tbuckley/cabot-search huggingface dataset:
Inhibition of radiographic progression with combination etanercept and methotrexate in patients with moderately active rheumatoid arthritis previously treated with monotherapy
Authors: D van der Heijde, G Burmester, J Melo-Gomes, C Codreanu, E M. Mola, R Pedersen, D Robertson, D Chang, A Koenig, B Freundlich
Journal: Annals of the Rheumatic Diseases (2008)

To determine the effect of changing from etanercept or methotrexate monotherapy to etanercept plus methotrexate combination therapy on radiographic progression in rheumatoid arthritis (RA) patients.Patients enrolled in this 1-year open-label study previously completed a 3-year blinded study in which they received methotrexate or etanercept monotherapy or the combination of both. All patients received the combination of etanercept 25 mg subcutaneously twice weekly plus oral methotrexate up to 20 mg/week. The primary radiographic endpoint was a change in modified total Sharp score (TSS), as assessed by blinded readers.At baseline, patients previously receiving methotrexate monotherapy (etanercept-added, n = 52) or etanercept monotherapy (methotrexate-added, n = 68) had moderate disease activity levels (mean disease activity score (DAS) of 2.6 and 2.5, respectively), whereas patients previously receiving combination therapy (n = 90) had a low disease activity level (mean DAS of 2.0). The addition of etanercept to methotrexate monotherapy resulted in a significant reduction in radiographic progression (p<0.05). Mean TSS changes in the previous year versus the current year were +1.79 versus +0.25 for the etanercept-added group (p<0.05); +0.51 versus -0.18 for the methotrexate-added group (NS) and +0.42 versus +0.24 for the combination group (NS).In these RA patients with on average moderate disease activity despite previous methotrexate monotherapy, combination treatment with etanercept and methotrexate inhibited radiographic progression and improved radiographic outcomes. These data, in conjunction with the previously published clinical data, support the use of combination therapy in RA patients with moderate disease activity.
Therapeutic Delivery of Cyclin A2 Induces Myocardial Regeneration and Enhances Cardiac Function in Ischemic Heart Failure
Authors: Y. Joseph Woo, Corinna M. Panlilio, Richard K. Cheng, George P. Liao, Pavan Atluri, Vivian M. Hsu, Jeffrey E. Cohen, Hina W. Chaudhry
Journal: Circulation (2006)

Background— Heart failure is a global health concern. As a novel therapeutic strategy, the induction of endogenous myocardial regeneration was investigated by initiating cardiomyocyte mitosis by expressing the cell cycle regulator cyclin A2. Methods and Results— Lewis rats underwent left anterior descending coronary artery ligation followed by peri-infarct intramyocardial delivery of adenoviral vector expressing cyclin A2 (n =32) or empty adeno-null (n =32). Cyclin A2 expression was characterized by Western Blot and immunohistochemistry. Six weeks after surgery, in vivo myocardial function was analyzed using an ascending aortic flow probe and pressure-volume catheter. DNA synthesis was analyzed by proliferating cell nuclear antigen (PCNA), Ki-67, and BrdU. Mitosis was analyzed by phosphohistone-H3 expression. Myofilament density and ventricular geometry were assessed. Cyclin A2 levels peaked at 2 weeks and tapered off by 4 weeks. Borderzone cardiomyocyte cell cycle activation was demonstrated by increased PCNA (40.1±2.6 versus 9.3±1.1; P &lt;0.0001), Ki-67 (46.3±7.2 versus 20.4±6.0; P &lt;0.0001), BrdU (44.2±13.7 versus 5.2±5.2; P &lt;0.05), and phosphohistone-H3 (12.7±1.4 versus 0±0; P &lt;0.0001) positive cells/hpf. Cyclin A2 hearts demonstrated increased borderzone myofilament density (39.8±1.1 versus 31.8±1.0 cells/hpf; P =0.0011). Borderzone wall thickness was greater in cyclin A2 hearts (1.7±0.4 versus 1.4±0.04 mm; P &lt;0.0001). Cyclin A2 animals manifested improved hemodynamics: Pmax (70.6±8.9 versus 60.4±11.8 mm Hg; P =0.017), max dP/dt (3000±588 versus 2500±643 mm Hg/sec; P &lt;0.05), preload adjusted maximal power (5.75±4.40 versus 2.75±0.98 mWatts/μL 2 ; P &lt;0.05), and cardiac output (26.8±3.7 versus 22.7±2.6 mL/min; P =0.004). Conclusions— A therapeutic strategy of cyclin A2 expression via gene transfer induced cardiomyocyte cell cycle activation yielded increased borderzone myofilament density and improved myocardial function. This approach of inducing endogenous myocardial regeneration provides proof-of-concept evidence that cyclin A2 may ultimately serve as an efficient, alternative therapy for heart failure.
A randomised, multicentre, double-blind, placebo-controlled trial of etanercept in adults with refractory heel enthesitis in spondyloarthritis: the HEEL trial
Authors: M. Dougados, B. Combe, J. Braun, R. Landewe, J. Sibilia, A. Cantagrel, A. Feydy, D. van der Heijde, V. Leblanc, I. Logeart
Journal: Annals of the Rheumatic Diseases (2010)

