tbuckley/cabot-search huggingface dataset:
Abstract 771: The antimetastasis mechanism of curcumin in colorectal cancer cells
Authors: YU-SHUANG LIN
Journal: Cancer Research (2010)

Abstract Colon cancer has become a more serious threat to public health due to the changes of the dietary habits in many developed countries. In clinic, the proper therapeutic strategies for colon cancers are complete surgery resection for local diseases, and systematic chemotherapy and radiotherapy for metastatic diseases. However, tumor metastasis is the primary cause resulting in cancer death. Curcumin has been used as an important traditional medicine in almost any kind of illness including cancers. Over the past years, curcumin has been proved to be a multifunctional chemotherapeutic agent. However, the anti-tumor mechanism of curcumin is not completely understood yet. In this study, we investigate the underlying anti-metastasis mechanism of curcumin in colon cancer. Our results showed that curcumin inhibits cell proliferation (IC20 at 20 μM), cell migration (99% of inhibition at 20 μM), cell invasion (99% of inhibition at 20 μM), and colony formation (100% of inhibition at 20 μM) in a dose-dependent manner in colon cancer cells. Additionally, the differentially expressed genes of colon cancer cells treated with 20 μM curcumin were analyzed by Affymetrix genechip compared with mocks. There are 1,239 genes with greater than 2-fold change (p&amp;lt;0.05, FPR). The pathway analysis by using MetaCore and IPA software indicated that cell adhesion and cytoskeleton remodeling pathways may be involved in the anti-metastasis activity of curcumin. Several metastasis-related genes were found to be regulated by curcumin including integrin α2, integrin β5, paxillin and fibronectin. These findings suggest that curcumin may execute anti-metastasis activity by altering cell adhesion/cytoskeleton remodeling pathways in colon cancer 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 771.
The Syndrome of Dehydration, Coma and Severe Hyperglycemia without Ketosis in Patients Convalescing from Burns
Authors: Steven A. Rosenberg, Donald K. Brief, John M. Kinney, Manuel G. Herrera, Richard E. Wilson, Francis D. Moore
Journal: New England Journal of Medicine (1965)

IN 1951 Evans and Butterfield1 first reported a syndrome of glycosuria, dehydration, coma and severe hyperglycemia without ketosis occurring during the recovery phase of patients with major burns. Nine years later Arney, Pearson and Sutherland2 described 2 more burned patients in whom an almost identical syndrome occurred. Bailey3 presented an additional case in 1960. In only 1 of these patients was there a history of diabetes, and in all survivors carbohydrate metabolism reverted to normal after the episode. To our knowledge, these reports represent the only adequately documented cases of this syndrome in the literature.We have had an opportunity . . .
P208 Obesity augments circulating neutrophil levels in asthma
Authors: M. C. Pynn, G. Davies, C. A. Thornton, A. Bryant, R. Jones
Journal: Thorax (2011)

<h3>Introduction</h3> Mechanisms underlying the association between obesity and asthma are not well understood. Obesity is characterised by chronic inflammation and adipose tissue, comprising up to 50% pro-inflammatory cells, produces many pro-inflammatory cytokines and hormones (adipokines). Enhanced systemic inflammation might provide the causal link between obesity and asthma. Although there are good mechanistic data that obesity can augment innate immune function and promote immune dysregulation by reducing regulatory T cell (Treg) numbers there is little work in this area in relation to asthma. <h3>Methods</h3> A case-control study is being conducted examining six groups of pre-menopausal women (n=120): normal weight (BMI 20–25 kg/m<sup>2</sup>), overweight (BMI 25–30 kg/m<sup>2</sup>) and obese individuals (BMI &gt;30 kg/m<sup>2</sup>) with and without asthma. Asthma diagnosis was physician confirmed, and severity graded. Measures of adiposity, lung function and blood were collected during menstruation. Automated haematology analysis was used to quantify major cell types and chemiluminesence to measure whole blood reactive oxygen species generation following stimulation. Flow cytometry was used to examine major lymphocyte subtypes including Treg cells. A number of circulating cytokines and adipokines will be measured on sample collection completion. <h3>Results</h3> Interim analysis of 36 individuals revealed a significant increase in circulating total leucocytes with increasing BMI which is more pronounced in asthmatics compared with controls (p=0.022). This appears to be due to a significant increase in neutrophils (Abstract P208 figure 1, (p=0.018)). In parallel, reactive oxygen species generation increased with each BMI category (p=0.026). Furthermore, the eosinophil count dropped significantly with increasing BMI in the asthma patients (p=0.045). <h3>Conclusion</h3> Preliminary data from this study suggests that obesity is associated with systemic inflammation resulting in increasing levels of circulating neutrophils and that this is more marked in asthmatics than controls. This is in keeping with recent work showing increased neutrophils locally in the sputum of obese asthmatics. Our findings could explain the reduced inhaled corticosteroid efficacy observed in this asthma phenotype.
Abstract 1023: Regulation of cell proliferation by GPR55/cannabinoid receptors using (R,R’)-4’-methoxy-1-naphthylfenoterol in rat C6 glioma cell line.
Authors: Rajib K. Paul, Artur Wnorowski, Fred E. Indig, Michel Bernier, Irving W. Wainer
Journal: Cancer Research (2013)

