tbuckley/cabot-search huggingface dataset:
Effect of HOXB13 and FOXA1 on the AR cistrome during prostate tumorigenesis in primary human tissue.
Authors: Mark M Pomerantz, Fugen Li, Apurva Chonkar, Francisca Vazquez, Matthew Chabot, Paloma Cejas, Michaela Bowden, Ramesh Shivdasani, William C Hahn, Myles Brown, Philip W. Kantoff, Massimo Loda, Henry Long, Matthew L Freedman
Journal: Journal of Clinical Oncology (2014)

5018 Background: The androgen receptor (AR) is central to prostate carcinogenesis and cancer progression. Current understanding of the prostate AR cistrome - the genome-wide set of AR binding sites (ARBS) - is driven largely by tumor model systems. The role of the AR cistrome in prostate tumorigenesis in human tissue is unknown. We map the AR cistrome in 20 normal and tumor human prostate samples using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Methods: Chromatin was extracted from 13 tumor and 7 matched histologically normal foci (>70% enrichment) from fresh-frozen radical prostatectomy specimens. Tissue was pulverized, fixed and sonicated then immunoprecipitated with antibody to AR; DNA was isolated; libraries were constructed for the Illumina platform; sequencing reads were aligned to the human genome using MACS (false discovery rate 0.01) Results: Median 19,602 ARBS were called per sample. In unsupervised pairwise analysis of each AR cistrome, specimens clustered distinctly into tumor and normal groups. 9,181 ARBS were consistently enriched in tumor relative to normal (T-ARBS) and 2,690 were enriched in normal relative to tumor (N-ARBS). DNA binding motif analysis showed that AR itself is the most significantly enriched motif in N-ARBS, while FOXA1, and HOXB13 and AR were most significantly enriched in T-ARBS (z-score < -15). HOXB13 ChIP and FOXA1 ChIP in VCaP cell line showed substantial overlap with T-ARBS (68% and 76% of T-ARBS, respectively) and their knockdown via shRNA adversely affects prostate cell line survival. We identified genes within 1 megabase of T-ARBS or N-ARBS that are differentially expressed in tumor and normal. Expression levels of these genes in large clinically annotated patient cohorts are highly associated with multiple clinical parameters, including tumor grade and development of metastasis. Conclusions: We performed the most comprehensive study of the AR cistrome in human tumor and normal prostate tissue. We demonstrate that the AR cistrome is dynamic and implicate HOXB13 and FOXA1 as factors that reprogram the AR during transformation. These findings attest to the power of performing epigenetic analysis in both normal and tumor human tissue.
APPROPRIATE PRIMARY PROPHYLACTIC IMPLANTATION OF DEFIBRILLATOR IN PATIENTS WITH BRUGADA SYNDROME: IS THERE ANY DIFFERENCE BETWEEN PATIENTS FROM WESTERN AND ASIAN COUNTRIES? DATA FROM A MULTICENTER SURVEY INVOLVING 246 PATIENTS WITH ARRHYTHMIC EVENTS
Authors: Anat Milman, Antoine Andorin, Jean-Baptiste Gourraud, Shingo Maeda, Tsukasa Kamakura, Giulio Conte, Eran Leshem, Pieter Postema, Carlo Napolitano, Aviram Hochstadt, Jean Champagne, Leonardo Calo, Jacob Tfelt-Hansen, Masahiko Takagi, Christian Veltmann, Pietro Delise, Domenico Corrado, Elijah Behr, Fiorenzo Gaita, Gan-Xin Yan, Josep Brugada, Antoine Leenhardt, Gi-Byoung Nam, Vincent Probst, Bernard Belhassen
Journal: Journal of the American College of Cardiology (2017)
A phase I study of sunitinib plus irinotecan in the treatment of patients with recurrent malignant glioma
Authors: H. S. Friedman, J. J. Vredenburgh, A. Desjardins, D. E. Janney, K. B. Peters, A. H. Friedman, S. Gururangan, D. A. Reardon
Journal: Journal of Clinical Oncology (2009)

