tbuckley/cabot-search huggingface dataset:
Plexin D1 Expression Is Induced on Tumor Vasculature and Tumor Cells: A Novel Target for Diagnosis and Therapy?
Authors: Ilse Roodink, Jos Raats, Bert van der Zwaag, Kiek Verrijp, Benno Kusters, Hans van Bokhoven, Marianne Linkels, Robert M.W. de Waal, William P.J. Leenders
Journal: Cancer Research (2005)

Abstract We previously reported that during mouse embryogenesis, plexin D1 (plxnD1) is expressed on neuronal and endothelial cells. Endothelial cells gradually loose plxnD1 expression during development. Here we describe, using in situ hybridization, that endothelial plxnD1 expression is regained during tumor angiogenesis in a mouse model of brain metastasis. Importantly, we found PLXND1 expression also in a number of human brain tumors, both of primary and metastatic origin. Apart from the tumor vasculature, abundant expression was also found on tumor cells. Via panning of a phage display library, we isolated two phages that carry single-domain antibodies with specific affinity towards a PLXND1-specific peptide. Immunohistochemistry with these single-domain antibodies on the same tumors that were used for in situ hybridization confirmed PLXND1 expression on the protein level. Furthermore, both these phages and the derived antibodies specifically homed to vessels in brain lesions of angiogenic melanoma in mice after i.v. injection. These results show that PLXND1 is a clinically relevant marker of tumor vasculature that can be targeted via i.v. injections.
Roles of Radiation Dose, Chemotherapy, and Hormonal Factors in Breast Cancer Following Hodgkin's Disease
Authors: F. E. van Leeuwen, W. J. Klokman, M. Stovall, E. C. Dahler, M. B. van't Veer, E. M. Noordijk, M. A. Crommelin, B. M. P. Aleman, A. Broeks, M. Gospodarowicz, L. B. Travis, N. S. Russell
Journal: JNCI Journal of the National Cancer Institute (2003)

Female survivors of Hodgkin's disease (HD) have a strongly elevated risk of breast cancer, but factors responsible for the increased risk are not well known.We investigated the effects of radiation dose, chemotherapy (CT), and reproductive factors on breast cancer risk in a nested case-control study in The Netherlands in a cohort of 770 female patients who had been diagnosed with HD before age 41. Detailed treatment information and data on reproductive factors were collected for 48 case patients who developed breast cancer 5 or more years after diagnosis of HD and 175 matched control subjects. The radiation dose was estimated to the area of the breast where the case patient's tumor had developed and to a comparable location in matched control subjects. Relative risks (RRs) of breast cancer were calculated by conditional logistic regression. Statistical tests were two-sided.The risk of breast cancer increased statistically significantly with radiation dose (P(trend) =.01); patients who received 38.5 Gy or more had an RR of 4.5 (95% confidence interval [CI] = 1.3 to 16) times that of patients who received less than 4 Gy. Patients who received both CT and radiotherapy (RT) had a statistically significantly lower risk than those treated with RT alone (RR = 0.45, 95% CI = 0.22 to 0.91). Breast cancer risk increased with increasing radiation dose among patients who received RT only (RR = 12.7, 95% CI = 1.8 to 86, for patients receiving > or =38.5 Gy) but not among patients treated with CT and RT. Sixty-nine percent of control subjects treated with RT and more than six cycles of CT, but only 9% of those who received RT alone, reached menopause before age 41. Reaching menopause before age 36 was associated with a strongly reduced risk of breast cancer (RR = 0.06, 95% CI = 0.01 to 0.45).Breast cancer risk increases with increasing radiation dose up to at least 40 Gy. The substantial risk reduction associated with CT may reflect its effect on menopausal age, suggesting that ovarian hormones promote tumorigenesis after radiation has produced an initiating event.
Antagonism of CXCR3 Inhibits Lung Metastasis in a Murine Model of Metastatic Breast Cancer
Authors: Tonya C. Walser, Salah Rifat, Xinrong Ma, Namita Kundu, Chris Ward, Olga Goloubeva, Michael G. Johnson, Julio C. Medina, Tassie L. Collins, Amy M. Fulton
Journal: Cancer Research (2006)

