tbuckley/cabot-search huggingface dataset:
ET-46 * ONCOLYTIC VIRAL THERAPY FOR MALIGNANT GLIOMAS USING MYXOMA VIRUS DELETED FOR ANTI-APOPTOTIC M11L GENE
Authors: A. Pisklakova, B. McKenzie, R. Kenchappa, G. McFadden, P. Forsyth
Journal: Neuro-Oncology (2014)

Brain Tumour Initiating Cells (BTICs) are stem-like cells hypothesized to mediate recurrence in high-grade gliomas. Myxoma virus (MyxV) is a promising oncolytic virus, which is highly effective in conventional long term resistant glioma cell lines and less effective in BTICs. We hypothesized that one possible factor limiting efficacy in BTICs is that cell death following infection with MyxV is inhibited by virally encoded anti-apoptotic proteins, such as the Bcl-2 structural homologue, M011L. To test this we evaluated and compared the efficacy of wtMYXV versus the viral construct MyxV-M011L-KO (in which the anti-apoptotic protein M11L has been deleted) in BTICs. We found that WT-MyxV does not induce significant level of apoptosis in infected BTICs, but that MyxV-M011L-KO induces dramatically more apoptosisas shown by caspase activation, PARP cleavage, and Cytochrome C release from the mitochondria M11L from the WT-MyxV localized to the mitochondrial membrane and prevented the association of Bax with the mitochondrial membrane. Finally, silencing of Bax using specific siRNAs significantly blocked the induction of apoptosis and cell death that occurs after infection with mutant MyxV-M011L-KO virus. Therefore MyxV-M011L-KO, which is has the anti-apoptotic virally derived gene M11L, dramatically improves the oncolytic efficacy in BTICs and this is dependent on the presence of the pro-apoptotic host protein, Bax. This is the first demonstration, that the MyxV mutant, genetically modified to promote apoptosis in tumor initiating cells, is significantly more efficacious than the wildtype virus. Strategies, such as this one, that promotes apoptosis in tumor initiating cells might be particularly effective.
PRAVASTATIN DECREASES SERUM LOX-1 LIGAND LEVELS AND MT1-MMP EXPRESSION IN CD14 POSITIVE MONONUCLEAR CELLS IN HYPERCHOLESTEROLEMIC PATIENTS
Authors: Hiroyasu Uzui, Hideki Hayashi, Izuru Nakae, Tetsuya Matsumoto, Hiroaki Uenishi, Hisae Hayasaki, Takayoshi Asaji, Shinobu Matsui, Kunihisa Miwa, Jong-Dae Lee, Tatsuya Sawamura, Masatoshi Fujita
Journal: Journal of the American College of Cardiology (2013)
Abstract 3988: Deregulated sphingosine 1-phosphate signaling contributes to a more aggressive phenotype in oral squamous cell carcinoma cells.
Authors: Steven Johnson, Lee Fah Yap, Sathya Narayanan, Ian Paterson
Journal: Cancer Research (2013)

Abstract Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide, accounting for more than 250,000 new cases each year. Early death usually occurs as a result of local invasion and regional lymph node metastases and overall five year mortality rates are approximately 50%. Novel therapeutic targets are urgently required. Sphingosine 1-phosphate (S1P) regulates many biological processes associated with tumour development and progression, with the specific effects of S1P being determined, in part, by the profile of receptor expression in tumor cells. Sphingosine kinase 1 (SphK1), an enzyme responsible for the production of S1P, has been reported to be overexpressed in OSCC tissues, but the effect of S1P on the behavior of OSCC cells and the expression of S1P receptors in OSCC has not been examined. The effect of S1P on OSCC cells was examined by treating OSCC cell lines in vitro. S1P inhibited the proliferation of OSCC cells but stimulated cell scattering in colony dispersal assays, causing colonies to disperse into single, highly migratory cells. S1P-induced cell migration was dependent on the MEK, ROCK and Rac-1 signaling pathways. Additionally, S1P enhanced tumor cell invasion in 3-dimensional organotypic invasion assays. S1P also protected OSCC cells from Cisplatin-induced apoptosis, as determined in clonogenic survival assays. Using QPCR, we show that OSCC cell lines express S1P receptors 1-3 and that the expression of S1P1 and S1P2 was significantly lower in 8/8 OSCC cell lines compared to normal oral keratinocytes (p&amp;lt;0.001), whilst S1P3 mRNA levels were significantly higher in 6/8 cell lines (p&amp;lt;0.001). S1P receptor expression was similarly deregulated in two dysplasia cell lines, suggesting that alterations in S1P signalling occur early in tumor progression. The results of the present study demonstrate that de-regulated S1P signaling contributes to a more motile, invasive and chemo-resistant phenotype in OSCC and indicate that the S1P-receptor axis may represent a promising target for therapy. Work is ongoing to examine the protein expression of S1P receptors in OSCC tissues and to determine the precise role of the S1P3 receptor in mediating the tumor promoting effects of S1P in OSCC cells. Citation Format: Steven Johnson, Lee Fah Yap, Sathya Narayanan, Ian Paterson. Deregulated sphingosine 1-phosphate signaling contributes to a more aggressive phenotype in oral squamous cell carcinoma 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 3988. doi:10.1158/1538-7445.AM2013-3988
Abstract 301: Microenvironmental regulation of epithelial-mesenchymal transitions in breast cancer metastasis.
Authors: Dingcheng Gao, Kari Fisher, Hyejin Choi, Andrew J. Dannenberg, Linda Vahdat, Nasser Altorki, Vivek Mittal
Journal: Cancer Research (2013)

