tbuckley/cabot-search huggingface dataset:
Abstract 13339: Biomarkers Release After Percutaneous Coronary Intervention in Patients Without Definitive Miocardial Infarction Assessed by Cardiac Magnetic Ressonance With Late Gadolinium Enhancement. a Prospective Trial Using the Third Universal Definition of Myocardial Infarction
Authors: Rodrigo M Vieira de Melo, Fernando T Oikawa, Leandro M Costa, Paulo C Rezende, Thiago L Scudeler, Cesar H Nomura, Alexandre V Villa, Alexandre C Hueb, Whady Hueb, Roberto Kalil Filho
Journal: Circulation (2014)

Introduction:  Biomarker release after percutaneous coronary intervention (PCI) is a common phenomenon. However, the correlation between the release and the diagnosis of type 4a myocardial infarction (MI) has generated considerable controversy, especially after the emergence of high-sensitive cardiac troponin (cTn) assays. We aim to evaluate the amount and pattern of cardiac biomarkers release after elective PCI in patients without the presence of late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR) after the procedure, and interpret these findings based on the third Task Force definitions for MI.   Methods:  In this prospective study, we evaluated stable multivessel coronary artery disease patients with preserved ventricular function and formal indication to PCI. CMR with LGE was performed in all patients before and after interventions. Measurements of cTn and creatine kinase (CK)-MB were performed systematically before and after the procedure, every 6 hours until 48h. Patients with a new LGE on the post procedure CMR were excluded. The release of troponin and CK-MB for diagnosis of procedure-related MI was defined as up to 5 times the 99 th  percentile.   Results:  62 patients completed this study. Of this, 07 (11.3%) were excluded because of the presence of a new LGE on the post procedure CMR. The 55 patients without a CMR-defined infarction were predominantly male 44 (65.7%), with a mean age of 61.2 (±12.6) years and Syntax score of 19.1 (±7.0). Despite the absence of a new LGE on post procedure CMR, 31 (56.4%) patients had a cTn peak higher than 5 times the 99 th  percentile, while only 1 (1.8%) patient had a CK-MB peak higher than 5 times the 99 th  percentile. The mean of cTn peak release was 1.06ng/dL (±1.67) that is 26.5 times higher the 99 th  percentile, with a maximum of 6.02ng/mL. The mean of CK-MB peak release was 4.78ng/dL (±5.5) that is 1.08 times higher the 99 th  percentile, with a maximum of 30.3ng/mL.   Conclusion:  Post-PCI elevation of high-sensitive cTn higher than currently cut-off recommendations occurred frequently, without evidence of CMR-defined infarction. We suggest that the cTn threshold to define type 4a MI should be much higher than the CK-MB. Until than, CK-MB should represent the marker of choice to detect post-PCI myocardial necrosis.
Noncanonical Wnt signaling promotes apoptosis in thymocyte development
Authors: Huiling Liang, Andrew H. Coles, Zhiqing Zhu, Jennifer Zayas, Roland Jurecic, Joonsoo Kang, Stephen N. Jones
Journal: The Journal of Experimental Medicine (2007)

The Wnt–β-catenin signaling pathway has been shown to govern T cell development by regulating the growth and survival of progenitor T cells and immature thymocytes. We explore the role of noncanonical, Wnt–Ca2+ signaling in fetal T cell development by analyzing mice deficient for Wnt5a. Our findings reveal that Wnt5a produced in the thymic stromal epithelium does not alter the development of progenitor thymocytes, but regulates the survival of αβ lineage thymocytes. Loss of Wnt5a down-regulates Bax expression, promotes Bcl-2 expression, and inhibits apoptosis of CD4+CD8+ thymocytes, whereas exogenous Wnt5a increases apoptosis of fetal thymocytes in culture. Furthermore, Wnt5a overexpression increases apoptosis in T cells in vitro and increases protein kinase C (PKC) and calmodulin-dependent kinase II (CamKII) activity while inhibiting β-catenin expression and activity. Conversely, Wnt5a deficiency results in the inhibition of PKC activation, decreased CamKII activity, and elevation of β-catenin amounts in thymocytes. These results indicate that Wnt5a induction of the noncanonical Wnt–Ca2+ pathway alters canonical Wnt signaling and is critical for normal T cell development.
Molecular engineering of high affinity single-chain antibody fragment for endothelial targeting of proteins and nanocarriers in rodents and humans
Authors: Colin F. Greineder, Elizabeth D. Hood, Anning Yao, Makan Khoshnejad, Jake S. Brenner, Ian H. Johnston, Mortimer Poncz, Claudia Gottstein, Vladimir R. Muzykantov
Journal: Journal of Controlled Release (2016)
Brief Communication: Tumor Suppression by a Lymphokine Released Into the Circulation of Mice With Delayed Hypersensitivity 2
Authors: S. B. Salvin, J. S. Youngner, Jane Nishio, Ruth Neta
Journal: JNCI Journal of the National Cancer Institute (1975)