Abstract Tumor cells aberrantly express chemokines and/or chemokine receptors, and some may promote tumor growth and metastasis. We examined the expression and function of chemokine receptor CXCR3 in a syngeneic murine model of metastatic breast cancer. By flow cytometry, CXCR3 was detected in all murine mammary tumor cell lines examined. All human breast cancer cell lines examined also expressed CXCR3, as did the immortalized but nontumorigenic MCF-10A cell line. Interaction of CXCR3 ligands, CXCL9, CXCL10, and CXCL11, with CXCR3 on the highly malignant murine mammary tumor cell line 66.1 resulted in intracellular calcium mobilization and chemotaxis in vitro. To test the hypothesis that tumor metastasis is facilitated by CXCR3 expressed by tumor cells, we employed a small molecular weight antagonist of CXCR3, AMG487. 66.1 tumor cells were pretreated with AMG487 prior to i.v. injection into immune-competent female mice. Antagonism of CXCR3 on 66.1 tumor cells inhibited experimental lung metastasis, and this antimetastatic activity was compromised in mice depleted of natural killer cells. Systemic administration of AMG487 also inhibited experimental lung metastasis. In contrast to the antimetastatic effect of AMG487, local growth of 66.1 mammary tumors was not affected by receptor antagonism. These studies indicate that murine mammary tumor cells express CXCR3 which facilitates the development of lung metastases. These studies also indicate for the first time that a small molecular weight antagonist of CXCR3 has the potential to inhibit tumor metastasis. (Cancer Res 2006; 66(15): 7701-7)
Time to stand up and make a difference
Authors: Annie S Anderson, Robert J C Steele
Journal: BMJ (2015)

Current estimates for cancer prevention (www.wcrf-uk.org/uk/preventing-cancer/cancer-preventability-statistics) suggest that around 30% of 13 of the most common cancers in the United Kingdom could be prevented through improvements in diet, physical activity, and body weight. The importance of sedentary behaviour is also becoming clearer.1

As organisers of the annual Scottish Cancer Prevention Network conference we think carefully about what we ask our colleagues to do at meetings. We explore meeting venues with care. Regular catering options include deep fried items, sausage rolls, and …
New Approaches to Inhibiting Platelets and Coagulation
Authors: Jeremiah P. Depta, Deepak L. Bhatt
Journal: The Annual Review of Pharmacology and Toxicology (2015)

Ischemic heart disease and stroke are major causes of death and morbidity worldwide. Coronary and cerebrovascular events are a consequence of thrombus formation caused by atherosclerotic plaque rupture or embolism, both of which result from platelet activation and aggregation and thrombin-mediated fibrin generation via the coagulation cascade. Current and emerging antiplatelet and anticoagulant agents are evolving rapidly. The use of aspirin for primary prevention continues to be controversial, as are the doses appropriate for secondary prevention. Development of new oral and intravenous adenosine diphosphate P2Y 12 inhibitors and novel antiplatelet agents continues to transform the landscape of antiplatelet therapy. Oral anticoagulation has advanced with the use of direct thrombin and factor Xa inhibitors that do not require therapeutic monitoring. In this review, we discuss the pharmacology and growing clinical evidence for traditional and new antiplatelet and anticoagulant therapies.
Rare α<sub>1</sub>-antitrypsin genotype in a grass seed worker
Authors: Tine H. Malling, Line Sloth Carlsen, Ilaria Ferrarotti, Øyvind Omland
Journal: European Respiratory Journal (2014)

pulmonary disease (COPD) caused by a combination of occupational dust exposure and severe a 1 -antitrypsin (a 1 -AT) deficiency.On evaluation of the genetics of this severe a 1 -AT deficiency, an apparent PiMM genotype was revealed to be heterozygotic for two different rare deficient alleles.
Benefit of the basophil activation test in deciding when to reintroduce cow’s milk in allergic children
Authors: A. Rubio, M. Vivinus-Nébot, T. Bourrier, B. Saggio, M. Albertini, A. Bernard
Journal: Allergy (2010)

