Medical Specialties Commons^™

High-Dose Ipilimumab And High-Dose Interleukin-2 For Patients With Advanced Melanoma., Ann W Silk, Howard L Kaufman, Brendan Curti, Janice M Mehnert, Kim Margolin, David Mcdermott, Joseph Clark, Jenna Newman, Praveen K Bommareddy, Lisa Denzin, Saltanat Najmi, Azra Haider, Weichung Shih, Michael P Kane, Andrew Zloza

Articles, Abstracts, and Reports

High-dose ipilimumab (IPI) and high-dose interleukin-2 (IL-2) are approved agents for metastatic melanoma, but the efficacy and safety of the combination are unknown. The objective of this study was to evaluate the feasibility, safety, and efficacy of combination high-dose IPI and high-dose IL-2 in patients with histologically confirmed advanced unresectable stage III and IV melanoma. This Phase II, multicenter, open-label, single-arm trial was conducted in nine patients enrolled between 12/2014 and 12/2015. Subjects were treated with high-dose IPI 10 mg/kg intravenous (IV) every 3 weeks for four doses starting at week 1 and high-dose IL-2 (600,000 IU/kg IV bolus every …

Using The Ketogenic Diet As An Adjuvant To Cancer Therapy: A Systematic Review, Melanie L. Risola

Honors Undergraduate Theses

Cancer is the second leading cause of death in the United States. Evidence shows that a conventional western diet may contribute to the proliferation of cancer cells, affecting their prognosis. The aim of this review is to examine the efficacy and safety of using the ketogenic diet as an adjuvant to traditional cancer therapy. The systematic literature search was performed in October 2018 on two search engines: EBSCOhost (Medline, CINHAL, Cochrane Central Register of Controlled Trials) and Web of Science using the following key terms: ketogenic diet, high fat & low-carbohydrate diet, Atkins diet, cancer or neoplasms+. The search limitations …

Proposed Biomedical Applications Of Zirconium-Based Metal-Organic Frameworks As Drug Delivery Systems, Ariel Margaret Perry-Mills

Honors Undergraduate Theses

Metal-organic frameworks (MOFs) are a class of highly crystalline nanoporous materials that self-assemble from inorganic metal oxide clusters and multitopic organic linkers. MOFs can be altered in terms of the types of metals and structures of organic linkers used, allowing for a high degree of customization and manipulation of the synergistic chemical or physical properties that arise from the precise coordination of their molecular components, including exceptionally large surface area and pore size. Zirconium-based MOFs, called UiOs in honor of their conception at the University of Oslo, also show remarkable chemical stability in both acidic and basic environments, making them …

Effects Of A Plant-Based Vegan Diet On The Risk Of Cancer: An Integrative Review Of The Literature, Chelsie M. Silavent

Honors Undergraduate Theses

Cancer, an aggressive chronic disease, impacts the lives of millions of people every day. There are numerous proposed triggers related to the diagnosis and much remains to be learned about the causes. Associated with this disease's variability is the challenge to identify a single causative agent that lead to its prevention. Specific topics that need additional evidence relate to environmental factors and lifestyle behaviors in the development, treatment and, in some instances, even suppression of disease progression. Specifically, a diet that excludes animal-based products but consists of a variety of fruits and vegetables (i.e., plant-based vegan diet) is reported to …

If We Build It They Will Come: Targeting The Immune Response To Breast Cancer., Margaret E Gatti-Mays, Justin M Balko, Sofia R Gameiro, Harry D Bear, Sangeetha Prabhakaran, Jami Fukui, Mary L Disis, Rita Nanda, James L Gulley, Kevin Kalinsky, Houssein Abdul Sater, Joseph A Sparano, David Cescon, David B Page, Heather Mcarthur, Sylvia Adams, Elizabeth A Mittendorf

Articles, Abstracts, and Reports

Historically, breast cancer tumors have been considered immunologically quiescent, with the majority of tumors demonstrating low lymphocyte infiltration, low mutational burden, and modest objective response rates to anti-PD-1/PD-L1 monotherapy. Tumor and immunologic profiling has shed light on potential mechanisms of immune evasion in breast cancer, as well as unique aspects of the tumor microenvironment (TME). These include elements associated with antigen processing and presentation as well as immunosuppressive elements, which may be targeted therapeutically. Examples of such therapeutic strategies include efforts to (1) expand effector T-cells, natural killer (NK) cells and immunostimulatory dendritic cells (DCs), (2) improve antigen presentation, and …

Mitochondrial Superoxide Disrupts The Metabolic And Epigenetic Landscape Of Cd4, Cassandra M. Moshfegh, Christopher W. Collins, Venugopal Gunda, A. Vasanthakumar, J. Z. Cao, Pankaj K. Singh, L. A. Godley, Adam J. Case

