tbuckley/cabot-search huggingface dataset:
Abstract 683: Toxicity of aerosolized azacytidine (Vidaza) in mice.
Authors: Xuan Qiu, Rani Sellers, Yuanxin Liang, Bilal Piperdi, Roman Perez-Soler, Yiyu Zou
Journal: Cancer Research (2013)

Abstract Background: Azacytidine, a prototypical demethylation agent, has been approved to treat myelodysplastic syndrome. Commercial azacytidine (Vidaza) is delivered to patients by subcutaneous or intravenous administration. In a previous study, we found that aerosolized azacytidine can 1) inhibit human orthotopic lung cancers in a mouse xenograft model, 2) demethylate several promoters of tumor suppressor genes reported to be hypermethylated in human lung cancer, and 3) be better tolerated and more effective than systemic administration. These studies specifically addressed toxicity associated with aerosolized delivery of Vidaza to the lungs; specifically hematologic and pulmonary toxicity. Methods: Vidaza was dissolved into sterile water for injection and aerosolized in a clinical standard aerosol system. Swiss mice male and female 6/group were restricted into a nose-only exposure system for receiving the aerosol. We treated the mice at 2 different doses, 7.5 mg/m2 daily x 7 days and 2.5 mg/m2 daily x 7 days. Blood, sternum (for bone marrow), and lung were collected at 3 and 6 weeks after the final aerosol treatment. The bone and lung were fixed in 10% neutral buffered formalin and routinely processed to paraffin blocks, sectioned, stained, and evaluated histologically. In a preliminary pharmacokinetic study, azacytidine concentrations in the blood and lung samples from mice receiving 2.5 mg/m2 of aerosolized azacytidine were determined by a MS-HPLC method previously described by others. Results: Neither dose of aerosolized Vidaza resulted in bone marrow changes. A mild pneumonitis was present in lungs from mice treated with 7.5 mg/m2 at 3 weeks but was not evident at six weeks (reversible). No pulmonary toxicity was observed at the 2.5 mg/m2 dose. The preliminary pharmacokinetic study data indicate very low drug concentrations in the blood and much higher concentrations in the lungs. Conclusion: Our study demonstrates that low dose aerosolized azacytidine can be safely administered to mice. Reversible pulmonary toxicity (pneumonitis) was observed at 7.5 mg/m2 at 3 weeks post treatment. The recommended starting dose of aerosolized azacytidine in human clinical phase I trial should be 2.5 mg/m2. Supported by NIH grant 5R01CA154755 to Roman Perez-Soler and Yiyu Zou. Citation Format: Xuan Qiu, Rani Sellers, Yuanxin Liang, Bilal Piperdi, Roman Perez-Soler, Yiyu Zou. Toxicity of aerosolized azacytidine (Vidaza) in mice. [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 683. doi:10.1158/1538-7445.AM2013-683
Sleep Apnea, Hypopnea and Oxygen Desaturation in Normal Subjects
Authors: A. Jay Block, Philip G. Boysen, James W. Wynne, Lynn A. Hunt
Journal: New England Journal of Medicine (1979)

