tbuckley/cabot-search huggingface dataset:
Abstract 3710: Facile Synthesis and Characterization of Pyropheophorbide-a -Taxol Conjugate
Authors: Hyo Jun Kim, Battogtokh Gantumur, Sook Hee Kim, Sumi Bae, Woong Shick Ahn
Journal: Cancer Research (2010)

Abstract Chlorin-based photosensitizers are considered the ideal photosensitizer (second generation) in photodynamic therapy (PDT). They have improved efficacy and have lesser side effects compared to porphyrin-based photosensitizers (first generation). Paclitaxel (PTX) is one of the most effective and widely used anticancer a drug. Although chemotherapy is a powerful and important modality in cancer treatment, the effectiveness of the chemotherapy is limited due to systemic toxicity and side effects. For the improvement of photosensitizers (chlorin; apoptosis, necrosis, local immune response) and increased anticancer drug (PTX; apoptosis), we combined photosensitizer and PTX. For the synthesis, naturally occurring chlorin derivative was used as a starting material. It was prepared with the acidic treatment of methyl pyropheophorbide-a from Spirulina maxima algae according to the previously reported methods [1-2]. PTX should contain three hydroxyl groups at 21-position and 1-position and 7-position, respectively. A hydroxyl group at 21-position has more reactivity than others. To the synthesize target compound, we carried out an esterification reaction between the hydroxyl group at 21-position for the PTX moiety and carboxyl group at 173-position for the pyropheophorbide-a. The conjugate was performed as reaction the pyropheophorbide-a and the commercial PTX by using DMAP/DCC coupling agent. The structure of chlorin- based PTX conjugate was fully characterized by 1D and 2D NMR techniques and also by MALDI-MS and UV-Vis. As well as, the conjugate was determined the purity of 99.45% by analytical reversed phase HPLC at 660 nm. This conjugate can be applied as anticancer agent and photosensitizer for PDT. This compound is promising to be able to afford some synergistic effects in tumor cell. References: 1. Smith, K. M.; Goff, D. A.; Simpson, D. J.; J. Am. Chem. Soc. 1985, 107, 4946-4954. 2. Galindev, O.; Badraa, N.; Dalantai, M.; Sengee, G.; Dorjnamjin, D.; Shim, Y. K. Photochem. Photobiol. Sci. 2008, 7, 1273-1281. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 3710.
Abstract 1185: Plakoglobin (β-catenin) interacts with the transcription factor p53 and regulates the expression of genes involved in tumorigenesis and metastasis
Authors: Zackie Aktary, Manijeh Pasdar
Journal: Cancer Research (2012)

Abstract Plakoglobin (β-catenin) and β-catenin are highly homologous proteins that function in cell-cell adhesion and signaling. Both proteins exist in a cadherin-associated form, which mediates adhesion, and in a distinct cytosolic/nuclear form, which plays a signaling role. Despite their interactions with common cellular partners, β-catenin has well documented oncogenic potential while plakoglobin expression is generally associated with tumor/metastasis suppression. The underlying mechanisms for this activity of plakoglobin are unclear. We previously showed that plakoglobin expression in oral squamous carcinoma cells (SCC9-PG) resulted in a mesenchymal-epidermoid transition, which was concurrent with increased N-cadherin and decreased β-catenin levels. Comparison of the RNA and protein profiles of SCC9 cells and SCC9-PG transfectants identified a number of differentially expressed proteins and transcripts, which suggested that plakoglobin regulates gene expression. Closer analysis of the mRNA profiles of SCC9 and SCC9-PG cells identified several p53 target genes that were differentially expressed upon plakoglobin expression, suggesting that plakoglobin may regulate gene expression in conjunction with p53. Here, we describe the ability of plakoglobin to regulate three potential p53 target genes: the tumor and metastasis suppressors 14-3-3α and Nm23 and the tumor promoter SATB1. We show, by RT-PCR and Western blot, that plakoglobin expression results in increased 14-3-3σ and Nm23 and decreased SATB1 mRNA and protein levels. Co-immunoprecipitation experiments show that plakoglobin and p53 interact, and that these interactions occur in both the cytoplasm and the nucleus. Chromatin immunoprecipitation and Electrophoretic mobility shift assays (EMSA) indicate that plakoglobin and p53 associate with the promoters of these target genes. Finally, luciferase reporter assays confirm that plakoglobin regulates the expression of these p53 target genes. Taken together, the results of these studies provide strong evidence that plakoglobin plays an active role in regulating gene expression, a function that has not often been associated with plakoglobin. 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 1185. doi:1538-7445.AM2012-1185
Molecular characterization and phylogeny of Shiga toxin–producing Escherichia coli isolates obtained from two Dutch regions using whole genome sequencing
Authors: M. Ferdous, A.W. Friedrich, H. Grundmann, R.F. de Boer, P.D. Croughs, M.A. Islam, M.F.Q. Kluytmans-van den Bergh, A.M.D. Kooistra-Smid, J.W.A. Rossen
Journal: Clinical Microbiology and Infection (2016)

