tbuckley/cabot-search huggingface dataset:
S142 The role of H3K27 methylation in vascular endothelial cell proliferation and function: implications for pulmonary arterial hypertension
Authors: D Shao, N Gambaryan, C Meng, F Perros, M Humbert, I Adcock, S Wort
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> There is increasing interest in the role of epigenetic gene regulation in the pathogenesis of pulmonary arterial hypertension (PAH), a condition associated with pulmonary vascular cell proliferation. Methylation on histone H3K27 (H3K27me3) has been found to be a key regulator of development and cell homeostasis. Methylation at H3K27 can be reversed by Jumonji C (JmjC) domain-containing proteins, JMJD3. We were interested to determine the immunohistochemical distribution of H3K27me3 and JMJD3 proteins in patients with IPAH and the effect of GSK-J4, an inhibitor of JMJD3, on markers of pulmonary vascular cell proliferation. <h3>Methods</h3> Immunohistochemistry for JMJD3 and H3K27me3 was performed on human lung from normal healthy controls and patients with idiopathic PAH. The role of JMJD3 on cell cycle regulator (cyclin) expression in response to serum stimulation, with and without GSK-J4, was performed on normal human pulmonary artery endothelial cells (HPAECs) and RT-qPCR was then performed using QuantiTec primer assays. Chromatin Immunoprecipitation (CHiP) was performed antibody against H3K27me3 on normal HPAECs and analysed by quantitative PCR. <h3>Results</h3> We found that the expression of JMJD3 protein is increased in the walls of pulmonary arteries of patients with idiopathic PAH compared to health control. This correlated to a decreased expression of H3K27me3. Treatment of HPAECs with GSK-J4, the inhibitor of JMJD3, <i><i>in vitro</i>,</i> significantly increased cell cycle regulator p19, p27, CDK4 and CDK6 mRNA expression (Fig. 1, n = 3), whilst having no effect on p14, p16, p21 and CDK2 (data not shown). Furthermore, CHiP using a specific H3K27me3 antibody, followed by RT-qPCR analysis, demonstrated that GSK-J4 treatment increased H3K27me3 occupation on the transcription start sites of p27 and CDK4, whilst the negative control compound GSK-J5 had no effect (n = 2). <h3>Conclusion</h3> Our data suggest that JMJD3 and H3K27 histone methylation could play an important role in cell cycle progression and cell cycle exit of pulmonary vascular cells in patients with idiopathic PAH. As such drugs such as GSK-J4 may provide a therapeutic option in the future to reverse pulmonary vascular remodelling.
False-Positive I-131 Uptake by an Ovarian Serous Cystadenofibroma
Authors: Jonathan Flug, Katherine Lameka, Raymond Lee, Douglas S. Katz, Wei-Wen Sung, Elizabeth Yung
Journal: Clinical Nuclear Medicine (2012)

We present the case of a 53-year-old woman after thyroidectomy with metastatic multifocal papillary carcinoma and encapsulated focal Hurthle cell carcinoma. Postoperatively, an I-131 whole-body scan revealed uptake in the low midline anterior neck. She was treated with 151.5 mCi of I-131. The 1-year follow-up I-131 whole-body scan revealed a new pelvic mass with I-131 uptake. Pelvic CT showed bilateral complex ovarian masses. She underwent surgical excision, revealing a right ovarian endometriotic cyst and a left ovarian cystadenofibroma, without thyroid tissue involvement. I-131 uptake in a cystadenofibroma is extremely rare and has been reported only once to our knowledge.
