tbuckley/cabot-search huggingface dataset:
Abstract 5385: Anticancer effects of a novel histone deacetylase inhibitor, SNUCH-1, in glioblastoma
Authors: Seung Ah Choi, Phi Ae Kwak, Young Eun Lee, Ji Hoon Phi, Jung Won Choi, Kyu-Chang Wang, Chul-Kee Park, Seung-Ki Kim
Journal: Cancer Research (2015)

Abstract Histone deacetylase inhibitors (HDACi) have been evaluated as promising anticancer drugs against glioblastoma cells. However, there are still lack of animal experiments and new HDAC inhibitors for clinical trials. In this study, we demonstrated the therapeutic efficacy of novel pan-HDACi, SNUCH-1, comparing with other traditional pan-HDACi such as trichostatin A (TSA) and vorinostat (SAHA) in vitro and vivo. We performed cell viability, proliferation, cell cycle, apoptosis, HDAC enzyme activity and western blot assay using the three glioblastoma cell lines and two primary cultured cells. Furthermore, we examined the effects of SNUCH-1 by intracisternal administration on the orthotopic human xenograft glioblastoma mice model. We showed that SNUCH-1 decreased cell viability in a dose-dependent manner and suppressed proliferation with a stronger apoptotic activity than TSA and SAHA. SNUCH-1 inhibited HDAC enzyme activity and blocked cell cycle progression at G2/M, regulating cell cycle related protein expression more effectively than TSA and SAHA. In addition, SNUCH-1 significantly reduced tumor volume and revealed more powerful anti-tumor effect in vivo than TSA. Our results suggest that the novel HDAC inhibitor, SNUCH-1, is a potent therapeutic candidate for glioblastoma. Key words: Histone deacetylase inhibitor, glioblastoma, intracisternal administration Citation Format: Seung Ah Choi, Phi Ae Kwak, Young Eun Lee, Ji Hoon Phi, Jung Won Choi, Kyu-Chang Wang, Chul-Kee Park, Seung-Ki Kim. Anticancer effects of a novel histone deacetylase inhibitor, SNUCH-1, in glioblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5385. doi:10.1158/1538-7445.AM2015-5385
Abstract 16117: Clinical and Angiographic Scoring System to Predict the Probability of Successful First Attempt PCI in Patients With Coronary Chronic Total Occlusion
Authors: Giuseppe Alessandrino, Yves Louvard, Thierry Lefevre, Philippe Garot, Francesca Sanguineti, Thierry Unterseeh, Thomas Hovasse, Bernard Chevalier, Marie-Claude Morice
Journal: Circulation (2014)

Background: Coronary chronic total occlusion (CTO) remains the lesion subtype in which angioplasty has the lowest success rate. Although many independent predictors of final procedural success have been identified, no studies have yet analyzed their combined impact on final procedural outcome. In order to obtain a scoring model to predict final CTO-PCI success, we analyzed a population of patients who underwent a percutaneous coronary intervention for a chronic total occlusion (CTO-PCI) at our institution. Methods: We included 1,657 consecutive patients who underwent a first-attempt CTO-PCI at ICPS from January 2004 to December 2013. Clinical, angiographic procedural and technical characteristics were prospectively collected. A backword stepwise logistic regression including clinical and angiographic variables was used to create a multivariable model of independent predictors of CTO-PCI success. Independent variables were then scored. Results: Overall procedural success rate was 72.5%. The backward logistic regression model showed that two clinical variables: previous CABG (OR2.28, 95%CI1.53-3.4), previous MI (1.56, 95%CI 1.19-2.0) and four angiographic variables: severe lesion calcification (OR 2.95, 95%CI 2.08-4.2), longer CTOs (≥20 mm: OR 2.04, 95%CI 1.62-2.58), non LAD location (OR 1.58, 95%CI 1.21-2-06) and blunt stump morphology (OR 1.57, 95%CI 1.24-1.99) were independent predictors of CTO-PCI failure. The OR values of these variables were used to create the Clinical and Angiographic Scoring System (CL-SCORE). CL-Score values of 0, 1-3, &gt;3 and ≤5 and &gt;5 indentified subgroups at high (class 0), intermediate (class 1), low (class 2), very low (class 3) probability of CTO-PCI success (80.3%, 64.2%, 49.4 and 29% respectively; p&lt;0,0001) Figure 1. The probability of CTO-PCI failure increased significantly from class 0 to class 1 (19.7% to 35.8%, p&lt;0.0001), from class 1 to class 2 (35.8 to 50.6 p&lt;0.0001) and from class 2 to class 3 (50.6% to 81% p=0.001), respectively. Conclusion: This clinical and angiographic score strongly predicted the final CTO-PCI procedural outcome of our study population. Further studies are required to validate this model.
Abstract 2688: Can Stress Echocardiography With Tissue Characterization Evaluate Noncritical Coronary Stenosis? A Validation Study Against Simultaneous Measurement of Fractional Flow Reserve
Authors: Tudor Poerner, Sisi Vilardi, Björn Goebel, Hans R Figulla, Tim Süselbeck
Journal: Circulation (2007)