Abstract Metastatic spread is the main cause of death in breast cancer patients. To successfully develop metastatic lesions, tumor cells exhibit plasticity to adapt to the changing microenvironment that they encounter at both the primary and distant sites. Notably, tumor cells undergo epithelial-mesenchymal transition (EMT) to acquire metastatic potential. In the metastatic organ, the disseminated tumor cells are thought to undergo mesenchymal to epithelial transition (MET) to form lethal macrometastatic lesions. However, while EMT/MET has been well demonstrated in cancer cell lines in vitro, whether such transitions occur in vivo is debated. Our study is based on an emerging paradigm that microenvironmental regulation of epithelial-mesenchymal transitions contributes to tumor growth and metastasis. To evaluate this, we have devised a lineage tracing approach where a unique EMT-induced Cre-mediated fluorescence switch system monitors epithhelial-mesenchymal transitions in physiologically relevant orthotopic and spontaneous breast cancer metastasis in vivo. Using this system, we found that the CD11b+F4/80+ tumor-associated macrophages promote EMT in the primary tumor by secreting TGFβ1 and PDGFA, while the CD11b+Gr1+ myeloid progenitors facilitate MET of disseminated tumor cells in metastatic lungs by secreting proteoglycan versican thereby providing novel mechanistic insights into how the tumor-stroma cross talk confers prometastatic properties. Our finding that different subsets of inflammatory cells are associated with EMT in the primary tumor and MET in the metastatic organ has provided clinical translation opportunities. Previously, the therapeutic targeting of EMT (i.e. TGFβ1 blockade) has been associated with the caveat that it may actually promote the formation of fatal macrometastases. Here, the identification of unique cellular EMT and MET regulators provides an opportunity for inhibiting one process without promoting the other, or inhibiting both EMT and MET simultaneously. Importantly, administration of non-steroidal anti-inflammatory drugs impaired metastases by targeting specific inflammatory populations that contribute to the EMT/MET-promoting microenvironment in preclinical mouse models of breast cancer. Citation Format: Dingcheng Gao, Kari Fisher, Hyejin Choi, Andrew J. Dannenberg, Linda Vahdat, Nasser Altorki, Vivek Mittal. Microenvironmental regulation of epithelial-mesenchymal transitions in breast cancer metastasis. [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 301. doi:10.1158/1538-7445.AM2013-301
NOVEL ECHOCARDIOGRAPHIC ASSESSMENT OF RIGHT VENTRICULAR MYOCARDIAL STIFFNESS IN PATIENTS WITH PULMONARY HYPERTENSION
Authors: Anusith Tunhasiriwet, Chayakrit Krittanawong, Panorkwan Toparkngarm, Mahmoud Alashry, Sorin Pislaru, Patricia Pellikka, Garvan Kane, Cristina Pislaru
Journal: Journal of the American College of Cardiology (2016)
Abstract 1127: Dysregulation of tumor suppress gene LKB1 in pancreatic cancer
Authors: Chongjuan Wei, Nianxiang Zhang, Qian Liu, Christopher Amos, Marsha Frazier
Journal: Cancer Research (2010)

