tbuckley/cabot-search huggingface dataset:
Abstract 2393: Pathological angiogenesis in vascular tumors is driven by endothelial Akt1 and inhibited by rapamycin
Authors: Thuy L. Phung, Qi Xue, Zeus Antonello, Damien Gerald, Carole Perruzzi, Rafael Rojano, Michael Cunningham, Marcelo Hochman, Laura E. Benjamin
Journal: Cancer Research (2010)

Abstract Vascular tumors are abnormal angiogenic proliferations of neoplastic endothelial cells with a wide spectrum of clinical diseases ranging from common hemangioma in children to malignant angiosarcoma in adults. To date, the mechanisms leading to vascular tumor formation are poorly understood and under-investigated. We found reduction in PTEN levels and increased Akt activation in benign and malignant human vascular tumors. Akt1 promoted the proliferation and migration of vascular tumor cells. Expression of constitutively active Akt1 in vascular endothelial cells was sufficient to induce hemangioma formation in vivo, and sustained endothelial Akt1 activation was necessary to maintain tumor growth. Inhibition of mTOR activity downstream of Akt1 with rapamycin blocked VEGF-induced angiogenesis in vascular tumor cells and tumor growth in animals. In vascular tumors, rapamycin inhibited the activities of both TORC1 (which phosphorylates p70 S6-Kinase downstream of mTOR) and TORC2 (which phosphorylates Akt) and may provide a mechanism for the high efficacy of rapamycin in these tumors. As a topical agent, rapamycin was effective in inhibiting cutaneous vascular tumors with minimal systemic blood levels of the drug. In summary, these studies showed that endothelial Akt1 plays a key role in vascular tumor formation, and topical rapamycin holds promising clinical utility in the treatment of cutaneous vascular tumors. 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 2393.
Pfizer and Allergan abandon merger after US tax loophole is closed
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

A merger between the United States drug company Pfizer and the Ireland based Allergan has been abandoned “by mutual agreement of the companies” after new tax rules in the US negated the advantages that the deal was supposed to have delivered.1

The deal, which was worth $160bn (£106bn; €150bn), was due to go ahead later this year, and would have created the biggest drug maker by sales. The purchase of Allergan by Pfizer, known as a “tax inversion deal,” would also have led to savings worth an estimated $2bn over three years because, …
AB0577 Effects of tocilizumab are predictable during the early stage of therapy-the petite study-
Authors: T. Okano, T. Koike, M. Tada, Y. Sugioka, K. Mamoto, S. Wakitani, H. Nakamura
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The outcomes of strategies using biologics to treat rheumatoid arthritis (RA) have been very successful. However, the responses of patients to such therapy are not predictable in advance and useful factors remain unclear despite investigations into the effects of biologics. Furthermore, the slow action of tocilizumab (TCZ) complicates understanding of its early clinical effect. <h3>Objectives</h3> We aimed to identify factors predicting the early effects of TCZ therapy in patients with RA in a clinical trial of the Predictors of Effectiveness in Tocilizumab Therapy (PETITE). The study registration number is UMIN000002246. <h3>Methods</h3> We selected patients with RA treated with TCZ at Osaka City University and related hospitals. Forty-eight patients (four males, 44 females; mean age, 59.6±14.2 y; disease duration, 11.9±10.1 y) were treated with TCZ for &gt;24 weeks. Serum IL-1 beta, D-dimer and fibrinogen were measured before and after four weeks of TCZ therapy. The effect of TCZ and clinical changes were assessed as changes in the DAS28-ESR between baseline and 24 weeks. <h3>Results</h3> The DAS28-ESR decreased from 5.49 to 2.71 and from 5.24 to 3.03 when serum IL-1β decreased after four weeks and was below detection limit at baseline, respectively, and from 5.02 to 3.33 in the group in which serum IL-1β increased after four weeks. A decrease in fibrinogen values significantly correlated with DAS28-ESR, whereas D-dimer did was not associated with predicting clinical outcomes. <h3>Conclusions</h3> The decrease in DAS28-ESR was larger in the group with decreased, than increased serum IL-1β levels at four weeks and a decrease in fibrinogen significantly correlated with DAS28-ESR. Thus, changes in baseline serum IL-1 β and fibrinogen values after four weeks ofTCZ administration are potent tools for identifying new candidate biomarkers to predict the response to TCZ at 24 weeks. <h3>References</h3> Gibbons LJ, Hyrich KL. Biologic therapy for rheumatoid arthritis: clinical efficacy and predictors of response. BioDrugs. 2009;23:111-24. Hyrich KL, Watson KD, Silman AJ, Symmons DP. Predictors of response to anti-TNF-alpha therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford). 2006;45:1558-65. <h3>Disclosure of Interest</h3> T. Okano: None Declared, T. Koike Grant/Research support from: Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical, Eisai, Abbott Japan, Teijin Pharma, Banyu Pharmaceutical and Ono Pharmaceutical, M. Tada: None Declared, Y. Sugioka: None Declared, K. Mamoto: None Declared, S. Wakitani: None Declared, H. Nakamura Grant/Research support from: Chugai Pharmaceutical, Astellas Pharma Inc.,Janssen Pharmaceutica, GlaxoSmithKline, Pfizer Inc. and Daiichi Sankyo, INC., Speakers Bureau: Ono Pharmaceutical
Unconventional Medicine in the United States -- Prevalence, Costs, and Patterns of Use
Authors: David M. Eisenberg, Ronald C. Kessler, Cindy Foster, Frances E. Norlock, David R. Calkins, Thomas L. Delbanco
Journal: New England Journal of Medicine (1993)

