tbuckley/cabot-search huggingface dataset:
Abstract 886: Metformin effect on multidrug resistant leukemia cells: metalloproteinases 2 and 9
Authors: Ligia P. Oliveira, Camila Perea, Caroline Baldi, Rodrigo F. Prata, Débora L. Renó, Luana P. Lima, Rodrigo Curvello, Ana Carolina S. Souza
Journal: Cancer Research (2018)

Abstract Besides the progress in studies of cancer, the rates of morbidity and mortality due to this disease still considerably elevated. Chronic myeloid leukemia (CML) is a hematological neoplasm, therefore chemotherapy is the main therapeutic approach used, however most patients develop resistance to chemotherapy. Several factors contribute to this scenario, among them the lack of selective treatment, the emergence of tumor cells resistant to the wide variety of cytotoxic agents during treatment and the formation of metastases, which accounts for the majority of cancer deaths. Therefore, application of new drugs in antitumor therapies has been constantly studied. Studies have shown that metformin, an oral euglycemic used in the treatment of type II diabetes, has potential use in the treatment of cancer, potentializing the effects of standard chemotherapy used in treatment. In this work the effects of metformin on the metastatic capacity of K562 (non-resistant leukemic cell), Lucena and FEPS (leukemic cells resistant to multiple drugs) were evaluated through the study of MMP2 and MMP9 metalloproteinases, enzymes essential for the metastatic process. Thus, the present project aimed to evaluate the gene expression and enzymatic activity of MMP2 and MMP9 metalloproteinases in CML cells, before and after treatment with metformin, seeking to verify the effects of metformin on the expression and activity of these enzymes. Gene expression was evaluated using quantitative PCR and the quantification of enzymatic activity was performed by the substrate degradation using the zymography method. The results showed that metformin has the potential to modulate the expression and activity of the studied metalloproteinases. Citation Format: Ligia P. Oliveira, Camila Perea, Caroline Baldi, Rodrigo F. Prata, Débora L. Renó, Luana P. Lima, Rodrigo Curvello, Ana Carolina S. Souza. Metformin effect on multidrug resistant leukemia cells: metalloproteinases 2 and 9 [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 886.
Abstract 19790: Cardiac Rehabilitation Not Clearly Associated With Reduction of MACE Events in the First 30 Days Post Hospital Discharge
Authors: Viet T Le, Heidi T May, Jose Benuzillo, Tami L Bair, Donald L Lappé, Kirk U Knowlton, Joseph B Muhlestein
Journal: Circulation (2016)

Background: There is an increased risk of cardiovascular events including death in patients who experience acute myocardial infarction (AMI). Cardiac rehabilitation (CR) results in long term benefits, reducing death, recurrent cardiovascular events, and reducing coronary symptoms in these patients. It is unclear whether early outpatient CR can significantly impact outcomes within the first 30 days. Methods: A total of 5,572 AMI patients seen at an Intermountain Healthcare hospital from January, 2012 to May, 2016 were studied. Patients were stratified by whether they did (n=3,093 [54.2%]) or did not (n=2611 [45.8%]) receive CR within 30 days of hospital discharge. A sub-analysis was performed on a propensity matched (±0.01) population. Patients were followed for the occurrence of MACE (death, MI, heart failure [HF] hospitalization, stroke). Results: In comparison to CR patients, no CR were older (68.9% vs 64%) and had more comorbidities: hypertension (85.1% vs 78.9%), diabetes (44.5% vs 34.6%), prior strok...
Cell Therapy for Modification of the Myocardial Electrophysiological Substrate
Authors: LiorYankelson, YairFeld, TalBressler-Stramer, IlanitItzhaki, IritHuber, AmiraGepstein, DoronAronson, ShimonMarom, LiorGepstein
Journal: Circulation (2008)

Background— Traditional antiarrhythmic pharmacological therapies are limited by their global cardiac action, low efficacy, and significant proarrhythmic effects. We present a novel approach for the modification of the myocardial electrophysiological substrate using cell grafts genetically engineered to express specific ionic channels. Methods and Results— To test the aforementioned concept, we performed ex vivo, in vivo, and computer simulation studies to determine the ability of fibroblasts transfected to express the voltage-sensitive potassium channel Kv1.3 to modify the local myocardial excitable properties. Coculturing of the transfected fibroblasts with neonatal rat ventricular myocyte cultures resulted in a significant reduction (68%) in the spontaneous beating frequency of the cultures compared with baseline values and cocultures seeded with naive fibroblasts. In vivo grafting of the transfected fibroblasts in the rat ventricular myocardium significantly prolonged the local effective refractory per...
Abstract 3641: Use of adjuvant interferon alfa-2b or ipilimumab 10 mg/kg for high-risk patients with melanoma, and associated adverse events and duration of therapy
Authors: Ahmad Tarhini, Komal Gupte-Singh, Min You, Amit Gupta, Le Trong Kim, Sumati Rao
Journal: Cancer Research (2018)

