tbuckley/cabot-search huggingface dataset:
P2-06-03: Differential Expression of Breast Cancer-Associated Genes between Stage- and Age-Matched Tumor Specimens from African- and Caucasian-American Women Diagnosed with Breast Cancer.
Authors: WE Grizzle, AD Steg, Q He, MR Steciuk, S Byan-Parker, MR Johnson, JM Grunda
Journal: Cancer Research (2011)

Abstract Background: Recent studies suggest that the poorer outcome of breast cancer patients observed in African-American women (AAW) may, in part, result from underlying genetic factors. The purpose of this study was to investigate gene expression differences between Caucasian-American women (CAW) and AAW that may contribute to this poorer prognosis. Methods: The expression of genes involved in breast carcinoma prognosis, response to therapy, estrogen signaling, and tumor aggressiveness was assessed in age- and stage-matched CAW and AAW paraffin-embedded breast cancer specimens. The Wilcoxon-Mann-Whitney Test was used to identify genes with a significant difference in expression between CAW and AAW. To determine if the differentially expressed genes could segregate between the CAW and AAW, we performed semi-supervised principle component analysis (SSPCA). Results: Twenty genes were differentially expressed between AAW and CAW. SSPCA incorporating these 20 genes separated AAW and CAW into two distinct groups. AAW were significantly (p &amp;lt; 0.05) more likely to display aberrations in G1/S cell-cycle regulatory genes, decreased expression of cell-adhesion genes, and low to no expression of ESR1, PGR, ERBB2 and estrogen pathway targets. Conclusions: The gene expression differences identified between AAW and CAW may contribute to more aggressive disease, resistance to therapy, enhanced metastatic potential and poor clinical outcome. Impact: These findings support the hypothesis that breast cancer specimens collected from AAW display distinct genetic differences compared to similar tissues obtained from CAW. Additional population-based studies are necessary to determine if these genetic variations contribute to the highly aggressive and treatment-resistant breast cancer phenotype frequently observed in AAW. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-06-03.
Abstract 4873: Protein complexes in cancer: A novel strategy to identify protein complexes through reduction of false discovery rate
Authors: Sudipto Das, Zhen Xiao, Allen D. Bosley, King C. Chan, Haleem J. Issaq, Timothy D. Veenstra, Thorkell Andresson, Jeffery E. Green
Journal: Cancer Research (2011)

Abstract Most cellular processes are controlled by protein-protein interactions, and aberrant protein-protein interactions can lead to human diseases such as cancer. Hence a comprehensive understanding of a protein interaction network and its dynamics response to different physiological conditions is essential for understanding a protein's function and may reveal novel therapeutic opportunities for fighting cancer. Affinity purification coupled with mass spectrometry has become the method of choice to study in vivo protein interactions and formation of protein complexes. However, the methodology has some limitations that reduce it application such as, under sampling of low abundant proteins and high background leading to an elevated false discovery rate (FDR). Herein we describe a strategy utilizing differential expression of the target protein followed by analysis using quantitative proteomics. By performing affinity purification on cells expressing increasing amounts of the polycomb complex protein Bmi-1, we show that known interacting proteins could be distinguished very efficiently from the background proteins based on their abundance profile. Applying this method to the data set significantly reduced the FDR and allowed us to identify potentially new interacting proteins for Bmi-1 that otherwise would have been considered non-specifically bound proteins. The method was also applied to characterize the interactome for Snail I, II and III a family of Zn-finger proteins thought to be involved in transcriptional repression. These proteins have been implicated in diverse biological function such as regulation of epithelial to mesenchymal transition, formation and maintenance of embryonic mesoderm, generation and migration of neural crest cells and metastasis. 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 4873. doi:10.1158/1538-7445.AM2011-4873
Altered C1 Inhibitor Genes in Type I Hereditary Angioedema
Authors: Dominique Stoppa-Lyonnet, Mario Tosi, Jérôme Laurent, Alain Sobel, Gilbert Lagrue, Tommaso Meo
Journal: New England Journal of Medicine (1987)

