tbuckley/cabot-search huggingface dataset:
THU0523 Down-Regulating Pgc-1β Alleviates the Proinflammatory Effect of Rheumatoid Arthritis Fibroblast-Like Synoviocytes through Inhibiting Erk, P38 and Nf-κB Activation
Authors: Z. Jing-Jing, Z. Lang-Jing, M. Jian-Da, Z. Dong-Hui, M. Ying-Qian, W. Xiu-Ning, D. Lie
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The peroxisome proliferator- activated receptor-gamma coactivator-1beta (PGC-1β) is a transcriptional coactivator which plays important roles in regulating multiple aspects of energy metabolism and cytokine signaling pathways. It was reported that enhanced expression of PGC-1β can attenuate inflammatory activation of macrophages. However, the specific role of PGC-1β in rheumatoid arthritis (RA) remains unclear. <h3>Objectives</h3> To investigate the expression of PGC-1β and its role in the proinflammatory effect of RA fibrolast-like synoviocyte (FLS). <h3>Methods</h3> Synovial tissue was obtained by needle biopsy from knees of 8 active RA patients and 6 osteoarthritis (OA) patients (as less inflamed control) and FLS was then cultured. PGC-1β expression of mRNA and protein was detected by quantitative real-time RT-PCR (qRT-PCR) and Western blot analysis respectively. PGC-1β was depleted by Lentiviral-PGC-1β-RNAi. In PGC-1β knockdown RA-FLS, the mRNA expression of proinflammatory cytokines and MMPs were analyzed by qRT-PCR, activation of the mitogen-activated protein kinases, ERK, JNK, and p38, as well as NF-κB were determined by Western blot analysis. <h3>Results</h3> (1) PGC1β mRNA and protein expression in FLS from RA patients was significantly enhanced than that in OA controls (3.18±1.72 vs 1.17±0.74, p=0.019, and 0.82±0.30vs0.36±0.10, p=0.003, respectively). (2) Retrovirally mediated stable expression of the distinct shRNA led to more than 60% knockdown of endogenous PGC-1β in RA-FLS., The mRNA expression of proinflammatory cytokines, including TNF-α, IL-6, IL-8, IL-1β, and MMP-3, MMP-13 in the PGC-1β knockdown RA-FLS was decreased, which implied down-regulating PGC-1β alleviates the proinflammatory effect of RA-FLS. Western blot results showed decreased p-ERK, p-p38 and p-NF-κB, but not p-JNK in the PGC-1β knockdown RA-FLS, which implied down-regulating PGC-1β visibly suppressed the activity of ERK, p38 and NF-κB except JNK (Fig. 1). <h3>Conclusions</h3> Our results indicated that PGC-1β may play an important role in the proinflammatory effect of RA-FLS through ERK, p38 and NF-κB pathway. <h3>Acknowledgements</h3> Supported by Chinese National Natural Science Research Grant (grant no. 81373183 and 81001334), Specialized Research Fund for the Doctoral Program of Higher Education (grant no.20130171110075) and the Guangdong Natural Science Foundation (grant no.S2013010014396). <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2679
Abstract 3307: Cell-surface glycoproteomics identifies CUB-domain containing protein 1 to be associated with prostate cancer metastasis
Authors: Lifang Yang, Dean A. Troyer, Julius O. Nyalwidhe, Richard R. Drake, Oliver J. Semmes
Journal: Cancer Research (2010)