Journal Articles: Eppley Institute

While the role of mitochondrial metabolism in controlling T-lymphocyte activation and function is becoming more clear, the specifics of how mitochondrial redox signaling contributes to T-lymphocyte regulation remains elusive. Here, we examined the global effects of elevated mitochondrial superoxide (O₂^-) on T-lymphocyte activation using a novel model of inducible manganese superoxide dismutase (MnSOD) knock-out. Loss of MnSOD led to specific increases in mitochondrial O₂^- with no evident changes in hydrogen peroxide (H₂O₂), peroxynitrite (ONOO^-), or copper/zinc superoxide dismutase (CuZnSOD) levels. Unexpectedly, both mitochondrial and glycolytic metabolism showed significant reductions …

Metabolic Alterations In Pancreatic Cancer Progression, Enza Vernucci, Jaime Abrego, Venugopal Gunda, Surendra K. Shukla, Aneesha Dasgupta, Vikrant Rai, Nina V. Chaika, Kyla Buettner, Alysha Illies, Fang Yu, Audrey J. Lazenby, Benjamin J. Swanson, Pankaj K. Singh

Journal Articles: Eppley Institute

Pancreatic cancer is the third leading cause of cancer-related deaths in the USA. Pancreatic tumors are characterized by enhanced glycolytic metabolism promoted by a hypoxic tumor microenvironment and a resultant acidic milieu. The metabolic reprogramming allows cancer cells to survive hostile microenvironments. Through the analysis of the principal metabolic pathways, we identified the specific metabolites that are altered during pancreatic cancer progression in the spontaneous progression (KPC) mouse model. Genetically engineered mice exhibited metabolic alterations during PanINs formation, even before the tumor development. To account for other cells in the tumor microenvironment and to focus on metabolic adaptations concerning tumorigenic …

Fascin Controls Metastatic Colonization And Mitochondrial Oxidative Phosphorylation By Remodeling Mitochondrial Actin Filaments, Shengchen Lin, Chongbiao Huang, Venugopal Gunda, Jianwei Sun, Srikumar P. Chellappan, Zengxun Li, Victoria Izumi, Bin Fang, John Koomen, Pankaj K. Singh, Jihui Hao, Shengyu Yang

Journal Articles: Eppley Institute

The deregulation of the actin cytoskeleton has been extensively studied in metastatic dissemination. However, the post-dissemination role of the actin cytoskeleton dysregulation is poorly understood. Here, we report that fascin, an actin-bundling protein, promotes lung cancer metastatic colonization by augmenting metabolic stress resistance and mitochondrial oxidative phosphorylation (OXPHOS). Fascin is directly recruited to mitochondria under metabolic stress to stabilize mitochondrial actin filaments (mtF-actin). Using unbiased metabolomics and proteomics approaches, we discovered that fascin-mediated mtF-actin remodeling promotes mitochondrial OXPHOS by increasing the biogenesis of respiratory Complex I. Mechanistically, fascin and mtF-actin control the homeostasis of mtDNA to promote mitochondrial OXPHOS. The …

Inhibition Of Geranylgeranyl Diphosphate Synthase Is A Novel Therapeutic Strategy For Pancreatic Ductal Adenocarcinoma, Staci L. Haney, Michelle L. Varney, Yashpal S. Chhonker, Simon Shin, Kamiya Mehla, Ayrianne J. Crawford, Heather Jensen Smith, Lynette M. Smith, Daryl J. Murry, Michael A. Hollingsworth, Sarah A. Holstein

Journal Articles: Eppley Institute

Rab proteins play an essential role in regulating intracellular membrane trafficking processes. Rab activity is dependent upon geranylgeranylation, a post-translational modification that involves the addition of 20-carbon isoprenoid chains via the enzyme geranylgeranyl transferase (GGTase) II. We have focused on the development of inhibitors against geranylgeranyl diphosphate synthase (GGDPS), which generates the isoprenoid donor (GGPP), as anti-Rab agents. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abnormal mucin production and these mucins play important roles in tumor development, metastasis and chemo-resistance. We hypothesized that GGDPS inhibitor (GGDPSi) treatment would induce PDAC cell death by disrupting mucin trafficking, thereby inducing the unfolded …

Evaluation Of Plan Quality And Treatment Efficiency For Single-Isocenter/Two-Lesion Lung Stereotactic Body Radiation Therapy, Lana Sanford, Janelle A. Molloy, Sameera S. Kumar, Marcus Randall, Ronald C. Mcgarry, Damodar Pokhrel

Radiation Medicine Faculty Publications

Purpose/objectives: To evaluate the plan quality and treatment delivery efficiency of single‐isocenter/two‐lesions volumetric modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT).

