tbuckley/cabot-search huggingface dataset:
Cannabinoid receptors: a novel target for the treatment of prostate cancer
Authors: Sami Sarfaraz, Farrukh Afaq, Vaqar M. Adhami, Arshi Malik, Imtiaz A. Siddiqui, Hasan Mukhtar
Journal: Cancer Research (2005)

2566   Because prostate cancer is the most common diagnosed invasive malignancy and second leading cause of cancer related deaths in US male population, developing novel targets and mechanism based agents for its treatment has become a challenging issue. In recent years cannabinoids, the active components of  Cannabis sativa linnaeus  (marijuana) and their derivatives are receiving renewed attention because of their diverse pharmacological activities such as cell growth inhibition, anti-inflammatory effects and tumor regression. Further interest in cannabinoid research came from the discovery of specific cannabinoid system and the cloning of specific cannabinoid receptors. These diversified effects of cannabinoids are now known to be mediated by the activation of specific G protein-coupled “central” CB 1  and “peripheral” CB 2  receptors that are normally bound by a family of endogenous ligands, the endocannabinoids. Here, we show that expression levels of both cannabinoid receptors CB 1  and CB 2  are significantly higher in CA-HPV-10 (virally transformed cells, derived from adenocarcinoma of human prostate tissue), and other human prostate cancer cells LNCaP, DU145, PC3, and CWR22Rν1 than in normal human prostate epithelial (PrEC) and PZ-HPV-7 (virally transformed cells, derived from normal human prostate tissue) cells. Extending this observation we found that WIN-55,212-2 (a mixed CB 1 /CB 2  agonist) treatment to androgen-responsive LNCaP cells resulted in (i) dose (1-10 μM) and time-dependent (24-72 h) inhibition of cell growth, (ii) induction of apoptosis, (iii) decrease in protein and mRNA expression of androgen receptor, (iv) decrease in intracellular protein and mRNA expression of prostate specific antigen (PSA), (v) decrease in secreted PSA levels, and (vi) decrease in protein expression of proliferation cell nuclear antigen and vascular endothelial growth factor. Cells pretreated with specific CB 1  receptor antagonist SR141716 were found to overcome WIN-55,212-2- induced inhibition in cell viability and apoptosis further suggesting a role of CB 1  receptor in WIN-55,212-2 induced cell death . To establish the relevance of these  in vitro  findings to  in vivo  situation, athymic nude mice (6-8 weeks old) were implanted with androgen responsive CWR22Rν1 cells which are known to secrete PSA in the blood stream of the host. As compared to controls mice treated with WIN-55,212-2 (0.5 mg/kg b.wt, i.p, alternate day) resulted in a significant inhibition in the growth of implanted tumors with significant reduction in PSA secretion in serum. In control animals, targeted tumor volume of 1200 mm 3  was reached at 28 days post-tumor inoculation; whereas this tumor volume was attained in 45 days in animals treated with WIN-55,212-2. Our results suggest that WIN-55,212-2 or other non-habit forming cannabinoid receptor agonists could be developed as novel therapeutic agents for the treatment of prostate cancer.
Abstract 132: Shear Stress--Induced Activation of Raf/MEK/ERK1/2 Signaling Contributes to tPA Expression in Human Endothelial Progenitor Cells
Authors: Jun Tao, Zhen Yang, Wenhao Xia, Bingbo Yu, Yanxia Qiu
Journal: Circulation (2011)

Background Shear stress increases the expression of tissue-type plasminogen activator (t-PA) in endothelial progenitor cells (EPCs. However, the underlying mechanism responsible for the shear stres...
Identification of unique and common low abundance tumor-specific transcripts by suppression subtractive hybridization and oligonucleotide probe array analysis
Authors: Bee Hui Liu, Christopher Goh, London Lucien Ooi, Kam Hui
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

