tbuckley/cabot-search huggingface dataset:
Abstract 4346: Genome-wide analysis of alternative splicing in pediatric medulloblastoma
Authors: Francesca Menghi, Thomas S. Jacques, Martino Barenco, Mike Hubank, Steven C. Clifford, Jonathan Ham
Journal: Cancer Research (2010)

Abstract Background Alternative pre-mRNA splicing (AS) is a key post-transcriptional mechanism for the generation of protein diversity. Abnormal alternative splicing can occur in cancer, and it results in the production of novel transcript variants or in an imbalance between normal mRNA isoforms. In both cases it can affect the global pattern of protein expression within a cell in ways that have the potential to sustain tumour growth. To investigate patterns of alternative splicing in human pediatric medulloblastoma, we used the Affymetrix Human Exon 1.0 ST array, and measured gene expression at the level of individual exons on a genome-wide scale for 14 medulloblastoma specimens and 5 samples of normal cerebellum. Results Through statistical analysis of differential splicing we identified 1260 genes potentially undergoing AS between normal cerebellum and medulloblastoma. We selected 9 examples of differential splicing of cassette exons and validated them by semi-quantitative RT-PCR and sequencing. Interestingly, 3 of the validated genes showed a pattern of AS specific for the molecular subgroup of medulloblastomas characterized by hyper-activation of the Sonic Hedgehog (Shh) signalling pathway. In an in vitro mouse granule cell progenitor (GCP) culture model in which cells depend on Shh for the maintenance of their progenitor state, the pattern of AS in the presence of Shh for 5 out of the 6 genes analyzed recapitulated the pattern observed in the tumor samples, suggesting that the preferential expression of specific transcript forms is regulated during normal cerebellar development. Similarly, by analyzing different stages of post-natal mouse cerebellar development, we observed that the switch between the two alternative transcript forms occurred between P7 and P14, at the time when GCPs mature into post-mitotic neurons. Conclusions We identified and validated AS events between normal cerebellum and medulloblastoma and showed that medulloblastomas display patterns of AS which are observed during the normal development of the mouse cerebellum. Further studies will investigate the regulation and biological role of AS events in cerebellar development and tumorigenesis. 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 4346.
P212 Screening for lung cancer: a qualitative study of the acceptability of screening and participation in the lung-SEARCH trial
Authors: A. Akporobaro, D. Patel, N. Chinyanganya, R. Butawan, A. Hackshaw, C. Seale, S. Spiro, C. Griffiths
Journal: Thorax (2010)

<h3>Introduction</h3> Lung cancer has the highest mortality of all cancers in the UK and, as such, constitutes a major public health problem. Lung-SEARCH is a UK multi-centre randomised control trial to determine whether screening (annual sputum cytology and if positive, followed by annual CT scanning and bronchoscopy) of smokers with mild COPD improves the detection of lung cancer at early stages when curative treatment is feasible. Acceptability is an ethical requirement of any screening programme. In addition, maximising participation of at-risk groups is key to any successful screening programme. We conducted a qualitative study to answer two questions: Are the screening methods of the Lung Search trial acceptable to patients Why do some people take part and others decline? <h3>Methodology</h3> A qualitative study using semi-structured face-to-face and telephone interviews involving three groups of respondents a) those giving an annual sputum sample; b) those undergoing annual bronchoscopy and CT scanning, and c) those who declined participation in the trial. We used the Framework technique to carry out a thematic analysis. Respondent validation was used to strengthen the research findings. <h3>Results</h3> 50 interviews were completed (group a: 16, group b: 11; group c: 23). Respondents felt sputum analysis and CT scanning was acceptable. Some recalled a negative experience of bronchoscopy but would not object to future bronchoscopies. The main reasons for declining the trial include travelling for CT scanning and bronchoscopy, negative experiences/perceptions of screening tests, and low perceived susceptibility of lung cancer. There were four main typological behaviours recognised within the declining group: ‘too old to be bothered’, ‘worriers’, ‘fatalists’ and ‘avoiders’. Declining patients perceived they were at low risk compared to those taking part. Risk was believed to be related to family history and current health rather than smoking. <h3>Conclusion</h3> Whilst screening methods in the Lung-SEARCH trial are largely acceptable to trial participants, strategies to increase acceptability and participation of this at-risk group should include providing tests locally, resolving anxieties concerning screening tests and addressing beliefs of those who underestimate or deny their risk of lung cancer.
CORONARY PRESSURE AND FLOW RELATIONSHIPS IN HUMANS: PHASIC ANALYSIS OF NORMAL AND PATHOLOGICAL CORONARY ARTERIES AND THE IMPLICATIONS FOR STENOSIS ASSESSMENT
Authors: Guus de Waard, Sukhjinder Nijjer, Tim van de Hoef, Sayan Sen, Ricardo Petraco da Cunha, Mauro Echavarria-Pinto, Martijn van Lavieren, Ibrahim Danad, Paul Knaapen, Javier Escaned, Jan Piek, Niels Van Royen, Justin Davies
Journal: Journal of the American College of Cardiology (2015)
A mathematical model to predict for pre-malignant or malignant diagnosis among patients with Birad 4 breast lesions
Authors: I. Laurent, C. Balleyguier, R. Rouzier, F. André, H. Marsiglia, M. Spielmann, P. Vielh, S. Delaloge
Journal: Journal of Clinical Oncology (2006)

