tbuckley/cabot-search huggingface dataset:
Abstract IA4: Normalizing the tumor microenvironment to enhance therapeutic outcome
Authors: Rakesh K. Jain
Journal: Cancer Research (2011)

Abstract A solid tumor is like an aberrant organ – comprised of cancer cells and a variety of host cells embedded in an extra-cellular matrix – nourished by blood vessels and drained by lymphatic vessels. Using an array of imaging technologies and animal models, we have shown that blood and lymphatic vessels as well as matrix associated with tumors are abnormal and these abnormalities can create a hostile tumor microenvironment (e.g., hypoxia, high interstitial fluid pressure). These abnormalities can fuel tumor progression as well as prevent treatments from reaching and attacking tumor cells. To this end, we proposed that “normalizing” tumor vessels and matrix would allow cancer therapies to penetrate the mass more uniformly and to function more effectively. We then showed first in mice and then in cancer patients that antiangiogenic drugs - originally designed to destroy tumor vessels - could, paradoxically, also “normalize” them, creating a window of opportunity to attack the cancer most effectively. More crucially, the extent of vascular normalization closely associated with the overall survival of patients receiving anti-angiogenic therapy. More recently, we have shown that the drugs approved by the FDA for lowering blood pressure can “normalize” the collagen matrix and improve the delivery of molecular and nanomedicine (3, 4). At this meeting, I will present emerging data on new targets for normalizing the tumor microenvironment and how normalization can potentiate the outcome of tumor vaccine therapy. References: 1. Jain RK. Normalization of the tumor vasculature: An emerging concept in anti-angiogenic therapy of cancer. Science. 2005;307:58–62. 2. Goel S et al. Normalization of the vasculature for treatment of cancer and other diseases. Physiological Reviews. 2011;91:1071–1121. 3. Jain RK, Stylianopoulos T. Delivering nanomedicine to solid tumors. Nature Reviews Clinical Oncology. 2010;7:653–64. 4. Diop-Frimpong B, Chauhan VP, Krane S, Boucher Y, Jain RK. Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors. PNAS. 2011;108:2909–14. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr IA4.
Adénome festonné et polype hyperplasique du côlon: critères de différenciation en endomicroscopie confocale de fluorescence
Authors: F Cholet, S Leblanc, J Le Meur, L Doucet, B Terris, J Jezequel, S Chaussade, F Prat, M Robaszkiewicz
Journal: Endoscopy (2012)

