tbuckley/cabot-search huggingface dataset:
Abstract LB-48: Cooperation of NF-κB, STAT3 and p300 on the growth and survival of plasma-cell neoplasia
Authors: Seong-Su Han, Dong-Ju Son, Kaylia Duncan, Siegfried Janz
Journal: Cancer Research (2011)

Abstract Collaboration of pro-inflammatory cytokine, interleukin 6 (IL-6), with oncogenic transcription factor, MYC, has been implicated in the natural history of human B-cell and plasma-cell neoplasms such as multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). To generate a mouse model of IL-6/MYC-driven B-lineage tumors, we intercrossed strain C.H2-Ld-IL6 mice, which carry a human IL6 cDNA gene under control of the major histocompatibility complex (MHC) H2-Ld promoter, with strain C.iMycEμ and C.iMycCα mice, which harbor a gene-insertion mutation that recapitulates the chromosomal T(12;15) translocation leading to deregulated expression of MYC in mouse plasmacytoma (PCT). Double-transgenic C.IL6/iMycEμ and C.IL6/iMycCα mice develop PCT with full penetrance (100% tumor incidence), short latencies (3–6 months) and remarkable phenotypic consistency. To test the hypothesis that nuclear factor-κB (NF-κB) signaling plays a role in malignant plasma-cell transformation in these mice, we performed electrophoretic mobility shift assays (EMSA) using splenic B cells from C.IL6/iMycΔEμ mice. We found that the splenocytes contained elevated levels of NF-κB and signal transducer and activator of transcription 3 (STAT3) DNA-binding activities compared to normal splenic B cells used as control. Super-shift assays demonstrated that in addition to p50, p65 and c-Rel (indicators of canonical NF-κB pathway activation), RelB was involved. This suggested the additional activation of alternative NF-kB signaling. NF-kB, pSTAT3 and co-transcription factor, p300, were shown to be physically associated in transgenic B cells. Ongoing studies are aimed at elucidating whether NF-κB/STAT3/p300 signaling underlies up-regulation of c-myc level in the course of PCT development. Using qPCR we also found that p21 – which is usually known as a tumor suppressor and direct target of NF-κB, STAT3, p53 and MYC – exhibited increased p53-independent expression in B cells obtained from C.IL6/iMycΔEμ mice, but not from C.IL6 or iMycΔEμ mice. In contrast, the expression of Aurora kinase A, a direct upstream regulator of both NF-kB and E2F1, was strongly up-regulated in B cells from C.IL6/iMycΔEμ, C.IL6 and iMycΔEμ mice. Likewise, E2F1, a direct upstream regulator of p21, and E2F3, a direct upstream regulator of both p21 and Aurora kinase A, were upregulated. Our findings suggest that p21 is up-regulated, either directly or indirectly, through Aurora kinase A and/or NF-κB/STAT3/p300 complex. Furthermore, they indicate the usefulness of the newly developed IL-6/MYC mouse tumor model for identifying potential targets for the treatment and prevention of MM and WM. 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 LB-48. doi:10.1158/1538-7445.AM2011-LB-48
P70 Does meeting the clinical criteria for the systemic inflammatory response syndrome equate to biochemical inflammation following cardiac surgery?
Authors: F. M. Conway, S. E. Gordon, G. J. Quinlan, T. W. Evans, N. S. MacCallum
