tbuckley/cabot-search huggingface dataset:
Impact of Common Medications on Serum Total Prostate-Specific Antigen Levels: Analysis of the National Health and Nutrition Examination Survey
Authors: Steven L. Chang, Lauren C. Harshman, Joseph C. Presti
Journal: Journal of Clinical Oncology (2010)

Purpose Previous studies suggest that some common medications alter prostate-specific antigen (PSA) levels. It remains unclear whether these reported medication effects are due to clinicodemographic factors or concurrent use of other medications. We investigated the impact of individual and combinations of common medications on PSA in a large cross-sectional study of the United States population. Patients and Methods The study included men ≥ 40 years old without prostate cancer from the 2003 to 2004 and 2005 to 2006 cycles of the National Health and Nutrition Examination Survey (NHANES). Men with recent prostate manipulation, prostatitis, and those on hormone therapy were excluded. Weighted multivariate linear regression was performed on log-transformed total PSA to determine the effect of the 10 most commonly prescribed medication classes, adjusting for potential confounders including demographics, clinical characteristics, physical examination, laboratory studies, and duration of medication use. Results In total, 1,864 men met inclusion criteria. Nonsteroidal anti-inflammatory drug (NSAID; P = .03), statin (P = .01), and thiazide diuretic (P = .025) intake was inversely related to PSA levels. Five years of NSAID, statin, and thiazide diuretic use was associated with PSA levels lower by 6%, 13%, and 26%, respectively. The combination of statins and thiazide diuretics showed the greatest reduction in PSA levels: 36% after 5 years. Concurrent calcium channel blocker use minimizes or negates the inverse relationship of statin use and PSA level. Conclusion We found that men using NSAIDs, statins, and thiazide diuretics have reduced PSA levels by clinically relevant amounts. The impact of regularly consuming these common medications on prostate cancer screening is unknown.
PTEN Up-Regulates the Tumor Metastasis Suppressor Gene <b> <i>Drg-1</i> </b> in Prostate and Breast Cancer
Authors: Sucharita Bandyopadhyay, Sudha K. Pai, Shigeru Hirota, Sadahiro Hosobe, Taisei Tsukada, Kunio Miura, Yukio Takano, Ken Saito, Therese Commes, David Piquemal, Misako Watabe, Steven Gross, Ying Wang, Jodi Huggenvik, Kounosuke Watabe
Journal: Cancer Research (2004)

Abstract PTEN (phosphatase and tensin homologue deleted on chromosome 10) has been shown to be inactivated in a wide variety of cancers, and the role of this gene as a tumor suppressor has been well established. On the other hand, results of recent animal studies as well as clinical evidence indicate that PTEN is also involved in tumor metastasis suppression. Although PTEN is known to play a key role in controlling cell growth and apoptosis, how PTEN exerts the metastasis suppressor function remains largely unknown. Recently, a microarray analysis identified the Drg-1 gene (differentiation related gene 1) as one of the potential targets of PTEN. The Drg-1 gene has been shown to suppress tumor metastasis in animal models of prostate and colon cancer, and the expression of this gene is significantly reduced with advancement of prostate and breast cancers in clinical setting. In this study, we explored the possibility that PTEN controls tumor metastasis by regulating the expression of the Drg-1 gene. Our results indicate that overexpression of PTEN significantly augments the endogenous expression of Drg-1 protein, whereas inhibition of PTEN by small interfering RNA decreases Drg-1 in a dose- and time-dependent manner. We also found that the control of the Drg-1 gene by PTEN seems to be at the transcriptional level, and that a phospho-Akt inhibitor restores the Drg-1 expression, indicating that PTEN controls Drg-1 by an Akt-dependent pathway. Consistent with these results, our immunohistochemical analysis revealed that PTEN expression correlates significantly with Drg-1 in both prostate and breast cancer cases. Furthermore, combination of the two markers, PTEN and Drg-1, emerged as a significantly better predictor of prostate and breast cancer patient survival than either marker alone.
Targeted Antiproliferative Drug Delivery to Vascular Smooth Muscle Cells With a Magnetic Resonance Imaging Nanoparticle Contrast Agent
Authors: Gregory M. Lanza, Xin Yu, Patrick M. Winter, Dana R. Abendschein, Kerry K. Karukstis, Michael J. Scott, Lori K. Chinen, Ralph W. Fuhrhop, David E. Scherrer, Samuel A. Wickline
Journal: Circulation (2002)

