tbuckley/cabot-search huggingface dataset:
γ-Glutamyltransferase and the Inhibition of Azo Dye-Produced Neoplasia by Concomitant Administration of Disulfiram23
Authors: Silvio Fiala, Edgar C. Trout, Harold Ostrander, Anna E. Fiala
Journal: JNCI Journal of the National Cancer Institute (1980)

The concentration and total amount of DNA in the livers of SD rats fed 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) gradually increased and reached a maximum in developing tumors. In SD rats fed 3'-Me-DAB plus disulfiram (DSF), the concentration of DNA was higher than in controls, but it soon became stabilzed and the total amount of DNA in the liver did not differ substantially from that in rats fed DSF alone. In rats given 3'-Me-DAB, neoplastic nodules and liver carcinomas appeared after 3 months, but in those fed both compounds these formations were absent even after 6 months. The activity of gamma-glutamyltransferase (GT-ase), a marker of chemically induced carcinogenesis in rat liver, gradually increased to extremely high levels in tumors even after 75 days when the diet of the animals was changed to a normal one. In rats fed 3'-Me-DAB plus DSF, GT-ase activity increased for the greater part of 80 days, gradually leveled off around the 100th day, and returned to almost normal levels when the rats were given a normal diet after 100 days. We concluded that DSF 1) did not interfere with 3'-Me-DAB-induced proliferation of preneoplastic cells and the increase in GT-ase associated with this reversible adaptation to the influx of 3'-Me-DAB; and 2) inhibited malignant transformation and, consequently, prevented the formation and proliferation of neoplastic cells and the increase in constitutive GT-ase related to neoplasia.
Interleukin 1: an important mediator of host resistance against Pneumocystis carinii.
Authors: W Chen, E A Havell, L L Moldawer, K W McIntyre, R A Chizzonite, A G Harmsen
Journal: The Journal of Experimental Medicine (1992)

The importance of endogenous interleukin 1 (IL-1) in resistance to Pneumocystis carinii infection was examined in a SCID mouse model. Naturally acquired pulmonary infection of P. carinii in SCID mice was completely cleared by reconstitution of the infected mice with immunocompetent spleen cells. IL-1 activity in the lung homogenate supernatant of these mice increased significantly after reconstitution and returned to baseline level after the clearance of P. carinii. Treatment of reconstituted SCID mice with 35F5, a monoclonal antibody against murine type I IL-1R almost completely inhibited the clearance of P. carinii. In contrast, treatment with control rat immunoglobulin G had no detectable effect. Further study revealed that for the complete clearance of P. carinii, IL-1 must be present at the early stage of immune responses induced by reconstitution, since clearance could be blocked by a single injection of 35F5 into SCID mice at 2 d, but not at either 8 or 13 d postreconstitution. Furthermore, pulmonary recruitment of neutrophils, macrophages, and lymphocytes was significantly inhibited in mice that received 35F5 treatment. These findings strongly suggest that, in reconstituted SCID mice, endogenous IL-1 is important in host resistance to P. carinii infection and that IL-1 may function early in the host response possibly by the recruitment of inflammatory cells into the lungs.
Breast Cancer Heterogeneity: A Mixture of At Least Two Main Types?
Authors: William F. Anderson, Rayna Matsuno
Journal: JNCI Journal of the National Cancer Institute (2006)

Journal of the National Cancer Institute, Vol. 98, No. 14, July 19, 2006 Affi liation of authors: Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD. Correspondence to: William F. Anderson, MD, MPH, Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Room 8036, 6120 Executive Blvd., Bethesda, MD 20892-7244 (e-mail: wanderso@ mail.nih.gov ). See “ Note ” following “ References. ”
Consensus Conference on Cancer Registration of Brain and Central Nervous System Tumors
Authors: Bridget J. McCarthy, Carol Kruchko
Journal: Neuro-Oncology (2005)