Many people use unconventional therapies for health problems, but the extent of this use and the costs are not known. We conducted a national survey to determine the prevalence, costs, and patterns of use of unconventional therapies, such as acupuncture and chiropractic.
MÉTODO POSE COMO TRATAMIENTO ENDOSCÓPICO DE LA OBESIDAD. NUESTRA EXPERIENCIA
Authors: RM Daza García, FM Bravo Castillo, F Moreno Baró, JL Esteller Ortiz
Journal: Endoscopy (2013)

Introducción: El método POSE (Primary Obesity Surgery Endolumenal) es una técnica relativamente novedosa para el tratamiento endoscópico de la obesidad. Consiste en realizar (vía endoscópica) una serie de pliegues en el fundus y antro gástricos para reducir la capacidad de la cavidad gástrica, y enlentecer el vaciamiento gástrico. Objetivo: Revisar las indicaciones y resultados de la técnica POSE, en los pacientes tratados en nuestra unidad en el último año. Material y Métodos: Se incluyeron 44 pacientes, previamente seleccionados por el equipo de Endocrinología y Nutrición a los que se realizó la técnica POSE. Se elaboró una base de datos que recoge el IMC basal de cada paciente, así como datos epidemiológicos, comorbilidad y posibles complicaciones de la técnica. Resultados: Del total de 44 pacientes sometidos a la técnica POSE, de edades entre 22 y 68 años, con claro predominio del sexo femenino 35/9. Todos ellos con IMC entre 30 – 42 Kg/m2. El 73% presentaban comorbilidades como diabetes, HTA o estatosis hepática/esteatohepatitis. La indicación más frecuente fue el fracaso de la dieta asociada o no a tratamiento médico coadyuvante o la recidiva tras retirada de BIG. En los 28 pacientes sometidos a técnica POSE ente abril 2012 y enero 2013: hemos podido evidenciar una pérdida media de peso de 19 Kg a los 6 meses con un descenso aproximado de 4 puntos en el IMC. Conclusiones: En nuestra experiencia la técnica POSE, es un método eficaz y seguro para el tratamiento endoscópico de la obesidad con baja tasa de complicaciones, siempre que se realice por endoscopistas específicamente entrenados que garantiza buenos resultados a corto y medio plazo, no obstante, se observa un estancamiento de la pérdida ponderal a partir del sexto mes. Aunque, para constatar esto, creemos que todavía se requieren más estudios de eficacia a largo plazo.
Abstract P1-11-16: Her2/neu Overexpressing Breast Cancer Patients Retain an Immunological Proficiency Compromised in Her2/neu-Negative Cases
Authors: SSS Simona, EME Muraro, GGM Miolo, DMD Martorelli, ETE Turchet, ECE Comaro, RTR Talamini, AVA Veronesi, DCD Crivellari, RDR. Dolcetti
Journal: Cancer Research (2010)