Background— Restenosis is a serious complication of coronary angioplasty that involves the proliferation and migration of vascular smooth muscle cells (VSMCs) from the media to the intima, synthesis of extracellular matrix, and remodeling. We have previously demonstrated that tissue factor–targeted nanoparticles can penetrate and bind stretch-activated vascular smooth muscles in the media after balloon injury. In the present study, the concept of VSMC-targeted nanoparticles as a drug-delivery platform for the prevention of restenosis after angioplasty is studied. Methods and Results— Tissue factor–targeted nanoparticles containing doxorubicin or paclitaxel at 0, 0.2, or 2.0 mole% of the outer lipid layer were targeted for 30 minutes to VSMCs and significantly inhibited their proliferation in culture over the next 3 days. Targeting of the nanoparticles to VSMC surface epitopes significantly increased nanoparticle antiproliferative effectiveness, particularly for paclitaxel. In vitro dissolution studies revealed that nanoparticle drug release persisted over one week. Targeted antiproliferative results were dependent on the hydrophobic nature of the drug and noncovalent interactions with other surfactant components. Molecular imaging of nanoparticles adherent to the VSMC was demonstrated with high-resolution T 1 -weighted MRI at 4.7T. MRI 19 F spectroscopy of the nanoparticle core provided a quantifiable approach for noninvasive dosimetry of targeted drug payloads. Conclusions— These data suggest that targeted paramagnetic nanoparticles may provide a novel, MRI-visualizable, and quantifiable drug delivery system for the prevention of restenosis after angioplasty.
Pharmacokinetics of Intermittent Intravenous Cefazolin and Tobramycin in Patients Treated with Automated Peritoneal Dialysis
Authors: HAROLD J. MANLEY, GEORGE R. BAILIE, REGINALD FRYE, LORRAINE D. HESS, M. DONALD MCGOLDRICK
Journal: Journal of the American Society of Nephrology (2000)

Abstract. There is increasing use of intermittent dosing of antibiotics to treat peritoneal dialysis (PD)-related peritonitis. The disposition of intravenous cefazolin and tobramycin was studied in automated PD (APD) patients. Ten patients were recruited and received a single intravenous dose of cefazolin (15 mg/kg) and tobramycin (0.6 mg/kg). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1 to 3 (on cycler), and at the end of dwells 4 to 5 (off cycler) for a 24-h period. Baseline and 24-h urine samples were collected. Pharmacokinetic parameters were calculated using a monoexponential model. Cefazolin and tobramycin half-lives were markedly different on cycler than off cycler (cefazolin on cycler: 10.67 ± 4.66 h; cefazolin off cycler: 23.09 ± 5.6 h; P = 0.001; tobramycin on cycler: 14.27 ± 4.53 h; tobramycin off cycler: 68.5 ± 26.47 h; P &lt; 0.001). Mean serum and dialysate concentrations were above minimum inhibitory concentrations of susceptible organisms throughout the 24-h period for both drugs with intravenous administration. A model was developed to examine serum and dialysate concentrations after intermittent intraperitoneal administration of 15 mg/kg cefazolin and 0.6 mg/kg tobramycin. Model-predicted intraperitoneal cefazolin provides adequate serum and dialysate concentrations for 24 h. Intermittent intraperitoneal tobramycin doses must be 1.5 mg/kg for one exchange during the first day and then given as 0.5 mg/kg thereafter. It is concluded that the current empiric dosing recommendations for PD-related peritonitis may be adequate for cefazolin (15 to 20 mg/kg); however, tobramycin doses must be changed to 1.5 mg/kg intraperitoneally on day 1, then to 0.5 mg/kg intraperitoneally thereafter in APD patients.
ESCMID and ECMM joint guidelines on diagnosis and management of hyalohyphomycosis: Fusarium spp., Scedosporium spp. and others
Authors: A.M. Tortorano, M. Richardson, E. Roilides, A. van Diepeningen, M. Caira, P. Munoz, E. Johnson, J. Meletiadis, Z.-D. Pana, M. Lackner, P. Verweij, T. Freiberger, O.A. Cornely, S. Arikan-Akdagli, E. Dannaoui, A.H. Groll, K. Lagrou, A. Chakrabarti, F. Lanternier, L. Pagano, A. Skiada, M. Akova, M.C. Arendrup, T. Boekhout, A. Chowdhary, M. Cuenca-Estrella, J. Guinea, J. Guarro, S. de Hoog, W. Hope, S. Kathuria, O. Lortholary, J.F. Meis, A.J. Ullmann, G. Petrikkos, C. Lass-Flörl
Journal: Clinical Microbiology and Infection (2014)
Targeting the Insulin-like Growth Factor Receptor-1R Pathway for Cancer Therapy
Authors: Jiping Zha, Mark R. Lackner
Journal: Clinical Cancer Research (2010)