The passage of Public Law 107-260, the Benign Brain Tumor Cancer Registries Amendment Act, in October 2002 has made the collection of all primary brain tumors a reality. However, at the first Consensus Conference on Brain Tumor Definition for Registration in 2002, and during the development of training materials for benign brain tumor collection, several issues were identified that were tabled for future discussion. These and other issues were addressed at the subsequent 2003 Consensus Conference on Cancer Registration of Brain and Central Nervous System Tumors, at which the Central Brain Tumor Registry of the United States facilitated a discussion among epidemiologists, neurosurgeons, and neuropathologists. Multidisciplinary consensus was reached on four points, for which the following recommendations were made: (1) amend the histology coding scheme for cysts and tumor-like lesions that currently have a code in the third edition of the International Classification of Disease for Oncology (ICDO), (2) collect data on all instances of specific cysts and tumor-like lesions that are located in brain and other CNS sites but currently lack ICDO codes, (3) establish a new ICDO topography site for skull base tumors for the brain and CNS, and (4) collect data on genetic syndromes in patients diagnosed with brain or CNS tumors. We view this conference as part of a continuing process. Because classification of primary intracranial and other CNS tumors is dynamic, and the registration and coding of these tumors will need to be periodically reviewed.
Examining variations in prescribing safety in UK general practice: cross sectional study using the Clinical Practice Research Datalink
Authors: S Jill Stocks, Evangelos Kontopantelis, Artur Akbarov, Sarah Rodgers, Anthony J Avery, Darren M Ashcroft
Journal: BMJ (2015)

<b>Study question</b> What is the prevalence of different types of potentially hazardous prescribing in general practice in the United Kingdom, and what is the variation between practices? <b>Methods</b> A cross sectional study included all adult patients potentially at risk of a prescribing or monitoring error defined by a combination of diagnoses and prescriptions in 526 general practices contributing to the Clinical Practice Research Datalink (CPRD) up to 1 April 2013. Primary outcomes were the prevalence of potentially hazardous prescriptions of anticoagulants, anti-platelets, NSAIDs, β blockers, glitazones, metformin, digoxin, antipsychotics, combined hormonal contraceptives, and oestrogens and monitoring by blood test less frequently than recommended for patients with repeated prescriptions of angiotensin converting enzyme inhibitors and loop diuretics, amiodarone, methotrexate, lithium, or warfarin. <b>Study answer and limitations</b> 49 927 of 949 552 patients at risk triggered at least one prescribing indicator (5.26%, 95% confidence interval 5.21% to 5.30%) and 21 501 of 182 721 (11.8%, 11.6% to 11.9%) triggered at least one monitoring indicator. The prevalence of different types of potentially hazardous prescribing ranged from almost zero to 10.2%, and for inadequate monitoring ranged from 10.4% to 41.9%. Older patients and those prescribed multiple repeat medications had significantly higher risks of triggering a prescribing indicator whereas younger patients with fewer repeat prescriptions had significantly higher risk of triggering a monitoring indicator. There was high variation between practices for some indicators. Though prescribing safety indicators describe prescribing patterns that can increase the risk of harm to the patient and should generally be avoided, there will always be exceptions where the indicator is clinically justified. Furthermore there is the possibility that some information is not captured by CPRD for some practices—for example, INR results in patients receiving warfarin. <b>What this study adds</b> The high prevalence for certain indicators emphasises existing prescribing risks and the need for their appropriate consideration within primary care, particularly for older patients and those taking multiple medications. The high variation between practices indicates potential for improvement through targeted practice level intervention. <b>Funding, competing interests, data sharing </b>National Institute for Health Research through the Greater Manchester Primary Care Patient Safety Translational Research Centre (grant No GMPSTRC-2012-1). Data from CPRD cannot be shared because of licensing restrictions.
APOLIPOPROTEIN E ALLELES AS RISK FACTORS IN ALZHEIMER'S DISEASE
Authors: Allen D. Roses, M.D
Journal: Annual Review of Medicine (1996)

▪ Abstract Alzheimer's disease (AD) is unique in medicine in that millions of people suffer from what appears to be the same form of disease, and unlike most other late-onset diseases, the genetic etiologies have been well identified. Three early onset forms of AD inherited as autosomal dominant traits account for less than 2% of prevalent AD. A major susceptibility locus, apolipoprotein E (APOE, gene; apoE, protein) is associated with risk and age of onset distributions for the common familial and sporadic late-onset AD. The identification of additional genetic susceptibility genes in the etiology of AD and the metabolic mechanisms leading to differences in age of onset and disease pathogenesis are active areas of current research.
Impact of MiRSNPs on Survival and Progression in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation
Authors: Carlos Fernández de Larrea, Alfons Navarro, Rut Tejero, Natalia Tovar, Tania Díaz, María Teresa Cibeira, Laura Rosiñol, Gerardo Ferrer, Montserrat Rovira, María Rozman, Mariano Monzó, Joan Bladé
Journal: Clinical Cancer Research (2012)

