tbuckley/cabot-search huggingface dataset:
S49 Telomere Attrition In Circulating White Blood Cells In Copd Relates To Lung Function And Outcomes
Authors: R. A. Rabinovich, G. Choudhury, R. Lahkdar, E. M. Drost, L. McGlynn, J. Bai, P. G. Shiels, B. E. Miller, R. Tal-Singer, A. Agusti, W. MacNee
Journal: Thorax (2014)

<h3>Introduction</h3> Increasing evidence suggests accelerated ageing as a pathogenic mechanism in COPD. <h3>Methods and results</h3> Telomere length in circulating WBC, a marker of biological ageing, was assessed in 200 ex-smoker COPD patients (108 male, age 61.5 ± 6.4 years, FEV<sub>1</sub> 45.6 ± 17.1% predicted), 50 ex-smokers with normal lung function (27 male, age 59.9 ± 7.3 years, FEV<sub>1</sub> 109.1 ± 13.4%predicted) and 50 non-smoker healthy subjects (27 male, age 59.3 ± 8.3 years, FEV<sub>1</sub> 113.2 ± 13.1% predicted). TL was assessed by qPCR and expressed as relative T/S ratio. TL was shorter in COPD (0.77 ± 0.2 relative T/S ratio) than in both ex-smokers (0.83 ± 0.2 relative T/S ratio) and non-smokers (0.84 ± 0.2 relative T/S ratio) (p &lt; 0.05). Furthermore TL correlated negatively with age (r -0.17, p 0.007), emphysema score (r -0.217, p 0.001), number of exacerbations in the previous year to inclusion in the study (r -0.129, p 0.04), number of hospitalisations over 3 years follow-up (r -0.167, p 0.004) and positively with FEV<sub>1</sub> (r 0.135, p = 0.03) and arterial oxygen saturation (r 0.161, p 0.01). <h3>Conclusion</h3> COPD patients have evidence of premature ageing (shortened TL) compared to normal subjects irrespective of their smoking history. TL relates to FEV<sub>1</sub>, SatO<sub>2</sub>, exacerbation rate and hospitalisations. The ECLIPSE study (GSK Study No. SCO104960, NCT00292552) was sponsored by GlaxoSmithKline.
Information needs of cancer patients (CP) in Argentina
Authors: R. H. Bordenave, A. A. Cuevas, M. M. Ferioli, M. Pelati, R. H. Mein, G. S. M. Paz, R. Brito
Journal: Journal of Clinical Oncology (2004)