Signaling through the insulin-like growth factor receptor (IGF-1R) is required for neoplastic transformation by a number of oncogenes, and preclinical validation studies have suggested IGF-1R is an attractive target for anticancer therapy. A number of small molecules and antibodies targeting IGF-1R have entered clinical development, and early results have suggested that these agents have generally acceptable safety profiles as single agents. Some evidence of antitumor activity has also been reported. This review highlights key aspects of the IGF-1R signaling pathway that implicate it as an attractive therapeutic target in the management of cancer, as well as some key lessons that have emerged from early clinical development of anti-IGF-1R targeting agents. In addition, we consider the importance of selecting indications characterized by pathological alterations in the signaling pathway, rational selection of combinations based on signaling pathway interactions, and strategies for patient selection based on analysis of predictive biomarkers.
Barium-Induced Automaticity in Relation to Calcium Ions and Norepinephrine in the Rabbit Left Atrium
Authors: NOBORU TODA
Journal: Circulation Research (1970)

Membrane potentials were recorded from a region of the left atrium close to the interatrial septum and from an atrial appendage. Pacemaker activity was induced after exposure to Ba 2+ . The magnitude of the resting potential and of the overshoot decreased with increasing [Ba 2+ ]o, whereas duration of the action potential and rise time increased with increasing [Ba 2+ ]o. Electrical stimulation for 5 sec at 1/sec to left atria showing automaticity produced bradycardia followed by tachycardia. Bradycardia was abolished by atropine; tachycardia was suppressed by propranolol and previous treatment with reserpine. At zero [Ca 2+ ]o, threshold concentrations of Ba 2+ for inducing automaticity were lower than those at normal [Ca 2+ ]o. Ba 2+ markedly prolonged the action potential plateau in solutions deprived of Ca 2+ . The size of the overshoot was increased and the rise time was shortened despite a significant reduction in the resting potential. Ba 2+ partly restored atrial contractility abolished at zero [Ca 2+ ]o. Each electrical discharge evoked an individual contraction, and a sufficiently fast discharge led to summation of the contractions. Pacemaker activity induced by Ba 2+ was suppressed by adding Ca 2+ and Mg 2+ . The threshold potential was raised by Ca 2+ and Mg 2+ . Threshold concentrations of Ba 2+ for inducing automaticity were not influenced by previous treatment with reserpine. It is postulated that Ba 2+ antagonizes the movement of K + across the membrane, resulting in a decrease in the resting potential and a prolongation of the action potential duration, and that Ba 2+ serves as a current-carrying ion at zero [Ca 2+ ]o. It seems unlikely that cardiac norepinephrine participates in pacemaker activity induced by Ba 2+ .
Secondary Rearrangements and Hypermutation Generate Sufficient B Cell Diversity to Mount Protective Antiviral Immunoglobulin Responses
Authors: Constantino López-Macías, Ulrich Kalinke, Marilia Cascalho, Matthias Wabl, Hans Hengartner, Rolf M. Zinkernagel, Alain Lamarre
Journal: The Journal of Experimental Medicine (1999)

Variable (V) region gene replacement was recently implicated in B cell repertoire diversification, but the contribution of this mechanism to antibody responses is still unknown. To investigate the role of V gene replacements in the generation of antigen-specific antibodies, we analyzed antiviral immunoglobulin responses of "quasimonoclonal" (QM) mice. The B cells of QM mice are genetically committed to exclusively express the anti-(4-hydroxy-3-nitrophenyl) acetyl specificity. However, approximately 20% of the peripheral B cells of QM mice undergo secondary rearrangements and thereby potentially acquire new specificities. QM mice infected with vesicular stomatitis virus (VSV), lymphocytic choriomeningitis virus, or poliovirus mounted virus-specific neutralizing antibody responses. In general, kinetics of the antiviral immunoglobulin responses were delayed in QM mice; however, titers similar to control animals were eventually produced that were sufficient to protect against VSV-induced lethal disease. VSV neutralizing single-chain Fv fragments isolated from phage display libraries constructed from QM mice showed VH gene replacements and extensive hypermutation. Thus, our data demonstrate that secondary rearrangements and hypermutation can generate sufficient B cell diversity in QM mice to mount protective antiviral antibody responses, suggesting that these mechanisms might also contribute to the diversification of the B cell repertoire of normal mice.
RUNX3 Attenuates β-Catenin/T Cell Factors in Intestinal Tumorigenesis
Authors: Kosei Ito, Anthony Chee-Beng Lim, Manuel Salto-Tellez, Lena Motoda, Motomi Osato, Linda Shyue Huey Chuang, Cecilia Wei Lin Lee, Dominic Chih-Cheng Voon, Jason Kin Wai Koo, Huajing Wang, Hiroshi Fukamachi, Yoshiaki Ito
Journal: Cancer Cell (2008)
Somatomedin activity in synovial fluid.
Authors: C L Coates, R G Burwell, P J Buttery, G Walker, P M Woodward
Journal: Annals of the Rheumatic Diseases (1977)

