tbuckley/cabot-search huggingface dataset:
Use of PET-measured response in involved mediastinal lymph nodes to predict overall survival (OS) in non-small cell lung cancer (NSCLC) patients treated with induction therapy (IT) and surgery.
Authors: S. Barnett, G. Plourde, J. Zheng, M. Pietanza, T. J. Akhurst, R. J. Downey, M. G. Kris, R. Shen, V. W. Rusch, B. J. Park
Journal: Journal of Clinical Oncology (2010)

7077 Background: Persistent N2 disease after IT for NSCLC identifies a group of patients with poor probability of extended survival even after a complete resection. It has been reported that the degree of FDG avidity in N2 nodes prior to treatment and PET measured response in the primary site of disease may be predictors of survival after subsequent resection. We hypothesize that in patients with stage cIIIA (N2) NSCLC, PET measured changes in N2 nodes during IT may help further define prognosis and determine appropriate management. Methods: An IRB approved retrospective review of a single institution surgical database was performed to identify cIIIA (histologically-proven N2) NSCLC patients who had pre- and post-IT PET scans and underwent resection. SUVmax of primary tumor and N2 nodes were recorded and percentage reduction (PR) after IT calculated. OS was defined from date of surgery to date of death or last follow-up. The association of OS with age, sex, histology, metabolic response, type of resection, tumor diameter and pN2 status after IT were assessed by uni- and multivariate logistic regression models. Results: From Jan 2000 to Dec 2006 76 eligible patients were identified. On univariate analysis PET response in the N2 nodes was associated with improved median OS at thresholds of PR ≥ 0% (31 months, range 22-48 versus 15 months, range 6-NA, p=0.048) and PR > 60% (34 months, range 22-NA versus 20 months, range 13-34, p=0.013). On multivariate analysis persistent N2 disease [HR = 2.41 (1.07-4.28), p=0.032], PR in the N2 nodes of < 60% [HR = 1.82 (1.06-3.03), p=0.028] and (excluding pN2 status from analysis) PR in the N2 nodes of < 0% (increase after IT) [HR = 2.38 (1.02-5.56), p=0.044] were associated with reduced OS. Conclusions: Metabolic response in N2 nodes reflected by reduction in SUVmax is associated with improved OS after resection, whereas metabolic progression predicts inferior outcomes despite complete resection. Reduction of SUVmax > 60% in the N2 nodes is associated with acceptable OS independent of complete pathological response in the mediastinum. No significant financial relationships to disclose.
TCT-37 Transcatheter Aortic Valve Replacement with a Repositionable Self-expanding Bioprosthesis in Patients With Severe Aortic Stenosis at High Risk for Surgery: One-Year Results from the Evolut R US Pivotal Study
Authors: Jeffrey J. Popma, J. Kevin Harrison, G. Chad Hughes, Susheel Kodali, Isaac George, Jae Oh, James Slater, Mathew Williams, Colleen Gilbert
Journal: Journal of the American College of Cardiology (2016)
Patients with stage IV lung cancer lose 25% of their valuable time in the office visits and hospital stay
Authors: J. Singh, S. Taylor, C. Huang, A. K. Malani, C. Gupta, M. Pabla
Journal: Journal of Clinical Oncology (2006)

18533 Background: Patients with stage IV lung cancer have median survival of 4–6 months. Randomized trials have shown chemotherapy may have small but significant survival benefit. To achieve this small gain,patients may have to spend their last few days of life in the office visits and hospitalization. Last few days of person’s life need to be spent comfortably and most effective manner in accordance to their wishes, desires and priorties.We attempted to study the “Time Lost” in the stage IV lung cancer patients who either did not choose or were not offered the palliative care/Hospice. Methods: We retrospectively reviewed charts of patients diagnosed with stage IV lung cancer (at their initial presentation) from Jan 2002 to Dec 2005 at our institution. We calculated their inpatient and out patient visit hrs and hence “Time Lost” during the last few days of their life. Patients were divided into two groups—Group A (n = 12): Patients who opted to choose palliative/hospice care immediately after the diagnosis and GroupB (n = 46): Patients who either refused or were not offered palliative/hospice care. Results: The median age at diagnosis was similar in both groups (71 vs 69.5 yrs). The median survival was also similar in both groups (4 months vs 4 months). Patients in group B (non hospice) had 1 month “Lost Time” out of their median survival of 4 months. In comparison patients in group A (hospice) had median survival of 4 months with “No Lost Time”. Thus patients who were not offered hospice or refused hospice spent 25% of their precious time during last stages of their life in inpatient stays and outpatient visits. Conclusions: Patients with stage IV lung cancer should be actively offered palliative/Hospice care, though studies with large number of patients is further required. [Table: see text] No significant financial relationships to disclose.
