tbuckley/cabot-search huggingface dataset:
A randomized phase II study of OGX-011 in combination with docetaxel and prednisone or docetaxel and prednisone alone in patients with metastatic hormone refractory prostate cancer (HRPC)
Authors: K. N. Chi, S. J. Hotte, E. Yu, B. J. Eigl, I. Tannock, F. Saad, S. North, J. Powers, E. Eisenhauer
Journal: Journal of Clinical Oncology (2007)

5069 Background: Clusterin, a cytoprotective chaperone protein that promotes cell survival, is associated with androgen independent progression and overexpressed in HRPC. OGX-011 (OGX, developed by OncoGenex Technologies/Isis Pharmaceuticals) is a 2’- methoxyethyl modified phosphorothioate antisense that inhibits clusterin expression in humans at doses of ≤640 mg and potentiates chemotherapy activity in prostate xenografts. The objective of this study was to determine the anti-tumor activity of OGX in combination with docetaxel (DOC) in patients (pts) with HRPC. Methods: Chemo-naive pts with metastatic HRPC were randomized to receive DOC 75mg/m 2 q3 weeks + OGX 640mg weekly as a 2-hour IV infusion (Arm A) + prednisone or DOC + prednisone (Arm B). Serum levels of clusterin were assessed serially. A single stage randomized phase II design was employed with PSA response rate (RR) as the primary endpoint (Bubley et al, J Clin Oncol 1999;17:3461). Planned sample size was 40 per arm: Arm A the hypotheses (H0:PSA RR&lt;40% vs. H1:PSA RR&gt;60%) could be tested at 10% β and 10% a, Arm B the true PSA RR could be estimated with half-width of the 90% confidence interval &lt;13% if observed PSA RR was 40%. Results: 82 pts (41/arm) were enrolled from September 2005 to December 2006 at 12 centers. Baseline characteristics are similar in both arms (available to date for 63 pts): median age 67 (range: 49–84), PSA 110 μg/L (5.6–1261), hemoglobin 128 g/L (96–158), alkaline phosphatase 133 U/L (47–1294), LDH 193 U/L (120–741). ECOG performance status was 0 in 49% and 1 in 51%; 67% had bone/nodal disease only and 33% had other metastatic sites. To date, 56 pts have received ≥2 cycles. Toxicity due to OGX included grade 1/2 fevers and rigors in 37% and 67% pts respectively, but other adverse events were similar in both arms. PSA response has occurred in 43%, progression in 9%, and 48% have not yet met criteria for response or progression. Conclusions: Combined docetaxel and OGX is well tolerated in pts with metastatic HRPC and PSA responses have been observed. Pt treatment, follow-up and analysis of serum clusterin levels continue. Results by arm will be available by June 2007. Supported by a grant from the NCI-Canada/Canadian Cancer Society. No significant financial relationships to disclose.
Product Attributes and Donor Factors in Reported Cases of Transfusion-Associated Graft Versus Host Disease: A Systematic Review
Authors: Ilana Kopolovic, Jackie Ostro, Christine Cserti, Walter Sunny Dzik, Hidacki Tsubota, Amy Keir, Hans A. Messner, Neal denHollander, Yulia Lin, Jeannie Callum
Journal: Blood (2014)
Different Platelet Count Thresholds to Guide Use of Prophylactic Platelet Transfusions for Patients With Hematological Disorders After Myelosuppressive Chemotherapy or Stem Cell Transplantation
Authors: Lise J. Estcourt, Simon J. Stanworth, Michael F. Murphy
Journal: JAMA Oncology (2016)

What is the optimal platelet count threshold for prophylactic platelet transfusions to minimize bleeding, platelet use, and adverse clinical outcomes in thrombocytopenic patients with hematological malignant neoplasms?Maintaining a higher platelet count threshold (≤20 × 109/L or ≤30 × 109/L) was not associated with less bleeding than the current standard (≤10 × 109/L), but required more platelet transfusions (low-quality evidence).
Efficient elimination of pancreatic cancer stem cells by hedgehog/GLI inhibitor GANT61 in combination with mTOR inhibition
Authors: Yumi Miyazaki, Shyuichirou Matsubara, Qiang Ding, Koichiro Tsukasa, Makoto Yoshimitsu, Ken-ichiro Kosai, Sonshin Takao
Journal: Molecular Cancer (2016)

