tbuckley/cabot-search huggingface dataset:
DC vaccination with anti-CD25 treatment leads to long-term immunity against experimental glioma
Authors: Wim Maes, Georgina Galicia Rosas, Bert Verbinnen, Louis Boon, Steven De Vleeschouwer, Jan L. Ceuppens, Stefaan W. Van Gool
Journal: Neuro-Oncology (2009)

We studied the feasibility, efficacy, and mechanisms of dendritic cell (DC) immunotherapy against murine malignant glioma in the experimental GL261 intracranial (IC) tumor model. When administered prophylactically, mature DCs (DCm) ex vivo loaded with GL261 RNA (DCm-GL261-RNA) protected half of the vaccinated mice against IC glioma, whereas treatment with mock-loaded DCm or DCm loaded with irrelevant antigens did not result in tumor protection. In DCm-GL261-RNA-vaccinated mice, a tumor-specific cellular immune response was observed ex vivo in the spleen and tumordraining lymph node cells. Specificity was also shown in vivo on the level of tumor challenge. Depletion of CD8(+) T-cells by anti-CD8 treatment at the time of tumor challenge demonstrated their essential role in vaccine-mediated antitumor immunity. Depletion of CD25(+) regulatory T-cells (Tregs) by anti-CD25 (aCD25) treatment strongly enhanced the efficacy of DC vaccination and was itself also protective, independently of DC vaccination. However, DC vaccination was essential to protect the animals from IC tumor rechallenge. No long-term protection was observed in animals that initially received aCD25 treatment only. In mice that received DC and/or aCD25 treatment, we retrieved tumor-specific brain-infiltrating cytotoxic T-lymphocytes. These data clearly demonstrate the effectiveness of DC vaccination for the induction of long-lasting immunological protection against IC glioma. They also show the beneficial effect of Treg depletion in this kind of glioma immunotherapy, even combined with DC vaccination.
Comparison of nitrogen mustard, cytarabine and dacarbazine as pleural sclerosing agents in rabbits
Authors: E Marchi, FS Vargas, LR Teixeira, DJ Fagundes, LM Silva, AO Carmo, RW Light
Journal: European Respiratory Journal (1997)

We have previously shown that the intrapleural injection of mitozantrone but not bleomycin resulted in pleural fibrosis. Mechlorethamine hydrochloride (nitrogen mustard) was used extensively in the past to control malignant effusions, with relatively good success. The objective of this study was to determine if the intrapleural injection of nitrogen mustard would produce pleural sclerosis in our experimental model in rabbits. We therefore evaluated sclerosing capabilities of nitrogen mustard as well as those of cytarabine and dacarbazine. Nitrogen mustard (0.4 and 0.8 mg x kg(-1)), cytarabine (3, 6 and 20 mg x kg(-1)) and dacarbazine (4, 8 and 20 mg x kg(-1)) were instilled intrapleurally into anaesthetized rabbits. Twenty eight days after the instillation, the animals were killed, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of 0.8 mg x kg(-1) nitrogen mustard was effective in creating pleural fibrosis, either grossly or microscopically. The mean degree (scale 0-4) of gross pleurodesis in the rabbits that received 0.8 mg x kg(-1) nitrogen mustard was 3.2+/-1.0 and the mean degree of microscopic pleural fibrosis was 3.5+/-0.8. The intrapleural injection of 0.4 mg x kg(-1) nitrogen mustard and the different doses of cytarabine (3, 6 and 20 mg x kg(-1)) and dacarbazine (4, 8 and 20 mg x kg(-1)) were ineffective in producing pleurodesis. From this study, we conclude that the intrapleural injection of 0.8 mg x kg(-1) of nitrogen mustard produces clinically significant pleurodesis in rabbits. Consideration should be given to future clinical studies utilizing 0.6-0.8 mg x kg(-1) nitrogen mustard intrapleurally for the treatment of malignant pleural effusion.
Lipolysis – A highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores
Authors: Achim Lass, Robert Zimmermann, Monika Oberer, Rudolf Zechner
Journal: Progress in Lipid Research (2010)

