tbuckley/cabot-search huggingface dataset:
Abstract 2873: Targeting RAGE for prostate cancer treatment
Authors: Kyle J. Ernzen, Subramanyam Dasari, Gnanasekar Munirathinam
Journal: Cancer Research (2018)

Abstract Prostate cancer (PCa) is the second most common cancer among men and is the third leading cause of cancer-related death in the United States. In 2017 alone, an estimated 161,360 men will be diagnosed with PCa and approximately 26,730 deaths will result from this disease in the United States. The most common methods for PCa treatment include surgery, radiotherapy, and hormone therapy. These treatment options unfortunately have serious drawbacks such as the possibility of organ damage, adverse side effects, and eventual PCa resistance to treatment. Due to the severe threat that PCa poses across the male population, it is vital that more effective and safe treatment options are explored. Previous research has indicated that the receptor for advanced glycation end products (RAGE) plays a vital role in the survival of prostate cancer cells, indicating that RAGE could be a potential therapeutic target. In the present study, we focused on targeting RAGE using two different antagonists, RAGE aptamer and azeliragon as potential alternative therapies for PCa. Confocal microscopy assays initially confirmed that RAGE aptamer expression strongly binds to VCaP cells while azeliragon treatment decreased the expression of RAGE in these cells. MTT cell viability assays indicated that RAGE aptamer and azeliragon decrease PCa cell proliferation in a dose-dependent manner for VCaP and DU-145 cell lines respectively. Cell cycle analysis suggested that RAGE aptamer and azeliragon-treated DU-145 cells enforced cellular G0/G1 phase arrest in a dose-dependent manner. Annexin V FITC and ROS immunofluorescence assays showed that RAGE aptamer and azeliragon induce apoptosis potentially by inducing oxidative stress in PCa cells. Apoptosis activation in RAGE aptamer and azeliragon-treated VCaP cells was confirmed by the detection of PARP-1 cleavage through western blotting. Taken together, our findings suggest that RAGE aptamer and azeliragon may be a promising alternative form of therapy for PCa patients. Citation Format: Kyle J. Ernzen, Subramanyam Dasari, Gnanasekar Munirathinam. Targeting RAGE for prostate cancer treatment [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 2873.
Simvastatin Prevents Vascular Hyporeactivity During Inflammation
Authors: JohannesPleiner, GeorgSchaller, FriedrichMittermayer, StefanZorn, ClaudiaMarsik, StefanPolterauer, StylianosKapiotis, MichaelWolzt
Journal: Circulation (2004)

Background— There is growing evidence that statins exert anti-inflammatory and antioxidative vascular actions that are independent of lipid lowering. We tested whether hyporeactivity to the endothelium-dependent vasodilator acetylcholine (ACh) and the vasoconstrictor norepinephrine (NE) during acute experimental inflammation could be prevented by simvastatin. Methods and Results— In a randomized, placebo-controlled, parallel group study, forearm blood flow (FBF) responses to NE, ACh, and the endothelium-independent vasodilator nitroglycerin (NTG) were assessed at baseline, after 4 days of simvastatin 80 mg PO or placebo treatment, and during Escherichia coli endotoxin (lipopolysaccharide [LPS])–induced inflammation in 20 healthy volunteers. Additionally, markers of inflammation and neutrophil oxidative burst were assessed. Simvastatin and placebo had no effect on FBF or oxidative/inflammatory markers. LPS administration decreased the responses of FBF to NE by 43% (P<0.05) and decreased responses to ACh by...
Gel immersion endoscopy simplifies hemostasis during endoscopic submucosal dissection using the pocket-creation method
Authors: Yoshimasa Miura, Tomonori Yano, Takahito Takezawa, Hirotsugu Sakamoto, Hiroyuki Osawa, Alan Lefor, Hironori Yamamoto
Journal: Endoscopy (2018)

