tbuckley/cabot-search huggingface dataset:
Abstract 4962: <i>ERG</i> expression levels in prostate tumors reflect functional status of the androgen receptor as a consequence of fusion of <i>ERG</i> with AR regulated gene promoters
Authors: Ahmed A. Mohamed, Albert Dobi, Chen Sun, Syed Shaheduzzaman, Shyh-Han Tan, Gyorgy Petrovics, Ying Hu, Yongmei Chen, Bungo Furusato, Isabell Sesterhenn, Taduru Sreenath, David G. McLeod, Shiv Srivastava
Journal: Cancer Research (2010)

Abstract Background: Androgen dependent overexpression of the TMPRSS2:ERG fusion is the most prevalent chromosomal rearrangement in prostate cancer. During our recent evaluations of the ERG downstream transcriptional targets, we identified 15-Hydroxyprostaglandin Dehydrogenase gene (HPGD) in response to ERG knock-down. HPGD is an enzyme that catalyzes the oxidation of prostaglandins and lipoxins by converting them into inactive keto-metabolites, and physiologically antagonizes COX-2, a prostaglandin-synthesizing enzyme. HPGD also behaves as a tumor suppressor in many cancers as overexpression of HPGD resulted in marked inhibition of cell growth. The objective of this study was to evaluate potential connection between ERG overexpression and prostaglandin signaling. Experimental procedures: Small interference RNA (siRNA) oligo duplex was used to knock-down endogenous ERG and HPGD expressions. Western blot assay and Immunofluorescence was used to detect protein expressions. QT-PCR (normalized to GAPDH) was used for transcriptome analysis. GeneChip, Chromatin immunoprecipitation assays and cell proliferation assay were utilized for functional analysis. Results: ERG knock-down in VCaP prostate tumor cells results in overexpression of HPGD, down regulation of the prostaglandin E2 receptor 4 (EP4), and inhibition of prostaglandin E2 induced Urokinase Plasminogen Activator (uPA) expression and cell growth. Comparison of HPGD between TMPRSS2:ERG positive and negative prostate tumors revealed a trend towards decreased HPGD expression in fusion positive tumors. Conclusions: Taken together, these data suggest that ERG over-expression in CaP cells may positively influence prostaglandin mediated signaling. Funding sources: NIH Grants RO1 DK065977 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 4962.
P17.15 * AUTOCRINE SPHINGOSINE-1-PHOSPHATE FUELS GROWTH AND STEMNESS IN GLIOBLASTOMA STEM CELLS
Authors: C. Di Vito, S. Navone, L. Abdel Hadi, P. Giussani, P. Viani, P. M. Rampini, M. Caroli, G. Marfia, R. Campanella, L. Riboni
Journal: Neuro-Oncology (2014)

Sphingosine-1-phosphate (S1P) is an onco-promoter lipid that, after interaction with specific membrane receptors, acts as a key regulator of growth, invasion, and therapy-resistance of different tumors, including human glioblastomas (GBMs). These are the most common and lethal primary brain cancer in adults, exhibiting a dismal prognosis, despite diverse therapeutic approaches. Accumulating reports suggest that human GBMs contain glioblastoma stem cells (GSCs), a small subpopulation of cells determinant in tumor growth, and malignant progression. Little is known about the role of S1P in GSCs. Using GSCs derived from human GBM specimens with different proliferative index and stemness marker expression, we investigated the possible role of S1P in the proliferative and stemness properties of GSCs. Metabolic studies demonstrated that GSCs can rapidly export newly synthesized S1P, this process being enhanced in fast proliferating cells. Released S1P levels reached nM concentrations in response to increased extracellular sphingosine. Moreover, EGF and bFGF, recognized autocrine factors in GSC, potentiated the constitutive capacity of GSCs to secrete S1P, suggesting that cooperation between S1P and these growth factors is of relevance in GSC maintenance and proliferation. Of relevance, we then found that S1P is able to act as a proliferative and pro-stemness autocrine factor for GSCs, promoting both cell cycle progression and stemness phenotypic profile, in a receptor-dependent fashion. Overall, our results suggest that the GSC population is critically modulated by microenvironmental S1P, that acts as an autocrine signal to maintain a pro-stemness microenvironment and favoring GSC survival, proliferation and maintenance of stem properties. These findings could open novel opportunities for the development of effective treatments for GBMs.
EFFECT OF INTRAVENOUS CALCIUM IN GASTRIC SECRETION
Authors: M. E. Fikry
Journal: Gut (1969)

