tbuckley/cabot-search huggingface dataset:
P3-01-11: Increased Gene Copy Number of c-KIT and VEGFR2 at 4q12 in Primary Breast Cancer Is Related to an Aggressive Phenotype and Impaired Prognosis.
Authors: L Rydén, I Johansson, A Ebbesson, D Grabau, C Wigerup, KE Aaltonen, I Hedenfalk
Journal: Cancer Research (2011)

Abstract Introduction: Triple-negative breast cancer (TNBC) accounts for approximately 15% of all female breast cancer and is associated with aggressive clinical behaviour. No targeted treatments are available for TNBC. Drugs inhibiting tyrosine kinases, such as vascular endothelial growth factor receptor 2 (VEGFR2) and c-KIT, have however shown some promising results for patients with TNBC. The aim of the present study was to investigate whether gains and/or amplifications of VEGFR2 and c-KIT occur in TNBC. These genes may constitute novel candidate biomarkers for selecting TNBC patients for treatment with tyrosine kinase inhibitors. Material &amp; Methods: Fluorescence in situ hybridization (FISH) was used to quantify gene copy numbers of VEGFR2 and c-KIT in 83 primary human breast cancers, of which 31 were classified as TNBC. Gains were defined as ≥4 gene copies in more than 40% of the cancer cells, while amplification was defined as gene copy/CEP ratio &amp;gt;2 in more than 10% of the cancer cells. A tumour was considered FISH positive for c-KIT and/or VEGFR2 if it displayed copy number gain and/or amplification. Immunohistochemical (IHC) staining was performed for assessment of c-KIT protein expression. Results: Ten (32%) of the TNBCs were VEGFR2 FISH positive and nine (29%) were c-KIT FISH positive, whereas non-TNBCs were FISH positive for VEGFR2 and c-KIT in nine (18%) cases for both genes. No significant difference in frequency between TNBCs and non-TNBCs was found. There was a correlation between FISH positivity for VEGFR2 and c-KIT (c2 test, P&amp;lt;0.001), and VEGFR2 and c-KIT FISH positivity correlated to ER/PgR negativity and high Nottingham histological grade (NHG). A significantly worse breast cancer specific survival (BCSS) was seen for FISH positive cases in the whole cohort as well as among untreated patients and non-TNBCs, but not among TNBC cases. Discussion: The high correlation between VEGFR2 and c-KIT FISH positivity suggests that the genes are co-amplified. Increased copy number of both genes was related to aggressive disease and a worse prognosis, and thus has the potential of functioning as a novel predictive biomarker for selected targeted therapy particularly in the difficult-to-treat TNBC patient category. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-01-11.
Diagnosis of polypoid portal hypertensive enteropathy due to superior mesenteric vein thrombosis by capsule endoscopy and double-balloon enteroscopy
Authors: Faidon-Marios Laskaratos, Christos Toumpanakis, Ian Clark, Peter Wylie, Sanjay Bhagani, Edward Despott
Journal: Endoscopy (2014)

A 46-year-old man with recently controlled retroviral infection was referred to our Neuroendocrine Tumour Unit for further investigation of recent onset, refractory ascites and a long-standing but stable mesenteric mass of indeterminate cause. There was no evidence of chronic liver disease. Analysis of the ascitic fluid revealed chylous ascites. Computed tomography of the abdomen showed a 2.6-cm mesenteric mass with associated desmoplasia encasing the superior mesenteric vein, ascites, and edema of the small bowel ([Fig. 1]). Although the radiologic appearances supported the presence of a neuroendocrine tumor, the results of biomarker (chromogranin A) and molecular imaging studies (octreotide scan, fluorodeoxyglucose positron emission tomography, and gallium Ga 68 octreotate positron emission tomography) were all negative. Small-bowel capsule endoscopy demonstrated features of segmental portal hypertension with mucosal congestion and multiple pseudopolyps ([Fig. 2]) but no primary small-bowel tumor. Anterograde double-balloon enteroscopy confirmed the presence of a congested jejunal mucosa with lymphatic oozing ([Fig. 3]). Multiple polypoid lesions were observed ([Fig. 4], [Fig. 5]) within parts of the jejunum, and histologic examination of one of these lesions, retrieved at double-balloon enteroscopy, showed villous thickening and the proliferation of small blood vessels with edema of the lamina propria, in keeping with polypoid portal hypertension enteropathy ([Fig. 6]). Radiologic and surgical interventions (superior mesenteric vein stent insertion and portosystemic anastomosis, respectively) were not technically feasible, and the patient's refractory chylous ascites was therefore successfully managed with a trial of octreotide (Sandostatin; Novartis Pharmaceuticals, Basel, Switzerland).
PREDICTION OF THE SEVERITY OF SEGMENTAL ASYNERGY BY QUANTIFICATION OF REGIONAL MYOCARDIAL PERFUSION.
Authors: Georges Baillet, F. Mathonnat, C. Adams, C. LePailleur, J. P. Metzger, P. Albarede, A. Vacheron
Journal: Clinical Nuclear Medicine (1986)

