tbuckley/cabot-search huggingface dataset:
Abstract 1475: Mutant p53 is a regulator of NADPH-oxidase 4 (Nox4) in TGF-beta-mediated migration of human lung and breast epithelial cells.
Authors: Howard E. Boudreau, Benjamin W. Casterline, Devin J. Burke, Thomas L. Leto
Journal: Cancer Research (2013)

Abstract The epithelial-to-mesenchymal transition (EMT) leads to development of increased cell plasticity that occurs normally during wound healing and embryonic development and can be coopted for cancer invasion and metastasis. TGF-beta induces EMT but the mechanism is unclear. We have previously shown that Nox4, a member of the NADPH oxidase (Nox) family, is a source of reactive oxygen species (ROS) affecting cell migration and fibronectin expression, an EMT marker, in normal and metastatic breast epithelial cells. Recent studies have shown that p53 plays an important role in TGF-beta-mediated signaling and epithelial cell migration. Our current study investigates whether p53 is mechanistically involved in TGF-beta-regulated Nox4 expression and cell migration. Our results indicate that wild-type p53 is a potent suppressor of TGF-beta-induced Nox4 expression, ROS production, and cell migration. In contrast, expression of tumor-associated mutant p53 proteins (R175H or R280K) correlated with enhanced Nox4 expression and cell migration in a TGF-beta dependent manner. Furthermore, knockdown of the endogenous p53 mutant (R280K) in MDA-MB-231 cells by p53-targeted siRNA resulted in decreased Nox4 protein as well as phosphorylated Src and FAK proteins. TGF-beta treatment of MDA-MB-231 cells overexpressing a dominant-negative form of Nox4 also showed a decrease in phosphorylated Src and FAK proteins, thereby indicating mutant p53 (R280K) and Nox4 are regulators of Src and FAK activity. Collectively, our findings suggest important physiological functions for both wild type and mutant p53 proteins in regulating Nox4-dependent signaling in TGF-beta-mediated cell migration. Citation Format: Howard E. Boudreau, Benjamin W. Casterline, Devin J. Burke, Thomas L. Leto. Mutant p53 is a regulator of NADPH-oxidase 4 (Nox4) in TGF-beta-mediated migration of human lung and breast epithelial 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 1475. doi:10.1158/1538-7445.AM2013-1475
Pyogenic granuloma of the small bowel
Authors: K. Yamashita, Y. Arimura, M. Saito, T. Iida, R. Suzuki, T. Niinuma, T. Furuhata, K. Kimura, T. Ohta, Y. Shinomura
Journal: Endoscopy (2013)

A 61-year-old man was referred to our hospital because of melena and progressive anemia requiring transfusion. He was on hemodialysis because of diabetic nephropathy. Although upper gastrointestinal endoscopy, colonoscopy, and a computed tomography (CT) scan were all normal, a subsequent capsule endoscopy revealed a tumor and blood in the middle part of the small intestine ([Video 1]).
Pyometra as a Lower Abdominal Doughnut Sign on a Ga-67 Scan
Authors: PAN-FU KAO, KAI-YUAN TZEN, MING-FONG TSAI, FANG-PING CHEN
Journal: Clinical Nuclear Medicine (2000)

KAO, PAN-FU M.D., Sc.M.; TZEN, KAI-YUAN M.D., Sc.M.; TSAI, MING-FONG M.D.; CHEN, FANG-PING M.D. Author Information
OC-034 Cortical and Brainstem Neurophysiological Mechanisms underlying Dysphagia in Parkinson’S Disease: A Transcranial Magnetic Stimulation Study’ ‘On’ and ‘Off’ Levodopa
Authors: E Michou, L Harris, S Hamdy
Journal: Gut (2013)