TCT-155 Prognostic Impact of the Residual SYNTAX Score on 2-years Outcomes in Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention
Authors: Ying Song, Yuan-liang Ma, Jia-Hui Zhang, Xiao-Fang Tang, Jing-jing Xu, Yi Yao, Chen He, Lin Jiang, Ping Jiang, Huan-Huan Wang, Na Xu, Changdong Guan, Ru Liu, Yuejin Yang, Run-Lin Gao, Shubin Qiao, Bo Xu, Jin-qing Yuan
Journal: Journal of the American College of Cardiology (2016)
HER2 and EGFR Overexpression Support Metastatic Progression of Prostate Cancer to Bone
Authors: Kathleen C. Day, Guadalupe Lorenzatti Hiles, Molly Kozminsky, Scott J. Dawsey, Alyssa Paul, Luke J. Broses, Rajal Shah, Lakshmi P. Kunja, Christopher Hall, Nallasivam Palanisamy, Stephanie Daignault-Newton, Layla El-Sawy, Steven James Wilson, Andrew Chou, Kathleen Woods Ignatoski, Evan Keller, Dafydd Thomas, Sunitha Nagrath, Todd Morgan, Mark L. Day
Journal: Cancer Research (2016)

Activation of the EGF receptors EGFR (ErbB1) and HER2 (ErbB2) drives the progression of multiple cancer types through complex mechanisms that are still not fully understood. In this study, we report that HER2 expression is elevated in bone metastases of prostate cancer independently of gene amplification. An examination of HER2 and NF-κB receptor (RANK) coexpression revealed increased levels of both proteins in aggressive prostate tumors and metastatic deposits. Inhibiting HER2 expression in bone tumor xenografts reduced proliferation and RANK expression while maintaining EGFR expression. In examining the role of EGFR in tumor-initiating cells (TIC), we found that EGFR expression was required for primary and secondary sphere formation of prostate cancer cells. EGFR expression was also observed in circulating tumor cells (CTC) during prostate cancer metastasis. Dual inhibition of HER2 and EGFR resulted in significant inhibition of tumor xenograft growth, further supporting the significance of these receptors in prostate cancer progression. Overall, our results indicate that EGFR promotes survival of prostate TIC and CTC that metastasize to bone, whereas HER2 supports the growth of prostate cancer cells once they are established at metastatic sites. Cancer Res; 77(1); 74-85. ©2016 AACR.
Optical coherence tomography compared with intravascular ultrasound and with angiography to guide coronary stent implantation (ILUMIEN III: OPTIMIZE PCI): a randomised controlled trial
Authors: Ziad A Ali, Akiko Maehara, Philippe Généreux, Richard A Shlofmitz, Franco Fabbiocchi, Tamim M Nazif, Giulio Guagliumi, Perwaiz M Meraj, Fernando Alfonso, Habib Samady, Takashi Akasaka, Eric B Carlson, Massoud A Leesar, Mitsuaki Matsumura, Melek Ozgu Ozan, Gary S Mintz, Ori Ben-Yehuda, Gregg W Stone
Journal: The Lancet (2016)
cDNA Microarray Analysis of Genes Up-Regulated by Treatment with 5-AZA-2′-Deoxycytidine in Combination with Trichostatin A Identifies Aberrant Metallothionein 1H Promoter Methylation at a High Frequency Iin Human AML.
