tbuckley/cabot-search huggingface dataset:
Abstract 5123: 1,25D3 regulates cell-matrix and cell-cell adhesion and reduces experimental metastasis in a squamous cell carcinoma model system
Authors: Yingyu Ma, Bing Su, Wei-Dong Yu, Mukund Seshadri, Steven G. Turowski, Rui-Xian Kong, Bryan M. Gillard, Donald L. Trump, Candace S. Johnson
Journal: Cancer Research (2010)

Abstract 1,25D3, the most active vitamin D metabolite, has broad spectrum anti-tumor activity. We demonstrated that 1,25D3 affects squamous cell carcinoma (SCC) cell adhesion to extracellular matrix and inhibits cell motility, markers of metastasis. In this study, we extended these observations. In situ zymography assay revealed that 1,25D3 strongly suppressed the ability of SCC cells to degrade gelatin. 1,25D3 reduced the adhesion of SCC cells to laminin, and by flow cytometry, the expression of the laminin receptors integrin α6 and β4. 1,25D3 promoted the activation of focal adhesion kinase (FAK) and the formation of focal adhesion as shown by immunofluorescence. To study the effects of 1,25D3 on cell-cell adhesion, the expression level of cadherins were examined by flow cytometry. 1,25D3 enhanced the expression of E-cadherin and R-cadherin, but did not alter that of N-cadherin. Of note, a 1,25D3-resistant variant of SCC (SCC-DR) was developed and these findings were not observed in SCC-DR cells. To investigate the in vivo effect of 1,25D3, C3H/HeJ mice were injected i.v. into tail vein with 104 SCC cells, and then half of the mice received 0.625 μg of 1,25D3 i.p. daily for 3 days while the other half received saline. Treatment with 1,25D3 dramatically inhibited the development of pulmonary tumor formation, as assessed by MRI analysis and colony counts. Our study suggests that 1,25D3 suppresses SCC metastasis, possibly through the promotion of E-cadherin-mediated cell-cell adhesion and the inhibition of cell motility and invasion. This study was supported by NIH/NCI grants CA067267, CA095045 and CA085142. 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 5123.
CMX001 to Prevent Cytomegalovirus Disease in Hematopoietic-Cell Transplantation
Authors: Francisco M. Marty, Drew J. Winston, Scott D. Rowley, Estil Vance, Genovefa A. Papanicolaou, Kathleen M. Mullane, Thomas M. Brundage, Alice T. Robertson, Susan Godkin, Hervé Momméja-Marin, Michael Boeckh
Journal: New England Journal of Medicine (2013)

The use of available antiviral agents for the prevention of cytomegalovirus (CMV) disease is limited by frequent toxic effects and the emergence of resistance. CMX001 has potent in vitro activity against CMV and other double-stranded DNA viruses. We evaluated the safety and anti-CMV activity of CMX001 in patients who had undergone allogeneic hematopoietic-cell transplantation.From December 2009 through June 2011, a total of 230 patients with data that could be evaluated were enrolled in the study. We randomly assigned these adult CMV-seropositive transplant recipients from 27 centers to oral administration of CMX001 or placebo. Patients were assigned in a 3:1 ratio to five sequential study cohorts according to a dose-escalating, double-blind design. Randomization was stratified according to the presence or absence of acute graft-versus-host disease and CMV DNA in plasma. Patients received the study drug after engraftment for 9 to 11 weeks, until week 13 after transplantation. Polymerase-chain-reaction analysis of CMV DNA in plasma was performed weekly. Patients in whom CMV DNA was detected at a level that required treatment discontinued the study drug and received preemptive treatment against CMV infection. The primary end point was a CMV event, defined as CMV disease or a plasma CMV DNA level greater than 200 copies per milliliter when the study drug was discontinued. The analysis was conducted in the intention-to-treat population.The incidence of CMV events was significantly lower among patients who received CMX001 at a dose of 100 mg twice weekly than among patients who received placebo (10% vs. 37%; risk difference, -27 percentage points; 95% confidence interval, -42 to -12; P=0.002). Diarrhea was the most common adverse event in patients receiving CMX001 at doses of 200 mg weekly or higher and was dose-limiting at 200 mg twice weekly. Myelosuppression and nephrotoxicity were not observed.Treatment with oral CMX001 at a dose of 100 mg twice weekly significantly reduced the incidence of CMV events in recipients of hematopoietic-cell transplants. Diarrhea was dose-limiting in this population at a dose of 200 mg twice weekly. (Funded by Chimerix; CMX001-201 ClinicalTrials.gov number, NCT00942305.).
A NEW BIOMARKER BASED RISK SCORE FOR PREDICTING STROKE OR SYSTEMIC EMBOLISM IN ATRIAL FIBRILLATION: THE BEST RISK SCORE
Authors: Ziad Hijazi, Johan Lindbck, John Alexander, Michael Hanna, Elaine Hylek, Renato Lopes, Jonas Oldgren, Agneta Siegbahn, Christopher Granger, Lars Wallentin
Journal: Journal of the American College of Cardiology (2014)
PTU-181 Relationship Between Barrett’s Oesophagus And Abdominal Adiposity Or Bmi And Activated Pathways In Progression To Cancer
Authors: S DiCaro, WH Cheung, R Haidry, L Fini, M Keane, L Lovat, R Batterham, M Banks
Journal: Gut (2014)

