tbuckley/cabot-search huggingface dataset:
FRI0191 The Cost-Effectiveness of Biologis for the Treatment of Rheumatoid Arthritis: A Systematic Review
Authors: J.T. Joensuu, K.J. Aaltonen, S. Huoponen, Y.T. Konttinen, D. Nordström, M. Blom
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Cost-effectiveness studies provide valuable information on the costs and benefits of the treatments. This information is needed to guide the optimal utilization of limited healthcare resources. Biological drugs for Rheumatoid arthritis (RA) are expensive, yet have great potential to improve patients9 quality of life. Therefore they are an important target for economic evaluation. <h3>Objectives</h3> The aim of this systematic review is to identify existing studies examining the cost-effectiveness of biologics for RA, assess their quality and report their results systematically. <h3>Methods</h3> The literature search covering Medline, Scopus, Cochrane library, ACP Journal club and Web of Science was performed in March 2013. The cost-utility analyses of one or more available biological drugs for the treatment of RA in adults were included in the current review. The information on patients, treatments, study design and outcomes were collected using a standardized data collection form. The quality of the studies was assessed using previously published checklists. The results of included studies were stratified by the patients9 previous treatments. <h3>Results</h3> Of the 4890 references found in the literature search, 38 cost-utility analyses were included in the current systematic review. Thirty-four of the included studies used a modelling approach, while remaining four were empiric studies. The incremental cost-effectiveness ratio (ICER) of the tumor necrosis factor (TNF) blockers ranged from 13,500 to 772,000 €/quality adjusted life year (QALY) in comparison to conventional disease modifying anti rheumatic drugs (cDMARD) in patients with no previous treatment with cDMARDs. Among patients with an insufficient response to cDMARDs, TNF blockers were associated with ICERs ranging from 6,700 to 317,000 €/QALY. Rituximab was found to be the most cost-effective alternative in contrast to other biologics among the patients with an insufficient response to TNF blockers. <h3>Conclusions</h3> Considering 50,000 €/QALY as an acceptable threshold for the ICER, TNF blockers are unlikely to be cost-effective among patients naïve to cDMARDs. Meanwhile, among patients with an insufficient response to cDMARDs they might be cost-effective. Heterogeneity in study designs was reflected in the results and made the comparison of studies difficult. The quality assessment revealed various types of biases in the included studies, potentially compromising the validity of their results. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3110
Collins Takes Helm Of NIH Genome Project
Authors: E. Blume
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Collins Takes Helm Of NIH Genome Project Get access Elaine Blume Elaine Blume Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 9, 5 May 1993, Pages 694–696, https://doi.org/10.1093/jnci/85.9.694 Published: 05 May 1993
Abstract P3-11-04: Male breast cancer: Overall survival in a single institution.
Authors: MA Bello, A Bergmann, CRA Costa, RR Pinto, EC Millen, LCS Thuler, PFM Bender
Journal: Cancer Research (2012)

Abstract Background: Male breast cancer is an uncommon disease and the therapy is mainly based on what is know from female breast cancer. Objective: To investigate the clinicopathologic characteristics of male breast cancer and the overall survival in a single institution. Methods: The clinical data and survival status of 75 male breast cancer treated in a Brazilian public cancer hospital from 2000 to 2009 were collected. The association with clinicopathological characteristics and overall survival was analyzed using Kaplan-Meier curves and the Cox proportional hazards regression (enter method) was used to assess survival differences after adjusting for confounders. The study was approved by National Cancer Institute Research and Ethics Committee (number 128/11). Results: The median patient age was 64 years (range 33–86). Estrogen receptor (ER) was positive in 58 (77.3%) patients, while progesterone receptor (PR) were positive in 47 (62.7%). Histology type was ductal infiltrant carcinoma for 57 (76.0%) and 51 (68.0%) patients underwent surgery. The median follow-up period was 43,1 months (range 2.7–147.8). The median survival from the diagnosis of breast cancer was 97.0 months (95%CI 53.6 −140.4) with a 61.7% 5-year overall survival (OS). In the final Cox regression model, independent factors associated with increased risk of death were metastasis at diagnosis (HR = 18.1; 95%CI: 5.9–55.2), ≥ 65 years old (HR = 4.3; 95%CI: 1.7–10.5); tumor stages ≥ IIb (HR = 3.5; 95%CI: 1.3–9.7) and smoking (HR = 1.6; 95%CI: 1.04–2.6). Conclusions: Invasive ductal carcinoma is the main pathologic type. The median survival from the diagnosis of breast cancer was 97.0 months and metastasis at diagnosis, patient age, tumor stage and smoking are independent prognostic factors. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-11-04.
Abstract 2912: F-box protein 10: A novel NF-κB–dependent antiapoptotic protein regulates TRAIL-induced apoptosis
Authors: Rongbin Ge, Zongwei Wang, Qing Zeng, Xiaoyin Xu, Aria F. Olumi
Journal: Cancer Research (2010)