only two normal.All my cases were normal.It goes without saying that the response of stomachs of duodenal ulcer patients to stimuli of acid and pepsin secretion cannot be considered normal.Similar hyperparathyroid patients cannot be considered normal in two respects: the continuous increased parathyroid hormone which was proved, in my department and elsewhere, to be a stimulus to gastric acidity, and the prolonged hyper- calcaemia present.3 The accordance of my results with animal experi- ments, carried on canine animals, is, I believe, ascribed to the attainment of nearly equal blood levels of calcium in my cases to those reported in animal experiments.Thus to my mind, in the two normal cases of Dr Smallwood, excluding all the duodenal ulcer and hyper- parathyroid not being comparable to my cases, the results he obtained differ from my results and animal results due to the small dose of calcium given to these patients, 630 and 945 mg in cases 3 and 1 respectively.
Cell surface antigens of chemically induced sarcomas of the mouse. I. Murine leukemia virus-related antigens and alloantigens on cultured fibroblasts and sarcoma cells: description of a unique antigen on BALB/c Meth A sarcoma.
Authors: A B DeLeo, H Shiku, T Takahashi, M John, L J Old
Journal: The Journal of Experimental Medicine (1977)

As background for a serological definition of the unique antigens of chemically induced sarcomas, we have typed a series of fibroblast and sarcoma cell lines of BALB/c and C57BL/6 origin by cytoxicity and absorption tests for murine leukemia virus (MuLV)-related cell surface antigens and known alloantigens. 7 of the 17 cultured lines expressed the range of cell surface antigens associated with MuLV (GIX, GCSA, gp70, p30), and this was invariably associated with MuLV production. In nonproducer lines of C57BL/6 (but not BALB/c) origin, a MuLV-gp70-like molecule was found on the surface of fibroblasts and sarcoma cells. The alloantigenic phenotype of these MuLV+ and MuLV- cell lines was H-2D+, H-2K+, Thy-1.2+ or -, PC.1+ or -, Lyt-1.2-, Lyt-2.2-, Ia.7-, and TL.2-. A unique antigen was defined on the BALB/c ascites sarcoma Meth A with antisera prepared in BALB/c or (BALB/c X C57BL/6)F1 mice. Tissue culture lines derived from this tumor were MuLV-, which facilitated serological study of the antigen. Absorption analysis indicated that the antigen was restricted to Meth A; it could not be detected in normal or fetal BALB/c tissue MuLV+ or MuLV- fibroblast lines, 12 syngeneic or allogeneic sarcomas, or normal lymphoid cells from 13 different inbred mouse strains.
Inflammatory Abdominal Aortic Aneurysm
Authors: David B. Hellmann, David J. Grand, Julie A. Freischlag
Journal: JAMA (2007)

Inflammatory abdominal aortic aneurysm (AAA) accounts for 5% to 10% of all cases of AAA and differs from typical atherosclerotic AAA in many important ways. Although both inflammatory and atherosclerotic AAA most commonly affect the infrarenal portion of the abdominal aorta, patients with the inflammatory variant are younger and usually symptomatic, chiefly from back or abdominal pain. Unlike patients with atherosclerotic AAA, most with the inflammatory variant have an elevated erythrocyte sedimentation rate or abnormalities of other serum inflammatory markers. Computed tomography and magnetic resonance imaging are both sensitive for demonstrating the cuff of soft tissue inflammation surrounding the aneurysm that is characteristic of inflammatory AAA. In contrast to atherosclerotic AAA, the inflammatory variant is characterized pathologically by marked thickening of the aneurysm wall, fibrosis of the adjacent retroperitoneum, and rigid adherence of the adjacent structures to the anterior aneurysm wall. An extraordinary expansion of the adventitia due to inflammation also distinguishes inflammatory from atherosclerotic AAA. Although the pathogenesis of inflammatory AAA appears to involve an immune response localized to the vessel wall, the etiology of the inflammatory reaction is unknown. Inflammatory AAA is almost never associated with inflammation of other arteries. Male sex and smoking, the main risk factors for atherosclerotic AAA, are even stronger risk factors for the inflammatory variant. Smoking cessation is the first step of medical therapy. Corticosteroids or immunosuppressive therapies may also have roles. Although inflammatory AAA appears less likely to rupture than atherosclerotic AAA, surgical intervention appears prudent once the diameter of the aneurysm exceeds 5.5 cm. Knowing the features of inflammatory AAA should allow physicians to distinguish it from atherosclerotic AAA or from systemic vasculitis and to treat it with the appropriate combination of medical and surgical therapies.
Ecteinascidin-743 (ET-743) for Chemotherapy-Naive Patients With Advanced Soft Tissue Sarcomas: Multicenter Phase II and Pharmacokinetic Study
Authors: R. Garcia-Carbonero, J.G. Supko, R.G. Maki, J. Manola, D.P. Ryan, D. Harmon, T.A. Puchalski, G. Goss, M.V. Seiden, A. Waxman, M.T. Quigley, T. Lopez, M.A. Sancho, J. Jimeno, C. Guzman, G.D. Demetri
Journal: Journal of Clinical Oncology (2005)