Pancreatic cancer is one of the most lethal malignancies. The innovative treatments are required and now the cancer stem cells (CSCs) are expected to be an effective target for novel therapies. Therefore we investigated the significance of hedgehog (Hh) signaling in the maintenance of CSC-like properties of pancreatic cancer cells, in order to discover the key molecules controlling their unique properties.Human pancreatic cancer cell lines, Capan-1, PANC-1, MIA PaCa-2 and Capan-1 M9 were used for our experiments in DMEM/F12 medium containing 10 % fetal bovine serum. Sphere formation assay, immunofluorescence staining, flow cytometric analysis and MTT cell viability assay were performed to investigate molecular signals and the efficacy in the treatment of pancreatic cancer cells.Inhibition of the Hh pathway significantly reduced the expression of stem cell marker CD133 and sphere formation, an index of self-renewal capacity, demonstrating the suppression of CSC-like properties. Moreover, the GLI inhibitor GANT61 induced greater reduction in sphere formation and cell viability of pancreatic cancer cells than the smoothened (SMO) inhibitor cyclopamine. This suggests that GLI transcription factors, but not SMO membrane protein, are the key molecules in the Hh pathway. The treatment using GANT61 in combination with the inhibition of mTOR, which is another key molecule in pancreatic CSCs, resulted in the efficient reduction of cell viability and sphere formation of an inhibitor-resistant cell line, showing the strong efficacy and wide range applicability to pancreatic CSC-like cells.Thus, this novel combination treatment could be useful for the control of pancreatic cancer by targeting pancreatic CSCs. This is the first report of the efficient elimination of pancreatic cancer stem-like cells by the double blockage of Hh/GLI and mTOR signaling.
Involvement of the MLL/ALL-1 gene associated with multiple point mutations of the N-ras gene in acute myeloid leukemia with t(11;17)(q23;q25) [letter]
Authors: T Naoe, K Kubo, H Kiyoi, R Ohno, Y Akao, J Yoshida, K Kato, S Kojima, T Matsuyama
Journal: Blood (1993)
Lung cancer in octogenarians. Retrospective study of clinical characteristics and therapy in a single-center and a 5-year experience.
Authors: Ana Laura Ortega Granados, Nuria Cárdenas Quesada, Carmen Rosa Garrido, María Ruiz Sanjuan, Mónica Fernández-Navarro, Yessica Plata Fernández, Natalia Luque Caro, Francisco José García Verdejo, Pedro Lopez Leiva, Miguel Angel Moreno Jimenez, Esther Martínez Ortega, Ana Jaén Morago, Rosario Dueñas García, Irene Gonzalez Cebrian, Jose Ales-Martinez, Pedro Sánchez Rovira
Journal: Journal of Clinical Oncology (2016)

