tbuckley/cabot-search huggingface dataset:
Characterization of an Antigen From the Myelogenous Leukemia Cell Line K-562 2
Authors: John L. Collins, Carl J. Wust, Bismarck B. Lozzio, Carmen B. Lozzio
Journal: JNCI Journal of the National Cancer Institute (1977)

A protein was solubilized from the myelogenous leukemia cell line K-562 with 3 m KCl that specifically inhibited the antibody-dependent, complement-mediated cytolysis of 51Cr-labeled K-562 cells by a monkey antiserum to K-562. When the crude 3 m KCI extract was fractionated with ammonium sulfate, an eightfold increase in specific activity (U inhibition/mg protein) resulted. This purified fraction migrated as a single protein band after polyacrylamide gel electrophoresis (PGE) with no detectable carbohydrate or lipid. The molecular weight of the denatured protein determined by sodium dodecyl sulfate-PGE was 77,000, similar to that of the native protein (80,000) determined by Sephadex exclusion chromatography. The protein was stable at pH 6-8, with an apparent isoelectric point between pH 5 and 6. In addition to being irreversibly denatured at pH 5 or less, it was unstable at osmolarities below 0.25 m (NaCl). It was denatured at temperatures of 56° C or above. Normal human peripheral blood leukocytes were extracted similarly with 3 m KCl and fractionated with ammonium sulfate. Neither the crude preparation nor any fraction purified as described for the specific antigen inhibited the cytolytic assay, which indicated at least a quantitative lack of the protein on the surfaces of normal leukocytes.
Combined Carcinogenic Effects of Dimethyl-nitrosamine and 3-Methylcholanthrene in the Rat&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Cornelia Hoch-Ligeti, Mary F. Argus, Joseph G. Arcos
Journal: JNCI Journal of the National Cancer Institute (1968)

To study the influence of increased tissue N-demethylase, induced by 3-methylcholanthrene (MCA), on the carcinogenicity of di-methylnitrosamine (DMN), the effect of the simultaneous feeding of these carcinogens to rats was studied. Feeding MCA alone unexpectedly induced subcutaneous sarcomas in adult rats. The combined feeding of MCA and DMN did not increase the number of hepatic tumors known to be induced by the nitrosamine. At the low total dose level used here, DMN alone did not induce tumors in the lung; it did, however, induce lung tumors when administered with MCA. The incidence of subcutaneous sarcomas was slightly increased by the simultaneous administration of DMN. Also skin tumors arose in the group receiving the 2 carcinogens simultaneously. These phenomena have been interpreted in the framework of the alkylation hypothesis of nitrosamine carcinogenesis.
A microRNA switch regulates the rise in hypothalamic GnRH production before puberty
Authors: Andrea Messina, Fanny Langlet, Konstantina Chachlaki, Juan Roa, Sowmyalakshmi Rasika, Nathalie Jouy, Sarah Gallet, Francisco Gaytan, Jyoti Parkash, Manuel Tena-Sempere, Paolo Giacobini, Vincent Prevot
Journal: Nature Neuroscience (2016)
Growth hormone-releasing factor stimulation test in depression
Authors: K R Krishnan, A N Manepalli, J C Ritchie, K Rayasam, M L Melville, G Daughtry, M O Thorner, J E Rivier, W W Vale, C B Nemeroff
Journal: American Journal of Psychiatry (1988)

The authors administered the growth hormone-releasing factor (GRF) stimulation test to 19 patients with major depression and 19 age- and sex-matched control subjects to test the hypothesis that a blunted growth hormone (GH) response to clonidine reflects a central alpha 2-adrenergic receptor subsensitivity in depression. GH response to GRF was significantly higher in patients with depression than in control subjects. This group difference was mainly attributable to three of the 19 depressed patients who exhibited markedly high GH responses to GRF. These results suggest that the blunted GH response to clonidine seen in patients with depression is not due to a pituitary defect in GH secretion.
Hepatic glycogen can regulate hypoglycemic counterregulation via a liver-brain axis
Authors: Jason J. Winnick, Guillaume Kraft, Justin M. Gregory, Dale S. Edgerton, Phillip Williams, Ian A. Hajizadeh, Maahum Z. Kamal, Marta Smith, Ben Farmer, Melanie Scott, Doss Neal, E. Patrick Donahue, Eric Allen, Alan D. Cherrington
Journal: Journal of Clinical Investigation (2016)

