tbuckley/cabot-search huggingface dataset:
Abstract 3820: Wnt signaling and telomerase activation in hepatoblastoma.
Authors: Eiso Hiyama, Yuka Ueda, Arata Kamimatsuse, Yoshiuki Onitake, Kaoru Ogura, Keiko Hiyama
Journal: Cancer Research (2013)

Abstract Purpose: The abnormal Wnt/β-catenin signaling plays a key role in hepatoblastoma (HBL) development. In HBL, CTNNB1 coding ß-catenin protein with mutated or deleted at hot-spot regions involving exon 3 stimulates this pathway. Previously we reported that the levels of telomerase reverse transcriptase (TERT) mRNA and telomerase activities were correlated with outcomes of the patients with HBL. In this study, we examined the correlation between Wnt/β-catenin signaling and telomerase activation in HBL. And, we investigated the location of β-catenin and TERT in HBL and the expression levels of the Wnt signal genes downstream of ß -catenin. Methods: Tumors derived from 212 HBL cases treated with the JPLT-2 protocol were analyzed for oncogenic mutations (missense mutations and interstitial deletions in the third exon) of the CTNNB1 gene encoding β-catenin and mutations of Wnt signal genes including APC, AXIN1, and 2. Moreover, these tumors were analyzed for the expression levels of TERT (telomerase reverse transcriptase) and the Wnt signal genes downstream of ß -catenin (MYC, cyclin D1 and MMP7) using Real time RT-PCR and immunohistochemistry. Results: Oncogenic mutations of CTNNB1 were detected in 163 cases (76.4%) and more than 80% showed abnormalities of Wnt signal genes. The expression levels of TERT were significantly higher in 49 cases without mutation (P &amp;lt; 0.05). Interestingly, Wnt/β-catenin target genes including MYC, cyclin D1 and MMP7 were significantly activated in the tumors with telomerase activation (P = 0.01). ß -catenin staining distinguished the CTNNB1 mutated tumors from others but cyclin D1 and MMP-7 did not. In advanced HBLs, double stain analysis of TERT and β-catenin showed that both were located in the same site in nucleus, suggesting that both proteins were co-localized in nucleus in hepatoblastoma.Conclusions: Wnt/β-catenin signaling in the HBLs without CNNB1 mutations was activated by telomerase activation. The clinical courses in HBLs with mutated Wnt signal gens and high TERT expression seemed to be unfavorable due to highly activated Wnt/β-catenin signaling. This correlated pathway might become molecular targets for advanced hepatoblastoma. Citation Format: Eiso Hiyama, Yuka Ueda, Arata Kamimatsuse, Yoshiuki Onitake, Kaoru Ogura, Keiko Hiyama. Wnt signaling and telomerase activation in hepatoblastoma. [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 3820. doi:10.1158/1538-7445.AM2013-3820
ECOG E3201: Intergroup randomized phase III study of postoperative irinotecan, 5- fluorouracil (FU), leucovorin (LV) (FOLFIRI) vs oxaliplatin, FU/LV (FOLFOX) vs FU/LV for patients (pts) with stage II/ III rectal cancer receiving either pre or postoperative radiation (RT)/ FU
Authors: A. B. Benson, P. Catalan, N. J. Meropol, B. J. Giantonio, E. R. Sigurdson, J. A. Martenson, R. P. Whitehead, F. Sinicrope, R. J. Mayer, P. J. O’Dwyer
Journal: Journal of Clinical Oncology (2006)

3526 Background: In the US pts with stage II/III rectal cancer routinely receive pre or postoperative RT/FU. To date, in addition to chemoradiation, standard adjuvant chemotherapy has been limited to single agent FU. Improved survival with irinotecan and oxaliplatin in pts with metastatic colorectal cancer led to exploration of combination chemotherapy in the adjuvant setting in pts with rectal cancer. Methods: Pts on E3201 (T 3–4 N any M 0 , T 1- 2 N + M 0 ) had the option to receive FU with either pre- or postoperative RT (50.4 Gy). Pts were randomized to postoperative chemotherapy: FU (500mg/m 2 ) + LV (500mg/m 2 ) weekly x 6/8 wks x 3 cycles or irinotecan (FOLFIRI) (180mg/m 2 ) vs oxaliplatin (FOLFOX) (85mg/m 2 ) both administered with LV (400 mg/m 2 ) FU (400mg/m 2 bolus) + continuous FU (2.4 gm/m 2 /46 hours) q 2 wks x 8 cycles. Results: 225 pts of 3150 planned were recruited. 178 pts were randomized and 126 pts submitted treatment completion forms (accrual period 10/03–4/05). The Data Monitoring Committee closed E3201 when the GI Intergroup developed an alternative trial with bevacizumab (E5204). Toxicity information is reported for 93% of pts (165/178) ( Table ). There were no significant differences in toxicity between those pts treated with pre- vs postoperative RT/FU, although, for the subset of pts who received adjuvant FOLFIRI after postoperative RT/FU, there was a trend towards more diarrhea. Conclusion: FOLFOX as rectal adjuvant therapy is a common platform for new clinical trials, although there have been limited toxicity data reported. E3201 provides important comparative toxicity information demonstrating that FOLFOX can be safely administered to rectal cancer pts following chemoradiation. [Table: see text] [Table: see text]
Abstract 4708: Short-term romidepsin treatment combined with mitogen-activated protein kinase and phosphatidylinositol 3-kinase inhibition causes increased Bim expression and cell death in KRAS mutant cell lines
Authors: Julian C. Bahr, Robert Robey, Arup Chakraborty, Victoria Luchenko, Susan E. Bates
Journal: Cancer Research (2012)