e21521 Background: In our institution, median age of patients with lung cancer is 71. We decide to study how are treated patients over 80 years. Methods: We performed a retrospective observational study, including all elderly patients with lung cancer referred to Medical Oncology in our institution (tertiary center in Spain) in a 5-year period (2010 to 2014), and followed until June 2015. The inclusion criteria is an age of 80 years or older at the time of diagnosis of the lung cancer. The study cohort is 48 patients Results: Most of patients, 77.1 % were male, and average age is 81 years (80-87). They represent a 6% of our global lung-cancer population (910 in this 5-year period). Just a 10% of patients had a SCLC (lower incidence than in all patients, with a SCLC rate of 21%), and a 88.6% had NSCLC. In the NSCLC group, squamous cell carcinomas represent a 49% of total, and adenocarcinoma a 27%. A 19% of patients harbour an EGFR mutation (slightly higher incidence than global population, our EGFR mutation rate is 16%) 51% of patients were diagnosed in stages II-III, and 49% in stage IV; but only 7.3% patients had a curative-intent therapy (2 surgery, 1 radiation therapy). About a third of patients (29%) did not receive any active cancer therapy. We study also the pattern of treatment in patients under active cancer therapy. We use up to 10 chemotherapy schedules, and in the 34 patients that we treated with first-line chemotherapy, 14 patients (41%) received a doublet with carboplatin plus another drug (15% pemetrexed, 10% vinorelbine, and 8% paclitaxel). A 35% of these patients received second-line therapy, and three patients received ≥ 3 lines. To date, 41 patients died (85.4 %), most of them at home (96%). Median survival time is 12.6 months; survival in active cancer treatment group is 14.56 months, and in palliative care-only group is 5.28 months (p-value: 0.001) Conclusions: Although our cohort is small, we can suggest that usual clinical assessment is enough to discern the evolution of elderly patients with lung cancer and decide about successful active cancer treatment. The median survival time suggests that there has been a proper management of patients.
Tragedy, Trade-offs, and the Demise of Morcellation
Authors: Hooman Noorchashm, Amy J Reed
Journal: New England Journal of Medicine (2016)

To the Editor: Rosenbaum’s article on morcellation (March 10 issue)1 contends that the practice receded from use in gynecology because of an “emotionally” publicized “N-of-1” complication at a prominent hospital.2 It is true that an N of 1 mobilized a large-scale focus on determining the actual risk of death from cancer upstaging owing to morcellation — on the order of 1 in 300, as now established by several notable studies.3 Until December 2013, most women had no idea that their fibroids were being morcellated or that they might be at risk for cancer upstaging — and this was a serious . . .
Activation of Direct and Indirect Pathway Medium Spiny Neurons Drives Distinct Brain-wide Responses
Authors: Hyun Joo Lee, Andrew J. Weitz, David Bernal-Casas, Ben A. Duffy, ManKin Choy, Alexxai V. Kravitz, Anatol C. Kreitzer, Jin Hyung Lee
Journal: Neuron (2016)

Highlights•Brain-wide influences of direct and indirect pathways are visualized with ofMRI•Direct and indirect pathway stimulations evoke opposing brain-wide activities•Direct and indirect pathways exert non-canonical control over STN and GPi•BOLD signal polarity reflects single-unit activity in basal ganglia and thalamusSummaryA central theory of basal ganglia function is that striatal neurons expressing the D1 and D2 dopamine receptors exert opposing brain-wide influences. However, the causal influence of each population has never been measured at the whole-brain scale. Here, we selectively stimulated D1 or D2 receptor-expressing neurons while visualizing whole-brain activity with fMRI. Excitation of either inhibitory population evoked robust positive BOLD signals within striatum, while downstream regions exhibited significantly different and generally opposing responses consistent with—though not easily predicted from—contemporary models of basal ganglia function. Importantly, positive and negative signals within the striatum, thalamus, GPi, and STN were all associated with increases and decreases in single-unit activity, respectively. These findings provide direct evidence for the opposing influence of D1 and D2 receptor-expressing striatal neurons on brain-wide circuitry and extend the interpretability of fMRI studies by defining cell-type-specific contributions to the BOLD signal.
Granulocyte colony-stimulating factor recruitment of CD34+ progenitors to peripheral blood: impaired mobilization in chronic granulomatous disease and adenosine deaminase--deficient severe combined immunodeficiency disease patients
Authors: S Sekhsaria, TA Fleisher, S Vowells, M Brown, J Miller, I Gordon, RM Blaese, CE Dunbar, S Leitman, HL Malech
Journal: Blood (1996)
Epidémie de trichinellose humaine liée à la consommation de viande chevaline en Italie
Authors: E Pozio, D Sacchini, P Boni, A Tamburrini, F Alberici, F Paterlini
Journal: Eurosurveillance (1998)