Les adénomes festonnés (AF) représentent environ 9% des polypes réséqués en coloscopie. Ces lésions ont longtemps été confondues sur le plan anatomopathologique avec les polypes hyperplasiques (PH) et leur première description ne date que de 1990. Leur distinction est essentielle car leur potentiel de cancérisation est au moins identique aux adénomes classiques. Des critères morphologiques ont été définis par les pathologistes pour mieux distinguer le PH de l'AF, mais cette différence est-elle appréciable in vivo par l'endomicroscopie confocale de fluorescence (ECF)?
AB1238 A comparison between automated and manual methods for detection antinuclear autoantibodies on human epithelial-2 cells
Authors: A.A. Novikov, E.N. Alexandrova, D. Roggenbuck, E.L. Nasonov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A variety of antinuclear antibodies (ANAs) are found in serum samples obtained from patients with rheumatic autoimmune diseases<sup>1</sup>. Identification of the corresponding antigens and measurement of the antibody titer are useful for diagnosis and to inform about the progress and prognosis of the disease<sup>2-4</sup>. The current gold standard method for ANA detection is manual indirect immunofluorescence (IIF) on human epithelial-2 (HEp-2) cells<sup>5</sup>. <h3>Objectives</h3> Automation of ANAs IIF interpretation including pattern recognition can improve intra- and inter- laboratory assay reproducibility. Comparing automated and visual interpretation of ANAs the usefulness for laboratory diagnostics was investigated. <h3>Methods</h3> Autoantibody detection by IIF on HEp-2 cells was performed in 234 serums of patients witch suspected and confirmed rheumatic disease. Automated evaluation ("Aklides platform", Medipan GmbH and "ANA HEp-2 Plus" kit, Generic Assays GmbH) were compared with visual interpretations. The screening dilution was 1:160. <h3>Results</h3> Automated method of recognition positive/negative results showed a moderate agreement with visual interpretation: kappa=0,5; case of mismatch is 30 (13%). The automated identification of the pattern (n=83, mixed patterns were excluded from this part of the study - this option is not available when using this automated platform) demonstrated a moderate agreement with visual assessment kappa=0,6; discrepant results: 22 (26,5%). <h3>Conclusions</h3> Use of this automated platform for ANAs screening provides reliable identification of negative/positive samples and main nuclear patterns. <h3>References</h3> Nakabayashi T, Kumagai T, PhD,Yamauchi K et al. Evaluation of the Automatic Fluorescent Image Analyzer, Image Titer, for Quantitative Analysis of Antinuclear Antibodies. Am J Clin Pathol 2001;115:424-429. Notman DD, Kurata N, Tan EM. Profiles of antinuclear antibodies in systemic rheumatic diseases. Ann Intern Med.1975; 83:464-469. Tan EM. Antinuclear antibodies in diagnosis and management. Hosp Pract (Off Ed). 1983;18:79-84. Tan EM. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989;44:93-151. Kiviti S, Gilburd B, Agmon-Levin N et al. A novel automated indirect immunofluorescence autoantibody evaluation. Clin Rheumatol. 2011 Nov 5. [Epub ahead of print] <h3>Disclosure of Interest</h3> None Declared
Abstract 1191: Managing the cross talk: BRCA1 and its regulation of the p53 family, E2f1/Rb and apoptosis
Authors: Kimberly A. Scata, Wafik S. El-Deiry
Journal: Cancer Research (2012)

Abstract Under constant assault from internal and external stresses, the cell constantly monitors cellular damage, repairing damage when it is able. If the cell deems the damage too great to repair, it activates the pathways that induce programmed cell death. This life or death decision is controlled, in part, by the activation of the tumor suppressor, p53. Upon stabilization and activation, p53 activates a variety of genes including those genes capable of inducing apoptosis. Our lab has previously demonstrated that the tumor suppressor, BRCA1, is capable of stabilizing p53 and directing it to cell cycle arrest genes at the expense of apoptotic genes. In our efforts to understand the mechanism by which BRCA1 is able to prevent expression of apoptotic genes, we have discovered that BRCA1 also stabilizes E2F1, an oncogene that is able to induce p53-dependent and p53-independent apoptosis. Interestingly, we have found that BRCA1 also induces DNp73, a pro-survival member of the p53 family. We hypothesize that BRCA1 may be interfering with the interaction between E2F1 and Rb that has been shown to be important for the apoptotic response to DNA damage. Furthermore, we are currently using siRNA to inhibit expression of these genes to determine the relative contribution of DNp63, DNp73 and E2F1/Rb signaling to control the cell's decision to undergo apoptosis in response to BRCA1 expression. 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 1191. doi:1538-7445.AM2012-1191
Association Between the Centers for Medicare and Medicaid Services Hospital Star Rating and Patient Outcomes
Authors: David E. Wang, Yusuke Tsugawa, Jose F. Figueroa, Ashish K. Jha
Journal: JAMA Internal Medicine (2016)

This study investigates whether hospitals with more stars (on the Centers for Medicare and Medicaid Services rating system) have lower risk-adjusted 30-day mortality and readmissions than hospitals with less stars.
Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis
Authors: Graham R. Foster, William L. Irving, Michelle C.M. Cheung, Alex J. Walker, Benjamin E. Hudson, Suman Verma, John McLauchlan, David J. Mutimer, Ashley Brown, William T.H. Gelson, Douglas C. MacDonald, Kosh Agarwal
Journal: Journal of Hepatology (2016)
Limitation of Multinucleation by Dibutyryl Adenosine 3′,5′-Cyclic Monophosphate in Tumor Cells Treated With Cytochalasin B2
Authors: Frank J. O'Neill
Journal: JNCI Journal of the National Cancer Institute (1976)

