tbuckley/cabot-search huggingface dataset:
Abstract P316: Alcohol Consumption and Incidence of Atrial Fibrillation and Heart Failure: Prospective Findings From the MOLI-SANI Study
Authors: Augusto Di Castelnuovo, Simona Costanzo, Livia Rago, Amalia de Curtis, Mariarosaria Persichillo, Marialaura Bonaccio, Francesca Bracone, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello
Journal: Circulation (2015)

Introduction: The connection between ethanol intake and atrial fibrillation (AF) or heart failure (HF) remains controversial. Hypothesis: We assessed the hypothesis that alcohol consumption predicts onset of AF or HF. Methods: We analyzed 22,420 (47% men, age≥35) AF or HF-free individuals randomly recruited from the general population included in the MOLI-SANI study, for whom complete data on HF, AF and alcohol were available. The cohort was followed for a median of 4.2 years (91,930 person-years). Alcohol intake was categorized in former, never, occasional (&lt;1 gr/day) drinkers and in four categories of consumers with different intake (Table). Incident cases were identified through linkage to the regional archive of hospital discharges. The end of follow-up was 31/12/2011. Hazard ratios (HRs) were calculated using Cox-proportional hazard models (Table). Results: We identified 546 incident cases of HF and 352 of AF. In comparison with never drinkers, both former or occasional drinkers showed an equal risk of developing HF (Table). Drinking at various amount of alcohol revealed a J-shaped protection against HF, with a 25% (95%CI: 1% to 44%) maximum protection at 2-4 drinks a day, independent from common confounders (Table). Concerning AF, we failed to observe any association of alcohol with onset of it. Very similar results were obtained after restriction of the analyses to only men/women or to type of alcoholic beverages (wine, beer or liquor). Conclusions: Consumption of alcohol in moderation prevent the incidence of heart failure of 25%, whereas it was not associated with development of atrial fibrillation.
Chemobiological screening for identification of molecular targets for thymic epithelial cancers.
Authors: O. D. Cano, Y. Polar, Y. Liu, M. Ivan, K. Fearn, J. Ding, S. S. Badve, G. W. Sledge, P. J. Loehrer, A. A. Cardoso
Journal: Journal of Clinical Oncology (2010)

10527 Background: Thymic epithelial cancers (TEC) are rare and understudied malignancies. More effective and disease-focused treatments are necessary for these cancers, and the identification and validation of molecular targets for these malignancies are greatly needed. Methods: A chemobiological screening and bioinformatics analyses were performed using a novel thymoma cell line, IU-TAB1. Molecular and functional studies were used for target validation. Biochemical analyses, reporter assays, and functional (survival, proliferation, morphogenesis) and mechanistic (apoptosis, cell cycle) studies were performed in biologically-relevant human and murine systems, to define the biological role of the molecules identified by this screening. Results: A chemobiological screening using >90 signaling-specific agents unveiled 16 compounds that significantly (>50%; p<0.05) inhibited thymoma cell survival. Three of such compounds are known to target STAT3, and validation studies showed that IU-TAB1 cells express activated STAT3 and genes transcriptionally regulated by STAT3. Immunoblotting confirmed that human and murine (Tim1 mice) thymoma and carcinoma cells express phospho-STAT3, and its transcriptional activity was demonstrated. Pharmacologic STAT3 blockade (STATTIC, S31- 201, WP1066) resulted in inhibition or abrogation of STAT3 activation, and marked inhibition of TEC cell survival, through a mechanism involving apoptosis. Lentiviral shRNA effectively silenced STAT3, inhibiting thymoma cells. Interestingly, STAT3 activation is markedly upregulated by hypoxia, a microenvironmental factor often present in these cancers; molecular studies underscored a reciprocal interplay between STAT3 and the hypoxia master regulator HIF-1 on thymoma cells. Studies are underway to assess the anti-tumor efficacy of STAT3 inhibitors in a xenograft model of human thymoma. Conclusions: Our studies identified novel molecular targets in TEC, and uncovered that STAT3 signaling as a significant player in the biology of malignant thymoma. These molecular and preclinical studies support the use of therapeutic strategies aiming at the targeted disruption of STAT3 for the treatment of these cancers. No significant financial relationships to disclose.
Tracing uptake of C3dg-conjugated antigen into B cells via complement receptor type 2 (CR2, CD21)
Authors: Michael W. Hess, Michael G. Schwendinger, Eeva-Liisa Eskelinen, Kristian Pfaller, Margit Pavelka, Manfred P. Dierich, Wolfgang M. Prodinger
Journal: Blood (2000)
Mindfulness-Based Stress Reduction for Veterans With PTSD—Reply
Authors: Paul Thuras, Melissa A. Polusny, Kelvin O. Lim
Journal: JAMA (2016)