Abstract Introduction and Objective Tumor necrosis factor-related apoptosis—inducing ligand (TRAIL) induces selective apoptotic death of human cancer cells while sparing normal human cells. Although TRAIL holds great promise as a potential anti—cancer agent, some tumors develop resistance to TRAIL. Previously, we have shown that the AP—1 family member, c—Fos, is an important modulator of apoptosis. Although FBXL10 has been implicated to regulate an AP—1 family protein, c—Jun, its role in mediating apoptotic pathways has not been previously investigated. Here, we report that FBXL10 is a novel NF—kB dependent anti—apoptotic molecule, which directly binds and represses c—Fos, another AP—1 family member, rather than c—Jun. Repression of c—Fos leads to resistance of cancer cells to TRAIL—induced apoptosis. Methods RT—PCR, Western blot and immunofluorescence assays were applied to evaluate protein expression level. RNAi, Chromatin immunoprecipitation (ChIP), EMSA, hydrodynamic—based transfection, oligonucleotide decoy technologies, plasmid reconstruction and site—directed mutation were performed to analyze the interaction between FBXL10, c—Fos and NF—kB. Orthotopic prostate xenografts were carried out for in—vivo analyses. Results FBXL10 was suppressed and c—Fos was upregulated in TRAIL sensitive cancer cells and xenografts after treatment with TRAIL. However, in TRAIL resistant cancer cells and xenografts, FBXL10 and c—Fos were not affected. Expression of FBXL11, a FBXL10 homologous protein and c—Jun, was not affected by TRAIL. Silencing of FBXL10 sensitized resistant cells to TRAIL. Conversely, over—expression of FBXL10 repressed TRAIL—induced apoptosis. To behave as an anti—apoptotic molecule, we found that FBXL10 directly binds and represses c—Fos promoter in vitro and in vivo. In addition, FBXL10 regulates c—FLIP, another anti—apoptotic molecule, by a c—Fos dependent pathway. We also found that expression of FBXL10 is NF—kB—dependent, and TRAIL or proteasome inhibitors down—regulate FBXL10 via inhibiting NF—kB signaling. Using ChIP and EMSA assays, we found that NF—kB—p65 directly binds the FBXL10 promoter in vivo and in vitro, and promotes expression of FBXL10. Conclusions Differentiating molecular mechanisms between TRAIL sensitive and TRAIL resistant cancer cells will improve the efficacy of apoptotic therapies for cancer patients. In this study, we demonstrates for the first time, that FBXL10 plays an anti—apoptotic role and indicates a novel NF—kB/FBXL10/c—Fos/c—FLIP signaling pathway in TRAIL—mediated 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 2912.
Impaired Expression of the Thrombopoietin Receptor by Platelets from Patients with Polycythemia Vera
Authors: Alison R. Moliterno, W. David Hankins, Jerry L. Spivak
Journal: New England Journal of Medicine (1998)

The cause of polycythemia vera, which originates from a multipotent hematopoietic progenitor cell, is unknown. Thrombopoietin is a hematopoietic growth factor that regulates the production of multipotent hematopoietic progenitor cells and platelets. To evaluate the possibility that an abnormality in thrombopoietin-mediated signal transduction might be involved in the pathogenesis of polycythemia vera, we examined thrombopoietin-induced tyrosine phosphorylation of proteins and the expression of the thrombopoietin receptor in platelets from patients with the disease.
Abstract 1480: Regulation of ovarian tumor growth and stromal cell infiltration by the HU177 biomechanical ECM switch
Authors: Jacquelyn Joan Ames, Jennifer M. Caron, Liangru Contois, Calvin Vary, Robert Friesel, Leonard Liebes, Peter C. Brooks
Journal: Cancer Research (2012)

