tbuckley/cabot-search huggingface dataset:
Potential Mortality Reduction With Optimal Implementation of Angiotensin Receptor Neprilysin Inhibitor Therapy in Heart Failure
Authors: Gregg C. Fonarow, Adrian F. Hernandez, Scott D. Solomon, Clyde W. Yancy
Journal: JAMA Cardiology (2016)

Angiotensin receptor neprilysin inhibition (ARNI) therapy provided incremental survival benefit to patients with heart failure and reduced ejection fraction (HFrEF) in clinical trials. To date, estimation of the potential benefits that could be gained from optimal implementation of ARNI therapy at the population level have not been quantified.To quantify the projected gains for deaths prevented or postponed with comprehensive implementation of ARNI therapy for patients with HFrEF in the United States.Eligibility criteria for ARNI therapy, population-based estimates of patients with HFrEF in the United States, and numbers needed to treat to overt death were obtained from published sources. The potential numbers of deaths prevented or postponed as a result of ARNI were estimated along with multiple-way sensitivity analysis.All-cause mortality.Of 2 736 000 patients with HFrEF patients in the United States, 2 287 296 (84%) were projected to be candidates for ARNI therapy. Optimal implementation of ARNI therapy was empirically estimated to prevent 28 484 deaths a year (range, 18 230-41 017 deaths per year).A substantial number of deaths in the United States could potentially be prevented by optimal implementation of ARNI therapy. These data support implementation of evidence into practice in a timely manner because this may have a material impact on population health among patients with HFrEF.
PO15DECREASED EXPRESSION OF THE MITOCHONDRIAL BCAT PROTEIN CORRELATES WITH IMPROVED PATIENT SURVIVAL IN IDH WILD-TYPE GLIOMAS
Authors: M.E. Conway, J. Hull, M. El Hindy, S.C. Taylor, F. El Amraoui, C. Paton-Thomas, P. White, M. Williams, H.R. Haynes, B.S.M. Hutson, K.M. Kurian
Journal: Neuro-Oncology (2015)

INTRODUCTION: Recent studies indicated that the human cytosolic branched chain aminotransferase protein (hBCATc), which metabolises the branched chain amino acids (BCAA), was significantly upregulated in IDH1/2 wild type (WT) glioblastomas and is associated with a worse prognosis compared with IDH mutant gliomas. The diagnostic and prognostic significance of markers of BCAA metabolism is currently under investigation. METHOD: 64 glioma tumour samples were compared for hBCATc, hBCATm and BCKDC expression using western blotting and IHC. DNA was extracted from fresh frozen tissue. Sanger sequencing of the p.Arg132 region of IDH1 and p.Arg172 region of IDH2 was undertaken. RESULTS: In IDH WT tumours, like hBCATc (p = 0.007), the mitochondrial isoform (hBCATm) is significantly (p = 0.036) expressed relative to IDH mutant gliomas. hBCATm additionally shows a more significant correlation with patient survival than hBCATc. In IDH WT tumours, low hBCATm expression is a positive prognostic factor (p = 0.003). hBCATm expression also correlated with WHO grade. Although previous reports indicate that increased hBCATc occurs exclusively in IDH-WT tumours, our studies demonstrate that 30% of IDH mutant tumours express hBCATc. Although hBCATc alone has been suggested as a putative therapeutic target, it is important to evaluate the expression of hBCATm as its expression may impact the efficacy of new treatments targeting hBCATc. CONCLUSION: IDH WT high grade gliomas traditionally have a poor prognosis. However we demonstrate for the first time that relatively low hBCATm may select for a better performing clinical cohort and may be a possible candidate target for drug therapy.
Targeting Epstein-Barr virus–transformed B lymphoblastoid cells using antibodies with T-cell receptor–like specificities
Authors: Junyun Lai, Wei Jian Tan, Chien Tei Too, Joanna Ai Ling Choo, Lan Hiong Wong, Fatimah Bte Mustafa, Nalini Srinivasan, Angeline Pei Chiew Lim, Youjia Zhong, Nicholas R. J. Gascoigne, Brendon J. Hanson, Soh Ha Chan, Jianzhu Chen, Paul A. MacAry
Journal: Blood (2016)
Biomonitoring in the Era of the Exposome
Authors: Kristine K. Dennis, Elizabeth Marder, David M. Balshaw, Yuxia Cui, Michael A. Lynes, Gary J. Patti, Stephen M. Rappaport, Daniel T. Shaughnessy, Martine Vrijheid, Dana Boyd Barr
Journal: Environmental Health Perspectives (2016)

