tbuckley/cabot-search huggingface dataset:
Abstract 5204: Nodal regulates invasive phenotypes in extravillous and choriocarcinoma trophoblast cells
Authors: Guihua Zhang, Lynne Marie Postovit
Journal: Cancer Research (2010)

Abstract Nodal, an embryonic morphogen and a member of the transforming growth factor-beta (TGF-ß) superfamily, is highly expressed in embryonic development and some cancers such as breast cancer and melanoma. It has been noticed that altered Nodal expression leads to changes in cellular invasiveness both during embryogenesis and cancer metastasis. However, the roles of Nodal in trophoblast invasion and tumor progression remain unclear. The present study characterizes and examines the effects of Nodal on cell migration, invasion and proliferation by using a highly invasive first trimester trophoblast cell line, HTR-8/svneo, and three Chrioncarcinoma cell lines as in vitro models. By knocking down Nodal expression with small hairpin RNA (shRNA) plasmid DNA and morpholino oligomers, stable and transient Nodal knockdown clones were created. RT-PCR and Western Blots were performed and analyzed to verify Nodal knockdown in comparison to the Non-transfected (control) cells. To further confirm successful Nodal knockdown, downstream Nodal signalling (phospho-Smad2) was tested and analyzed by Western Blot. Nodal knockdown cells were then subjected to: (1) growth curves to evaluate the effect of nodal level on cell growth capacity and viability; (2) transwell migration assays to assess the effect of Nodal on cell movement and mobility; (3) transwell invasion assays to investigate the effect of nodal on cell invasive potential. The data show that knockdown of Nodal results in a decrease in cell migration and invasion, but does not significantly alter proliferation in vitro. Furthermore, the addition of human recombinant Nodal results in a restoration of cell migration and invasion. In order to further confirm the involvement of Nodal in trophoblast invasion, and to correlate Nodal levels to trophoblast cell phenotype, we then quantified the amount of Nodal in three chrioncarcinoma cell lines (Jar, Jeg-3 and Bewo) with Western Blot, and checked their migratory and invasive potential by Transwell migration and invasion assays. The data show strong positive correlation between Nodal protein level and the cell migration and invasion capacity. Our data indicate that Nodal does play a significant role in trophoblast cell migration and invasion, the two major processes of tumor progression. By studying the first trimester invasive trophoblast cell line, a greater understanding about the role of Nodal shared by trophoblast invasion and tumor metastasis may be gained. 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 5204.
Abstract 4451: Targeted therapy of lung cancer using ScFvEGFR-Heparin-Cisplatin nanoparticles
Authors: Xianghong Peng, Yiqing Wang, Yuxiang Wang, Donghai Huang, Zuo Georgia Chen, Shuming Nie, Dong M. Shin
Journal: Cancer Research (2011)

Abstract The clinical use of cis-diamminedichloridoplatinum(II) (cisplatin, CDDP) is restricted by severe side effects, including nephrotoxicity, peripheral neuropathy, and ototoxicity. Although the nanoparticles has been used for CDDP delivery in animal models and demonstrated to reduce the side effects and increase the antitumor effects of CDDP, most of studies used none-targeted nanoparticles for CDDP delivery via enhanced permeability and retention (EPR) effect. However, utilizing EPR effect for delivery of CDDP achieves only passive tumor targeting. We have developed novel nanoparticles by conjugating single-chain antibodies to epidermal growth factor receptor (ScFvEGFR) to modified heparin, and loaded CDDP into the targeted nanoparticles (EHDDP). Our results showed that the intracellular Pt was significantly higher in EHDDP treated cells (27.91± 2.45 ng Pt/105 cells) than that of free DDP (2.49± 0.39 ng Pt/105 cells) (P=0.004) and non-targeted nanopartcles HDDP(2.14± 0.20 ng Pt/105 cells) (P=0.003) at 4 hrs, while the internalization of Pt in free CDDP treated cells didn't show any significant difference as compared with that in HDDP (P=0.25). The Pt (166.05±21.17pg Pt/ug DNA) which was intercalated into DNA