tbuckley/cabot-search huggingface dataset:
AB0295 Patient’s satisfaction with the disease status represents fatigue better than DAS28, SDAI and CDAI in RA
Authors: J. Sautner, B. Rintelen, A. Maktari, I. Andel, T. Nothnagl, B.F. Leeb
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Fatigue as such is a cardinal symptom in RA patients. DAS28, SDAI and CDAI are common disease activity measurement tools in Rheumatoid arthritis (RA) patients. However, none of those adresses fatigue. Patient's satisfaction with the course of the disease (PATSAT) to be answered on a numerical scale from 1 representing "excellent" up to 5 representing "unsatisfactory" is a simple way to assess the patient's personal impression of the disease activity. It was of interest to investigate how the above mentioned disease activity assessments are influenced by fatigue. <h3>Methods</h3> 189 outclinic RA patients (74% female, mean age 63,6 years, mean disease duration 112 months) were asked to indicate the amount of fatigue during the last week on an 11 point numerical rating scale (from 0 representing "no fatigue at all" to 10 representing "extreme fatigue"). Patients were clinically assessed and DAS28, SDAI and CDAI were calculated. Furthermore patients were asked to indicate PATSAT. To correlate fatigue and the disease activity parameters Spearman's rho was calculated. <h3>Results</h3> Mean DAS28 amounted to 3.09 (95%CI 2.91 - 3.27), mean SDAI 8.32 (95%CI 7.20 - 9.44) and mean CDAI 7.47 (95%CI 6.42 - 8.52) indicating mild disease activity. Mean PATSAT was 2.6 (95%CI 2.42 - 2.74) indicating good to average satisfaction with the disease activity. Mean fatigue reached 4.11 (95%CI 3.73 – 4.49). Between fatigue and DAS28 and CDAI a moderate correlation (rho 0.421 and 0.457 respectively) could be shown. The correlation between fatigue and SDAI was weak (rho 0.332). The best correlation could be shown between fatigue and PATSAT: rho 0.602 (all p's &lt;0.01). <h3>Conclusions</h3> Correlations between fatigue and DAS28 as well as CDAI are moderate; for the SDAI only weak. The best correlation could be shown for fatigue and PATSAT representing the patient's subjective assessment of disease activity. <h3>Disclosure of Interest</h3> None Declared
Abstract 4107: p38-HSP27 as modulators from survival to apoptosis: Combined treatment with TRAIL and curcumin to prostate cancer cells
Authors: Hyo R. Yoon, Bo K. Sun, Hoan N. Nguyen, So Y. Kim, Seeun Oh, Hye J. Choi, Joo-Hang Kim, Jae J. Song
Journal: Cancer Research (2011)

Abstract The effect of combination of TRAIL and curcumin enhanced apoptotic cell death in many other studies. However, the exact molecular mechanism of enhanced apoptotic cell death by TRAIL plus curcumin was not yet completely understood. In this study, we clearly observed the depression of phosphorylated Akt and increase of phosphorylated p38 during combined treatment with TRAIL and curcumin. Previously, we observed that TRAIL induced the catalytic activation of Akt in TRAIL-sensitive cells and here, the catalytic activation of Akt was reversely decreased by curcumin pretreatment followed by TRAIL. We also found that significant increase of p38 phosphorylation was deeply linked to the decrease of Akt catalytic activity by regulation of the level of phosphorylated HSP27, which leads to the change of interaction between TRAF6 and Src, and subsequent Src-Akt inactivation. For the examination of relationship of p38-HSP27 with Akt activity, in vitro Akt kinase assay, and siRNA technique were used to confirm the biological effect of p38-HSP27 as modulators from survival to apoptosis by combined treatment with TRAIL and curcumin to prostate cancer cells. 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 4107. doi:10.1158/1538-7445.AM2011-4107
Abstract 4744: Sequence-specific p53-DNA binding to gene regulatory elements is altered by single-nucleotide polymorphisms
Authors: Omari Bandele, Xuting Wang, Maher Noureddine, Michelle Campbell, Gary Pittman, Douglas Bell
Journal: Cancer Research (2010)

