tbuckley/cabot-search huggingface dataset:
Reversing Cardiac Hypertrophy in Hypertension
Authors: Marc A. Pfeffer, Janice M. Pfeffer
Journal: New England Journal of Medicine (1990)

The heart has an inherent capacity to adjust its mass and shape in response to a sustained alteration in workload. Under conditions of heightened demand, myocytes add contractile units (to increase their diameter, length, or both) in a pattern that generally offsets the augmentation of ventricular wall stress (a force per unit area, defined in general terms as the ratio of the product of pressure and radius to wall thickness) that is consequent to an abnormal hemodynamic load. In this respect, the hypertrophic response can be viewed as adaptive, since the remodeled ventricular chamber is capable of maintaining workloads in . . .
P1136 TRIPLE THERAPY WITH BOCEPREVIR PLUS PEGINTERFERON ALFA-2a/RIBAVIRIN IN A REAL-LIFE SETTING: IS IT POSSIBLE TO ACHIEVE SVR RATES COMPARABLE TO PIVOTAL TRIALS?
Authors: P. Buggisch, A. Schober, H.R. Bruch, C. Antoni, H. Loehr, A. Herrmann, H. Steffens, G. Moog, J. Haessner, H.-G. Hoerster, C. John, H.-J. Schlueter, R. Link, R. Heyne, U. Spengler, U. Alshuth, D. Hueppe
Journal: Journal of Hepatology (2014)
THE EFFECTS OF FATIGUE ON PEAK TORQUE, MUSCLE STIFFNESS, AND MUSCULOARTICULAR STIFFNESS OF THE KNEE JOINT IN YOUNG MALE ATHLETES
Authors: D Wang, G De Vito, M Ditroilo, D Fong, E Delahunt
Journal: British Journal of Sports Medicine (2014)

Background Appropriate levels of muscle strength, muscle stiffness (MS) and musculoarticular stiffness (MAS) are important factors linked to athletic performance. Alterations in knee joint mechanical behavior induced by neuromuscular fatigue may have implications for injury susceptibility. Objective To investigate the acute effects of fatigue on peak torque of the knee joint extensor musculature, MS of the vastus lateralis and MAS of the knee joint in young male athletes. Design Experimental study. Setting University biomechanics laboratory. Participants 27 male recreational athletes. Interventions A 15-minute cycle ergometer fatiguing protocol. Main outcome measurements Peak torque of the knee joint extensor musculature was assessed on a leg-extension dynamometer, whilst MS of the vastus lateralis was measured using a myometer (Müomeetria AS, Tallinn, Estonia) in both relaxed and contracted conditions. MAS was evaluated by the free oscillation technique on a leg-extension dynamometer. These measures were performed before and after the fatiguing intervention. Results A significant decrease in peak torque was observed from pre-fatigue (208.2±47.1 Nm) to post-fatigue (189.3±52.5 Nm) (P&lt;.01). Absolute MS was significantly increased from pre-fatigue (362.7±49.4 Nm −1 – relaxed ; 493.6±71.2 Nm −1 – contracted ) to post-fatigue (454.3±82.8 Nm −1 – relaxed ; 551.3±89.7 Nm −1 – contracted ) (P&lt;.01). Normalized MS ( MS/load supported ) was significantly increased from pre-fatigue (26.4±6.9 Nm −1 ·kg −1 ) to post-fatigue (230.8±6.5 Nm −1 ·kg −1 ) (P&lt;.01). MAS was decreased significantly from pre-fatigue (1518.8±502.6 Nm −1 ) to post-fatigue (1421.6±445.7 Nm −1 ) (P&lt;.05). However, for normalized MAS ( MAS/load supported ) no significant difference was observed (P=.06). Conclusions It is hypothesized that the observed increase in MS may be a compensatory mechanism to offset the fatigue induced decrease in peak torque and MAS, with the aim of preserving knee joint stability.
AI-05 * IMPACT OF GBM MICROENVIRONMENT ON EXPRESSION PROFILE OF BONE MARROW DERIVED PROGENITOR CELLS
Authors: K. Burrell, S. Singh, S. Agnihotri, R. Hill, K. Aldape, G. Zadeh
Journal: Neuro-Oncology (2014)