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Phase I study of danusertib (D) in combination with bevacizumab (B) in solid tumors.
Authors: P. J. Rosen, A. W. Tolcher, P. Lee, M. Smitley, M. Fuerst, R. Spinelli, S. Crippa, M. G. Jannuzzo, S. Comis, K. Papadopoulos
Journal: Journal of Clinical Oncology (2010)

3066 Background: D is a small molecule that inhibits Aurora Kinases, proteins regulating mitosis and overexpressed in many tumors. Investigation of the combination is based on additive effect of the drugs in preclinical models, their different mechanism of action and non-overlapping toxicity profiles. Methods: Objectives: to define first cycle (C) dose limiting toxicities (DLTs) and thereby the recommended phase 2 dose (RP2D), safety, PK profiles and antitumor activity. Cohorts of 3-6 pts were sequentially allotted to dose levels (DL) 1, 2, 3 of D (190, 250, 330 mg/m2, respectively, on days [d] 1 and 8) and fixed dose of B (15 mg/kg, on d1) given IV every 3 weeks. DLTs were defined as grade 4 neutropenia (G4 ANC) for >7d, febrile neutropenia (FN), neutropenic infection, G4 thrombocytopenia (PLT), G3 PLT for >7d or with bleeding, any G3/4 non-hematologic toxicities, failure to administer 80% of D in C1, >2 week-delay in starting C2. Results: 20 pts (10 males), median age 54 [22-70] were treated. Primary tumor types: 11 colorectal ca, 2 pancreatic ca and 7 others. All pts had metastatic disease. Median ECOG PS: 1 [0-1]. Four pts were treated at DL1, 10 at DL2 and 6 at DL3. DLTs consisted of G3 diarrhea and G3 nausea in 1 pt each at DL3. DL2 was then expanded to 6 pts; one of them experienced G3 fatigue as DLT. This DL was again expanded to 10 pts for completing PK evaluations at RP2D and 1 pt experienced a DLT (failure to administer due to G2 bilirubin). Treatment emergent G3/4 hematological toxicities were ANC and PLT (63 and 5% of pts, respectively). The most frequent treatment-related events were usually of G1/2 severity and included fatigue, nausea, diarrhea, anorexia, mucosal inflammation and vomiting. PK parameters were dose and time independent and characterized by low inter-pt variability. B did not change the PK profile of D. Conclusions: The RP2D of 250 mg/m2 of D and 15 mg/kg of B is safe and allows a dose increase of D to 330 mg/m2 from C2 if no toxicities are experienced in C1 since reported toxicities at DL3 (essentially non-hematological) were easily manageable. One PR at DL3 in a rectal ca. pt progressing under previous B and 5 clinically relevant SD (> 6 months) have been reported (2 at DL3, 3 at DL2). Further investigations in phase II trials should be warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Accelera, Nerviano Medical Sciences Chemotherapy Foundation Nerviano Medical Sciences
The characterization and function of human immunoregulatory T lymphocyte subsets.
Authors: E L Reinherz, S F Schlossman
Journal: Pharmacological Reviews (1982)

Functional T lymphocyte subpopulations can be identified in humans by antibodies which detect stable glycoprotein antigens on their surface. Thus, inducer T lymphocytes bear an antigen termed T4 while suppressor T lymphocytes bear an antigen termed T5. Immune homeostasis results from a delicate balance between inducer and suppressor subsets within the T-cell circuit and perturbation in subset dynamics may initiate a wide variety of immunopathological disorders. Here Ellis Reinherz and Stuart Schlossman discuss the present understanding of this circuit, its role in the pathogenesis of a number of diseases, and how the human immune response can be manipulated in an orderly way through modulation of selected T-cell subsets.
Abstract 15110: Exercise Training for Management of Peripheral Arterial Disease: a Systematic Review and Meta-Analysis
Authors: Belinda Parmenter, Gudrun Dieberg, Neil A Smart
Journal: Circulation (2014)