Abstract Single nucleotide polymorphisms (SNPs) may influence disease susceptibility by modifying cellular responses to environmental stresses. Regulatory SNPs occur in non-coding gene regions and can modify gene expression in an allele-specific manner by altering transcription factor binding. The tumor suppressor p53, a transcription factor, coordinates the expression of an intricate network of genes in response to DNA damage. Importantly, sequence-specific DNA binding is essential for p53 tumor suppressive activity. Unfortunately, lack of robust computational methods and laborious experimental assays have hampered the discovery and characterization of the effects of SNPs in p53 response elements (p53REs). Therefore, we developed a refined bioinformatics approach to identify SNPs in bona fide and putative p53-DNA binding sites. We also developed the microsphere assay for protein-DNA binding (MAPD) to assess the impact of genetic variation on p53-RE binding following cellular exposure to DNA-damaging agents. Thirty-two SNPs (within 12 bona fide and 20 putative p53REs) identified by our bioinformatics approach were evaluated using the MAPD assay. We monitored p53-DNA binding in nuclear extracts from doxorubicin- or IR-treated human lymphoblastoid and U2OS osteosarcoma cells. Significant increases in p53 binding over the negative control were observed for the majority of the p53REs. p53 bound several candidate elements at levels comparable to the positive control (p21 p53RE). Alleles that were predicted to lower p53 binding indeed displayed reduced binding toward 23 of the 32 sequences. Of these alleles, 10 diminished p53 binding by ≥50%. Base substitutions at conserved C and G bases had the greatest impact on p53-DNA binding. In addition, five p53RE SNPs altered gene expression in a set of genotyped lymphoblastoid cell lines. Cellular binding of p53 to putative REs are currently being validated by ChIP-seq. These findings demonstrate that our bioinformatics approach combined with MAPD and gene expression analysis can identify SNPs that alter p53 activity in response to DNA damage and discover novel genes within the p53 transcriptional network. This strategy also can be employed to identify functional SNPs for future studies in human populations. 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 4744.
Subcutaneous Fat Necrosis on Gallium Scan After Abdominal Surgery
Authors: SURJIT S. WADHWA, ROBERT MANSBERG, VIVIAN B. FERNANDES
Journal: Clinical Nuclear Medicine (1998)

Pancreatic trauma and inflammation are common after upper abdominal surgery. Pancreatitis can lead to systemic fat necrosis and has been observed in areas such as the subcutaneous, skeletal, synovial, pericardial, pleural, and osseous tissues. Scintigraphic findings of fat necrosis are not well described. A case of subcutaneous fat necrosis after upper abdominal surgery for lymphoma that demonstrated significant gallium uptake is described.
Imatinib plus Peginterferon Alfa-2a in Chronic Myeloid Leukemia
Authors: Claude Preudhomme, Joëlle Guilhot, Franck Emmanuel Nicolini, Agnès Guerci-Bresler, Françoise Rigal-Huguet, Frederic Maloisel, Valérie Coiteux, Martine Gardembas, Christian Berthou, Anne Vekhoff, Delphine Rea, Eric Jourdan, Christian Allard, Alain Delmer, Philippe Rousselot, Laurence Legros, Marc Berger, Selim Corm, Gabriel Etienne, Catherine Roche-Lestienne, Virginie Eclache, François-Xavier Mahon, François Guilhot
Journal: New England Journal of Medicine (2010)

Imatinib (400 mg daily) is considered the best initial therapy for patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase. However, only a minority of patients treated with imatinib have a complete molecular remission.
Synovial Osteochondromatosis Presenting as a Mass in the Buttock
Authors: Robert Elliott, Bruce Dennien, Anthony Leong, Hans van der Wall
Journal: Clinical Nuclear Medicine (2001)

A 42-year-old woman, who had received a radiologic diagnosis of synovial osteochondromatosis many years before, was examined for a painful right hip and a large immobile mass in the right buttock. Findings of radiologic and scintigraphic imaging were consistent with synovial osteochondromatosis. The patient underwent arthrotomy and excision of the large mass and several smaller masses to control pain and to identify possible malignant change.
Abstract 3884: Targeting ATX and LPA receptors melanoma invasion and metastasis.
Authors: Gabor Tigyi, Yuko Fujiwara, SueChin Lee, Jianxiong Liu, Renukadevi Patil, Renuka Gupte, Duane D. Miller, Tamas Oravecz, Louisa Balazs
Journal: Cancer Research (2013)