A3.14 Lymphocyte surface interleukin-6 (IL-6) receptor chains are similarly decreased in SLE and seropositive RA, but not in seronegative RA
Authors: Skwarek Martyna, Fantana Julia, Heschel Babett, Aringer Martin
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> IL-6 plays a definite role in RA and has been found increased in SLE. However, differences in serum CRP suggest differences in signalling. We therefore analysed serum IL-6, IL-6 receptors, and phosphorylated Stat3, as the main signalling molecule involved, in patients with SLE and RA. <h3>Materials and Methods</h3> Peripheral blood mononuclear cells (PBMC) of 46 SLE, 20 RF and ACPA positive RA patients (RA+), 14 seronegative RA (RA-) patients, and 68 healthy individuals (HC) were compared. PBMC were immediately prepared from peripheral venous blood. For determining the percentage of IL-6Rα (CD126), gp130 (CD130), PBMC were stained with PE-labelled or control antibodies. For the determination of pStat3, cells were fixed with formaldehyde (2%), permeabilised with methanol (80%), and stained with PE-labelled anti-pStat3 or control antibodies. Cells were analysed on a Becton Dickinson FACSCalibur fluorocytometer, gating for lymphocytes. Mean fluorescence intensity (mfi) was used as a semiquantitative measure of pStat3 contents. Serum levels of IL-6 and soluble IL-6 receptor (sIL-6R) were measured by ELISA. <h3>Results</h3> The percentage of CD126+ lymphocytes, as compared to HC (mean ± SD 60 ± 8%) was similarly decreased in SLE (50 ± 17%, p = 0.0002) and RA+ (52 ± 13%, p = 0.01), but not RA- (60 ± 12%, p = 0.98) patients. SLE was significantly (p = 0.02) different from RA-. Likewise, CD130+ lymphocytes were decreased in SLE and RA+ , but not RA- patients (HC 59 ± 10%; SLE 49 ± 19% (p = 0.006); RA+ 53 ± 12% (p = 0.08); RA- 62 ± 9% (p = 0.3)). SLE and RA+ were different from RA- (p = 0.002, and p = 0.003, respectively). In contrast, both serum levels of IL-6 and intracellular pStat3 were increased in all three groups compared to HC: serum IL-6 was a median (range) 0 (0-4.8) pg/ml in HC, 3 (0.5-69.3) pg/ml (p&lt;0.0001) in SLE, 8.6 (2.4-158.5) pg/ml (p&lt;0.0001) in RA+ , and 4.2 (0.9-17.5) pg/ml (p = 0.0001) in RA-. Median pStat3 mfi, as compared to HC (10 (5.4-23)) was 18 (10-70), p&lt;0.0001, in SLE, 17 (9.8-39), p&lt;0.0001, in RA+ , and 13 (10-29), p = 0.008, in RA-. Serum IL-6 levels were higher in RA+ than SLE (p = 0.0004) and RA- (p = 0.009), while pStat3 was similar for all groups. Serum IL-6R levels were increased in all patient groups (HC 38.1 (18.1-57) ng/ml; SLE 45.1 (20.8-109.6) ng/ml, p = 0.02; RA+ 54.3 ± 17.1ng/ml, p = 0.0004; RA- 48.5 ± 14 ng/ml, p = 0.02) without differences between patient groups. <h3>Conclusions</h3> While IL-6 and sIL-6R levels were most elevated in RA+, as expected, Stat3 phosphorylation was similarly increased in all patient groups. Intriguingly, regarding both surface IL-6 receptor chains, SLE grouped with RA+ , suggesting an influence of immune complex disease.
Intrauterine Infection and Preterm Delivery
Authors: Robert L. Goldenberg, John C. Hauth, William W. Andrews
Journal: New England Journal of Medicine (2000)

Preterm delivery is the chief problem in obstetrics today, accounting for 70 percent of perinatal mortality and nearly half of long-term neurologic morbidity.1,2 Approximately 10 percent of all births are preterm, but most of the serious illness and death is concentrated in the 1 to 2 percent of infants who are born at less than 32 weeks of gestation and who weigh less than 1500 g. Approximately 20 percent of preterm births are the result of a physician's decision to bring about delivery for maternal or fetal indications, and the remainder follow the spontaneous onset of labor or rupture . . .
