tbuckley/cabot-search huggingface dataset:
Abstract 4724: Anti-tumor effects of SC-2001, a novel STAT3 inhibitor, in breast cancer cells
Authors: Ling-Ming Tseng, Chun-Yu Liu, Yuan-Ping Kao, Chung-Wai Shiau, Jung-Chen Su, Kung-Chi Chang, Kuen-Feng Chen
Journal: Cancer Research (2012)

Abstract Background: STAT3 has been shown to play an important role in breast carcinogenesis and is often overexpressed in primary breast tumors. STAT3 has emerged as a novel potential anti-cancer target. Previously, we have designed SC-2001 ((Z)-2-((3-methoxy-2H-pyrrol-2-ylidene)methyl)-1H-pyrrole) and reported its efficacy in HCC cells (AACR 2011, abstract#4516). SC-2001 is structurally related to the Mcl-1 inhibitor obatoclax, and showed better antitumor effects than obatoclax in HCC cells. Here, we examined the efficacy and drug mechanism of SC-2001 in breast cancer cells. Methods: breast cancer cell lines were used for in vitro studies. Apoptosis was examined by both flow cytometry and Western blot. Signal transduction pathways in cells were assessed by Western Blot. Tyrosine Phosphatase Assay Kit was used for SHP-1 activity assay. Gene silencing was done by small interference RNA (siRNA). Results: SC-2001 inhibited tumor cell growth (by MTT assay) and induced apoptosis in several breast cancer cell lines (MDA MB-468, MDA MB-231, MDA MB-453, MCF-7). SC-2001 inhibited the protein-protein interactions between Mcl-1 and Bak similar to obatoclax. In addition, SC-2001 downregulated Mcl-1 expression by reducing its transcription, whereas obatoclax had no such effect. SC-2001 downregulated the phosphorylation of STAT3 (Tyr 705) and subsequently inhibited its transcriptional activities in a dose-dependent manner. Moreover, STAT3-regulated proteins, including Mcl-1, survivin and cyclin D1, were also repressed by SC-2001. Over-expression of STAT3 in MDA MB-468 cells protected cells from SC-2001-induced apoptosis. Importantly, SC-2001 enhanced the expression of SHP-1, a negative regulator of STAT3. Inhibition of SHP-1 by either specific inhibitor or siRNA reduced the apoptotic effects of SC-2001, indicating that SHP-1 plays a key role in mediating SC-2001-induced cell death. Conclusions: our results suggest that SC-2001 induced apoptosis in breast cancer cells, and that this effect is mediated through SHP-1-dependent STAT3 inactivation. (Supported by NSC100-2325-B-002-036, NSC98-2320-B-010-005-My3 and NSC-100-2325-B-010-007, VGHTPE V100D-005-4, 101DHA0100318, and 101DHA0100230.) Keyword: obatoclax, breast cancer, STAT3, SHP-1, apoptosis Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4724. doi:1538-7445.AM2012-4724
Abstract 5127: G6-mediated inhibition of Jak2 tyrosine kinase correlates with the cleavage and cellular reorganization of vimentin
Authors: Anurima Majumder, Annet Kirabo, Kanchana Karrupiah, Shigeharu Tsuda, Jennifer Caldwell-Busby, Arturo J. Cardounel, Peter P. Sayeski
Journal: Cancer Research (2011)