<h3>Introduction</h3> Dysphagia in Parkinson's disease (PD) patients, persisting despite dopaminergic medication, affects nutritional and drug intake with reduced quality-of-life (Michou &amp; Hamdy, Exp Rev Neurother 2010). Here we explore the potential neurophysiological mechanisms underlying dysphagia in PD when 'on' and 'off' Levodopa with transcranial magnetic stimulation (TMS). <h3>Methods</h3> 26 verified PD patients (65 ± 8 yoa, 10 male) completed the Swallowing Disturbance Questionnaire (Manor <i>et al</i> Mov Dis 2007) and SWAL-QOL (McHorney <i>et al</i> Dysphagia 2002). After 12 hours 'off' L-dopa, patients underwent a) cortical TMS mapping for pharyngeal musculature, b) brainstem reflexes TMS stimulation, c) lung function tests with spirometry before and after (d) videofluroscopy (VFS) of liquid, pureed boluses and saliva. These were repeated following the administration of L-dopa to the patients. Factorial and non-parametric statistical tests were applied. <h3>Results</h3> VFS identified dysphagia in 10 patients (Group A), while 6 patients showed swallowing difficulties only 'On-L-dopa'(Group B), with the remainder 10 subjects being non-dysphagic (Group C). Swal-QOL score was reduced in Group A (p &lt; 0.05), while aspiration-penetration scores (thin and puree consistencies) and additional 'clearing swallows' worsened after administration of L-dopa (p &lt; 0.05) for Group B. After Levodopa intake, cortical pharyngeal excitability was decreased significantly in Group A (p &lt; 0.005), but increased in Group C (p &lt; 0.001) compared to 'off-state' (Figure 1). No significant change in lung function was observed during the off-or on-state, nor did lung function correlate with dysphagia. The amplitudes of the brainstem reflexes were different between the 3 groups 'on-Levodopa'. Patients experiencing dysphagia only when on Levodopa (Group B) showed significant decrease (inhibition) in brainstem reflexes amplitude after Levodopa. <h3>Conclusion</h3> Different patterns of cortical and brainstem activity, reflecting different mechanisms of compensation with Levodopa intake, can differentiate dysphagic PD groups. Moreover, physiology was negatively affected by L-dopa in groups with inhibition of brainstem reflexes. Our novel brain stimulation data demonstrate the dysphagia in PD patients is associated with altered cortical and brainstem activity, modulated by L-dopa differentially across the PD groups, providing the platform for research on rehabilitation for dysphagia in PD. <h3>Disclosure of Interest</h3> None Declared
Accuracy and patient preference in evaluating perianal fistulas using hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and endoanal magnetic resonance imaging
Authors: R West, S Dwarkasing, RJF Felt-Bersma, WR Schouten, SM Hussain, SM Hussain, EJ Kuipers
Journal: Endoscopy (2006)

Objectives: Surgery for perianal fistula is often complicated and therefore accurate preoperative assessment of perianal fistulas is necessary. The aim of this study was to determine agreement between hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography (3D HPUS) and endoanal magnetic resonance imaging (MRI) in preoperative assessment of perianal fistulas and to assess patient preference with regard to these techniques.
Lymphoscintigraphy in a Patient with Polyserositis of Unknown Origin
Authors: John O Prior, Ariane Boubaker, Francois Spertini, Angelika Bischof Delaloye
Journal: Clinical Nuclear Medicine (2002)

PRIOR, JOHN O. M.D., Ph.D.; BOUBAKER, ARIANE M.D.; SPERTINI, FRANCOIS M.D.; BISCHOF DELALOYE, ANGELIKA M.D. Author Information
In Vitro Immunomodulatory Effects of FAHF-2 (Food Allergy Herbal Formula-2) On PBMCs From Food Allergy Patients
Authors: Xiu-Min Li, Ying Song, Julie Wang, Paul Faybusovich, Min-Li Hong, Jaime Ross, Scott Sicherer, June Straw, Stacie M. Jones, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2013)
Giant Esophageal Ulcers
Authors: Raymond A. Rubin, Marc S. Levine
Journal: New England Journal of Medicine (1996)