Liver glycogen is important for the counterregulation of hypoglycemia and is reduced in individuals with type 1 diabetes (T1D). Here, we examined the effect of varying hepatic glycogen content on the counterregulatory response to low blood sugar in dogs. During the first 4 hours of each study, hepatic glycogen was increased by augmenting hepatic glucose uptake using hyperglycemia and a low-dose intraportal fructose infusion. After hepatic glycogen levels were increased, animals underwent a 2-hour control period with no fructose infusion followed by a 2-hour hyperinsulinemic/hypoglycemic clamp. Compared with control treatment, fructose infusion caused a large increase in liver glycogen that markedly elevated the response of epinephrine and glucagon to a given hypoglycemia and increased net hepatic glucose output (NHGO). Moreover, prior denervation of the liver abolished the improved counterregulatory responses that resulted from increased liver glycogen content. When hepatic glycogen content was lowered, glucagon and NHGO responses to insulin-induced hypoglycemia were reduced. We conclude that there is a liver-brain counterregulatory axis that is responsive to liver glycogen content. It remains to be determined whether the risk of iatrogenic hypoglycemia in T1D humans could be lessened by targeting metabolic pathway(s) associated with hepatic glycogen repletion.
Final Results Of A Phase 2 Study Of Vorinostat Plus Rituximab In Newly Diagnosed, Relapsed Or Refractory Indolent Non-Hodgkin's Lymphoma
Authors: Robert Chen, Paul Frankel, Leslie Popplewell, Tanya Siddiqi, Wei Ye, Joel Conrad, Michelle Mott, Auayporn Nademanee, Myo Htut, Stephen J. Forman, Mark Kirschbaum
Journal: Blood (2013)
CD23 surface density on B cells is associated with IgE levels and determines IgE-facilitated allergen uptake, as well as activation of allergen-specific T cells
Authors: Regina Selb, Julia Eckl-Dorna, Alina Neunkirchner, Klaus Schmetterer, Katharina Marth, Jutta Gamper, Beatrice Jahn-Schmid, Winfried F. Pickl, Rudolf Valenta, Verena Niederberger
Journal: Journal of Allergy and Clinical Immunology (2016)
11q13 Is an Allergic Risk-Locus That Increases Eoe Risk and Increases LRRC32 Expression
Authors: Leah C. Kottyan, Rahul J. D'Mello, Daniel Miller, Avery Maddox, Emily Stucke, Mark Rochman, Zubin Patel, Joelle A. Rothenberg, Benjamin P. Davis, Mirna Chehade, Hugh A. Sampson, Robert A. Wood, Robbie D. Pesek, Stacie M. Jones, Brian P. Vickery, A. Wesley Burks, David M. Fleischer, Donald Y. Leung, Robert W. Lindblad, Peter Dawson, Matthew T. Weirauch, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2016)
Ustekinumab for the treatment of refractory giant cell arteritis
Authors: Richard Conway, Lorraine O'Neill, Eileen O'Flynn, Phil Gallagher, Geraldine M McCarthy, Conor C Murphy, Douglas J Veale, Ursula Fearon, Eamonn S Molloy
Journal: Annals of the Rheumatic Diseases (2016)

Giant cell arteritis (GCA) is the most common form of systemic vasculitis.1 Glucocorticoids are the mainstay of therapy, required in high doses for prolonged periods, with consequent serious complications in 86% of patients.2 There is a critical unmet need for a proven safe and effective immunosuppressive therapy in GCA, as agents such as methotrexate and infliximab have shown disappointing results in GCA.3 ,4 Interleukins 12 (IL-12) and 23 (IL-23) are implicated in Th1 and Th17 responses, respectively, both inflammatory pathways relevant to GCA pathogenesis.5 ,6 A recent case series reported the use of ustekinumab in three patients with Takayasu arteritis.7 The aim of this study was to evaluate the glucocorticoid-sparing efficacy of ustekinumab, an IL-12/IL-23-blocking monoclonal antibody, in patients with refractory GCA.

