tbuckley/cabot-search huggingface dataset:
Effect of prior hypomethylating agent (HMA) use on clinical outcome of patients (Pts) with secondary acute myeloid leukemia (sAML) arising from myelodysplastic syndrome (MDS) when treated with standard induction chemotherapy (7+3).
Authors: Salih Subari, Firas Baidoun, Muhanad Hreh, Mrinal M. Patnaik, Shahrukh Hashmi, Michelle A. Elliott, William J. Hogan, Mark Robert Litzow, Aref Al-Kali
Journal: Journal of Clinical Oncology (2015)

e18041 Background: Pts with sAML arising from a prior MDS have poor prognosis. Anthracycline plus cytarabine (7+3) is a standard treatment option for pts who are fit for intensive therapy. However, clinical outcome data for pts who were exposed to prior HMA for MDS is unknown. We aim to study the clinical outcome of 7+3 on pts with sAML arising from MDS. Methods: A retrospective single institution study chart review of cases with sAML arising from a prior MDS at Mayo Clinic between 1993- 2014 was done. Pts treated with 7+3 for their MDS or HMA for sAML were excluded. Appropriate IRB approval was obtained. Comparison between groups medians was done using Wilcoxon test, while survival estimates were calculated using Kaplan-Meier curves using JMP V10. Results: Out of 828 pts, 96 (11.6%) had sAML. Median age was 69 years, with 61 (64%) pts being males. Median white blood cell (WBC) was 3.2 x109, Hemoglobin (Hg) 9.2 g/dL, platelet (PLT) 42 x109, peripheral blood (PB) blasts 10%, bone marrow (BM) blasts 30%. Cytogenetics were intermediate (Int) in 49 pts (56%) and poor in 38 pts (44%). FLT3 was mutated in 2/14 (14%) pts. Median OS was 132 days with 1 year-OS of 21%. Median OS was longer in Int- vs poor-risk (6 vs 2 months, p = 0.0003). Out of 96 sAML pts, 22 (23%) were treated with 7+3. Median age was 61.5, with median WBC 3.7 x109, Hg 9 g/dL, PLT 57 x109, PB blasts 8%, BM blasts 32%. Cytogenetics were Int in 13 (59%) and poor in 9 (41%) pts. Median OS was 294 days. Responses were complete response (CR) in 5 (23%), CR with incomplete recovery (CRi) in 8 (36%), partial response (PR) in 2 (9%) pts. CR/CRi was 59%. HMA were given for MDS in 6 (28%) pts. When evaluating prior HMT group, the CR/CRi was 50% for those with prior HMT exposure and 63% for those without HMT exposure (p = 0.6). Median OS was 418 days for prior HMT exposure vs 294 days for no prior HMT (p = 0.9). Conclusions: The outcome of sAML pts who were treated with 7+3 continues to be poor with mOS of 10 months. No statistical significant difference was found between response rates and mOS of prior HMT exposure and no prior HMT exposure groups. Additional larger studies are needed to confirm our results.
Melanoma-associated leukoderma and vitiligo cannot be differentiated based on blinded assessment by experts in the field
Authors: Janny E. Lommerts, Hansje-Eva Teulings, Khaled Ezzedine, Nanja van Geel, Anke Hartmann, Reinhart Speeckaert, Phyllis I. Spuls, Albert Wolkerstorfer, Rosalie M. Luiten, Marcel W. Bekkenk
Journal: Journal of the American Academy of Dermatology (2016)
Activity of SYK and PLCγ2 Predict Apoptotic Response of Chronic Lymphocytic Leukemia Cells to SRC Tyrosine Kinase Inhibitor Dasatinib.