8180 Background: Many times, doctors have difficulties to inform CP on their condition, because of a great degree of unjustified cultural pre-juices turning around cancer. While in some cultures disclosing cancer diagnosis is clearly established, in Argentina, it is unclear. In order to assess needs of CP to information and treatment, this study was conducted. Methods: From July to November 2003, 637 subjects completed a questionnaire. Questions were: 1) Do you think that cancer is a curable disease? 2) Do you think cancer is the worst existing illness? 3) If you have cancer, would you appreciate, your doctor explain everything about it? 4) In case a near relative have cancer, would you appreciate, your doctor explain everything about it? 5) In case you have cancer, would you accept all treatments indicated by your doctor? 6) In case a near relative have cancer, would you accept all treatments indicated by your doctor?. Answers were 1–2: yes/no, 3–4-5–6: nothing/a bit/enough(E)/much(M). Results: 216 patients, 126 relatives, 114 doctors, and 181controls, screened by age, sex, and socioeconomic status, representative of our population in South Buenos Aires, completed questionnaires. Median age was 45,70. Sex was 456(71.5%) females vs. 182(28.5%) males. 90%(n=568) think that cancer may be curable, and 35.8%(n=225) think that cancer is the worst existing disease. 95.5% wanted M+E information about their cancer, while 88.2% accept same information to a relative. Most people(93.8%) agree with treatments prescribed, and (94.2%) to a relative. Doctors agree to inform relatives M+E=84.1% Vs. CP: M+E=94.4% (p=0.002) and to receive treatments prescribed: M+E=88.2% vs. CP; M+E=97.2% (p=0.0004), Conclusions: Most people think cancer may be curable, and most want M/E information about their own cancer. While patients, relatives and controls agree about information or treatments to receive, doctors do not entirely agree with their colleague's prescriptions of treatment, and, as relatives, while wanting much information, reject giving same amount to a relative. No significant financial relationships to disclose.
Detection of myeloperoxidase gene expression by in situ hybridization in a case of granulocytic sarcoma associated with AML-M0
Authors: H Miyazato, H Sono, Y Naiki, J Miyatake, Y Nozaki, T Yamaguchi, M Matsuda, Y Tatsumi, Y Maeda, A Kanamaru
Journal: Leukemia (2001)
CS-22 * MIXED LINEAGE KINASE SIGNALING IS REQUIRED FOR GLIOBLASTOMA CELL MIGRATION AND INVASION
Authors: S. Misek, J. Chen, K. Gallo
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM) tumors are the most deadly of brain tumors due to their diffuse infiltrative nature and tremendous heterogeneity. EGFR signaling is aberrantly activated in most GBM tumors, and clearly contributes to malignancy. However, targeting EGFR directly has been largely unsuccessful, for multiple reasons, including compensatory upregulation of other receptor tyrosine kinases (RTKs). Identifying and targeting key common signaling nodes downstream of multiple RTKs that drive invasion may be an effective therapeutic strategy. The Mixed Lineage Kinases (MLKs) are a family of MAP3Ks that activate multiple MAPK pathways, including c-Jun N-terminal kinase (JNK). Binding of GTP-bound Rac/Cdc42 activates MLK3. We investigated the role of MLK signaling on GBM cell migration and 3D spheroid invasion using an ATP-competitive pan-MLK inhibitor, as well as siRNA-mediated silencing of MLK3. Our data demonstrate that both MLK inhibition and MLK3 silencing dramatically reduce GBM migration and 3D invasion. EGF-induced GBM cell migration, as well as JNK activation, is blocked by a pan-MLK inhibitor and by MLK3 silencing. The Rac GEF, Dock180, is critical for GBM invasion. Based upon Drosophila genetics, the Dock180 homolog (MBC), a Rac GEF, acts upstream of Rac, the MLK homolog (slipper) and JNK. Therefore we hypothesized that Dock180 might be an upstream activator of MLKs. Our data show that Dock180 complexes with MLK3; and that ectopic expression of Dock180 activates both MLK3 and JNK in a Rac-dependent manner. Furthermore, silencing of either Dock180 or MLK3 leads to a similar reduction in EGF-induced JNK activation. Finally, ectopic expression of MLK3 (which leads to its auto-activation) is sufficient to rescue the defect in migration due to Dock180 silencing. Based upon these data, we propose that an EGFR-Dock180-Rac-MLK-JNK signaling axis drives GBM migration and 3D invasion, and that targeting MLKs may be a useful therapeutic approach for treating patients with GBM.
What Is a Cluster?
Authors: K. Ruddon
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article What Is a Cluster? Get access Kate Ruddon Kate Ruddon Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 9, 3 May 1989, Page 653, https://doi.org/10.1093/jnci/81.9.653 Published: 03 May 1989
David Oliver: A mandate for mismanagement
Authors: David Oliver
Journal: BMJ (2016)

The 2015 Conservative election manifesto committed to make England “the first nation in the world to have a genuinely seven day NHS,” including “seven day a week access for everyone to a GP” and “hospitals properly staffed, so that the quality of care is the same every day of the week.”1

Conservative ministers, government communications teams, and some journalists have repeatedly argued that the outright election victory has given the party an “electoral mandate” to govern, albeit in a system where only 37% of the electorate voted for it.2 …
Abstract LB-60: A Local Consumer Research Panel's Role in the work of the National Institute for Health Research (NIHR) in the U.K
Authors: David Ardron
Journal: Cancer Research (2011)