<h3>Introduction</h3> Barrett’s oesophagus (BE) remains the strongest risk factor for oesophageal adenocarcinoma (OAC). Several studies describe an association between BE and obesity through mechanical and metabolic consequences. Visceral fat is a recognised endocrine organ. Adipokines and insulin resistance impact upon obesity-related diseases and cancer pathways. Our aims were to evaluate the relationship between BE, abdominal adiposity/BMI and pathways in the progression to cancer. <h3>Methods</h3> Height, weight, waist-hip ratio, blood pressure assessment and fasting blood samples were obtained from sequential patients (pts), undergoing gastroscopy. BMI, fasting glucose and insulin, lipids, leptin and adiponectin were measured. Pts were then classified as normal-weight, overweight or obese and the presence of abdominal obesity (AO) and/or metabolic syndrome (MS, defined by WHO criteria) documented., to evaluate the relationship between BMI and abdominal adiposity with metabolic indices and adipokines in BE compared to controls. Biopsies were obtained from BE and histological progression to cancer was correlated with metabolic indexes. Chi square, Fisher, t-Student test and logistic analysis were used for comparison. <h3>Results</h3> 480 patients were enrolled (250 cases: F/M: 57/193; mean age: 63.7; 230 controls: F/M: 136/94; mean age: 51.9). Metabolic derangements were more common in BE compared to controls; Metabolic syndrome (33.2 <i>vs</i> 20%; OR 1.95; p = 0.0017), insulin levels (10.2 <i>vs</i> 7.2µIU/ml; p = 0.001), HbA1c (5.8 <i>vs </i>5.1%; p &lt; 0.01), insulin resistance (47 <i>vs</i> 27%; OR 1.54; p &lt; 0.01), dyslipidaemia (72.8 <i>vs</i> 53.9; OR 2.3; p &lt; 0.0001) and hypertension (37.4 <i>vs</i> 21.3%; OR 2.4; p &lt; 0.001). MS was present in 39.7 <i>vs</i> 34.2% (OR 3.05; p &lt; 0.001), 43.7 <i>vs</i> 21.9% (OR 5.2; p &lt; 0.001), 92.1 <i>vs</i> 54.9% (OR 8.08; p &lt; 0.0001), in overweight, obese, AO pts with BE and controls, respectively. Insulin resistance was present in 39.2 <i>vs </i>33.8% (OR 1.3; p &lt; 0.05), 38 <i>vs</i> 22.3% (OR 1.7; p &lt; 0.01) and in 82.5 <i>vs </i>54.5% (OR 1.5; p &lt; 0.001) in overweight, obese and AO pts, respectively. A trend was observed for decreased adiponectin levels in BE <i>vs</i> controls while leptin levels showed no correlation. In BE pts, the presence of dysplasia was associated with MS (42 <i>vs</i> 25%; p = 0.005) and and insulin resistance (51.4<i> vs</i> 34.0%; p = 0.005). <h3>Conclusion</h3> BE association with insulin resistance and MS suggests activation of specific metabolic pathways in pts with abdominal obesity or BMI. Progression to cancer appears driven by metabolic dysfunction in MS and a carcinogenic insulin pathway. <h3>Disclosure of Interest</h3> None Declared.
Underdiagnosis of Genital Herpes by Current Clinical and Viral-Isolation Procedures
Authors: Laura A. Koutsky, Claire E. Stevens, King K. Holmes, Rhoda L. Ashley, Nancy B. Kiviat, Cathy W. Critchlow, Lawrence Corey
Journal: New England Journal of Medicine (1992)