Protein expression comparison and physiological profiling of matched pairs DCIS/normal and invasive/normal primary epithelial cells.
Authors: A Minkeu, JN Quong, A Rosenberg, KL Brill, AA Quong
Journal: Cancer Research (2009)

Abstract Abstract #6031 Background: Approximately 50% of patients who are diagnosed with Ductal Carcinoma In-Situ (DCIS) develop invasive breast cancer. The progression from DCIS to invasive cancer is not well understood. To better understand the range of biological processes involved in this progression, we have successfully isolated primary epithelial cell cultures from patient breast tissue and are using mass spectrometry-based methods to identify differentially expressed proteins in these different cell types. Bioinformatics analysis was used to identify differences in the underlying pathways.&amp;#x2028; Methods: Primary Human Mammary epithelial cells from DCIS and Stage 3 Invasive tumors and normal tissue from the same patient were isolated immediately after surgery. Cells were maintained in defined CNT27 media for up to 2 passages and were characterized for epithelial and breast cancer markers by immunohistochemistry and western blot. Tamoxifen response was measured by cell proliferation assay. Protein lysates were labeled with the ITRAQ isobaric tags. Two-dimensional high-pressure liquid chromatography and mass spectrometry were used to identify differentially expressed proteins.&amp;#x2028; Results: The proliferation rate of cells from DCIS tissue was 33% higher than the matched control cells and 50% higher from invasive tissue. Furthermore, Tamoxifen was more effective at inhibiting DCIS cell proliferation than the invasive cells in a dose- and time-dependent manner. We identified 50-100 proteins differentially expressed between the different tissue types. Validated tumor markers such as members of protein S100 family were significantly different between the tumor and normal samples. Thrombospondin, a known angiogenesis inhibitor, had similar concentrations in normal and DCIS tissues but was down-regulated (ratio=0.4) in the invasive tumor samples.&amp;#x2028; Discussion: Using the analogous methods from gene expression studies, we found that pathways associated with processes such as differentiation, angiogenesis, and invasion are enriched in the proteome of the invasive tumors. Further comparisons of additional samples is continuing with the goals of better understanding the underlying biology that drives DCIS to invasive breast cancer and ultimately defining markers that could be used in better prognosis for DCIS patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6031.
FDG PET/CT of a Late-term Pregnant Woman With Breast Cancer
Authors: Te-Chun Hsieh, Yu-Chin Wu, Shung-Shung Sun, Lu-Yen Chu, Kuo-Yang Yen, Chia-Hung Kao
Journal: Clinical Nuclear Medicine (2012)

A 38-year-old pregnant woman at 26-week gestation with left breast cancer requested an FDG PET/CT scan for more detailed staging of her breast cancer before treatment. After discussing the potential radiation-related risk and estimating possible absorbed dose to fetus, she consented for examination. By using a low-radiation-dose CT protocol and administration of routine 370-MBq FDG without diuresis, the resultant calculated (using existing models to predict fetal radiation exposure) fetal dose from CT and FDG would be 3.60 mGy and 6.29 mGy, respectively. In contrast to the existing few literatures, our case also demonstrated previously unreported uptake in the fetal kidneys.
Detection of Antibodies Directed against a Liver-Specific Membrane Lipoprotein in Patients with Acute and Chronic Active Hepatitis
Authors: Donald M. Jensen, Ian G. McFarlane, Bernard S. Portmann, A. L. W. F. Eddleston, Roger Williams
Journal: New England Journal of Medicine (1978)

A specific and sensitive radioimmunoassay was used to measure the levels of antibody to a liver-specific membrane lipoprotein in patients with acute and chronic liver disease. Antibody was detected in 29 of 30 patients with chronic active hepatitis (all of 15 HBsAg-negative and 14 of 15 HBsAg-positive cases), and in 10 of 17 patients with chronic persistent hepatitis but at significantly lower titer. The titer of antibody to the lipoprotein showed a significant correlation with activity of disease as judged histologically and biochemically. Transiently elevated levels were found in 20 of 21 patients with acute viral hepatitis, but there was no correlation with the degree of liver damage. Antibody to liver-specific membrane protein may be part of the final common pathway of liver-cell damage in both HBsAg-positive and HBsAg-negative chronic activite hepatitis, whereas other immune mechanisms determine the liver-cell injury in acute viral hepatitis.
