tbuckley/cabot-search huggingface dataset:
Abstract 3404: NDRG2 suppresses growth and invasion of gallbladder carcinoma via regulation of matrix metalloproteinase 19/slug interaction
Authors: Nayoung Kim, Jeong-Ki Min, Jin-Man Kim, Hyo Jin Lee
Journal: Cancer Research (2015)

Abstract Background: Gallbladder cancer is a relatively uncommon tumor worldwide but it has a feature of highly invasive and malignant tumor with poor prognosis. However, relevant molecules and/or genes associated with growth and metastasis of gallbladder carcinoma are poorly understood. Although NDRG2 is known as a tumor suppressor gene, its exact role in gallbladder carcinoma remains unknown. Materials and method: For deciphering biological roles of NDRG2 in gallbladder carcinoma, first, we examined the expression of NDRG2 in tumor specimens from 86 gallbladder carcinoma patients by immunostaining and analyzed the correlation between NDRG2 expression and clinicopathologic parameters as well as patient survival. Second, we investigated the functional significance of NDRG2 in gallbladder carcinoma progression by stable knock-down or overexpression of NDRG2 in in vitro and in vivo studies. Results: NDRG2 was differentially expressed in gallbladder carcinoma tissues. The negative expression of NDRG2 was significantly associated with a pathological T stage (P = 0.015), high histological grade (P = 0.020), and perineural invasion (P = 0.016). Multivariate analyses clearly showed that the loss of NDRG2 expression was an independent poor prognostic factor for cancer-specific survival. The stable expression of NDRG2 shRNA in gallbladder carcinoma cell lines significantly increased cell proliferation, anchorage-independent growth, migration and invasion. In addition, NDRG2 shRNA remarkably increased metastasis from the spleen to the liver in mice. Furthermore, loss of NDRG2 expression in cells caused an epithelial-mesenchymal transition through Slug induction by MMP-19 interaction with Slug promoter. Conclusions: In the present study, we showed that loss of NDRG2 expression leads to poor prognosis and enhanced metastasis in gallbladder carcinoma. NDRG2 suppresses MMP-19 which causes an epithelial-mesenchymal transition through Slug induction. These data indicate that NDRG2 suppresses tumor progression via regulating MMP19/Slug axis in gallbladder carcinoma. The loss of NDRG2 is a novel prognostic factor suggesting it could be a useful biomarker in patients with gallbladder carcinoma and a potential therapeutic target. Citation Format: Nayoung Kim, Jeong-Ki Min, Jin-Man Kim, Hyo Jin Lee. NDRG2 suppresses growth and invasion of gallbladder carcinoma via regulation of matrix metalloproteinase 19/slug interaction. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3404. doi:10.1158/1538-7445.AM2015-3404
Clonal evolution leading to ibrutinib resistance in chronic lymphocytic leukemia
Authors: Inhye E. Ahn, Chingiz Underbayev, Adam Albitar, Sarah E. M. Herman, Xin Tian, Irina Maric, Diane C. Arthur, Laura Wake, Stefania Pittaluga, Constance M. Yuan, Maryalice Stetler-Stevenson, Susan Soto, Janet Valdez, Pia Nierman, Jennifer Lotter, Liqiang Xi, Mark Raffeld, Mohammed Farooqui, Maher Albitar, Adrian Wiestner
Journal: Blood (2017)
Mouthwash reduces gonorrhoea in mouth, study finds
Authors: Jacqui Wise
Journal: BMJ (2016)

Gargling daily with the antiseptic mouthwash Listerine may be a useful control measure against gonorrhoea, say Australian researchers in the journal Sexually Transmitted Infections .1