e13024 Background: Malignant glioma (MG), an incurable primary CNS tumor, are highly angiogenic due to overexpression of VEGF/VEGFR. The current study was designed to determine the MTD and DLT of sunitinib (S), a once-daily, oral selective inhibitor of VEGFR when combined with irinotecan (I), a topoisomerase-1 inhibitor among recurrent MG patients. Methods: We employed a ‘3+3‘ dose escalation design to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of S, administered once daily for the first 28 days of each 42 day cycle, with I, administered every 2 weeks. The initial S and I doses were 25 mg/day and 75 mg/m 2 . Key eligibility criteria included KPS ≥ 70%, adequate organ function and no concurrent CYP3A-inducing anti-epileptics. Pharmacokinetic studies for S are obtained during cycle 1 among 6 additional patients treated at the MTD. Results: Eleven patients (grade 4 MG, n = 6; grade 3 MG, n = 5) have enrolled. No DLTs were observed in cohort 1, but 2 patients experienced hematologic DLT (grade 3 thrombocytopenia, n = 2; grade 4 neutropenia, n = 1) in cohort 2. Therefore the MTD for this regimen is 25 mg of S plus 75 mg/m 2 of I. Evidence of therapeutic benefit to date includes 8 patients (73%) with stable disease including 3 who continue on therapy. Conclusions: Combination of sunitinib plus irinotecan is well tolerated in recurrent MG patients at the defined MTD dose level. Accrual to the PK dose expansion cohort continues. No significant financial relationships to disclose.
Participation in adjuvant clinical breast cancer trials: Is there a difference in survival compared to guideline adherent adjuvant treatment? A retrospective multicenter cohort study of 5,326 patients.
Authors: Achim Wöckel, Reyn Van Ewijk, Isabell Hoffmann, Jochem König, Rolf Kreienberg, Maria Blettner, Lukas Schwentner
Journal: Journal of Clinical Oncology (2012)

1082 Background: Clinical trials (CT) usually compare a standard treatment regime versus innovative new substances or regimens. However participation in CT is available for only few patients and exclusion criteria is usually very strict. Therefore this study tries to answer the following questions: (1) Does participation in adjuvant CT improve survival in breast cancer (BC)? (2) Is there a difference in survival compared to guideline adherence and what is the role of the other treatments surrounding adjuvant breast cancer treatment? Methods: This German multi-center [17 participating hospitals all are certified as breast cancer centers] retrospective cohort study called BRENDA (BRENDA = quality of breast cancer care under evidence-based guidelines) included 5326 patients obtained from 1992 until 2005. The definition of guideline adherence was based on the German national S3 guideline for diagnosis and treatment of breast cancer (2004). Results: 554 (10,4%) patients participated adjuvant clinical trials and 4772 (89,6%) not. There was a trend towards a significantly impaired RFS [p=0.17; HR=0.87 (95% CI: 0.71-1.06)] and OAS [p=0.65; HR=0.84 (95% CI: 0.65-1.09)] when comparing participants (PA) versus non-participants (NPA). When stratifying for guideline adherence (compared to PA-guideline conform in all adjuvant therapies) the outcome was not different in NPA-guideline adherent [RFS: p=0.13; HR=1.25 (95% CI: 0.94-1.67)] [OAS: p=0.83; HR=1.41 (95% CI: 0.96-2.06)]. However survival parameters were significantly impaired in non-guideline conform PA [RFS: p=0.005; HR=1.66 (95% CI: 1.16-2.38)] [OAS: p=0.01; HR=1.83 (95% CI: 1.15-2.92)] and non-guideline conform NPA [RFS: p&gt;0,001; HR=1.70 (95% CI: 1.27-2.26)] [OAS: p=0.002; HR=1.82 (95% CI: 1.24-2.67)]. Conclusions: There is a strong association between guideline adherence in adjuvant treatment in BC and survival. PA in clinical trials trended to an improved survival, but only if guideline adherent treatment was applied. Patients who don`t have access to clinical seem to profit substantially of guideline adherent adjuvant treatment.
