bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4053: Formin-binding protein-17 (FBP17) is a target of p53 and promotes invadopodia formation in breast cancer cells
Authors: Chander Harish , Watts Kathleen , Pogmore Justin , Truesdell Peter , Brien Colin , Craig Andrew W B 
Published: May 2015

Abstract
Invadopodia are extracellular matrix (ECM)-degrading structures that promote tissue invasion and metastasis of tumor cells. A family of adaptor proteins with F-BAR and SH3 domains, including FBP17 and Toca-1, have been identified as key scaffolds for recruiting actin regulatory proteins (eg. Cdc42, formins, N-WASP, dynamin) to promote formation of invadopodia in bladder and breast cancers, respectively. In this study, we investigated the potential role of FBP17 in breast cancer models. We observed FBP17 expression in normal breast epithelial cells (MCF10A), and at higher levels in basal breast cancer cell lines (MDA-MB-231) compared to luminal cell lines. Since basal breast cancers frequently harbor mutations in tumor suppressor p53, we tested whether wild-type (WT) p53 regulates expression of FBP17, which may explain higher expression in basal breast cancers. Camptothecin (CPT) treatment of WT p53-expressing breast cancer cells (MCF-7, DU4475) led to a dose dependent reduction in FBP17 mRNA and protein levels, and this was inversely correlated with p53 levels or its target p21WAF1. The downregulation of FBP17 was also observed using Nutlin-3, an Mdm2 inhibitor, indicating that WT p53 activation by multiple methods causes a rapid downregulation of FBP17. Currently we are testing whether this is a direct or indirect effect of p53 on FBP17 gene expression. As expected, FBP17 formed complexes with actin regulatory proteins (dynamin, cortactin, Arp2/3) that accumulate and promote invadopodia formation in MDA-MB-231 cells. Stable silencing of FBP17 in these cells led to a significant reduction in ECM degradation. This is consistent with FBP17 promoting invadopodia formation. Tumor xenograft models are in progress to determine whether FBP17 also promotes tumor metastasis. FBP17 expression levels in human breast tumors are currently being tested to determine whether altered expression occurs in molecular subtypes with frequent mutations in p53 (HER2, basal) and in their metastases. Overall, these results are consistent with FBP17 participating in cancer cell invasion, and supports further studies of its role in cancer metastasis.
Citation Format: Harish Chander, Kathleen Watts, Justin Pogmore, Peter Truesdell, Colin Brien, Andrew W B Craig. Formin-binding protein-17 (FBP17) is a target of p53 and promotes invadopodia formation in breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4053. doi:10.1158/1538-7445.AM2014-4053
Abstract 4080: Smad and NFAT pathways cooperate to regulate CD103 expression in human CD8 T lymphocytes and TCR-mediated epithelial tumor cell killing
Authors: Mami-Chouaib Fathia , Mokrani M'barka , Bismuth Georges 
Published: May 2015

Abstract
The interaction of integrin αE(CD103)β7, often expressed on tumor-infiltrating lymphocytes (TIL), with epithelial cell marker E-cadherin on tumor cell surface plays a major role in antitumor cytotoxic T lymphocyte (CTL) responses. CD103 is encoded by ITGAE gene and is induced in CD8 T cells upon T-cell receptor (TCR) engagement and exposure to transforming growth factor (TGF)-β1, abundant within the tumor microenvironment. However, the transcriptional mechanisms underlying the cooperative role of these two signaling pathways in inducing CD103 expression in CD8 T cells remain unknown. Using a model system based on a CD8+/CD103- T-cell clone, we demonstrated that the transcription factors Smad2/3 and NFAT-1 are required for CD103 induction on T lymphocytes activated with a combination of TGF-β1 and anti-CD3 monoclonal antibodies. We also identified the promotor and enhancer elements of human ITGAE gene, and showed that Smad2/3 and NFAT-1 are necessary for the activity of the ITGAE enhancer, and thus for CD103 expression. Overall, our results explain how TGF-β1 induces CD103 expression on locally activated CD8 T cells, thus contributing to antitumor CTL responses and malignant cell killing.
Citation Format: Fathia Mami-Chouaib, M'barka Mokrani, Georges Bismuth. Smad and NFAT pathways cooperate to regulate CD103 expression in human CD8 T lymphocytes and TCR-mediated epithelial tumor cell killing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4080. doi:10.1158/1538-7445.AM2014-4080
Abstract 4082: CD47 blockade to enhance adaptive anti-tumor immune responses
Authors: Anderson Katie L. , Ito Daisuke , Lins Debra C. , Curtsinger Julie M. , Mescher Matthew F. , Modiano Jaime F. 
Published: May 2015