Aim of this study was to evaluate the ability of different echocardiographic modalities to detect myocardial ischemia due to non-critical coronary stenosis, compared to the fractional flow reserve (FFR) as gold standard. Material and Methods: We investigated 22 consecutive patients presenting with stable angina, negative exercise tests and coronary 1-vessel disease with 50–75% diameter stenosis. TDE/SRI was performed at baseline and at peak hyperemia during 0.14 mg/kg/min adenosine infusion simultaneously with intracoronary FFR measurements. Angioplasty was carried out if FFR &lt; 0.75, repeating TDE/SRI during first balloon inflation. Visual wall motion score, peak systolic values for myocardial velocity (Vs), strain rate (SRs), strain (Ss) and peak overall strain (Smax) were determined in the region of interest. Postsystolic shortening (PSS), accepted as typical marker of acute myocardial ischemia, was defined as (Smax-Ss)/Smax &gt; 0.3, with reduced Ss &lt; 15%. Results: Pathologic FFR &lt; 0.75 was found in 11 patients (Table 1 ), who underwent angioplasty. Myocardial contractility reflected by SRs increased during hyperemia only in the patient group with FFR &gt; 0.75 and decreased markedly during balloon inflation. Hyperemic SRs variation correlated with FFR (r = 0.5, p = 0.018) and predicted significantly pathologic FFR with an area under ROC curve of 0.86 (p &lt;0.01). PSS was identified in 10 of 11 patients during vessel occlusion, but had a low sensitivity (2 of 11 patients with FFR &lt; 0.75) for the more subtle changes during hyperemia. Conclusion: Functional assessment of moderate-to-severe coronary stenosis remains a diagnostic challenge. PSS occurrence cannot serve as a reliable noninvasive alternative to FFR. However, the blunted hyperemic variation of systolic strain rate was able to predict a pathologic FFR, even in this small group of patients. Therefore, TDE/SRI emerges as a promising tool to enhance the diagnostic accuracy of adenosine stress echocardiography. Table 1
Abstract 16348: Does the 6 Minute Walk Test Provide Useful Prognostic Information in Systolic Heart Failure Patients?
Authors: Daniel E Forman, Jerome Fleg, Dalane Kitzman, Clinton Brawner, Ann Swank, Robert McKelvie, Robert Clare, Stephen Ellis, Mark Dunlap, Vera Bittner
Journal: Circulation (2011)