Cord Blood Hematopoietic Progenitor Cell in Co-Culture with Bone Marrow Mesenchymal Stromal Cells: A Synergic Effect
Authors: Camillo Almici, Arabella Neva, Rosanna Verardi, Simona Braga, Andrea Di Palma, Andrea Bianchetti, Domenico Russo, Mirella Marini
Journal: Blood (2011)
Time to testosterone (T) and PSA rises during first “off treatment” interval (1OFF-2ON) of intermittent androgen deprivation (IAD) as prognostic for time to castration resistance (CRPC) and prostate cancer mortality (PCM) in men with biochemical relapse (BR).
Authors: Evan Y. Yu, Kevin F Kuo, Rachel Hunter-Merrill, Roman Gulati, Suzanne P Hall, Teresa E Gambol, Ruth D Etzioni, Celestia S. Higano
Journal: Journal of Clinical Oncology (2012)

4557 Background: A recent phase III trial of intermittent vs. continuous AD supports IAD as standard of care for men treated with AD for BR. To identify potential prognostic factors during 1OFF, times to T and PSA rises from our prospective trial of IAD in men with BR were analyzed in relation to times to CRPC and PCM. Methods: 72 men with BR after definitive local therapy were treated with IAD, each cycle consisting of 9 months of leuprolide and flutamide followed by a variable “off treatment” interval. T and PSA were followed monthly; AD was resumed when PSA reached a pre-specified value. Cycles repeated until CRPC, defined as ≥2 PSA rises with T≤50 ng/dL. Markers of interest from 1OFF-2ON were time to first T&gt;50, time from first T&gt;50 to first PSA rise ≥0.1 ng/mL, time to first PSA rise ≥0.1, and PSA doubling time (PSAdt), calculated using the first 3 PSA measurements starting from first PSA ≥0.1. The associations of these markers with CRPC and PCM were evaluated using Cox proportional hazards models (or logistic regression if the Cox proportional hazards assumption was not met), controlling for age at study entry and Gleason score categorized to ≤7 or &gt;7. Results: A 30-day increase in time to first T&gt;50 was significantly associated with a 75% increase in the risk of PCM. A 30-day increase in time to PSA rise from 1OFF or after T&gt;50 was significantly associated with a 23% or 72% reduction in the risk of CRPC, respectively. While neither of the associations of PSAdt with CRPC or PCM were significant, they were of moderate size: PSAdt displayed a moderate reduction in risk of CRPC by 35% and PCM by 38%. Conclusions: During the first “off treatment” interval of IAD, the time to first T&gt;50 is prognostic for PCM. Time to first PSA rise after 1OFF and after first T&gt;50 are both prognostic for CRPC. [Table: see text]
The effectiveness of tositumomab and iodine I 131 tositumomab in relapsed/refractory follicular grade 1/2 and small lymphocytic non-Hodgkin's lymphoma (NHL)
Authors: J. O. Armitage, J. P. Leonard, S. A. Gregory, S. J. Horning, A. D. Zelenetz, M. S. Kaminski, R. I. Fisher
Journal: Journal of Clinical Oncology (2004)

6573 Background: In an overall population of 995 pts, Iodine I 131 Tositumomab was administered to 740 eligible pts with relapsed/refractory follicular grade 1/2 (n = 651) and small lymphocytic (n = 89) NHL. To be eligible, pts had to have a platelet count ≥ 100,000/mm3 and ≤ 25% of bone marrow involvement with lymphoma. Methods: Independently assessed data from 5 clinical trials (N = 230) were integrated with investigator-assessed data from an expanded access program (N = 765). Correlation between investigator- and independently reviewed responses was > 90%. The median follow-up was 25.5 mo (range, 0.1–117.7 mo). Results: Demographics (for follicular vs small lymphocytic NHL): male: 55%, 64%; age >65: 23%,37%; stage III/IV: 88%,92%; median time from diagnosis: 42mo,41mo; ≥ 4 prior therapies: 30%,35%; BM involvement: 44%, 62%; tumor diameter ≥ 5 cm: 48%,44%; prior Rituximab: 45%,60%; prior radiation: 21%,17%. The OR rate for follicular grade 1/2 NHL was significantly higher than for small