Lymphokines such as migration inhibitory factor and type II interferon were released into the circulation of tuberculin-sensitive mice after iv injection of old tuberculin. Daily administration of such sera into the tumor sites of mice given implants of sarcoma MC-36 markedly suppressed tumor growth.
Abstract 11317: Outcomes of Atrial Arrhythmia Surgery for Atrial Tachyarrhythmias in Patients With Repaired Tetralogy of Fallot
Authors: Jiwoon Chang, Sajan Patel, Tristan R Grogan, Jamil A Aboulhosn
Journal: Circulation (2014)

Background: Atrial tachyarrhythmia is common in adults with tetralogy of Fallot (TOF) due to surgical scarring from repairs and atrial enlargement. The maze procedure refers to surgical ablation within the right atrium to disrupt arrhythmogenic circuits and is sometimes performed concomitantly during reoperation on repaired TOF patients. Our study aims to evaluate the effectiveness of maze in TOF patients. Methods: We performed a retrospective chart review that identified 30 TOF patients who underwent a pulmonary valve replacement (PVR) with maze and 38 TOF patients who underwent a PVR without maze from 1994 to 2011 and had at least 2 years of post-surgical follow-up at the Ahmanson/UCLA Adult Congenital Heart Disease Center. Preoperative and postoperative arrhythmia status and management were compared in maze and non-maze groups. Results: Before the procedure, the most common pre-operative arrhythmias in the maze group were a history of atrial fibrillation (AFib)(n=16), atrial flutter (AFL)(n=10), and other supraventricular tachycardia (SVT)(n=6). Isolated right atrial maze was performed in 26 patients, and combined right and left atrial maze-cox procedure was performed in 4 patients. Of the 16 patients in the maze group with pre-op Afib, 6 had recurrent Afib within the first 2 years of follow-up (62.5% relative reduction, p=0.012). Of the 10 patients with pre-op AFL, only 1 had recurrence (90% relative reduction, p=0.012). Of the 6 patients with pre-op SVT, 4 had recurrence (33.3% relative reduction, p=0.727). There was no significant arrhythmia status change in the non-maze group at 2 years. Comparing patients with and without maze, the average cardiopulmonary bypass times were 155 minutes and 97 minutes, respectively (p=0.064), and aortic cross clamp times were 122 minutes and 64 minutes, respectively (p=0.004). On average, patients with maze spent 3.7 more days in the hospital compared to those without maze (p=0.001). Conclusions: Performing a concomitant maze procedure in patients undergoing TOF repair was associated with a moderate improvement in atrial tachyarrhythmia burden over 2 years. TOF patients who had the concomitant maze procedure required longer cardiopulmonary bypass time, aortic cross clamp time, and total hospital stay.
Higher specialist urology trainees’ opinions on preparation for the consultant role
Authors: P. Cleaveland, A. Parnham, V. Tang, Z. Ali, S. Brown
Journal: International Journal of Surgery (2015)

Introduction:Trainees are objectively assessed during their surgical training rotations in order to be awarded the certificate of completion of training, thereby allowing independent consultant practice. Our study looks at senior trainees’ opinions on UK urology training in preparation to becoming a consultant.Patients and methods:A questionnaire was sent to UK senior urology trainees ST 6 or above and new consultants. Parameters including demographics, qualifications, sub-specialist interests and questions related to the candidates’ perceived readiness to carry out a range of activities as a consultant were recorded.Results:Twenty-eight candidates completed the questionnaire. All trainees thought the FRCS exam covered topics useful for consultant practice. The majority of respondents felt comfortable dealing with emergencies, general urological procedures and managing research/audit (85%, 96% and 90%, respectively). However, a number of respondents felt unprepared for educational and leadership/managemen...
Letter by Lavine Regarding Article, “Cardiovascular, Bleeding, and Mortality Risks in Elderly Medicare Patients Treated With Dabigatran or Warfarin for Nonvalvular Atrial Fibrillation”
Authors: Jay B. Lavine
Journal: Circulation (2015)