The term "exposome" was coined in 2005 to underscore the importance of the environment to human health and to bring research efforts in line with those on the human genome. The ability to characterize environmental exposures through biomonitoring is key to exposome research efforts.Our objectives were to describe why traditional and nontraditional (exposomic) biomonitoring are both critical in studies aiming to capture the exposome and to make recommendations on how to transition exposure research toward exposomic approaches. We describe the biomonitoring needs of exposome research and approaches and recommendations that will help fill the gaps in the current science.Traditional and exposomic biomonitoring approaches have key advantages and disadvantages for assessing exposure. Exposomic approaches differ from traditional biomonitoring methods in that they can include all exposures of potential health significance, whether from endogenous or exogenous sources. Issues of sample availability and quality, identification of unknown analytes, capture of nonpersistent chemicals, integration of methods, and statistical assessment of increasingly complex data sets remain challenges that must continue to be addressed.To understand the complexity of exposures faced throughout the lifespan, both traditional and nontraditional biomonitoring methods should be used. Through hybrid approaches and the integration of emerging techniques, biomonitoring strategies can be maximized in research to define the exposome.
Preoperative Parameters Related to the Improvement of Semen Characteristics after Surgical Repair of Varicocele in Subfertile Men
Authors: E. Koh, N. Kondoh, M. Takeyama, M. Nakamura, M. Namiki, H. Fujioka, M. Matsuda, A. Okuyama, H. Fujisue, T. Matsui, Y. Doi
Journal: European Urology (1988)
The Bon Secours St. Francis Cancer Survivorship Program: A model for community-based multidisciplinary survivorship care.
Authors: Kaitlin Bomar, Nicole Vickery, Meagan Duggan, Tina Redenz, Tracey Lukker, Kristin Jensen, Eugene Paciarelli, Terra Dillard, Robert D. Siegel, Hal E. Crosswell
Journal: Journal of Clinical Oncology (2016)

45 Background: In 1974, Giulio D' Angio,MD, stated “Cure Is Not Enough” and the concept of Survivorship was ignited. Multidisciplinary survivorship clinics have since become a mainstay of many pediatric cancer programs; few such clinics exist in adult cancer programs, especially in community practice. We report on the development of a survivorship care plan and a community-based clinic designed to provide guideline-driven after care for cancer survivors. Methods: An overview of the vision and mission of the Bone Secours St. Francis Cancer Center Survivorship Program is provided. Descriptive analysis of the components and metrics of success are provided, in the context of accrediting organizations requirements for current and future goals for survivorship care. Results: BSSF, which is a non-academic, community-based cancer program, and receives over 1300 referrals annually from a referral population of 1.32 million in 10 counties. St. Francis , accredited by both the Commission on Cancer and National Accreditation Program for Breast Centers, has been providing cancer‐related services to the Upstate South Carolina region for a decade. The survivorship program at St. Francis is a STAR‐certified program and is a patient‐centered service provided in a comprehensive and coordinated multidisciplinary team approach, including integrated psychologic care. A custom survivorship care plan was developed and efforts, including successes and barriers, to implementation of plans for all cancer survivors in accordance with CoC and NAPBC goals are addressed. Conclusions: The BSSF Cancer Center Survivorship Program has developed a practical, yet comprehensive SCP, which is risk-adapted and guideline-driven in order to provide customized survivorship education and monitoring. The MDC provides comprehensive evaluations and recommendations in order to maximize health and well-being of patients navigating life after cancer diagnosis and treatment. Our efforts have demonstrated that survivorship clinics of this nature can be established and successful in a non-academic community setting.
Hospitalization After a Return Visit to the Emergency Department—Reply
Authors: Amber K. Sabbatini, Anirban Basu, Renee Y. Hsia
Journal: JAMA (2016)

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Abstract 12630: Cardiovascular Safety of Liraglutide: Pooled Analysis of Major Adverse Cardiovascular Events across Weight Management and Type 2 Diabetes Development Programs
Authors: Ian D Caterson, Stephen C Bain, Jorge Gross, John House, Adam C Salisbury, Florian M Baeres, Morten Donsmark, Steven P Marso
Journal: Circulation (2015)

