tbuckley/cabot-search huggingface dataset:
Characterization of innate effector cells involved in the anti-tumor activity of talabostat (PT-100)
Authors: Barry Jones, Sharlene Adams
Journal: Cancer Research (2006)

4659   Talabostat (PT-100) is L-valinyl-L-boroproline, an orally available anti-tumor agent. In immunocompetent and immunodeficient ( Rag2 -/-  ) mice, PT-100 can upregulate cytokine and chemokine expression in tumor and lymphoid tissue. Consistent with targeting of both adaptive and innate immune effector cells by the cytokines/chemokines involved, PT-100 can stimulate specific anti-tumor responses that cause tumor rejection in immunocompetent mice and T-cell independent activity that inhibits tumor growth by 50-90% in immunodeficient mice inoculated with mouse or human tumor cell lines. Natural killer cells appear to be non-essential for T-cell independent activity because anti-tumor activity of PT-100 was undiminished in SCID/beige mice. Innate effector cells involved in anti-tumor activity of PT-100 have now been characterized utilizing immunocompetent and immunodeficient mice depleted of either neutrophils by treatment with anti-Ly6G mAb or macrophages by treatment with carrageenan. Both neutrophils and macrophages appear to contribute to the anti-tumor activity of PT-100 in immunocompetent BALB/c mice inoculated with WEHI 164 fibrosarcoma cells because depletion of either reduced the frequency of tumor rejection from 70% to ≤ 2%. Depletion of macrophages in C.B-17 SCID mice has now been shown to significantly ( P   Rag2 -/-   mice. Growth of A549 tumors was significantly inhibited by PT-100 (day 60: 79% reduction in tumor size,  P
Guideline-Based Standardized Care Is Associated With Substantially Lower Mortality in Medicare Patients With Acute Myocardial Infarction
Authors: Kim A. Eagle, Cecelia K. Montoye, Arthur L. Riba, Anthony C. DeFranco, Robert Parrish, Stephen Skorcz, Patricia L. Baker, Jessica Faul, Sandeep M. Jani, Benrong Chen, Canopy Roychoudhury, Mary Anne C. Elma, Kristi R. Mitchell, Rajendra H. Mehta
Journal: Journal of the American College of Cardiology (2005)
Abstract 2416: Progressive Improvement in Cardiac Performance produced by Continuous Aortic Flow Augmentation in Patients Hospitalized with Acute Decompensated Heart Failure: Results from the MOMENTUM Trial
Authors: Michael R Zile, Paolo Colombo, Mandeep Mehra, Barry Greenberg, Scott Brown, Marvin Konstam
Journal: Circulation (2008)

Previous studies indicate that superimposing continuous aortic flow augmentation (CAFA) on pulsatile aortic flow yields vasodilation, unloading, and improved cardiac performance. Whether improvement in indices of cardiac performance are dependent or independent of changes in hemodynamic load has not been examined. Multi-center Trial of Orqis® Medical Cancion® System for Enhanced Treatment of heart failure (HF) Unresponsive to Medical Therapy (MOMENTUM) is a randomized trial comparing CAFA plus medical therapy (n = 109) vs. medical therapy alone (n = 59) in patients hospitalized with HF inadequately responsive to therapy. Entry required reduced LVEF and cardiac index, elevated pulmonary capillary wedge pressure (PCWP), and either impaired renal function or high diuretic requirement, despite IV inotrope or vasodilator treatment. CAFA was achieved for up to 96 hrs using an arterial-to-arterial circuit (flow up to 1.5 L/min). Changes in cardiac performance were assessed using the relationship between stroke work (stroke volume x [Mean blood pressure-PCWP] x 0.00133, kg*cm) and PCWP. Figure shows hemodynamic effects (mean ± SEM) at baseline (B) and at hours post-B time. CAFA progressively improves LV performance (↑ Stroke Work and ↓ PCWP, p &lt; 0.05 for both) resulting in an upward-leftward shift in the Starling function curve. In contrast, medical therapy alone resulted in no change in cardiac performance (↓ Stroke Work and ↓ PCWP, p &lt; 0.05 for both), no shift in Starling curve. CAFA treatment, independent of changes in both preload and afterload, increased stroke work and decreased PCWP by progressively improving cardiac performance.
Nano-enabled delivery of diverse payloads across complex biological barriers
Authors: Kathleen A. Ross, Timothy M. Brenza, Andrea M. Binnebose, Yashdeep Phanse, Anumantha G. Kanthasamy, Howard E. Gendelman, Aliasger K. Salem, Lyric C. Bartholomay, Bryan H. Bellaire, Balaji Narasimhan
Journal: Journal of Controlled Release (2015)
Abstract 2276: Competitive and Reversal Flow in Sequential and Composite Arterial Grafts in Off-Pump Coronary Revascularization: A 7-Year Experience of Angiographic Flow Grading
Authors: Hiroyuki Nakajima, Junjiro Kobayashi, Toshihiro Funatsu, Yutaka Iba, Yusuke Shimahara, Toshikatsu Yagihara, Soichiro Kitamura
Journal: Circulation (2008)
Abstract 15322: Echocardiographic Estimation of Left Ventricular Filling Pressures and of the Isovolumic Time Constant of Relaxation Validated by an Implantable Pressure Sensor
Authors: Tudor C Poerner, Bjorn Goebel, Sylvia Otto, Eva Luthardt, Christiane Schmidt-Winter, Jan Gummert, Hans R Figulla
Journal: Circulation (2010)
Abstract 3792: SKP2 supports cell proliferation and is regulated by Notch signaling in myoblasts and embryonal rhabdomyosarcoma
Authors: Rossella Rota, Laura Adesso, Beatrice Conti, Roberta Ciarapica, Lavinia De Raimondi, Maria Salvo, Sonia Rodriguez, Nadia Carlesso, Lucio Miele, Franco Locatelli
Journal: Cancer Research (2015)