La trichinellose sauvage est endemique en Italie ; bien qu’elle ne cause que peu d’infections chez l’homme, elle est generalement liee a la consommation de viande provenant de porcs en pâturage dans des regions sauvages ou de sangliers (1). En Italie, la plupart des cas de trichinellose humaine sont dus a la consommation de viande de cheval (902 cas dans quatre epidemies de 1975 a 1990) (2). Le 22 janvier 1998, 27 chevaux etaient importes de Pologne pour etre tues dans l’abattoir d’une entreprise privee a Brescia, au nord de l’Italie.
Nationwide outbreak of Salmonella enterica serotype Kedougou infection in infants linked to infant formula milk, Spain, 2008
Authors: P Soler, S Herrera, J Rodríguez, J Cascante, R Cabral, A Echeita-Sarriondia, S Mateo, Collective on behalf of the National Surveillance Network of Spain
Journal: Eurosurveillance (2008)

On 5 August 2008, the National Reference Laboratory of Salmonella (NRLS) noted an increase in the number of isolates of Salmonella enterica serotype Kedougou. As of 22 August, 29 isolates have been reported during 2008, which is ten times more than the average number of isolates identified by the NRLS during 2002-2007. All isolates have a typical, indistinguishable Pulse Field pattern (SALKEDXB-1, Spanish code) and are fully sensitive to the standard suite of antimicrobials.
Methylated estrogen receptor alpha in tumors and sera of melanoma patients
Authors: S. R. Martinez, T. Mori, N. Umetani, S. L. Nguyen, M. Kitago, A. Tanemura, D. L. Morton, S. J. O’Day, D. S. Hoon
Journal: Journal of Clinical Oncology (2006)

8026 Background: The mechanisms regulating the variable expression of estrogen receptor alpha (ER-α) in melanoma are unknown. Silencing of ER-α expression in melanoma may be regulated by the hypermethylation of promoter region CpG islands. To determine the significance of ER-α hypermethylation-induced transcription silencing in melanoma progression, we assessed hypermethylation of ER-α DNA in primary tumors, metastatic tumors, and sera of AJCC stage I-IV melanoma patients. Methods: The methylation status of theER-α DNA promoter region in tumor (n = 107) and sera (n = 119) from AJCC stage I-IV melanoma patients was examined by methylation-specific PCR (MSP) and capillary array electrophoresis (CAE). To determine the significance of free circulating hypermethylated ER-α DNA, we assessed the therapeutic response, progression-free and overall survival among AJCC stage IV melanoma patients receiving biochemotherapy. Results: The frequency of ER-α DNA methylation in AJCC stage I, II, and III primary melanomas was 36% (4 of 11), 26% (5 of 19), and 35% (8 of 23), respectively. The frequency of methylated ER-α DNA detected in stage III and IV metastatic melanomas was 42% (8 of 19) and 86% (30 of 35), respectively. ER-α DNA was methylated in 38 of 54 (70%) metastatic tumors, a more than two-fold increase compared to primaries (p = 0.0003). In the analysis of 109 melanoma patients’ sera, the frequency of methylated ER-α DNA in AJCC stage I, II, III, and IV was 10% (2 of 20), 15% (3 of 20), and 26% (5 of 19), and 32% (16 of 50), respectively. The frequency of methylated ER-α DNA detected in stage III/IV was significantly higher than in stage I/II (p=0.034). In a multivariate analysis, circulating hypermethylated ER-α DNA was the only independent factor predicting progression-free (risk ratio 2.64, 95% CI 1.36–5.13, p = 0.004) and overall survival (risk ratio 2.31, 95% confidence interval 1.41–5.58, p = 0.003) among stage IV patients receiving biochemotherapy. Conclusion: Hypermethylation of ER-α DNA in primary and metastatic melanoma tumors and serum is a significant factor in melanoma progression. The detection of methylated serum ER-α DNA predicts poor response to systemic therapy and is an unfavorable prognostic factor in advanced melanoma. [Table: see text]
2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: Executive Summary
Authors: L. David Hillis, Peter K. Smith, Jeffrey L. Anderson, John A. Bittl, Charles R. Bridges, John G. Byrne, Joaquin E. Cigarroa, Verdi J. DiSesa, Loren F. Hiratzka, Adolph M. Hutter, Michael E. Jessen, Ellen C. Keeley, Stephen J. Lahey, Richard A. Lange, Martin J. London, Michael J. Mack, Manesh R. Patel, John D. Puskas, Joseph F. Sabik, Ola Selnes, David M. Shahian, Jeffrey C. Trost, Michael D. Winniford
Journal: Journal of the American College of Cardiology (2011)
Electron Microscopic Study of Epidermal Carcinoma Induced by Methylcholanthrene in the Mouse
Authors: A VON ALBERTINI
Journal: JNCI Journal of the National Cancer Institute (1953)

