tbuckley/cabot-search huggingface dataset:
Abstract 4909: Olig2 phosphorylation by CDK2 implicated in glioma proliferation.
Authors: Jun Fu, Dimpy Koul, Siyuan Zheng, Vivek Singh, Jun Yao, Yanhua Zheng, Zhimin Lu, Erik P. Sulman, Frederick F. Lang, Alfred W.K Yung
Journal: Cancer Research (2013)

Abstract Oligodendrocyte transcription factor 2 (Olig2) is an important proneural transcription factor that regulates early development of the central nervous system and formation of glioma. Although recent studies established the role of developmentally regulated Olig2 phosphorylation in promoting the proliferation of both normal and malignant neural stem/progenitor cells, the molecular mechanisms by which Olig2 phosphorylation is regulated and functions as a pro-proliferative factor are not completely understood. Here we identified Olig2 as a critical phosphorylation target for cyclin-dependent kinase 2 (CDK2). CDK2 stabilizes and activates Olig2, thereby regulating G1-to-S phase progression by repressing the expression of Cyclin-dependent kinase inhibitor p27kip1. After phosphorylation by CDK2, Olig2 exerts pro-proliferative effects that are reflected in normal neural/glioma stem cells and in murine xenograft models of glioma. Olig2 phosphorylation regulates its binding to E-box sequence in p27 gene promoter and represses p27 expression. We show that constitutive p27 expression antagonizes CDK2-mediated Olig2 phosphorylation and attenuates cell proliferation both in in-vitro and in-vivo glioma models. Expression analysis of TCGA GBM samples also showed that high Olig2 expression is always accompanied with high CDK2 expression in the proneural, classical, and neural subclasses, which could provide a convincing evidence to use a CDK2 inhibitor to treat Olig2-high gliomas. Treatment with CDK2 inhibitor preferentially suppresses proliferation of Olig2-high glioma cells. Thus, we conclude that a CDK2 inhibitor could be of great therapeutic value in patients with Olig2-high glioma and Olig2 might be used as a biological marker for CDK2 inhibitors in the future studies. Citation Format: Jun Fu, Dimpy Koul, Siyuan Zheng, Vivek Singh, Jun Yao, Yanhua Zheng, Zhimin Lu, Erik P. Sulman, Frederick F. Lang, Alfred W.K Yung. Olig2 phosphorylation by CDK2 implicated in glioma proliferation. [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 4909. doi:10.1158/1538-7445.AM2013-4909
Initial experience of glove port technique in single incision laparoscopic cholecystectomy using conventional laparoscopic instruments
Authors: AM Abdelaziz Hassan, M Mahmoud, AH Helmy
Journal: Endoscopy (2012)

Introduction: Single-incision laparoscopic surgery is an attractive approach for cholecystectomy. However, its widespread application has many limitations. A significant obstacle of application in developing countries is the expensive and non-affordable specialized single port systems and roticulating instruments.
Be Aware of Disseminated Sarcoidosis With Diffuse Subcutaneous Nodules on F-18 FDG PET
Authors: Poyan Rafiei, Vani Vijayakumar
Journal: Clinical Nuclear Medicine (2011)

Sarcoidosis is a multisystem granulomatous disorder of unknown etiology that typically affects young adults. Definitive diagnosis requires compatible clinical and radiologic manifestations and histopathologic detection of noncaseating granulomas. In recent years, F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has been proposed to play a role in the diagnosis and management of sarcoidosis. Although disseminated sarcoidosis has been reported in nearly all organs including the skin, subcutaneous sarcoidosis is relatively rare with few reports using F-18 FDG PET. We report a case of disseminated sarcoidosis with diffuse subcutaneous nodules demonstrating avid F-18 FDG uptake on PET.
Abstract 4027: Myc controls mRNA stability through the agency of AU-binding proteins to promote lymphomagenesis
Authors: Robert J. Rounbehler, Mohammad Fallahi, Meredith A. Steeves, Weimin Li, Chunying Yang, Joanne R. Doherty, John L. Cleveland
Journal: Cancer Research (2011)