Abstract Background: Rhabdomyosarcoma (RMS) in a pediatric tumor of myogenic origin. It includes two subtypes: embryonal and alveolar. Embryonal RMS (ERMS) cells express key myogenic factors such as MyoD and Myogenin, but proliferate indefinitely and have lost the ability to terminally differentiate into skeletal myofibers. Differently from the alveolar tumors bearing specific chromosomal translocations, ERMS has cytogenetic aberrations and molecular deregulations of pathways regulating senescence, proliferation and differentiation. It has been shown that SKP2, an F-box protein and a component of the ubiquitin protein ligase complex SCFs (SKP1-cullin-F-box), is over-expressed in RMS primary samples and correlates with a dismal outcome. Therefore, we sought here to investigate the regulation of SKP2 and its role in ERMS. Methods: We modulated SKP2 expression through silencing, by using a siRNA validated in the literature, and forcing its expression through retroviral infection. In parallel, we investigate the effect of Notch signaling modulation on SKP2 expression. Results: SKP2 silencing resulted in cell cycle slowdown in both normal myoblasts and ERMS cells. Down-regulation of Notch1 led to SKP2 reduction while that of Notch3 supported SKP2 expression. Cosilencing SKP2 and Notch3 gave raise to myoblast-like structure formation in ERMS and facilitated myoblasts fusion. Finally, using a SKP2 inhibitor ERMS cell proliferation was completely blocked. Conclusion: Altogether, these preliminary experiments suggest that SKP2 could be regulated by Notch signaling in ERMS and that its inhibition hampers tumor cell proliferative capability. Note: This abstract was not presented at the meeting. Citation Format: Rossella Rota, Laura Adesso, Beatrice Conti, Roberta Ciarapica, Lavinia Raimondi, Maria De Salvo, Sonia Rodriguez, Nadia Carlesso, Lucio Miele, Franco Locatelli. SKP2 supports cell proliferation and is regulated by Notch signaling in myoblasts and embryonal rhabdomyosarcoma. [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 3792. doi:10.1158/1538-7445.AM2015-3792
Cytokine-mediated changes associated with improvements in cancer-related fatigue induced by exercise: Results from a randomized pilot study of cancer patients receiving radiotherapy
Authors: K. M. Mustian, S. Fisher, J. Adams, M. Janelsins, O. Palesh, T. Darling, L. Peppone, C. Heckler, J. Williams, G. Morrow
Journal: Journal of Clinical Oncology (2009)