Abstract Hyperkinetic Jak2 tyrosine kinase signaling has been implicated in several human diseases including various leukemias, lymphomas, myelomas and the myeloproliferative neoplasms. Using structure-based virtual screening, our lab previously identified a novel Jak2 inhibitor named G6. We showed that G6 has a specific inhibitory effect on Jak2 tyrosine kinase activity and potently suppresses Jak2-mediated cellular proliferation. To elucidate the biochemical and cellular mechanisms by which G6 inhibits Jak2-mediated cell proliferation, we treated Jak2-V617F expressing human erythroleukemia (HEL) cells for 12 hours with either vehicle control (DMSO) or 25 µM of the drug and then compared their protein expression profiles using two-dimensional gel electrophoresis. One protein that was found to be differentially expressed was the intermediate filament protein vimentin. Specifically, we found that full length vimentin was robustly expressed in untreated cells and absent in G6 treated cells. We hypothesized that inhibition of Jak2-V617F dependent pathogenic cell growth by G6 correlates with the cleavage and cellular reorganization of intermediate vimentin filaments. To this end, we found that the treatment of HEL cells with G6 induced a time- and dose-dependent cleavage of vimentin. This G6-induced cleavage of vimentin was both Jak2-dependent and calpain-mediated. Using indirect immunofluorescence, we found that G6 treatment resulted in a marked reorganization of vimentin filaments within cells. Finally, using a mouse model of Jak2-V617F mediated neoplasia, we found that G6 decreased the levels of vimentin protein within the bone marrow of G6 treated mice when compared to animals that received vehicle control. Overall, these results demonstrate that G6-mediated inhibition of Jak2-dependent pathogenic cell growth correlates with the proteolytic cleavage of full length vimentin and the reorganization of intermediate vimentin filaments within cells. As such, we may have identified a biochemical and cellular mechanism whereby G6 inhibits Jak2-V617F mediated cellular proliferation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5127. doi:10.1158/1538-7445.AM2011-5127
WHAT DRIVES FOLLOW-UP OF PEDIATRIC BICUSPID AORTIC VALVE: PROVIDER PREFERENCE OR DISEASE CHARACTERISTICS?
Authors: Melissa Yamauchi, Michael Puchalski, Hsin-Yi Weng, Nelangi Pinto, L. LuAnn Minich, Susan Etheridge, Angela P. Presson, Richard Williams
Journal: Journal of the American College of Cardiology (2016)
Abstract 15927: Glutaredoxin-1 Regulation of Interleukin-33 Induction in Macrophages
Authors: Ellen O Weinberg, Colin E Murdoch, Reiko Matsui
Journal: Circulation (2011)

Glutaredoxin-1 (Glrx) is a cytosolic enzyme that removes glutathione (GSH) adducts from S-glutathiolated proteins. S-glutathiolation inhibits translocation or DNA binding of transcription factors i...
AB0375 Lengthening of Recommended Dose Range of Anti-TNF Therapy in Patients with Rheumatoid Arthritis and Peripheral Psoriatic Arthritis in Remission:
Authors: C. Nuñez_cornejo Piquer, I. Chalmeta Verdejo, C. Molina Almela, I. Martinez Cordellat, C. Feced Olmos, E. Grau, C. Alcañiz Escandell, L. Gonzalez Puig, J. Ivorra Cortes, R. Negueroles Albuixech, M.L. Muñoz Guillen, J.L. Valero Sanz, J.A. Roman Ivorra
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Anti-TNF therapy has been a great advance in the treatment of rheumatic diseases. However, these drugs have a high cost and potentially severe adverse effects, therefore it would be useful to analyze their use at lower doses with a longer dosing interval. <h3>Objectives</h3> The aim of this study is to analyze whether lengthening the recommended dosing interval with anti-TNF therapies in rheumatoid arthritis and psoriatic peripheral arthritis in remission provides good control of the disease. <h3>Methods</h3> We collected the clinical data of patients diagnosed with rheumatoid arthritis (RA) and peripheral psoriatic arthritis (PSA) in subcutaneous anti-TNF therapy (adalimumab, etanercept and golimumab), which were in remission/low activity at two successive consultations and in which the anti-TNF dosing interval has been lengthened according to the following pattern: etanercept 50 mg/15 days, adalimumab 40 mg/21 days, and golimumab 50mg/5 weeks. In order to evaluate disease activity, we used the DAS28, serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) before changing the dosing interval at 6, 12, 18, 24 and 30 months of follow-up. Biostatistical analysis was performed using linear regression models. <h3>Results</h3> We included a total of 67 patients from February 2011 (42 AR and 25 PSA) who were treated with anti-TNF therapy (39 with adalimumab, 23 with etanercept and 5 with golimumab). The mean DAS28 score at different intervals is shown in the table below. During follow-up, there were 9 interruptions in lengthening (4 RA and 5 PSA), 5 exacerbations and 3 transfers to another hospital. According to the data obtained, DAS28 in RA cases slightly increased with lengthening of the dosing interval but does not reach values exceeding low disease activity. Linear regression revealed a tendency that the adalimumab and biological therapy combined with methotrexate maintained low disease activity more efficiently. <h3>Conclusions</h3> Although no statistically significant results were obtained due to the small number of patients, in all cases the disease control was achieved. Furthermore, better control was achieved with the combined use of biological therapy and methotrexate, as well as with adalimumab. However, a larger number of cases and longer follow-up period is needed in order to confirm that prolonging the anti-TNF dosing interval is useful for disease control. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4944
Abstract 1633: The sphingosine kinase inhibitor SKI-II blocks survival and MAPK signaling in human breast cancer in vitro
Authors: Martin D. White, James W. Antoon, William D. Meacham, Evelyn M. Slaughter, Matthew E. Burow, Barbara S. Beckman
Journal: Cancer Research (2010)