Materials/methods: Eight consecutive patients with two peripherally located early stage nonsmall‐cell‐lung cancer (NSCLC) lung lesions underwent single‐isocenter highly conformal noncoplanar VMAT SBRT treatment in our institution. A single‐isocenter was placed between the two lesions. Doses were 54 or 50 Gy in 3 and 5 fractions respectively. Patients were treated every other day. Plans were calculated in Eclipse with AcurosXB algorithm and normalized to at least 95% of the planning target volume (PTV) receiving 100% of the prescribed …

Minimal Information For Studies Of Extracellular Vesicles 2018 (Misev2018): A Position Statement Of The International Society For Extracellular Vesicles And Update Of The Misev2014 Guidelines, Clotilde Théry, Kenneth W. Witwer, Elena Aikawa, Maria Jose Alcaraz, Johnathon D. Anderson, Ramaroson Andriantsitohaina, Anna Antoniou, Tanina Arab, Fabienne Archer, Georgia K. Atkiin-Smith, D. Craig Ayre, Jean-Marie Bach, Daniel Bachurski, Hossein Baharvand, Leonora Balaj, Shawn Baldacchino, Natalie N. Bauer, Amy A. Baxter, Mary Bebawy, Carla Beckham, Apolonija Bedina Zavec, Abderrahim Benmoussa, Anna C. Berardi, Paolo Bergese, Ewa Bielska, Cherie Blenkiron, Sylwia Bobis-Wozowicz, Eric Boilard, Wilfrid Boireau, Antonella Bongiovanni, Francesc E. Borràs, Steffi Bosch, Chantal M. Boulanger, Xandra Breakefield, Andrew M. Breglio, Meadhbh Á. Brennan, David R. Brigstock, Alain Brisson, Marike L.D. Broekman, Jacqueline F. Bromberg, Paulina Bryl-Górecka, Shilpa Buch, Amy H. Buck, Dylan Burger, Sara Busatto, Dominik Buschmann, Benedetta Bussolati, Edit I. Buzás, James Bryan Byrd, Giovanni Camussi, David R.F. Carter, Sarah Caruso, Lawrence W. Chamley, Yu-Ting Chang, Chichen Chen, Shuai Chen, Lesley Cheng, Andrew R. Chin, Aled Clayton, Stefano P. Clerici, Alex Cocks, Emanuele Cocucci, Robert J. Coffey, Anabela Cordeiro-Da-Silva, Yvonne Couch, Frank A.W. Coumans, Beth Coyle, Rossella Crescitelli, Miria Ferreira Criado, Crislyn D’ Souza-Schorey, Saumya Das, Amrita Datta Chaudhuri, Paola De Candia, Eliezer F. De Santana Junior, Olivier De Wever, Hernando A. Del Portillo, Tanguy Demaret, Sarah Deville, Andrew Devitt, Bert Dhondt, Dolores Di Vizio, Lothar C. Dieterich, Vincenza Dolo, Ana Paula Dominguez Rubio, Massimo Dominici, Mauricio R. Dourado, Tom A.P Driedonks, Filipe V. Duarte, Heather M. Duncan, Ramon M. Eichenberger, Karin Ekström, Samir El Andaloussi, Celine Elie-Caille, Uta Erdbrügger, Juan M. Falcón-Pérez, Farah Fatima, Jason E. Fish, Miguel Flores-Bellver, András Försönits, Annie Frelet-Barrand, Fabia Fricke, Gregor Fuhrmann, Susanne Gabrielsson, Ana Gámez-Valero, Chris Gardiner, Kathrin Gärtner, Raphael Gaudin, Yong Song Gho, Bernd Giebel, Caroline Gilbert, Mario Gimona, Ilaria Giusti, Deborah C.I. Goberdhan, André Görgens, Sharon M. Gorski, David W. Greening, Julia Christina Gross, Alice Gualerzi, Gopal N. Gupta, Dakota Gustafson, Aase Handberg, Reka A. Haraszti, Paul Harrison, Hargita Hegyesi, An Hendrix, Andrew F. Hill, Fred H. Hochberg, Karl F. Hoffmann, Beth Holder, Harry Holthofer, Baharak Hosseinkhani, Guoku Hu, Yiyao Huang, Veronica Huber, Stuart Hunt, Ahmed Gamal-Eldin Ibrahim, Tsuneya Ikezu, Jameel M. Inal, Mustafa Isin, Alena Ivanova, Hannah K. Jackson, Soren Jacobsen, Steven M. Jay, Muthuvel Jayachandran, Guido Jenster, Lanzhou Jiang, Suzanne M. Johnson, Jennifer C. Jones, Ambrose Jong, Tijana Jovanovic-Talisman, Stephanie Jung, Raghu Kalluri, Shin-Ichi Kano, Sukhbir Kaur, Yumi Kawamura, Evan T. Keller, Delaram Khamari, Elena Khomyakova, Anastasia Khvorova, Peter Kierulf, Kwang Pyo Kim, Thomas Kislinger, Mikael Klingeborn, David J. Klinke Ii, Miroslaw Kornek, Maja M. Kosanović, Árpád Ferenc Kovács, Eva-Maria Krämer-Albers, Susanne