To the Editor:Studies comparing the risks of warfarin versus other oral anticoagulant therapy for the treatment of nonvalvular atrial fibrillation, such as the recently published study by Graham et al, 1 generally have not controlled for dietary change in patients undergoing warfarin therapy.Most such patients are advised to eliminate dark, leafy green vegetables from their diets or at least limit their consumption to 1 serving per day, inappropriately so, because the only necessity is to ensure consistency in the number of servings consumed per day.Dark, leafy greens, whose phytochemicals manifest an array of vascular protective properties, are a staple of a healthful diet.Eliminating them from the diets of patients undergoing warfarin therapy may prejudice the results, not only of observational studies, but also of clinical trials.Adjusting for this possible confounding factor should be strongly considered in future studies.
Epigenomic analysis detects aberrant super-enhancer DNA methylation in human cancer
Authors: Holger Heyn, Enrique Vidal, Humberto J. Ferreira, Miguel Vizoso, Sergi Sayols, Antonio Gomez, Sebastian Moran, Raquel Boque-Sastre, Sonia Guil, Anna Martinez-Cardus, Charles Y. Lin, Romina Royo, Jose V. Sanchez-Mut, Ramon Martinez, Marta Gut, David Torrents, Modesto Orozco, Ivo Gut, Richard A. Young, Manel Esteller
Journal: Genome biology (2016)

One of the hallmarks of cancer is the disruption of gene expression patterns. Many molecular lesions contribute to this phenotype, and the importance of aberrant DNA methylation profiles is increasingly recognized. Much of the research effort in this area has examined proximal promoter regions and epigenetic alterations at other loci are not well characterized. Using whole genome bisulfite sequencing to examine uncharted regions of the epigenome, we identify a type of far-reaching DNA methylation alteration in cancer cells of the distal regulatory sequences described as super-enhancers. Human tumors undergo a shift in super-enhancer DNA methylation profiles that is associated with the transcriptional silencing or the overactivation of the corresponding target genes. Intriguingly, we observe locally active fractions of super-enhancers detectable through hypomethylated regions that suggest spatial variability within the large enhancer clusters. Functionally, the DNA methylomes obtained suggest that transcription factors contribute to this local activity of super-enhancers and that trans-acting factors modulate DNA methylation profiles with impact on transforming processes during carcinogenesis. We develop an extensive catalogue of human DNA methylomes at base resolution to better understand the regulatory functions of DNA methylation beyond those of proximal promoter gene regions. CpG methylation status in normal cells points to locally active regulatory sites at super-enhancers, which are targeted by specific aberrant DNA methylation events in cancer, with putative effects on the expression of downstream genes.
Inhibition of the Heat Shock Protein 90 (Hsp90) chaperone with the novel agent IPI-504 to overcome resistance to tyrosine kinase inhibitors (TKIs) in metastatic GIST: Updated results of a phase I trial
Authors: G. D. Demetri, S. George, J. A. Morgan, A. Wagner, M. T. Quigley, K. Polson, J. Pokela, A. van den Abbeele, J. Adams, D. Grayzel
Journal: Journal of Clinical Oncology (2007)

10024 Background: Prior work from our team demonstrates that inhibition of the Hsp90 chaperone protein results in preferential destruction of the mutated KIT kinase in human GIST cell lines regardless of TKI-resistance mutations. To translate this into clinical application, we are conducting a phase I trial of IPI-504, a novel Hsp90 inhibitor, for patients (pts) with metastatic TKI-resistant GIST. Methods: Pts with metastatic TKI-resistant GIST were eligible to enter and receive IPI-504, IV in 250 cc of normal saline over 30 mins, on days 1, 4, 8 and 11 of a 21 day cycle. Serial monitoring with 18 FDG-PET/CT imaging at baseline, day 11, and day 21, as well as PK profiling of IPI- 504 and its major active metabolites (17-AAG and 17-AG), were performed on all pts. Results: 21 pts with progressive GIST after both prior imatinib and sunitinib have been entered at 5 dose levels (90 mg/m 2 IPI-504 [n=6], 150 [3], 225 [3], 300 [3], 400 [6]); 18 are now evaluable. The maximal tolerated dose has not been reached, and enrollment is ongoing. AEs possibly related to IPI-504 include Grade 1–2 elevation of alkaline phosphatase, fatigue, and headache; one DLT was observed in the 1 st and 5 th dose levels. PET demonstrated decreases in tumor FDG avidity in 1/6 pts, 1/3, 3/3, 1/3, and 2/3 at the respective dose levels in this schedule (3 patients were inevaluable by PET). Reactivation of tumor FDG uptake by PET was seen during the planned 10-day breaks in IPI-504 administration with reinduction of decreased tumor FDG avidity upon re-treatment with IPI-504. Although no RECIST-defined “anatomic responses” were noted, stable disease has allowed 7 pts to continue on study treatment for ≥ 4 cycles. Conclusions: Targeting Hsp90 is a novel therapeutic strategy in TKI-resistant GIST. IPI-504 has been well-tolerated overall, and the activity seen with decreased FDG avidity of GIST lesions, as well as the induction of SD in pts with documented prior progression, is promising with this non-TKI agent. Reactivation of PET signal in lesions during breaks in IPI-504 dosing is similar to flares with TKI discontinuation. To address this, a new schedule of continuous BIW dosing of IPI-504 has been added to optimize drug exposure. No significant financial relationships to disclose.
Doxorubicin-loaded nanoparticles consisted of cationic- and mannose-modified-albumins for dual-targeting in brain tumors
Authors: Hyeong Jun Byeon, Le Quang Thao, Seunghyun Lee, Sun Young Min, Eun Seong Lee, Beom Soo Shin, Han-Gon Choi, Yu Seok Youn
Journal: Journal of Controlled Release (2016)
Preliminary report of the mutation status of KRAS and BRAF-V600E in an Argentinean population of primary colorectal tumors
Authors: F. Perazzo, V. Denninghoff, G. Pasccon, M. G. Pallotta, M. Tatangelo, V. Cuartero, R. Kirchuck, M. Chacón, L. Gennari, K. Vera, A. Avagnina
Journal: Journal of Clinical Oncology (2009)