To cite this article: Rubio A, Vivinus-Nébot M, Bourrier T, Saggio B, Albertini M, Bernard A. Benefit of the basophil activation test in deciding when to reintroduce cow’s milk in allergic children. Allergy 2011; 66: 92–100. Abstract Background: Oral challenges are required to establish the persistence or resolution of IgE-mediated cow’s milk allergy (CMA). Determining the appropriate timing for challenging is the main difficulty. The benefit of the basophil activation test (BAT) in predicting a child’s reaction to the oral challenge was evaluated and compared to the specific IgE and skin prick tests’ (SPT) results. Methods: One hundred and twelve consecutive children with CMA admitted for an oral challenge to reassess their allergy were included. Allergen-induced basophil activation was detected as a CD63-upregulation by flow cytometry. Results: Thirty-six children (32%) had a positive oral challenge. The percentage of activated basophils in patients with a positive challenge (mean = 20.9; SD = 18.8) was significantly higher than that of patients with a negative challenge (mean = 3.9; SD = 9.8, P < 0.0001), and was well correlated with the eliciting dose of cow’s milk (P < 0.0001). The BAT had an efficiency of 90%, a sensitivity of 91%, a specificity of 90%, and positive and negative predictive values of 81% and 96% in detecting persistently allergic patients. The area under the ROC curve was 0.866. These scores were higher than those obtained with SPT and IgE values, whichever positivity cut-point was chosen. Referring to a decisional algorithm combining BAT, specific IgE and SPT allowed the correct identification of 94% of patients as tolerant or persistently allergic to cow’s milk proteins (CMP) in our cohort. Conclusion: The BAT could be a valuable tool in the management of paediatric CMA in addition to specific IgE quantification and SPT, by contributing in determining whether an oral challenge can safely be undertaken.
Arterial air embolism
Authors: R. Nicks
Journal: Thorax (1967)

Targeted α-particle radiation using the radioisotope <sup>225</sup>Ac is a promising form of therapy for various types of cancer. Historic obstacles to the use of <sup>225</sup>Ac have been the difficulty in finding suitable chelators to stably attach it to targeting vehicles such as peptides and monoclonal antibodies, the low specific activities of the products, and the lack of cost-effective radiolabeling procedures. We initially solved the first problem with a procedure involving 2 chemical steps that has been used as a standard in preclinical and clinical studies. However, this procedure involves the loss of 90% of the input <sup>225</sup>Ac. A more efficient, economical process is needed to facilitate the more widespread use of <sup>225</sup>Ac. <b>Methods:</b> We conjugated representative antibodies with 2 forms of DOTA as well as other chelators as controls. We developed conditions to radiolabel these constructs in 1 chemical step and characterized their stability, immunoreactivity, biodistribution, and therapeutic efficacy in healthy and tumor-bearing mice. <b>Results:</b> DOTA–antibody constructs were labeled to a wide range of specific activities in 1 chemical step at 37°C. Radiochemical yields were approximately 10-fold higher, and specific activities were up to 30-fold higher than with the previous approach. The products retained immunoreactivity and were stable to serum challenge in vitro and in mice. Labeling kinetics of DOTA–antibody constructs linked through a benzyl isothiocyanate linkage were more favorable than those linked through an <i>N</i>-hydroxysuccinimide linkage. Tissue distribution was similar but not identical between the constructs. The constructs produced specific therapeutic responses in a mouse model of acute myeloid leukemia. <b>Conclusion:</b> We have characterized an efficient, 1-step radiolabeling method that produces stable, therapeutically active conjugates of antibodies with <sup>225</sup>Ac at high specific activity. We propose that this technology greatly expands the possible clinical applications of <sup>225</sup>Ac monoclonal antibodies.
Enhanced structural variant and breakpoint detection using SVMerge by integration of multiple detection methods and local assembly
Authors: Kim Wong, Thomas M Keane, James Stalker, David J Adams
Journal: Genome biology (2010)

