tbuckley/cabot-search huggingface dataset:
Effects of synthetic human atrial natriuretic peptide on the human coronary circulation in subjects with normal coronary arteries.
Authors: Kensuke Egashira, Tetsuzi Inou, Tsutomu Imaizumi, Hitonobu Tomoike, Akira Takeshita
Journal: Circulation (1991)

Atrial natriuretic peptide (ANP) is recognized as anendogenous vasodilator. The purpose of this study was to determine the effects of a clinical therapeutic dose of synthetic alpha-human ANP on the coronary circulation in 15 subjects with normal coronary arteries and normal ventricular function. The epicardial coronary arterial diameter was measured by selective coronary arteriography. Coronary blood flow was estimated from the arterial cross-sectional area and the flow velocity determined using an subselective intracoronary Doppler catheter. ANP, 0.03 micrograms/min/kg given intravenously over 15 minutes, caused a dilation of the large epicardial coronary artery (n=8): the diameter of the proximal left anterior descending artery dilated from 2.6±0.4 to 3.1±0.5mm (p<0.01). Mean anterial pressure decreased from 89±5 to 83±5mmHg (p<0.01): heart rate did not change during ANP infusion. Estimated coronary blood flow significantly increased (n=6, p<0.01). and thus the coronary vascular resistance decreased after ANP infusion. suggesting an ANP-induced dilation of resistance vessels. The present study demonstrates that in human subjects a clinical dose of ANP by intravenous infusion dilates both the large epicardial and small resistance coronary vessels. These results suggest a potenitally beneficial role for ANP in reducing the severity of myocardial ischemia in patients with ischemic heart disease.
Impact of Plasmacytoid Dendritic Cell (PDC) Recovery on Outcome after Reduced-Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (Allo-SCT).
Authors: Mohamad Mohty, Didier Blaise, Catherine Faucher, Valerie-Jeanne Bardou, Jean-Albert Gastaut, Patrice Viens, Daniel Olive, Beatrice Gaugler
Journal: Blood (2004)
Resistance training interventions across the cancer control continuum: a systematic review of the implementation of resistance training principles
Authors: C M Fairman, P N Hyde, B C Focht
Journal: British Journal of Sports Medicine (2016)

Objectives The primary purpose of this systematic review is to examine the extant resistance training (RT) cancer research to evaluate the proportion of RT interventions that: (1) implemented key RT training principles (specificity, progression, overload) and (2) explicitly reported relevant RT prescription components (frequency, intensity, sets, reps). Design A qualitative systematic review was performed by two reviewers (CMF and PNH) who inspected the titles and abstracts to determine eligibility for this systematic review. Identified papers were obtained in full and further reviewed. Data were extracted to evaluate the application of principles of training, along with specific RT components. Data sources Electronic databases (PubMed, EMBASE, CINAHL, Cochrane, PEDro, PsychInfo, Cancer Lit, Sport Discus, AMED, Cochrane Central Register of Controlled Trials) and reference lists of included articles from inception to May 2016. Results 37 studies were included. The principle of specificity was used appropriately in all of the studies, progression in 65% and overload in 76% of the studies. The most common exercise prescription (∼50%) implemented in the studies included in this review were 2–3 days/week, focusing on large muscle groups, 60–70% 1 repetition maximum (RM), 1–3 sets of 8–12 repetitions. Conclusions Reporting of RT principles in an oncology setting varies greatly, with often vague or non-existent references to the principles of training and how the RT prescription was designed.
PO74EFFECTS OF LANGUAGE MAPPING AND INTRA-OPERATIVE SPEECH AND LANGUAGE THERAPY (SALT) ON AWAKE CRANIOTOMY TUMOUR RESECTIONS: A SINGLE CENTRE EXPERIENCE
Authors: Catherine Zhang, Phillip Copley, Mandy McLeod, Sorin Bucur, Giles Critchley
Journal: Neuro-Oncology (2015)

