tbuckley/cabot-search huggingface dataset:
Eliminating Established Tumor in nu/nu Nude Mice by a Tumor Necrosis Factor-α-Related Apoptosis-Inducing Ligand–Armed Oncolytic Adenovirus
Authors: Fengqin Dong, Li Wang, John J. Davis, Wenxian Hu, Lidong Zhang, Wei Guo, Fuminori Teraishi, Lin Ji, Bingliang Fang
Journal: Clinical Cancer Research (2006)

The tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) and oncolytic viruses have recently been investigated extensively for cancer therapy. However, preclinical and clinical studies have revealed that their clinical application is hampered by either weak anticancer activity or systemic toxicity. We examined whether the weaknesses of the two strategies can be overcome by integrating the TRAIL gene into an oncolytic vector.We constructed a TRAIL-expressing oncolytic adenovector designated as Ad/TRAIL-E1. The expression of both the TRAIL and viral E1A genes is under the control of a synthetic promoter consisting of sequences from the human telomerase reverse transcriptase promoter and a minimal cytomegalovirus early promoter. The transgene expression, apoptosis induction, viral replication, antitumor activity, and toxicity of Ad/TRAIL-E1 were determined in vitro and in vivo in comparison with control vectors.Ad/TRAIL-E1 elicited enhanced viral replication and/or stronger oncolytic effect in vitro in various human cancer cell lines than a TRAIL-expressing, replication-defective adenovector or an oncolytic adenovector-expressing green fluorescent protein. Intralesional administration of Ad/TRAIL-E1 eliminated all s.c. xenograft tumors established from a human non-small cell lung cancer cell line, H1299, on nu/nu nude mice, resulting in long-term, tumor-free survival. Furthermore, we found no treatment-related toxicity.Viral replication and antitumor activity of oncolytic adenovirus can be enhanced by the TRAIL gene and Ad/TRAIL-E1 could become a potent therapeutic agent for cancer therapy.
Stem Cell Transfusion Restores Immune Function in Radiation-Induced Lymphopenic C57BL/6 Mice
Authors: Vaishali Kapoor, Arpine Khudanyan, Pilar de la Puente, Jian Campian, Dennis E. Hallahan, Abdel Kareem Azab, Dinesh Thotala
Journal: Cancer Research (2015)

Abstract Radiation-induced lymphopenia (RIL) is associated with treatment of different tumors (lung, colon, pancreas, breast, sarcomas, and glioblastoma). It is a significant clinical problem affecting the survival of cancer patients. The biologic mechanisms leading to RIL are not clearly understood. In this study, we established a mouse model of RIL representing therapeutic clinical regimen for lung cancer. Flow cytometry was used to analyze circulating levels of T and B cells and bone marrow (BM) stem cells. We found that fractionated radiation to the thorax significantly reduced circulating T and B cells as well as BM stem cells. Ex-vivo irradiation of blood and autologous reinjection to mice also significantly induced lymphopenia. Furthermore, we found that mobilization of stem cells from the BM and autologous stem cell transplant rescued RIL in mice. Overall, our results suggest that RIL has not only direct effect on circulating lymphocytes, but also has indirect effect on circulating lymphocytes as well as stem cells in the nonirradiated BM. These results open a new window for investigating the direct and indirect biologic mechanisms leading to RIL, and provide a preclinical basis to test the effect of stem cell transplantation for treatment of RIL in cancer patients. Cancer Res; 75(17); 3442–5. ©2015 AACR.
Antitumor Effects of Thalidomide Analogs in Human Prostate Cancer Xenografts Implanted in Immunodeficient Mice
Authors: Sylvia S. W. Ng, Gordon R. MacPherson, Michael Gütschow, Kurt Eger, William D. Figg
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Thalidomide has demonstrated clinical activity in various malignancies including androgen-independent prostate cancer. The development of novel thalidomide analogs with better activity/toxicity profiles is an ongoing research effort. Our laboratory previously reported the in vitro antiangiogenic activity of the N-substituted thalidomide analog CPS11 and the tetrafluorinated analogs CPS45 and CPS49. The current study evaluated the therapeutic potential of these analogs in the treatment of prostate cancer in vivo. Experimental Design: Severely combined immunodeficient mice bearing s.c. human prostate cancer (PC3 or 22Rv1) xenografts were treated with the analogs at their maximum tolerated doses. Tumors were then excised and processed for ELISA and CD31 immunostaining to determine the levels of various angiogenic factors and microvessel density (MVD), respectively. Results: CPS11, CPS45, and CPS49 induced prominent and modest growth inhibition in PC3 and 22Rv1 tumors, respectively. Thalidomide had no effect on tumor growth in either xenograft. Vascular endothelial growth factor and basic fibroblast growth factor levels were not significantly altered by any of the thalidomide analogs or thalidomide in both PC3 and 22Rv1 tumors. CPS45, CPS49, and thalidomide significantly reduced PC3 tumor platelet-derived growth factor (PDGF)-AA levels by 58–82% (P &amp;lt; 0.05). Interestingly, treatment with the analogs and thalidomide resulted in differential down-regulation (≥1.5-fold) of genes encoding PDGF and PDGF receptor isoforms as determined by DNA microarray analysis. Intratumoral MVD of 22Rv1 xenografts was significantly decreased by CPS45 and CPS49. CPS49 also reduced MVD in PC3 xenografts. Conclusions: Thalidomide analogs CPS11 and 49 are promising anti-cancer agents. PDGF signaling pathway may be a potential target for these thalidomide analogs. Detailed microarray and functional analyses are under way with the aim of elucidating the molecular mechanism(s) of action of these thalidomide analogs.
Association Between Use of the 21-Gene Recurrence Score Assay and Receipt of Chemotherapy Among Medicare Beneficiaries With Early-Stage Breast Cancer, 2005-2009
Authors: Michaela A. Dinan, Xiaojuan Mi, Shelby D. Reed, Gary H. Lyman, Lesley H. Curtis
Journal: JAMA Oncology (2015)

