tbuckley/cabot-search huggingface dataset:
P196 Healthcare utilisation by patients with Idiopathic Pulmonary Fibrosis; observations from the UK pirfenidone Named Patient Programme
Authors: H Parfrey, C Leonard, MA Gibbons, E Armstrong, E Harris, R Frank, C Sharp, F Percival
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> There are limited data on the healthcare resource use that arises as a consequence of idiopathic pulmonary fibrosis (IPF). Navaratnam <i>et al</i><sup>1</sup> have recently reported rising hospital admissions due to IPF but utilisation of other health related services by individuals with IPF is unknown. As part of a real world assessment of the clinical experience of pirfenidone via the UK Named Patient Program data were collected to determine the burden placed on healthcare resources as a consequence of IPF. <h3>Methods</h3> A multi-centre, retrospective, cohort review was undertaken across 4 NHS Trusts. Hospital resource use data were collected from the clinical records of individuals starting pirfenidone for IPF through the NPP before June 2012. <h3>Results</h3> Data were available from 100 patients (76% male) at baseline and 67 through to nine months from baseline. At baseline, the mean ± S.D. age was 69.3 ± 7.5 years, mean ± S.D. FVC% predicted was 70% ± 19% and 62 patients were on oxygen therapy. In the first 6 months from baseline, 11 patients had 15 IPF-related hospitalisations of which 6 were for an acute exacerbation. One patient was hospitalised in the 6–9 months period. The mean ± S.D. and median (IQR) hospital bed days in the first 6 months were 11.0 ± 7.5 and 11.0 (6.0–13.5) days respectively for hospitalised patients and mean ± S.D. 1.2 ± 4.2 days for all patients. One patient was admitted to the Intensive Care Unit, for 5 days. Eighteen patients had IPF-related Accident and Emergency department visits, 3 had an IPF-related day-case and 67 outpatient clinic visits, with a mean of 2.1 ± 2.0 outpatient clinic visits per patient in the first 6 months of the observation period. <h3>Conclusion</h3> IPF is a terminal disease associated with significant morbidity and mortality. This is reflected in the high level of resource use and frequent accessing of health care services by this severely ill cohort of patients. Whether resource use has been positively impacted by the introduction of pirfenidone is unknown but merits prospective assessment. <h3>Reference</h3> Navaratnam V, Fogarty AW, McKeever T, Hubbard RB. The Increasing Secondary Care Burden of Idiopathic Pulmonary Fibrosis Hospital Admission Trends in England &gt;From 1998 to 2010. CHEST 2013; 143(4):1078–1084
TRIGLYCERIDE LEVELS AND ITS RELATIONSHIP WITH HEMOGLOBIN A1C IN PATIENTS WITH DIABETES
Authors: Reynaria Pitts, Katelyn Garcia, Paul Ribisl, Mara Vitolins, Lawrence Cheskin, Stephen Glasser, Ashok Balasubramanyam, Henry J. Pownall, Lynne Wagenknecht, Robert Eckel
Journal: Journal of the American College of Cardiology (2016)
Strains of Rhinovirus Associated with Asthma in Costa Rican Children
Authors: P.W. Heymann, D. Erdman, M. Soto-Quiros, L. Avila, H.T. Carper, D.D. Murphy, T.A.E. Platts-Mills, J.L. Kennedy, J.W. Steinke
Journal: Journal of Allergy and Clinical Immunology (2012)
Abstract SY30-01: Molecular characterization of single circulating tumor cells.
Authors: Daniel A. Haber, Min Yu, Emre Ozkumar, David Ting, David Miyamoto, Richard Lee, Ajay Shah, Aditya Bardia, Shannon Stott, Mehmet Toner, Shyamala Maheswaran
Journal: Cancer Research (2013)