Abstract Prostate cancer is still the most common and second leading cause of cancer death in men in the United States and is overwhelmingly lethal when metastatic. Evidence from histochemical analysis and experimental tumor models indicates alterations in cell-surface sialylation as a general observation associated with the metastatic potential of tumor cells. Our preliminary data from lectin staining also demonstrates changes of cell-surface sialylation in a syngeneic prostate cancer cell model, which includes two PC3 sublines, N2 (non-metastatic) and ML2 (highly metastatic). Characterization of cell-surface sialylated glycoproteins in this model system could provide new information related to the metastatic phenotype in prostate cancer. Thus, cell-surface sialoglycoproteins in the N2 and ML2 cell lines were metabolicly labeled with with an unnatural mannose analogue (AC4ManNAz); This was followed by chemoselective conjugation of the azido sugars with a biotinylated alkyne capture reagent via Cu (I) catalyzed click chemistry and affinity detection and enrichment by streptavidin-conjugated beads (or fluorescein). Captured glycoproteins were separated by 1D gel electrophoresis, in-gel proteolytic digestion, and protein identification by means of tandem mass spectrometry (LC-MS/MS). The expression of the targeted sialoglycoproteins was verified in our prostate cancer cell lines and clinical samples by means of Western blot, confocal microscopy and fluorescent immunohistochemistry. Forty three cell-surface N-linked glycoproteins were identified as differentially expressed between the PC3 metastasis variants, including CUB-domain containing protein 1 (CDCP1). Western blot analysis of the cell-surface glycoprotein enriched fractions and total cell lysate confirmed that CDCP1 was over-expressed in the metastatic ML2 cells. Expression of CDCP1 is dysregulated in prostate cancer tissues, with malignant glands showing a more intense cell surface staining pattern, whereas normal glands demonstrated weak membrane and intracellular granular staining on the basal side. We conclude that glycan metabolic labeling technology combined with mass spectrometry analysis provides a powerful tool for the identification of specific cell-surface glycoproteins that may contribute to prostate cancer metastasis, like CDCP1. Further studies are warranted to evaluate the clinical value of CDCP1 and to understand its function in prostate cancer progression. 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 3307.
METHODOLOGICAL ISSUES FOR DOUBLE LABEL GASTRIC EMPTYING STUDIES: ACQUISITION AND AUTOMATED PROCESSING.
Authors: Donna Marciano, Christina Carlson, Steve Clickman, Aaron Fink, A. Ippoliti, Randall A. Hawkins
Journal: Clinical Nuclear Medicine (1987)

Marciano, Donna; Carlson, Christina; Clickman, Steve; Fink, Aaron; Ippoliti, A.; Hawkins, Randall A.Author Information
BCIRG 005 main efficacy analysis: a phase III randomized trial comparing docetaxel in combination with doxorubicin and cyclophosphamide (TAC) versus doxorubicin and cyclophosphamide followed by docetaxel (AC→T) in women with Her-2/neu negative axillary lymph node positive early breast cancer.
Authors: W Eiermann, T Pienkowski, J Crown, L Chap, M Pawlicki, M Martin, M Saleh, S Sehdev, L Provencher, G Von Minckwitz, V Semiglazov, D Slamon, I Tabah-Fisch, M Buyse, A Riva, H Taupin, G Sauter, J Mackey
Journal: Cancer Research (2009)