Abstract Pancreatic cancer is the fourth leading causes of cancer-related death in USA and the most common seen neoplsams in Peutz-Jeghers syndrome (PJS). PJS is an autosomal dominant disorder characterized by gastrointestinal hamartoma and predisposition to cancer. Patients with PJS have a 100-fold higher risk for development of pancreatic cancer than the general population. Tumor suppressor LKB1 is the causative gene for PJS. LKB1 mutations have also been observed in a significant proportion of sporadic pancreatic cancer, suggesting a role for LKB1 in pancreatic cancer although the underlying mechanism has not been elucidated yet. To evaluate the role of LKB1 in pancreatic tumorigenesis, we extracted RNA from our unique collection of fifty-three tumor/normal pairs of snap frozen pancreatic cancer and adjacent normal tissue from the same patient. RT-PCR results showed that LKB1 is downregulated in ∼74% of the cancer tissue compared to adjacent normal pair, and in ∼40% of pairs the downregaulation is greater than 2 folds. To confirm our result, we analyzed the publically available gene expression microarray data on 36 pancreatic cancer samples and 12 normal controls. We observed downregulation of LKB1 in these data and the difference in LKB1 expression levels in pancreatic cancer vs normal was statistically significant (p=0.0003). LKB1 has been reported to negatively regulate mTOR signaling. Therefore, we further analyzed whether there was correlation between the expression of LKB1 and key protein in mTOR signaling pathway. Our results showed that the expression of LKB1 is inversely correlated with that of EIF4A and EIF4E, which are translation initiation factors. These findings suggest that dysregulation of LKB1 and its downstream signaling pathway may play an important role in pancreatic tumorigenesis. 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 1127.
Biomarkers Help Advance Chemoprevention Research
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Biomarkers Help Advance Chemoprevention Research Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 19, 2 October 1991, Pages 1368–1370, https://doi.org/10.1093/jnci/83.19.1368 Published: 02 October 1991
EVALUATION OF THE IMMUNOGENICITY OF THE DABIGATRAN REVERSAL AGENT IDARUCIZUMAB: POOLED ANALYSIS OF PHASE I DATA
Authors: Joanne van Ryn, Stephen Norris, Steven Ramael, Ippei Ikushima, Wouter Haazen, Akiko Harada, Viktoria Moschetti, Susumu Imazu, Paul Reilly, Benjamin Lang, Joachim Stangier, Stephan Glund
Journal: Journal of the American College of Cardiology (2016)
Pure transgastric NOTES ovarian cystectomy: the first human procedure
Authors: Bing-Rong Liu, Guang-Xing Cui, Xue-Yan Zhang, Kavanjit Kaur, Ji-Tao Song, Yu Si, Xian-Chao Kong
Journal: Endoscopy (2014)