Gel immersion endoscopy (GIE) is a novel method to secure the visual field using gel with an appropriate viscosity, even during ongoing bleeding [1], and is effective in the narrow lumen of the gastrointestinal tract. Recently, GIE was reported to be useful for unexpected arterial bleeding during endoscopic submucosal dissection (ESD) [2]. However, the gel may be difficult to apply in the large lumen of the stomach. The pocket-creation method (PCM) is a new ESD strategy, which is characterized by entering the submucosal layer with a minimal mucosal incision and dissecting the submucosal layer completely under the lesion before the circumferential mucosal incision, as if a "pocket" is made [3]. In this narrow "pocket," GIE can be applied easily, even when there is massive arterial bleeding where water infusion alone cannot secure the endoscopic view ([Fig. 1], [Fig. 2]).
KEYNOTE-522: Phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo + chemo as neoadjuvant therapy followed by pembro vs placebo as adjuvant therapy for triple-negative breast cancer (TNBC).
Authors: Peter Schmid, Javier Cortes, Jonas C. S. Bergh, Lajos Pusztai, Carsten Denkert, Sunil Verma, Heather L. McArthur, Sherko Kummel, Yu Ding, Vassiliki Karantza, Thao Dang, Rebecca Alexandra Dent
Journal: Journal of Clinical Oncology (2018)

TPS602 Background: Recently presented data from the I-SPY 2 trial showed that pembrolizumab, a humanized, anti–PD-1 monoclonal antibody, significantly increased the pathologic complete response (pCR) rate in early-stage TNBC, when combined with neoadjuvant chemotherapy (Nanda et al. ASCO 2017. Abs 506). KEYNOTE-522 (NCT03036488) is a phase III study of pembro+chemo vs placebo+chemo as neoadjuvant treatment, followed by pembro vs placebo as adjuvant treatment in pts with TNBC. Methods: Approximately 855 pts with TNBC, defined as combined primary tumor (T) and regional lymph node (N) staging per AJCC (investigator-assessed: T1c N1-2, T2-4 N0-2), will be randomly assigned to 1 of 2 arms. Stratification will be by tumor nodal status (positive vs negative), size (T1/T2 vs T3/T4), and carboplatin regimen choice (Q3W vs QW). In arm 1, pts will receive 4 cycles of pembro 200 mg Q3W+paclitaxel (80 mg/m2 QW on d 1, 8, 15)+carboplatin (AUC 5 Q3W on d 1 or AUC 1.5 QW on d 1, 8, 15) and then 4 cycles of pembro+[doxorubicin (60 mg/m2 Q3W on d 1) or epirubicin (90 mg/m2 Q3W on d1)]+cyclophosphamide (600 mg/m2 Q3W on d 1) as neoadjuvant therapy. In arm 2, placebo will replace pembro. Definitive surgery will be 3-6 wk after the last cycle, then pts will receive 9 cycles of pembro (200 mg Q3W) or placebo as adjuvant therapy. All cycles = 21d; treatment is up to 17 cycles or until disease progression/unacceptable toxicity. Primary end points are pCR rate using ypT0/Tis ypN0 and EFS. Secondary end points include safety, OS, and pCR rate by ypT0 ypN0, and ypT0/Tis in all pts; and OS, EFS, and pCR rate by ypT0/Tis ypN0, ypT0 ypN0, and ypT0/Tis in pts with PD-L1+ tumors (combined positive score, CPS≥1). Eligible pts are aged ≥18 y with previously untreated, locally advanced, nonmetastatic TNBC. Pts with inflammatory breast cancer or bilateral or multifocal primary tumors are allowed. Adequate organ function and ECOG PS 0-1 are required. Pts with a history of invasive malignancy that was diagnosed and/or treated within the last 5 y are excluded. Clinical trial information: NCT03036488.
Abstract LB-159: A multi-omic study reveals <i>BTG2</i> as a reliable prognostic marker for early-stage non-small cell lung cancer
Authors: Sipeng Shen, Li Su, Ruyang Zhang, Elizabeth Loehrer, Michael Lanuti, Nancy Diao, David Christiani
Journal: Cancer Research (2018)