Hamster BHK21 tumor cells and human rhabdomyosarcoma (RD) cells responded to cytochalasin B (CB) by becoming highly multinucleated. Nearly 80% of the BHK cells contained four or more nuclei after 7 days of exposure to CB, and 35% of these had at least seven nuclei. Similar frequencies of multinucleation were obtained with RD cells. Administration of 10-3 M theophylline and dibutyryl adenosine 3′,5′cyclic monophosphate (Bu2cAMP) at 5×0-4 M or 10-3 M to CB-treated RD or BHK cells greatly reduced the frequency of cells with five or more nuclei. The frequency of cells with seven or more nuclei was reduced to less than 5%. Along with this reduction in highly multinucleated cells was an increase in the incidence of binucleated cells. Bu2cAMP was toxic and caused many CB-treated BHK cells to detach from the culture surface, but not all cells were killed. Bu2cAMP had little toxic effect on CB-treated RD cells. These observations indicated that the inhibition of high degrees of multinucleation were ,not the result of nonspecific toxic effects of Bu2cAMP but that nuclear division was limited by it. The effect of Bu2cAMP on densitydependent inhibition of growth was also studied. Addition of only theophylline and Bu2cAMP to either BHK or RD cells resulted in growth to significantly lower saturation densities. The toxicity of Bu2cAMP on cells in crowded cultures apparently caused the limited propagation. Bu2cAMP resulted in significant cell killing or detachment but, once the lower saturation densities were reached, cell death was minimized. Thus Bu2cAMP did not restore contact inhibition per se. It was also found that untreated RD cells grew to lower concentration densities than expected from the microscopic inspection of cells in situ. Microscopic inspection revealed high concentration densities and numerous mitoses. This apparent contradiction was due to the ability of RD cells to fuse upon the attainment of confluence and to produce multinucleated cells without the aid of CB.
OC-022 Addressing the interplay between apoptosis and glucose metabolism in liver cirrhosis and HCC
Authors: V Iansante, PM Choy, S Chokshi, R Williams, RA Anders, C Bubici, S Papa
Journal: Gut (2015)

<h3>Introduction</h3> Pro-inflammatory signalling in the liver promotes the appearance of a metabolic phenotype that involves the transition from mitochondrial respiration to aerobic glycolysis. It was demonstrated that this metabolic shift occurs during the transition from healthy and early stage of liver injury (NAFLD/NASH, ALD to late stage of disease (i.e. cirrhosis), and further escalates during HCC development.<sup>1,2</sup>This metabolic signature enables dividing cells to satisfy anabolic and energetic needs for biomass production and to suppress apoptotic signalling, which is consistent with increased compensatory hepatic cell proliferation typical of cirrhotic and HCC livers. However other studies in contrast have suggested that hepatocytes are unable to sustain glycolysis during late stage of chronic liver disease.<sup>3</sup> <h3>Method</h3> We used unbiased gene expression analyses of microarray datasets to investigate the expression of glycolytic genes in cirrhotic and HCC livers and correlated their expression with patient outcome. Furthermore, by using a combination of <i><i>in vitro</i></i>and <i><i>in vivo</i></i>analyses we have characterised the abilities of a novel anti-apoptotic gene to regulate aerobic glycolysis in liver cirrhosis and HCC. <h3>Results</h3> mRNA profiling showed significantly higher expression of glycolytic transcripts in cirrhotic and HCC livers compared to normal quiescent livers (P &lt; 0.05). Up regulation of <i>Glut1</i>, <i>Hk1</i>, <i>Hk2</i>, <i>G6PI</i>, and <i>PFKL</i>was seen in HCC livers compared to their adjacent non-tumour tissues (P &lt; 0.001). Notably, expression of enzymes regulating mitochondrial activity (<i>Pdha</i>, <i>Pdk</i>) was unchanged between non-tumour tissues and late stage of HCC. Moreover, up regulation of a novel anti-apoptotic gene positively correlated with increased expression of glycolytic transcripts in a group of cirrhotic patients prospectively classified as poor prognosis based on HCC development, and promotes the aerobic glycolysis of hepatoma cells. <h3>Conclusion</h3> In summary, our findings delineate a putative link between aerobic glycolysis and suppression of apoptosis that is an important part of the progression of cirrhosis to HCC. The identification of the mechanism regulating this link may lead to design new therapeutic strategies for human liver disease. This abstract is funded by Foundation for Liver Research <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Beyoğlu D, Idle JR. J Hepatol. 2013;59:842–858 Kakazu E, Kondo Y, Kogure T, <i>et al</i>. Plasma amino acids imbalance in cirrhotic patients disturbs the tricarboxylic acid cycle of dendritic cell. Sci. Rep. 2013;3:3459 Nishikawa T, <i>et al</i>. J Hepatol. 2014;60:1203–1211
Devotions upon Emergent Occasions
Authors: J. Foell
Journal: BMJ (2012)