The cardiovascular safety of liraglutide in individuals with overweight/obesity and those with type 2 diabetes (T2D) is unknown. A meta-analysis of five phase II/III liraglutide (dose up to 3.0 mg) weight management (WM) trials was performed. Additional sensitivity meta-analyses of 21 liraglutide T2D trials (dose up to 1.8 mg) and a pre-specified pooled analysis of all WM and T2D trials (27 trials; WM+T2D) were also conducted. The primary endpoint was first occurrence of adjudicated major adverse cardiovascular events (MACE) (non-fatal myocardial infarction, non-fatal stroke or cardiovascular death) with liraglutide (any dose) or pooled total comparator (placebo, active) and analysis was using a Cox proportional hazards model stratified by trial. Prospective adjudication (blinded, independent) was implemented in three of the WM trials; post-hoc adjudication was conducted for all other trials. For WM trials, the observation period was from the first drug dose to the last drug dose plus a 30-day follow-up; for the SCALE Obesity and Prediabetes trial, data to October 1, 2014 were included. For WM trials (liraglutide: n=3,872; comparator: n=2,036), baseline characteristics were: 71% women; history of CV disease, 9%; mean age, 47 yrs; mean BMI, 38 kg/m 2 . For T2D trials (liraglutide: n=5,511; comparator: n=2,748): 43% women; history of CV disease, 13%; mean age, 56 yrs; mean BMI, 30 kg/m 2 . In WM trials (n=20 events), the hazard ratio (HR) [95% confidence interval (CI)] for MACE (liraglutide/comparator) was 0.45 [0.18; 1.10] (Figure 1A). In T2D trials (n=49 events), the HR was 0.64 [0.35, 1.15] (Figure 1A). For the WM+T2D analysis (n=69 events), the HR was 0.57 [0.35, 0.94] (Figure 1B). In a pooled analysis of WM+T2D trials, MACE was significantly lower in patients treated with liraglutide. The dedicated cardiovascular outcomes trial, LEADER, will provide further insights into the cardiovascular safety of liraglutide.
Study on the comparability of 6 versus 12 cycles of adjuvant cyclophosphamide, methotrexate, and fluorouracil.
Authors: L F Diehl, D J Perry, D B Tang
Journal: Journal of Clinical Oncology (1983)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1983.1.10.663 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 6689422 Study on the comparability of 6 versus 12 cycles of adjuvant cyclophosphamide, methotrexate, and fluorouracil. L F DiehlxL F DiehlSearch for articles by this author , D J PerryxD J PerrySearch for articles by this author , D B TangxD B TangSearch for articles by this author https://doi.org/10.1200/JCO.1983.1.10.663 PDF "Study on the comparability of 6 versus 12 cycles of adjuvant cyclophosphamide, methotrexate, and fluorouracil.." Journal of Clinical Oncology, 1(10), pp. 663–664© 1983 by American Society of Clinical Oncology
Response to Comment on Mita et al. Sitagliptin Attenuates the Progression of Carotid Intima-Media Thickening in Insulin-Treated Patients With Type 2 Diabetes: The Sitagliptin Preventive Study of Intima-Media Thickness Evaluation (SPIKE): A Randomized Controlled Trial. Diabetes Care 2016;39:455–464
Authors: Tomoya Mita, Naoto Katakami, Iichiro Shimomura, Hirotaka Watada
Journal: Diabetes Care (2016)

We appreciate the thoughtful comments raised by Maiorino et al. (1) on our recent articles on attenuation of progression of carotid intima-media thickness (IMT) by dipeptidyl peptidase 4 inhibitors in patients with type 2 diabetes mellitus (T2DM) free of apparent cardiovascular disease (CVD), the SPIKE and SPEAD-A studies (the Sitagliptin Preventive Study of Intima-Media Thickness Evaluation and the Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis, respectively) (2,3). As pointed out by Maiorino et al., comparison of baseline data of the two studies showed that carotid artery IMT at baseline was not …
False-positive blood pooling adjacent to hepatic malignant fibrous histiocytoma on Tc-99m RBC liver SPECT.
Authors: Seok Tae Lim, Myung-Hee Sohn, Jae-Yong Kwak, Chang-Yeol Yim
Journal: Clinical Nuclear Medicine (2002)