Abstract
The success of immunotherapy has been hindered by the ability of tumors to evade or inhibit the host immune system. One strategy tumors use to achieve this is upregulation of CD47, a cell surface protein that delivers a “don't eat me” signal. CD47 binds to SIRP-alpha on the surface of macrophages and disables their phagocytic function. Previous data showed CD47 blockade enhanced phagocytosis of tumor cells in vitro and improved survival of mice transplanted with human tumors. However, CD47 blockade has yet to be examined in a fully syngeneic system where the potential for tumor phagocytosis by macrophages and/or dendritic cells to promote presentation of tumor antigens to T cells can be defined. It has been reported that CD47 blockade can hinder T cell activation; however, this also has not been examined in a syngeneic system. Our hypothesis was that inducing tumor cell phagocytosis by CD47 blockade would enhance T-cell-mediated anti-tumor responses. Our data show that CD47 was expressed on the EL4 thymoma and B16-F10 melanoma cell lines that are syngeneic to H-2b, as well as on their ovalbumin-expressing derivatives EG7 and B16-OVA. CD47 also was expressed on CD8+ T cells and was further upregulated upon stimulation, suggesting it might play a role in immune effector function. However, in our hands CD47 blockade using antibody MIAP-301 did not inhibit activation of CD8+ T cells in vitro, and in preliminary experiments, CD47 blockade appeared to enhance activation of antigen-specific CD8+ T cells in vivo. Ongoing work is evaluating the effects of CD47 blockade and phagocytosis on antigen presentation in vitro and the effects of CD47 blockade on the generation of tumor-specific CD4 and CD8 T cells in vivo. We also plan to confirm that T cells activated under conditions of CD47 blockade can recognize endogenous tumor antigens to which there may be self-tolerance.
Supported by an HHMI Medical Student Fellowship (to KA), by the GREYlong Foundation, and by grant P01 AI035296 (to MFM).
Citation Format: Katie L. Anderson, Daisuke Ito, Debra C. Lins, Julie M. Curtsinger, Matthew F. Mescher, Jaime F. Modiano. CD47 blockade to enhance adaptive anti-tumor immune responses. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4082. doi:10.1158/1538-7445.AM2014-4082
In VivoAntineoplastic Effects of the NSAID Sulindac in an Oral Carcinogenesis Model
Authors: Katoumas Konstantinos , Nikitakis Nikolaos , Perrea Despina , Dontas Ismene , Sklavounou Alexandra 
Published: May 2015

