tbuckley/cabot-search huggingface dataset:
Abstract 3582: In vitro pharmacological studies of water soluble garlic extract (WSGE) in the management of acute promyelocytic leukemia (APL)
Authors: Clement G. Yedjou, Paul B. Tchounwou
Journal: Cancer Research (2010)

Abstract Garlic (allium sativum) is one of the oldest cultivated plants, used in spices, food, and herbal medicine for over 4000 years. The therapeutic efficacy of garlic has a wide variety of ailments, including cardiovascular, cancer, hepatic and microbial infections. Although the therapeutic efficacy of garlic in the prevention of cancer and other diseases has received increasing attention in recent years, little is known about its mechanism for therapeutic action. In this research, we hypothesize that the pharmacological effect of garlic may be mediated through oxidative stress, DNA damage, modulation of annexin-5 and caspase-3 in human leukemia (HL-60) cells. To test this hypothesis, HL-60 cells were treated with various doses of water soluble garlic extract (WSGE) for 12 h. Cell survival was determined by MTT-assay. The extent of oxidative cell/tissue damage was determined by measuring the level of malonaldiahyde (MDA) concentrations. Cell apoptosis was measured by flow cytometry using annexin V and caspase-3 kits, respectively. MTT assay indicated a strong dose-response relationship with regard to the cytotoxic efficacy of WSGE in HL-60 cells. There was a slight increase in MDA concentrations in WSGE-treated cells compared to the control, but this was not statistically significant (P &amp;gt; 0.05) probably due to the antioxidant property of garlic. WSGE-induced apoptosis was characterized by a significant (P &amp;lt; 0.05) increase in the percentages of annexin-5 and caspase-3 positive cells. In summary, the pharmacotherapy of WSGE may be associated through induction of moderate toxicity, induction of DNA damage, phosphatidylserine externalization and caspase-3 activation characteristic of apoptosis. 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 3582.
IN-HOSPITAL RESOURCE UTILIZATION ASSOCIATED WITH GASTROINTESTINAL BLEEDING IN PATIENTS WITH CONTINUOUS FLOW-LEFT VENTRICULAR ASSIST DEVICES
Authors: Anthony Carnicelli, Anjali Thakkar, David Deicicchi, Andrew Storm, Jean Connors, Gregory Couper, Mandeep Mehra, John Groarke, Michael Givertz
Journal: Journal of the American College of Cardiology (2016)
Abstract 2174: Progesterone receptor, AP-1 and Stat3 cooperative transcriptional complex in breast cancer
Authors: María C. Díaz Flaqué, Wendy Béguelin, Rocio Vicario, Cecilia Proietti, Martín Rivas, Mercedes Tkach, Franco Izzo, Eduardo Charreau, Roxana Schillaci, Patricia Elizalde
Journal: Cancer Research (2011)

Abstract We have previously demonstrated that progestin induces the rapid activation of AP-1 transcription factor and its nuclear interaction with the progesterone receptor (PR) by tethering in C4HD cells an experimental model of hormonal carcinogenesis in which the synthetic progestin medroxyprogesterone acetate (MPA) induced mammary adenocarcinomas in female Balb/c mice and in the human breast cancer line T47D. In this work, we demonstrated that MPA induces AP-1 transcriptional activation through the activation of MAPKs signaling pathways. Our recent findings have demonstrated that MPA induces the recruitment of Stat3 and PR to the GAS site in the cyclin D1 promoter. Here, we identified a novel PR/AP-1/Stat3 transcriptional complex in breast cancer cells. Cyclin D1 is a cancer-related protein whose promoter contains AP-1 binding sites (TRE sites) and Stat3 binding sites (GAS sites) in a very close proximity and lacks progesterone response elements (PRE sites). By using quantitative chromatin immunoprecipitation (ChIP) and sequential ChIP, we demonstrated that progestin induces the recruitment of c-jun, c-fos and PR to the TRE site and this recruitment is abolished when we pretreat the cells with the MAPKs inhibitor U0126. When cells were transfected with c-jun and c-fos Dominant Negatives Forms (TAM-67 and A-Fos respectively) none