in EHDDP treated cells increased significantly as compared with that in CDDP(42.34±10.57pg Pt/ug DNA) (P=0.015) and HDDP(20.27±2.88 pg Pt/ug DNA) (P=0.008) treated cells. We found that the CDDP-loaded nanoparticles could significantly change the biodistribution of Pt in mice comparing with the free CDDP. Accumulation of Pt in subcutaneous tumor lesions in EHDDP group (13.45±2.15ng/mg dry tissue) was significant higher than that in HDDP (4.87±0.67ng/mg dry tissue) (P=0.026) and CDDP groups (1.48±0.52ng/mg dry tissue) (P=0.02) 24 hours after the intravenously injection (Pt, 2.5mg/kg) into nude mice bearing H292 tumors. The systemic delivery of EHDDP (2.5 mg/kg; 5 times treatment at 3 days intervals) to mice showed significant enhanced antitumor activity with no body weight loss or damages to kidney, liver, and spleen, while the mice that received free CDDP had significant weight loss and massive organ damages. Our results suggest that EHDDP nanoparticles have the potential to be used for targeted therapy of cancer which expresses EGFR with reduced side effects. (Supported by P50CA128613). 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 4451. doi:10.1158/1538-7445.AM2011-4451
Acute Spinal Injury
Authors: Bennie W. Chiles, Paul R. Cooper
Journal: New England Journal of Medicine (1996)

The goal of management of injury of the spinal cord or cauda equina is, if possible, to reduce the resultant neurologic deficit and prevent any additional loss of neurologic function. In a patient with a suspected bony injury of the spine, the spine must be immobilized to prevent neural injury, and the anatomy of the injury must be analyzed as a first step in providing effective treatment.Resuscitation and Initial EvaluationThe specific steps in resuscitation and initial evaluation may be carried out either at the scene of the trauma or in the emergency room, depending on the urgency of . . .
Former NSABP Chief Grilled at Congressional Hearing
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Former NSABP Chief Grilled at Congressional Hearing Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 13, 6 July 1994, Pages 963–964, https://doi.org/10.1093/jnci/86.13.963 Published: 06 July 1994
Abstract 5290: Motility of B16 mouse melanoma cells is driven by phospho-MARCKS
Authors: Susan A. Rotenberg, Xiangyu Chen
Journal: Cancer Research (2010)

Abstract Phosphorylation of Myristoylated Alanine-rich C-Kinase Substrate (MARCKS) by protein kinase Cα (PKCα) is known to trigger its release from the plasma membrane/cytoskeleton into the cytoplasm, thereby promoting actin reorganization during migration. This study shows that cytoplasmic phosphoMARCKS directly promotes motile behavior of melanoma cells. Aggressively motile B16 F10 mouse melanoma cells express high levels of phosphoMARCKS, whereas weakly motile F1 cells express negligible levels. When treated with okadaic acid (OA) (a protein phosphatase inhibitor), F1 cells exhibit a dramatic increase in phosphoMARCKS coincident with a 5-fold increase in motility. This motility is lost if OA-treated cells are also treated with a shRNA reagent targeted to MARCKS. Pre-treatment of cells with calphostin C (a PKC inhibitor) prevents OA-mediated elevation of phosphoMARCKS. These findings imply that PKC is highly active in F1 cells but that its phosphorylation of MARCKS is efficiently reversed by protein phosphatases. The mechanistic significance of phosphoMARCKS to motility is established with a pseudo-phosphorylated mutant of GFP-MARCKS in which Asp residues replaced Ser residues known to be phosphorylated by PKCα. This mutant localizes to the cytoplasm and engenders three-fold higher motility in F1 cells. However, when the mutant is fused to a nuclear localization signal, motility is substantially decreased. Expression of an unmyristoylated, phosphorylation-resistant MARCKS mutant that localizes to the cytoplasm, blocks motility by 40-50% of both OA-stimulated F1 cells and intrinsically motile F10 cells. These findings demonstrate the importance of phosphoMARCKS to the metastatic potential of melanoma cells, and reveal a previously undocumented cytoplasmic role for this phospho-protein. 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 5290.