Authors: Stuart A. Scott, Derek S. Pearson, Matthew N. Bainbridge, Wei-Feng Dong, Naoto Takahashi, David P. Sheridan, Ryo Ichinohasama, C. R. Geyer, John F. DeCoteau
Journal: Blood (2004)
TCT-1 Microvascular Obstruction Is Independently Associated with Adverse Events Following Primary PCI for STEMI: A Patient-Level Pooled Analysis from 7 Randomized Trials
Authors: Suzanne de Waha, Manesh Patel, Christopher Granger, E. Magnus Ohman, Akiko Maehara, Ingo Eitel, Ori Ben-Yehuda, Paul Jenkins, Holger Thiele, Gregg Stone
Journal: Journal of the American College of Cardiology (2016)
TCT-193 Zotarolimus eluting stent compared with GENOUS stent in patients with ST-elevation myocardial infarction undergoing primary PCI
Authors: Wouter Remkes, Vincent Roolvink, Saman Rasoul, Jan-Henk Dambrink, Jan Paul Ottervanger, Marcel Gosselink, Elvin Kedhi, Arnoud van't Hof
Journal: Journal of the American College of Cardiology (2016)
TCT-253 Temporal trends in frequency, management and outcomes of coronary perforations
Authors: Rafael Romaguera, Agustin Fernández Cisnal, Marcos Ñato, Josep Gomez Lara, Jose Luis Ferreiro, Gerard Roura Ferrer, Ana Lucrecia Marcano, Lara Fuentes, Joan Antoni Gomez-Hospital, Angel Cequier
Journal: Journal of the American College of Cardiology (2016)
Assessment of barriers to patient participation in clinical trials among oncology outpatients at a community teaching hospital in Toronto
Authors: L. Shamrakov, H. Sampson, J. Nyhof-Young, Y. Rahim
Journal: Journal of Clinical Oncology (2009)

e17547 Background: This study investigated barriers to patient participation in clinical trials (CTs). In particular, the effect of educational attainment on the understanding of, interest about, and past participation in CTs among cancer patients at a Toronto community teaching hospital was assessed. Methods: A survey was administered to cancer outpatients, containing Yes/No answers, and likert scales. Responses were analyzed quantitatively (SPSS). Results: 101 questionnaires were completed out of 112 administered (90% response rate). 76% of patients self-reported as knowledgeable about clinical trials. Patients education level correlated to their perceived knowledge of clinical trials: 37.5% of patients with a less than grade 9, 59.4% with a high school, and 90.2% with a university background identified themselves as knowing what CTs are. All patients scored poorly on details and held common misconceptions of CTs (e.g. knowing little about placebos and experimental drug testing). Overall, 27% of patients had been previously enrolled in CTs. Of the 34% of patients who had been previously approached, 79% had agreed to participate. The majority were willing to participate or unsure of participating in CTs. A minority stated they will never participate in a trial. Patients also identified concern about lack of hospital resources about CTs and a desire to have a doctor present when learning about CTs. Patients with less education identified a greater desire for a doctor's presence than those with more education. Conclusions: This study revealed lack of staff recruitment, low patient awareness, and lack of availability of trial facilities as potential barriers to participation. Targeted information to patients with different education levels may be appropriate, given variable knowledge about CTs. Education and counseling regarding placebos and experimental drugs should be targeted towards all patients to reduce barriers to patient participation, diminish myths, and increase understanding and interest. In response, this institution will design a brochure for all patients describing clinical trials, providing a glossary of terms, and offering a list of key resources in order to improve awareness and trial recruitment. No significant financial relationships to disclose.
