tbuckley/cabot-search huggingface dataset:
Mediation of LA-4 lung epithelial cell injury by alloreactive donor T cells.
Authors: S. V. Radhakrishnan, T. Obermeier, G. Mueller, G. C. Hildebrandt
Journal: Journal of Clinical Oncology (2011)

6575 Background: Acute noninfectious lung injury is associated with significant mortality in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). While alloantigen-reactive donor T cells migrating into the lung seem critical, the role of T cell-mediated lung epithelial cell apoptosis is still unclear. Methods: Mouse LA-4 lung epithelial cells (H2-Dd) were analyzed for their surface marker expression by FACS. For cytotoxic T lymphocyte (CTL) chromium release assays, murine alloreactive C57BL/6 effector T cells (H2-Db) were purified following stimulation using allogeneic A/He mouse splenocytes (H2-Dd) and then plated against syngeneic EL-4 (H2-Db) or allogeneic LA-4 (H2-Dd) target cells. Results: Unstimulated LA-4 cells were H2-Kk - (MHCI), H2-Dd ++ (MHCI), I-Ak - (MHCII), TNFRI (+), TNFR II (+), Fas +, FasL -, CD86 -, CD80 (+), ICAM-1 -. Stimulation with lipopolysaccharide but not IFN gamma resulted in strong upregulation of H2-Dd and Fas, and neither stimulus changed any of the other markers tested. While LA-4 cells, consistent with their lack of MHCII expression, were not able to induce a significant proliferative T cell response, it seemed likely, that constitutive and inducible MHCI expression as well as TNRI/TNFRII and/or Fas expression rendered LA-4 cells as targets of alloreactive CD8+ T cell toxicity. While alloantigen specific lysis of LA-4 cells through C57BL/6 effector CD8+ T cells occurred in direct relation to the effector:target cell ratio applied in the CTL assay, no lysis was seen using syngeneic EL-4 target controls. To determine, whether perforin/granzyme, TNF or FasL:Fas were involved in T cell mediated LA-4 cell killing, we next used either effector T cells from perforin-deficient (pfp-/-) donor mice or targeted TNF or FasL using neutralizing antibodies (Ab). Anti-TNF Ab’s decreased cytotoxicity by 25%, whereas anti- FasL Ab’s only showed a minor and the use of pfp-/- T cells showed no effect. Conclusions: Our data demonstrate, that LA-4 lung epithelial cells are prone to alloreactive T cell injury involving TNF as a major cytotoxic mediator, and strengthen the concept of the lung as a target organ of GVHD.
An Institutional Experience: Correlation Between Absolute Lymphocyte Count and Survival Outcome After Reduced Intensity Conditioning Allogeneic Stem Cell Transplant in Patients with Hematologic Malignancies
Authors: Kehinde U.A. Adekola, John P. Galvin, Vaibhav Sahai, Oluwatoyosi A. Onwuemene, Joanne Monreal, John Cashy, Jayesh Mehta
Journal: Blood (2012)
Impact of Autologous Transplantation Vs. Chemotherapy Plus Lenalidomide in Newly Diagnosed Myeloma According to Patient Prognosis: Results of a Pooled Analysis of 2 Phase III Trials
Authors: Francesca Gay, Chiara Cerrato, Roman Hajek, Francesco Di Raimondo, Tommaso Caravita, Antonietta Pia Falcone, Francesca Patriarca, Stefano Pulini, Paola Finsinger, Giovannino Ciccone, Paolo Corradini, Agostina Siniscalchi, Francesca Donato, Dina Ben Yehuda, Massimo Offidani, Jiri Minarik, Roberto Ria, Federica Cavallo, Lucio Catalano, Maide Cavalli, Ludek Pour, Maria Teresa Petrucci, Izhar Hardan, Mario Boccadoro, Andrew Spencer, Antonio Palumbo
Journal: Blood (2014)
TKI258 (dovitinib lactate) in metastatic renal cell carcinoma (mRCC) patients refractory to approved targeted therapies: A phase I/II dose finding and biomarker study
Authors: E. Angevin, J. A. Lopez, A. Pande, C. Moldovan, M. Shi, J. C. Soria, X. Wang, A. Harzstark, J. Saro, B. Escudier
Journal: Journal of Clinical Oncology (2009)