Abstract OBJECTIVE: Adjuvant systemic therapy with interferon alfa-2b (IFN) or ipilimumab 10 mg/kg (IPI10) has been the standard for high-risk patients with melanoma who have undergone surgery; however, a high proportion of patients remain untreated. This analysis examines the adverse events (AEs) and duration of therapy (DoT) associated with IFN or IPI10. METHODS: A retrospective cohort study was conducted among each of the four US healthcare databases: OptumInsight, IMS PharMetrics, Truven Commercial, and Truven Medicare Supplemental. Patients receiving melanoma-related surgery (lymph node dissection) from July 1, 2006, to September 30, 2016, were identified. The study estimated the incidence rate (IR) per patient per year of AEs that commonly occur with IFN or IPI10 across different DoT levels among patients with melanoma following surgery. RESULTS: Of 46,401 eligible patients with melanoma surgery claims, 2423 (5%) were treated: 2316 with IFN and 107 with IPI10. Mean age was 51.7 years (60.5% male), and mean (standard deviation) Charlson comorbidity index score was 6.6 (2.8) and 7.5 (2.5) for patients prescribed IFN or IPI10, respectively. The DoT (median, mean (SD)) for IFN was 142, 182 (162) days and for IPI10 was 84, 73 (26) days. Similarly, the number of prescriptions (median, mean (SD)) for IFN were 20, 26 (28) and for IPI10 were 4, 3 (1). The overall AE IR per year was 4.4 in patients receiving IFN and 4.9 for those receiving IPI10. Among patients receiving IFN, the most common AEs were hepatitis, nausea, and fatigue (IRs: 0.92, 0.67, and 0.66, respectively). The most common AEs among IPI10-treated patients were fatigue, rash, nausea, and diarrhea (IRs of 0.95, 0.71, 0.66, and 0.63, respectively). AE rates were greater in patients with low DoT compared with those with a high DoT for most AEs in both IFN and IPI10 cohorts. CONCLUSION: Only 5% of high-risk patients with melanoma following lymph node dissection surgery were treated with adjuvant IPI10 or IFN, while the remaining were untreated. Patients treated with IPI10 or IFN had high AE rates impacting their ability to remain on therapy. Newer adjuvant treatments with more favorable AEs and DoT profiles are urgently needed for high-risk patients with melanoma. Disclosure: This research was funded by Bristol-Myers Squibb. Citation Format: Ahmad Tarhini, Komal Gupte-Singh, Min You, Amit Gupta, Le Trong Kim, Sumati Rao. Use of adjuvant interferon alfa-2b or ipilimumab 10 mg/kg for high-risk patients with melanoma, and associated adverse events and duration of therapy [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 3641.
Activation of p38 Mitogen-Activated Protein Kinase by Oxidized LDL in Vascular Smooth Muscle Cells
Authors: QingJing, Sun-MeiXin, Zhi-JieCheng, Wen-BoZhang, RuZhang, Yong-WenQin, GangPei
Journal: Circulation Research (1999)

Abstract—Oxidized low-density lipoproteins (oxLDL) have been shown to play a crucial role in atherosclerosis, but the underlying molecular mechanisms have not been fully understood. The present study showed that oxLDL strongly evoked phosphorylation and activation of p38 mitogen-activated protein kinase (MAPK) in rat vascular smooth muscle cells (VSMCs) in concentration- and time-dependent manners, reaching the maximal activation at 100 μg/mL within 5 minutes. The results from immunofluorescence staining also revealed that p38 MAPK was activated by oxLDL in 5 minutes, and the activated p38 MAPK was translocated from cytoplasm to nucleus of VSMCs in 15 minutes. Activation of p38 MAPK by oxLDL was apparently not mediated by their classical scavenger receptors and was not affected by tyrosine kinase inhibitors. However, activation of p38 MAPK was effectively blocked by pretreatment with pertussis toxin and was significantly reduced by phospholipase C inhibitor U-73122. OxLDL also inhibited forskolin-stimulat...
Abstract 12579: Efficacy and Safety of Transcatheter Aortic Valve Replacement in Low-Moderate Surgical Risk Patients: A Systematic Review and Meta-analysis
Authors: Abdur R Khan, Sobia Khan, Herman Simo, Faraz K Luni, Aref A Bin Abdulhak, Chirag Bavishi, Haris Riaz, Michael P Flaherty
Journal: Circulation (2015)