Abstract Circulating Tumor Cells (CTCs) are present at extraordinarily low levels in the blood of patients with advanced epithelial cancers. Our group has developed and tested three generations of microfluidic devices for the isolation of CTCs, each with further improvements in automation, processing throughput and downstream analytical capabilities. Isolation and molecular analyses of these cells has a number of significant potential clinical applications: rising or declining numbers of CTCs are well correlated with tumor progression or therapeutic response. Furthermore, CTCs bear genetic hallmarks of the primary cancer, offering a noninvasive “liquid biopsy” to enable initial and serial monitoring of tumor genotypes during cancer therapy. Most significantly, CTCs hold the key to understanding the process of blood-borne metastasis. Using next generation RNA sequencing strategies, we have initiated studies of expression profiles within CTCs. These have identified cellular pathways implicated in resistance of epithelial cells to anoikis in the circulation and in epithelial-mesenchymal transition - a phenomenon implicated in cancer invasion. The heterogeneity of CTC populations is evident in single cell imaging analyses and sequencing studies, with implications for understanding the complexity of therapeutic responses. Taken together, the application of novel bioengineering technologies to the isolation and analysis of CTCs across multiple different cancer types offers a unique window into the properties of cancer cells that invade into the bloodstream and give rise to metastases. Citation Format: Daniel A. Haber, Min Yu, Emre Ozkumar, David Ting, David Miyamoto, Richard Lee, Ajay Shah, Aditya Bardia, Shannon Stott, Mehmet Toner, Shyamala Maheswaran. Molecular characterization of single circulating tumor 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 SY30-01. doi:10.1158/1538-7445.AM2013-SY30-01
EFFECT OF MYOCARDIAL FIBROSIS ON THE LEFT VENTRICULAR REMODELING, LEFT AND RIGHT VENTRICULAR FUNCTION AND PROGNOSIS IN PATIENTS WITH ACQUIRED HEART DISEASE USING CONTRASTING MRI AND 2D SPECKLE TRACKING
Authors: Olga Bockeria, Olga Kislitsina, Aleksandrova Svetlana, Irina Averina
Journal: Journal of the American College of Cardiology (2016)
P4-07-07: Circulating Tumor Cells Predict Survival in Non-Metastatic Breast Cancer.
Authors: A Lucci, S Krishnamurthy, A Bhattacharyya, A Lodhi, C Hall, B Singh, A Anderson, I Bedrosian, H Kuerer
Journal: Cancer Research (2011)

Abstract Background: Circulating tumor cells (CTCs) predict outcome in metastatic breast cancer (BC), but their prognostic significance in non-metastatic BC is unclear. This study determined whether CTCs could be identified in non-metastatic BC patients and 2) if CTCs predict relapse-free and overall survival. Methods: Clinical stage I-III BC patients seen at a single tertiary cancer center provided informed consent to participate in an IRB-approved study involving collection of blood (7.5 ml x 2 tubes) before systemic therapy and at the time of surgery for their primary BC. CTCs were detected using the Cell SearchTM system. A positive result was defined as the presence of two or more cells per 7.5 ml blood since a threshold for positivity has not been established in primary BC. Statistical analyses were done using STATA-IC 11 software. Results: We prospectively evaluated 291 patients. Mean age was 54 years, and median follow-up was 30 months. 54% (157) had T1 tumors, 36%(104) T2, 6% (18) T3, and 4%(12) had T4 disease; 37% (107/289) were clinically node-positive (LNs) by axillary ultrasound and FNA. Two or more CTCs were identified in 10% (29) patients. Seventy-seven percent (225) patients were hormone receptor positive, 11% (32) were HER2 positive while 16% (48) expressed no receptors. Sixteen percent (48) were tumor grade 1, 50% (143) were grade 2 and 34% (98) were grade 3. Systemic chemotherapy and/or endocrine therapy were administered in 80% (233/289) of patients. Sixty-eight percent (167/244) of patients were post-menopausal. Additionally, there was no significant correlation between CTCs with primary tumor size, lymph node status, estrogen or progesterone receptor status, HER2 amplification or tumor grade. Thirty-eight percent (6/16) of all relapses occurred in patients with 2 or more CTCs (HR: 4.48 (95% C.I. 1.61−12.45), Logrank P 0.002) while 40% (4/10) of all deaths occurred in patients with 2 or more CTCs (HR: 4.54 (95% C.I. 1.27−16.25), Logrank P 0.011). Conclusions: CTCs were a significant predictor of disease-free and overall survival in non-metastatic breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-07.
Abstract 1190: SIRT1 links tumor suppressive NOTCH signaling to p53
Authors: Jozef Ban, Argyro Fourtouna, Isidro Machado, Dave NT Aryee, Gunhild Jug, Antonio Llombart-Bosch, Max Kauer, Heinrich Kovar
Journal: Cancer Research (2012)