Patients with GCA attending our centre are enrolled in a prospective registry and managed according to standardised …
Trabectedin-Related Liver Toxicity in Soft Tissue Sarcoma Patients: Always a Good Reason to Discontinue the Treatment?
Authors: B. Vincenzi, A.M. Frezza, G. Maltese, L. Cerbone, D. Delisi, M. Silletta, M. Spalato, G. Badalamenti, D. Santini, G. Tonini
Journal: Annals of Oncology (2014)
Abstract 19116: Assessment of Perioperative Minute Ventilation in Obese versus Non-Obese Patient Using a Non-Invasive Respiratory Volume Monitor
Authors: Christopher Voscopoulos, Jenny Freeman, Kathleen Campbell, Edward George
Journal: Circulation (2014)

Introduction: Adequate respiration is critical to survival and can be influenced by opioids, sedatives and apnea. Direct monitoring of ventilation has previously not been available for non-intubated patients. Reliance on indirect measures (SpO2, RR) may delay needed interventions and obese patients may be at further risk. A non-invasive respiratory volume monitor (RVM) providing real-time direct measures of MV, TV &amp; RR in non-intubated patients is used to assess respiratory status in obese and non-obese patients. Methods: Data collected from an impedance-based RVM (ExSpiron-1Xi, Respiratory Motion, Waltham, MA) in 62 orthopedic patients (65.4 ±12.0 yrs, BMI: 30.8 ±6.0 kg/m 2 ) before, during &amp; after surgery (PACU arrival &amp; discharge) were compared to predicted MV (MV PRED ) based on IBW. Ventilator MV (Apollo, Draeger, Telford, PA) during GA was assumed to be adjusted to maintain appropriate end-tidalCO 2 . Patients were stratified based on obesity status (cutoff BMI=30). The distributions of MV at various times were compared (non-obese vs obese) using an un-paired 1-sided t-test &amp; a 2-sample F-test. Results: Despite similar MV PRED in both groups (6.2±0.2; 6.1±0.2 L/min, p&gt;0.3) obese patients were managed at a higher MV during surgery (6.1±0.2; 5.3±0.2 L/min, p&lt;0.01). MV differences were far greater preoperatively (9.7±0.4 vs. 6.7±0.3 L/min), at PACU arrival (11.4 ±1.2; 6.8±0.7 L/min) &amp; discharge (7.7±0.5; 5.0±0.6 L/min, p&lt;0.01 all, Fig 1). Patient-to-patient variability in MV was similar in both groups pre-op, but larger in obese patients. Even with the large average MV in obese patients, 6% of them left the PACU with MV&lt;40% MV PRED . Conclusions: On average, obese patients have greater MV than predicted by IBW formula, likely due to greater metabolic demand. Post-op, obese patients have greater variability in ventilation when treated with standard opioid doses &amp; may be at greater risk for hypoventilation. RVM can provide data for individualized treatment plans.
Phase 2 Study of the Safety and Antitumor Activity of Apalutamide (ARN-509), a Potent Androgen Receptor Antagonist, in the High-risk Nonmetastatic Castration-resistant Prostate Cancer Cohort
Authors: Matthew R. Smith, Emmanuel S. Antonarakis, Charles J. Ryan, William R. Berry, Neal D. Shore, Glenn Liu, Joshi J. Alumkal, Celestia S. Higano, Edna Chow Maneval, Rajesh Bandekar, Carla J. de Boer, Margaret K. Yu, Dana E. Rathkopf
Journal: European Urology (2016)