AbstractThe antineoplastic properties of the NSAID sulindac have long been studied. The purpose of this study was to explore sulindac's in vivo effects on oral squamous cell carcinoma (SCC) oncogenesis using the hamster cheek pouch oral carcinogenesis model (HOCM). Thirty Syrian golden hamsters were divided into three experimental and two control groups (n = 6 each). The animals' right buccal pouches were treated with carcinogen for 9 weeks in one experimental and one control group and for 14 weeks in all other three groups. The animals of two experimental groups received sulindac from the 1st week and those of the third experimental group from the 10th week. After the end of carcinogenesis, treated buccal pouches were removed and examined. In animals treated with carcinogen for 14 weeks, development of oral SCC and tumor volume were significantly lower in animals that received sulindac from the first week of the experiment. Oral SCC developing in animals that received sulindac were more frequently well differentiated compared with the control group. In animals treated with carcinogen for 9 weeks, the animals that received sulindac developed lower grade of epithelial dysplasia. Proliferation index Ki-67 and positivity for the antiapoptotic molecule survivin were lower in the animals that received sulindac. Treatment with sulindac appears to delays the progression of oral premalignant lesions to oral SCC in the HOCM, also resulting in smaller and better differentiated tumors. These in vivo antineoplastic effects may be related to sulindac's ability to decrease cell proliferation and to prevent survivin expression. Cancer Prev Res; 8(7); 642–9. ©2015 AACR.
Autonomia, pluralidade e razão pública
Authors: O'Neill Onora 
Published: May 2015

<p>Pretendo oferecer uma leitura da concepção kantiana de autonomia, distingui-la de algumas outras concepções que recebem o nome de autonomia e propor algumas razões para pensar que a autonomia no sentido que Kant atribui ao termo é decerto tanto uma concepção de razão prática como também fundamental para a moralidade. A linha de pensamento que seguirei é, espero, compatível com as afirmações queSchneewind faz sobre a posição de Kant e, ao mesmo tempo, uma ampliação que favorece essas afirmações.</p>
Rich Club Organization and Cognitive Performance in Healthy Older Participants
Authors: Baggio Hugo C. , Segura Barbara , Junque Carme , de Reus Marcel A. , Sala-Llonch Roser , Van den Heuvel Martijn P. 
Published: May 2015

Abstract
The human brain is a complex network that has been noted to contain a group of densely interconnected hub regions. With a putative “rich club” of hubs hypothesized to play a central role in global integrative brain functioning, we assessed whether hub and rich club organizations are associated with cognitive performance in healthy participants and whether the rich club might be differentially involved in cognitive functions with a heavier dependence on global integration. A group of 30 relatively older participants (range = 39–79 years of age) underwent extensive neuropsychological testing, combined with diffusion-weighted magnetic resonance imaging to reconstruct individual structural brain networks. Rich club connectivity was found to be associated with general cognitive performance. More specifically, assessing the relationship between the rich club and performance in two specific cognitive domains, we found rich club connectivity to be differentially associated with attention/executive functions—known to rely on the integration of distributed brain areas—rather than with visuospatial/visuoperceptual functions, which have a more constrained neuroanatomical substrate. Our findings thus provide first empirical evidence of a relevant role played by the rich club in cognitive processes.
Adaptation of Irrigation Infrastructure on Irrigation Demands under Future Drought in the United States*
Authors: Zhang Tianyi , Lin Xiaomao , Rogers Danny H. , Lamm Freddie R. 
Published: May 2015

Abstract
More severe droughts in the United States will bring great challenges to irrigation water supply. Here, the authors assessed the potential adaptive effects of irrigation infrastructure under present and more extensive droughts. Based on data over 1985–2005, this study established a statistical model that suggests around 4.4% more irrigation was applied in response to a one-unit reduction in the Palmer drought severity index (PDSI), and approximately 5.0% of irrigation water application could be saved for each 10% decrease in the areas supplied by surface irrigation infrastructure. Based on the results, the model-projected irrigation infrastructure has played a greater role in changes in irrigation than drought in most areas under the current climate except some southwestern counties. However, under the predicted future more severe drought in 2080–99 under the representative concentration pathways 4.5 scenario, the model projected that the drought will require 0%–20% greater irrigation amounts assuming the current irrigation efficiency. Under the predicted drought scenario, irrigation depth can be maintained at or below the baseline level in the western United States only when better irrigation infrastructure replaced 40% of the current surface irrigation infrastructure areas. In the northeast United States, limited changes in irrigation depth were predicted under different irrigation infrastructure scenarios because the percentage of surface irrigation area is already low under the baseline climate, and thus there is limited opportunity to adapt to future drought with advanced irrigation infrastructure. These results indicate that other effective solutions are required to complement these measures and aid U.S. agriculture in the future, more extensive drought.
Carbon dioxide insufflation and neurocognitive outcome of open heart surgery
Authors: Ganguly Gautam , Dixit Vikas , Patrikar Seema , Venkatraman Ravishankar , Gorthi Satya Prakash , Tiwari Nikhil 
Published: May 2015