Background: The efficacy of transcatheter aortic valve replacement (TAVR) in patients at high surgical risk has been established. The data in patients with low-moderate risk for surgery is still not conclusive. We sought to perform a meta-analysis of studies comparing the safety and efficacy of TAVR with surgical aortic valve replacement (SAVR). Methods: Several databases were searched from inception to February 2015, which yielded 10 eligible studies. Studies were selected if they compared TAVR to SAVR in patients at low-moderate risk for surgery. The measured outcomes of efficacy were all-cause and cardiovascular mortality. Data on safety included cerebrovascular events (CVA), permanent pacemaker implantation (PPI), aortic regurgitation (AR), vascular access complications and major bleeding reported during the procedure. Outcomes were pooled and relative risk was calculated using the Mantel-Haenszel method using a random effects or a fixed effect model based on heterogeneity. If studies had zero events in any of the arms, Peto odds ratio was used to pool data. Results: There were 10 studies with 3107 participants in our analysis. There was no difference in either short-term (RR, 0.85; CI: 0.57–1.28; p=0.44; I2=0%) or medium to long-term all-cause mortality (RR, 0.97; CI: 0.80–1.18; p=0.78; I2=0%). Our analysis suggested a decreased risk of cardiovascular mortality in the short-term (RR, 0.42; CI: 0.19–0.91; p=0.03; I2=0%) and a statistically non-significant trend towards decrease in long-term mortality (RR, 0.53; CI: 0.26–1.08; p=0.08; I2=0%) with TAVR. There was increased incidence of AR (RR, 4.01; CI: 2.24–7.19; p&lt; 0.00001; I2=0%), PPI (RR, 5.00; CI: 3.47–7.19; p&lt; 0.00001; I2=21%) and vascular access complications (RR, 6.36; CI: 3.75–10.76; p&lt; 0.00001; I2=27%) in patients with TAVR. There was no difference in the risk of stroke between TAVR and SAVR (RR, 1.17; CI: 0.62–2.21; p=0.64; I2=15%) and an increased risk of major bleeding with SAVR was found (RR, 1.81; CI: 1.08–3.03; p&lt; 0.0001; I2=86%). Conclusions: In this meta-analysis we found that TAVR may be an acceptable alternative to SAVR in patients with low-moderate risk for surgery. However, more evidence is needed from the current randomized trials before more widespread adoption of the procedure.
Current trends in the interventional treatment of hepatocellular carcinoma: A cross-sectional survey of transarterial embolization techniques.
Authors: Paul Craig, Shamar Young, Scott Lunos, Jafar Golzarian
Journal: Journal of Clinical Oncology (2017)

