tbuckley/cabot-search huggingface dataset:
Abstract B18: A role for E2f3 in DNA damage‐induced apoptosis
Authors: Luis A. Martinez
Journal: Cancer Research (2009)

Abstract The E2F transcription factors have emerged as critical apoptotic effectors. Herein we report that the E2F family member, E2f3a, can be induced by DNA damage through transcriptional and post-translational mechanisms. We demonstrate that the post-translational induction of human E2f3a is dependent on the checkpoint kinases. Moreover, we show that human E2f3a is a substrate for the chk kinases and that mutation of the chk phosphorylation site eliminates the DNA damage inducibility of the protein. Furthermore, we demonstrate that all three activating E2Fs (E2f1, E2f2 and E2f3a) are transcriptionally induced by DNA damage. siRNA knockdown of E2f3 in human cells or E2f3 genetic deficiency in mouse embryonic fibroblasts eliminates the DNA damage induction of the transactivating E2fs. Finally, using both in vitro and in vivo approaches, we establish that E2f3 is required for DNA damage induced apoptosis, regardless of p53 status. Thus, our data reveal the novel ability of E2f3 to function as a master regulator of the DNA damage response. Citation Information: Cancer Res 2009;69(23 Suppl):B18.
A Second Honeymoon for Parkinson's Disease?
Authors: Caroline M. Tanner
Journal: New England Journal of Medicine (2013)

Parkinson's disease is a chronic, progressively disabling neurodegenerative disorder that occurs late in life, causing motor, autonomic, emotional, and cognitive symptoms. The cost of Parkinson's disease is substantial, including reduced quality of life, lost productivity, and increased health care expenditures. The number of persons with Parkinson's disease worldwide is, conservatively, expected to nearly double by 2030, owing to overall aging of the population.1 Effective treatments for Parkinson's disease are an imperative.Medical therapy for Parkinson's disease is most effective in treating the motor symptoms of resting tremor, bradykinesia, and rigidity. Levodopa remains the most effective current treatment for motor symptoms; . . .
Abstract IA-4: Studying tumor evolution in mouse models of cancer
Authors: Tyler Jacks
Journal: Cancer Research (2009)

Abstract Like other solid tumors, lung adenocarcinoma progresses through multiple stages including tumor initiation, expansion in the lung, and metastasis of the primary tumor to distant organs. Dissection of this process requires quantitative and tractable models that recapitulate the human disease at the genetic and histological level. We have employed autochthonous mouse models of lung adenocarcinoma that recapitulate tumor initiation, progression and metastasis in the human disease both genetically, and pathologically. We have established oncogenic Kras as the initiating event in lung adenoma and amplification of the oncogenic signaling is associated with progression to adenocarcinoma. The p53 tumor suppressor limits tumor progression in this model. Restoration of the Trp53 locus has pinpointed the adenoma-adenocarcinoma transition as the stage in which p53 function is critical for tumor suppression. Expression of oncogenic Kras in the absence of p53 leads to the development of distant metastases after long latency. This suggests that unknown cooperating genetic events are required for metastatic spread and we are utilizing multiple tools to identify these changes. Use of lentiviral vectors that drive stable GFP expression in tumors allows for identification and purification of tumor cells. Additionally, identification of the lentiviral integration site in each tumor allows the clonal relationship between metastases and the primary tumors to be unequivocally established. Gene expression and DNA copy number analyses of metastasis-derived cell lines and primary lung tumors have uncovered a metastasis associated gene expression signature and recurrent genomic alterations. Integration of these datasets, other genome-wide analyses and human tumor data are providing insights into the molecular mechanism and biology of lung cancer progression and metastasis. Citation Information: Cancer Res 2009;69(23 Suppl):IA-4.
AB0414 Predisposing factors in the development of lesions of the cervical spine in patients with rheumatoid arthritis
Authors: O. Teplyakova, R. Reznichenko
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Involment of the cervical spine in patients with RA is particulary important for the injury of the neurogical structures. <h3>Objectives</h3> The main aim of the present study was to determine the predisposing factors in the development of lesions of the cervical spine by magnetic resonance imaging (MRI) in patients with rheumatoid arthritis. <h3>Methods</h3> The study was conducted on 21 patients with definite rheumatoid arthritis (ACR criteria, 2010). Disease duration, age of onset, disease activity for 28 joint indices score (DAS-28), serology (RF and ACPA) were recorded. All patients underwent an MRI examination of the cervical spine as well as hands and feet X-ray examination. Bone oedema, MRI bone erosions, presence of pannus anterior and posterior atlantodental intervals were identifided. The Simple Erosion Narrowing Score (SENS) was applied to assess the number of eroded joints and the number of narrowed joints for hands and feet. <h3>Results</h3> In 6/21 (28.6%) cases MRI found signs indicative of lesion of the cervical spine. Presence of erosions was detected in 6/21; bone oedema – in 4/21; pannus – in 3/21; atlantoaxial subluxatiuon - in 3/21 patients. In 15/21 (71.4%) patients (comparison group) cervical spine injuries were not detected. There were no relationships between the detection of lesions of the cervical spine and age of onset, disease activity at the time of examination, evaluation of cervical rotation, serology.Duration of RA (13.9±7.8) in the group of the patients with lesions of the cervical spine exceed the duration of the disease among patients of comparison group (7.8±5.8), but not significantly: p=0.09. The SENS score was significantly higher in patients with RA and damage to the cervical spine than in the comparison group (52.5±27.9 and 21.0±11.8 respectively; p=0,016). As well the number of eroded joints for hands and feet showed higher score compared with patients without identified of spine lesion (25.8±16.7 and 9.87±7.7 respectively; p=0,038). <h3>Conclusions</h3> Our results indicate that clinical criteria are not sufficient to suggest damage in the cervical spine in patients with RA. While changes in the joints of hands and feet revealed by X-ray, more the number of eroded joints, may be predictive factor for the development of lesions in the cervical region. <h3>Disclosure of Interest</h3> None Declared
Rescue endoscopic bleeding control for nonvariceal upper gastrointestinal hemorrhage using clipping and detachable snaring
Authors: J. Lee, B. Kim, D. Seol, S. Byun, K. Park, I. Sung, H. Park, C. Shim
Journal: Endoscopy (2013)