Baillet, Georges; Mathonnat, F.; Adams, C.; LePailleur, C.; Metzger, J. P.; Albarede, P.; Vacheron, A. Author Information
Abstract P4-07-06: Yes-Associated Protein, a Proposed Tumour Suppressor, Is Inversely Correlated to Cyclin D1 in Breast Tumours and Associated with a Worse Prognosis
Authors: S Lehn, NP Tobin, AH Sims, K Jirström, G. Landberg
Journal: Cancer Research (2010)

Abstract Background: In breast cancer, cyclin D1 over-expression and CCND1 (11q13) gene amplification have been linked to a worse prognosis. Conversely, lower levels of cyclin D1 have also been correlated to an unfavourable outcome. In a microarray analysis of cyclin D1 silenced MDA-MB-231 cells we identified Yes-associated protein (YAP), located at 11q22, as one of the most down-regulated genes. As such, we aimed to determine the importance of YAP in relation to cyclin D1 in breast cancer biology. Material and methods: Validation of cyclin D1, YAP antibodies and protein levels were performed in MDA-MB-231, MDA-MB-468 and MCF-7 by western blot. YAP protein expression was examined by screening 144 breast tumours and gene expression assessed by meta-analysis of six previously published breast cancer datasets totalling 1107 tumours with clinical follow-up. Subsequent data analysis was performed in SPSS. Results: YAP protein levels were down-regulated in cyclin D1 silenced MDA-MB-231, MDA-MB-468 and MCF-7 cell lines as predicted by microarray analysis. Surprisingly, YAP and cyclin D1 were inversely correlated at both protein and gene level in primary tumours (p=0.004 and P&amp;lt;0.001). Amplification of the CCND1 gene was correlated to low YAP protein expression (P&amp;lt;0.001) in the screening tumour material. Low YAP mRNA was an independent prognostic factor of recurrence (HR= 1.30, 95% CI 1.009-1.678, p=0.043) in the gene expression dataset. This effect was particularly pronounced in the luminal A subtype of breast tumours. Discussion: The independent prognostic value of YAP strengthens the notion of this protein as a tumour suppressor in breast cancer. The regulation of YAP by cyclin D1 appears to occur on both the protein level as seen in cell lines, and on the chromosomal level in terms of 11q aberrations. The inverse correlation observed in the tumour materials between cyclin D1 and YAP may be partly explained by chromosomal rearrangements; the amplification of the CCND1 gene (11q13) is often accompanied by loss of the 11q22 region of the chromosome, harbouring the YAP locus. Further studies are ongoing to clarify the link between YAP and cyclin D1 in breast cancer biology. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-07-06.
Absolute Quantitative Evaluation of 67Ga Scintigraphy in Lupus Nephritis
Authors: Shih-Chuan Tsai, Tsu-Yi Hsieh, Ping-Wun Huang, Wan-Yu Lin
Journal: Clinical Nuclear Medicine (2016)