Abstract Although breast cancers overexpressing HER2/neu are associated with a worse prognosis, a high rate of complete responses is usually induced in these patients by current therapeutic strategies, such as Trastuzumab, that also directly mediates antibody-dependent cellular cytotoxicity and possesses immunomodulating properties. Moreover, other chemotherapeutics used in this setting, i.e. doxorubicin and Taxol, were shown to enhance antigen-specific immune responses. On these grounds, a thorough evaluation of the immunologic profile of breast cancer patients may be helpful to predict clinical responses to such therapies. We therefore analyzed at diagnosis different immunological parameters of patients with locally advanced HER2+ (n=18) and HER2- (n=30) breast cancer eligible for neoadjuvant chemotherapy, respectively treated with weekly Paclitaxel (80 mg/mq/ev) and Trastuzumab (4mg/kg/ev day 1 followed by 2 mg/kg/ev weekly), or Epirubicin (90 mg/mq/ev) and Docetaxel (75mg/mq/ev) every 3 weeks. Immunophenotyping of circulating immune cells disclosed several differences in HER2- cases as compared with HER2+ patients and healthy controls (n=20). In particular, HER2- patients showed a higher percentage of NK and B cells (10.2 and 10.0%, respectively) and a lower CD4/CD8 T cell ratio (1.8; with a prevalence of naïve and central memory cells in the CD8+ population) if compared to HER2+ patients (NK 5.8%, B cells 8.2%, and CD4/CD8=2.3) and healthy controls (NK 5.5%, B cells 7.7%, and CD4/CD8=2.2). In addition, HER2- cases had higher numbers of circulating CD4+ regulatory T cells (1.6% FoxP3+CD25+CD127- of CD4+ T cells) with respect to donors (0.9%). Moreover, IFN-gamma ELISPOT assay demonstrated spontaneous T cell responses to a broad spectrum of HLA-A*0201-restricted peptides derived from breast cancer-associated antigens (HER2/neu, MUC-1, mammaglobin-A, Taxol resistance-associated gene-3, survivin, and Bcl-xL) in both groups of tumour patients, although the extent of these responses was usually higher in HER2+ cases. Finally, a multiparametric evaluation of the serum levels of 9 different cytokines revealed a comparable profile in HER2+ cases and in controls, whereas HER2- patients showed significantly lower cytokine amounts compared to healthy donors (IL-2, IL-6, and IL-8) and to HER2+ breast cancers (IL-6, IL-8, and IL-10). Preliminary data revealed a pathological complete response (pCR) in 44.4% of HER2+ patients (8/18), compared to 16.7% of the HER2- arm (5/30). These results are consistent with a retained immunologic proficiency of HER2+ patients, showing an innate tumor-specific immune response. Such features may at least partly account for the clinical benefit of drugs acting through, but also promoting, immunemediated effects. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-16.
OPTIMAL DURATION OF DUAL ANTIPLATELET THERAPY AMONG PATIENTS UNDERGOING DRUG ELUTING STENT PLACEMENT: A BAYESIAN NETWORK META-ANALYSIS
Authors: Ravi Parikh, Harsh Golwala, Sushil Garg, Ambarish Pandey, Abdallah El Sabbagh, Christopher DeFilippi
Journal: Journal of the American College of Cardiology (2016)
Extreme Elevation of Serum Transcobalamin I in Patients with Metastatic Cancer
Authors: Ralph Carmel
Journal: New England Journal of Medicine (1975)

Elevation of transcobalamin I and serum vitamin B12 levels has usually been associated with increased granulocytic proliferation, such as occurs in chronic myelogenous leukemia. Two patients with metastatic cancer had extremely high serum vitamin B12 and transcobalamin I levels--greater than those seen in even the most intense granulocytic proliferation--that were not explainable by leukocytosis. The subjects' serum vitamin B12 levels were 18,750 and 21,221 pg per milliliter (normal, 471 plus or minus 174 pg per milliliter, mean plus or minus S.D.) and unsaturated vitamin B12 binding capacity 158,750 and 5,400 pg per milliliter (normal, 1153 plus or minus 313 pg per milliliter) respectively. The abnormally elevated serum binder was shown to be identical with transcobalamin balamin I in every respect. Levels of transcobalamin II and serum third binder were normal. The cause of the binder abnormality is unknown, but factors other than granulocyte proliferation may control or contribute to the production or accumulation of transcobalamin I.
Prevalence of prostate cancer (PC) clinical states (CS) in the United States: Estimates using a dynamic progression model.
Authors: K. Solo, M. Mehra, R. Dhawan, J. Valant, H. I. Scher
Journal: Journal of Clinical Oncology (2011)

