tbuckley/cabot-search huggingface dataset:
<b> <i>In vitro</i> </b> Toxicity of A-431 Carcinoma Cells with Antibodies to Epidermal Growth Factor Receptor and Epithelial Glycoprotein-1 Conjugated to Radionuclides Emitting Low-Energy Electrons
Authors: Rosana B. Michel, Mary Ellen Castillo, Philip M. Andrews, M. Jules Mattes
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The ability of antibodies (Abs) conjugated to radionuclides emitting low-energy electrons to specifically kill nonadherent lymphoma target cells in vitro was demonstrated previously. This study extends this work to adherent carcinoma cells. The fact that these cells are spread out on plastic can potentially make it more difficult to deliver radiation to the nucleus from decays in the cytoplasm or on the cell surface. Experimental Design: The Abs tested were anti-epidermal growth factor receptor and anti-epithelial glycoprotein-1, conjugated to indium-111 or iodine-125, which emit low-energy Auger and conversion electrons. Conjugates of the β-particle emitter, iodine-131, also were tested, for comparison. Abs were incubated with the cells for 2 days, and then the treated cells were assayed for colony-forming units. The radiation dose delivered to the nucleus was calculated from the cumulative decays per cell. Results: With conjugates of 111In, very potent killing was obtained with both of the Abs, with 100% kill (approximately 4–5 logs) even at subsaturating Ab concentrations. Lower levels of kill were obtained with 125I or 131I conjugates. Conjugates with 131I, a β-particle emitter, produced greater nonspecific toxicity. The greater potency of 111In could be attributed to the higher specific activity that was obtained routinely with this radiolabel, up to 70 mCi/mg. Uptake of radioactivity peaked at approximately 200 cpm per cell. Dosimetry calculations, using subcellular S values, demonstrated that the toxicity observed was consistent with the amount of radiation delivered to the nucleus. Conclusions: These results are similar to previous results obtained with B lymphoma cells and indicate that this approach is applicable to a wide range of tumor types. Radionuclides emitting low-energy electrons are effective at killing target cells with relatively little nonspecific toxicity, if sufficient activity is delivered to the cell. Most Abs to high-density cell surface antigens would probably be effective.
Caseload midwifery care versus standard maternity care for women of any risk: M@NGO, a randomised controlled trial
Authors: Sally K Tracy, Donna L Hartz, Mark B Tracy, Jyai Allen, Amanda Forti, Bev Hall, Jan White, Anne Lainchbury, Helen Stapleton, Michael Beckmann, Andrew Bisits, Caroline Homer, Maralyn Foureur, Alec Welsh, Sue Kildea
Journal: The Lancet (2013)
Homeobox gene Rhox5 is regulated by epigenetic mechanisms in cancer and stem cells and promotes cancer growth
Authors: Qiang Li, Mark E O'Malley, David L Bartlett, Sheng Guo
Journal: Molecular Cancer (2011)

Abstract Background Homeobox genes murine Rhox5 and human RHOXF1 are expressed in early embryonic stages and then mostly restricted to germline tissues in normal adult, yet they are aberrantly expressed in cancer cells in vitro and in vivo . Here we study the epigenetic regulation and potential functions of Rhox5 gene. Findings In Rhox5 -silenced or extremely low expresser cells, we observed low levels of active histone epigenetic marks (H3ac, H4ac and H3K4me2) and high levels of repressive mark H3K9me2 along with DNA hypermethylation in the promoter. In Rhox5 low expresser cells, we typically observed modest levels of both active and repressive histone marks along with moderate DNA methylation. In Rhox5 highly expressed CT26 cancer cells, we observed DNA hypomethylation along with high levels of both active and repressive histone marks. Epigenetic drugs (retinoic acid and MS-275) induced F9 cell differentiation with enhanced Rhox5 expression and dynamic changes of epigenetic marks. Finally, Rhox5 knockdown by small hairpin RNA (shRNA) in CT26 colon cancer decreased cell proliferation and migration in vitro and tumor growth in vivo . Conclusions Both DNA methylation and histone methylation/acetylation play key roles in modulating Rhox5 expression in various cell types. The stem cell-like "bivalent domain", an epigenetic feature originally identified in key differentiation genes within stem cells, exists in the Rhox5 gene promoter in not only embryonic stem cells but also cancer cells, cancer stem cells, and differentiated Sertoli cells. As Ras signaling-dependent Rhox5 expression promotes tumor growth, Rhox5 may be an ideal target for therapeutic intervention in cancer.
Nonalcoholic Fatty Liver Disease and Low-Carbohydrate Diets
Authors: Linda Wasserbach York, Swathy Puthalapattu, George Y. Wu
Journal: Annual Review of Nutrition (2009)

Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance, obesity, and other features of metabolic syndrome and is known to be the most common cause for abnormal liver enzymes. The recent surge in the number of patients with NAFLD has been accompanied by an increase in research on potential treatment options, particularly weight loss and dietary interventions. Given the growing interest on the role of carbohydrates in the prevention and treatment of NAFLD, this review discusses the relationship between the amount of carbohydrates in the diet and effects on NAFLD, with special emphasis on a low-carbohydrate diet. We discuss the role of insulin resistance in the pathophysiology of NAFLD and provide an overview of various popular diets and their role as a treatment option for NAFLD. Additional large, longer-duration trials studying the efficacy of a low-carbohydrate diet in the treatment and prevention of NAFLD are eagerly awaited.
Retrorectal Cystic Hamartoma As Benign Cause of CA 19-9 Elevation
Authors: Jesus Garcia-Donas, Nuria Rodriguez, Carlos Jara, Miguel Urioste, Manuel Nevado, Marta Cañamero, Victoria Cuartero, Jose Albillos, Daniel Vega, Antonio Quintans
Journal: Journal of Clinical Oncology (2007)

inflammatory bowel diseases, autoimmune disorders, pregnancy, and malignancies are other associated conditions. 1 Although EN has been occasionally reported to occur with leukemias, lymphomas, and solid tumors, its association with childhood AML is extremely rare.The nature of the causal relationship between EN and malignancy has not been defined. 2,3kin involvement in leukemias may be the consequence of specific infiltration (leukemia cutis), such condition being very rare in acute leukemias; on the contrary, the more frequent secondary nonspecific lesions do not contain leukemic cells and include purpura, maculopapules, erythroderma, herpes zoster or simplex lesions, bullae, furuncles, exfoliation, eczema, and EN.In our patient, EN was evident at diagnosis of AML, and although a causal relationship between the two conditions could not be ascertained, the complete resolution of EN after the first course of chemotherapy strongly suggests its correlation to leukemia.
α-2a interferon therapy and antibody formation in patients with essential thrombocythemia and polycythemia vera with thrombocytosis
Authors: E. Törnebohm‐Roche, M. Merup, D. Lockner, C. Paul
Journal: American Journal of Hematology (1995)

Abstract In ten patients with essential thrombocythemia and polycythemia Vera with thrombocytosis we have investigated the therapeutic effect of recombinant α‐2a interferon (Roceron A®) given subcutaneously in a maintenance dosage of 3 million units three times weekly. The aim was to normalize the platelet count (⩽ 400 × 10 9 /L). One of the secondary aims was to study platelet activity measured as β‐thromboglobulin (β‐TG) in urine. All but one patient could administer the injections and in all patients a significant reduction in platelet values was seen. The treatment was discontinued in three patients due to side effects of interferon, two because of hair loss (one with irreversible alopecia), and one because of depression. Three patients developed antibodies to α‐2a interferon and a concomitant rise in the platelet level; in one patient therapy was switched to leukocyte α‐interferon with an excellent response. The initial levels of β‐TG were elevated in 9/10 patients and were significantly reduced at 6 months in 4/5 patients not developing antibodies. Six patient are still on α‐interferon therapy with a long‐term follow‐up of 3‐3.5 years. We conclude that α‐interferon therapy may be an alternative in patients with thrombocytosis and/or complications necessitating treatment. ©1995 Wiley‐Liss, Inc.
Pharmacogenomic Discovery Using Cell-Based Models
Authors: Marleen Welsh, Lara Mangravite, Marisa Wong Medina, Kelan Tantisira, Wei Zhang, R. Stephanie Huang, Howard McLeod, M. Eileen Dolan
Journal: Pharmacological Reviews (2009)