3563 Background: TKI258 is a potent receptor tyrosine kinase inhibitor (TKI) that selectively targets VEGFR, PDGFR, FGFR, CSF1R, c-KIT, RET, TrKA, and FLT3. Compared to other TKI agents, TKI258 additionally targets FGFR. FGF has been reported as an important escape mechanism of anti-VEGFR therapies. Methods: The primary objective of this phase I was to determine the maximum tolerated dose (MTD) of TKI258, administered orally on a 5 days on / 2 days off schedule in repeated 28 day cycles, in mRCC pts refractory to standard therapies. A two-parameter Bayesian logistic regression model and safety data for at least 21 pts will be used to determine MTD. Results: A phase I study is ongoing. As of December 2008, 11 pts (9 m, 2 f), median age: 55 (29–66 yrs) have been enrolled. Four pts have been treated at 500 mg/day (start dose): 2 are ongoing at cycle (C) 7; 1 pt discontinued due to PD and 1 due to sinus bradycardia. Five pts received 600 mg/day: 2 DLTs (G4 hypertension and G3 fatigue - pts discontinued) leading to dose reduction of all patients to 500mg/day; 2 pts in C5 and C4, 1 pt discontinued for PD. Two pts just entered the extension cohort at 500 mg. Other toxicities ≥G2 included fatigue, nausea, vomiting, diarrhea, neutropenia, folliculitis and dizziness. PK data showed C Max range (180–487 ng/mL, n = 8), and AUC range (2200–8251 ng/mL*h). Preliminary biomarker data indicated pts had high baseline VEGF (506 ± 203 pg/ml, n=6) and bFGF (220 ± 185 pg/ml, n = 6) levels, which may reflect failure of previous anti-VEGF agents. Induction of plasma FGF23 levels, a pharmacodynamic biomarker of FGFR1 inhibition, was observed in pts from the first 500 mg/day dosing cohort. Preliminary evidence of efficacy is observed with one minor response (-17% at C4), 4 stable disease and 1 dramatic shrinkage/necrosis of some target lesions (lymph node &amp; suprarenal mass). Conclusions: TKI258 500mg/day seems a feasible schedule in heavily pre-treated mRCC patients with some indications of clinical benefit. These preliminary findings will be confirmed in the extension cohort. [Table: see text]
Functional Analysis and Gene Expression Profile of Umbilical Cord Blood Regulatory T Cells.
Authors: Giovanni Fernando Torelli, Roberta Maggio, Nadia Peragine, Sabina Chiaretti, Maria Stefania De Propris, Maria Screnci, Barbarella Lucarelli, Maria Grazia Mascolo, Anna Paola Iori, Gabriella Girelli, Anna Guarini, Robert Foà
Journal: Blood (2009)
Can a conventional schedule of radiation therapy be administered to elderly patients with glioblastoma multiforme?
Authors: S. Manfrida, G. R. D’Agostino, C. Anile, G. Mantini, G. Colicchio, M. A. Gambacorta, F. De Renzi, V. Valentini, D. Smaniotto, M. Balducci
Journal: Journal of Clinical Oncology (2007)

12516 Background: We retrospectively evaluate the tolerance and the efficacy of a conventional schedule of radiotherapy in elderly patients with glioblastoma multiforme (GBM). Methods: Eighty-three consecutive patients affected by glioblastomas were treated between 2001 and 2006. We divided our series in two groups: patients under 65 years (n=52) and patients ≥ 65 years old (n=31). In the elderly group, median age was 68 years (range, 65–80). 17 patients (54,8%) were female, 14 male (45,2%); 20 patients (64,5%) &lt;70 years, 11 patients (35,5%) ≥70 years. Among the younger patients, median age was 51 years (range 25–64), male/female ratio 32/20 (61.5%/38.5%).Twenty-seven out of 31 elderly patients (87,1%) were treated with conformal radiotherapy (CRT, 5940 cGy, 180 cGy/day; CTV2: tumor bed + residual tumor if present + oedema, 3960 cGy; CTV1: tumor bed + residual tumor if present + margins, 1980 cGy). Four out of 31 patients received an intensification dose of xxxx cGy by stereotactic conformal radiotherapy (SRT, 12,9%); among the younger patients, 25/52 were treated with CRT (48,1%) and 27/52 with SRT (51,9%). Concomitant and adjuvant chemotherapy was administered by temozolomide (TMZ).Toxicity was evaluated according to RTOG score. Survival analysis were performed using Kaplan-Meier method and log-rank testing was used for comparison of groups. Results: In the elderly group, neurological acute toxicity was observed in 6/31 patients (19,4%), with grade 3 in two patients. In the under 65 group, 5/52 patients (9,6%) had neurotoxicity (Grade 3 in two patients).This difference was not statistically different.At a median follow-up period of 28 months (range, 3–61), median progression-free survival (PFS) was 11 months in the ≥65 group and 10 months in the under 65 group; median overall survival (OS) was respectively 17 months and 22 months. 1- year survival was respectively 77.6% and 74.5%. Conclusions: In our analysis age did not seem to be a limiting factor in the choice of the therapeutic strategy for patients with glioblastoma multiforme. No significant financial relationships to disclose.