Authors: Y. Lynn Wang, Zibo Song, Pin Lu, Richard R Furman, John P. Leonard, Peter Martin, Lauren Tyrell, Francis Y. Lee, Daniel M. Knowles, Morton Coleman
Journal: Blood (2009)
Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer
Authors: Qiaoyi Liang, Jonathan Chiu, Yingxuan Chen, Yanqin Huang, Akira Higashimori, Jingyuan Fang, Hassan Brim, Hassan Ashktorab, Siew Chien Ng, Simon Siu Man Ng, Shu Zheng, Francis Ka Leung Chan, Joseph Jao Yiu Sung, Jun Yu
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Gut microbiota have been implicated in the development of colorectal cancer. We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for colorectal cancer diagnosis. Experimental Design: Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two independent Asian cohorts were included. Probe-based duplex quantitative PCR (qPCR) assays were established for the quantification of bacterial marker candidates. Results: Candidates identified by metagenome sequencing, including Fusobacterium nucleatum (Fn), Bacteroides clarus (Bc), Roseburia intestinalis (Ri), Clostridium hathewayi (Ch), and one undefined species (labeled as m7), were examined in fecal samples of 203 colorectal cancer patients and 236 healthy controls by duplex-qPCR. Strong positive correlations were demonstrated between the quantification of each candidate by our qPCR assays and metagenomics approach (r = 0.801–0.934, all P &amp;lt; 0.0001). Fn was significantly more abundant in colorectal cancer than controls (P &amp;lt; 0.0001), with AUROC of 0.868 (P &amp;lt; 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity, Fn discriminated colorectal cancer from controls with a sensitivity of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of four bacteria (Fn + Ch + m7-Bc) showed an improved diagnostic ability compared with Fn alone (AUROC = 0.886, P &amp;lt; 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of Fn alone (sensitivity 92.8%, specificity 79.8%) and four bacteria (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal immunochemical testing for the detection of colorectal cancer. Conclusions: Stool-based colorectal cancer–associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer. Clin Cancer Res; 23(8); 2061–70. ©2016 AACR.
Effect of statins on disease-related outcomes in patients with idiopathic pulmonary fibrosis
Authors: Michael Kreuter, Francesco Bonella, Toby M Maher, Ulrich Costabel, Paolo Spagnolo, Derek Weycker, Klaus-Uwe Kirchgaessler, Martin Kolb
Journal: Thorax (2016)

<h3>Background</h3> Data are conflicting regarding the possible effects of statins in patients with idiopathic pulmonary fibrosis (IPF). This post hoc analysis assessed the effects of statin therapy on disease-related outcomes in IPF. <h3>Methods</h3> Patients randomised to placebo (n=624) in three controlled trials of pirfenidone in IPF (CAPACITY 004 and 006, ASCEND) were categorised by baseline statin use. Outcomes assessed during the 1-year follow-up included disease progression, mortality, hospitalisation and composite outcomes of death or ≥10% absolute decline in FVC and death or ≥50 m decline in 6-minute walk distance (6MWD). <h3>Results</h3> At baseline, 276 (44%) patients were statin users versus 348 (56%) non-users. Baseline characteristics were similar between groups, except statin users were older and had higher prevalence of cardiovascular disease and risk factors. In multivariate analyses adjusting for differences in baseline characteristics, statin users had lower risks of death or 6MWD decline (HR 0.69; 95% CI 0.48 to 0.99, p=0.0465), all-cause hospitalisation (HR 0.58; 95% CI 0.35 to 0.94, p=0.0289), respiratory-related hospitalisation (HR 0.44; 95% CI 0.25 to 0.80, p=0.0063) and IPF-related mortality (HR 0.36; 95% CI 0.14 to 0.95, p=0.0393) versus non-users. Non-significant treatment effects favouring statin use were observed for disease progression (HR 0.75; 95% CI 0.52 to 1.07, p=0.1135), all-cause mortality (HR 0.54; 95% CI 0.24 to 1.21, p=0.1369) and death or FVC decline (HR 0.71; 95% CI 0.48 to 1.07, p=0.1032). <h3>Conclusions</h3> This post hoc analysis supports the hypothesis that statins may have a beneficial effect on clinical outcomes in IPF. Prospective clinical trials are required to validate these observations. <h3>Trial registration numbers</h3> NCT01366209, NCT00287729 and NCT00287716.