<h3>ABSTRACT</h3> Diverse microbial ecosystems underpin life in the sea. Among these microbes are many unicellular eukaryotes that span the diversity of the eukaryotic tree of life. However, genetic tractability has been limited to a few species, which do not represent eukaryotic diversity or environmentally relevant taxa. Here, we report on the development of genetic tools in a range of protists primarily from marine environments. We present evidence for foreign DNA delivery and expression in 13 species never before transformed and advancement of tools for 8 other species, as well as potential reasons for why transformation of yet another 17 species tested was not achieved. Our resource in genetic manipulation will provide insights into the ancestral eukaryotic lifeforms, general eukaryote cell biology, protein diversification and the evolution of cellular pathways.
Universal Marker and Detection Tool for Human Sarcoma Circulating Tumor Cells
Authors: Arun Satelli, Abhisek Mitra, Jeffry J. Cutrera, Marcos Devarie, Xueqing Xia, Davis R. Ingram, Denada Dibra, Neeta Somaiah, Keila E. Torres, Vinod Ravi, Joseph A. Ludwig, Eugenie S. Kleinerman, Shulin Li
Journal: Cancer Research (2014)

Abstract To date, no specific marker exists for the detection of circulating tumor cells (CTC) from different types of sarcomas, though tools are available for detection of CTCs in peripheral blood of patients with cancer for epithelial cancers. Here, we report cell-surface vimentin (CSV) as an exclusive marker on sarcoma CTC regardless of the tissue origin of the sarcoma as detected by a novel monoclonal antibody. Utilizing CSV as a probe, we isolated and enumerated sarcoma CTCs with high sensitivity and specificity from the blood of patients bearing different types of sarcoma, validating their phenotype by single cell genomic amplification, mutation detection, and FISH. Our results establish the first universal and specific CTC marker described for enumerating CTCs from different types of sarcoma, thereby providing a key prognosis tool to monitor cancer metastasis and relapse. Cancer Res; 74(6); 1645–50. ©2014 AACR.
Identification of expressed genes linked to malignancy of human colorectal carcinoma by parametric clustering of quantitative expression data
Authors: Shizuko Muro, Ichiro Takemasa, Shigeyuki Oba, Ryo Matoba, Noriko Ueno, Chiyuri Maruyama, Riu Yamashita, Mitsugu Sekimoto, Hirofumi Yamamoto, Shoji Nakamori, Morito Monden, Shin Ishii, Kikuya Kato
Journal: Genome biology (2003)
Supersensitive PSA-Monitored Neoadjuvant Hormone Treatment of Clinically Localized Prostate Cancer: Effects on Positive Margins, Tumor Detection and Epithelial Cells in Bone Marrow
Authors: M.W. K&ouml;llermann, K. Pantel, Th. Enzmann, U. Feek, J. K&ouml;llermann, M. Kossiwakis, U. Kaulfuss, W. Martell, J. Spitz
Journal: European Urology (1998)
Significant Differences in the Effects of Magnetic Field Exposure on 7,12-Dimethylbenz(<b><i>a</i></b>)anthracene-Induced Mammary Carcinogenesis in Two Substrains of Sprague-Dawley Rats
Authors: Maren Fedrowitz, Kenji Kamino, Wolfgang Löscher
Journal: Cancer Research (2004)

