tbuckley/cabot-search huggingface dataset:
Abstract 2069: Regulation of nucleostemin by reactive oxygen species
Authors: Min Huang, Patrick Whang, Jayanth V. Chodaparambil, Daniel A. Pollyea, Brenda Kusler, Liwen Xu, Dean W. Felsher, Beverly S. Mitchell
Journal: Cancer Research (2011)

Abstract Nucleostemin (NS) is a nucleolar-nucleoplasmic shuttle protein that is a key regulator of cell proliferation, binds p53 and Mdm2, and is highly expressed in tumor cells and embryonic stem cells. We have identified NS as a previously unreported target of redox regulation in transformed hematopoietic cells. NS oligomerization is present in HL-60 leukemic cells and Raji B lymphoblasts that express high levels of c-Myc and have high intrinsic levels of reactive oxygen species (ROS); exposure of these cells to reducing agents including N-acetylcysteine results in the dissociation of NS into monomers and dimers. On the other hand, exposure of other cell types that have relatively low levels of intrinsic ROS to low levels of H2O2 induces disulfide bond-mediated oligomerization of NS and, with prolonged exposure, immobilizes NS within the nucleolus, preventing its translocation to the nucleoplasm in response to nucleolar stress. Increasing levels of ROS also result in significantly increased NS protein stability. The redox-and oncogene-mediated regulation of NS was validated in a murine lymphoma tumor model in which c-Myc is overexpressed and in CD34+ cells from four patients with chronic myelogenous leukemia in blast crisis in which the BCR-ABL oncogene is expressed. In both instances, increased intrinsic ROS levels were associated with markedly increased expression of NS protein and oligomerization that was reversed by exposure of cells to N-acetylcysteine. These results demonstrate that NS is a highly redox-sensitive protein. Increased intracellular ROS levels, such as those that result from oncogenic transformation in hematopoietic malignancies, increase the oligomerization of NS, enhance its stability and most likely impair its ability to regulate Mdm2-p53 interactions in the nucleus. 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 2069. doi:10.1158/1538-7445.AM2011-2069
Enhancement of Exercise-Induced Asthma by Cold Air
Authors: Richard H. Strauss, E. R. McFadden, R. H. Ingram, James J. Jaeger, David R. Stearns
Journal: New England Journal of Medicine (1977)

To study the possibility that the inhalation of cold air accentuates the bronchoconstrictor response to exercise in asthma, eight subjects exercised while breathing air at ambient or subfreezing temperatures. On a separate day, cold air was breathed at rest so as to isolate the effects of this stimulus. Pulmonary mechanics were measured before and after each experiment. In all subjects acute bronchoconstriction followed the control exercise challenge. With cold-air breathing, however, the magnitude of the response was markedly enhanced. Residual volume increased 158 per cent more than it did previously, and specific conductance and one-second forced expiratory volumes changed an additional 85 and 100 per cent, respectively. The effects of cold air at rest were very small. The results demonstrate a positive interaction of two common naturally occurring stimuli in the induction of asthmatic attacks, and constitute objective verification of a frequent clinical complaint.
P391 CD2-SPECIFIC OVEREXPRESSION OF CREM ALPHA AGGRAVATES ACUTE CONCANAVALIN A-INDUCED HEPATITIS
Authors: L. Hammerich, C. Schönherr, M. Stefkova, K. Ohl, T. Luedde, C. Trautwein, K. Tenbrock, F. Tacke
Journal: Journal of Hepatology (2014)
“Endoscopic resection” of superficial gastrointestinal neoplasia: a single key opening all the doors
Authors: L. Cipolletta, G. Rotondano, M. Bianco
Journal: Endoscopy (2011)

We have read with great interest the position statement by Deprez et al. on the current practice with endoscopic submucosal dissection (ESD) in Europe [1]. The great effort made by the panel of experts should definitely be commended, as the article is extremely clear and gives a very balanced perspective on the potential role of ESD. The training and educational needs, as well as the technical proficiency required to safely perform this technique in standard practice are sharply focused and correctly addressed.
NHS must win over patients and staff to achieve a paperless future, conference hears
Authors: M. Limb
Journal: BMJ (2014)

The NHS is a long way from meeting its ambition to become paperless and is still seen by many to be stuck in a pre-digital age, a top NHS official has said.