Hereditary angioedema is an inherited disease transmitted as an autosomal dominant trait and characterized by deficient activity of C1 inhibitor, a glycoprotein that limits intravascular activation of complement. The unavailability of markers for the C1 inhibitor locus has so far precluded access to the genetic bases of the disorder. Using a recombinant-DNA probe for the C1 inhibitor gene, we identified a cluster of four distinctive DNA restriction sites in a multigeneration family. The strict cosegregation of these markers with a low C1 inhibitor level supports the conclusion that a defective structural gene is responsible for the disease. The occurrence of distinct DNA markers in patients from unrelated kinships indicates that, like forms of the condition displaying dysfunctional C1 inhibitor variants, those characterized by protein deficiency are also genetically heterogeneous. Although multiple restriction-site changes in the C1 inhibitor gene are carried by certain patients, DNA markers for this locus are strikingly infrequent among normal persons. These findings indicate that the gene alterations responsible for hereditary angioedema arise more often from DNA rearrangements than from nucleotide substitutions. Such variations in the structure of the C1 inhibitor gene may provide the basis for early and direct identification of persons at risk.
CARDIAC POSITRON EMISSION TOMOGRAPHY TO QUANTIFY ABNORMAL CORONARY FLOW RESERVE AND RISK STRATIFY A PROSPECTIVE COHORT OF END STAGE RENAL DISEASE PATIENTS
Authors: Yehuda Paz, Rachelle Morgenstern, Richard Weinberg, Mariana Chiles, Navdeep Bhatti, Ziad Ali, Sumit Mohan, Sabahat Bokhari
Journal: Journal of the American College of Cardiology (2016)
AB0094 Genipin Inhibits Rankl-Induced Osteoclast Differentiation Through
Authors: C.-H. Lee, J.-Y. Kim, J.-M. Oh, W.-H. Yoo, S.-H. Beak, J.-J. Choi, W.-S. Lee, M.-S. Lee
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> People over the age of 50 are at risk of osteoporotic fracture, which may lead to increased morbidity and mortality. Osteoclasts are responsible for bone resorption in bone-related disorders. Genipin is a well-known geniposide aglycon derived from Gardenia jasminoides, which has long been used in oriental medicine for controlling diverse conditions such as inflammation and infection. <h3>Objectives</h3> We aimed to evaluate the effects of genipin on RANKL-induced osteoclast differentiation and its mechanism of action. <h3>Results</h3> Genipin dose-dependently inhibited early stage RANKL-induced osteoclast differentiation in bone marrow macrophages (BMMs) during culture. Genipin inhibited RANKL-induced IκB degradation and suppressed the mRNA expression of osteoclastic markers such as NFATc1, TRAP, and OSCAR in RANKL-treated BMMs, but did not affect c-Fos mRNA expression. Interestingly, genipin markedly inhibited c-Fos protein expression in BMMs, which was reversed in the presence of the proteosome inhibitor MG-132. Furthermore, genipin inhibited RANKL-mediated osteoclast differentiation, which was also rescued by overexpression of c-Fos and NFATc1 in BMMs. <h3>Conclusions</h3> Taken together, our findings indicate that genipin down-regulated RANKL-induced osteoclast differentiation through inhibition of c-Fos protein proteolysis as well as inhibition of IκB degradation. Our findings indicate that genipin could be a useful drug candidate that lacks toxic side effects for the treatment of osteoporosis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2308
Designing 3D Mesenchymal Stem Cell Sheets Merging Magnetic and Fluorescent Features: When Cell Sheet Technology Meets Image-Guided Cell Therapy
Authors: Gabriel Rahmi, Laetitia Pidial, Amanda K. A. Silva, Eléonore Blondiaux, Bertrand Meresse, Florence Gazeau, Gwennhael Autret, Daniel Balvay, Charles André Cuenod, Silvana Perretta, Bertrand Tavitian, Claire Wilhelm, Christophe Cellier, Olivier Clément
Journal: Theranostics (2016)

Cell sheet technology opens new perspectives in tissue regeneration therapy by providing readily implantable, scaffold-free 3D tissue constructs.Many studies have focused on the therapeutic effects of cell sheet implantation while relatively little attention has concerned the fate of the implanted cells in vivo.The aim of the present study was to track longitudinally the cells implanted in the cell sheets in vivo in target tissues.To this end we (i) endowed bone marrow-derived mesenchymal stem cells (BMMSCs) with imaging properties by double labeling with fluorescent and magnetic tracers, (ii) applied BMMSC cell sheets to a digestive fistula model in mice, (iii) tracked the BMMSC fate in vivo by MRI and probe-based confocal laser endomicroscopy (pCLE), and (iv) quantified healing of the fistula.We show that image-guided longitudinal follow-up can document both the fate of the cell sheet-derived BMMSCs and their healing capacity.Moreover, our theranostic approach informs on the mechanism of action, either directly by integration of cell sheet-derived BMMSCs into the host tissue or indirectly through the release of signaling molecules in the host tissue.Multimodal imaging and clinical evaluation converged to attest that cell sheet grafting resulted in minimal clinical inflammation, improved fistula healing, reduced tissue fibrosis and enhanced microvasculature density.At the molecular level, cell sheet transplantation induced an increase in the expression of anti-inflammatory cytokines (TGF-ß2 and IL-10) and host intestinal growth factors involved in tissue repair (EGF and VEGF).Multimodal imaging is useful for tracking cell sheets and for noninvasive follow-up of their regenerative properties.
“Single” Abdominal Vessel Due to Clot-Filled Inferior Vena Cava
Authors: PRASANTA KARAK, JOHN A. VENTO, RICHARD P. SPENCER
Journal: Clinical Nuclear Medicine (1996)