Thirty asymptomatic men and 19 asymptomatic women were monitored during one night's sleep to determine the incidence of breathing abnormalities and oxygen desaturation in normal subjects. Twenty men accounted for 264 episodes of nocturnal oxygen desaturation or abnormal breathing. Women never experienced oxygen desaturation, and only three had a total of nine episodes of apnea. These sex differences were highly significant (P less than 0.003). In men, increasing age and obesity correlated positively with the incidence of nocturnal oxygen desaturation and abnormal breathing. Four asymptomatic men weighing more than 90 kg dropped their saturation to very low levels (68 to 72 per cent). Abnormal breathing and oxygen desaturation during sleep in subjects with chronic obstructive lung disease of the syndrome of hypersomnolence with periodic breathing may represent the superimposition of smoking or obesity on a normal tendency to snoring and oxygen desaturation in men.
AB0892 NT-PROBNP in ankylosing spondylitis patients undergoing TNF blockage therapy: Correlation with inflammatory status independent of cardiovascular disease
Authors: J.C. Moraes, A.C.D.M. Ribeiro, C.G.S. Saad, A.C. Lianza, C.A. Silva, E. Bonfa
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Inflammation may influence levels of N-terminal pro-brain natriuretic peptide (NT-proBNP)<sup>1-3</sup> discrimination of this confounding variable is of particular interest in rheumatic diseases.<sup>4</sup> <h3>Objectives</h3> We evaluated NT-proBNP levels in ankylosing spondylitis (AS) patients without systolic myocardial dysfunction pre- and post-TNF blocker initiation to determine the possible association between NT-proBNP levels and inflammatory parameters. <h3>Methods</h3> Forty-five consecutive AS patients without previous/current cardiovascular disease, who were eligible to receive anti-TNF therapy, were prospectively enrolled. All patients were treated with TNF blockers, and they were evaluated for clinical and laboratory parameters of disease activity, traditional cardiovascular risk factors, conventional and tissue Doppler imaging echocardiography, and circulating NT-proBNP levels at baseline (BL) and six months after (6M) treatment. <h3>Results</h3> All patients had active disease at BL [ASDAS-CRP=3.58 (1.11); ASDAS-ESR=3.02 (1.12); BASDAI=5.1 (2.2); CRP=1.89 (0.80-4.19) mg/dL; and ESR=16 (8-32.5) mm/1st h]. At BL, NT-proBNP levels were 36 (20-72) pg/ml, and multiple linear regression analysis revealed that this peptide was independently correlated with age (r=0.458, p=0.002) and ESR (r=0.398, p=0.007). From BL to 6M, all parameters improved, and NT-proBNP levels were significantly reduced [24 (16-47) pg/mL, p=0.037]. Changes in NT-proBNP levels were significantly correlated with ESR changes from BL to 6M (r=0.39, p=0.008) (Figure 1). Cardiovascular risk factors and echocardiography remained unchanged. <h3>Conclusions</h3> NT-proBNP levels should be interpreted with caution in active AS patients with no evidence of CV disease. The prospective reduction of NT-proBNP in parallel with ESRsuggests that this peptide level is, to some degree, modifiable by inflammation status independent of cardiovascular disease. (ClinicalTrials.gov number, NCT01072058). <h3>References</h3> Jensen J, Ma LP, Fu MLX, et al. Inflammation increases NT-proBNP and the NT-proBNP/BNP ratio. Clin Res Cardiol 2010;99:445-52. Meirovich YF, Veinot JP, de