Krasemann, Mirja Krause, Igor V. Kurochkin, Gina D. Kusuma, Sören Kuypers, Saara Laitinen, Scott M. Langevin, Lucia R. Languino, Joanne Lannigan, Cecilia Lässer, Louise C. Laurent, Gregory Lavieu, Elisa Lázaro-Ibáñez, Soazig Le Lay, Myung-Shin Lee, Yi Xin Fiona Lee, Debora S. Lemos, Metka Lenassi, Aleksandra Leszczynska, Isaac T.S. Li, Ke Liao, Sten F. Libregts, Erzsebet Ligeti, Rebecca Lim, Sai Kiang Lim, Aija Linē, Karen Linnemannstöns, Alicia Llorente, Catherine A. Lombard, Magdalena J. Lorenowicz, Ákos M. Lörincz, Jan Lötvall, Jason Lovett, Michelle C. Lowry, Xavier Loyer, Quan Lu, Barbara Lukomska, Taral R. Lunavat, Sybren L.N. Maas, Harmeet Malhi, Antonio Marcilla, Jacopo Mariani, Javier Mariscal, Elena S. Martens-Uzunova, Lorena Martin-Jaular, M. Carmen Martinez, Vilma Regina Martins, Mathilde Mathieu, Suresh Mathivanan, Marco Maugeri, Lynda K. Mcginnis, Mark J. Mcvey, David G. Meckes, Jr., Katie L. Meehan, Inge Mertens, Valentina R. Minciacchi, Andreas Möller, Malene Møller Jørgensen, Aizea Morales-Kastresana, Jess Morhayim, François Mullier, Maurizio Muraca, Luca Musante, Veronika Mussack, Dillon C. Muth, Kathryn H. Myburgh, Tanbir Najrana, Muhammad Nawaz, Irina Nazarenko, Peter Nejsum, Christian Neri, Tommaso Neri, Rienk Nieuwland, Leonardo Nimrichter, John P. Nolan, Esther N.M. Nolte-’ T Hoen, Nicole Noren Hooten, Lorraine O’Driscoll, Tina O’Grady, Ana O’Loghlen, Takahiro Ochiya, Martin Olivier, Alberto Ortiz, Luis A. Ortiz, Xabier Osteikoetxea, Ole Ostegaard, Matias Ostrowski, Jaesung Park, D. Michiel Pegtel, Hector Peinado, Francesca Perut, Michael W. Pfaffl, Donald G. Phinney, Bartijn C.H. Pieters, Ryan C. Pink, David S. Pisetsky, Elke Pogge Von Strandmann, Iva Polakovicova, Ivan K.H. Poon, Bonita H. Powell, Ilaria Prada, Lynn Pulliam, Peter Quesenberry, Annalisa Radeghieri, Robert L. Raffai, Stefania Raimondo, Janusz Rak, Marcel I. Ramirez, Graça Raposo, Morsi S. Rayyan, Neta Regev-Rudzki, Fran L. Ricklefs, Paul D. Robbins, David D. Roberts, Silvia C. Rodrigues, Eva Rohde, Sophie Rome, Kasper M.A. Rouschop, Aurelia Rughetti, Ashley E. Russell, Paula Saá, Susmita Sahoo, Edison Salas-Huenuleo, Catherine Sánchez, Julie A. Saugstad, Meike J. Saul, Raymond M. Schiffelers, Raphael Schneider, Tine Hiorth Schøyen, Aaron Scott, Eriomina Shahaj, Shivani Sharma, Olga Shatnyeva, Faezeh Shekari, Ganesh Vilas Shelke, Ashok K. Shetty, Kiyotaka Shiba, Pia R-M Siljander, Andreia M. Silva, Agata Skowronek, Orman L. Snyder Ii, Rodrigo Pedro Soares, Barbara W. Sódar, Carolina Soekmadji, Javier Sotillo, Philip D. Stahl, Willem Stoorvogel, Shannon L. Stott, Erwin F. Strasser, Simon Swift, Hidetoshi Tahara, Muneesh Tewari, Kate Timms, Swasti Tiwari, Rochelle Tixeira, Mercedes Tkach, Wei Seong Toh, Richard Tomasini, Ana Claudia Torrecilhas, Juan Pablo Tosar, Vasilis Toxavidis, Lorena Urbanelli, Pieter Vader, Bas W.M. Van Balkom, Susanne G. Van Der Grein, Jan Van Deun, Martijn J.C. Van Herwijnen, Kendall Van Keuren-Jensen, Guillaume Van Niel, Martin E. Van Royen, Andre J. Van Wijnen, M. Helena Vasconcelos, Ivan J. Vechetti Jr., Tiago D. Veit, Laura J. Vella, Émilie Velot, Frederik J. Verweij, Beate Vestad, Jose L. Viñas, Tamás Visnovitz, Krisztina V. Vukman, Jessica Wahlgren, Dionysios C. Watson, Marca H.M. Wauben, Alissa Weaver, Jason P. Webber, Viktoria Weber, Ann M. Wehman, Daniel J. Weiss, Joshua A. Welsh, Sebastian Wendt, Asa M. Wheelock, Zoltán Wiener, Leonie Witte, Joy Wolfram, Angeliki Xagorari, Patricia Xander, Jing Xu, Xiaomei Yan, María Yáñez-Mó, Hang Yin, Yuana Yuana, Valentina Zappulli, Jana Zarubova, Vytautas Žėkas, Jian-Ye Zhang, Zezhou Zhao, Lei Zheng, Alexander R. Zheutlin, Antje M. Zickler, Pascale Zimmermann, Angela M. Zivkovic, Davide Zocco, Ewa K. Zuba-Surma