Abstract We present a pipeline, SVMerge, to detect structural variants by integrating calls from several existing structural variant callers, which are then validated and the breakpoints refined using local de novo assembly. SVMerge is modular and extensible, allowing new callers to be incorporated as they become available. We applied SVMerge to the analysis of a HapMap trio, demonstrating enhanced structural variant detection, breakpoint refinement, and a lower false discovery rate. SVMerge can be downloaded from http://svmerge.sourceforge.net .
Anastrozole as an Adjuvant Endocrine Treatment for Postmenopausal Patients with Breast Cancer: Emerging Data
Authors: Aman U. Buzdar, Jack Cuzick
Journal: Clinical Cancer Research (2006)

Abstract The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial compared the efficacy and safety of anastrozole versus tamoxifen versus the combination as initial adjuvant treatment for early breast cancer in over 9,000 postmenopausal women. Analyses at 33 and 47 months median follow-up showed that anastrozole significantly prolonged disease-free survival and time to recurrence and reduced the incidence of contralateral breast cancer compared with tamoxifen. Results of the completed treatment analysis at 68 months median follow-up confirmed the earlier findings, showing that the absolute difference in disease-free survival continued to increase beyond completion of treatment. Mature safety data from the ATAC trial show that, overall, anastrozole has a favorable safety profile compared with tamoxifen. In the absence of current data on further follow-up or the outcome of trials investigating proactive sequencing of endocrine therapies, we present a model based on several trials, including ATAC. This model suggests that using an aromatase inhibitor as initial adjuvant therapy is a better option than switching to an aromatase inhibitor after ≥2 years of tamoxifen. The relative toxicities of the three approved third-generation aromatase inhibitors, anastrozole, letrozole, and exemestane, are discussed. These data suggest that long-term safety profiles may differ between aromatase inhibitors, although comprehensive comparative data for letrozole and exemestane versus tamoxifen are lacking.
Age-Dependent Spontaneous Coronary Arterial Thrombosis in Transgenic Mice That Express a Stable Form of Human Plasminogen Activator Inhibitor-1
Authors: Mesut Eren, Corrie A. Painter, James B. Atkinson, Paul J. Declerck, Douglas E. Vaughan
Journal: Circulation (2002)