Prevalence of pathological features in advanced seminoma: Implications for managment of stage I disease.
Authors: S. H. Baxi, P. R. Warde, J. Sweet, T. Panzarella, K. Shun, M. K. Gospodarowicz, M. A. Jewett, M. J. Moore, J. F. Sturgeon, P. W. Chung
Journal: Journal of Clinical Oncology (2010)

e15018 Background: Risk classification based on pathologic characteristics of the primary tumour in stage I seminoma patients has been attempted but has, thus far, had limited clinical application. Such features, if present, in stage II/III patients may be an alternative means with which those with occult disease might be distinguished from those with tumour confined to the testis. Methods: From 1995 to 2006, 392 patients with testicular seminoma were managed and had pathology review of the primary tumour. Patients with stage I disease were routinely managed with surveillance (Group I, N=330) and stage II/III patients (Group 2, N=62) with radiotherapy/chemotherapy as indicated. Pathological features present in stage I patients were compared to those in stage II and III patients. A multivariable analysis based on a logistic regression model with outcome presence of nodal and/or distant metastatic disease (Yes vs. No) was implemented. Results: Univariate analysis identified the following factors as being significantly different in prevalence between Groups 1 and 2: tumour size (as continuous variable), tunica albuginea involvement, lympho-vascular invasion, epididymal involvement and extra-testicular soft tissue involvement (all p < 0.02). In multivariable analysis tumour size (Odds Ratio 1.35, 95% confidence interval 1.13 to 1.61, p=0.0008) and lymphovascular invasion (Odds Ratio 3.53, 95% confidence interval 1.46 to 8.51, p=0.0051) remained more prevalent in advanced disease. Conclusions: Both tumor size and lymphovascular invasion were more prevalent in patients with advanced testicular seminoma at initial presentation and support previously proposed risk models. However, a powerful discriminatory model based on conventional pathological features is unlikely to be forthcoming. Future investigation with molecular markers/gene expression profiling may reveal distinctive molecular signatures of these tumors with prognostic significance allowing individualized management of patients with testicular seminoma. No significant financial relationships to disclose.
Phase I study of safety and pharmacokinetics (PK) of GDC-0917, an antagonist of inhibitor of apoptosis (IAP) proteins in patients (Pts) with refractory solid tumors or lymphoma.
Authors: Anthony W. Tolcher, Kyriakos P. Papadopoulos, Amita Patnaik, Wayne J. Fairbrother, Harvey Wong, Nageshwar R. Budha, Walter C. Darbonne, Franklin V. Peale, Michael J. Mamounas, Stephanie Royer-Joo, Ron Yu, Chia C. Portera, Johanna C. Bendell, Howard A. Burris, Jeffrey R. Infante
Journal: Journal of Clinical Oncology (2013)