The current clinical strategy for diagnosing genital herpes simplex virus (HSV) infection in women relies on clinical findings plus the selective use of viral culture. The effectiveness of this approach for identifying women with genital herpes is unknown.
TRADEOFF BETWEEN MYOCARDIAL INFARCTION VERSUS BLEEDING TYPES ON MORTALITY AFTER ACUTE CORONARY SYNDROME: LESSONS FROM THE THROMBIN RECEPTOR ANTAGONIST FOR CLINICAL EVENT REDUCTION IN ACUTE CORONARY SYNDROME (TRACER) RANDOMIZED TRIAL
Authors: Francesco Costa, Marco Valgimigli, Yuliya Lokhnygina, Robert Clare, Lars Wallentin, David Moliterno, Paul Armstrong, Harvey White, Claes Held, Philip Aylward, Frans Van de Werf, Robert Harrington, Kenneth Mahaffey, Pierluigi Tricoci
Journal: Journal of the American College of Cardiology (2016)
A Placebo-Controlled Trial of Maintenance Therapy with Fluconazole after Treatment of Cryptococcal Meningitis in the Acquired Immunodeficiency Syndrome
Authors: Samuel A. Bozzette, Robert A. Larsen, Joseph Chiu, Mary Ann E. Leal, Jan Jacobsen, Paul Rothman, Patrick Robinson, Gene Gilbert, J. Allen McCutchan, Jeremiah Tilles, John M. Leedom, Douglas D. Richman
Journal: New England Journal of Medicine (1991)

In patients with the acquired immunodeficiency syndrome (AIDS), the rate of relapse after primary treatment for cryptococcal meningitis remains high. We conducted a controlled, doubleblind trial to evaluate the efficacy of maintenance therapy with fluconazole. At entry into the study, all participants had sterile cultures of cerebrospinal fluid, blood, and urine after following a standardized course of therapy for culture-proved cryptococcal meningitis. The patients were randomly assigned to take either fluconazole or placebo as maintenance therapy. The dose of fluconazole was 100 mg daily in the first phase of the study and 200 mg daily in the second phase.
Abstract 2661: C11 Acetate and 18F FDG PET/CT imaging of MDR2-/- mouse model of hepatocellular carcinoma.
Authors: Nicholas J. Skill, Paul R. Territo, Amanda A. Riley, Brian P. McCarthy, Mary A. Maluccio
Journal: Cancer Research (2013)

Abstract Our previous research reveals a link between the enzyme autotaxin (ATX) and its product lysophosphatidic acid (LPA) in hepatocellular carcinoma (HCC). We have shown a shift in ATX levels and LPA variant biosynthesis associated with HCC in patients that was corrected by liver transplantation. Moreover we have demonstrated a reduction in hepatic tumor burden in the MDR2-/- mouse model of HCC by treatment with commercial ATX inhibitors. The purpose of this study was to establish the relevance of FDG PET versus 11C acetate imaging to monitor response to ATX inhibition in the in-vivo MDR2 /- mouse model of HCC whereby we would be able to test the impact of novel inhibitors on both the initiation and progression of HCC. Methods: Dynamic high-resolution Positron Emission Tomography (PET) images of 12 month MDR-/- mice and FVB controls were acquired using 18F-FDG or 11C-Acetate (N=3 per group). At the end of the PET imaging session whole body CT images were acquired. Image segmentation for discrete volumes of interests (VOI) was manually constructed from parametric images for the liver for 18F-FDG images while for 11C-Acetate VOIs were submitted to kinetic modeling, using a 3-compartment, 4-parameter model. Results. MDR2-/- mice had significant hepatic tumors at 12 month (7.9±1.8mm) whereas no tumors were observed in FVB controls. MDR2-/- mice had significantly higher hepatic 11C-Acetate uptake and metabolic rates when compared to FVB controls (0.6±0.04 vs 0.49±0.02ml/g/min P=0.038). In contrast there was no significant difference in 18F-FDG metabolism or uptake in the livers of MDR2-/- mice when compared to wild type FVB controls (1.1±0.23 v 1.32±0.2 and 3.61±0.97 vs. 4.3±0.6SUV respectively p=ns). Conclusion: The biology of HCC formation in MDR2-/- is better suited to 11C acetate PET/CT imaging than 18F FDG. 11C acetate is the most effective imaging method available to test response to treatment in an in-vivo model of HCC. Citation Format: Nicholas J. Skill, Paul R. Territo, Amanda A. Riley, Brian P. McCarthy, Mary A. Maluccio. C11 Acetate and 18F FDG PET/CT imaging of MDR2-/- mouse model of hepatocellular 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 2661. doi:10.1158/1538-7445.AM2013-2661 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Do Factors Known to Alter Infant Microbial Exposures Alter the Risk of Food Allergy and Eczema in a Population-based Infant Study?
Authors: J.J. Koplin, P.E. Martin, M.L.K. Tang, L.C. Gurrin, A.J. Lowe, N.J. Osborne, M.N. Robinson, A. Ponsonby, S.C. Dharmage, K.J. Allen
Journal: Journal of Allergy and Clinical Immunology (2012)
ESTUDIO DE COSTE-EFECTIVIDAD: SEDACIÓN POR ENDOSCOPISTA VS ANESTESISTA EN PACIENTES ASA I-III
Authors: JM Riesco, P García, J Rizo, A Díaz, M Rivero, R Manzano, E Moya, R González, R Campos
Journal: Endoscopy (2014)