Plasminogen activator inhibitor-1 (PAI-1) regulates fibrinolysis and has been reported to be an independent risk factor for ischemic cardiovascular events. This study describes the age-dependent development of spontaneous coronary arterial thrombi that are associated with evidence of subendocardial myocardial infarction in mice transgenic for human PAI-1.We generated two independent transgenic mice founder lines that express a stable variant of active human PAI-1 under control of the murine preproendothelin-1 (mPPET-1) promoter. Backcrossed homozygous transgenic animals from founder line I had plasma PAI-1 levels of 23+/-12 ng/mL. PAI-1 transgenic animals younger than 4 months do not exhibit any evidence of arterial or venous thrombosis. Ninety percent of transgenic animals (n=10) older than 6 months developed spontaneous occlusions of typically multiple, penetrating coronary arteries, with histological evidence of subendocardial infarction identified in 50% of animals.This study shows that chronically elevated levels of PAI-1 are associated with age-dependent coronary arterial thrombosis in mice transgenic for human PAI-1. This is the first study of a murine model of coronary thrombosis that occurs in the absence of severe hypercholesterolemia or multiple genetic manipulations. These findings provide new evidence to support the hypothesis that PAI-1 excess contributes to the development of coronary arterial thrombosis.
Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
Authors: Cristen J. Willer, Elizabeth K. Speliotes, Ruth J. F. Loos, Shengxu Li, Cecilia M. Lindgren, Iris M. Heid, Sonja I. Berndt, Amanda L. Elliott, Anne U. Jackson, Claudia Lamina, Guillaume Lettre, Noha Lim, Helen N. Lyon, Steven A. McCarroll, Konstantinos Papadakis, Lu Qi, Joshua C. Randall, Rosa Maria Roccasecca, Serena Sanna, Paul Scheet, Michael N. Weedon, Eleanor Wheeler, Jing Hua Zhao, Leonie C. Jacobs, Inga Prokopenko, Nicole Soranzo, Toshiko Tanaka, Nicholas J. Timpson, Peter Almgren, Amanda Bennett, Richard N. Bergman, Sheila A. Bingham, Lori L. Bonnycastle, Morris Brown, Noel L. P. Burtt, Peter Chines, Lachlan Coin, Francis S. Collins, John M. Connell, Cyrus Cooper, George Davey Smith, Elaine M. Dennison, Parimal Deodhar, Paul Elliott, Michael R. Erdos, Karol Estrada, David M. Evans, Lauren Gianniny, Christian Gieger, Christopher J. Gillson, Candace Guiducci, Rachel Hackett, David Hadley, Alistair S. Hall, Aki S. Havulinna, Johannes Hebebrand, Albert Hofman, Bo Isomaa, Kevin B. Jacobs, Toby Johnson, Pekka Jousilahti, Zorica Jovanovic, Kay-Tee Khaw, Peter Kraft, Mikko Kuokkanen, Johanna Kuusisto, Jaana Laitinen, Edward G. Lakatta, Jian'an Luan, Robert N. Luben, Massimo Mangino, Wendy L. McArdle, Thomas Meitinger, Antonella Mulas, Patricia B. Munroe, Narisu Narisu, Andrew R. Ness, Kate Northstone, Stephen O'Rahilly, Carolin Purmann, Matthew G. Rees, Martin Ridderstrale, Susan M. Ring, Fernando Rivadeneira, Aimo Ruokonen, Manjinder S. Sandhu, Jouko Saramies, Laura J. Scott, Angelo Scuteri, Kaisa Silander, Matthew A. Sims, Kijoung Song, Jonathan Stephens, Suzanne Stevens, Heather M. Stringham, Y. C. Loraine Tung, Timo T. Valle, Cornelia M. Van Duijn, Karani S. Vimaleswaran, Peter Vollenweider, Gerard Waeber, Chris Wallace, Richard M. Watanabe, Dawn M. Waterworth, Nicholas Watkins, Jacqueline C. M. Witteman, Eleftheria Zeggini, Guangju Zhai, M. Carola Zillikens, David Altshuler, Mark J. Caulfield, Stephen J. Chanock, I. Sadaf Farooqi, Luigi Ferrucci, Jack M. Guralnik, Andrew T. Hattersley, Frank B. Hu, Marjo-Riitta Jarvelin, Markku Laakso, Vincent Mooser, Ken K. Ong, Willem H. Ouwehand, Veikko Salomaa, Nilesh J. Samani, Timothy D. Spector, Tiinamaija Tuomi, Jaakko Tuomilehto, Manuela Uda, Andre G. Uitterlinden, Nicholas J. Wareham, Panagiotis Deloukas, Timothy M. Frayling, Leif C. Groop, Richard B. Hayes, David J. Hunter, Karen L. Mohlke, Leena Peltonen, David Schlessinger, David P. Strachan, H-Erich Wichmann, Mark I. McCarthy, Michael Boehnke, Ines Barroso, Goncalo R. Abecasis, Joel N. Hirschhorn
Journal: Nature Genetics (2008)
Comparison of Acute Alterations in Left Ventricular Relaxation and Diastolic Chamber Stiffness Induced by Hypoxia and Ischemia
Authors: Takashi Serizawa, W. Mark Vogel, Carl S. Apstein, William Grossman
Journal: Journal of Clinical Investigation (1981)