“I have had three births, one, natural, when I came into the world; one, supernatural, when I entered into the ministry; and now a preternatural birth, in returning to life, from this sickness . . . In this last birth, I myself am born a father, this child of mine, this book, comes into the world, from me, with me.” So wrote the 17th century poet John Donne in the prologue of his book in 1624. Donne is struck by a “malignant and pestilential sickness” that renders his physicians helpless; he senses their …
QUALITY OF NEOINTIMA, NOT QUANTITY DETERMINES STENT THROMBOGENECITY AFTER FIRST AND SECOND GENERATION DRUG-ELUTING STENT IMPLANTATION BY CHRONIC ANGIOSCOPIC STUDY
Authors: Hideo Kawakami, Toru Miyoshi, Akira Oshita, Hiroshi Matsuoka
Journal: Journal of the American College of Cardiology (2016)
Impact of Bone Scintigraphy on the Clinical Management of a Patient With Sickle Cell Anemia and Recent Chest Pain
Authors: RAQUEL SISAYAN, ABDELHAMID H. ELGAZZAR, PETER J. WEBNER, DEO GALEON RELIGIOSO
Journal: Clinical Nuclear Medicine (1996)

The authors present a cases of acute chest syndrome that was originally thought to be due to pneumonia, in which bone imaging obtained 4 weeks later for knee pain showed a secondary finding of multiple rib infarcts that clarified the etiology of the patient's chest manifestations and led to a change in the management of the patient. Bone scintigraphy should be considered in the work-up of patients with sickle cell anemia and concurrent chest symptoms.
Abstract 827: Proximity-based c-MET activation assay development in formalin-fixed paraffin-embedded (FFPE) samples and profiling c-MET/HGF axis in human cancer-derived tumors
Authors: Dua Rajiv, Jianhuan Zhang, Gordon Parry, John Winslow, Elicia Penuel
Journal: Cancer Research (2010)

Abstract Aberrant activation of membrane receptors frequently occurs in human carcinomas. Measurement of receptor phosphorylation is commonly used as an indicator of receptor activation in formalin-fixed paraffin embedded (FFPE) sections. This format is used to preserve human tissue samples and is the most common format for readily-available tissues from clinical trials and patient disease management. However, preservation of the labile phosphorylation signal is often inconsistent and consequently, results can be ambiguous. Here, we describe an alternative, novel approach to detect and quantify both receptor and ligand expression, as well as, activation status in FFPE samples. Specifically, we describe the development and validation of VeraTag based assays to measure total c-Met, total HGF and HGF/c-Met interactions. Using, the VeraTag technology, proximity-based assays, were used to detect and quantify c-MET, HGF, and HGF/c-MET interactions resulting from both exogenous and endogenous ligand stimulation in FFPE-prepared cell line pellets. The developed assays were subsequently used to profile human carcinomas including non-small cell lung, stomach, and head and neck tumors. Our data demonstrate a novel approach to detect and quantify c-Met activation which enables profiling and characterization of the c-Met activation status in FFPE human tissue samples. Furthermore, these data also demonstrate a basic approach to detect and quantify ligand-receptor interactions by VeraTag proximity-based assays that can be widely applied to measure activation of receptors in archived FFPE human tissue samples. 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 827.
Sustained Efficacy of Insulin Pump Therapy in Type 2 Diabetes: 9-Year Follow-up in a Cohort of 161 Patients
Authors: Julia Morera, Michael Joubert, Remy Morello, Anne Rod, Barbara Lireux, Yves Reznik
Journal: Diabetes Care (2016)