Renal biopsy is crucial for management of lupus nephritis. However, it is invasive and can cause bleeding and infection. In our previous study, we developed a semiquantitative method for gallium renal imaging and demonstrated a good correlation between the left kidney-to-spine ratio (K/S ratio) and the results of renal biopsy. However, the accuracy of left K/S ratio is compromised by the variation of spinal gallium uptake, especially in patients with extraordinarily high or low gallium uptakes in the spine. In this study, we developed an absolute quantitative method and compared the results of quantitative gallium images, semiquantitative gallium images, visual methods, and renal biopsies.Thirty-four patients with lupus nephritis were enrolled and underwent renal biopsy to determine activity index (AI) and chronicity index. A delayed 48-hour gallium scan was also performed and interpreted by visual, semiquantitative, and absolute quantitative methods. For absolute quantitative analysis, a standard solution with activities of approximately 555 KBq (15 μCi) was prepared and poured into a 5-mL tube, which was placed close to the patient. ROIs were drawn around the outer edge of the left kidney as well as around the outer edges of the standard. A kidney uptake index (KUI) was calculated, and the results were compared with K/S ratio, visual grading, and renal biopsies.Kidney uptake index had the best correlation with AI among the 3 methods using Spearman rank correlation test. The Spearman R values were 0.78, 0.71, and 0.61 for KUI, K/S ratio and visual grading, respectively. Chronicity index did not correlate well with the results of any of the 3 methods. In addition, AI was significantly higher in patients with a KUI equal to or greater than 1.5, when compared with patients with a KUI lower than 1.5 (P = 0.00001 by Mann-Whitney U test). Using a K/S ratio of 0.95 as a cutoff value, AI also showed a statistically significant difference with P = 0.0001. When a visual grading of 2 was used as a cutoff value, P = 0.0008. The difference in AI was most significant when the statistical value was based on the KUI.The KUI showed better correlation with the results of renal biopsy than the K/S ratio and the visual grading. We suggest that the KUI from the absolute quantitative renal gallium scintigraphy may be a useful parameter for evaluating the disease activity in lupus nephritis.
T-TYPE CALCIUM CHANNEL BLOCKER EXERTS SIMILAR EFFICACY AS IRON CHELATORS IN ATTENUATING CARDIOVASCULAR AND MITOCHONDRIAL DYSFUNCTION IN IRON-OVERLOAD THALASSEMIC MICE
Authors: Sirinart Kumfu, Siriporn Chattipakorn, Suthat Fucharoen, Nipon Chattipakorn
Journal: Journal of the American College of Cardiology (2015)
SAT0298 Systematic review and network meta-analysis of biological therapy for the management of active psoriatic arthritis:
Authors: D. Spurden, M. Orme, S. Mitchell, A. Bird
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Psoriatic arthritis (PsA) is a chronic systemic inflammatory disease with articular and dermatological manifestations. PsA varies in severity and type of tissue involvement and may significantly impact patients' function and quality of life. <h3>Objectives</h3> To determine the relative effectiveness of UK licensed biological disease-modifying anti-rheumatic drugs (bDMARDs) for the treatment of active, progressive PsA in patients with inadequate response to previous DMARDs. <h3>Methods</h3> A systematic review was conducted to identify relevant randomised controlled trials (RCTs) of bDMARDS. The main outcomes of interest included number of patients meeting Psoriatic Arthritis Response Criteria (PsARC) at follow-up and change in Health Assessment Questionnaire (HAQ) score from baseline conditional on PsARC response. Literature searches were conducted in relevant electronic databases and the grey literature. Data were extracted by two independent reviewers. A Bayesian network meta-analysis (NMA) was conducted in WinBUGs using a fixed and random-effects logit model fitted to the binomial data and an identity model for the continuous data. <h3>Results</h3> 2,099 citations were identified and on reviewing full-text papers, 30 publications of 12 studies met the criteria for inclusion in the review. On review of the dataset, seven placebo-controlled studies of licensed bDMARDs were included in the NMA: two studies of adalimumab (ADA) 40 mg every other week (n=204) vs PLA (n=211); two studies of etanercept (ETN) 25 mg twice weekly (n=131) vs placebo (PLA) (n=134); one study of golimumab (GOL) 50 mg every 4 weeks (n=146) vs PLA (n=113) (plus unlicensed arm: not shown); and two studies of infliximab (IFX) 5 mg/kg (n=152) vs PLA (n=152). The table summarises the fixed-effect NMA results for PsARC, and change in HAQ (for all patients and conditional on PsARC response) based on 12 to 16 week follow-up data. Similar results were obtained with random-effects NMA and results were subject to a sensitivity analysis. <h3>Conclusions</h3> In these selected studies, all bDMARDs were significantly more effective than placebo in achieving PsARC response in patients with active PsA. Of the studies included in the analysis, ADA, ETN and IFX were significantly more effective than placebo in improving HAQ scores in all patients regardless of PsARC response and in subgroups who achieved a PsARC response and PsARC non-responders. <h3>Disclosure of Interest</h3> D. Spurden Employee of: Pfizer Ltd, M. Orme Consultant for: Pfizer Ltd, S. Mitchell Consultant for: Pfizer Ltd, A. Bird Employee of: Pfizer Ltd.