9632 Background: Radiation therapy (RTH) results in dysregulated inflammatory profiles which increase cancer-related fatigue (CRF). Research suggests physical exercise can have a positive influence on CRF during RTH. Exercise may mediate improvements in CRF through a self-regulating inflammatory exercise response involving cytokines and myokines (muscle contraction-induced cytokines known as exercise factors that mediate exercise benefits in other tissues) which help the body adapt to inflammation. We explored the influence of a home-based exercise intervention (HBEX), including resistance and aerobic training, on mediators of inflammation, as well as the association between changes in these mediators and CRF. Methods: Breast and prostate cancer patients (N=38; mean age=57; 71% breast/female), beginning at least 28 sessions of RTH, were randomized to a 4wk HBEX (7 days/wk) or standard care (SC; RTH with no exercise). Cytokines (IL-8, TNFα, TNFαr 1 , IL-8, IL-1β and IFNγ) and the myokine IL-6 were measured by enzyme-linked immunoassays and CRF was assessed via valid self-report questionnaires pre- and post-intervention. Results: ANCOVAs, controlling for baseline, revealed significant differences between groups in mean levels of IFNγ and IL-6 (p=&lt;0.05) and a trend toward differences in IL-8 and TNFαr 1 (p&lt;0.10) with significant baseline interactions for IFNγ, IL-6 and IL-8 (p&lt;0.05) post-intervention. ANCOVAs revealed no significant differences between groups in mean levels of TNFα and IL-1β. Pearson correlations revealed a significant inverse association between changes in IL-8 (p&lt;0.05;r=-0.64) and CRF and a trend toward an inverse association between changes in IL-6 (p=0.10;r=-0.44) and CRF in the HBEX condition but not in the SC condition. Conclusions: These data suggest that exercise-induced changes in IL-8 and IL-6 may mediate improvements in CRF. Future phase III randomized controlled trials are needed with larger samples to fully investigate these relationships. Funded by NCI grant 1R25CA102618. No significant financial relationships to disclose.
Abstract 3638: Pitavastatin Augments Angiogenetic Activity in Human Endothelial Cells via Notch Signal Activation
Authors: Ryosuke Kikuchi, Takeshita Kyosuke, Megumi Kondo, Toru Aoyama, Xian W Cheng, Koji Yamamoto, Toyoaki Murohara
Journal: Circulation (2008)

We have reported that Notch1 plays an important role in embryonic vasculogenesis and the activation of endothelial Notch1, which is induced by crosstalk between VEGF-mediated activation of PI3K/Akt and gamma-secretase, is essential for postnatal vasculogenesis in response to tissue ischemia. Meanwhile pleiotropic effects of statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, have been recently reported to modulate angiogenesis. However it has been under investigation whether Notch signal would be involved in the effects of statins on angiogenesis. We determined whether Notch1 was required for statin-induced promotion of angiogenesis using hindlimb ischemia model in wild type (WT) and Notch1 heterozygous deficient mice. The statin treatment (pitavastatin, 3mg / kg / day, p.o.) did not efficiently restore blood flow in ischemic limbs in Notch1mutant mice as measured by Laser Doppler image and capillary density analyses although the treatment augmented collateral flow in WT mice. Treatment of human umbilical vein endothelial cells (HUVECs), but not human aortic smooth muscle cells, with pitavastatin (100nM) increased the expression of cleaved Notch1 (active form) and Hes-1 (a downstream transcriptional factor of Notch signaling) within 30 min without an increase in total Notch1 and Notch ligand, Jagged-1. The rapid activation of Notch1 and gamma-secretase by pitavastatin was blocked by mevalonic acid (Mev, 500 uM), and inhibitors of PI3K (LY294002, 10 uM), Akt (SH-5, 10 uM), and gamma-secretase (DAPT, 20 uM). Knockdown of Akt using an siRNA approach also reduced Notch1 activation by pitavastatin. Pitavastatin also augmented endothelial proliferation and tube formation on Matrigel in a dose dependent manner, which were suppressed by an inhibition of gamma-secretase. Pitavastatin activated Notch1 via PI3K-Akt-dependent activation of gamma-secretase in endothelial cells, and stimulated angiogenic activity. Our findings indicate that Notch signaling pathway would be, at least in part, involved in statin-induced augmentation of angiogenesis.
Abstract 14034: Follistatin-like 1 Protein Attenuates Cardiac Hypertrophy Following Pressure Overload.
Authors: Masayuki Shimano, Noriyuki Ouchi, Toyoaki Murohara, Kenneth Walsh
Journal: Circulation (2010)