Abstract Romidepsin (FK228) is a histone deacetylase inhibitor (HDI) that modulates chromatin and activates apoptotic pathways in vitro. Clinical efficacy observed in peripheral and cutaneous T-cell lymphoma has not been replicated in solid tumors, as for other HDIs. We thus sought drug combinations that might improve the activity of romidepsin in solid tumors. Mutations in KRAS induce the mitogen activated protein kinase pathway (MAPK) and the phosphatidylinositol 3-kinase (PI3K) pathway. Laboratory data have suggested that activated MEK or AKT can confer resistance to HDIs. To determine if mitogen-activated protein kinase kinase (MEK) or AKT inhibitors could increase sensitivity to romidepsin, we measured cell death by annexin assay in a panel of 20 cell lines, nine KRAS mutants and eleven KRAS wild-type (WT). Cells were exposed to 25 ng/ml romidepsin for 6 h in the presence of 250 nM MEK inhibitor PD0325901 and/or 1 µM AKT inhibitor MK2206, after which romidepsin was removed and cells were incubated with the inhibitors alone for an additional 42 h. Among the 20 solid tumor cell lines examined, those harboring a KRAS mutation had a higher percentage of cell death than lines with WT KRAS when treated with the PD0325901/romidepsin combination (46.1±18% vs. 21.6±7.6% respectively, p-value .0057), the MK2206/romidepsin combination (43.8±15.8% vs. 28.6±13.6%, respectively, p-value .0470), or the PD0325901/MK2206/romidepsin combination (66.5±14.8% vs. 35.0±18.8%, respectively, p-value .0008). There was no statistically significant difference (p-value &amp;gt; .05) in cell death between KRAS and WT cell lines treated with any of the compounds alone. As expression of the pro-apoptotic protein Bim has been associated with romidepsin-mediated cell death, and as the MAPK pathway has been shown to phosphorylate and inactivate Bim, we examined Bim expression in cell lines sensitive to combined treatment with romidepsin and inhibitors. In the OVCAR5 cell line, which harbors a G12V KRAS mutation, we noted that romidepsin induced Bim expression and that combined treatment with PD0325901 led to higher expression by western blot. The high levels of Bim expression were associated with increased poly ADP ribose polymerase cleavage. These data demonstrate the benefit of combining an HDI with MEK and AKT inhibitors in KRAS mutant cell lines. Romidepsin and MAPK pathway inhibitor combinations should be further evaluated in patients with mutant KRAS cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4708. doi:1538-7445.AM2012-4708
Diana Mary Brinkley
Authors: H. G. F. Calman
Journal: BMJ (2014)