Abstract We have shown previously (S. Thun-Battersby et al., Cancer Res., 59: 3627–3633, 1999) that power-line frequency (50-Hz) magnetic fields (MFs) at μT-flux densities enhance mammary gland tumor development and growth in the 7,12-dimethylbenz(a)anthracene (DMBA) model of breast cancer in female Sprague-Dawley (SD) rats. We also demonstrated that MF exposure results in an enhanced proliferative activity of the mammary epithelium of SD rats (M. Fedrowitz et al., Cancer Res., 62: 1356–1363, 2002), which is a likely explanation for the cocarcinogenic or tumor-promoting effects of MF exposure in the DMBA model. However, in contrast with our data, in a similar study conducted by Battelle in the United States, no evidence for a cocarcinogenic or tumor-promoting effect of MF exposure was found in the DMBA model in SD rats (L. E. Anderson et al., Carcinogenesis, 20: 1615–1620, 1999). Probably the most important difference between our and the Battelle studies was the use of different substrains of SD rats; the United States rats were much more susceptible to DMBA than the rats used in our studies. This prompted us to compare different substrains of SD outbred rats in our laboratory in respect to MF effects on cell proliferation in the mammary gland, susceptibility to DMBA-induced mammary cancer, and MF effects on mammary tumor development and growth in the DMBA model. The SD substrain (termed “SD1”) used in all of our previous studies was considered MF-sensitive and used for comparison with another substrain (“SD2”) obtained from the same breeder. In contrast with SD1 rats, no enhanced cell proliferation was determined after MF exposure in SD2 rats. MF exposure significantly increased mammary tumor development and growth in SD1 but not SD2 rats. These data indicate that the genetic background plays a pivotal role in effects of MF exposure. Different strains or substrains of rats may serve to evaluate the genetic factors underlying sensitivity to cocarcinogenic or tumor-promoting effects of MF exposure.
Echinococcal cysts with primary cutaneous localization
Authors: A. Baldi, L. Rossiello, R. Rossiello, F. Baldi
Journal: British Journal of Dermatology (2002)

Journal Article Echinococcal cysts with primary cutaneous localization Get access A. Baldi, A. Baldi Department of Biochemistry and Biophysics ‘F. Cedrangolo’, Section of Anatomic Pathology, Second University of Naples, Naples, Italy Alfonso Baldi MD. E‐mail: alfonsobaldi@tiscali.it Search for other works by this author on: Oxford Academic Google Scholar L. Rossiello, L. Rossiello Department of Biochemistry and Biophysics ‘F. Cedrangolo’, Section of Anatomic Pathology, Second University of Naples, Naples, Italy Search for other works by this author on: Oxford Academic Google Scholar R. Rossiello, R. Rossiello Department of Biochemistry and Biophysics ‘F. Cedrangolo’, Section of Anatomic Pathology, Second University of Naples, Naples, Italy Search for other works by this author on: Oxford Academic Google Scholar F. Baldi F. Baldi Department of Biochemistry and Biophysics ‘F. Cedrangolo’, Section of Anatomic Pathology, Second University of Naples, Naples, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 147, Issue 4, 1 October 2002, Page 807, https://doi.org/10.1046/j.1365-2133.2002.04805.x Published: 01 October 2002 Article history Accepted: 28 November 2001 Published: 01 October 2002
Electromotive instillation of mitomycin immediately before transurethral resection for patients with primary urothelial non-muscle invasive bladder cancer: a randomised controlled trial
Authors: Savino M Di Stasi, Marco Valenti, Cristian Verri, Emanuele Liberati, Arcangelo Giurioli, Gioia Leprini, Francesco Masedu, Antonio R Ricci, Francesco Micali, Giuseppe Vespasiani
Journal: The Lancet Oncology (2011)
On the Role of Cell Signaling Models in Cancer Research
Authors: Alejandra C. Ventura, Trachette L. Jackson, Sofia D. Merajver
Journal: Cancer Research (2009)

Abstract The main objective of this review is to emphasize the role and importance of the careful mathematical/computational modeling of signaling networks for the understanding of aberrant signaling in cancer and for the development of targeted therapies. [Cancer Res 2009;69(2):400–2]
Reversibility of diffusion capacity abnormalities in patients with clinical hypothyroidism with establishment of euthyroid state
Authors: Blagoi Marinov, Boyan Nonchev, Miroslava Todorova, Maria Orbetzova, Stefan Kostianev
Journal: European Respiratory Journal (2013)