Electron Microscopic Study of Epidermal Carcinoma Induced by Methylcholanthrene in the Mouse Get access A. von Albertini A. von Albertini Department of Anatomy3, Division of Cancer Research, Washington University, St. Louis, Mo., and Laboratory of Physical Biology4National Institute of Arthritis and Metabolic Diseases5Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 13, Issue 6, June 1953, Pages 1473–1495, https://doi.org/10.1093/jnci/13.6.1473 Published: 01 June 1953 Article history Received: 29 January 1953 Published: 01 June 1953
PD2-2-8: The impact of epidermal growth factor receptor gene status on carcinogenesis of small adenocarcinoma of the lung
Authors: Junichi Soh, Shinichi Toyooka, Shuji Ichihara, Naruyuki Kobayashi, Hiroshi Suehisa, Hiroaki Asano, Kouichi Ichimura, Masaomi Yamane, Takahiro Oto, Yoshifumi Sano, Katsuyuki Kiura, Hiroshi Date
Journal: Journal of Thoracic Oncology (2007)
Dysregulation of Prefrontal Cortex-Mediated Slow-Evolving Limbic Dynamics Drives Stress-Induced Emotional Pathology
Authors: Rainbo Hultman, Stephen D. Mague, Qiang Li, Brittany M. Katz, Nadine Michel, Lizhen Lin, Joyce Wang, Lisa K. David, Cameron Blount, Rithi Chandy, David Carlson, Kyle Ulrich, Lawrence Carin, David Dunson, Sunil Kumar, Karl Deisseroth, Scott D. Moore, Kafui Dzirasa
Journal: Neuron (2016)
Using NHS data to improve health
Authors: N M R Perrin
Journal: BMJ (2016)

Data guardian demands much more extensive dialogue with public 

The information in health records has great potential to improve the delivery of healthcare and to advance medical research. But the public and healthcare professionals must have confidence that access to patient data is appropriately managed. Two reports published last week take an important step towards this goal.1 2

Last September, the secretary of state for health commissioned the Care Quality Commission (CQC) to review current approaches to data security across the NHS and, in parallel, asked the national data guardian, Fiona Caldicott, to develop data security standards and a method of ensuring compliance. Caldicott was also asked to recommend a new consent model for data sharing in the NHS and social care. Both reports were published on 6 July and led to the immediate closure of the NHS England’s controversial data sharing programme care.data.2 3

This is the third time Caldicott has examined these issues. In 1997, she chaired a review on patient confidentiality, which led to the introduction of Caldicott guardians in every NHS organisation.5 In 2013, she called for a better balance between protecting and sharing patient information to improve health.6 In her most recent report, she highlights her frustrations that so little has improved since then.