Abstract ATX, a lysophospholipase D that generates LPA, is highly up-regulated in metastatic and chemotherapy-resistant carcinomas. Many cancers secrete ATX, and it contributes to their invasive properties. LPA produced by ATX activates LPA1-8 G protein-coupled receptors on the cell surface. Many cancers over-express multiple subtypes of LPAR and the overexpression of LPAR leads to malignant transformation, metastasis, and resistance to therapy. Therefore, ATX-LPA signaling axis is an emerging target for cancer therapy. We have previously shown that knockdown of ATX expression in B16F10 melanoma cells decreased tumor invasion in vitro and metastasis in vivo. In this study, we sought to understand the roles of the LPA GPCRs both in the tumor cells and tissues targeted by metastatic cancer cells. Using the in vivo B16 melanoma metastasis model syngeneic to the C57BL/6 mouse strain, we found that the incidence of lung metastasis was greatly reduced in the LPA5KO mice compared to WT, LPA1KO, and LPA2KO mice, respectively. In addition, we found that the selective inhibitor of LPA1&amp;3, Ki16425 also reduced lung metastasis, suggesting that inhibition of LPA5 and LPA1 receptors in the target tissues may prevent cancer metastasis. B16 melanoma cells predominantly express LPA5 receptor. These cells do not invade across a matrigel layer in response to LPA. We found that siRNA knockdown of LPA5 receptors in B16 melanoma cells relieves this inhibition and resulted in an increase in invasion. These results suggest that the LPAR, in particular LPA5 receptors in tumor and stromal cells may play different roles in invasion and metastasis. Citation Format: Gabor Tigyi, Yuko Fujiwara, SueChin Lee, Jianxiong Liu, Renukadevi Patil, Renuka Gupte, Duane D. Miller, Tamas Oravecz, Louisa Balazs. Targeting ATX and LPA receptors melanoma invasion and metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3884. doi:10.1158/1538-7445.AM2013-3884
SAT0089 The impact of periodontal disease on early inflammatory arthritis persists even after all teeth are lost:
Authors: G. Westhoff, T. Dietrich, G. Schett, P. de Pablo, A. Zink
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Data suggests that individuals with periodontal disease (PD) may be more likely to develop rheumatoid arthritis (RA) and have worse disease activity. PD is a common inflammatory disease characterized by gingival accumulation of inflammatory cells with endothelial cell proliferation and matrix degradation that may worsen joint inflammation. Since PD is a major cause of tooth loss, tooth loss may be a surrogate marker for chronic PD, an inflammatory process that may possibly end when the last tooth is lost. We therefore hypothesized that partial vs. complete tooth loss (edentulism) may be differentially associated with disease activity in persons with early arthritis naive to DMARD-therapy. <h3>Objectives</h3> To determine whether tooth loss and arthritis activity are interrelated by comparing DMARD-naive patients with complete tooth loss to those with partial or no tooth loss with regards to disease activity at arthritis onset. <h3>Methods</h3> The study included 1,009 patients with early arthritis (&lt;6 months) naive to DMARD-treatment, enrolled in a longitudinal study (CAPEA 2010-2013). Data collection included disease activity (DAS28 calculated by TJC28, SJC28, ESR and Patient Global (PG; NRS 0-10)), the 2010 ACR-EULAR RA classification criteria and self-reported number of teeth. Patients were categorized according to number of teeth at study entry (no teeth, 1-19, 21-27, all teeth). Analysis of covariance was done to determine baseline disease activity by number of teeth. <h3>Results</h3> Study participants (65% female) were 55±14 years old and had mean symptom duration of 12±7 weeks. 56% were RF or ACPA pos. and 66% fulfilled the 2010 criteria for RA. No patient had received any DMARDs at baseline. Sample characteristics by tooth loss categories are shown on Table. Significantly more patients with edentulism met ACR/EULAR classification compared with those with complete dentition (OR 1.9, 95% CI 1.01-3.35; adj. for age, sex, BMI, smoking, and DAS28). Edentulous patients had neither lower nor higher disease activity (DAS28) than patients with considerable tooth loss (1-19 teeth). However, compared with those with moderate tooth loss (20-27; P=0.046) or complete dentition (P=0.006), they had significantly worse disease activity. <h3>Conclusions</h3> Tooth loss was associated with disease activity at disease onset in a large cohort of patients with early inflammatory arthritis (IA) naïve to DMARD-therapy. Contrary to the assumption that exposure to PD ends once all affected teeth are lost, edentulism does not improve the interrelation of dental health and IA. The impact of PD on IA starts before IA onset, and obviously persists even after all teeth have been lost. The data also support the notion that there might be a common underlying pathobiology for both conditions. <h3>Disclosure of Interest</h3> None Declared
Abstract 2726: Salivary biomarkers for breast cancer detection
Authors: Lei Zhang, Hua Xiao, Scott Karlan, Hui Zhou, Ziding Feng, David Elashoff, David Akin, Xinmin Yan, David Chia, Jenny Gross, Beth Karlan, David T. Wong
Journal: Cancer Research (2010)