Their preliminary study included 196 gay or bisexual men who had previously tested positive for Neisseria gonorrhoea and were returning to the Melbourne Sexual Health Centre for treatment. Of the 58 men who still tested positive for the bacteria in their throat at this return visit, 33 were randomly assigned to gargle with Listerine Cool Mint and 25 with …
Afatinib vs erlotinib as second-line therapy of patients with advanced SCC of the lung following platinum-based chemotherapy: OS analysis from the global phase III trial LUX-Lung 8 (LL8)
Authors: A. Morabito, A.A. Brandes, A. Sibau, L. Ciuffreda, A. Favaretto, F. Cappuzzo, A. Santoro, E. Vasile, M. Brighenti, F. Ferraù, P. Giordano, M. Tiseo, J. Soria, E. Felip, S. Lu, G.D. Goss, S. Gadgeel, V. Georgoulias, V.K. Chand, A. Ardizzoni
Journal: Annals of Oncology (2015)
Abstract 1318: A protein microarray signature of autoantibody biomarkers for the detection of HER2+ breast cancers
Authors: Benjamin A. Katchman, Rizwan Alam, Matthew S. Field, Jennifer Viloria, Garrick Wallstrom, Joshua LaBaer, Paul Engstrom, Karen S. Anderson
Journal: Cancer Research (2015)

Abstract Introduction: Breast cancer is a heterogeneous disease, clinically defined by expression of the biomarkers ER, PR, and HER2, with 15-30% of breast cancers overexpressing the HER2 protein. Antibodies to tumor antigens that are present in patient sera are potential biomarkers for early detection and prognosis of breast cancer. The purpose of this study is to identify a panel of novel serum biomarkers for the early diagnosis of HER2+ breast cancer. Methods: We screened sera from breast cancer patients for autoantibodies using custom nucleic acid programmable protein microarrays (NAPPA). Plasmid cDNAs encoding 10,000 full-length human proteins with c-terminal GST or FLAG tags were printed on arrays with anti-GST or anti-FLAG antibodies, and transcribed and translated in situ using HeLa expression lysate. Serum samples were obtained at diagnosis from patients with stage I-III HER2+ breast cancer classified by IHC and/or FISH testing (HER2+/ER-/PR-, 47%; HER2+/ER+/PR+, 48%; HER2+/ER-/PR+, 5%). Control sera were age-matched and obtained from women undergoing screening mammography or diagnostic mammography for benign breast disease. The microarrays were screened with sera from 29 cases and 29 controls. 850 antigens were selected, displayed in microarray format, and screened with an independent set of sera 27 cases, 29 benign breast disease controls, and 25 healthy controls. Bound IgG was detected by fluorescence. Results: From the initial 10,000 proteins, we identified 850 proteins using cutoff values of AUC (0.68), sensitivity (0.29), and pAUC (0.0075) at 94% specificity for further analysis. From these, 50 candidate autoantibody biomarkers for the detection of HER2+ breast cancer were identified based on visual analysis and statistical cutoff values of 15% sensitivity at 98% specificity and K-statistic (≥ 0.9). Conclusion: We identified a 50-autoantibody serum signature for the detection of HER2+ breast cancer. Blinded validation studies are ongoing. Citation Format: Benjamin A. Katchman, Rizwan Alam, Matthew S. Field, Jennifer Viloria, Garrick Wallstrom, Joshua LaBaer, Paul Engstrom, Karen S. Anderson. A protein microarray signature of autoantibody biomarkers for the detection of HER2+ breast cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1318. doi:10.1158/1538-7445.AM2015-1318
S-1 plus intravenous and intraperitoneal paclitaxel for gastric cancer with peritoneal metastasis: A report of 100 cases.
Authors: H. Ishigami, S. Kaisaki, H. Yamaguchi, H. Yamashita, S. Emoto, H. Nagawa, J. Kitayama
Journal: Journal of Clinical Oncology (2011)