INTRODUCTION: Language mapping during awake craniotomy is commonly used to guide tumour resection, but there is little description of its outcome. We present a series of 22 patients who underwent awake craniotomies with language mapping for glioma resection between 2007 and 2015. METHOD: Patients who had awake craniotomies with language mapping at a single centre were identified and included in this retrospective study. Details of patient demographics, tumour characteristics, treatment, speech and language assessments (SALT) and outcomes were recorded and analysed. 10 of these patients were also noted to have undergone pre-operative functional MRI (fMRI) with motor and language mapping. RESULTS: The majority were primary gliomas (16), of which 8 were WHO Grade 1-2. 5 out of the 6 recurrent cases were Grade 3-4. 9 were astrocytomas, and the rest were oligodendrogliomas (3), mixed astrocytoma/oligodendroglioma (6), and glioblastomas (4). Pre-operative SALT assessment identified language disorders in 11 patients. Intra-operative language mapping with direct cortical stimulation (DCS) was negative in 7 patients, and extent of tumour resection was guided by positive mapping in 14 patients. Post-operatively, 12 patients' speech remained unchanged, 8 developed worsening speech, and 2 had improved speech. Patients with a pre-operative fMRI were noted to have mildly lower rate of post-operative speech or neurological deficits compared to those who did not (20% vs 33% respectively). CONCLUSION: From our experience and this series, language mapping during awake craniotomies is a helpful tool for safer surgery without increasing complication rate. The addition of pre-operative fMRI may further reduce post-operative speech deficits.
331. CRISPR-Cas9 Can Inhibit HIV-1 Replication but Also Facilitates Virus Escape
Authors: Ben Berkhout, Gang Wang, Na Zhao, Atze T. Das
Journal: Molecular Therapy (2016)

Several recent studies demonstrated that the CRISPR-associated endonuclease Cas9 can be used for guide RNA (gRNA)-directed, sequence-specific cleavage of HIV proviral DNA in infected cells. We here demonstrate profound inhibition of HIV-1 replication by harnessing T cells with Cas9 and antiviral gRNAs. However, the virus rapidly and consistently escaped from this inhibition. Sequencing of the HIV-1 escape variants revealed nucleotide insertions, deletions and substitutions around the Cas9/gRNA cleavage site that are typical for DNA repair by the NHEJ pathway. We thus demonstrate the potency of CRISPR-Cas9 as antiviral approach, but any therapeutic strategy should consider the viral escape options.
100. Evaluation of Ion-Exchange Membranes for the Purification of AAV8 from Culture Media
Authors: Bryan A. Piras, David J. McNally, Timothy D. Lockey, Amit C. Nathwani, Michael M. Meagher
Journal: Molecular Therapy (2016)

Introduction: AAV is the vector of choice for over 6% of all gene therapy clinical trials, with 111 clinical trials open worldwide as of July 2015. However, production of clinical material often relies on inefficient (e. g., size exclusion chromatography, cesium chloride centrifugation) or expensive and highly serotype-specific (e.g., affinity) downstream processes. Therefore, we investigated scalable and potentially serotype-agnostic alternative primary capture and purification methods. Here, we evaluate three ion-exchange membranes with different ligands for their ability to capture and purify AAV8 from culture media, and show highly efficient capture and purification using a Sartobind salt-tolerant interaction chromatography (STIC) with a primary amine (PA) ligand membrane. Methods: AAV8 particles were produced in adherent 293 cells using either serum-free DMEM or DMEM supplemented with 1% FBS. AAV was harvested at day 6 post-transfection, at which point approximately 90% of AAV8 particles were in the culture media. Media was sterile filtered and, in equal volumes using an AKTA Explorer, run over one of three ion-exchange membranes: Sartobind Q or STIC PA anion-exchange membranes, and a Sartobind S cation-exchange membrane. Load, flow-through, wash, and elution fractions were analyzed by qPCR or AAV8 capsid ELISA to determine purification efficiency and BCA was used to quantify total protein in each fraction. Results: Recovery with Sartobind Q and S membranes was very poor, with 12% and 15% recovery, respectively, in the elution fractions and the vast majority of AAV present in the flow-through fractions. The STIC PA membrane performed considerably better, with 99.9% of particles captured by the membrane and approximately 67% of particles in the eluate when the media was adjusted to pH 9 prior to loading and the elution was performed with a gradient of 2M NaCl. However, adjusting the pH to 7 and using a gradient of 3M NaCl led to recoveries of greater than 90% as measured by AAV8 particle ELISA. In addition, the eluate showed an 80% decrease in total protein compared to the load. Results were comparable using both serum-free DMEM and DMEM supplemented with 1% FBS, which showed a dynamic binding capacity of approximately 1×1014 capsids per mL of membrane at 6% breakthrough. Conclusions: While Sartobind Q and S membranes inefficiently captured AAV8, the Sartobind STIC PA membrane captured AAV8 highly efficiently and eluted AAV in a pH and salt-dependent manner with concomitant reduction in total protein. While it remains to be determined whether this modality is suitable for serotypes other than AAV8, the membrane format would allow for processing of an equivalent batch of AAV in less than 1% of the time of a size exclusion column, without the requirement for column packing, and with more efficient recovery.
Abstract 3186: Role of Interleukin 1 signaling in tumor elicited inflammation and colon cancer
Authors: Oxana Dmitrieva, David Possoco, Ralph A. Francescone, Vivianty Hou, Debora B. Vendramini-Costa, Sergey Grivennikov
Journal: Cancer Research (2015)