Effect of early postextubation high-flow nasal cannula vs conventional oxygen therapy on hypoxaemia in patients after major abdominal surgery: a French multicentre randomised controlled trial (OPERA)
Authors: Emmanuel Futier, Catherine Paugam-Burtz, Thomas Godet, Linda Khoy-Ear, Sacha Rozencwajg, Jean-Marc Delay, Daniel Verzilli, Jeremie Dupuis, Gerald Chanques, Jean-Etienne Bazin, Jean-Michel Constantin, Bruno Pereira, Samir Jaber
Journal: Intensive Care Medicine (2016)
GW26-e1525 Hydroxysafflor Yellow A Inhibits Angiotensin II-Induced Differentiation of Human Cardiac Fibroblasts Into Myofibroblasts In Vitro Via TGF-B1/Smad3 Signaling Pathway
Authors: Tangting Chen, Huan Lan, Miaoling Li, Xiaorong Zeng
Journal: Journal of the American College of Cardiology (2015)
“Nudging” Deceased Donation Through an Opt-Out System: A Libertarian Approach or Manipulation?
Authors: David Rodrıguez-Arias, Myfanwy Morgan
Journal: The American Journal of Bioethics (2016)

Nudges involve designing social “choice contexts” to promote what “experts” regard as beneficial for individuals and the society, by making the “right” choices easier. The most common form of nudge...
Comparison of Outcomes of Unrelated BM and CB Transplants in Young Adult Leukemia Patients. Updated Results of Japanese Registration Study
Authors: Seitaro Terakura, Yoshiko Atsuta, Nobuhiro Tsukada, Takeshi Kobayashi, Masatsugu Tanaka, Junya Kanda, Kazuteru Ohashi, Takahiro Fukuda, Naoyuki Uchida, Takahashi Satoshi, Tokiko Nagamura-Inoue, Yasuo Morishima, Koichi Miyamura
Journal: Blood (2014)
The Integrin LFA-1 Controls T Follicular Helper Cell Generation and Maintenance
Authors: Alexandre P. Meli, Ghislaine Fontés, Danielle T. Avery, Scott A. Leddon, Mifong Tam, Michael Elliot, Andre Ballesteros-Tato, Jim Miller, Mary M. Stevenson, Deborah J. Fowell, Stuart G. Tangye, Irah L. King
Journal: Immunity (2016)
A dose escalation, pharmacokinetic, and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors
Authors: D. Mahadevan, R. Plummer, M. S. Squires, D. Rensvold, T. Dragovich, J. Adams, V. Lock, D. Smith, D. D. Von Hoff, H. Calvert
Journal: Journal of Clinical Oncology (2008)

3533 Background: AT7519M is a structure-based rationally designed Nan molar small molecular Cyclin-dependent Kinase (CDK) inhibitor (CDK 1, 2, 4, 5). It has been evaluated in a first in human trial for primary endpoints of safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD). Methods: AT7519 was administered in a dose escalation format according to observed toxicity using 3–6 evaluable patients per cohort. Eligible patients had refractory solid tumors with adequate bone marrow, hepatic and renal function. AT7519M was administered as a 1-hour intravenous infusion on days 1 through 5 of a 21 day cycle (starting dose 1.8 mg/m2/day). Patients were monitored closely for hematologic, non-hematologic and symptoms of dose limiting toxicities (DLT). Pre- and post-treatment PK and PD (serum and skin biopsies) were obtained for each patient. Results: At dose level 6 (34mg/m2/day) DLT was reached due to fatigue (grade 4), mucositis (grade 3) and neutropenia (grade 4) that occurred on day 2 but recovered by day 4 (grade 2). Several patients treated at the 28.8mg/m2/day dose experienced nausea/vomiting, fatigue and reversible thrombocytopenia (grade 2). Dose dependent QTc-prolongation was observed, which manifested as a fatal SAE in one patient at dose level 6. Four patients have received treatment for at least six months including one partial response of 80% (lung adenocarcinoma). The PK profile of AT7519M revealed only modest inter-patient variation (<3-fold) with exposure increasing linearly with dose. Significant changes in PCNA levels in skin biopsies were observed in a number of patients across all dose levels, perhaps reflecting a direct effect of CDK inhibition on this cell cycle marker. All samples processed for cohort 5 exhibited a reduction in PCNA staining but also an increase in the apoptosis marker cleaved cytokeratin in serum samples. A reduction in Ki-67 expression was also observed in 66% of samples at this dose level. Conclusions: AT7519M shows evidence of clinical and PD activity but the appearance of QTc prolongation precludes further exploration of this dose schedule. Alternative administration schedules are being investigated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Astex Therapeutics Ltd Astex Pharmaceuticals, Inc.
