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david piwnica-worms

Geng Ku, Qian Huang, Xiaoxia Wen, John Ye, David Piwnica-Worms, Chun Li
To date, a few studies have investigated the potential use of a short-pulsed laser in selective tumor cell destruction or its mechanism of cell killing. Computer simulation of the spatial and temporal profiles of temperature elevation after pulsed laser irradiation on an infinitesimal point source estimated that the temperature reached its highest point at ∼35 ns after a single 15 ns laser pulse. Moreover, temperature elevation was confined to a radius of sub-micrometer and returned to baseline within 100 ns...
May 31, 2018: ACS Omega
Niki Zacharias, Jaehyuk Lee, Sumankalai Ramachandran, Sriram Shanmugavelandy, James McHenry, Prasanta Dutta, Steven Millward, Seth Gammon, Eleni Efstathiou, Patricia Troncoso, Daniel E Frigo, David Piwnica-Worms, Christopher J Logothetis, Sankar N Maity, Mark A Titus, Pratip Bhattacharya
PURPOSE: Androgen receptor (AR) signaling affects prostate cancer (PCa) growth, metabolism, and progression. Often, PCa progresses from androgen-sensitive to castration-resistant prostate cancer (CRPC) following androgen-deprivation therapy. Clinicopathologic and genomic characterizations of CRPC tumors lead to subdividing CRPC into two subtypes: (1) AR-dependent CRPC containing dysregulation of AR signaling alterations in AR such as amplification, point mutations, and/or generation of splice variants in the AR gene; and (2) an aggressive variant PCa (AVPC) subtype that is phenotypically similar to small cell prostate cancer and is defined by chemotherapy sensitivity, gain of neuroendocrine or pro-neural marker expression, loss of AR expression, and combined alterations of PTEN, TP53, and RB1 tumor suppressors...
May 10, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Kelly Flentie, Caleb Gonzalez, Brandon Kocher, Yue Wang, Hongtu Zhu, Jayne Marasa, David Piwnica-Worms
Bacterial flagellin is a potent activator of NFκB signaling, inflammation, and host innate immunity, and recent data indicate that flagellin represents a novel antitumor ligand acting through toll-like receptor 5 (TLR5) and the NFκB pathway to induce host immunity and aid in the clearance of tumor xenografts. To identify innate signaling components of TLR5 responsible for these antitumor effects, a loss-of-function high-throughput screen was employed utilizing carcinoma cells expressing a dynamic NFκB bioluminescent reporter stimulated by Salmonella typhimurium expressing flagellin...
March 9, 2018: Molecular Cancer Research: MCR
Jun Zhao, Huamin Wang, Cheng-Hui Hsiao, Diana S-L Chow, Eugene J Koay, Yaan Kang, Xiaoxia Wen, Qian Huang, Ying Ma, James A Bankson, Stephen E Ullrich, Willem Overwijk, Anirban Maitra, David Piwnica-Worms, Jason B Fleming, Chun Li
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. It has an excessive desmoplastic stroma that can limit the intratumoral delivery of chemotherapy drugs, and protect tumor cells against radiotherapy. Therefore, both stromal and tumor compartments need to be addressed in order to effectively treat PDAC. We hereby co-deliver a sonic hedgehog inhibitor, cyclopamine (CPA), and a cytotoxic chemotherapy drug paclitaxel (PTX) with a polymeric micelle formulation (M-CPA/PTX). CPA can deplete the stroma-producing cancer-associated fibroblasts (CAFs), while PTX can inhibit tumor proliferation...
March 2018: Biomaterials
Andrew Nickless, Abigael Cheruiyot, Kevin C Flanagan, David Piwnica-Worms, Sheila A Stewart, Zhongsheng You
Persistent DNA damage induces profound alterations in gene expression that, in turn, influence tissue homeostasis, tumorigenesis, and cancer treatment outcome. However, the underlying mechanism for gene expression reprogramming induced by persistent DNA damage remains poorly understood. Here, using a highly effective bioluminescence-based reporter system and other tools, we report that persistent DNA damage inhibits nonsense-mediated RNA decay (NMD), an RNA surveillance and gene-regulatory pathway, in noncycling cells...