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> The systemic inflammatory response syndrome (SIRS) criteria were developed in part as entry criteria for clinical trials of generalised inflammation from various causes. Despite being commonly used to assess inflammation in cardiac surgery, no one has evaluated whether the clinical defining criteria for inflammation equate to biochemical inflammation in this patient population. Our aim was to investigate whether the SIRS criteria equate to established biochemical indices of inflammation following cardiac surgery. <h3>Methods</h3> Retrospective analysis of prospectively collected data from an adult intensive care unit of a specialist cardiothoracic centre in the UK. 93 adult patients undergoing cardiac surgery admitted over a 34-month period between March 2004 and January 2007 were included. Patients were scored on the SIRS criteria from before to 72 h post-surgery. ELISAs were performed on archived plasma samples taken before surgery and at 4, 24, 48 and 72 h post-operatively to determine concentrations of IL-1ß, IL-1RA, IL-6, IL-8, IL-10, myeloperoxidase (MPO) and C reactive protein (CRP). <h3>Results</h3> Significantly elevated levels of all inflammatory indices were detected post-operatively with the exception of IL-1ß. Patients meeting SIRS criteria demonstrated higher levels of IL-6, IL-1RA and CRP compared to those who did not meet the criteria. An absence or only weak correlation was found between SIRS and mass of biomarker. <h3>Conclusions</h3> The clinical defining criteria for inflammation (SIRS criteria) do not equate to established biochemical indices of inflammation in cardiac surgery patients; hence the criteria alone should not be used to assess inflammation in this patient population.
AB0958 Assessment of quality of life in patients undergoing total joint replacement for OA of the lower limb
Authors: A. Neuprez, G. François, O. Bruyère, V. Kovats, T. Thirion, H. Van Cauwenberge, C. Daniel, P. Gillet, J.-Y. Reginster
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoarthritis is a major burden worldwide. <h3>Objectives</h3> Arthritic conditions are extremely painful for the patient and are associated with a significant reduction in health related quality of life (HRQOL), mainly in term of physical and functional impairment. Therefore, the demand for total joint replacement (TJR) is increasing. The objective of the present study was to access the clinical profil of osteoarthritic patients undergoing of total joint replacement. <h3>Methods</h3> We analyzed the clinical status of 443 consecutive patients (180 men and 263 women) undergoing total joint replacement for symptomatic osteoarthritis of the lower limb aged from 22 to 86 years (mean 65,5±10,4). Generic HRQOL was assessed with the Short-Form 36 (SF36). This questionnaire was administered preoperatively. <h3>Results</h3> 249 of them received a total hip arthroplasty (THA) and 194 a total knee arthroplasty (TKA). The mean duration of OA was 3004.4 days ±3286.4 (SD) or 8.2 years ±9 years. They were all diagnosed with primary OA following the ACR criteria. We calculated the various dimensions of a validated tool for the assessment of quality of life, the short form 36 (SF-36). The results were (mean ± SD/lower score on the SF 36 reflect poorer health): <h3>Conclusions</h3> We concluded that patients undergoing total joint replacement in university setting, in Belgium, have a significant impairment in QO mainly affecting these two variables: "role limitations due to physical problems" and "pain". <h3>Disclosure of Interest</h3> None Declared
Auditory Fatigue and Predicted Permanent Hearing Defects from Rock-and-Roll Music
Authors: Frederick L. Dey
Journal: New England Journal of Medicine (1970)