Background:  Transforming growth factor (TGF)-β family cytokines have diverse actions in the maintenance of cardiac homeostasis. Follistatin-like 1 (Fstl1) is expressed in the normal adult heart and is induced in response to conditions that promote myocardial hypertrophy and heart failure. Fstl1 has an anti-proliferative effect but its function in the heart is largely unknown. The aim of this study was to investigate the role of Fstl1 in cardiac hypertrophy. Here we identified Fstl1 as a novel secreted anti-hypertrophic regulatory factor in the heart.   Methods and Results:  To elucidate the loss of Fstl1 function in the heart, we generated cardiaomyocyte specific Fstl1 knock-out (CKO) mice and investigated Fstl1-CKO mice and their wild-type (WT) littermates, which were subjected to pressure overload caused by transverse aortic constriction (TAC). Fstl1-CKO mice showed enhanced cardiac hypertrophic growth following pressure overload stimulation. Fstl1-CKO mice also demonstrated a pronounced loss in ventricular performance following 4 weeks of pressure overload stimulation compared to WT controls and this is accompanied by reduced AMPK activity. In addition, administration of Fstl1 in Fstl1-CKO mice cancelled this loss of ventricular functions following pressure overload. Conversely, to elucidate the gain of Fstl1 function, we generated transgenic mice with muscle specific over-expression and examined these Fstl1 transgenic (TG) mice following TAC compared with their WT littermates. Fstl1-TG mice were resistant to pressure overload-induced hypertrophy. Administration of Fstl1 promoted activation of AMPK and antagonized phenylephrine-induced hypertrophy in cultured neonatal rat cardiomyocytes. Inhibition of AMPK attenuated an anti-hypertrophic effect by Fstl1 treatment, whereas block of LKB1 attenuated AMPK phosphorylation.   Conclusions:  These results identify Fstl1 as a novel autocrine factor that antagonizes the hypertrophic response and loss of ventricular performance, possibly through a mechanism involving AMPK axis.
The role of CD74 in experimental and clinical acute lung injury
Authors: Guosheng Wu, Yu Sun, Xingtong Wang, Bing Ma, Zhaofan Xia
Journal: European Respiratory Journal (2014)

A soluble form of CD74 was recently discovered in autoimmune liver disease. With its ligand, macrophage migration inhibitory factor (MIF), they might be suitable candidates for evaluation as biomarkers of disease activity. As our previous study, consistent with others, has shown that MIF was highly expressed in acute lung injury (ALI), in present study, we investigated the existence of soluble form of CD74 in serum and bronchoalveolar lavage fluid (BALF) in lipopolysaccharide (LPS)-induced ALI mouse model and burn or trauma related ALI patients, preliminarily exploring the possibility of CD74 as a biomarker of ALI. We found that soluble CD74 did exist in serum from both patients and healthy people and its levels from ALI patients (n=67) were significantly higher than those from healthy controls (n=58). In ALI mouse model, similar results were obtained in serum. Furthermore, the soluble CD74 was also found in BALF and was obviously elevated in ALI group when compared with control group as well. Next, the expression of CD74 in lung tissue was significantly increased by Real-time PCR and Western blot after LPS induction in mouse model. In addition, the levels of soluble CD74 positively correlated with levels of IL-6, TNFα and MCP-1 in serum both from ALI patients and mouse model. In summary, our data provided the first evidence of existence of soluble CD74 both in serum and BALF from ALI patients and experimental model. Elevated soluble CD74 in serum and BALF of ALI might be released from lung parenchyma and was closely related to accepted inflammatory factors. These results raise the possibility that CD74 may play an important role in ALI and soluble CD74 may be a promising protein to be a biomarker of ALI.
Abstract 19916: Effect of Whole Soy and Purified Daidzein on Ambulatory Blood Pressure and Endothelial Function-A Six-month Randomized Controlled Trial among Chinese Equol-producing Postmenopausal Women with Prehypertension or Untreated Early Hypertension
Authors: Zhao-min Liu, Suzanne Ho, Jean Woo
Journal: Circulation (2014)

Objective: Although observational studies suggest soy foods or isoflavones are cardio-protective, clinical trials on whole soy or isoflavone daidzein (one major isoflavone and also the precursor of equol) on blood pressure (BP) and endothelial function are few and have not been specifically conducted among equol producers,a population most likely to benefit from soy treatment.

Methods: We performed a 6-month double-blind, randomized, placebo-controlled trial to examine the effect of whole soy (soy flour) or purified daidzein on BP, endothelial function and other cardiovascular risk factors in 270 prehypertensive or untreated hypertensive postmenopausal women verified to be equol-producers. Eligible women were randomized to either one of the three treatment groups: 40g soy flour (whole soy group), 40g low-fat milk powder +63mg daidzein (daidzein group) or 40g low-fat milk powder (placebo group) daily, each given as a solid beverage for 6 months. The primary outcome measures were 24h ambulatory BP and endothelial function assessed by ultrasound determined brachial flow mediated dilation.