Abstract 1606: SON is a novel therapeutic target for pancreatic cancer
Authors: Toru Furukawa, Etsuko Tanji
Journal: Cancer Research (2010)

Abstract To find novel therapeutic molecular targets for pancreatic cancer, we conducted a systematic knockdown screening of signaling-associated molecules in pancreatic cancer cells. During the course of screening, we found that knockdown of SON, a DNA binding protein of unknown function, by short interference RNA induced a strong inhibitory effect on proliferation of cultured pancreatic cancer cells in vitro. The colony formation assay employing the short hairpin RNA vector targeting SON (shRNA-SON) revealed a strong suppression of survival of cells. Flowcytometry analysis uncovered that the knockdown of SON induced G2/M arrest and apoptosis. Stable transfectants of cancer cells with shRNA-SON showed marked retardation of tumor formation in xenograft model. Knockdown of SON induced less suppressive effect on HPDE, the immortalized normal pancreatic duct epithelial cell, which indicated that the suppressive effect on proliferation was specific for cancer cells. We established 293-cell clones stably expressing EGFP-SON and found that SON was confined in speckles in intercalated nuclei and released in cytoplasm during mitosis. These results indicated that SON was a novel therapeutic target for pancreatic cancer. 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 1606.
Systematic review in<i>The BMJ</i>leads to changes to Australian guidelines on hydrolysed formula
Authors: Clever Banda
Journal: BMJ (2016)

The peak professional body of clinical Australasian immunologists and allergists, the Australasian Society of Clinical Immunology and Allergy (ASCIA), has published updated guidelines on the prevention of allergies in infants.1 The guidelines acknowledge Boyle and colleagues’ recent systematic review and meta-analysis published in The BMJ , which found no consistent convincing evidence to …
SAT0426 Prevalence of joint hypermobility and hypermobility syndrome in 100 IRAQI patients with asthma
Authors: F.I. Gorial, Z.S. Al-rawi, A.D. Mohammad
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Benign joint hypermobility syndrome (BJHS) is a hereditable disorder of connective tissue (1). Asthma may be caused by a connective tissue defect (2). Changes in the mechanical properties of the bronchial airways and lung parenchyma may underlie the increased tendency of the airways to collapse (3,4) <h3>Objectives</h3> To assess joint hypermobility (JHM) and hypermobility syndrome (HMS) in Iraqi patients with asthma &amp; to evaluate the predictors of this relationship if present. <h3>Methods</h3> A sample of 100 Iraqi patients with asthma, and another 100 healthy individuals matched for age and sex, serving as control group were studied. Full history was taken and complete clinical examination was done for all individuals in both groups. Bieghton score and Brighton Criteria were performed on patients &amp; controls. <h3>Results</h3> Both JHM and HMS were significantly more in patients with asthma than control group [68 (70.1%) versus 29 (29.9%) (p=0.000, OR (95% CI=2.26 (1.65-3.09))]. JHM (only) was observed in 16 (59.3%) asthmatic patients while it was 11 (40.7%) in controls (p=0.007, OR (95% CI)=3.23 (1.35-7.73)). Also HMS was observed in 52 (74.3%) asthmatic patients while it was 18 (25.7%) in controls (p=0.000, OR (95%CI)=6.41 (3.25-12.64)). Mean age, female sex, Family history (FH) of JHM, low body mass index (BMI), and low