Abstract (R,R’)-4’-Methoxy-1-naphthylfenoterol (MNF) is a potent inhibitor of the proliferation of rat C6 glioma cells with an IC(50) of 0.45 nM and initial in vivo data indicate that the compound may be potentially useful in the treatment of malignant gliomas. MNF is an agonist of the β(2)-adrenergic receptor and an antagonist of the GPR55 receptor. Previous studies have demonstrated that MNF inhibits proliferation in 1321N1 astrocytoma cells via the β(2)-adrenergic receptor and in HepG2 hetapocallular carcinoma cells via GPR55. In this study, the mechanism of the observed MNF effect in C6 cells was investigated using [(3)H]-thymidine incorporation, cell motility assay, and internalization of the fluorescent GPR55 ligand, Tocrifluor 1117 (T1117). The anti-mitogenic response of MNF was not affected by the β(2)-AR antagonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol (ICI 118,551). Cell treatment with synthetic agonists of cannabinoid receptors 1 and 2 (WIN-55212,2 and CP55940) led to growth inhibition, whereas pretreatment with AM251 (0.1-5 μM) dose-dependently blocked the anti-mitogenic responses of MNF. Both AM251 and the atypical cannabinoid O-1602 increased cell motility, which was blocked by MNF. Finally, there was marked inhibition in the cellular accumulation of T1117 in MNF-treated C6 glioma cells. These results indicate that MNF inhibits proliferation of C6 cells via GPR55/cannabinoid receptors and not via the β(2)-adrenergic receptor. This work was supported entirely by the Intramural Research Program of the NIA, NIH. Citation Format: Rajib K. Paul, Artur Wnorowski, Fred E. Indig, Michel Bernier, Irving W. Wainer. Regulation of cell proliferation by GPR55/cannabinoid receptors using (R,R’)-4’-methoxy-1-naphthylfenoterol in rat C6 glioma cell line. [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 1023. doi:10.1158/1538-7445.AM2013-1023
Abstract 972: Mythbusters: Cancer research in jeopardy
Authors: Jane Kennedy, Angela Boutte, Lynne Cargen, Stephanie Crowe, Caroline Hanson, Gail Hardin, Kathy Hallock, Diane Lancaster, Patricia Lee, Nick Markham, Pamela Martin, Dan McCollum, Nancy McCullough, Jeanne Moses, Ardeth Obenauf, Gary Piper, Janet Piper, Aubie K. Shaw, Jacob Weiss
Journal: Cancer Research (2010)

Abstract In the United States, less than 5% of eligible adult cancer patients participate in clinical trials. Lack of information and commonly held beliefs or myths are among the biggest barriers to enrollment in cancer clinical trials. Additionally, traditional methods of education can be intimidating, frightening or even boring and the most difficult time to educate patients about cancer clinical trials is at the time of diagnosis. Thus, there is a need to develop novel strategies to educate individuals and the community about clinical trials prior to a cancer diagnosis. The Vanderbilt-Ingram Cancer Center Patient Advocacy Program and the Vanderbilt Postdoctoral Association collaborated to develop and deliver an innovative, interactive pilot program aimed at dispelling myths commonly associated with cancer clinical trials. Patient advocates, researchers, and clinicians scripted and participated in a “Jeopardy” game show format to provide factual information in a relaxed and entertaining environment. For a community audience of 50, a response to each myth was surveyed electronically prior to the presentation. After the preliminary response of audience members was noted, an expert clarified each myth by presenting factual information. After the presentation of ten myths, a post-test was administered to assess changes in knowledge. We found that audience knowledge was significantly increased by 20%. 96% of audience members indicated that the game show format was an effective method for learning. 87% indicated that they would discuss cancer clinical trials with family, friends or co-workers. We conclude that “Mythbusters: Cancer Research in Jeopardy” is an effective learning tool and significantly increases community knowledge about cancer clinical trials. The results of this pilot will provide a model for effective community education and may ultimately impact participation in cancer clinical trials. 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 972.
Abstract 1751: The E2F activators signal centrosome amplification in breast cancer cells through centrosome regulatory molecules.
Authors: Mi-Young Lee, Harold Ivan Saavedra
Journal: Cancer Research (2013)

