tbuckley/cabot-search huggingface dataset:
Hypermethylation of the<i>GABRE∼miR-452∼miR-224</i>Promoter in Prostate Cancer Predicts Biochemical Recurrence after Radical Prostatectomy
Authors: Helle Kristensen, Christa Haldrup, Siri Strand, Kamilla Mundbjerg, Martin M. Mortensen, Kasper Thorsen, Marie Stampe Ostenfeld, Peter J. Wild, Christian Arsov, Wolfgang Goering, Tapio Visakorpi, Lars Egevad, Johan Lindberg, Henrik Grönberg, Søren Høyer, Michael Borre, Torben F. Ørntoft, Karina D. Sørensen
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Available tools for prostate cancer diagnosis and prognosis are suboptimal and novel biomarkers are urgently needed. Here, we investigated the regulation and biomarker potential of the GABRE∼miR-452∼miR-224 genomic locus. Experimental Design: GABRE/miR-452/miR-224 transcriptional expression was quantified in 80 nonmalignant and 281 prostate cancer tissue samples. GABRE∼miR-452∼miR-224 promoter methylation was determined by methylation-specific qPCR (MethyLight) in 35 nonmalignant, 293 prostate cancer [radical prostatectomy (RP) cohort 1] and 198 prostate cancer tissue samples (RP cohort 2). Diagnostic/prognostic biomarker potential of GABRE∼miR-452∼miR-224 methylation was evaluated by ROC, Kaplan–Meier, uni- and multivariate Cox regression analyses. Functional roles of miR-224 and miR-452 were investigated in PC3 and DU145 cells by viability, migration, and invasion assays and gene-set enrichment analysis (GSEA) of posttransfection transcriptional profiling data. Results: GABRE∼miR-452∼miR-224 was significantly downregulated in prostate cancer compared with nonmalignant prostate tissue and had highly cancer-specific aberrant promoter hypermethylation (AUC = 0.98). Functional studies and GSEA suggested that miR-224 and miR-452 inhibit proliferation, migration, and invasion of PC3 and DU145 cells by direct/indirect regulation of pathways related to the cell cycle and cellular adhesion and motility. Finally, in uni- and multivariate analyses, high GABRE∼miR-452∼miR-224 promoter methylation was significantly associated with biochemical recurrence in RP cohort 1, which was successfully validated in RP cohort 2. Conclusion: The GABRE∼miR-452∼miR-224 locus is downregulated and hypermethylated in prostate cancer and is a new promising epigenetic candidate biomarker for prostate cancer diagnosis and prognosis. Tumor-suppressive functions of the intronic miR-224 and miR-452 were demonstrated in two prostate cancer cell lines, suggesting that epigenetic silencing of GABRE∼miR-452∼miR-224 may be selected for in prostate cancer. Clin Cancer Res; 20(8); 2169–81. ©2014 AACR.
Long-Term Update of US GI Intergroup RTOG 98-11 Phase III Trial for Anal Carcinoma: Survival, Relapse, and Colostomy Failure With Concurrent Chemoradiation Involving Fluorouracil/Mitomycin Versus Fluorouracil/Cisplatin
Authors: Leonard L. Gunderson, Kathryn A. Winter, Jaffer A. Ajani, John E. Pedersen, Jennifer Moughan, Al B. Benson, Charles R. Thomas, Robert J. Mayer, Michael G. Haddock, Tyvin A. Rich, Christopher G. Willett
Journal: Journal of Clinical Oncology (2012)