waist circumference were significant predictors for increased JHM in patients with asthma. The majority of asthmatics on steroids have HMS. <h3>Conclusions</h3> There is increased frequency of JHM and HMS (70.1%) in Iraqi patients with asthma compared to healthy controls. Mean age, female sex, FH of JHM, low BMI, and low waist circumference are significant predictors for JHM and HMS among asthmatic patients <h3>References</h3> Malfait F, Hakin AJ, De Paepe A, Grahame R. The genetic basis of the joint hypermobility syndromes. Rheumatology (Oxford) 2006;45:502–7. Morgan A W, Pearson S B, Davies S, et al. Asthma and airways collapse in two heritable disorders of connective tissue. Ann Rheum Dis 2007;66:1369–1373. doi: 10.1136/ard.2006.062224 Ober C, Hoffjan S. Asthma genetics 2006: the long and winding road to gene discovery. Genes Immun 2006;7:95–100. Zweers MC, Bristow J, Steijlen PM, et al. Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers– Danlos Syndrome. Am J Hum Genet 2003; 73:214–7. <h3>Disclosure of Interest</h3> None Declared
Abstract 705: Crosstalk with stromal fibroblasts contributes to EGFR inhibitor resistance in colorectal cancer cells
Authors: David Liska, Chin-Tung Chen, Pei-Rong Ding, Martin R. Weiser
Journal: Cancer Research (2010)

Abstract The mechanism for resistance to EGFR targeted therapies in colorectal cancer (CRC) with intact KRAS is still unknown. Host stromal cells contribute to tumorigenicity; however their effect on the sensitivity to EGFR targeted therapies has still to be determined. We hypothesized that crosstalk between stromal fibroblasts and CRC cancer cells contributes to cetuximab resistance via activation of the HGF/MET axis. Primary CRC associated fibroblasts (CAFs) were isolated and expanded from five surgical specimens. Fibroblasts were enriched by magnetic activated cell sorting (MACS®) and activated fibroblast lineage was confirmed by alpha smooth muscle actin (SMA) immunofluorescence. Supernatant HGF content and cellular mRNA expression levels in primary CRC CAFs, an embryonic lung fibroblast cell line (MRC-5), and a normal colon fibroblast cell line (CCD18) were determined by ELISA and quantitative RT-PCR. The effect of fibroblasts or HGF (75ng/ml) on the CRC cell lines LIM1215 and DiFi treated with cetuximab (5nM) for 72 hours was determined by co-culture using Transwells and WST-1 cell proliferation assays. Alterations in proliferation were compared by ANOVA. Mean fibroblast HGF secretion (8.3 ng/ml) and relative mRNA expression (2.0) could be augmented by co-culture with conditioned media (CM) from the CRC cell LIM1215 (14.1 ng/ml and 4.1, respectively) (Table). Further, co-culture of CRC cells with HGF, CCD18 cells, or primary CAFs reversed cetuximab-induced growth inhibition. LIM1215 proliferation was inhibited by cetuximab (55.3 ± 14.4%) which could be reversed by co-culture with either HGF (93.1 ± 10.2%) or CCD18 cells (107.2 ± 10.8%) (p&amp;lt;0.01 for both). Stromal-tumor interactions may play an important role in CRC resistance to cetuximab via the HGF/MET axis. Inhibition of both EGFR and MET may be necessary to realize the full potential of EGFR targeted therapies in CRC.Supernatant HGF levels and relative mRNA expression in fibroblasts treated with LIM1215 CM LIM1215 (Control)MRC5CCD18CAF3CAF4CAF5CAF6HGF (ng/ml) Ctrl&amp;lt;0.11.217.310.97.24.08.9LIM1215-CM&amp;lt;0.10.840.015.08.45.015.5 HGF mRNA Ctrl00.81.82.63.01.6 LIM1215-CM01.07.65.44.91.8 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 705.