Abnormalities of synovial fluid, as a lubricant and nutrient, may have relevance to the causation of certain articular diseases. The somatomedin activity in normal synovial fluid obtained from the knee joint of the ox has been studied and compared with the activity in serum from the same animal. The porcine costal cartilage bioassay of Van den Brande and Du Caju (1974) has been used with the isotopes 35S-sulphate and 3H-thymidine. The mean potency ratio of ox synovial fluid in terms of ox serum for 35S-sulphate incorporation was 0-28 (range 0-19-0-47) and for 3H-thymidine incorporation 0-35 (range 0-21-0-63). A significant correlation was found between the somatomedin activity (as measured by 35S-sulphate incorporation) and the total protein and albumin concentrations in the ox synovial fluids and the ox sera, but there was no significant relationship between the somatomedin potency ratios and the globulin concentrations. The possible relevance of these findings to injury and disease in synovial joint is discussed.
Inhibition of Cd83 Cell Surface Expression during Dendritic Cell Maturation by Interference with Nuclear Export of Cd83 mRNA
Authors: Monika Kruse, Olaf Rosorius, Friedrich Krätzer, Dorian Bevec, Christine Kuhnt, Alexander Steinkasserer, Gerold Schuler, Joachim Hauber
Journal: The Journal of Experimental Medicine (2000)

Dendritic cells (DCs), nature's adjuvant, must mature to sensitize T cells. However, although the maturation process is essential, it is not yet fully understood at the molecular level. In this study, we investigated the course of expression of the unique hypusine-containing protein eukaryotic initiation factor 5A (eIF-5A), which is part of a particular RNA nuclear export pathway, during in vitro generation of human DCs. We show that eIF-5A expression is significantly upregulated during DC maturation. Furthermore, an inhibitor of the hypusine modification, GC7 (N1-guanyl-1,7-diaminoheptane), prevents CD83 surface expression by apparently interfering with nucleocytoplasmic translocation of the CD83 mRNA and, importantly, significantly inhibits DC-mediated T lymphocyte activation. The data presented suggest that CD83 mRNA is transported from the nucleus to the cytoplasm via a specific nuclear export pathway and that hypusine formation appears to be essential for the maturation of functional DCs. Therefore, pharmacological interference with hypusine formation may provide a new possibility to modulate DC function.
Molecular Pathways: Toll-like Receptors in the Tumor Microenvironment—Poor Prognosis or New Therapeutic Opportunity
Authors: Lisa A. Ridnour, Robert Y.S. Cheng, Christopher H. Switzer, Julie L. Heinecke, Stefan Ambs, Sharon Glynn, Howard A. Young, Giorgio Trinchieri, David A. Wink
Journal: Clinical Cancer Research (2012)