Paul Rice, NHS England’s head of technology strategy, said that more had to be done to win the “hearts and minds” of patients and staff in terms of technology; otherwise, reforms such as personal care budgets and seven day working could falter. “We have to be better at telling the story about why it’s vital, and why it will transform care and make it efficient, optimal, and sustainable,” he said. Rice spoke on 11 September at the International Digital Health and Care Congress, held in London over three days by the King’s Fund.

Chris Ham, King’s Fund chief executive, asked Rice, …
Abstract 3020: The gep protooncogene Gα12 mediates LPA-stimulated activation of CREB in ovarian cancer cells.
Authors: Ji Hee Ha, Danny Dhanasekaran, Jeremy Ward, Yoon Mi Yang, Sang Geon Kim, Lakshmi Varadarajalu
Journal: Cancer Research (2013)

Abstract Lysophosphatidic acid (LPA), plays a critical role in the pathophysiology of ovarian cancers. Our previous studies have shown that LPA stimulates the proliferation of ovarian cancer cells through GNA12, the gep protooncogene Gα12. The present study is focused on identifying the Gα12-dependent mechanism through which LPA stimulates the proliferation of ovarian cancer cells. Using ovarian cancer cells in which the expression of Gα12 is silenced, we demonstrate here that Gα12-dependent mitogenic signaling by LPA involves the atypical activation of the transcription factor, cAMP-response element binding protein (CREB). Protein/DNA array analyses using LPA-stimulated Hey8 cells in which the expression of Gα12 was silenced indicated the potent but Gα12-dependent activation of CREB by LPA. After validating the array data with immunoblot analysis using antibodies specific to Ser133-phosphorylated active form of CREB, we demonstrate that the expression of the constitutively activated mutant of Gα12 stimulate the activation of CREB even in the absence of LPA whereas silencing of Gα12 abrogates such LPA-stimulated activation in multiple ovarian cancer cell lines. Furthermore, our results indicate that the robust activation of CREB by LPA is an early event, which can be monitored upon LPA stimulation from 3 minutes onwards. In addition, we establish that LPA/Gα12-dependent activation of CREB involves an atypical cAMP-independent mechanism involving Ras and ERK. More significantly, our findings indicate that the expression of the dominant negative mutant of CREB (S133A) leads to a reduction in LPA-stimulated increase in Cyclin A levels along with an attenuation of LPA-stimulated proliferation of these cells. Thus, these studies unravel a novel Gα12-dependent mechanism involving CREB through which LPA stimulates the proliferation of ovarian cancer cells. Citation Format: Ji Hee Ha, Danny Dhanasekaran, Jeremy Ward, Yoon Mi Yang, Sang Geon Kim, Lakshmi Varadarajalu. The gep protooncogene Gα12 mediates LPA-stimulated activation of CREB in ovarian 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 3020. doi:10.1158/1538-7445.AM2013-3020
Preoperative Angiocardiography Diagnosis of Left Atrial Thrombi in Mitral Stenosis
Authors: Brent M. Parker, Marvin J. Friedenberg, Arch W. Templeton, Thomas H. Burford
Journal: New England Journal of Medicine (1965)

THE preoperative clinical diagnosis of left atrial thrombi is difficult. A history of systemic embolization does not necessarily indicate the presence of an atrial thrombus. A reliable method of diagnosing such thrombi in mitral stenosis before surgery is needed, because the presence of clot influences the choice of surgical technic and the operative risk. This report describes our experience with pulmonary-artery angiocardiography in the diagnosis of left atrial thrombi in 113 patients with mitral stenosis.Materials and MethodsThe records were reviewed of all 113 patients with predominant mitral stenosis who had cardiac catheterization with pulmonary-artery angiocardiography between July 1, . . .
Abstract 2785: Modulating the interaction between cdk2 and cyclin A: Screening, synthesis and characterization of a quinoline-based inhibitor
Authors: William T. Windsor, Yongqi Deng, Gerald W. Shipps, Lianyun Zhao, Arshad Siddiqui, Janeta Popovici-Muller, Patrick Curran, Thierry Fischmann, Jose S. Duca, Alan Hruza, Rumin Zhang, Charles McNemar, Todd Mayhood, Rosalinda Syto, David A. Parry, Emma Lees, Paul Kirschmeier
Journal: Cancer Research (2011)

