tbuckley/cabot-search huggingface dataset:
Abstract 5480: Colorectal cancer cell lines harboring mutation in Wnt/β-catenin pathway shows enhanced sensitivity to the stearoyl-CoA desaturase (SCD) inhibitor, DSP-0692
Authors: Yudai Furuta, Yuichi Fukunaga, Satoshi Ikeda, Erina Koga, Hiroki Umehara, Tsuguteru Otsubo, Manabu Watanabe, Futoshi Hasegawa, Hitoshi Ban, Eiji Sugaru
Journal: Cancer Research (2018)

Abstract Colorectal cancer (CRC) is one of the most frequent malignant diseases worldwide. Recent studies suggest that a small subpopulation of cells known as cancer stem cells (CSCs) may promote the high metastasis and relapse associated with CRC. It has been reported that Wnt/β-catenin signaling is aberrantly activated in a variety of cancer including colorectal cancer, and plays a critical role in CSC maintenance. Here it is shown that a novel SCD inhibitor, DSP-0692, may inhibited Wnt/β-catenin signaling pathway through two different mechanisms in CRC. The effect of SCD inhibition on Wnt3A secretion, in which process post-translational fatty acylation (with palmitoleic acid) is required, was investigated. DSP-0692 led to reduced Wnt3A protein levels secreted in the media in Wnt3A-overexpressing cell line. This result was further confirmed by the TCF/LEF reporter assay in HCT116 incubated with conditional media from L-Wnt3A cells, with or without DSP-0692. DSP-0692 also inhibited exogenous Wnt3A-induced reporter activity. This indicates DSP-0692 may inhibit the β-catenin/Tcf transactivation by additional mechanism in addition to inhibiting Wnt secretion. To clarify this additional mechanism, the effect of DSP-0692 on nuclear translocation of β-catenin was investigated. SCD inhibition led to a decrease of β-catenin amounts within the nucleus. Currently, how SCD inhibition affects nuclear translocation of β-catenin is being investigated. It was confirmed that DSP-0692 exhibited lower IC50 value to sphere cells carrying mutations related to Wnt/β-catenin signaling pathway than those without these mutations. Next, the effect of SCD inhibition on Wnt/β-catenin signaling pathway in vivo was investigated. Treatment with DSP-0692 in a SW620 colorectal cancer xenograft model suppressed mRNA expression of the Wnt/β-catenin target genes, as well as CSC marker gene. Taken together, these results suggest fatty acid desaturation in tumor cells may have an impact on Wnt/β-catenin signaling pathway and involve in CSC maintenance. The approaches targeting SCD could be a new therapeutic strategy for anti-CSC therapy in CRC. Citation Format: Yudai Furuta, Yuichi Fukunaga, Satoshi Ikeda, Erina Koga, Hiroki Umehara, Tsuguteru Otsubo, Manabu Watanabe, Futoshi Hasegawa, Hitoshi Ban, Eiji Sugaru. Colorectal cancer cell lines harboring mutation in Wnt/β-catenin pathway shows enhanced sensitivity to the stearoyl-CoA desaturase (SCD) inhibitor, DSP-0692 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5480.
Abstract 12360: Coronary Stent Information via Smartphone: A New Application Improving Health-care Quality of Patients Having Undergone Percutaneous Coronary Intervention
Authors: Hiroshi Imagawa, Takayoshi Yagi, Hirokatsu Taniguchi
Journal: Circulation (2015)

Introduction: There are a huge number of patients who have been treated by percutaneous coronary intervention (PCI) with stenting. For PCI two types of stent are used commonly; bare-metal stent and drug-eluting stent. Although choice of the stent has high clinical importance, the information is usually hard to obtain because of onset of unexpected pathological events in emergency cases, the needs to concentrate on treatment of urgent disorders resulting in not enough attention paid to the information itself, and so on. The lack of the information may, however, lead to inadequate decision, i.e. interruption of antiplatelet therapy. Many studies have reported that cessation of antiplatelet medications produces in-stent thrombosis in patients, especially those with drug-eluting stent during early post-operative period. This complication might lead to a lethal condition in clinical practice. Hypothesis: Smartphone based ubiquitous system of recording coronary stent information would be useful in managing patients, who underwent percutaneous coronary intervention. Methods and Results: We developed a smartphone application archiving PCI data. The operation date and type of coronary stent are recorded in the memory of smartphone. The information will enable an optimal decision about continuation or discontinuation of medications including antiplatelet in the emergency setting. The time-series record about of PCI data can be accessed anytime and anywhere in the world. Feasibility and usefulness were evaluated by both volunteer patients and cardiologits. Eighty-six percent of PCI patients satisfied with and the 80% of cardiologists espoused this application. Conclusions: Coronary stent data recording system using smartphone technology is a simple and valuable method in managing coronary artery disease patients after interventional stent deployment. This ubiquitous application would improve health-care quality of patients who have undergone PCI.
Abstract 181: Possible Favorable Marker of Positive Head-up Tilt and Negative T-Wave Alternans During Test in Patients with Suspected High-Risk Reflex Syncope
Authors: BonpeiTakase
Journal: Circulation (2014)

