tbuckley/cabot-search huggingface dataset:
Epstein Barr Virus (EBV) Reactivation After Reduced Intensity Conditioning (RIC) Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Zinaida Peric, Xavier Cahu, Patrice Chevallier, Eolia Brissot, Florent Malard, Thierry Guillaume, Jacques Delaunay, Sameh Ayari, Viviane Dubruille, Steven Le Gouill, Beatrice Mahe, Thomas Gastinne, Nicolas Blin, Beatrice Saulquin, Jean-Luc Harrouseau, Philippe Moreau, Noel Milpied, Marianne Coste-Burel, Berthe-Marie Imbert-Marcille, Mohamad Mohty
Journal: Blood (2010)
Predictive biomarkers in circulating tumor cells (CTC) from patients with castration-resistant prostate cancer (CRPC) through genomic analysis.
Authors: Daniel Costin Danila, Aseem Anand, Jianchao Yao, Magdalena Gierszewska, Melissa Kramer, Stephanie Muller, Martin Fleisher, William R. McCombie, Howard I. Scher
Journal: Journal of Clinical Oncology (2012)

4562 Background: Mutations in the ligand binding domain of androgen receptor (AR) in prostate cancer cells may alter their sensitivity to treatment with specific antiandrogens. To predict for tumor sensitivity to treatment with novel AR targeted therapies, we explored the frequency of mutation detection and copy number alteration in CTC isolated from patients with CRPC enrolled on trials with these targeted therapies. Methods: We used fluorescence-activated cell sorting (FACS) methodology to enrich EpCAM + , CD45 - , DAPI - cells. For mutation detection and genomic copy number alteration in CTC in low number of cancer cells found in clinical samples, we optimized next-gen deep sequencing by Illumina. Results: In patients with progressive CRPC , &gt;10 or &gt;50 EpCAM + events (EPE) were isolated by FACS in 88% or 58% of patients, in whom 32% and 10% had unfavorable (&gt;5 cells/7.5 ml) CTC counts using CellSearch. EPE, expressing prostate-specific mRNAs, provide sufficient high quality DNA for genomic sequencing and copy number analysis. Adequate coverage was obtained from as few 50 EPE, with a recovery rate of 89% from FACS sorted samples. The detection threshold of a mutation was established at 1:4 alleles. To further expand genomic profiling in CTC, we optimized Nimblegen exome mutation detection by deep sequencing on HiSeq PE101. Our initial analysis established the polymorphism frequency detection thresholds in heterogeneous cell populations, and confirmed the sequencing coverage. Somatic missense mutations in AR, APC and TP53 found in CTC but not in paired WBC were confirmed by Sanger sequencing. In parallel, copy number alterations in CTC are studied. Conclusions: Somatic mutations detected in CTC isolated from patients with CRPC can serve as predictive markers of tumor sensitivity to targeted therapies. We established standard operating procedures for specimen processing, and confirmed the sequencing coverage and polymorphism detection thresholds in heterogeneous cell population. Currently we are proceeding to clinical samples to study the associations between specific molecular alterations in CTC as predictive markers of sensitivity and clinical outcomes.
Death In Complete Remission Among Patients with Acute Myeloid Leukemia: A Preventable Problem?
