tbuckley/cabot-search huggingface dataset:
Abstract 3133: Regulatory sequences of the ATP-Binding Cassette Transporter A1 gene are hypermethylated in prostate cancer resulting in loss of gene expression
Authors: Byron H. Lee, Peggy Robinet, Jonathan Smith, Cristina Magi-Galluzzi, Eric A. Klein, Angela H. Ting
Journal: Cancer Research (2012)

Abstract Introduction/Objective: Cholesterol homeostasis is altered in prostate cancer resulting in increased levels of cholesteryl esters and free cholesterol, but the mechanism behind these perturbations is not complete understood. We examine the role of DNA methylation in the regulation of ABCA1 expression. Methods: Genome wide methylation analysis using MBD-isolated Genome Sequencing (MiGS) was performed on the normal prostate epithelial cell line PrEC, the prostate cancer cell lines LNCaP and DU 145, 3 benign prostate specimens obtained from radical cystoprostatectomy, and 6 prostate cancer specimens obtained from radical prostatectomy. Bisulfite genomic sequencing was performed on the ABCA1 CpG island in PrEC and LNCaP to verify the methylation patterns discovered by MiGS. Real time RT-PCR was performed to assess ABCA1 mRNA levels in PrEC and LNCaP. LNCaP was treated with 5-aza-2′-deoxycytidine (5-aza), the LXR agonist T0901317, or a combination of the two drugs; and ABCA1 CpG island methylation was assessed by methylation-specific PCR (MSP) and gene expression was assessed by real time RT-PCR. Results: MiGS analysis revealed that ABCA1 CpG island methylation was present in LNCaP and 6 prostate cancer specimens but not PrEC, DU 145, or 3 benign prostate specimens. Bisulfite genomic sequencing primers were used to amplify fragments from the CpG island spanning −404 to +1,301 of the ABCA1 gene. LNCaP showed dense methylation in the entire region while PrEC showed only minimal methylation from −236 to −404. Real time RT-PCR revealed that there was 10-fold more ABCA1 mRNA in PrEC when compared with LNCaP. Treatment of LNCaP with 10µM T0901317 for 24 hours increased ABCA1 mRNA to 14 fold above untreated LNCaP without detectable changes in DNA methylation. Treatment with 5µM 5-aza for 1 week increased ABCA1 mRNA to 50 fold above control and resulted in loss of DNA methylation in the ABCA1 CpG island as detected by MSP. The combination of 5µM 5-aza and 10µM T0901317 increased ABCA1 mRNA expression in LNCaP to 320 fold above control. Conclusions: ABCA1 is hypermethylated in a subset of prostate cancers, but not normal prostate, resulting in loss of gene expression. Therapeutic strategies aimed at reducing intracellular cholesterol content solely by inhibiting HMG-CoA reductase may be hindered by this acquired deficiency in cholesterol export. 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 3133. doi:1538-7445.AM2012-3133
P2-02-10: Differential Targeting of the RB-Pathway To Expand the Therapeutic Index in the Treatment of Triple Negative Breast Cancer.
Authors: ES Knudsen, J Dean, C Thangavel, A Ertel, AK Witkiewicz, AK McClendon
Journal: Cancer Research (2011)