Impact of Frailty on Hematopoietic Cell on Early Transplant Outcomes in Older Recipients
Authors: Mukta Arora, Smita Bhatia, Todd E. DeFor, Manju Nayar, Hewan Belete, Troy Lund, Bharat Thyagarajan, Celalettin Ustun, Daniel Weisdorf
Journal: Blood (2015)
TCT-491 Comparative analysis of the right radial vascular access vs. left at more than 10,000 diagnostic coronary angiography
Authors: Etelberto Hernandez, Victor Jimenez Diaz, Pablo Juan-Salvadores, Jorge Vitela, Jose Antonio Baz Alonso, Alberto Ortiz, Guillermo Bastos Fernández, Saleta Fernández Barbeira, Antonio De Miguel Castro, Jorge Andrade Pacheco, Carlos Enrique Saldaña Luna, Giovanny Ponte, Josue Ponce, Jorge SepúlvedaSepúlveda, Angel Salgado, Andres Iñiguez
Journal: Journal of the American College of Cardiology (2016)
TCT-660 Efficacy and Safety of the cerebral embolic protection device during TAVI
Authors: MICHELE DALLAGO, STEFANO BRANZOLI, MARTA TURELLA, Giuseppe Braito, Alberto Menotti, Simone Muraglia, DANIELE PENZO, ANGELO GRAFFIGNA, Roberto Bonmassari
Journal: Journal of the American College of Cardiology (2016)
TCT-690 Influence of calcium, implantation depth and oversizing on the occurrence of conduction disturbances and need for pacemaker implantation after implantation of the balloon-expandable Edwards Sapien 3 valve
Authors: Birgid Gonska, Alexander Von Keil, Julia Seeger, Christoph Rodewald, Sergiu Dragomir, Dominik Scharnbeck, Wolfgang Rottbauer, Jochen Wöhrle
Journal: Journal of the American College of Cardiology (2016)
Human Chorionic Gonadotropin Does Not Correlate with Risk for Maternal Breast Cancer: Results from the Finnish Maternity Cohort
Authors: Renée T. Fortner, Helena Schock, Rudolf Kaaks, Matti Lehtinen, Eero Pukkala, Hans-Åke Lakso, Minna Tanner, Raija Kallio, Heikki Joensuu, Jaana Korpela, Adetunji T. Toriola, Göran Hallmans, Kjell Grankvist, Anne Zeleniuch-Jacquotte, Paolo Toniolo, Eva Lundin, Heljä-Marja Surcel
Journal: Cancer Research (2016)

Human chorionic gonadotropin (hCG) is necessary for the maintenance of early pregnancy and promotes normal breast cell differentiation. Administered hCG reduces risk of carcinogen-induced breast cancer in animal models, and higher circulating hCG concentrations were associated with significantly lower long-term risk of breast cancer in a prior nested case-control study. In this study, we investigated early-pregnancy hCG concentrations and subsequent breast cancer risk. We conducted a nested case-control study with 1,191 cases and 2,257 controls (matched on age and date at blood collection) in the Finnish Maternity Cohort, a cohort with serum samples from 98% of pregnancies registered in Finland since 1983. This study included women with a serum sample collected early (<140 days gestation) in their first pregnancy resulting in a live, term birth. Breast cancer cases were identified via the Finnish Cancer Registry. Age at breast cancer diagnosis ranged from 22 to 58 years (mean: 41 years). hCG was measured using a solid-phase competitive chemiluminescence assay. Odds ratios (OR) were calculated using conditional logistic regression. We observed no association between hCG and breast cancer risk, overall [Quartile 4 vs. 1, OR, 1.14; 95% confidence interval (CI), 0.94-1.39], by estrogen and progesterone receptor status, or by ages at first-term birth or diagnosis. Associations did not differ by time between pregnancy and diagnosis (e.g., <5 years, ORQ4 vs. Q1, 1.10; 95% CI, 0.64-1.89; ≥15 years, ORQ4 vs. Q1, 1.36; 95% CI, 0.86-2.13; pheterogeneity = 0.62). This large prospective study does not support an inverse relationship between early pregnancy serum hCG concentrations and breast cancer risk. Cancer Res; 77(1); 134-41. ©2016 AACR.