Abstract The poster explains how patient advocacy fits into the world of health research, the relationship between research networks, and how research is planned at both the national and local levels in the United Kingdom. It describes the role of a local consumer research panel in helping to enhance research for maximum patient benefit. David Ardon has been a member and chair of a local panel for eight years and of the national consumer research group for seven years. The poster explains where in the research cycle patients and caregivers have been active, demonstrating the logos of local and national research organizations, and in diagrammatic form, showing the kind of activities that a consumer researcher tackles. The North Trent Cancer Research Network Consumer Research Panel was established in 2001 by the Academic Unit of Supportive Care at the University of Sheffield. North Trent is an area in the North East Midlands of England. The panel works alongside and is a constituent of the National Cancer Research Institute Consumer Liaison Group. The panel, composed of 40 past and current cancer patients and caregivers, is funded by the North Trent Cancer Network and the South Yorkshire CLRN to provide a consumer perspective at strategic meetings within North Trent and for individual research studies within the network. The panel has hosted and led ten conferences aimed at raising awareness of clinical research. The objective of the panel is to improve the quality of communication and information exchange between health care professionals, patients, and caregivers by providing a consumer perspective at all stages of cancer research and clinical trials. The governing body of health research in the U.K. is the National Institute for Health Research, which monitors eight research areas, one of which is cancer. Cancer research is governed and managed by the National Cancer Research Institute (NCRI), and the National Cancer Research Network (NCRN). Health research locally is delivered by a Comprehensive Local Research Network (CLRN). Mr. Ardon's local CLRN is the South Yorkshire CLRN, and this group includes the North Trent Cancer Research Network. 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-60. doi:10.1158/1538-7445.AM2011-LB-60
Abstract C75: Granulin-expressing bone marrow cells promote the outgrowth of indolent tumors
Authors: Sandra S. McAllister, Christina Scheel, Björn Nilsson, Ann M. Gifford, Ferenc Reinhardt, Mark Bray, Ann E. Carpenter, Benjamin L. Ebert, Robert A. Weinberg
Journal: Cancer Research (2009)

Abstract We previously demonstrated that certain vigorously growing xenografted human carcinomas (“instigators”) stimulate the growth of otherwise-indolent carcinoma cells and metastases (“responders”) implanted at distant anatomical sites — a process we termed “systemic instigation” (S. McAllister, et al.; Cell, 2008). We showed that systemic instigation is largely the result of activation of bone marrow cells (BMCs) that subsequently contribute to the stroma of the responding tumors; however, the identity of the activated BMCs and their contribution to outgrowth of the once-indolent cells was unknown. Here, we demonstrate that Sca1+/cKit− BMCs of hosts bearing instigating tumors are activated prior to their mobilization into the circulation and are very potent in their ability to promote outgrowth of the responding tumors. Strikingly, responding tumors, which result from either the presence of a contralateral instigating tumor or the admixture of Sca1+/cKit− BMCs harvested from instigator-bearing mice, form with a desmoplastic stroma. Stromal desmoplasia, the accumulation of a myofibroblast-rich reactive connective tissue, is almost always observed in malignant human adenocarcinomas. The Sca1+/cKit− BMCs do not directly give rise to stromal myofibroblasts; instead, we found that factors secreted by these BMCs induce fibroblasts to express alpha-smooth muscle actin (ACTA2), a myofibroblast marker. Gene expression profiling of the Sca1+/cKit− BMCs from instigator- and non-instigator-bearing mice identified granulin, a pluripotent secreted growth factor, as the most highly upregulated gene in the activated BMCs. We found: i) that granulin is indeed expressed by bone marrow-derived cells that are recruited into the responding tumor stroma; ii) that treatment of human mammary fibroblasts with granulin induces ACTA2 expression; iii) that granulin treatment is sufficient to enhance responding tumor growth in vivo. Mining of existing microarray datasets revealed that high granulin expression is correlated with the expression of ACTA2 in human breast cancers and is associated with shorter disease-free survival of breast cancer patients. Our results indicate that the formation of desmoplastic stroma, a condition that is associated with invasive carcinomas, can be instigated systemically by certain tumors via activation of granulin-expressing Sca1+/cKit− in the bone marrow. Citation Information: Cancer Res 2009;69(23 Suppl):C75.
Abstract 126: miR-221 promotes tumorigenesis in human triple negative breast cancer cells
Authors: Min-Jean Yin, Rounak Nassirpour, Pramod P. Mehta, Sangita M. Baxi
Journal: Cancer Research (2012)

