tbuckley/cabot-search huggingface dataset:
Abstract 3341: TP508 sensitizes cancer stem cells to radiation and delays brain cancer cell relapse in vitro
Authors: Stephanie M. Moya, Carla Kantara, Laurie Sower, Darrell H. Carney
Journal: Cancer Research (2015)

Abstract In 2014, approximately 70,000 adults and 4,500 children are expected to be diagnosed with brain cancer in the U.S alone, making this disease the second leading cause of cancer related deaths in children and young adults. Currently available therapies such as radio/chemotherapy are ineffective in completely eradicating the tumor bulk and cancer stem cells within the tumor, thus allowing recurrence of the disease. Therefore, it is important to develop novel therapeutics that sensitize cancer cells to make them more susceptible to radiation therapy and reduce the number of viable cancer stem cells. Preliminary data showed that injection of TP508, a 23 amino acid thrombin derived peptide drug, increased brain tumor shrinkage post-radiation therapy (RT) in mice. To study this phenomenon, we chose to use an in vitro model of tumor relapse that selects for and allows quantification of tumor stem cells in 3D spheroid cultures. Our goal was to determine whether TP508 could specifically sensitize cancer stem cells to the effects of RT and prevent or delay stem cell mediated in vitro tumor relapse. Medulloblastoma (Daoy) cells were grown as 3D spheroids in vitro to select for the growth of stem cells. Primary spheroids were treated on day 5 with either saline or TP508 (0.5mg/mL), and exposed to radiation (10Gy) on day 7 using a Cs137 source. One day post-RT, cells were dissociated and cultured as secondary spheroids to determine the stemness or relapse potential of the cells following RT. Daily images were taken to quantify neurosphere formation. Spheroids were also analyzed for viability, apoptosis, proliferation (PCNA), and for stem cell markers (CD133/LGR5/CD44/DCLK1/Sox-2), using western blots, flow cytometry, and immuno-fluorescent staining. TP508 treatment of Daoy cell spheroids prior to RT significantly delayed the formation of secondary spheroids, decreased cell viability, number of proliferating cells, and the number of cells expressing cancer stem cell markers. Thus, in this in vitro assay, TP508 sensitized cancer stem cells to the effects of RT and delayed relapse of brain tumor stem cells in vitro. These findings suggest that injection of TP508 prior to RT treatment may sensitize cancer stem cells to radiation and help prevent brain tumor relapse. Studies are underway to determine the mechanism by which TP508 sensitizes cancer stem cells to RT and whether TP508 has similar effects on other types of cancer stem cells. This work was supported by NCI Contract # HHSN261201300076C to DC. Citation Format: Stephanie M. Moya, Carla Kantara, Laurie Sower, Darrell H. Carney. TP508 sensitizes cancer stem cells to radiation and delays brain cancer cell relapse in vitro. [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 3341. doi:10.1158/1538-7445.AM2015-3341
Pharmacokinetic Profile and Pharmacodynamic Effects of ASP2215, a Selective, Potent Inhibitor of FLT3/AXL, in Patients with Relapsed or Refractory Acute Myeloid Leukemia: Results from a First-in-Human Phase 1/2 Study
Authors: Catherine C. Smith, Mark J. Levis, Mark R Litzow, Alexander E. Perl, Jessica K. Altman, Stanley C. Gill, Takeshi Kadokura, Geoffrey J. Yuen, Ogert Fisniku, Charles Liu, Itsuro Nagase, Briana Sargent, Noreen Welter, Erkut Bahceci
Journal: Blood (2015)
Author’s reply to Hanretty and Ford
Authors: Danny Dorling
Journal: BMJ (2016)

I thank Hanretty and Ford for their comment.1 They make an interesting point, but I think that this has been over-made recently.