Purpose To evaluate the response rate, toxicity profile, and pharmacokinetics of ecteinascidin-743 (ET-743) as first-line therapy in patients with unresectable advanced soft tissue sarcoma (STS). Patients and Methods Thirty-six patients with STS were enrolled onto the study between September 1999 and August 2000. Patients were treated with 1.5 mg/m 2 of ET-743 given as a 24-hour continuous intravenous (IV) infusion every 21 days. Pharmacokinetic sampling was performed in 23 patients. Results One complete and five partial responses were achieved in 35 assessable patients for an overall response rate of 17.1% (95% CI, 6.6% to 33.6%). In addition, one patient had a minor response, leading to an overall clinical benefit of 20%. Neutropenia and transaminitis were the main grade 3 to 4 toxicities, which occurred in 33% and 36% of the patients. The estimated 1-year progression-free and overall survival rates were 21% (95% CI, 11% to 41%) and 72% (95% CI, 59% to 88%), respectively. Total body clearance (L/h) was not significantly correlated with body-surface area (r = −0.28; P = .21). Mild hepatic impairment or the extent of prior cytotoxic therapy does not seem to contribute significantly to the high interpatient variability (49%) in the clearance of this drug. Severity of treatment-related toxicity was not correlated with pharmacokinetic variables. Conclusion ET-743 demonstrates clinical activity as first-line therapy against STS with acceptable toxicity. Additional studies to establish empirical dosing guidelines may be necessary to improve the safety of the drug in patients with varying degrees of hepatic dysfunction and definitively establish the role of ET-743 for patients with these malignancies.
Talent identification and development in children with reference to India
Authors: G L Khanna
Journal: British Journal of Sports Medicine (2010)

Talent identification is an ongoing process. Talent is measured by the rate of improvement in the training situation. Various researchers have indicated that it can be classified into three stages. First phase: of talent identification is below 10–12 years of age. The second: stage of talent identification would need to be carried out between 13 and 16 years of age. Third stage: selected athletes are ultimately directed to elite junior programmes. The third phase of talent identification is mainly concerned with high calibre athletes for example, national team members. Selection of Indian talent is based on various scheme run by Government of India. Continuous study and evaluation of scheme children of India has indicated that the initial weight and physiological capacity of talented children is higher. However gain in physical and physiological parameters in trained population was not significantly different. Indicating that most of initial selected children were early maturer or chronological age declared was wrong. The long term development and training, coaching methods can play a better role. During long term training plan of development parameters most sensitive to change during certain periods of physical growth and development needs to be considered. In talent development the skills and physiological capacities relations with other factors at later stages of development needs to be also considered. The observation on growth and development of various parameters in Indian talented children will be discussed.
Consensus statement on the initiation and continuation of tumour necrosis factor blocking therapies in rheumatoid arthritis
Authors: J. S Smolen
Journal: Annals of the Rheumatic Diseases (2000)

This group of rheumatologists gathered in Vienna out of concern about the absence of a uniform view and guidance on the introduction of tumour necrosis factor (TNF)-blocking therapies in our clinics. With our growing experience, evaluation of drug treatment of rheumatoid arthritis (RA), and previous participation in consensus statements,1 we have had the opportunity of discussing the accrued knowledge as well as personal experiences in the use of TNF-blocking agents and of formulating our jointly shared views on:



For the present, TNF blockade should be reserved for patients with RA whose symptoms and signs are resistant to disease modifying antirheumatic drug (DMARD) treatment. It is generally agreed that all patients with active disease should be treated with DMARDs, as such treatment ameliorates symptoms and slows progression of structural damage.2 However, long term efficacy of DMARDs is limited and toxicity accumulates.3 Currently, two TNF-blocking agents, etanercept and infliximab, have received regulatory authority approval for the treatment of RA. Both compounds, alone or in combination with methotrexate, have proved to be successful in significantly reducing inflammatory activity …
Controlled trial of dexamethasone and mannitol for the cerebral oedema of fulminant hepatic failure.
Authors: J Canalese, A E Gimson, C Davis, P J Mellon, M Davis, R Williams
Journal: Gut (1982)

A controlled trial of 44 patients was undertaken to evaluate the use of dexamethasone (32 mg stat, 8 mg qds) in preventing, and intravenous mannitol (1 g/kg) in reversing the cerebral oedema of fulminant hepatic failure. Diagnosis of cerebral oedema was based on intracranial pressure recordings or the presence of defined clinical signs. Cerebral oedema developed in 34 patients with similar frequency in those treated with and without dexamethasone (16 of 21 and 18 of 23 respectively). In those 34 patients episodes of cerebral oedema resolved significantly more frequently in the 17 patients who received mannitol than in the 17 patients who did not (44 of 53 and 16 of 17 respectively, p less than 0.001). Dexamethasone did not affect survival but among patients who developed cerebral oedema those who received mannitol had a significantly better survival than those who did not receive it (47.1% and 5.9% respectively, p 0.008, Fisher's one-tail test).
Impact of reinduction regimens for relapsed and refractory acute lymphoblastic leukemia in adults
Authors: Jeanna L. Welborn
Journal: American Journal of Hematology (1994)

The clinical outlook for adults with acute lymphoblastic leukemia (ALL) has improved with the use of intensive chemotherapy. Complete remissions (CR) are achieved in 80% of adults but the majority relapse on maintenance chemotherapy and a few exhibit primary resistance to induction therapy. This report compares the various salvage treatments and provides guidance in selecting a regimen with the optimum clinical outcome. Regimens using high-dose ara-C (HDAC) in combination with mitoxantrone, amsacrine, or idarubicin are superior to HDAC alone or with L-asparaginase. The sequential administration of methotrexate and L-asparaginase is equally effective. The duration of second CR is short for all chemotherapeutic regimens.
State anxiety and subjective well-being responses to acute bouts of aerobic exercise in patients with depressive and anxiety disorders
Authors: J Knapen, E Sommerijns, D Vancampfort, P Sienaert, G Pieters, P Haake, M Probst, J Peuskens
Journal: British Journal of Sports Medicine (2008)

Acute aerobic exercise is associated with a reduction in state anxiety and an improvement in subjective well-being. The objective of the present study was to contrast the effects of aerobic exercise at self-selected intensity versus prescribed intensity on state anxiety and subjective well-being (negative affect, positive well-being and fatigue) in patients with depressive and/or anxiety disorders. In addition, the potential impact of heart rate feedback was assessed.Nineteen men and 29 women performed three test conditions on a bicycle ergometer during 20 minutes: two tests at self-selected intensity; one with and another without heart rate feedback, and a third test at the prescribed intensity of 50% of the maximal heart rate reserve according to Karvonen. Tests were executed in random order. State anxiety and subjective well-being were evaluated using the state anxiety inventory and the subjective exercise experiences scale.After 20 minutes cycling, patients showed significantly decreased state anxiety and negative affect in the three conditions. The magnitude of the reduction did not differ significantly between the three conditions. Only cycling at self-selected intensity enhanced positive well-being. Cycling at 50% of the maximal heart rate reserve decreased fatigue, whereas cycling at self-selected intensity increased fatigue.The response in state anxiety and negative affect was unaffected by the type of aerobic exercise. Self-selected intensity influenced exercise-induced changes in positive well-being and fatigue in a positive and negative way, respectively.
Organization of intra-amygdaloid circuitries in the rat: an emerging framework for understanding functions of the amygdala
Authors: Asla Pitkänen, Vesa Savander, Joseph E. LeDoux
Journal: Trends in Neurosciences (1997)