Abstract Myc oncoproteins regulate transcription by binding to target genes harboring E-boxes or Initiator elements, yet these responses explain only a fraction of the genes Myc affects. mRNA turnover is controlled via binding of AU-binding proteins (AUBPs) to AU-rich elements (AREs) found within many transcripts. Expression analyses of precancerous and malignant Myc-expressing B cells revealed Myc regulates hundreds of ARE-containing genes and several AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP), an mRNA-destabilizing AUBP, and TTP suppression is a hallmark of Myc-driven lymphoma in mice and man. Furthermore, TTP has profound effects on tumorigenesis, where restoring TTP impairs Myc-induced lymphoma development and abolishes maintenance of the malignant state; thus, TTP functions as a tumor suppressor. Finally, the Myc-to-TTP pathway regulates a very select cast of ARE-containing genes that control cell proliferation and transformation. Thus, Myc utilizes AUBPs to target ARE-containing genes in its efforts to control cell fate and transformation. 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 4027. doi:10.1158/1538-7445.AM2011-4027
Abstract P5-14-05: Improved Survival of Patients with Primary Distant Metastatic Breast Cancer in the Period of 1995 — 2007
Authors: J Ruiterkamp, MF Ernst, L de Munck, der Loo M van der Heiden-van, E Bastiaannet, LV van de Poll-Franse, K Bosscha, VCG Tjan-Heijnen, AC. Voogd
Journal: Cancer Research (2010)

Abstract Introduction During the last fifteen years, important changes have taken place concerning the sy stemic treatment for patients with metastasized breast cancer. It would be interesting to know whether these improvements have also taken place patients with primary distant metastatic breast cancer. Additionally, several retrospective studies have shown an improvement in overall survival in patients who have received breast surgery. Therefore, we also analyzed the role of surgical resection of the primary breast tumor. Methods According to the database of the Dutch Cancer Registry 7,358 (5.0%) patients were diagnosed with primary distant metastases between 1997 and 2007. To establish whether improvement of prognosis had taken place, patients were divided into three periods of diagnosis, based on the year of diagnosis of their disease; 1995-1999, 2000-2003 and 2004-2007. The follow-up of these patients was completed until January 1, 2009. Results The median survival was 1.42 years for patients diagnosed in the period 1995-1999, 1.56 years in the period 2000-2003 and 2.0 years in the period 2004-2007. Only the difference between the periods 2000-2003 and 2004-2007 was statistically significant (P&amp;lt;0.0001). When analyzed according to age group, the improvement of the median survival was most pronounced for patients of 50 years or younger, with an increase of 2.18 to 3.01 years (P&amp;lt;0.0002). The median survival of the patients undergoing surgery was 2.5 years, compared to 1.3 years for the patients without surgical treatment of the primary tumor. Nevertheless, the proportion of patients who underwent a resection of the breast tumor decreased from 31% in the period 1995-1999 to 24% in the last period. In the multivariable analysis, the hazard ratio's (HRs) for mortality in the second and third period as compared to the first period were 0.95 (P=0.13) and 0.86 (P&amp;lt;0.0001), respectively. Older age and larger tumor size were associated with a higher mortality risk. Patients receiving systemic treatment (HR 0.36), locoregional radiotherapy (HR 0.79) or breast surgery (HR 0.65) had a significantly lower risk of death compared to the patients not receiving these treatments. Conclusion An improvement of six months is seen in the median survival of patients with primary distant metastatic breast cancer, resulting in a median survival of two years in 2007. Maybe, if surgery was more performed in the most recent time period, the improvement of the median survival was even better. However, it seems reasonable to argue that this improvement is due to new developments in systemic treatment. Figures available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-14-05.