Aim Neurocognitive dysfunction continues to be the bane of open heart surgery despite vast improvements in surgical, anesthetic, and postoperative management. This observational cohort study was carried out to evaluate the efficacy of intraoperative CO2 insufflation by the field flooding technique in reducing postoperative neurocognitive dysfunction. Methods Three hundred randomly selected patients undergoing open heart surgery were observed: 150 (group A) were exposed to CO2 insufflation, and the other 150 (group B) were not exposed to CO2. Anesthetic, cardiopulmonary bypass, and myocardial protection techniques were standardized and similar in both groups. Neurocognitive function tests were performed preoperatively, 1 week postoperatively, and after 1 month. Results The analysis revealed that neurocognitive dysfunction occurred in 8 of 150 patients in group A (incidence p1 = 0.053) and 27 of 150 in group B (incidence p2 = 0.18). The relative risk of neurocognitive dysfunction was 0.30 ( p = 0.001, 95% confidence interval 0.14–0.63), implying that CO2 insufflation is protective against neurocognitive dysfunction. The risk difference was 0.13 ( p2– p1); this implies that 13% of patients can be prevented from developing neurocognitive dysfunction if exposed to CO2. Conclusion This study confirms the known advantage of the relatively underutilized practice of CO2 insufflation. We recommend that CO2 insufflation be performed in all open heart surgery cases to bring down the incidence of neurocognitive dysfunction. This technique is simple to use without any major paraphernalia or additional cost.
Dexmedetomidine in combination with midazolam after pediatric cardiac surgery
Authors: Hasegawa Tomomi , Oshima Yoshihiro , Maruo Ayako , Matsuhisa Hironori , Tanaka Akiko , Noda Rei , Matsushima Shunsuke 
Published: May 2015

Objective Although midazolam is one of the most commonly used sedatives for infants in the intensive care unit, it has well-known disadvantages including a dose-dependent potential to induce tolerance, withdrawal, and hemodynamic depression. The aim of this study was to evaluate the clinical effects of dexmedetomidine combined with midazolam in postoperative intensive care following pediatric cardiac surgery. Methods Forty consecutive infants who underwent cardiac surgery for isolated ventricular septal defects from January 2011 to July 2013 were enrolled in this retrospective study. They were divided into two groups according to postoperative sedation regimen: dexmedetomidine sedation with midazolam ( n = 20), or midazolam sedation without dexmedetomidine (control group, n = 20). Perioperative variables were compared between the two groups. Results There were no significant differences in patient characteristics between the two groups. During the first 24 h after intensive care unit admission, heart rate and serum lactate levels were significantly lower in the dexmedetomidine group compared to the control group ( p = 0.0292 and p = 0.0027, respectively). The maximal midazolam dose was also significantly lower in the dexmedetomidine group (0.12 ± 0.09 vs. 0.20 ± 0.08 mg kg−1 h−1, p = 0.0059). There were no adverse effects of dexmedetomidine such as bradycardia, hypotension, agitation, or seizures. Three (15%) patients in the control group and none in the dexmedetomidine group experienced sudden cardiopulmonary decompensation. Conclusions Dexmedetomidine can provide favorable sedative properties with a reduced requirement for concomitant midazolam and stable hemodynamics with tachycardia prevention, for postoperative intensive care following pediatric cardiac surgery.
CT assessment of right colonic arterial anatomy pre and post cancer resection – a potential marker for quality and extent of surgery?
Authors: Kaye Tom L , West Nick P , Jayne David G , Tolan Damian JM 
Published: May 2015