Purpose On initial publication of GI Intergroup Radiation Therapy Oncology Group (RTOG) 98-11 [A Phase III Randomized Study of 5-Fluorouracil (5-FU), Mitomycin, and Radiotherapy Versus 5-Fluorouracil, Cisplatin and Radiotherapy in Carcinoma of the Anal Canal], concurrent chemoradiation (CCR) with fluorouracil (FU) plus mitomycin (MMC) decreased colostomy failure (CF) when compared with induction plus concurrent FU plus cisplatin (CDDP), but did not significantly impact disease-free survival (DFS) or overall survival (OS) for anal canal carcinoma. The intent of the updated analysis was to determine the long-term impact of treatment on survival (DFS, OS, colostomy-free survival [CFS]), CF, and relapse (locoregional failure [LRF], distant metastasis) in this patient group. Patients and Methods Stratification factors included sex, clinical node status, and primary size. DFS and OS were estimated univariately by the Kaplan-Meier method, and treatment arms were compared by log-rank test. Time to relapse and CF were estimated by the cumulative incidence method and treatment arms were compared by using Gray's test. Multivariate analyses used Cox proportional hazard models to test for treatment differences after adjusting for stratification factors. Results Of 682 patients accrued, 649 were analyzable for outcomes. DFS and OS were statistically better for RT + FU/MMC versus RT + FU/CDDP (5-year DFS, 67.8% v 57.8%; P = .006; 5-year OS, 78.3% v 70.7%; P = .026). There was a trend toward statistical significance for CFS (P = .05), LRF (P = .087), and CF (P = .074). Multivariate analysis was statistically significant for treatment and clinical node status for both DFS and OS, for tumor diameter for DFS, and for sex for OS. Conclusion CCR with FU/MMC has a statistically significant, clinically meaningful impact on DFS and OS versus induction plus concurrent FU/CDDP, and it has borderline significance for CFS, CF, and LRF. Therefore, RT + FU/MMC remains the preferred standard of care.
Continuous assessment of regional myocardial perfusion in dogs using krypton-81m.
Authors: A P Selwyn, T Jones, H Turner, T Pratt, J Clark, P Lavender
Journal: Circulation Research (1978)

Krjplon-81m has been continuously eluted in 5% dextrose from a cyclotron-made rubidium-81 generator.The unique physical properties of this inert freely diffusible gas (half-life 13 seconds) have allowed the development of a technique for the constant infusion of this tracer into the aortic sinuses of 25 dogs.Theoretical considerations suggest that an equilibrium of "*Kr activity in the myocardium is principally dependent on blood flow.Experiments have tested the delivery of this indicator and have recorded quantitative high spatial resolution images of the heart with a gamma camera and digital computer.The systematic error was determined by comparing changes in regional blood flow (in ml/g per min, using an electromagnetic flow probe) and changes in calculated flow (ml/g per min) using the regional activity of 81m Kr (P = < 0.001; r = 0.97; y = 908 X + 0.105; n = 60).The random error and uncertainties concerning mixing and streaming of the indicator were tested by repeating measurements with alterations in heart rate, blood pressure, coronary flow, and total myocardial *""Kr activity using different interventions (reproducibility, P = 0.001, r = 0.982; y = 0.982x + -0 . 2 5 7 , n = 100 observations).Any quantification of changes in the myocardial activity of 81m Kr must consider the stability of the arterial concentration of this indicator and washout of """Kr at high values of myocardial blood flow.This ultra-short-lived radionuclide will, however, provide an assessment of changes in the distribution of regional myocardial perfusion.
The main lytic factor of Trypanosoma brucei brucei in normal human serum is not high density lipoprotein.
Authors: J Raper, V Nussenzweig, S Tomlinson
Journal: The Journal of Experimental Medicine (1996)

Natural immunity of humans to the cattle pathogen Trypanosoma brucei brucei has been attributed to the presence in normal human serum (NHS) of lytic factors for the parasites. We and others have shown that NHS contains two trypanolytic factors (herein termed TLF1 and TLF2) that can be separated by gel filtration. TLF1 copurifies with a subclass of high density lipoprotein (HDL), whereas TLF2 has a much higher molecular weight and does not appear to be a lipoprotein. We find that the trypanolytic activity of purified TLF1 is totally inhibited by exogenous haptoglobin (Hp) at concentrations (0.1 mg/ml) lower than those present in NHS (0.2-2 mg/ml). In contrast, exogenous Hp (up to 2.5 mg/ml) has no effect on the lytic activity of either NHS or isolated TLF2. Hp-depleted sera from patients with intravascular hemolysis is severalfold more trypanolytic than NHS. These sera contain only TLF1, and their lytic activity is totally abolished upon the addition of Hp (0.1 mg/ml). When NHS containing different Hp allotypes is fractionated by gel filtration, TLF1 activity is either revealed or remains masked, depending on whether it coelutes with Hp. Masked TLF1 activity in the column fractions is revealed if Hp is removed by density gradient ultracentrifugation. We conclude that endogenous Hp inhibits TLF1 activity, and that TLF2 is the main trypanolytic factor in NHS.
Phase II Studies of Gemcitabine and Cisplatin in Heavily and Minimally Pretreated Metastatic Breast Cancer
Authors: Helen K. Chew, James H. Doroshow, Paul Frankel, Kim A. Margolin, George Somlo, Heinz-Josef Lenz, Michael Gordon, Wu Zhang, Dongyun Yang, Christy Russell, Darcy Spicer, Tim Synold, Robert Bayer, Alexander Hantel, Patrick J. Stiff, Merry L. Tetef, David R. Gandara, Kathy S. Albain
Journal: Journal of Clinical Oncology (2009)