of these proteins are able to activate cyclin D1 promoter or are recruited to the TRE site and there is not MPA-induced Stat3 recruitment to the GAS site. In the same way when we pre-treat the cells with siRNAs against Stat3 neither c-jun, c-fos, PR or Stat3 are recruited to the AP-1 or GAS siteS in the cyclin D1 promoter. Inhibition of MPA-induced AP-1 transcriptional activation by transfection of breast cancer cells with TAM-67 and A-Fos resulted in complete abrogation of progestin-induced in vitro and in vivo breast cancer growth. Our findings reveal a novel MPA-induced PR/AP-1/Stat3 cooperative transcriptional complex in breast cancer cells. Interestingly the blockage of any of the members of the complex prevents its assembly and inhibits the MPA-induced cyclin D1 up-regulation and cell 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 2174. doi:10.1158/1538-7445.AM2011-2174
Abstract 4701: Integrated chemo-genomics approach for the identification of therapeutically amenable targets in small cell lung cancer
Authors: Martin L. Sos, Steffi Heynck, Martin Peifer, Roman K. Thomas
Journal: Cancer Research (2011)

Abstract Small-cell lung cancer (SCLC) is the third most common lung cancer type and with a median overall survival of only 9.3 month for extended disease patients also one of the deadliest worldwide. While analyses of the genetic landscape of non-small cell lung cancers led to the identification of therapeutically amenable targets such as mutant EGFR or EML4-ALK fusions, the characterization of oncogenic pathways that drive tumorigenesis in SCLC lags behind this development, resulting in a lack of treatment options for SCLC patients. To address this therapeutic need systematically we performed high-resolution gene-copy number (6.0 SNP-arrays) in a cohort of 108 SCLC specimens (n=47 primary samples; n=61 cell lines). This analysis revealed novel recurrent amplifications and deletions that are specifically enriched in SCLC when compared to non-small cell lung cancer specimen. We next annotated the significant genetic lesions found in our SCLC set and linked these with the activity profiles of a library of 270 novel proprietary compounds as well as compounds currently in clinical develop, which were screened in 51 SCLC cell lines. Using an integrated genomics approach we detected genetic predictors for the activity and resistance to known PI3K/AKT-pathway inhibitors as well as novel inhibitors previously not associated with activity in SCLC. Using orthogonal functional assays we validated genetic alterations that predicted cytotoxicity of Pi3-kinase inhibition in SCLC cell lines and we validated compounds that exhibited exquisite cytotoxicity in MYC-amplified tumors. Overall, our data provides the first detailed genetic landscape of small-cell lung cancer with a functional annotation and implies that PI3K/AKT-pathway inhibitors represent therapeutics that warrant further clinical investigation in SCLC patients. 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 4701. doi:10.1158/1538-7445.AM2011-4701
F-18 FDG Uptake in Congestive Splenomegaly
Authors: NAHEEL ALNAFISI, MIJIN YUN, ABASS ALAVI
Journal: Clinical Nuclear Medicine (2002)

From the Division of Nuclear Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania Received for publication April 24, 2001. Revision accepted September 25, 2001. Reprint requests: Abass Alavi, Division of Nuclear Medicine, Hospital of the University of Pennsylvania, Donner Building, Room 110, 3400 Spruce Street, Philadelphia, Pennsylvania 19104. E-mail: [email protected]
P1103 IMPACT OF THE LOW-DENSITY LIPOPROTEIN CHOLESTEROL ON RESPONSE TO TELAPREVIR-BASED TRIPLE THERAPY FOR CHRONIC HEPATITIS C PATIENTS
Authors: E. Ogawa, N. Furusyo, M. Nakamuta, E. Kajiwara, H. Nomura, K. Dohmen, K. Takahashi, T. Satoh, K. Azuma, A. Kawano, Y. Tanabe, K. Kotoh, S. Shimoda, J. Hayashi
Journal: Journal of Hepatology (2014)
Effect of GTx-024, a selective androgen receptor modulator (SARM), on stair climb performance and quality of life (QOL) in patients with cancer cachexia.