Diana Mary Brinkley (nee Rawlence) started her medical studies at the Royal Free Hospital in September 1939, within days of the outbreak of the second world war. The students were evacuated to St Andrew’s and then Exeter before returning to London for clinical studies at the height of the Blitz, where Diana gained hands-on experience treating and operating …
FRI0586-HPR Biomechanical mechanisms underlying treatment effects of exercise therapy in patients with knee osteoarthritis: data from a randomized controlled trial.
Authors: J. Knoop, M. P. Steultjens, L. D. Roorda, W. F. Lems, M. van der Esch, C. A. Thorstensson, J. W. Twisk, S. M. Bierma-Zeinstra, M. van der Leeden, J. Dekker
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Underlying mechanisms of exercise-induced effects in knee osteoarthritis (OA) are unclear. <h3>Objectives</h3> To evaluate longitudinal associations between changes in biomechanical functions and changes in pain and activity limitations in knee OA patients treated with exercise therapy. <h3>Methods</h3> Data were used from a randomized controlled trial (NTR1475) in which two exercise programs of 12 weeks were compared. One hundred forty nine patients with knee OA, who completed a 12-week exercise program, were measured at baseline and at 6-, 12- and 38-week follow-up. Generalized Estimating Equations (GEE) analyses were used to determine longitudinal associations of changes in biomechanical functions (upper leg muscle strength, knee joint proprioception, self-reported knee instability and knee flexion and extension range of motion) with changes in pain severity (numeric rating scale) and activity limitations (WOMAC, physical function and Get up and go test) over time (i.e. baseline, 6-, 12- and 38-week follow-up). Univariable and multivariable associations, analyzing all biomechanical functions together, were performed. <h3>Results</h3> Improvements in upper leg muscle strength (both quadriceps and hamstrings strength) and self-reported knee stability were longitudinally associated with outcome of exercise therapy, i.e. improvements in pain and activity limitations, while improvements in proprioceptive accuracy or knee range of motion were not (see Table 1). <h3>Conclusions</h3> Muscle strengthening and knee stabilization were consistently associated with outcome of exercise therapy in knee OA patients. These findings provide better insight in underlying biomechanical mechanisms of exercising in OA, contributing to optimal effectiveness of exercise therapy. <h3>Disclosure of Interest</h3> None Declared
Abstract P1-14-18: Overall survival results of a multicenter randomized phase II study in locally advanced breast cancer patients treated with or without celecoxib for HER2 negative tumor (Remagus 02 trial)
Authors: S Giacchetti, J-Y Pierga, S Delaloge, B Asselain, E Brain, JM Guinebretière, J Che-Lehman, M-C Mathieu, B Sigal, M Marty
Journal: Cancer Research (2012)

Abstract Background: Cox 2 is frequently over expressed in breast cancers. Celecoxib is a COX-2 inhibitor with anti angiogenic and pro-apoptotic activities. There are few data of anti-COX2 treatment in breast cancers. and no data on the impact of neoadjuvant anti COX 2 agent on survival. Patients and methods/: From May 2004 to October 2007, 340 stage II-III breast cancer patients were included in a phase II randomized trial and received 4 cycles (c) of epirubicin (75 mg/m2)–cyclophosphamide (750 mg/m2) q 3 w followed by 4 (c) of docetaxel (100 mg/m2) q 3 w. Pts with HER2 negative tumors (220 pts) were randomized to receive or not neoadjuvant celecoxib (200 mg bid) combined with docetaxel. All pts with hormone receptors positive tumor received hormonal treatment according to menopausal status (Pierga et al BCRT 2010). We report here overall survival (OS) and disease free survival (DFS) data and prognostic factors analyses at 5 years. Results/: At a median follow up of 49 months, the median DFS and OS are not reached for the whole population and none of them is significantly different between pts who received celecoxib or who did not (p = respectively 0.62 and 0.36). Celecoxib had no impact either on clinical and pathological complete response rate (pCR). DFS is significantly higher in patients who achieved pCR as compared to those who did not (p = 0.017; RR = 0.21 [0.051–0.88], whereas OS is borderline significant [p = 0.07; RR = 0.19 (0.026–1.4)]. Patients with triple negative (TN) tumors (78 pts) achieved worst DFS (p = 0.02) and OS (p &amp;lt;0.001) than non triple negative ones despite their higher pCR rate, 29.5 % [95 % CI 19;7-40;9 %] vs 11.4 % in all the other subgroups. At multivariate analysis including 7 factors [tumor size, clinical lymph node, grade (1 vs. 2and 3), pCR, ER, PR, TN], factors which influenced OS and DFS were pCR (p = 0.034 &amp; 0.013 and PgR expression (p = 0.046 &amp; 0.01). Conclusion/: Celecoxib had no influence on pCR, DFS or OS. Despite higher pCR rate triple negative breast cancer patients' subgroup remains with the poorest outcome. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-18.
Abstract 850: 32H2, a new diagnostic tool for HER2 CTFs
Authors: Josep L. Parra Palau, Vicente Peg, Marta Escorihuela, Sandra Mancilla, Joaquín Arribas
Journal: Cancer Research (2010)