2503 Background: GDCE0917 is a small molecule that triggers tumor cell apoptosis by selectively antagonizing IAP proteins. Preclinical studies demonstrated antitumor efficacy of GDC-0917 alone or in combination with chemotherapeutic agents. Methods: Oral GDC-0917 was given on Day (d) 1 followed by 2d off and a 2-week (w) on/ 1w off treatment (tx) schedule (21d cycle) starting d4. A modified continual reassessment method was used for dose escalation. Dose-limiting toxicity (DLT, assessed d1-24), PK, adverse events (AEs), pharmacodynamics (PD), and clinical activity were evaluated. Results: 42 pts of age 36-86 (median 60.5) were enrolled in 11 cohorts (5-600 mg) and received 1-15 cycles (median 2) of GDC-0917. One DLT, Grade (G) 3 fatigue, was observed at 450 mg. The maximum tolerated dose was not determined although plasma concentrations of preclinically defined IC90 were reached. The most frequent AEs were diarrhea, fatigue and nausea (26.2% each), vomiting (23.8%), and constipation (19%). The most frequent AEs reported as tx-related were mostly G1-2 and included fatigue and nausea (21.4% each), vomiting (14.3%), rash (11.9%) and pruritus (9.5%). AEs reported as tx-related that were ≥ G3 in &gt; 1 pt were elevated AST and ALT (2 pts, at 450 and 600 mg). AEs reported as tx-related that resulted in tx discontinuation were G3 fatigue, G2 QTc prolongation, G2 drug hypersensitivity, G2 pneumonitis (1 pt each), and G3 pruritus/G2 rash (same pt). GDC-0917 peak concentrations were observed 2-3h post dosing. Exposure was dose-proportional with a mean plasma elimination t 1/2 of 4-8h and no apparent accumulation at steady state. Rapid down-modulation of cIAP1 was observed in PBMCs at all dose levels. Evaluation of tumor biopsies demonstrated decreases in cIAP1 (2 pts total, at 40 and 200 mg) and increases in activated caspase-3 and cPARP (1 pt at 200 mg). Two pts (4.8%) had a complete response (both unconfirmed, ovarian Ca and MALT lymphoma [PET]); 4 pts (9.5%) had stable disease for ≥ 3 months. Conclusions: GDC-0917 had a favorable safety, PK and PD profile in pts with advanced malignancies. These encouraging results support further clinical evaluation of this agent. Clinical trial information: NCT01226277.
Daily Weight-Based Busulfan with Cyclophosphamide and Etoposide (Bu/Cy/VP) Produces Comparable Outcomes to 4-Times-Daily Busulfan Dosing for Lymphoma Patients Undergoing Autologous Stem Cell Transplantation (ASCT)
Authors: Brian T. Hill, Lisa A. Rybicki, Catherine Weber, Deepa Jagadeesh, Aaron T. Gerds, Betty K. Hamilton, Hien K. Liu, Robert M. Dean, Ronald M. Sobecks, Brad Pohlman, Steven Andresen, Matt Kalaycio, Brian J. Bolwell, Navneet S. Majhail
Journal: Blood (2015)
Direct Measurement of Correlation Responses in Drosophila Elementary Motion Detectors Reveals Fast Timescale Tuning
Authors: Emilio Salazar-Gatzimas, Juyue Chen, Matthew S. Creamer, Omer Mano, Holly B. Mandel, Catherine A. Matulis, Joseph Pottackal, Damon A. Clark
Journal: Neuron (2016)
LBA-05 First-line FOLFOX-4 ± cetuximab in patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC): the open-label, randomized phase 3 TAILOR trial
Authors: S. Qin, J. Xu, L. Wang, Y. Cheng, T. Liu, J. Chen, S.P. Eggleton, J. Liu, J. Li
Journal: Annals of Oncology (2016)
Painful Ulcerative Lesions on Bilateral Lower Extremities
Authors: Kevin X. Liu, Adam B. Raff, Margaret S. Lee
Journal: JAMA Dermatology (2016)

A young black woman with Graves disease had painful lesions on both legs; chills; lower extremity swelling; and small, painful, ulcers on her bilateral lower legs; her medications included methimazole and atenolol for Graves disease. What is your diagnosis?