Abstract Based on the elevated frequencies of centrosome amplification in premalignant breast lesions and in breast tumors, centrosome amplification is proposed to play a role in breast tumorigenesis. The coordination between cell and centrosome cycles is of paramount importance to maintain genomic stability and to the prevention of mammary tumorigenesis. Thus, both cell cycle regulators and molecules that regulate centrosome duplication work together to prevent abnormal centrosome duplication. E2Fs are transcription factors that regulate various cellular processes, such as DNA replication, DNA repair, cell proliferation and apoptosis; their role on centrosomal and mitotic regulation is understood poorly. We hypothesize that the E2F activators (E2F1, E2F2, E2F3a) play key roles in regulating centrosome amplification in HER2 positive breast cancer cells. We found that the E2Fs activators are deregulated or overexpressed in HER2 positive breast cancer cells displaying centrosome amplification, since serum withdrawal does not downregulate the E2F activators (which occurs in control MCF10A cells upon serum-withdrawal). Upregulated E2Fs correlated with the transcriptional overexpression of cell cycle and centrosome regulatory targets, including cylin D, cyclin E, Nek2 and Plk4. Knockdown of E2Fs in HER2 positive cells decreased centrosome amplification without affecting the cell cycle, or entry into S phase. The chromatin immunoprecipitation (ChIP) assay showed binding of E2F1, E2F2 and E2F3 into the promoter of Nek2 and between exons 1 and 2 of Plk4. In two out of three of the Her2+ breast cancer cell lines displaying centrosome amplification, extinguishing E2F expression leads to downregulation of Nek2 and cyclin D1 -potent inducers of centrosome amplification-. In conclusion, centrosome amplification in Her2+ breast cancer cells is dependent on the E2Fs activators and is mediated by molecules that play critical roles in centrosome duplication. We have identified a novel mechanism where E2F-generated centrosome amplification may contribute to breast carcinogenesis. Citation Format: Mi-Young Lee, Harold Ivan Saavedra. The E2F activators signal centrosome amplification in breast cancer cells through centrosome regulatory molecules. [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 1751. doi:10.1158/1538-7445.AM2013-1751
PWE-019 Mitochondrial instability is elevated in Barrett's oesophagus and dimethyloxalylglycine has a potential role in reversing this dysfunction
Authors: N J O'Farrell, R Feighery, S L Picardo, N Lynam-Lennon, E J Fox, J N O'Sullivan, J V Reynolds
Journal: Gut (2012)

<h3>Introduction</h3> Deoxycholic acid (DCA), a component of bile, has been associated with the development and progression of Barrett9s oesophagus (BO). In addition, the “mutator-phenotype hypothesis” states benign cells with high rates of random mutations have an inherent predisposition for malignant conversion. Mitochondria are highly susceptible to random mutations due to inefficient DNA repair mechanisms. The role of mitochondrial mutations and dysfunction in Barrett9s progression is unknown. The aim of this study was to investigate the levels of random mitochondrial mutations (RMMs) and dysfunction in BO and determine if DCA drives progression. In parallel, determine if a hydroxylase inhibitor, dimethyloxalylglycine (DMOG), could rescue these effects. <h3>Methods</h3> We assessed mitochondrial dysfunction and mutagenesis using different models in vitro, ex vivo and in vivo. RMMs in BO extending to oesophageal adenocarcinoma (OAC) were examined. Mitochondrial function (reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial mass and cytochrome c) +/− DCA +/− DMOG were measured. A large scale gene array assessing oxidative stress and antioxidant defence was used to determine potential genes DMOG therapy may target. <h3>Results</h3> In vitro; RMMs were higher in Qh (intestinal metaplasia [IM] cells) compared with GO (high grade dysplasia [HGD] cells) (p=0.06) and OE33 (OAC cells) (p=0.01). DCA induced mitochondrial dysfunction at all stages of disease progression (p&lt;0.04). DCA increased mutagensis in Qh cell lines only. Using ex vivo explants, cytochrome c release was significantly increased in Barrett9s compared to matched normal controls (p=0.0006). DCA significantly decreased cytochrome c secretion in Barrett9s patients (p=0.015). In vivo; two distinct Barrett9s IM groups were evident; those with low RMMs and a small cohort with significantly higher levels of RMMs (p&lt;0.005). DMOG caused a significant reduction in mitochondrial dysfunction in Go and OE33 cells (p&lt;0.05). DMOG down-regulated 3 genes, CYGB, FOXM1 and GLRX2 (13, 6 and 4 fold respectively), validations of these are being performed. <h3>Conclusion</h3> Mitochondrial instability appears to be an early event in BO. DCA significantly alters mitochondrial function. Two distinct Barrett9s patient groups are evident. Applying the “mutator-phenotype hypothesis”; random mitochondrial mutation may act as a potential biomarker in differentiating IM patients into low and high risk groups for malignant conversion. DMOG may have the potential to reduce this mitochondrial instability in Barrett9s oesophagus. <h3>Competing interests</h3> None declared.
Surgical Correction of Bladder-Neck Obstruction in Children
Authors: Robert E. Gross, Judson Randolph, Henry M. Wise
Journal: New England Journal of Medicine (1963)