Abstract Endocrine resistance is a major contributor to treatment failure in breast cancer. A close examination of the signaling mechanisms by which cells may impart their resistance presents an attractive strategy for the development of viable treatment options. Sphingosine kinase (SK), and its product, sphingosine-1-phosphate (S1P), have been increasingly implicated in many disease states and SK/S1P signaling is a known regulator of apoptosis and cell survival. Furthermore, inhibition of sphingosine kinase has been shown to be anti-proliferative as well as apoptotic in a multitude of human cancer cell lines. In this study, we investigated the biological activity of the sphingosine kinase inhibitor, SKI-II (4-[[4-(4-Chlorophenyl)-2-thiazolyl]amino]phenol) and its ability to disrupt cell signaling in estrogen-dependent and endocrine-resistant breast cancer. SKI-II blocked both viability and survival at low micromolar IC50 concentrations in endocrine therapy-resistant MDA-MB-231, MDA-MB-468 and MDA-MB-361 cells in addition to endocrine therapy-sensitive MCF-7 breast cancer lines. Additionally, treatment with SKI-II significantly (p&amp;lt;0.05) decreased proliferation, as seen in Ki-67 immunostaining. The potent biological activity of this inhibitor led us to characterize the precise molecular mechanisms in which SKI-II imparts its effects. Sphingosine kinase is known to affect various signaling cascades, and its effect on the MAPK and PI3K/Akt pathways are cell line dependent. Growth factor signals such as MAPK can cross-talk with estrogen receptor and confer hormone therapy resistance. Therefore, we chose to investigate several signaling cascades to determine if SK inhibition mediates its effect through disruption of signaling. SKI-II diminished phosphorylation of ERK1/2 in both a time-dependent and dose-dependent manner. Treatment with SKI-II also inhibited phosphorylation of p38/MAPK at similar concentrations. This blockade of MAPK signaling may contribute to SKI-II's dual anti-cancer effect, which can target ER activation in an estrogen-dependent and an estrogen-independent manner. Targeting the production of sphingosine-1-phosphate through pharmacological inhibition presents a potentially useful method to reset the cell signaling aberrations -which lead to endocrine resistance, and may contribute to overall greater efficacy of current therapeutic interventions by re-sensitizing cells to endocrine therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1633.
P124NAADP as a novel downstream mediator of cardiac beta-adrenergic pathway
Authors: W Lin, E Bolton, R Capel, Y Wang, A Galione, D A Terrar
Journal: Cardiovascular Research (2014)

Background: Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent endogenous Ca2+ mobilizing second messenger that is known to release Ca2+ from the acidic endolysosomal vesicles. Our previous work showed that intracellular application of NAADP led to the increase in contractions of electrically stimulated guinea pig ventricular cardiomyocytes. These observations were accompanied by an increase in sarcoplasmic reticulum (SR) Ca2+ load. Previously, it has been reported that beta-adrenergic activation increases the level of NAADP in guinea pig whole heart experiments, and we therefore hypothesized that the inotropic effect of beta-adrenergic activation is partly mediated by NAADP. This study aims to test this possibility and subsequently dissect the related pathway.
A Controlled Trial of Two Acellular Vaccines and One Whole-Cell Vaccine against Pertussis
Authors: Donato Greco, Stefania Salmaso, Paola Mastrantonio, Marina Giuliano, Alberto E. Tozzi, Alessandra Anemona, Marta L. Ciofi degli Atti, Anna Giammanco, Pietro Panei, William C. Blackwelder, David L. Klein, Steven G.F. Wassilak
Journal: New England Journal of Medicine (1996)

Concern about both safety and efficacy has made the use of whole-cell pertussis vaccines controversial. In some European countries, including Italy, the rate of vaccination against pertussis is low.
ACE INHIBITOR USE AND MAJOR CARDIOVASCULAR OUTCOMES IN TYPE 2 DIABETES TREATED WITH THE DPP-4 INHIBITOR ALOGLIPTIN
Authors: William B. White, Craig Wilson, George Bakris, Richard Bergenstal, Christopher Cannon, William Cushman, Penny Fleck, Simon Heller, Stuart Kupfer, Cyrus Mehta, Steven Nissen, Alfonso Perez, Venu Menon, Faiez Zannad
Journal: Journal of the American College of Cardiology (2015)
And the Walls Come Tumbling Down
Authors: Maxwell Finland
Journal: New England Journal of Medicine (1978)

