tbuckley/cabot-search huggingface dataset:
Operationalisation of social cohesion interventions in Latin America and Europe
Authors: Michael A Rodriguez, Ron Brooks, Alexandra Mendoza, David Eisenman, Anne M Dubois, Ondine von Ehrenstein
Journal: The Lancet Global Health (2016)

Background Social cohesion is a complex environmental construct used for development and health promotion. Many governments, along with global and regional agencies, have begun to use social cohesion strategies to promote development and health equity. However, there is little understanding of how the concept of social cohesion is applied practically—that is, operationalised—in interventions. Our aim was to examine stakeholder perspectives on how social cohesion interventions are operationalised in Latin America and Europe to inform development of social cohesion strategies in the USA.
European-Based Cancer INDs Increasing
Authors: Hugh McIntosh
Journal: JNCI Journal of the National Cancer Institute (1992)

European-Based Cancer INDs Increasing Get access Hugh McIntosh Hugh McIntosh Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 1, 1 January 1992, Pages 14–15, https://doi.org/10.1093/jnci/84.1.14 Published: 01 January 1992
Abstract 621: Targeting phosphatidylserine to improve androgen deprivation therapy of prostate cancer
Authors: Yi Yin, Philip E. Thorpe
Journal: Cancer Research (2011)

Abstract Androgen deprivation therapy (ADT) is effective against androgen-dependent prostate cancer, but patients usually relapse from the outgrowth of androgen-independent disease. Here, we tested the hypothesis that relapse can be prevented by combining ADT with treatment with a monoclonal antibody that binds exposed phosphatidylserine (PS). The rationale behind this hypothesis is that ADT will create hypoxia which induces PS exposure on the tumor vascular endothelial cells, leading to immune cell attack on tumor vasculature, collapse of the vessels and death of hormone-resistant and hormone-sensitive tumor cells through deprivation of oxygen and nutrients. In addition, the antibody should block the immunosuppressive effects of PS and induce reactivation of T-cell immunity. To test this hypothesis, we used ADT and anti-PS antibodies (2aG4 or murine chimeric 1N11) to treat mice bearing hormone-sensitive prostate tumors. The tumor models were: i) immunocompromised mice bearing human LNCaP prostate tumors; ii) transgenic (TRAMP) mice which spontaneously develop adenocarcinoma of the mouse prostate. Castration induced exposure of PS on blood vessels and tumor cells in both models. Vascular PS exposure corresponded with hypoxia, as judged by pimonidazole staining. In the LNCaP model, castration alone delayed tumor growth but all animals relapsed with hormone-independent disease, whereas mice treated with castration plus anti-PS antibody did not relapse. In TRAMP mice castrated at 15-weeks of age, only 54% (7/13) of mice treated with castration alone survived beyond 40-weeks of age, as compared with 92% (12/13) of mice treated with castration and 1N11. No toxicity to the mice was caused by the antibody treatment. Tumor blood flow and perfusion were markedly reduced in mice treated with castration and anti-PS antibody. Histological studies revealed extensive disruption of tumor vasculature and abundant infiltration of immune cells, principally M1 macrophages. These results demonstrate that PS becomes exposed on prostate cancer tumor vasculature and tumor cells in response to hypoxia caused by ADT in the tumor microenvironment. The exposed PS could serve as a target to enhance the efficacy of ADT against prostate cancer. 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 621. doi:10.1158/1538-7445.AM2011-621
Abstract 4683: Inducible knockdown of DNA topoisomerase IIα affects drug sensitivity and cell growth
Authors: Cheng-Fen Chen, Xiaolong He, William T. Beck
Journal: Cancer Research (2011)