Abstract MicroRNAs (miRNAs) are non-coding, single-stranded RNAs of ∼22 nucleotides that act as agents of the RNA interference pathway and negatively regulate their targets by either cleaving mRNA molecules or by inhibiting their translation. miRNAs are frequently located at fragile sites and genomic regions susceptible to amplification, deletion, or translocation during tumor development, and growing evidence indicates that miRNAs can function as tumor suppressors and oncogenes. Additionally, miRNA expression profiling analyses have revealed characteristic miRNA signatures in human cancers. MicroRNA-221 (miR-221) is up-regulated in many cancers including HCC, glioblastoma, pancreatic cancer, prostate cancer, and tamoxifin-resistant breast cancer. Overexpression of miR-221 has previously been shown to promote cancer cell proliferation, most likely by its ability to modulate the expression of the oncogenic proteins c-kit and cyclin dependent kinase inhibitor (CDKI) CDKN1B/p27. In this study, we demonstrate that in comparison to normal mammary tissues, miR-221 is overexpressed in triple negative breast cancer cell lines (TNBC) and downregulated in non-TNBC breast cancer cell lines. Stable knockdown of miR-221 expression reduced cell proliferation and induced apoptosis in TNBC cell lines. Overexpression of miR-221 promoted cell migration and cell invasion, while knockdown of miR-221 inhibited both cell migration and cell invasion and increased E-cadherin expression in TNBC lines but not in the non-TNBC lines. Furthermore, downregulation of miR-221 in MDA-MB-231 xenografts decreased the tumor growth rate in mice. Therefore, our results suggest that miR-221 is a potential oncomiR that promotes cell proliferation, migration, and invasion in triple negative breast cancer cells, and that knockdown of miR-221 is able to induce in vitro and in vivo anti-tumor activity in these TNBC cell lines. 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 126. doi:1538-7445.AM2012-126
PMO-100 Outcome of minimally invasive pancreatic necrosectomy without irrigation
Authors: D J Malde, S S Raza, N Khan, A Aldouri, K Menon, A M Smith
Journal: Gut (2012)

<h3>Introduction</h3> Necrotizing Pancreatitis with secondary infection of the pancreatic tissue is associated with significant morbidity and mortality. Current evidence suggests that a minimally invasive retroperitoneal necrosectomy (MIRP) is feasible, well tolerated and beneficial for the patient when compared with open surgery. <h3>Methods</h3> A total of 16 patients who underwent MIRP from September 2007 to April 2011 were included in the study. Current minimal access techniques all recommend routine irrigation but we aim to show that comparable results can be achieved without irrigation. <h3>Results</h3> The mean age was 52.5 years with 13 patients transferred from other centres. The aetiology was gallstones (13), alcohol (1), idiopathic (1) and hyperlipidaemia (1). The average time before 1st necrosectomy was 50.2 days. The mean number of procedures was 3.3 (range 1–7) with one patient requiring an open procedure. One patient required post-necrosectomy ICU admission. 13 patients had nasojejunal feed and four patients started with parenteral feed which was later converted to nasojejunal. Five patients developed a pancreatic fistula, three patients developed colonic fistula and two patients died. Mean inpatient stay was 82.6 days (range 31–182). <h3>Conclusion</h3> This series suggests that doing MIRP without irrigation has results comparable to other centres carrying out routine irrigation. <h3>Competing interests</h3> None declared.
ET-20 * INTERFERING WITH GLIOBLASTOMA MULTIFORME METABOLISM TO COMPLEMENT THERAPEUTIC EFFECTS OF TEMOZOLOMIDE
Authors: D. Garrett, S. Mukherjee, R. Tobin, S. Rogers, S. Henderson, H. Motal, J. Kain, E. Fonkem, M. K. Newell-Rogers
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM) is an aggressive malignant brain tumor that has a very poor prognosis. In fact, the average life expectancy at the time of diagnosis is approximately 1.2 years. The cells that make up GBM, like cells in other difficult-to-treat cancers, use available glucose at a very high rate (high rate glycolysis, also known as the Warburg effect). The cells also exhibit metabolic plasticity allowing the growing tumor to quickly adapt to available nutrient even under conditions of starvation. In fact, during stress or starvation, GBM utilize autophagy, a process whereby the tumor cell engulfs its own organelles to fuel its energetic needs. Taken together, these unique features of GBM metabolism suggest that GBM-specific metabolic pathways could serve as novel therapeutic targets for GBM. Thus, the advantages of metabolic targets as therapies are at least two-fold: (1) the cancer cell can no longer use an efficient strategy for energy production, and (2) metabolic disruption results in stresses that can alter the cell surface and potentially lead to recognition of the danger by immune cells from the tumor microenvironment. Temozolomide (TMZ), the current standard-of-care therapy for treating GBM, was designed to cause DNA damage, cell cycle checkpoint arrest, oxidative stress, and apoptosis. However, some GBM overcome TMZ treatment by activating DNA repair enzymes, such as the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) or poly-ADP-ribose polymerase (PARP). In this study, we address the possibility that combination treatment using TMZ to promote DNA damage combined with an inhibitor of GBM-specific energy strategies (that may be required for effective DNA damage repair) will potentiate the effectiveness of TMZ alone.
Initial Experience with Endoscopic Ultrasound in Determining Uncertain Cases of Biliary and Pancreatic Duct Disorders
Authors: JK Mokamad, SR Trecero, DH Que, J Co, E Ong
Journal: Endoscopy (2011)