A 74-year-old woman had documented pulmonary emboli. She was started on heparin therapy, but heparin-associated thrombocytopenia developed. An inferior vena cava filter was placed, but renal function deteriorated. A renal dynamic study revealed aortic and renal perfusion; however, the inferior vena cava was not visualized. The inference was that the abdominal vena cava was totally obstructed or was filled with clots; the latter was confirmed radiographically.
Endometrial Carcinoma after Stilbestrol Therapy in Gonadal Dysgenesis
Authors: Bruce S. Cutler, Anne P. Forbes, Francis M. Ingersoll, Robert E. Scully
Journal: New England Journal of Medicine (1972)

Among 24 patients with gonadal dysgenesis who had been treated for five or more years with stilbestrol, endometrial carcinoma developed in two and possibly in a third. Three cases of endometrial carcinoma in patients with gonadal dysgenesis have previously been reported by others. Three of the five definite carcinomas were of an unusual mixed, or adenosquamous, type. The cancers were detected at an average age of 31 years. The only reported case of endometrial carcinoma in an untreated patient with primary amenorrhea occurred at the age of 79 years. The early age at occurrence of this unusual type of tumor suggests a carcinogenic role of exogenous estrogens in these patients.
Germline variation of TNFAIP3 in primary Sjögren's syndrome-associated lymphoma
Authors: Gaetane Nocturne, Jessica Tarn, Saida Boudaoud, James Locke, Corinne Miceli-Richard, Eric Hachulla, Jean-Jacques Dubost, Simon Bowman, Jacques-Eric Gottenberg, Lindsey A Criswell, Christopher J Lessard, Kathy L Sivils, Raphael Carapito, Siamak Bahram, Raphaèle Seror, Wan-Fai Ng, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2015)

A germline and coding polymorphism (rs2230926) of TNFAIP3 (A20), a central gatekeeper of nuclear factor-kappa B (NF-kB) activation, was recently found associated with primary Sjögren's syndrome (pSS)-associated lymphoma in a French cohort. We aimed to replicate this association.The rs2230926 polymorphism was genotyped in cases and controls of European ancestry from two independent cohorts from UK and France. Case control association tests were performed (Fisher's test) in the two cohorts, followed by a meta-analysis of the two cohorts.The UK cohort included 308 controls and 590 patients with pSS including 31 with a history of lymphoma. The French cohort consisted of 448 controls and 589 patients with pSS including 47 with lymphoma. In both cohorts, the rs2230926 missense polymorphism was not associated with pSS. However, in the UK cohort, the rs2230926G variant was significantly associated with pSS-associated lymphoma (OR=2.74, 95% CI (1.07 to 7.03), p=0.0423, compared with patients with pSS without lymphoma, and OR=3.12, 95% CI (1.16 to 8.41), p=0.0314, compared with healthy controls) as observed in the French cohort. The meta-analysis of the two cohorts confirmed these results (OR=2.48, 95% CI (1.87 to 3.28) p=0.0037 and OR=2.60, 95% CI (1.91 to 3.53) p=0.0031, respectively).This study confirms the role of A20 impairment in pSS-associated lymphoma. Subtle germline abnormalities of genes leading to impaired control of NF-kB activation in B cells continuously stimulated by autoimmunity enhance the risk of lymphoma.
Impact of Onco<i>Type</i> DXTM Recurrence Score and Tumor Size on Making Chemotherapy Decisions in Breast Cancer Patients.
Authors: M. Goodwin, J. Hughes, M. Diego, T. Frazier
Journal: Cancer Research (2009)