GW26-e2184 The short- and long-term effects of ischemic postconditioning in STEMI patients:a meta-analysis
Authors: Jing Gao, Fen Liu, Yingying Zheng, Bangdang Chen, Qingjie Chen, Hui Zhai, Junyi Luo, Yitong Ma
Journal: Journal of the American College of Cardiology (2015)
Final Results of a Phase II Trial of the Novel Oral Akt Inhibitor Perifosine in Relapsed and/or Refractory Waldenstrom Macroglobulinemia (WM).
Authors: Irene M. Ghobrial, Xavier Leleu, Nancy Rubin, Wanling Xie, Fangxin Hong, Stacey Chuma, Renee Leduc, Marybeth Nelson, Kelly O’Connor, Amy Sam, Brianna Harris, Diane Warren, Peter Sportelli, Steven P. Treon, Edie Weller, Kenneth C. Anderson, Paul G. Richardson
Journal: Blood (2008)
Trends in the Incidence of Parkinson Disease
Authors: Antonella Macerollo, Jui-Cheng Chen
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Salvage radiotherapy (SR) in patients (pts) with prostate cancer (PC) and rising prostate specific antigen (PSA) after radical prostatectomy (RP): Results from a single-center study
Authors: T. Wiegel, G. Lohm, S. Hoecht, D. Bottke, K. Neumann, W. Hinkelbein
Journal: Journal of Clinical Oncology (2006)

14556 Background: In pts with PC and biochemical relapse after RP SR is well established. However, the significance of pre-radiotherapeutic variables for guidance of treatment decisions is less clear. We analyzed prognostic factors in a large cohort of pts treated with SR after RP. Methods: 163 pts with PC and persisting PSA-levels (n = 60) or PSA-elevation following undetectable PSA-levels (n = 103) after RP received three-dimensional conformal radiotherapy (RT). None received androgen depriving therapy between prostatectomy and start of RT. We evaluated the impact of age, stage, surgical margin status (SMS), Gleason score and PSA-kinetics by survival and regression analysis. Biochemical progression (BP) was defined as PSA-increases at 3 consecutive time points after the post RT nadir. To detect thresholds for significant prognostic variables, we calculated receiver operating characteristic (ROC) curves. Results: Medians for pre-RT variables were: 11.97 ng/ml for pre-prostatectomy PSA (Pre-OP PSA), 5.4 months for PSA doubling time (PSADT) and 0.339 ng/ml for pre-radiotherapy PSA (Pre-RT PSA). Probability for a projected 4-year PFS was 50% (median follow-up: 33.5 months). Logistic regression revealed a significant impact on the probability of BP for Pre-OP PSA (p = 0.036), PSADT (p = 0.024) and tumor-stage (p = 0.043), whereas Pre-RT PSA and SMS had a significant impact on achievement of undetectable post-RT PSA (p = 0.009 and p = 0.028 respectively). Analysis of ROC-curves for Pre-OP PSA, Pre-RT PSA, PSADT revealed an area under the curve not exceeding 0.704 for any of these parameters. Conclusions: By analyzing ROC-curves we could not detect clear thresholds for PSA kinetic variables. In accordance with recently published data we found similar independent significant variables predicting a therapeutic success. However, we observed a lower median Pre-RT PSA and a higher probability of PFS in our patient cohort. This suggests, that early radiotherapeutic intervention improves PFS. No significant financial relationships to disclose.