Apalutamide is a potent androgen receptor (AR) antagonist that targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets. To evaluate the activity and safety of apalutamide in patients with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC). We conducted a multicenter phase 2 study of nmCRPC patients with a high risk for progression (prostate-specific antigen [PSA] ≥8 ng/ml or PSA doubling time [PSA DT] ≤10 mo). Patients received 240 mg/d apalutamide while continuing on androgen-deprivation therapy. Primary end point was 12-wk PSA response (Prostate Cancer Working Group 2 criteria). Secondary end points included safety, time to PSA progression (TTPP), and metastasis-free survival (MFS). A total of 51 patients were enrolled; four patients with metastatic disease were excluded from the efficacy analysis. Patient characteristics included median age, 71 yr; Eastern Cooperative Oncology Group performance status 0 (76%); Gleason score ≤7 (57%); median PSA 10.7 ng/ml; and PSA DT ≤10 mo (45%). At median follow-up of 28.0 mo, 18 patients (35%) remained in the study. Overall, 89% of patients had ≥50% PSA decline at 12 wk. Median TTPP was 24.0 mo (95% confidence interval [CI], 16.3 mo–not reached [NR]); median MFS was NR (95% CI, 33.4 mo–NR). Most of the patients discontinued study treatment (n = 33) due to disease progression (n = 11 [22%]) or adverse events (AEs) (n = 9 [18%]). The most common AE was fatigue (any grade, n = 31 [61%]) although grade ≥3 fatigue was uncommon (n = 2 [4%]). These represent the first apalutamide nmCRPC patient clinical data. In high-risk nmCRPC patients, apalutamide was safe with robust activity based on durable PSA responses and disease control. Antitumor activity and the safety of apalutamide in patients with nonmetastatic castration-resistant prostate cancer support continued development in this setting. ClinicalTrials.gov identifier NCT01171898
P1289 : Understanding and preventing the HCV epidemic among men who have sex with men in the UK: A mathematical modelling analysis
Authors: N.K. Martin, M. Hickman, M. Nelson, A. Thornton, C. Sabin, S. Lattimore, T.C.S. Martin, G.S. Cooke, V. Delpech, M. Ruf, H. Price, E.C. Thomson, P. Vickerman
Journal: Journal of Hepatology (2015)
Prevention by Vitamin E of Experimental Oral Carcinogenesis2
Authors: Diane Trickler, Gerald Shklar
Journal: JNCI Journal of the National Cancer Institute (1987)

In the standard model for hamster buccal pouch, using a 0.5% solution of 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6], it was shown that vitamin E (alpha-tocopherol) inhibited carcinogenesis. With a less potent carcinogen (0.1% DMBA), vitamin E was shown to prevent tumor development. Eighty (total) male and female Syrian hamsters (Mesocricetus auratus) were divided into 4 equal groups. After 28 weeks, animals in group 2 that had left buccal pouches painted with 0.1% DMBA (in heavy mineral oil) three times/week and that had been given 10 mg DL-alpha-tocopherol on alternate days (i.e., two times/wk) showed no tumors there. However, the pouches of group 1 animals that had been similarly painted with DMBA but that had received no vitamin E demonstrated grossly and microscopically the presence of epidermoid carcinomas.
Isolation of &lt;italic&gt;Mycoplasma orale&lt;/italic&gt; From Leukemic Bone Marrow and Blood by Direct Culture
Authors: Michael F. Barile, Gerald P. Bodey, Joseph Snyder, Donald B. Riggs, Marion W. Grabowski
Journal: JNCI Journal of the National Cancer Institute (1966)

Mycoplasma were isolated from 5 bone marrow specimens and 1 blood specimen obtained from 4 of 1 0 patients with acute leukemia by use of modified Eaton agent media supplemented with arginine, glutamine, glucose, and vitamins. Mycoplasma were recovered in either an aerobic or a 5 percent carbon dioxide and 95 percent nitrogen atmosphere. Isolates from 3 of the 4 patients were identified as Mycoplasma orale but those from the fourth patient were not typed. Isolations were made during the early clinical stages of leukemia-before the initiation of antileukemic therapy in 3 of 4 instances and before the patients showed evidence of infection. Control cultures of 10 bone marrow specimens obtained from patients during heart surgery were negative for Mycoplasma. The significance of the findings is discussed.
The Alliance for Quality Psychosocial Cancer Care: An Innovative Model for Disseminating and Improving Implementation of National Quality Care Recommendations
Authors: Ruth McCorkle, Rebecca Kirch, Kim Thiboldeaux, Julie Taylor, Mark Gorman
Journal: Journal of the National Comprehensive Cancer Network (2014)