Introduction: The Six Minute Walk (6MW) test is a convenient and inexpensive test of physical function, but concerns remain regarding reliability of the information it provides for systolic heart f...
Cyclosporine or Cyclosporine Plus Methylprednisolone for Prophylaxis of Graft-Versus-Host Disease: A Prospective, Randomized Trial
Authors: H. Joachim Deeg, Danyu Lin, Wendy Leisenring, Michael Boeckh, Claudio Anasetti, Frederick R. Appelbaum, Thomas R. Chauncey, Kristine Doney, Mary Flowers, Paul Martin, Richard Nash, Gary Schoch, Keith M. Sullivan, Robert P. Witherspoon, Rainer Storb
Journal: Blood (1997)
Genome-wide transcriptome analysis of nerve sheath tumors
Authors: Subbaya Subramanian, Robert B. West, Torsten O. Nielsen, Brian P. Rubin, Erinn Downs-Kelly, John R. Goldblum, Shirley Zhu, Kelli Montgomery, Pancras C.w Hogendoorn, Christopher L. Corless, Andre M. Oliveira, Christopher D.m Fletcher, Matt Van de Rijn
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

824 

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue tumors that arise from neurofibromas in patients with neurofibromatosis but also occur sporadically. Malignant transformation is a life threatening complication in patients with neurofibromatosis. The transformation of neurofibromas into MPNSTs is not completely understood at a molecular level. The goal of this study is to identify genes that will serve as molecular markers for progression of neurofibroma to MPNST, and to identify novel potential therapeutic targets. Gene expression profiling using 43000 spot cDNA microarrays was performed on 32 cases of MPNSTs, 23 schwannomas, 20 neurofibromas and 16 synovial sarcomas. Using unsupervised hierarchical clustering, most tumors grouped together according to tumor type. There appear to be at least two subtypes of MPNSTs. Analysis employing ‘significance analysis of microarrays' identified genes that were differentially expressed in various nerve sheath tumors. A major trend in transformation from neurofibroma towards MPNST is accompanied by the loss of expression of a large number of genes, rather than widespread de novo increase in gene expression upon transformation. NF1 is one of the genes for which loss of expression was noticed in most of the MPNSTS. Potential signaling pathways were identified using ‘Gene Set Enrichment Analysis' method. The expression of genes associated with MET and TFGB signaling pathways in the majority of neurofibromas, but not in MPNST, suggest that these pathways are affected during malignant transformation. A detailed list of genes and the signaling pathways that are associated with various nerve sheath tumors will be discussed.
Abstract 9875: Ho-1/co Mediated Human Cardiac Stem Cell Survival Through Activation of Survival Signal Pathways and Cytokine Effects
Authors: Chuanxi Cai, Lei Teng, Jia-Qiang He, Duc Vu, Xian-Liang Tang, Yiru Guo, Qianghong Li, Kyung Hong, Gregg Rokosh, Roberto Bolli
Journal: Circulation (2011)