We have recently shown that bone marrow derived cells (BMDC) provide a distinct tumor region dependent contribution to glioblastoma multiforme (GBM) neovascularization. The influence of GBM microenvironment on differentiation and modulation of expression factors by BMDC however remains unknown. In this study we establish the differential expression profile of BMDC as a consequence of recruitment and interaction with the GBM microenvironment and in response to radiation (RTx) and anti-angiogenic therapy (AATx). Chimeric mice with reconstituted green-fluorescent bone marrow were used to create intracranial GBM xenografts, by implanting red fluorescent glioma stem cells or U87 into the frontal lobes. Subsequently, BMDC recruited to the GBM were isolated from the GBM cells using FACS during GBM growth, and following treatment (RTx and AATx). RNA was extracted from both FACS-purified BMDC and GBM cells, and mRNA and miRNA array analyses were performed. We compared the expression profiles to systemic BMDC derived from control donor mice. BMDCs were found to exhibit significant plasticity and altered their expression profiles based on stage of GBM growth and in response to therapy. TGFb was significantly upregulated in BMDCs following recruitment to GBMs, with a compensatory increase in expression of IL6,4,8 by GBM cells. BMDC up-regulate cytokines, IFNG, CXCL and TNF pathways, and transcriptional regulators, SMAD2, all of which are able to influence the tumor microenvironment. BMDCs also prove to express angiogenic factors and angioMIRs, with a distinct differential expression pattern based on stage of GBM growth and in response to therapy. We demonstrate that a significant cross-talk exists between BMDC in the tumor microenvironment and GBM cells. There is a distinct angiogenic and invasive profile of BMDC once recruited to the GBM. Furthermore, recruited BMDC provide a source of angiogenic factors, that are differentially expressed based on the stage of GBM growth and in response to therapy.
A Controlled Trial of Immunotherapy for Asthma in Allergic Children
Authors: N. Franklin Adkinson, Peyton A. Eggleston, Donald Eney, Eugene O. Goldstein, Kenneth C. Schuberth, John R. Bacon, Robert G. Hamilton, Michael E. Weiss, Hasan Arshad, Curtis L. Meinert, James Tonascia, Barbara Wheeler
Journal: New England Journal of Medicine (1997)

Injections of allergens are widely prescribed for patients with asthma, but little is known about the effectiveness of immunotherapy.
HG-07 * DETECTION OF K27M MUTANT PEDIATRIC GLIOBLASTOMAS BY IMMUNOHISTOCHEMISTRY
Authors: S. Venneti, M. Santi, M. M. Felicella, D. Yarilin, J. Phillips, L. Sullivan, D. Martinez, A. Perry, P. Lewis, C. Thompson, A. Judkins
Journal: Neuro-Oncology (2015)

Pediatric glioblastomas (GBM) are lethal and fatal tumors and ∼30% of GBM and ∼80% of diffuse intrinsic pontine gliomas show K27M mutations in the H3F3A gene, a variant encoding histone H3.3. These mutations lead to global reduction in H3K27me3. Our goal was to develop biomarkers for the histopathologic detection of these tumors. Therefore, we evaluated the utility of measuring H3K27me3 global reduction as a biomarker and tested an antibody directed specifically against the K27M mutation in 290 samples of 203 pediatric (including 38 pediatric high-grade astrocytomas), 38 adult brain tumors of various subtypes and grades and 49 non-neoplastic reactive brain tissues. Detection of K27M by immunohistochemistry showed 100% sensitivity and specificity and was superior to reduction in H3K27me3 as a biomarker. Moreover, cases that stained positive for K27M showed a significantly poor prognosis compared to corresponding negative tumors. These results suggest that immunohistochemical detection of K27M is a sensitive and specific surrogate for K27M mutations and a prognostic marker.
P04.19 * METABOLIC IMPACT OF ANTI-ANGIOGENIC AGENTS ON GLIOMA CELLS
Authors: T. Mesti, P. Savarin, M. N. Triba, J. Ocvirk, C. Banissi, A. F. Carpentier
Journal: Neuro-Oncology (2014)