e15627 Background: Since two randomized controlled trials demonstrated the superiority of Transarterial chemoembolization (TACE) to supportive care, it has been a mainstay of treatment for unresectable hepatocellular carcinoma (HCC). The technical aspects of the TACE procedure, including drug type, embolic agent, bead type and size, procedural endpoint and follow up are heterogeneous throughout the literature, making meaningful comparisons less impactful. The goal of this study was to determine the common technical practices in the interventional therapy of HCC over several geographical areas. Methods: An anonymous 18 question online survey was distributed via email to practicing members of the Cardiovascular and Interventional Radiology Society of Europe (CIRSE), Chinese Society of Interventional Radiology (CSIR), Japanese Society of Interventional Radiology (JSIR), Korean Society of Interventional Radiology (KSIR), and the Society of Interventional Radiology (SIR). An estimated 15,700 surveys were distributed and 1160 responses obtained from 62 countries for a total response rate of 7.4%. Results: Excluding bead size, responses were statistically different by region (p &lt; 0.05). Doxorubicin was more commonly used among SIR, CIRSE, and KSIR members than JSIR and CSIR members (p &lt; 0.05). A fixed dose of cytotoxin was favored by SIR and CIRSE members, while dosing dependent on tumor-size was used by KSIR, JSIR, and CSIR members (p &lt; 0.05). Drug eluting bead-TACE (DEB-TACE) was most popular in SIR and CIRSE, while classical TACE (cTACE) was most popular in Japan, Korea, and China (p &lt; 0.05). For DEB-TACE procedures, the favored bead size was 100 μm – 300 μm for all groups. Procedural endpoint, type of embolic agent, and use of additives and antibiotics varied among groups (p &lt; 0.05). CT was the most commonly used modality for follow up amongst all respondents, but MR was used more by SIR members than all other groups (p &lt; 0.05). Conclusions: This study demonstrated that there is clear evidence that the TACE technique differs by region. Understanding and reporting the current practice trends is an important step to optimize and standardize future randomized controlled trials.
Cladribine and low-dose cytarabine alternating with decitabine as front-line therapy for elderly patients with acute myeloid leukaemia: a phase 2 single-arm trial
Authors: Tapan M Kadia, Jorge Cortes, Farhad Ravandi, Elias Jabbour, Marina Konopleva, Christopher B Benton, Jan Burger, Koji Sasaki, Gautam Borthakur, Courtney D DiNardo, Naveen Pemmaraju, Naval Daver, Alessandra Ferrajoli, Xuemei Wang, Keyur Patel, Jeffrey L Jorgensen, Sa Wang, Susan O'Brien, Sherry Pierce, Carla Tuttle, Zeev Estrov, Srdan Verstovsek, Guillermo Garcia-Manero, Hagop Kantarjian
Journal: The Lancet Haematology (2018)
Abstract P024: Blood Pressure Levels, Aggressiveness of Antihypertensive Therapy, and Prevalence of Left Ventricular Hypertrophy
Authors: SindhuLakkur, SayedSoliman, SuzanneOparil, SuzanneJudd, GeorgeHoward
Journal: Circulation (2015)

A major cause of left ventricular hypertrophy (LVH) is an excessive hemodynamic load, making LVH more common among people with hypertension. Clinical trials of antihypertensive medication have found that treatment reduces left ventricular mass among those with hypertension, but little is known about the prevalence of LVH in the general population that are taking, and not taking, antihypertensive medication. We examined the cross-sectional association between blood pressure control and LVH among 28,106 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, to test the hypotheses that: 1) within strata of blood pressure control, LVH will be more prevalent in those requiring more intensive treatment, and 2) that within strata of intensiveness of blood pressure treatment, that LVH will be more prevalent at higher blood pressure levels. The REGARDS study enrolled black and white participants, aged 45 and older, from 2003-2007. Systolic blood pressure was defined as normal ...
Coronary Artery Calcification: Pathophysiology, Epidemiology, Imaging Methods, and Clinical Implications
Authors: LewisWexler, BruceBrundage, JohnCrouse, RobertDetrano, ValentinFuster, JamshidMaddahi, JohnRumberger, WilliamStanford, RichardWhite, KathrynTaubert
Journal: Circulation (1996)
Abstract LB-056: Novel molecular mechanism underlying cancer drug resistance: Involvement of p58IPKchaperone pathway
Authors: Mohammad Athar, Ritesh Srivastava
Journal: Cancer Research (2018)

Abstract Rhabdomyosarcoma (RMS) is an aggressive and highly malignant form of pediatric cancer that develops from skeletal muscle cells. A third of these cancers become drug resistant, metastatic and fatal. Current therapeutic approaches have not resulted in significant improvement in outcome for patients with recurrent and/or metastatic disease. Here, employing two RMS-derived cell lines (RH30, a drug sensitive and RD, a drug resistant), we demonstrate a novel underlying molecular mechanism of drug resistance in these tumor subtypes. We show that in response to chemotherapeutics drugs [actinomysin D, torisol, etoposide and arsenic trioxide (ATO)], endoplasmic reticulum (ER) stress associated unfolded protein response (UPR) signaling pathway could be induced in RH30 cell only, while drug resistance RD cells largely lack this ability. The mechanism underlying UPR induction involves activation of multifunctional molecular chaperone P58IPK that besides regulating protein homeostasis is an inhibitor of the interferon-induced double-stranded RNA-activated protein kinase (PKR). We observed that the expression of p58IPK is high in drug resistance RD cells as compared to drug sensitive RH30 cells. To confirm its role in drug resistance, we ablated or overexpressed p58IPK respectively in drug resistant RD and drug sensitive RH30 cells. The p58IPK depleted RD cells became sensitive to chemotherapeutic agents while overexpressing p58IPK RH30 cells manifested drug resistance. To further demonstrate the known functional consequences of manipulation in the expression of p58IPK we found that P58IPK over-expression in RH30 cells inhibited eIF2α phosphorylation and diminished apoptosis by downregulating ATF4/CHOP/Cleaved caspase-3, while silencing of p58IPK in RD cells enhanced eIF2α phosphorylation and increased ATF4/CHOP/Cleaved caspase-3-dependent apoptosis in response to chemotherapeutic drug treatment. The underlying mechanism by which P58IPK alters drug sensitivity in RMS cells involves its chaperone function by its binding to drug transporters ABCB-1 and ABCC-1. At baseline, in RD cells with high p58IPK manifest significantly higher dye efflux as compared to RH30 with low p58IPK. This baseline drug exclusion profile correlated with the ATPase activity of these ABC transporters. However, ablation or overexpression of p58IPK respectively, in RH30/RD cells reversed their drug resistance phenotype. Thus, we have identified a novel drug resistance mechanism in RMS. These results may have translational implications in overcoming drug-resistance in deadly neoplasm. These studies are in progress in our laboratory. Citation Format: Mohammad Athar, Ritesh Srivastava. Novel molecular mechanism underlying cancer drug resistance: Involvement of p58IPKchaperone 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 LB-056.
Role of Autonomic Nervous System in the Pathogenesis of Prinzmetal's Variant Form of Angina
Authors: Hirofumiyasue, Masatotouyama, Mitsuomishimamoto, Hirofumikato, Satorutanaka, Fumiyaakiyama
Journal: Circulation (1974)