Abstract Background: The retinoblastoma tumor suppressor (RB) is inactivated in a significant fraction of triple negative breast cancers (TNBC). RB loss is believed to contribute to tumor initiation and progression, and provocative data suggest that RB loss is associated with improved response to cytotoxic chemotherapy. Unfortunately, such therapies have significant side effects that impinge on patient quality of life. Here we explored the ability to specifically target RB loss in TNBC to expand the therapeutic index by protecting against undesired side-effects of chemotherapy. Experimental Design: A combination of cell culture and xenograft models of triple negative breast cancer were used to evaluate how RB-status impinges on sensitivity to chemotherapy. These models were complemented by the analyses of clinical specimens from patients treated with chemotherapy. Parallel use of agents that activate RB function with high specificity were interrogated as potential tissue protectors to ameliorate side effect of chemotherapy. Results: RB loss in preclinical models is associated with increased sensitivity to conventional cytotoxic chemotherapies that are frequently employed in the treatment of TNBC. The findings were recapitulated through the analyses of clinical specimens, and suggest that the loss of RB could be particularly useful in defining TNBC patients with improved response to chemotherapy. Combination studies of pharmacological activation of the RB pathway and cytotoxic chemotherapies commonly used to treat TNBC demonstrated that activation of RB can modulate the efficacy of cytotoxic compounds in the treatment of TNBC. Importantly, functional studies indicated that RB pathway activation limits cardiotoxicity associated with anthracycline based treatments and correspondingly improve cardiac function in animal studies. Conclusions: Combined, these studies indicate that RB pathway status could be utilized in the clinic to direct combination treatments that would exploit the sensitivity of RB-deficient tumors to cytotoxic chemotherapies while simultaneously providing protection for normal tissues. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-02-10.
AB0020 Vascular endothelial growth factor gene polymorphism in patients with rheumatoid arthritis
Authors: M. Korolev, V. Konenkov, V. Prokofyev, A. Shevchenko, E. Zonova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Vascular endothelial growth factor (VEGF) have recently reported to be expressed in human rheumatoid arthritis (RA), suggesting that VEGF could be implicated in the pathogenesis of this disease. <h3>Objectives</h3> The aim of this study was to investigate the frequency of occurrence of certain alleles and genotypes of VEGF gene among Caucasoid RA patients living for a long time in the Siberian region of Russia, in comparison with a group of healthy individuals. <h3>Methods</h3> A total of 509 Russian individuals were enrolled in this study, including 135 patients with RA satisfied (ACR, 1987) criteria and 374 healthy controls. Eight different polymorphisms of the VEGF gene and pro- and anti-inflammatory cytokines genes were analyzed using method of restriction analysis of amplified products (PCR-RLFP) with matching restrictases (VEGF -2578 A/C – BlgII, TNFA C-863A - Bst BAI, TNFA G-308A - Bsp19 I, TNFA G-238A - Msp I, IL-1B T-31C - Alu I, IL-4 C-590T - Bme 18 I, IL-6 G-174C - SfaN I, IL-10 C-592A - RsaI). <h3>Results</h3> The resulting study data suggest that the combination of genotypes of VEGF gene polymorphism in the promoter region at -2578 A/C genotypes with genes IL1B -311C/T, IL4 -590 C/T, IL10 -592 A/C, IL6 -174 G/C and TNFA gene may be genetic factors that allow population to discriminate against women in Russian Caucasoid descent into groups with high risk of developing RA and with a certain level of constitutive resistance to its development. <h3>Conclusions</h3> Our conclusion indicates the need for a comprehensive study of the role of the growth factors family with proangiogenic and proinflammatory activity in the pathogenesis of RA. <h3>Disclosure of Interest</h3> None Declared
P2-11-07: Expression of Selected Predictive Markers in African American Women with Atypical Hyperplasia of the Breast.
Authors: S Bandyopadhyay, M Cote, DW Visscher, J Ruterbusch, B Albashiti, B Alosh, MH Frost, LC Hartmann, RA Fehmi
Journal: Cancer Research (2011)

Abstract Invasive breast carcinoma in African American (AA) women differs significantly from their Caucasian (CA) counterparts in its incidence, morphology and outcome. These tumors are more likely to be high grade, hormone receptor negative, present at a younger age and at a higher stage. Evaluation and a better understanding of precursor lesions may help delineate the mechanisms underlying the development of breast cancer in these two groups. Atypical hyperplasia (AH) in the breast has been associated with an increased risk of developing cancer (relative risk∼4.0). Risk stratification of these women by identification of predictive biomarkers would be beneficial for optimal patient care. In our study we evaluated the expression of the following prognostic biomarkers: estrogen receptor (ER), Cyclooxygenase-2 (COX-2) enzyme and Ki-67 in AH in a cohort of AA women with benign breast biopsies. AA women with benign breast biopsies from years 1997–2000 were retrieved from our departmental database. Clinical and follow up data was obtained from the SEER database. The hematoxylin and eosin (H &amp; E) slides for these cases were reviewed by 2 pathologists, who were blinded to the outcome, and those with atypia were included in this study. Paraffin blocks were retrieved for immunohistochemical (IHC) analysis and standardized scoring methods applied. A total of 1608 AA women had benign breast biopsies during the study period. We performed IHC analysis on 37 (2.3%) who were diagnosed with atypia (25 cases of atypical ductal hyperplasia (ADH) and 12 cases of atypical lobular hyperplasia (ALH)). Increased COX-2 expression was seen in 19 of 28 (67.8%) cases with AH. Of these, 13 of 19 cases (68.4%) were of ADH and 6 of 9 cases (66.7%) were of ALH. Twenty of 25 cases had a high expression of ER overall. Of these, 15 of17 (88.2%) of the positive cases was in the ADH category and 3 of 7 (42.8%) was in the ALH group. Of 32 cases, only 3 cases showed a proliferation rate of &amp;gt; 2% (9.4%) with Ki-67 IHC stain. All of these cases belonged to the ADH (21) category. In summary, the majority of AH cases showed increased COX-2 expression, although no differences were observed between lobular and ductal lesions. In contrast, ADH lesions appeared to exhibit increased reactivity for ER compared to ALH. Similarly, although rare, more ADH cases showed an increased proliferation rate compared to ALH. From our data, COX-2 and ER might be of prognostic significance in AA patients with AH. Larger studies with follow up are needed to understand this disease further. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-11-07.
Acute Renal Failure of Glomerular Origin during Visceral Abscesses
Authors: Michel Beaufils, Liliane Morel-Maroger, Jean-Daniel Sraer, Alain Kanfer, Olivier Kourilsky, Gabriel Richet
Journal: New England Journal of Medicine (1976)