The term “size of the denominator population” explains that some population groups are bigger than others and that this matters greatly. The map published with the article shows the number of voters polled in each region, adjusted …
Gene-based analysis of regulatory variants identifies 4 putative novel asthma risk genes related to nucleotide synthesis and signaling
Authors: Manuel A.R. Ferreira, Rick Jansen, Gonneke Willemsen, Brenda Penninx, Lisa M. Bain, Cristina T. Vicente, Joana A. Revez, Melanie C. Matheson, Jennie Hui, Joyce Y. Tung, Svetlana Baltic, Peter Le Souëf, Grant W. Montgomery, Nicholas G. Martin, Colin F. Robertson, Alan James, Philip J. Thompson, Dorret I. Boomsma, John L. Hopper, David A. Hinds, Rhiannon B. Werder, Simon Phipps
Journal: Journal of Allergy and Clinical Immunology (2016)
Medical Examiners, Coroners, and Organ Recovery in the United States-Reply
Authors: Teresa Shafer
Journal: JAMA (1995)

In Reply.  —Dr Hanzlick presents the usual litany of  medical examiners' objections to mandates that compel the ME/C to cooperate with the release of organ donors. The appropriate response to these criticisms is to ask whether the objections are valid or merely excuses. If Hanzlick's objections are valid, then those objections should stand up to public scrutiny. With 38 000 people awaiting organs, it is not possible to defend the fact that approximately 10% of ME/C cases are denied annually. His contention that some transplant recipients die during or following  misconstrues the reality that 98% of patients survive surgery and that most liver, heart, and lung recipients are willing to take the risk of a 2% operative mortality.  In most areas of the country, there is currently no public scrutiny when these denials occur. No one would argue that for those rare cases where the ME/C presence is
Granzyme A Contributes to Inflammatory Arthritis in Mice Through Stimulation of Osteoclastogenesis
Authors: Llipsy Santiago, Cheikh Menaa, Maykel Arias, Praxedis Martin, Paula Jaime‐Sánchez, Sunil Metkar, Laura Comas, Nadina Erill, Victor Gonzalez‐Rumayor, Erica Esser, Eva M. Galvez, Sri Raja, Markus M. Simon, Stuart M. Sprague, Cem Gabay, Luis Martinez‐Lostao, Julian Pardo, Christopher J. Froelich
Journal: Arthritis & Rheumatology (2016)

Granzyme A (GzmA) levels are elevated in the plasma and synovium of patients with rheumatoid arthritis (RA), suggesting involvement of this protease in the pathogenesis of the disease. GzmA contributes to sepsis by regulating the production of proinflammatory cytokines. The purpose of this study was to evaluate the contribution of GzmA to the pathogenesis of RA in vivo and to examine the possibility that GzmA acting via tumor necrosis factor (TNF) stimulates osteoclastogenesis. Inflammatory arthritis induced by type II collagen was evaluated in wild-type, GzmA-deficient, and perforin-deficient mice. The osteoclastogenic potential of GzmA was examined in vitro using bone marrow cells and colony-forming unit-granulocyte-macrophage (CFU-GM) cells and in vivo using GzmA-deficient mice. Gene deletion of GzmA attenuated collagen-induced arthritis, including serum levels of proinflammatory cytokines, joint damage, and bone erosion in affected mice, suggesting that osteoclast activity is reduced in the absence of GzmA. Accordingly, GzmA-treated bone marrow cells produced multinucleated cells that fulfilled the criteria for mature osteoclasts: tartrate-resistant acid phosphatase (TRAP) activity, β integrin expression, calcitonin receptor expression, and resorptive activity on dentin slices. GzmA appeared to act without accessory cells, and its activity was not affected by osteoprotegerin, suggesting a minor contribution of RANKL. It also induced the expression and secretion of TNF. Neutralization of TNF or stimulation of CFU-GM cells from TNF-/- mice prevented GzmA-induced osteoclastogenesis. GzmA-deficient mice had reduced osteoclastogenesis in vivo (fewer calcitonin receptor-positive multinucleated cells and fewer transcripts for cathepsin K, matrix metalloproteinase 9, and TRAP in joints) and reduced serum levels of C-terminal telopeptide of type I collagen. GzmA contributes to the joint destruction of RA partly by promoting osteoclast differentiation.
Inhibition of glioblastoma tumorspheres by combined treatment with 2-deoxyglucose and metformin
Authors: Eui Hyun Kim, Ji-Hyun Lee, Yoonjee Oh, Ilkyoo Koh, Jin-Kyoung Shim, Junseong Park, Junjeong Choi, Mijin Yun, Jeong Yong Jeon, Yong Min Huh, Jong Hee Chang, Sun Ho Kim, Kyung-Sup Kim, Jae-Ho Cheong, Pilnam Kim, Seok-Gu Kang
Journal: Neuro-Oncology (2016)

