News Article | May 25, 2017
NASHVILLE, Tenn.--(BUSINESS WIRE)--Sarah Cannon announced today that it will present cancer research insights through more than 90 presentations selected by the American Society of Clinical Oncology (ASCO®) at the 2017 Annual Meeting. Hosted in Chicago, June 2-6, the meeting brings together more than 30,000 cancer experts from around the world to review the latest research to improve the diagnosis and treatment of cancer. “2017 marks the 20th anniversary of our community-based drug development program, which was the first of its kind,” said Howard A. “Skip” Burris III, MD, President of Clinical Operations and Chief Medical Officer at Sarah Cannon. “Since our program’s inception, we have conducted more than 260 first-in-human clinical trials and made countless contributions to the advancement of cancer therapies. As we look to the future, the team at Sarah Cannon remains excited about our clinical research into how novel agents can provide an even greater benefit to patients and looks forward to sharing insights with our colleagues participating in the Annual Meeting.” Highlights of Sarah Cannon’s research include a presentation in a Clinical Science Symposium by Dr. Burris, who will discuss a study of combined inhibition of IDO1 and PD-L1 in patients with locally-advanced or metastatic solid tumors. Dr. Burris’ presentation, in the symposium titled "Check" This Out: The Step Beyond PD-1 Blockade, will take place on Sunday, June 4 during the session from 9:45-11:15 a.m. in Hall D1. Dr. Burris will also participate as a discussant in a Clinical Science Symposium, Hitting the Target: Antibody-Drug Conjugates, on Monday, June 5 from 9:45-11:15 a.m. in Hall D1, at which David Spigel, MD, Chief Scientific Officer and Director, Lung Cancer Research Program, Sarah Cannon Research Institute, will moderate the discussion. Additionally, Ian Flinn, MD, PhD, Director, Blood Cancer Research Program, Sarah Cannon Research Institute, will present an Oral Abstract on results of the BRIGHT 5-year follow-up study, a first-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP, on Saturday, June 3 in the session from 3-6 p.m. in room S100BC. This abstract has also been selected as part of the Best of ASCO® program, which will be held this summer following the meeting, and highlights significant data impacting oncology research and care. Several other Sarah Cannon investigators are presenting noteworthy studies and insights at ASCO®: For a full listing of all presentations authored by Sarah Cannon investigators, visit sarahcannon.com/asco. Additional authors presenting for Sarah Cannon at the conference include: Hendrik-Tobias Arkenau, MD, PhD, FRCP, Raid Aljumaily, MD, Todd Bauer, MD, Johanna Bendell, MD, William Donnellan, MD, Professor Paul Ellis, MD, FRACP, Gerald Falchook, MD, MS, Carol Greenlees, PhD, Camille Gunderson, MD, Erika Hamilton, MD, John Hainsworth, MD, Lowell Hart, MD, Maen Hussein, MD, Jeffrey Infante, MD, Suzanne Jones, PharmD, Kathleen Moore, MD, Manish Patel, MD, DK Strickland, MD, Professor Charles Swanton, FRCP, BSc, PhD, Judy Wang, MD and Denise Yardley, MD. The researchers represent Sarah Cannon’s global network of strategic sites: Sarah Cannon Research Institute at Tennessee Oncology, Sarah Cannon Research Institute at HealthONE, Sarah Cannon Research Institute - United Kingdom, Colorado Blood Cancer Institute, The Center for Cancer and Blood Disorders - Ft. Worth, Sarah Cannon Research Institute at Florida Cancer Specialists, Sarah Cannon Research Institute at HCA Midwest Health and The Stephenson Cancer Center at the University of Oklahoma. Sarah Cannon Research Institute is the research arm of HCA Healthcare’s global cancer institute, Sarah Cannon. Focused on advancing therapies for patients, it is one of the world’s leading clinical research organizations conducting community-based clinical trials throughout the United States and United Kingdom. Sarah Cannon’s network of strategic sites includes more than 275 physicians who engage in research. The organization has led more than 260 first-in-man clinical trials since its inception in 1993, and has been a clinical trial leader in the majority of approved cancer therapies over the last 10 years. Additionally, Sarah Cannon offers management, regulatory, and other research support services for drug development and industry sponsors as well as strategic investigator sites through its contract research organization (CRO), Sarah Cannon Development Innovations. For more information, visit sarahcannon.com.
Dohadwala M.,Lung Cancer Research Program |
Dohadwala M.,Veterans Affairs Greater Los Angeles Healthcare System |
Wang G.,Lung Cancer Research Program |
Heinrich E.,Lung Cancer Research Program |
And 12 more authors.