We studied 11 patients who had visceral abscesses and in whom acute renal failure developed. All renal biopsies showed a diffuse proliferative and crescentic glomerulonephritis. In seven patients blood cultures were repeatedly negative. Endocarditis could be ruled out in six patients. Seven patients had circulating cryoglobulins; serum complement levels were normal in seven and decreased in four; circulating immune complexes were found in the three patients studied. The evolution of the glomerulonephritis, documented by serial biopsies, closely paralleled the course of the infection. A complete recovery of renal function occurred in four cases in which a rapid and complete cure of the infection was obtained. Of five patients in whom the infection was not cured, four died, and chronic renal failure developed in one. In two patients in whom therapy was delayed, chronic renal failure also developed. Deep suppuration, even in the absence of bacteremia, may be responsible for a severe but possibly reversible glomerulonephritis with circulating immune complexes. (N Engl J Med 295:185–189, 1976)
Abstract 3318: Phenotypic heterogeneity and instability of tumor-initiating cells in high-grade serous cancer
Authors: Jocelyn M. Stewart, Patricia A. Shaw, Marcus Q. Bernardini, Laurie E. Ailles, Benjamin G. Neel
Journal: Cancer Research (2012)

Abstract Serous ovarian cancer (SOC) is the leading cause of morbidity/mortality from gynecologic malignancy. Current therapies significantly increase survival, yet 70-90% of SOC patients recur within five years and die of their disease. The cancer stem cell (CSC) hypothesis holds that only some tumor cells have the potential to initiate and maintain tumors. Moreover, CSC might be resistant to many therapeutic agents that are effective against bulk tumor cells, which could contribute to treatment failure. We have established a large collection of primary human SOC samples and developed a robust, quantitative assay for SOC tumor-initiating cells (TIC). Using this assay, we found that TIC from primary SOC can be identified based on their expression of the surface marker CD133. However, we also observed heterogeneity and instability of the TIC phenotype with disease progression. We examined whether instability in the TIC phenotype may be due to the acquisition of additional genetic alterations in the CD133- compared to the CD133+ fraction. Preliminary analysis suggests that most genetic alterations are common in both fractions; however, in 3/6 cases, additional genetic alterations were observed in the CD133- fraction, suggesting the emergence of CD133- TIC might be, at least in part, genetically driven. The mechanism of genetic instability is currently under investigation. In addition, we have used expression microarrays to examine differences between CD133+ and CD133- populations. We find that &amp;gt;1000 probes are differentially expressed in these two groups. We have identified several pathways with altered expression in TIC-enriched fractions. The biological role of these pathways in HG-SOC is under investigation. Our ability to identify and characterize TIC in this disease may facilitate development of new and more effective therapeutic strategies for ovarian cancer, thereby benefitting patients with this devastating disease. 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 3318. doi:1538-7445.AM2012-3318
Conscious Sedation for Minor Procedures in Adults
Authors: Jean-Pierre Tourtier, Yves Diraison, Yves Auroy
Journal: New England Journal of Medicine (2011)