10578 Background: Preoperative cytological or histological diagnosis of breast lesions is mandatory in order to avoid unnecessary surgical biopsies, but on the other side preoperative work-up may dangerously delay specific care of breast cancer. Solid lesions or microcalcifications (M) scored as Birad 4 are increasingly prevalent in western countries. A highly variable proportion of these lesions (20–80%) are breast cancer. Tools to help clinicians recognize cancers and preneoplastic lesions among true benign conditions may be very helpful in clinical practice. Methods: Radiological, clinical and pathological data of consecutive patients with Birad 4 breast M (N = 384 biopsies among 354 patients) or nodular lesions (N = 172 FNAC among 167 patients) seen in a multidisciplinary breast clinic were prospectively recorded. A multivariate analysis of factors predicting for a final cancer or pre-malignant diagnosis was performed and two nomograms were constructed using the R statistical package for both nodular lesions and M. They were validated by bootstrapping. Variables tested included age, size and palpability of lesion, Gail score, menopausal status, HRT use, progression of lesion (M), and presence of associated symptoms. Results: Median age was 57 years (18–92) for the entire population. Patients with nodular lesions were menopausal in 64.5%, median size of their lesion was 12 mm (4–50), 32% were palpable; 43% had a final diagnosis of breast cancer and 3.5% of atypical hyperplasia or LCIS. 69% of patients with M were menopausal, 31.25% had a final diagnosis of breast cancer and 9.8% of atypical hyperplasia or LCIS. Among patients with nodular lesions, age and palpability were the sole independent predictors of cancer or precancerous lesions (p = 0.04 and 0.004), but the other variables (Gail, menopause, HRT) added discrimination with a concordance index of 0.71. Among patients with M, the only independent predictive variable was the recent progression of the lesions (p = 0.01). The nomogram had a concordance index of 0.69. Conclusion: Our study provides two original nomograms for the prediction of the pre-malignant or malignant nature of recently discovered solid breast lesions and M. Gail model alone is not a highly useful tool in daily individual cancer prediction. No significant financial relationships to disclose.
Efficacy of Prothrombin-Complex Concentrates in Hemophiliacs with Antibodies to Factor VIII
Authors: Jeanne M. Lusher, Sandor S. Shapiro, Joseph E. Palascak, A. Vijaya Rao, Peter H. Levine, Philip M. Blatt
Journal: New England Journal of Medicine (1980)