Nonvariceal upper gastrointestinal (UGI) bleeding recurs after appropriate endoscopic therapy in 10 % – 15 % of cases. The mortality rate can be as high as 25 % when bleeding recurs, but there is no consensus about the best modality for endoscopic re-treatment. The aim of this study was to evaluate clipping and detachable snaring (CDS) for rescue endoscopic control of nonvariceal UGI hemorrhage. We report a case series of seven patients from a Korean tertiary center who underwent endoscopic hemostasis using the combined method of detachable snares with hemoclips. The success rate of endoscopic hemostasis with CDS was 86 %: six of the seven patients who had experienced primary endoscopic treatment failure or recurrent bleeding after endoscopic hemostasis were treated successfully. In conclusion, rescue endoscopic bleeding control by means of CDS is an option for controlling nonvariceal UGI bleeding when no other method of endoscopic treatment for recurrent bleeding and primary hemostatic failure is possible.
Long-Term Clinical Efficacy of Grass-Pollen Immunotherapy
Authors: Stephen R. Durham, Samantha M. Walker, Eva-Maria Varga, Mikila R. Jacobson, Fiona O'Brien, Wendy Noble, Stephen J. Till, Qutayba A. Hamid, Kayhan T. Nouri-Aria
Journal: New England Journal of Medicine (1999)

Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis, although it is questionable whether there is long-term benefit after the discontinuation of treatment.
AORTIC VALVE DISEASE IN ELDERLY: TRENDS OF HOSPITALIZATIONS IN US, 2000-2012
Authors: Apurva Badheka, Vikas Singh, Nileshkumar Patel, Shilpkumar Arora, Nilay Patel, Badal Thakkar, Sunny Jhamnani, Ankit Chothani, Sidakpal Panaich, Jay Patel, Abhishek Deshmukh, Sohilkumar Manvar, Abeel Mangi, Steven Pfau, Michael Cleman, John Forrest
Journal: Journal of the American College of Cardiology (2015)
PTU-110 Reduction In Serum Sodium (na) In Patients Treated With Terlipressin For Varcieal Bleeding (vb) And Hepatorenal Syndrome (hrs)
Authors: A Sugumaran, E Lougher, M Czajkowski, A Yeoman
Journal: Gut (2014)

