tbuckley/cabot-search huggingface dataset:
Molecular portraits of ependymoma recurrence by paired analysis of microarray data
Authors: M. Peyre, F. Commo, C. Dantas-Barbosa, S. Puget, R. Bhangoo, P. Varlet, P. Dessen, C. Sainte-Rose, G. Vassal, J. Grill
Journal: Journal of Clinical Oncology (2008)

10048 Background: Relapse is a frequent phenomenon in intracranial childhood ependymomas. To gain new insights into this process and identify pathways associated with relapse, we compared the genomic and gene expression profiles of the relapses with the corresponding initial tumors. Methods: We studied 27 relapses in 17 patients by comparing their gene expression profile to the one obtained at diagnosis in the same child. Recurrences analyzed occurred after surgery alone in seven, surgery plus chemotherapy in 10 and any treatment plus radiotherapy in 11 cases. For each recurrence, gene expression levels were compared by dual color competitive hybridization on Agilent 44K gene expression microarrays. Statistical analysis was performed after initial filtering which retained only sequences differentially expressed (p<0.05) on at least 50% of experiments. Filtering criteria as well as the research of a common signature in recurrences and group comparisons were performed with Rosetta Resolver. Genomic profiling at diagnosis and at recurrence was performed using Agilent 44K oligo-CGH DNA microarrays and expression signatures were compared to gene copy number changes. Results: A subset of 48 sequences appeared to be significantly associated with recurrences (p<0.01) in at least 60% of cases. Among the genes upregulated at recurrence, some belonged to the Wnt and Notch pathways; 15 genes involved in proliferation and mitotic spindle were also upregulated. Metallothioneins were the genes most frequently (85%) downregulated at recurrence. RT-PCR and IHC data on selected genes confirmed the microarray results. Most frequent copy number changes were 3p and 6p losses and 9q and 1q gains. Copy number changes increased at recurrence compared with diagnosis in 9 patients and remained stable or decreased in 8. Comparison of microarray data with genomic imbalances revealed that most of the modifications in gene expression were not related to copy number changes. Conclusions: The most frequent molecular events associated with ependymoma relapse include increased proliferation associated with over-expression of kinetochore proteins and down-regulation of metallothioneins. Targeting of these pathways may offer novel therapeutic options in these refractory brain tumors. No significant financial relationships to disclose.
P229 Use of Inhaled Antibiotics in CF Burkholderia spp Chronic Infection: Abstract P229 Table 1
Authors: JE Marlow, K Delisle, S Ajab, M Ledson, J Greenwood, M Walshaw
Journal: Thorax (2015)