Abstract Numerous reports have described Toll-like receptor (TLR) expression in the tumor microenvironment as it relates to cancer progression, as well as their involvement in inflammation. While TLRs mediate immune surveillance, clinical studies have associated TLR expression in the tumor with poor patient survival, indicating that TLR expression may affect cancer treatment and survival. This review will examine mechanisms in which TLR activation upregulates protumorigenic pathways, including the induction of inducible nitric oxide synthase (iNOS2) and COX2, which in turn increase TLR expression and promote a feed-forward loop leading to tumor progression and the development of more aggressive tumor phenotypes. These propagating loops involve cancer cell, stroma, and/or immune cell TLR expression. Because of abundant TLR expression in many human tumors, several TLR agonists are now in clinical and preclinical trials and some have shown enhanced efficacy when used as adjuvant with radiation, chemotherapy, or cancer vaccines. These findings suggest that TLR expression influences cancer biology and therapeutic response, which may involve specific interactions within the tumor microenvironment, including mediators of inflammation such as nitric oxide and the arachidonic acid signaling pathways. Clin Cancer Res; 19(6); 1340–6. ©2012 AACR.
Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial
Authors: Ralf Trappe, Stephan Oertel, Veronique Leblond, Peter Mollee, Monica Sender, Petra Reinke, Ruth Neuhaus, Hans Lehmkuhl, Heinz August Horst, Gilles Salles, Franck Morschhauser, Arnaud Jaccard, Thierry Lamy, Malte Leithäuser, Heiner Zimmermann, Ioannis Anagnostopoulos, Martine Raphael, Hanno Riess, Sylvain Choquet
Journal: The Lancet Oncology (2011)
A controlled clinical trial of the efficacy of the hepatitis B vaccine (heptavax B): A final report
Authors: Wolf Szmuness, Cladd E. Stevens, Edith A. Zang, Edward J. Harley, Aaron Kellner
Journal: Hepatology (1981)

A controlled, randomized, double-blind trial in 1,083 homosexual men from New York confirmed that a highly purified, formalin-inactivated vaccine against hepatitis B prepared from HBsAg positive plasma, is safe immunogenic, and highly efficacious. Over 95% of vaccinated subjects developed antibody against the surface antigen. Vaccine-induced antibody persisted for the entire 24-month follow-up period. The attack rate of all hepatitis B virus infections (excluding conversions of anti-HBc alone) was 3.2% in vaccine recipients compared with 25.6% in placebo recipients (p &lt; 0.0001). In those who received all three doses of vaccine, of 40 μg each, the protective efficacy rate was close to 100%. The vaccine protects against acute hepatitis B, asymptomatic infection, and chronic antigenemia. There is reason to assume that the vaccine is also partially effective when given postexposure.
Survival in medically treated coronary artery disease.
Authors: P J Harris, F E Harrell, K L Lee, V S Behar, R A Rosati
Journal: Circulation (1979)

In 1214 symptomatic medically treated patients with coronary artery disease, 57 noninvasive baseline clinical characteristics and 24 catheterization descriptors were analyzed by a multivariable analysis technique to determine the characteristics that were independent predictors of survival and, in particular, to determine whether noninvasive characteristics contributed prognostic information in addition to catheteriza- tion findings.When the noninvasive characteristics were analyzed, 31 characteristics were significant (p < 0.05) univariate predictors of survival, but only 12 contained significant independent prognostic information.Fiveand 7-year survival rates in 197 patients who had none of the independently significant noninvasive characteristics were both 90%.Nineteen variables were significant when the catheterization descriptors were analyzed individually.Only seven were independently significant when they were analyzed jointly.When all 81 baseline characteristics were analyzed jointly, seven noninvasive characteristics (history of peripheral vascular disease, New York Heart Association class IV heart failure, nonspecific intraventricular conduction defect, progressive chest pain, nocturnal pain, premature ventricular complexes on the resting ECG, and left bundle branch block) and six invasive characteristics (left-main stenosis, arteriovenous oxygen difference, number of diseased vessels, abnormal left ventricular contraction, left ventricular end-diastolic pressure and anterior asynergy) were independently significant.Different survival rates may occur in subsets that are uniform with respect to only one or two important characteristics (e.g., coronary anatomy and ventricular function) because of differences in other important baseline characteristics.Both noninvasive and invasive characteristics must be taken into account to define prognosis in coronary disease fully.EARLY STUDIES of patients with clinically diagnosed coronary artery disease identified clinical characteristics such as age, sex, previous myocardial infarction, ECG abnormalities and heart failure as im- portant predictors of survival.1-5With the use of cor- onary angiography, the extent of coronary disease6-9 and the quality of left ventricular (LV) function'0' 11 were shown to be accurate predictors of survival.Although noninvasive descriptors still receive some attention,9 12 until recently the relationship between noninvasive and invasive descriptors in predicting sur- vival has not been extensively examined.Patients with coronary disease are usually classified by the number of diseased vessels and the quality of LV function.Survival within these categories is con- sidered a manifestation of the natural history of the disease.13 While such a classification produces a clinically useful stratification of the survival rates, the outcomes in each category vary significantly.For ex- ample, 2-year survival rates have varied from ap- proximately 93%14 to approximately 83%12 in patients