Cisplatin and gemcitabine have single-agent activity in metastatic breast cancer, and preclinical data support synergy of the combination. Two parallel, phase II trials were conducted to evaluate the response rate, response duration, and toxicities of the combination. Genetic polymorphisms were analyzed for correlation with outcomes.Eligible women had measurable disease and heavily or minimally pretreated metastatic breast cancer. The heavily pretreated protocol required prior anthracycline and taxane therapy; cisplatin as part of high-dose therapy was allowed. All patients received cisplatin 25 mg/m(2) on days 1 through 4 and gemcitabine 1,000 mg/m(2) on days 2 and 8 of a 21-day cycle with prophylactic granulocyte colony-stimulating factor in the heavily pretreated group. Sera from a subset of patients were evaluated by polymerase chain reaction restriction fragment length polymorphism for polymorphisms in 10 genes of interest.Of 136 women enrolled, 74 were heavily pretreated. Both protocols accrued to their two-stage design. The response rate for both the heavily and minimally pretreated cohorts was 26%, and the median durations of response were 5.3 and 5.9 months, respectively. In a multivariate analysis, hormone receptor-negative disease was associated with a higher response rate. The most common grades 3 or 4 toxicities were thrombocytopenia (71%), neutropenia (66%), and anemia (38%). In a subset of 55 patients, the xeroderma pigmentosum group D (XPD)-751, x-ray cross-complementing group 3 (XRCC3) and cytidine deaminase polymorphisms were significantly associated with clinical outcomes.Combination cisplatin and gemcitabine is active in metastatic breast cancer regardless of prior therapy. Genetic polymorphisms may tailor which patients benefit from this regimen.
Sertraline Treatment of Major Depression in Patients With Acute MI or Unstable Angina
Authors: Alexander H. Glassman
Journal: JAMA (2002)

LTHOUGH A CONNECTION BEtween mood and the heart has been a part of language and literature from antiquity, for some time scientific verification was lacking.In the mid 1970s, epidemiologists began to report consistent associations between depression and cardiovascular morbidity and mortality.[12][13][14][15][16]
High Dose ACNU Chemotherapy with Autologous Bone Marrow Transplantation for Human Malignant Brain Tumors
Authors: J. Yamashita, K. Shoin, M. Soma
Journal: Neuro-Oncology (1991)

We investigated the usefullness of autologous bone marrow transplantation to alleviate bone marrow suppression after adnimistration of high dose ACNU. Eight cases with malignant glioma were treated by this method. Bone marrow blood (10ml/ kg) was aspirated from the iliac bones under general anesthesia. ACNU 8–12 mg/kg was given intravenously. Three days after the administration of ACNU, the autologous bone marrow cells (1–9 × 108 viable cells) were quickly thawed and intravenously administered. The average nadir of WBC was on the 21st day. The average nadir of PLT was on the 20th day. One case with recurrent glioblastoma died of septicemia as a direct complication of this treatment. In summary, high dose ACNU chemotherapy combined with autologous bone marrow transplantation could be a useful option of treatment for malignant brain tumors.
1260 SPECIFIC INHIBITION OF THE REDOX ACTIVITY OF THE MULTIFUNCTIONAL APE1/REF-1 PROTEIN BY E3330 BLOCKS TNF-A-INDUCED ACTIVATION OF IL-8 PRODUCTION IN HEPATIC CELL LINES
Authors: E. Codarin, L. Cesaratto, A. Caragnano, S. Bellentani, M.R. Kelley, C. Tiribelli, G. Tell
Journal: Journal of Hepatology (2011)
ASSOCIATION OF SERUM NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN AND CYSTATIN-C WITH ARTERIAL STIFFNESS IN PATIENTS WITH HEART FAILURE
Authors: Stavroula Michalea, Gerasimos Siasos, Dimitris Tousoulis, Evangelos Oikonomou, Christina Kollia, Stamatios Kioufis, Konstantinos Zisimos, Konstantinos Maniatis, Antigoni Miliou, Nikolaos Gouliopoulos, Panagiotis Tourikis, Athanasios G. Papavassiliou, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2012)
Prognostic Factors and Survival in 324 Patients with Pancreatic Endocrine Tumor Treated at a Single Institution
Authors: Sara Ekeblad, Britt Skogseid, Kristina Dunder, Kjell Öberg, Barbro Eriksson
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Unequivocal pathologic markers for the prognosis of pancreatic endocrine tumors are often lacking. Suggestions for prognostic guidance include the WHO classification. Recently, a tumor-node-metastasis (TNM) staging system was proposed. We evaluate this system, as well as assess other potential prognostic factors such as tumor Ki67, size, endocrine syndrome, heredity, body mass index (BMI), and plasma chromogranin A, in a large patient material treated at a single institution. Experimental Design: A total of 324 patients with pancreatic endocrine tumor, consecutively diagnosed and treated at a tertiary referral center, were retrospectively evaluated. Median follow-up was 54 months (range, 1-423 months). Patient and tumor data were extracted from medical records. Univariate and multivariate analyses were done to recognize factors of prognostic value. Results: The median overall survival was 99 months (95% confidence interval, 81-117). Five- and 10-year survival rates were 64% and 44%, respectively. In univariate analysis, TNM stage, radical surgery, WHO classification, nonfunctioning tumor, Ki67 ≥2%, chromogranin A ≥3 times the upper normal limit, BMI &amp;lt;20 kg/m2, sporadic tumor, tumor size, and referral from our primary uptake area had a significant prognostic effect. In multivariate analysis, TNM stage, WHO classification, radical surgery, and Ki67 ≥2% retained their significance. Having a nonfunctioning tumor was not an independent marker of poor prognosis and neither was heredity. Conclusions: The recently suggested TNM staging system emerged as a useful clinical tool.
Frontiers in Nephrology
Authors: Gordon Letts, Joseph Loscalzo
Journal: Journal of the American Society of Nephrology (2007)