Lipolysis is the biochemical pathway responsible for the catabolism of triacylglycerol (TAG) stored in cellular lipid droplets. The hydrolytic cleavage of TAG generates non-esterified fatty acids, which are subsequently used as energy substrates, essential precursors for lipid and membrane synthesis, or mediators in cell signaling processes. Consistent with its central importance in lipid and energy homeostasis, lipolysis occurs in essentially all tissues and cell types, it is most abundant, however, in white and brown adipose tissue. Over the last 5years, important enzymes and regulatory protein factors involved in lipolysis have been identified. These include an essential TAG hydrolase named adipose triglyceride lipase (ATGL) [annotated as patatin-like phospholipase domain-containing protein A2], the ATGL activator comparative gene identification-58 [annotated as α/β hydrolase containing protein 5], and the ATGL inhibitor G0/G1 switch gene 2. Together with the established hormone-sensitive lipase [annotated as lipase E] and monoglyceride lipase, these proteins constitute the basic "lipolytic machinery". Additionally, a large number of hormonal signaling pathways and lipid droplet-associated protein factors regulate substrate access and the activity of the "lipolysome". This review summarizes the current knowledge concerning the enzymes and regulatory processes governing lipolysis of fat stores in adipose and non-adipose tissues. Special emphasis will be given to ATGL, its regulation, and physiological function.
Chemotherapy Induces the Expression of Cyclooxygenase-2 in Non–Small Cell Lung Cancer
Authors: Nasser K. Altorki, Jeffrey L. Port, Fan Zhang, Dragan Golijanin, Howard T. Thaler, Anna J. Duffield-Lillico, Kotha Subbaramaiah, Andrew J. Dannenberg
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To determine the effect of taxane-based chemotherapy on intratumoral levels of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in patients with non–small cell lung cancer (NSCLC). Experimental Design: Lung specimens obtained at the time of surgery were used to measure levels of COX-2 and PGE2 in tumors and adjacent nontumorous tissues in three subsets of NSCLC patients who underwent: (A) surgical resection only (n = 16); (B) surgical resection after preoperative taxane-based chemotherapy (n = 13); or (C) surgical resection after preoperative chemotherapy coadministered with the selective COX-2 inhibitor, celecoxib 400 mg bid (n = 17). Results: Levels of intratumoral PGE2 were nearly 3-fold higher among patients who received preoperative chemotherapy compared with those treated by surgery alone (P &amp;lt; 0.001). This difference was abrogated by the addition of celecoxib to preoperative chemotherapy (P &amp;lt; 0.001). Amounts of intratumoral COX-2 were ∼3-fold higher in groups of patients who received preoperative chemotherapy with celecoxib (P &amp;lt; 0.0001) or without celecoxib (P &amp;lt; 0.001), compared with the group who underwent surgical resection only. Importantly, statistically significant positive correlations between COX-2 and PGE2 were observed in the surgery only (r = 0.502, P = 0.047) and preoperative chemotherapy groups (r = 0.740, P = 0.004); this correlation was abrogated when celecoxib was given with chemotherapy (r = 0.005, P = 0.98). Conclusions: Treatment with chemotherapy led to increased amounts of COX-2 and PGE2 in NSCLC. Cotreatment with celecoxib abrogated the increase in levels of PGE2 but not COX-2 induced by chemotherapy. Importantly, these results clearly show that levels of a pharmacologic target (i.e., COX-2) can be affected by both the intrinsic molecular properties of a tumor and therapy.
Prostanoid Receptors: Subtypes and Signaling
Authors: Richard M Breyer, Carey K Bagdassarian, Scott A Myers, Matthew D Breyer
Journal: The Annual Review of Pharmacology and Toxicology (2001)