Background: Delivery of c-kit positive cardiac stem cells (CSCs) is a promising approach to repairing the infarcted heart, but is severely limited by the poor survival of donor cells, &gt;90% of which disappear within 7 days of transplantation. Carbon monoxide (CO), a byproduct of heme oxygenase 1 (HO-1), has potent anti-apoptotic, cytoprotective, and preconditioning actions. Cobalt protoporphyrin (CoPP) is a well-known HO-1 inducer and has been used to promote CO generation and protect against ischemia/reperfusion injury. Therefore, we determined whether preconditioning CSCs with CoPP promotes CSC survival. Methods and Results: C-kit positive, lineage negative CSCs were isolated from human hearts. Lactate dehydrogenase (LDH) release assays demonstrated that preconditioning CSCs with CoPP markedly enhanced cell survival after oxidative stress (1 mM H 2 O 2 ), concomitant with upregulation of HO-1 and other antiapoptotic proteins (e.g., Bcl2, Bcl2-A1, and Xiap). Conversely, knocking down HO-1 by shRNA inhibited the cytoprotective and antiapoptotic effects of CoPP. Both the annexin V/PI assay and the caspase-3 activity assay showed that pretreatment of CSCs with CoPP enhanced the cells’ resistance to apoptosis induced by oxidative stress. Preconditioning CPCs with CoPP also induced phosphorylation of NF-kappaB, Nrf-2, Erk1/2, and STAT1/3, which are known to modulate multiple cardioprotective genes. Further, preconditioning CSCs with CoPP led to a significant decrease in ROS generation and a global increase in release of cytokines such as EGF, FGFs, CSFs, and CXCL. Conditioned medium from cells pretreated with CoPP conferred naïve CSCs remarkable resistance to apoptosis, demonstrating that cytokines released by preconditioned cells play a key role in the antiapoptotic effects of CoPP. Conclusions: Preconditioning human cardiac stem cells with CoPP promotes cell survival and resistance to oxidative stress. The mechanism appears to involve activation of survival signaling pathways such as the NF-kappaB and ERK pathways, as well as paracrine effects via release of cytokines. These results provide a simple and effective strategy to enhance survival of CSCs after transplantation and, therefore, their efficacy in repairing infarcted myocardium.
Chemopreventive effect of Korean red ginseng extract in rat hepatocarcinogenesis
Authors: Hae-Jeung Lee, Mi-Kyung Hong, Hyemee Kim, Haymie Choi
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

3943 

This study was conducted to examine the effects of Korean red ginseng (KRG) extract on preneoplastic foci formation and glutathione-dependent detoxifying enzyme activities in rat hepatocarcinogenesis. We used KRG extract prepared from Cheong-Kwan-Jang, Korean red ginseng root (6-year-old). Basal diet was composed of 20g casein, 54.7g corn starch, 15g corn oil, 1g vitamin and 4g minerals, 5g α-cellulose and 0.3g DL-methionine per 100g diet. Male Sprague-Dawley rats (4 week-old) were fed with one of KRG extract (0, 0.5, 1.0, or 2.0%) supplemented diets for 10 weeks, and induced hepatocarcinogenesis by diethylnitrosamine (200mg/kg body weight) and 2/3 partial hepatectomy. The areas and numbers of placental glutathione S -transferase (GST) positive foci were significantly decreased in rats fed KRG diets, and 1.0% diet was the most effective on suppressing the foci formation (62% of number and 64% of area of basal diet group). The hepatic glutathione level and GST activity were increased in KRG diet groups. However, the activities of glutathione peroxidase and glutathione reductase were not different between groups. Hepatic thiobarbituric acid reactive substances (TBARS) content was significantly reduced dose dependently. Triglyceride (TG) level and the activity of gamma-glutamyl transferase (GGT) in serum were significantly reduced in all KRG diet groups. Fatty acid synthase (FAS) activity and its protein expression were reduced and GST protein expression was induced in KRG diet groups. Conclusively, Korean red ginseng extract exerts chemopreventive effects in hepatocarcinogenesis by inducing a GST, lowering of lipid peroxidation and TG content, and the suppressing fatty acid synthase.
Abstract 831: Functional Analysis of S127 and D374 Residues of PCSK9: Distinct Hot Spots for Gain of Function
Authors: Timothy S Fisher, Shilpa Pandit, Douglas Wisniewski, Joseph C Santoro, Rose M Cubbon, Sookhee Ha, Richard T Cummings, Samuel D Wright, Carl P Sparrow, Ayesha Sitlani
Journal: Circulation (2007)