Figure 1. Acute, severe odynophagia developed in a 52-year-old man known to be positive for the human immunodeficiency virus (HIV). A double-contrast esophagogram (Panel A) shows two giant, ovoid ulcers (arrows) measuring 3 cm and 6 cm in length in the middle and distal thirds of the esophagus, respectively. An endoscopic photograph of the mid-portion of the esophagus (Panel B) shows the proximal ulcer to be a deep lesion with well-demarcated margins (arrows). The distal ulcer had a similar appearance, and the mucosa between the lesions was grossly normal, without exudates or plaques. Endoscopic brushings, biopsy specimens, and cultures obtained . . .
Space–Time Covariation of Mortality with Temperature: A Systematic Study of Deaths in France, 1968–2009
Authors: Nicolas Todd, Alain-Jacques Valleron
Journal: Environmental Health Perspectives (2015)

BackgroundThe temperature–mortality relationship has repeatedly been found, mostly in large cities, to be U/J-shaped, with higher minimum mortality temperature (MMT) at low latitudes being interpreted as indicating human adaptation to climate.ObjectivesOur aim was to partition space with a high-resolution grid to assess the temperature–mortality relationship in a territory with wide climate diversity, over a period with notable climate warming.MethodsThe 16,487,668 death certificates of persons &gt; 65 years of age who died of natural causes in continental France (1968–2009) were analyzed. A 30-km × 30-km grid was placed over the map of France. Generalized additive model regression was used to assess the temperature–mortality relationship for each grid square, and extract the MMT and the RM25 and RM25/18 (respectively, the ratios of mortality at 25°C/MMT and 25°C/18°C). Three periods were considered: 1968–1981 (P1), 1982–1995 (P2), and 1996–2009 (P3).ResultsAll temperature–mortality curves computed over the 42-year period were U/J-shaped. MMT and mean summer temperature were strongly correlated. Mean MMT increased from 17.5°C for P1 to 17.8°C for P2 and to 18.2°C for P3 and paralleled the summer temperature increase observed between P1 and P3. The temporal MMT rise was below that expected from the geographic analysis. The RM25/18 ratio of mortality at 25°C versus that at 18°C declined significantly (p = 5 × 10–5) as warming increased: 18% for P1, 16% for P2, and 15% for P3.ConclusionsResults of this spatiotemporal analysis indicated some human adaptation to climate change, even in rural areas.Citation:Todd N, Valleron AJ. 2015. Space–time covariation of mortality with temperature: a systematic study of deaths in France, 1968–2009. Environ Health Perspect 123:659–664; http://dx.doi.org/10.1289/ehp.1307771
A novel method to perform endoscopic myotomy for Zenker’s diverticulum using submucosal dissection techniques
Authors: Prashant Kedia, Norio Fukami, Nikhil Kumta, Michel Kahaleh, Reem Sharaiha
Journal: Endoscopy (2014)

A Zenker’s diverticulum arises from the cervical esophagus and results in a mucosal outpouching through Killian’s triangle. Treatment for symptomatic Zenker’s diverticulum is a diverticulotomy. Traditional therapy has been surgical cricopharyngeal myotomy via an open or transoral rigid endoscopic approach. Flexible endoscopic diverticulotomy for Zenker’s diverticulum has similar efficacy and is associated with fewer complications. Various techniques and devices have been used for myotomy including needle-knife, hook-knife, monopolar forceps, argon plasma coagulation, and harmonic scalpel. The limitation of current techniques is the difficulty in gauging the extent to which the most inferior part of the septum should be cut in order to treat the disease adequately while minimizing the risk of perforation and subsequent mediastinitis. In the cases described here, diverticulotomy using an endoscopic submucosal dissection technique was employed for muscular fiber exposure and septal dissection (myotomy) using a multipurpose knife. The utilization of a multipurpose knife with injection capability may further improve the success and safety of this procedure. Larger, randomized, prospective trials are needed to confirm this notion, standardize the technique, and identify the appropriate patient population for different endoscopic options.
Abstract 451: Smad2 is the TGF-β receptor-regulated Smad to suppress the immunogenicity of mouse and human dendritic cells.
Authors: Jeong-Hwan Yoon, Jin-Soo Han, Seok Hee Park, Michael Weinstein, Susumu Nakae, Tadashi Yamashita, In-Kyu Lee, Takayuki Sumida, Katsuko Sudo, Masahiko Kuroda, Mizuko Mamura
Journal: Cancer Research (2013)