Abstract Colorectal cancer (CRC) is the 2nd most common cause of cancer deaths in the United States and other developed countries, despite important advances in detection, surgery and chemotherapy. It becomes increasingly clear that not only cell autonomous events in cancer cells are required for tumor growth and progression. Growing CRC tumors possess the ability to recruit inflammatory cells and upregulate inflammatory cytokines - a phenomenon recently introduced as “Tumor elicited inflammation”(TEI). The mechanisms of TEI induction and tumor promotion are not yet well defined. IL23/IL17 pathway is one of the established regulators of TEI. While in mice the ablation of IL-23 signaling results in a uniform loss of IL-17 response and in a decrease in tumor growth; in humans IL23/IL-23R gene expression signature is not always consistent with elevated IL-17 signature, implicating that there should be other regulators of IL-17 and TEI induction in tumors. IL-1 pathway is important for the induction of T helper IL-17 producing cells (Th17) and for the production of IL-17 by innate lymphoid cells (ILC), both in mice and in humans. IL-1 pathway is also implicated in host defense, immunity and tumorigenesis, with some of its functional characteristics similar to IL-23 pathway. In addition, IL-1, much alike IL-23, can be also induced by various microbial derived and host derived ‘danger signals’ readily available within the tumor microenvironment. Our own data suggests that components of IL-1 pathway are upregulated in CRC tumors. Therefore, we hypothesized, that IL-1 pathway might be an important regulator of TEI and CRC tumorigenesis. Using genetic tools and animal models, we examined if IL-1 has the potential role in different stage of CRC and whether it serves as an important regulator of TEI and CRC tumor cells proliferation and survival. Citation Format: Oxana Dmitrieva, David Possoco, Ralph A. Francescone, Vivianty Hou, Debora B. Vendramini-Costa, Sergey Grivennikov. Role of Interleukin 1 signaling in tumor elicited inflammation and colon cancer. [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 3186. doi:10.1158/1538-7445.AM2015-3186
Weekly High-Dose Cidofovir Is an Effective Treatment for Symptomatic BK Virus (BKV)-Associated Hemorrhagic Cystitis (HC) after Allogeneic Stem Cell Transplantation (Allo-SCT).
Authors: Ioannis Baltathakis, Michael Michael, Eirini Grispou, Georgia Kourti, Maria Bouzani, Maria Anagnostopoulou, John Apostolidis, Dimitrios Karakassis, Nicholas Harhalakis, Olga Paniara, Emmanuel Nikiforakis
Journal: Blood (2006)
Abstract 3999: MicroRNA expression links obesity and recurrence in renal cell carcinoma
Authors: Xiang Shu, Michelle A. Hildebrandt, Jian Gu, Nizar M. Tannir, Surena Matin, Jose A. Karam
Journal: Cancer Research (2015)

Abstract Obesity is an established risk factor for clear cell renal cell carcinoma (ccRCC) development and prognosis; however, the mechanisms underlying this link remain unclear. In the present study, we set to assess whether microRNAs (miRNAs) can serve as a molecular link between obesity and recurrence in ccRCC. Through bioinformatics tools and literature search, we identified 126 obesity-related miRNAs. Supplemented with 25 miRNAs which were differentially expressed between ccRCC from normal kidney, we tested the association of these miRNAs with ccRCC recurrence. Significantly decreased levels of hsa-miR-204-5p were found in recurrent ccRCC patients with an over 2-fold increased risk of recurrence (HR = 2.15, p = 0.028, MST = 25.6 vs. 47.2 months). Correlations between miRNA expression and the predicted target genes were tested using gene profiling data generated from these same patients. We found strong inverse correlations between miR-204 expression and several obesity-related genes, including IGF2BP2 (r = -0.40, p = 4.14×10−4), a member of the insulin growth receptor signaling pathway. This correlation was further validated in TCGA data (r = -0.58, p = 1.40×10−22). We also found that low level of hsa-miR-139-5p was significantly associated with increased recurrence risk (HR = 2.37, p = 0.026, MST = 32.2 vs. 51.3 months). In conclusion, we found a set of obesity-related miRNAs that are dysregulated in ccRCC tissues, and some of these miRNAs, such as hsa-miR-204-5p, were associated with the recurrence of RCC, potentially through regulating obesity-related gene expression. Citation Format: Xiang Shu, Michelle A. Hildebrandt, Jian Gu, Nizar M. Tannir, Surena Matin, Jose A. Karam. MicroRNA expression links obesity and recurrence in renal cell carcinoma. [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 3999. doi:10.1158/1538-7445.AM2015-3999
Abstract LB-164: Ran Binding Protein 9 (RanBP9) is a novel mediator of cellular DNA damage response in lung cancer cells
Authors: Dario Palmieri, Mario Scarpa, Anna Tessari, Rexhep Uka, Foued Amari, Cindy Lee, Timothy Richmond, Tyler Sheetz, Jeffrey Parvin, Thomas Ludwig, Carlo M. Croce, Vincenzo Coppola
Journal: Cancer Research (2015)