Phosphorylation of CHOP (C/EBP Homologous Protein) by the AMP-Activated Protein Kinase Alpha 1 in Macrophages Promotes CHOP Degradation and Reduces Injury-Induced Neointimal Disruption In Vivo
Authors: Xiaoyan Dai, Ye Ding, Zhaoyu Liu, Wencheng Zhang, Ming-Hui Zou
Journal: Circulation Research (2016)

Rationale: Elevated levels of CHOP (C/EBP homologous protein), a member of the C/EBP transcription factor family, in advanced atherosclerotic plaques is reported to be associated with atherosclerotic plaque rupture in humans. However, the molecular mechanism by which CHOP accumulation occurs is poorly defined. Objective: The aim of this study was to investigate if (1) macrophage AMPK (AMP-activated protein kinase) regulates cellular CHOP accumulation and (2) whole-body Ampk deletion leads to neointimal disruption. Methods and Results: In isolated or cultured macrophages, Ampkα1 deletion markedly increased apoptosis and CHOP, whereas pharmacological activation of AMPK dramatically reduced CHOP protein level via promoting CHOP degradation by proteasome. In addition, cotransfection of Chop -specific siRNA, but not control siRNA, markedly reduced apoptosis in macrophages transfected with Ampkα1 -specific siRNA. Mechanistically, AMPKα1 was found to coimmunoprecipitate with CHOP and phosphorylate CHOP at serine 30. Furthermore, serine 30 phosphorylation of CHOP triggered its ubiquitination and proteasomal degradation. In a mouse model of plaque stability, deletion of Ampkα1 but not Ampkα2 promoted injury-induced neointimal disruption. This was paralleled by increased CHOP expression and apoptosis in vivo. Finally, transfection of Chop -specific siRNA but not control siRNA reduced both CHOP level and injury-induced neointimal disruption in vivo. Conclusions: Our results indicate that AMPKα1 mediates CHOP ubiquitination and proteasomal degradation in macrophages by promoting the phosphorylation of CHOP at serine 30. We conclude that AMPKα1 might be a valid therapeutic target in preventing atherosclerotic vulnerable plaque formation.
GlycoPEGylated Filgrastim XM22 Demonstrates Dose-Dependent Activity in Comparison to Pegfilgrastim in a Dose-Escalating Study in Healthy Volunteers after Body-Weight Dependent Single Dose.
Authors: Heinz Lubenau, Rolf Pokorny, Luis Lopez-Lazaro, Peter Bias, Bruce Wallin, Walter Hinderer, Anne-Katrin Maly, Michael Seiberling
Journal: Blood (2007)
TCT-297 Percutaneous Coronary Intervention of Chronic Total Occlusions in Patients with Low Left Ventricular Ejection Fraction
Authors: Alfredo Galassi, Marouane Boukhris, None zied Belhadj, Lobna Laaroussi, Islam Ghanem, Davide Tomasello, Aurel Toma, Oliver Gaemperli, Thomas Luscher, Kambis Mashayekhi
Journal: Journal of the American College of Cardiology (2016)
Urine biomarkers of tubular injury do not improve on the clinical model predicting chronic kidney disease progression
Authors: Chi-yuan Hsu, Dawei Xie, Sushrut S. Waikar, Joseph V. Bonventre, Xiaoming Zhang, Venkata Sabbisetti, Theodore E. Mifflin, Josef Coresh, Clarissa J. Diamantidis, Jiang He, Claudia M. Lora, Edgar R. Miller, Robert G. Nelson, Akinlolu O. Ojo, Mahboob Rahman, Jeffrey R. Schelling, Francis P. Wilson, Paul L. Kimmel, Harold I. Feldman, Ramachandran S. Vasan, Kathleen D. Liu, Lawrence J. Appel, Harold I. Feldman, Alan S. Go, Jiang He, John W. Kusek, James P. Lash, Akinlolu Ojo, Mahboob Rahman, Raymond R. Townsend
Journal: Kidney International (2016)
Approaches to modernize the combination drug development paradigm
Authors: Daphne Day, Lillian L. Siu
Journal: Genome Medicine (2016)

Recent advances in genomic sequencing and omics-based capabilities are uncovering tremendous therapeutic opportunities and rapidly transforming the field of cancer medicine. Molecularly targeted agents aim to exploit key tumor-specific vulnerabilities such as oncogenic or non-oncogenic addiction and synthetic lethality. Additionally, immunotherapies targeting the host immune system are proving to be another promising and complementary approach. Owing to substantial tumor genomic and immunologic complexities, combination strategies are likely to be required to adequately disrupt intricate molecular interactions and provide meaningful long-term benefit to patients. To optimize the therapeutic success and application of combination therapies, systematic scientific discovery will need to be coupled with novel and efficient clinical trial approaches. Indeed, a paradigm shift is required to drive precision medicine forward, from the traditional “drug-centric” model of clinical development in pursuit of small incremental benefits in large heterogeneous groups of patients, to a “strategy-centric” model to provide customized transformative treatments in molecularly stratified subsets of patients or even in individual patients. Crucially, to combat the numerous challenges facing combination drug development—including our growing but incomplete understanding of tumor biology, technical and informatics limitations, and escalating financial costs—aligned goals and multidisciplinary collaboration are imperative to collectively harness knowledge and fuel continual innovation.