T-wave alternans (TWA) is the noninvasive index for predicting lethal arrhythmias and sudden cardiac death. Since the syncope is the important warning sign for sudden cardiac, the measures of TWA in high risk patients with syncope give us useful information in the clinical settings. Thus, we measured TWA during head-up tilt testing (HUT) by ambulatory ECG monitoring (AECG) in either exercise-induced syncope (EX-Group) or HUT-induced prolonged asystole (asystole>30 sec) previously named “malignant vasovagal syncope” (MLVVS-Group). Both of them have been considered as high risk patients. Among consecutive 302 syncope patients who underwent HUT and measured TWA during test, followings were selected as study populations: 12 patients belong to EX-Group (22±5 years); 6 patients to MLVVS-Group (22±11 years) and another age and sex matched 18 patients with suspected reflex syncope who underwent HUT with positive results (C-Group; 22±8 years, as control). Patients in C-Group have similar clinical characteristics t...
Abstract 11845: Impaired Peripheral Endothelial Function Assessed by Digital Reactive Hyperemia Peripheral Arterial Tonometry and Risk of In-Stent Restenosis
Authors: Naohiro Komura, Kenichi Tsujita, Kenshi Yamanaga, Kenji Sakamoto, Takashi Miyazaki, Noriaki Tabata, Masanobu Ishii, Tomonori Akasaka, Yuichiro Arima, Takamichi Ono, Sunao Kojima, Shinji Tayama, Koichi Kaikita, Seigo Sugiyama, Seiji Hokimoto, Kiyoshi Hibi, Kazuo Kimura, Satoshi Umemura, Hisao Ogawa
Journal: Circulation (2014)

Introduction: Drug-eluting stents (DESs) are replacing bare-metal stents (BMSs), but in-stent restenosis (ISR) remains a problem. Impaired endothelial function is a key event in the atherosclerosis process and a predictor of future cardiovascular events. Reactive hyperemia index (RHI) assessed by peripheral arterial tonometry (PAT) evaluates endothelial function noninvasively. Hypothesis: We prospectively assessed the prognostic value of RHI in predicting ISR after percutaneous coronary intervention (PCI). Methods: RHI was measured using Endo-PAT 2000 before PCI (initial RHI) and at follow-up angiography (F/U RHI) in 249 consecutive patients who had successful PCI. F/U angiography was performed at six and nine months after PCI with BMS and DES, respectively. ISR was defined as percent diameter stenosis &gt;50% at F/U angiography assessed by quantitative coronary angiography. Results: At F/U, ISR was seen in 68 patients (27.3%). F/U ln(RHI) was significantly lower in patients with ISR than in those without (0.52 ± 0.23 vs. 0.65 ± 0.27, p &lt; 0.01); no between-group difference in initial ln(RHI) was seen (0.60 ± 0.26 vs. 0.62 ± 0.25, p = 0.56). By multivariate logistic regression analysis, even after adjusting for other significant parameters in univariate analysis (BMS use, total stent length, HDL-Cholesterol, HbA1c, calcium antagonist use, and post-PCI minimum lumen diameter), F/U ln(RHI) independently predicted ISR (odds ratio: 0.13; 95% confidence interval [CI]: 0.04-0.48; p = 0.002). In receiver operating-characteristic analysis, F/U RHI was the strongest predictor of ISR (area under the curve [AUC]: 0.67; 95% CI: 0.60-0.75; p &lt; 0.01; RHI &lt; 1.73 had 67.6% sensitivity, 64.1% specificity); AUC significantly improved from 0.62 to 0.70 when RHI was added to traditional ISR risk factors (diabetes mellitus, total stent length, minimum stent diameter) (p = 0.02). Net reclassification index was significant after addition of RHI (26.5%, p = 0.002). Conclusions: To our knowledge, this is the first study indicating that impaired RHI at F/U angiography independently predicts occurrence of ISR. The simple and noninvasive assessment of endothelial function by RH-PAT adds incremental prognostic value to ISR-risk stratification following PCI.
Abstract 15881: GlycA Predicts Vascular Inflammation by 18-FDG PET/CT Beyond hsCRP in Psoriasis at Baseline and 1-year Follow-up
Authors: Aditya A Joshi, Joseph B Lerman, Tsion M Aberra, Mohammad T Kabbany, Amit K Dey, Abhishek Chaturvedi, Heather L Teague, Joanna I Silverman, Qimin Ng, Tarek Z Aridi, Balaji Natarajan, Mark A Ahlman, Justin Rodante, Martin P Playford, Joel Gelfand, Nehal N Mehta
Journal: Circulation (2016)