Little by little we are experiencing the erosion of the strongest bulwarks against serious bacterial infections in the modern antibacterial era. In 1955, I reviewed the extensive literature on the emergence of antibiotic-resistant bacteria,1 and more recently summarized some of the subsequent developments.2 Some highlights of these developments are worth noting.When the sulfonamide drugs were introduced they were widely and successfully used in the treatment of gonorrhea and of Group A hemolytic streptococcal infections. It was not long before the effectiveness of the sulfonamides against these infections was essentially lost. In gonorrhea, which is transmitted exclusively by person-to-person contact, . . .
AB0732 Pregnancy outcome in lupus patients with previous adverse outcomes: Experience with protocol based, multidisiplinary care
Authors: V. Ravindran, K.P. Balakrishnan, M. Diwakaran, R. Ramakrishnan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In patients with SLE with previous adverse obstetric outcome(s) the risk of an adverse outcome in subsequent pregnancy rises. <h3>Objectives</h3> The primary objective of this study was to assess the impact of a protocol based multidisciplinary care on pregnancy outcome(s) in a prospective cohort of patients with SLE with previous adverse obstetric outcome(s). <h3>Methods</h3> Between March 2010 and March 2011 all patients with SLE fulfilling the ACR classification criteria with previous at least one adverse obstetric outcome (maternal; preterm labour, pre ecalampsia or previous medical termination of pregnancy (MTP) in view of SLE flare, foetal; miscarriage, IUGR, preterm birth, low birth weight (LBW), intrauterine death or still birth) desirous of having more children were prospectively enrolled. Briefly the protocol comprised of pre natal counselling, pre-natal drug and disease status review, risk stratification, periodic ante-natal visits for the monitoring of pregnancy (including with obstetric ultrasounds) and disease, 2D echocardiogram at weeks 18 and 32 if Ro/La were positive and post natal disease and drug review and contraception advice. Therapeutic changes were made as necessary at each stage. <h3>Results</h3> Fourteen patients (age mean±SD years; 29±3) were enrolled. Previous poor obstetric outcomes were: miscarriage(s) in 6, MTP in 3, preterm labour with IUGR in 2, intrauterine death, still birth and pre ecalapmsia in 1 each. Four patients had secondary APS and 6 had both or either Ro/La positive. Three had lupus nephritis (LN); &gt;6months ago in 2. There were 10 (71%) live births (2 LBW, instrumentation or caesarean section in 3). Three patients had miscarriages (one had ongoing LN). One decided against becoming pregnant after initial counselling. Five patients (35%) had lupus flare (2 mild, 2 moderate and 1 severe based on SLEDAI). <h3>Conclusions</h3> Majority of patients in our prospective cohort had acceptable pregnancy outcome. This highlights that for high risk lupus pregnancies a multidisciplinary input with protocol based care offers a superior chance of improved pregnancy outcome. <h3>Disclosure of Interest</h3> None Declared
HIGH PERFUSION PRESSURE AS A PREDICTOR OF REPERFUSION PULMONARY INJURY AFTER BALLOON PULMONARY ANGIOPLASTY FOR CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION
Authors: Hiroto Kinutani, Toshiro Shinke, Hiromasa Otake, Tomofumi Takaya, Tsuyoshi Osue, Akihide Konishi, Masaru Kuroda, Hachidai Takahashi, Daisuke Terashita, Kenzo Uzu, Daiji Kashiwagi, Koji Kuroda, Natsuko Tahara, Yoshinori Nagasawa, Noriaki Emoto, Kazuhiko Nakayama, Yu Taniguchi, Yuto Shinkura, Ken-ichi Hirata
Journal: Journal of the American College of Cardiology (2015)
The Risk of Cancer Associated with Specific Mutations of<i>BRCA1</i>and<i>BRCA2</i>among Ashkenazi Jews
Authors: Jeffery P. Struewing, Patricia Hartge, Sholom Wacholder, Sonya M. Baker, Martha Berlin, Mary McAdams, Michelle M. Timmerman, Lawrence C. Brody, Margaret A. Tucker
Journal: New England Journal of Medicine (1997)