Bold MLK, et al. Relationship between natriuretic peptides and inflammation: proteomic evidence obtained during acute cellular cardiac allograft rejection in humans. J Heart Lung Transplant 2008;27:31-7. de Bold AJ. Cardiac natriuretic peptides gene expression and secretion in inflammation. J Investig Med 2009;57:29-32. Peters MJL, Welsh P, McInnes IB, et al. Tumour necrosis factor α blockade reduces circulating N-terminal pro-brain natriuretic peptide levels in patients with active rheumatoid arthritis: results from a prospective cohort study. Ann Rheum Dis 2010;69:1281-5. <h3>Disclosure of Interest</h3> None Declared
P429The activity of monoamine oxidases is tightly related to mitochondrial membrane fluidity altered by aging, obesity and oxidative stress
Authors: F Di Lisa, R Menabo, A Carpi
Journal: Cardiovascular Research (2014)

Background and Purpose: The relevance of mitochondria in the generation of oxidative stress is well established. In this respect the mitochondrial enzymes monoamine oxidases (MAO) are a relevant source of reactive oxygen species (ROS) and their inhibition has been shown to prevent both reperfusion injury and maladaptive remodeling. However, the mechanisms responsible for the increase in MAO activity in injured cardiomyocytes have not been elucidated. This study aims at characterizing fluidity changes of mitochondrial membranes as a factor modulating MAO activity. Methods: Membrane fluidity in mitochondria isolated from mouse hearts was evaluated as changes in fluorescence anisotropy of added hematoporphyrin that probes phospholipid heads interacting with protein polar domains. Previous studies have shown that an increase in mitochondrial membrane fluidity (MMF) is associated with abnormalities, such as a decreased respiration and an increased propensity to opening of the permeability transition pore. However, its relationship with mitochondrial ROS generation was never investigated. Mitochondrial integrity and function were assessed by measuring membrane potential with Rhodamine123. The activity of MAO using tyramine as substrate was measured by assessing H2O2 formation. Results: The addition of the omega3 fatty acid docohexanoic acid (DHA) caused a 60±4% increase in membrane rigidity that was paralleled by a 40±7.8% decrease in MAO activity. The effect of DHA was abrogated by doxorubicin. This cardiotoxic agent promotes oxidative stress by interacting with mitochondria. The anisotropy measurement of its intrinsic fluorescence showed a dose-dependent increase in MMF associated with an increase in MAO activity. The relationship between MMF and MAO activity was supported by measurements in mitochondria isolated from hearts of mice subjected to pathophysiological conditions, such as high fat diet and aging. Eight weeks of high fat diet resulted in a significant increase (25±8.3%) in both MMF and MAO activity. Similar results were obtained by comparing young mice (4 months old (mo.)) with adult (14 mo.) and senescent (24 mo.) littermates. In a time-dependent fashion aging increased MMF and MAO activity. Conclusions: For the first time evidence is provided of a tight relationship between membrane fluidity of heart mitochondria and the ROS producing activity of MAO. Mitochondrial membrane fluidity is likely to contribute to cardiac oxidative stress by means of MAO modulation.
Older smokers are left out of antismoking policies
Authors: C. White
Journal: BMJ (1997)