Introduction: Recent studies suggest that hsCRP may not accurately capture CV risk in patients with inflammatory disorders such as psoriasis (PSO). GlycA, a novel inflammatory biomarker, predicted ...
Abstract 4195: β-elemene inhibits the metastasis of multidrug-resistant gastric cancer cells through the Cbl-b-EGFR-ERK/Akt signaling pathway
Authors: Ruoxi Yu, Mingming Deng, Huicong Song, Dan Zou, Ling Xu, Xiujuan Qu, Yunpeng Liu, Yuee Teng, Xuejun Hu, Ye Zhang
Journal: Cancer Research (2018)

Abstract Background/Aims: β-elemene, a Curcuma wenyujin plant extract, has been widely used as an adjuvant therapeutic agent in cancer treatment. The emergence of drug-resistant tumor cells is defined as multidrug resistance (MDR), and is one of the major ways cancer therapy can fail. Our previous study indicated that, compared to chemo-sensitive human gastric cancer cells, drug-resistant cells have a stronger ability for migration. The aim of this study was to explore the anti-metastasis effects and mechanism of β-elemene in multi-drug resistance human gastric cancer cells. Methods: A cell viability assay was used to assess the resistance of adriamycin-resistant human gastric cancer SGC7901 cells (SGC7901/ADR) and the cytotoxic effects of β-elemene on SGC7901/ADR cells. A wound healing assay and transwell assay were used to explore the anti-metastasis effects of β-elemene. Human matrix metalloproteinase (MMP) antibody array and Western blot analysis were used to explore the potential mechanism. A murine tumor metastasis assay was used to confirm the anti-metastasis effects in vivo. Immunohistochemistry analysis was performed to examine the expressions of related proteins in xenograft tumors. Results: At sub-lethal concentrations (1 μg/ml and 5 μg/ml), β-elemene significantly inhibited cell migration and invasion of SGC7901/ADR cells. The human MMP antibody array indicated that β-elemene could regulate almost all proteins of the MMP family, and changes of MMP-2 and MMP-9 were the most obvious. Western blotting showed an increase of E-cadherin and decrease of vimentin in β-elemene-treated cells. Downregulation of transcription factor ZEB1 and ZEB2 was also detected. Treatment of SGC7901/ADR cells with β-elemene led to downregulation of Akt, ERK, and EGFR phosphorylation, and significant upregulation of the E3 ubiquitin ligase, Cbl-b. Changes of these proteins were confirmed in xenograft tumors. Hematoxylin and eosin staining showed significantly decreased numbers of metastatic tumor colonies in the lungs of nude mice injected with SGC7901/ADR cells and β-elemene compared with those only injected with SGC7901/ADR cells. Conclusions: The results strongly suggest that β-elemene inhibits the metastasis of multidrug-resistant gastric cancer cells in vitro and in vivo by regulating the Cbl-b-EGFR-ERK/Akt signaling pathway. β-elemene may be a promising treatment for multidrug resistant human gastric cancer. Citation Format: Ruoxi Yu, Mingming Deng, Huicong Song, Dan Zou, Ling Xu, Xiujuan Qu, Yunpeng Liu, Yuee Teng, Xuejun Hu, Ye Zhang. β-elemene inhibits the metastasis of multidrug-resistant gastric cancer cells through the Cbl-b-EGFR-ERK/Akt signaling pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4195.
Abstract LB-057: Hypoxia regulation of antigen presentation machinery expression in breast cancer
Authors: Mei Rosa Ng, Francesco Sabbatino, Mark Duquette, Kamila Naxerova, Mark Badeaux, Gino B. Ferraro, Shan M. Chin, Divya Bezwada, Elena F. Brachtel, Soldano Ferrone, Rakesh K. Jain
Journal: Cancer Research (2018)