Abstract TGF-β plays pivotal roles in the regulation of DCs. However, the molecular mechanisms by which TGF-β regulates DCs are undetermined. Here, we show that one of the TGF-β receptor-regulated Smads (R-Smads), Smad2 is the predominant intermediary for TGF-β to suppress the immunogenicity of DCs. Notably, Smad2 remained expressed, whereas Smad3 was down-regulated in mouse BM-derived DCs (BMDCs) and human monocyte-derived DCs (MoDCs) upon differentiation by GM-CSF and IL-4. Smad2 mediated the inhibitory effect of TGF-β on the expression of co-stimulatory molecules (CD80, CD86, CD40) on BMDCs. One of the TGF-β superfamily cytokines, Activin-A did not affect their expression, although it shares Smad2 and Smad3 as R-Smads. Deletion of Smad2 up-regulated the dendrite formation, co-stimulatory molecule expression, and effector cytokine production by DCs, thereby efficiently activating allogeneic T cells. Furthermore, DC-specific deletion of Smad2 by Cd11cCre-loxP system suppressed the progression of a mouse EL4 lymphoma model by enhancing anti-lymphoma cytotoxic activity. Thus, our results suggest that TGF-β signaling through Smad2 in DCs could be a therapeutic target to enhance anti-tumor immunity. Citation Format: Jeong-Hwan Yoon, Jin-Soo Han, Seok Hee Park, Michael Weinstein, Susumu Nakae, Tadashi Yamashita, In-Kyu Lee, Takayuki Sumida, Katsuko Sudo, Masahiko Kuroda, Mizuko Mamura. Smad2 is the TGF-β receptor-regulated Smad to suppress the immunogenicity of mouse and human dendritic 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 451. doi:10.1158/1538-7445.AM2013-451
IMPACT OF PITAVASTATIN ON NEW-ONSET DIABETES IN ACUTE MYOCARDIAL INFARCTION
Authors: Cheol Ung Choi, Sung Hun Park, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Eun Jin Park, Jah Yeon Choi, Jae Joong Lee, Sunki Lee, Jin Oh Na, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Seung-Woon Rha, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh, Myung Ho Jeong
Journal: Journal of the American College of Cardiology (2016)
CS-26 * FIBULIN-3 REGULATES CANONICAL NFkB SIGNALING IN GLIOMA CELLS AND SURROUNDING STROMAL CELLS TO PROMOTE TUMOR INVASION
Authors: M. Nandhu, A. Kwiatkowska, B. Hu, M. Viapiano
Journal: Neuro-Oncology (2014)