A54 

Most human cancers are characterized by genetic aberrations accompanied by altered expression and function of numerous genes. Applying genome-wide, microarray gene expression analysis to identify deregulated genes in different tumor types can provide potential gene candidates as diagnostic and prognostic tools and promising targets for drug development. However, the detection of genes with low levels of expression remains a major challenge. In this study, we have designed a strategy, termed modified suppression subtractive hybridization (mSSH), to identify genes encoding rare transcripts. The strategy entails incorporating the T7-promoter sequence at the 5’end of the non-coding cDNA strand during first strand cDNA synthesis so as to generate uni-directional anti-sense RNA from the resultant cDNA following conventional SSH. These transcripts are subsequently analyzed by Affymetrix oligonucleotide gene arrays. Biopsies from five hepatocellular carcinoma (HCC), five breast carcinoma, and four nasopharyngeal carcinoma (NPC) were employed separately as testers and their corresponding normal biopsies as drivers to enrich for low abundance tumor type-specific transcripts. The total detectable number of probe sets following mSSH was reduced by an order of magnitude of almost ten in comparison to those detected for the same tumor resected tissues without undergoing subtraction, thus yielding a subtraction efficacy of over 90%. Using this experimental approach, we have identified 48 HCC-specific, 45 breast carcinoma-specific, and 83 NPC-specific genes. In addition, 115 genes were up-regulated in all the three cancer types. When compared to gene-profiling data obtained without mSSH, the majority of these identified transcripts were of low abundance in the original cancer tissues. mSSH can therefore serve as a comprehensive and unbiased molecular strategy for pursuing functional genomic studies of human cancers.
Metabolic Syndrome and Risk of Acute Myocardial Infarction
Authors: Andrew Mente, Salim Yusuf, Shofiqul Islam, Matthew J. McQueen, Supachai Tanomsup, Churchill L. Onen, Sumathy Rangarajan, Hertzel C. Gerstein, Sonia S. Anand
Journal: Journal of the American College of Cardiology (2010)
Abstract 486: Down-regulation of type 1 cGMP-dependent Protein Kinase by the ubiquitin/proteasome pathway
Authors: NUPUR DEY, Jennifer L Busch, Sharron H Francis, Jackie D Corbin, Thomas M Lincoln
Journal: Circulation (2007)

Type 1 cGMP-dependent protein kinase (PKG-I) is a widely expressed serine/threonine protein kinase, and is a major mediator of nitric oxide (NO) signaling in vascular smooth muscle cells (VSMC). PKG-I level is highly variable in VSMC and several studies have shown that atherogenic inflammatory cytokines lower the steady-statel levels of PKG-I. The mechanism of action of down-regulation is not well defined, but induction of type II NO synthase (iNOS) and subsequent persistent elevation of cGMP appear to contribute to PKG-I down regulation. In the present study, we examined the role of the ubiquitin/proteasome pathway in PKG-Iα down-regulation in response to elevated cGMP. Incubation of cultured VSMC with 8-Br-cGMP for 6–12 hr lowered PKG-I expression as assessed by western blotting. To further examine the mechanism, Cos7 cells, which do not express PKG-I mRNA or protein, were transfected with PKG-Iα/pcDNA vector and incubated with 8-Br-cGMP. 8-Br-cGMP suppressed PKG-Iα protein level in Cos7 cells (half-maximal concentration = 250 μM). Pretreatment of these cells with the proteasome inhibitor, MG132, followed by 8-Br-cGMP treatment prevented the decline suggesting the involvement of the ubiquitin/26S proteasome pathway. Immunoprecipitation of PKG-I followed by immunoblotting with anti-ubiquitin revealed multiple ubiquitinated PKG bands in the 8-Br-cGMP treated samples but not in untreated samples. Ubiquitination and down-regulation were also inhibited by the specific PKG-I catalytic inhibitor DT-2, suggesting the possible involvement of PKG autophosphorylation in the 8-Br-cGMP induced down-regulation. Mutation of the PKG-Iα autophosphorylation sites to alanines was performed to identify the phosphorylated site responsible for cGMP-dependent ubiquitination. In contrast to wild type PKG-Iα, PKG-Iα S64A, but not the S50A mutant, was not down-regulated by 8-Br-cGMP suggesting that autophosphorylation of serine-64 is required for the ubiquitination and down-regulation of PKG-I. Autophosphorylation and cGMP-mediated down-regulation of PKG-I may be an important mechanism to control excess cGMP signaling in VSMC.
Abstract 15801: Mitochondria-Targeted Antioxidant Therapy Prevents Angiotensin II Mediated Connexin43 Remodeling and Sudden Arrhythmic Death
Authors: Ali A Sovari, Eu-Myoung Jeong, Shadi Zandieh, Lianzhe Gu, Shahriar Iravanian, Marcelo G Bonini, Samuel C Dudley
Journal: Circulation (2011)