BACKGROUND: The direct impact on glioma cells metabolism of drugs targeting the VEGF pathway, such as Bevacizumab (Bev) or VEGFR Tyrosine Kinase Inhibitor (TKI), is poorly known. Glioma cells not only secrete high levels of vascular endothelial growth factor (VEGF)but also express VEGF receptors (VEGFR), supporting the existence of an autocrine loop. MATERIAL AND METHODS: U87 cells were treated with Bev or SU1498, a selective VEGFR2 TKI. VEGFR expression was checked with FACS flow cytometry and Quantitative Real-Time PCR.VEGF secretion into the medium was assessed with an ELISA kit. Metabolomic studies on cells were performed using High Resolution Magic Angle Spinning Spectroscopy (HR-MAS). RESULTS: U87 cells secreted VEGF and expressed low level of VEGFR2, but no detectable VEGFR1. Exposure to SU1498, but not Bev, significantly impacted cell proliferation and apoptosis. Metabolomic studies with HR MAS showed that Bev had no significant effect on cell metabolism, while SU1498 induced a marked increase in lipids and a decrease in glycerophosphocholine. Accordingly, accumulation of lipid droplets was seen in the cytoplasm of SU1498-treated U87 cells. CONCLUSION: In patients treated with VEGFR TKI, monitoring lipids with magnetic resonance spectroscopic (MRS) might be a valuable marker to assess drug cytotoxicity. Although both drugs target the VEGF pathway, only SU1498 showed a clear impact on cell proliferation, cell morphology and metabolism. Bevacizumab is thus less likely to modify glioma cells phenotype due to a direct therapeutic pressure on the VEGF autocrine loop.
Abstract 474: Tumor CD57+ immune cell infiltration is a strong independent prognostic factor in stage II-III colorectal cancer
Authors: Valerie Boige, Clara Locher, Magali Svreck, Anne Auperin, Nathalie Chaput
Journal: Cancer Research (2011)