Fibulin-3 (also known as EFEMP1) is an extracellular matrix protein secreted by glioma cells but absent from normal brain, which increases tumor invasion and resistance to apoptosis. Fibulin-3 activates the Notch pathway in glioma but its downstream mechanisms are unknown. Here we show that fibulin-3 activates canonical NFkB by TNFα- and Notch-dependent mechanisms, both in glioma and surrounding normal cells in the brain. Moreover, we demonstrate that activation of NFkB is necessary to mediate the pro-invasive effects of fibulin-3 in glioma. Addition of purified fibulin-3 to glioma cells activated the classical NFkB cascade (IKKa/b, IkBa, and p65/RelA), increasing the expression of NFkB-regulated genes (MMP9, MMP13, TnC, MLCK, VEGF). Conversely, fibulin-3 knockdown inhibited NFkB signaling, even in presence of TNFα, and reduced the expression of NFkB-downstream genes. Further mechanistic analysis demonstrated that fibulin-3 activated the TNFα convertase ADAM17 that releases soluble TNFα to activate NFkB signaling. At the same time, fibulin-3 downregulated the expression of the deubiquitinase CYLD, which is regulated by Notch and inhibits canonical NFkB signaling. Soluble fibulin-3 activated RelA/p65 not only in glioma cells but also in cultured astrocytes and brain microvascular endothelial cells. Moreover, quantitative immunohistochemistry demonstrated increased expression of phosphor-p65 in GFAP-positive cells surrounding fibulin-3-overexpressing tumors compared to control tumors. Inhibition of NFkB signaling, both pharmacologically and with p65-specific siRNAs, significantly reduced the pro-invasive effects of fibulin-3 in glioblastoma cells seeded in cultured brain slices. Taken together, our results suggest that NFkB is a novel major mechanism triggered by fibulin-3 in glioma cells and their microenvironment, and underlies the pro-invasive role of this ECM protein. Given the specific expression of fibulin-3 by glioma cells and its tight control of NFkB we hypothesize that targeting fibulin-3 may provide an avenue for tumor-specific reduction of NFkB signaling with little collateral effect in normal tissue.
Abstract PD04-08: Cell cycle algorithm correlates with grade of DCIS and p53 status, allows elimination of ‘intermediate grade’ disease and gives clinically meanignful information.
Authors: R Sainsbury, M Loddo, I Proctor, K Stoeber, G Williams, M Thorat, J Cuzick
Journal: Cancer Research (2012)

Abstract We have previously shown that multi-parameter analysis of the DNA replication initiation machinery (Mcm2-7, geminin) and mitotic proteins (Plk1, Aurora A, H3S10ph), expressed during various phases of the cell division cycle, provides a method to accurately assess the proliferative state of dynamic tumour cell populations. We have shown that this novel form of cell cycle biomarker analysis allows separation of breast cancers into three discrete cell cycle phenotypes of major prognostic significance including (i) an out-of-cycle state, (ii) a G1-delayed/arrested state and (iii) an actively cycling state. Importantly, we identified groups of patients with apparently good grade cancers on routine clinicopathological criteria but who nevertheless exhibited the poor prognostic actively cycling phenotype (iii) and might therefore benefit from adjuvant chemotherapy. Additionally, we identified patients with typically poor prognosis tumours but which were actually cycling slowly (phenotype i or ii) and therefore likely not to have benefited from chemotherapy. Notably, when this cell cycle algorithm was used in a multi-variate analysis, the effect of Ki-67 disappeared. We have now applied the algorithm to 72 cases of DCIS (all of which were re-graded by one pathologist for consistency) and also to a TMA of 136 cases with known outcome from the UK DICS trial. There was excellent correlation between tumour grade and p53 status. The high grade DCIS was positively associated with a high cell cycle score (actively cycling phenotype iii; 28 out of 34 tumours) and low grade DCIS was associated with a low score (namely phenotypes i and ii; 13 out of 19). Interestingly, 7 of the 10 intermediate grade DCIS could be classified as phenotype, i or iii suggesting that the algorithm may be useful in stratifying this group of patients. A clinical correlation between phenotype III and recurrence and/or progression to invasive disease was evident. Further analysis of this from data derived from the TMAs generated from the UK DCIS trial will be presented. If the early findings are confirmed we may be able to solve the dilemma of which cases of DCIS need treatment and which we currently overtreat. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD04-08.
Bone Metastases from Breast Cancer Localized to the Pelvis
Authors: Sami Boughattas, Habib Hassine, Kaouther Chatti, Slim Ben Ahmed, Habib Essabbah
Journal: Clinical Nuclear Medicine (2002)

BOUGHATTAS, SAMI M.D.,*; HASSINE, HABIB M.D.,*; CHATTI, KAOUTHER M.D.,*; BEN AHMED, SLIM M.D.†; ESSABBAH, HABIB M.D.* Author Information
Abstract 548: Interaction between mammary adenocarcinoma cells and macrophages in a three-dimensional model of tumor spheroids
Authors: Julieta S. Roldan, Ana C. Najenson, Fernanda Roca, Lina Marino, Maria A. Jasnis, Gabriel L. Fiszman
Journal: Cancer Research (2010)