Continuous subcutaneous insulin infusion (CSII) is a valuable option for patients with type 2 diabetes in whom glycemic targets are not met despite multiple daily injections (MDIs) at high insulin doses, as recently demonstrated in the multicenter randomized OpT2mise trial (1). However, data on the durability of glucose control with CSII are lacking (1,2). We report here the long-term efficacy of CSII in a cohort of 161 patients (51% female) with type 2 diabetes who started pump therapy between 1998 and 2012. The patients’ mean age was 58.3 ± 9.8 years, and mean BMI was 33.2 ± 6.6 kg/m2. The mean duration of diabetes was 15 ± 8.1 years, and mean glycated hemoglobin (HbA1c) was 9.0 ± 1.7% (74 ± 18.6 mmol/mol). At baseline, 96% of patients were receiving insulin: 48% were receiving basal-bolus regimens, 37% were receiving premixed …
Abstract 3680: Targeting IGF-1R for inhibition of pancreatic cancer metastasis by pomegranate fraction.
Authors: Manicka V. Vadhanam, Ramesh C. Gupta, Lacey R. McNally
Journal: Cancer Research (2013)

Abstract Patients with pancreatic adenocarcinoma have the lowest 5-year survival rate with more than 95% of the patients dying within 5 years and median survival of &amp;lt;6 months. The incidence of pancreatic cancer is also increasing by 1.5% per year since 2004. At present, there are limited treatment options and no early detection strategies for the disease. Although ∼ 20% of patients are eligible for surgical and chemotherapy intervention, these patients typically die of metastasis. Therefore, the prevention of these metastases would greatly improve patient care. Insulin-like growth factor receptor 1 (IGF-1R) is commonly over-expressed in metastases as compared to primary tumor. The aggressive forms of tumors overexpress the receptor when compared to less aggressive, non-metastatic tumors. In order to test this concept, we tested two metastatic pancreatic cell lines, S2VP10 and S2CP9 and three non-metastatic cell lines, Panc-1, AsPc-1 and MiaPaCa-2. Immunoblotting revealed the overexpression of IGF-1R specifically in the metastatic pancreatic cell lines. Pomegranate has recently gained much attention for its chemopreventive efficacy. We had previously demonstrated that the less-polar pomegranate component of the peel target IGF-1R signaling pathway in prostate cells. To test the efficacy of the pomegranate component against pancreatic cancer cells, we treated the highly aggressive S2VP10 cells with fractions derived from different parts of pomegranate. The water-insoluble fraction of pomegranate peel was most efficacious with an IC50 of 62 μg/ml. Molecules related to IGF-1R signaling were analyzed by immunoblotting. IRS-1, a docking protein for the receptor decrease significantly in a dose-dependent manner. A dose-dependent decrease of phosphorylation of the IGF-1R receptor was also observed. Dose-dependent decreased protein levels of BCL2 and increased levels of caspase 9 confirmed the effect of pomegranate fraction on apoptosis; and increased levels of p21 protein and decreased levels of cyclin D1 confirmed the effect on cell proliferation. Thus, we hypothesize that targeting IGF-1R signaling axis with pomegranate fraction will decrease survival of pancreatic tumor cells and decrease metastasis. Studies are currently underway to assess the anti-metastatic effect in vivo. Citation Format: Manicka V. Vadhanam, Ramesh C. Gupta, Lacey R. McNally. Targeting IGF-1R for inhibition of pancreatic cancer metastasis by pomegranate fraction. [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 3680. doi:10.1158/1538-7445.AM2013-3680