Authors: Gloria Mattiuzzi, Hagop Kantarjian, Farhad Ravandi, Guillermo Garcia-Manero, Gautam Borthakur, Stefan Faderl, Tapan Kadia, Zeev Estrov, Gloria Iliescu, Sherry A. Pierce, Jorge E. Cortes
Journal: Blood (2010)
Recognition of Myeloma by MAGE-A3 Specific Cytotoxic T Lymphocytes Induced by Treatment with Azacitidine and MGCD0103
Authors: Amberly Moreno-Bost, Susann Szmania, Katie Stone, Jumei Shi, Tarun K. Garg, John Shaughnessy, Bart Barlogie, Hugh Grant Prentice, Frits van Rhee
Journal: Blood (2008)
Azacitidine Low-Dose Schedule In Low-Risk Myelodysplastic Syndromes. Preliminary Results of a Multicenter Phase II Study
Authors: Carla Filì, Carlo Finelli, Marco Gobbi, Giovanni Martinelli, Ilaria Iacobucci, Emanuela Ottaviani, Lucio Cocco, Matilde Follo, Anna Candoni, Erika Simeone, Maurizio Miglino, Francesco Lauria, Monica Bocchia, Marzia Defina, Cristina Clissa, Francesco Lanza, Antonio Curti, Stefania Paolini, PierAngelo Spedini, Cristina Skert, Cesare Bergonzi, Michele Malagola, Annalisa Peli, Alessandro Turra, Federica Cattina, Chiara Colombi, Domenico Russo
Journal: Blood (2010)
Prevalence of Extracranial Internal Carotid Arteriopathy in Stroke-Free SCA-Children: A New Risk Factor for Silent Strokes
Authors: Suzanne Verlhac, Malika Benkerrou, Stephane Balandra, Florence Kasbi, Ahmed Kheniche, Isabelle Cussenot, Ghislaine Ithier, Cécile Arnaud, Florence Missud, Annie Kamdem, Laurent Holvoet, Clément Tassel, Manuela Vasile, Francoise Bernaudin
Journal: Blood (2012)
Reduced Intensity Conditioning Is Safe and Effective for Transplantation of Patients with Shwachman Diamond Syndrome.
Authors: D. Bhatla, Stella M. Davies, R.E. Harris, M. Crockett, L. Shoultz, S. Shenoy, J. Bleesing, M. Hansen, S. Jodele, M. Jordan, A.H. Filipovich, Parinda A. Mehta
Journal: Blood (2007)
Autologous HSCT for Ph-Positive Adult Acute Lymphoblastic Leukemia: A Curative Option in the Era of Tyrosine Kinase Inhibitors? an Analysis From the Acute Leukemia Working Party of the EBMT
Authors: Sebastian Giebel, Myriam Labopin, Norbert Claude Gorin, Denis Caillot, Thibaut Leguay, Nicolaas Schaap, Mauricette Michallet, Gerard Socie, Mohamad Mohty
Journal: Blood (2012)
Treatment of Philadelphia-Positive Acute Lymphocytic Leukemia (Ph+ ALL) in the Elderly with Imatinib Mesylate (STI571) and Chemotherapy. an Interim Analysis of the GRAALL AFR09 Trial.
Authors: Andre Delannoy, Véronique Lhéritier, Xavier Thomas, Sylvie Castaigne, Hassan Farhat, Françoise Rigal-Huguet, Emmanuel Raffoux, Remy Gressin, Ollivier Legrand, Francis Witz, Viviane Dubruille, Pascal Turlure, Xavier Troussard, Martine Delain, Chrystele Bilhou-Nabera, Elizabeth Macintyre, Eric Delabesse, Jean-Paul Vernant, Hervé Dombret, Denis Fière
Journal: Blood (2004)
Erratum: EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia (Nature Neuroscience (2013) 16 (1745-1753 ))
Authors: Jiali Li, Ronald Hart, Elyse Mallimo, Mavis Swerdel, Alexander Kusnecov, Karl Herrup
Journal: Nature Neuroscience (2014)
MPTH-20ALTERATIONS IN THE IRON REGULATORY GENE SIGNATURE ARE ASSOCIATED WITH DECREASED SURVIVAL IN LOW GRADE GLIOMA
Authors: Cody Weston, Joseph Klobusicky, James Connor, Steven Toms, Nicholas Marko
Journal: Neuro-Oncology (2015)

BACKGROUND: Iron is a tightly regulated micronutrient that is necessary for cell division in normal tissue. Previous studies have established that a signature of iron regulatory genes can predict survival in breast tumors. Recent evidence suggests that dysregulation of iron regulatory proteins may play a role in brain cancer pathophysiology. METHODS: We use public data from The Cancer Genome Atlas (TCGA) to study the association between survival and expression levels of 61 genes coding for iron regulatory proteins in patients with low grade brain gliomas (LGG). Specifically, we utilized the Coxnet package to perform feature selection using elastic net regularization and compared this model to the 1-Nearest Neighbor algorithm and random selection. To prevent overfitting in our Coxnet model, 10-fold cross-validation was implemented. RESULTS: Using feature reduction strategies we identified a novel, optimized subset of 10 iron regulatory genes (STEAP3, HFE, TMPRSS6, SFXN1, TFRC, SLC25A37, ALAD, SLC25A28, TFR2, and HIF1AN) whose differential expression defines two phenotypic groups with differential survival of 62.9 months (94.5 vs 31.6 months, p< 10−6). The correlation between predicted relative risks and survival on the Coxnet model was -0.27, compared to a 0.30 correlation for the 1NN algorithm performed on all 61 iron regulatory genes. Therefore, feature selection eliminated 51 of the candidate genes with only a slight reduction in accuracy. CONCLUSIONS: This work indicates that iron metabolism affects tumor progression in multiple types, promising broader applicability for therapeutic and predictive strategies focusing on iron metabolism. The genes identified in this study are risk factors in other cancers, suggesting that targeting these genes could provide therapeutic and prognostic tools with utility beyond low grade glioma.