e14670 Background: Peritoneal metastasis is the most life-threatening metastasis in patients with gastric cancer, and no standard therapy has been established in spite of recent advances in chemotherapy. We previously verified the safety and efficacy of S-1 plus intravenous (IV) and intraperitoneal (IP) paclitaxel (PTX) in phase I and II studies (Oncology 2009, Ann Oncol 2010). We hereby report the results of 100 patients treated with this regimen at the University of Tokyo Hospital. Methods: Gastric cancer patients with macroscopic peritoneal metastasis were implanted with peritoneal access ports, and received combination chemotherapy of S-1 plus IV and IP PTX. PTX was administered IV at 50 mg/m2 and IP at 20 mg/m2 on days 1 and 8. S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. Radical gastrectomy was performed when macroscopic curative resection was made achievable after the chemotherapy. Efficacy and safety were evaluated in all the patients. Results: Between February 2005 and January 2011, 100 patients with peritoneal metastasis were treated, including 80 with primary tumors, 10 after palliative gastrectomy, and 10 with peritoneal recurrence. The median number of courses was 8 (range 1-48). The median survival time (MST) was 22.6 months (95% CI, 17.9-28.9 months). The MSTs of subgroups were as follows: Metastasis to the adjacent peritoneum, 49.6 months (n=10); metastases to the distant peritoneum, 19.7 months (n=90): Ascites negative, 39.3 months (n=29); ascites positive, 19.0 months (n=71): With primary tumors, 20.6 months (n=80); after palliative gastrectomy, 49.6 months (n=10); with peritoneal recurrence, 22.6 months (n=10). Out of 80 patients with primary tumors, 37 patients underwent gastrectomy after response to chemotherapy, and had a MST of 34.9 months. The frequent grade 3/4 toxic effects included neutropenia (36%), leukopenia (20%) and anemia (8%). Infection and obstruction of peritoneal access device were observed in 7 and 6 patients, respectively. There were no treatment-related deaths. Conclusions: Combination chemotherapy of S-1 plus IV and IP PTX is well tolerated and active in gastric cancer patients with peritoneal metastasis.
Abstract 1776: Synergistic anticancer effects of triptolide with celastrol, two main compounds from Thunder God Vine
Authors: Qi-Wei Jiang, Ke-Jun Cheng, Xing Wei, Zhi Shi
Journal: Cancer Research (2015)

Abstract Objective: Triptolide and celastrol are two most widely studied and promising compounds isolated from Thunder God Vine (Trypterigium wilfordii Hook F) with promising anticancer activity. However, their clinical application was limited by toxicity. We aim to investigate the synergistic anti-proliferative effects of triptolide with celastrol in cancer and the molecular mechanism. Methods: The effects of triptolide and celastrol in cancer cells and the molecular mechanism were assessed by using MTT assay in vitro, xenografts mouse model in vivo, flow cytometry, fluorescence microscope and Western blot analysis. Results: The combination of triptolide with celastrol induced strong cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the increasing intracellular ROS accumulation in cancer cells. Pretreatment with ROS scavenger N-acetyl-L-cysteine totally blocked the apoptosis induced by triptolide with celastrol. Treatment with celastrol alone decreased many Hsp90 client proteins including Akt, Cdks, EGFR and Raf1, but lead to stress-induced increase of Hsp70 and Hsp27. Adding triptolide to celastrol treatment abrogated this phenomenon and induced more apoptosis. In xenografts mouse model, the lower-dose combination of triptolide with celastrol significant inhibited the growth of tumors without obvious toxicity. Conclusions: Triptolide in combination with celastrol showed outstanding synergistic anticancer effect, suggesting that this beneficial combination may offer a promising treatment option for cancer patients. Citation Format: Qi-Wei Jiang, Ke-Jun Cheng, Xing Wei, Zhi Shi. Synergistic anticancer effects of triptolide with celastrol, two main compounds from Thunder God Vine. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1776. doi:10.1158/1538-7445.AM2015-1776
Abstract 5270: IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas
Authors: Adriana Olar, Khalida Wani, Kristin Diefes, Lindsey Heathcock, Hinke van Thuijl, Mark Gilbert, Terri Armstrong, Erik Sulman, Daniel Cahill, Jaap Reijneveld, Bauke Ylstra, Pieter Wesseling, Kenneth Aldape
Journal: Cancer Research (2015)