Metformin Represses Interferonopathy Through Suppression of Melanoma Differentiation–Associated Protein 5 and Mitochondrial Antiviral Signaling Protein Activation: Comment on the Article by Wang et al
Authors: Yu‐Jih Su, Hung‐Yu Lin, Shao‐Wen Weng, Cheng‐Hsien Lu, Ching‐Yi Lin, Wen‐Chan Chiu, Pei‐Wen Wang
Journal: Arthritis & Rheumatology (2016)
Tumor Suppressors Btg1 and Btg2 Regulate B Lineage Commitment through Modulation of Ebf1 Activity
Authors: Esther Tijchon, Liesbeth van Emst, Dorette van Ingen Schenau, Laurensia Yuniati, Jorn Havinga, Felice Tirone, Jean-Pierre Rouault, Peter M Hoogerbrugge, Frank N. van Leeuwen, Blanca Scheijen
Journal: Blood (2014)
Right heart thrombi in pulmonary embolism
Authors: Deisy Barrios, Vladimir Rosa-Salazar, David Jiménez, Raquel Morillo, Alfonso Muriel, Jorge del Toro, Luciano López-Jiménez, Dominique Farge-Bancel, Roger Yusen, Manuel Monreal
Journal: European Respiratory Journal (2016)

There is a lack of comprehensive data on the prevalence, predictors and prognostic significance of right heart thrombi (RHT) in pulmonary embolism.In this study of patients with pulmonary embolism from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry, we assessed the prevalence and predictors of RHT, and the association between the presence of RHT and the outcomes of all-cause mortality, pulmonary embolism-related mortality, recurrences, and major bleeding through 30 days after initiation of pulmonary embolism treatment.Of 12 441 patients with pulmonary embolism and baseline echocardiographic data, 2.6% had RHT. The following increased the risk of RHT: younger age, previous bleeding, congestive heart failure, cancer, syncope, systolic blood pressure <100 mmHg, and arterial oxyhaemoglobin saturation <90%. Patients with RHT were significantly more likely to die from any cause (adjusted OR 2.50 (95% CI 1.62-3.84); p<0.001) and from pulmonary embolism (adjusted OR 4.29 (95% CI 2.45-7.48); p<0.001) during follow-up. RHT was associated with an increased risk of recurrence during follow-up (1.8% versus 0.7%; p=0.04). Major bleeding was similar in patients with and without RHT.In patients presenting with pulmonary embolism, RHT is relatively infrequent. Patients with RHT had a worse outcome when compared with those without RHT.
Imaging Epigenetics in the Human Brain
Authors: Tracy Hampton
Journal: JAMA (2016)

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Inhibition of Notch and tumor regression
Authors: A. A. Epenetos, C. Kousparou, S. Stylianou
Journal: Journal of Clinical Oncology (2009)

e14623 Background: Notch signaling is an evolutionary-conserved pathway in vertebrates and invertebrates which is involved many developmental processes, including cell fate decisions, apoptosis, proliferation, and stem-cell self renewal. There is increasing evidence that the same molecular pathways regulating the self renewal of stem cells are also being employed in cancer progression. The Notch signal transduction pathway has been implicated in the self-renewal of stem cells in hematopoietic, skin, neural, germ and breast tissue. Increasing evidence suggests that the Notch signaling pathway is frequently up regulated in many forms of cancer including acute T-cell lymphoblastic leukemia, cervical, prostate, lung, breast and others. Thus,inhibition of the pathway could provide a novel treatment of cancer and cancer stem cells. Methods: We have genetically engineered a fusion protein, consisting of the Drosophila transcription factor Antennapedia (ANTP) and with the truncated version of Mastermind-like (MAML) that behaves in a dominant negative (DN) fashion and inhibits Notch activation (ANTP/DN MAML, TR4). This novel fusion protein has been tested for its ability to target tumor cells in vitro and in vivo. Results: Our data show that ANTP/DN MAML fusion protein, TR4 contains signals for proper cell targeting, internalization and nuclear transport. Furthermore, TR4 inhibits human mammary and colon xenograft tumor growth and metastases in immuno deficient mice.TR4 presence and activity was also detected in the brains of treated animals demonstrating that TR4 can cross the blood-brain barrier and potentially eliminate brain tumors and metastases, unlike other anticancer drugs and biological such as monoclonal antibodies that cannot cross the blood brain barrier. TR4 was found to be non- immunogenic following repeat administration in healthy animals. At very high doses (&gt;10x therapeutic dose) it caused anorexia and weight loss in mice. Conclusions: The TR4 protein, a Notch inhibitor, can induce tumor regression and resolution of breast and colon cancer xenografts. It is non- immunogenic following repeat administration and has acceptable toxicity profile. No significant financial relationships to disclose.