Abstract Solid tumors contain heterogeneous cellular subpopulation due to a limit supply of oxygen, nutrients and wastes. This microenvironment affects local cell growth, survival and overall therapeutic efficacy. Three-dimensional (3D) cell model reflect this situation and is a good model to study of the interaction with the immune system. Spheroids of the murine LM3 and human MCF-7 mammary adenocarcinoma cell lines were cultured with RAW 264.7 macrophages and human monocytes isolated from peripheral blood from normal volunteers respectively Spheroids were maintained in culture dishes pre-treated with 1.5% agar. In both tumor models, macrophages/monocytes were added after 10-13 days spheroids growth. Control cultures were maintained as monolayers in normoxic and hypoxic conditions (hypoxic chamber 1% O2 saturated during 4-6h). A growth curve of the spheroids were performed, reaching a peak of &amp;gt;300um (+/-) at day 15. In MCF-7 model, cell viability, monocyte distribution inside spheroids and protein expression were determined by hematoxiline-eosine staining and immunohitochemistry with specific antibodies. Results showed that 3D growth followed a concentric organization of proliferant (Ki67+), quiescent (Ki67-/Bcl-2+) and dead cells (CAS+) from periphery towards the hypoxic core (HIF-1+). In LM3 spheroids an enhanced arginase activity (140,64±2,05 vs. 18,17±1,22, p&amp;lt;0,05) and nitric oxide (NO) levels (10,21±1,15 vs 0,55±0,50, p&amp;lt;0,05) were also detected compared to LM3 cells growing as monolayer. It was also detected a decrease NO levels during spheroids growth (4 days: 38,7±8,3 vs. 13 days: 10,21±1,15). On the other hand, arginase activity and NO levels of spheroids cocultured with macrophages were lower than the spheroids alone (96,41±3,63 vs.317,7048±8,82 and 4,1±1,56 vs. 10,22±1,15; p&amp;lt;0,05 respectively). These results show that arginine metabolic pathways, either by NOS or arginase, are both more activated in spheroids than in tumor cell monolayer and coculture spheroids. In MCF7 and LM3 models, HIF-1alpha and iNOS expression was detected by western blot using hypoxic monolayers as a control. Culture system in 3D appears to be an ideal model to analyze the role of hypoxia and the mechanisms that modulate interactions between tumor and immune cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 548.
Abstract 3013: Elucidating the functional role of microfibril-associated glycoprotein-2 (MAGP-2) in human ovarian cancer.
Authors: Young-Jeong Na, Vinod Vathipadiekal, Wei Wei, Tim Kwok, Michael Birrer
Journal: Cancer Research (2013)

Abstract Epithelial ovarian cancer, is the most fatal gynecologic cancer, resulting in approximately 15,000 deaths annually in the US. Our understanding of molecular events relating to the patient survival and overall prognosis is not clear. Using transcriptional profiling technology combined with Cox regression analysis in microdissected serous ovarian cancers, we have identified microfibril-associated glycoprotein 2 (MAGP-2) as a strong prognostic factor toward poor patient outcome. Ectopic overexpression of MAGP-2 was employed to evaluate its functional role in ovarian cancer. MAGP-2 overexpression increased cell migration and resistance to cisplatin in vitro. Moreover, the conditioned medium from MAGP-2 overexpression cells promoted endothelial cell motility. In an orthotopic model using luciferase labeled ovarian cancer cells, MAGP-2 overexpression increased the intraperitoneal tumor growth. In addition, the tumor with high MAGP-2 expression showed increased microvessel density. Our results suggest MAGP2 positively modulates the ovarian cancer tumorigenecity and angiogenesis, which may subsequently lead to poor patient survival. Citation Format: Young-Jeong Na, Vinod Vathipadiekal, Wei Wei, Tim Kwok, Michael Birrer. Elucidating the functional role of microfibril-associated glycoprotein-2 (MAGP-2) in human ovarian cancer. [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 3013. doi:10.1158/1538-7445.AM2013-3013