September 15, 2017: Journal of Biological Chemistry
Triparna Sen, Pan Tong, C Allison Stewart, Sandra Cristea, Aly Valliani, David S Shames, Abena B Redwood, You Hong Fan, Lerong Li, Bonnie S Glisson, John D Minna, Julien Sage, Don L Gibbons, Helen Piwnica-Worms, John V Heymach, Jing Wang, Lauren Averett Byers
Effective targeted therapies for small-cell lung cancer (SCLC), the most aggressive form of lung cancer, remain urgently needed. Here we report evidence of preclinical efficacy evoked by targeting the overexpressed cell-cycle checkpoint kinase CHK1 in SCLC. Our studies employed RNAi-mediated attenuation or pharmacologic blockade with the novel second-generation CHK1 inhibitor prexasertib (LY2606368), currently in clinical trials. In SCLC models in vitro and in vivo , LY2606368 exhibited strong single-agent efficacy, augmented the effects of cisplatin or the PARP inhibitor olaparib, and improved the response of platinum-resistant models...
July 15, 2017: Cancer Research
Federica Pisaneschi, Lindsay E Kelderhouse, Amanda Hardy, Brian J Engel, Uday Mukhopadhyay, Carlos Gonzalez-Lepera, Joshua P Gray, Argentina Ornelas, Terry T Takahashi, Richard W Roberts, Stephen V Fiacco, David Piwnica-Worms, Steven W Millward
Radiolabeling of substrates with 2-[(18)F]fluoroethylazide exploits the rapid kinetics, chemical selectivity, and mild conditions of the copper-catalyzed azide-alkyne cycloaddition reaction. While this methodology has proven to result in near-quantitative labeling of alkyne-tagged precursors, the relatively small size of the fluoroethylazide group makes separation of the (18)F-labeled radiotracer and the unreacted precursor challenging, particularly with precursors >500 Da (e.g., peptides). We have developed an inexpensive azide-functionalized resin to rapidly remove unreacted alkyne precursor following the fluoroethylazide labeling reaction and integrated it into a fully automated radiosynthesis platform...
February 15, 2017: Bioconjugate Chemistry
Sandun Perera, David Piwnica-Worms, Mian M Alauddin
Anaplastic lymphoma kinase (ALK), an oncogenic receptor tyrosine kinase, has emerged as a therapeutic target in solid and hematologic tumors. Although several ALK inhibitors have gained recent approval for therapy, non-invasive indicators of target engagement or for use as predictive biomarkers in vivo are lacking. Therefore, we designed and synthesized a radiolabeled analogue of the ALK inhibitor ceritinib, [(18)F]fluoroethyl-ceritinib ([(18)F]-FEC), for use with positron emission tomography. We used two methods to synthesize [(18)F]-FEC...
March 2016: Journal of Labelled Compounds & Radiopharmaceuticals
Emily Powell, Jiansu Shao, Yuan Yuan, Hsiang-Chun Chen, Shirong Cai, Gloria V Echeverria, Nipun Mistry, Keith F Decker, Christopher Schlosberg, Kim-Anh Do, John R Edwards, Han Liang, David Piwnica-Worms, Helen Piwnica-Worms
BACKGROUND: Despite advances in early diagnosis and treatment of cancer patients, metastasis remains the major cause of mortality. TP53 is one of the most frequently mutated genes in human cancer, and these alterations can occur during the early stages of oncogenesis or as later events as tumors progress to more aggressive forms. Previous studies have suggested that p53 plays a role in cellular pathways that govern metastasis. To investigate how p53 deficiency contributes to late-stage tumor growth and metastasis, we developed paired isogenic patient-derived xenograft (PDX) models of triple-negative breast cancer (TNBC) differing only in p53 status for longitudinal analysis...