Abstract Background: CD3+ CD45RO+ tumor infiltrating lymphocytes (TIL) density within colorectal cancer (CRC) has been shown to be a better predictor of outcome than UICC TNM. Conversely, Laghi and coll. showed that CD3+ TIL density was not a prognostic factor in stage III CRC. The aim of our study was to evaluate the prognostic role of immune infiltrating tumor cells in stage II and III CRC patients using a tissue microarray (TMA) analysis. Methods: A tissu-array was constructed using 202 stage II and III resected CRC (154 CC, 48 rectal cancers) and their matched non tumor tissue (NT). Tumors exhibiting deficient mismatch repair phenotype have been excluded. On the basis of previous data on the prognostic role of immune response in CRC, the following stainings were quantified in tumor (TT) and NT: CD3, CD68, CD57, CD8 and CD4 in order to quantify macrophage, lymphocyte cell infiltration as effectors of IFN-γ production, CXCL9/MIG, PPAR γ, CXCL10/IP-10, INDO, CXCL13/BCA-1. For prognostic analysis, immunohistochemistry (IHC) data was dichotomized at the median value. Results: All proteins (except CXCL10/IP-10, INDO for which no reliable IHC data could be obtained) were significantly underexpressed in TT as compared to NT (p&amp;lt;0.0001, paired t-test). CD57 expression was significantly correlated with both CD3 and CD8 expression in TT (Spearman rank correlation coefficients equal to 0.41 (p&amp;lt;0.001) and 0.22 (p=0.002) respectively). After the exclusion of patients who received preoperative irradiation for rectal cancer (n=38), and after adjustment for tumor stage, adjuvant chemotherapy and tumor site in Cox models, CD3 and CD57 tumor staining were associated to recurrence-free survival (RFS) (HR=0.48 and 0.33 and p-value=0.02 and 0.003 respectively) whereas none of the NT staining was found to be prognostic. When CD3 and CD57 tumor staining were included together in the Cox model, only CD57 remained significantly associated with RFS (HR=0.37, p=0.015), especially in stage III CRC but without statistically significant interaction between stage and CD57. Conclusion: Tumor CD57+ immune cell infiltration is associated with prolonged recurrence-free survival in stage II and III colorectal 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 474. doi:10.1158/1538-7445.AM2011-474
A2.41 Modulator role of inducible costimulator (ICOS) in spondyloarthritis animal model
Authors: LM Araujo, Q Jouhault, B Cherqaoui, I Fert, G Chiocchia, M Breban
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and aim</h3> HLA-B27/human β2m transgenic rats (B27-rats), a model of spondylarthritis (SpA) develop spontaneous colitis and arthritis. Recently, we demonstrated that altered DCs function could be critical for triggering SpA since DCs from B27 rats promote a biassed expansion of pro-inflammatory Th17 cells, which might have a pathogenic role. Furthermore, the altered interaction of DC/T cell induces a modification of regulatory T cells function, resulting in decreased IL-10 and enhanced IL-17 production by those cells. Interestingly, <i><i>in vitro</i></i> blockade of ICOS-ICOSL interaction demonstrated that ICOS signalling plays a key role in generation and maintenance of IL-10/IL-17 imbalance production by regulatory T cells, and biassed-Th17 cells expansion. Thus, we hypothesised that <i><i>in vivo</i></i> modulation of ICOS-ICOSL pathway may have therapeutic utility in this model. To investigate this hypothesis we used <b>a genetic approach </b>producing<b> B27. ICOS </b>(B27. ICOS-KO) <b>knockout rats.</b> <h3>Material and methods</h3> Using TALEN technology for disrupt the ICOS locus, Dr Anegon and colleagues produced the ICOS. Kcnockout rats that were backcrossed onto the B27 transgenic background. B27 and B27. ICOS-KO rats were weekly weighted, examined and scored for clinical symptoms, including colitis (intensity of diarrhoea), arthritis (severity of swelling), alopecia, orchitis and nail dystrophy <h3>Results</h3> As expected, chronic diarrhoea was the most common and persistent finding, being present in all B27 rats. Arthritis and alopecia developed only in some B27 rats. The clinical disease score progressively worsened in B27 rats. In contrast, the B27. ICOS-KO rats did not develop any symptom of disease until age of 16 weeks. Attenuated symptoms were observed in B27. ICOS-KO animals until 24 weeks compared to B27 rats. <h3>Conclusions</h3> Our preliminary clinical results suggest a protective role of <i>Icos</i> deletion in onset and severity of the disease in B27 rats.
Comparison of Synchrotron Images of DCIS of the Breast with Their Pathologic Findings.
Authors: S. Park, J. Bong, J. Hong, H. Wang, H. Kim, J. Kim, H. Oh, S. Jheon, J. Huang
Journal: Cancer Research (2009)