Abstract Besides its important role in organismal development, NOTCH receptor signaling exerts tissue specific proliferative or antiproliferative functions. While the oncogenic role of NOTCH has been extensively investigated due to its constitutive activation in T-cell leukemias and several epithelial cancers, little is known about NOTCH mediated tumor suppression. We have previously reported that in Ewing's sarcoma, a pediatric bone tumor driven by the chimeric ETS oncogene EWS-FLI1, auto-stimulatory NOTCH signaling is suppressed and that reactivation results in p53 and consequently growth inhibitory p21 induction via activation of the NOTCH effector HEY1. We now demonstrate that HEY1-mediated p53 stimulation is accompanied by C-terminal p53 acetylation as a consequence of downregulation of nuclear deacetylase sirtuin 1 (SIRT1). We found that both EWS-FLI1 and HEY1 bind to the SIRT1 promoter with opposite transcriptional consequences. Thus, knockdown of EWS-FLI1 and ectopic HEY1 expression resulted in similar SIRT1 modulation and p53 acetylation which could be reversed by ectopically expressed SIRT1. Consistent with these results, treatment of Ewing's sarcoma cell lines with the sirtuin inhibitor Tenovin 6 resulted in massive cell death. Immunohistochemical analysis of more than 310 Ewing's sarcoma samples identified moderate (25%-50% positive nuclei) to strong (&amp;gt;50% positive nuclei) SIRT1 expression in 35% of cases. Additional 20% showed sporadic positivity (between 10-25% positive nuclei). The involvement of SIRT1 in tumor suppressive NOTCH signaling is not restricted to Ewing's sarcoma, but also relevant at least to B-cell malignancies and some normal tissues, since we found that in several B-cell leukemia and lymphoma cell lines and in keratinocytes HEY1 was able to lead to activating p53 acetylation in a SIRT1 suppression-dependent manner. Supported by grants from the Austrian Science Fund (P22328-B09) and the European Comission (EU-FP7 STREP 259348). 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 1190. doi:1538-7445.AM2012-1190
A Lysosome‐Targeting AIEgen for Autophagy Visualization
Authors: Chris Wai Tung Leung, Zhiming Wang, Engui Zhao, Yuning Hong, Sijie Chen, Ryan Tsz Kin Kwok, Anakin Chun Sing Leung, Rongsen Wen, Bingshi Li, Jacky Wing Yip Lam, Ben Zhong Tang
Journal: Advanced Healthcare Materials (2015)

In this work, a morpholine-functionalized aggregation-induced emission luminogen (AIEgen), AIE-LysoY, is reported for lysosomal imaging and autophagy visualization. To attain outstanding imaging contrast, AIE-LysoY is equipped with excited state intramolecular proton transfer (ESIPT) characteristic. AIE-LysoY provides a new platform for lysosome visualization with good biocompatibility, large Stokes shift, superior signal-to-noise ratio, and high photostability. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Abstract LB-296: Allikrein 14 induces epithelial-mesenchymal transition-like changes in colon cancer cells
Authors: Dalila Darmoul
Journal: Cancer Research (2012)

Abstract Accumulating evidence indicates that serine proteinase family of the kallikrein-related-peptidases (KLK1-KLK15) are deregulated in cancer and their up-regulation is often associated with poor patient prognosis. Although primarily known as cancer biomarkers, recent evidence implicates KLKs in many cancer-related processes, including cell-growth, angiogenesis, invasion and metastasis. In addition, KLKs have emerged as signalling molecules by selectively targeting members of a unique subfamily of cell surface G-protein coupled receptors termed, proteinase-activated receptors (PARs). PARs are now considered important players in the development of human colon cancer. Indeed, we have previously demonstrated that in colonic tumours, upregulated PAR-2 and aberrantly expressed PAR-1 and PAR-4 control human colon cancer cell migration and proliferation. Recently, we showed that some members of the aberrantly expressed KLKs mediate these responses by signalling of through PARs. We hypothesized that KLK14 induced-cell migration and colonic tumour invasion are the consequence of epithelial-mesenchymal transition. We focused on KLK14 for which morphological changes were observed when colon cancer cells were treated with KLK14. We found that: 1) microscopic analysis showed redistribution of perijunctional F-actin in KLK14 treated HT29 cells, a colon cancer derived adenocarcinmoma; 2) HT29 cell treatment with KLK14 induced loss of E-cadherin-mediated cell-cell adhesion; 3) Biochemical studies showed down regulation of epithelial markers and upregulation of mesenchymal markers, the molecular mechanisms involved are under investigation. These results suggest for the first time that some KLKs are key mediators of induced ETM in human colonic tumors. 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 LB-296. doi:1538-7445.AM2012-LB-296
Successful Hand Transplantation — One-Year Follow-up
Authors: W P Cooney, V R Hentz
Journal: New England Journal of Medicine (2001)