January 27, 2016: Breast Cancer Research: BCR
Kelsey L Tinkum, Kristina M Stemler, Lynn S White, Andrew J Loza, Sabrina Jeter-Jones, Basia M Michalski, Catherine Kuzmicki, Robert Pless, Thaddeus S Stappenbeck, David Piwnica-Worms, Helen Piwnica-Worms
Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to high-dose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing demonstrated that multiple SI stem cell populations, marked by Lgr5, Bmi1, or HopX expression, contributed to fasting-induced survival...
December 22, 2015: Proceedings of the National Academy of Sciences of the United States of America
Maximillian Rosario, Bai Liu, Lin Kong, Lynne I Collins, Stephanie E Schneider, Xiaoyue Chen, Kaiping Han, Emily K Jeng, Peter R Rhode, Jeffrey W Leong, Timothy Schappe, Brea A Jewell, Catherine R Keppel, Keval Shah, Brian Hess, Rizwan Romee, David R Piwnica-Worms, Amanda F Cashen, Nancy L Bartlett, Hing C Wong, Todd A Fehniger
PURPOSE: Anti-CD20 monoclonal antibodies (mAb) are an important immunotherapy for B-cell lymphoma, and provide evidence that the immune system may be harnessed as an effective lymphoma treatment approach. ALT-803 is a superagonist IL-15 mutant and IL-15Rα-Fc fusion complex that activates the IL-15 receptor constitutively expressed on natural killer (NK) cells. We hypothesized that ALT-803 would enhance anti-CD20 mAb-directed NK-cell responses and antibody-dependent cellular cytotoxicity (ADCC)...
February 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Rajarshi Sengupta, Amy Barone, Jayne Marasa, Sara Taylor, Erin Jackson, Nicole M Warrington, Shyam Rao, Albert H Kim, Jeffrey R Leonard, David Piwnica-Worms, Joshua B Rubin
Tumor growth is not solely a consequence of autonomous tumor cell properties. Rather, tumor cells act upon and are acted upon by their microenvironment. It is tumor tissue biology that ultimately determines tumor growth. Thus, we developed a compound library screen for agents that could block essential tumor-promoting effects of the glioblastoma (GBM) perivascular stem cell niche (PVN). We modeled the PVN with three-dimensional primary cultures of human brain microvascular endothelial cells in Matrigel. We previously demonstrated stimulated growth of GBM cells in this PVN model and used this to assay PVN function...
July 30, 2015: Oncotarget
Sonia A Melo, Linda B Luecke, Christoph Kahlert, Agustin F Fernandez, Seth T Gammon, Judith Kaye, Valerie S LeBleu, Elizabeth A Mittendorf, Juergen Weitz, Nuh Rahbari, Christoph Reissfelder, Christian Pilarsky, Mario F Fraga, David Piwnica-Worms, Raghu Kalluri
Exosomes are lipid-bilayer-enclosed extracellular vesicles that contain proteins and nucleic acids. They are secreted by all cells and circulate in the blood. Specific detection and isolation of cancer-cell-derived exosomes in the circulation is currently lacking. Using mass spectrometry analyses, we identify a cell surface proteoglycan, glypican-1 (GPC1), specifically enriched on cancer-cell-derived exosomes. GPC1(+) circulating exosomes (crExos) were monitored and isolated using flow cytometry from the serum of patients and mice with cancer...
July 9, 2015: Nature
David Piwnica-Worms
No abstract text is available yet for this article.
May 2015: Cancer Journal
Linda G Eissenberg, Michael P Rettig, Julie K Ritchey, Julie L Prior, Sally W Schwarz, Jennifer Frye, Brian S White, Robert S Fulton, Armin Ghobadi, Matthew L Cooper, Daniel R Couriel, Muhammad Esa Seegulam, David Piwnica-Worms, Farrokh Dehdashti, Kenneth Cornetta, John F DiPersio
Described herein is a first-in-man attempt to both genetically modify T cells with an imagable suicide gene and track these transduced donor T cells in allogeneic stem cell transplantation recipients using noninvasive positron emission tomography/computerized tomography (PET/CT) imaging. A suicide gene encoding a human CD34-Herpes Simplex Virus-1-thymidine kinase (CD34-TK75) fusion enabled enrichment of retrovirally transduced T cells (TdT), control of graft-versus-host disease and imaging of TdT migration and expansion in vivo in mice and man...