Abstract Accumulating evidence indicates that the malignant behavior of tumors depends not only on tumor cells themselves, but also on the stromal cells that comprise the malignant tumor mass. Experimental findings suggest that stromal cells such as cancer-associated fibroblast (CAF) may play important roles in promoting tumor growth and metastasis as well as regulating the efficacy of certain chemotherapeutic drugs. However, developing novel clinical strategies that selectively and simultaneously impacts tumor and stromal cells remains challenging. Alterations in the integrity and molecular composition of the extracellular matrix (ECM) are hallmarks of tumor progression. Our previous studies have shown that structural remodeling of the ECM can result in localized triggering of what we have termed “biomechanical ECM switches” or changes in the three-dimensional structure of pre-existing ECM molecules. A humanized antibody (TRC093/D93) specifically directed to the HU177 cryptic collagen epitope that is selectively exposed following triggering of a biomechanical ECM switch has been developed, and a human phase-I clinical trial was recently completed with encouraging results. Here we provide evidence that the HU177 biomechanical ECM switch is triggered within human ovarian tumors resulting in the exposure of the HU177 cryptic collagen epitope. The relative exposure of the HU177 cryptic site was significantly (P&amp;lt;0.05) enhanced in biopsies of malignant ovarian tumors as compared to benign ovarian lesions. Selective targeting of the HU177 cryptic collagen epitope by Mab D93 significantly (P&amp;lt;0.05) inhibited SKOV-3 tumor growth by approximately 70% as compared to controls. Tumors from these mice exhibited reduced angiogenesis, elevated levels of apoptosis and a significant reduction in infiltration of alpha smooth muscle cell actin (αSMC-actin) positive stromal fibroblasts. Importantly, while Mab D93 inhibited SKOV-3 tumor cell adhesion to denatured collagen type-I and enhanced the expression of the cyclin dependent kinase inhibitor P27KIP1, it also selectively inhibited (80%) fibroblast migration on denatured collagen type-I that was induced by either FGF-2 or SKOV-3 condition medium. Collectively these studies provide evidence that specific targeting of the HU177 cryptic collagen epitope may represent a highly selective strategy to inhibit ovarian tumor growth in part by limiting stromal cell invasion. 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 1480. doi:1538-7445.AM2012-1480
Increased incidence of invasive meningococcal disease of serogroup C / clonal complex 11, Tuscany, Italy, 2015 to 2016
Authors: Paola Stefanelli, Alessandro Miglietta, Patrizio Pezzotti, Cecilia Fazio, Arianna Neri, Paola Vacca, Fabio Voller, Fortunato P. D’Ancona, Raniero Guerra, Stefania Iannazzo, Maria Grazia Pompa, Giovanni Rezza
Journal: Eurosurveillance (2016)

We report an increase of serogroup C Neisseria meningitidis invasive meningococcal disease in Tuscany. From January 2015 to end February 2016, 43 cases were reported, among which 10 were fatal, compared to two cases caused by serogroup C recorded in 2014 and three in 2013. No secondary cases occurred. Thirty–five strains belonged to C:P1.5–1,10–8:F3–6:ST-11(cc11). Control measures have been adopted and immunisation campaigns implemented. Studies on risk factors and carriage are ongoing.
Abstract 830: Angiotensin converting enzyme inhibitor and angiotensin receptor blocker suppress obesity-related colonic preneoplastic lesions in male C57BL/KsJ-db/db obese mice
Authors: Masaya Kubota, Masahito Shimizu, Yoichi Yasuda, Hiroyasu Sakai, Takuji Tanaka, Hisataka Moriwaki
Journal: Cancer Research (2011)