Abstract Abstract #77 Background: The relative benefits of adjuvant breast cancer chemotherapy with docetaxel in combination with anthracycline, or given sequentially after an anthracycline-based regimen, are unknown.&amp;#x2028; Material and Methods: We randomized women with axillary lymph node positive, central HER-2 nonamplified, breast cancer to either TAC (75/50/500 mg/m2 q3wk x 6 cycles) or AC (60/600 mg/m2 q3wk x 4 cycles) followed by T (100 mg/m2 q3wk x 4 cycles). Patients were prospectively stratified by number of positive nodes (1-3 vs. 4+) and hormone receptor status. Patients with ER and/or PR positive (HR+) tumors received hormonal therapy after chemotherapy. The primary endpoint was disease-free survival (DFS) with 80% power to detect an absolute difference of 5%. Secondary endpoints included overall survival and safety.&amp;#x2028; Results: A total of 3298 patients (1649 per arm) were recruited between August 2000 and February 2003. Baseline characteristics were well balanced: age&amp;lt;50 yrs 47%, 1-3 nodes 61%, HR+ 82%, T &amp;gt; 2 cm 58%. The planned 6 cycles of TAC were given to 93.5% of patients and 8 cycles of AC-T to 90.5%. Febrile neutropenia (17.9% vs. 8.5%) was more frequent with TAC, while grade 3 / 4 neutropenic infections were equivalent (8.7% with TAC vs. 8.0%). One septic death occurred in the TAC arm. Grade 3 / 4 non-hematological toxicity rates were fatigue (5.2% vs. 6.3%), nausea (4.5% vs. 4.1%), vomiting (4.2% vs. 4.1%), diarrhea (2.9% vs. 3.1%), stomatitis (2.6% vs. 3.0%), peripheral edema (1.3% vs. 2.6%), neuropathy-sensory (0.6% vs. 2.0%) and CHF (0.1% vs. 0.4%) in the TAC and AC-T arms, respectively. The other Garde 3 / 4 docetaxel specific toxicities (nail and skin toxicities were observed in less than 0.5% in both arms. The protocol specified main efficacy analysis triggered by 688 DFS events will be presented, with a median follow-up of 60 months.&amp;#x2028; Discussion: The safety profile of the two docetaxel-based adjuvant chemotherapy regimens is comparable with the exception of a higher incidence of febrile neutropenia with TAC. This analysis will define the relative efficacy of combination vs. sequential docetaxel-containing chemotherapy in the adjuvant treatment of women with node positive, HER-2 negative breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 77.
False-Positive Indium 111 Pentetreotide Scan for Recurrent Meningioma Due to Radiation Fibrosis
Authors: Saiyyeda Rahman, Shankar Raja, Bruce L. Ehni
Journal: Clinical Nuclear Medicine (2010)

A patient with recurrent meningioma in the right frontal lobe, treated with resection and radiation, had a routine magnetic resonance imaging scan that was suspicious for recurrent disease. Follow-up Octreoscan showed moderately increased focal uptake in same region, compatible with recurrence of meningioma; however, the histopathology was consistent with radiation fibrosis. There are reported cases of uptake on Octreoscans at other sites of the body due to chronic inflammation, but only one other case has been reported in the brain. Caution must be taken in interpretation of brain tumors on Octreotide scan, when treatment history includes prior radiation therapy.
201Tl Heart-Liver Radioactivity Uptake Ratio and Prediction of Decompensation in Patients With Cirrhosis
Authors: Min-Ho Lee, Hae-Jin Tae, Dae-Won Jun, Seong-Eon Ryu, Yun-Young Choi, Min-Jeong Kwak, Ju-Seop Kang
Journal: Clinical Nuclear Medicine (2013)

The present study aimed to determine the predictive value of the heart-liver uptake ratio (H/L ratio) of rectally administered (201)Tl scintigraphy for hepatic decompensation, which was conducted in 107 patients with cirrhosis.We retrospectively assessed the predictive value of a noninvasive parameter, H/L ratio, for decompensation during a median follow-up period of 45.4 months using follow-up data from 1996 through 2008 for 107 patients with compensated cirrhosis. Logistic regression analysis and odds ratio estimates were used to estimate independent value of the H/L ratio on the risk of decompensation with 95% confidence intervals.At first visit, all subjects were confirmed as patients with compensated cirrhosis, 39 by liver biopsy and 68 by standard laboratory and radiological criteria. At end of the evaluation time, 81 patients remained compensated, whereas 26 patients decompensated as evidenced by ascites in 23, hepatic encephalopathy in 8, and variceal bleeding in 1 patient. First-visit parameters except bilirubin level, alanine aminotransferase (ALT), and H/L ratio and last visit parameters except ALT and aspartate aminotransferase-ALT ratio were significantly different between the 2 groups as ascertained by Wilcoxon rank sum test (P < 0.05). Among those parameters, we found that the last visit H/L ratio was a strongly reliable predictor of decompensation with an odds ratio estimates of 14.443, area under the receiver operating characteristic curve of 0.825, cutoff of 0.4, sensitivity of 73.1 %, and specificity of 71.6%.This evidence indicates that in patients with compensated cirrhosis, an increased H/L ratio at follow-up may be a useful predictive parameter showing a high risk of progression to a decompensated state.
Abstract P4-12-05: Enrichment of aldosterone synthase (<i>CYP11B2</i>) gene C-allele carriers in women at high risk in the OncoVue® polyfactorial risk model
Authors: ER Jupe, TW Pugh, NS Knowlton, DC DeFreese
Journal: Cancer Research (2012)