Mutations within proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with dominant forms of familial hypercholesterolemia. Recent studies have shown that PCSK9 directly binds the LDL receptor (LDLR) and that addition of PCSK9 to cells promotes degradation of LDLR. Mutations associated with hypercholesterolemia (S127R and D374Y) bind the LDLR stronger and are more potent in decreasing LDL-uptake. Based on these data, we sought to better understand the mechanism by which mutations at both the S127 and D374 residues of PCSK9 affect PCSK9 function. A limited vertical scanning mutagenesis was done, resulting in the following mutants: S127(R, A, D, K, L, T) and D374(Y, A, E, F, K, L). Expression of several S127 alleles in HEK293 cells resulted in less efficient processing of PCSK9, with S127L severely defective in processing. In contrast, all D374 alleles tested had no effect on PCSK9 processing. In a cell-based functional assay of PCSK9 activity, both S127R and S127K proteins were significantly more potent (2– 4 fold) in decreasing LDL-uptake than wild-type PCSK9, while all other S127 mutants were similar to wild-type. Each D374 mutant tested was more potent than wild-type PCSK9 in reducing LDL-uptake (D374Y, F &gt; A, L &gt; E, K &gt; wild-type). To determine if the potencies of S127 and D374 mutations in lowering LDL-uptake correlated with their ability to interact with the LDLR, each mutant was tested in a PCSK9-LDLR time-resolved FRET assay. Results indicate that potency in the cell-based LDL-uptake assay correlates with PCSK9’s binding affinity for the LDLR. Combination of S127R and D374Y was also found to have an additive effect in enhancing PCSK9’s ability to reduce LDL-uptake. Molecular modeling indicates that mutations at S127 and D374 which enhance PCSK9 function stabilize or destabilize the protein, respectively. In conclusion, these results suggest a model in which mutations at S127 and D374 residues modulate PCSK9’s ability to regulate LDLR function through distinct mechanisms.
Abstract 2421: Differential Effects of Nesiritide versus Nitroglycerin on Inflammatory Biomarkers in Patients with Acute Decompensated Heart Failure
Authors: Sheryl L Chow, Stephen A O'Barr, Jessica T Peng, Eric E Chew, Firooz Pak, Paryus Patel, Mark P Okamoto, J. H Patterson, J T Heywood
Journal: Circulation (2008)
Abstract 20236: Differential Expression of Genes Associated With Cardiovascular Disease in Cardiac Allograft Vasculopathy
Authors: Monica Colvin-Adams, Nonyelum Harcourt, Ying Zhang, Adam Mitchell, Kenneth Liao, Kenneth Beckman
Journal: Circulation (2014)

BACKGROUND:  Cardiac allograft vasculopathy (CAV) accounts for significant mortality after heart transplant (HT). The identification of molecular pathways involved in CAV may provide targets for preventive therapies and development of risk markers.   METHOD:  Gene expression profiling and transcriptome analysis using Illumina HiSeq 2000, was performed in 23 HT recipients, 12 with ISHLT grade 3 CAV and 11 without CAV matched on age, gender, and HT duration. Fastqc, Tophat, Samtools, and CuffDiff were utilized for quality control of raw reads, mapping short reads to reference genomes and testing differential expression between healthy subjects and HT recipients. Ingenuity pathway analysis (IPA) was performed to identify molecular pathways demonstrating differential expression.   RESULT:  Mean age was 54.6yrs, mean duration of transplant 8.1yrs, 69% were men, and etiology of HT was ischemic in 47.8%. IPA analysis revealed abnormalities in the following pathways: disease and biological functions, molecular and cellular functions, catonical pathways and toxicity. When cardiovascular pathways were evaluated, CAV was associated with differential expression in genes involved in cardiac arteriopathy, inflammation, fibrosis, heart failure, and arrhythmia. (Table 1)   Conclusion:  Genes associated with inflammation, arteriopathy, fibrosis, heart failure, and arrhythmias are differentially expressed in CAV. Longitudinal evaluation is required to determine the relationship of these genes and pathways to risk and development of CAV and their response to specific therapies.
Abstract 15865: Persistent Activation of FoxO Contributes to Insulin Resistance and Diabetic Cardiomyopathy
Authors: Pavan K Battiprolu, Joseph W Spellman, Tien-Chun Chen, Xiang Luo, Nan Jiang, Anwarul Ferdous, Beverly A Rothermel, Thomas G Gillette, Sergio Lavandero, Joseph A Hill
Journal: Circulation (2010)
Final Analysis, Cytogenetics, Long-Term Treatment, and Long-Term Survival In MM-003, A Phase 3 Study Comparing Pomalidomide + Low-Dose Dexamethasone (POM + LoDEX) Vs High-Dose Dexamethasone (HiDEX) In Relapsed/Refractory Multiple Myeloma (RRMM)
Authors: Meletios A. Dimopoulos, Katja Weisel, Kevin W. Song, Michel Delforge, Lionel Karlin, Hartmut Goldschmidt, Philippe Moreau, Anne Banos, Albert Oriol, Laurent Garderet, Michele Cavo, Valentina Ivanova, Adrian Alegre, Joaquin Martinez-Lopez, Christine I. Chen, Andrew Spencer, Stefan Knop, Nizar J. Bahlis, Christoph Renner, Xin Yu, Kevin Hong, Lars Sternas, Christian Jacques, Mohamed H. Zaki, Jesús F. San Miguel
Journal: Blood (2013)
Abstract 3997: Impact of Cytochrome P450 2C19*17 Polymorphism on Post-Treatment Platelet Reactivity after a 600-mg Loading Dose of Clopidogrel in a Large Cohort of Patients Undergoing PCI
Authors: Dietmar Trenk, Willibald Hochholzer, Martin F Fromm, Oliver Zolk, Andreas Pahl, Christian Stratz, Christian M Valina, Franz-Josef Neumann
Journal: Circulation (2008)