THU0307 Pulmonary Arterial Hypertension &amp; Systemic Lupus Erythematosus: Clinical Profile
Authors: C. O. Ciang, M. H. Leung
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> A retrospective case-control study to estimate prevalence of pulmonary arterial hypertension (PAH) in systemic lupus erythematosus (SLE) and to study the associated clinical variables. <h3>Methods</h3> Clinical records of SLE patients followed up from 2006 to 2011 were retrieved. PAH was diagnosed by echocardiogram (systolic pulmonary artery pressure ≧ 40 mmHg)(1) or cardiac catheterization (mean pulmonary artery pressure ≧ 25 mmHg)(2). Controls were randomly selected from SLE patients with echocardiogram showing no PAH. PAH case: control ratio is 1:2 matching for age and gender. Clinical and serologic profiles were analyzed. <h3>Results</h3> Thirty nine PAH patients were identified, the prevalence was 10.1%. The mean onset of PAH was 7.5 ± 8.3 (mean ± SD) years after SLE diagnosis. Compared with controls, significantly more PAH patientss had pericardial effusion (43.6 vs 15.9%), pleural effusion (43.6 vs 13%), psychosis (12.8 vs 1.4%), interstitial lung disease (25.6 vs 8.7%), hemolytic anemia (38.5 vs 14.5%), lower hemoglobin at presentation (10.5 ± 2.5 vs 11.8 ± 2.0 g/dL), higher anti- ds DNA at presentation (242.8 ± 204.1 vs 166.0 ± 121.6 IU/ml), proteinuria of more than 0.5g /day (76.9 vs 53.6%), worse serum creatinine at end of study (180.7 ± 236.6 vs 105.2 ± 98.8 umol/L), anti RNP positivity (57.9 vs 27.5%), higher SLEDAI (median of 4.0 vs 2.0) and SLICC(median of 2.0 vs 1.0). Significantly fewer PAH patients had malar rash (46.2 vs 79.7%) and photosensitivity (7.7 vs 39.1%). Clinical pattern of anti RNP positivity with negative malar rash gave odds ratio of 5.60 for PAH. These two variables remained significant after multiple logistic regression. PAH group had higher right ventricular systolic pressure (RVSP) than controls in echocardiogram, with mean RVSP of 51.7 ± 15.4 mmHg vs 25.3 ± 5.2 mmHg (p &lt;0.001). In PAH group, deceased patients had higher RVSP than surviving patients (60.4 ± 8.9 mmHg vs 50.4 ± 15.9 mmHg with p = 0.034). There was no significant difference in RVSP among those who were symptomatic of PAH and those who were asymptomatic (p = 0.195) <h3>Conclusions</h3> Clinical association of PAH with anti RNP positivity and absence of malar rash was noted. Awareness of factors associated with PAH in SLE aids early recognition and prompt treatment. <h3>References</h3> Galiè N, Hoeper MM, Humbert M, et al. ESC Committee for Practice Guidelines. Guidelines for the diagnosis and treatment of pulmonary hypertension. <i>Eur Heart J.</i> 2009 Oct;30(20):2493-537 Hoeper MM, Lee SH, Voswinckel R, et al. Complications of right heart catheterization procedures in patients with pulmonary hypertension in experienced centers. <i>J Am Coll Cardiol</i> 2006;48:2546–2552 <h3>Disclosure of Interest</h3> None Declared
CORRELATION OF I-131 NECK-CHEST SCANS WITH RADIOIODINE UPTAKES IN PATIENTS WITH DIFFERENTIATED THYROID CANCER (DTC): IS THERE A CORRELATION?
Authors: Lalitha Ramanna, Alan Waxman, Geoffrey Binney, Dennis Chapman, Michael Brachman
Journal: Clinical Nuclear Medicine (1987)