Authors: M. S. Steiner, K. G. Barnette, M. L. Hancock, S. T. Dodson, D. Rodriguez, R. A. Morton
Journal: Journal of Clinical Oncology (2010)

9147 Background: Cancer cachexia is a catabolic muscle wasting condition that leads to a reduction in lean body mass (LBM). The associated changes not only affect patient's health, but also QOL. We conducted a randomized, double-blind, placebo-controlled multi-center study to evaluate the effect of GTx-024, a SARM, on total LBM in patients with cancer cachexia. Methods: Subjects (n=159) were randomized to oral GTx-024 (3 mg or 1 mg) or placebo daily for 16 weeks. Subjects were males >45 years and postmenopausal females, had experienced ≥2% weight loss, had a BMI <35 kg/m2 and were diagnosed with either non-small cell lung cancer, colorectal cancer, non-Hodgkin's lymphoma, chronic lymphocytic leukemia or breast cancer. The primary endpoint was change in total LBM measured by dual energy X-ray absorptiometry (DXA). Secondary endpoints included muscle performance and QOL assessments. QOL questionnaires were analyzed to determine if there was a correlation between improvement in stair climb and QOL. Clinically meaningful differences were defined as 6 points between groups for FAACT-TOI and 3 points for FACIT-F TOI and the Fatigue sub-scale. Results: We observed a statistically significant increase in LBM in both treatment groups compared to baseline (1 mg, p=0.001; 3 mg, P=0.045). Ninety-five subjects were eligible for QOL analyses. Responders were defined as follows: stair climb time (SCT) >1 second decrease; stair climb power (SCP) >9.8 watt increase. SCT responders showed an 8.46 point improvement in FACIT-F TOI (p=0.020) and a 9.02 point increase in FAACT TOI (p=0.012). SCP responders showed a 9.96 point improvement in the FACIT-F TOI (p=0.006) and 10.75 point improvement in the FACCT TOI (p=0.002). In the Fatigue sub-scale, SCT and SCP responders demonstrated a change of 4.69 (p=0.028) and 5.44 points (p=0.016), respectively. Subjects with the greatest improvement in stair climb had the greatest improvement in QOL measures. Conclusions: GTx-024 improved LBM, muscle performance and QOL. These data suggest that GTx-024 not only provides benefit in muscle mass, but is also associated with clinically meaningful improvements in physical function and QOL. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GTx GTx
Abstract 3597: Further studies on cadmium-adapted lung epithelial cells: evidence for the attenuation of general stress response, enhancement of metallothionein-induction response, and loss of p53 expression.
Authors: Yan-Ming Xu, Yuan Zhou, Dong-Yang Huang, Jian Zhang, Jen-Fu Chiu, Andy T. Y. Lau
Journal: Cancer Research (2013)

Abstract Adaptation is a cellular process in which cells are progressed from the starting sensitive state to the later adapted state to the exposing agent. Acute exposure of cells to cadmium (Cd) can cause cell death; however, chronic exposure of Cd can develop acquired tolerance where cell death is suppressed. We previously reported that during Cd adaptation in lung epithelial cells, cells develop tolerance to cell death, generally due to perturbation of the c-Jun N-terminal kinase (JNK) signaling pathway and the nonresponsiveness of JNK phosphorylation is critical for the Cd-tolerance in these cells (1, 2). In this study, we further studied the properties of these Cd-adapted cells. Our results indicate that Cd-adapted cells, when compared with Cd-treated parental Cd-sensitive cells, show negligible general stress response to the same dosage of cadmium exposure. Moreover, although metallothionein (MT) is induced in both Cd-sensitive and Cd-adapted cells, Cd-adapted cells show enhanced MT-induction response and this was not due to MT gene amplification. Lastly, we showed that the tumor suppressor p53 protein level is severely abrogated in these Cd-adapted cells, suggesting that the normal p53 function is lost and may account for the death tolerance, genome instability, as well as the progression of carcinogenesis. Citation Format: Yan-Ming Xu, Yuan Zhou, Dong-Yang Huang, Jian Zhang, Jen-Fu Chiu, Andy T. Y. Lau. Further studies on cadmium-adapted lung epithelial cells: evidence for the attenuation of general stress response, enhancement of metallothionein-induction response, and loss of p53 expression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3597. doi:10.1158/1538-7445.AM2013-3597
AB0588 Golimumab in Refractory Uveitis to Other Anti-TNFα Drugs
Authors: F.M. Ortiz Sanjuán, R. Blanco, J. Cañal, M. Cordero-Coma, A. Adán, M. Mesquida, M.V. Hernández, E. Rubio-Romero, Ά. M. García-Aparicio, A. Atanes, I. Torre, F. Francisco, M.C. Fernández-Espartero, N. Palmou, V. Calvo-Río, J. Loricera, J. Ventosa-Ayarza, T. Pina, M.A. González-Gay