Abstract Diffuse gliomas are up till now graded based upon morphology. Recent findings indicate that isocitrate dehydrogenase (IDH) mutation status defines biologically distinct groups of tumors. The role of tumor grade and mitotic index in patient outcome has not been evaluated following stratification by IDH mutation status. To address this, we interrogated 558 WHO grade II-III diffuse gliomas for IDH1/2 mutations and investigated the prognostic impact of WHO grade within IDH-mutant and wild-type tumor subsets independently. The prognostic impact of grade was modest in IDH-mutant [hazard ratio (HR) = 1.21, 95% confidence interval (CI) = 0.91-1.61] compared to IDH-wild type tumors (HR = 1.74, 95% CI = 0.95-3.16). Using a dichotomized mitotic index cut-off of 4/1000 tumor cells, we found that while mitotic index was significantly associated with outcome in IDH-wild type tumors (log-rank p&amp;lt;0.01, HR = 4.41, 95% CI = 2.55-7.63), it was not associated with outcome in IDH-mutant tumors (log-rank p = 0.471, HR = 1.10, 95% CI = 0.80-1.51), and could demonstrate a statistical interaction (p&amp;lt;0.01) between IDH mutation and mitotic index. Patient age, an established prognostic factor in diffuse glioma, was associated with outcome only in the IDH-wild type subset, and consistent with prior data, 1p/19q co-deletion conferred improved outcome in the IDH-mutant cohort. These findings suggest that stratification of grade II-III gliomas into subsets defined by the presence or absence of IDH mutation leads to subgroups with distinct prognostic characteristics. Further evaluation of grading criteria and prognostic markers is warranted within IDH-mutant versus IDH-wild type diffuse grade II-II gliomas as independent entities. Citation Format: Adriana Olar, Khalida Wani, Kristin Diefes, Lindsey Heathcock, Hinke van Thuijl, Mark Gilbert, Terri Armstrong, Erik Sulman, Daniel Cahill, Jaap Reijneveld, Bauke Ylstra, Pieter Wesseling, Kenneth Aldape. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5270. doi:10.1158/1538-7445.AM2015-5270
Lack of Drug-Drug Interaction Between ATI-5923, a Novel Vitamin K Epoxide Reductase Inhibitor, and Amiodarone, in Beagle Dog
Authors: Anges Choppin, Ian Irwin, Leang Lach, Adrian Davies, Lei Shao, Cyrus Becker, Monica P. Palme, Xavier Paliard, Scott Bowersox, Donn Dennis, Paliard Druzgala
Journal: Blood (2008)
Durable Remissions with Single Agent As2O3 in the Treatment of Newly Diagnosed Cases of Acute Promyelocytic Leukemia: Risk Stratification within This Group and Potential Impact on Future Algorithms.
Authors: Vikram Mathews, Biju George, Kavitha M. Lakshmi, Auro Viswabandya, Ashish Bajel, Alok Srivastava, Mammen Chandy
Journal: Blood (2005)
PWE-027 Aspirin in the aetiology of Crohn's disease and ulcerative colitis: results from a European prospective cohort study
Authors: S S Chan
Journal: Gut (2010)

<h3>Introduction</h3> Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, have detrimental effects on the mucosa of the gastrointestinal tract and may potentially play a role in the aetiology of inflammatory bowel diseases (IBD). The aim of this study was to investigate, for the first time, in a prospective study if aspirin usage is associated with the development of Crohn9s disease (CD) and ulcerative colitis (UC). <h3>Methods</h3> A total of 138 239 men and women, aged 30–74 years, were recruited between 1993 and 1997 into a prospective cohort study (EPIC European Prospective Investigation into Cancer and Nutrition). Participants were resident in Denmark, Germany or Sweden and completed questionnaires which detailed if they had taken aspirin regularly. Participants were followed up to identify those who developed either CD or UC. Each case was matched with four controls for age, gender and recruitment centre. Odds ratios (OR) were calculated by conditional logistic regression, adjusted for cigarette smoking. <h3>Result</h3> A total of 37 participants developed CD and 93 developed UC after a median follow-up time of 4.7 years (range 1.5–9.6 years) and 4.0 years (range 1.7–11.3 years), respectively. The regular intake of aspirin was positively associated with the risk of developing CD (OR 6.84, 95% CI 1.87 to 25.08, p&lt;0.01). In participants who took aspirin, but did not smoke, the odds ratio increased (OR 9.38, 95% CI 2.18 to 40.34, p&lt;0.01) while in those who took aspirin and smoked there was no effect (OR 0.32, 95% CI 0.03 to 3.2). No association was found between aspirin usage and UC (OR 1.11, 95% CI 0.54 to 2.30). <h3>Conclusion</h3> The data suggest that aspirin may be involved in the aetiology of CD for which there are plausible mechanisms, although an interaction occurred between aspirin use and smoking. Further epidemiological studies are required to determine if the association is consistent, but suggest aspirin use should be measured in work investigating the aetiology of CD.
Clinical utility of closure times using the platelet function analyzer‐100/200
Authors: Emmanuel J. Favaloro
Journal: American Journal of Hematology (2016)