Otolaryngology - Head and Neck Surgery (United States) | Year: 2010
OBJECTIVES: To determine the role of ZEB1 in the inflammation-induced promotion of the epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: A molecular biology study. Real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemical staining of human HNSCC tissue sections were used to determine how inflammation affects the transcriptional repressor, ZEB1. SETTING: An academic hospital laboratory. SUBJECTS AND METHODS: Relative ZEB1 RNA levels were determined by RT-PCR, and protein expression was evaluated in situ by immunohistochemical staining of human HNSCC tissue sections. RESULTS: IL-1-treated HNSCC cell lines demonstrated a significant decrease in E-cadherin mRNA and an increase in the mRNA expression of the transcriptional repressor ZEB1. IL-1β exposure led to enhanced ZEB1 binding at the chromatin level, as determined by chromatin immunoprecipitation assays (ChIP). An inverserelaion between ZEB1 and E-cadherin was demonstrated in situ by immunohistochemical staining of human HNSCC tissue sections. CONCLUSIONS: Our recent investigations indicate that inflammatory mediators are potent regulators of EMT in HNSCC. This is the first report indicating the role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC. This newly defined pathway for transcriptional regulation of E-cadherin in HNSCC has important implications for targeted chemoprevention and therapy. © 2010 American Academy of Otolaryngology-Head and Neck-Surgery Foundation. All rights reserved.
Gomperts B.N.,Mattel Childrens Hospital |
Gomperts B.N.,University of California at Los Angeles |
Gomperts B.N.,Lung Cancer Research Program |
Walser T.C.,Lung Cancer Research Program |
And 4 more authors.
Cancer Prevention Research | Year: 2013
The "field of cancerization" refers to histologically normal-appearing tissue adjacent to neoplastic tissue that displays molecular abnormalities, some of which are the same as those of the tumor. Improving our understanding of these molecular events is likely to increase our understanding of carcinogenesis. Kadara and colleagues attempt to characterize the molecular events occurring temporally and spatially within the field of cancerization of patients with early-stage non-small cell lung cancer (NSCLC) following definitive surgery. They followed patients with bronchoscopies annually after tumor resection and extracted RNA from the serial brushings from different endobronchial sites. They then conducted microarray analysis to identify gene expression differences over time and in different sites in the airway. Candidate genes were found that may have biologic relevance to the field of cancerization. For example, expression of phosphorylated AKT and ERK1/2 was found to increase in the airway epithelium with time. Although there are limitations in the study design, this investigation demonstrates the utility of identifying molecular changes in histologically normal airway epithelium in lung cancer. In addition to increasing our understanding of lung cancer biology, studying the field of cancerization has the potential to identify biomarkers from samples obtained in a minimally invasive manner. © 2012 AACR.
St John M.A.,Jonsson Comprehensive Cancer Center |
Wang G.,Lung Cancer Research Program |
Wang G.,University of California at Los Angeles |
Luo J.,Lung Cancer Research Program |
And 14 more authors.
British Journal of Cancer | Year: 2012
Background: Despite focused research in conventional therapies and considerable advances in the understanding of the molecular carcinogenesis of head and neck squamous cell carcinoma (HNSCC), the 5-year survival rate for patients with advanced disease remains 15-20%. The major causes of HNSCC-related deaths are cervical node and distant metastasis. E-cadherin has a key role in epithelial intercellular adhesion and its downregulation is a hallmark of epithelial-mesenchymal transition (EMT), which is associated with invasion, metastasis, and poor prognosis. Epithelial-mesenchymal transition is the major mechanism responsible for mediating invasiveness and metastasis of epithelial cancers. Recently, we reported the role of E-cadherin transcriptional repressors in the inflammation-induced promotion of EMT in HNSCC, which is mediated by COX-2. These findings suggest that therapies targeting the cyclooxygenase pathway may diminish the propensity for tumour metastasis in HNSCC by blocking the PGE2-mediated induction of E-cadherin transcriptional repressors.Methods: Herein, we evaluate the efficacy of the COX-2 inhibitor, apricoxib, in HNSCC cell lines. Apricoxib is effective in preventing tumour cell growth in three-dimensional, and anchorage-independent growth assays, as well as decreasing the capacity for tumour cell migration.Results:Herein, we evaluate the efficacy of the COX-2 inhibitor, apricoxib, in HNSCC cell lines. Apricoxib is effective in preventing tumour cell growth in three-dimensional, and anchorage-independent growth assays, as well as decreasing the capacity for tumour cell migration. Treatment of HNSCC cells with apricoxib also causes greater upregulation of E-cadherin and Muc1 expression and downregulation of vimentin, as compared with celecoxib treatment. This has significant implications for targeted chemoprevention and anti-cancer therapy because E-cadherin expression has been implicated as a marker of sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor and other therapies. We show for the first time the molecular mechanisms underlying the efficacy of apricoxib in HNSCC cells.Conclusion:In addition to reversing EMT via inhibition of COX-2, apricoxib upregulates 15-prostaglandin dehydrogenase and the prostaglandin transporter, thereby reducing the levels of active PGE2 by both suppressing its synthesis and increasing its catabolism. These findings have significant implications for metastasis and tumour progression in HNSCC. © 2012 Cancer Research UK All rights reserved.