Objective: To quantify expected benefits of exercise training in people with peripheral arterial disease (PAD). Hypothesis: Walking as a training modality and training to mild pain were optimal for improving peak VO 2 and symptoms. Methods: We conducted a systematic search (PubMed, CINAHL, Cochrane controlled trials registry; 1966-May 31, 2014).We included randomized controlled trials (RCT’s) of exercise training versus usual medical care in persons with PAD, 42 of 60 (70%) RCT’s met selection criteria. Results: Exercise training produced significant peak VO 2 improvements with Mean Difference (MD) 0.62 ml/kg/min (95% CI 0.47 to 0.77; p&lt;0.00001); 6 minute walk initial claudication MD 52.7m (95%CI 24.7 to 80.6m; p=0.0002); total walking distance MD 34.9m (95%CI 25.6 to 44.1m; p&lt;0.00001); graded treadmill initial claudication MD 68.8m (95%CI 54.4 to 83.2m; p&lt;0.00001); absolute claudication distance MD 41.0m (95%CI 28.8 to 53.2m; p&lt;0.00001)); but not ABI (p=0.12) or FMD (p=0.96). Sub-analyses of maximum change in Peak VO 2 showed arm cranking to be the superior modality MD 1.91 ml.kg -1 .min -1 (95% CI 1.28 to 2.54, p&lt;0.00001). Sub-analysis of peak VO 2 according to pain thresholds suggested that exercise training with no or mild pain may be superior MD 0.79 ml.kg -1 .min -1 (95% CI 0.45 to 1.14, p&lt;0.00001) to moderate/maximum pain MD 0.49 ml.kg -1 .min -1 (95% CI 0.31 to 0.66, p&lt;0.00001). Exercise training significantly improved Walking Impairment Questionnaire (WIQ) speed [MD 9.90 (95% CI 7.10 to 12.71, p&lt;0.00001)]; WIQ distance [MD 7.04 (95% CI 3.98 to 10.10, p&lt;0.00001)] and WIQ stair climbing [MD 4.99 (95% CI 3.03 to 6.69, p&lt;0.00001)]. Perceived symptoms were not improved. SF-36 physical score was significantly improved compared to control [MD 1.27 (95% CI 0.41 to 2.13, p=0.004)], but not SF-36 mental score. Conclusions and Relevance: Various modes of exercise improve cardio-respiratory fitness, pain free and total flat ground walking distances and graded treadmill performance in PAD. Alternative modes of exercise are understudied in terms of quality of life, however walking to some level of claudication pain improves WIQ speed, distance and stair climbing scores in PAD as well as SF-36 physical component score.
Abstract 14903: SPECT-CT and Bioluminescence Imaging Reveal the Important Contribution of Cellular Bioenergetics on the Molecular Imaging Signal from Stem Cells Expressing Luciferase and The Sodium-Iodide Symporter
Authors: Angel Chan, Connie Chang, Jianhua Yu, Junaid Afzal, Takahiro Higuchi, Dongdong Sun, Xijing Hosp, Richard Wahl, Martin Pomper, Benjamin Tsui, Maria Roselle Abraham
Journal: Circulation (2012)

Angel Chan, 2012 Finalist and Presenting Author
Abstract 20586: Predictors of Long-Term Survival of Acute Coronary Syndrome Patients Over 90 Years of Age Discharged Alive From a Tertiary Care Center
Authors: Nicolas W Shammas, Gail A Shammas, Michael Jerin, Carolyn Shanks, Amanda Dvorak, Patricia Serrano, Christine Harb, Cara M Voelliger, Christopher Koepke
Journal: Circulation (2014)

Introduction: Predictors of long-term mortality of patients over the age of 90 years treated for an acute coronary syndrome (ACS) at a tertiary medical center and discharged alive remain poorly defined.