A distinctive new group of polymorphisms is constituted by single-nucleotide polymorphism (SNP) in miRNA processing machinery in miRNA precursor molecules and in miRNA-binding sites, known as miRSNPs. The aim of this study was to ascertain the prognostic impact of six miRSNPs in patients with multiple myeloma and analyze the functional consequences.One hundred and thirty-seven patients with chemosensitive multiple myeloma (73M/64F) intensified with autologous stem cell transplantation (ASCT) were studied. The median follow-up was 4 years. The genes and SNPs evaluated in genomic DNA by allelic discrimination were KRT81 (rs3660), AFF1 (rs17703261), FAM179b (rs1053667), and MIR196A2 (rs11614913) for miRNA target genes and TRBP (rs784567) and XPO5 (rs11077) for miRNA biogenesis pathway.Overall survival (OS) was significantly longer in patients with KRT81 rs3660 C/C variant (P = 0.037). Functional analysis showed that the presence of C variant in KRT81 3' untranslated region (UTR) is related with a reduction of the protein levels. Moreover, the reduction of KRT81 protein levels by siRNA in multiple myeloma cell lines is related to a decreased proliferation. On the other hand, OS was significantly longer in patients with C/C or A/C variant in XPO5 rs11077 (P = 0.012). There was also a significantly longer progression-free survival (PFS) for this SNP (P = 0.013). This SNP retained its prognostic impact on PFS and OS in a multivariate regression analysis (P = 0.028 and P = 0.014, respectively).This is the first report that relates miRSNPs with prognosis in multiple myeloma either in a keratin gene (KRT81), target of diverse miRNA multiple myeloma clusters, or in the miRNA biogenesis pathway-related protein exportin-5.
Prevention and Treatment of Pneumocystis Carinii Pneumonia
Authors: W T Hughes
Journal: Annual Review of Medicine (1991)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
THE EFFECT OF HYALURONIDASE ON THE ABSORPTION OF PARENTERALLY ADMINISTERED RADIOACTIVE PLASMA PROTEINS IN THE DOG 1
Authors: Henry H. Banks, Arnold M. Seligman, Jacob Fine
Journal: Journal of Clinical Investigation (1949)

There are numerous circumstances in which it would be desirable to administer substances sub- cutaneously, intramuscularly or intraperitoneally that cannot or should not be given intravenously.Since the need for parenterally administered protein and fat is one of the most urgent problems in clinical medicine, we felt it worthwhile to ex- plore the possibility of facilitating their absorption from the tissues by the use of hyaluronidase,2 a non-antigenic "spreading factor" first isolated from the testicle (1-3).Sannella (4) observed that this enzyme hastened the absorption of saline solution from the subcutaneous tissues of the rab- bit.Hechter (5) found this to be true also in man, not only for saline solution but for plasma as well.Studies were therefore undertaken for a more pre- cise determination of the facts for plasma by the use of plasma tagged with radioactive iodine.Similar observations with respect to fat will be reported (6). METHODPreparation of radioactive iodo-plasma protein Plasma was iodinated as previously described (7) with the following new modifications.About 2 millicuries of I"~(as NaI) (half life, eight days) 3 were added to 5 mgm. of carrier iodine (as a KI solution) and diluted to 15 cc.with distilled water.One cc. of this solution was diluted 100,000 times with distilled water as standard.The remaining 14 cc.was mixed with 25 cc. of carbon tetrachloride and to this mixture was added 20 mgm. of potassium iodate and 0.1 cc. of concentrated hydrochloric acid.Free iodine was extracted by the carbon tetra- 1 Aided by a grant from the Patrons of Research of the Beth Israel Hospital, Boston.2The hyaluronidase used in these experiments was obtained as "Hyronase" through the courtesy of Schering Corporation, Bloomfield, New Jersey.The preparation used contained approximately 50 turbidity reducing units per mgm.
Blood-Based Gene Expression Signatures in Non–Small Cell Lung Cancer
Authors: Thomas Zander, Andrea Hofmann, Andrea Staratschek-Jox, Sabine Classen, Svenja Debey-Pascher, Daniela Maisel, Sascha Ansén, Moritz Hahn, Marc Beyer, Roman K. Thomas, Birgit Gathof, Cornelia Mauch, Karl-Stefan Delank, Walburga Engel-Riedel, H.-Erich Wichmann, Erich Stoelben, Joachim L. Schultze, Jürgen Wolf
Journal: Clinical Cancer Research (2011)