Kachroo P.,Lung Cancer Research Program |
Kachroo P.,University of California at Los Angeles |
Lee M.-H.,Lung Cancer Research Program |
Lee M.-H.,University of California at Los Angeles |
And 15 more authors.
Journal of Experimental and Clinical Cancer Research | Year: 2013
Background: Interleukin-27 signaling is mediated by the JAK-STAT pathway via activation of STAT1 and STAT3, which have tumor suppressive and oncogenic activities, respectively. Epithelial-mesenchymal transition (EMT) and angiogenesis are key processes in carcinogenesis. Although IL-27 has been shown to have potent anti-tumor activity in various cancer models, the role of IL-27 in EMT and angiogenesis is poorly understood. In this study, we investigated the role of IL-27 in regulating EMT and angiogenesis through modulation of the STAT pathways in human non-small cell lung carcinoma (NSCLC) cells. Methods. STAT activation following IL-27 exposure was measured in human NSCLC cell lines. Expression of epithelial (E-cadherin, γ-catenin) and mesenchymal (N-cadherin, vimentin) markers were assessed by Western blot analysis. Production of pro-angiogenic factors (VEGF, IL-8/CXCL8, CXCL5) were examined by ELISA. Cell motility was examined by an in vitro scratch and transwell migration assays. Selective inhibitors of STAT1 (STAT1 siRNAs) and STAT3 (Stattic) were used to determine whether both STAT1 and STAT3 are required for IL-27 mediated inhibition of EMT and secretion of angiogenic factors. Results: Our results demonstrate that IL-27 stimulation in NSCLC resulted in 1) STAT1 and STAT3 activation in a JAK-dependent manner, 2) development of epithelial phenotypes, including a decrease in the expression of a transcriptional repressor for E-cadherin (SNAIL), and mesenchymal marker (vimentin) with a reciprocal increase in the expression of epithelial markers, 3) inhibition of cell migration, and 4) reduced production of pro-angiogenic factors. STAT1 inhibition in IL-27-treated cells reversed the IL-27 effect with resultant increased expression of Snail, vimentin and the pro-angiogenic factors. The inhibition of STAT3 activation had no effect on the development of the epithelial phenotype. Conclusion: IL-27 induces mesenchymal to epithelial transition and inhibits the production of pro-angiogenic factors in a STAT1-dominant pathway. These findings highlight the importance of STAT1 in repressing lung carcinogenesis and describe a new anti-tumor mechanism of IL-27. © 2013 Kachroo et al.; licensee BioMed Central Ltd.
Ooi A.T.,University of California at Los Angeles |
Mah V.,University of California at Los Angeles |
Nickerson D.W.,University of California at Los Angeles |
Gilbert J.L.,University of California at Los Angeles |
And 20 more authors.
Cancer Research | Year: 2010
Smoking is the most important known risk factor for the development of lung cancer. Tobacco exposure results in chronic inflammation, tissue injury, and repair. A recent hypothesis argues for a stem/progenitor cell involved in airway epithelial repair that may be a tumor-initiating cell in lung cancer and which may be associated with recurrence and metastasis. We used immunostaining, quantitative real-time PCR, Western blots, and lung cancer tissue microarrays to identify subpopulations of airway epithelial stem/progenitor cells under steady-state conditions, normal repair, aberrant repair with premalignant lesions and lung cancer, and their correlation with injury and prognosis. We identified a population of keratin 14 (K14)-expressing progenitor epithelial cells that was involved in repair after injury. Dysregulated repair resulted in the persistence of K14+ cells in the airway epithelium in potentially premalignant lesions. The presence of K14+ progenitor airway epithelial cells in NSCLC predicted a poor prognosis, and this predictive value was strongest in smokers, in which it also correlated with metastasis. This suggests that reparative K14+ progenitor cells may be tumor-initiating cells in this subgroup of smokers with NSCLC. ©2010 AACR.
Heinrich E.L.,University of California at Los Angeles |
Walser T.C.,University of California at Los Angeles |
Walser T.C.,Lung Cancer Research Program |
Krysan K.,University of California at Los Angeles |
And 7 more authors.
Cancer Microenvironment | Year: 2012
The inflammatory tumor microenvironment (TME) has many roles in tumor progression and metastasis, including creation of a hypoxic environment, increased angiogenesis and invasion, changes in expression of microRNAs (miRNAs) and an increase in a stem cell phenotype. Each of these has an impact on epithelial mesenchymal transition (EMT), particularly through the downregulation of E-cadherin. Here we review seminal work and recent findings linking the role of inflammation in the TME, EMT and lung cancer initiation, progression and metastasis. Finally, we discuss the potential of targeting aspects of inflammation and EMT in cancer prevention and treatment. © 2011 Springer Science+Business Media B.V.