The antiplatelet effect of clopidogrel requires formation of an active metabolite by two metabolic reactions with distinct contribution of various isoenzymes of the cytochrome P450 (CYP) system inv...
Abstract P3-07-34: Breast cancer pathologic subtype and fetal microchimerism
Authors: David A Mahoney, Veronica L Winget, VK Gadi, Christopher I Li, Peggy L Porter, Jean A McDougall
Journal: Cancer Research (2015)

Abstract Background: Stably persistent offspring-origin cells in a woman’s circulation and tissues decades after pregnancy, also known as fetal microchimerism, is deficient in women with biologically unselected breast cancer and suggests a protective role. Although the finding is in harmony with the well-known association of parity with protection against future breast cancer, it has recently emerged that certain tumor types such as triple negative breast cancer are positively associated with parity. Here we tested the hypothesis that fetal microchimerism is positively associated with triple negative breast cancer in young women. Methods: Buffy coat specimens were obtained from a subset (n=450) of pathologically confirmed low-risk luminal and high-risk triple negative breast cancer patients and control participants from a population-based cohort study of all women aged 20-44 diagnosed with invasive breast cancer in the three county Seattle-Puget Sound metropolitan area from 2004-2010. Using quantitative PCR, DNA extracts from these specimens were tested for the presence and concentration of Y chromosome sequence DYS14, a marker of male fetal microchimerism. Results: At this interim analysis of 405 specimens, 29.3% (56/191) of the healthy controls tested positive. Using controls as a reference group, 37.8% (34/90; OR .68; 95% CI .39-1.2) of women who developed luminal breast cancer tested positive for the presence of DYS14, while 26.6% (33/124; OR 1.14; 95% CI .67-1.96) of women who developed triple negative breast cancer tested positive. Discussion: A preliminary analysis does not suggest an association between fetal microchimerism and breast cancer pathologic subtype in young women. Additional analyses are pending and will be presented at the meeting. Young women may regulate fetal microchimerism differently and surprisingly our data may suggest that as fetal microchimerism emerges later in life in the circulation, so does the protection against breast cancer – a finding consistent with population based studies of parity as a risk factor for breast cancer. Citation Format: David A Mahoney, Veronica L Winget, VK Gadi, Christopher I Li, Peggy L Porter, Jean A McDougall. Breast cancer pathologic subtype and fetal microchimerism [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 P3-07-34.