Department of Cancer Biology Faculty Papers

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines …

A Microbial-Based Cancer Vaccine For Induction Of Egfrviii-Specific Cd8+ T Cells And Anti-Tumor Immunity., Lauren Zebertavage, Shelly Bambina, Jessica Shugart, Alejandro Alice, Kyra D Zens, Peter Lauer, Bill Hanson, Michael J. Gough, Marka R Crittenden, Keith S Bahjat

Articles, Abstracts, and Reports

Dysregulated signaling via the epidermal growth factor receptor (EGFR)-family is believed to contribute to the progression of a diverse array of cancers. The most common variant of EGFR is EGFRvIII, which results from a consistent and tumor-specific in-frame deletion of exons 2-7 of the EGFR gene. This deletion generates a novel glycine at the junction and leads to constitutive ligand-independent activity. This junction forms a novel shared tumor neo-antigen with demonstrated immunogenicity in both mice and humans. A 21-amino acid peptide spanning the junctional region was selected, and then one or five copies of this 21-AA neo-peptide were incorporated into …

Lipid-Polymer Hybrid Nanoparticles As A Next-Generation Drug Delivery Platform: State Of The Art, Emerging Technologies, And Perspectives., Anubhab Mukherjee, Ariana K Waters, Pranav Kalyan, Achal Singh Achrol, Santosh Kesari, Venkata Yenugonda

Articles, Abstracts, and Reports

Lipid-polymer hybrid nanoparticles (LPHNPs) are next-generation core-shell nanostructures, conceptually derived from both liposome and polymeric nanoparticles (NPs), where a polymer core remains enveloped by a lipid layer. Although they have garnered significant interest, they remain not yet widely exploited or ubiquitous. Recently, a fundamental transformation has occurred in the preparation of LPHNPs, characterized by a transition from a two-step to a one-step strategy, involving synchronous self-assembly of polymers and lipids. Owing to its two-in-one structure, this approach is of particular interest as a combinatorial drug delivery platform in oncology. In particular, the outer surface can be decorated in multifarious ways …

An Inflammatory Landscape For Preoperative Neurologic Deficits In Glioblastoma., Amal Katrib, Hyun-Hwan Jeong, Nina L Fransen, Kristin S Henzel, Jeremy A Miller

Articles, Abstracts, and Reports

No abstract provided.

Ensuring Quality Standards And Reproducible Research For Data Analysis Services In Oncology: A Cooperative Service Model., Frank Emmert-Streib, Matthias Dehmer, Olli Yli-Harja

Articles, Abstracts, and Reports

Modern molecular high-throughput devices, e.g., next-generation sequencing, have transformed medical research. Resulting data sets are usually high-dimensional on a genomic-scale providing multi-factorial information from intertwined molecular and cellular activities of genes and their products. This genomics-revolution installed precision medicine offering breathtaking opportunities for patient's diagnosis and treatment. However, due to the speed of these developments the quality standards of the involved data analyses are lacking behind, as exemplified by the infamous Duke Saga. In this paper, we argue in favor of a two-stage cooperative serve model that couples data generation and data analysis in the most beneficial way from the …