e22183 Background: Several studies have suggested that KRAS somatic mutations predict resistance to Cetuximab treatment in colorectal cancers. The aim of this report is to present the mutational status of KRAS, BRAF and epidemiological data of an Argentinean population of CR tumors which may have future clinical practice implications. Methods: Patients were prospectively selected from the databases of 8 Argentinean public and private hospitals with colorectal cancer between January and December 2008. We analyzed the presence of KRAS point mutations in codons 12 and 13, and the BRAF-V600E from formalin fixed sections with Polymerase Chain Reaction (PCR) amplification-sequencing. Results: A total of 146 patients, 41.8% (61) F and 57.2% (85) M, with a median age of 58.1 years (range, 17–88), 45.2% (66) were current smokers, 50% (73) never smoke. 41.4% (60) have family history of cancer and 9.6% (14) have personal history of a previous tumor. 63.2% were European Caucasian, 30.3% American Caucasian and 0.7% of Asian origin. The media BMI was 25.9 (range, 16- 47). The primary tumor site was 21.9% (32) right colon, 5.5% (8) transverse colon, 45.2% (66) left colon and 27.4%(40) rectal cancer. Adenocarcinoma was the unique histotype and mucinous differentiation was observed in 14.7% (21). The Pathological Stage at diagnosis was Stage I 3.42% (5), II 24% (35), III 33.6% (49) and IV 39% (57). 60.3% (88) where found to be wild type, while the other 39.7% (58) showed the KRAS mutation in the following amino acids: GLY12ALA 5.2% (3), GLY12ASP 25.9% (15), GLY12CYS 3.4% (2), GLY12SER 1.7% (1), GLY12VAL 62.1 % (36), GLY13ARG 1.7% (1). We analyzed in 49 patients the mutational status of BRAF-V600E, only 2 patients showed the presence of both mutations, 23 presented BRAF and KRAS wild type, 20 had a KRAS mutation while the BRAF was wild type, only 4 patients reveled a mutation of BRAF in the presence of a KRAS wild type. Conclusions: This is the first Argentinean collaborative study of the mutational status of KRAS and BRAF. Our preliminary report based in 146 patients, revealed similar mutational KRAS results in codon 12 and 13 than the reports of Europe. This is probably due to the ethnic origin of Argentinean population. No significant financial relationships to disclose.
Abstract P4-06-03: Targeting the insulin receptor with a small peptide (S961) in cancer
Authors: Kelly LaPara, Douglas Yee
Journal: Cancer Research (2015)