Introduction:  Angiotensin II activation and associated elevation in ROS have been implicated in pathogenesis of arrhythmia. Nevertheless, commonly used antioxidants have been ineffective in clinical trials. We created a transgenic mouse model of cardiac restricted overexpression of ACE (ACE8/8). These mice show spontaneous VT/ VF, sudden cardiac death (SCD), and a reduction in Cx43 level, which impairs conduction and predisposes to arrhythmia. We sought to determine the role and the major source of ROS in angiotensin II mediated VT/ VF and Cx43 remodeling.   Method:  Wild type and ACE8/8 mice with and without two weeks of treatment with a NOS inhibitor (L-NIO, 25 mg/Kg IP injections daily), a mitochondria-targeted antioxidant (Mito-TEMPO, 0.7 mg/Kg IP injections daily), and a NADPH oxidase inhibitor (apocynin 80 mg/L in drinking water) were studied. Crossing ACE8/8 mice with a P67 dominant negative (P67DN) mouse was used to confirm the NADPH oxidase role. Western blotting to detect oxidized protein levels (OxyBlot), detection of superoxide production in mitochondria by confocal microscopy and flow cytometry using MitoSOX red, and immunohistochemistry staining for Cx43 were performed. EP study was performed by a 1.1F octapolar catheter and a burst pacing protocol.   Results:  Proteins were more oxidized, mitochondrial ROS levels were increased by 6 fold (P    Conclusion:  Mitochondria-targeted antioxidant prevents VT/VF/SCD and Cx43 remodeling in an angiotensin II activated state. This result suggests a central role for mitochondria oxidative stress in ROS-induced arrhythmia and that mitochondria-targeted antioxidants may be effective antiarrhythmic drugs.
Erythroid Transcription Factor GATA-1 Binds and Represses PU.1 Gene – Candidate Mechanism Of Epigenetic Repression Of PU.1 and Inefficient Erythropoiesis In MDS
Authors: Pavel Burda, Nikola Curik, Nina Dusilkova, Giorgio L Papadopoulos, John Strouboulis, Anna T Jonasova, Tomas Stopka
Journal: Blood (2013)
Caroli's disease misdiagnosed as intraductal papillary neoplasm of the bile duct
Authors: Dae Hoe Gu, Min Seon Park, Chang Ho Jung, Yang Jae Yoo, Jae Young Cho, Yun Ho Lee, Yeon Seok Seo, Hyung Joon Yim, Soon Ho Um, Ho Sang Ryu
Journal: Clinical and Molecular Hepatology (2015)

Caroli's disease is a rare autosomal-recessive disorder caused by malformation of the ductal plate during embryonic development. Although it is present at birth, Caroli's disease is typically not diagnosed until between the second and fourth decades of life, as it was in the present patient. Here we report a rare case of Caroli's disease limited to one liver segment, which was initially misdiagnosed as an intraductal papillary neoplasm of the bile duct. The asymptomatic patient was treated with liver segmentectomy. Keywords: Caroli's disease; Intraductal papillary neoplasm of the bile duct; Segmentectomy
Surgical Management of Lateral Ventricular Tumors
Authors: Joseph M. Piepmeier, Kimberlee J. Sass
Journal: Neuro-Oncology (1991)

A series of 17 consecutive patients with lateral ventricular tumors were reviewed to determine their range of pathology and to assess the morbidity and mortality associated with their surgical treatment. This review demonstrated that these tumors rarely cause localizing findings on neurologic examination. They create severe memory problems and deficits in cognitive function as demonstrated by a relative deficit in the Performance IQ compared to the Verbal IQ. Operative procedures were divided into transcortical and transcallosal approaches and examined with regard to the relative liabilities of each procedure. Optimal tumor exposure and preservation of neurologic function most often was obtained with transcallosal surgery. In addition, excessive retraction and the risk of seizures can be reduced by exposing the tumor through the corpus callosum. Recognition of the potential problems the can occur in the surgery for lateral ventricular tumors can improve the management of these patients.
Using Medications to Decrease the Risk for Breast Cancer in Women: Recommendations From the U.S. Preventive Services Task Force
Authors: Virginia A Moyer
Journal: Annals of Internal Medicine (2013)

