tbuckley/cabot-search huggingface dataset:
Abstract 4942: Deletion of the asymmetry regulator Lgl1 contributes to tumor stemness and invasiveness.
Authors: Robin G. Lerner, Loan Nguyen, Claudia Petritsch
Journal: Cancer Research (2013)

Abstract In the developing and adult brain asymmetric cell division (ACD) maintains a balance between self-renewing and differentiated progeny of neural stem and progenitor cells. The WD protein lethal giant larvae 1 (Lgl1) regulates the distribution of polarity proteins in dividing cells and thereby establishes an axis of polarity, which is crucial for proper asymmetric divisions to occur (Baek et al. Mutat Res. 1999; 436; 131-6). Lgl, along with other asymmetry regulators, have been identified as a putative tumor suppressor gene in Drosophila. There remains debate as to whether disrupting ACD by itself is sufficient to cause tumor initiation by mammalian stem and progenitor cells. We have previously shown that expression of multiple asymmetry regulators is disrupted in human glioma (Sugiarto et al. Cancer Cell; 2011; 20; 320-340). Here we address our hypothesis that ACD defects are crucial for tumorigenesis, by delineating the role of Lgl1 in tumor initiation and progression. Using mouse neural stem cells (NSCs) isolated from genetically modified Lgl1lox/lox mice (Klezovitch et al. Genes Dev. 2004; 18; 559-71) we investigated the contribution of Lgl1 to various hallmarks of cancer in vitro and in vivo. We demonstrate that loss of Lgl1 in mouse NSC and oligodendrocyte precursor cells disrupts ACD and increases the expression of early-stage precursor cell markers. Deletion of Lgl1 does not increase proliferation in vitro and deletion of Lgl1 alone does not transform cells transplanted into immunocompromised mice. However properties associated with a high-grade tumor, including invasiveness and stem cell marker expression, are increased when Lgl1 is deleted in the context of oncogenic EgfrVIII expression. Increase in tumor invasiveness has previously been demonstrated to be associated with an increase in stem cell marker expression (Molina et al. Neoplasia. 2010; 12; 453-63). Our data suggest that loss of asymmetry in tumor precursor cells blocks differentiation and contributes to tumor progression by increasing stemness and hence invasiveness. Citation Format: Robin G. Lerner, Loan Nguyen, Claudia Petritsch. Deletion of the asymmetry regulator Lgl1 contributes to tumor stemness and invasiveness. [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 4942. doi:10.1158/1538-7445.AM2013-4942
Surfactant-Replacement Therapy
Authors: Mary Ellen Avery, T. Allen Merritt
Journal: New England Journal of Medicine (1991)

SURFACTANT-REPLACEMENT therapy for premature infants born with inadequate stores of pulmonary surfactants is here to stay. A growing number of prospective, randomized, controlled clinical trials testify to both the efficacy and safety of the tracheal instillation of surfactant in treating premature infants with the respiratory distress syndrome.1 Respiratory distress syndrome, also known as hyaline membrane disease, was previously the leading cause of death in live-born preterm infants. Approximately 10,000 deaths per year were recorded in the United States in the early 1970s; the number was closer to 5000 per year in the 1980s, before the advent of surfactant-replacement therapy. Respiratory . . .
The Trials of Olestra: Is a Fat-free Lunch Too Costly?
Authors: E. Blume
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article The Trials of Olestra: Is a Fat-free Lunch Too Costly? Get access Elaine Blume Elaine Blume Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 23, 6 December 1995, Pages 1741–1743, https://doi.org/10.1093/jnci/87.23.1741 Published: 06 December 1995
US panel recommends HIV screening for everyone aged 15 to 64 years
Authors: M. McCarthy
Journal: BMJ (2013)