Abstract Background: Models for accurately assessing breast cancer risk are utilized for guiding clinical decisions regarding early detection and prevention. We developed a polyfactorial risk model (PFRM; OncoVue) from analysis of a large case-control database including both functional gene polymorphism and clinical factor data. A multivariate logistic regression based statistical protocol was used to derive a single risk model consisting of 22 single nucleotide polymorphisms (SNPs) in 19 genes and 5 traditional risk factors. Several studies have shown that the PFRM is significantly improved in individualized risk estimation compared to the Breast Cancer Risk Assessment Tool (BCRAT) or Gail model. Here we have examined the genotype frequencies of women placed in the highest decile of risk by the PFRM compared to both the overall control population and to women in the control population placed at the lowest decile of risk. Materials and Methods: Analyses were performed on 1671 breast cancer cases and 3351 controls that enrolled in a case-control study conducted in six regions of the United States. DNAs were genotyped for the 22 genetic polymorphisms and combined with clinical risk factor information to calculate PFRM risk estimates for the individual participants. The PFRM lifetime scores were used to stratify the upper and lower deciles of risk. The genotype frequencies for these stratified risk groups were determined and compared to the overall control population and to each other (upper vs. lower decile). Odds Ratios (OR) were determined for the CYP11B2 genotypes because they exhibited the largest differences in frequency among the groups. Results: For CYP11B2 comparison of the genotype frequencies in the highest decile risk group to the overall genotype frequencies of controls identified significant enrichment of the C-allele carriers in the highest risk group. The OR for C-allele carriers (C/C+C/T) compared to the most common T/T genotype was 3.0 (1.9, 4.8; 95% C.I.) with a p-value &amp;lt;0.0001. Similarly for the upper decile risk group compared to the lower decile risk group the association of C-allele carriers was even stronger with OR = 11.0 (6.6,18.4; p &amp;lt;0.0001). In the upper decile of risk 86% of the individuals were C-allele carriers compared to only 38% in the lower decile of risk. Conclusions: Our previous studies have shown an age dependent association of the CYP11B2 C/C and C/T genotypes with breast cancer risk. The enrichment of these genotypes in women in the upper decile risk group as determined by the PFRM further reinforces the role of this genotype in influencing breast cancer risk and suggests that intervention in the aldosterone synthase pathway be explored as a method of breast cancer prevention. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-12-05.
Abstract IA-3: The regulation of p53 tumor suppressing activities
Authors: Guillermina Lozano
Journal: Cancer Research (2009)

Abstract The p53 tumor suppressor is often altered in tumors via single nucleotide changes that alter critical amino acids in the DNA binding domain. These p53 mutants lose DNA binding activity and some mutants exhibit a gain-of-function phenotype that is manifested as metastasis in vivo. We have discovered that p53 mutants are normally unstable similar to wild type p53, and become stable in some tumors leading to the increased metastasis. Mdm2, a negative regulator of wild type p53 also negatively regulates mutant p53. Decreased Mdm2 gene dosage delays a cancer phenotype in tumor prone mouse models. In humans, an Mdm2 single nucleotide polymorphism (SNP) increases the levels of MDM2 and correlates with an earlier age of tumor onset. We have generated mice with the human MDM2 SNP and show that the SNP accelerates a tumor phenotype in mice. Citation Information: Cancer Res 2009;69(23 Suppl):IA-3.
Leuprolide Acetate Therapy in Luteinizing Hormone–Dependent Cushing's Syndrome
Authors: André Lacroix, Pavel Hamet, Jean-Marie Boutin
Journal: New England Journal of Medicine (1999)