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To assess the efficacy and safety of Golimumab in patients with refractory uveitis to other anti-TNFα drugs. <h3>Methods</h3> Study of patients from a single center with refractory uveitis to previous standard synthetic immunosuppressive drugs and at least 1 anti-TNFα drug. Golimumab was given at the standard dose of 50 mg/sc/month. <h3>Results</h3> A total of 25 patients (39 affected eyes) (19 men/6 women); mean age, 32.5±8.9 years (range 11-47); fulfilled the above-mentioned criteria. In 14 cases uveitis was bilateral and in 11 cases it was unilateral. The underlying diseases were spondylarthritis (n=7), psoriatic arthropathy (n=4), juvenile idiopathic arthritis (n=4), sarcoidosis (n=3), Behçet disease (n=2), uveitis associated with HLA-B27 and ulcerative colitis (n=1), pars planitis (n=1) and Vogt-Koyanagi-Harada (n=1). Besides oral steroids and before Golimumab onset they had received: intraocular corticosteroids (n=10), methylprednisolone i.v. boluses (n=6), methotrexate (n=20), cyclosporine A (n=6), azathioprine (n=6), adalimumab (n=17), infliximab (n=14), abatacept (n=2) and certolizumab (n=1). Golimumab was started because inefficacy (n=23) and/or toxicity (n=2) to other biologics. Golimumab was used as monotherapy (n=9) or in combination with methotrexate (n=9), azathioprine (n=3), leflunomide (n=2) and mycophenolate (n=2). There was a rapid (from 1st week) and maintained (1st year) improvement of visual acuity, anterior chamber inflammation, vitritis and OCT. The mean OCT improved from 319.9±77.9 μm (baseline) to 270.2±54.8 μm (1st month) (p&lt;0.01) and to 244.3±43.2 μm (1st year) (p=0.02). After a mean follow-up of 13.3±8.3 (range 2-30) months the most important side-effects observed were local erythema in injection area (n=1) and herpes zoster (n=1). <h3>Conclusions</h3> Golimumab seems an effective and safe treatment for those patients with uveitis even refractory to other anti-TNFα drugs. <h3>Acknowledgements</h3> This study was supported by a grant from “Fondo de Investigaciones Sanitarias” PI12/00193 (Spain). This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain). <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4758
SP0185 The Metabolic Syndrome in SLE
Authors: I. Bruce
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> The increased cardiovascular burden in patients with SLE is now well recognised and represents a significant cause of mortality and morbidity in these conditions. Recent studies continue to highlight the excess burden of cardiovascular disease in SLE and this continues to be a problem almost 40 years after its first description. A number of studies have also highlighted the importance of studying sub-clinical markers of cardiovascular risk as these might help us to better understand the pathogenesis of accelerated arthrosclerosis in lupus. We have recently focussed attention on the development of metabolic syndrome in the context of SLE as this is an interesting model of future cardiovascular risk. The presence of metabolic syndrome in the general population is associated with an excess risk of future coronary heart disease and we have noted that metabolic syndrome is more common in patients with SLE. Recent work from a large international cohort has also demonstrated that corticosteroid therapy contributes to the development of metabolic syndrome. Interestingly however, we have also noted a significant contribution of active inflammatory disease and certain ethnic backgrounds are particularly prone to metabolic syndrome most notably from patients from a Korean and Hispanic background. All of this suggests that stratifying patients according to cardiovascular risk maybe possible from early on in disease and future work will focus on how changing our therapeutic regimes may impact on cardiovascular risk in lupus. The management of cardiovascular risk should therefore be multifactorial and multidisciplinary. Close attention to traditional risk factors and the metabolic syndrome should be a cornerstone of management. We should also aim to suppress disease as completely as possible whilst minimising the use of the dose of corticosteroid therapy and ensuring patients without contra indications are treated with anti-malarial agents. Clinical trials will be required to prove the efficacy of key therapies but such trials will require a concerted international effort. <h3>Disclosure of Interest</h3> I. Bruce Grant/research support from: Genzyme, Roche, UCB, Pfizer, Consultant for: UCB, Roche, GSK, Medimmune, Pfizer, Speakers bureau: UCB, Roche, GSK, Medimmune, Pfizer
AB1068 Efficacy of anakinra in pseudogout: Report of 3 cases
Authors: M. Couderc, S. Mathieu, B. Glace, M. Soubrier