<h3>Introduction</h3> Although CF guidelines recommend that patients chronically infected with Pseudomonas aeruginosa should be offered inhaled antibiotics to help maintain pulmonary function and reduce exacerbation frequency, there is no such advice for those infected with Burkholderia spp, some of which confer a much worse prognosis. <h3>Methods</h3> To look at the potential for this, we reviewed the microbiology of all adults attending our large unit (300 patients), paying attention to those with chronic Burkholderia infection, any co-existing pathogens, antibiotic sensitivity patterns, and the use of inhaled antibiotics. <h3>Results</h3> Twenty two patients (7.3%) are infected with Burkholderia spp (6 multivorans, 8 cenocepacia, 1 genomovar IIIa cable pilus negative, 3 genomovar IIIb, 3 vietnamensis, and 1 dolosa. For sensitivity patterns (defined as &gt;10 mm inhibition by disc diffusion) see Table 1. 9 patients (41%) are co-infected (4 with Pseudomonas aeruginosa, 3 Staph aureus, 2 MRSA, 1 Stenotrophomonas maltophilia). Ten patients (none with cenocepacia) are using inhaled antibiotics (3 colistin, 1 Colobreath, 2 TOBI, 2 Cayston, 1 ceftazidime, 1 alternating Cayston and Promixin). <h3>Conclusion</h3> This study shows that a significant proportion of our Burkholderia spp infected patients have organisms that are sensitive to currently available inhaled antibiotics. Given our positive experience, and with the expected availability of new inhaled antibiotics in the near future, perhaps the time has come to formally look at the use of inhaled anti-microbial therapy in this small but important cohort of CF patients.
Phase II Study of Rituximab Given in Conjunction with Standard Chemotherapy in Primary Central Nervous System Lymphoma (PCNSL)[E1F05]
Authors: Lode J. Swinnen, Anne O'Neill, Philip H Imus, Sachin Gujar, David Schiff, Lawrence Kleinberg, Ranjana Advani, Erin Dunbar, Dennis F. Moore, Stuart Grossman
Journal: Blood (2015)
Flt3 and MLL internal tandem duplications and topoisomerase II breakages reflect a common category of genotoxic stress: An EORTC study
Authors: M Libura, Asnafi, A Tu, I Tigaud, F Cymbalista, AL Bennaceur, D Leboeuf, E Delabesse, K Beldjord, G Solbu, Anne Hagemeijer-Hausman, O Hermine, E Macintyre
Journal: Blood (2002)
A phase Ib study of selumetinib (AZD6244, ARRY-142886) in combination with sorafenib in advanced hepatocellular carcinoma (HCC)
Authors: W.M. Tai, W.P. Yong, C. Lim, L.S. Low, C.K. Tham, T.S. Koh, Q.S. Ng, W.W. Wang, L.Z. Wang, S. Hartano, C.H. Thng, H. Huynh, K.T. Lim, H.C. Toh, B.C. Goh, S.P. Choo
Journal: Annals of Oncology (2016)
Predicting 30-Day Readmission or Death in Patients With Heart Failure
Authors: Isuru Ranasinghe, Harlan M. Krumholz
Journal: JAMA Cardiology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
FGF2 from Marrow Microenvironment Promotes Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia
Authors: Elie Traer, Jacqueline Martinez, Nathalie Javidi-Sharifi, Anupriya Agarwal, Jennifer Dunlap, Isabel English, Tibor Kovacsovics, Jeffrey W. Tyner, Melissa Wong, Brian J. Druker
Journal: Cancer Research (2016)

Potent FLT3 inhibitors, such as quizartinib (AC220), have shown promise in treating acute myeloid leukemia (AML) containing FLT3 internal tandem duplication (ITD) mutations. However, responses are not durable and resistance develops within months. In this study, we outline a two-step model of resistance whereby extrinsic microenvironmental proteins FLT3 ligand (FL) and fibroblast growth factor 2 (FGF2) protect FLT3-ITD+ MOLM14 cells from AC220, providing time for subsequent accumulation of ligand-independent resistance mechanisms. FL directly attenuated AC220 inhibition of FLT3, consistent with previous reports. Conversely, FGF2 promoted resistance through activation of FGFR1 and downstream MAPK effectors; these resistant cells responded synergistically to combinatorial inhibition of FGFR1 and FLT3. Removing FL or FGF2 from ligand-dependent resistant cultures transiently restored sensitivity to AC220, but accelerated acquisition of secondary resistance via reactivation of FLT3 and RAS/MAPK signaling. FLT3-ITD AML patients treated with AC220 developed increased FGF2 expression in marrow stromal cells, which peaked prior to overt clinical relapse and detection of resistance mutations. Overall, these results support a strategy of early combination therapy to target early survival signals from the bone marrow microenvironment, in particular FGF2, to improve the depth of response in FLT3-ITD AML. Cancer Res; 76(22); 6471-82. ©2016 AACR.
Why should we care about upper airway inflammation in obstructive sleep apnoea?
Authors: Malcolm Kohler
Journal: European Respiratory Journal (2016)