Thalidomide Alone and in Combination with Fludarabine Exerts Distinct Molecular and Antileukemic Effects in B-Cell Chronic Lymphocytic Leukemia.
Authors: Krzysztof Giannopoulos, Anna Dmoszynska, Malgorzata Kowal, Ewa Wasik-Szczepanek, Paulina Wlasiuk, Agnieszka Bojarska-Junak, Jacek Rolinski, Stephan Stilgenbauer, Lars Bullinger
Journal: Blood (2007)
Elevations of Tumor Necrosis Factor-Receptor-1 at Day 7 and Acute Graft-Versus-Host Disease After Allogeneic Hematopietic Cell Transplantation with Nonmyeloablative Conditioning.
Authors: Stéphanie Humblet-Baron, Evelyne Willems, Olivier Dengis, Laurence Seidel, Yves Beguin, Frederic Baron
Journal: Blood (2009)
First-in-human, multicenter, dose-escalation, phase I study of the investigational drug TAK-733, an oral MEK inhibitor, in patients (pts) with advanced nonhematologic malignancies and melanoma.
Authors: J. A. Sosman, A. A. Adjei, P. LoRusso, S. A. Michael, G. K. Dy, A. Bowditch, B. Chmielowski, S. Lee, R. M. Walker, S. Faucette, E. S. Izmailova, V. Bozon, A. Ribas
Journal: Journal of Clinical Oncology (2011)

TPS145 Background: The Ras/Raf/MEK/ERK cascade is frequently activated in human cancers; MEK inhibition is an attractive therapeutic target for preventing tumor growth and angiogenesis. The investigational drug TAK-733 is a novel, orally available, selective, non-ATP competitive, allosteric inhibitor of MEK1/2. It has shown in-vivo antitumor activity against multiple human tumor xenograft models, particularly tumors with activating BRAF mutations or RAS mutations, mediated through induction of caspase-driven apoptosis. This study is the first clinical evaluation of TAK-733. Methods: The primary objectives of this phase I study are to evaluate the safety profile, characterize the pharmacokinetics (PK), and determine the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of oral TAK-733. Secondary objectives include evaluating the antitumor activity of TAK-733, including in melanoma pts with BRAF V600E mutation or wild-type. Exploratory objectives include the investigation of potential pharmacodynamic effects in peripheral blood (pERK), and assessment of any associations between antitumor activity and N/KRAS and BRAF mutations that may predict response to treatment. The study is composed of two stages. In the dose-escalation stage, approximately 30 pts with advanced nonhematologic malignancies will receive TAK-733 QD on days 1–21 of 28-day cycles from a starting dose of 0.2 mg; dose escalation will proceed via a single pt-cohort design (100% increments) and then a modified 3+3 design (40% increments) based on DLTs in cycle 1. Dosing of TAK-733 will then be investigated at or below the MTD, until the RP2D is determined. In the expansion stage, approximately 30 MEK/BRAF inhibitor-naïve pts with advanced unresectable melanoma, with either BRAF V600E or BRAF-wild type tumors, will be treated at the RP2D. For both stages, pts aged ≥18 years, with ECOG PS 0–2 and radiographically or clinically evaluable tumors are eligible. To date, 22 pts have been enrolled to the dose-escalation stage. This study is registered with ClinicalTrials.gov (NCT00948467).