Abstract Objectives: The high burden of breast cancer in women worldwide underscores the unmet potential of biomarker for early detection. New strategies and biomarkers for early detection of breast cancer are sorely needed. In this study, we have conducted a prospective sample collection and retrospective blinded validation (PRoBE design) to evaluate the performance and translational utilities of salivary biomarkers for the non-invasive detection of breast cancer. Methods: The Affymetrix HG U133 Plus 2.0 Array and 2D-DIGE were used to profile transcriptomes and proteomes in saliva supernatant from patients with invasive ductal carinoma and matched controls respectively. The discovered transcriptomic and proteomic candidate biomarkers were subjected to a clinical validation using an independent sample set of 31 breast cancer (invasive ductal carcinoma, stages I and II) and 62 healthy controls. Transcriptomic biomarkers were validated by qPCR and proteomic biomarkers were validated by quantitative immuno-blot. Results: Significant variations of salivary transcriptomic and proteomic profiles were observed between breast cancer patients and healthy controls. Eleven mRNA biomarker candidates and two protein biomarker candidates were selected for independent validation. Eight mRNA biomarkers and one protein biomarker have been validated for breast cancer detection, yielding ROC-plot AUC values between 0.665 and 0.959. Six biomarkers have known associations with breast cancer. Conclusion: Salivary biomarkers possess discriminatory power for the detection of breast cancer, with high specificity and sensitivity. This report provides proof of concept of salivary transcriptomic and proteomic biomarkers for the non-invasive detection of breast cancer. The salivary biomarkers' discriminatory power paves the way for a pivotal clinical validation. Supported by NIH grant U01DE016275, U01DE017790 and R21CA126733 (DTW). 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 2726.
AB1469-HPR Exercise: the new prescription in rheumatoid arthritis (RA) patients:
Authors: J.K. Cooney, J. Thom, J. Moore, Y. Ahmad
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Despite the potential benefits of exercise, 68% of RA patients are considered to be physically inactive in the UK<sup>1</sup>. This extreme physical inactivity plays an important role in terms of patient health and disease progression. It also highlights the need to encourage exercise amongst this population as part of routine care. <h3>Objectives</h3> To determine whether a short term group exercise programme supervised by an exercise physiologist in a clinical setting can improve fatigue, QoL and general well being of RA patients without any worsening of disease activity. <h3>Methods</h3> 10 RA patients (mean±SD age 64.2±5.9 yrs; disease duration 10.7±11.5 yrs) attended a physiotherapy gym for group exercise classes 3 times a week for 8 weeks. Each exercise class lasted one hour and comprised of a warm up, three 10 minute aerobic and resistance exercises. Heart rate and perceived exertion (RPE) were recorded regularly throughout the session to monitor exercise intensity. RA activity, QoL, body composition, fitness and function were assessed at baseline and after the 8 week programme. Fitness was measured using a validated step test that provides an estimation of VO<sub>2max</sub> (maximal oxygen uptake). <h3>Results</h3> Table 1 shows the RA disease, body composition and physical function measures at baseline and post exercise. RA patients had well controlled disease at baseline. Reported disability, and quality of life improved with a significant reduction in fatigue. Pain, global health and disease activity also improved significantly. Body fat, waist and hip circumference significantly improved as did fitness, lower body strength and agility. <h3>Conclusions</h3> This study has shown that in an 8 week supervised exercise programme there were significant improvements in RA patient's fatigue and quality of life. Benefits were also seen in disease activity and pain. There was a significant reduction in body fat percent and improvement of physical fitness and function. An important element of this study was the exercise physiologist who was able to encourage, monitor and motivate the group to their maximum exercise potential. This type of exercise prescription should be encouraged as part of a RA's chronic disease management. However further work is needed regarding the skill and cost benefits of the supervisory input and also how to maintain the healthy lifestyle long term. <h3>References</h3> Sokka T, Hakkinen A, Kautiainen H, et al. (2008). Physical inactivity in patients with rheumatoid arthritis: data from twenty-one countries in a cross-sectional, international study. Arthritis Rheum.59:42–50 <h3>Disclosure of Interest</h3> None Declared
NHS staff launch judicial review against junior contract imposition
Authors: Abi Rimmer
Journal: BMJ (2016)