Update of the 2002 U.S. Preventive Services Task Force (USPSTF) recommendation on the use of medications for breast cancer risk reduction.The USPSTF reviewed evidence on the effectiveness,adverse effects, and subgroup variations of medications to reduce the risk for breast cancer—specifically, the selective estrogen receptor modulators tamoxifen and raloxifene. The USPSTF also reviewed a meta-analysis of placebo-controlled trials to understand the relative benefits and harms of tamoxifen and raloxifene.This recommendation applies to asymptomatic women aged 35 years or older without a prior diagnosis of breast cancer,ductal carcinoma in situ, or lobular carcinoma in situ.The USPSTF recommends that clinicians engage in shared, informed decision making with women who are at increased risk for breast cancer about medications to reduce their risk.For women who are at increased risk for breast cancer and at low risk for adverse medication effects, clinicians should offer to prescribe risk-reducing medications, such as tamoxifen or raloxifene. (B recommendation)The USPSTF recommends against the routine use of medications,such as tamoxifen or raloxifene, for risk reduction of primary breast cancer in women who are not at increased risk for breast cancer. (D recommendation).
Abstract 284: The Relation Between Serum Procalcitonin and Perfusion Parameters After the Return of Spontaneous Circulation Following Out-of-Hospital Cardiac Arrest
Authors: Koji Sato, Takumi Taniguchi
Journal: Circulation (2012)

&lt;Introduction&gt;Procalcitonin (PCT) has been broadly used as an infectious biomarker. However we often found that the patients without infection showed high level of PCT. In past research, PCT has been reported to be a useful biomarker in predicting neurological outcome after the return of spontaneous circulation (ROSC) following out-of-hospital cardiac arrest (OHCA). &lt;Hypothesis&gt;Our hypothesis is that the level of PCT in the patients after ROSC following OHCA may relate to time from cardiac arrest and reflect tissue hypoxia. Moreover it may predict outcome. This study was aimed to evaluate relation between the serum level of PCT and perfusion parameters in OHCA patients. &lt;Methods&gt;Twenty sequential patients who admitted to the ICU after ROSC following OHCA were included. Infectious patients, trauma patients and extracorporeal CPR patients were excluded. This study was a retrospective, single-center analysis, conducted in the ICU of the university hospital. We evaluated the maximum PCT level within 48hr after admission, cardio-pulmonary arrest time, serum lactate level at admission, Glasgow outcome scale at 28 day. &lt;Results&gt;Twelve of twenty patients were cardiogenic patients. Average ROSC time from OHCA was 27±17 minutes. The maximum PCT was significantly higher in patients who died in the hospital (2.2±2.6 V.S 15.3±17 ng/mL, p=0.01). We defined Glasgow outcome scale 4-5 as favorable outcomes and eight patients showed favorable outcomes. Serum PCT in patients with favorable outcomes was lower than that of unfavorable outcomes, but there was no statistical significance (1.2±2.5 V.S 9.4±13.5 ng/mL). The maximum PCT significantly correlated with serum lactate at admission (r=0.63, p&lt;0.01), and ROSC time from OHCA (r=0.54, p=0.01). &lt;Conclusions&gt;In conclusion, the maximum PCT after cardiac arrest did not predict neurological outcome. But PCT correlated with degree of tissue hypoxia. The serum PCT may reflect ischemia-reperfusion injury.
Abstract 1179: REFORM: Registry Evaluating Functional Outcomes of Resynchronization Management
Authors: Paul Nguyen, Christina Murray, John Spertus, Sam Sears, Alison Graves-Calhoun, Brian Ramza
Journal: Circulation (2009)

Background: Implantable cardioverter defibrillators (ICDs) prolong survival. However, ICD shocks are associated with diminished psychosocial function (Psyf) and quality of life (QOL). Cardiac resyn...
High rates of false positives are likely in diabetes screening programmes in India
Authors: Sanjeet Bagcchi
Journal: BMJ (2015)

Large scale community based diabetes screening in India is likely to be associated with a high rate of false positive results, particularly when using risk score questionnaires, a simulation study published in PLOS Medicine has found.

India recently started a diabetes screening programme using either risk scoring questionnaires or random blood glucose testing, and the government plans to expand this over the next few years. But even though up to 53 million people have been screened so far, no data have been collected on the performance of the screening programme.