Abstract 4078: Antitumor effect of the histone deacetylase inhibitor MS-275 in combination with retinoic acid Am80 in human cutaneous T-cell lymphoma
Authors: Yukihiko Kato, Chizu Egusa, Tatsuo Maeda, Ryoji Tsuboi
Journal: Cancer Research (2012)

Abstract Resistance to chemotherapy is a major hurdle in the treatment of cutaneous T cell lymphoma. Histone deacetylase (HDAC) inhibitors are known to display antitumor activity in different tumor types, including melanoma, and to reverse epigenetic repression of tumor suppressor genes, such as retinoic acid receptor ≤ (RARα). Some HDAC inhibitors have begun to be used for cutaneous T cell lymphoma patients in Japan. In this study, we tested the antitumor effect of the HDAC inhibitor MS-275 in combination with retinoic acid Am80 on two human cutaneous T cell lymphoma cell lines in vitro. Treatment of MS-275 showed a dose-dependent inhibitory effect on SeAx and MJ cell lines in a MTT assay. These cell lines were relatively resistant to Am80. A greater inhibitory effect (up to 80%) was achieved with a combination of MS-275 and Am80 compared with each agent alone. The lack of RARα2 gene expression was associated with histone deacetylation and gene methylation at the promoter level. Treatment with the combination of MS-275 and Am80 restored retinoid sensitivity by reversing RARα2 epigenetic silencing, which was verified by ChIP assay using histone H4. P21 was induced in both cell lines but the biological effect of MS-275 was G1cell cycle arrest in MJ and apoptosis in the SeAx cell line. These results suggest that the HDAC inhibitor MS-275 has a greater antitumor activity in combination with Am80 in cutaneous T cell lymphomas but that the degree of induced cell death may vary. The combination of HDAC inhibitors and retinoids represents a novel therapeutic approach for cutaneous T cell lymphoma that warrants clinical testing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4078. doi:1538-7445.AM2012-4078
P04.03 * GLIOMA SPECIFIC TARGET IDENTIFICATION WITH APTAMERS
Authors: M. Arora
Journal: Neuro-Oncology (2014)

DESIGN: Aptamers are in vitro generated, short DNA and RNA sequences which are randomly created as a library. They are created with multiple permutations and combinations automatically within set primer ends. These are then exposed to the target structure against which we want an aptamer ‘selected’, using Sequential Enumeration of Ligands by Exponential enrichment (SELEX). Modified aptamers based on published sequences against glioma cell lines and newly generated sequences were used in the project to identify their binding targets. SUBJECTS: Commercially available glioma and glial cell lines were used along with in-house generated primary glioma cultures. METHODS: Cy3 and biotin- conjugated aptamers were incubated with live glioma cell cultures and imaged using confocal or light microscopy. This established proof of concept that the aptamers were binding to the glial cell more specifically than control. To determine the target ligand, aptamers were then reacted with glial cell lysate and subjected to precipitation using streptavidin agarose beads and SDS polyacrylamide gel electrophoresis. Proteins were then analysed by mass spectroscopy. RESULTS: Known and unknown aptamer protein ligands were co-precipitated. X ray cross complementing protein 6 (XRCC6 or Ku70) and x ray cross complementing protein 5 (XRCC5 or Ku80) were precipitated along with nucleolin and other related proteins. Heterogenous nuclear ribonuclear proteins or hnRNP's were also isolated. Ku70 and Ku80 were also precipitated in primary cell cultures. KU70 and Ku80 appear in the KEGG pathway and Non-homologus end joining pathway or NHEJ for DNA repair. CONCLUSIONS: The aptamer has shown preferential binding to glioma cells and could act as a delivery system for therapeutic payloads. The aptamer targets Ku70 and Ku80, which are known to be over expressed in other forms of cancer but their role in gliomagenesis has not been fully elucidated. Other novel proteins have also been identified. Thus the aptamer co-precipitation technique has identified potential glioma biomarkers that may be of clinical significance.