tbuckley/cabot-search huggingface dataset:
Abstract 4347: Interphase reduction in ZEB1 and tubulin isotypes in breast cancer cells associated with antimitotic drug treatment
Authors: Sharon Lobert, Mary E. Graichen
Journal: Cancer Research (2014)

Abstract We recently demonstrated that paclitaxel treatment (10X IC50) reduces mRNA for the epithelial to mesenchymal protein ZEB1 and β-tubulin isotype classes I, III and IVB in MDA-MB-231 breast cancer cells, commonly used as a model for triple-negative breast cancers [Lobert et al., Biochemistry Aug 13;52(32):5482-9]. This work showed that miR-200c, which regulates ZEB1, contributes to the changes in β-tubulin isotype mRNA. The current question is whether these parallel changes in ZEB1 and β-tubulin isotype mRNA were unique to antimitotic drug treatment. We treated MDA-MB-231 cells with equipotent (3X IC50) concentrations of paclitaxel, vincristine, eribulin or doxorubicin for 24 hours. Flow cytometry demonstrated that 27-30% of cells were in G2/M (paclitaxel, vincristine and eribulin) compared to 25% of control cells. Thus the cells had similar cell cycle profiles and were not blocked in mitosis. At 24 hours, there were no measurable changes in total tubulin protein by Western blotting. As shown previously, paclitaxel treatment significantly reduced ZEB1 and β-tubulin isotype classes I, III and IVB mRNA. Eribulin treatment significantly reduced ZEB1 and β-tubulin isotype classes I and IVB mRNA, but not β-tubulin class III. Vincristine treatment only reduced β-tubulin class I mRNA. These data together indicate that although antimitotic drugs all target tubulin, they alter signaling pathways that do not overlap. Doxorubicin did not reduce ZEB1 or β-tubulin isotypes; nor did it increase levels of miR-200c, suggesting that these changes may require tubulin or microtubules as a mediator of the effects. These data show that signaling during interphase is altered by antimitotic drug treatment, leading to changes in β-tubulin isotype mRNA levels. A reduction in β-tubulin isotype class III mRNA in interphase cells is associated specifically with paclitaxel treatment. Next generation sequencing for micro-RNAs comparing control cells to those treated with paclitaxel under the conditions described above suggests that nineteen micro-RNAs are either up or downregulated, indicating that the efficacy of paclitaxel may in part be due to micro-RNA regulation of mRNA. (supported by funding from UMMC School of Nursing) Note: This abstract was not presented at the meeting. Citation Format: Sharon Lobert, Mary E. Graichen. Interphase reduction in ZEB1 and tubulin isotypes in breast cancer cells associated with antimitotic drug treatment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4347. doi:10.1158/1538-7445.AM2014-4347
Mobile-Phone Dispatch of Laypersons for CPR in Out-of-Hospital Cardiac Arrest
Authors: Mattias Ringh, Mårten Rosenqvist, Jacob Hollenberg, Martin Jonsson, David Fredman, Per Nordberg, Hans Järnbert-Pettersson, Ingela Hasselqvist-Ax, Gabriel Riva, Leif Svensson
Journal: New England Journal of Medicine (2015)

Cardiopulmonary resuscitation (CPR) performed by bystanders is associated with increased survival rates among persons with out-of-hospital cardiac arrest. We investigated whether rates of bystander-initiated CPR could be increased with the use of a mobile-phone positioning system that could instantly locate mobile-phone users and dispatch lay volunteers who were trained in CPR to a patient nearby with out-of-hospital cardiac arrest.
Three-Month Real-Time Dengue Forecast Models: An Early Warning System for Outbreak Alerts and Policy Decision Support in Singapore
Authors: Yuan Shi, Xu Liu, Suet-Yheng Kok, Jayanthi Rajarethinam, Shaohong Liang, Grace Yap, Chee-Seng Chong, Kim-Sung Lee, Sharon S.Y. Tan, Christopher Kuan Yew Chin, Andrew Lo, Waiming Kong, Lee Ching Ng, Alex R. Cook
Journal: Environmental Health Perspectives (2015)