Chimeric molecules are single-chemical entities that possess at least two separate functions. In the design of new chimeric medicines, the two biologic actions are often designed to be synergistic and, thereby, complement each other in activating a specific target, such as a gene, a receptor, or an enzyme. In most chimeric molecules, one functionality is designed to provide a high affinity to a designated site, thereby permitting the targeting of the second functionality, which is usually nonspecific. This review focuses on the development of two classes of chimeric medicines, anti-inflammatory and diuretic chimeric agents, both of which incorporate a nitric oxide moiety into the parent pharmacophore.
Effect of Membrane Potential on the Initiation of Acetylcholine-Induced Ca <sup>2+</sup> Transients in Isolated Guinea Pig Coronary Myocytes
Authors: Vladimir Y. Ganitkevich, Gerrit Isenberg
Journal: Circulation Research (1996)

The muscarinic stimulation of single voltage-clamped coronary arterial smooth muscle cells of the guinea pig was used to evaluate the effect of membrane potential on the inositol 1,4,5-tris-phosphate (IP3)-mediated changes of ionized [Ca2+] in the cytoplasm (Ca2+ transient) measured with indo 1. When applied at the membrane potential of -50 mV, 10 micromol/L acetylcholine (ACh) induced a [Ca2+]i increase after the mean latency of 2.6+/-0.9 s. The latency was reduced to 1.1 +/- 0.3 s when the same dose was applied at a holding potential of +50 mV. In paired experiments in the same cells, the latency of response at +50 mV was reduced by a factor of 2.2 +/- 0.3 compared with the response at -50 mV. Supramaximal [ACh] (100 micromol/L) induced Ca2+ transients with a 0.4 +/- 0.1-s latency, which was independent of membrane potential. When applied repetitively at -50 mV, ACh induced Ca2+ transients with a progressively reduced amplitude and slower rate of rise. Depolarization to +50 mV accelerated the rate of rise of the Ca2+ transient by a factor of 3.4 +/- 0.4 without affecting the amplitude. The modulation of the initiation of Ca2+ transient by a 100-mV depolarization can be explained by an approximately threefold increase in the rate of IP3 accumulation.
Unique Metabolic Features of Stem Cells, Cardiomyocytes, and Their Progenitors
Authors: John Antonydas Gaspar, Michael Xavier Doss, Jan Georg Hengstler, Cristina Cadenas, Jürgen Hescheler, Agapios Sachinidis
Journal: Circulation Research (2014)