Deprivation of tumor bioenergetics by inhibition of multiple energy pathways has been suggested as an effective therapeutic approach for various human tumors. However, this idea has not been evaluated in glioblastoma (GBM). We hypothesized that dual inhibition of glycolysis and oxidative phosphorylation could effectively suppress GBM tumorspheres (TS). Effects of 2-deoxyglucose (2DG) and metformin, alone and in combination, on GBM-TS were evaluated. Viability, cellular energy metabolism status, stemness, invasive properties, and GBM-TS transcriptomes were examined. In vivo efficacy was tested in a mouse orthotopic xenograft model. GBM-TS viability was decreased by the combination of 2DG and metformin. ATP assay and PET showed that cellular energy metabolism was also decreased by this combination. Sphere formation, expression of stemness-related proteins, and invasive capacity of GBM-TS were also significantly suppressed by combined treatment with 2DG and metformin. A transcriptome analysis showed that the expression levels of stemness- and epithelial mesenchymal transition–related genes were also significantly downregulated by combination of 2DG and metformin. Combination treatment also prolonged survival of tumor-bearing mice and decreased invasiveness of GBM-TS. The combination of 2DG and metformin effectively decreased the stemness and invasive properties of GBM-TS and showed a potential survival benefit in a mouse orthotopic xenograft model. Our findings suggest that targeting TS-forming cells by this dual inhibition of cellular bioenergetics warrants expedited clinical evaluation for the treatment of GBM.
Comparison of Phase 3 Ibrutinib Results Versus Standard of Care in Sweden in Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)
Authors: Anders Österborg, Anna Asklid, Joris Diels, Johanna Repits, Frans Söltoft, Lotta Hansson, Ulrich Jäger
Journal: Blood (2015)
PWE-066 Endoscopic Versus Histological Assessment Of Colonic Polyp Size: Abstract PWE-066 Table 1
Authors: WJ Gashau, C Kong, HY Lee, R Willert
Journal: Gut (2014)