Abstract DNA topoisomerase IIα (Top2α) is an essential nuclear enzyme and target for important anti-cancer drugs, such as etoposide and doxorubicin (Dox). Our teniposide-resistant human leukemic lymphoblastic cells (CEM/VM-1-5) (Danks MK et al., Biochemistry 27(24):8861-8869, 1998) express reduced Top2α protein. To determine the role of Top2α in drug resistance, we knocked down Top2α in parental CEM cells by RNAi. Compared to control cells, CEMshTop2α cells were more resistant to the Top2 inhibitors, etoposide and Dox. The mechanism by which knockdown of Top2α caused resistance to Top2 inhibitors is probably caused by a reduction in Top2-DNA complexes leading to fewer broken DNA strands (Wang JC, Nat Rev Mol Cell Biol 3(6):430-440, 2002). The level of reduced Top2α expression in Top2α knockdown CEM cells was confirmed by Western blot. Importantly, we found no compensatory regulation by Top1 or Top2α overexpression under these conditions. It has been reported that knocking-out of Top2α will cause early embryonic death (Jenkins JR et al. Nucleic acids research 20(21):5587-5592, 1992), but in our cultured CEM cells, knocking Top2α down to 40% of control level had little or no impact on cell growth rate. We subsequently generated and characterized stable CEM-tTR-shTop2α cells where Top2α can be conditionally knocked down to 5% of control levels, as determined by Western blot, through a tetracycline-induced expression of short hairpin RNAs. CEM-tTR-shTop2α cells grow significantly more slowly than the control cells, which indicates that while cells can proliferate with ∼40% of Top2α expression, when Top2α is reduced by 95%, cells can apparently remain viable, but are severely impaired in their ability to grow. Present studies are focused on identifying genes that are targets of Top2α knockdown to provide insights into those genes involved in drug resistance. (Supported in part by CA40570 from NCI and in part by UIC) 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 4683. doi:10.1158/1538-7445.AM2011-4683
THU0297 Prevalence and Clinical Significance of Severe Flares in a Cohort of Systemic Lupus Erythematosus
Authors: R. López, C. Erausquin, C. Rodríguez-Lozano, A. Naranjo, S. Ojeda, F. Francisco, J. C. Quevedo, L. Cáceres, M. García-Bello, I. Rúa-Figueroa
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) is a systemic autoinmune disorder of relapsing-remitting nature. However, we don´t have enough knowing about severe flare´s relevance on damage, severity or death in SLE patients. <h3>Objectives</h3> To analyze the cumulative incidence and clinical significance of severe flares (SF) in a monocentric, well characterized SLE cohort. <h3>Methods</h3> Cumulative clinical data were retrospectively collected at the moment of the last assessment. SF was defined using Selena-Sledai Flare Index (SFI) tool. Persistently active disease was not considered. SLICC/ACR/DI (SDI) was used to assess damage. Fisher exact test was used for qualitative variables and Kruskal-Wallis for quantitative ones. We compared patients with SF with patients without SF antecedents using bivariate analysis, and also analyzed the impact of SF on SLE-related mortality. <h3>Results</h3> We studied 286 SLE patients (1997 ACR criteria); 3 patients were excluded by insufficient data about flare; 283 were finally included. Female: 91%; caucasian 94.5 %; mean age 48.5 (±13.3); mean SLE duration: 17.1 (±8.8) years; mean follow-up 14.3 (±10.2) years. Median SLE criteria: 6.0 (5.0-7.0); major organ involvement 49 %; class III or IV (OMS) lupus nephritis : 30%; hospitalization by SLE:64 %; median SLICC/ACR/DI 1.0 (0.0 2.0): 7.8 % of the patients had died at the study moment. Severe infection (SInf): 32% hospitalization by SInf : 30%. Cumulative treatment: 84% had received antimalarials at any time, 81%, corticosteroids (≥ 60mg/day: 45 %) and 54 % inmunosupressants; 272 (96.4%) patients had ≥1 flare, median 2 (IQR:1-3). Median SF:1.00 (IQI:0-2), (range: 0-13), mean: 1.4. Median SF per year:0.073 (IQR:0.00-0.17). SF was associated to more damage, Sinf, hospitalization by SInf, more number of hospitalization by infectionand number of SLE criteria (table1). <h3>Conclusions</h3> In our SLE cohort, a history of severe flare was associated to dead, more damage and severe infection. <h3>Disclosure of Interest</h3> None Declared
P4-07-18: Prospective Assessment of Circulating Tumor Cells and Serum Markers for PFS Prediction in Metastatic Breast Cancer.
Authors: F-C Bidard, D Hajage, T Bachelot, S Delaloge, E Brain, M Campone, P Cottu, P Beuzeboc, C Mathiot, J-Y Pierga
Journal: Cancer Research (2011)