The Induction of Inhibitory Pathways in Dendritic Cells May Hamper the Efficient Activation of Anti-Leukemia T Cells within Chemotherapy-Induced Immunogenic Cell Death
Authors: Darina Ocadlikova, Mariangela Lecciso, Elisa Orioli, Elena De Marchi, Sabina Sangaletti, Sara Trabanelli, Camilla Jandus, Valentina Salvestrini, Pedro Romero, Mario Paolo Colombo, Francesco Di Virgilio, Roberto M Lemoli, Michele Cavo, Elena Adinolfi, Antonio Curti
Journal: Blood (2015)
When Should Everolimus Be Administered in the Natural History of Pancreatic Neuroendocrine Tumors?
Authors: Vito Amoroso, Nicola Fazio, Alessandra Mosca, Elisa Roca, Francesca Spada, Chiara Foroni, Giorgio Maria Agazzi, Alfredo Berruti
Journal: Journal of Clinical Oncology (2017)
Unrelated Single Cord Blood Transplant Supported by Co-Infusion of a Low Number of Mobilized Peripheral Blood Highly Purified CD34+ Cells from a Third Party Donor after Low Toxicity Myeloablative Conditioning. a Strategy That Makes Cord Blood Transplant Feasible for Most Patients. (An “Allostem” Study).
Authors: Manuel N. Fernandez, Carmen Regidor, Rafael Cabrera, Elena Magro, Rafael Fores, Guiomar Bautista, Jorge Gayoso, Elena Ruiz, Belen Navaro, Santiago Gil, Isabel Sanjuan, Jose A. Garcia-Marco
Journal: Blood (2004)
Promoting End-of-Life Discussions in Advanced Cancer: Effects of Patient Coaching and Question Prompt Lists
Authors: Rachel A. Rodenbach, Kim Brandes, Kevin Fiscella, Richard L. Kravitz, Phyllis N. Butow, Adam Walczak, Paul R. Duberstein, Peter Sullivan, Beth Hoh, Guibo Xing, Sandy Plumb, Ronald M. Epstein
Journal: Journal of Clinical Oncology (2017)

Purpose To build on results of a cluster randomized controlled trial (RCT) of a combined patient-oncologist intervention to improve communication in advanced cancer, we conducted a post hoc analysis of the patient intervention component, a previsit patient coaching session that used a question prompt list (QPL). We hypothesized that intervention-group participants would bring up more QPL-related topics, particularly prognosis-related topics, during the subsequent oncologist visit. Patients and Methods This cluster RCT with 170 patients who had advanced nonhematologic cancer (and their caregivers) recruited from practices of 24 participating oncologists in western New York. Intervention-group oncologists (n = 12) received individualized communication training; up to 10 of their patients (n = 84) received a previsit individualized communication coaching session that incorporated a QPL. Control-group oncologists (n = 12) and patients (n = 86) received no interventions. Topics of interest identified by patients during the coaching session were summarized from coaching notes; one office visit after the coaching session was audio recorded, transcribed, and analyzed by using linear regression modeling for group differences. Results Compared with controls, more than twice as many intervention-group participants brought up QPL-related topics during their office visits (70.2% v 32.6%; P < .001). Patients in the intervention group were nearly three times more likely to ask about prognosis (16.7% v 5.8%; P =.03). Of 262 topics of interest identified during coaching, 158 (60.3%) were QPL related; 20 (12.7%) addressed prognosis. Overall, patients in the intervention group brought up 82.4% of topics of interest during the office visit. Conclusion A combined coaching and QPL intervention was effective to help patients with advanced cancer and their caregivers identify and bring up topics of concern, including prognosis, during their subsequent oncologist visits. Considering that most patients are misinformed about prognosis, more intensive steps are needed to better promote such discussions.
A novel risk stratification to predict local-regional failures in urothelial carcinoma of the bladder after radical cystectomy.