Older smokers are consistently ignored by antismoking initiatives, yet no one is ever too old to give up smoking, according to several papers in Tobacco Control .

Older people represent the fastest growing segment of the population in industrialised countries. So although the prevalence of smokers in this group is low, sheer numbers will ensure that this sector of the community will be a major contributor to healthcare …
Abstract 2431: 89Zr-bevacizumab PET as an early biomarker for response to everolimus treatment in an ovarian cancer xenograft model
Authors: Anton G.T. Terwisscha van Scheltinga, Arne R.M. van der Bilt, Hetty Timmer-Bosscha, Carolien P. Schröder, Linda Pot, Jos G.W. Kosterink, Ate G.J. van der Zee, Marjolijn N. Lub-de Hooge, Steven de Jong, Elisabeth G.E. de Vries, An K.L. Reyners
Journal: Cancer Research (2012)

Abstract The mammalian target of rapamycin (mTOR) pathway is activated in the majority of ovarian cancers and is involved in tumor angiogenesis. Inhibitors of mTOR, like everolimus, are potentially interesting drugs as they can exert antitumor activity in part through reducing downstream vascular endothelial growth factor-A (VEGF-A) production. We investigated whether early effects of everolimus treatment could be monitored with 89Zr-bevacizumab positron emission tomography (VEGF-PET). Methods: The effect of everolimus on VEGF-A secretion was determined in three human ovarian cancer cell lines and in A2780luc+ ovarian cancer cells xenografted subcutaneously in BALB/c mice. Mice received daily everolimus (10 mg/kg intraperitoneally) for 14 days. PET scans with the tracer 89Zr-labeled bevacizumab were performed to monitor tumor VEGF-A expression before (baseline) and after treatment. Images were obtained 6 days after tracer injection. Tracer uptake was quantified and expressed as mean standardized uptake values (SUVmean). For ex vivo 89Zr-bevacizumab biodistribution and correlative tissue analyses, control animals were sacrificed after the baseline scans. Tumor VEGF-A levels were measured with ELISA in tumor lysates and mean vascular density (MVD) was determined with immunohistochemistry. Results: Everolimus treatment lowered VEGF-A levels in the supernatant of all cell lines. Everolimus lowered 89Zr-bevacizumab tumor uptake by 21.7 ± 4.0% (SUVmean 2.26 ± 0.18 versus 2.89 ± 0.20, p &amp;lt; 0.01). Ex vivo 89Zr-bevacizumab biodistribution showed less tracer uptake in the tumors of treated compared to control animals (7.78 ± 0.84 %ID/g versus 14.02 ± 1.68 %ID/g, p &amp;lt; 0.01), while no differences were observed for other tissues. VEGF-A protein levels in tumor lysates were lower in treated versus untreated tumors (p = 0.04), as was the MVD (p &amp;lt; 0.01). Conclusion: 89Zr-bevacizumab PET showed reduced tumor VEGF-A levels in vivo in response to everolimus therapy, coinciding with inhibition of tumor angiogenesis. Currently there are 2 clinical trials ongoing to study the value of 89Zr-bevacizumab PET to monitor tumor VEGF-A levels as an early biomarker of response to mTOR inhibitor therapy. 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 2431. doi:1538-7445.AM2012-2431
P152 The Relationship Between Educational Qualifications, Access To Information Technologies And Clinical Outcomes In Patients With Acute Exacerbation Of Copd (aecopd)
Authors: R. Wijayarathna, E. Suh, S. Mandal, N. Hart
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Although socioeconomic factors are known to influence clinical outcome in COPD patients, few studies have addressed the impact of educational attainment. This is particularly relevant in light of the fact that telehealth, using often complex technologies, are increasingly used in the management of chronic diseases. We therefore aimed to ascertain the proportion of patients hospitalised with AECOPD who have formal educational qualifications and access to information technologies. <h3>Method</h3> Clinical and physiological data were prospectively gathered from consecutive patients admitted to a metropolitan teaching hospital with AECOPD between April and December 2013. Patient data were analysed according to the possession of educational qualifications, and access to a personal computer and the internet. <h3>Results</h3> 100 patients were admitted with AECOPD (40% female, age 70.5 ± 9.3 years). 51% of patients lived alone, 38% were current smokers with a FEV1 0.70 ± 0.39 L at admission, and 13% were receiving long term oxygen therapy. Median symptomatic days prior to admission was 4.0 (IQR 1 to 14), with an annual admission frequency of 2.0 (IQR 1 to 6). 14% of patients had access to both a computer and the internet. Patients with no access to these technologies were older (71.2 ± 9.2 vs. 64.8 ± 7.7 years, p &lt; 0.02). Patients with no educational qualifications had a lower%predicted FEV1 (31.2 ± 23.6 vs. 38.7 ± 20.9, p &lt; 0.05), and were less likely to have access to information technologies (7% vs. 93%, p &lt; 0.05). They were more likely to be readmitted within 28 days (11% vs 3%, p=ns), but presented with a lower symptom burden on admission as measured by the numerical rating scale (3.6/10 vs. 5.0/10, p=ns). <h3>Conclusion</h3> These data suggest there may be difficulties in implementing the use of telehealth within this metropolitan COPD population. Only 14% had access to a computer and the internet. Patients with no educational qualifications had worse spirometry at admission, but surprisingly a lower symptom burden. This may be due to the fact that those with educational qualifications may have a greater awareness of the symptoms of an exacerbation, and therefore present to hospital at an earlier stage.
Experimental Production of Carotid Aneurysms
Authors: William J. German, Samuel P. W. Black
Journal: New England Journal of Medicine (1954)