Abstract Purpose: Circulating tumors cells (CTC) have been recently proposed as a new dynamic blood marker whose positivity at baseline is a prognostic factor and whose changes under treatment are correlated with progression-free survival (PFS) in metastatic breast cancer patients. However, serum markers levels are also used for the same purpose, and no clear comparison as been reported to date. Patients and methods: The IC 2006–04 enrolled prospectively 267 metastatic breast cancer patients treated by first line chemotherapy and confirmed that CTC levels are an independent prognostic factor for PFS and Overall survival (OS). A pre-planned endpoint was to compare prospectively the positivity rates and the value of CTC (CellSearch®), of serum tumor markers (CEA, CA 15–3, CYFRA 21.1), and of serum non-tumor markers (LDH, ALP) at baseline and under treatment for PFS prediction, independently from the other known prognostic factors, using univariate analyses and concordance indexes. Results: Table 1 shows the incidence of each of the 6 blood markers. Assessing all the 6 markers retrieved 90% of patients with at least one elevated marker at baseline. Interestingly, a combination of two markers (CA 15–3 and CYFRA 21.1, often used in lung cancer) retrieved 86% of patients with at least one marker elevated at baseline. All 6 markers were correlated with poor performance status, high number of metastatic sites and with each other. Each marker was associated, when elevated at baseline, with a significantly shorter PFS in univariate anlaysis. Serum marker changes during treatment, assessed either between baseline and week 3 or between baseline and week 6–9, were significantly associated with PFS, as reported for CTC. Concordance indexes comparison showed no clear superiority of any of the serum marker or CTC for PFS prediction. Conclusion: In the largest prospective CTC study in metastatic breast breast cancer, we previously reported that CTC count, but not serum markers, is an independent prognostic factor for PFS and overall survival. However, for the purpose of PFS prediction by measuring blood marker changes during treatment, currently available blood-derived markers (CTC and serum markers) had globally similar performances. Besides CEA and CA 15–3, CYFRA 21.1 is commonly elevated in metastatic breast cancer and has a strong prognostic value. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-18.
ANGIOTENSIN-CONVERTING ENZYME INHIBITION EARLY AFTER CARDIAC TRANSPLANTATION: A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND TRIAL COMPARING RAMIPRIL VERSUS PLACEBO
Authors: Yuhei Kobayashi, Kozo Okada, Kiran Khush, Sean Sana, Tiffany Daun, Seema Sinha, Garrett Cohen, Yasuhiro Honda, Helen Luikart, Hannah Valantine, Alan Yeung, Jon Kobashigawa, William Fearon
Journal: Journal of the American College of Cardiology (2016)
Massive obscure overt gastrointestinal bleeding secondary to an ileal carcinoid diagnosed and treated using double-balloon enteroscopy
Authors: K. Mönkemüller, L. Fry, R. Kuhn, S. Rickes
Journal: Endoscopy (2011)

A 49-year-old woman was transferred to our hospital because of hematochezia, which had lasted for 24 hours. Her past medical history was positive for osteogenesis imperfecta type 4 and asthma. On clinical examination, the patient was pale and tachycardic with a resting pulse rate of 110. Her blood pressure was 80/40. Hemoglobin was 4.4 mmol/L (reference values 7.4 – 10.0) and hematocrit 0.21 (0.35 – 0.47). The remaining laboratory parameters were within the reference range.
Preventive Health Services in Adults
Authors: Harold J. Sox
Journal: New England Journal of Medicine (1994)

We have set a high standard of evidence for the evaluation of preventive services to be widely used. Cost is one reason. Since everyone is a candidate for preventive services, the aggregate cost is high. Professional ethics is another reason. By seeking out a physician, a sick patient initiates an episode of care. The physician's responsibility is to help, not to guarantee a good outcome. The obligation is more stringent when a physician makes a recommendation to a healthy person: the physician must be sure that the benefits exceed the harm (primum non nocere). For example, screening for a disease . . .
O6.04 * GRANULOCYTIC MYELOID-DERIVED CELLS OBTAINED FROM BLOOD MAINLY SUPPRESS T-CELL PROLIFERATION IN PATIENTS WITH GLIOBLASTOMA
Authors: O. M. Grauer, J. Wolfer, M. Hasselblatt, D. Dubinski, U. Bogdahn, W. Stummer, H. Wiendl
Journal: Neuro-Oncology (2014)