The "platelet function analyzer" (PFA)-100 was first introduced to us in 1995. Since then, the instrument has appeared in over 50 reviews and almost 1000 publications. Recently, the PFA-100 has been "upgraded" to the PFA-200, which has transformed the user interface and electronic management, but retained the fundamental mechanics, and essentially provides the same results. The PFA-100/200 has conceivable clinical utility to screen for von Willebrand Disease (VWD) and platelet disorders, and in monitoring desmopressin (DDAVP) therapy in both, and possibly anti-platelet therapy. Its great strengths are its usage simplicity and sensitivity to conditions affecting primary hemostasis. However, as a "global" test, its limitation is that closure time (CT) test results are neither predictive of, nor specific for, any individual disorder. However, utilized properly, the PFA-100/200 reflects a valuable addition to hemostasis laboratories involved in identification or therapeutic-monitoring of disorders of primary hemostasis.
Effect of Various Concentrations of Dimethyl Sulfoxide (DMSO) on Cell Recovery and Clonogenic Potential of Cryopreserved Peripheral Blood Hematopoietic Progenitors
Authors: Andrzej Smagur, Iwona Mitrus, Sebastian Giebel, Maria Sadus-Wojciechowska, Jacek Najda, Tomasz Kruzel, Tomasz Czerw, Joanna Gliwinska, Magdalena Prokop, Magdalena Glowala-Kosinska, Agata Chwieduk, Jerzy Holowiecki
Journal: Blood (2011)
Comprehensive Kinase Profile of Pacritinib, a Non-Myelosuppressive JAK2 Kinase Inhibitor in Phase 3 Development in Primary and Post ET/PV Myelofibrosis
Authors: Jack Singer, Suliman Al-Fayoumi, Haiching Ma, Rami S Komrokji, Ruben Mesa, Srdan Verstovsek
Journal: Blood (2014)
Persistent Telomeric Loss and Functional Impairment of Ph-Negative Hematopoiesis after Successful Treatment of Chronic Myelogenous Leukemia
Authors: Chiara Lobetti Bodoni, Dario Ferrero, Elisa Genuardi, Daniela Sia, Mariella Genuardi, Valentina Giai, Alberto Rocci, Luigia Monitillo, Daniela Drandi, Alessandra Risso, Simone Ferrero, Barbara Mantoan, Rossana Critelli, Serena Bussano, Monia Lunghi, Roberto Passera, Corrado Tarella, Gianluca Gaidano, Mario Boccadoro, Carmelo Carlo-Stella, Marco Ladetto
Journal: Blood (2008)
Outcome of Patients with CML Treated with Dasatinib or Nilotinib after Failure of Second Prior TKIs
Authors: Antonella Russo Rossi, Massimo Breccia, Fausto Castagnetti, Luigiana Luciano, Antonella Gozzini, Mario Annunziata, Bruno Martino, Fabio Stagno, Francesco Cavazzini, Mario Tiribelli, Giuseppe Visani, Patrizia Pregno, Pellegrino Musto, Carmen Fava, Paolo Avanzini, Diamante Turri, Nicola Sgherza, Francesco Albano, Giorgina Specchia
Journal: Blood (2010)
Thrombospondin-1 (TSP1), Transforming Growth Factor-Beta (TGFb) and Connective Tissue Growth Factor (CTGF) are Involved in the Pathophysiology of Diabetic Retinopathy,
Authors: Raul A. De La Cadena, Mario C Rico, Fabiola Del Carpio-Cano, Fayez Safadi, Satya P. Kunapuli, Geoffrey Smith, Omesh Gupta, Jeffrey Henderer, Ann Igbre
Journal: Blood (2011)
408. Oncolytic Vaccines in Combination with PD-L1 Blockade for the Treatment of Melanoma
Authors: Cristian Capasso, Davide Cardella, Martin Muller, Mariangela Garofalo, Lukasz Kuryk, Karita Peltonen, Vincenzo Cerullo
Journal: Molecular Therapy (2016)