Abstract Cyclin dependent kinase 2 (CDK2) is aberrantly regulated in a wide range of cancers and small molecule inhibitors should be beneficial in the treatment of cancer. Preclinical and clinical CDK2 inhibitors are ATP competitive and bind at the ATP site in a canonical mode. A novel binding mode for a new class of quinoline-based inhibitors of CDK2 has been discovered using the affinity-based Automated Ligand Identification System (ALIS) technology. While the inhibitors do bind to the ATP site the key mechanism of action for inhibition is the induction of a novel protein conformational change that enables the compound to bind into the core of the kinase domain. Global changes to CDK2 upon compound binding result in a conformation that can no longer bind to its activating protein cyclin A. Therefore, these inhibitors are both ATP competitive and are protein-protein interaction disrupters. The key strategy for discovering this class of protein-protein disrupter compounds was to screen the unphosphorylated monomer CDK2 in ALIS and to perform secondary binding and enzyme mechanism of action assays that identified quinoline-based compounds that only bound to the inactive CDK2 monomer and not the active CDK2/cyclin A heterodimer. Through a series of chemical modifications the affinity (Ki) of the original hit improved from 0.9 μM to 0.005 μM. The screening strategy utilized and the discovery of this new kinase inhibitor binding mode may be applicable to other kinase programs. 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 2785. doi:10.1158/1538-7445.AM2011-2785
Abstract 3026: Targeting aberrantly activated AREG-EGFR signaling in CRTC1-MAML2-positive mucoepidermoid carcinoma.
Authors: Zirong Chen, Yumei Gu, Chengbin Hu, Jian-Liang Li, Shuibin Lin, Huangxuan Shen, Chunxia Cao, Jie Chen, Jiancheng Li, Patick K. Ha, Federic J. Kaye, James D. Griffin, Lizi Wu
Journal: Cancer Research (2013)