Blood-based surrogate markers would be attractive biomarkers for early detection, diagnosis, prognosis, and prediction of therapeutic outcome in cancer. Disease-associated gene expression signatures in peripheral blood mononuclear cells (PBMC) have been described for several cancer types. However, RNA-stabilized whole blood-based technologies would be clinically more applicable and robust. We evaluated the applicability of whole blood-based gene expression profiling for the detection of non-small cell lung cancer (NSCLC).Expression profiles were generated from PAXgene-stabilized blood samples from three independent groups consisting of NSCLC cases and controls (n = 77, 54, and 102), using the Illumina WG6-VS2 system.Several genes are consistently differentially expressed in whole blood of NSCLC patients and controls. These expression profiles were used to build a diagnostic classifier for NSCLC, which was validated in an independent validation set of NSCLC patients (stages I-IV) and hospital-based controls. The area under the receiver operator curve was calculated to be 0.824 (P < 0.001). In a further independent dataset of stage I NSCLC patients and healthy controls the AUC was 0.977 (P < 0.001). Specificity of the classifier was validated by permutation analysis in both validation cohorts. Genes within the classifier are enriched in immune-associated genes and show specificity for NSCLC.Our results show that gene expression profiles of whole blood allow for detection of manifest NSCLC. These results prompt further development of gene expression-based biomarker tests in peripheral blood for the diagnosis and early detection of NSCLC.
Cell Surface Lactate Receptor GPR81 Is Crucial for Cancer Cell Survival
Authors: Christina L. Roland, Thiruvengadam Arumugam, Defeng Deng, Shi He Liu, Bincy Philip, Sobeyda Gomez, William R. Burns, Vijaya Ramachandran, Huamin Wang, Zobeida Cruz-Monserrate, Craig D. Logsdon
Journal: Cancer Research (2014)

Abstract The mechanisms that allow cancer cells to adapt to the typical tumor microenvironment of low oxygen and glucose and high lactate are not well understood. GPR81 is a lactate receptor recently identified in adipose and muscle cells that has not been investigated in cancer. In the current study, we examined GPR81 expression and function in cancer cells. We found that GPR81 was present in colon, breast, lung, hepatocellular, salivary gland, cervical, and pancreatic carcinoma cell lines. Examination of tumors resected from patients with pancreatic cancer indicated that 94% (148 of 158) expressed high levels of GPR81. Functionally, we observed that the reduction of GPR81 levels using shRNA-mediated silencing had little effect on pancreatic cancer cells cultured in high glucose, but led to the rapid death of cancer cells cultured in conditions of low glucose supplemented with lactate. We also observed that lactate addition to culture media induced the expression of genes involved in lactate metabolism, including monocarboxylase transporters in control, but not in GPR81-silenced cells. In vivo, GPR81 expression levels correlated with the rate of pancreatic cancer tumor growth and metastasis. Cells in which GPR81 was silenced showed a dramatic decrease in growth and metastasis. Implantation of cancer cells in vivo was also observed to lead to greatly elevated levels of GPR81. These data support that GPR81 is important for cancer cell regulation of lactate transport mechanisms. Furthermore, lactate transport is important for the survival of cancer cells in the tumor microenvironment. Cancer Res; 74(18); 5301–10. ©2014 AACR.
Genes of the T-Cell Antigen Receptor in Normal and Malignant T Cells
Authors: B Toyonaga, T W Mak
Journal: Annual Review of Immunology (1987)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Wrist-actigraphic estimation of sleep time under nCPAP treatment in sleep apnoea patients
Authors: F. Gagnadoux, X.L. Nguyen, D. Rakotonanahary, S. Vidal, B. Fleury
Journal: European Respiratory Journal (2004)