Corticotropin-independent Cushing's syndrome is usually caused by cortisol-secreting adrenal adenomas, carcinomas, or (rarely) bilateral adrenal hyperplasia. In some patients with this syndrome, the excess secretion of cortisol is caused by abnormal adrenal expression and function of receptors for various hormones, including gastric inhibitory polypeptide,1–6 vasopressin,7–9 β-adrenergic agonists,10 and interleukin-1.11 These findings suggest that diverse other hormone receptors could be implicated in other patients.12 We describe a woman with bilateral adrenal hyperplasia and corticotropin-independent Cushing's syndrome that was clinically manifested transiently during her pregnancies and became constant only after menopause. The patient's cortisol secretion was stimulated by luteinizing hormone . . .
Extraosseus Uptake of F-18 Fluoride in the Primary Malignancy and Cerebral Metastasis in a Case of Non–Small-Cell Lung Cancer
Authors: Yuxin Li, Bashir A. Tafti, Wisam Shaba, Gholam R. Berenji
Journal: Clinical Nuclear Medicine (2011)

A 68-year-old man with history of heavy smoking was admitted for increasing falls during the past 4 weeks. Chest x-ray revealed a right upper lobe mass. Biopsy demonstrated poorly differentiated non-small-cell carcinoma. F-18 fluoride positron emission tomography/computer tomography (PET/CT) was performed to evaluate bone metastasis. Review of the sectional PET images demonstrated extraosseous fluoride uptake in the primary lung mass, as well as ring-shaped fluoride uptake in the cerebral metastatic lesion. Neither of these lesions demonstrated calcifications on CT images. The patient received radiation treatment of the brain metastasis after F-18 fluoride PET/CT study.
P781 SPONTANEOUS CLEARANCE RATES INCREASE WITH HCV REINFECTION EPISODE IN HIV-POSITIVE MEN WHO HAVE SEX WITH MEN (MSM) INDEPENDENT OF HCV SUBTYPE
Authors: P. Ingiliz, C. Boesecke, T.C. Martin, S. Mauss, A. Rodger, M. Mandorfer, A. Baumgarten, H.-J. Stellbrink, S. Bhagani, J.K. Rockstroh, M. Nelson
Journal: Journal of Hepatology (2014)
Gene Expression Profiling of Phenotypically-Defined Hormone-Receptor Positive Breast Cancer: Evidence for Increased Transcriptional Activity of the Insulin Growth Factor Receptor Pathway and Other Pathways.
Authors: J. Sparano, R. Gray, L. Goldstein, B. Childs, D. Brassard, R. Bugarini, S. Rowley, J. Baker, S. Shak, S. Badve, F. Baehner, P. Kenny, E. Perez, L. Shulman, S. Martino, G. Sledge, N. Davidson
Journal: Cancer Research (2009)