Cyclooxygenases metabolize arachidonate to five primary prostanoids: PGE(2), PGF(2 alpha), PGI(2), TxA(2), and PGD(2). These autacrine lipid mediators interact with specific members of a family of distinct G-protein-coupled prostanoid receptors, designated EP, FP, IP, TP, and DP, respectively. Each of these receptors has been cloned, expressed, and characterized. This family of eight prostanoid receptor complementary DNAs encodes seven transmembrane proteins which are typical of G-protein-coupled receptors and these receptors are distinguished by their ligand-binding profiles and the signal transduction pathways activated on ligand binding. Ligand-binding selectivity of these receptors is determined by both the transmembrane sequences and amino acid residues in the putative extracellular-loop regions. The selectivity of interaction between the receptors and G proteins appears to be mediated at least in part by the C-terminal tail region. Each of the EP(1), EP(3), FP, and TP receptors has alternative splice variants described that alter the coding sequence in the C-terminal intracellular tail region. The C-terminal variants modulate signal transduction, phosphorylation, and desensitization of these receptors, as well as altering agonist-independent constitutive activity.
Heterogeneous Models Place the Root of the Placental Mammal Phylogeny
Authors: Claire C. Morgan, Peter G. Foster, Andrew E. Webb, Davide Pisani, James O. McInerney, Mary J. O’Connell
Journal: Molecular Biology and Evolution (2013)

Heterogeneity among life traits in mammals has resulted in considerable phylogenetic conflict, particularly concerning the position of the placental root. Layered upon this are gene- and lineage-specific variation in amino acid substitution rates and compositional biases. Life trait variations that may impact upon mutational rates are longevity, metabolic rate, body size, and germ line generation time. Over the past 12 years, three main conflicting hypotheses have emerged for the placement of the placental root. These hypotheses place the Atlantogenata (common ancestor of Xenarthra plus Afrotheria), the Afrotheria, or the Xenarthra as the sister group to all other placental mammals. Model adequacy is critical for accurate tree reconstruction and by failing to account for these compositional and character exchange heterogeneities across the tree and data set, previous studies have not provided a strongly supported hypothesis for the placental root. For the first time, models that accommodate both tree and data set heterogeneity have been applied to mammal data. Here, we show the impact of accurate model assignment and the importance of data sets in accommodating model parameters while maintaining the power to reject competing hypotheses. Through these sophisticated methods, we demonstrate the importance of model adequacy, data set power and provide strong support for the Atlantogenata over other competing hypotheses for the position of the placental root.
Administration of Spores of Nontoxigenic<i>Clostridium difficile</i>Strain M3 for Prevention of Recurrent<i>C difficile</i>Infection
Authors: Dale N. Gerding, Thomas Meyer, Christine Lee, Stuart H. Cohen, Uma K. Murthy, Andre Poirier, Trevor C. Van Schooneveld, Darrell S. Pardi, Antonio Ramos, Michelle A. Barron, Hongzi Chen, Stephen Villano
Journal: JAMA (2015)

Clostridium difficile is the most common cause of health care-associated infection in US hospitals. Recurrence occurs in 25% to 30% of patients.To determine the safety, fecal colonization, recurrence rate, and optimal dosing schedule of nontoxigenic C. difficile strain M3 (VP20621; NTCD-M3) for prevention of recurrent C. difficile infection (CDI).Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from June 2011 to June 2013 among 173 patients aged 18 years or older who were diagnosed as having CDI (first episode or first recurrence) and had successfully completed treatment with metronidazole, oral vancomycin, or both at 44 study centers in the United States, Canada, and Europe.Patients were randomly assigned to receive 1 of 4 treatments: oral liquid formulation of NTCD-M3, 10(4) spores/d for 7 days (n = 43), 10(7) spores/d for 7 days (n = 44), or 10(7) spores/d for 14 days (n = 42), or placebo for 14 days (n = 44).The primary outcome was safety and tolerability of NTCD-M3 within 7 days of treatment. Exploratory secondary outcomes included fecal colonization with NTCD-M3 from end of study drug through week 6 and CDI recurrence from day 1 through week 6.Among 168 patients who started treatment, 157 completed treatment. One or more treatment-emergent adverse events were reported in 78% of patients receiving NTCD-M3 and 86% of patients receiving placebo. Diarrhea and abdominal pain were reported in 46% and 17% of patients receiving NTCD-M3 and 60% and 33% of placebo patients, respectively. Serious treatment-emergent adverse events were reported in 7% of patients receiving placebo and 3% of all patients who received NTCD-M3. Headache was reported in 10% of patients receiving NTCD-M3 and 2% of placebo patients. Fecal colonization occurred in 69% of NTCD-M3 patients: 71% with 10(7) spores/d and 63% with 10(4) spores/d. Recurrence of CDI occurred in 13 (30%) of 43 placebo patients and 14 (11%) of 125 NTCD-M3 patients (odds ratio [OR], 0.28; 95% CI, 0.11-0.69; P = .006); the lowest recurrence was in 2 (5%) of 43 patients receiving 10(7) spores/d for 7 days (OR, 0.1; 95% CI, 0.0-0.6; P = .01 vs placebo]). Recurrence occurred in 2 (2%) of 86 patients who were colonized vs 12 (31%) of 39 patients who received NTCD-M3 and were not colonized (OR, 0.01; 95% CI, 0.00-0.05; P < .001).Among patients with CDI who clinically recovered following treatment with metronidazole or vancomycin, oral administration of spores of NTCD-M3 was well tolerated and appeared to be safe. Nontoxigenic C. difficile strain M3 colonized the gastrointestinal tract and significantly reduced CDI recurrence.clinicaltrials.gov Identifier: NCT01259726.
Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID): an extension of the STROBE statement
Authors: Nigel Field, Ted Cohen, Marc J Struelens, Daniel Palm, Barry Cookson, Judith R Glynn, Valentina Gallo, Mary Ramsay, Pam Sonnenberg, Duncan MacCannell, Andre Charlett, Matthias Egger, Jonathan Green, Paolo Vineis, Ibrahim Abubakar
Journal: The Lancet Infectious Diseases (2014)
Recombinant human hepassocin stimulates proliferation of hepatocytes in vivo and improves survival in rats with fulminant hepatic failure
Authors: C. Y. Li, C. Z. Cao, W. X. Xu, M. M. Cao, F. Yang, L. Dong, M. Yu, Y. Q. Zhan, Y. B. Gao, W. Li, Z. D. Wang, C. H. Ge, Q. M. Wang, R. Y. Peng, X. M. Yang
Journal: Gut (2009)