With its tropical rainforest climate, rapid urbanization, and changing demography and ecology, Singapore experiences endemic dengue; the last large outbreak in 2013 culminated in 22,170 cases. In the absence of a vaccine on the market, vector control is the key approach for prevention.We sought to forecast the evolution of dengue epidemics in Singapore to provide early warning of outbreaks and to facilitate the public health response to moderate an impending outbreak.We developed a set of statistical models using least absolute shrinkage and selection operator (LASSO) methods to forecast the weekly incidence of dengue notifications over a 3-month time horizon. This forecasting tool used a variety of data streams and was updated weekly, including recent case data, meteorological data, vector surveillance data, and population-based national statistics. The forecasting methodology was compared with alternative approaches that have been proposed to model dengue case data (seasonal autoregressive integrated moving average and step-down linear regression) by fielding them on the 2013 dengue epidemic, the largest on record in Singapore.Operationally useful forecasts were obtained at a 3-month lag using the LASSO-derived models. Based on the mean average percentage error, the LASSO approach provided more accurate forecasts than the other methods we assessed. We demonstrate its utility in Singapore's dengue control program by providing a forecast of the 2013 outbreak for advance preparation of outbreak response.Statistical models built using machine learning methods such as LASSO have the potential to markedly improve forecasting techniques for recurrent infectious disease outbreaks such as dengue.Shi Y, Liu X, Kok SY, Rajarethinam J, Liang S, Yap G, Chong CS, Lee KS, Tan SS, Chin CK, Lo A, Kong W, Ng LC, Cook AR. 2016. Three-month real-time dengue forecast models: an early warning system for outbreak alerts and policy decision support in Singapore. Environ Health Perspect 124:1369-1375; http://dx.doi.org/10.1289/ehp.1509981.
A randomized comparative trial of sequential versus alternating cyclophosphamide, doxorubicin, and cisplatin and mitomycin, lomustine, and methotrexate in metastatic non-small-cell lung cancer.
Authors: R T Eagan, S Frytak, R L Richardson, E T Creagan, T M Therneau, D T Coles, J R Jett
Journal: Journal of Clinical Oncology (1988)

One hundred eight eligible patients with advanced, metastatic non-small-cell lung cancer (NSCLC) were randomized to treatment with either cyclophosphamide, doxorubicin, and cisplatin (CAP) followed by mitomycin, lomustine, and methotrexate (MCM) on progression (sequential, 54 patients) or to CAP alternating with MCM (alternating, 54 patients). The regression rate (30%) was identical for both treatments. In addition, there were no statistically significant differences noted between treatments for regression duration (6.9 months v 7.6 months), time to progression (2.1 months v 4.4 months), or overall survival (5.5 months v 6.9 months). The lack of advantage for the theoretically superior alternating approach was probably due to a combination of relative ineffectiveness of each treatment and lack of complete non-cross resistance.
Apelin targets gut contraction to control glucose metabolism via the brain
Authors: Audren Fournel, Anne Drougard, Thibaut Duparc, Alysson Marlin, Stuart M Brierley, Joel Castro, Sophie Le-Gonidec, Bernard Masri, André Colom, Alexandre Lucas, Perrine Rousset, Nicolas Cenac, Nathalie Vergnolle, Philippe Valet, Patrice D Cani, Claude Knauf
Journal: Gut (2015)