Abstract Antigen presentation plays a major role in tumor cell recognition and targeting by immune cells, and is critical to the success of many cancer immunotherapies. How the abnormal tumor microenvironment affects tumor cell antigen presentation is unclear. Hypoxia is a prevalent feature of the tumor microenvironment. Here, we showed that the expression of major histocompatibility complex class I (MHCI) is associated with regions of hypoxia in human breast tumors. The association between hypoxia and MHCI is independent of the breast tumor hormone receptor and HER2 expression status. In vitro studies revealed that hypoxia directly regulates the expression levels of MHCI along with other components of the antigen presentation machinery. Multiple kinase regulators of MHCI expression are responsive to hypoxia. These results suggest that hypoxia effects on cancer cell antigen presentation may be a potential mechanism of tumor immune evasion and treatment resistance. Citation Format: Mei Rosa Ng, Francesco Sabbatino, Mark Duquette, Kamila Naxerova, Mark Badeaux, Gino B. Ferraro, Shan M. Chin, Divya Bezwada, Elena F. Brachtel, Soldano Ferrone, Rakesh K. Jain. Hypoxia regulation of antigen presentation machinery expression in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-057.
Active Transport of Potassium Ion in Heart Mitochondria
Authors: Briansafer, Arnoldschwartz
Journal: Circulation Research (1967)

Several factors affecting K+ transport by rabbit heart mitochondria were examined, using a K+-sensitive electrode. The histone fractions f2a and β-7 produced an energy-dependent efflux of K+. Inorganic phosphate was required for optimal activity; Km for phosphate was 60 µM. Both rate and extent of K+ efflux decreased as K+ concentration in the reaction medium was increased. The direction of valinomycin-induced K+ movements was shown to depend on the net resultant of an active transport mechanism and increased membrane permeability. The detergent triton X-100 produced a nonspecific increase in membrane permeability that led to a rapid efflux of K+. Evidence is presented for competition between ion transport and ATP formation for some common energy intermediate. Possible mechanisms of action of histones and other agents affecting heart mitochondrial K+ transport are considered.
Abstract 2308: Salicylic acid metabolites and derivatives inhibit CDK activity: Novel insights into aspirin's chemopreventive effects against colorectal cancer
Authors: Ranjini Sankaranarayanan, Rakesh Dachineni, D. Ramesh Kumar, Eduardo Callegari, Siddharth S. Kesharwani, Teresa Seefeldt, Hemachand Tummala, Jayarama B. Gunaje
Journal: Cancer Research (2018)

Abstract Aspirin's potential as a drug continues to be evaluated for the prevention of colorectal cancer (CRC). Although multiple targets for aspirin and its metabolite, salicylic acid, have been identified, no unifying mechanism has been proposed to clearly explain its chemopreventive effects. Our goal here was to investigate the ability of salicylic acid metabolites, known to be generated through cytochrome P450 (CYP450) enzymes, and also its derivatives as cyclin dependent kinase (CDK) inhibitors to gain new insights into aspirin's chemopreventive actions. Using in vitro kinase assays, for the first time, we demonstrate that salicylic acid metabolites, 2,3-dihydroxybenzoic acid (2,3-DHBA) and 2,5-dihydroxybenzoic acid (2,5-DHBA), as well as derivatives 2,4-dihydroxybenzoic acid (2,4-DHBA), 2,6-dihydroxybenzoic acid (2,6-DHBA), inhibited CDK1 enzyme activity. 2,3-DHBA and 2,6-DHBA did not inhibit CDK2 and 4; however, both inhibited CDK-6 activity. Interestingly, another derivative, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) was highly effective in inhibiting CDK1, 2, 4 and 6 activity. Molecular docking studies showed that these compounds potentially interact with CDK1. Immunoblotting experiments showed that aspirin acetylated CDK1, and preincubation with salicylic acid and its derivatives prevented aspirin-mediated CDK1 acetylation, which supported the data obtained from molecular docking studies. We suggest that intracellularly generated salicylic acid metabolites through CYP450 enzymes within the colonic epithelial cells, or the salicylic acid metabolites generated by gut microflora may significantly contribute to the preferential chemopreventive effect of aspirin against CRC through inhibition of CDKs. This novel hypothesis and mechanism of action in aspirin's chemopreventive effects opens a new area for future research. In addition, structural modification to salicylic acid derivatives may prove useful in the development of novel CDK inhibitors in cancer prevention and treatment. Citation Format: Ranjini Sankaranarayanan, Rakesh Dachineni, D. Ramesh Kumar, Eduardo Callegari, Siddharth S. Kesharwani, Teresa Seefeldt, Hemachand Tummala, Jayarama B. Gunaje. Salicylic acid metabolites and derivatives inhibit CDK activity: Novel insights into aspirin's chemopreventive effects against colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2308.
Abstract 10014: The Impact of Fractional Excretion of Potassium, a Possible Marker of Renin-angiotensin-aldosterone Activation or Low Output, on the Survival Rate of Heart Failure Patients Treated With Tolvaptan
Authors: Ken-ichi Hiasa, Takeo Fujino, Takafumi Sakamoto, Tomomi Ide, Taiki Higo
Journal: Circulation (2015)