There is a number of reasons why the article by Vincente et al. [1] published in this issue of the European Respiratory Journal deserves a second thought. It is one of the very few studies that addresses the hypothesis that there may be some "spill-over" effect of inflammation from the upper airway into the blood circulation in patients with obstructive sleep apnoea (OSA) [1–3]. According to this hypothesis, which has also been proposed as a mechanism to explain raised blood inflammatory marker levels in other diseases, such as chronic obstructive pulmonary disease [4], local inflammation results in an increased production of inflammatory cytokines and proteins that reach the plasma. These enhance systemic inflammation and thereby contribute to pathophysiological effects of chronic inflammation, such as disturbed lipid and glucose metabolism, and ultimately, development of atherosclerosis. However, recently the spill-over hypothesis has been discussed controversially [4]. Treatment of upper airway inflammation may be a novel therapeutic approach in obstructive sleep apnoea <http://ow.ly/jeal302QSqc>
PLACENTAL GROWTH FACTOR/NEUROPILIN 1 SIGNALING IS A THERAPEUTIC TARGET IN PEDIATRIC MEDULLOBLASTOMA
Authors: Matija Snuderl, Ana Batista, Nathaniel Kirkpatrick, Carmen Ruiz de Almodovar, Lars Riedemann, Ellen Knevels, Thomas Schmidt, Teresa Peterson, Sylvie Roberge, Carlos Bais, Stephen Yip, Martin Hasselblatt, Claudia Rossig, Napoleone Ferrara, Michael Klagsbrun, Dan Duda, Dai Fukumura, Lei Xu, Peter Carmeliet, Rakesh Jain
Journal: Neuro-Oncology (2013)
A Simplified, Langendorff-Free Method for Concomitant Isolation of Viable Cardiac Myocytes and Nonmyocytes From the Adult Mouse Heart
Authors: Matthew Ackers-Johnson, Peter Yiqing Li, Andrew P. Holmes, Sian-Marie O’Brien, Davor Pavlovic, Roger S. Foo
Journal: Circulation Research (2016)

Cardiovascular disease represents a global pandemic. The advent of and recent advances in mouse genomics, epigenomics, and transgenics offer ever-greater potential for powerful avenues of research. However, progress is often constrained by unique complexities associated with the isolation of viable myocytes from the adult mouse heart. Current protocols rely on retrograde aortic perfusion using specialized Langendorff apparatus, which poses considerable logistical and technical barriers to researchers and demands extensive training investment.To identify and optimize a convenient, alternative approach, allowing the robust isolation and culture of adult mouse cardiac myocytes using only common surgical and laboratory equipment.Cardiac myocytes were isolated with yields comparable to those in published Langendorff-based methods, using direct needle perfusion of the LV ex vivo and without requirement for heparin injection. Isolated myocytes can be cultured antibiotic free, with retained organized contractile and mitochondrial morphology, transcriptional signatures, calcium handling, responses to hypoxia, neurohormonal stimulation, and electric pacing, and are amenable to patch clamp and adenoviral gene transfer techniques. Furthermore, the methodology permits concurrent isolation, separation, and coculture of myocyte and nonmyocyte cardiac populations.We present a novel, simplified method, demonstrating concomitant isolation of viable cardiac myocytes and nonmyocytes from the same adult mouse heart. We anticipate that this new approach will expand and accelerate innovative research in the field of cardiac biology.
T Cell Lymphoblastic Leukemia with PICALM-MLLT10/t(10;11)(p13;q21) in a Fraction of Childhood ETP-ALL. -Molecular Study of Childhood T Cell Lymphoblastic Leukemia,
Authors: Keisuke Kato, Ai Yoshimi, Tomohei Nakao, Chie Kobayashi, Kazutoshi Koike, Nobutaka Kiyokawa, Masahiro Tsuchida
Journal: Blood (2011)
Common Self-Renewal Pathways Contribute to the Induction of Acute Myeloid Leukemias Associated with Different Oncogenes
Authors: Brynn T Kvinlaug, Wai-In Chan, Lars Bullinger, Christopher Sears, Donna Paul, Rachel Okabe, Benjamin H Lee, Inusha De Silva, Scott Armstrong, Hartmut Dohner, D. Gary Gilliland, Brian JP Huntly
Journal: Blood (2008)
Prognostic Factors in Primary Chronic Myelofibrosis in Patients Aged Less Than 70 Years: A Report on 207 Patients with the Description of a Scoring System and Its Validation on 100 Other Patients.
Authors: Tetsuya E. Tanimoto, Kazuya Shimoda, Takuhiro Yamaguchi, Takashi Okamura, Hideaki Mizoguchi, Mitsuhiro Omine, Yoshiyuki Niho, Mine Harada
Journal: Blood (2004)
Regional right ventricular strain rate imaging following a senning repair how do ultrasound based regional function indices compare with global ejection fraction assessed by magnet resonance imaging
Authors: Frank Weidemann, B Eyskens, F Jamal, Luc Mertens, Jan D'hooge, Bart Bijnens, L Hatle, Marc Gewillig, George Sutherland
Journal: Journal of the American College of Cardiology (2001)
Characteristics of out-of-pocket costs for cancer patients in Ontario, Canada
Authors: C. J. Longo, R. Deber, M. Fitch, A. P. Williams
Journal: Journal of Clinical Oncology (2004)