Recordings of music played by a typical rock band in a discotheque for young adults showed that sound-pressure levels in the octaves most damaging to hearing were of the order of 105 decibels (db). Tape loops of this sound were then presented by earphone to 15 young men with normal hearing at levels of 100 and 110 db for five to 120 minutes. With the use of temporary hearing threshold shifts of 40 db (after two minutes of recovery) as a damage-risk criterion, the data indicated that, after listening for two hours to such music at 100 db, two persons in 100 would recover far too slowly, whereas at 110-db, 16 percent would be adversely and probably permanently affected.
PWE-190 Outcome of Investigations for Iron Deficiency Anaemia in Men under 50 Years
Authors: O D Patani, S Bharathi, S Khalid
Journal: Gut (2013)

<h3>Introduction</h3> Iron-deficiency anaemia (IDA) occurs in 2–5% of men and postmenopausal women in the developed world. IDA is commonly due to blood loss from lesions in the gastrointestinal (GI) tract and malabsorption, accounting for 4–13% of referrals to gastroenterologists. In men over the age of 50 years and postmenopausal women there is established data on the incidence of GI pathologies causing IDA but such data for men under 50 years of age is not as robust. We carried out a retrospective analysis of outcomes of investigations for IDA in men under the age of 50 years over a period of 10 years in our hospital serving about 325,000 population. <h3>Methods</h3> Through the audit and clinical code department all male patients between 17 and 50 years of age investigated for IDA from 2000–2010 were identified retrospectively. The criteria used for diagnosis of IDA included haemoglobin level below the lower limit of normal, low ferritin and corresponding abnormalities of red cell indices. Data on outcome of investigations for IDA was collected from patient case notes and endoscopy, radiology and pathology records. <h3>Results</h3> 52 patients were identified over the study period. The median haemoglobin was 9.3g/dl. The median age of the patients was 44 years. 44/52 (85%) had investigations recorded. 18/52 (33%) had gastroscopy (OGD) only. 26/52 (48%) had both OGD and colonic investigations. 7/52 (13%) had further investigations following normal bi-directional endoscopy including bone marrow, small bowel barium studies, capsule endoscopy and abdominal ultrasound with none of these additional investigations yielding further diagnostic information. With regards to colonic investigations 21/26 (81%) had colonoscopy, 3/26 (11%) had barium enema plus flexible sigmoidoscopy and 2/26 (8%) had CT scan. The findings of OGD were normal investigation 25/44 (57%), oesophagitis 5/44 (12%), peptic ulcer disease (PUD) 4/44 (9%), hiatus hernia 4/44 (9%), oesophageal cancer 1/44 (2%) and coeliac disease 2/25 patients with duodenal biopsies at OGD. The findings of lower GI investigations were normal investigations 16/29 (55%), haemorrhoids 5/29 (17%), inflammatory bowel disease (IBD) 3/29 (10%), polyps 2/29 (7%), colorectal cancer 2/29 (7%) and diverticulosis 1/29 (4%). <h3>Conclusion</h3> Significant findings including PUD, malignancy and IBD constituted 19.2%. Malignancy accounted for 5.8% and this was comparable with previously reported prevalence of GI malignancy in patients with IDA (6–13%). In addition a proportion of investigations also yielded other diagnosis including oesophagitis and coeliac disease. Therefore it will be justified to investigate men under 50 years with IDA similarly to those over 50 years and postmenopausal women as suggested in most international guidelines <h3>Disclosure of Interest</h3> None Declared.
Abstract 2915: p53 isoforms Δ133p53 and p53β are endogenous regulators of replicative cellular senescence
Authors: Kaori Fujita, Abdul M. Mondal, Izumi Horikawa, Giang H. Nguyen, Kensuke Kumamoto, Jane J. Sohn, Elise D. Bowman, Mathe A. Mathe, Aaron J. Schetter, Sharon R. Pine, Helen Ji, Borivoj Vojtesek, Jean-Christophe Bourdon, David P. Lane, Curtis C. Harris
Journal: Cancer Research (2010)

Abstract The finite proliferative potential of normal human cells leads to replicative cellular senescence, which is a critical barrier to tumor progression in vivo. The p53 signaling pathway plays central roles in the regulation of cellular senescence. Humans, as well as Drosophila and zebrafish, have p53 isoforms; however, their regulation and function are poorly understood. We here examine the expression profiles of two human p53 isoforms, p53β (lacking the C-terminal oligomerization domain due to an alternative mRNA splicing) and Δ133p53 (lacking the N-terminal transactivation and proline-rich domains due to the transcription from an alternative promoter in intron 4), during in vitro and in vivo cellular senescence and their biological activities in regulating cellular senescence. Induced p53β and diminished Δ133p53 were associated with replicative senescence, but not oncogene-induced senescence, in normal human fibroblasts. The replicatively senescent fibroblasts also expressed increased levels of miR-34a, a p53-induced microRNA, the antisense inhibition of which delayed the onset of replicative senescence. The siRNA-mediated knockdown of endogenous Δ133p53 induced cellular senescence, which was attributed to the regulation of p21WAF1 and other p53 transcriptional target genes. In overexpression experiments, while p53β cooperated with full-length p53 to accelerate cellular senescence, Δ133p53 repressed miR-34a expression and extended cellular replicative lifespan, providing a functional connection of this microRNA to the p53 isoform-mediated regulation of senescence. The senescence-associated signature of p53 isoform expression (i.e., elevated p53β and reduced Δ133p53) was observed in vivo in colon adenomas with senescent phenotypes. The decreased p53β and increased Δ133p53 expression found in colon carcinomas might signal an escape from the senescence barrier during the progression from premalignant to malignant tumors in vivo. This study shows that natural p53 isoforms constitute an endogenous regulatory mechanism for p53-mediated replicative senescence and may open up a new p53-based, senescence-mediated strategy to manipulate carcinogenesis and aging. The molecular details of the senescence-associated Δ133p53 repression and p53β induction are currently under investigation. 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 2915.
P415Effect of erythrocytes indexes and plasma aldosterone concentration on development of left ventricle hypertrophy in hypertensive men:
Authors: MV Krestjyaninov, VI Ruzov, RH Gimaev
Journal: Cardiovascular Research (2014)