Abstract Salivary gland tumors (SGT) are a group of highly heterogeneous head and neck malignancies with widely varied clinical outcomes and no standard effective treatments. The CRTC1-MAML2 gene fusion, encoded by a recurring chromosomal translocation t(11;19)(q14-21;p12-13), is a highly specific genetic alteration in more than 50% of mucoepidermoid carcinoma (MEC), the most common malignant SGT. In this study, we aimed to define the role of the CRTC1-MAML2 oncogene in the maintenance of MEC tumor growth and to investigate critical downstream target genes and pathways for therapeutic targeting of MEC. By performing gene expression analyses and functional studies via RNA interference and pharmacological modulation, we determined the importance of the CRTC1-MAML2 fusion gene and its downstream AREG-EGFR signaling in human MEC cancer cell growth ad survival in vitro and in vivo using human MEC xenograft models. We found that CRTC1-MAML2 fusion oncogene was required for the growth and survival of fusion-positive human MEC cancer cells in vitro and the in vivo. CRTC1-MAML2 induced the up-regulation of the EGFR ligand AREG by co-activating the transcription factor CREB and AREG subsequently activated EGFR signaling in an autocrine manner that promoted MEC cell growth and survival. Importantly, CRTC1-MAML2-positive MEC cells were highly sensitive to EGFR signaling inhibition. Therefore, our study revealed that aberrantly activated AREG-EGFR signaling is required for CRTC1-MAML2-positive MEC cell growth and survival, suggesting that EGFR-targeted therapies will benefit patients with unresectable CRTC1-MAML2-positive MEC. Citation Format: Zirong Chen, Yumei Gu, Chengbin Hu, Jian-Liang Li, Shuibin Lin, Huangxuan Shen, Chunxia Cao, Jie Chen, Jiancheng Li, Patick K. Ha, Federic J. Kaye, James D. Griffin, Lizi Wu. Targeting aberrantly activated AREG-EGFR signaling in CRTC1-MAML2-positive mucoepidermoid carcinoma. [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 3026. doi:10.1158/1538-7445.AM2013-3026
FRI0314 Lupusqol correlates with sf36, but not with sledai in patients with systemic lupus erythematosus in turkey
Authors: S. Yilmaz öner, F. M. Doğukan, A. Velioğlu, S. Tuğlular, P. Atagündüz, H. Direskeneli
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To assess the value of disease-specific LupusQoL questionnaire and compare it with a general QoL scale, SF36, in patients with SLE from Turkey. <h3>Methods</h3> Patients with SLE followed in the Rheumatology Clinics (F/M: 87/2, mean age: 40,9±1,2 years, mean disease duration: 8,5±6,8 years) were enrolled to the study. All patients were asked to complete a LupusQoL questionnaire, Short Form 36 (SF-36) and hospital anxiety and depression scales. Data were analyzed using SPSS16 program. <h3>Results</h3> A total of 89 patients were included and 27% (n= 24) of these were active. Mean SLEDAI score was 3,17±4,36, mean LupusQoL score was 59,15±2,44 and mean SF36 score was 46,29±1,77. There was a significant correlation between LupusQoL and SF36 global scores (r=0,623, p=0.000). SLEDAI scores and SF36 (r=-0,297, p=0,005) also correlated. However, no significant correlation between SLEDAI and LupusQoL scores were observed (r=-0,05, p=0,689). Longer education time period correlated with a higher LupusQoL and SF36 scores (p=0,01). Both lupusQoL and SF36 scores of patients with high anxiety and depression scores (cut-off ≥ 10 for anxiety and ≥ 7 for depression score) were also observed to be lower (Mean SF36 global score: anxiety: 38,33±10,36 vs. 50,12±16,41 and depression: 38,42± 9,61 vs. 52,13± 16,81 and mean LupusQoL score: anxiety: 35,81±15,08 vs. 68,78± 20,77 and depression: 41,92± 19,33 vs. 71,99± 19,45, all p&lt;0,05). <h3>Conclusions</h3> LupusQoL and SF36 have the similar efficiency for measuring quality of life in patients with SLE. However, SLEDAI scores were not associated with LupusQoL and SF36, suggesting that QoL in these patients might be affected by other factors beside the disease activity, such as anxiety and depression. <b>Disclosure of Interest</b>: None Declared
P661 APRI AND FIB-4 VS HISTOLOGY IN CHB PATIENTS IN TENOFOVIR DISOPROXIL FUMARATE (TDF) CLINICAL TRIALS
Authors: W.R. Kim, T. Berg, T. Asselah, R. Flisiak, S. Fung, S. Gordon, H.L.A. Janssen, P. Lampertico, D. Lau, J.D. Bornstein, R.A. Schall, P. Dinh, L.J. Yee, E.B. Martins, S.G. Lim, R. Loomba, J. Petersen, M. Buti, P. Marcellin
Journal: Journal of Hepatology (2014)
Abstract 1930: Early post-operative adoptive multiple-cellular immunotherapy in gastric cancer: A 3-year follow-up report
Authors: Yingxin Xu, Zhi Qiao, Zheng Peng, Shaoyou Xia, Li Li, Xin Wu, Yanjun Zhang, Ning Ning, Jie Li, Rong Li
Journal: Cancer Research (2010)

Abstract Objective Adoptive immunotherapy is an active approach, but efficacy is limited in the clinic for most solid tumor. We hypothesized that there are three factors might lead to improved clinical outcome in the patients with gastric cancer that include: 1) the combination of multiple immune cells, 2) more effector cells reaching at the site of the tumor by infusion in peritoneal cavity, 3) performing of immunotherapy as soon as possible after operation. Patients &amp; Methods 51 gastric cancer patients (stage III-IV 42/51) who underwent operation from September 2005 to March 2008 were retrospectively analyzed. Data were censored in 39 months (January 2009),Group A patients (n=22) received a course of immunotherapy which included autologous tumor lysate-pulsed dendritic cell (DC) via intradermic injection, cytokine induced killer cells (CIK) by iv, as well as DC-CIK by intraperitoneal injection in 11-14 days after operation, then a standard chemotherapy (18/22) and immunotherapy again. Group B patients (n=29) only received postoperative chemotherapy. Overall survival (OS) and disease-free survival (DFS) were calculated by the Kaplan-Meier method. Results In total, 24 patients died, giving a median survival time of 25 months. The estimated 2-year OS and DFS of group A were 63.6% and 67.3%, while that of group B were 25.2% and 33.2%, respectively. Both of the estimated 3-year OS and DFS were significantly superior in group A (log-rank test, P&amp;lt;0.01). Conclusions Early post-operative adoptive multiple-cellular immunotherapy with infusion in peritoneal cavity significantly improved overall survival and disease-free survival in gastric cancer patients. Key words gastric cancer; early; postoperative; adoptive cellular immunotherapy 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 1930.
Breast-Cancer Therapy — Looking Back to the Future
Authors: Anne Moore
Journal: New England Journal of Medicine (2007)