AB0037 Antibodies to Mitotic Apparatus: Prevalence Andassociateddiseases
Authors: V. Pascual, G. Candelas, A. Comins, M. Nuñez, S. Sanchez
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The mitotic spindle apparatus (MSA) is the structure responsible for directing the movement of chromosomes during cell division. The autoantibodies directed to the MSAshow characteristic patterns in the indirect immunofluorescence staining of cells in metaphase. These patterns are slightly different depending on the specificity of the autoantigen. <h3>Objectives</h3> The clinical associations of these ANA patterns have not been clearly established. We aim to carry a descriptive study in patients with antibodies directed to the MSA. In this setting, we studiedthe possible association of these patterns with age, sex or clinical manifestations. On the other hand, weaim to establish the prevalence of these patterns in the studied population. <h3>Methods</h3> We revised all patients sera with positive anti-nuclear antibodies (ANA) diagnosed by the Clinical Immunology Department of the Hospital Clínico San Carlos, between January 2013 to December 2013. The determination of these patterns was performed by the reference9s technique, indirect immunofluorescence on HEp-2 human carcinoma cells with HELIOS autoanalyzer (Aesku, Wendesheilm, Germany) that enable a high output of good quality 2D images. Subsequently,a manual reading was performed with the fluorescence microscope Nikon Eclipse E400. <h3>Results</h3> Were studied 1,788 patients with positive ANA, out of 7,280 sera tested representing a 24.56%. Within the group of positive ANA, 78 patients disclosed autoantibodies tothe MSA, with a prevalence of 4.36%. No significant differences were found by sex between the groups formed by the different patterns (p=0.5). The age of the patients showed a great variability, with an overall mean of 60.6±17.6 years.We observed a clear predominance of liver disorders (n=25, 32.0%); thyroid abnormalities (n=9,11.5%), and rheumatic diseases (n=8, 10.0%). <h3>Conclusions</h3> The prevalence of autoantibodies to the mitotic spindle apparatus in our series represents the5% of all positive ANAs. Patients with autoantibodies to mitotic apparatus showed a high prevalence of liver abnormalities that deserves further characterization. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4956
SAT0388 Effect of Etanercept Therapy on Lipid Profile in Patients with Psoriatic Arthritis:
Authors: C. Van Dongen, R. Agca, L. Trivino, E. Vogelzang, M. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Patients with rheumatoid arthritis have about a twofold risk to develop cardiovascular disease compared to the general population. There is accumulating evidence that anti-TNF therapy lowers this risk for cardiovascular disease in these patients by reducing inflammatory activity in the vascular wall. In addition, studies suggest that anti-TNF therapy might also decrease the cardiovascular risk through beneficial effects on the lipid metabolism. Psoriatic arthritis is also an auto-inflammatory disease, where the literature suggests that TNF inhibitors may lower the risk for cardiovascular disease by modulation of the lipid metabolism. However, thus far, this has not been investigated appropriately in this group of patients. <h3>Objectives</h3> To explore the effect of TNF inhibiting therapy on lipid metabolism in patients with psoriatic arthritis. <h3>Methods</h3> Observational cohort study to assess the long term safety and efficacy of therapy with etanercept in patients with psoriatic arthritis who did not respond to non-biological DMARD therapy. <h3>Results</h3> The lipid metabolism was studied in a total of 157 consecutive patients (mean age (SD) was 47.1 (12.7) years and 75 (48%) males). The mean disease duration (range) at baseline was 9.0 (0.2 – 38.1) years. DAS, HAQ, CRP and ESR decreased significantly during therapy with anti-TNF. Outcomes that are related to lipid profile, such as HDL-cholesterol, LDL-cholesterol, triglycerides, total cholesterol/HDL-cholesterol ratio, Apo A-I and Apo B did not change significantly during follow up (Table 1). <h3>Conclusions</h3> Therapy with etanercept in patients with psoriatic arthritis is effective and results in sustained improvement in DAS28, HAQ, CRP and ESR during five year therapy.However, serum lipid concentrations did not change significantly during therapy with etanercept. Therefore, lipids modulation can not explain the (postulated) favourable cardiovascular effects of TNF-blockers. Hence, further (mechanistic) research is necessary to explore the cardiovascular effects of TNF inhibitors in patients with psoriatic arthritis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5166
Researchers Transfer Immunity To a Woman With Cancer
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Researchers Transfer Immunity To a Woman With Cancer Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 10, 17 May 1995, Pages 711–712, https://doi.org/10.1093/jnci/87.10.711 Published: 17 May 1995
Effects of Estrogen Replacement on the Progression of Coronary-Artery Atherosclerosis
Authors: David M. Herrington, David M. Reboussin, K. Bridget Brosnihan, Penny C. Sharp, Sally A. Shumaker, Thomas E. Snyder, Curt D. Furberg, Glen J. Kowalchuk, Thomas D. Stuckey, William J. Rogers, David H. Givens, David Waters
Journal: New England Journal of Medicine (2000)