Ramanna, Lalitha; Waxman, Alan; Binney, Geoffrey; Chapman, Dennis; Brachman, Michael Author Information
Myocardial Infarction in Nine Patients with Radiologically Patent Coronary Arteries
Authors: A. Hafeez Khan, L. Julian Haywood
Journal: New England Journal of Medicine (1974)

Myocardial infarction with normal or near normal coronary arteries on cineangiography and without any other type of heart disease was found in nine (12 per cent) of a series of 78 consecutively studied patients. This combination occurred predominantly in young male patients, and its clinical, laboratory and electrocardiographic features, and its initial course were similar to those of acute myocardial infarction with coronary-artery disease. Multiple risk factors were present in only two patients. Hemodynamic findings were normal or near normal in seven. Areas of localized dyskinesia or hypokinesia were demonstrated in six on left ventricular cineangiography. The long-term clinical course has been benign; in no patient has congestive heart failure, major arrhythmias or recurrence of acute myocardial Infarction developed. It is possible that prolonged, localized coronary-artery spasm or platelet thrombi that subsequently resolved are a part of the pathogenic mechanism. (N Engl J Med 291:427–431, 1974)
Trends in Death from Lung and Breast Cancer Among American Women *
Authors: Brenda K. Edwards
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Trends in Death from Lung and Breast Cancer Among American Women Get access Brenda K. Edwards Brenda K. Edwards Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 5, 6 March 1991, Page 318, https://doi.org/10.1093/jnci/83.5.318 Published: 06 March 1991
OP0239 Systemic Sclerosis: A Pathological Model Linking Oxidative Stress, DNA Damage and Fibrosis
Authors: T. Spadoni, S. Svegliati, M. Vinciguerra, E. Avvedimento, A. Gabrielli
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Fibroblasts isolated from lesional areas of Systemic Sclerosis (SSc) patients overproduce reactive oxygen species (ROS), overexpress type I collagen and a-smooth muscle actin (a-SMA) and show chromosomal aberrations (1, 2). Recent studies have demonstrated a prominent role for ATM pathway in fibrosis (3). ATM (ataxia telangiectasia mutated) is regarded as the major regulator of the cellular response to DNA damage, in particular to DNA double strand breaks (DSBs). In response to DSBs, ATM undergoes catalytic activation and phosphorylates intermediary protein substrates, such as CHK2, p53 and H2AX, leading to cell cycle arrest and DNA repair or apoptosis. Moreover, ATM has also been implicated in the regulation of oxidative stress, and its effects in this pathway were recently shown to modulate cytoplasmatic pathways (4). <h3>Objectives</h3> The aim of this study was to demonstrate a possible correlation between ROS induced-DNA damage and fibrosis in SSc. <h3>Methods</h3> Fibroblasts were isolated from skin biopsies of SSc patients or healthy volunteers. AT fibroblasts were obtained from Coriell Institute. Cells were transiently transfected with specific siRNA against ATM with Lipofectamine (Invitrogen). Total RNA was isolated, reverse-transcribed, and quantitative real-time PCR reactions were performed using SYBR-Green Master Mix. To analyzed protein expression, cells were lysed and subjected to western blot with specific antibodies. For immunocytochemistry, cells were fixed in PFA, permeabilized and labelled with specific antibodies to be evaluated through fluorescence microscopy. <h3>Results</h3> SSc fibroblasts show higher levels of activated ATM compared to normal cells. Normal fibroblasts stimulated by bleomycin shift to a SSc like-phenotype with high levels of ROS, overexpression of type I collagen and phosphorylation of ATM. Incubation of SSc fibroblasts or activated normal fibroblasts with a synthetic inhibitor of ATM (KU55933) or trasfection with specific siRNA against ATM lead to downregulation of ROS production and type I collagen expression. AT fibroblasts, lacking of functional ATM, show no changes in type I collagen transcript abundance after bleomycin tretament. <h3>Conclusions</h3> DNA damage leads to changes in gene-profiles, and also in protein synthesis, degradation and trafficking. Our data suggest an important link between DNA damage induced by ROS and overexpression of type I collagen in SSc fibroblasts. Modulation of ROS levels and ATM activation may provide novel therapeutic targets to prevent fibrosis, key feature of Systemic Sclerosis. <h3>References</h3> Sambo P, Arhtritis Rheum 2001; 44: 2653-2664. Baroni S, N Engl J Med 2006; 354:2667-76. Daugherity EK, Cell Cycle 2012; 11: 1918-1928. Shiloh Y, Nature Reviews 2013; 14: 197-210. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2836
Abstract 1476: Mesenchymal stromal cells induce epithelial-to-mesenchymal transition in human colorectal cancer cells through the expression of surface-bound TGF-β.
Authors: Valentina Mele, Manuele Giuseppe Muraro, Diego Calabrese, Nunzia Amatruda, Francesca Amicarella, Dennis Pfaff, Brynn Kvinlaug, Chiara Bocelli-Tyndall, Ivan Martin, Therese J. Resink, Luigi M. Terracciano, Giulio Cesare Spagnoli, Giandomenica Iezzi
Journal: Cancer Research (2013)

Abstract Mesenchymal stem/stromal cells (MSC) are multipotent precursors endowed with the ability to home to primary and metastatic tumor site. Because of this feature, they are currently being used in preclinical models and in clinical trials as potential vehicles for delivery of targeted anti-cancer therapies. Clinical applications of MSC however, require a deeper understanding of their biology and, in particular, of their interaction with cancer cells. In this study we have investigated the effects mediated by human bone marrow-derived MSC on human colorectal cancer (CRC) cells in vitro and in vivo. We found that MSC induced upregulation of epithelial-to-mesenchymal (EMT)-related genes and downregulation of E-cadherin in tumor cells. These effects required cell-to-cell contact and were mediated by expression of surface-bound TGF-β, induced in MSC upon coculture with tumor cells. CRC cells exposed to MSC formed larger tumor masses in vivo, characterized by higher vessel density and increased mesenchymal marker expression, and displayed enhanced invasive capacity. Thus, by promoting cell expansion, EMT-related phenomena and tumor angiogenesis, MSC appear to favor the acquisition of an aggressive phenotype by CRC cells. These findings raise concerns regarding the safety of MSC administration for clinical purposes in patients with cancer. Citation Format: Valentina Mele, Manuele Giuseppe Muraro, Diego Calabrese, Nunzia Amatruda, Francesca Amicarella, Dennis Pfaff, Brynn Kvinlaug, Chiara Bocelli-Tyndall, Ivan Martin, Therese J. Resink, Luigi M. Terracciano, Giulio Cesare Spagnoli, Giandomenica Iezzi. Mesenchymal stromal cells induce epithelial-to-mesenchymal transition in human colorectal cancer cells through the expression of surface-bound TGF-β. [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 1476. doi:10.1158/1538-7445.AM2013-1476
Ehrlichiosis in a Golf-Oriented Retirement Community
Authors: Steven M. Standaert, Jacqueline E. Dawson, William Schaffner, James E. Childs, Kristine L. Biggie, Joseph Singleton, Reid R. Gerhardt, Marilyn L. Knight, Robert H. Hutcheson
Journal: New England Journal of Medicine (1995)