Abstract Background: Synchrotron radiation x-ray imaging have opened a new door to explore breast tissue below the micron scale providing detailed internal structures of the samples with a great magnification and an excellent resolution. Using phase contrast technique, we got monochromated synchrotron images of DCIS (Ductal Carcinoma In Situ) of the breast tissue section. To figure out relation with their optical microscopic features, we compared the synchrotron images of the DCIS with their histopathologic findings of the same stained section.Material and Methods: A x-ray microscope was installed on 1B2 beamline of Pohang Light Source, a third generation synchrotron radiation facility with operating energy of 2.5 GeV in Pohang, Korea. The x-ray energy was set at 11.1 keV, and the x-ray beam was monochromatized by a W/B4C monochromator. Zernike phase-shifter was adapted for phase contrast x-ray microscopy. Formalin-fixed 5µm-thick breast tissue sample was attached onto the Kapton film, and positioned 25 m away from the beam source. The synchrotron image of sample was converted into a visual image on the CsI(TI) scintillation crystal, and this visual image was captured by a full frame CCD camera. After scanning, we patched these images one and another to show the large area of the tissue section. For the comparative analysis with their synchrotron image, synchrotron-scanned breast tissue sections were stained, and the histopathologic findings of the samples were captured by image analyzer. The magnifying power of this microscope was 100x.Results: The monochromated x-ray microscopic images of DCIS of the breast tissue were obtained with a good resolution. These images revealed various structures of DCIS lesion with a good contrast and high visibility by phase contrast technique. They include prominent and intact periductal basement membrane - a hallmark of DCIS lesion, and stippled fine microcalcifications which were indistinct in the histologic section, and a shadow of intense peritumoral inflammatory cell infiltration. But the minute changes of each cancer cell showing the features of cancer tissue such as, cellular differentiation and nuclear grade, were not identified well.Discussion: The x-ray microscopic imaging of DCIS of the breast tissue section with synchrotron radiation showed a good correspondence with the histopathologic findings of their stained tissue sections. And the synchrotron image of DCIS had some unique radiologic features differentiating from histopathogic findings. Therefore the synchrotron images of the DCIS lesion appear to have a new possibility of use for the clinical and research purposes in near future. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5015.
Abstract P1-01-14: Intraoperative Injection of Technetium-99m- Dextran 500 for the Identification of Sentinel Lymph Nodes in Breast Cancer
Authors: MS Graudenz, GJ Delazeri, NL Xavier, CH Menke, BL. Spiro
Journal: Cancer Research (2010)

Abstract Background: The intraoperative injection of radiocolloid before a sentinel node biopsy (SLN) in breast cancer has been recently described.The advantages of this approach would be precluding the performance of a scintigram, cost reduction and elimination of pain and anxiety related to the preoperative procedure. Objectives: To evaluate the efficacy of intraoperative injection of Dextran 500-99m-Tc and to analyze whether different radiocolloid doses, breast volume and Body Mass Index (BMI) influence the migration time to the axilla. Material and Methods: This is a prospective study of 74 SLN biopsies of breast cancer patients, stages T1N0 and T2N0. After anesthesia induction, patients underwent subareolar dermal injection of 0.5 to 1.5 mCi (18 to 55 MBq) of filtered Dextran 500-99m-Tc (0.22µl) in a volume of 5 ml along with 2 ml of blue dye. Results: The probe identification rate was 98% (73/74 cases) and the medium radiocolloid dose used was 0.97 mCi ± 0.22. The radiocolloid migration time to the axila was 10 min and 43 s (± 5:43 s). An average of 1.66 lymphnodes were identified through the use of radiocolloid and 1.53 through the use of bue dye. Different radiocolloid doses did not modify migration time to SLN (p=0.73). However, larger breast volumes were associated with longer migration time to the axilla (Pearson Correlation 0.393 p&amp;lt; 0.01). The same correlation was observed with BMI (Pearson Correlation 0.469 p&amp;lt; 0.01). Discussion: The intraoperative injection of Dextran 500-99m-Tc is efficient in the identification of SLN in breast patients. Higher BMI and larger breasts determine longer migration time, however injection of larger doses of radiocolloid do not reduce transit time to the axilla. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-14.
Abstract 189: 5-azacytidine radiosensitizes androgen-independent prostate cancer cells by impairing DNA double-strand break repair
Authors: Eric Weterings, Pamela M. Dino, Yi Feng, Sunil Sharma, Giuseppe Pizzorno
Journal: Cancer Research (2010)