Abstract Currently, most of the anti-neoplastic treatments for lung cancer patients are based on DNA-damaging cytotoxic therapies such as platinum-containing compounds and radiotherapy. Therefore, a better understanding of the molecular mechanisms involved in the cellular response to genotoxic stresses is required in order to improve the clinical management of lung cancer. Ran Binding Protein 9 (RanBP9, also known as RanBP-M) is a ubiquitous and evolutionary conserved scaffold protein that shuttles between the nucleus and the cytoplasm, and interacts with many major players in tumor biology. However, its biological functions are not well studied and still debated. Here, we show that RanBP9 interacts with and is phosphorylated by ATM, one of the apical activators of the DNA damage response (DDR) following DNA Double-Strand Breaks (DSBs). Following ATM-dependent phosphorylation, RanBP9 rapidly accumulates into the nucleus of lung cancer cells. By using three different lung cancer cell lines (A549, H460, and H1299), we found that stable silencing of RanBP9 (ShRanBP9) significantly affects the DDR. In fact, stable ShRanBP9 clones display a delayed and/or reduced activation of key components of the cellular response to Ionizing Radiation (IR), including ATM, Chk2, H2AX-γ and p53. Accordingly, abrogation of RanBP9 expression significantly affected Homology-Directed repair of damaged DNA. On the other hand, stable silencing of RanBP9 results in increased IR-induced senescence and apoptosis. In summary, here we present evidence that RanBP9 is a novel mediator of the cellular DDR, whose recruitment into the nucleus upon IR is dependent on ATM kinase activity. In turn, nuclear RanBP9 participates to the efficient activation of cellular DDR. On the contrary, its absence hampers the repair of damaged DNA following DSBs, resulting in enhanced lung cancer sensitivity to genotoxic stresses. Taken together, our findings suggest that targeting RanBP9 might represent a new potential approach to increase sensitivity of lung cancer cells to genotoxic anti-neoplastic treatments. Citation Format: Dario Palmieri, Mario Scarpa, Anna Tessari, Rexhep Uka, Foued Amari, Cindy Lee, Timothy Richmond, Tyler Sheetz, Jeffrey Parvin, Thomas Ludwig, Carlo M. Croce, Vincenzo Coppola. Ran Binding Protein 9 (RanBP9) is a novel mediator of cellular DNA damage response in lung cancer cells. [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 LB-164. doi:10.1158/1538-7445.AM2015-LB-164
The Lymphoblastic Leukemia Gene 1 (Lyl1) Regulates Lymphoid Specification and Maintenance of Early T Lineage Progenitors
Authors: Fabian Zohren, George Souroullas, Min Luo, Ulrike Gerdemann, Nicola K Wilson, Berthold Göttgens, Georgi L. Lukov, Margaret Goodell
Journal: Blood (2011)
A Phase I-II Study of Vorinostat and Low Dose Cytarabine for Patients Treated for High Risk Myelodysplastic with Azacytidine Failure: The GFM-VOR2007 Study
Authors: Thomas Prebet, Thorsten Braun, Odile Beyne Rauzy, Francois Dreyfus, Aspasia Stamatoullas, Eric Wattel, Shanti Ame, Emmanuel Raffoux, Jacques Delaunay, Celia Salanoubat, Isabelle Mathieu, Fatiha Chermat, Lionel Ades, Pierre Fenaux, Norbert Vey
Journal: Blood (2010)
SRF/myocardin: a novel molecular axis regulating vascular smooth muscle cell stiffening in hypertension
Authors: Patrick Lacolley, Zhenlin Li, Pascal Challande, Véronique Regnault
Journal: Cardiovascular Research (2016)

This editorial refers to ‘Inhibition of SRF/myocardin reduces aortic stiffness by targeting vascular smooth muscle cell stiffening in hypertension’ by Zhou et al ., pp. 171–182. 