lymphocytic (P < .001; Table) NHL, whereas the durations of response were comparable. Multivariate analyses: ≥ 4 prior therapies and tumor diameter < 5 cm were significant predictors for a higher OR in pts with either follicular or small lymphocytic NHL. Different factors were predictive of a higher CR rate: follicular: tumor < 5cm (P < .001), < 4 prior chemotherapies (P = .001), age ≤ 65 yrs (P = .002), and female (P = .010). Small lymphocytic: no bone marrow involvement (P = .007) and > 4 yr from diagnosis (P = .036). Conclusions: Among 740 pts, Iodine I 131 Tositumomab produced a significantly higher OR rate and CR rate in follicular lymphoma grades 1/2 than in small lymphocytic lymphoma. However, the duration of remission was similar for responders with either diagnosis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Corixa Corporation
A Combined PD-1/C5a Blockade Synergistically Protects against Lung Cancer Growth and Metastasis
Authors: Daniel Ajona, Sergio Ortiz-Espinosa, Haritz Moreno, Teresa Lozano, María J. Pajares, Jackeline Agorreta, Cristina Bértolo, Juan J. Lasarte, Silvestre Vicent, Kai Hoehlig, Axel Vater, Fernando Lecanda, Luis M. Montuenga, Ruben Pio
Journal: Cancer Discovery (2017)

Disruption of the programmed cell death protein 1 (PD-1) pathway with immune checkpoint inhibitors represents a major breakthrough in the treatment of non-small cell lung cancer. We hypothesized that combined inhibition of C5a/C5aR1 and PD-1 signaling may have a synergistic antitumor effect. The RMP1-14 antibody was used to block PD-1, and an L-aptamer was used to inhibit signaling of complement C5a with its receptors. Using syngeneic models of lung cancer, we demonstrate that the combination of C5a and PD-1 blockade markedly reduces tumor growth and metastasis and leads to prolonged survival. This effect is accompanied by a negative association between the frequency of CD8 T cells and myeloid-derived suppressor cells within tumors, which may result in a more complete reversal of CD8 T-cell exhaustion. Our study provides support for the clinical evaluation of anti-PD-1 and anti-C5a drugs as a novel combination therapeutic strategy for lung cancer.Significance: Using a variety of preclinical models of lung cancer, we demonstrate that the blockade of C5a results in a substantial improvement in the efficacy of anti-PD-1 antibodies against lung cancer growth and metastasis. This study provides the preclinical rationale for the combined blockade of PD-1/PD-L1 and C5a to restore antitumor immune responses, inhibit tumor cell growth, and improve outcomes of patients with lung cancer. Cancer Discov; 7(7); 694-703. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 653.
Automated Multiparameter Flow Cytometry (MFC) Immunophenotyping for Reproducible Identification of High Risk Smoldering Multiple Myeloma (SMM)
Authors: Bruno Paiva, Sarah K. Johnson, Maria-Victoria Mateos, Daisy V. Alapat, Noemi Puig, Miguel-T Hernandez, Fernando Escalante, Alfonso Garcia de Coca, Joan Bladé, Juan Jose Lahuerta, Quentin Lecrevisse, Jacques J.M. van Dongen, Alberto Orfao, Gareth J Morgan, Bart Barlogie, Jesus San Miguel
Journal: Blood (2016)
MYOCARDITIS, HEART FAILURE AND ARRHYTHMIAS IN PATIENTS WITH ZIKA
Authors: Karina Auristela Gonzalez Carta, Ivan Mendoza, Igoor Morr, Ivan Mendoza, Francesca Misticchio, Yolimar Meza, Vicente Finizola, Gerardo Chazzin, Juan Marques
Journal: Journal of the American College of Cardiology (2017)
ASSOCIATION BETWEEN BODY MASS INDEX AND OUTCOMES AMONG PATIENTS WITH PREVALENT ATRIAL FIBRILLATION: A META-ANALYSIS
Authors: Shah Bano, Usman Salahuddin, Sushil Garg, Nitin Kulkarni, Vidhu Anand, Helen Mayo, Shreya Rao, Ambarish Pandey
Journal: Journal of the American College of Cardiology (2017)
Induction of UBC9 and the Sumoylation Pathway in Multiple Myeloma Promotes Plasma Cell Growth and Correlates with Decreased Patient Survival.