Both new reviews found widespread commitment to keeping data secure across the …
A Genome-Wide Association Study of Risk of Coronary Artery Disease in European and South Asian Populations
Authors: J C Hopewell, J Peden, D Saleheen, J Chambers, R Clarke, R Collins, J Danesh, P Deloukas, P Elliott, M Farrall, J Hager, A Hamsten, J Kooner, M Lathrop, S Parish, H Watkins
Journal: Circulation (2010)
2016 ACC/AHA Clinical Performance and Quality Measures for Adults With Atrial Fibrillation or Atrial Flutter
Authors: Paul A. Heidenreich, Penelope Solis, N. A. Mark Estes, Gregg C. Fonarow, Corrine Y. Jurgens, Joseph E. Marine, David D. McManus, Robert L. McNamara
Journal: Journal of the American College of Cardiology (2016)
Observations of a large Dent disease cohort
Authors: Anne Blanchard, Emmanuel Curis, Tiphaine Guyon-Roger, Diana Kahila, Cyrielle Treard, Véronique Baudouin, Etienne Bérard, Gérard Champion, Pierre Cochat, Julie Dubourg, Renaud de la Faille, Olivier Devuyst, Georges Deschenes, Michel Fischbach, Jérôme Harambat, Pascal Houillier, Alexandre Karras, Bertrand Knebelmann, Marie-Pierre Lavocat, Chantal Loirat, Elodie Merieau, Patrick Niaudet, François Nobili, Robert Novo, Rémi Salomon, Tim Ulinski, Xavier Jeunemaître, Rosa Vargas-Poussou
Journal: Kidney International (2016)
Lactonase and C-Acylase Activity of Hepatoma
Authors: A MEISTER
Journal: JNCI Journal of the National Cancer Institute (1949)

Journal Article Lactonase and C-Acylase Activity of Hepatoma Get access Alton Meister Alton Meister senior assistant surgeon National Cancer Institute, National Institutes of Health, Public Health Service, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 1, August 1949, Pages 75–80, https://doi.org/10.1093/jnci/10.1.75 Published: 01 August 1949 Article history Received: 21 December 1948 Published: 01 August 1949
A double-blind dose-reduction trial of fluphenazine decanoate for chronic, unstable schizophrenic patients
Authors: L B Inderbitzin, R R Lewine, G Scheller-Gilkey, C D Swofford, G J Egan, B A Gloersen, B P Vidanagama, C Waternaux
Journal: American Journal of Psychiatry (1994)

This study evaluated the feasibility and impact of gradually reducing relatively high doses of fluphenazine decanoate by one-half for chronically impaired, poor inner-city patients with schizophrenia.Forty-three patients currently receiving an average of 23 mg (0.3 mg/kg) of fluphenazine decanoate every 2 weeks were divided alternately into a group to remain at current doses (control group) and a group to undergo stepwise 50% dose reduction over 5 months under double-blind conditions. Clinical status and side effects were assessed quarterly for a year. Relapse was determined clinically and by changes in psychopathology ratings.Eighty-six percent (N = 37) of the patients (control group, N = 17; reduced-dose group, N = 20) completed the study. The groups did not differ at baseline in demographic or clinical variables or neuroleptic dose. In the reduced-dose group, doses were lowered to an average of 11.5 mg every 2 weeks. The two groups did not differ throughout the year in number of relapses, and hospitalization rates fell similarly in both (overall, by about 67%). Clinical measures changed little. Extrapyramidal symptoms worsened in the control group but improved slightly in the reduced-dose group. Tardive dyskinesia worsened in both groups, but less in the reduced-dose group.Maintenance neuroleptic doses much lower than the conventional ones can be achieved safely in schizophrenic patients by gradual reduction, without clinical worsening and perhaps with fewer extrapyramidal symptoms and less tardive dyskinesia. The two-thirds lower hospitalization rate, with substantial financial savings, apparently was due to nonspecific effects of research intervention.
Influence of Renal Impairment and Genetic Risk Factors on Response to Induction Therapy in the HD4 and MM5 Trials of the GMMG
Authors: Christof Scheid, Thomas Hielscher, Uta Bertsch, Christina Kunz, Hans Salwender, Mathias Haenel, Maximilian Merz, Elias Karl Mai, Dirk Hose, Baerbel Schurich, Markus Munder, Ingo Schmidt-Wolf, Christian Gerecke, Walter Lindemann, Matthias Zeis, Katja Weisel, Jan Duerig, Anna Jauch, Hartmut Goldschmidt
Journal: Blood (2014)