Objective The gut–brain axis is considered as a major regulatory checkpoint in the control of glucose homeostasis. The detection of nutrients and/or hormones in the duodenum informs the hypothalamus of the host's nutritional state. This process may occur via hypothalamic neurons modulating central release of nitric oxide (NO), which in turn controls glucose entry into tissues. The enteric nervous system (ENS) modulates intestinal contractions in response to various stimuli, but the importance of this interaction in the control of glucose homeostasis via the brain is unknown. We studied whether apelin, a bioactive peptide present in the gut, regulates ENS-evoked contractions, thereby identifying a new physiological partner in the control of glucose utilisation via the hypothalamus. Design We measured the effect of apelin on electrical and mechanical duodenal responses via telemetry probes and isotonic sensors in normal and obese/diabetic mice. Changes in hypothalamic NO release, in response to duodenal contraction modulated by apelin, were evaluated in real time with specific amperometric probes. Glucose utilisation in tissues was measured with orally administrated radiolabeled glucose. Results In normal and obese/diabetic mice, glucose utilisation is improved by the decrease of ENS/contraction activities in response to apelin, which generates an increase in hypothalamic NO release. As a consequence, glucose entry is significantly increased in the muscle. Conclusions Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders.
Comparative immunohistochemical analysis of Beclin-1 &amp; MDM-2 in benign &amp; malignant ameloblastomas
Authors: MA Elbarrawy
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Ameloblastoma is the most frequently encountered neoplasm arising from the odontogenic epithelium. Beclin-1 protein plays a critical role in autophagy as a tumor suppressor gene. Whereas, the Murine Double Minute 2 (MDM-2) is a cellular proto-oncogene capable, if amplified, of
Extensive Families of miRNAs and<i>PHAS</i>Loci in Norway Spruce Demonstrate the Origins of Complex phasiRNA Networks in Seed Plants
Authors: Rui Xia, Jing Xu, Siwaret Arikit, Blake C. Meyers
Journal: Molecular Biology and Evolution (2015)

In eudicot plants, the miR482/miR2118 superfamily regulates and instigates the production of phased secondary small interfering RNAs (siRNAs) from NB-LRR (nucleotide binding leucine-rich repeat) genes that encode disease resistance proteins. In grasses, this miRNA family triggers siRNA production specifically in reproductive tissues from long noncoding RNAs. To understand this functional divergence, we examined the small RNA population in the ancient gymnosperm Norway spruce (Picea abies). As many as 41 miRNA families in spruce were found to trigger phasiRNA (phased, secondary siRNAs) production from diverse PHAS loci, with a remarkable 19 miRNA families capable of targeting over 750 NB-LRR genes to generate phasiRNAs. miR482/miR2118, encoded in spruce by at least 24 precursor loci, targets not only NB-LRR genes to trigger phasiRNA production (as in eudicots) but also noncoding PHAS loci, generating phasiRNAs preferentially in male or female cones, reminiscent of its role in the grasses. These data suggest a dual function of miR482/miR2118 present in gymnosperms that was selectively yet divergently retained in flowering plants. A few MIR482/MIR2118 precursors possess an extremely long stem-loop structure, one arm of which shows significant sequence similarity to spruce NB-LRR genes, suggestive of an evolutionary origin from NB-LRR genes through gene duplication. We also characterized an expanded miR390-TAS3 (TRANS-ACTING SIRNA GENE 3)-ARF (AUXIN RESPONSIVE FACTOR) pathway, comprising 18 TAS3 genes of diverse features. Finally, we annotated spruce miRNAs and their targets. Taken together, these data expand our understanding of phasiRNA network in plants and the evolution of plant miRNAs, particularly miR482/miR2118 and its functional diversification.
nCounter® PanCancer Immune Profiling Panel (NanoString Technologies, Inc., Seattle, WA)
Authors: Alessandra Cesano
Journal: Journal for ImmunoTherapy of Cancer (2015)

The nCounter PanCancer Immune Profiling Panel is a unique 770-plex gene expression panel to measure the human immune response in both solid and liquid cancer types. The panel measures many features of the immune response to facilitate rapid development of clinical actionable gene expression profiles
Highly Disordered Array of Silicon Nanowires: an Effective and Scalable Approach for Performing and Flexible Electrochemical Biosensors
Authors: Luca Maiolo, Davide Polese, Alessandro Pecora, Guglielmo Fortunato, Yosi Shacham‐Diamand, Annalisa Convertino
Journal: Advanced Healthcare Materials (2015)