Results: Total 253 subjects completed the study according to the protocol. Urinary isoflavones indicated a good compliance to the interventions. Intention to treat and per-protocol analysis indicated that there was no significant difference in the 6-month changes or % changes in parameters of ambulatory BP and brachial flow mediated dilation among the 3 treatment groups. A further subgroup analysis among hypertensive women (n=138) did not alter the conclusions.

Conclusion: Whole soy and purified daidzein had no significant effect on BP and vascular function among equol producing postmenopausal women with prehypertension or untreated hypertension.
Management of appendicitis.
Authors: E B Perry
Journal: BMJ (1976)

Appendicitis is one of the most common causes of acute abdomen with life time risk between 6 and 8% and it's a most common non obstetric surgical emergency during pregnancy.Appendicitis is claimed to be unknown in the villages of India and China in paper by A. M. Spencer.The reason is simply due to the fact that diagnostic facilities do not exist and cases are not recognized.So diagnosing acute appendicitis accurately and efficiently can reduce morbidity and mortality from perforation and other complications.Surgical intervention is the first choice for appendicitis with medical management being reserved for special situations.
CDC Grand Rounds: Getting Smart About Antibiotics
Authors: Alicia Demirjian, Guillermo V. Sanchez, Jonathan A. Finkelstein, Shari M. Ling, Arjun Srinivasan, Lori A. Pollack, Lauri A. Hicks, John K. Iskander
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Each year in the United States, approximately two million persons become infected with antibiotic-resistant bacteria, at least 23,000 persons die as a direct result of these infections, and many more die from conditions complicated by a resistant infection. Antibiotic-resistant infections contribute to poor health outcomes, higher health care costs, and use of more toxic treatments. Although emerging resistance mechanisms are being identified and resistant infections are on the rise, new antibiotic development has slowed considerably.
Abstract 5552: Notch-peroxisome Proliferator Activated Receptor Gamma 2 Pathway Regulates Transendothelial Fatty Acid Transport via Induction of Fatty Acid Binding Protein 4 and Fatty Acid Translocase in Capillary Endothelial Cells in Heart
Authors: Kosaku Goto, Tatsuya Iso, Toshihiro Suga, Hiroki Matsui, Masashi Arai, Frank J Gonzalez, Masahiko Kurabayashi
Journal: Circulation (2009)

Notch signaling, an evolutionarily conserved pathway for cell fate determination, is essential for normal vascular development and maintenance as well as other multiple aspects of vascular function. We have reported that fatty acid binding protein 4 (FABP4), also known as aP2, is a potential candidate of Notch target genes in capillary endothelial cells (EC) of heart, skeletal muscle and adipose tissue. Given that FABP4 is well known as an adipocyte-specific marker and downstream of PPAR- γ , we hypothesized that Notch signaling may regulate several genes abundant in adipocyte via induction of peroxisome proliferator activated receptor- γ (PPAR- γ ). Here we show that Notch signaling induces several adipocyte-related genes in capillary EC via induction of PPAR- γ 2, an isoform known to play a major role in adipocyte differentiation. Overexpression of Notch intracellular domain (NICD), an activated form of Notch, in human cardiac microvessel endothelial cells (HCMEC) induced expression of FABP4, lipoprotein lipase (LPL), but not fatty acid translocase (FAT/CD36). The induction was accompanied by expression of PPAR- γ 2, but not PPAR- γ 1. Administration of synthetic PPAR- γ ligands, thiazolidindione (TZD), markedly enhanced expression of these genes including even FAT/CD36. Their induction was mediated by PPAR- γ 2 because their expression by NICD plus TZD was abolished by administration of GW9662, a PPAR- γ inhibitor. Of importance, the gene induction by NICD and the enhancement by TZD were not observed in other cells such as human umbilical vein EC and 3T3L1 fibroblast/adipocyte, suggesting capillary EC-specific effect of Notch-PPAR- γ pathway. The gene induction was observed in HCMEC when co-cultured with cells expressing Dll4, a Notch ligand, in the presence of TZD. Consistent with these findings, these genes including a Notch receptor Notch1, Dll4, FABP4 and FAT/CD36 were co-localized in capillary EC. Given that long chain fatty acids are central source of energy metabolism in heart, skekletal muscle and adipocyte, adipocyte-related genes such as FABP4 and FAT/CD36 induced by Notch-PPAR pathway in capillary EC may play a crucial role in fatty acid transport system through endothelial layer to supply adequate fatty acids to the fatty acid-burning organs.