8251 Background: What costs do cancer patients still incur in Ontario's publicly-funded healthcare system, which requires universal comprehensive coverage for hospital and physician costs? Methods: We surveyed 282 patients (74 breast, 70 colorectal, 68 lung, 70 prostate) at five Ontario cancer clinics between Oct 2001 and April 2003. Among the data collected in the self-administered questionnaire was information on “out-of-pocket” (OOP) costs paid in the previous month for: drugs, homecare, homemaking, complementary and alternative medicines, vitamins and supplements, family care, travel, accommodations, devices, other direct costs, as well as a question on patient burden. Results: Incurred direct costs were highest for travel and accommodations, with average reported costs per month of $372 for imputed mileage (range $0- $6180), parking/fares ($47, range $0 -$450), and accommodations ($43, range $0- $1500). Significant average costs were also reported for devices ($46, range $0 - $2350) and drugs ($45, range $0 - $1400). This data is highly skewed by the small number of patients with non-zero OOP costs. For example, only 39 of 277 reported any costs for devices in the reporting month, but those who did often paid significant amounts. Analysis of variance and regression analysis revealed that the OOP costs had statistically significant differences between the types of cancer surveyed. Factors that increase OOP costs include: younger age, no private insurance coverage, longer distances to the clinic, and more intense treatment, although these factors collectively do not explain the majority of the variation in costs (R2<0.15). Conclusions: Ontario's health care system adequately covers the majority of direct medical costs for most cancer patients; residual OOP costs tend to be moderate (excepting travel cost). However, there still remains a noticeable population that reports their financial burden associated with cancer treatment to be “significant” (16.5%) or “unmanageable” (3.9%). Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Canada, Inc. Eli Lilly & Co.
Change to Australasian College of Sport and Exercise Physicians—position statement: the place of mesenchymal stem/stromal cell therapies in sport and exercise medicine
Authors: Hamish Osborne, Adam Castricum
Journal: British Journal of Sports Medicine (2016)

The Board of the Australasian College of Sport and Exercise Physicians has recently learnt concerns of the Australian Government, other medical colleges and our own fellowship regarding the safety of procedures involved with the provision of stem cell therapy to patients. These concerns are partially driven by reports recently published in the lay media, scientific literature and a coroner’s report.

A recent case report in the New England Journal of Medicine 1 of a glioproliferative tumour in the spine after treatment with a mixture of mesenchymal, embryonic and fetal allogeneic stem cells for residual effects of a stroke warrants significant concern regarding the safety of unregulated innovative procedures.

Closer to home, a coroner’s recent report into the death of …
PD-1+ T Cell Subsets in Follicular Lymphoma Tumor Microenvironment and Their Implications for Prognosis and Therapy
Authors: Fuliang Chu, Wencai Ma, Tomohide Yamazaki, Myriam Foglietta, Durga Nattama, Seema Rawal, Zhiqiang Wang, Yanli Gao, Natalia M Orozco, Luis Vence, Laszlo Radvanyi, Chen Dong, Richard Eric Davis, Sattva S. Neelapu
Journal: Blood (2011)
A first-in-human, phase I study of an oral hedgehog (HH) pathway antagonist, BMS-833923 (XL139), in subjects with advanced or metastatic solid tumors.
Authors: L. L. Siu, K. Papadopoulos, S. R. Alberts, R. Kirchoff-Ross, B. Vakkalagadda, L. Lang, C. M. Ahlers, K. L. Bennett, J. M. Van Tornout
Journal: Journal of Clinical Oncology (2010)