Hypothesis: We hypothesized that patients over the age of 90 years presenting with an ACS at a tertiary medical center, treated with percutaneous coronary intervention (PCI) and discharged alive have an improved survival compared to those treated conservatively.

Methods: All patients admitted to a tertiary medical center between 2008 and 2012 with ACS and are over the age of 90 were included in this study. Patients were divided into 2 cohorts based on mortality post discharge at one-year follow-up (alive vs dead). Demographics, clinical and procedural variables were collected on all patients from medical records. Univariate and Cox Regression analysis were performed to model for predictors of mortality. Variables included in the multivariate analysis were admission systolic blood pressure (SBP), creatinine (cr), PCI vs medical treatment, history of stroke, dementia and diabetes.

Results: 109 patients (13.9% males) were included. ACS symptoms consisted of unstable angina (UA) 23.9%, NSTEMI 65.4%, STEMI 11%. Coronary intervention was performed in 43.5%. Mean syntax score was 23.2 ±14.5. In-hospital death occurred in 9 patients (8 for non-cardiac and 1 for cardiac reasons). Outpatient follow up data was available on 90% of patients (n=90). Out of hospital death was 41.1% (n=37). Univariate analysis showed no difference in mean age (93.5 ± 2.7), history of CAD, renal insufficiency, HT, heart failure, tobacco use, EF, DM, acuity on presentation or peak CK enzyme level. Index SBP was lower in the cohort that died (121.6 mmHg vs 134.3 mmHg, p=0.005). There was also significantly more PCI in the alive group vs those who died (56.6% vs 43.4%, p=0.051). Cox Regression analysis showed that PCI (HR 2.2, p=0.036) and a higher SBP (HR 0.979, p=0.014) were independent predictor of survival at one year follow up in this patient cohort.

Conclusions: PCI and a higher blood pressure on admission appear to be an independent predictor of long-term survival in patients over the age of 90 admitted with an acute coronary syndrome and discharged alive from a tertiary medical center.
Three-way reciprocal chromosomal translocation in an acute lymphoblastic leukemia patient with hypereosinophilia syndrome.
Authors: T S McConnell, K Foucar, W R Hardy, J Saiki
Journal: Journal of Clinical Oncology (1987)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1987.5.12.2042 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3479532 Three-way reciprocal chromosomal translocation in an acute lymphoblastic leukemia patient with hypereosinophilia syndrome. T S McConnellxT S McConnellSearch for articles by this author , K FoucarxK FoucarSearch for articles by this author , W R HardyxW R HardySearch for articles by this author , J SaikixJ SaikiSearch for articles by this author https://doi.org/10.1200/JCO.1987.5.12.2042 First Page PDF © 1987 by American Society of Clinical Oncology
Abstract 16120: Extracellar Matrix Preserving Decellulerized Heart Valve Maintain Valvular Function in vivo by Enhancing Functional Cell Recellularization
Authors: Hideto Ozawa, Shigeru Miyagawa, Satsuki Fukushima, Akima Harada, Emiko Ito, Atsuhiro Saitou, Takayoshi Ueno, Koichi Toda, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2014)