Abstract Obesity and related metabolic abnormalities, including a state of chronic inflammation and oxidative stress, are risk factors for colon cancer. Dysregulation the renin-angiotensin system (RAS) also plays a critical role in obesity-related metabolic disorders and certain types of carcinogenesis. In the present study, we examined the effects of angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB), both of which target RAS, on the development of azoxymethane (AOM)-initiated colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Male db/db mice were given 4 weekly subcutaneous injections of AOM (15 mg/kg body weight) and then they received drinking water containing captopril (ACE inhibitor, 5 mg/kg/day) or telmisartan (ARB, 5 mg/kg/day) for 7 weeks. At sacrifice, administration of captopril and telmisartan significantly reduced the total number of colonic premalignant lesions, aberrant crypt foci and β-catenin accumulated crypts, compared with the control untreated-group. Both agents decreased the expression levels of TNF-α mRNA on the colonic mucosa of experimental mice. The expression levels of TNF-α, COX-2, IL-1β, IL-6, and PAI-1 mRNAs on the visceral fat were also decreased by administration of these agents. In addition, captopril and telmisartan significantly decreased the levels of urinary 8-OHdG, a surrogate marker of oxidative damage to DNA, in the experimental mice. These findings suggest that both ACE inhibitor and ARB suppress obesity-related colon carcinogenesis by attenuating chronic inflammation and reducing oxidative stress. Targeting the dysregulation of RAS might be, therefore, one of the effective strategies for the chemoprevention of obesity-related colon cancer. 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 830. doi:10.1158/1538-7445.AM2011-830
THE PROGNOSTIC IMPACT OF RENAL DYSFUNCTION AND ANEMIA IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Koki Shishido, Satoshi Takeshita, Shinji Tanaka, Takeshi Akasaka, Saeko Takahashi, Junya Matsumi, Yutaka Tanaka, Masato Murakami, Hidetaka Suenaga, Ken Arima, Shingo Mizuno, Nobuhiro Okamura, Futoshi Yamanaka, Kazuya Sugitatsu, Yumiko Osaka, yu nomura, Yoichi Imori, Kazuki Tobita, Kazuma Oyama, Shigeru Saito
Journal: Journal of the American College of Cardiology (2013)
PREDICTING THE LIKELIHOOD FOR CORONARY ARTERY BYPASS GRAFTING IN NON ST ELEVATION MYOCARDIAL INFARCTION PATIENTS
Authors: Ali Shafiq, Faraz Kureshi, Jae-Sik Jang, Timothy Fendler, Kensey Gosch, Philip Jones, Richard Bach, David Cohen, John Spertus
Journal: Journal of the American College of Cardiology (2015)
Bone Marrow, Cytokines, and Bone Remodeling — Emerging Insights into the Pathophysiology of Osteoporosis
Authors: S C Manolagas, R L Jilka
Journal: New England Journal of Medicine (1995)