The therapeutic efficacy of prothrombin-complex concentrates in patients with hemophilia and inhibitors (antibodies) to factor VIII has been increasingly debated. We therefore entered 51 hemophiliacs with factor VIII inhibitors into a double-blind randomized crossover study to compare two commercial prothrombin-complex concentrates (Konȳne and Proplex) and an albumin placebo. Acute hemarthrosis of the elbow, knee, or ankle was treated with a single dose of a test preparation and assessed six hours later with objective and subjective criteria. In all measurements the concentrates were significantly more effective than the placebo. The data indicate that although prothrombin-complex concentrates, when used in a single dose, are only partially effective in the treatment of joint hemorrhage in hemophiliacs with inhibitors, their continued use for acute hemarthrosis is justified in the absence of any other effective and readily available therapy for this disorder. (N Engl J Med. 1980; 303:421–5.)
c-myc mRNA expression and genomic alterations in mantle cell lymphomas and other nodal non-Hodgkin’s lymphomas
Authors: L Hernández, S Hernández, S Beà, M Pinyol, A Ferrer, F Bosch, A Nadal, PL Fernández, A Palacín, E Montserrat, E Campo
Journal: Leukemia (1999)
OP0164 Long-term TNF blockade induces joint repair in psoriatic arthritis:
Authors: K. de Vlam, R. Lories
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Psoriatic arthritis (PsA) is characterized by a variety of radiographic changes which include both signs of joint destruction (joint space narrowing reflecting cartilage loss and bone erosions) and joint remodeling (new bone formation possible leading to joint ankylosis). These changes are considered irreversible. Actual radiographic scoring methods focus largely on joint space narrowing and joint erosions. The use of TNF blockade has dramatically changed the clinical and radiographic outcome of PsA,showing to be effective in retarding or halting the progression of destructive joint disease. The effects on new bone formation and ankylosis in particular have not been extensively studied. The latter aspect may occur over a longer time frame than that usually evaluated for joint destruction (2 years). <h3>Objectives</h3> to evaluate radiographic changes in PsA patients treated with etanercept over an extended time interval. <h3>Methods</h3> 20 patients with DMARD resistant polyarticular PsA were previously included in a open observational study of etanercept treatment<sup>1</sup>. X-rays of hand &amp; feet were read using the Ratingen scoring system, evaluating both erosions and new bone formation. X-rays were scored at baseline and year 1 and 6 (or longer) by one observer blinded for the order. Joint remodeling specifically leading to joint repair for the individual joints of hands and feet was recorded. Joint repair was defined as the reappearance of a joint space combined with clearly delineated joint margins. <h3>Results</h3> Results of the Ratingen score are given in table 1. Erosion scores in the patients did not deteriorate over time. Five out of 20 patients showed striking joint repair in six joints, all but one in the feet: three patients in MTP joints (MTP 1 &amp; 5) and two patients in PIP joints. One patient showed repair in a DIP joint of the dominant hand. <h3>Conclusions</h3> Treatment with etanercept stops in a sustainable manner radiographic signs of joint destruction in patients with severe PsA. In the feet, true repair of destructed joints occurs. <h3>References</h3> de Vlam K, Lories RJ.1Efficacy, effectiveness and safety of etanercept in monotherapy for refractory psoriatic arthritis: a 26-week observational study. Rheumatology. 2006 Mar;45(3):321-4. <h3>Disclosure of Interest</h3> None Declared
PWE-271 Ratio of IL 10 over IL 12 is a novel surrogate to evaluate the severity of non-alcoholic steatohapatitis (NASH)—a prospective clinical pilot study
Authors: P Basu, T Nair, S Farhat, M Jafri, K Mittimani, N James Shah, L Ang, S Foustin
Journal: Gut (2012)

<h3>Introduction</h3> Non-alcoholic steatohepatitis (NASH) is a growing global epidemic progressing to cirrhosis, liver failure, HCC, warrants liver transplant. The natural history is still not well defined, inflammatory cytokines, intrahepatic immune traffic, degree of apoptosis and path of fibrogenesis are the sequel of the disease process. This study evaluates a novel inflammatory cytokines (IL 10 and IL 12) ratio to predict NAFLD to NASH and its severity index. <h3>Methods</h3> Ninety (n=90) patients, mean age of 45 (28–54) were divided into Group A (n=30) BMI (mean) &lt;25% with normal lipids, healthy control. Group B NAFL D (n=30) BMI &gt;29% with NAFLD (hepatic steatosis, Waist/Hip ratio &gt;0.9, high lipids, HOMA &gt;1.8, mean normal ALT, AST, RBP 4, 2.5, Leptin, Adiponectin, TNF α, serum NASH score &lt;0.8, mean fibrotic score &lt;0.1, mean IL 10/IL 12 ratio &lt;0.9. NASH C (n=30), BMI &gt;30, W/H ratio &gt;1.1, high lipids, HOMA &gt;2.2, high AST, ALT, RBP &gt;4.5, high leptin, low adiponectin, high TNF α, IL10/IL12 ratio &gt;2.5. Serums NASH score &gt;0.6, fibrotic score over 0.2. Liver biopsy in NASH group, macrovascular fat 18/30 (60%), balloning 12/30 (40%), Mallory body 7/30 (23%), METAVIR score F2 12/30 (40%), F3 9/30 (30%), F4 3/30 (10%). Exclusion Criteria: Diabetes, viral hepatitis, autoimmune liver disease, alcohol consumption over 20 g daily, steatogenic medications including herbs. <h3>Results</h3> <h3>Conclusion</h3> IL 10/12 ratio correlated positively with the progression of NAFLD to NASH. IL 10/12 ratio &gt;2.5 has NASH with high steatosis and fibrotic state and elevated inflammatory cytokines. Larger study will establish the predictive index of IL10/IL 12 NASH severity and prognosis. <h3>Competing interests</h3> None declared.
Vaginal Changes and Sexuality in Women with a History of Cervical Cancer
Authors: K Bergmark, E Avall-Lundqvist, P W Dickman, L Henningsohn, G Steineck
Journal: New England Journal of Medicine (1999)