Background On the basis of positive results in studies of the transplantation of pig extremities and the information exchanged at an international symposium on composite-tissue transplantation, we developed a protocol for human hand transplantation. Methods After a comprehensive pretransplantation evaluation and informed-consent process, the left hand of a 58-year-old cadaveric donor, matched for size, sex, and skin tone, was transplanted to a 37-year-old man who had lost his dominant left hand 13 years earlier. Immunosuppression consisted of basiliximab for induction therapy and tacrolimus, mycophenolate mofetil, and prednisone for maintenance therapy. Results The cold-ischemia time of the donor hand was 310 minutes. There were no intraoperative or early postoperative complications. Moderate acute cellular rejection of the skin of the graft developed 6, 20, and 27 weeks after transplantation. All three episodes resolved completely after treatment with intravenous methylprednisolone and topical tacrolimus...
Bilateral Breast Uptake of Tl-201 Chloride in a Nursing Woman
Authors: NAOYUKI WATANABE, MITSUOMI MATSUMOTO, HIDENORI OHTAKE, TSUNEO HIRANO, KEIKO AOYAGI, MASASHI YUKIHIRO, YUMI FUKUSHIMA, TETSUYA HIGUCHI, KATSUMI TOMIYOSHI, TOMIO INOUE, KEIGO ENDO
Journal: Clinical Nuclear Medicine (1996)

A 35-year-old woman with a 10-month-old infant was evaluated with pulmonary SPECT using Tl-201 chloride to assess the probability of malignant liver for a pulmonary nodule in left upper lobe. No increased Tl-201 uptake in her pulmonary lesion was found. However, there was bilateral breast uptake on early images. This uptake diminished by approximately 50% on delayed images without excretion of milk from the breasts. Tl-201 breast uptake in a nursing woman might be caused by diffusion of Tl-201 into the extravascular space, and the mechanism appears to be different from Ga-67 citrate breast uptake in a nursing woman.
Efficacy and Safety of the Neuraminidase Inhibitor Zanamivir in the Treatment of Influenzavirus Infections
Authors: Frederick G. Hayden, Albert D.M.E. Osterhaus, John J. Treanor, Douglas M. Fleming, Fred Y. Aoki, Karl G. Nicholson, Arthur M. Bohnen, Hilary M. Hirst, Oliver Keene, Kevin Wightman
Journal: New England Journal of Medicine (1997)

The sialic acid analogue zanamivir (GG167) is a selective inhibitor of influenza A and B virus neuraminidases. These viral enzymes are essential for the release of virus from infected cells, and they may also reduce the inactivation of virus by respiratory secretions. When administered experimentally directly to the respiratory tract, zanamivir has potent antiviral effects. We assessed the therapeutic activity of zanamivir in adults with acute influenza.
P4-09-24: Correlation of Aurora Family Member Expression with Clinical Breast Cancer Prognosis.
Authors: A Annakesavan, AJ Sanders, KG Harding, WG Jiang
Journal: Cancer Research (2011)

Abstract Introduction: Aurora-A, Aurora-B and Aurora-C are a family of protein kinases which have been identified as key regulators of the mitotic cell division process. Members of this group have been linked with pro-tumorigenic effects and have been reported as being up-regulated in certain cancers. Our current study examines the expression profile of the Aurora-A, Aurora-B and Aurora-C members in a breast cancer cohort in relation to a number of predictive factors. Materials and Methods: The expression of Aurora-A, Aurora-B and Aurora-C was examined in a breast cancer cohort using quantitative real time PCR (normal samples n = 34, tumour samples n = 109) and immunhistochemistry (IHC). Expression of the aurora members was related to clinical parameters such as staging and Nottingham prognostic index (NPI). Results: Examination of Aurora-A levels in the breast cancer cohort revealed an association of Aurora-A expression with NPI grouping. High levels of Aurora-A levels were seen in NPI-1 and NPI-2 stages (NPI-1 median = 66.0, NPI-2 median = 64.3), with expression reducing significantly at the higher NPI-3 group (NPI-3 median = 20.3; p = 0.029 vs NPI-2 and p = 0.009 vs NPI-1 respectively). Additionally, Aurora-A levels were found to be significantly lower in grade 3 cancers compared to grade 1 (median grade 1 = 86.5 vs median grade 3 levels = 52.6, p = 0.04). In contrast to this, examination of Aurora-C levels in the cohort identified a relatively low level of Aurora-C in NPI-1 and NPI-2 group (median values NPI-1 = 88, NPI-2 = 34.4) compared to a substantial increase in Aurora-C expression in NPI-3 (median value = 1602, p = 0.05 vs NPI-1 and p = 0.06 vs NPI-2). Aurora-B expression levels did not exhibit any significant differences within the breast cancer cohort. Conclusions: Differential expression of Aurora-A, Aurora-B and Aurora-C were observed within the breast cancer cohort. Higher Aurora-A expression was associated with low NPI groups and grades and potentially with better patient prognosis whereas lower levels were seen in the poorer prognostic NPI-3 group and higher grades. An opposite trend was seen in Aurora-C where lower levels were associated with the NPI-1 and NPI-2 groups and significantly higher levels were seen in the NPI-3 group. Aurora-B levels appeared to have no predictive function. This data suggests that together Aurora-A and Aurora-C levels, within a patient may be useful for predicting patient outcome. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-24.
Mortality In Sickle Cell Disease -- Life Expectancy and Risk Factors for Early Death
Authors: Orah S. Platt, Donald J. Brambilla, Wendell F. Rosse, Paul F. Milner, Oswaldo Castro, Martin H. Steinberg, Panpit P. Klug
Journal: New England Journal of Medicine (1994)