IN the recent literature considerable attention has been paid to recognition and management of obstructions at the bladder neck in children. This condition is relatively uncommon when compared to the numerous other anomalies of the urinary system, but it is highly important to detect, since it can insidiously lead to extensive destruction of kidney and excretory tracts. It is now known that the institution of appropriate therapy can effectively ward off renal damage and minimize superimposed infection.The entity has been recognized and described for decades, but it has not come into focus until the past few years. In 1915 . . .
Abstract 1946: Detecting protein-protein interactions between MUC16 CDΔ102 (80AA) and a SKOV-3 cDNA library using yeast two-hybrid screening
Authors: Stephan Polterauer, Ryan Parlett, Dharmarao Thapi, Nestor Rosales, David R. Spriggs, Xiu J. Yan
Journal: Cancer Research (2011)

Abstract MUC16 is a membrane-bound mucin that extends from the surface of ovarian cancer cells. Recent studies suggest that MUC16 influences carcinogenesis and metastasis of ovarian cancer cells. It is expected that protein-protein interactions play a crucial role in MUC 16 signaling and oncogenic transformation. To define the mandatory molecular partners for MUC16 signaling and transformation, we investigated potential protein binding partners, using a classic yeast two-hybrid screening. The 80AA MUC16-CDΔ102 construct (ectodomain deletion mutant) was cloned into the bait plasmid pGBKT7 and transformed into Y2HGold yeast cells, allowing expression of MUC16-CDΔ102 fused to the Gal4 DNA-binding domain (BD). A SKOV-3 cDNA library was generated and cloned into the prey plasmid pGADT7 and transformed into yeast cells, allowing expression of cDNAs fused to the Gal4 activation domain (AD). Bait and prey yeast cells were allowed to bind to potential partners and bringing the BD and AD into proximity to each other, which then activated transcription of three reporter genes. An array of diploid yeast clones was produced, by co-culturing the two strains overnight, each co-expressing the bait with a different library prey protein. The clone pool was plated on selective media (basic SD-/Trp with Agar) and incubated to screen for individual clones that express the appropriate reporter genes and markers, indicating the presence of interacting hybrid protein pairs. Prey plasmids were then isolated from yeast cells and DNA fragments of the positive clones were amplified by PCR to determine the interacting binding partner. Seven potential binding proteins (no. of colonies), i.e. TTC1 (4), DARS (1), MAPK1IP1L (1), FAM175B (1), SEPT2 (1), CAMLG (4), and SKAP2 (3), were identified. Protein-complex immuno-precipitation analysis is planned to confirm the interactions between the seven potential binding proteins in human ovarian cancer cell lines, in order to verify that each identified member of the protein complex was a valid identification. 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 1946. doi:10.1158/1538-7445.AM2011-1946
Case 14-2009
Authors: Henning A. Gaissert, Nitra Piyavisetpat, Eugene J. Mark
Journal: New England Journal of Medicine (2009)

A 36-year-old man was admitted to the hospital because of chest pain, dysphagia, and pleural and mediastinal calcifications. He had had intermittent chest pain for 6 years after an athletic injury; dysphagia, dyspnea, and weight loss had developed over the past 2 years. Imaging studies showed pleural and mediastinal calcifications, with an esophageal stricture. Surgical procedures were performed to relieve esophageal stricture and obtain tissue for diagnosis, but symptoms recurred and biopsy specimens disclosed bony tissue with no malignant cells.
The ACO Model — A Three-Year Financial Loss?
Authors: Trent T. Haywood, Keith C. Kosel
Journal: New England Journal of Medicine (2011)