<h3>Introduction</h3> Terlipressin is used in the management of VB and HRS. Studies have suggested decrease in Na levels on terlipressin, usually in VB. We set out to report the incidence of fall in serum Na in patients receiving terlipressin for VB or HRS. <h3>Methods</h3> Consecutive patients admitted to Gwent Liver Unit who received terlipressin were identified. Main outcome measure was fall in Na level during and up to 5 days post therapy. <h3>Results</h3> 60 patients were analysed (32 HRS, 28 VB). Median Na pre-treatment was 133 and 29/60 (48%) had existing hyponatraemia; 16 (27%) had Na &lt;125mmol/l. Na fell in 34/60 patients (57%) and was less likely if baseline hyponatraemia existed (38% VS 74% p = 0.004). A fall of ≥5mmol/l occurred in 23%. Median time to nadir Na was 3 days and time to recovery to pre-treatment Na was 6.5 days. No complications of hyponatremia were observed. Patients with VB were more likely (vs HRS patients) to have any fall in Na or a ≥5mmol/l reduction (68% vs 47% p = 0.1 and 32% vs 16% p = 0.12 respectively) but failed to reach significance. Mortality was 22% overall and a fall in Na was actually associated with reduced mortality –9% vs 34% (p = 0.01). <h3>Conclusion</h3> Serum Na falls in &gt;50% receiving terlipressin and a fall ≥5mmol/l noted in 23%. However, no significant complications occurred and a fall in serum Na was actually associated with improved mortality. Patients with VB treated with terlipressin trended towards a greater likelihood of Na reduction versus those with HRS. <h3>Disclosure of Interest</h3> None Declared.
Abstract 3658: 5F 203 modulates oxidative stress, induces single-strand break formation and promotes mitochondrial membrane potential loss in sensitive breast cancer cells
Authors: Eileen J. Brantley, Cheri Watkins, Lancelot McLean, Louisa Amis, Willie Davis
Journal: Cancer Research (2010)