Factor XIII Deficiency As Underlying Cause Of Unexplained Bleeding
Authors: Marta Ruiz Mercado, Silvia Verdesoto Cozzarelli, Cristina Calderón-Cabrera, Ramiro Núñez Vázquez, Reyes Jiménez Bárcenas, Rosario Pérez Garrido, Jose Antonio Pérez-Simón, Francisco Javier Rodríguez Martorell
Journal: Blood (2013)
O-019 Distant-relapse analysis of STAR-01, a randomized phase III trial comparing preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer
Authors: S. Lonardi, L. Cionini, C. Pinto, S. Cordio, G. Rosati, A. Sartore Bianchi, A. Tagliagambe, M. Frisinghelli, V. Zagonel, P. Rosetti, M.E. Negru, A. Bonetti, M.C. Tronconi, G. Luppi, A.R. Marsella, C. Corsi, A.M. Bochicchio, G. Aprile, R. Niespolo, C. Granetto, L. Boni, C. Aschele
Journal: Annals of Oncology (2016)
Cardiovascular Biomarker Score and Clinical Outcomes in Patients With Atrial Fibrillation
Authors: Christian T. Ruff, Robert P. Giugliano, Eugene Braunwald, Sabina A. Murphy, Karen Brown, Petr Jarolim, Michele Mercuri, Elliott M. Antman, David A. Morrow
Journal: JAMA Cardiology (2016)

Treatment decisions in atrial fibrillation (AF) are based on clinical assessment of risk. The CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age 65-74 [1 point] or ≥75 years [2 points], diabetes mellitus, and stroke, transient ischemic attack or thromboembolism [2 points]-vascular disease, and sex category [female]) risk score is pragmatic and widely used but has only moderate discrimination.To develop and test a cardiovascular biomarker score for indication of risk in patients with AF.The ENGAGE AF-TIMI 48 trial was a randomized, double-blind, double-dummy clinical trial comparing 2 once-daily edoxaban dose regimens with warfarin in 21 105 patients with AF at moderate to high risk of stroke. This prespecified subanalysis was performed in 4880 patients enrolled at randomization in the biomarker substudy. Cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and d-dimer levels were measured at baseline. A multimarker risk score was developed to determine the probability of stroke, systemic embolic events, or death by assigning tiered points for higher concentrations of the biomarkers.Risk score and clinical outcomes based on cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and d-dimer levels at baseline.Of the 5002 patients enrolled in the biomarker substudy of the ENGAGE AF-TIMI 48 trial, 4880 patients (97.6%) had all 3 biomarkers available at randomization (1820 [37.3%] were women; median [interquartile range] age, 71 [64-77] years). After adjustment for the CHA2DS2-VASc score, each biomarker was associated with a 2.8-fold to 4.2-fold gradient of risk comparing the highest vs lowest concentrations across groups of increasing concentrations (P < .001 for trend for each). The multimarker risk score identified a more than 15-fold gradient of risk after adjustment for CHA2DS2-VASc score. When added to the CHA2DS2-VASc score, the biomarker score significantly enhanced prognostic accuracy by improving the C statistic from 0.586 (95% CI, 0.565-0.607) to 0.708 (95% CI, 0.688-0.728) (P < .001) and reclassification with a net reclassification improvement of 59.4% (P < .001).A prototype multimarker risk score significantly enhanced risk assessment for stroke, systemic embolic events, or death compared with traditional clinical risk stratification. Incorporation of biomarkers into clinical decision making to define therapeutic management in AF warrants consideration.clinicaltrials.gov Identifier: NCT00781391.
Potential Synergy of TRAIL with CDK9 Inhibition in Selective Killing of HIV Infected Cell Lines and Primary CD4+ T Cells
Authors: David Kotlyar, Constantinos Petrovas, Arik Cooper, David Ambrozak, Christina Annunziata, Lidia Hernandez, Takuya Yamamoto, Sara Ferrando-Martinez, Joseph Casazza, Richard Koup
Journal: Blood (2014)