Natural orifice transluminal endoscopic surgery (NOTES) is an evolving minimally invasive procedure that aims to eliminate abdominal trauma as well as its related complications such as incisional hernia, infection, or abscess. However, most current NOTES procedures are performed with the help of laparoscopic instruments, which deviates from the initial NOTES purpose of no-scar surgery [1] [2]. After safely and successfully accomplishing pure transgastric NOTES salpingostomy for ectopic pregnancy in a young woman [3], we went on to perform transgastric NOTES in a 23-year-old woman with an ovarian cyst.
OP0058 CCR6+ T-cells in children with juvenile idiopathic arthritis
Authors: K.N. Sustal, G. Almanzar, R. Trippen, K. Höfner, M. Prelog
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Previous studies have demonstrated a plasticity of effector-T-cells regarding CCR6 expression in autoimmune disorders. In healthy humans, CCR6+ T-cells have been shown to belong mainly to the Th17 phenotype (characterized by IL-17 production) and CCR6- T-cells to the Th1 phenotype (IFNγ production). <h3>Objectives</h3> The present study was aimed to investigate the CCR6+ T-cell phenotype and its plasticity in children with Juvenile idiopathic arthritis (JIA). <h3>Methods</h3> Peripheral blood mononuclear cells (PBMCs) of children with JIA (n=25 in clinical remission on medication; n=10 with disease flare) and age-matched healthy donors (HD) (n=21) were analyzed by flowcytometry to assess the phenotype, cytokine production and proliferation of T-cells expressing the chemokine receptor CCR6+. CCR6+ T-cells were separated via magnetic bead isolation. <h3>Results</h3> The proportion of CCR6+ T-cells (CD4+ gate) was significantly increased in patients with disease flare (mean 6.3±3.7%) compared to those in remission (3.3±2.7%) or HD (4.0±1.9%) (p&lt;0.05). Regarding the phenotype, almost all CCR6+ T-cells expressed RORgt and CD45RO, but some were CCR7- (77%). Additionally, in JIA patients in remission, about 12.5% of CCR6+ T-cells showed CD161 expression, a marker for the concomitant Th1/Th17 phenotype found in some cases of adult arthritis. CCR6- T-cells were mainly CD45RA+ (50%) and CCR7+ (51.3%), but lost CD161 expression (2.2%). Separated CCR6+ T-cells of JIA patients showed a 17.7-fold higher IL-17 production compared to CCR6- T-cells. However, no significant difference in IFNγ production was determined between CCR6+ or CCR6- T-cell subsets. <h3>Conclusions</h3> Our preliminary results confirmed that the CCR6+ T-cell-pool mainly represents the IL-17-producing T-cell subset in JIA patients with disease flare, as well as in remission. Whether CCR6+ T-cells in JIA patients appear to be stable under various cytokine milieus or treatments with biologicals and, thus, offer to be a promising target for future therapies has to be investigated. <h3>Disclosure of Interest</h3> None Declared
ASSOCIATIONS OF HOSPITAL STRATEGIES AND 30-DAY RISK-STANDARDIZED READMISSION RATES IN PERCUTANEOUS CORONARY INTERVENTION
Authors: Karl E. Minges, Jeph Herrin, Nihar Desai, John Messenger, Brahmajee Nallamothu, John Rumsfeld, Mary Anne Elma, Peggy Chen, Henry Ting, Jeptha Curtis
Journal: Journal of the American College of Cardiology (2016)
Endoscopic ampullectomy: to inject or not to inject? The underwater technique
Authors: Antonino Granata, Gabriele Curcio, Dario Ligresti, Luca Barresi, Tarantino Ilaria, Rosa Liotta, Mario Traina
Journal: Endoscopy (2014)

Corrected by: Endoscopic ampullectomy: to inject or not to inject? The underwater techniqueEndoscopy 2014; 46(S 01): E633-E633DOI: 10.1055/s-0034-1389836
UNIVERSITY HOSPITALS OF LEICESTER COLONOSCOPY AUDIT 2011–2012 AND COMPARISON WITH HISTORICAL DATA
Authors: N Hossain, A Sasegbon
Journal: Gut (2013)

<h3>Introduction</h3> Colonoscopy is an important investigation having a diagnostic and therapeutic role. Over five years an audit of colonoscopies has been conducted at UHL NHS Trust. <h3>Aims/Background</h3> Assess: 1. Success rate of colonoscopies performed in UHL between September 2011 and 2012. This will be compared with the results of audits in 2006–2007, 2007–2008, and 2010–2011. 2. Complication rate Standards: 1. Caecal Intubation: &gt;90% &amp; 2. Perforation rate: &lt;1:1000 <h3>Method</h3> The colonoscopy database was searched for all colonoscopies performed on patients aged eighteen and above in UHL between September 2011 and 2012. The procedural notes were analysed looking for: caecal visualisation; reasons for failure and complications. Additionally all patients presenting to UHL hospitals with a diagnosis of perforation were compared against the database to identify potential late perforations. <h3>Results</h3> 4001 colonoscopies were performed over the audit period. 3680 (92%) were successful. There were 80 complications (2%) in total. The commonest complications were difficult intubation and patient distress with 52 (1.3%) and 16 (0.4%) instances respectively. 3 (0.07%) perforations occurred. 1 perforation occurred during colonoscopy and 2 potential delayed perforations presented 15 and 18 days post colonoscopy. Success rate over 5 years: 69% 2006–2007, 89% 2007–2008, 93% 2010–2011 and 92% 2011–2012. <h3>Conclusion</h3> UHL achieved its colonoscopy targets with a success rate of 92% and a perforation rate of 3:4001. Over the past five years the success rate has improved from 69% to 92%. For the last two years UHL has achieved its targets with success rates of 93% and 92%. This shows the value of these audits in highlighting poor practice and prompting reflection and improvement.
Abstract 2102: Investigational agent 5F 203 modulates apoptotic regulatory gene expression and induces lysosomal membrane permeabilization in breast cancer cells.
Authors: Eileen J. Brantley, Gabriell Thorne, Devin Daly, Dain Zylstra, Lancelot McLean
Journal: Cancer Research (2013)