2501 Background: Aberrant HH pathway signaling has been suggested to play a role in the development of multiple solid tumors and hematological malignancies. BMS-833923 is a potent, oral, small molecule antagonist of the HH signaling component Smoothened. Methods: The trial is designed to identify a maximum tolerated dose and evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics. All subjects receive a single dose 1 week prior to continuous daily dosing, which allows for single dose PK collection for 1 week. To identify the pharmacologically active dose range, skin samples are collected prior to day 1 and again on day 22 of the first cycle to assess GLI1 protein expression levels. Results: As of October 21, 2009, eighteen subjects (mean age of 56 [range 21-78]; ECOG performance 0--1) have been treated at four dose levels: 30 mg (n=5), 60 mg (n=3), 120 mg (n=3), and 240 mg (n=7). No subjects in the first three dose cohorts experienced drug-related CTCAE adverse events greater than grade 2. One subject with medulloblastoma in the 30 mg dose cohort continues on study for >11 months with stable disease. Treatment of subjects in the fourth cohort at 240 mg is ongoing. In this cohort, a 50 year old female subject with Gorlin Syndrome, caused by germline mutation in the HH pathway gene Patched, experienced an ongoing confirmed partial response. This subject experienced drug-related CTCAE grade 2 lipase elevation and pancreatitis that quickly resolved when drug was withheld. The subject is currently receiving a single 60 mg dose every other week. BMS-833923 PK properties showed dose proportionality between the 30, 60, and 120 mg dose cohorts and greater than dose proportionality between the 120 mg and 240 mg dose cohorts. All dose cohorts show a prolonged terminal half-life of >7 days with drug accumulation of 3-6 fold between days 1 and 22 as measured by changes in the Cmax. Measurement of GLI1 protein expression in the skin biopsies shows a decrease at all dose levels. Conclusions: BMS-833923 is generally well tolerated at the dose levels tested, which include dose levels that are clinically active. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb, Merck, Millennium Bristol-Myers Squibb Bayer, Bristol-Myers Squibb, Cyclacel Pharmaceuticals, GlaxoSmithKline, Merck, Novartis, Pfizer, Regeneron, Roche Bristol-Myers Squibb Bristol-Myers Squibb
What can we learn from blood granulocyte patterns in patients with asthma?
Authors: Kirsty Hambleton, Ian D. Pavord
Journal: European Respiratory Journal (2016)

There has been an explosion in interest in the utility of the blood eosinophil count as a biomarker in patients with airway disease. It is a readily accessible measure, and studies have shown a consistent positive relationship between the blood eosinophil count and the risk of exacerbations [1–6], and the extent to which this can be reduced by inhaled corticosteroids (ICS) [3–5] and anti-interleukin-5 monoclonal antibodies [6–8]. Much of the work to date has been carried out in patients with severe asthma or has involved post hoc analysis of intervention studies of ICS in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Much less is known about the relationship between blood eosinophil counts and outcomes in patients with less severe asthma, and there is almost no information available from longitudinal studies. The study by Nadif et al. [9] published in this issue of the European Respiratory Journal is therefore welcome, as it provides new and interesting information in both areas. Blood eosinophil counts are a potentially informative biomarker in airway disease <http://ow.ly/aOHt3032iz0>
Mutational profiling of a MonoMAC syndrome family with GATA2 deficiency
Authors: L-W Ding, T Ikezoe, K-T Tan, M Mori, A Mayakonda, W Chien, D-C Lin, Y-Y Jiang, M Lill, H Yang, Q-Y Sun, H P Koeffler
Journal: Leukemia (2016)
Incidence of Centrosome Amplification in Multiple Myeloma.
Authors: Jana Smejkalova, Elena Dementyeva, Pavel Nμmec, Kryukov Fedor, Karthick Raja Muthu Raja, Henrieta Grešlíková, Jan Smetana, Romana Zaoralova, Renata Kupska, Petr Kuglik, Roman Hajek
Journal: Blood (2009)