<sup>99m</sup>Tc(N)-DBODC(5) is the lead compound of a new series of monocationic <sup>99m</sup>Tc(N)-based potential myocardial imaging agents that exhibit original biodistribution properties. This study was addressed to elucidate the mechanisms of distribution, retention, and elimination of this promising <sup>99m</sup>Tc(N)-agent. <b>Methods:</b> The sex-related in vitro and in vivo stability and the subcellular distribution of <sup>99m</sup>Tc(N)-DBODC(5) were investigated. Studies were performed by considering binding to the serum proteins; stability in rat serum, human serum, and rat liver homogenates; and the chemical integrity of the complex after extraction from rat tissues such as heart, liver, and kidney, as well as from intestinal fluids and urine. The effect of cyclosporin A on the in vivo pharmacokinetic properties of <sup>99m</sup>Tc(N)-DBODC(5) was also evaluated. Subcellular distribution of <sup>99m</sup>Tc(N)-DBODC(5) in ex vivo rat heart was determined by standard differential centrifugation techniques. <b>Results:</b> No significant in vitro serum protein binding and no notable biotransformation of the native compound into different species by the in vitro action of the serum and liver enzymes was evidenced. In vivo experiments showed that sex affects the pharmacokinetic profile of the <sup>99m</sup>Tc(N)-complexes including metabolism and excretion. Chromatographic profiles of <sup>99m</sup>Tc(N)-radioactivity extracted from tissues and fluids of female rats were always coincident with the control. Conversely, a small percentage of metabolized species was detected by high-performance liquid chromatography in liver extracts of male rats. Furthermore, administration of cyclosporin A caused a significant reduction of lung, liver, and kidney washout along with a considerable variation in activity distribution in the intestinal tract in both male and female rats, thus indicating a possible implication of Pgp transporters in determining the biologic behavior of <sup>99m</sup>Tc(N)-DBODC(5). However, this phenomenon was more pronounced in females. Subcellular distribution studies showed that 86.3% ± 7.4% of <sup>99m</sup>Tc(N)-DBODC(5) was localized into mitochondrial fraction as a result of the interaction with the negative membrane potential. <b>Conclusion:</b> Evidence showing that the new <sup>99m</sup>Tc(N)-myocardial tracers behave as multidrug resistance–associated protein P-glycoprotein substrates, combined with their selective mitochondrial accumulation, strongly supports the possibility that diagnostic application of <sup>99m</sup>Tc(N)-DBODC(5) can be extended to tumor imaging and noninvasive multidrug resistance studies.
European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition – Professional requirements and training
Authors: R. Steele, J.-F. Rey, R. Lambert
Journal: Endoscopy (2012)

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on professional requirements and training includes 23 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of surveillance and other elements in the screening process, including multi-disciplinary diagnosis and management of the disease.
Abstract P6-01-06: Identification of Molecular Subtypes of DCIS and Invasive Breast Cancer Using Computerized Image Analysis for Data Integration
Authors: OO Adeyanju, A Khramtsov, A Verma, L Liu, X Wang, H Sattar, OI Olopade, D. Huo
Journal: Cancer Research (2010)

Abstract Background: Breast cancer is a heterogeneous disease with different putative therapeutic targets based upon the particular subtype. The particular subtype can have profound implications for therapy, as in the case of basal-like carcinomas which tend to be more aggressive with less therapeutic options. Although many studies have examined the transition from Ductal Carcinoma in-situ (DCIS) to Invasive Breast Cancer (IBC), the mechanisms involving the transformation are poorly understood. DCIS cases that are more likely to progress to IBC can be treated more aggressively. This study used image analysis to examine the association between predictive molecular biomarkers between pure DCIS, DCIS associated with IBC and IBC. Methods: With approval by the Institutional Review Board, we evaluated tissue microarrays comprising 453 tissue cores from 149 patients. Five immunohistochemical biomarkers were utilized: estrogen (ER), progesterone (PR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin 5/6 (CK-5/6). We then employed the Automated Cellular Image Analysis (ACIS) to score the biomarker status. We compared regional scoring (rated 0, 1, 2, or 3) between an experienced pathologist's subjective assessment and an automated score derived from ACIS. An image library was generated and integrated to our Translational Data Mart (TraM: http://tram.uchicago. edu). Statistical analyses included a comparison of histological grade, race, age, tumor size, and lymph node status associated with the prevalence of subtypes between pure DCIS tumors and those that advanced to IBCs. Results: The concordance between ACIS-based and pathologist-based scoring was moderate (kappa = 0.38). There was more variability in the pathologist's scoring with a standard deviation of 1.14 as compared to 0.85 for ACIS. Subtypes associated with IBC were also present in DCIS. In the pure DCIS cases, there was a higher proportion of the luminal A subtype (74.1%, n = 54) as compared to DCIS adjacent to IBC (54.2%, n=24) or pure IBC cases (57.4%, n = 115) (p=0.05). In contrast, there was more basal-like subtypes in DCIS juxtaposed with IBC (20.8%) and IBC (27.8%) than in pure DCIS tumors (9.3%). Discussion: Molecular subtype analysis of DCIS could be useful in predicting DCIS with high risk of progressing to invasive cancer. The resemblance between subtypes bolsters the hypothesis that IBCs and DCIS originate from the same precursor lesion. Although the automated scoring featured by ACIS would be useful in expediting readings, it must be validated by a pathologist's assessment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-06.
RENTABILIDAD DE LA PUNCIÓN ASPIRACION CON AGUJA FINA GUIADA POR ECOENDOSCOPIA (USE-PAAF) EN EL ESTUDIO DE MASAS PANCREATICAS. EXPERIENCIA EN NUESTRO CENTRO
Authors: MI Castro Novo, E Sánchez Hernández, P Quintas Lorenzo, MC Penin Corderi, P Vega Villaamil, F Valentín Gomez, MT Alves Perez, JJ Fernández Seara
Journal: Endoscopy (2012)