Abstract Background B-cell translocation gene 2 (BTG2), which functions as a tumor suppress gene, has been reported to be involved in several cancers. However, no study has focused on its role in lung cancer progression or prognosis. We aimed to investigate the role of BTG2 in early-stage non-small cell lung cancer (NSCLC) survival. Patients and methods This study included 1,230 early-stage (1-2) surgically treated NSCLC patients with methylation and expression data from five international cohorts. We built a prognostic model based on methylation. Then, we explored BTG2 expression and NSCLC survival in 3,038 cases, including the above-mentioned cohorts as well as 17 extended public datasets by meta-analysis. Further, we integrated the clinical information, expression, and methylation to build an integration model and evaluated its prediction ability for 5-year survival. Results Three risk CpG probes (cg01798157, cg06373167, cg23371584) were associated with overall survival. The prognostic model could distinguish patient survival in the four cohorts [hazard ratio (HR) range, 1.51 to 2.21] and the independent validation set (HR = 1.85). In the expression analysis, BTG2 acted as a tumor-suppress gene in each cohort (HR range, 0.28 to 0.68). A meta-analysis showed high BTG2 expression was associated with better survival (HR = 0.61, 95%CI: 0.54-0.68). The three CpG probes were all negatively correlated with BTG2 expression. Additionally, the integration model showed a better prediction ability in the training set [area under the curve (AUC) = 0.78] and the validation set (AUC = 0.77). The integrated signature showed a better predictive ability among cases with adjuvant therapy (AUC = 0.85). In addition, 17 miRNAs including miR-21 and miR-23a were associated with BTG2 expression and survival. Conclusions: methylation and integrated prognostic signatures of BTG2 are stable and reliable biomarkers for early-stage NSCLC. These markers may have new applications for appropriate clinical adjuvant trials and personalized treatments in the future. Citation Format: Sipeng Shen, Li Su, Ruyang Zhang, Elizabeth Loehrer, Michael Lanuti, Nancy Diao, David Christiani. A multi-omic study reveals BTG2 as a reliable prognostic marker for early-stage non-small cell lung 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-159.
Abstract 10881: Importance of Stroke Volume Index Assessed by Echocardiography for Stratification of Low Gradient Severe Aortic Stenosis With Normal Left Ventricular Function
Authors: Hong Shen, Brandon Stacey, Bob Applegate, David Zhao, Sujethra Vasu, Bharathi Upadhya, Sanjay Gandhi, Min Pu
Journal: Circulation (2015)

