Surge gery y Resear search ch Con Conference Novel el Inhib ibit itio ion Strat ategie gies s for Panc ncre reatic Canc ncer r using ng Mice To receive 1.0 credit for this session, text the SMS code: NARHA HAL to 414-206-1776. This code will expire in 5 days ACCME A Accre reditation on S Statement: : The Medical College of Wisconsin is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. AMA Cr Credi dit D Desig ignation St Stat atement: The Medical College of Wisconsin designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity. Hours o of Partic icip ipat atio ion f for Alli lied H Health C h Care P Professionals ls: : The Medical College of Wisconsin designates this activity for up to 1.0 hours of participation for continuing education for allied health professionals.
Research ch H Hig ighlig ights DEPARTMENT O OF SURGERY Division on o of R Research
DEPARTMENT O OF SURGERY Division on o of R Research
Congratulations Erin Strong, MD, MBA, MPH! Research Resident, General Surgery 2019-2020 Collaborative for Healthcare Delivery Science (CHDS) fellowship: The fellowship is one component of the educational arm of CHDS, which seeks to provide an instructional framework for trainees interested in projects that improve safety, quality, or patient experience, and that will improve patient outcomes for the same or lower costs. • Erin in St Strong: : The R Rothman I n Index & physician uti n utilization o n of early clinical warni ning ng s systems ( (Gene neral S Sur urgery) David Vyles: Penicillin Allergy and the Effect on the CHW • Health System (Emergency Medicine) DEPARTMENT O OF SURGERY Division on o of R Research
Office e of Resea earch 2020-21 F Fac aculty AHW Limi mited d Needs eeds Fundi ding g Vit ital alit ity A Awar ard Re Request Workshop Wo Awar ard S d Summar ary: to enable or augment research studies Awar ard S d Summar ary: The award provides financial support for requiring additional resources to support the work, equipment formalized, faculty-defined projects over a concentrated purchases include lab equipment, scientific instruments, period of time which benefit both the faculty member and software purchases and specialty reagents. Priority will be MCW given to projects that fit within the focus areas of the AHW funded award, Impro rovi ving H Heart H Healt lth, S h, Suppor orting H Healt lthy Spo ponso sor: Faculty Affairs Min inds, a and D d Dis isman antling Can Cancer Workshop hop D Date: : Tuesday, November 5 th Time: : 8-9 am Maximu mum A Awa ward: $30,000 Locat atio ion: HUB A1520 Awar ard Pe d Perio iod: d: 18 months Applic icat atio ion D Due D Date: Friday, January 10 th Application Due in REDCap: October 1 st at 5pm Co Contact: Kimara Ellefson, Associate VP Talent Strategy and Notification of Award: November 15 th Faculty Affairs Project Start Date: December 2 nd Contact: Lizzy Schneidler DEPARTMENT O OF SURGERY Division on o of R Research
Pu Publicat ations August 2 2019 Surgical Oncology Pediatric Surgery When to Intervene for Subclinical Cushing's Syndrome. The Surgical Clinics of Multi-institutional trial of non-operative management and surgery for North America. Hsieh LB, Mackinney E, & Wang TS) uncomplicated appendicitis in children: Design and rationale. Contemporary Clinical Trials. Should We Be Doing Cytoreductive Surgery with HIPEC for Signet Ring Cell (Gadepalli S, Helmrath MA, Leys CM, Sato TT, Lal DR, Landman MP, Kabre Appendiceal Adenocarcinoma? A Study from the US HIPEC Collaborative. R, Fallat ME, Fischer BA, Cooper JN, Deans KJ, Midwest Pediatric Surgery Journal of Gastrointestinal Surgery. (Levinsky NC, Morris MC, Wima K, Consortium) Sussman JJ, Ahmad SA, Cloyd JM, Kimbrough C, Fournier K, Lee A, Dineen S, Dessureault S, Veerapong J, Baumgartner JM, Clarke C, Zaidi MY, Staley CA, Non-operative management of solid organ injuries in children: An Maithel SK, Leiting J, Grotz T, Lambert L, Hendrix RJ, Ronnekleiv-Kelly S, American Pediatric Surgical Association Outcomes and Evidence Based Pokrzywa C, Raoof M, Eng OS, Johnston FM, Greer JPatel SH) Practice Committee systematic review. Journal of Pediatric Surgery. (Lal DR, Jancelewicz T, Shelton J, Diefenbach KA, Grabowski J, Kawaguchi General Surgery A, Dasgupta R, Downard C, Goldin A, Petty JK, Stylianos S, Williams R) Buyer's