Cord Blood Methylmercury and Fetal Growth Outcomes in Baltimore Newborns: Potential Confounding and Effect Modification by Omega-3 Fatty Acids, Selenium, and Sex
Authors: Ellen M. Wells, Julie B. Herbstman, Yu Hong Lin, Jeffery Jarrett, Carl P. Verdon, Cynthia Ward, Kathleen L. Caldwell, Joseph R. Hibbeln, Frank R. Witter, Rolf U. Halden, Lynn R. Goldman
Journal: Environmental Health Perspectives (2015)

Methylmercury (MeHg) may affect fetal growth; however, prior research often lacked assessment of mercury speciation, confounders, and interactions.Our objective was to assess the relationship between MeHg and fetal growth as well as the potential for confounding or interaction of this relationship from speciated mercury, fatty acids, selenium, and sex.This cross-sectional study includes 271 singletons born in Baltimore, Maryland, 2004-2005. Umbilical cord blood was analyzed for speciated mercury, serum omega-3 highly unsaturated fatty acids (n-3 HUFAs), and selenium. Multivariable linear regression models controlled for gestational age, birth weight, maternal age, parity, prepregnancy body mass index, smoking, hypertension, diabetes, selenium, n-3 HUFAs, and inorganic mercury (IHg).Geometric mean cord blood MeHg was 0.94 μg/L (95% CI: 0.84, 1.07). In adjusted models for ponderal index, βln(MeHg) = -0.045 (g/cm(3)) × 100 (95% CI: -0.084, -0.005). There was no evidence of a MeHg × sex interaction with ponderal index. Contrastingly, there was evidence of a MeHg × n-3 HUFAs interaction with birth length [among low n-3 HUFAs, βln(MeHg) = 0.40 cm, 95% CI: -0.02, 0.81; among high n-3 HUFAs, βln(MeHg) = -0.15, 95% CI: -0.54, 0.25; p-interaction = 0.048] and head circumference [among low n-3 HUFAs, βln(MeHg) = 0.01 cm, 95% CI: -0.27, 0.29; among high n-3 HUFAs, βln(MeHg) = -0.37, 95% CI: -0.63, -0.10; p-interaction = 0.042]. The association of MeHg with birth weight and ponderal index was affected by n-3 HUFAs, selenium, and IHg. For birth weight, βln(MeHg) without these variables was -16.8 g (95% CI: -75.0, 41.3) versus -29.7 (95% CI: -93.9, 34.6) with all covariates. Corresponding values for ponderal index were -0.030 (g/cm(3)) × 100 (95% CI: -0.065, 0.005) and -0.045 (95% CI: -0.084, -0005).We observed an association of increased MeHg with decreased ponderal index. There is evidence for interaction between MeHg and n-3 HUFAs; infants with higher MeHg and n-3 HUFAs had lower birth length and head circumference. These results should be verified with additional studies.
A8.09 Trained immunity in monocytes from rheumatoid arthritis patients and healthy individuals
Authors: TC Messemaker, HMM Mikkers, TW Huizinga, REM Toes, AHM van der Helm- van Mil, F Kurreeman
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objective</h3> Rheumatoid Arthritis (RA) is a heterogeneous disease affecting approximately 1–2% of the European population. Development of RA is affected by both genetic and environmental triggers. In the present study we hypothesised that these environmental triggers might induce changes in the epigenome of immune cells. A concept that describes such a mechanism is known as ‘trained immunity’, which shows that isolated monocytes previously exposed to micro-organisms display elevated H3K4me3 on the promotor regions of immune genes resulting in enhanced RNA- and protein levels of TNFa and IL6 upon re-stimulation with inflammatory triggers. The phenomenon that innate cells triggered by past insults more readily react to new non-specific stimuli could contribute to the onset of auto-immunity. We wished to test whether the innate immune system of RA patients displays signs of “trained immunity” by analysing immune responsiveness and epigenetic changes of CD14<sup>+</sup> monocytes isolated from both untreated RA patients and age-matched healthy controls. <h3>Methods</h3> CD14<sup>+</sup> monocytes were isolated from both untreated RA patients and age-matched healthy controls. Secreted TNFa and IL6 levels were measured using ELISA in the supernatant of naïve and LPS-stimulated monocytes from both RA patients and non-RA controls. RNA levels of TNFa and IL6 in naïve and LPS-stimulated monocytes from both groups were examined using RT-qPCR. <h3>Results</h3> Both RNA and protein levels of TNFa and IL6 were low in unstimulated monocytes isolated from RA patients and healthy controls but no large differences were observed. After LPS-stimulation, the relative RNA levels (expressed in fold change relative to household gene) increased but were similar between patients and controls for TNFa (RA: 1.7 ± 0,4, non-RA: 1.8 ± 0.9) and IL6 (RA: 2.9 ± 1,3, non-RA: 3.3 ± 2.6). Concordantly, no large differences were detected for secreted cytokine levels, although secreted TNFa (RA: 4.3ng/ml ±&nbsp;2.9, non-RA: 2.8ng/ml ±&nbsp;2.6) and IL6 (RA: 67.2mg/ml ±&nbsp;14.6, non-RA: 50.8mg/ml ±&nbsp;17.3) levels seem slightly elevated in RA monocytes. <h3>Conclusions</h3> In general, we could not detect large differences on RNA level or protein level of TNFa and IL6 between RA and non-RA patients. Therefore, we did not find evidence that the concept of trained immunity may contribute to the development of RA.