Background: The prognosis and need for aortic valve intervention in patients with low-gradient (LG) severe aortic stenosis (AS) and normal left ventricular (LV) function remain controversial. We hypothesized that echocardiography (echo) could be used for the stratification of high risk patients when accurate assessment of stroke volume (SV) is obtained. Methods: The study included 207 patients with LG severe AS (aortic valve area (AVA) ≤ 1.0cm2, mean gradient &lt; 40mmHg) and normal LV function (LVEF ≥ 50%). In order to improve the accuracy of SV calculation by echo, we measured the LV outflow tract diameter (LVOT) at two locations: 5mm below the aortic annulus (recommended by the American Society of Echocardiography) and at the aortic valve annulus (common in clinical practice). Patients were divided into two groups based on SV index (SVi). Group I had SVi &lt; 35mL/m2 (n=75) and Group II had SVi ≥ 35mL/m2 (n=97) calculated based on both locations using continuity equation. Patients with discrepancy in SVi calculation at the two LVOT locations (potential LVOT-velocity mismatch) were excluded (n=35). Mean follow-up time was 3.0±1.6 years. Results: There was no significant difference in age (78±11 vs. 77±11 years), LVEF (58±6 vs. 60±6%), mean aortic valve gradient (30±5 vs. 31±5 mmHg) and LV mass index (115±34 vs. 109±31 g/m2) between Group I and Group II. Group I had larger body surface area (1.97±0.25 vs. 1.84±0.25 m2), smaller AVA index (0.36±0.08 vs. 0.50±0.09 cm2/m2), higher valvuloarterial impedance (6.1±1.6 vs. 4.0±0.8 mmHg/mL/m2) and lower 3-year cumulative survival (61% vs. 75%, p=0.03) than Group II. Multivariable analysis showed SVi was a strong predictor of mortality among LG severe AS patients (HR 0.95, CI: 0.91-0.99, P=0.02). For Group I, those with medical management had a two-fold increased risks of death compared to those who underwent AS intervention (HR: 2.74, CI: 1.13-6.67, p=0.03). However, there was no survival benefit associated with AS intervention in Group II (HR: 0.73, CI: 0.29-1.80, p=0.49). Conclusion: LG severe AS with normal LV function consists of heterogeneous patients carrying different prognosis depending on SVi. If low SVi is accurately assessed by Doppler echo, AS intervention may be beneficial. Further clinical trials are warranted.
Molecular Imaging of Atherosclerosis for Improving Diagnostic and Therapeutic Development
Authors: ThibautQuillard, PeterLibby
Journal: Circulation Research (2012)

Despite recent progress, cardiovascular and allied metabolic disorders remain a worldwide health challenge. We must identify new targets for therapy, develop new agents for clinical use, and deploy them in a clinically effective and cost-effective manner. Molecular imaging of atherosclerotic lesions has become a major experimental tool in the last decade, notably by providing a direct gateway to the processes involved in atherogenesis and its complications. This review summarizes the current status of molecular imaging approaches that target the key processes implicated in plaque formation, development, and disruption and highlights how the refinement and application of such tools might aid the development and evaluation of novel therapeutics.
Precapillary Servo Control of Blood Pressure and Postcapillary Adjustment of Flow to Tissue Metabolic Status
Authors: KarlfriedGroebe
Journal: Circulation (1996)

Background There are several shortcomings in current understanding of how the microvasculature maintains tissue homeostasis. Presently unresolved issues include (1) integration of the potentially conflicting needs for capillary perfusion and hydrostatic pressure regulation, (2) an understanding of signal transmission pathways for conveying information about tissue energetic status from undersupplied tissue sites to the arterioles, (3) accounting for the experimentally observed interrelations between precapillary and postcapillary resistances, and (4) an explanation of how precise local adjustment of perfusion to metabolic demands is achieved. Methods and Results A novel conceptualization of how local microvascular control mechanisms are coordinated is proposed, according to which blood flow is adjusted to the metabolic needs of the tissue by the venules. Arteriolar action is merely called on for controlling capillary pressure through myogenic response and shear stress–induced vasodilation. A mathematical ...
Adrenomedullin Administration Immediately After Myocardial Infarction Ameliorates Progression of Heart Failure in Rats
Authors: RyosaiNakamura, JohjiKato, KazuoKitamura, HisamitsuOnitsuka, TakurohImamura, YuanningCao, KousukeMarutsuka, YujiroAsada, KenjiKangawa, TanenaoEto
Journal: Circulation (2004)

Background— Adrenomedullin (AM) is expressed in cardiac tissue, and plasma AM levels increase in patients with acute myocardial infarction (MI). This study was performed to determine whether AM administration immediately after acute MI inhibits progression of heart failure in rats. Methods and Results— Rats were infused with 1.0 μg/h IP AM or saline over 7 days immediately after MI inducted by left coronary ligation and were examined 9 weeks after MI. Compared with the saline infusion, AM infusion significantly improved survival (59% versus 81%; P<0.05) and body weight gain (32%; P<0.01) and reduced heart weight (−28%; P<0.01), lung weight (−26%; P<0.01), left ventricular (LV) end-diastolic pressure (11.4±2.0 versus 4.0±0.6 mm Hg, mean± SEM; P<0.01), collagen volume fraction of noninfarcted LV (−39%; P<0.05), and plasma levels of endogenous rat AM (−38%; P<0.05) without affecting infarct size. To investigate the mechanism of AM actions, another series of MI rats infused with AM were killed on day 7. AM in...
Abstract 4312: 3-Hydroxyterphenyllin induces S phase arrest in ovarian cancer cells
Authors: Yi C. Chen
Journal: Cancer Research (2018)