<h3>Introduction</h3> Colonic polyp size is a factor in determining management and prognosis of patients. Polyp diameters greater than 9 mm require ongoing colonoscopic surveillance.<sup>1</sup> Accurate endoscopic estimation of polyp size can be affected by depth perception and parallax errors. We compared endoscopic versus histological size assessments to determine if accurate estimation was operator-dependent. <h3>Methods</h3> Symptomatic and asymptomatic (bowel screening) patients were identified from hospital databases. Endoscopic and histological polyp diameters were reviewed. Agreement levels between these were analysed by deriving intraclass correlation coefficient (ICC) using SPSS software (Version 20). <h3>Results</h3> Sixteen colonoscopists were included: 5 bowel screening, 7 non-bowel screening and 4 trainees. Five hundred and ten polyps (n = 510) were found among 299 patients (186 males, 104 females). Two hundred eighteen polyps were enbloc resected, retrieved whole and analysed. Overall accuracy of polyp size assessment was good (ICC &gt; 0.70) with variability between skill levels (Table 1). Accuracy was best among polyps ≥20 mm diameter (ICC 0.99, p &lt; 0.001); all removed by bowel screening colonoscopists. Polyps between 8 to 12 mm demonstrated poor correlation (ICC (absolute agreement) 0.535, P = 0.002). <h3>Conclusion</h3> While endoscopic estimation of polyp diameter is accurate, variability exists. Estimations are more accurate among bowel screening endoscopists suggesting experience and/or colonoscopy workload contribute to this skill. Poor diameter estimations among polyps 8–12 mm has implications for polyp surveillance intervals. Standardising diameter using against closed or open biopsy forceps (width 2.2 and 8 mm respectively) to optimise accuracy should be used. <h3>Reference</h3> 1 Cairns, <i>et al</i>. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). <i>Gut</i> 2010;59:666–690 <h3>Disclosure of Interest</h3> None Declared.
Ex-Vivo Expanded Peripheral Blood Stem Cells (EVEC) Compared with Un Manipulated Peripheral Blood Stem Cells (PBSC) Autologous Transplantation for Multiple Myeloma: A Pair Match Analysis.
Authors: Noel-Jean Milpied, Gerald Marit, Bernard Dazey, Jean-Michel Boiron, Zoran Ivanovic, Carine Foucaud, Fontanet Bijou, Krimo Bouabdallah, Anna Schmitt, Mathieu Sauvezie, Christian Cailliot, Josy Reiffers
Journal: Blood (2009)
Absence of Prognostic Impact Associated with the Use of Statins in Patients with Follicular Lymphoma in the Rituximab Era: An Exploratory Analysis From the PRIMA Study.
Authors: Emmanuel Bachy, John F. Seymour, Pierre Feugier, Fritz Offner, Dolores Caballero, Reda Bouabdallah, Lars Möller Pedersen, Pauline Brice, David Belada, Luc Xerri, Gilles Salles
Journal: Blood (2012)
Основные симптомы и синдромы при заболеваниях органов пищеварения
Authors: I.N. Kononov, M.V. Chalyi, О.M. Kovalenko
Journal: GASTROENTEROLOGY (2016)

В статье приводятся основные клинические симптомы и синдромы, которые встречаются при различных заболеваниях брюшной полости. Представлены как широко известные, так и редкие признаки гастроэнтерологических заболеваний. Описанные симптомы и синдромы подтверждают важность применения физикальных методов в диагностике заболеваний пищеварительных органов.
Targeted Resequencing of MLL-PTD Positive AML Patients Reveals a High Prevalence of Co-Ocurring Mutations in Epigenetic Regulator Genes
Authors: Sylvia Herold, Thoralf Stange, Matthias Kuhn, Ingo Roeder, Christoph Röllig, Gerhard Ehninger, Christian Thiede
Journal: Blood (2014)
Peripheral Blood Stem Cells Versus Bone Marrow Grafts For HLA-Matched Unrelated Donor Transplantation In Adult Patients With Acute Myeloid Leukemia; The Role Of Low-Dose Rabbit Anti-Thymocyte Globuline In The Prophylaxis Of Graft-Versus-Host Disease
Authors: Seung-Hwan Shin, Jung-Ho Kim, Young-Woo Jeon, Jae-Ho Yoon, Seung-Ah Yahng, Sung-Eun Lee, Byung-Sik Cho, Ki-Sung Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min, Chong-Won Park, Hee-Je Kim
Journal: Blood (2013)
Venous thromboembolism (VTE) in patients with lung cancer (LC).
Authors: M. Campayo, C. Font, B. Farrús, J. C. Reverter, D. Tàssies, N. Reguart, N. Vinolas, P. Gascon
Journal: Journal of Clinical Oncology (2010)