Abstract 5298: Two distinctive single nucleotide polymorphisms determine liver metastases responses to docetaxel plus thiotepa for metastatic breast cancer patients.
Authors: Jing Yu, Ningning Dong, Ying Yan, Bin Shao, Lijun Di, Guohong Song, Li Che, Jun Jia, Hanfang Jiang, Xu Liang, Yulin Zhu, Chaoying Wang, Jie Zahng, Budong Zhu, Xinna Zhou, Xiaoli Wang, Huabing Yang, Jun Ren, Herbert Kim Lyerly
Journal: Cancer Research (2013)

Abstract The successful predictively treatment of metastatic breast cancer (MBC) remains a major challenge. Until now there is no definite marker to distinguish responder from non-responder and more and more important, metastasis occurred within different organs lead to serious variations of overall survival. In this study, paclitaxel and anthracyclines pretreated153 patients with MBC received 606 cycles of docetaxel plus thiotepa. 65 of 153 patients were concurrently diagnosed as MBC involved liver metastasis (LM). Among 153 patients, the response were 1 complete response (CR) (0.7%), 25 partial responses (PR) (16.3%), 73 stable diseases (SD) (47.7%), 46 progressive diseases (PD) (30.1%) and 8 unevaluable(5.2%). For LM patients, the localized liver response were 2 CR (3.1%), 20 PR (30.8%), 16 SD (24.6%), 22 PD (33.8%),5 unevaluable (7.7%). Median PFS and OS for both entire and LM subgroup were 6.5 (95% CI, 5.6 to 7.4) versus 4.2 (95%CI, 2.3-6.1), and 20.0 (95% CI, 15.6 to 24.4) versus 14.2 (95%CI, 9.5-18.9) months respectively. 79 SNPs in CYP450, whose minor allele frequency were ≥ 10% were genotyped. There was no significant difference of SNPs in therapeutic responses, PFS or OS. Of importance, there were two distinctive SNPs, rs2277119 and rs4646487 *2/*3 alleles, which tended to have the better liver metastases response than *1 when choosing a false discovery rate as 12%. It seemed that docetaxel plus thiotepa might be regarded as an active specific regimen for MBC with liver metastasis. The generation of conceptually specific chemotherapy targeting the organ with cancer metastasis should be considered in the future. Citation Format: Jing Yu, Ningning Dong, Ying Yan, Bin Shao, Lijun Di, Guohong Song, Li Che, Jun Jia, Hanfang Jiang, Xu Liang, Yulin Zhu, Chaoying Wang, Jie Zahng, Budong Zhu, Xinna Zhou, Xiaoli Wang, Huabing Yang, Jun Ren, Herbert Kim Lyerly. Two distinctive single nucleotide polymorphisms determine liver metastases responses to docetaxel plus thiotepa for metastatic breast cancer patients. [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 5298. doi:10.1158/1538-7445.AM2013-5298 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
CHRONIC JUNCTIONAL BRADYCARDIA IS A POTENTIAL RISK FACTOR OF THROMBOEMBOLIC EVENTS
Authors: Gwang Sil Kim, Jae-Sun Uhm, Tae-Hoon Kim, Hancheol Lee, Boyoung Joung, Hui-Nam Pak, Moon-Hyoung Lee
Journal: Journal of the American College of Cardiology (2015)
AB0761 TNF inhibitors for the treatment of ANCA associated vasculitis: A systematic review
Authors: L. Silva, R. Blanco, V. Martínez-Taboada, E. Loza, J.M. Pego, I. Rúa-Figueroa, S. Muñoz-Fernández
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cyclophosphamide (CYC) and corticosteroids (CS) are widely used in the treatment of ANCA-associated vasculitis (AAV). However, not all patients achieve remission and these drugs are associated with important adverse events. New treatments like TNF inhibitors have been proposed. <h3>Objectives</h3> To systematically review the efficacy and safety of anti-TNF drugs in AAV. <h3>Methods</h3> We systematically searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials up to October 2011 using a comprehensive search strategy for anti-TNF drugs, AAV, efficacy and safety (mesh terms and text words). Selection criteria were predefined by protocol. We selected meta-analysis, systematic literature reviews, clinical trials (CT), cohort studies and case series with &gt;3 cases, that included &gt;18 year-old patients with AAV on anti-TNF drugs. Studies including patients with Behçet disease, cryoglobulinemia, large vessel and secondary vasculitis, and basic science studies were excluded. Title and