In the last decade, the number of hypertensive patients continues to increase in the world. Experimental and clinical studies have shown that ischemic or hypertrophied myocardium is more sensitive for a slight decrease in haemoglobin levels than the unmodified myocardium which causes dysfunction of the heart. At the same time there are no studies devoted to the investigation of the relations between erythrocyte homoeostasis indicators (in the frontiers of the normal values) and hypertensive remodelling of LV. Also well known the role of aldosterone in the development of LV remodelling and it the influence on the state of erythrocyte homoeostasis. The purpose of the study is to identify relationships between PAC, state of erythrocyte homoeostasis and hypertensive remodelling of the heart. Were enrolled 30 men and 20 women with arterial hypertension 2 grade complicated by HF I-II NYHA functional class. The age of men - 48 (42;52) years, women - 50 (42; 53). Patients with symptomatic hypertension, arrhythmias, diabetes mellitus, haematological disorders were excluded from the study. In all patients were carried determination of mean corpuscular haemoglobin concentration (MCHC, g%) as one of the most informative indicators of the state of erythrocyte homoeostasis and plasma aldosterone concentration (PAC) (pg/ml). Echocardiography was performed according to ASE/EAE recommendations 2005. Statistical significance was defined at the level of methods for p<0,05. Results of measurements of MCHC and aldosterone levels are shown in Table 1. Performing of regression analysis revealed the combined effect of MCHC and PAC on development of left ventricular hypertrophy in men (ILVmass=-607.7+0.369*PAC+0.6*MCHC; R2= 0,7, p= 0.0016), but not in women (ILVmass=-365+0.1*PAC+0.173*MCHC; R2=0.05, p=0.73). Thus, in hypertensive men was observed combined effect of MCHC and PAC on the development of left ventricular hypertrophy. Results are shown in M (SD). ILV mass - left ventricle mas index * - p<0.05 in comparison with men Results are shown in M (SD). ILV mass - left ventricle mas index * - p<0.05 in comparison with men
Comparison of the Effects of Oat Bran and Low-Fiber Wheat on Serum Lipoprotein Levels and Blood Pressure
Authors: J F Swain, I L Rouse, C B Curley, F M Sacks
Journal: New England Journal of Medicine (1990)

Previous studies have shown that supplementation of the diet with oat bran may lower serum cholesterol levels. However, it is not known whether oat-bran diets lower serum cholesterol levels by replacing fatty foods in the diet or by a direct effect of the dietary fiber contained in oat bran. To determine which is the case, we compared the effect of isocaloric supplements of high-fiber oat bran (87 g per day) and a low-fiber refined-wheat product on the serum lipoprotein cholesterol levels of 20 healthy subjects, 23 to 49 years old. After a one-week base-line period during which they consumed their usual diets, the subjects were given each type of supplement for six-week periods in a double-blind, crossover trial.
Abstract 5113: Filopodial actin machinery cooperates with microtubules and vimentin intermediate filaments in the elongation of invadopodia
Authors: Marie Schoumacher, Daniel Louvard, Danijela Vignjevic
Journal: Cancer Research (2010)

Abstract Invasive cancer cells breach the basement membrane (BM) using specialized protrusions, called invadopodia. Here, we found that the crossing of a native BM is a three-stage process: invadopodia form and perforate the BM; elongate into mature invadopodia; and then guide the cell towards the stromal compartment. We have studied the remodeling of cytoskeleton networks during invadopodia formation and elongation using ultrastructural analysis, spatial distribution of molecular markers and RNAi silencing of protein expression. We show that formation of invadopodia requires only the actin cytoskeleton, both filopodia- and lamellipodia-associated proteins. On contrary, using a novel in vitro assay, we demonstrate that elongation of invadopodia is mostly dependent on filopodial actin machinery, microtubules and vimentin intermediate filaments. These findings indicate that invadopodia form by assembly of dendritic/diagonal and bundled actin networks and then maturate by elongation of actin bundles together with the infiltration of microtubules and vimentin intermediate filaments. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5113.
Abstract 1830: Cancer-associated variants at 8q24 are correlated with expression of adjacent long non-coding RNAs involved in cell cycle regulation.
Authors: Taewan Kim, Carlo M. Croce
Journal: Cancer Research (2013)