Authors: Brian Christopher Baumann, Thomas J. Guzzo, Jiwei He, Stephen Michael Keefe, Kai Tucker, Justin E. Bekelman, Wei-Ting Hwang, David J. Vaughn, S. Bruce Malkowicz, John Paul Christodouleas
Journal: Journal of Clinical Oncology (2012)

262 Background: Invasive urothelial bladder carcinoma is typically treated with radical cystectomy (RC) plus pelvic lymph node dissection (PLND) +/− chemotherapy. Local-regional failures (LF) following cystectomy are a significant problem. Adjuvant radiation therapy (RT) could potentially reduce LF but currently has no defined role because of previously reported morbidity. Modern RT techniques with improved normal tissue sparing have rekindled interest in adjuvant RT. Stratifying patients by differing LF risk could facilitate selection for adjuvant RT. Methods: From 1990–2008, 442 patients with urothelial bladder carcinoma were prospectively followed at the University of Pennsylvania after RC+PLND +/− chemotherapy with routine pelvic CT or MRI. Univariate and multivariate competing risk analyses identified subgroups with differing LF risk. Results: On univariate analysis, stage pT3-4, total nodes removed (&lt;10 vs. ≥10), positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology were significant predictors of LF, while use of chemotherapy, number of positive nodes, surgical diversion type, age, gender, race, smoking history and BMI were not. Node density was a marginal predictor of LF. On multivariate analysis, only stage ≥pT3-4 and nodes removed (&lt;10) were significant independent predictors of LF with hazard ratios of 3.17 and 2.37 respectively (p&lt;0.01). Analysis identified 3 patient subgroups with significantly different LF risk: low-risk (pT0-2), intermediate-risk (pT3-4, ≥10 nodes), and high-risk (pT3-4, &lt;10 nodes) with 5-year LF rates of 8%, 23%, and 42% (p &lt;0.01). Conclusions: This study of local-regional recurrence risk factors after RC is based on the largest reported, prospectively maintained patient database with routine follow-up pelvic CT surveillance. LF after RC varies significantly among different subgroups. This risk stratification model could facilitate selection for future adjuvant radiotherapy trials.
Abstract 3382: Three-Dimensional Color Doppler Echocardiography for Direct Measurement of Mitral Regurgitation Vena Contracta Area: A Clinical Experience
Authors: Stephen H Little, Rahul Kumar, Bahar Pirat, Marti L McCulloch, William A Zoghbi
Journal: Circulation (2007)

Introduction: 3D color Doppler allows a direct measurement of Vena Contracta (VC) area in patients with mitral regurgitation (MR), without the need for geometric assumptions. Hypothesis: 3D color Doppler VC area provides a more accurate assessment of MR severity than the conventional 2D color Doppler VC diameter. Methods: Patients with ≥ mild MR underwent 2D and 3D color Doppler and a quantitative echo-Doppler study. 2D VC diameter was measured from a zoomed parasternal long-axis view. 3D VC area was acquired using real-time 3D (Philips) and measured off-line (TomTec). MR severity was assessed both quantitatively, as effective regurgitant orifice area from pulsed Doppler [EROA = (mitral stroke volume - aortic stroke volume)/MR time velocity integral], and semi-quantitatively as recommended by the American Society of Echocardiography. Results: 61 patients (65 ± 15 years) were studied. MR severity was mild in 25%, moderate in 36%, and moderate to severe or severe in 39%. Mitral valve pathology was prolapse in 33%, restricted closure in 44% and annular calcification in 7%. Regurgitant MR jet was eccentric in 49% of patients. For all patients, 3D VC area correlated significantly with EROA, better than 2D VC diameter (figure ). The advantage of 3D VC area over 2D VC diameter was more pronounced in eccentric jets (r=0.76, p&lt; 0.001 vs. r=0.5, p =0.006, respectively) and in moderate to severe or severe MR (r=0.65, p&lt;0.001 vs. r =0.13, p=0.54, respectively). Conclusions : Measurement of VC area is feasible with real-time 3D and provides a simple parameter that accurately reflects MR severity, particularly in eccentric and clinically significant MR where geometric assumptions may be challenging.