Abstract Epithelial ovarian cancer is the fifth most common cause of cancer-related death among women in the United States. 3-Hydroxyterphenyllin is a secondary metabolite of Aspergillus fungi. In this study, we evaluated 3-hydroxyterphenyllin as a potential anti-cancer agent using human ovarian cancer cells. The cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum at 37°C in a humidified incubator with 5% CO2. The [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, flow cytometry and western blot analysis were used to confirm that 3-hydroxyterphenyllin exhibited a potent growth inhibitory effect against human ovarian cancer OVCAR-3 and A2780/CP70 cells. 3-hydroxyterphenyllin (2, 4, 8, 12 and 16 μM) reduced the viability of OVCAR-3 and A2780/CP70 cells in a concentration-dependent manner. 3-hydroxyterphenyllin (2, 4 and 8 μM) induced S phase cellular arrest for OVCAR-3 and A2780/CP70 cells by upregulating CyclinB1 and Cdc25A expression and inhibiting Cdk4, CyclinA2 and CyclinE1 expression. These results suggest that 3-hydroxyterphenyllin has the potential to fight ovarian cancer cell growth by preventing progression past the S phase of the cell cycle. Citation Format: Yi C. Chen. 3-Hydroxyterphenyllin induces S phase arrest in ovarian cancer cells [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 4312.
Development of Antibody Against Epitope of Lipoprotein(a) Modified by Oxidation
Authors: ShingoYamada, RyuichiMorishita, ShigefumiNakamura, ToshioOgihara, YoshiakiKusumi, IsamuSakurai, NobuhikoKubo, IkunosukeSakurabayashi
Journal: Circulation (2000)

Background—Recently, the biological effects of oxidized lipoprotein(a) [Lp(a)] have been reported to be more potent than Lp(a), the arteriosclerosis-relevant lipoprotein. Thus, investigations with oxidized Lp(a) are expected to provide viewpoints different from the conventional ones based on Lp(a). Methods and Results—An anti-Lp(a) monoclonal antibody (161E2) was produced against synthetic peptide antigen (Arg-Asn-Pro-Asp-Val-Ala-Pro). This epitope was characterized as having various properties because its external exposure was induced as a result of oxidative modification. Using 161E2 antibody, we developed a new enzyme-linked immunosorbent assay to measure Lp(a) modified by oxidative stress. The present data demonstrated that oxidized Lp(a) that contains the epitope of 161E2 antibody was present in the serum of humans. Therefore, we used this new enzyme-linked immunosorbent assay to evaluate the role of oxidized Lp(a) in patients with hypertension, which induces oxidative stress . Interestingly, hyperte...
Physiological and Phenotypic Characteristics of Late Survivors of Tetralogy of Fallot Repair Who Are Free From Pulmonary Valve Replacement
Authors: AlessandraFrigiola, MarinaHughes, MarkTurner, AndrewTaylor, JanMarek, AlessandroGiardini, Tain-YenHsia, KateBull
Journal: Circulation (2013)