Shiga toxin–producing Escherichia coli (STEC) is one of the major causes of human gastrointestinal disease and has been implicated in sporadic cases and outbreaks of diarrhoea, haemorrhagic colitis and haemolytic uremic syndrome worldwide. In this study, we determined the molecular characteristics and phylogenetic relationship of STEC isolates, and their genetic diversity was compared to that of other E. coli populations. Whole genome sequencing was performed on 132 clinical STEC isolates obtained from the faeces of 129 Dutch patients with gastrointestinal complaints. STEC isolates of this study belonged to 44 different sequence types (STs), 42 serogenotypes and 14 stx subtype combinations. Antibiotic resistance genes were more frequently present in stx1-positive isolates compared to stx2 and stx1 + stx2–positive isolates. The iha, mchB, mchC, mchF, subA, ireA, senB, saa and sigA genes were significantly more frequently present in eae-negative than in eae-positive STEC isolates. Presence of virulence genes encoding type III secretion proteins and adhesins was associated with isolates obtained from patients with bloody diarrhoea. Core genome phylogenetic analysis showed that isolates clustered according to their ST or serogenotypes irrespective of stx subtypes. Isolates obtained from patients with bloody diarrhoea were from diverse phylogenetic backgrounds. Some STEC isolates shared common ancestors with non-STEC isolates. Whole genome sequencing is a powerful tool for clinical microbiology, allowing high-resolution molecular typing, population structure analysis and detailed molecular characterization of strains. STEC isolates of a substantial genetic diversity and of distinct phylogenetic groups were observed in this study.
Improved outcome of elderly patients with poor-prognosis diffuse large B-cell lymphoma (DLBCL) after dose-dense rituximab: Results of the DENSE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL)
Authors: M. Pfreundschuh, S. Zeynalova, V. Poeschel, M. Haenel, N. Schmitz, A. D. Ho, M. Reiser, M. Loeffler, J. Schubert
Journal: Journal of Clinical Oncology (2008)