Heart disease is a major cause of illness and death in women. To understand better the role of estrogen in the treatment and prevention of heart disease, more information is needed about its effects on coronary atherosclerosis and the extent to which concomitant progestin therapy may modify these effects.
From the authors:
Authors: M. Infante
Journal: European Respiratory Journal (2009)

In our paper 1, we summarised the expertise and practical guidelines we have built in recent years for the differential diagnosis and management of focal ground-glass opacities (GGOs) detected by spiral computed tomography (CT), either in a screening programme or incidentally.

As J-J. Hung and co-workers rightly point out, malignant GGOs may show a mixed evolution pattern over time with a decrease in their overall size but an actual increase of the central solid component. This should not be mistaken for a regression, but rather for progression to solid adenocarcinoma 2. Regression in response to antibiotic trial was defined by us as fading or disappearance of the entire lesion, which occurred in five (12.5%) cases.

Six patients were evaluated retrospectively, as their GGOs were visible on previous CT scans months before the lesion was actually reported. Antibiotics were not prescribed at that point as we did not expect them to have an effect on such lesions. …
OP0212 Very Long-Term Effects of the “4 Plus 2 Infusion Protocol” of Rituximab Alone in Patients with HCV-Associated Mixed Cryoglobulinemia with Diffuse Membranoproliferative Glomerulonephritis, Severe Polyneuropathy and Necrotic Ulcers of Skin
Authors: D. Roccatello, S. Sciascia, S. Baldovino, D. Rossi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Mixed cryoglobulinemia syndrome (MCs) is a systemic vasculitis characterized by multiple organ involvement due to the vascular deposition of IgMk/IgG cryoglobulins. B cells expansion usually triggered by HCV infection plays a central role in MCs. <h3>Objectives</h3> to evaluate the long term effects of B-cells depletion in MCs <h3>Methods</h3> Twenty seven patients, (mean age 60.2 [range 35-78] years, HCV infection in 96% of cases) with symptomatic type-II MCs with systemic manifestations, including renal involvement (diffuse membranoproliferative glomerulonephritis in 15 cases), peripheral neuropathy (26 cases) and large skin ulcers (9 case, in 7 necrotizing) were considered eligible for Rituximab (RTX) therapy. RTX was administered at a dose of 375 mg/m<sup>2</sup> on days 1, 8, 15 and 22. Two more doses were administered 1 and 2 months later. No other immunosuppressive drugs were added. Response was evaluated by assessing the changes in clinical signs, symptoms, laboratory parameters and electromyographic indices for a very long term follow-up (mean 54.3 months [12-96]) <h3>Results</h3> Complete remission of pre-treatment active manifestations was observed in all the cases of skin purpuric lesions and non-healing vasculitic leg ulcers, and in 80% of cases of peripheral neuropathy. A significant improvement in the clinical neuropathy disability score was observed. Electromyography revealed that the amplitude of compound motor action potential had increased. Cryoglobulinemic glomerulonephritis, observed in 15 patients, significantly improved during the follow-up starting from the second month after RTX (serum creatinine from 2.2±1.9SD to 1.6±1.2SD mg/dl, p≤.05; 24-hour proteinuria from 2.3±2.1SD to 0.9±1.9SD g/24h, p≤.05). Significant improvement of serological hallmarks, such as cryocrit and low complement C4, were also detected (p≤.05). The safety of RTX was confirmed by the absence of side effects recorded during the mean 54-month follow-up. Re-induction was performed in 9 relapsed cases (after a mean of 31.1 months, range 12-54) with resolutive beneficial effects. <h3>Conclusions</h3> In this open prospective study, the “4 plus 2 infusion protocol” of RTX appeared to be very effective and safe in the treatment of patients with MCs-associated membranoproliferative nephritis, polyneuropathy and severe skin involvement. <h3>Disclosure of Interest</h3> None Declared