Objetivo: Evaluar la rentabilidad diagnóstica de la USE-PAAF en el estudio de masas pancreáticas en nuestro centro. Material y método: Se realizó una revisión retrospectiva de los pacientes sometidos a USE-PAAF de masas de páncreas entre enero 2007 y diciembre 2011 en el Complejo Hospitalario de Orense. Las exploraciones se realizaron con el ecoendoscopio lineal Olympus GF-UE160-AL5, puncionándose las masas pancreáticas con aguja de 22G. Criterios de inclusión: pacientes remitidos a nuestra unidad de endoscopia y sometidos a USE-PAAF para estudio de masas de páncreas. El patrón de referencia empleado para definir si la lesión era benigna o maligna al realizar las pruebas de exactitud diagnóstica fue la anatomía patológica de la pieza quirúrgica, si el paciente fue intervenido, o la evolución clínica y respuesta a tratamiento en el resto de los casos. Se compararon los resultados de la USE-PAAF con el diagnóstico final para calcular la sensibilidad y especificidad. Resultados: Se realizaron 99 USE-PAAF de masas de páncreas, 64.6% de varones, con una edad media de 68,61 (35–87) años. El tamaño medio de las lesiones fue de 35.21±15.44mm. Los diagnósticos citológicos obtenidos mediante la punción fueron: 47 adenocarcinomas; 2 carcinomas; 3 tumor endocrino; 1 recidiva de tumor germinal; 1 sarcoma y 27 sin datos de malignidad. 18 (18.2%) de las muestras citológicas no fueron concluyentes. Se obtuvo una sensibilidad 84.12%, especificidad 94.44%, valor predictivo positivo 98.14% y valor predictivo negativo 62.96%. No se produjeron complicaciones durante ni derivadas del procedimiento. Conclusión: La ecoendoscopia con punción es un procedimiento seguro y con una alta especificidad y VPP; lo que hace de ella una prueba idónea para el estudio de las masas de páncreas.
Primary Squamous Cell Carcinoma of the Thyroid on FDG PET/CT
Authors: Liang Cai, Yue Chen, Zhanwen Huang, Jingbo Wu
Journal: Clinical Nuclear Medicine (2014)

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NOVEL HIGH-POTENCY ORAL ANTIPLATELET DRUGS VERSUS CLOPIDOGREL IN PATIENTS UNDERGOING COMPLEX PERCUTANEOUS CORONARY INTERVENTION: RESULTS FROM A LARGE SINGLE-CENTER ALL-COMERS REGISTRY
Authors: Gennaro Giustino, Usman Baber, Melissa Aquino, George Dangas, Jason Kovacic, Pedro Moreno, Roy Swathi, Prakash Krishnan, Joseph Sweeny, Roxana Mehran, Annapoorna Kini, Samin Sharma
Journal: Journal of the American College of Cardiology (2015)
Time course for reversal of electrophysiological and ultrastructural abnormalities in subendocardial Purkinje fibers surviving extensive myocardial infarction in dogs.
Authors: P L Friedman, J J Fenoglio, A L Wit
Journal: Circulation Research (1975)

The electrophysiological properties of subendocardial Purkinje fibers surviving in myocardial infarcts were studied with intracellular microelectrodes in isolated superfused preparations and correlated with subsequent light and electron microscopic studies. Transmembrane action potentials could always be recorded from one or two cell layers of subendocardial Purkinje fibers in infarcted regions 3 days to 7 weeks after coronary artery occlusion; ventricular muscle action potentials were rarely found. Microscopic studies also demonstrated several layers of intact subendocardial Purkinje fibers; the subjacent ventricular muscle cells were irreversibly injured and replaced by scar. At all time intervals, surviving Purkinje fibers had significantly reduced maximum diastolic potentials, action potential amplitudes, and depolarization velocities as well as prolonged action potential durations. These parameters normalized between 24 hours and 7 weeks after coronary artery occlusion. Surviving Purkinje fibers with electrophysiological abnormalities at 24 hours and 3 days contained vast lipid deposits. Lipid was less prevalent at 10 days when action potential characteristics had improved. By 7 weeks, action potentials were nearly normal and lipid was absent. Subendocardial Purkinje fibers surviving in infarcts are subject to conditions which cause electrophysiological and ultrastructural abnormalities. Persistent abnormalities in the electrophysiological properties of these surviving Purkinje fibers may cause persistent altered electrophysiological properties of the infarcted heart.
Intrathoracic and Intra-abdominal Tl-201 Abnormalities Seen on Rotating Raw Cine Data on Dual Radionuclide Myocardial Perfusion and Gated SPECT
Authors: Wei-jen Shih, Vickie Kiefer, Kelly Gross, Becky Wierzbinski, Judy Collins, Calixto Pulmano, Yun U Ryo
Journal: Clinical Nuclear Medicine (2002)