Introducción: Las guías de práctica clínica (GPC) afirman que no existen estudios de coste-efectividad comparando la sedación con propofol por endoscopista (SPE) vs. anestesista (SPA) en endoscopia digestiva, pero señalan que la SPA en pacientes de bajo riesgo anestésico resultaría ineficiente.
Heroin Addiction and Drug Policy: the British System
Authors: N. Heather
Journal: BMJ (1995)

<b>Objective.</b> To examine and summarize policies and procedures for peer evaluation of teaching/instructional coaching (PET/IC) programs within departments, schools, and colleges of pharmacy and to identify opportunities for improving these based on best practices. <b>Methods.</b> A survey was sent to all ACPE-accredited pharmacy programs to collect information regarding procedures to support and evaluate PET/IC programs across institutions. Descriptive statistics were used to summarize the general features of PET/IC programs and inferential statistics were used to make group comparisons based on institutional control (public, private) and institution age (0-10 year, older than 10 years). <b>Results.</b> Surveys for 91 institutions were completed (response rate = 64.5%). Most institutions (78.4%) reported having a PET/IC program. Most institutions with PET/IC programs reported using a combination of formative and summative evaluations (57.4%). Faculty development (35.8%) and improving teaching (35.8%) were the top purposes for PET/IC programs. Almost half of the PET/IC programs (46.3%) were mandatory for all faculty at the institutions. Most institutions (66.7%) had one standardized instrument used in their PET/IC program. Few institutions (11.9%) reported evaluating or being in the process of evaluating the effectiveness or success of their PET/IC program. Private institutions were more likely to incentivize observers than public institutions (17.1% vs. 0%). <b>Conclusion.</b> PET/IC programs are needed to assess and provide feedback to instructors about their teaching practices. While most institutions report having a PET/IC program, wide variability exists in how the programs are implemented. Opportunities exist for institutions to evaluate the effectiveness of their program and identify best practices.
Abstract 107: p53 mutation at codon 273 in colorectal cancer and colitis-derived ALDHhigh cells promotes sphere formation in vitro
Authors: Anitha K. Shenoy, Robert Fisher, Elizabeth Ashley Butterworth, Edward Scott, Emina Huang
Journal: Cancer Research (2012)

Abstract Introduction: p53 protein is a cell cycle regulator that functions as a tumor suppressor. Mutations in the p53 gene results in uncontrolled cell division, leading to diverse types of human cancer. In the case of colorectal cancer, p53 is the last gene to be mutated in the adenoma-to-carcinoma sequence. However, in colitis, early mutations in p53 occur in the course of dysplasia-to-carcinoma transition. Analysis of these mutations in colitis and colorectal cancer can provide clues regarding the pathogenesis of colitis to cancer.Recently, we have isolated and propagated ALDHhigh colon cancer stem cells (CCSCs) from colorectal cancer patients and precursor-CCSCs (pCCSCs) from colitic patients, which may be propagated as spheres. These CCSCs and pCCSCs may be used as a model system to study the transition from colitis to cancer. To determine if any of the p53 mutations correlate with sphere formation we analyzed p53 mutations in the existing sphere isolates. Methods: We performed sequence analysis of p53 mRNA and genomic DNA on 6 ALDHhigh sphere isolates derived from human colon cancer and 2 from colitic colon. Results: 5 out of 6 (83%) colorectal cancer derived ALDHhigh sphere isolates showed mutation at 273rd codon on the 8th exon (Arg→ His), which is one of the hot spots of p53 mutations in colorectal cancer. The same mutation was also observed in the ALDHhigh sphere isolates derived from colitic patients. This mutation corresponds to the amino acid residue that is in direct contact with DNA (contact mutants), but this mutation does not result in alterations in the spatial structure of p53. However, the defect in DNA binding ability of p53 allows the cell cycle to proceed unchecked and thus this mutation correlates with sphere forming ability. Conclusions: Mutations of p53 at codon 273 on exon 8 correlates with the sphere forming ability of the ALDHhigh cells derived from human colon cancer and colitic colon. Mutational knock-in and wild-type p53 overexpression studies would be vital to further confirm the role of this mutation in sphere formation. 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 107. doi:1538-7445.AM2012-107
Case 25-2010
Authors: Mark S. Klempner, Elizabeth A. Talbot, Susanna I. Lee, Sherif Zaki, Mary Jane Ferraro
Journal: New England Journal of Medicine (2010)