The direct integration of disordered arranged and randomly oriented silicon nanowires (SiNWs) into ultraflexible and transferable electronic circuits for electrochemical biosensing applications is proposed. The working electrode (WE) of a three‐electrode impedance device, fabricated on a polyimide (PI) film, is modified with SiNWs covered by a thin Au layer and functionalized to bind the sensing element. The biosensing behavior is investigated through the ligand–receptor binding of biotin–avidin system. Impedance measurements show a very efficient detection of the avidin over a broad range of concentrations from hundreds of micromolar down to the picomolar values. The impedance response is modeled through a simple equivalent circuit, which takes into account the unique WE morphology and its modification with successive layers of biomolecules. This approach of exploiting highly disordered SiNW ensemble in biosensing proves to be very promising for the following three main reasons: first, the system morphology allows high sensing performance; second, these nanostructures can be built via scalable and transferable fabrication methodology allowing an easy integration on non‐conventional substrates; third, reliable modeling of the sensing response can be developed by considering the morphological and surface characteristics over an ensemble of disordered NWs rather than over individual NWs.
Systemic Immune Activity Predicts Overall Survival in Treatment-Naïve Patients with Metastatic Pancreatic Cancer
Authors: Matthew R. Farren, Thomas A. Mace, Susan Geyer, Sameh Mikhail, Christina Wu, Kristen Ciombor, Sanaa Tahiri, Daniel Ahn, Anne M. Noonan, Miguel Villalona-Calero, Tanios Bekaii-Saab, Gregory B. Lesinski
Journal: Clinical Cancer Research (2015)

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a 5-year survival rate <7% and is ultimately refractory to most treatments. To date, an assessment of immunologic factors relevant to disease has not been comprehensively performed for treatment-naïve patients. We hypothesized that systemic immunologic biomarkers could predict overall survival (OS) in treatment-naïve PDAC patients.Peripheral blood was collected from 73 patients presenting with previously untreated metastatic PDAC. Extensive immunologic profiling was conducted to assess relationships between OS and the level of soluble plasma biomarkers or detailed immune cell phenotypes as measured by flow cytometry.Higher baseline levels of the immunosuppressive cytokines IL6 and IL10 were strongly associated with poorer OS (P = 0.008 and 0.026, respectively; HR = 1.16 and 1.28, respectively), whereas higher levels of the monocyte chemoattractant MCP-1 were associated with significantly longer OS (P = 0.045; HR = 0.69). Patients with a greater proportion of antigen-experienced T cells (CD45RO(+)) had longer OS (CD4 P = 0.032; CD8 P = 0.036; HR = 0.36 and 0.61, respectively). Although greater expression of the T-cell checkpoint molecule CTLA-4 on CD8(+) T cells was associated with significantly shorter OS (P = 0.020; HR = 1.53), the TIM3 molecule had a positive association with survival when expressed on CD4(+) T cells (P = 0.046; HR = 0.62).These data support the hypothesis that baseline immune status predicts PDAC disease course and overall patient survival. To our knowledge, this work represents the largest cohort and most comprehensive immune profiling of treatment-naïve metastatic PDAC patients to date. Clin Cancer Res; 22(10); 2565-74. ©2015 AACR.
P0878 : First ribavirin-free sofosbuvir and simeprevir treatment of Hepatitis C genotype 1 patients with severe renal impairment (GFR &lt;30 ml/min or dialysis)
Authors: F. Czul, E. Schiff, A. Peyton, C. Levy, M. Hernandez, L. Jeffers, C. O’Brien, P. Martin, K.R. Bhamidimarri
Journal: Journal of Hepatology (2015)
Decision Making in a Data-Poor Environment: Management of Brain Metastases From Testicular and Extragonadal Germ Cell Tumors
Authors: Timothy Gilligan
Journal: Journal of Clinical Oncology (2015)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 32-year-old man with a history of a mixed germ cell tumor of the testis presented with acute-onset, right-sided weakness and numbness. His previous treatment included orchiectomy, which revealed a 5-cm tumor that was 95% yolk sac tumor and 5% embryonal carcinoma, and retroperitoneal lymph node dissection for clinical stage I disease in January 2010, which revealed no nodal metastases. Starting in June 2010, he was treated with four cycles of etoposide and cisplatin for pulmonary and thoracic lymph node metastases and a rising serum alpha-fetoprotein (AFP) level. He subsequently received four cycles of paclitaxel, ifosfamide, and cisplatin for relapse in the lungs and mediastinal nodes with a rising AFP level starting in January 2011. He reported having a 2-week history of intermittent headaches in December 2011, when he presented with acute-onset, right-sided weakness and numbness. Computed tomographs of the head was obtained and demonstrated a left parietal intracranial hemorrhage without midline shift or hydrocephalus. Brain magnetic resonance imaging (MRI) showed a complex, 4.5-cm mass consistent with a hemorrhagic metastasis. His serum AFP level was elevated at 47 ng/mL. The patient became progressively obtunded and underwent emergency surgical decompression and resection of the tumor. Histopathologic evaluation of the resected tissue showed metastatic germ cell tumor predominantly consisting of a yolk sac element ( Fig 1 ). His AFP level declined rapidly after resection, and computed tomography of the chest, abdomen, and pelvis showed no evidence of metastatic disease. However, 2 weeks later, his AFP level rose again, and repeat MRI of the brain showed a 3-cm mass in the left mesial parietal lobe adjacent to the resection site. He started treatment with filgrastim to facilitate collection of circulating hematopoietic stem cells. Several days later, after apheresis, he received his first of two cycles of high-dose carboplatin 700 mg/m 2 on days −5, −4, and −3 and etoposide 750 mg/m 2 on days −5, −4, and −3. The patient had a complete response to high-dose chemotherapy and no major acute complications. His cancer remains in complete remission 3 years later without additional treatment. His three lines of chemotherapy left him with chronic peripheral neuropathy.
Phase II trial of weekly docetaxel and carboplatin for recurrent ovarian and peritoneal cancer: Preliminary results including prevention of carboplatin hypersensitivity
Authors: D. M. Kushner, E. M. Hartenbach, F. Sanchez, J. C. Schink, J. P. Connor, H. H. Bailey, L. S. Harris, S. L. Stewart
Journal: Journal of Clinical Oncology (2004)