Abstract The mechanism by which cancer risk variants at 8q24.21 increase cancer risk is unclear for lack of protein-coding genes in the region, although such variants have been strongly associated with cancer development. By sequencing three colorectal cancer-associated variants and examining the expression levels of the lncRNAs at 8q24.21, we show that expression of long non-coding RNAs (lncRNAs) in the region is correlated with risk alleles of the cancer-associated variants. We further report that the lncRNAs regulate cell cycle by modulating expression of cell cycle-related genes such as CDKN1A and GADD45, suggesting the potential oncogenic functions of the lncRNAs. Our data provide new insight of disease-related variants in a gene desert. Citation Format: Taewan Kim, Carlo M. Croce. Cancer-associated variants at 8q24 are correlated with expression of adjacent long non-coding RNAs involved in cell cycle regulation. [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 1830. doi:10.1158/1538-7445.AM2013-1830
Lapatinib (L) with weekly paclitaxel (P) as first-line therapy for patients (pts) with HER2+ metastatic breast cancer (MBC).
Authors: A Jagiello-Gruszfeld, S Tjulandin Sergei, N Dobrovolskaya, A Manikhas, T Pienkowski, A Knott, M DeSilvio, C Oliva
Journal: Cancer Research (2009)

Abstract Abstract #3145 L, an oral tyrosine kinase inhibitor of EGFR/HER2, is active as monotherapy and in combination with chemotherapy for HER2+ MBC. In a planned subgroup analysis of a Ph III trial, EGF30001, L (1500mg QD) + P (175mg/m2 q3w), significantly improved overall response rate (ORR) and progression free survival (PFS) compared with P alone as initial therapy for HER2+ MBC. Here we report final results of a phase II, single-arm multicenter trial, EGF105764, assessing activity of L with weekly P in first line MBC.&amp;#x2028; Methods: Safety and efficacy of L (1500 mg QD)+P (80 mg/m2/wk x 3q wk) was evaluated in 57 pts with newly diagnosed, HER2 FISH+, Stage IV MBC. Primary endpoint was ORR.&amp;#x2028; Results and Discussion: All pts had ECOG PS ≤1, no pt received previous trastuzumab but 61% received prior adjuvant/neo-adjuvant chemo- or anti-hormonal therapy. Median time from prior chemotherapy was 63 weeks. No patient had suspected baseline CNS disease. At time of data cut-off, 41 (72%) pts progressed or withdrawn. The median duration of L treatment was 45 (range 2-87) wks, and 26 (range 0 to 80) wks for P. The investigator-assessed ORR was 77% (44/57), with 3 CR and 41 PR, (95% CI: 64.2, 87.3) with a median duration of response (DoR) of 42.3 wks (95% CI: 37.7, 64.1). The independently confirmed ORR was 51% (29/57), with 0 CR and 29 PR, (95% CI: 37.3, 64.4) with a median DoR of 39.7 wk (95% CI: 26.9, 50.0). CNS relapse was reported in 4/41 pts (10%). Most common AEs were diarrhoea (56%, ≥gr3: 5%), neutropenia (44%, ≥gr3: 26%), rash (40%, ≥gr3: 3%), fatigue (25%, ≥gr3: 0%), and neurological (25%, ≥gr3: 0%). Four pts had 1 dose reduction of L (2 due to diarrhoea) and 19 pts had ≥1 dose delay (6 due to diarrhoea). Dose reductions for P occurred in 7 pts; 45 pts had ≥1 dose delay (63% due to toxicity). There were no protocol defined LVEF decreases.&amp;#x2028; In the 86pt subset with HER2+ tumors in EGF30001, the investigator reported ORR was 63% in the L+q3w P and 38% for P+placebo. The safety profile of L+P used qw or q3w is comparable: diarrhoea all grades (56% vs 58%), rash all grades (40% vs 43%), and neurological events all grades (25% vs 26%). Neutropenia (all grades) was more common in the qw schedule of P (44% vs 26%), but the incidence of ≥gr3 was comparable (26% vs 21%, for qw vs 3qw respectively).&amp;#x2028; Conclusions: L + weekly P as first-line therapy for HER2+ MBC was well tolerated and produced a high, investigator assessed ORR of 77%. These data suggest that the combination of L and P (at any schedule) may be an option for newly diagnosed patients with HER2+ MBC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3145.