Recently, growing attention has been directed toward stem cell metabolism, with the key observation that the plasticity of stem cells also reflects the plasticity of their energy substrate metabolism. There seems to be a clear link between the self-renewal state of stem cells, in which cells proliferate without differentiation, and the activity of specific metabolic pathways. Differentiation is accompanied by a shift from anaerobic glycolysis to mitochondrial respiration. This metabolic switch of differentiating stem cells is required to cover the energy demands of the different organ-specific cell types. Among other metabolic signatures, amino acid and carbohydrate metabolism is most prominent in undifferentiated embryonic stem cells, whereas the fatty acid metabolic signature is unique in cardiomyocytes derived from embryonic stem cells. Identifying the specific metabolic pathways involved in pluripotency and differentiation is critical for further progress in the field of developmental biology and regenerative medicine. The recently generated knowledge on metabolic key processes may help to generate mature stem cell-derived somatic cells for therapeutic applications without the requirement of genetic manipulation. In the present review, the literature about metabolic features of stem cells and their cardiovascular cell derivatives as well as the specific metabolic gene signatures differentiating between stem and differentiated cells are summarized and discussed.
Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review
Authors: Nienke ter Haar, Helen Lachmann, Seza Özen, Pat Woo, Yosef Uziel, Consuelo Modesto, Isabelle Koné-Paut, Luca Cantarini, Antonella Insalaco, Bénédicte Neven, Michael Hofer, Donato Rigante, Sulaiman Al-Mayouf, Isabelle Touitou, Romina Gallizzi, Efimia Papadopoulou-Alataki, Silvana Martino, Jasmin Kuemmerle-Deschner, Laura Obici, Nicolae Iagaru, Anna Simon, Susan Nielsen, Alberto Martini, Nicolino Ruperto, Marco Gattorno, Joost Frenkel
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To evaluate the response to treatment of autoinflammatory diseases from an international registry and an up-to-date literature review. <h3>Methods</h3> The response to treatment was studied in a web-based registry in which clinical information on anonymised patients with autoinflammatory diseases was collected retrospectively as part of the Eurofever initiative. Participating hospitals included paediatric rheumatology centres of the Paediatric Rheumatology International Trial Organisation network and adult centres with a specific interest in autoinflammatory diseases. The following diseases were included: familial Mediterranean fever (FMF), cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor (TNF)-receptor associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), pyogenic arthritis pustulosis acne (PAPA) syndrome, deficiency of interleukin-1 receptor antagonist (DIRA), NLRP12-related periodic fever and periodic fever aphthosis pharyngitis adenitis (PFAPA) syndrome. Cases were independently validated by experts for each disease. A literature search regarding treatment of the abovementioned diseases was also performed using Medline and Embase. <h3>Results</h3> 22 months from the beginning of the enrolment, complete information on 496 validated patients was available. Data from the registry in combination with evidence from the literature confirmed that colchicine is the treatment of choice for FMF and IL-1 blockade for DIRA and CAPS. Corticosteroids on demand probably represent a valid therapeutic strategy for PFAPA, but also for MKD and TRAPS. Patients with poorly controlled MKD, TRAPS, PAPA or FMF may benefit from IL-1 blockade; anti-TNF treatment may represent a possible valuable alternative. <h3>Conclusions</h3> In the absence of high-grade evidence, these results could serve as a basis for therapeutic guidelines and to identify candidate drugs for future therapeutic trials.
Receptor for immunoglobulin Fc on pathogenic but not on nonpathogenic protozoa of the Trypanosomatidae.
Authors: I K De Miranda-Santos, A Campos-Neto
Journal: The Journal of Experimental Medicine (1981)

Members of the Trypanosomatidae were studied for their ability to acquire host IgG through a possible Fc receptor. A simple rosette test was devised in which the different species and forms of protozoa were mixed with SRBC sensitized with subagglutinating does of IgG, IgM, and F (ab') 2 anti-SRBC, and the pelleted mixture was observed for the number of clumps (rosettes) formed between the parasites and SRBC. Rosettes were formed between parasites and SRBC sensitized with IgG but not with IgM or F(ab')2, indicating the presence of a receptor for IgG Fc. The specificity of this receptor for Fc was confirmed by inhibition experiments with normal rabbit aggregated gammaglobulins or with purified normal rabbit Fc. The receptor is sensitive to treatment with trypsin but regenerates after a short period of incubation (1 h), which indicates that it is synthesized by the parasite itself. Interesting was the observation that only pathogenic members of the Trypanosomatidae formed rosettes with sensitized SRBC. In none of the nonpathogenic forms studied could we demonstrate the Fc receptor. Also important was the finding that freshly isolated blood stream forms of Trypanosoma cruzi from infected mice did not form rosettes. However, after trypsinization, these forms clearly displayed the ability to do so, possibly indicating a previous acquisition of the host IgG by the parasites in the mouse blood stream. These findings point to a possible and important means of parasite evasion of the host immune response by masking their surface with host IgG.