e19565 Background: VTE is a leading cause of death and morbidity in cancer patients. A better knowledge of the epidemiology and the behavior of VTE can contribute to a better prevention and optimal management. The aim of our study was to determine the clinical characteristics and outcome of cancer patients with VTE with regards tumor type. Methods: A prospective observational study of consecutive cancer patients newly diagnosed with VTE was performed between May 2006 and April 2009. VTE was treated in accordance with the 2004 American College of Chest Physicians Guidelines. Data analysis was performed in July 2009. Results: 339 cancer patients with VTE were included. LC was the most frequent tumor in our series 25.4% (66 male, 20 female; median age 62 ± 11 years). Histologies were: adenocarcinoma 40 (46%), squamous cell carcinoma 18 (21%), undifferentiated 15 (17%) and small-cell carcinoma 9 (10%). The proportion of patients treated with chemotherapy in both LC and other tumors (OT) was similar (70% vs. 62%, p = 0.19). In LC, pulmonary embolism was the most frequent VTE event (51% vs. 29%, p<0.0001) and it presented earlier than in OT (median time after first cancer diagnose of 4 vs. 7 months respectively, p<0.0001). Rethrombosis was frequent in tumors (17% LC and 13% OT, p = 0.362) with a higher actuarial probability of rethrombosis in the LC group (median time from the initial VTE event of 6 vs. 17 months, p<0.0001). Conclusions: VTE in patients with LC is a common adverse event that occurs soon after tumor diagnosis, with a higher incidence of pulmonary embolism and a worse outcome regarding venous rethrombosis than in patients with OT. No significant financial relationships to disclose.
A methods study to define the performance specifications of MHC tetramer assays for immune monitoring of tumor immunotherapy
Authors: B. Comin-Anduix, A. Gualberto, J. Glaspy, R. Renteria, D. Reardon, E. Seja, J. S. Economou, B. Littman, J. Gomez-Navarro, A. Ribas
Journal: Journal of Clinical Oncology (2004)

9682 Background: Monitoring tumor antigen-specific immunotherapy requires accurate and reproducible assays to identify pts that elicit an immune response. However, the performance specifications of cellular immunology assays, such as MHC-restricted tetramer assays, have not been well defined. Methods: Following informed consent and screening, 10 healthy subjects and 20 pts with melanoma (all HLA-A2.1) not receiving active therapy underwent 4 blood draws within 2 months. Peripheral blood mononuclear cells were cryopreserved and later subjected to iTAg™ Tetramer assays. Tetramers tested using sequential gating FACS analysis: MART-1 26–35, HIVgag77–85, Flu M1 58–66, CMVpp65, EBV BMLF1, AFP 325–334 and a Negative Tetramer (a non-relevant peptide control, all from Beckman Coulter). Optimal signal was obtained when at least 50,000 CD8+ events were accrued. Results: Primary objectives were to define the performance specifications of the MART-1 tetramer assay, and to identify positive and negative controls. Using the Negative Tetramer, the low limit of detection (LLD) was 0.034% CD8+ cells. Positivity (> 0,034% MART-1-specific CD8+ cells) in at least 2 of 4 samples was found in 26 of 30 subjects. 21 were positive in all samples analyzed. Higher reactivity was noted in pts with melanoma compared to healthy volunteers (p < 0.05). HIVgag77–85 was not a universal negative control, while AFP tetramer was usually negative. The widely used Flu M1 was not a reliable positive control, while the CMV and EBV were positive in seropositive subjects. Using the MART-1 and EBV tetramers, a functional sensitivity of 0.025–0.050% and a reportable range up to 7% CD8+ cells were defined. Conclusions: MART-1-tetramer assay is precise enough at the LLD and within the reportable range to allow the definition of a positive response, making it a robust endpoint for immunotherapy studies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Beckman Coulter, Inc.; Pfizer Pfizer Pfizer Inc.
Prognositc value of combining cancer metabolism related biomarkers in glioma patients.
Authors: Chengcheng Guo, Jing Wang, Qun-ying Yang, Zhongping Chen
Journal: Journal of Clinical Oncology (2016)