A 24-year-old woman was transferred from another hospital because of abdominal pain and shock. Computed tomographic scans of the abdomen showed ascites, thickening of a segment of small bowel, and mesenteric lymphadenopathy. Laparotomy revealed two areas of necrotic small bowel, which were resected. Despite broad-spectrum antimicrobial therapy, she remained critically ill. On the seventh hospital day, a diagnostic test result was received.
Abstract 5255: The comparison between MAPK and PI3K signaling pathway inhibition in KRAS mutant NSCLC cell lines.
Authors: Irem Dogan, Ayla Cihan, Abdullah Ekmekci
Journal: Cancer Research (2013)

Abstract Introduction: KRAS mutations are found 15-25% of patients with lung adenocarcinoma and they lead to constitutive activation of KRAS signaling pathway that results in sustained cell proliferation. Currently, there are no direct anti-KRAS therapies available. Therefore, it is rational to target the downstream molecules of KRAS signaling pathway. MAPK signaling pathway (RAF-MEK-ERK) and the PI3K pathway (PI3K-AKT-mTOR PI3K/Akt) are the activated pathways by KRAS signaling and crucial for cell survival and proliferation in non-small cell lung cancer (NSCLC). Here, we examined the inhibition of both these pathways combination and alone and analyzed the anti-proliferative and apoptotic events in KRAS mutant NCSLC cell lines, A549 and Calu-1. Materials and Methods: Cytotoxicity was determined by MTT assay after the cells were treated with LY294002 (PI3K inhibitor), U0126 (MEK inhibitor) and RAD001 (mTOR inhibitor) for 24 hour. The expression levels of p-EGFR, EGFR, p-ERK, ERK, AKT, p-AKT, p53, cyclinD1, c-myc, p27kip1, BAX, BIM and GAPDH were detected by Western blot after 6 and 24 hour treatment. Results: In proliferation assays, combination of RAD001 (100nM) with U0126 (10uM) and LY294002 (10uM) resulted in higher cytotoxic activity than single agents alone at 24 hour in both cell lines. Western blots revealed that U0126 directly inhibited the phosphorylation of ERK at 6 and 24 hour, followed by inhibiting the activations of its downstream molecules, including cyclinD1 and c-myc but increased the expression of p27kip1, BAX and BIM at 6 and 24 hour. On the other hand, LY294002 downregulated p-AKT signaling only at 6 hour, but not in 24 hour. However, LY294002 and RAD001 combination was effective on cyclinD1 and c-myc expression at 24 hour which can correlate with their cytotoxic effect. Although PI3K/mTOR inhibition is more effective in cytotoxicity, MEK/mTOR inhibition markedly decreases cell proliferation protein marker expressions. Conclusion: These findings suggest that the combination of MEK and mTOR inhibitors and PI3K and mTOR inhibitors compared with either drug alone can inhibit cell proliferation, induce apoptosis and effect downstream signaling pathways. Also, in molecular level, U0126/RAD001 combination is a better option than LY294002/RAD001 combination in A549 and Calu-1 cells. Citation Format: Irem Dogan, Ayla Cihan, Abdullah Ekmekci. The comparison between MAPK and PI3K signaling pathway inhibition in KRAS mutant NSCLC cell lines. [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 5255. doi:10.1158/1538-7445.AM2013-5255 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Nonsyphilitic Interstitial Keratitis and Bilateral Deafness (Cogan's Syndrome) Associated with Essential Polyangitis (Periarteritis Nodosa)
Authors: Leo Oliner, Matthew Taubenhaus, Theodore M. Shapira, Norman Leshin
Journal: New England Journal of Medicine (1953)

IN 1945, Cogan1 described a syndrome consisting of nonsyphilitic interstitial keratitis with deafness. Subsequently, a number of other cases were reported, mostly in the ophthalmologic literature. Although these authors speculated on an association with systemic disease, no definite etiology could be found in fifteen cases 1 2 3 4 5 6 reported up to the present. We have had the opportunity of observing an additional case in which two episodes of oculo-aural symptoms occurred before the onset of extensive vascular lesions, pointing to a possible association between essential polyangitis (periarteritis nodosa) and the initial symptoms. In view of the rarity of the syndrome, it may be . . .