In women with cervical cancer, treatment causes changes in vaginal anatomy and function. The effect of these changes on sexual function and the extent, if any, to which they distress women are not known.
<i>Helicobacter pylori</i>Infection and Gastric Carcinoma among Japanese Americans in Hawaii
Authors: Abraham Nomura, Grant N. Stemmermann, Po-Huang Chyou, Ikuko Kato, Guillermo I. Perez-Perez, Martin J. Blaser
Journal: New England Journal of Medicine (1991)

Helicobacter pylori are gram-negative spiral bacteria that are associated with chronic gastritis, a known precursor of gastric carcinoma. Persons at high risk for gastric carcinoma have been shown to have a high prevalence of H. pylori infection.
Abstract P2-09-06: The structure design and biological activities of inhibitory peptides, which block the interactions among polycomb repressive complex 2
Authors: KK LI, L Luo, X Kong, L Li, C Luo
Journal: Cancer Research (2012)

Abstract Polycomb repressive complex (PRC2) contains several proteins, including embryonic ectoderm development (EED), suppressor of zeste 12 (SUZ12) and enhancer of zeste homolog 2 (EZH2). Excessive EZH2 concentrations have been reported as a marker of aggressive breast cancer and associated with invasion and cancer progression. EZH2 levels were elevated in patients with invasive breast carcinoma relative to normal or atypical hyperplasia. Except for the C-terminal SET domain, which functions as a histone-lysine N-methyltransferases, EZH2 has an N-terminal alpha helix region, which forms tight complex with EED protein. The in vivo enzymatic activity of EZH2 relies on and be tightly regulated by the interaction with EED. We designed series of artificial peptides trying to block the interaction between EZH2 and EED. By using label-free surface plasmon resonance (SPR) technology, the dynamic binding capacities of these peptides were tested. There were 3 leading structures standing out from the screening of more 80 peptides. After several round of co-crystal structure based optimization, the binding capacity of one inhibitor was reached to several nM levels, which indicated the availability for being a drug candidate. Finally, the biological activities of the inhibitory peptides were tested in several breast cancer cell lines. The PRC2 inhibitory peptides in this study are the first time reported PRC2 targeting epigenetic molecules with biological activity in breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-09-06.
SAT0296 Comparison of Clinical Cut-Offs For Diagnosis of Psoriatic Arthritis in Psoriasis Patients in European/North American Dermatology Clinics
Authors: P. Helliwell, O. FitzGerald, D. Alvarez, A. Szumski, H. Jones
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Prompt diagnosis and treatment of psoriatic arthritis (PsA) are essential to reduce the risk of permanent joint damage. Although composite measures established in rheumatoid arthritis are often used in PsA for monitoring disease activity, their utility as an aid to identification of PsA, compared to the utility of other features of PsA such as dactylitis and enthesitis, has not been established. <h3>Objectives</h3> To compare various clinical assessments in their ability to diagnose PsA in a post-hoc analysis of findings from the PREPARE study, a multicenter non-interventional study conducted to estimate PsA prevalence in patients with psoriasis. <h3>Methods</h3> Consecutive psoriasis patients seen in dermatology centers were evaluated by rheumatologists to establish/exclude a clinical diagnosis of PsA based on physical examination, medical history, and laboratory findings. With the latter diagnosis serving as the standard for comparison, several rheumatologic signs/symptoms/indexes were assessed. The cutoff value for each assessment that best corresponded to the clinical PsA diagnosis was obtained by maximizing sensitivity plus specificity in receiver operating characteristic (ROC) analyses. Kappa (K) coefficient analyses determined the level of agreement between the clinical PsA diagnosis and assessment cutoffs (1=perfect agreement). <h3>Results</h3> Of 949 psoriasis patients assessed by rheumatologists, 285 (30%) had PsA based on clinical diagnosis (95% CI: 27%, 33%). Results varied from dactylitis in ≥1 joint, a cutoff with low sensitivity and high specificity, to a tender joint count of ≥1, a cutoff with surprisingly high sensitivity and specificity in lower and upper extremities (Table). K values were modest for all cutoffs. Of the composite tools, DAS44 (including foot joints) performed better than DAS28. <h3>Conclusions</h3> In this large prevalence study, nearly one third of psoriasis patients seen in dermatology centers received a clinical diagnosis of PsA by a rheumatologist. Although a statistically significant level of agreement was observed between the clinical PsA diagnosis and the cutoffs for the various assessment tools analyzed, none of the K values were high, suggesting that clinicians may be using combinations of recorded features with or without unrecorded features to make the diagnosis. <h3>Acknowledgements</h3> This study was sponsored by Pfizer Inc. Medical writing support was provided by Donna McGuire of UBC Scientific Solutions and was funded by Pfizer Inc. <h3>Disclosure of Interest</h3> P. Helliwell Speakers bureau: Pfizer, O. FitzGerald Grant/research support from: Abbott, BMS, Pfizer, MSD, Consultant for: Abbott, UCB, Pfizer, Speakers bureau: Abbott, Pfizer, MSD, D. Alvarez Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. Szumski Consultant for: Pfizer Inc, H. Jones Employee of: Pfizer Inc
Abstract LB-269: PPARγ maintains ERBB2-positive breast cancer stem cells.
Authors: Xianhui Wang, Yan Sun, Jason Wong, Douglas Conklin
Journal: Cancer Research (2013)