To clarify conflicting reports concerning the effects of ischemia on left ventricular chamber stiffness, we compared the effects of hypoxia at constant coronary perfusion with those of global ischemia on left ventricular diastolic chamber stiffness using isolated, perfused rabbit hearts in which the left ventricle was contracting isovolumically. Since chamber volume was held constant, increases in left ventricular end diastolic pressure (LVEDP) reflected increases in chamber stiffness. At a control coronary flow rate (30 ml/min), 2 min of hypoxia and pacing tachycardia (4.0 Hz) produced major increases in postpacing LVEDP (10±1 to 24±3 mm Hg, P < 0.01) and the relaxation time constant, T, (40±4 to 224±37 ms, P < 0.001), while percent lactate extraction ratio became negative (+ 18±2 to −48±15%, P < 0.001). Coronary perfusion pressure decreased (72±5 to 52±3 mm Hg, P < 0.01), and since coronary flow was held constant, the fall in coronary perfusion pressure reflected coronary dilation and a decrease in coronary vascular resistance. Following an average of 71±6s reoxygenation and initial heart rate (2.0 Hz), LVEDP and relaxation time constant T returned to control. Hypoxia alone (without pacing tachycardia) produced similar although less marked changes (LVEDP, 10±1 to 20±3 mm Hg; and T, 32±3 to 119±22 ms; P < 0.01 for both) and there was a strong correlation between LVEDP and T (r = 0.82, P < 0.001).
Specific antibody to hog renal renin and its application to the direct radioimmunoassay of renin in various organs.
Authors: S Hirose, R J Workman, T Inagami
Journal: Circulation Research (1979)

We produced anti-hog renin antibodies using as antigens pure hog renal renin that either had been insolubilized or conjugated to tetanus toxoid. High titer antibodies were obtained, which demonstrated different cross-reactivity with renins from other species. A direct radioimmunoassay for renin was developed using antibody, monoiodinated 125I-hog renin, and various methods for separating free and antibody-bound trace. This assay was capable of detecting 40 pg of hog renin and was applied to the determination of renin in hog blood and other organs. Based on the direct measurement of renin by this radioimmunoassay, the renin-like activity (i.e., the ability to generate angiotensin I from renin substrate preparations) of the pituitary gland was found to be due mostly to true renin, whereas the renin activity of other hog tissues, including the adrenal gland, liver, lung, spleen, and submaxillary gland, was not identified as renin and may have been due to cathepsins.
World Health Organization–European Organization for Research and Treatment of Cancer classification of cutaneous lymphoma in Korea: A retrospective study at a single tertiary institution
Authors: Ji-Hye Park, Hyun-Tae Shin, Dong-Youn Lee, Joo-Heung Lee, Jun-Mo Yang, Kee-Taek Jang, Young-Hyeh Ko
Journal: Journal of the American Academy of Dermatology (2012)
Alveolar development after ligation of left pulmonary artery in newborn pig: clinical relevance to unilateral pulmonary artery.
Authors: S G Haworth, S A McKenzie, M L Fitzpatrick
Journal: Thorax (1981)

The left pulmonary artery and ductus arteriosus were ligated in 14 pigs at birth. Animals were killed at intervals between two and 24 weeks of age. In all animals, serial chest radiographs were taken. In eight animals, nitrogen-13 lung function studies showed normal fractional ventilation in both lungs and continued growth of the small left lung. After death, the fixed inflated volume was determined in each lung an alveolar development was analysed using quantitative morphometric techniques. In the right lung, after operation alveolar size increased considerably and at two weeks was similar to the normal at six months. The normal phase of rapid postnatal alveolar multiplication was delayed from the first to the second month of life. In all animals aged 20-24 weeks alveolar size was almost normal for age and an abnormal increase in alveolar number produced an abnormally large right lung. In the left lung, the alveoli multiplied to achieve a normal alveolar number in all animals sacrificed at 20 and 24 weeks, but the alveoli were abnormally small. Total lung volume was normal in all animals aged 20 and 24 weeks. The structural findings explained the radiographic and radionuclide investigations. The experimental findings are discussed in relation to lung growth in patients with an interrupted pulmonary artery.