4637 Background: Understanding the prognosis at all stages in the PC disease continuum is essential to improve treatment and reduce morbidity and mortality. We provide a dynamic progression model to estimate prevalence of distinct PC CSs. This model enables estimation of annual prevalence of each CS, annual flows between CSs and provides a framework to evaluate impact of novel therapies. Methods: This PC dynamic progression model uses U.S. estimates of PC incidence from SEER and progression from one CS to another and mortality for each CS from published clinical trials. The simulation begins in 1990, introducing incident patient (pt) cohorts allocated across initial CSs (Table). Each year additional incident PC cohorts are layered into the model. Results: The model provides estimates of point prevalence for each PC CS. Results indicate that after 19 years of simulation, 95.5% (N=2,179,270) of prevalent PC patients have localized or locally advanced PC (L1-L3) and 4.5% (N=102,464) have metastatic PC (M1-M4). Conclusions: This dynamic PC progression model allows quantification of individual disease CSs by accounting explicitly for pt movement through the disease continuum. The model incorporates clinical data on available therapies for each CS and can be adapted easily to account for changing benefits from future therapies. Clinical state Definition 2009 prevalence Active disease* Annual progression hazard (%) Annual mortality hazard (%) Active surveillance Localized: no treatment 160,670 NA L1 Localized: definitive local therapy (tx) 1,195,060 83,380 5.2 3.8 L2 Rising PSA noncastrate, nonmetastatic: hormone tx 747,370 142,840 5.3 7.2 L3 Nonmetastatic castrate-resistant PC (CRPC): rising PSA postsurgery/radiation/hormone tx 76,170 48,450 36.6 14.5 M1 Metastatic noncastrate: newly diagnosed metastatic PC 35,880 17,493 16.9 19.5 M2 Asymptomatic metastatic CRPC (mCRPC): 1st line chemo 4,579 3,712 30.4 35.6 M3 Symptomatic mCRPC: 1st line chemo 30,839 26,928 46.3 29.4 M4 Symptomatic mCRPC: failed 1st line chemo, 2nd line chemo 31,166 27,406 NA 49.9 Total prevalence 2,281,734 350,209 * Excludes pts in remission and/or not on tx.
Use of the tissue slice technique for evaluation of renal transport processes.
Authors: W O Berndt
Journal: Environmental Health Perspectives (1976)

A detailed discussion of the tissue slice technique for evaluation of transport phenomena is presented. Information is given concerning the preparation of tissue slices and the advantages of this procedure over corresponding in vivo techniques. In addition, the relationship of the in vitro renal transport of organic substances to in vivo renal function is discussed in detail. Finally, certain pitfalls related to in vitro slice transport studies are presented.
European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition – Communication
Authors: J. Austoker, L. Giordano, P. Hewitson, P. Villain
Journal: Endoscopy (2012)

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on communication includes 35 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of screening programmes and services.
IMMEDIATE AND LATE OUTCOMES AFTER COLORECTAL CANCER SURGERY IN EXTREME ELDERLY PATIENTS: Table 1
Authors: R McBride, B Dasari, E Epanomeritakis, E Mackle
Journal: Gut (2013)

<h3>Introduction</h3> A retrospective study was performed to evaulate the immediate and late results of colorectal surgery in extreme elderly patients. <h3>Aims/Background</h3> The aim of this retrospective study was to evaluate the results of immediate and late (2 years) outcomes of colorectal surgery in extreme elderly patients (over 80 years) at a district general hospital. <h3>Method</h3> A total of 577 patients underwent colorectal surgery for colonic or rectal cancer at Southern Health and Social Care Trust between 01/04/2007 and 31/08/2011. Of these, 96 patients were aged equal to or over 80 years (Group I). From the remaining 483 patients (&lt;80 yrs), 100 patients were randomly chosen using the Random function on microsoft excel (Group II). We were able to retrieve 60 and 54 charts from Groups I and II respectively that were included in data analysis. The charts were retrospectively reviewed for analysis of postoperative mortality, morbidity and 2 year survival rates. Comparative analysis between the groups was performed using SPSS. <h3>Results</h3> Both patient groups were well matched with respect to sex, co morbidities, the type of surgery. The median age was 83.5 (range, 80–96) years in Gr I and was 69 (range, 45–79) years in Gr II. While the patients in ASA grade 1 were significantly more in Gr II (p=0.002), patients in ASA grade 4 were significantly more in Gr I (p=0.001). The overall postoperative morbidity and mortality rates were similar. Median duration of hospital stay was 14 days in Gr I and 9 days in Gr II. Colorectal cancer patients aged under 80 years at the time of surgery had statistically significantly higher observed survival than those aged 80 years or more (P&lt;0.05). <h3>Conclusion</h3> In this retrospective review, there was no significant difference in the immediate postoperative mortality and morbidity between the &lt;80 years group and &gt;/=80 years group following colorectal cancer resectional surgery. However, the survival rates at 2 years follow up were much better in those under 80years group.
Reply to Oh et al.
Authors: Frederike van Vilsteren, Erik Schoon, Jacques Bergman
Journal: Endoscopy (2014)