Abstract Overexpression of the adverse prognostic marker ERBB2 occurs in 30% of breast cancers and is associated with aggressive disease and poor outcomes. Our recent findings have shown that NR1D1 and the peroxisome proliferator-activated receptor (PPAR) γ-binding protein (PBP) act through a common pathway in upregulating several genes in the de novo fatty acid synthesis network, which is highly active in ERBB2-positive breast cancer cells. NR1D1 and PBP are functionally related to PPARγ, a well-established positive regulator of adipogenesis and lipid storage. Here we report that inhibition of the PPARγ pathway reduces the ALDH positive population in ERBB2 positive breast cancer cells. Conversely, fatty acid synthase inhibitor C75 increases the fraction of ALDH-positive cells. In vitro tumorsphere formation assays demonstrate that the PPARg antagonist GW9662 decreases the tumorsphere formation in ERBB2-positive cells, but not other breast cells. We show that the mechanism by which GW9662 treatment causes a reduction in ALDH-positive population cells, is partially due to ROS, as it can be rescued by treatment with NAC. Furthermore, global gene expression analyses show that GW9662 treatment suppresses the expression of several lipogenic genes including ACLY, MIG12, FASN and NR1D1; and the stem cell related genes KLF4 and ALDH in BT474 cells. GW9662 also decreased the level of acetylation in histone 3 and histone 4 in BT474 cells, compared with MCF7 cells. In vivo, GW9662 pre-treatment inhibits the tumor-seeding ability of BT474 cells. Together, these results show that the PPARγ pathway is critical for the cancer stem cell properties of ERBB2 positive breast cancer cells. Citation Format: Xianhui Wang, Yan Sun, Jason Wong, Douglas Conklin. PPARγ maintains ERBB2-positive breast cancer stem cells. [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 LB-269. doi:10.1158/1538-7445.AM2013-LB-269
P651Cardioprotective potential of seabuckthorn pulp oil against ischemia reperfusion induced myocardial injury in rats through upregulation of Akt/eNOS pathway:
Authors: K Suchal, S Malik, N Gamad, R Kumar, A Tomar, J Bhatia, D S Arya
Journal: Cardiovascular Research (2014)

Purpose: Seabuckthorn pulp oil obtained from the fruits of Seabuckthorn (Hippophae rhamnoides L.) has been used since ancient times for its medicinal and nutritional properties. So the present study was done to investigate the cardioprotective effect of Seabuckthorn (SBT) pulp oil in Ischemia-Reperfusion (IR) induced model of myocardial infarction in rats and to evaluate whether this cardioprotective effect involves activation of Akt/eNOS signaling pathway.
Tc-99m MDP Uptake by an Advanced Colon Cancer Lesion in a Juvenile Patient
Authors: T Yamada, N Shuke, K Takahashi, R Katada, M Mineta, K Nagasawa, H Hanaoka, T Aburano, K Miyamoto, Y Suzuki
Journal: Clinical Nuclear Medicine (2000)

Extraosseous uptake of Tc-99m MDP has been reported in various pathologic conditions. In colon cancer, Tc-99m MDP uptake in the primary lesion is unusual, although uptake in metastatic lesions has been observed frequently. Presented here is a rare case of juvenile colon cancer in which Tc-99m MDP uptake by the primary lesion was clearly demonstrated on bone scintigraphy.