8508 Background: While 6 to 8 cycles of CHOP in combination with rituximab (R) are widely accepted as standard regimen of care for aggressive lymphomas, the optimal dose and number of R application have not been determined to date. In a previous pharmacokinetic study we had shown that the concomitant application of CHOP and R does not achieve a plateau of R trough levels until cycle 5 (Reiser, Blood 108, 778a, 2006). In order to achieve high R levels early, we increased the number of R applications. Methods: 100 elderly pat. with aggressive CD20+ B-cell lymphoma received 6 cycles of biweekly CHOP-14 combined with 12x R (375 mg/m2) on days 0,1,4,8,15,22,29,43,57,71,85, and 99. Radiotherapy was planned to sites of initial bulk and/or extranodal involvement. The primary endpoint was event-free survival (EFS). 306 pat. treated within the RICOVER-60 trial (Pfreundschuh et al., Blood 64a, 2006) with 6xCHOP-14 and 8 applications of R served as control. Results: 97/100 pat. are evaluable for response. Plateau trough serum levels were achieved by day 1 of the first chemotherapy cycle and higher R levels were maintained throughout the treatment compared to 8 bi-weekly applications. Because 3 therapy-associated deaths were observed among the first 20 pat. treated, prophylaxis with levofloxacin, acyclovir and cotrimoxazol became mandatory for the following pat.. Despite a less favorable study population DENSE-R-CHOP-14 resulted in a somewhat higher CR (83% vs. 78%) and lower progression under therapy rate (5% vs. 7%) rate, but event free and overall survival were not different compared to 8 biweekly applications of R. However, a subgroup analysis of pat. according to IPI risk group showed that DENSER-R-CHOP-14 resulted in a higher complete response rate of pat. with poor-prognosis (IPI:3–5) disease (81% vs. 68%) and in a better 1-year event-free survival rate (74% vs. 65%) of these pat.. Conclusion: Densification of R results in higher serum levels and in higher complete remission and event-free survival rates in elderly pat. with poor-prognosis DLBCL. An update of the results of the completed trial with 125 pat. will be presented. Supported by Dt. Krebshilfe and Roche. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech, Lilly, Roche Genentech, Lilly, Roche Roche
THU0220 Impact of Meniscal Extrusion on the Progression of Knee Osteoarthritis Structural Changes and the Effects of Treatment: Data from the Osteoarthritis Initiative Progression Cohort
Authors: J.-P. Pelletier, C. Roubille, F. Abram, P. Delorme, J.-P. Raynauld, J. Martel-Pelletier
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The Osteoarthritis Initiative (OAI) is the largest knee osteoarthritis (OA) observational cohort. It provides the possibility to study the evolution of OA structural changes over time and the associated risk factors. It also allows the potential disease-modifying OA drug (DMOAD) effects to be explored in patients over time. <h3>Objectives</h3> To determine, using data from participants enrolled in the progression cohort of the OAI, the effects of existing meniscal extrusion on the extent of cartilage loss and structural changes over time, and response to pharmacological treatment including the combination of glucosamine and chondroitin sulfate (Glu/CS). <h3>Methods</h3> Knee OA patients were stratified based on the presence/absence of medial meniscal extrusion at baseline and on whether or not they received conventional OA pharmacological treatment (analgesics/non-steroidal anti-inflammatory drugs [NSAIDs]) and/or Glu/CS for 24 consecutive months. The main outcomes were knee structural changes including the cartilage volume measured by quantitative magnetic resonance imaging (MRI) and of loss of joint space width (JSW). <h3>Results</h3> Participants reported taking (+) (n=300) or not taking (−) (n=300) OA treatment (analgesics/NSAIDs). The participants with meniscal extrusion had more severe disease at baseline. In the −analgesics/NSAIDs group with meniscal extrusion, participants taking Glu/CS had significantly reduced loss of cartilage volume at 24 months in the medial tibiofemoral compartment (p=0.02) and lateral plateau (p=0.05). No effect of Glu/CS was observed in patients without extrusion. In the +analgesic/NSAIDs group without meniscal extrusion, those taking Glu/CS had significantly reduced loss of cartilage volume in the global knee (p=0.055), medial compartment (p=0.05), lateral plateau (p=0.007), and trochlea (p=0.04). No effect of Glu/CS treatment occurred in participants with extrusion. No significant reduction in JSW was found between those taking (+) and not taking (−) Glu/CS treatment. <h3>Conclusions</h3> This study confirms that combined administration of Glu/CS has significant protective effects on structure in knee OA. The presence of meniscal extrusion was found to be an important factor that can influence the drug effect on cartilage volume. X-rays were found to be much less sensitive than MRI at documenting the protective effect of treatment on structural changes. <h3>Disclosure of Interest</h3> : J.-P. Pelletier Shareholder of: ArthroLab Inc., Consultant for: Bioiberica, C. Roubille: None declared, F. Abram Employee of: ArthroLab Inc., P. Delorme: None declared, J.-P. Raynauld Consultant for: ArthroLab Inc., J. Martel-Pelletier Shareholder of: ArthroLab Inc., Consultant for: Bioiberica <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2248
Use of unlabelled and off licence drugs in children
Authors: F A. I Riordan
Journal: BMJ (2000)

<h3>Background</h3> Neonatal jaundice is a common medical problem in postnatal wards. With the introduction of NICE guidelines in UK, the management of jaundice of newborn infants has achieved clarity. <h3>Aims</h3> An audit was undertaken to check if local team were adhering to the NICE guidelines on neonatal jaundice management (May 2010) and to make recommendations to improve compliance. <h3>Methods</h3> Prospective audit was conducted between January 2011 to August 2011 and 48 newborn infants with jaundice in postnatal ward were randomly selected and included. Data was collected using proforma, baby/maternal notes and blood results on computer system. <h3>Results</h3> Poor performance was demonstrated in identifying the risk factor for jaundice-whether baby’s previous sibling had jaundice requiring treatment (15% as compared to 100% standard). There was 90% compliance with NICE guidelines (standard 100%) with regards to serum bilirubin (SBR) measured for infants with jaundice &lt;24 hours. 83% of infants (29/35) with jaundice onset &gt;24 hours had transcutaneous bilirubinometry(TCB) measurement which reduced the number of blood tests performed on these infants. Only 75% of the parents of infants with jaundice received information leaflets on newborn jaundice. <h3>Conclusion</h3> When used appropriately, TCB reduces need for invasive blood tests and the workload of paediatric doctors on postnatal wards. The midwives and junior doctors should receive training for TCB use and management of jaundice in accordance with NICE guidelines. All parents of newborn infants with jaundice should receive NICE information leaflets on jaundice to increase awareness of the condition.
GPs fail to report food poisoning
Authors: J. Warden
Journal: BMJ (1998)

A parliamentary committee has accused family doctors of neglecting their legal responsibilities to notify cases of food poisoning. This hampers efforts to understand the extent of the problem to be tackled by the planned Food Standards Agency.