June 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
Reece J Goiffon, Sara C Martinez, David Piwnica-Worms
Myeloperoxidase (MPO) is a circulating cardiovascular disease (CVD) biomarker used to estimate clinical risk and patient prognosis. Current enzyme-linked immunosorbent assays (ELISA) for MPO concentration are costly and time-intensive. Here we report a novel bioluminescence assay, designated MPO activity on a polymer surface (MAPS), for measuring MPO activity in human plasma samples using the bioluminescent substrate L-012. The method delivers a result in under an hour and is resistant to confounding effects from endogenous MPO inhibitors...
2015: Nature Communications
Lulu Sun, Hiroyuki Miyoshi, Sofia Origanti, Timothy J Nice, Alexandra C Barger, Nicholas A Manieri, Leslie A Fogel, Anthony R French, David Piwnica-Worms, Helen Piwnica-Worms, Herbert W Virgin, Deborah J Lenschow, Thaddeus S Stappenbeck
The host immune system functions constantly to maintain chronic commensal and pathogenic organisms in check. The consequences of these immune responses on host physiology are as yet unexplored, and may have long-term implications in health and disease. We show that chronic viral infection increases epithelial turnover in multiple tissues, and the antiviral cytokines type I interferons (IFNs) mediate this response. Using a murine model with persistently elevated type I IFNs in the absence of exogenous viral infection, the Irgm1(-/-) mouse, we demonstrate that type I IFNs act through nonepithelial cells, including macrophages, to promote increased epithelial turnover and wound repair...
January 14, 2015: Cell Host & Microbe
Linda G Eissenberg, Michael Rettig, Farrokh Dehdashti, David Piwnica-Worms, John F DiPersio
Clinical trials increasingly incorporate suicide genes either as direct lytic agents for tumors or as safety switches in therapies based on genetically modified cells. Suicide genes can also be used as non-invasive reporters to monitor the biological consequences of administering genetically modified cells to patients and gather information relevant to patient safety. These genes can monitor therapeutic outcomes addressable by early clinical intervention. As an example, our recent clinical trial used (18)F-9-(4-fluoro-3-hydroxymethylbutyl)guanine ((18)FHBG) and positron emission tomography (PET)/CT scans to follow T cells transduced with herpes simplex virus thymidine kinase after administration to patients...
2014: Frontiers in Pharmacology
Vijay Sharma, Jothilingam Sivapackiam, Scott E Harpstrite, Julie L Prior, Hannah Gu, Nigam P Rath, David Piwnica-Worms
Lipophilic cationic technetium-99m-complexes are widely used for myocardial perfusion imaging (MPI). However, inherent uncertainties in the supply chain of molybdenum-99, the parent isotope required for manufacturing 99Mo/99mTc generators, intensifies the need for discovery of novel MPI agents incorporating alternative radionuclides. Recently, germanium/gallium (Ge/Ga) generators capable of producing high quality 68Ga, an isotope with excellent emission characteristics for clinical PET imaging, have emerged...
2014: PloS One
Brandon A Kocher, Lynn S White, David Piwnica-Worms
UNLABELLED: Death-associated protein kinase (DAPK3) is a serine/threonine kinase involved in various signaling pathways important to tissue homeostasis and mammalian biology. Considered to be a putative tumor suppressor, the molecular mechanism by which DAPK3 exerts its suppressive function is not fully understood and the field lacks an appropriate mouse model. To address these gaps, an in vitro three-dimensional tumorigenesis model was used and a constitutive DAPK3-knockout mouse was generated...
February 2015: Molecular Cancer Research: MCR
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