<h3>Background</h3> Human hepassocin (HPS) was originally detected by subtractive and differential cDNA cloning as a liver-specific gene that was markedly upregulated during liver regeneration. Previous studies suggested that HPS showed mitogenic activity on isolated hepatocytes in vitro. However, its in vivo functions remained largely unknown. Therefore, the function of recombinant human HPS during liver regeneration and chemically induced liver injury was investigated. <h3>Methods</h3> The proliferation of primary hepatocytes was examined by [<sup>3</sup>H]thymidine incorporation and immunohistological staining of proliferating cell nuclear antigen (PCNA). RNA interference was performed to knock down the endogenous expression of HPS. The proliferation of L02 cells was examined by MTS assay. The phosphorylation of ERK1/2 (extracellular signal-regulated kinase 1/2) was investigated by western blotting analysis. Assessment of liver injury (histology, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels) and of apoptosis, by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay, was performed. <h3>Results</h3> Purified recombinant human HPS showed specific mitogenic activity on primary hepatocytes and normal liver cell lines in a mitogen-activated protein kinase (MAPK)-dependent manner and stimulated the proliferation of hepatocytes in rats with 70% partial hepatectomy. Administration of HPS to rats after d-galactose and carbon tetrachloride (CCl<sub>4</sub>) treatment protected against liver injury (minimal liver necrosis, depressed ALT and AST levels, and decreased lethality), reduced apoptosis and enhanced proliferation. Knock-down of endogenous HPS in vivo enhanced the liver injury induced by d-galactose by increasing the apoptosis and elevating ALT and AST levels. <h3>Conclusions</h3> HPS is a hepatic growth factor which can accelerate hepatocyte proliferation in vivo and protect against liver injury. These data point to the potential interest of HPS in the treatment of fulminant hepatic failure.
Heterocyclic Amine Content of Cooked Meat and Risk of Prostate Cancer
Authors: A. E. Norrish, L. R. Ferguson, M. G. Knize, J. S. Felton, S. J. Sharpe, R. T. Jackson
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Some epidemiologic studies have described positive associations between prostate cancer risk and meat consumption, but underlying mechanisms have not been identified. Heterocyclic amines are mutagens formed during the cooking of meat. Well-done meat has been associated with increased risks of colorectal and breast cancers in humans. This study examined associations between prostate cancer risk and 1) estimated daily intake of heterocyclic amines from cooked meat and 2) level of cooked-meat doneness. METHODS: A population-based, case-control study involving 317 case patients with prostate cancer and 480 age-matched control subjects was carried out in Auckland, New Zealand. Levels of meat doneness and daily intake of heterocyclic amines were determined from self-reported dietary data and experimentally measured heterocyclic amine levels in locally sourced meat samples cooked under controlled conditions to varying degrees of doneness. RESULTS: The heterocyclic amines found in the highest concentrations in meat samples were 2-amino-1,6-dimethylfuro[3,2- e ]imidazo[4,5- b ]pyridine (IFP) and 2-amino-1-methyl-6-phenylimidazo [ 4,5- b ]pyridine (PhIP) from well-done chicken and pork and very well-done beefsteak. Meat doneness was weakly and inconsistently associated with prostate cancer risk for individual types of meat, but increased risk was observed for well-done beefsteak (relative risk = 1.68; 95% confidence interval = 1.02-2.77; two-sided P for trend = .03). A weak positive gradient of increased risk was associated with estimated daily exposure to IFP but not with the other major heterocyclic amines. CONCLUSIONS: Meat doneness and estimated intake of heterocyclic amines from cooked meat were not clearly associated with prostate cancer risk.
CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: a retrospective substudy of the HERA trial (BIG 1-01)
Authors: Bernhard C Pestalozzi, Eileen Holmes, Evandro de Azambuja, Otto Metzger-Filho, Laurence Hogge, Matt Scullion, István Láng, Andrew Wardley, Mikhail Lichinitser, Roberto I Lopez Sanchez, Volkmar Müller, David Dodwell, Richard D Gelber, Martine J Piccart-Gebhart, David Cameron
Journal: The Lancet Oncology (2013)
Rapid detection of Mycobacterium tuberculosis from clinical specimens using a new target
Authors: Davood Darban-Sarokhalil, Mohammad Mehdi Feizabadi, Abbas Ali Imani Fooladi, Zakaria Bameri, Mohammad Javad Nasiri
Journal: European Respiratory Journal (2012)