5041 Background: Results of the ICON 4/AGO-OVAR-2.2 trial suggest that a platinum/taxane combination provides a survival benefit in relapsed, platinum-sensitive ovarian cancer compared to platinum alone. The optimal combination, in terms of response rate and patient tolerance, has yet to be determined. Methods: Twenty patients have enrolled in this phase II trial of weekly docetaxel (35 mg/m2) and carboplatin (AUC =2) administered days 1, 8, and 15 of a 28-day cycle. In patients without measurable disease, strict CA-125 criteria were used for evaluation. Premedication initially consisted of dexamethasone (4mg po x 3 doses, every 12 hours) and a serotonin antagonist (i.e. dolasetron 100mg po x 1). Results: To date, 16 patients are evaluable for toxicity (14 ovarian, 2 peritoneal), 13 of which have data to determine response. Median treatment-free interval from initial platinum-based therapy to recurrence was 11.5 months (range 4–36 months). Fourteen patients entered the study at first recurrence; 2 received one prior treatment for recurrent disease. Eleven patients had measurable disease; 5 utilized CA-125 criteria. Overall response rate was 54% (7/13), with an average of 3 cycles completed. Grade 3 neutropenia was observed in 3 patients (19%) and grade 4 in 1 (6%). Nine patients enrolled in the trial with grade 1 neuropathy. Only 1 patient experienced worsening symptoms, which resolved with a treatment delay. The most dramatic morbidity was carboplatin hypersensitivity. In the first 40 doses, 6 reactions occurred (15%; 2 grade 1, 1 grade 2, 3 grade 3). The protocol was subsequently amended to include pretreatment with either diphenhydramine or hydroxyzine (50mg). Of those with reactions, two continued on study without incident. The remaining 4 patients came off study. No further reactions occurred in the next 100 doses. Conclusions: Preliminary results suggest that weekly docetaxel and carboplatin is active and well tolerated in recurrent platinum-sensitive ovarian and peritoneal cancer. Carboplatin hypersensitivity can be largely avoided with the addition of H1 receptor blockers. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Watson Pharmaceuticals Watson Phermaceuticals Aventis Pharmaceuticals