Abstract Targeted pharmacotherapeutic agents have been successful in treating women with breast cancer that either over-expresses human epidermal growth factor receptor 2 (Her2/neu) or is dependent upon estrogen receptor signaling. However, patients with Her2/neu-negative or hormone-independent breast cancer do not benefit from these targeted agents. A candidate anticancer agent 2-(4-amino-3-methylphenyl)-5-benzothiazole (5F 203) targets the aryl hydrocarbon receptor signaling pathway and potently inhibits the growth of breast cancer cells irrespective of either estrogen receptor or Her2/neu status. 5F 203 may represent a promising agent for women who lack targeted therapeutic options. We have previously assessed the role reactive oxygen species (ROS) play in mediating the anticancer activity of 5F 203. In our current studies, we pretreated 5F 203-sensitive breast cancer cells with rotenone prior to treatment with 5F 203. This pretreatment diminished 5F 203-mediated ROS formation as measured by DCF-DA staining followed by flow cytometry. This suggests 5F 203-induced ROS production is partially derived from the mitochondria. Using the comet assay and a JC1 dye-based fluorometry assay respectively, we found 5F 203 induced single-strand break formation and mitochondrial membrane potential loss in sensitive breast cancer cells. Pretreatment with the antioxidant N-acetyl-L-cysteine partially diminished apoptosis as assessed by relief contrast microscopy and the Annexin V/PI assay. This implies that 5F 203-induced apoptosis depends at least in part on ROS derived from mitochondria. We also analyzed 84 oxidative stress-responsive genes using PCR-array and determined that 5F 203 significantly increased the expression of cytoglobin, a novel tumor suppressor, in sensitive breast cancer cells. These data imply ROS and cytoglobin contribute to the anticancer activity of 5F 203. 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 3658.
THU0466 Unraveling the Genetic Basis of Familial SAPHO Syndrome with Next-Generation Sequencing
Authors: F.J. Del Castillo, T. Caniego, M. Hurtado-Nédélec, S. Chollet-Martín, E. Gόmez-Rosas, M.-F. Kahn, O. Meyer, G. Hayem
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO) syndrome is a rare autoinflammatory disorder of skin and bone that can be classified with the inflammatory spondyloarthropathies (1). Genetic predisposing factors for SAPHO syndrome have been long suspected because of (i) reported familial clustering of the syndrome - although most cases are sporadic - (2), and (ii) the existence of two mouse models of the syndrome (the <i>cmo</i> and Lupo strains), each with a different spontaneous recessive mutation in the <i>Pstpip2</i> gene (3,4). Previous studies excluded a role for the genes <i>PSTPIP2</i>, <i>LPIN,</i><i>NOD2</i>, <i>IL1RL2</i>, <i>IL1RN</i>, <i>IL36RN</i> and <i>SIGLEC15</i> in the pathogenesis of the syndrome (5,6). <h3>Objectives</h3> Identify and validate candidate genes involved in the pathogenesis of familial SAPHO syndrome by performing whole-exome sequencing (WES) of affected subjects and unaffected relatives. <h3>Methods</h3> We investigated a cohort of 44 SAPHO subjects that includes 5 families segregating the syndrome. After obtaining written informed consent, we extracted DNA from peripheral blood samples by using automated magnetic-bead technology (Chemagen). Exomes captured with Agilent SureSelect V5+UTR kit were subjected to paired-end sequencing on an Illumina HiSeq200 sequencer (Sistemas Genόmicos). Candidate genes and putatively pathogenic variants were identified by using Variant Analysis software (Ingenuity). Validation was undertaken by Sanger sequencing, segregation analysis and functional assays when appropriate. <h3>Results</h3> We identified several potentially pathogenic variants in our cohort in genes whose products are potentially involved in the pathogenesis of SAPHO syndrome. In affected subjects we also found variants known to predispose to autoinflammatory/autoimmune disease in genes such as <i>NOD2</i>/<i>CARD15</i>. <h3>Conclusions</h3> WES is a very powerful tool to investigate the genetic factors underlying rare inherited autoinflammatory disorders that cannot be analyzed by classical genetic methods such as positional cloning. <h3>References</h3> Clin Exp Rheumatol 1988; 6: 109-112. Joint Bone Spine 2007; 74: 123-126. Bone 2006; 38: 41-47. Blood 2006, 107; 3350-3358. J Rheumatol 2010; 37; 401-409. Ann Rheumat Dis 2013; 72 - Suppl 3; 169. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4251
Abstract 1861: PPAR γ mediated involucrin induction in aerodigestive preneoplasia in vitro
Authors: Rolando R. Rosas, Nathan R. Handley, Patrick M. Gaffney, Beverly R. Wuertz, Frank G. Ondrey
Journal: Cancer Research (2011)

Abstract Effective prevention and monitoring of head and neck malignancy is a critical component of disease control which is significantly underdeveloped. Currently, no validated biomarkers or therapies for human aerodigestive preneoplasia exist. We have increasing interest in PPARγ mediated therapy for oral leukoplakia reversal based on our preliminary clinical trial results. Involucrin expression is associated with squamous differentiation and we hypothesize involucrin would be involved with PPARγ upregulation in differentiation therapies. In our present study we examined the use of involucrin as marker of PPARγ activity in response to treatment and effect of bexarotene on pioglitazone mediated PPARγ activation in oral leukoplakia. In an analysis of an Affymetrix database of human head and neck tumors (41 tumors compared to 13 normal oral mucosa samples), we found involucrin is expressed 5.6fold higher in normal versus tumor samples (P&amp;lt;0.0001). We found pioglitazone upregulates PPARγ DNA binding activity and involucrin promoter activity via reporter gene assay. Bexarotene positively effects pioglitazone upregulation of these genes via reporter gene assay and increases protein expression via western blot analysis We conclude the PPARγ activator, pioglitazone, can activate involucrin, which may be useful in upregulating differentiation in oral preneoplasia in clinical trialsin combination with bexarotene. Also involucrin has potential use as a biomarker of disease response to treatment. 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 1861. doi:10.1158/1538-7445.AM2011-1861
ATPS-15CANNABIDIOL REDUCES GLIOMA CELLS PROLIFERATION AND VIABILITY
Authors: Liting Deng, Nephi Stella
Journal: Neuro-Oncology (2015)