Abstract Background: Oncotype DXTM is a 21 gene assay that calculates recurrence score(RS) and recurrence risk(RR) over 10 years. Despite the contention that this genomic assay is more accurate than tumor size(TS) and age in predicting outcome, these factors continue to have major impact in decision-making regarding chemotherapy(CT). We analyzed the impact of TS, RS, and age on the decision to give CT.Methods: An IRB-approved chart review of 105 lymph node(LN) negative patients with ER+ T1 and T2 tumors was performed, reviewing age, RS, TS, CT history, Her-2 status, and pathology. RS was low(0-17), intermediate(18-30), or high(&amp;gt;30). TS was divided into T1a(0.1-0.5 cm), T1b(0.51–1.0 cm), T1c(1.1–2.0 cm), and T2(2.1-5.0 cm).Results: Mean patient age was 60.9 years(range 35-82 years). Average(AVG) RS was 20.9; AVG RR at 10 years, 13.6%. Mean TS was 1.5 cm(median 1.3 cm). Overall, 29 patients(27.6%) received CT; 76(72.4%) did not. AVG TS for CT patients was 1.8cm, AVG RS was 29.5, and AVG age was 56.4(range 35-75). Non-CT patients' AVG TS was 1.4cm; AVG RS, 17.7; AVG age, 62.6(range 44-86). 9 patients(8.5%) had T1a tumors with an AVG RS of 19.1, and no patient received CT. 25(23.8%) had T1b tumors with an AVG RS of 21.0, and 5(20.0%) received CT. 51(48.6%) had T1c tumors with an AVG RS of 20.4, and 15(29.4%) received CT. 20(19.0%) had T2 tumors with an AVG RS of 23.1; 9(45.0%) received CT. 41 patients(39.0%) had low RS: 4(9.8%) received CT; 37(90.2%) did not. AVG TS and RS were 1.6cm and 15.0 respectively for CT patients, and 1.5cm and 11.6 for no CT patients. 49 patients(46.7%) had intermediate RS: 13(26.5%) received CT; 36(73.5%) did not. AVG TS and RS were 1.9cm and 22.7 for CT patients; 1.3cm and 22.2 for no CT patients. 15 patients(14.3%) had high RS: 12(80.0%) received CT; 3(20.0%) did not. AVG TS and RS were 1.7cm and 44.7 for CT patients; 1.3cm and 39.3 for no CT patients. 10 patients were Her-2+, 5 with high, 4 with intermediate, and 1 with low RS. 7 had CT. 5 of the 15(33.3%) high RS patients were Her-2+. AVG RS for the Her-2+ patients was 36.2, and AVG TS was 1.9cm. AVG RS was 19.3 for the non-Her-2+ patients. 16 patients were &amp;lt;50 years old. AVG TS was 1.5cm and AVG RS was 24.2. 8 received CT and 8 did not. 89 patients were ≥50. AVG TS was 1.5cm and AVG RS was 20.3. 21(23.6%) received CT and 68 did not. Discussion: AVG RS was 20.9 for all T stages. Overall, 27.6% of patients received CT. Of the 64 with RS&amp;gt;18, only 25(39.1%) received CT; 4(9.8%) of low RS patients still received CT. Patients with larger tumors and younger age were more likely to receive CT. Neither RS, TS, nor age alone seemed to influence the final decision. Multiple factors are still considered by oncologists when making CT decisions, and conversely, patients may not accept CT despite high RS. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6039.
Abstract 5071: KGP94, a small-molecule cathepsin L inhibitor with antitumor activity.
Authors: Thomas Wittenborn, Mary Lynn Trawick, Kevin G. Pinney, David J. Chaplin, Dietmar W. Siemann, Michael R. Horsman
Journal: Cancer Research (2013)