Abstract The tyrosine kinase receptor HER2 belongs to the Epidermal Growth Factor Receptor (EGFR) family and is amplified in 30% of breast cancer patients. These patients are currently treated with Herceptin (Trastuzumab), a monoclonal antibody against the extracellular domain of HER2. A group of HER2 positive patients express a series of carboxy terminal fragments (CTFs) of the receptor. These patients have worse prognosis and are more likely to develop metastasis. In addition, CTFs positive patients are resistant to treatment with Herceptin. Functional characterization of the different CTFs shows that only those containing the transmembrane domain are active. Furthermore, the CTF generated by alternative initiation of translation at Methionine 611, CTF-611, seems to be a hyperactive due to its ability to constitutively form dimers maintained by disulfide bonds. These hyperactive dimers specifically control the expression of genes causally involved in malignant transformation, providing a likely mechanism for the clinical observations made in patients expressing CTFs. To date, the presence of CTFs in breast tumors have been studied by Western blot or by double immunoflourescence, using two antibodies, one targeting the intracellular domain and the other the extracellular domain of the receptor. However, both techniques are not able to distinguish between active and inactive CTFs. In addition, only careful comparison of the electrophoretic migration of the species found in tumor samples with those expressed in cell lines transfected with individual CTFs allows the identification of individual CTF. Obviously these techniques cannot be used to effectively determine the presence of active CTFs in large-scale clinical studies. Furthermore, given its hyperactivity, it would be useful to have a specific antibody against 611-CTF. Here we present the generation and characterization of a monoclonal antibody that recognize specifically 611-CTFs. The low affinity of the antibody for the full-length HER2 may be explained by structural features of the antibody epitope. Using the antibody in a collection of paraffin embedded tumors, we were able to identify a subgroup in the HER2 positive tumors with worst clinical outcome. 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 850.
Reply to Dumonceau
Authors: A. Sahai
Journal: Endoscopy (2011)

We thank Dr. Dumonceau for his extremely insightful comments. His points are well taken. In order to answer his queries we needed to review all our data. As we will show below, this further analysis only strengthens our impression that the stylet does not improve the results of EUS-FNA. Furthermore, since our publication, at least three other groups have presented data that confirm our results. Therefore, we stand by our conclusions.
P180 Sputum eosinophil positivity to tailor steroid management of severe asthmatics
Authors: G. Tavernier, C. Pris-Picard, R. Gore, R. Niven
Journal: Thorax (2010)

The use of sputum eosinophil count in asthma clinics is rapidly expanding as it has been reported as being a useful indicator of the worsening of asthma symptoms and that its normalisation reduces asthma exacerbations and admissions. Without additional steroids, levels of sputum eosinophils have been shown to be highly variable in severe asthmatic patients. Furthermore, precise patient phenotyping is increasingly becoming important as our understanding of the physiopathology of severe asthma widens. We introduced sputum differential cell counting in our severe asthma clinic, with a view to first reducing sputum eosinophils below 3% by augmenting anti-inflammatory therapy, and attempting steroid withdrawal once patients became sputum eosinophil negative (E−). To date, 264 patients have been investigated for sputum eosinophils, using induction with nebulised sodium chloride if necessary and suitable. This paper presents our yearly update of the anti-inflammatory (steroid) therapy of the first successive patients with at least two successful sputum counts (current n=71), specifically investigating patients’ management in the light of their positive sputum eosinophil levels at baseline assessment. Twenty patients were sputum eosinophil positive (E+) on their initial visit and 25 had reduced eosinophil levels (p=0.001) on a subsequent visit, including 14 becoming E−. Nineteen were offered a trial of steroid augmentation: 11 patients with a trial of IM triamcinolone (all patients had subsequent reduced eosinophils levels, 9 becoming E−, p=0.003); 5 patients with increased oral prednisolone treatment (four patients with reduced eosinophils levels, one becoming E−); 3 with increased inhaled steroid therapy (all with reduced eosinophil levels, 1 becoming E−). 66% of patients with uncontrolled sputum eosinophilia were treated with an increase in anti-inflammatory maintenance therapy. Sputum eosinophil levels decreased for 95% of these as already reported, but only 11/19 achieved full control of sputum eosinophilia with 2/11 failing to normalise eosinophils despite IM triamcinolone (representing a population of confirmed steroid resistance. Sputum eosinophil negativity used as a surrogate marker for asthma control has been shown to be an essential tool in identification and management of patients with asthma at risk of deterioration and admission.
Impact of co-mutations on the immune microenvironment of KRAS-mutant lung adenocarcinoma
Authors: Ferdinandos Skoulidis, Warren Denning, Lixia Diao, Pan Tong, You Hong Fan, Vassiliki Papadimitrakopoulou, Julie Izzo, Carmen Behrens, Humam Kadara, Edwin R. Parra Cuentas, Jaime Rodriguez Canales, Jing Wang, Lauren A. Byers, Ignacio I. Wistuba, John V. Heymach
Journal: Journal of Thoracic Oncology (2016)
Treatment of Rheumatoid Arthritis with a Recombinant Human Tumor Necrosis Factor Receptor (p75)–Fc Fusion Protein
Authors: Larry W. Moreland, Scott W. Baumgartner, Michael H. Schiff, Elizabeth A. Tindall, Roy M. Fleischmann, Arthur L. Weaver, Robert E. Ettlinger, Stanley Cohen, William J. Koopman, Kendall Mohler, Michael B. Widmer, Consuelo M. Blosch
Journal: New England Journal of Medicine (1997)

Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis, and antagonism of TNF may reduce the activity of the disease. This study evaluated the safety and efficacy of a novel TNF antagonist — a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1 (TNFR:Fc).
Technetium-99m Sestamibi SPECT Imaging of Bilateral Pulmonary Carcinoid Tumors
Authors: &NA; D. NGUYEN, MICHAEL C. ROARKE, RICHARD P. UMFRID, NELS A. DUTTON
Journal: Clinical Nuclear Medicine (2000)

The authors present a case of pulmonary carcinoid tumors detected incidentally on cardiac technetium-99m sestamibi scintigraphy. Characteristics of lung carcinoids and the available imaging techniques for their detection are reviewed and discussed briefly.
EFFICACY OF EZETIMIBE AND STATIN VERSUS STATIN: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Hemantha Koduri, Arun Kanmanthareddy, Abhilash Akinapelli, Ojas Bansal, Jitendra Pandya, Saurabh Aggarwal, Muhammad Soubhi Azzouz, Michael Del Core, Aryan Mooss
Journal: Journal of the American College of Cardiology (2016)
Abstract 4711: Silencing of miR-221 with anti-microRNA oligonucleotides is an effective therapeutic for hepatocellular carcinoma
Authors: Jong Kook Park, Takayuki Kogure, Gerard J. Nuovo, Lei He, Ji Hye Kim, Mitch A. Phelps, Carlo M. Croce, Tushar Patel, Thomas D. Schmittgen
Journal: Cancer Research (2011)

Abstract Patients with advanced hepatocellular carcinoma (HCC) face a dismal prognosis as there are no standardized therapies to treat this stage of the disease. Inhibition of microRNAs that are overexpressed in the tumor with antisense oligonucleotides represents a novel option to treat HCC. For antisense oligonucleotides to be effective, they must reach the target tumor tissue, inhibit the miRNA, modulate the miRNAs target protein levels and prolong survival. We evaluated anti-miR-221 in normal and tumor bearing mice. Of eight different chemistries evaluated, the cholesterol labeled, 2’ O methyl, phosphorothioate modified anti-miR-221 (chol-anti-miR-221) was the most effective at reducing proliferation in vitro. In the absence of transfection reagents, the in vitro proliferation was reduced by the chol-anti-miR-221 but not the scrambled control. Non specific toxicity was observed in vitro for each of the chemically modified scrambled control oligos when transfected with lipid reagent. Chol-anti-miR-221 had improved pharmacokinetics and liver tissue distribution compared to the non cholesterol labeled oligonucleotide in C57Bl/6 mice. Endogenous miR-221 levels in the liver were reduced by chol-anti-miR-221 in C57Bl/6 mice by 90%, 7 days following the start of the dosing schedule. In situ hybridization demonstrated that chol-anti-miR-221 accumulated in the tumor cells of orthotopic mice. Chol-anti-miR-221 reduced endogenous miR-221 levels in the tumors of orthotopic xenograft mice by &amp;gt; 95% and increased p27Kip1 target protein by 3-fold, 7 days after dosing. Chol-anti-miR-221 produced a survival advantage in orthotopic mice compared to those mice treated with a scrambled control oligo (P &amp;lt; 0.05). Our data demonstrate that chol-anti-miR-221 is efficacious in an orthotopic mouse model of HCC and suggests that such a therapy may be beneficial in patients with advanced HCC. 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 4711. doi:10.1158/1538-7445.AM2011-4711
A Clinical Trial of Active Management of Labor
Authors: Fredric D. Frigoletto, Ellice Lieberman, Janet M. Lang, Amy Cohen, Vanessa Barss, Steven Ringer, Sanjay Datta
Journal: New England Journal of Medicine (1995)

Active management of labor is a multifaceted program that, as implemented at the National Maternity Hospital in Dublin, is associated with a lower rate of cesarean delivery than the rate usually found in the United States. We conducted a randomized trial to evaluate the efficacy of this approach in lowering the rate of cesarean section among women delivering their first babies.