Abstract The insulin-like growth factor (IGF)/insulin receptors are members of the superfamily of growth factor receptor tyrosine kinases. The insulin and type I IGF-I receptors (IGF-1R) have very similar structure and share high homology (∼84%) in the kinase domain. Their dimeric structure allows for the formation of either holo or hybrid receptors. Thus, targeting of any individual receptor has been a challenge. We have previously shown that the insulin receptor is expressed in tamoxifen resistant breast cancer cell lines. Therefore, specific targeting might be a useful strategy to block this pathway. The antagonist S961 is a single chain peptide that binds insulin receptor and has been reported to have partial antagonist activity. The affinity of S961 for the insulin receptor is comparable to that of insulin and the selectivity of the insulin receptor versus IGF1 is higher than that of insulin itself (Sturis et al). To determine if S961 has activity in breast cancer cells, we tested its ability to disrupt insulin and IGF-I signaling and growth in a panel of cancer cell lines (MCF-7L, MCF-7L TamR, MDA-231, and HepG2 cells). MCF-7L cells express high levels of IGF1, while HepG2 express mostly insulin receptor. Pre-incubation with S961 significantly suppressed p-Akt and p-MAPK after insulin stimulation in the HepG2, but not in MCF-7L. In contrast, insulin receptor stimulation in MCF-7L TamR cells, which do not express IGF1R, was inhibited by S961. Even a 1000-fold increase in S961 was unable to suppress insulin receptor activation in cells expressing both insulin receptor and IGF1R. S961 inhibits insulin-stimulate cell cycle progression in MCF7L TamR cells. In these TamR cells, S961 also suppresses colony formation in anchorage independent growth assays. These data suggest S961 is an effective inhibitor of insulin receptor activation but only when little IGF1R is expressed. Thus, insulin receptor targeting might be useful in the management of endocrine resistant breast cancer. Citation Format: Kelly LaPara, Douglas Yee. Targeting the insulin receptor with a small peptide (S961) in cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-06-03.
Integration between primary care providers and the cancer system: Gaps and opportunities
Authors: J. Sussman, W. Evans, T. Whelan, D. Bainbridge, S. Schiff, A. Hasler
Journal: Journal of Clinical Oncology (2009)

6584 Background: A number of reports suggest that family physicians (FPs) are poorly integrated with the cancer care system. The specific gaps in care integration are poorly understood. In this study we examine specific processes of care associated with integration between FPs and regional cancer programs. Methods: Cross sectional survey of all identified primary care providers within a representative health region in Ontario, Canada. The survey instrument was created specifically for this study with items generated from published literature and expert input and pilot tested in a representative sample. A modified dilman method was used. Results: 500 physicians responded (response rate 60%). Overall 90% of respondants reported confidence in the workup of a new cancer case for the major disease sites but only half (54%) knew the process of referring to the regional cancer program. Only 57% felt investigations necessary could be done in a timely manner and 44% indicated that coordination of care needs to be improved. Most indicated preferance for an active navigation structure for newly diagnosed patients. Despite over 80% of respondents indicating use of the internet only 10% reported accessing cancer program web portals for information on the regional cancer program (such as waiting times). The majority of respondants (75%) indicated ongoing involvement in care during the active treatment phase, mostly for non cancer related medical issues but 20% indicated that they were not properly infomed of patients’ health status by the oncology program and only 57% indicated that they felt their role was valued by the cancer program during this phase in the care trajectory. In the follow up phase, 35% were unclear of their role specific to monitoring and surveillance. 60% felt their current compensation model was inadequate to support care of cancer patients. This did not vary by compensation model reported. Factors associated with better integration included attendance at educational sessions and years in practice. Conclusions: Cancer systems need to be more responsive to the needs of FPs to better integrate them and support optimal quality of care for cancer patients. Policies to clarify and support roles and responsibilites are necessary to ensure that FPs are integrated team members. No significant financial relationships to disclose.
춘계학술대회 : 구연 ; C형간염에 의한 간경변 환자에서 신기능 장애 발생의 위험 인자에 관한 연구
Authors: 김영남, 권소영, 정낙소, 박철희, 권오상, 김선숙, 최덕주, 김주현
Journal: Clinical and Molecular Hepatology (2005)

배경/목적: 간경변 환자에서 신장 기능 장애는 자발성세균성복막염(SBP)이나 심한 간기능 장애가 동반된 경우에 빈번하며, 다양한 원인들에 의한 신장 혈관 수축에 기인한다. C형간염은 당뇨병과 밀접한 관계가 있으며 당뇨병이 이들 환자에서 신기능에 미치는 영향은 확실치 않다. 연자 등은 C형간염에 의한 간경변 환자에서 신기능 장애 발생 빈도를 조사하고 신기능 장애 발생에 영향을 미치는 위험인자들을 알아보고자 하였다. 대상 및 방법: 2001년부터 2004년
Avoiding negligent release: contemporary clinical and risk management strategies
Authors: N G Poythress
Journal: American Journal of Psychiatry (1990)

Mental health professionals often must decide whether to release a psychiatric patient who has been committed for treatment on the basis of being mentally ill and dangerous. This decision involves liability risks if the patient becomes violent after release. The author draws together several recommendations made in the literature regarding the careful development and implementation of hospital release procedures, including 1) special consultation at the policy development stage, 2) preemptive judgments regarding the adequacy of hospital policies in relation to the professional standard of care, and 3) the use of videotaped exit interviews with patients at the time of their release.