Ehrlichiosis due to Ehrlichia chaffeensis usually occurs sporadically or in small clusters, with an annual incidence estimated at 3 to 5 cases per 100,000 population in areas of endemic disease. The putative principal vector is the Lone Star tick (Amblyomma americanum). We investigated an outbreak of ehrlichiosis that occurred in June 1993 among members of a golf-oriented retirement community (community A) in Tennessee. The community is densely wooded and borders a wildlife-management area where deer are numerous.We conducted a case-control study, using medical-history reviews, serologic testing, and testing with the polymerase chain reaction for E. chaffeensis infection. We also surveyed a sample of 10 percent of the households in community A and in another golf-oriented community (community B) more than 20 miles (32 km) from the wildlife-management area. Survey participants completed a questionnaire and provided specimens for serologic testing. In both communities, searches for ticks were undertaken.Eleven cases of symptomatic ehrlichiosis were identified in the case-control study, 10 of which were in community A (attack rate, 330 per 100,000). Of 311 surveyed residents of community A, 12.5 percent had serologic evidence of past E. chaffeensis infection, as compared with 3.3 percent of 92 in community B (relative risk in community A as compared with community B, 3.9; 95 percent confidence interval, 1.2 to 12.2). The risk of infection was associated with tick bites, exposure to wildlife, golfing, and among golfers, retrieving lost golf balls from the rough. Persons who never used insect repellent were more likely to have had infection than persons who did. In community A, thousands of Lone Star ticks were found; in community B, only three ticks were found.The high rate of E. chaffeensis infection in community A resulted from its proximity to a wildlife reserve. When outdoor recreational activities are common and concentrations of ticks are high, outbreaks of arthropod-borne zoonoses can be anticipated.
Abstract 4481: Vitamin D pathway gene variants associated with vitamin D deficiency in African Americans
Authors: Ken Batai, Ebony Shah, Maria Ruden, Jennifer Newsome, Adam Murphy, Rick A. Kittles
Journal: Cancer Research (2012)

Abstract Background: Cancer incidence and mortality rate is disproportionate among the racial/ethnic groups in the U.S. and higher in African Americans (AAs) due to a combination of genes and environmental factors. The difference in serum vitamin D3, 25(OH)D, concentration among racial groups is suspected to be one of the sources of cancer health disparities. Vitamin D has protective effects against several types of cancer, and vitamin D deficiency is more common among AAs than the European Americans (EAs). Genome-Wide Association Studies (GWAS) among EAs found vitamin D pathway gene (VDPG) variants associated with serum 25(OH)D level, but association between VDPG variants and serum 25(OH)D level has not examined in AAs. Here, we tested if thirty-nine VDPG variants are associated with serum 25(OH)D concentration. Samples and Methods: Nineteen variants in GC, VDR, CYP3A4, CYP2R1, and CYP24A1 were genotyped in a total of 462 AAs from Washington, D.C. and Chicago area. Twenty GWAS identified VDPG variants were genotyped in a subset of subjects (n=332). West Africa Ancestry (WAA) was estimated using STRUCTRE from 105 ancestry informative markers typed. Then, we tested for association adjusting for WAA, age, and skin color. Results: Eight GWAS identified SNPs (five in GC, one in CYP2R1, and two in DHCR7/NADSYN1) were associated with serum 25(OH)D levels and/or vitamin D deficiency. Among darker-skinned AAs, the VDR SNP rs11568820 (Cdx2), was significantly associated (P&amp;lt;0.05) with the risk of vitamin D deficiency (&amp;lt;20 ng/ml) (OR=1.94; CI 1.11-3.38). Conclusion: We found VDPG variants associated with serum 25(OH)D level and/or vitamin D deficiency in AAs. We also replicated the findings from a previous GWAS in EAs and found that the same variants were associated with serum 25(OH)D in AAs. Additional studies are necessary to assess whether these variants are associated with cancer risk. Impact: Increased attention is focused on the role of vitamin D in cancer risk. Our findings provide insights on the biological and environmental modifiers of serum vitamin D3 and will help guide future studies on the role of vitamin D in cancer in high risk populations such as AAs. 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 4481. doi:1538-7445.AM2012-4481