Large artery stiffening is a main risk factor for chronic diseases including aging-related hypertension, heart failure, renal disease, stroke and dementia, which represent major causes of morbidity and mortality. Arterial stiffening is caused primarily by excessive fibrosis due to exuberant accumulation of collagen. More recently the mechanisms of arterial stiffness in hypertension were extended to proteins regulating vascular smooth muscle cell (VSMC) plasticity and cellular stiffness.1

Despite earlier studies showing involvement of the cytoskeletal network, there is a gap in our knowledge regarding underlying mechanisms that initiate cellular stiffness and sustain this process. In this issue Zhou et al 2 provide evidence that VSMC stiffness assessed by atomic force microscopy (AFM) is increased in spontaneously hypertensive rats (SHR) at the level of large arteries but not in small arteries. RNA and protein expression of serum response factor (SFR)/myocardin as well as their downstream targets caldesmon, calponin, and RhoA are increased in thoracic aorta from SHR compared with arteries from Wistar-Kyoto rats (WKY) at 4 months of age. The hypertension induced-increase in SRF represents one of the main mechanisms, as supported by normalization of cellular stiffness measurements in the presence of an inhibitor of SRF activity in both in vitro and in vivo conditions. Normalization of cellular stiffness is paralleled by an improvement of aortic elasticity preceding the reduction of blood pressure in SHR. This finding suggests that …
Abstract 856: Correlation of prognosis and histologic patterns by the IASLC/ATS/ERS classification in invasive pulmonary adenocarcinoma: A meta-analysis
Authors: Keon Uk Park, Jin Young Kim, Hun Mo Ryoo, Ilseon Hwang
Journal: Cancer Research (2015)

Abstract Background: Invasive pulmonary adenocarcinoma is composed of five histologic patterns including lepidic, papillary, acinar, solid, and micropapillary patterns by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society classification. Many researches for histologic pattern and survival rates were performed, but confirmative relationships of histologic pattern and patient's prognosis are unclear. Methods: We searched PubMed using the keywords “IASLC/ATS/ERS classification” and “International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society”. Review articles and case reports were excluded, and duplicated data, insufficient data, and overlapping articles are also excluded. The pooled analysis was performed with the Comprehensive Meta-analysis Software version 2.0. Results: Lepidic predominant pattern had significantly lower recurrence and expire than acinar, papillary, solid or micropapillary pattern. Acinar or papillary pattern had significantly lower recurrence and expire than solid or micropapillary pattern. Conclusions: Invasive adenocarcinoma with lepidic predominant pattern has better prognosis than that with the other predominant patterns. Acinar and papillary predominant patterns have better prognosis than solid and micropapillary predominant patterns in invasive pulmonary adenocarcinoma. There are no different prognoses between acinar and papillary predominant patterns, and solid and micropapillary predominant patterns of invasive pulmonary adenocarcinoma. Citation Format: Keon Uk Park, Jin Young Kim, Hun Mo Ryoo, Ilseon Hwang. Correlation of prognosis and histologic patterns by the IASLC/ATS/ERS classification in invasive pulmonary adenocarcinoma: A meta-analysis. [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 856. doi:10.1158/1538-7445.AM2015-856
Liver sinusoidal endothelial cell cross-priming is supported by CD4 T cell-derived IL-2
Authors: Michaela Wittlich, Michael Dudek, Jan P. Böttcher, Oliver Schanz, Silke Hegenbarth, Tobias Bopp, Edgar Schmitt, Christian Kurts, Christoph Garbers, Stefan Rose John, Percy A. Knolle, Dirk Wohlleber
Journal: Journal of Hepatology (2016)
Depletion of Circulating Plasmacytoid Dendritic Cells in Chronic Myelogenous Leukemia and Their Restoration after Interferon-alpha or Imatinib Mesylate.
Authors: Alexis Rossignol, Anne Barra, Lydia Roy, Francois Guilhot, Ali G. Turhan, Jean-Marc Gombert
Journal: Blood (2006)