Quantitative variation in response to drugs in human populations is multifactorial; genetic factors probably contribute to a significant extent. Identification of the genetic contribution to drug response typically comes from clinical observations and use of classic genetic tools. These clinical studies are limited by our inability to control environmental factors in vivo and the difficulty of manipulating the in vivo system to evaluate biological changes. Recent progress in dissecting genetic contribution to natural variation in drug response through the use of cell lines has been made and is the focus of this review. A general overview of current cell-based models used in pharmacogenomic discovery and validation is included. Discussion includes the current approach to translate findings generated from these cell-based models into the clinical arena and the use of cell lines for functional studies. Specific emphasis is given to recent advances emerging from cell line panels, including the International HapMap Project and the NCI60 cell panel. These panels provide a key resource of publicly available genotypic, expression, and phenotypic data while allowing researchers to generate their own data related to drug treatment to identify genetic variation of interest. Interindividual and interpopulation differences can be evaluated because human lymphoblastoid cell lines are available from major world populations of European, African, Chinese, and Japanese ancestry. The primary focus is recent progress in the pharmacogenomic discovery area through ex vivo models.
Long-Term Outcomes of Invasive Ipsilateral Breast Tumor Recurrences After Lumpectomy in NSABP B-17 and B-24 Randomized Clinical Trials for DCIS
Authors: I. L. Wapnir, J. J. Dignam, B. Fisher, E. P. Mamounas, S. J. Anderson, T. B. Julian, S. R. Land, R. G. Margolese, S. M. Swain, J. P. Costantino, N. Wolmark
Journal: JNCI Journal of the National Cancer Institute (2011)

BackgroundIpsilateral breast tumor recurrence (IBTR) is the most common failure event after lumpectomy for ductal carcinoma in situ (DCIS). We evaluated invasive IBTR (I-IBTR) and its influence on survival among participants in two National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized trials for DCIS.
Uncoupling the Proinflammatory from the Immunosuppressive Properties of Tumor Necrosis Factor (Tnf) at the P55 TNF Receptor Level
Authors: George Kassiotis, George Kollias
Journal: The Journal of Experimental Medicine (2001)

Multiple sclerosis (MS) is a disabling inflammatory demyelinating disease of the central nervous system, considered to result from self-reactivity to myelin antigens. Tumor necrosis factor (TNF) and the p55 TNF receptor (TNFR) have been strongly implicated in MS pathogenesis. We reveal in this study a dual role for TNF in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. In addition to its well-established proinflammatory effects, TNF exhibits potent immunosuppressive properties, providing one possible explanation for the immune and disease activating effect of anti-TNF treatment of MS. We show that in TNF-deficient mice, myelin-specific T cell reactivity fails to regress and expansion of activated/memory T cells is abnormally prolonged, leading to exacerbated EAE. Strikingly, immnosuppression by TNF and protection against EAE does not require the p55 TNFR, whereas the same receptor is necessary for the detrimental effects of TNF during the acute phase of the disease. Thus, blocking the function of the p55 TNFR in autoimmune demyelination may inhibit the noxious proinflammatory activities of TNF without compromising its immunosuppressive properties.
Fludarabine alone compared to CHVP plus interferon in elderly patients with follicular lymphoma and adverse prognostic parameters: A GELA study
Authors: B. Coiffier, E.M. Neidhardt-Bérard, H. Tilly, C. Belanger, R. Bouabdallah, C. Haioun, P. Brice, P.Y. Péaud, J.L. Pico, M. Janvier, P. Solal-Celigny, N. Brousse
Journal: Annals of Oncology (1999)
Identification of Cancer Stem Cells in Ewing's Sarcoma
Authors: Mario-Luca Suvà, Nicolò Riggi, Jean-Christophe Stehle, Karine Baumer, Stéphane Tercier, Jean-Marc Joseph, Domizio Suvà, Virginie Clément, Paolo Provero, Luisa Cironi, Maria-Chiara Osterheld, Louis Guillou, Ivan Stamenkovic
Journal: Cancer Research (2009)