The House of Commons agriculture committee reports that 1997 was the first year in which the number of food poisoning notifications in the United Kingdom exceeded 100000 (with between 100 and 200 deaths). There has been a worrying increase in outbreaks associated with strains of Salmonella typhimurium DT104 showing resistance to antibiotics, along with two other pathogens, Campylobacter spp, and Escherichia coli O157.

Moreover, …
P667 HEPATITIS B CORE-RELATED ANTIGEN (HBcrAg) LEVELS IN THE NATURAL HISTORY OF HEPATITIS B INFECTION IN A LARGE EUROPEAN COHORT
Authors: B. Maasoumy, S. Wiegand, J. Jaroszewicz, K. Deterding, B. Bremer, P. Lehmann, M.P. Manns, H. Wedemeyer, M. Cornberg
Journal: Journal of Hepatology (2014)
Sickle Cell Disease as a Cause of Osteonecrosis of the Femoral Head
Authors: Paul F. Milner, Alfred P. Kraus, Jeno I. Sebes, Lynn A. Sleeper, Kimberly A. Dukes, Stephen H. Embury, Rita Bellevue, Mabel Koshy, John W. Moohr, Jeanne Smith
Journal: New England Journal of Medicine (1991)

Osteonecrosis of the femoral head is an important complication of sickle cell disease. We studied 2590 patients who were over 5 years of age at entry and followed them for an average of 5.6 years. Patients were examined twice a year, and radiographs of the hips were taken at least twice: at study entry and approximately three years later.
Effect of Lidocaine on Ventricular Arrhythmias in Patients with Coronary Heart Disease
Authors: Ralph Gianelly, J. O. von der Groeben, Alfred P. Spivack, Donald C. Harrison
Journal: New England Journal of Medicine (1967)