Abstract Background: Approximately 70% of all breast cancers are hormone receptor (HR)-positive tumors that are sensitive to endocrine therapy, but some patients have recurrence despite adjuvant endocrine therapy. We performed an exploratory analysis of gene expression in HR-pos operable breast cancer in order to identify potential novel therapeutic targets and biomarkers associated with recurrence. Methods: RNA was extracted from primary tumor samples obtained from 776 patients with stage I-III breast cancer treated with adjuvant chemohormonal therapy in trial E2197 (JCO 2008; 26: 4092-4099), of whom 458 had HR-pos disease (defined in a central lab; JCO 2008; 26: 2473). We evaluated RNA expression patterns (by quantitative RT-PCR using a panel of 371 rationally selected genes) in HR-pos cases compared with the HR-neg cases using weighted T statistics, and determined which genes in the HR-pos, HER2-neg group were associated with recurrence (using Cox proportional hazards model score test, Korn's adjusted P value &amp;lt;5% with false discovery rate &amp;lt; 10%).Results: The top 10 genes exhibiting significantly higher expression in the HR-pos group (p≤ 6.17e-160) included ESR1 plus 5 estrogen regulated genes, confirming our approach of evaluating gene expression in phenotypically-defined subsets. Other pathways that exhibited higher expression in the HR-pos group (among the 40 top genes with higher expression, p&amp;lt;8.66e-53) included the insulin growth factor (IGF) (IRS1, IGFR1, IGFB2), Ras (RhoB, RhoC, RAB27B, GGPS1), and HER pathways (ERBB2, ERBB3, ERBB4), and other genes involved in apoptosis (BCL2, BCL2L1, BAG1, NME6, BBC3), signaling (MAPK3, SEMA3F, RXRA), mismatch repair (MSH3), cell cycle regulation (CCND1), stress response (HSPB1), and tumor suppressor genes (TP53BP1, APC). These patterns were similar in HER2-pos cases. Pathway analysis (Ingenuity) revealed substantial interconnectivity among these genes, especially between IGFR1, ERB2/3/4, MAPK3, BCL2, and CCND1, but not RhoB/RhoC. Genes for which increased expression was associated with increased recurrence included those associated with proliferation (TOP2A, AURKB, PLK1) and apoptosis (BIRC5 - survivin).Conclusions: This exploratory analysis reveals several pathways that exhibit higher transcriptional expression in HR-pos disease, some of which are also associated with a higher risk of recurrence, suggesting that they may be potential therapeutic targets. This provides rationale for testing agents currently available in the clinic that inhibit the IGF and other pathways. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5165.
Abstract 3952: New advances in regulation of senescence by PML and the PML nuclear bodies
Authors: Mariana D. Acevedo Aauino, Véronique Bourdeau, Mathieu Vernier, Gerardo Ferbeyre
Journal: Cancer Research (2012)

Abstract Senescence is a cellular defense mechanism activated by short telomeres, DNA damage or expression of oncogenes. The program includes the expression of high levels of the promyelocytic leukemia protein PML that form nuclear spherical bodies, known as PML-nuclear bodies (PML-NB). The expression of PML in normal fibroblasts is sufficient to induce senescence while genetic inactivation of PML inhibits the process. These results suggest that PML is a critical component of the senescence tumor suppressor mechanism. Accordingly PML is poorly expressed in malignant human tumors but highly expressed in benign tumors. We recently discovered a new mechanism of regulation of RAS-induced senescence by PML, which implicates the recruitment of the RB/E2F complex to the PML-NB via RB-PML interaction. This leads to inhibition of cell cycle and DNA repair genes, DNA damage, p53 activation and ultimately to senescence. We show now that the cyclin dependent kinase CDK4 blocks the ability of PML to regulate E2F gene expression and senescence and that CDK inhibitors potentiate the ability of PML to restore the senescence program in tumor cells. 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 3952. doi:1538-7445.AM2012-3952
Sucrase-Isomaltase Deficiency
Authors: Gary M. Gray, Kenneth A. Conklin, R.R.W. Townley
Journal: New England Journal of Medicine (1976)

Deficiency of sucrase-isomaltase, an intestinal enzyme complex that is essential for digestion of nutritionally important carbohydrates, appears to be inherited as an autosomal recessive in 0.2 per cent of North Americans. The molecular basis of the deficiency has not been elucidated. To characterize the enzyme defect quantitatively, papain-solubilized intestinal biopsies were analyzed for total enzyme protein by radioimmunoassay and for enzyme activity by hydrolytic assay. Normal intestine had a close correlation between immunologically reactive enzyme and enzymic activity. In contrast, seven patients with sucrase-isomaltase deficiency were found to have complete absence of the enzyme protein by radioimmunoassay even though up to 10 times more intestinal protein was present than with normal tissue. This absence of an inactive enzyme variant can be explained by a major (no-sense) mutation of the structural gene or by a complete repression of the regulatory mechanism that controls structural gene function.