The amygdala is located in the medial aspects of the temporal lobe. In spite of the fact that the amygdala has been implicated in a variety of functions, ranging from attention to memory to emotion, it has not attracted neuroscientists to the same extent as its laminated neighbours, in particular the hippocampus and surrounding cortex. However, recently, principles of information processing within the amygdala, particularly in the rat, have begun to emerge from anatomical, physiological and behavioral studies. These findings suggest that after the stimulus enters the amygdala, the highly organized intra-amygdaloid circuitries provide a pathway by which the representation of a stimulus becomes distributed in parallel to various amygdaloid nuclei. As a consequence, the stimulus representation may become modulated by different functional systems, such as those mediating memories from past experience or knowledge about ongoing homeostatic states. The amygdaloid output nuclei, especially the central nucleus, receive convergent information from several other amygdaloid regions and generate behavioral responses that presumably reflect the sum of neuronal activity produced by different amygdaloid nuclei.
A Role for the Endothelium in Vascular Calcification
Authors: Yucheng Yao, Medet Jumabay, Albert Ly, Melina Radparvar, Mark R. Cubberly, Kristina I. Boström
Journal: Circulation Research (2013)

Vascular calcification is a regulated process that involves osteoprogenitor cells and frequently complicates common vascular disease, such as atherosclerosis and diabetic vasculopathy. However, it is not clear whether the vascular endothelium has a role in contributing osteoprogenitor cells to the calcific lesions.To determine whether the vascular endothelium contributes osteoprogenitor cells to vascular calcification.In this study, we use 2 mouse models of vascular calcification, mice with gene deletion of matrix Gla protein, a bone morphogenetic protein (BMP)-inhibitor, and Ins2Akita/+ mice, a diabetes model. We show that enhanced BMP signaling in both types of mice stimulates the vascular endothelium to contribute osteoprogenitor cells to the vascular calcification. The enhanced BMP signaling results in endothelial-mesenchymal transitions and the emergence of multipotent cells, followed by osteoinduction. Endothelial markers colocalize with multipotent and osteogenic markers in calcified arteries by immunostaining and fluorescence-activated cell sorting. Lineage tracing using Tie2-Gfp transgenic mice supports an endothelial origin of the osteogenic cells. Enhancement of matrix Gla protein expression in Ins2Akita/+ mice, as mediated by an Mgp transgene, limits the generation of multipotent cells. Moreover, matrix Gla protein-depleted human aortic endothelial cells in vitro acquire multipotency rendering the cells susceptible to osteoinduction by BMP and high glucose.Our data suggest that the endothelium is a source of osteoprogenitor cells in vascular calcification that occurs in disorders with high BMP activation, such as deficiency of BMP-inhibitors and diabetes mellitus.
Phagocytic properties and organelle motility of pulmonary macrophages from smokers and nonsmokers estimated in vitro by magnetometric means
Authors: V Im Hof, M Klauser, P Gehr
Journal: European Respiratory Journal (1990)

Monolayer cultures of pulmonary macrophages (PM) from 11 smokers (S) and 9 nonsmokers (NS) were incubated with submicrometric ferromagnetic Fe3O4 particles for one hour. After magnetization by an externally applied pulse magnetic field, the aligned Fe3O4 particles, located in the phagosomes and secondary lysosomes of the PM, emanated a remanent magnetic field which decayed with time. The initial field strength, B0, which is proportional to the amount of phagocytosed Fe3O4 particles, was 13.24 nT (SE 0.79 nT) in S and 11.74 nT (SE 1.39 nT) in NS. Ten nT correspond to roughly 4 micrograms Fe3O4. The initial rate of decay of the remanent field (during the first 60 s after magnetization), lambda 0, is proportional to the rate of particle misalignment. Therefore, lambda 0, is hypothesized to be an estimate of organelle motility. It was found to be the same in S and in NS, being 3.14 x 10(-3).s-1 (SE 0.18 x 10(-3).s-1) in S and 3.17 x 10(-3).s-1) (SE 0.22 x 10(-3).s-1) in NS. These results suggest that, in vitro, there is no difference in phagocytic activity and organelle motility in PM from S and NS.
Why measure thiopurine methyltransferase activity? Direct administration of 6-thioguanine might be the alternative for 6-mercaptopurine or azathioprine
Authors: D de JONG
Journal: Gut (2001)

Editor,—6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) are effective in inflammatory bowel disease (IBD), mainly by their active 6-thioguanine (6-TG) metabolites. Efficacy and also myelotoxicity of 6-MP and AZA seem to be related to the 6-TG levels achieved. Instead of activation to 6-thioguanine nucleotides, 6-MP and AZA can be inactivated to 6-methylmercaptopurine (6-MMP) by the enzyme thiopurine methyltransferase (TPMT). High interindividual variability in TPMT activity is known. Therefore, measuring TPMT activity could be …