"The Alliance for Quality Psychosocial Cancer Care: An Innovative Model for Disseminating and Improving Implementation of National Quality Care Recommendations" published on Jun 2014 by Harborside Press, LLC.
Loss of Chromosome 8p Governs Tumor Progression and Drug Response by Altering Lipid Metabolism
Authors: Yanyan Cai, Jonathan Crowther, Tibor Pastor, Layka Abbasi Asbagh, Maria Francesca Baietti, Magdalena De Troyer, Iria Vazquez, Ali Talebi, Fabrizio Renzi, Jonas Dehairs, Johannes V. Swinnen, Anna A. Sablina
Journal: Cancer Cell (2016)
UM-164: A Potent c-Src/p38 Kinase Inhibitor with <i>In Vivo</i> Activity against Triple-Negative Breast Cancer
Authors: Rabia A. Gilani, Sameer Phadke, Li Wei Bao, Eric J. Lachacz, Michele L. Dziubinski, Kristoffer R. Brandvold, Michael E. Steffey, Frank E. Kwarcinski, Carrie R. Graveel, Kelley M. Kidwell, Sofia D. Merajver, Matthew B. Soellner
Journal: Clinical Cancer Research (2016)

Abstract Purpose: c-Src has been shown to play a pivotal role in breast cancer progression, metastasis, and angiogenesis. In the clinic, however, the limited efficacy and high toxicity of existing c-Src inhibitors have tempered the enthusiasm for targeting c-Src. We developed a novel c-Src inhibitor (UM-164) that specifically binds the DFG-out inactive conformation of its target kinases. We hypothesized that binding the inactive kinase conformation would lead to improved pharmacologic outcomes by altering the noncatalytic functions of the targeted kinases. Experimental Design: We have analyzed the anti–triple-negative breast cancer (TNBC) activity of UM-164 in a comprehensive manner that includes in vitro cell proliferation, migration, and invasion assays (including a novel patient-derived xenograft cell line, VARI-068), along with in vivo TNBC xenografts. Results: We demonstrate that UM-164 binds the inactive kinase conformation of c-Src. Kinome-wide profiling of UM-164 identified that Src and p38 kinase families were potently inhibited by UM-164. We further demonstrate that dual c-Src/p38 inhibition is superior to mono-inhibition of c-Src or p38 alone. We demonstrate that UM-164 alters the cell localization of c-Src in TNBC cells. In xenograft models of TNBC, UM-164 resulted in a significant decrease of tumor growth compared with controls, with limited in vivo toxicity. Conclusions: In contrast with c-Src kinase inhibitors used in the clinic (1, 2), we demonstrate in vivo efficacy in xenograft models of TNBC. Our results suggest that the dual activity drug UM-164 is a promising lead compound for developing the first targeted therapeutic strategy against TNBC. Clin Cancer Res; 22(20); 5087–96. ©2016 AACR.
Inhibition by Deoxycytidine, Cytidine, and β-Cytosine Arabinoside of the Induction of Alkaline Phosphatase Activity in Hela Cells2
Authors: Barry Goz, Clifton Orr, Walker Wharton
Journal: JNCI Journal of the National Cancer Institute (1980)

Journal Article Inhibition by Deoxycytidine, Cytidine, and β-Cytosine Arabinoside of the Induction of Alkaline Phosphatase Activity in Hela Cells Get access Barry Goz, Barry Goz Search for other works by this author on: Oxford Academic PubMed Google Scholar Clifton Orr, Clifton Orr Search for other works by this author on: Oxford Academic PubMed Google Scholar Walker Wharton Walker Wharton Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 64, Issue 6, June 1980, Pages 1355–1361, https://doi.org/10.1093/jnci/64.6.1355 Published: 01 June 1980 Article history Received: 01 February 1979 Revision received: 07 November 1979 Accepted: 03 January 1980 Published: 01 June 1980
Generation of Genetically Engineered Precursor T-Cells From Human Umbilical Cord Blood Using an Optimized Alpharetroviral Vector Platform
Authors: Juwita Hübner, Shahabuddin S Hoseini, Julia D Suerth, Dirk Hoffmann, Marcel Maluski, Jessica Herbst, Holger Maul, Arnab Ghosh, Britta Eiz-Vesper, Qinggong Yuan, Michael Ott, Michael Heuser, Axel Schambach, Martin G Sauer
Journal: Molecular Therapy (2016)