Background: Hypothyroidism is associated with significant reduction of parameters of diffusion capacity and slight peripheral obstruction. However, it is not quite clear whether these abnormalities are reversible.  Aim: To evaluate the reversibility of diffusion capacity (D L,CO ) abnormalities in patients with clinical hypothyroidism with establishment of euthyroid state.  Patients and methods: Sixteen patients with different forms of autoimmune thyroiditis in clinical hypothyroid state (male/female – 4/12; age = 43.0±13.4 (mean±SD), TSH=101.6±52.3 mIU.L -1 , FT4=4.9±3.8 pmol.L -1 ) and 14 age and sex matched controls were included in the study. Pulmonary function assessment included slow vital capacity, forced spirometry and diffusion measurements (MasterScreen Diffusion, E. Jaeger, Germany).  Results: Most of the patients with hypothyroidism (13/16) revealed significantly reduced diffusion capacity for carbon monoxide (D L,CO  %pred. = 70.5±6.7 vs 93.8±12.9 in controls; p -1 ) diffusion capacity was significantly improved (D L,CO =80.3±10.3 vs. 70.5±6.7 before treatment; p=0.020). No changes were aparent in the other pulmonary function parameters.  Conclusions: Hypothyroidism is associated with significant reduction of diffusion capacity. Restoring euthyroid state reverses these abnormalities as seen by the substantial improvement of D L,CO .
Insulin Receptor Isoform A and Insulin-like Growth Factor II as Additional Treatment Targets in Human Osteosarcoma
Authors: Sofia Avnet, Laura Sciacca, Manuela Salerno, Giovanni Gancitano, Maria Francesca Cassarino, Alessandra Longhi, Mahvash Zakikhani, Joan M. Carboni, Marco Gottardis, Armando Giunti, Michael Pollak, Riccardo Vigneri, Nicola Baldini
Journal: Cancer Research (2009)

Despite the frequent presence of an insulin-like growth factor I receptor (IGFIR)-mediated autocrine loop in osteosarcoma (OS), interfering with this target was only moderately effective in preclinical studies. Here, we considered other members of the IGF system that might be involved in the molecular pathology of OS. We found that, among 45 patients with OS, IGF-I and IGFBP-3 serum levels were significantly lower, and IGF-II serum levels significantly higher, than healthy controls. Increased IGF-II values were associated with a decreased disease-free survival. After tumor removal, both IGF-I and IGF-II levels returned to normal values. In 23 of 45 patients, we obtained tissue specimens and found that all expressed high mRNA level of IGF-II and >IGF-I. Also, isoform A of the insulin receptor (IR-A) was expressed at high level in addition to IGFIR and IR-A/IGFIR hybrids receptors (HR(A)). These receptors were also expressed in OS cell lines, and simultaneous impairment of IGFIR, IR, and Hybrid-Rs by monoclonal antibodies, siRNA, or the tyrosine kinase inhibitor BMS-536924, which blocks both IGFIR and IR, was more effective than selective anti-IGFIR strategies. Also, anti-IGF-II-siRNA treatment in low-serum conditions significantly inhibited MG-63 OS cells that have an autocrine circuit for IGF-II. In summary, IGF-II rather than IGF-I is the predominant growth factor produced by OS cells, and three different receptors (IR-A, HR(A), and IGFIR) act complementarily for an IGF-II-mediated constitutive autocrine loop, in addition to the previously shown IGFIR/IGF-I circuit. Cotargeting IGFIR and IR-A is more effective than targeting IGF-IR alone in inhibiting OS growth.
Characteristics of CD44 alternative splice pattern in the course of human colorectal adenocarcinoma progression
Authors: Balázs Bánky, Lívia Rásó-Barnett, Tamás Barbai, József Tímár, Péter Becságh, Erzsébet Rásó
Journal: Molecular Cancer (2012)

CD44 is considered as 'a' metastasis associated gene, despite the fact that it is an umbrella term for a group of molecules produced from a single gene by alternative splicing. However, little consideration is given to the above in the literature of colorectal carcinomas as well as other tumour types, leading to confusion and contradictory results about its possible role in tumour progression. We compared the CD44 alternative splice pattern (ASP) of three genetically different human colorectal cancer cell lines (HT25, HT29, HCT116) using a series of PCR reactions and next- generation sequencing method, as well as identified a colorectal adenocarcinoma specific CD44 ASP. This ASP was further investigated in terms of its qualitative and quantitative stability in our experimental iso- and xenograft mouse models for colorectal cancer progression. A complex preclinical experimental set-up was established to separately test the different steps of tumour progression and the role of tumour microenvironment, respectively, focusing on the role of 'CD44' in this process. We managed to present a colorectal cancer-specific CD44 ASP, which remained unchanged from cell lines throughout primary tumour formation and metastatic progression. Furthermore, we report a unique roster of all expressed CD44 variant isoforms characteristic to colorectal cancer. Finally, on quantitative assessment of the variable exons v3 and v6, higher co-expression levels were found to be characteristic to metastatically potent tumour cells. Particular CD44 variant isoforms seem to act as "metastasis genes" via tumour microenvironment-driven shifts in v3 and v6 expressions. However, this function may just affect a minority of tumour subclones. This fact and the huge potential number of different CD44 splice variants that can contain v3 and v6 domains can explain incoherence of clinical studies regarding functional asessment of CD44 variants, as well as diminish the chances of using CD44 variants for predictive purpose.
Effect of Apolipoprotein E epsilon4 on the association between health behaviors and cognitive function in late midlife
Authors: Severine Sabia, Mika Kivimaki, Meena Kumari, Martin J Shipley, Archana Singh-Manoux
Journal: Molecular Neurodegeneration (2010)