Authors: James J. Driscoll, Konstantinos Lefkimmiatis, Mariateresa Fulciniti, Rao Prabhala, Dheeraj Pelluru, Philip R. Greipp, Nikhil C. Munshi
Journal: Blood (2007)
Neurodevelopmental Abnormalities and Congenital Heart Disease
Authors: Paul D. Morton, Nobuyuki Ishibashi, Richard A. Jonas
Journal: Circulation Research (2017)

In the past 2 decades, it has become evident that individuals born with congenital heart disease (CHD) are at risk of developing life-long neurological deficits. Multifactorial risk factors contributing to neurodevelopmental abnormalities associated with CHD have been identified; however, the underlying causes remain largely unknown, and efforts to address this issue have only recently begun. There has been a dramatic shift in focus from newly acquired brain injuries associated with corrective and palliative heart surgery to antenatal and preoperative factors governing altered brain maturation in CHD. In this review, we describe key time windows of development during which the immature brain is vulnerable to injury. Special emphasis is placed on the dynamic nature of cellular events and how CHD may adversely impact the cellular units and networks necessary for proper cognitive and motor function. In addition, we describe current gaps in knowledge and offer perspectives about what can be done to improve our understanding of neurological deficits in CHD. Ultimately, a multidisciplinary approach will be essential to prevent or improve adverse neurodevelopmental outcomes in individuals surviving CHD.
Beyond white light: optical enhancement in conjunction with magnification colonoscopy for the assessment of mucosal healing in ulcerative colitis
Authors: Marietta Iacucci, Ralf Kiesslich, Xianyong Gui, Remo Panaccione, Joan Heatherington, Oluseyi Akinola, Subrata Ghosh
Journal: Endoscopy (2017)

Abstract Background and study aim The I-SCAN optical enhancement (OE) system with magnification is a recently introduced combination of optical and digital electronic virtual chromoendoscopy, which enhances mucosal and vascular details. The aim of this pilot study was to investigate the use of I-SCAN OE in the assessment of inflammatory changes in ulcerative colitis (UC). Patients and methods A total of 41 consecutive patients with UC and 9 control patients were examined by I-SCAN OE (Pentax Medical, Tokyo, Japan). Targeted biopsies of the imaged areas were obtained. A new optical enhancement score focusing on mucosal and vascular changes was developed. The diagnostic accuracy of I-SCAN OE was calculated against histology using two UC histological scores – Robarts Histopathology Index (RHI) and ECAP (Extent, Chronicity, Activity, Plus additional findings). Results The overall I-SCAN OE score correlated with ECAP (r = 0.70; P &lt; 0.001). The accuracy of the overall I-SCAN OE score to detect abnormalities by ECAP was 80 % (sensitivity 78 %, specificity 100 %). I-SCAN OE vascular and mucosal scores correlated with ECAP (r = 0.65 and 0.71, respectively; P &lt; 0.001). The correlation between overall I-SCAN OE score and RHI was r = 0.61 (P &lt; 0.01), and the accuracy to detect abnormalities by RHI was 68 % (sensitivity 78 %, specificity 50 %). The majority of patients with Mayo 0 had abnormalities on I-SCAN OE. Conclusion In UC, the new I-SCAN OE technology accurately identified mucosal inflammation, and correlated well with histological scores of chronic and acute changes.