The lower thorax and upper abdomen are visualized during cardiac acquisition of rest Tl-201 and stress Tc-99m tetrofosmin gated SPECT. Thus, abnormal Tl-201 localization in these areas and in organs such as parts of the lungs, liver, spleen, and kidneys can be observed, including rotating raw cine data.Other than cardiac images, the authors retrospectively reviewed Tl-201 rotating (raw data) images of 235 patients. Abnormal findings in the lungs, liver, spleen, and kidneys were identified that correlated with the patients' clinical information; radiographic findings, including computed tomography and ultrasonography of the abdomen; other scintigraphic studies; and laboratory findings.In 53 patients, 54 abnormalities were detected. Intrathoracic abnormalities included focal areas of increased uptake, one in the right lower lung and another in the right upper lung that confirmed lung cancer, in 2 patients; diffuse uptake in both lungs in 11 patients; photopenia in the lung bases, which had resulted from pleural effusions, in 3 patients; and abnormal right liver configuration caused by elevation of the right hemidiaphragm in 1 patient. Of the intra-abdominal abnormalities, 12 patients with splenomegaly were identified. Six patients had focal areas of increased uptake in the gastric area. Nonvisualization of one kidney resulted from a congenitally absent right kidney in 1 patient, from right nephrectomy in 1 patient, from end-stage renal disease in another, and from a lower position of the left or right kidneys in 5 patients. Small and decreased uptake of both kidneys resulted from end-stage renal disease in 1 patient. Small and decreased uptake of one kidney was noted in 1 patient with renal scarring, in 1 patient with a renal stone, in 3 patients with chronic pyelonephritis, and in 5 patients with renal cyst(s).Discernible intrathoracic and intra-abdominal abnormalities using rotating raw cine data from imaging in three-dimensional displays include diffuse or focal pulmonary uptake, pleural effusion, elevation of a hemidiaphragm, splenomegaly, increased uptake in the gastric area, renal abnormalities including absent or small kidneys, end-stage renal disease, renal scarring, renal cyst(s), and lower position of a kidney. The incidental finding of such abnormalities may prompt further clinical investigation.
Hyperglucagonemia and Blood Glucose Regulation in Normal, Obese and Diabetic Subjects
Authors: Robert S. Sherwin, Merrick Fisher, Rosa Hendler, Philip Felig
Journal: New England Journal of Medicine (1976)

Glucagon was infused to maintain plasma concentrations three to six times the basal level (300 to 600 pg per milliliter) into 16 normal and seven nondiabetic obese subjects. Hyperglucagonemia caused only a transient rise of 5 to 10 mg per 100 ml in basal glucose levels and had no effect on oral glucose tolerance or plasma insulin. In three patients with adult and two with juvenile-onset diabetes on maintenance insulin, hyperglucagonemia maintained for two to four days caused no change in plasma glucose or ketone concentration. In contrast, in nine insulin-withdrawn patients the glycemic response to hyperglucagonemia was five to 15 times greater (P < 0.05) than in normal controls. Hyperglucagonemia does not cause glucose intolerance in normal subjects or bring about deterioration of diabetic control when insulin is available. Glucagon in the insulin-deprived patient can worsen the diabetic state. These findings suggest the primary role of insulin deficiency in the diabetogenic action of glucagon. (N Engl J Med 294:455–461, 1976)
Amiodarone in Patients with Congestive Heart Failure and Asymptomatic Ventricular Arrhythmia
Authors: Steven N. Singh, Ross D. Fletcher, Susan Gross Fisher, Bramah N. Singh, H. Daniel Lewis, Prakash C. Deedwania, Barry M. Massie, Cindy Colling, Diane Lazzeri
Journal: New England Journal of Medicine (1995)

Asymptomatic ventricular arrhythmias in patients with congestive heart failure are associated with increased rates of overall mortality and sudden death. Amiodarone is now used widely to prevent ventricular tachycardia and fibrillation. We conducted a trial to determine whether amiodarone can reduce overall mortality in patients with congestive heart failure and asymptomatic ventricular arrhythmias.