The extent to which the effect of risk factors on cognitive ageing is dependent on APOE ε4 remains unclear. The objective of this study is to examine whether APOE ε4 allele modifies the association between health behaviors and cognition in late midlife. Data are drawn from 5447 participants of the Whitehall II study, health behaviors were assessed in 1997-1999 (mean age = 55.6, Standard Deviation (SD) = 6.0) and APOE genotype and cognitive function in 2002-2004 (mean age = 60.9, SD = 5.9). Among APOE ε4 non-carriers, current smokers had lower scores on memory (difference in T-score = -2.49, 95%CI: -3.37, -1.60), reasoning (-2.88, 95%CI: -3.74, -2.01), phonemic (-2.66, 95%CI: -3.56, -1.76) and semantic (-2.38, 95%CI: -3.28, -1.47) fluency compared to never smokers. In APOE ε4 carriers, difference between current and never smokers was seen only for reasoning (-1.92, 95%CI: -3.31, -0.51). Interaction terms supported differential effects of smoking as a function of APOE ε4 status for memory (p = 0.01), and phonemic (p = 0.008) and semantic fluency (p = 0.02). Cognitive scores were lower among non-drinkers compared to moderate drinkers, among the sedentary participants and those who ate fruits and vegetable less than 2 times per day irrespective of APOE ε4 status. This study suggests that the APOE ε4 allele modifies the association of smoking but not that of other health behaviors - alcohol consumption, physical activity, fruit and vegetable consumption - with cognitive function in late midlife.
Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions
Authors: David J. Greensmith, Gina L.J. Galli, Andrew W. Trafford, David A. Eisner
Journal: Cardiovascular Research (2014)

AimsMost of the calcium that activates contraction is released from the sarcoplasmic reticulum (SR) through the ryanodine receptor (RyR). It is controversial whether activators of the RyR produce a maintained increase in the amplitude of the systolic Ca transient. We therefore aimed to examine the effects of activation of the RyR in large animals under conditions designed to be as physiological as possible while simultaneously measuring SR and cytoplasmic Ca.
1 ALTERED HCV SPECIFIC T CELL IMMUNITY VERY EARLY IN INTERFERON FREE HCV DAA THERAPY
Authors: L. Barrett, G. Shivasabesan, C. Wang, A. Osinusi, A. Kohli, E.G. Meissner, L. Heytens, A. Nelson, M.A. Polis, H. Masur, W. Symonds, J. McHutchinson, S. Kottilil
Journal: Journal of Hepatology (2013)
Identification and functional characterization of cis-regulatory elements in the apicomplexan parasite Toxoplasma gondii
Authors: Nandita Mullapudi, Sandeep J Joseph, Jessica C Kissinger
Journal: Genome biology (2009)

Toxoplasma gondii is a member of the phylum Apicomplexa, which consists entirely of parasitic organisms that cause several diseases of veterinary and human importance. Fundamental mechanisms of gene regulation in this group of protistan parasites remain largely uncharacterized. Owing to their medical and veterinary importance, genome sequences are available for several apicomplexan parasites. Their genome sequences reveal an apparent paucity of known transcription factors and the absence of canonical cis-regulatory elements. We have approached the question of gene regulation from a sequence perspective by mining the genomic sequence data to identify putative cis-regulatory elements using a de novo approach. We have identified putative cis-regulatory elements present upstream of functionally related groups of genes and subsequently characterized the function of some of these conserved elements using reporter assays in the parasite. We show a sequence-specific role in gene-expression for seven out of eight identified elements. This work demonstrates the power of pure sequence analysis in the absence of expression data or a priori knowledge of regulatory elements in eukaryotic organisms with compact genomes.