Introduction: Although hyponatremia is known to negatively impact on survival in heart failure, sodium (Na) sparing aquaresis by tolvaptan (TLV) failed to demonstrate survival benefit. Hypothesis: We hypothesized TLV may reduce GFR or activate renin-angiotensin-aldosterone (RAAS) system via augmentation of intravascular free water clearance, therefore, these compensational mechanism may exacerbate the prognosis in heart failure. Methods: A retrospective cohort design was used to assess 82 patients treated with TLV. We analyzed intravascular free water clearance, serum Na change, and fractional excretion of potassium (FEK), which correlates RAAS activation or GFR reduction. Results: Positive intravascular free water clearance significantly correlated with increases in serum Na. TLV tended to increase FEK in all groups. However, there was significant deference in the increase rate of FEK between short-term administration group and other groups, especially in poor prognostic groups as follows: the necessity of surgical intervention or renal replacement therapy (ex. ventricular asssist device, valve replacement or hemodialysis) or death, 5.5 vs 5.7%, 25.3 vs 35.3%, 28.9 vs 106.2%, respectively. Conclusions: Long-term administration of TLV reduces intravascular free water, sodium excretion, urine volume and GFR and in turn activates RAAS. FEK can be a useful biomarker for detection of RAAS activation/ GFR reduction in patients treated with TLV.
Corrigendum to “Recipient characteristics and morbidity and mortality after liver transplantation” [J hepatol 69 (2018) 43–50]
Authors: Sumeet K. Asrani, Giovanna Saracino, Jacqueline G. O'Leary, Stevan Gonzalez, Peter T. Kim, Greg J. McKenna, Goran Klintmalm, James Trotter
Journal: Journal of Hepatology (2018)
Soundings: The empty chair
Authors: Colin Douglas
Journal: BMJ (2000)

Sir Henry Raeburn (1756-1823) was an Edinburgh painter whose output reflected his role in the Scottish Enlightenment. Agreeably, fluently, and for a decent fee, he painted everyone who was anyone, leaving hundreds of portraits, most of them unremarkable but for the distinction of their sitters.

A few are memorable. His skating clergyman glided briefly across the nation's postage stamps a few years ago. His portrait of Mrs Scott-Moncrieff is also widely reproduced. Once, in a frigate in the South China Sea and perhaps a bit homesick, I tried to draw it from a postcard, and found that it was actually a rather mechanical assemblage of triangles within triangles, but no less appealing for that.

The sitter looks shyly out to her left: a young woman, pretty rather than beautiful, dark eyed, thoughtful, and—like most of Raeburn's folk—indefinably but indisputably Scottish in appearance.

A few years after the portrait was done she was dead. Her grieving widower never remarried, but grew old in Edinburgh, dining each night in his New Town home, alone except for her picture.

About 10 years ago I thought of Mrs Scott-Moncrieff again. On a rainy evening, I had driven a senior colleague back from a meeting in our royal and ancient college to the south Edinburgh suburb where we both lived. He invited me in for a drink. A whisky by the fireside seemed a good idea.

In the armchair opposite his was propped a portrait in oils, roughly in the manner of Augustus John, of a young woman in a blue 1920s dress. I knew his wife had died quite recently. We talked about her, and her younger self, the girl in the fireside chair. It seemed the right thing to do.

For some, pictures are unnecessary. The sudden reappearance of a lost loved one may be part of normal bereavement. I have listened to widows for whom it has been quite disturbing. After all, didn't seeing things mean you were going mad?

For other it is less troubling. Once, when I was on a home visit to a little tenement flat, an old woman seemed quite happy to talk to me about her experience. “Yes,” she said, “he comes back to see me quite a lot. It's a wee secret, between him and me.” She smiled, then her eyes filled with tears. “Maybe I shouldn't have told you.”

Henry Raeburn's Mrs Scott-Moncrieff can be viewed at www.scotlandsource.com/about/raeburn.htm