Abstract Despite advances in targeted therapeutic agents for women with breast cancer that either express estrogen receptor (ER) alpha or over-expresses human epidermal growth factor receptor 2 (Her2), nearly 40,000 women die each year due to this malignancy. An investigational anticancer agent 2-(4-amino-3-methylphenyl)-5-benzothiazole (5F 203) potently inhibits the growth of breast cancer cells irrespective of either ER or Her2 status. In our current studies we used the Annexin V/PI assay to determine that 5F 203 induced a dose-dependent increase in the percentage of ER/Her2-positive T47D cells and ER/Her2-negative MDA-MB-468 breast cancer cells in early apoptosis. Cell death was not entirely caspase-dependent as pretreatment with pan-caspase inhibitor z-VAD-fmk only partially suppressed apoptosis. A pathway specific PCR-array revealed the ability for 5F 203 to increase the mRNA expression of pro-apoptotic genes bcl-2-antagonist/killer 1 (BAK1) and lymphotoxin alpha (LTA). Using the Acridine Orange assay, we found that 5F 203-mediated cell death was associated with lysosomal membrane permeabilization in both T47D and MDA-MB-468 cells. Additionally, we determined using the Cathepsin B assay that 5F 203 promoted the release of cathepsin B from the lysosomes in both breast cancer cell types. These data indicate 5F 203 upregulates BAK1 and LTA expression and promotes lysosomal cell death triggering the release of cathepsin B in breast cancer cells to confer its anticancer action. Citation Format: Eileen J. Brantley, Gabriell Thorne, Devin Daly, Dain Zylstra, Lancelot McLean. Investigational agent 5F 203 modulates apoptotic regulatory gene expression and induces lysosomal membrane permeabilization in breast cancer 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 2102. doi:10.1158/1538-7445.AM2013-2102
Assessment of breast cancer risk prediction models in a high-risk population.
Authors: J Chun, F Schnabel, O Ogunyemi
Journal: Cancer Research (2009)

Abstract Abstract #4074 Background: A variety of risk assessment models have been developed to quantify a woman's risk for developing breast cancer. Although the Gail model (GM) is the most widely utilized model, there are limitations. The Tyrer-Cuzick model (TCM), which has been validated in the United Kingdom (UK), addresses these limitations but its performance in other populations is unclear. The purpose of this study was to evaluate the predictive ability of the TCM in a cohort of high-risk women from the New York metropolitan area and compare the results to the GM.&amp;#x2028; Methods: The Women At Risk (WAR) Registry provided the study population. Due to the age limitation of the Gail model, we excluded women who were under 35 and over 80 years of age. Calculation of lifetime Gail scores included the following: age, race, age at first menses, age at first live birth, number of first degree relatives with breast cancer, number of previous breast biopsies, and atypical hyperplasia. These variables were also included in the lifetime Tyrer-Cuzick scores as well as information on menopausal status, use of hormone replacement therapy, LCIS, and age at diagnosis for relatives with ovarian and breast cancer. The Receiver Operating Characteristic (ROC) and estimated area under the ROC curve (AUC) with 95% confidence intervals (CI) were used to assess prediction accuracy of both models.&amp;#x2028; Results: Out of a total study population of 1523 women, 82 (5%) developed breast cancer during a median follow-up of 56 months. The median age of women without breast cancer was 49 years, and the median age of women who developed breast cancer was 54 years. The AUC and 95% CI for the Gail model was 0.547 (0.479 to 0.615) and 0.501 (0.433 to 0.569) for the Tyrer-Cuzick model. Our results indicate poor discriminatory accuracy for both models, which performed no better than pure chance (0.5).&amp;#x2028; &amp;#x2028; Discussion: Quantitative breast cancer risk assessment models are critically important in developing effective risk management strategies. Although the TCM addresses some limitations of the GM, it is unclear how well it performs in populations outside the UK due to the wide variation in international breast cancer rates. In addition, the TCM excludes more recently identified risk factors such as breast density. Bayesian techniques may ultimately lead to a better risk assessment tool as they allow continual modification of the model as new risk factors are identified. Accurate breast cancer risk prediction is a complex undertaking and further studies are warranted in order to achieve truly comprehensive and widely applicable models. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4074.