We thank Oh et al. for their interest in our study. Oh and colleagues suggest studying the effect of pre-emptive fundoplication in Barrett’s patients with erosive reflux disease refractory to proton pump inhibitors (PPIs), prior to radiofrequency ablation (RFA) treatment. They present a case of a Barrett’s patient with high grade dysplasia and a grade D reflux esophagitis that was successfully treated with RFA after laparoscopic fundoplication. We congratulate Oh et al. on their successful treatment of this challenging case. However, we feel that a conservative and stepwise approach towards management of reflux disease in this patient category should be preferred.
AB0151 Differential Regulation of C-Met Signal to Synovial Cell Functions in Rheumatoid Arthritis
Authors: T. Iwasaki, M. Sekiguchi, S. Tsunemi, S. Shibasaki, S. Kitano, H. Sano
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is characterized by the aggressive synovial expansion due to angiogenesis and subsequent destruction of the underlying cartilage and bone. Synovial cells produce inflammatory mediators, proteases, and angiogenic growth factors such as prostaglandin (PG) E2, IL-6, matrix metalloproteinase-3 (MMP-3) and vascular endothelial growth factor (VEGF). We previously demonstrated that blocking hepatocyte growth factor (HGF) receptor, c-Met signal by HGF antagonist, NK4 inhibited arthritis in RA model of SKG mice. <h3>Objectives</h3> In the present study we examined the role of c-Met signal for the production of PGE2, IL-6, MMP-3 and VEGF by synovial cells. <h3>Methods</h3> HGF or c-Met expressions in synovial tissues were examined by immunohistochemistry using either anti-human HGF Ab or anti-human c-Met Ab. Human MH7A synovial cell line was established by transfection with SV40 T antigen to synovial cells which was isolated from knee joint intraarticular soft tissue of RA patients. PGE2, IL-6, MMP-3 and VEGF productions from MH7A cells were determined by ELISA. Extracellular signal-regulated kinase (ERK) 1/2 and AKT phosphorylation was determined by Western blot analysis. The effect of MEK1/2 inhibitor, PI3 kinase inhibitor or c-Met kinase inhibitor was examined by the treatment of the cells with PD98059, LY294002 or SU11274, respectively. <h3>Results</h3> HGF and c-Met expressions in RA synovium were increased comparing to those in osteoarthritis synovium, suggesting the increased c-Met signal in RA synovial cells. We also detected c-Met expressions in MH7A. Blocking c-Met signal by SU11274 or NK4 inhibited ERK1/2 and AKT phosphorylation by HGF-stimulated MH7A cells. Both MEK and PI3K inhibitor suppressed PGE2, IL-6, MMP-3 and VEGF production. These results indicate that positive c-Met-MEK-ERK and c-Met-PI3K-AKT signal pathways are involved in MH7A cells. Although blocking c-Met signal by SU11274 or NK4 inhibited the production of MMP-3 and VEGF, however, it enhanced the production of PGE2 and IL-6 by MH7A cells. <h3>Conclusions</h3> These results indicate that positive c-Met-MEK-ERK and c-Met-PI3K-AKT signal pathways are involved in MMP-3 and VEGF production by MH7A cells. Although positive MEK-ERK and PI3K-AKT signal pathways are involved, negative c-Met signals independent to MEK-ERK and PI3K-AKT signal pathways are involved in PGE2 and IL-6 production. Blocking c-Met signal may be useful for the inhibition of angiogenesis and cartilage and bone destruction by the inhibition of VEGF and MMP-3 production, while it enhances PGE2 and IL-6 production by synovial cells in RA. <h3>References</h3> Arthritis. Res. Ther. 22 (2013) R75. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2551
ICD Leads and Postmarketing Surveillance
Authors: Mark D. Carlson
Journal: New England Journal of Medicine (2012)

To the Editor: Product quality is our highest priority at St. Jude Medical (SJM). To ensure accuracy and address misperceptions, we are providing responses to assertions in the Perspective article by Hauser in this issue of the Journal.1 Assertion: Recommendations for following patients with Riata silicone-only leads for implantable cardioverter–defibrillators (ICDs) are not based on meaningful data, and SJM has not instituted clinical studies. Facts: We have conducted extensive bench and short-term studies, and on the basis of the scientific data and clinical experience, in which 85% of externalized conductors in returned leads functioned normally, we have worked with . . .