remorse: what predicts post-decision dissonance after bariatric surgery? Surgery for Obesity and related Diseases: Official Journal of the Neural monitoring during H-type tracheoesophageal fistula division: A American Society for Bariatric Surgery. way to decrease recurrent laryngeal nerve injury? Journal of Pediatric (Wallace L, Horecki EK, Helm MC, Higgins RM, Gould JC, Lak K, Kindel TL) Surgery. Journal of Pediatric Surgery. Wright TN (Grant C, Hirschl RB, Lal DR, Minneci PC, Fallat ME, Midwest Pediatric Surgery Consortium) Pediatric Congenital Cardiac Surgery Extracorporeal Life Support and Increased Risk of Stroke with Carotid Cannulation. American Society for Artificial Internal Organs (ASAIO). (Woods, RK)
Next M Month: 2017 We e Ca Care A e Award U d Upda pdates: Optimizing Cardiopulmonary Bypass to Support Cerebral and Somatic Perfusion During Aortic Arch Reconstruction Viktor H Hraska, M , MD, P PhD Professor and Chief Pediatric Congenital Cardiac Department of Surgery 9 th , 2 Octo tober 9 201 019 Plea lease n note t the e HRC 1 1210/1230/1250 ROOM C CHANGE GE 5:00-6:00pm
Novel Inhibition Strategies for Pancreatic Cancer using Mice Macrophage Stellate Cell CD45 α SMA EpCAM Clin Cancer Res; 18(16); 4266–76 PDAC Cell
Cancer TME
Outline A. Tools & Methods 1. Cell Lines 2. Mouse Models 3. Histology & Molecular Biology B. People - the TEAM and I C. TGF β Paradox: Compartment makes the difference D. A New TGF β family member & Target for PC: Activin E. Therapy turned foe in a High Fat setting: PI3K Inhibition F. Implications
Tools and Methods
Cell Lines HPDE HPDE-Kras cells Stellate cells MiaPaCa2 BxPC3 Panc1
Mouse Models Tools & Switches 1. a candidate gene - usually altered in human cancer mt Kras, mt p53, Smad4, p16 loss a gene switch (promoter) that can target specific cell types 2. Elastase (EL), Pdx1, p48 ability to genetically manipulate in order to insert the gene 3. transgenesis, targeted manipulation,
Transgenesis: EL-Kras 112 bp 180 bp 160 bp 115 bp EL 1 2 3 4B hGH 5’ MT hss 3’ MT hss polyA human KRAS G12D mutation
ES Cell Manipulation Gene Targeting Technology for Knockout/Knockin Mice
Mouse Pancreatic Lesions Resemble Human Cystic Neoplasms PanINs human mus EL -KRAS G12D Cancer Res . 2003 May 1;63(9):2016-9
Mouse Pancreatic Lesions Resemble Human PanINs PDAC human mus Pdx1-Cre/LSL-Kras/p53 R172H (KPC) Pdx1-Cre/LSL-Kras (KC) Cancer Cell . 2005 May;7(5):469-83 Cancer Cell . 2003 Dec;4(6):437-50
Mouse vs. Human Cystic Neoplasms PanINs human mus EL-Kras Pdx1-Cre/LSL-Kras Cancer Res. 2003 May 1;63(9):2016-9 Cancer Cell . 2003 Dec;4(6):437-50
Histology & Molecular Biology A. Gross & Microscopic Pathology 1. Tissue histology (pancreas, liver, GI tract, spleen) 2. Cell culture (cytospin and/or grown on chamber slides) 3. IHC/IF staining of proteins (biomarkers) & localization 4. Lesion and stain scoring B. Protein Quantitation: Western blot analyses C. Cell mobility: scratch wound assay
People: The TEAM & I
The Investigator
The PIMP
TGF β Paradox: Compartment/Timing makes the difference
TGF β Paradox Common Alterations in PC Science . 2008 Sep 26;321(5897):1801-6.
TGF β Paradox TGF β & Kras in PC Subtypes Nature . 2016 Mar 3;531(7592):47-52.
TGF β Paradox Biochem Soc Trans . 2016 Oct 15;44(5):1441-1454
TGF β Paradox Team Dr. Boris Pasche Dr. Barbara Jung The Research Team Then Danny Principe Emman Mascariñas Dr. David Bentrem Brian DeCant Dr. Morgan Barron Kevin Adrian
TGF β Paradox What are the roles of TGF β signals during the development of pancreatic neoplasms? How do TGF β and Kras signals interact and are there differences depending on cancer state?
TGF β Paradox EL-Kras/ Tgfbr1 +/ - have less lesions vs. EL-Kras Penetrance, Frequency, and Size of CPN lesions Cancer Res . 2009 Dec 15;69(24):9169-74
TGF β Paradox What we do know about TGF β signals in PC 1. enforce immunosuppression to protect pancreatic tumor cells 2. promote EMT and the expansion of the TME
TGF β Paradox EL-Kras EL-Kras/Tgfbr2 EL-Kras/Tgfbr1 H&E Trichrome EL-Kras altered TGF β signals +
TGF β Paradox EL-Kras EL-Kras/Tgfbr2 EL-Kras/Tgfbr1 Cleaved Caspase-3 Granzyme B Tgfbr1 +/ - may increase T-cell Cytotoxicity
TGF β Paradox EL-Kras EL-Kras/Tgfbr2 EL-Kras/Tgfbr1 CD3/FoxP3 CD8 TGF β signals support Treg cell function
Recommend
More recommend