TCT-656 Prolong Blood Stasis on Transcatheter Aortic Valve Leaflets as a Possible Mechanism for Thrombogenesis
Authors: Koohyar Vahidkhah, Mohammad Barakat, Mostafa Abbasi, Shahnaz Javani, Peyman Azadani, Anwar Tandar, Danny Dvir, Ali Azadani
Journal: Journal of the American College of Cardiology (2016)
Autologous Stem Cell Transplantation for Multiple Myeloma in Patients over 70 Years: A Matched Comparison with Patients under 65 Years.
Authors: Shaji Kumar, Martha Lacy, Angela Dispenzieri, Suzzane Hayman, William Hogan, Luis Poratta, Michelle Elliot, Stephen Ansell, Patrick Johnston, Ivana Micallef, David Inwards, Dennis Gastineau, Mark Litzow, Morie Gertz
Journal: Blood (2005)
<i>LBH</i> Gene Transcription Regulation by the Interplay of an Enhancer Risk Allele and DNA Methylation in Rheumatoid Arthritis
Authors: Deepa Hammaker, John W. Whitaker, Keisuke Maeshima, David L. Boyle, Anna‐Karin H. Ekwall, Wei Wang, Gary S. Firestein
Journal: Arthritis & Rheumatology (2016)

Objective To identify nonobvious therapeutic targets for rheumatoid arthritis (RA), we performed an integrative analysis incorporating multiple “omics” data and the Encyclopedia of DNA Elements (ENCODE) database for potential regulatory regions. This analysis identified the limb bud and heart development ( LBH ) gene, which has risk alleles associated with RA/celiac disease and lupus, and can regulate cell proliferation in RA. We identified a novel LBH transcription enhancer with an RA risk allele (rs906868 G [Ref]/T) 6 kb upstream of the LBH gene with a differentially methylated locus. The confluence of 3 regulatory elements, rs906868, an RA differentially methylated locus, and a putative enhancer, led us to investigate their effects on LBH regulation in fibroblast‐like synoviocytes (FLS). Methods We cloned the 1.4‐kb putative enhancer with either the rs906868 Ref allele or single‐nucleotide polymorphism (SNP) variant into reporter constructs. The constructs were methylated in vitro and transfected into cultured FLS by nucleofection. Results We found that both variants increased transcription, thereby confirming the region's enhancer function. Unexpectedly, the transcriptional activity of the Ref risk allele was significantly lower than that of the SNP variant and is consistent with low LBH levels as a risk factor for aggressive FLS behavior. Using RA FLS lines with a homozygous Ref or SNP allele, we confirmed that homozygous Ref lines expressed lower LBH messenger RNA levels than did the SNP lines. Methylation significantly reduced enhancer activity for both alleles, indicating that enhancer function is dependent on its methylation status. Conclusion This study shows how the interplay between genetics and epigenetics can affect expression of LBH in RA.
TCT-51 In hospital and one month outcomes of 983 patients implanted with bioresorbable vascular scaffolds for Acute Coronary Syndroms ; subgroup of the prospective, all comers, controlled, multicenter, FRANCE ABSORB Registry.
Authors: Joel Sainsous, Jean Fajadet, None didier CARRIE, Simon Elhadad, René Koning, Hervé Le Breton
Journal: Journal of the American College of Cardiology (2016)
TCT-220 Is Inhibition of Platelet Aggregation by Endogenous Endothelial Platelet Antagonists Enhanced by Oral Ticagrelor Mediated P2Y12 Blockade in Patients With Coronary Artery Disease?
Authors: Jennifer Rossington, Angela Hoye, Benjamin Spurgeon, Konstantinos Aznaouridis, Michael Cunnington, Shouaib Qayyum, Richard Oliver, Adam Mather, Joseph John, Benjamin Davison, Raj Chelliah, Albert Alahmar, Khalid Naseem
Journal: Journal of the American College of Cardiology (2016)