Abstract Purpose: Cathepsins are a class of proteolytic enzymes recognized to play an important role in tumour progression, invasion and angiogenesis. The present study evaluated the anti-tumour activity of the small-molecule cathepsin L inhibitor KGP94 in a murine breast tumour model. Materials and Methods: Male CDF1 mice were inoculated on the right rear foot with a C3H mammary carcinoma. A solution of KGP94 was prepared each day by dissolving in a mixture of 10% Tween 80 and 90% HEPES-buffer. It was intraperitoneally injected at 0.01ml/g mouse bodyweight. Various doses (5-20mg/kg) were administered between 5-20 days, starting either from the day of tumour implant or when tumours had reached a volume of 200mm3. Tumour response was assessed by determining the tumour growth time, which was either the time in days to reach a volume of 500mm3 (TGT500) for animals treated from the day of tumour implant, or 1000mm3 (TGT1000) for animals treated when tumours were at a volume of 200mm3. Results are listed as Mean (± Standard Error). One-way ANOVA with a posthoc Student-Newman-Keuls comparison of group means was performed, and a P&amp;lt;0.05 was considered significant. Results: The TGT500 for control animals was 18.3 days (± 0.4). Treating tumours with 10mg/kg for 5 days significantly increased the TGT500 to 21.9 days (± 0.7). When the time of treatment with this dose was increased to 10 or 20 days, no additional growth inhibition was observed. Varying the drug dose for this 5 days treatment period showed that the TGT500 with 5mg/kg and 20mg/kg were 23.5 days (± 1.9) and 23.4 days (± 1.1), respectively. For experiments in which treatments were started when tumours had already reached 200mm3 an effect on TGT1000 was only observed with the highest drug dose at 20mg/kg; the respective TGT1000 being 5.9 days (± 0.2) for controls and 8.3 days (± 0.7) for KGP94. Conclusion: This synthetic, small-molecule cathepsin L inhibitor significantly delayed tumour growth, but the effect was primarily on the early phase following tumour inoculation. Such an effect suggests that KGP94 may have a role to play in inhibiting metastatic development rather than influencing the growth of established tumours. Supported by The Danish Cancer Society, The Danish Council for Independent Research: Medical Sciences, and OXiGENE Inc. Citation Format: Thomas Wittenborn, Mary Lynn Trawick, Kevin G. Pinney, David J. Chaplin, Dietmar W. Siemann, Michael R. Horsman. KGP94, a small-molecule cathepsin L inhibitor with antitumor activity. [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 5071. doi:10.1158/1538-7445.AM2013-5071
OC-063 Pain and Anxiety Experienced by Patients following Peg Placement: Abstract OC-063 Table 1
Authors: P Oppong, N Pitts, V Chudleigh, S Lewis
Journal: Gut (2013)

Introduction Abdominal pain following percutaneous endoscopic gastrostomy (PEG) placement is a recognised complication considered to be secondary to a chemical peritonitis. However, the prevalence and degree of severity of pain is poorly characterised. Abdominal pain following liver biopsy is strongly linked to preprocedural anxiety levels1. We assessed abdominal pain and anxiety associated with PEG placement. Methods A prospective questionnaire assessed patient anxiety and abdominal pain 1 hour (h) pre PEG placement, 1h post and 24h post using a 10-point Likert scale. The questionnaire was completed by the patient where possible or clinician if not. Abdominal pain was assessed by examination at 1h post procedure. 24h post procedure complications and analgesia requirements were recorded. Patient’s Mini Mental Score (MMSE, 0–30) and Barthel index (0–20) were completed. Results 70 consecutive patients (M:F 45:25) median age 61.5 (19–94) were assessed. The commonest indications were head and neck malignancies (44%) and stroke (11%). PEG placement was on first attempt in 68 cases, with no clinical complications. Mean (StD), MMSE, Barthel, anxiety and pain scores. 24 self-reporting patients had a pain score of 1–3 at 1h post placement and 20 at 24 h. 3 patients reported a pain score of 7–10 at 1 h post placement and 7 at 24 h. 21/49 self-reporting patients and 0/21 non self-reporting had PEG site and/or general abdominal tenderness on clinical examination at 1h. Pain post PEG placement was noted in only 1 clinician-assessed patient. This was at 24 h. 50.7% of patients took analgesia at 24 hours post procedure (all self-reporting). Regression showed no relationship between pre placement anxiety and post placement pain. View this table: Abstract OC-063 Table 1 Conclusion Pain at 1h post PEG placement was common in self-reporting patients and usually mild. By 24h, 41% reported moderate to severe pain often taking analgesia. Preprocedural anxiety did not predict post procedural pain. Clinician examination of all patients at 1h did correlate with self-reported discomfort or predict self reported pain at 24h. Clinician assessment at 1h and 24h where patients could not self assess failed to identify pain. After PEG placement patients should be offered advice on pain and given access to analgesia. It is likely that pain is not identified in debilitated patients and clinicians need to be more alert to its possible presence. Disclosure of Interest None Declared Reference 1. Riley T. Predictors of pain medication use after percutaneous liver biopsy. Digest Dis Sci 2002; 47:2151–53.
PATIENTS WITH GENOTYPE-POSITIVE HYPERTROPHIC CARDIOMYOPATHY ARE AT INCREASED RISK OF HEART FAILURE RELATED DEATH
Authors: H.G. van Velzen, P.A. Vriesendorp, R.A. Oldenburg, M.A. van Slegtenhorst, A.F.L. Schinkel, M. Michels
Journal: Journal of the American College of Cardiology (2015)