OBJECTIVE: To study the importance of myeloid-derived suppressor cells (MDSC) in primary glioblastomas, we investigated the frequency, phenotype, and immune-suppressive function of different myeloid-derived cells (MDC) in the blood and freshly resected tumors of 40 patients. RESULTS: Multicolour flow cytometric analysis showed that the frequency of CD14lowCD15+ granulocytic CD11bhighCD33b+ MDC was higher in peripheral blood and tumor samples of glioblastoma patients compared to healthy controls and positively correlated with the tumor volume before resection. Granulocytic MDC expressed CD16, CD66b, CD114, CD195 and could be further divided into CD14lowCD15high neutrophilic and CD14lowCD15int eosinophilic MDC. Moreover, we could detect an intratumoral accumulation of CD14highCD15+ monocytic CD11bhighCD33b+ MDC expressing CD115, CD124, CD184, CD206 and CX3CR1. All MDC subsets stained positively for reactive oxygen species, but Arginase 1 was specifically expressed in tumor-infiltrating MDC. T cell suppression assays with FACS-sorted MDC revealed that granulocytic and most prominently eosinophilic MDC obtained from the blood, but not the tumor could efficiently suppress non-specific T cell proliferative responses. Contrary to blood-derived MDC, HLA-DR expression was significantly increased on tumor-infiltrating MDC. Upon LPS or R848 stimulation, blood-derived MDC showed an increased production of IL-10, in contrast to tumor-infiltrating MDC that were resistant to Toll-like-receptor (TLR) stimulation. Although the frequency of granulocytic MDC inversely correlated with CD4+ and CD8+ T memory cells in the blood, no association with time to tumor progression in glioblastoma patients could be found. CONCLUSION: Our findings provide a detailed characterization of the nature and suppressive function of MDC in glioblastoma patients and indicate that granulocytic MDC obtained from the blood but not from the tumor mainly suppress T-cell proliferation.
PMO-111 Should all patients with locally advanced pancreatic cancer be offered intraoperative assessment?
Authors: V Rao, K Chantladze, S Kugathasan, O Byass, A Razack, K Wedgwood
Journal: Gut (2012)

<h3>Introduction</h3> Surgery is the only potentially curative option in patients with pancreatic cancer. Hence it is extremely important that the diagnostic tests used to ascertain resectability is very reliable before this curative option is denied to this unfortunate group of patients. CT and Endoscopic Ultrasound (EUS) which are commonly used as part of pre operative staging was compared with intraoperative findings to assess diagnostic reliability in determining resectability in patients with pancreatic cancer. <h3>Methods</h3> All patients diagnosed with pancreatic adenocarcinoma over a 2-year period who underwent trial dissection or resection after routine staging with CT and EUS were included in the study. CT and EUS images were retrospectively reviewed by two radiologists in a double blinded manner and the findings were compared with operative findings and final histology in those patients who underwent radical resection. Sensitivity, Specificity, Positive Predictive value (PPV), Negative predictive value and Accuracy were determined for assessing major vessel involvement which in most cases preclude radical resection. <h3>Results</h3> 23 patients (M:F=13:10; mean age=68; range=56–78) underwent trial dissection or radical resection over a 2-year period. 13 were inoperable (nine inoperable due to locally advanced tumour, 1 inoperable due to liver mets, three both locally advanced and liver mets) and 10 underwent radical resection (three resected with cuff of portal vein (all R1), seven resected with six of them R1). Predictably EUS had superior sensitivity and accuracy over CT for both major vessel involvement (88% vs 53% &amp; 87% vs 65%) and nodal involvement (43% vs 10% &amp; 56% vs 30%). However CT was superior to EUS in excluding major vessel involvement (specificity = 100% vs 86%) and comparable to EUS in ruling out nodal disease (specificity = 100%). Importantly, three patients declared as having major vessel involvement by either of the modality underwent radical resection, two of them with PV resection. One patient who was staged as resectable with no vascular involvement was found to have major vessel involvement and underwent resection (R1). <h3>Conclusion</h3> Though CT and EUS have important role in staging of patients with pancreatic cancer, a significant minority of patients will still be amenable to radical surgery and should be offered trial dissection with a view to radical surgery as surgery is the only realistic curative therapeutic option. <h3>Competing interests</h3> None declared.
Thyroid Carcinoma Found at Parathyroidectomy
Authors: Andreas D Fotopoulos, Sophia Koukouraki, George Schoretsanitis, Antigoni Velidaki, Dimitris Tsiftsis, Nicolas Karkavitsas
Journal: Clinical Nuclear Medicine (2002)