LIDOCAINE (Xylocaine) has become one of the most frequently used drugs in the treatment of ventricular arrhythmias, particularly those associated with acute myocardial infarction. It has been shown to terminate ventricular tachycardia, and it has been given to suppress multiple ventricular extrasystoles.1 , 2 The drug has been administered as an intravenous bolus or as a constant intravenous infusion. Although the use of lidocaine as an antiarrhythmic in postoperative cardiac surgery has been investigated,3 little objective information is available regarding the therapeutic and toxic doses in patients with myocardial infarction. Its effect on ventricular tachycardia can readily be shown, but the evaluation . . .
OP0186 Analysis of Uveitis Events in the BIOLOGICS in Pediatric Rheumatology (BIKER)-Registry: Table 1
Authors: G. Horneff, I. Foeldvari, K. Minden, K. Tenbrock, H.I. Huppertz, I. Becker
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Uveitis is one of the major extraarticular manifestations of JIA. Open studies demonstrate efficacy of Adalimumab (ADA) and Infliximab. It remains unclear if uveitis can occur as an adverse drug reaction, especially in pts. exposed to Etanercept (ETA). <h3>Methods</h3> The BIKER registry data base was used for analysis. Patient9s history of uveitis, JIA category, the first occurrence of uveitis and exposure to Methotrexate (MTX), ETA, ADA and steroids were searched for. The number of first uveitis events occurring in each treatment category, the no. of exposed patients and exposure time until event were calculated. <h3>Results</h3> Of 3467 pts, 1700 were exposed to ETA, 364 to ADA and 1403 to MTX only. 335 pts (9.4%) had a history of uveitis before. In 75 pts (2.2%) uveitis was reported as an adverse event. Pts. with a known history of uveitis were more likely to have a new uveitis event (n=22; 6.8%; OR 2.9 [1.5-5.5]; p&lt;0.001) than patients without. In 16 pts the first occurrence of uveitis was reported: 11 in the MTX cohort, 5 in the biologics cohort, 2 with ETA monotherapy and 3 with ETA&amp;MTX. Uveitis events occurred more frequently in pts. with ext.oligoJIA (OR 2.4[1.4-3.9]; p=0,0005) and less likely systemic JIA (OR 0.22[0,03-1,59; p=0.1) or rheumatoid factor pos. polyJIA (OR 0.19[0.03-1.34]; p=0.06) and more likely had ANA (OR 2.5 [1.5-4.1]; p&lt;0.0003). Moreover, pts with an uveitis event were younger (4.6±4.1 years vs. 7.6±4.6 years; p&lt;0.0001). Pts. with a history of uveitis before treatment with a biologic were more likely to receive ADA than ETA (OR 2.90 [2.06-4.08]; p&lt;0.0001). To analyze the influence of drug treatment on the occurrence of a first uveitis flare pts9 treatments were categorised (table). Compared to the control group (MTX only) OR was significantly higher in pts receiving ETA monotherapy. It was not increased in combination with MTX. There were more uveitis events in pts on ADA±MTX in combination. Univariate analysis revealed that treatment with corticosteroids seems not to protect from uveitis, while MTX did. Pts. on ADA had significantly higher rates, while pts on ETA did not. <h3>Conclusions</h3> Risk factors for uveitis as an adverse event were history of uveitis and ETA mono therapy. MTX treatment did reduce the likelihood of uveitis whereas corticosteroids had no such effect. Few pts developed first uveitis when exposed to ETA with a rate comparable to the control group. <h3>Disclosure of Interest</h3> G. Horneff Grant/research support: Abbvie, Pfizer, Roche/Chugai, I. Foeldvari: None declared, K. Minden: None declared, K. Tenbrock: None declared, H. Huppertz: None declared, I. Becker: None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2702
BLUNTED HEART RATE RESPONSE TO REGADENOSON IS AN INDEPENDENT PREDICTOR OF ALL-CAUSE MORTALITY IN PATIENTS WITH END-STAGE RENAL DISEASE: A SUBSTUDY OF THE ASSUAGE AND ASSUAGE-CKD TRIALS
Authors: Tania Campagnoli, Maria Rangel, Wael AlJaroudi, Rami Doukky
Journal: Journal of the American College of Cardiology (2015)
P1-11-12: Patterns of Care of Newly Diagnosed Patients with Breast Cancer in Mexico.
Authors: Y Chavarri-Guerra, PER Liedke, H Symecko, EE Hammond, MJ Higgins, D Finkelstein, PE Goss
Journal: Cancer Research (2011)

Abstract Background: Breast cancer is the most common form of cancer and the leading cause of cancer death in women worldwide. More than 55% of breast cancer deaths occur in low and middle income countries. Although incidence rates for breast cancer are lower in developing countries, mortality rates are higher. This phenomenon has been attributed to limited access to care for breast cancer patients, including screening and early diagnosis as well as primary surgical, radiation and systemic therapies. Similar to trends in other poor and middle income countries, breast cancer mortality in Mexico is rising. The goal of this survey of physicians caring for patients with breast cancer in Mexico is to obtain information about current treatment patterns of newly diagnosed patients and to describe their clinical characteristics. Methods: A web-based closed survey has been sent to 854 physicians providing care to newly diagnosed breast cancer patients across Mexico, including medical oncologists and breast cancer surgeons. The survey instrument contains 35 questions assessing demographic data, access to diagnosis and treatment in a variety of clinical patient scenarios. The responses will be anonymous and entered automatically into a secure database for analysis. Fisher exact test will be used for the frequency analysis. Chi-squared statistics and Kendall correlation will be used for nominal and ordinal variables respectively. Results: The results will be presented at the 2011 San Antonio Breast Cancer Symposium. Conclusions: The results of this survey will highlight potential disparities in care received by breast cancer patients across the full geographic and socioeconomic spectrum of Mexico in order to highlight the need for uniform, quality based approaches for the diagnosis and treatment of breast cancer patients in Mexico, and will serve as an example of how one middle income country faces challenges and unmet medical needs regarding access to care of women with breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-12.
SEX-BASED DIFFERENCES IN SHORT TERM SURVIVAL AFTER PRIMARY PERCUTANEOUS CORONARY INTERVENTION: THE ROLE OF SYSTEM DELAY
Authors: Edina Cenko, Beatrice Ricci, Sasko Kedev, Zorana Vasiljevic, Bozidarka Knezevic, Mirza Dilic, Olivia Manfrini, Davor Miličić, Maria Dorobantu, Akos Koller, Lina Badimon, Raffaele Bugiardini
Journal: Journal of the American College of Cardiology (2016)