The simulation study used data from 58 cohort studies of diabetes in India and applied the …
A Clinical Trial of Retroviral-Mediated Transfer of arev-Responsive Element Decoy Gene Into CD34+Cells From the Bone Marrow of Human Immunodeficiency Virus-1–Infected Children
Authors: Donald B. Kohn, Gerhard Bauer, C. Robert Rice, J.C. Rothschild, Denise A. Carbonaro, Penelope Valdez, Qian-lin Hao, Chen Zhou, Ingrid Bahner, Karen Kearns, Kate Brody, Sarah Fox, Elizabeth Haden, Kathy Wilson, Cathy Salata, Cathy Dolan, Charles Wetter, Estuardo Aguilar-Cordova, Joseph Church
Journal: Blood (1999)
Abstract 12494: Association of Plasma n-3 Polyunsaturated Acids Levels with Metabolic and Inflammatory Biomarkers in Patients With Chronic Heart Failure. Data from the GISSI-HF Trial
Authors: Serge Masson, Roberto Latini, Maria Teresa Tacconi, Roberto Bernasconi, Luana Dragani, Valentina Milani, Roberto Marchioli, Aldo P Maggioni, Luigi Tavazzi
Journal: Circulation (2010)

Aims: Inverse associations between circulating n-3 polyunsaturated acids (n-3 PUFA) levels and inflammatory biomarkers have been reported in subjects with cardiovascular risk factors or with coronary artery disease. We assessed here their relation to metabolic, inflammatory, and cardiac markers in a large cohort of patients with stable chronic heart failure (HF). Methods: Plasma levels of n-3 PUFA (% of total fatty acids in phospholipids, assayed by gas chromatography) and metabolic (adiponectin), inflammatory (C-reactive protein (hsCRP), pentraxin-3 (PTX3), osteoprotegerin (OPG)), or cardiac biomarkers (natriuretic peptide (NT-proBNP), troponin T (hs-cTnT)) were measured at baseline in 1,203 patients with CHF of any etiology and age enrolled in the GISSI-HF trial. Results: Patients with n-3 PUFA levels in the upper third (>5.4%) had more frequently HF of ischemic etiology, lower SBP, milder symptoms of HF (NYHA class II), less often COPD. Levels of n-3 PUFA were inversely related to adiponectin (Spearman...
Abstract 9595: Generation of Transgene-Free Induced Pluripotent Stem Cells from Fibroblasts by Small Molecule Chemicals
Authors: Ji W Han, Changwon Park, Min-Young Lee, Hyongbum Kim, JiYoon Lee, Young-sup Yoon
Journal: Circulation (2011)

Backgrounds: Reprogramming of somatic cells using viral- and non-viral vectors encoding defined transcription factors to generate induced pluripotent stem (iPS) cells has successfully been achieved over the past few years. However, the current established methods to create iPS cells require viral vectors or plasmids to deliver transgenes into the cells. Methods and Results: To obviate the putative problems of genetic contamination in the cells for future clinical application, it is highly demanded to develop new methods to create “safer” iPS cells without any genetic modifications. Here, we for the first time demonstrate successful generation of iPS cell line from mouse fibroblasts with only combinations of small-molecule chemicals such as GSK-3 beta inhibitor, histone deacetylase inhibitor, and G9a histone methyltransferase inhibitor, which act as epigenetic modulators and self-renewal activators. These chemical induced pluripotent stem (ChemiPS) cells have almost the same properties of embryonic stem cells in the expression patterns of pluripotency-related markers, epigenetic status in promoter regions of Oct4 and Nanog, spontaneous differentiation into three germ layers by in vitro embryoid body formation, and formation of teratoma in vivo after injection into mice. Conclusion: This study provides the first evidence that sole chemical combinations can reprogram somatic cells, resulting in transgene-free iPS cells. This method will advance the use of iPS cells in clinical application and disease investigation.
BMJ should use "paracetamol" instead of "acetaminophen" in its index
Authors: N. Bradley
Journal: BMJ (1996)

ent from the international non-proprietary name.On the other hand, the World Health Organisation cannot impose on these countries a name that they consider to be unacceptable.The most logical solution would be to set up bilateral discussions between the organisation's experts and the national nomenclature committees with a view to the adoption of a single non- proprietary name for those drugs for which discrepancies exist.
A new TNM classification is better than ISS at predicting survival in stage III unresectable non-small cell lung cancer (NSCLC)
Authors: Thierry Berghmans, Jean-Jacques Lafitte, Jacques Thiriaux, Paul Van Houtte, Jean-Paul Lecomte, Anna Efremidis, Vicente Giner, Marianne Paesmans, Jean Klastersky, Jean-Paul Sculier
Journal: European Respiratory Journal (2003)