Determining the impact of the U.S. mammography screening guidelines on patient survival in a predominantly African American population treated in a public hospital.
Authors: I. Habtes, C. Raskind-Hood, K. Adams, E. R. Becker, C. D'Orsi, G. Birdsong, K. Gundry, R. O'Regan, S. G. A. Gabram
Journal: Journal of Clinical Oncology (2011)

1573 Background: In November 2009, the U.S. Preventive Service Task Force (USPSTF) published an updated set of breast cancer screening guidelines. This was a change from the 2002 recommendation and represents a marked divergence from the American Cancer Society (ACS) guidelines. In this study we compared the effect of the revised USPSTF with the ACS guidelines on patient stage and survival. Methods: A cross-sectional study of 84 patients (pts) diagnosed with stage I-III breast cancer was performed for 2008 in a public hospital. We excluded stages 0 and IV pts due to restriction of the staging model. Using known tumor volume doubling times, we estimated prospective and retrospective tumor sizes based on ACS and USPSTF guidelines. Stages were assigned and pt survival rates were estimated based on prognostic stages. Results: Study pts averaged 55 years old and 85% of pts were African American (AA). Almost half (49%) had Medicaid coverage, 23% had Medicare coverage, 19% were self-pay, and 8% had private insurance. The actual stage and predicted stages are reported in the table and shifts in stages are statistically significant. Conclusions: Among the cohort of women in our study a large stage migration was predicted
Activation of NF-kB by ionizing radiation: A role for nitric oxide
Authors: Vasily Yakovlev, Christopher Rabender, Ross B. Mikkelsen
Journal: Cancer Research (2005)

1658  A constitutive, Ca2+ dependent nitric oxide synthase (NOS) is activated within minutes of exposing epithelial cells to therapeutic doses of ionizing radiation (IR). One consequence is the transient generation of peroxynitrite (ONOO) as determined by protein Tyr nitration (Leach et al, JBC 277, 15400, 2002). Previously we also showed that IR stimulated the DNA-binding activity of transcription factor NFkB, a principal regulator of the cellular response to the different kinds of stress. NFkB DNA binding activity measured by gel shift assay as well as promoter activity determined with a luciferase reporter construct were blocked by either pharmacological or genetic inhibition of NOS. Furthermore, IR stimulated the Tyr nitration of IkB. Herein we demonstrate that Tyr-nitration of IκB is necessary for radiation-induced activation of NFκB. CHO cell lysates were treated with nitrated 100 to 400 μM ONOO. The amount of IkBa free and in complex with NF-kB was determined by two consecutive immunoprecipitations with anti-NFkB and anti-IkBa. After SDS-PAGE fractionation Western blots were probed with anti-IkBa and anti-nitroTyr. Nitration of cell-lysate by ONOO resulted in a dose dependent decrease in complex formation between NFkB and IkBa. Probing with anti-nitroTyr revealed Tyr-nitration of the free form of IkBa only. To determine which Tyr(s) is nitrated in IkBa, we constructed individual mutants with each Tyr converted to Phe. Cells were transfected with wild type and mutant types of IkBa. 48 hours after transfection cells were irradiated (5 Gy) and anti-nitroTyr immunoprecipitates were prepared by standard procedures. After SDS-PAGE fractionation Western blots were probed with anti-IkBa. Absence of nitration was shown for the 195-Tyr-to-Phe mutant. Tyr-195 is found between the two helices that compose the 4th ankyrin repeat of IkBa. The fingers connecting ankyrin repeats 3, 4 and 5 of IκBα are at the interface of the NFκB dimer. Mass spectroscopic studies are in progress to confirm that this site is nitrated after radiation treatment.
Rituximab, Fludarabine, Mitoxantrone, and Dexamethasone (R-FND) for Relapsed Indolent Lymphomas (RIL).
Authors: F.B. Hagemeister, P. McLaughlin, L. Fayad, F. Samaniego, N. Dang, A. Goy, J. Romaguera, B. Pro, V. Beasley, F. Cabanillas, M. Rodriguez
Journal: Blood (2005)