Abstract Cancer stem cells that display tumor-initiating properties have recently been identified in several distinct types of malignancies, holding promise for more effective therapeutic strategies. However, evidence of such cells in sarcomas, which include some of the most aggressive and therapy-resistant tumors, has not been shown to date. Here, we identify and characterize cancer stem cells in Ewing's sarcoma family tumors (ESFT), a highly aggressive pediatric malignancy believed to be of mesenchymal stem cell (MSC) origin. Using magnetic bead cell separation of primary ESFT, we have isolated a subpopulation of CD133+ tumor cells that display the capacity to initiate and sustain tumor growth through serial transplantation in nonobese diabetic/severe combined immunodeficiency mice, re-establishing at each in vivo passage the parental tumor phenotype and hierarchical cell organization. Consistent with the plasticity of MSCs, in vitro differentiation assays showed that the CD133+ cell population retained the ability to differentiate along adipogenic, osteogenic, and chondrogenic lineages. Quantitative real-time PCR analysis of genes implicated in stem cell maintenance revealed that CD133+ ESFT cells express significantly higher levels of OCT4 and NANOG than their CD133− counterparts. Taken together, our observations provide the first identification of ESFT cancer stem cells and demonstration of their MSC properties, a critical step towards a better biological understanding and rational therapeutic targeting of these tumors. [Cancer Res 2009;69(5):1776–81]
Risk Stratification for Arrhythmic Sudden Cardiac Death
Authors: Jeffrey J. Goldberger, Alfred E. Buxton, Michael Cain, Otto Costantini, Derek V. Exner, Bradley P. Knight, Donald Lloyd-Jones, Alan H. Kadish, Byron Lee, Arthur Moss, Robert Myerburg, Jeffrey Olgin, Rod Passman, David Rosenbaum, William Stevenson, Wojciech Zareba, Douglas P. Zipes
Journal: Circulation (2011)
Scope and significance of non-uniform classification practices in breast cancer with non-inflammatory skin involvement: a clinicopathologic study and an international survey
Authors: U. Güth, G. Singer, A. Schötzau, I. Langer, H. Dieterich, C. Rochlitz, L. Herberich, W. Holzgreve, E. Wight
Journal: Annals of Oncology (2005)
Autonomic Neural Control of Dynamic Cerebral Autoregulation in Humans
Authors: Rong Zhang, Julie H. Zuckerman, Kenichi Iwasaki, Thad E. Wilson, Craig G. Crandall, Benjamin D. Levine
Journal: Circulation (2002)

The purpose of the present study was to determine the role of autonomic neural control of dynamic cerebral autoregulation in humans.We measured arterial pressure and cerebral blood flow (CBF) velocity in 12 healthy subjects (aged 29+/-6 years) before and after ganglion blockade with trimethaphan. CBF velocity was measured in the middle cerebral artery using transcranial Doppler. The magnitude of spontaneous changes in mean blood pressure and CBF velocity were quantified by spectral analysis. The transfer function gain, phase, and coherence between these variables were estimated to quantify dynamic cerebral autoregulation. After ganglion blockade, systolic and pulse pressure decreased significantly by 13% and 26%, respectively. CBF velocity decreased by 6% (P<0.05). In the very low frequency range (0.02 to 0.07 Hz), mean blood pressure variability decreased significantly (by 82%), while CBF velocity variability persisted. Thus, transfer function gain increased by 81%. In addition, the phase lead of CBF velocity to arterial pressure diminished. These changes in transfer function gain and phase persisted despite restoration of arterial pressure by infusion of phenylephrine and normalization of mean blood pressure variability by oscillatory lower body negative pressure.These data suggest that dynamic cerebral autoregulation is altered by ganglion blockade. We speculate that autonomic neural control of the cerebral circulation is tonically active and likely plays a significant role in the regulation of beat-to-beat CBF in humans.
A survey of roller discotheque injuries.
Authors: K. E. Dowey
Journal: British Journal of Sports Medicine (1982)

Dancing on roller skates at discothecques has become very popular among the youth in the last number of years.During 1980 a number of these roller disco- theques were opened in Belfast and it soon became apparent that significant numbers of young people were attending the Accident and Emergency Departments of hospitals in the city with injuries received while parti- cipating in this leisure activity.As these injuries were becoming more frequent, it was decided to analyse those presenting at the Accident and Emergency Department of the Belfast City Hospital for the period September 1 980-September 1981. CLINICAL DATAIn all 158 patients were assessed.The patients numbered 107 females and 51 males.The female:male ratio was 2:1.The ages ranged from 5-43 years, the average age being 16.5 years.A peak is evident in the 12-16 age
HDL from CETP-deficient subjects shows enhanced ability to promote cholesterol efflux from macrophages in an apoE- and ABCG1-dependent pathway
Authors: F. Matsuura
Journal: Journal of Clinical Investigation (2006)