Abstract 5-azacytidine is a cytidine analogue with cytotoxic and cytostatic activity, currently utilized for the treatment of myelodysplastic syndromes. The cytostatic activities of low-dose 5-azacytidine are attributed to its incorporation into the DNA and RNA of mammalian cells, which influences epigenetic regulation, cell cycle progression, and protein expression. We observed that treatment with 5-azacytidine significantly radio-sensitizes androgen-independent prostate cancer cells, synergistically enhancing the overall efficiency of radiation treatment both in vivo and in vitro. Furthermore, we found that exposure of androgen-independent prostate cancer cells to 5-azacytidine impairs or delays the repair of radiation induced DNA double-strand breaks through the non-homologous end-joining pathway. This observation explains the radio-sensitizing potential of 5-azacytidine and constitutes the first conclusive evidence for a DNA repair defect introduced by this compound. In addition, we found that this DNA repair defect was not introduced by the 2’-deoxy derivative of 5-azacytidine. From this finding we infer that the inhibitory effects of 5-azacytidine on DNA repair are primarily mediated by its incorporation into the RNA. We suggest that a combined treatment with 5-azacytidine and ionizing radiation would be a good candidate for clinical trials, not necessarily limited to prostate cancers. 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 189.
Global Analysis of Posttranscriptional Gene Expression in Response to Sodium Arsenite
Authors: Lian-Qun Qiu, Sarah Abey, Shawn Harris, Ruchir Shah, Kevin E. Gerrish, Perry J. Blackshear
Journal: Environmental Health Perspectives (2014)

Inorganic arsenic species are potent environmental toxins and causes of numerous health problems. Most studies have assumed that arsenic-induced changes in mRNA levels result from effects on gene transcription.We evaluated the prevalence of changes in mRNA stability in response to sodium arsenite in human fibroblasts.We used microarray analyses to determine changes in steady-state mRNA levels and mRNA decay rates following 24-hr exposure to noncytotoxic concentrations of sodium arsenite, and we confirmed some of these changes using real-time reverse-transcription polymerase chain reaction (RT-PCR).In arsenite-exposed cells, 186 probe set-identified transcripts were significantly increased and 167 were significantly decreased. When decay rates were analyzed after actinomycin D treatment, only 4,992 (9.1%) of probe set-identified transcripts decayed by > 25% after 4 hr. Of these, 70 were among the 353 whose steady-state levels were altered by arsenite, and of these, only 4 exhibited significantly different decay rates between arsenite and control treatment. Real-time RT-PCR confirmed a major, significant arsenite-induced stabilization of the mRNA encoding δ aminolevulinate synthase 1 (ALAS1), the rate-limiting enzyme in heme biosynthesis. This change presumably accounted for at least part of the 2.7-fold increase in steady-state ALAS1 mRNA levels seen after arsenite treatment. This could reflect decreases in cellular heme caused by the massive induction by arsenite of heme oxygenase mRNA (HMOX1; 68-fold increase), the rate-limiting enzyme in heme catabolism.We conclude that arsenite modification of mRNA stability is relatively uncommon, but in some instances can result in significant changes in gene expression.
Circle predicted "unprecedented" savings from running Hinchingbrooke, says watchdog
Authors: G. Iacobucci
Journal: BMJ (2012)

NHS managers failed to adequately assess whether the savings that private firm Circle said it could make from running Hinchingbrooke Hospital were achievable before handing over the franchise, the national spending watchdog has found. 

All other potential franchises currently being considered by the Department of Health, such as George Elliot Hospital NHS Trust in Nuneaton, should be put on hold until a detailed review of the Hinchingbrooke case has been carried out, said the National Audit Office in its report on the deal.1

Circle took over the management of Hinchingbrooke Healthcare NHS Trust in Cambridgeshire in February 2012 on a 10 year franchise deal, and assumed responsibility for the trust’s debts of around £40m (€50m; $64m). 

But despite plans to achieve £311m in projected savings by the end of the 10 year …
REGIONAL VARIATION IN OUTCOMES IN PATIENTS WITH IMPAIRED FASTING GLUCOSE: INSIGHTS FROM THE NAVIGATOR TRIAL
Authors: Abhinav Sharma, Marilia Harumi Higuchi dos Santos, Jie-Lena Sun, Laine Thomas, Steven M. Haffner, Rury Holman, Renato Lopes
Journal: Journal of the American College of Cardiology (2016)