Outcomes of Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) Vs. Classical Hodgkin Lymphoma (cHL) at Princess Margaret Cancer Centre
Authors: Jeffery Ames, Manjula Maganti, Bethany E Monteith, David C. Hodgson, Vishal Kukreti, John G. Kuruvilla, Anca Prica, Richard Tsang, Alex Sun, Mary Gospodarowicz, Melania Pintilie, Michael Crump
Journal: Blood (2015)
Fitness Trade-Offs Lead to Suppressor Tolerance in Yeast
Authors: Jing Hou, Joseph Schacherer
Journal: Molecular Biology and Evolution (2016)

Genetic variation among individuals within a population provides the raw material for phenotypic diversity upon which natural selection operates. Some given variants can act on multiple standing genomic variations simultaneously and release previously inaccessible phenotypes, leading to increased adaptive potential upon challenging environments. Previously, we identified such a variant related to a tRNA nonsense suppressor in yeast. When introduced into other genetic backgrounds, the suppressor led to an increased population phenotypic variance on various culture conditions, conferring background and environment specific selective advantages. Nonetheless, most isolates are intolerant to the suppressor on rich media due to a severe fitness cost. Here, we found that the tolerance to suppressor is related to a surprising level of fitness outburst, showing a trade-off effect to accommodate the cost of carrying the suppressor. To dissect the genetic basis of such trade-offs, we crossed strains with contrasting tolerance levels on rich media, and analyzed the fitness distribution patterns in the offspring. Combining quantitative tetrad analysis and bulk segregant analysis, we identified two genes, namely MKT1 and RGA1, involved in suppressor tolerance. We showed that alleles from the tolerant parent for both genes conferred a significant gain of fitness, which increased the suppressor tolerance. Our results present a detailed dissection of suppressor tolerance in yeast and provide insights into the molecular basis of trade-offs between fitness and evolutionary potential.
Serum Ferritin Level As a Prognostic Factor for Patients with Extranodal NK/T-Cell Lymphoma, Nasal Type.
Authors: Etsuko Yamazaki, Naoto Tomita, Satoshi Koyama, Kumiko Kishimoto, Eriko Ogusa, Yoshimi Ishii, Hiroyuki Takahashi, Kazuho Miyashita, Shiro Matsuura, Takayoshi Tachibana, Hirotaka Takasaki, Sachiya Takemura, Katsumichi Fujimaki, Rika Sakai, Shin Fujisawa, Yoshiaki Ishigatsubo
Journal: Blood (2012)
Rifaximin has no effect on hemodynamics in decompensated cirrhosis: A randomized, double‐blind, placebo‐controlled trial
Authors: Nina Kimer, Julie Steen Pedersen, Troels Malte Busk, Lise Lotte Gluud, Lise Hobolth, Aleksander Krag, Søren Møller, Flemming Bendtsen
Journal: Hepatology (2016)

Decompensated cirrhosis is characterized by disturbed systemic and splanchnic hemodynamics. Bacterial translocation from the gut is considered the key driver in this process. Intestinal decontamination with rifaximin may improve hemodynamics. This double-blind, randomized, controlled trial (clinicaltrials.gov, NCT01769040) investigates the effects of rifaximin on hemodynamics, renal function, and vasoactive hormones. We randomized 54 stable outpatients with cirrhosis and ascites to rifaximin 550 mg twice a day (n = 36) or placebo twice a day (n = 18). Forty-five patients were male, mean age 56 years (±8.4), average Child score 8.3 (±1.3), and Model for End-Stage Liver Disease score 11.7 (±3.9). Measurements of hepatic venous pressure gradient, cardiac output, and systemic vascular resistance were made at baseline and after 4 weeks. The glomerular filtration rate and plasma renin, noradrenaline, lipopolysaccharide binding protein, troponin T, and brain natriuretic peptide levels were measured. Rifaximin had no effect on hepatic venous pressure gradient, mean 16.8 ± 3.8 mm Hg at baseline versus 16.6 ± 5.3 mm Hg at follow-up, compared to the placebo, mean 16.4 ± 4 mm Hg at baseline versus 16.3 ± 4.4 mm Hg at follow-up, P = 0.94. No effect was found on cardiac output, mean 6.9 ± 1.7 L/min at baseline versus 6.9 ± 2.3 L/min at follow-up, compared to placebo, mean 6.6 ± 1.9 L/min at baseline compared to 6.5 ±2.1 L/min at follow-up, P = 0.66. No effects on the glomerular filtration rate, P = 0.14, or vasoactive hormones were found. Subgroup analyses on patients with increased lipopolysaccharide binding protein and systemic vascular resistance below the mean (1,011 dynes × s/cm5 ) revealed no effect of rifaximin.Four weeks of treatment with rifaximin did not reduce the hepatic venous pressure gradient or improve systemic hemodynamics in patients with cirrhosis and ascites; rifaximin did not affect glomerular filtration rate or levels of vasoactive hormones. (Hepatology 2017;65:592-603).