SEOK, TAE LIM M.D.; MYUNG-HEE, SOHN M.D.; JAE-YONG, KWAK M.D.; CHANG-YEOL, YIM M.D. Author Information
Targeting hyaluronan (HA) in tumor stroma: Interim safety and translational evaluation of pegylated hyaluronidase (PEGPH20) in patients (pts) with advanced solid tumors—A focus on gastrointestinal malignancies.
Authors: Jeffrey R. Infante, Ramesh K. Ramanathan, Mitesh J. Borad, Lee S. Rosen, Ronald Korn, Samuel Simon Dychter, Harold Michael Shepard, Daniel C. Maneval, Ping Jiang, Deborah Carson, Daniel D. Von Hoff, Gregory Ian Frost
Journal: Journal of Clinical Oncology (2012)

249 Background: HA, a glycosaminoglycan in the tumor matrix, accumulates in 20-30% of solid tumors and ≥28%, ≥42% and ≥87% of colon, gastric and pancreatic ductal adenocarcinoma (PDA) tumors, respectively. Tumors that accumulate HA can develop high interstitial fluid pressure (IFP) and are resistant to chemotherapy. HA in human PDA is associated with disease progression and poor prognosis. In animal models, PEGPH20 reduced tumor-associated HA, tumor IFP and tumor growth, and increased efficacy of chemotherapy. Pharmacodynamic (PD) activity of PEGPH20 is being evaluated in Phase 1 (Ph1) trials. Methods: Two Ph1 studies in pts with advanced solid tumors refractory to prior therapy examined the safety, tolerability, PK, PD and MTD of single-agent IV PEGPH20. Dosing in Study 1 was 2x/wk and then reduced to q21d and in Study 2 is 1-2x/wk x 4wks and 1x/wk thereafter with dexamethasone pre-medication regimen. Biomarkers evaluated: Histochemistry to detect depletion of tumor HA, serum HA catabolites, Dynamic Contrast Enhanced (DCE)-MRI and FDG-PET. Results: In Study 1, the first 3 pts demonstrated musculoskeletal events (MSE; 2 pts dosed with 50 µg/kg 2x/wk, severe; 1 pt dosed with 0.5µg/kg 2x/wk, moderate) not predicted from GLP safety studies. The frequency of drug administration was reduced to q21d and the next 10 pts tolerated ≤1.5 µg/kg. In Study 2, dexamethasone pre-medication regimen was evaluated while dosing at 1-2x/wk. Nine pts were dosed ≤5.0 µg/kg. Doses ≤3.0 µg/kg administered 2x/wk were tolerated with intermittent Grade 1-2 MSE. Activity of PEGPH20 was reflected by increased HA serum catabolites. Pre- and post-dose biopsies from 2 colon pts demonstrated a 23-60% reduction in tumor HA after 4 wks of PEGPH20 dosing. DCE-MRI of PDA and FDG-PET of lung metastases increased tumor perfusion (K trans ) and decreased metabolic activity 8 and 24hrs post-PEGPH20 dose and was still apparent after 4 wks of treatment with PEGPH20. Conclusions: Ongoing Ph1 studies have shown in vivo activity of PEGPH20 through HA plasma catabolites, tumor HA depletion, DCE-MRI and FDG-PET.
A New Multinational Observational Study In Multiple Myeloma: Initial Report Of The PREAMBLE Study
Authors: Ravi Vij, Mehdi M. Moezi, Robin Foà, Gordon Cook, Antonio Palumbo, Hakan Kaya, Brian Durie, David Cella, Lieven Annemans, Yun Su, Pralay Mukhopadhyay, Trong K. Le, Maria Teresa Petrucci
Journal: Blood (2013)
Clinicopathologic features of lung cancer patients harboring de novo <i>EGFR </i>T790M mutation.
Authors: Young Joo Lee, Geon Kook Lee, Yeon-Su Lee
Journal: Journal of Clinical Oncology (2014)