The aim of this study was to correlate daily use of nasal continuous positive airway pressure (nCPAP) with total sleep time (TST) evaluated by home actigraphy. Actigraphy was validated by comparing TST determined by actigraphy (aTST) and polysomnography (pTST) in 24 untreated patients with suspected sleep apnoea. The % sleep time spent under nCPAP was estimated on 3 consecutive days in 28 patients receiving long-term nCPAP, by comparing machine-use periods with sleep periods identified by home actigraphy. The mean difference between pTST and aTST was 2.5 min. The correlation coefficient between aTST and pTST was 0.90. Daily use of nCPAP over the 3 study days was 388±114 min. nCPAP was used 41–100% (82±17% (mean±sd)) of sleep time detected by actigraphy. Some patients used nCPAP during nonsleep periods. In conclusion, comparison of nasal continuous positive airway pressure use with sleep time estimated by home actigraphy shows marked individual differences in the % sleep time under nasal continuous positive airway pressure. These results suggest that actigraphic estimation of sleep time under nasal continuous positive airway pressure could provide a better index than simple daily use of the device to evaluate the impact of treatment in sleep apnoea.
Macrophage-Derived SPARC Bridges Tumor Cell-Extracellular Matrix Interactions toward Metastasis
Authors: Sabina Sangaletti, Emma Di Carlo, Silvia Gariboldi, Silvia Miotti, Barbara Cappetti, Mariella Parenza, Cristiano Rumio, Rolf A. Brekken, Claudia Chiodoni, Mario P. Colombo
Journal: Cancer Research (2008)

Other than genetic imprinting and epithelial to mesenchymal transition, cancer cells need interaction with the nearby stroma toward metastasis. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein known to regulate extracellular matrix (ECM) deposition and cell-ECM interaction. Gene expression profiles associate SPARC to malignant progression. Using reciprocal bone marrow chimeras between SPARC knockout and wild-type mice, we show that SPARC produced by inflammatory cells is necessary for spontaneous, but not experimental, i.v. metastasis. Macrophage-derived SPARC induces cancer cell migration and enhances their migration to other ECM proteins at least through alpha(v)beta(5) integrin. Indeed, RNA interference knockdown of beta(5) integrin expression reduces cell migration in vitro and metastasis in vivo. Together these results show that macrophage-derived SPARC takes part in metastasis, acting at the step of integrin-mediated migration of invasive cells.
ACUPUNCTURE IN HEROIN ADDICTS: CHANGES IN MET-ENKEPHALIN AND $beta;-ENDORPHIN IN BLOOD AND CEREBROSPINAL FLUID
Authors: Vicky Clement-Jones, P.J Lowry, Lorraine Mcloughlin, G.M Besser, LesleyH Rees, H.L Wen
Journal: The Lancet (1979)
Quality of Life in Advanced Prostate Cancer: Results of a Randomized Therapeutic Trial
Authors: C. M. Moinpour, L. C. Lovato, M. Yee, B. A. Blumenstein, M. J. Savage, A. Troxel, M. Eisenberger, R. W. Veith, B. Higgins, R. Skeel, E. D. Crawford, F. L. Meyskens
Journal: JNCI Journal of the National Cancer Institute (1998)

Background . For patients with metastatic prostate cancer, treatment is primarily palliative, relying mainly on the suppression of systemic androgen hormone levels. To help document the achievement of palliation and to characterize positive and negative effects of treatment, we evaluated qualityof-life (QOL) parameters in patients with metastatic prostate cancer who were randomly assigned to two methods of androgen deprivation. Methods : Patients (n = 739) with stage M 1 (bone or soft tissue metastasis) prostate cancer were enrolled in a QOL protocol that was a companion to Southwest Oncology Group INT-0105, a randomized doubleblind trial comparing treatment with bilateral orchiectomy (surgical castration) plus either flutamide or placebo. Patients completed a comprehensive battery of QOL questionnaires at random assignment to treatment and at 1, 3, and 6 months later. Data were collected on three treatment-specific symptoms (diarrhea, gas pain, and body image), on physical functioning, and on emotional functioning. All P values are two-sided. Results : Questionnaire return rates for this study never dropped below 80%; only 2% of the patients did not submit baseline QOL assessments. Cross-sectional analyses (corrected for multiple testing) identified statistically significant differences that favored orchiectomy plus placebo for two of the five primary QOL parameters as follows: patients receiving flutamide reported more diarrhea at 3 months ( P = .001) and worse emotional functioning at 3 and 6 months (both P <.003). Longitudinal analyses replicated these findings. Other analyzed QOL parameters favored the group receiving placebo but were not statistically significant after adjustment for multiple testing. Conclusions : We found a consistent pattern of better QOL outcomes at each follow-up assessment during the first 6 months of treatment for orchiectomized patients with metastatic prostate cancer who received placebo versus flutamide. Improvement over time was evident in both treatment groups but more so for patients receiving placebo. [J Nall Cancer Inst 1998;90:1537-44]