Retroviral engineering of hematopoietic stem cell-derived precursor T-cells (preTs) opens the possibility of targeted T-cell transfer across human leukocyte antigen (HLA)-barriers. Alpharetroviral vectors exhibit a more neutral integration pattern thereby reducing the risk of insertional mutagenesis. Cord blood-derived CD34+ cells were transduced and differentiated into preTs in vitro. Two promoters, elongation-factor-1-short-form, and a myeloproliferative sarcoma virus variant in combination with two commonly used envelopes were comparatively assessed choosing enhanced green fluorescent protein or a third-generation chimeric antigen receptor (CAR) against CD123 as gene of interest. Furthermore, the inducible suicide gene iCaspase 9 has been validated. Combining the sarcoma virus-derived promoter with a modified feline endogenous retrovirus envelope glycoprotein yielded in superior transgene expression and transduction rates. Fresh and previously frozen CD34+ cells showed similar transduction and expansion rates. Transgene-positive cells did neither show proliferative impairment nor alteration in their lymphoid differentiation profile. The sarcoma virus-derived promoter only could express sufficient levels of iCaspase 9 to mediate dimerizer-induced apoptosis. Finally, the CD123 CAR was efficiently expressed in CD34+ cells and proved to be functional when expressed on differentiated T-cells. Therefore, the transduction of CD34+ cells with alpharetroviral vectors represents a feasible and potentially safer approach for stem cell-based immunotherapies for cancer.
NIMG-17CENTRAL NEUROPATHOLOGY REVIEW TO ASSIST IN THE EVALUATION OF IMMUNE-RELATED TREATMENT CHANGES VERSUS DISEASE PROGRESSION IN CHECKMATE-143
Authors: Shak Ramkissoon, John Sampson, Gordana Vlahovic, Solmaz Sahebjam, Antonio Omuro, Joachim Baehring, Robert Latek, Eric Vandeloise, Vlad Coric, Timothy Cloughesy, Michael Lim, David Reardon, Keith Ligon
Journal: Neuro-Oncology (2015)

BACKGROUND: Subsets of cancer patients treated with immune modulating therapies show progression using conventional response criteria before ultimately exhibiting objective responses and/or stable disease. This is particularly challenging in glioblastoma (GBM) trials since standard treatments may also be associated with pseudoprogression (RT/temozolomide) or pseudoresponses (bevacizumab) by imaging. To minimize premature discontinuation of immunotherapy in patients who may be demonstrating an immune-mediated tumor response, or correctly identify disease progression, direct histopathologic examination may be needed to inform management on these agents. METHODS: Central neuropathology review was incorporated into the CHECKMATE-143 trial to evaluate immune-related treatment effects versus disease progression. Patients with recurrent GBM in Cohort 1 (n = 20) were randomized 1:1 to receive nivolumab 3 mg/kg every 2 weeks (Q2W) or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (Q3W) for 4 doses followed by nivolumab 3 mg/kg Q2W. Patients who underwent tumor biopsy for suspected progression after trial enrollment were eligible for central neuropathologic review of these post-treatment samples. Post-treatment samples were scored visually by two neuropathologists for percentage of necrosis/reactive changes and viable solid tumor. Any distinct morphological changes were also noted. Comparison was made to unrelated samples treated previously with RT/temozolomide. RESULTS: Post-treatment samples were examined in 6 patients and all demonstrated immune treatment-related effects. Lymphocytic infiltrates were minimal. Characterization of the histopathology findings and treatment-effects will be reported. CONCLUSIONS: The challenges in distinguishing tumor progression from SOC or immune-related tumor necrosis, immune infiltrates and possible morphological changes at the tumor site highlight the importance of tissue resampling and central neuropathology review to accurately assess for treatment-related changes. Immune-related treatment effects observed in this preliminary safety cohort suggest biologic activity of checkpoint inhibition at the GBM tumor site but minimal lymphocytic infiltration at the time point analyzed.