The accountable care organization (ACO) model is rather controversial among health care experts. Its proponents tout the potential savings and coordinated care that could be achieved through this model.1Others, however, point out that the model is not without risks, such as the potential for anticompetitive effects as providers leverage it to concentrate market power.2,3 While experts are trying to clarify such matters, many health care executives and physician practices are deciding whether to move forward with becoming ACOs. Yet they may be unaware that the limited data suggest that most organizations will lose money in the first 3 . . .
Radiofrequency ablation of Barrett's esophagus using an overtube
Authors: S. Peter, C. Wilcox, K. Mönkemüller
Journal: Endoscopy (2013)

We report on the use of an overtube and thin enteroscope to perform radiofrequency ablation (RFA) using the HALO90 system (BARRX Medical, Sunnyvale, California, USA) in a 73-year-old man who had undergone radiotherapy to a head and neck squamous cell carcinoma and distal esophagectomy for adenocarcinoma of the esophagus (Ivor Lewis operation). He still had Barrett's epithelium present in the remaining esophagus with tongues extending 4 cm proximally to the anastomosis. Histology revealed low grade dysplasia.
CS-32 * SapC-DOPS INDUCES Smac-AND Bax-MEDIATED MITOCHONDRIAL APOPTOSIS IN NEUROBLASTOMAS
Authors: M. K. Sulaiman, V. Blanco, Z. Chu, S. Valabhurapu, R. Franco, X. Qi
Journal: Neuro-Oncology (2014)

SapC-DOPS nanovesicles are a stable protein-lipid mixture assembled from saposin C (SapC) and dioleylphosphatidylserine (DOPS). It shows selective tumor-targeting activity in multiple animal tumor models and specific induction of apoptosis in various cancer cell lines. The preferential targeting is due to higher levels of exposed phosphatidylserine on the outer cell membrane of cancer cells. Importantly, induction of apoptosis by SapC-DOPS was shown to occur through intracellular ceramide elevation. Ceramide is known to be a tumor suppressor molecule capable of acting synergistically with Bax and regulating mitochondrial-mediated apoptosis. Effectors that mediate SapC-DOPS-induced apoptosis downstream of ceramide are currently unknown. Therefore, we hypothesized that mitochondria could play a major role during SapC-DOPS induced apoptotic cancer cell death. Cell death following SapC-DOPS treatment was assessed by several indices such as: G6PD release assay to estimate necrosis, DAPI staining and cell cycle analysis to estimate apoptosis and DNA fragmentation, JC-1 assay to estimate mitochondrial membrane potential (ΔΨM) and caspase-3 activation by Western blotting. SapC-DOPS treatment induced significant apoptosis as denoted by the appearance of a subG1 peak, loss of ΔΨM, mitochondrial release of Smac, Cyto c and AIF, as well as mitochondrial Bax translocation and oligomerization. ShRNA-mediated Smac knockdown and Bax inhibition with V5 peptide led to retention of ΔΨM and abrogation of apoptosis with decreased caspase-3 activation. Our results indicate that Smac and Bax play major roles in SapC-DOPS-induced mitochondria-mediated apoptotic pathway in human neuroblastoma cells
HOSPITAL READMISSIONS AMONG PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION TREATED WITH THE NEW ORAL ANTICOAGULANTS, APIXABAN, DABIGATRAN, AND RIVAROXABAN
Authors: Steven Deitelzweig, Kiran Gupta, Anagha Nadkarni, Jeffrey Trocio, Jay Lin, Melissa Lingohr-Smith
Journal: Journal of the American College of Cardiology (2016)
S6K-STING interaction regulates cytosolic DNA–mediated activation of the transcription factor IRF3
Authors: Fuan Wang, Tommy Alain, Kristy J Szretter, Kyle Stephenson, Jonathan G Pol, Matthew J Atherton, Huy-Dung Hoang, Bruno D Fonseca, Chadi Zakaria, Lan Chen, Zainab Rangwala, Adam Hesch, Eva Sin Yan Chan, Carly Tuinman, Mehul S Suthar, Zhaozhao Jiang, Ali A Ashkar, George Thomas, Sara C Kozma, Michael Gale, Katherine A Fitzgerald, Michael S Diamond, Karen Mossman, Nahum Sonenberg, Yonghong Wan, Brian D Lichty
Journal: Nature Immunology (2016)