Adjuvant therapy for breast cancer — treatment after surgical removal of the tumor — is a major therapeutic advance that has had a considerable effect on prolonging disease-free and overall survival. Not all patients benefit from adjuvant therapy, however, and certain types of adjuvant therapy are not appropriate for some patients. For example, adjuvant treatment with tamoxifen, a selective estrogen-receptor modulator, has improved the 15-year survival rate among women with estrogen-receptor–positive breast cancer by 31%, but it does not benefit women with estrogen-receptor–negative disease.1 Trastuzumab, a monoclonal antibody against the human epidermal growth factor receptor type 2 (HER2), is associated . . .
Abstract 3129: XPC protein attenuation and deficiency in tobacco smoke-induced DNA hypermethylation of tumor suppressor genes
Authors: Gan Wang, Xiaoxin S. Xu, Le Wang
Journal: Cancer Research (2012)

Abstract DNA hypermethylation of tumor suppressor genes is a hallmark for many types of cancer, including lung cancer. The mechanism that leads to hypermethylation of these tumor suppressor genes in tumor cells is not fully understood. Importantly lung cancer is strongly associated with environmental factors, especially cigarette smoking. DNA damage generated by environmental carcinogens and their metabolites is believed to play an important role in lung cancer development. XPC is a DNA damage recognition protein required for nucleotide excision repair (NER) and many other DNA damage responses (e.g. checkpoint regulation and apoptosis). Attenuated levels of XPC protein have been detected in a majority of lung cancer patients. We studied the role of XPC protein attenuation and deficiency in cigarette smoke-caused DNA hypermethylation. Using primary human normal fibroblast (NF) and XPC-deficient human fibroblasts (XPC−), our DNA methylation studies revealed that the XPC deficiency caused greatly elevated levels of DNA hypermethylation in Brca1, Mlh1, and Xpc genes after exposure to tobacco smoke condensate (TSC). Our chromatin immunoprecipitation (ChIP) results indicated that the XPC deficiency led to a more increased binding of DNA methyltransferase 3A (DNMT3A) at the promoters of these genes following the TSC treatment; however, this binding was partially diminished when the XPC cells were treated with caffeine prior to the TSC treatment. The results of our IP studies further revealed that the ATR protein interacted with DNMT3A. In addition, our western blots revealed that the level of ATR protein phosphorylation at serine 428 was greatly increased in XPC cells after the TSC treatment. These results suggest that the XPC protein attenuation and deficiency may cause lung cancer as a result of tobacco smoking through activation of the ATR protein, which enhances the binding of DNMT3A at selected target sequences, resulting in hypermethylation of important tumor suppressor genes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3129. doi:1538-7445.AM2012-3129
Most Frequently Cited Cancer Journals
Authors: K. Nagy
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Most Frequently Cited Cancer Journals Get access Kate Nagy Kate Nagy Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 2, 19 January 1994, Page 89, https://doi.org/10.1093/jnci/86.2.89 Published: 19 January 1994
ADVERSE PARASYMPATHETIC REMODELING POST MYOCARDIAL INFARCTION AND ELECTRICAL STABILIZATION BY VAGAL NERVES STIMULATION
Authors: Marmar Vaseghi, William R. Woodward, Daigo Yagishita, Kentaro Yamakawa, Stephanie Midtling, Tadanobu Irie, Eileen L. So, Kalyanam Shivkumar
Journal: Journal of the American College of Cardiology (2015)