Bone is remodeled continuously during adulthood through the resorption of old bone by osteoclasts and the subsequent formation of new bone by osteoblasts. These two closely coupled events are responsible for renewing the skeleton while maintaining its anatomical and structural integrity. Under normal conditions, bone remodeling proceeds in cycles in which osteoclasts adhere to bone and subsequently remove it by acidification and proteolytic digestion. Shortly after the osteoclasts have left the resorption site, osteoblasts invade the area and begin the process of forming new bone by secreting osteoid (a matrix of collagen and other proteins), which is eventually mineralized. After . . .
SAT0019 Preliminary Data Supporting the Feasibility and Construct Validity of Promis Fatigue Instrument in an Academic Rheumatoid Arthritis Clinic.
Authors: S. J. Bartlett, A.-M. Orbai, T. Duncan, E. De Leon, M. Jones, C. O. Bingham
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The Patient-Reported Outcomes Measurement Information System (PROMIS) initiative of the National Institutes of Health has created item banks to measure patient-reported health outcomes for physical, mental, and social well–being across domains relevant to chronic medical conditions. PROMIS scores have a mean of 50 and standard deviation of 10, in reference to general US adult and pediatric populations. However, the feasibility of using PROMIS scales in busy settings as part of clinic visits and the validity of most PROMIS measures in persons with rheumatoid arthritis (RA) has not been demonstrated. <h3>Objectives</h3> To contribute preliminary data on the feasibility and construct validity of the PROMIS fatigue item banks in an academic RA clinic. <h3>Methods</h3> Consecutive RA patients enrolled in a longitudinal study completed selected patient reported outcomes (PROs) at the Johns Hopkins Arthritis Center. PROMIS fatigue items were administered using computerized adaptive test (CAT) administered on a tablet computer linked directly to the internet-based PROMIS Assessment Center immediately before a routine clinic visit. Variables were transformed as needed and descriptive statistics, correlations and multiple regression analyses were performed using IBM SPSS ver 20. <h3>Results</h3> Participants were 69 RA patients with a mean (SD) age of 55.1 ± 13.7 yrs and RA duration of 10 ± 9 yrs, who were mostly female (77%), white (83%) and well educated (74% had some college). PROMIS fatigue t-scores ranged from 32 to 76, with a mean of 55.7 ± 10.0 and were highly correlated with fatigue VAS ratings (r=.83), moderately correlated with stiffness (r=.55), patient global (r=.66), pain VAS (r=.60), and only weakly with MHAQ (r=.39). Fatigue was moderately associated with CDAI (r=.50) though only weakly with DAS28 (r=.27), SJC (r=.24) and TJC (r=.29)(all p's &lt;.05), but not age or sex. Patients with any level of disease activity reported fatigue levels on average 1 SD higher than those in CDAI remission (59.1 ± 8.3 vs. 49.6 ± 8.3; p&lt;.01). In multivariate regression, after controlling for pain, fatigue was a significant predictor of Patient Global scores; together pain and fatigue explained 83% of the variance. <h3>Conclusions</h3> Fatigue is common in RA. These results contribute preliminary evidence of the feasibility and construct validity of the PROMIS Fatigue instrument in RA with both RA PROs as well as clinician disease activity ratings. Further testing and validation of PROMIS Fatigue and other PROMIS domain instruments in RA populations is needed. <h3>Disclosure of Interest</h3> None Declared
UTILIDAD DE LA ECOENDOSCOPIA EN LA ESTADIFICIACIÓN PREOPERATORIA DEL CANCER GÁSTRICO: RENTABILIDAD DIAGNÓSTICA E IMPACTO TERAPÉUTICO
Authors: M Del Mar Lombera, A Repiso, R Gómez, JM Carrobles
Journal: Endoscopy (2010)

Objetivos: Valorar la rentabilidad diagnóstica de la ecoendoscopia en la estadificación locorregional del cáncer gástrico en nuestro medio; y determinar el impacto de la técnica sobre el manejo terapéutico posterior.
Abstract 3016: The value of microRNAs in the detection and staging of colorectal cancer
Authors: Nadia Ilyayev, Alexander Stojadinovic, David Halle, Marina Roistacher, Vera Pavlov, Stella Mitrani-Rosenbaum, Aviram Nissan
Journal: Cancer Research (2010)

Abstract Introduction: MicroRNAs (miRNAs) are a large class of single strand RNA molecules consistent of 18-25 nucleotides, involved in post transcriptional gene silencing. miRNAs show tissue-specific expression and play an important role in carcinogenesis. The aim of the present study was: A. to identify colorectal cancer (CRC)-specific miRNAs. B. To study the potential value of CRC-specific miRNAs in CRC detection and staging. Methods: This study was approved by the Institutional Review Board (IRB). RNA was extracted from paired samples of normal and tumor tissue of CRC patients (n=10). miRNA expression was tested using a commercially available array. Differential expression between normal and tumor tissues was identified in 30 human miRNAs and in additional 16 miRNAs identified from database mining. Differential expression was validated by quantitative (real-time) PCR in a larger cohort of samples (n=20). RNA was extracted from sentinel lymph nodes (SLN) of CRC patients. A calibration plot was generated using a CRC cell line (HT29) mixed with peripheral blood lymphocytes (PBL) of healthy donors in a range of concentrations. Results: After validation, only 8 miRNAs were found to be overexpressed in CRC. The detection threshold for all 8 miRNAs measured by the calibration plot was 1:1000 (one HT-29 cell in 1000 PBMCs). The expression of the 8 miRNAs was then tested in SLNs (n=86). Fourteen lymph nodes (16.3%) were positive by standard pathological examination (H&amp;E staining) and 25/86 (29.1%) were positive by miRNA expression analysis (p&amp;lt;0.01). miRNA expression was detected in all sera from CRC patients (n=3) and in none of the sera obtained from healthy individuals (n=5, p&amp;lt;0.0001). Conclusions: A panel of 8 miRNAs was found to be overexpressed in CRC patients. Occult residual disease was indentified in lymph nodes and serum of CRC patients using this miRNA panel. 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 3016.