An NHS staff group has launched a judicial review challenging the government’s decision to impose a new contract on junior doctors in England.

The move comes after the BMA launched its own judicial review to challenge the legality of the contract imposition on equality grounds.1

Just Health, an NHS staff campaign group, served a “letter of action” on health secretary Jeremy Hunt on Monday 4 April that challenged his …
Abstract P6-13-02: Overcoming therapy resistance of metastatic breast cancer by enhanced tumor delivery of polymeric doxorubicin
Authors: H Shen, R Xu, J Mai, Y Huang, M Ferrari
Journal: Cancer Research (2012)

Abstract Metastatic breast cancers are treated with chemotherapy drugs in clinic. However, patients usually develop therapy resistance quickly due to intrinsic and acquired mechanisms. Poor drug delivery to tumor cells may also contribute to therapy resistance. To address both biological and mass transport barriers to effective therapy, we developed a new doxorubicin-based formulation, polymeric doxorubicin (pDox), to be delivered using a porous silicon drug carrier, the multistage vector (MSV). We show the novel, rationally designed MSV/pDox drug enriches in tumor tissues and has considerable therapeutic efficacy in two animal models of triple negative breast cancer lung metastasis, conferring a significant survival advantage to animals treated with MSV/pDox over all other control groups (80% survival for the MSV/pDox group at 24 weeks post treatment vs. 0% survival for all others, log-rank test, p &amp;lt; 0.001). Mechanistically, pDox is released from the MSV as nanoparticles by controlled, sustained kinetics, and enters tumor cells by vesicular transport. The active doxorubicin is released in the acidic environment in lysosomes, exits vesicles in the perinuclear region, and enters the nucleus for drug action. This effective mass transport mechanism kills both the bulk and therapy resistant cells, but avoids cardiac damage. As a result, this new nanodrug has a significantly higher therapeutic window over doxorubicin and Doxil. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-13-02.
Abstract 1123: Transforming growth factor α signaling in pancreatic acinar-to-ductal metaplasia
Authors: Geou-Yarh Liou, Peter Storz
Journal: Cancer Research (2011)

Abstract Pancreatic cancer is the most lethal type of cancer due to its high proliferation, metastasis and resistance to chemotherapy. In pancreatic cancer, pancreatic ductal adenocacinoma (PDAC) is the most common form. Current opinion is that PDAC originates from acinar or centroacinar cells though a process called “acinar-to-ductal metaplasia” (ADM). During ADM, acinar cells undergo a transformation to ductal PanIN (pancreatic intraepithelial neoplasia) cells, which is believed as the first step in PDAC formation. Transforming growth factor α (TGFα) is produced by pancreatic cancer cells and promotes tumor growth. In an ex vivo explant culture system, TGFα transforms murine pancreatic acinar cells into ductal cells. Here we describe a cell signaling pathway that TGFα utilizes to induce acinar-to-ductal transformation. We show that K-ras is downstream of TGFα and is sufficient to drive ADM. We further show the mechanisms that K-ras uses to induce cell structural rearrangement of acinar cells. 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 1123. doi:10.1158/1538-7445.AM2011-1123