To the Editor: In their online video, Jones and colleagues (June 23 issue)1 describe conscious sedation in adults. According to the recommendations of the American Society of Anesthesiologists, the authors propose to discriminate conscious sedation from minimal and deep sedation on the basis of the response to verbal commands or painful stimulation.2 The crucial problem with conscious sedation is to ensure sedation without respiratory depression. In real-life experience, during conscious sedation, respiratory signs are correlated with changes in the patient's eyes. To illustrate, changes in both respiration and eye movement are the keystones of Guedel's stages in anesthesia.3 Today, the . . .
Abstract 1270: Metabolic alterations impair breast cancer cell viability following detachment from the extracellular matrix
Authors: Zachary T. Schafer
Journal: Cancer Research (2011)

Abstract The ability of cancer cells to survive in the absence of normal matrix is critical for tumor progression and metastasis. Normal (non-tumorigenic) cells that lose attachment to extracellular matrix (ECM) undergo caspase-dependent death (known as anoikis), a phenomenon that is frequently defective in cancer cells. However, recent findings reveal that inhibition of anoikis is not sufficient to allow for cell survival in abnormal matrix environments. We have recently discovered that breast cancer cells must rectify detachment-induced metabolic alterations in order to survive in the absence of ECM attachment. Using MCF-10A cells, we have discovered that cells that are detached from the ECM exhibit a decrease in ATP levels and glucose uptake that is independent of the anoikis program. Interestingly, the treatment of detached cells with antioxidants is sufficient to elevate ATP levels without affecting glucose uptake, suggesting that ROS contribute to the reduction of ATP levels in detached cells. In addition, overexpression of ErbB2 induces a striking rescue of detachment-induced ATP/glucose uptake deficiencies while lowering cellular ROS levels. We found that pentose phosphate pathway (PPP) generated NADPH is essential for ErbB2 to elevate ATP levels and reduce cellular ROS in detached cells. Furthermore, we have discovered that eliminating cellular ROS on its own is sufficient to enhance the viability of matrix-deprived cells. Using a 3-dimensional cell culture system (in which luminal cells lack ECM contact), we have found that antioxidant treatment promotes the filling of the luminal space. We have now expanded on these studies and found a role for these detachment-induced metabolic alterations in inflammatory breast cancer cells and have discovered an Akt-independent signaling pathway downstream of oncogenic Ras that also promotes detachment-induced viability. Our current studies are also focused on understanding the role of ROS in regulating ATP generation by fatty acid oxidation. Furthermore, we are examining the role of the tumor microenvironment in the regulation of caspase activation and metabolism in detached epithelial cells. These studies could lead to the identification of novel molecular mechanisms that could be targeted for the selective elimination of ECM-detached cancerous cells. 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 1270. doi:10.1158/1538-7445.AM2011-1270
Isolated Rupture of the Right Hemidiaphragm With Eventration of the Liver Demonstrated by Liver Scan
Authors: TON-HO YOUNG, YOU-CHEN CHAO, HUNG-SHANG TANG
Journal: Clinical Nuclear Medicine (1998)

A case of isolated rupture of the right hemidiaphragm secondary to blunt abdominal trauma with hepatic herniation into the right thorax is described. Early diagnosis was established by a liver scan obtained in the acute stage of injury. Primary repair was followed by uneventful recovery. This case indicates that liver imaging is a very helpful method in the early diagnosis of traumatic diaphragmatic hernia as well as in hepatic injury.
PTU-194 Does metabolic syndrome impact tumour pathology in oesophageal adenocarcinoma?
Authors: L A Healy, J Howard, J V Reynolds
Journal: Gut (2012)

