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A Comprehensive Patient-Derived Xenograft Collection Representing The Heterogeneity Of Melanoma., Clemens Krepler, Katrin Sproesser, Patricia Brafford, Marilda Beqiri, Bradley Garman, Min Xiao, Batool Shannan, Andrea Watters, Michela Perego, Gao Zhang, Adina Vultur, Xiangfan Yin, Qin Liu, Ioannis N Anastopoulos, Bradley Wubbenhorst, Melissa A. Wilson, Wei Xu, Giorgos Karakousis, Michael Feldman, Xiaowei Xu, Ravi Amaravadi, Tara C. Gangadhar, David E. Elder, Lauren E. Haydu, Jennifer A. Wargo, Michael A. Davies, Yiling Lu, Gordon B. Mills, Dennie T. Frederick, Michal Barzily-Rokni, Keith T. Flaherty, Dave S. Hoon, Michael Guarino, Joseph J. Bennett, Randall W. Ryan, Nicholas J. Petrelli, Carol L. Shields, Mizue Terai, Takami Sato, Andrew E. Aplin, Alexander Roesch, David Darr, Steve Angus, Rakesh Kumar, Ensar Halilovic, Giordano Caponigro, Sebastien Jeay, Jens Wuerthner, Annette Walter, Matthias Ocker, Matthew B. Boxer, Lynn Schuchter, Katherine L Nathanson, Meenhard Herlyn Nov 2017

A Comprehensive Patient-Derived Xenograft Collection Representing The Heterogeneity Of Melanoma., Clemens Krepler, Katrin Sproesser, Patricia Brafford, Marilda Beqiri, Bradley Garman, Min Xiao, Batool Shannan, Andrea Watters, Michela Perego, Gao Zhang, Adina Vultur, Xiangfan Yin, Qin Liu, Ioannis N Anastopoulos, Bradley Wubbenhorst, Melissa A. Wilson, Wei Xu, Giorgos Karakousis, Michael Feldman, Xiaowei Xu, Ravi Amaravadi, Tara C. Gangadhar, David E. Elder, Lauren E. Haydu, Jennifer A. Wargo, Michael A. Davies, Yiling Lu, Gordon B. Mills, Dennie T. Frederick, Michal Barzily-Rokni, Keith T. Flaherty, Dave S. Hoon, Michael Guarino, Joseph J. Bennett, Randall W. Ryan, Nicholas J. Petrelli, Carol L. Shields, Mizue Terai, Takami Sato, Andrew E. Aplin, Alexander Roesch, David Darr, Steve Angus, Rakesh Kumar, Ensar Halilovic, Giordano Caponigro, Sebastien Jeay, Jens Wuerthner, Annette Walter, Matthias Ocker, Matthew B. Boxer, Lynn Schuchter, Katherine L Nathanson, Meenhard Herlyn

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint …


Cancer-Associated Fibroblasts Neutralize The Anti-Tumor Effect Of Csf1 Receptor Blockade By Inducing Pmn-Mdsc Infiltration Of Tumors., Vinit Kumar, Laxminarasimha Donthireddy, Douglas Marvel, Thomas Condamine, Fang Wang, Sergio Lavilla-Alonso, Ayumi Hashimoto, Prashanthi Vonteddu, Reeti Behera, Marlee A. Goins, Charles Mulligan, Brian Nam, Neil Hockstein, Fred Denstman, Shanti Shakamuri, David W. Speicher, Ashani T. Weeraratna, Timothy Chao, Robert H. Vonderheide, Lucia R. Languino, Peter Ordentlich, Qin Liu, Xiaowei Xu, Albert Lo, Ellen Puré, Chunsheng Zhang, Andrey Loboda, Manuel A. Sepulveda, Linda A. Snyder, Dmitry I. Gabrilovich Nov 2017

Cancer-Associated Fibroblasts Neutralize The Anti-Tumor Effect Of Csf1 Receptor Blockade By Inducing Pmn-Mdsc Infiltration Of Tumors., Vinit Kumar, Laxminarasimha Donthireddy, Douglas Marvel, Thomas Condamine, Fang Wang, Sergio Lavilla-Alonso, Ayumi Hashimoto, Prashanthi Vonteddu, Reeti Behera, Marlee A. Goins, Charles Mulligan, Brian Nam, Neil Hockstein, Fred Denstman, Shanti Shakamuri, David W. Speicher, Ashani T. Weeraratna, Timothy Chao, Robert H. Vonderheide, Lucia R. Languino, Peter Ordentlich, Qin Liu, Xiaowei Xu, Albert Lo, Ellen Puré, Chunsheng Zhang, Andrey Loboda, Manuel A. Sepulveda, Linda A. Snyder, Dmitry I. Gabrilovich

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Tumor-associated macrophages (TAM) contribute to all aspects of tumor progression. Use of CSF1R inhibitors to target TAM is therapeutically appealing, but has had very limited anti-tumor effects. Here, we have identified the mechanism that limited the effect of CSF1R targeted therapy. We demonstrated that carcinoma-associated fibroblasts (CAF) are major sources of chemokines that recruit granulocytes to tumors. CSF1 produced by tumor cells caused HDAC2-mediated downregulation of granulocyte-specific chemokine expression in CAF, which limited migration of these cells to tumors. Treatment with CSF1R inhibitors disrupted this crosstalk and triggered a profound increase in granulocyte recruitment to tumors. Combining CSF1R inhibitor with …


Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations In Prostate Cancer., Alfonso Urbanucci, Stefan J. Barfeld, Ville Kytölä, Harri M. Itkonen, Ilsa M. Coleman, Daniel Vodák, Liisa Sjöblom, Xia Sheng, Teemu Tolonen, Sarah Minner, Christoph Burdelski, Kati K. Kivinummi, Annika Kohvakka, Steven Kregel, Mandeep Takhar, Mohammed Alshalalfa, Elai Davicioni, Nicholas Erho, Paul Lloyd, R. Jeffrey Karnes, Ashley E. Ross, Edward M. Schaeffer, Donald J. Vander Griend, Stefan Knapp, Eva Corey, Felix Y. Feng, Peter S. Nelson, Fahri Saatcioglu, Karen E. Knudsen, Teuvo L.J. Tammela, Guido Sauter, Thorsten Schlomm, Matti Nykter, Tapio Visakorpi, Ian G. Mills Jun 2017

Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations In Prostate Cancer., Alfonso Urbanucci, Stefan J. Barfeld, Ville Kytölä, Harri M. Itkonen, Ilsa M. Coleman, Daniel Vodák, Liisa Sjöblom, Xia Sheng, Teemu Tolonen, Sarah Minner, Christoph Burdelski, Kati K. Kivinummi, Annika Kohvakka, Steven Kregel, Mandeep Takhar, Mohammed Alshalalfa, Elai Davicioni, Nicholas Erho, Paul Lloyd, R. Jeffrey Karnes, Ashley E. Ross, Edward M. Schaeffer, Donald J. Vander Griend, Stefan Knapp, Eva Corey, Felix Y. Feng, Peter S. Nelson, Fahri Saatcioglu, Karen E. Knudsen, Teuvo L.J. Tammela, Guido Sauter, Thorsten Schlomm, Matti Nykter, Tapio Visakorpi, Ian G. Mills

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene …


Firing Up Instead Of Burning Out: Tales From The Front Line Of The Cake Committee, Britainy Stephens, Msw, Lsw, Lora Rhodes, Msw, Lsw, Alison Petok, Msw, Lcsw, Gregory Garber, Msw, Lcsw May 2017

Firing Up Instead Of Burning Out: Tales From The Front Line Of The Cake Committee, Britainy Stephens, Msw, Lsw, Lora Rhodes, Msw, Lsw, Alison Petok, Msw, Lcsw, Gregory Garber, Msw, Lcsw

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

This presentation will focus on an underutilized model of supportive care that can help bring back some of the human moments that can often be lost in delivering supportive oncology care. Handling the often complicated issues that arise in oncology care can take a toll on social workers and our oncology co-workers in other disciplines. In oncology care, especially in an outpatient setting, social workers often fulfill the role of emotional support not just for our patients but also for other oncology professionals. Though we are not employed to act as such, we dually assume the position of therapist and …


Opinion: Inhibition Of Blood-Brain Barrier Repair As A Mechanism In Hiv-1 Disease., Monique E. Maubert, Brian Wigdahl, Michael R. Nonnemacher Apr 2017

Opinion: Inhibition Of Blood-Brain Barrier Repair As A Mechanism In Hiv-1 Disease., Monique E. Maubert, Brian Wigdahl, Michael R. Nonnemacher

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

No abstract provided.


Functional Studies Of Ccaat/Enhancer Binding Protein Site Located Downstream Of The Transcriptional Start Site., Yujie Liu, Michael R. Nonnemacher, Aikaterini Alexaki, Vanessa Pirrone, Anupam Banerjee, Luna Li, Evelyn Kilareski, Brian Wigdahl Mar 2017

Functional Studies Of Ccaat/Enhancer Binding Protein Site Located Downstream Of The Transcriptional Start Site., Yujie Liu, Michael R. Nonnemacher, Aikaterini Alexaki, Vanessa Pirrone, Anupam Banerjee, Luna Li, Evelyn Kilareski, Brian Wigdahl

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Previous studies have identified a CCAAT/enhancer binding protein (C/EBP) site located downstream of the transcriptional start site (DS3). The role of the DS3 element with respect to HIV-1 transactivation by Tat and viral replication has not been characterized. We have demonstrated that DS3 was a functional C/EBPβ binding site and mutation of this site to the C/EBP knockout DS3-9C variant showed lower HIV-1 long terminal repeat (LTR) transactivation by C/EBPβ. However, it was able to exhibit similar or even higher transcription levels by Tat compared to the parental LTR. C/EBPβ and Tat together further enhanced the transcription level of the …


Camp Signaling Enhances Hiv-1 Long Terminal Repeat (Ltr)-Directed Transcription And Viral Replication In Bone Marrow Progenitor Cells., Anupam Banerjee, Luna Li, Vanessa Pirrone, Fred C. Krebs, Brian Wigdahl, Michael R. Nonnemacher Mar 2017

Camp Signaling Enhances Hiv-1 Long Terminal Repeat (Ltr)-Directed Transcription And Viral Replication In Bone Marrow Progenitor Cells., Anupam Banerjee, Luna Li, Vanessa Pirrone, Fred C. Krebs, Brian Wigdahl, Michael R. Nonnemacher

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

CD34+ hematopoietic progenitor cells have been shown to be susceptible to HIV-1 infection, possibly due to a low-level expression of CXCR4, a coreceptor for HIV-1 entry. Given these observations, we have explored the impact of forskolin on cell surface expression of CXCR4 in a cell line model (TF-1). The elevation of intracellular cyclic adenosine monophosphate (cAMP) by forskolin through adenylyl cyclase (AC) resulted in transcriptional upregulation of CXCR4 with a concomitant increase in replication of the CXCR4-utilizing HIV-1 strain IIIB. Transient expression analyses also demonstrated an increase in CXCR4-, CCR5-, and CXCR4-/CCR5-utilizing HIV-1 (LAI, YU2, and 89.6, respectively) promoter …