Phytocannabinoids exert antineoplastic activities in several types of cancers, including gliomas. However, psychotropic effects, such as dizziness and physical dependence produced by the major active ingredient of cannabis Δ9-tetrahydrocannabinol, limit their clinical application. Emerging evidence suggests that cannabidiol (CBD), a non-psychoactive component of plant cannabis, also reduces tumor growth in several glioma models; however, the molecular and cellular mechanisms by which CBD produces antitumor activities are yet to be further explored. To better understand how CBD produces antitumor actions, we studied its effects on the viability and proliferation of human GBM cell line T98G cells using cell proliferation reagents WST-1 and [3H]-thymidine incorporation assay, respectively. Multiple doses and time points were used to assess the dose response and time course of the antitumor actions produced by CBD and the DNA alkylating agent carmustine (BCNU) as comparator. Both CBD and BCNU produced a dose-dependent suppression on the viability of T98G cells. Specifically, the half maximal inhibitory concentration of CBD (IC50 = 1.55 µM) is approximately 30 times lower than BCNU (IC50 = 47.17 µM) at 72hr time point, indicating that CBD is more potent than BCNU in reducing cell viability. Both CBD and BCNU at their maximal effective dose suppressed proliferation of T98G cells in a time-dependent manner. Specifically, the inhibitory effects of CBD (1 µM) on cell viability and proliferation started at 24hr, whereas the inhibitory effects of BCNU (1mM) on cell viability and proliferation started at 4hr. The differences between the two compounds on viability and proliferation are consistent with the notion that they act through distinct mechanism of action. The strong sensitivity of T98G cells to both CBD and BCNU suggest that it is a suitable model system for the study of the molecular and cellular mechanisms of action and potential interaction of these compounds. Supported by {type:entrez-nucleotide,attrs:{text:DA026430,term_id:78765130,term_text:DA026430}}DA026430 (NS).
Abstract PD06-02: Are Outcomes Really Similar after Lumpectomy and Mastectomy for Early Stage Invasive Breast Cancer? Evidence from Population-Based Data
Authors: ES Hwang, SL Gomez, D Lichtensztajn, B Fowble, CA. Clarke
Journal: Cancer Research (2010)

Abstract Background: Randomized clinical trials have established equivalent survival for patients undergoing breast conserving therapy and radiation (BCT) compared to those undergoing mastectomy (M). However, these studies were conducted over two decades ago prior to the era of widespread systemic therapy and improved locoregional therapy and did not assess separately effects by age and tumor type types. We examined survival in a contemporary and representative series of women undergoing BCT or M without radiation for early stage (I-II) breast cancer to assess observationally whether survival varied by surgical treatment among age groups and tumor types. Methods: We used the population-based California Cancer Registry supported by the NCI's Surveillance, Epidemiology and End Results (SEER) Program. We included women diagnosed with stage I and II breast cancer between 1990 and 2003, treated with either BCT or M, and followed for vital status for through the end of 2008. Overall survival (OS) and disease-specific survival (DSS) were compared between BCT and M groups using the Cox proportional hazards model, adjusting for tumor stage at diagnosis, tumor size, grade, number of positive nodes and race. Analysis was stratified by age group (&amp;lt;50 years and ≥50 years) and tumor estrogen receptor (ER) status. Results: 139,430 women fulfilling eligibility criteria and 15,917deaths were identified in the cohort between 1990 and 2003; overall 5-year survival was 93.7% (95% CI 93.6-93.9%). 26% of the total cohort were &amp;lt;50 years of age at diagnosis; 62% were ER-positive. Stage at diagnosis, tumor size, grade, number of positive nodes and race differed significantly among the BCT and M groups. Adjusting for all of these factors, women undergoing BCT had a significantly lower hazard of mortality when compared to women who had M (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.79 - 0.89), with a more pronounced survival difference among women &amp;gt;50 (HR 0.76, 95% CI 0.73 — 0.79). This effect did not differ by ER status among women aged &amp;lt;50. However, among women aged ≥50, this effect was significantly stronger among ER(+) (HR 0.76, 95% CI 0.71-0.80) than ER(-) tumors (HR 0.81, 95% CI 0.75-0.89). Conclusion: In a large, representative series of patients with early stage breast cancer, irrespective of age group or ER status, BCT was independently associated with a significant 19-32% improvement in OS. Although it is highly likely that at least some of this difference relates to unmeasured tumor characteristics or baseline health characteristics influencing treatment choice or overall survival, these findings are provocative and should be further explored in data resources with greater clinical detail. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD06-02.