Genetic deficiency or inhibition of cholesteryl ester transfer protein (CETP) leads to a marked increase in plasma levels of large HDL-2 particles. However, there is concern that such particles may be dysfunctional in terms of their ability to promote cholesterol efflux from macrophages. Recently, the ATP-binding cassette transporter ABCG1, a macrophage liver X receptor (LXR) target, has been shown to stimulate cholesterol efflux to HDL. We have assessed the ability of HDL from subjects with homozygous deficiency of CETP (CETP-D) to promote cholesterol efflux from macrophages and have evaluated the role of ABCG1 and other factors in this process. CETP-D HDL-2 caused a 2- to 3-fold stimulation of net cholesterol efflux compared with control HDL-2 in LXR-activated macrophages, due primarily to an increase in lecithin:cholesterol acyltransferase–mediated (LCAT-mediated) cholesteryl ester formation in media. Genetic knockdown or overexpression of ABCG1 showed that increased cholesterol efflux to CETP-D HDL was ABCG1 dependent. LCAT and apoE contents of CETP-D HDL-2 were markedly increased compared with control HDL-2, and increased cholesterol esterification activity resided within the apoE-HDL fraction. Thus, CETP-D HDL has enhanced ability to promote cholesterol efflux from foam cells in an ABCG1-dependent pathway due to an increased content of LCAT and apoE.
Relative abundance of big and little gastrins in the tumours and blood of patients with the Zollinger Ellison syndrome.
Authors: G J Dockray, J H Walsh, E Passaro
Journal: Gut (1975)

The relative concentrations of big gastrin (G-34) and little gastrin (G-17) were compared in the sera and tumours (gastrinomas) of Zollinger-Ellison syndrome patients. Big and little gastrins were identified in all 10 serum samples and in all 10 tumour biopsies examined. In serum, G-34 (range of concentrations 58-220 000 fmol/ml) was the major form of gastrin and G-17 (22-78 000 fmol/ml) was a minor component; the mean relative abundance of G-17/[G17 + G34]) in serum was 0-18 and the mean relative abundance of G-34 was 0-82. In tumour, however, the opposite was true: G-17 (49-869 000 pmol/g) was the major component and G-34 (45-464 pmol/g) a minor component, and the relative proportions of G-17 and G-34 were 0-73 and 0-27 respectively. Following an intravenous injection of porcine secretin (2-0 U/kg) there was a rapid increase in concentration of all forms of gastrin in the blood, but the increase in G-17 was proportionately greater than that of G-34 (relative abundance of G-17 in basal serum was 0-21 compared with 0-37, five minutes after secretin). Differences in the half lives of G-17 and G-34 may partly explain their relative abundancies in serum and tumour tissue.
The efficacy number as a predictor of morbidity and mortality in peritoneal dialysis patients.
Authors: M V Rocco, J R Jordan, J M Burkart
Journal: Journal of the American Society of Nephrology (1993)

The efficacy number has been proposed as a predictor of clinical outcome in patients on chronic ambulatory peritoneal dialysis (CAPD). The usefulness of this parameter in a large group of CAPD patients was analyzed. Forty-five patients who have received chronic CAPD therapy for at least 1 yr were included in the study. The efficacy number was compared with outcome as defined by mortality and days of hospitalization. Other demographic and laboratory parameters, including gender; race; presence of diabetes; serum albumin, serum creatinine, and BUN levels; and measures of peritoneal transport, including dialysate-to-plasma creatinine and dialysate-to-plasma urea ratios, were also assessed for their role in predicting outcome. Laboratory values were obtained at the initiation of CAPD and at 12 months after the start of CAPD. By univariate analysis, a low 12-month serum albumin level was the best predictor of mortality (P < 0.005), followed by a high 12-month efficacy number (P < 0.05). After adjusting for age and the presence of diabetes, these two variables remained the best predictors of mortality (P < 0.08 and < 0.09, respectively). A low initial serum albumin level was also a strong predictor of mortality (P < 0.09). By univariate analysis, the best predictor of hospitalization was a low serum albumin level obtained either initially or at 12 months (P < 0.005 for both time periods). After adjusting for age and the presence of diabetes, the 12-month serum albumin level remained a significant predictor of hospitalization (P < 0.03), whereas efficacy number was not a strong predictor (P = 0.27).(ABSTRACT TRUNCATED AT 250 WORDS)