The Immunological escape of tumors represents one of the main obstacles to the treatment of malignancies. The approval of drugs able to disrupt the immune suppressive pathways through anti-CTLA-4 monoclonal antibodies represented a milestone in the history of immunotherapy. However, treatment with these immune checkpoint inhibitors (ICIs) seems to be effective only in small cohorts of patients. It has been proposed that the efficacy of ICIs relies on the presence of an undergoing immunological response. For this reason, we hypothesized that oncolytic vaccines, able to elicit a tumor specific response, would synergize with anti-PD-L1 therapy. B16 murine melanomas were established in immunocompetent C57 mice. Then mice were treated with anti-PD-L1 monotherapy, PeptiCRAd (oncolytic vaccine) monotherapy or a combination of the two. The growth of the tumors was analyzed. At the end of the experiment, all the mice mice were euthanized and organs collected for immunological analysis. We investigated antigen-specific T-cell responses and immune suppressive background by flow cytometry and ELISPOT assays.
218. Monitoring ER Stress Activation of the ATF6 Pathway Using Nanoluciferase
Authors: Emily S. Wires, Doug Howard, Mark J. Henderson, Xiaokang Yan, Kathleen A. Trychta, Emily J. Heathward, Yajun Zhang, Molly Lutrey, Christopher Richie, Brandon K. Harvey
Journal: Molecular Therapy (2016)

The endoplasmic reticulum (ER) is an invaluable component of the secretory pathway; serving as the main site for protein synthesis and modification, lipid metabolism, lipoprotein secretion, and calcium homeostasis. In response to "stress", the ER maintains homeostasis through the unfolded protein response (UPR). The UPR is an adaptive response employed by the ER to alleviate stress caused by misfolded proteins. UPR activation is mediated by three transmembrane proteins; IRE1 (inositolrequiring protein-1), ATF6 (activating transcription factor- 6), and PERK (protein kinase RNA-like ER kinase). Here we describe the construction and characterization of a Nanoluciferase-based assay to look at the activation of the ATF6 prong of the UPR. We demonstrate the ability to simultaneously monitor ER calcium homeostasis using a novel Gaussia luciferase-based sensor. Using in vitro and in vivo assays, we demonstrate the ability to monitor ATF6 activation in human neuroblastoma cells, rat hepatoma cell line, and rat liver. With this approach we hope to gain better understanding of the contributions of ATF6 activation and ER calcium depletion in disease pathogenesis. Ongoing studies will examinegenetically or pharmacologically augmenting or inhibiting these pathways as a therapeutic approach.
FDG PET/CT in Carcinoma of the Tongue With Bilateral Adrenal Metastases
Authors: Krishan Kant Agarwal, Girish Kumar Parida, Madhavi Tripathi, Manas Kumar Sahoo, Alok Thakar, Chander Shekhar Bal, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2016)

Squamous cell carcinoma is the most common malignant neoplasm of the oral cavity, and it contributes approximately 90% of all oral malignancies. We present a case of a squamous cell carcinoma of the tongue with rare site of bilateral adrenal metastases on 18F-FDG PET/CT with response evaluation after chemotherapy.