Information on life expectancy and risk factors for early death among patients with sickle cell disease (sickle cell anemia, sickle cell-hemoglobin C disease, and the sickle cell-β-thalassemias) is needed to counsel patients, target therapy, and design clinical trials.
Abstract 3089: The role of p63 regulation during epithelial to mesenchymal transition (EMT) and subsequent accumulation of malignant features of primary immortalized prostate cells
Authors: Jan Roger Olsen, Xi-Song Ke, Yi Qu, Kari Rostad, Margrete R. Hellem, James B. Lorens, David R. Micklem, Hallvard Haugen, Karsten Gravdal, Ole Johan Halvorsen, Varda Rotter, Lars A. Akslen, Anne Margrete Oyan, Karl H. Kalland
Journal: Cancer Research (2011)

Abstract A family of transcription factors is constituted by p53, p63 and p73. Unlike p53, which is expressed in response to environmental stress, p63 (TP73L) is constitutively expressed at high levels in a variety of epithelial tissues including prostate. Our genome-wide gene expression analysis identified p63 as one of the most consistently under-expressed genes in prostate cancer samples compared to matched benign prostate tissue. All benign prostate samples including benign prostate hyperplasias (BPH) exhibited high p63 expression. Two alternative p63 promoters generate two different N-terminal variants, TA or ΔN which contains and lacks the transactivating domain, respectively. Differential splicing generates multiple additional isoforms. The activity and interactions of the different isoforms remain unresolved. Using isoform-specific TaqMan real-time quantitative PCR assays, we have found that ΔNp63α is the predominant isoform in prostate tissues, but the other isoforms are detectable. Our group has established a new experimental cell culture model based upon primary, immortalized prostate epithelial cells (EP156T cells), where p63 was found to be shut-down as EP156T cells underwent epithelial-to-mesenchymal transition (EMT) to become EPT1 cells. Subsequently, EPT2 cells were derived from EPT1 cells and p63 stayed shut-down. EPT2 cells had acquired several malignant features in contrast to the progenitors, including anchorage independent growth in soft agar and ability to grow at much higher density in monolayers. To dissect the role of p63 in EMT and in gene expression modules associated with carcinogenesis, we have stably re-expressed the predominant isoform ΔNp63α in both EPT1 and EPT2 cells using retroviral vector transductions. Microarray analysis shows that p63 re-expression leads to re-expression of genes participating in several cell-junction components, such as hemidesmosomes, focal adhesions and gap junctions. These genes were down-regulated during EMT. There were also morphological changes and a decreased ability to migrate following p63 re-expression. This indicates that ΔNp63α re-expression might result in a partial mesenchymal-to-epithelial transition (MET). The present focus is to identify co-factors that may act complementary or synergetically with p63 to induce a complete MET in EPT1 cells and to identify p63 target genes and regulatory cross-talk with relevance for anti-cancer strategies. 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 3089. doi:10.1158/1538-7445.AM2011-3089
P222 DISTINCT ESCAPE PATHWAY BY HCV GENOTYPE 1A FROM A DOMINANT CD8+ T CELL RESPONSE BY SELECTION OF ALTERED EPITOPE PROCESSING
Authors: A. Walker, K. Skibbe, D.A. Megger, T. Kuntzen, S. Groten, G.M. Lauer, A.Y. Kim, B. Sitek, T.M. Allen, J. Timm
Journal: Journal of Hepatology (2014)
EFFICACY PROFILE OF IVABRADINE IN PATIENTS WITH HEART FAILURE PLUS ANGINA PECTORIS
Authors: Jeffrey S. Borer, Karl Swedberg, Michel Komajda, Ian Ford, Luigi Tavazzi, Michael Boehm, Christophe Depre, Chao-Yin Chen, Jae Kim, Fabienne Dominjon
Journal: Journal of the American College of Cardiology (2015)