Background—Pulmonary valve replacement (PVR) after repair of tetralogy of Fallot is commonly required and is burdensome. Detailed anatomic and physiologic characteristics of survivors free from late PVR and with good exercise capacity are not well described in a literature focusing on the indications for PVR. Methods and Results—Survival and freedom from PVR were tracked in 1085 consecutive patients receiving standard tetralogy of Fallot repair in a single institution from 1964 to 2009. Of 152 total deaths, 100 occurred within the first postoperative year. Surviving patients between 10 and 50 years of age had an annual risk of death of 4 (confidence limit, 2.8–5.4) times that of normal contemporaries. To date, 189 patients have undergone secondary PVR at mean age of 20±13 years (36% of those alive at 40 years of age). A random sample of 50 survivors (age, 4–57 years) free from PVR underwent cardiovascular magnetic resonance, echocardiography, and exercise testing. These patients had mildly dilated right v...
Serum Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Levels Are Elevated in Acute Coronary Syndrome
Authors: KazutakaHayashida, NoriakiKume, TakatoshiMurase, ManabuMinami, DaisukeNakagawa, TsukasaInada, MasaruTanaka, AkiraUeda, GoroKominami, HirofumiKambara, TakeshiKimura, ToruKita
Journal: Circulation (2005)

Background— Markers of cardiac injury, including troponin-T (TnT), are used to diagnose acute coronary syndrome (ACS); however, markers for plaque instability may be more useful for diagnosing ACS at the earliest stage. Lectin-like oxidized LDL receptor-1 (LOX-1) appears to play crucial roles in the pathogenesis of atherosclerotic plaque rupture and ACS onset. LOX-1 is released in part as soluble LOX-1 (sLOX-1) by proteolytic cleavage. Methods and Results— We examined serum sLOX-1 levels in 521 patients, consisting of 427 consecutive patients undergoing coronary angiography, including 80 ACS patients, 173 symptomatic coronary heart disease patients, 122 patients with significant coronary stenosis without ischemia, and 52 patients without apparent coronary atherosclerosis plus 34 patients with noncardiac acute illness and 60 patients with noncardiac chronic illness. Time-dependent changes in sLOX-1 and TnT levels were analyzed in an additional 40 ACS patients. Serum sLOX-1 levels were significantly higher ...
Abstract 18: The Impact of an Ambulation Orderly Program on Hospital Outcomes for Patients with Recent Open Heart Surgery
Authors: Quinn R Pack, Saki Miwa, Erin Woodbury, Richard Engelman, Tara Lagu, Paul Visintainer, Peter Lindenauer
Journal: Circulation (2016)

Introduction: The detriments of prolonged bedrest are well described, yet most hospitals fail to provide enough ambulation to their patients to prevent significant deconditioning and patient harm. One potential strategy for overcoming this problem is the use of an ambulation orderly (AO), an employee whose primary responsibility is to walk patients up to 3-4 times per day. In May 2013, our hospital instituted an AO program among post-operative cardiac surgical patients. We hypothesized that the introduction of an AO program would be associated with improved patient outcomes. Methods: We evaluated all patients undergoing either coronary artery bypass and/or cardiac valve surgery between September 2012 and March 2014. We evaluated the impact of the AO program on post-operative length of stay (LOS), hospital complications, discharge disposition, and 30-day hospital readmission with both a pre-post study design and an interrupted time-series analysis. Results: We identified 925 patients (68.3 years, 68% male, 92% white) during the study period, with no major shifts observed in patient demographics over the study period. Compared to the pre-AO group, the median post-operative LOS (IQR) decreased from 8 (6 to 11) to 7 (6 to 10) days, p &lt; 0.001 for the post-AO group. Additionally, variability around the median length of stay decreased significantly (Brown-Forsythe p = 0.05). See Figure. Time series analysis found that there was no significant baseline trend in LOS (+0.07, p =0.53), but that initiation of the AO program was associated with decreased post-operative LOS (-1.1 ±0.8 days, p =0.16), and a favorable change in the post-AO slope (- 0.30 ± 0.15 days, p = 0.048). Other outcomes were unaffected. Conclusions: The institution of an AO program at our hospital was associated with both a significantly reduced LOS as well as reduced LOS variability, without a change in the rate of hospital complications or 30-day readmission. These results suggest that an AO program is a promising strategy for improving quality and decreasing costs.