The diagnosis of biliary and pancreatic tract diseases is usually straight forward when both the clinical picture and ancillary procedures demonstrate the disease in question. However, some cases are difficult to diagnose especially when diagnostic results are obscured. Endoscopic ultrasound (EUS) is a diagnostic modality that can be utilized in identifying biliary and pancreatic tract diseases in uncertain cases.
Abstract LB-384: Targeting overexpressed Aurora kinases in childhood medulloblastoma: Antiproliferative effects of small molecule inhibitors ZM44739, VX680 and shRNA
Authors: Martin I. Holst, Ellen Westerhout, Marcel Kool, Rogier Versteeg, Huib Caron, Steve Clifford, Stefan Rutkowski, Torsten Pietsch
Journal: Cancer Research (2010)

Abstract Kids Cancer Kinome (KCK) is a European research project investigating aggressive childhood cancers. Focusing on the human protein kinase family nine research centers explore different highly malignant pediatric tumors (medulloblastoma, Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, neuroblastoma, ALL) to validate novel drug targets and develop novel therapeutic options. Medulloblastomas of the cerebellum represent the most frequent malignant brain tumors of childhood. Previous studies revealed Aurora kinase A (STK15) as independent predictor for an unfavorable outcome of medulloblastoma patients. The Aurora kinases belong to the family of serine/threonine kinases which are involved in the cell cycle by controlling chromatid segregation. It is commonly approved, that defects in the process of cell division are associated with tumorigenesis. Using mRNA expression profiling (Affymetrix) we compared the Aurora kinase mRNA expression of 62 medulloblastoma tumor samples with normal cerebellar tissue (n=9) and an extensive dataset of various other tumor types (n=2028). We discovered a significant overexpression of Aurora kinase mRNA in primary medulloblastoma tumors, as well as 14 medulloblastoma cell lines compared to non-neoplastic tissues (n=685). Kaplan-Meier scans revealed an inverse correlation between overall survival rates and mRNA expression levels of Aurora kinases. To investigate the effects of Aurora kinase inhibition on medulloblastoma cells, we first evaluated the effects of the small molecule inhibitors ZM447439 andVX680 on the proliferation of medulloblastoma cell lines. Incubation of medulloblastoma cells with ZM447439 and VX680 for 72h resulted in a concentration dependent decrease of the proliferative activity as measured by MTS proliferation assays. The GI50 for ZM447439 ranged from 0.2 to 20 µm and for VX680 from 0.02 to 10.0 µm. Cytologically, the cells appeared enlarged and multinucleated after Aurora kinase inhibition. In a second approach, we transduced cell lines with lentiviral particles carrying shRNA targeting Aurora A and B kinase. The specific downregulation of the Aurora kinases with lentiviral shRNA was confirmed by Western blotting and had a negative effect on the viability of the medulloblastoma cells. In conclusion, these data suggest that the inhibition of Aurora kinases may represent a promising approach for novel targeted strategies for the treatment of medulloblastoma. 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 LB-384.
CORRELATION OF A NEW ECHOCARDIOGRAPHIC INDEX OF RIGHT VENTRICULAR REMODELING IN PULMONARY HYPERTENSION WITH INVASIVE HEMODYNAMICS IN RAT MODEL
Authors: Akiko Goda, Masataka Sugahara, Antonia Delgado-Montero, Bhupendar Tayal, Dmitry Goncharov, Rebecca Vanderpool, Jeffrey Baust, Elena Goncharova, John Gorcsan
Journal: Journal of the American College of Cardiology (2016)
A Study of Dental Health in American Children of Italian Origin and Comparable Groups in Italy
Authors: Harben Boutourline Young
Journal: New England Journal of Medicine (1962)

REPORTS on the dental health of Italian children1 , 2 called attention to the relative freedom from caries of these children, often in poor nutritional state, as compared to American subjects of Italian origin, who have also been demonstrated to be little different in caries prevalence to the American North European ethnic group.3 These studies were separated by a ten-year interval; the assignment to ethnic groups in the American study was stated to be "somewhat arbitrary"; social-class distributions of the two groups were not comparable, and the observations were made by different investigators. For these reasons it was decided to examine the . . .