Regeneration Enhances Metastasis: A Novel Role For Neurovascular Signaling In Promoting Melanoma Brain Metastasis., Roshini Prakash, Sivan Izraely, Nikita S Thareja, Rex H Lee, Maya Rappaport, Riki Kawaguchi, Orit Sagi-Assif, Shlomit Ben-Menachem, Tsipi Meshel, Michal Machnicki, Shuichi Ohe, Dave S B Hoon, Giovanni Coppola, Isaac P Witz, S Thomas Carmichael

Articles, Abstracts, and Reports

Neural repair after stroke involves initiation of a cellular proliferative program in the form of angiogenesis, neurogenesis, and molecular growth signals in the surrounding tissue elements. This cellular environment constitutes a niche in which regeneration of new blood vessels and new neurons leads to partial tissue repair after stroke. Cancer metastasis has similar proliferative cellular events in the brain and other organs. Do cancer and CNS tissue repair share similar cellular processes? In this study, we identify a novel role of the regenerative neurovascular niche induced by stroke in promoting brain melanoma metastasis through enhancing cellular interactions with surrounding niche …

Glioblastoma Mimicking Viral Encephalitis Responds To Acyclovir: A Case Series And Literature Review., Keenan J Piper, Haidn Foster, Brandon Gabel, Burt Nabors, Charles Cobbs

Articles, Abstracts, and Reports

Viral encephalitis and glioblastoma are both relatively rare conditions with poor prognoses. While the clinical and radiographic presentations of these diseases are often distinctly different, viral encephalitis can sometimes masquerade as glioblastoma. Rarely, glioblastoma can also be misdiagnosed as viral encephalitis. In some cases where a high-grade glioma was initially diagnosed as viral encephalitis, antiviral administration has proven effective for relieving early symptoms. We present three cases in which patients presented with symptoms and radiographic findings suggestive of viral encephalitis and experienced dramatic clinical improvement following treatment with acyclovir, only to later be diagnosed with glioblastoma in the region of …

Selective Inhibition Of Histone Deacetylases 1/2/6 In Combination With Gemcitabine: A Promising Combination For Pancreatic Cancer Therapy, Richard S. Laschanzky, Lisa E. Humphrey, Jihyun Ma, Lynette M. Smith, Thomas J. Enke, Surendra K. Shukla, Aneesha Dasgupta, Pankaj K. Singh, Gillian M. Howell, Michael G. Brattain, Quan P. Ly, Adrian R. Black, Jennifer D. Black

Journal Articles: Eppley Institute

Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of <10% due in part to a lack of effective therapies. Pan-histone deacetylase (HDAC) inhibitors have shown preclinical efficacy against PDAC but have failed in the clinic due to toxicity. Selective HDAC inhibitors may reduce toxicity while retaining therapeutic efficacy. However, their use requires identification of the specific HDACs that mediate the therapeutic effects of HDAC inhibitors in PDAC. We determined that the HDAC1/2/3 inhibitor Mocetinostat synergizes with the HDAC4/5/6 inhibitor LMK-235 in a panel of PDAC cell lines. Furthermore, while neither drug alone synergizes with gemcitabine, the combination of Mocetinostat, LMK-235, and gemcitabine showed strong synergy. Using small interfering (si)RNA-mediated knockdown, this synergy was attributed to inhibition of HDACs 1, 2, and 6. Pharmacological inhibition of HDACs 1 and 2 with Romidepsin and HDAC6 with ACY-1215 also potently synergized with gemcitabine in a panel of PDAC cell lines, and this drug combination potentiated the antitumor effects of gemcitabine against PDAC xenografts in vivo. Collectively, our data show that inhibition of multiple HDACs is required for therapeutic effects of HDAC inhibitors and support the development of novel strategies to inhibit HDACs 1, 2, and 6 for PDAC therapy.

Human Islet Response To Selected Type 1 Diabetes-Associated Bacteria: A Transcriptome-Based Study, Ahmed M. Abdellatif, Heather Jensen Smith, Robert Z. Harms, Nora Sarvetnick

Journal Articles: Eppley Institute

Type 1 diabetes (T1D) is a chronic autoimmune disease that results from destruction of pancreatic β-cells. T1D subjects were recently shown to harbor distinct intestinal microbiome profiles. Based on these findings, the role of gut bacteria in T1D is being intensively investigated. The mechanism connecting intestinal microbial homeostasis with the development of T1D is unknown. Specific gut bacteria such as Bacteroides dorei (BD) and Ruminococcus gnavus (RG) show markedly increased abundance prior to the development of autoimmunity. One hypothesis is that these bacteria might traverse the damaged gut barrier, and their constituents elicit a response from human islets that causes …

Alkylaminophenol Induces G1/S Phase Cell Cycle Arrest In Glioblastoma Cells Through P53 And Cyclin-Dependent Kinase Signaling Pathway., Phuong Doan, Aliyu Musa, Nuno R Candeias, Frank Emmert-Streib, Olli Yli-Harja, Meenakshisundaram Kandhavelu

