRATED PROFICIENCY - BASED SKILLS AND COGNITIVE CURRICULUM FOR SURGERY INTERNS. Mouza T. Goova, Lisa A. Hollett, Seify T. Tesfay, Deborah C. Hogg, Linda S. Hynan, Daniel J. Scott; UT Southwestern Medical Center, Dallas, TX Introduction: The Fundamentals of Laparoscopic Surgery (FLS) program has been extensively validated. We have shown that pretraining on other simulators decreases consumable costs for FLS. The goal of this study was to evaluate feasibility, benefit, and cost of
ORAL SESSION: THU 2/14 7:30 AM EDUCATION II/FOREIGN SOCIETY PAPERS 105. AN INTEGRATED FIRST YEAR SURGICAL SKILLS TRAINING CURRICULUM ENHANCES STUDENTS’ SKILLS AND IMPROVES INTEREST IN SURGERY. Harras Zaid1, Derek Ward1, Amanda Sammann1, Kim Topp1,
Frank Tendick1, John Maa2; 1University of California, San Francisco, School of Medicine, San Francisco, CA; 2University of California, San Francisco, Department of Surgery, San Francisco, CA Introduction: Reports from the Institute of Medicine have emphasized the pivotal role of pre-clinical education in enhancing the quality of patient care and promoting patient safety. Implementing early exposure to surgical skills training and surgical mentors in medical school has been rising in importance, and is a priority set forth by the 2004 Blue Ribbon committee report on undergraduate surgical education. Importantly, early exposure to tasks such as basic suturing, combined with positive surgical role models, could enhance skills retention, increase confidence, and improve patient care. Objective: The Departments of Surgery and Anatomy at the UCSF School of Medicine developed a novel curriculum to teach suturing in the first year of medical school and to provide students with exposure to potential surgical mentors in the classroom environment. We subsequently assessed the efficacy of this intervention as a teaching tool for basic surgical skills and also addressed changes in student perceptions regarding careers in surgery. Methods: A needs assessment of rising fourth year UCSF medical students with no formal pre-clinical training in surgical skills was performed. Respondents identified a need for earlier skills exposure which guided the development of a first year curriculum emphasizing basic suturing. These teaching sessions were based in the anatomy lab and were staffed by surgeon volunteers, with instruction being standardized with a teacher handbook. Groups of six students rotated through a suturing station in the anatomy lab where 30 minutes of dedicated teaching, feedback, and practice was provided. An online module supplemented the in-class instruction, and materials were provided after the sessions for students to practice. Students completed a survey asking about their experience. Results: 56 rising fourth year medical students completed the needs assessment survey. Over 75% agreed or strongly agreed that it would have been helpful to have had pre-clinical training in the following areas: identifying and handling tools, knot tying, and suturing. After implementation of the new skills curriculum, 90 first year students out of 144 (62.5%) responded to the survey. Respondents agreed or strongly agreed that the suturing session was enjoyable (97%); they gained valuable skills (88%); and they would recommend the suturing exercise for future students (97%). Furthermore, 33% of respondents stated their level of interest in surgery increased following the exercise; among reasons listed for this change was positive interaction with the surgeon instructors (18 respondents) and enjoyment of the suturing exercise (22 respondents). Qualitative data praised the suturing exercise (“one of the first true hand-on experiences” in medical school) and instructors specifically (“it was so helpful to have them in lab”). Conclusions: A needs-driven training intervention can be built into the framework of a current medical curriculum with minimal investment and without detracting from anatomy instruction. This intervention required successful collaboration at many levels, particularly between the School of Medicine and Department of Surgery. Perhaps most importantly, students received early exposure to surgical mentors and skills training, which may translate into enhanced confidence on the wards and increased interest in surgical careers. 106. UNIFORM MASTERY OF BASIC LAPAROSCOPY USING AN INTEGRATED PROFICIENCY - BASED SKILLS AND COGNITIVE CURRICULUM FOR SURGERY INTERNS. Mouza T. Goova, Lisa A. Hollett, Seify T. Tesfay, Deborah C. Hogg, Linda S. Hynan, Daniel J. Scott; UT Southwestern Medical Center, Dallas, TX Introduction: The Fundamentals of Laparoscopic Surgery (FLS) program has been extensively validated. We have shown that pretraining on other simulators decreases consumable costs for FLS. The goal of this study was to evaluate feasibility, benefit, and cost of