8075 Background: EGFR T790M mutation drives acquired drug resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI) in lung cancer harboring sensitive EGFR mutations. However, several studies reported the preexistence of this resistant mutation before EGFR-TKI exposure is not rare event when identified by more sensitive sequencing methods. This study aimed to evaluate clinicopathological features of lung cancer with de novo EGFRT790M mutations. Methods: We collected pretreatment tissues from 124 advanced non-small cell lung cancer patients with sensitizing EGFR mutations (exon 19 deletion and exon 21 L858R) that had been detected by direct sequencing at our institute between January 2009 and August 2011. Genotyping for EGFRT790M mutation was further performed using matrix-assisted laser desorption/ionization-time of flight/mass spectrometry. Results: The T790M mutation was found in 31 (25.0%) patients. The patients with T790M-positive tumor had shorter time to progression (TTP) after EGFR-TKI than those with T790M-negative tumor (median 6.3 months vs. 11.5 months; P < 0.001). The T790M mutation frequency at which the risk of progression to EGFR-TKI begins to increase was estimated to be 3.2%. The T790M-positive group harboring ≥3.2% of T790M (n= 24) had higher proportion of never smoker (83% vs 62%; P = 0.047), EGFR exon 21 L858R mutation (75% vs 25%; P = 0.051), and ≥3 of metastatic organ (71% vs 50%; P = 0.066) compared to the opposite group (n= 100). However, there was no significant difference in age, gender, histology, stage, and anatomical location. Peak SUV value of tissue sample sites on PET scan was not different between two groups (6.0 vs 7.9; P = 0.317). In terms of chemotherapy response, there was no difference in response to platinum (20% vs 33%; P = 0.529) and pemetrexed (10% vs 21%; P = 0.470) but taxane (33% vs 7%; P = 0.057). In the T790M-positive group, first-line EGFR-TKI users did not show longer TTP than second-line or more EGFR-TKI users (median 6.0 months vs. 3.9 months; P = 0.197). Conclusions: Lung cancer patients with 3.2% or more of de novo T790M mutation frequency showed decreased efficacy to EGFR-TKI. De novo T790M mutation are significantly associated with never smoking history and EGFR exon 21 L858R mutations.
A Cell-Penetrating Peptide Targeting AAC-11 Specifically Induces Cancer Cells Death
Authors: Léonard Jagot-Lacoussiere, Ewa Kotula, Bruno O. Villoutreix, Heriberto Bruzzoni-Giovanelli, Jean-Luc Poyet
Journal: Cancer Research (2016)

Abstract AAC-11 is an antiapoptotic protein that is upregulated in most cancer cells. Increased expression of AAC-11 confers a survival advantage when cancer cells are challenged with various stresses and contributes to tumor invasion and metastases, whereas its deregulation reduces resistance to chemotherapeutic drugs. The antiapoptotic effect of AAC-11 may be clinically relevant as its expression correlates with poor prognosis in several human cancers. Thus, inactivation of AAC-11 might constitute an attractive approach for developing cancer therapeutics. We have developed an AAC-11–derived cell-penetrating peptide, herein named RT53, mimicking in part the heptad leucine repeat region of AAC-11, which functions as a protein–protein interaction module, and that can prevent AAC-11 antiapoptotic properties. In this study, we investigated the anticancer effects of RT53. Our results indicate that RT53 selectively kills cancer cells while sparing normal cells. RT53 selectively inserts into the membranes of cancer cells, where it adopts a punctate distribution and induces membranolysis and release of danger-associated molecular pattern molecules. Systemic administration of RT53 inhibited the growth of preexisting BRAF wild-type and V600E mutant melanoma xenograft tumors through induction of apoptosis and necrosis. Toxicological studies revealed that repetitive injections of RT53 did not produce significant toxicity. Finally, RT53-killed B16F10 cells induced tumor growth inhibition in immunocompetent mice following a rechallenge with live cancer cells of the same type. Collectively, our data demonstrate that RT53 possesses tumor-inhibitory activity with no toxicity in mice, suggesting its potential as a therapeutic agent for the treatment of melanoma and probably other cancers. Cancer Res; 76(18); 5479–90. ©2016 AACR.
A Phase II Trial Of Bortezomib-Rituximab Followed By Autologous Stem Cell Harvest (SCH) and Cladribine-Cyclophosphamide-Rituximab (2CdA-Cy-Rit) Consolidation As Primary Therapy Of Waldenström's Macroglobulinemia (WM)
Authors: Sheeba K. Thomas, Tamara M Haygood, Muzaffar H. Qazilbash, A. Georgina Melendez, Roxana Galvis, Kay B Delasalle, Lei Feng, Tiffany A. Richards, Felipe Samaniego, Luhua Wang, Jatin J. Shah, Robert Z. Orlowski, Donna M. Weber
Journal: Blood (2013)