Background There is conflicting opinion as to the optimum extent of resection for right-sided colonic cancer, which is currently graded by pathological analysis of the resected specimen. It is not known if computed tomography (CT) analysis of residual post-resection arterial stump length could be used as an alternative in vivo marker for extent of mesenteric resection. Ileocolic artery stumps have been demonstrated previously on CT after right hemicolectomy, but only in the early postoperative period. Purpose To analyze preoperative right colonic arterial anatomy using portal venous colorectal cancer staging CT and subsequently determine if post-resection arterial stumps (a potential in vivo marker of surgical resection) could be consistently identified using routine follow-up CT scans many months after cancer resection. Material and Methods A retrospective analysis of routine staging and follow-up CT scans for 151 patients with right-sided colorectal cancer was performed. Preoperative right colonic arterial anatomy and postoperative arterial stumps were analyzed and measured. Results Preoperative ileocolic (98.8%), middle (94.7%), and right colic artery (23.8%) identification was comparable to catheter angiogram studies. Postoperative ileocolic stumps were consistently demonstrated (88.3%) many months (average, 2 years and 42 days) after resection and were significantly longer than expected for a standard D2 resection (paired t-test, t(127) = −11.45, P ≤ 0.001). Conclusion This is the first study to successfully demonstrate ileocolic arterial stumps many months (and years) after cancer resection using routine portal venous CT. Further prospective research should assess whether arterial stumps can be used as an in vivo marker of surgical quality and extent.
Effect of Anterior Capsular Laxity on Horizontal Abduction and Forceful Internal Impingement in a Cadaveric Model of the Throwing Shoulder
Authors: Mihata Teruhisa , McGarry Michelle H. , Neo Masashi , Ohue Mutsumi , Lee Thay Q. 
Published: May 2015

Background: Excessive anterior capsular laxity (elongation of the anterior capsular ligaments) causes shoulder subluxation during acceleration of the throwing motion, leading to a disabled throwing shoulder. Few biomechanical studies have investigated the relationship between anterior capsular laxity and internal impingement, another cause of the disabled throwing shoulder. Purpose/Hypothesis: The purpose of this study was to assess the effect of anterior capsular laxity on forceful internal impingement during the late cocking phase. The hypothesis was that excessive anterior shoulder laxity caused by elongation of the anterior capsular ligaments will increase the horizontal abduction angle to increase glenohumeral contact pressure. Study Design: Controlled laboratory study. Methods: Eight fresh-frozen cadaveric shoulders were tested with the shoulder abducted to 90° and at maximal external rotation to simulate the late cocking phase of the throwing motion. The angle of external rotation, anterior translation, angle of horizontal abduction, locations of the articular insertion of the rotator cuff tendons (supraspinatus and infraspinatus) on the greater tuberosity relative to the glenoid, and the glenohumeral contact pressure and area during internal impingement were measured. All data were compared between intact and elongated anterior capsule, which was created by repeatedly applying external rotational stretching. Results: Elongation of the anterior capsular ligaments was confirmed by the increase in glenohumeral external rotation and anterior translation after our stretching technique. Location data showed that the posterior half of supraspinatus tendon, the entire infraspinatus tendon, and the posterosuperior labrum were impinged between the greater tuberosity and glenoid. Maximal glenohumeral horizontal abduction (2.2% increase; P = .003) and glenohumeral contact pressure (27.3% increase; P = .04) were significantly increased in the shoulder joint with increased anterior capsular laxity as compared with the intact condition. Conclusion: Increased anterior capsular laxity created by applying repetitive excessive external rotational torque significantly increased horizontal abduction and contact pressure in the glenohumeral joint. Concurrently, the supraspinatus and infraspinatus tendons and posterosuperior labrum were impinged between the greater tuberosity and glenoid. Clinical Relevance: Increased anterior capsular laxity may exacerbate forceful internal impingement during the late cocking phase of the throwing motion.