In ten patients with Prinzmetal's variant form of angina the effects of various drugs were assessed: subcutaneous injection of methacholine (10 mg), atropine (0.7 mg), and epinephrine (0.7 mg); intravenous infusion of isoproterenol (20-25 µg/min); and in the three of the above patients who were having recurrent spontaneous attacks at the time of the examination, oral administration of atropine (0.6-1.2 mg), propranolol (30-90 mg), and phenoxybenzamine (10 mg in one patient). Master's triple two-step test and selective coronary arteriography were done on all the patients. In the three patients who were having spontaneous attacks at the time of the examination, the administration of methacholine induced the attacks and that of atropine suppressed the attacks. Epinephrine induced the attacks in two patients and propranolol was without effect in suppressing the attacks. Phenoxybenzamine (in one patient) suppressed the attacks. Neither Master's triple two-step test nor isoproterenol infusion precipitated the a...
Preconditioning Results in S-Nitrosylation of Proteins Involved in Regulation of Mitochondrial Energetics and Calcium Transport
Authors: JunhuiSun, MeghanMorgan, Rong-FongShen, CharlesSteenbergen, ElizabethMurphy
Journal: Circulation Research (2007)

Nitric oxide has been shown to be an important signaling messenger in ischemic preconditioning (IPC). Accordingly, we investigated whether protein S-nitrosylation occurs in IPC hearts and whether S-nitrosoglutathione (GSNO) elicits similar effects on S-nitrosylation and cardioprotection. Preceding 20 minutes of no-flow ischemia and reperfusion, hearts from C57BL/6J mice were perfused in the Langendorff mode and subjected to the following conditions: (1) control perfusion; (2) IPC; or (3) 0.1 mmol/L GSNO treatment. Compared with control, IPC and GSNO significantly improved postischemic recovery of left ventricular developed pressure and reduced infarct size. IPC and GSNO both significantly increased S-nitrosothiol contents and S-nitrosylation levels of the L-type Ca2+ channel α1 subunit in heart membrane fractions. We identified several candidate S-nitrosylated proteins by proteomic analysis following the biotin switch method, including the cardiac sarcoplasmic reticulum Ca2+-ATPase, α-ketoglutarate dehydr...
Thyroid Disease and the Heart
Authors: IrwinKlein, SaraDanzi
Journal: Circulation (2007)

The cardiovascular signs and symptoms of thyroid disease are some of the most profound and clinically relevant findings that accompany both hyperthyroidism and hypothyroidism. On the basis of the understanding of the cellular mechanisms of thyroid hormone action on the heart and cardiovascular system, it is possible to explain the changes in cardiac output, cardiac contractility, blood pressure, vascular resistance, and rhythm disturbances that result from thyroid dysfunction. The importance of the recognition of the effects of thyroid disease on the heart also derives from the observation that restoration of normal thyroid function most often reverses the abnormal cardiovascular hemodynamics. In the present review, we discuss the appropriate thyroid function tests to establish a suspected diagnosis as well as the treatment modalities necessary to restore patients to a euthyroid state. We also review the alterations in thyroid hormone metabolism that accompany chronic congestive heart failure and the appr...