Articles, Abstracts, and Reports

Glioblastoma (GBM) is the most common type of malignant brain tumor in adults. We show here that small molecule 2-[(3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl]phenol (THTMP), a potential anticancer agent, increases the human glioblastoma cell death. Its mechanism of action and the interaction of selective signaling pathways remain elusive. Three structurally related phenolic compounds were tested in multiple glioma cell lines in which the potential activity of the compound, THTMP, was further validated and characterized. Upon prolonged exposer to THTMP, all glioma cell lines undergo p53 and cyclin-dependent kinase mediated cell death with the IC

Reverting Immune Suppression To Enhance Cancer Immunotherapy., Bella S Guerrouahen, Cristina Maccalli, Chiara Cugno, Sergio Rutella, Emmanuel T Akporiaye

Articles, Abstracts, and Reports

Tumors employ strategies to escape immune control. The principle aim of most cancer immunotherapies is to restore effective immune surveillance. Among the different processes regulating immune escape, tumor microenvironment-associated soluble factors, and/or cell surface-bound molecules are mostly responsible for dysfunctional activity of tumor-specific CD8

Subcellular Compartmentalization Of Pkm2 Identifies Anti-Pkm2 Therapy Response In Vitro And In Vivo Mouse Model Of Human Non-Small-Cell Lung Cancer., Akiko Suzuki, Sachin Puri, Pamela Leland, Ankit Puri, Tarsem Moudgil, Bernard A Fox, Raj K Puri, Bharat H Joshi

Articles, Abstracts, and Reports

Pyruvate kinase M2 (PKM2) is an alternatively spliced variant, which mediates the conversion of glucose to lactate in cancer cells under normoxic conditions, known as the Warburg effect. Previously, we demonstrated that PKM2 is one of 97 genes that are overexpressed in non-small-cell lung cancer (NSCLC) cell lines. Herein, we demonstrate a novel role of subcellular PKM2 expression as a biomarker of therapeutic response after targeting this gene by shRNA or small molecule inhibitor (SMI) of PKM2 enzyme activity in vitro and in vivo. We examined two established lung cancer cell lines, nine patients derived NSCLC and three normal lung …

Primary Cardiac Sarcoma: A Rare, Aggressive Malignancy With A High Propensity For Brain Metastases., Brittany L Siontis, Lili Zhao, Monika Leja, Jonathan B Mchugh, Maryann M Shango, Laurence H Baker, Scott M Schuetze, Rashmi Chugh

Articles, Abstracts, and Reports

Introduction: Primary cardiac sarcoma (PCS) has a poor prognosis compared to other sarcomas due to late presentation, challenging resection, incidence of metastases, and limited efficacy of systemic therapies.

Methods: A medical record search engine was queried to identify patients diagnosed with PCS from 1992 to 2017 at the University of Michigan.

Results: Thirty-nine patients with PCS had a median age of 41 years (range 2-77). Common histologies were angiosarcoma (AS, 14), high-grade undifferentiated pleomorphic sarcoma (UPS, 10), and leiomyosarcoma (LMS, 5). Sites of origin were left atrium (18), right atrium (16), and pericardium (5). AS was the most common right-sided …

Intratumoral Delivery Of Plasmid Il12 Via Electroporation Leads To Regression Of Injected And Noninjected Tumors In Merkel Cell Carcinoma, Shailender Bhatia, Natalie V. Longino, Natalie J. Miller, Rima Kulikauskas, Jayasri G. Iyer, Dafina Ibrani, Astrid Blom, David R. Byrd, Upendra Parvathaneni, Christopher Twitty, Jean S. Campbell, Mai H. Le, Sharron Gargosky, Robert H. Pierce, Richard Heller, Adil Daud, Paul Nghiem

Bioelectrics Publications

Purpose: Interleukin-12 (IL12) promotes adaptive type I immunity and has demonstrated antitumor efficacy, but systemic administration leads to severe adverse events (AE), including death. This pilot trial investigated safety, efficacy, and immunologic activity of intratumoral delivery of IL12 plasmid DNA (tavo) via in vivo electroporation (i.t.-tavo-EP) in patients with Merkel cell carcinoma (MCC), an aggressive virus-associated skin cancer.