e13520 Background: The reprogrammed cancer cell metabolism is instrumental and may allow for discovery of novel cancer biomarkers and therapeutic targets in glioma. Our previous study showed that RNA-dependent protein kinase (PKR) depleted nutrients, inducing phosphorylation of AMP-activated kinase(AMPK).However, their clinical significance in human glioma has not yet to be understood.To explore the contribution of cellular metabolism to glioma, we analyse the combination value of PKR and AMPK in glioma patients. Methods: We determined the levels of the expression of PKR and AMPK by Immunohistochemistry for 194 glioma samples, including 48 low-grade glioma and 146 high-grade glioma from Sep 2000 to Dec 2011 Results: We found that PKR was associated with AMPK in glioma. High PKR expression was correlated with a poor outcome in patients with glioma (5yOS:low-expression group 31.7％VS high-expression group 18.5％,p= 0.048). Similarly, low AMPK expression was correlated with a better outcome(5yOS:low-expression group33.3％VS high-expression group 14.2％,p= 0.017). What’s more, the prognostic information provided by the combination of PKR and AMPK was significantly more accurate than that provided by either marker alone. The 5-year overall survival rate in PKRlow/AMPKlow patients (37.3%) was significantly higher than that of PKRhigh/AMPKlow patients (23%),PKRhigh/AMPKhigh patients (13%), and PKRlow/AMPKhigh patients (15%) (p = 0.039). Conclusions: Our findings first indicate that PKR/AMPK expression, as a combined metabolism related biomarker, is an prognostic variable in glioma patients.
Comparing Three Different Techniques for Magnetic Resonance Imaging-targeted Prostate Biopsies: A Systematic Review of In-bore versus Magnetic Resonance Imaging-transrectal Ultrasound fusion versus Cognitive Registration. Is There a Preferred Technique?
Authors: Olivier Wegelin, Harm H.E. van Melick, Lotty Hooft, J.L.H. Ruud Bosch, Hans B. Reitsma, Jelle O. Barentsz, Diederik M. Somford
Journal: European Urology (2016)
Abstract 14147: The Non-Linear Relationship of Pulse Pressure to Mortality at the 22 year Follow-Up of the Systolic Hypertension in the Elderly Program
Authors: John B Kostis, Fei Wang, William J Kostis, Dhammika Amaratunga, John S Pantazopoulos, Javier Cabrera, Franz H Messerli
Journal: Circulation (2015)

Introduction: An association of pulse pressure (PP) with mortality has been reported. However, scant data are available on long-term follow-up in placebo controlled clinical trials and on the shape of the relationship between PP and all-cause and cardiovascular (CV) death. Hypothesis: We examined the relationship between PP with mortality at 22 years in the placebo and active treatment groups of the Systolic Hypertension in the Elderly Program (SHEP). Methods: SHEP enrolled participants aged 60 and older (mean 72) with isolated systolic hypertension (systolic blood pressure 160 mm Hg or higher and diastolic blood pressure below 90 mm Hg). The relationship between all-cause and CV mortality with baseline PP was examined in 4,211 SHEP participants. Results: A J curve relationship of mortality and PP was observed for all-cause death in an unadjusted analysis: linear term p&lt;0.0001, quadratic term (green) p=0.01743 and tricubic (red). In this analysis highest risk was at a PP of 118 mm Hg (left figure). When the analysis was adjusted for age, gender, co-morbidities and risk factors for CV disease, the non-linear relationship was markedly attenuated with the quadratic term not statistically significant (right figure). Age (p&lt;0.0001) and female gender (p=0.0215) were significant predictors of mortality. The effects on CV mortality were similar to those of all-cause mortality. Conclusions: In patients with isolated systolic hypertension, there is a non-linear (quadratic) relationship between PP and all-cause and CV mortality at 22 years of follow-up. This relationship is primarily mediated by age, gender, co-morbidities and CV risk factors and is attenuated after adjustment.
Conditional Risk of Relapse in Surveillance for Clinical Stage I Testicular Cancer
Authors: Madhur Nayan, Michael A.S. Jewett, Ali Hosni, Lynn Anson-Cartwright, Philippe L. Bedard, Malcolm Moore, Aaron R. Hansen, Peter Chung, Padraig Warde, Joan Sweet, Martin O’Malley, Eshetu G. Atenafu, Robert J. Hamilton
Journal: European Urology (2016)
Phase I study of SCH 900105 (SC), an anti-hepatocyte growth factor (HGF) monoclonal antibody (MAb), as a single agent and in combination with erlotinib (E) in patients (pts) with advanced solid tumors.
Authors: A. Patnaik, G. J. Weiss, K. Papadopoulos, R. Tibes, A. W. Tolcher, F. C. Payumo, M. M. Cotreau, J. Jac, R. Isaacs, R. K. Ramanathan
Journal: Journal of Clinical Oncology (2010)

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