FOTOPOULOS, ANDREAS D. M.D.*; KOUKOURAKI, SOPHIA M.D.†; SCHORETSANITIS, GEORGE M.D.†; VELIDAKI, ANTIGONI M.D.†; TSIFTSIS, DIMITRIS M.D.‡; KARKAVITSAS, NICOLAS M.D.† Author Information
RENAL DENERVATION IMPROVES POST-INFARCTION REMODELING AND HEMODYNAMICS THROUGH MODULATION OF CARDIOPROTECTIVE PLASMA PEPTIDES
Authors: David Polhemus, Juan Gao, Amy L. Scarborough, Jessica M. Bradley, Rishi K. Trivedi, Frank Smart, Daniel R. Kapusta, David J. Lefer
Journal: Journal of the American College of Cardiology (2016)
Abstract 204: Breast cancer stem and non-stem-like cells express varying levels of selectin ligand activities.
Authors: Venktesh S. Shirure, Chengkai Xiong, Fabian Benencia, Monica M. Burdick
Journal: Cancer Research (2013)

Abstract Cancer stem cells are a subset of tumor cells proposed to possess traits enabling metastatic invasion. Independently, selectins and their ligands are believed to play major roles in mediating the adhesion of circulating tumor cells to vascular endothelium during hematogenous metastasis. We thus hypothesized that the expression level of selectin ligands on breast cancer cells is related to breast cancer stem cell (BSC) or non-BSC phenotypes. Five breast carcinoma cell lines analyzed by flow cytometry were categorized as BSCs by the surface expression profile CD44+/CD24-/low, or non-BSCs marked by alternative expression of these proteins. All cell lines positively expressed E-, P-, and L-selectin ligand activity by flow cytometric analysis as well as under physiological flow conditions. Consistent with their E-selectin ligand activities, all cell lines expressed putative glycans for E-selectin binding, including sLeX, sLeA, and/or VIM-2 glycans, found by flow cytometric analysis. Yet the level of selectin ligand activity and glycan expression in BSCs was conspicuously lower than in non-BSCs. The abundant production of selectin-reactive glycans in non-BSCs was associated with α-(1,3)- and α-(1,4)-fucosyltransferases, as indicated by qRT-PCR analysis. Importantly, BSCs as well as non-BSCs expressed molecules, such as CD44, that are capable of carrying carbohydrates necessary for E-selectin ligand function. Furthermore, BSCs were mesenchymal-like and non-BSCs were epithelial-like cells, as found by immunostaining of breast cancer cells for E-cadherin and N-cadherin in fluorescence microscopy. Significantly, treatment of a non-BSC cell line with TGF-β induced epithelial-to-mesenchymal transition (EMT) marked by changes in cell morphology, increases in expression levels of N-cadherin, and increases in E-cadherin suppressor genes. These EMT cells showed reduced levels of E-selectin ligand activity under physiological flow conditions, indicating loss of selectin ligand activity upon acquisition of mesenchymal properties. In summary, the selectin ligand activity of BSCs is lower than that of non-BSCs, and the level of selectin ligand activity of breast cancer cells is potentially controlled by BSC and EMT states. Citation Format: Venktesh S. Shirure, Chengkai Xiong, Fabian Benencia, Monica M. Burdick. Breast cancer stem and non-stem-like cells express varying levels of selectin ligand activities. [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 204. doi:10.1158/1538-7445.AM2013-204