Experimental Design: Fifteen patients with MCC with superficial injectable tumor(s) received i.t.-tavo-EP on days 1, 5, and 8 of each cycle. Patients with locoregional MCC (cohort A, N = 3) received one cycle before definitive surgery in week 4. …

Nanosecond Pulsed Electric Fields Induce Endoplasmic Reticulum Stress Accompanied By Immunogenic Cell Death In Murine Models Of Lymphoma And Colorectal Cancer, Alessandra Rossi, Olga N. Pakhomova, Peter A. Mollica, Maura Casciola, Uma Mangalanathan, Andrei G. Pakhomov, Claudia Muratori

Bioelectrics Publications

Depending on the initiating stimulus, cancer cell death can be immunogenic or non-immunogenic. Inducers of immunogenic cell death (ICD) rely on endoplasmic reticulum (ER) stress for the trafficking of danger signals such as calreticulin (CRT) and ATP. We found that nanosecond pulsed electric fields (nsPEF), an emerging new modality for tumor ablation, cause the activation of the ER-resident stress sensor PERK in both CT-26 colon carcinoma and EL-4 lymphoma cells. PERK activation correlates with sustained CRT exposure on the cell plasma membrane and apoptosis induction in both nsPEF-treated cell lines. Our results show that, in CT-26 cells, the activity of …

Inhibition Of Cancer Stem Cells By Glycosaminoglycan Mimetics, Connor P. O'Hara

Theses and Dissertations

Connor O’Hara July 29, 2019

Inhibition of Cancer Stem Cells by Glycosaminoglycan Mimetics

In the United States cancer is the second leading cause of death, with colorectal cancer (CRC) being the third deadliest cancer and expected to cause over 51,000 fatalities in 2019 alone.¹ The current standard of care for CRC depends largely on the staging, location, and presence of metastasis.² As the tumor grows and invades nearby lymph tissue and blood vessels, CRC has the opportunity to invade not only nearby tissue but also metastasize into the liver and lung (most commonly).³ The 5-year survival rate …

Recent Advances In The Vibrational Spectroscopic Diagnosis Of Non-Small Cell Lung Cancer, Declan O'Dea, Fiona Lyng, Siobhan Nicholson, Finbar O'Connell, Aoife Maguire, Alison Malkin

Articles

Lung cancer is the leading cause of cancer deaths worldwide accounting for 1.69 million deaths in 2015. Studies have indicated a 5 year survival rate of 8%–15% in western countries, although a survival rate as low as 1% has been demonstrated for late stage diagnosis. With the advent of targeted therapies, it is imperative to accurately differentiate non-small cell lung cancer (NSCLC) subtypes in order to ensure efficacy of treatment for patients. Immunohistochemistry and molecular techniques for the diagnosis of NSCLC are increasingly part of the diagnostic algorithm and clinical work-up of lung cancer patients, however due to the limitation …

The Role Of P62/Imp2 In Hepatocellular Carcinoma Progression, Mengtao Xing

Open Access Theses & Dissertations

The family of insulin- like growth factor 2 mRNA binding proteins (IMPs) contains three members: IMP1, p62/IMP2 and IMP3. All these proteins are oncofetal proteins, expressed during embryogenesis and lost in most tissues in adults. However, p62/IMP2 were found overexpressed in various cancers but its function in carcinogenesis remains to be investigated. Our previous studies found that p62/IMP2 was not only overexpressed in hepatocellular carcinoma (HCC) tissues, but also overexpressed in HCC cell lines. To explore the biological roles of p62/IMP2 in HCC progression, p62/IMP2 was knockout in two p62/IMP2 positive HCC cell lines (SNU449, HepG2). Due to the low …

The Effects Of Resveratrol On Dbc1 & Cadherin Expression In Prostate Cancer, Micah Bower-Kaiser

PCOM Biomedical Studies Student Scholarship

Prostate cancer (PCa) is an incredibly common disease in the United States, with approximately 170,000 new diagnoses and 30,000 deaths occurring on an annual basis. The current mainstay of treatment for PCa is known as androgen deprivation therapy (ADT), which has proven to be an effective short-term option in earlier stages of the disease. Unfortunately, longer periods of ADT risk accelerating progression of the cancer to the point where 25% of all treated patients relapse to an incurable, metastatic, and highly lethal form known as castration-resistant prostate cancer (CRPC). In approximately 60% of CRPC cases, a splice variant of androgen …

Benefits Of 3d Breast Tomosynthesis Combined With 2d Digital Mammography In Screening Women For Breast Cancer, Danielle M. Swanson

Physician Assistant Scholarly Project Posters

• Breast cancer screening imaging options have progressed greatly over • the years in sensitivity, specificity, and image quality. According to DynaMed Plus, in 2012 there were 522,000 deaths by breast cancer and 1,677,000 total cases of breast cancer documented (Dynamed, 2018). For years, traditional screening for breast cancer involved 2D digital mammography which obtains two views of each breast. With advances in technology, the use of 3D breast tomosynthesis has become an advantageous addition to routine breast cancer screening protocols at many health care facilities.

• My literature review of articles was found in PubMed, DynaMed Plus, Cochrane Library, …