Carriers of germ-line mutations in BRCA1 and BRCA2 from families at high risk for cancer have been estimated to have an 85 percent risk of breast cancer. Since the combined frequency of BRCA1 and BRCA2 mutations exceeds 2 percent among Ashkenazi Jews, we were able to estimate the risk of cancer in a large group of Jewish men and women from the Washington, D.C., area.We collected blood samples from 5318 Jewish subjects who had filled out epidemiologic questionnaires. Carriers of the 185delAG and 5382insC mutations in BRCA1 and the 6174delT mutation in BRCA2 were identified with assays based on the polymerase chain reaction. We estimated the risks of breast and other cancers by comparing the cancer histories of relatives of carriers of the mutations and noncarriers.One hundred twenty carriers of a BRCA1 or BRCA2 mutation were identified. By the age of 70, the estimated risk of breast cancer among carriers was 56 percent (95 percent confidence interval, 40 to 73 percent); of ovarian cancer, 16 percent (95 percent confidence interval, 6 to 28 percent); and of prostate cancer, 16 percent (95 percent confidence interval, 4 to 30 percent). There were no significant differences in the risk of breast cancer between carriers of BRCA1 mutations and carriers of BRCA2 mutations, and the incidence of colon cancer among the relatives of carriers was not elevated.Over 2 percent of Ashkenazi Jews carry mutations in BRCA1 or BRCA2 that confer increased risks of breast, ovarian, and prostate cancer. The risks of breast cancer may be overestimated, but they fall well below previous estimates based on subjects from high-risk families.
Platelet Survival in Patients with Substitute Heart Valves
Authors: Hugh S. Weily, Peter P. Steele, Hywel Davies, George Pappas, Edward Genton
Journal: New England Journal of Medicine (1974)

To determine the relation of thromboembolism to the presence of substitute heart valves platelet studies were performed in 55 patients. Average platelet survival was normal in patients with homograft valves and Beall prostheses, but was short in those with older prosthetic mitral valves. Short platelet survival time and the frequency of thromboembolism were significantly related. Thromboembolism had occurred in 62 per cent of patients with short survival but in only 9 per cent of those with normal survival, and average platelet survival was significantly shorter in 13 patients with thromboembolism than in 42 patients without thromboembolism. In postoperative patients with newer mitral valves, average platelet survival was abnormally short in those who had had thromboembolism before operation. Postoperative thromboembolism occurred in 30 per cent of these patients but in none of those without preoperative thromboembolism in whom meah platelet survival also was normal. Results demonstrate that platelet survival correlates with a history of thromboembolism in patients with substitute heart valves. (N Engl J Med 290:534–537, 1974)
Case 2-2001
Authors: Carl B. Sherter, Eugene J. Mark
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 42-year-old woman was admitted to another hospital because of worsening dyspnea and cough.During the year before admission, the patient had had mild dyspnea on exertion, a cough that was occasionally productive of whitish mucus, slight fatigue, and a weight loss of 7 kg. Three weeks before admission, the dyspnea and cough suddenly worsened and were accompanied by fever. Use of a codeine–guaifenesin cough syrup was ineffective. The patient came to the emergency room.The patient worked at a sedentary occupation, without known exposure to industrial dusts. She had smoked one and a half packs of . . .
Safe and prolonged survival with long-term exposure to pomalidomide in relapsed/refractory myeloma
Authors: G. Fouquet, B. Pegourie, M. Macro, M.O. Petillon, L. Karlin, D. Caillot, M. Roussel, B. Arnulf, C. Mathiot, G. Marit, B. Kolb, A.M. Stoppa, S. Brechiniac, V. Richez, P. Rodon, A. Banos, M. Wetterwald, L. Garderet, B. Royer, C. Hulin, L. Benbouker, O. Decaux, M. Escoffre-Barbe, J.P. Fermand, M. Attal, H. Avet-Loiseau, P. Moreau, T. Facon, X. Leleu
Journal: Annals of Oncology (2016)
MEASUREMENT OF THE PERIPHERAL ARTERIAL TONE: A NEW DIAGNOSTIC DEVICE FOR DETECTING SLEEP DISORDERED BREATHING IN PATIENTS WITH CHRONIC HEART FAILURE
Authors: Florian Schindhelm, Martin Braun, Olaf Oldenburg, Henrik Fox, Zisis Dimitriadis, Dieter Horstkotte, Thomas Bitter
Journal: Journal of the American College of Cardiology (2016)
236 BONE MARROW AND NON-BONE MARROW TLR4 REGULATES ACUTE HEPATIC INJURY INDUCED BY ENDOTOXEMIA
Authors: Z. Ben Ari, O. Avlas, O. Pappo, Y. Cheporko, L. Bachmatov, R. Zemel, A. Shainberg, E. Hochhauser
Journal: Journal of Hepatology (2012)