abstract selection and subsequent detailed review of selected articles were independently performed by two reviewers. The included studies quality was graded using the Oxford Levels of Evidence Scale, and results expressed as level of evidence (LE), recommendation grade (RG). <h3>Results</h3> The search strategy identified 2,762 potentially relevant articles, of which 80 were selected for full paper review and eventually 12 were selected for the analysis. The selection included 2 randomized CT, 3 open trials, 1 case-control study, 1 cohort study and 4 case series, which analyzed 328 patients. Studies main characteristics and results are shown in the table. <h3>Conclusions</h3> Infliximab is not more effective than CYC regarding remission induction in AVV patients (LE 1b; GR A), although is effective as steroid-sparing agent (LE 1b; GR A). Etanercept is not effective to maintain remission in patients with Wegener's granulomatosis (LE 1b; GR A) and serious adverse events have been reported especially solid cancers. The addition of adalimumab to CS and CYC in severe AAV patients is associated with response rates and adverse events similar to CS and CYC but reduced CS exposure (LE 2b; GR B). <h3>Disclosure of Interest</h3> None Declared
INCIDENCE AND PROGNOSTIC SIGNIFICANCE OF NEW ONSET ATRIAL FIBRILLATION/FLUTTER IN PATIENTS WITH A FIRST EPISODE OF ACUTE PERICARDITIS: A PROSPECTIVE COHORT STUDY
Authors: Massimo Imazio, George Lazaros, Elisa Picardi, Dimitris Tousoulis, Riccardo Belli
Journal: Journal of the American College of Cardiology (2015)
A5.14 Serum CXCL13 is a non-invasive synovitis marker holding non-redundant information compared with acute phase reactants and autoantibodies in patients with rheumatoid arthritis
Authors: S Bugatti, B Vitolo, F Benaglio, C Montecucco, R Caporali, A Manzo
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Newly identified B-cell related markers beyond autoantibodies may help better stratifying and predicting the heterogeneous outcome of rheumatoid arthritis (RA). The aim of this study was to investigate whether serum levels of the B-cell chemoattractant CXCL13 can implement information provided by traditional laboratory markers in patient with early RA. <h3>Materials and methods</h3> The pathological correlates of CXCL13, acute phase reactants and autoantibodies were determined in 60 RA patients with paired serum and synovial tissue samples. Baseline associations, responsiveness to change and predictive validity for response to therapy were assessed in a prospective cohort of 213 early RA patients undergoing treatment with methotrexate aiming at low disease activity (LDA). <h3>Results</h3> In paired serum and synovial samples, CXCL13 covaried with tissue levels of the chemokine (rho 0.56, p = 0.01) and was the only laboratory marker able to discriminate high degrees of B-cell infiltration (AUROC [95% CI] 0.74 [0.61 to 0.85]). Serum CXCL13 showed lower correlation with disease activity and lower responsiveness to change after 2 months of therapy compared with acute phase reactants. Levels were increased in anti-citrullinated protein antibody-positive (ACPA) subjects, approximatively half of whom had high CXCL13 (3<sup>rd</sup> tertile, &gt;106 pg/ml), and correlated with rheumatoid factor (RF) titres. High CXCL13 alone independently predicted failure to achieve LDA after 12 months of therapy with an adjusted OR (95% CI) of 2.87 (1.42 to 5.82) (p = 0.003), a high negative predictive value (NPV) (79.9%, 95% CI 72.1% to 86.3%) but a quite low positive predictive value (PPV) (50.7%, 95% CI 38.4% to 63%). Combining high CXCL13 with autoantibody positivity (ACPA and/or RF) significantly increased the PPV (61%, 95% CI 44.5% to 75.8%) without affecting the NPV (77.2%, 95% CI 69.9% to 83.4%). <h3>Conclusions</h3> In early RA patients treated with conventional synthetic disease-modifying anti-rheumatic drugs,<b> s</b>erum CXCL13 appears a novel lymphoid-linked biomarker holding non-redundant information with respect to acute phase reactants and autoantibodies, and able to stratify patients into different prognostic subgroups.