Irinotecan in first line therapy of elderly and non-elderly patients with metastatic colorectal cancer: Meta-analysis of four trials investigating 5-FU and irinotecan
Authors: G. Folprecht, P. Rougier, L. Saltz, E. Van Cutsem, J. Y. Douillard, J. Sastre, E. Mitry, H. Hecker, U. Schubert, C. H. Köhne
Journal: Journal of Clinical Oncology (2006)

3578 Background: Irinotecan has been shown to improve response rate and progression free survival in three randomized studies. In a recent metaanalysis showed that elderly patients have a similar benefit from 5-FU containing palliative treatment as younger patients (Folprecht 2004). Methods: We performed a metaanalysis of three randomized trials investigating 5-FU/FA/irinotecan vs. 5-FU/FA (Saltz 2000, Douillard 2000, Köhne 2005 [EORTC 40986]), and one phase II trial with 5-FU/irinotecan (Sastre 2005) to explore the efficacy and toxicity in elderly (≥70 years) and non-elderly (&lt; 70 years) patients. Only data from randomized trials were used to compare the treatment arms 5-FU/FA plus irinotecan (IFL, FOLFIRI or Irinotecan/AIO) vs. 5-FU/FA (Mayo clinic regimen, LV5FU2 or AIO). Results: In total, 303 patients ≥70 y. and 1181 patients &lt; 70 y were analyzed. Overall response rate was 39.5% in elderly and 33.1% in non-elderly patients (p=.055). Progression free survival was 6.7 (5.6–7.8) and 5.7 (5.2–6.1) months in elderly and younger patients (p=.12), respectively, overall survival 15.9 (13.6–18.3) vs. 15.4 (14.3–16.5) months (p=.9). Neutropenia gr. 3/4 and stomatitis gr. 3/4 was found to be more frequent in elderly patients. No differences were found in the other toxicities. Conclusion: The analysis confirms that neutropenia and stomatitis is moderately increased in elderly patients. However elderly patients benefit from treatment with irinotecan/5-FU in a similar way as younger patients do, and (fit) elderly should be offered the irinotecan-containing therapy in the same way as younger patients. [Table: see text] No significant financial relationships to disclose.
ASSOCIATION BETWEEN SERUM COLLAGEN BIOMARKERS AND CORONARY ARTERY CALCIUM: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA)
Authors: Aristotelis Papayannis, Daniel Duprez, Chetan Shenoy, Joachim Ix, Myron Gross, Jorge Kizer, Jose Luchsinger, David Jacobs
Journal: Journal of the American College of Cardiology (2017)
A Programmed Nanoparticle with Self-Adapting for Accurate Cancer Cell Eradication and Therapeutic Self-Reporting
Authors: Yingping Luo, Liwei Huang, Ye Yang, Xianfei Zhuang, Siyao Hu, Huangxian Ju, Bo-Yang Yu, Jiangwei Tian
Journal: Theranostics (2017)

To achieve the best therapeutic efficacy and good prognosis, the drugs necessitate tailored profiles of excellent spatiotemporal control and therapeutic monitoring.Here we introduce a programmed theranostic nanoparticle with self-adapting properties for tumor-specific systemic treatment, including stealthy surface to prolong circulation time in blood, surface charge-reversion for tumor targeting, receptor-mediated internalization to increase intracellular accumulation, "proton sponge effect" for controllable drug release and escape from endo/lysosome.Encouragingly, in the process of drug-induced apoptosis, the therapeutic efficacy can be reported by fluorescence imaging in vivo, in situ and in real time.Therefore, this work provides a new paradigm for design of programmed theranositc nanomedicine and offers promising prospects for precise tumor treatment.
TIMELY USE OF RIGHT HEART CATHETERIZATION IS ASSOCIATED WITH REDUCED IN-HOSPITAL MORTALITY IN PATIENTS WITH CONGESTIVE HEART FAILURE: INSIGHT FROM THE UNITED STATES NATIONAL INPATIENT SAMPLE DATABASE
Authors: Reza Masoomi, Zubair Shah, Deepak Parashara, Buddhadeb Dawn, Kamal Gupta
Journal: Journal of the American College of Cardiology (2017)