Background:  Maintanance of the valve function and the growth of the implanted heart valves are of great concerns for the treatment of heart valve insufficiency in congenital heart disease. Recently, several reports suggest that the fresh, not for freezing, decellularized heart valves maintained their structure and function after the implantation. However, the detailed process of recellurlarization of scaffold tissue after implantation remain unclear. We examined the long-term function of fresh decellularized heart valves implanted in the pulmonary valve position of porcine hearts in vivo, together with the recellularization and growth potential of the valve scaffolds.   Methods:  We used the pulmonary heart valve from heart transplant recipient heart or from mini-pigs. The valve were decellularized with 0.5% sodium deoxycholate and 0.5% sodium dodecyl sulfate with shaking condition for 36 hours. We implanted theses valves to mini-pigs in orthotropic position with cardiopulmonary machine(human heart valve: 5(xenograft), pig heart valve 5 (allograft)),without immunosuppressant drugs. Valve function was examined by UCG and MRI every month after implantation and by histological examination at 8 months after implantation..   Results:  The nuclei of the cells were removed completely and extracellular matrix components such as collagen I and III were maintained in the decellularized pulmonary valves. UCG and MRI examination revealed that valve function was maintained in all cases. We did not detect calcification in implanted valves at 8 months after the implantation. The leaflet was covered with CD31-positive cells and synthetic-type smooth muscle cells, which expressed both vimentin and SMA at 8 months after implantation. Also, vimentin positive-cells surrounded collagen I were also detected at the graft border.   Conclusions:  The fresh decellularized heart valve may be recelluralized by recipient originated somatic stem cells which are responsible for production of ECM proteins and endothelialization on leaflet or artery wall after in vivo implantation, promising a long term maintenance of valvular function.
Suppression of Dibutylnitrosamine-lnduced Bladder Carcinomas in Hamsters by Dietary Indole 2
Authors: Michio Matsumoto, Ryoichi Oyasu, Martin L. Hopp, Takuya Kitajima
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Suppression of Dibutylnitrosamine-lnduced Bladder Carcinomas in Hamsters by Dietary Indole Get access Michio Matsumoto, Michio Matsumoto Search for other works by this author on: Oxford Academic PubMed Google Scholar Ryoichi Oyasu, Ryoichi Oyasu 5 5Address reprint request to Dr. Oyasu. Search for other works by this author on: Oxford Academic PubMed Google Scholar Martin L. Hopp, Martin L. Hopp Search for other works by this author on: Oxford Academic PubMed Google Scholar Takuya Kitajima Takuya Kitajima Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 6, June 1977, Pages 1825–1829, https://doi.org/10.1093/jnci/58.6.1825 Published: 01 June 1977 Article history Received: 05 October 1976 Accepted: 06 December 1976 Published: 01 June 1977
Pak1 and Pak 2 kinases contribute to COX-2 expression in respiratory papillomas
Authors: Rong Wu, Salvatore Coniglio, Amanda Chan, Marc Symons, Bettie Steinberg
Journal: Cancer Research (2007)

416   Recurrent respiratory papillomas, caused primarily by HPV types 6 and 11, are characterized by a hyperplastic epithelium that displays increased proliferation, defects in terminal differentiation and resistance to apoptosis. Papilloma cells overexpress the epidermal growth factor receptor (EGFR) and have increased phosphoinositol -3-kinase (PI3K) activity. Papilloma tissues have elevated NF-κB DNA-binding activity and decreased levels of IκBβ, but not IκBα. We have reported that cyclooxygenase-2 (COX-2) and its product PGE 2  are induced in papilloma cells, that COX-2 expression requires EGFR and PI3K activity but not Erk activation, and that exogenous PGE 2  increases papilloma cell proliferation while a selective COX-2 inhibitor reduces proliferation and increases spontaneous apoptosis. We are now studying additional signal transduction pathways that contribute to COX-2 induction in papilloma cells.  Rac1, a member of the Rho family of GTPases, regulates a wide variety of cellular functions, including motility, proliferation, differentiation and apoptosis. We recently found that Rac1 is required for EGFR-mediated COX-2 expression, that Rac1 acts upstream of p38 MAPK in primary papilloma cells, but not in normal cells, and that inhibition of p38 MAPK suppresses COX-2 expression in papilloma cells. Moreover, Rac1 protein levels are markedly increased in papilloma cells and this increase is mediated by EGFR activation. The p21-activated kinase (Pak) family members are serine/threonine kinases that can be activated by Rac and related GTPases. Recent studies have shown that, like Rac1, they play a role in many cancers. We have now found that Pak1  and  Pak2 phosphorylation is markedly increased in papillomas in comparison to normal laryngeal epithelium. Knockdown of Pak1 or Pak2 in papilloma cells, using siRNAs, reduced expression of COX-2, indicating that these kinases also contribute to induction of COX-2. Knocking down Pak 1/2 caused an increase in the levels of IκBβ in papilloma cells, which is expected to result in a decrease of NF-κB activation. Depletion of Pak1/2 did not, however, affect p38 MAPK activation. Thus, our studies suggest that Rac1 regulates COX-2 expression in respiratory papilloma cells in a dual fashion, by stimulating Pak1/2 - NF-κB signaling on the one hand, and p38 MAPK on the other. Signaling elements that act in these pathways could potentially be effective therapeutic targets for HPV-induced tumors.