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anakinra has shown modest efficacy in rheumatoid arthritis and there is proof of principle for its efficacy in gout. Several case reports have suggested it is effective in pseudogout [1-2]. <h3>Methods</h3> We report a small study of 3 patients treated with anakinra for pseudogout. <h3>Results</h3> Three patients, two men and one woman aged 49, 68 and 68 years, respectively, were treated with subcutaneous anakinra 100mg/day for pseudogout. Diagnosis was based on the association of polyarthralgia and typical X-ray features of pseudogout. In two patients, pseudogout was secondary to haemochromatosis. All three patients had previously received non-steroidal anti-inflammatory drugs and colchicine. Two had been treated unsuccessfully with methotrexate. The first patient did not respond to anakinra (delta DAS +0.3) and treatment was discontinued after 3 months. Anakinra was also stopped in the second patient after 2 months, because of lack of response (delta DAS -0.72) and adverse event. In the last patient, after 3 months of treatment, DAS 28 decreased from 4.83 to 2.31 (delta DAS -2.5) and HAQ from 1.5 to 0.875 and anakinra was continued. Significant side-effects occurred with moderate reaction at the site of injection in two patients and interstitial lung disease in one that could have been due to anakinra. <h3>Conclusions</h3> In contrast with previous case-reports, this study showed low efficacy of anakinra in pseudogout. The efficacy of Il-1 blockade treatment in pseudogout needs to be confirmed by randomised controlled studies. <h3>References</h3> McGonagle D, Tan AL, Madden J, Emery P, McDermott MF. Successful treatment of resistant pseudogout with anakinra. Arthritis Rheum. 2008;58:631-3. Announ N, Palmer G, Guerne PA, Gabay C. Anakinra is a possible alternative in the treatment and prevention of acute attacks of pseudogout in end-stage renal failure.Joint Bone Spine. 2009;76:424-6. <h3>Disclosure of Interest</h3> None Declared
PMO-256 The reality of the tolerance and efficacy of oral iron in patients with inflammatory bowel disease (IBD)
Authors: F Beal, S Lugg, D Rattehalli, C Tselepis, T Iqbal
Journal: Gut (2012)

<h3>Introduction</h3> Iron deficiency anaemia (IDA) is the most common complication of Inflammatory Bowel Disease (IBD) and impacts negatively on patients9 quality of life. The aim of this audit was to explore the use and tolerability of oral iron supplementation in IBD practice. <h3>Methods</h3> We used a patient directed questionnaire aimed at adult IBD outpatients over a 7-week period at the Queen Elizabeth Hospital. The use of oral iron therapy was ascertained in patients treated over 20 years. Patients were asked about the type of iron taken, dosing frequency, duration, side-effects and completion of therapy. We calculated the number of patients whose anaemia had resolved and where the data were available, the efficacy of treatment was determined by the mean change in haemoglobin (Hb) from baseline. <h3>Results</h3> 91 IBD patients who received iron were surveyed, (62 Crohn9s disease, 27 ulcerative, 2 microscopic colitis). All received oral iron (73 ferrous sulphate, 15 ferrous fumarate and 3 ferrous gluconate) and 17 also received intravenous (IV) iron. There were 56 females and 35 males. Variable dosing regimens were followed: 31.5% taking iron once, 37% twice and 31.5% three times daily. Although 69% patients were able to complete the course of oral iron, 31% had to abort treatment due to intolerance, which was unrelated to dose frequency. Only 35 patients (38%) were able to complete their intended course of oral iron without any side effects. Of these patients, the baseline Hb (mean 11.1 g/dl, range 8.9–13.3) returned to reference baseline in only 51% patients, with average Hb change 1.43 (range −0.7–4.7). Side effects were reported in 52% patients who received oral iron, including nausea and vomiting (21%), abdominal pain (19%), constipation (19%) and diarrhoea (18%.) However, despite side effects the average duration of treatment in this cohort was 10.3 months (range 0.03–156), 19.3 months (range 1–240) in patients without side effects and 5.2 months (range 0.03–36) in intolerant patients who had to cease treatment. No adverse effects were reported in the 17 who received IV iron. <h3>Conclusion</h3> Although oral iron is a cheap and convenient treatment for IDA, over half of the patients in this study experienced gastro-intestinal side effects, a large proportion remained anaemic and for many the treatment course was long. Despite iron therapy IDA prevalence in this group remains high and it seems the efficacy of oral iron treatment is poor in this setting. We propose that prescription of iron therapy in IBD patients should be trialled with a defined duration of treatment and a target end point Hb. Those who fail to tolerate or do not respond adequately should consider an alternative form of iron therapy such as IV iron. <h3>Competing interests</h3> None declared.