Background:   Different DNA targets have been introduced for detection of  M. tuberculosis.  Of these targets,  IS 6110 has been used frequently. However, certain strains of  M. tuberculosis , particularly those identified in Southeast Asia, lack this insertion sequence.   Aims and objectives:   Cytochrome P450 CYP141 has not been used as target for detection of  M. tuberculosis . The aim of this study was to develop a new sensitive and specific PCR method for detection of  M. tuberculosis  directly from respiratory specimens.   Method:   The identification of  M. tuberculosis  isolates was confirmed using standard biochemical tests. Primer 3 plus software was used to design primers from CYP141. The expected size of the amplicon was 173 bp. We collected sputa from 247 suspected patients of different cities of Iran.   Results:    With the exception of  M. tuberculosis  complex, no amplification was obtained with DNA from other mycobacteria, potentially pathogenic bacteria in the respiratory tract and human cells. These results give evidence that CYP141 can be used as a target for direct detection of  M. tuberculosis  from respiratory specimens. The sensitivity of this target in smear positive- culture positive and smear negative-culture positive samples was 92% and 62.5%, respectively, and the specificity of the PCR was 97.8%.   Discussion   We obtained positive results with a trace amount of template DNA, as little as 1pg. Rv3121 or CYP141 exists in all  M. tuberculosis  isolates used in this study. The high overall specificity (97.8%) and sensitivity (85.7%) of this target in gene amplification illustrates that CYP141 can be a good target for detection of  M. tuberculosis  complex from sputum and possibly other clinical specimens.
England spends the least on healthcare but has highest life expectancy, audit of UK's four nations shows
Authors: A. O'Dowd
Journal: BMJ (2012)

While traditional forms of investment products such as public funds still dominate the investment industry, both traditional and alternative investments have experienced recent innovations in their structure. Many of these (structured notes, swaps) are much simpler than they appear, and can offer highly tailored exposure to unique sources of return. Expanding the set of investment opportunities through new structures results in unique return patterns that cannot be replicated through traditional stock, bond, and real estate investment strategies. As a result, these new product forms may increase the economic benefits available to current investors. In this article, the economic bases for new product forms and security design are discussed, and simulation examples of the return opportunities made available through both guaranteed structured notes and swaps are offered.