RUPTURE of an intracranial aneurysm is one of the most common causes of sudden death in young adults. The surgical treatment of these "berry" aneurysms has now developed to a stage where knowledge concerning their hemodynamic characteristics is desirable. The present report is concerned with a method of producing "berry" aneurysms of the common carotid arteries of dogs, together with preliminary studies of intra-aneurysmal hemodynamics.The initial attempts at aneurysm production were by injury to the arterial walls. Incision of the adventitia and media did not cause an aneurysm to form. In the words of John Hunter,1 who tried this . . .
Abstract 1596: Human choriocarcinomas: Placental growth factor-dependent preclinical tumor models
Authors: Rebecca G. Bagley, Yi Ren, Leslie Kurtzberg, William Weber, Dinesh Bangari, Beverly A. Teicher
Journal: Cancer Research (2011)

Abstract Choriocarcinomas are an aggressive form of cancer that develops in the uterus from tissue that would normally become the placenta. Choriocarcinomas are a trophoblastic gestational disease and the tumors are highly angiogenic. Human placental growth factor (hPlGF) is an angiogenic growth factor that promotes the growth of blood vessels in the placenta. hPlGF levels can be higher under pathological conditions such as cancer. Some human tumor specimens have higher PlGF levels than normal tissue, thus hPlGF is a target for anti-angiogenic therapy. The human choriocarcinoma cell lines BeWo, JAr, and JEG-3 were evaluated as preclinical models of hPlGF overexpression. The levels of hVEGF-A and hPlGF secreted by the choriocarcinomas and 11 human and mouse cancer cell lines in culture were measured by ELISA. The choriocarcinomas secreted higher levels of hPlGF and lower levels of hVEGF-A than 10/11 other cancer cell lines. The hPlGF serum levels in mice bearing subcutaneous choriocarcinoma tumors correlated with tumor volume and reached &amp;gt;2,000 pg/ml. By comparison, no hPlGF was detected in the serum of mice bearing H460 non-small lung carcinoma, HT29 colon carcinoma or MOLM-13 acute myeloid leukemia xenograft tumors. Although choriocarcinoma cells secreted both hPlGF and hVEGF-A in culture, serum levels of hVEGF-A in mice bearing choriocarcinoma xenografts were undetectable or &amp;lt;50 pg/ml at the time points serum was collected indicating that angiogenic factor secretion by the cells in culture was not the same in vivo. JEG-3 tumors grew faster than JAr tumors following the subcutaneous implantantion of 1×106 cells into nude mice. BeWo tumors grew the slowest and had the highest serum PlGF levels. Immunohistochemical methods confirmed expression of hPlGF in the choriocarcinoma xenografts. Studies involving double immunofluorescence on the xenograft tumors are ongoing to investigate endothelial cell and pericyte interactions and stromal involvement in the tumors. sFLT01, a novel fusion protein that neutralizes PlGF and VEGF-A, was added to choriocarcinoma cells in culture and administered to mice bearing choriocarcinoma xenografts in efficacy studies. Exposure of JAr and JEG-3 cells in culture to sFLT01 resulted in a phenotypic change whereby the cells produced less hPlGF and no significant hVEGF-A. In vivo, sFLT01 (25 mg/kg, IP injection, 2x per week) slowed tumor growth in JAr and JEG-3 tumors and increased median survival by 5-30 days compared to vehicle controls. These results indicate that human choriocarcinoma xenograft models are a valuable research tool for evaluating anti-angiogenic agents that target hPlGF. 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 1596. doi:10.1158/1538-7445.AM2011-1596
Abstract 5528: Identification of compounds modifying radiation-therapy using a 3D-microtissue technology.
Authors: Natasa Anastasov, Ines Höfig, Jan Lichtenberg, Simon Stroebel, Michael Salomon, Christian Thirion, Jens Kelm, Michael J. Atkinson
Journal: Cancer Research (2013)

Abstract The two key issues in chemo- and radiation therapy is the development of tumor resistance as well as toxic effects on normal tissue. In this sense new strategies are required to increase efficacy of radiation to improve the therapeutic impact and reduce toxicological side effects. The performance of 3D cell culture systems over classical 2D culture systems has been shown to provide a closer representation of tissue-level biology. This has led to the rapid adoption of 3D systems for both drug discovery and toxicology. InSphero has developed a highly reproducible hanging drop technology able to generate monotypic cell spheroids (microtissues) in a 96-well format. The innovative 3D-microtissue plate technology has been adapted for analysis of the cellular response of radioresistant T47D breast cancer cells to combined radio-chemotherapy (RCTx). We have validated the model by comparing the treatment of microtissues with 10 different chemotherapeutic compounds, each tested alone and in combination with an acute 2Gy radiation exposure. The T47D cells were stably transduced with GFP-lentiviral vector enabling faster high throughput quantification of 3D microtissue growth assessment using an Operetta working Software and detection system ‘Harmony 3.0’ (PerkinElmer, USA). We studied the ability of RCTx to modify 3D-microtissue growth 3, 6 and 10 days after treatment. Results for five compounds (Actinomycin D, Staurosporine, Docetaxel, Doxorubicin and Vinblastine) showed that the IC50 values were improved by the addition of the single 2Gy radiation dose, indicating that they are capable of inducing a radiosensitation effect on radioresistant breast cancer cells. Panels of commercial secondary functional assays were adapted to the 3D-microtissue high throughput assay. Cellular viability and cytotoxicity were measured directly in microtissues using the CellTiter-Glo Reagent (Promega, USA). Apoptosis was measured using an ELISA based M30-Apoptosense assay (TECOmedical AG, Switzerland). These results all confirm that the assay operated with the 3D-microtissue model system is able to detect compounds that modulate tumors cell survival after irradiation. Citation Format: Natasa Anastasov, Ines Höfig, Jan Lichtenberg, Simon Stroebel, Michael Salomon, Christian Thirion, Jens Kelm, Michael J. Atkinson. Identification of compounds modifying radiation-therapy using a 3D-microtissue technology. [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 5528. doi:10.1158/1538-7445.AM2013-5528
Women Flock to ABMT for Breast Cancer Without Final Proof
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Women Flock to ABMT for Breast Cancer Without Final Proof Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 13, 5 July 1995, Pages 952–955, https://doi.org/10.1093/jnci/87.13.952 Published: 05 July 1995