<h3>Introduction</h3> Obesity is an established risk factor for both the increased incidence of oesophageal adenocarcinoma cancer (OAC), and adverse outcomes by increasing risk of recurrence and reducing survival in obese patients post oesophagectomy. The exact mechanism of this relationship is unclear but the pattern of fat distribution pattern is likely important. Abdominal obesity more closely reflects an increased visceral fat area and is associated with alterations in metabolic risk profile. The clustering of central obesity, hypertension, and raised plasma glucose, triglycerides and HDL cholesterol is also known as the metabolic syndrome (MetS). The processes underling the metabolic syndrome especially insulin resistance and increased leptin, can provide a favourable growth environment for malignant cells and may have a role in cancer progression. <h3>Methods</h3> The aim of this prospective observational study of OAC patients was to examine the incidence of MetS and its relationship to tumour pathology in an Irish population. Patients underwent a metabolic and nutritional assessment prior to initiation of treatment. Visceral fat area was measured using CT scans. MetS was defined according to the International Diabetes Federation definition.<sup>1</sup> <h3>Results</h3> 83 OAC patients (71 male: 12 female) were recruited with a median age of 64.6 years ± 1.0 (range 48–86). All patients underwent an oesophagectomy, with 42% (n=35) receiving neoadjuvant chemoradiotherapy. 58% of patients were either overweight or obese with a further 60% centrally obese. Males had significantly greater visceral fat area (p=0.031) despite no difference in total abdominal fat compared to females (p=0.757). The incidence of obesity may be underestimated as 41% of patients reported unintentional weight loss with 18% losing &gt;5% of their usual body weight. MetS was diagnosed in 39% patients, which exceeds the population norms reported at 21%.<sup>2</sup> The presence of MetS was not associated with tumour length, depth of invasion, lymph node positive disease, clinical or overall pathological stage in males or females. Individual features of MetS were also not significantly related to the pathological staging of oesophageal cancer. <h3>Conclusion</h3> We report an increased prevalence of MetS and central obesity in a cohort of Irish patients with OAC. Dysphagia and weight loss are common in the presentation of oesophageal cancer and may mask the effect of obesity and metabolic syndrome on the clinical pathological features of OAC in this cohort. Further research is needed to fully understand the underlying biological mechanisms linking obesity to oesophageal cancer. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Alberti KGMM</b>, <i>et al.</i><i>Diabetic Medicine</i> 2006;<b>23</b>:469–80. 2. <b>Waterhouse DF</b>, <i>et al.</i><i>Ir J Med Sci</i> 2009;<b>178</b>:161–6.
Abstract 2261: Antitumor and anti-inflammatory effect of a novel nutrient mixture on human lymphoma cell line U-937
Authors: M. Waheed Roomi, Nusrath M. Roomi, Matthias Rath, Aleksandra Niedzwiecki
Journal: Cancer Research (2010)

Abstract Introduction: Phytochemicals and dietary antioxidants are known to decrease the risk of inflammation and prevent cancer development. We have developed strategies to inhibit cancer progression and its spread by natural products. A nutrient mixture (NM) containing ascorbic acid, lysine, proline and green tea extract has exhibited anticancer activity in vitro and in vivo in a number of cancer cell lines. Objective: We investigated the effect of NM on human lymphoma cell line U-937 in vitro by measuring: cell proliferation, MMP expression, invasion, apoptosis, and Cox-2 and Cox-1 protein expression. Materials and Methods: Human lymphoma cell line U-937 (ATCC) was cultured in RPMI medium supplemented with fetal bovine serum and antibiotics. U-937 cells were seeded on 24-well tissue culture plates with 40nM phorbol 12-myristate 13-acetate (PMA). After 24 hrs, the cells were treated with NM at 0, 50, 100, 250, 500 and 1000 mcg/ml, in triplicate at each dose. Cell proliferation was evaluated by MTT assay, MMP expression by gelatinase zymography, invasion through Matrigel, apoptosis by using live green caspase detection kit (Molecular Probe), and COX-2 and COX-1 expression by Western blot. Results: NM was not toxic to U-937 cells at a concentration of 250 mcg/ml and exhibited an antiproliferative effect at 500 mcg/ml concentration. Zymography demonstrated only one band corresponding to MMP-9, which was inhibited by NM in a dose-dependent manner. Matrigel invasion was significantly reduced (by 95%) at 250 mcg/ml NM and completely blocked at 500 mcg/ml NM. NM induced slight apoptosis at 100 mcg/ml and moderate at 500 and 1000 mcg/ml concentration. NM inhibited Cox-2 expression in a dose-dependent fashion and had no effect on Cox-1 expression. Conclusions: Our results suggest that NM is an excellent candidate for therapeutic use in the treatment of hematological malignancies. 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 2261.
P618 INFLAMMATORY RESPONSE OF PRIMARY MOUSE HEPATIC STELLATE CELLS TO LIPOPOLYSACCHARIDE IN VITRO
Authors: R. Liebe, K. Breitkopf-Heinlein, U. Albrecht, M. Thomas, V. Costina, P. Findeisen, J. Bode, S. Dooley
Journal: Journal of Hepatology (2014)