<h3>Importance</h3> Guidelines recommend consideration of chemotherapy for most patients with early-stage, estrogen receptor–positive, invasive breast cancer in the absence of additional prognostic information. The 21-gene recurrence score (RS) assay has been shown in limited academic settings to reduce physician recommendations for adjuvant chemotherapy. Associations between the adoption of the assay and receipt of chemotherapy in the general population have not been examined. <h3>Objective</h3> To examine whether adoption of the RS assay in a nationally representative sample of patients with early-stage breast cancer was associated with use of chemotherapy. <h3>Design, Setting, and Participants</h3> Retrospective cohort study of Medicare beneficiaries who received a diagnosis of incident breast cancer between 2005 and 2009 using Surveillance, Epidemiology, and End Results data set with linked Medicare claims. <h3>Main Outcomes and Measures</h3> Receipt of chemotherapy within 12 months after diagnosis. <h3>Results</h3> A total of 44 044 patients had low-risk (24.0%), intermediate-risk (51.3%), or high-risk disease (24.6%, lymph node positive) as defined by National Comprehensive Cancer Network (NCCN) guidelines and met the study criteria. We observed no overall association between receipt of the RS assay and chemotherapy (odds ratio [OR], 1.03 [99% CI, 0.88-1.19]). In multivariable analysis, there was a significant interaction between NCCN risk and use of the RS assay, with assay use associated with lower chemotherapy use in high-risk patients (OR, 0.36 [99% CI, 0.26-0.50]) and greater chemotherapy use in low-risk patients (OR, 3.71 [99% CI, 2.30-5.98]), compared with no receipt of the assay (<i>P</i> = .006 for the overall interaction). Results were similar in prespecified subgroup analyses of patients 70 years and younger, with the exception of a shift toward lower chemotherapy use during 2008 (OR, 0.90 [99% CI, 0.77-.1.05];<i>P</i> = .09) and 2009 (OR, 0.81 [99% CI, 0.66-0.99];<i>P</i> = .007). In unadjusted analyses, overall chemotherapy use decreased over time in patients 70 years or younger with high-risk disease and those receiving the assay. <h3>Conclusions and Relevance</h3> The impact of the adoption of the RS assay on receipt of chemotherapy was strongly population dependent and was associated with relatively lower chemotherapy use in groups with high-risk disease and relatively higher chemotherapy use in patients with low-risk disease. Overall use of chemotherapy decreased during the study period in patients who were most likely to receive chemotherapy.
Expression, Release, and Biological Activity of Parathyroid Hormone–Related Peptide From Coronary Endothelial Cells
Authors: K.-D. Schlüter, C. Katzer, K. Frischkopf, S. Wenzel, G. Taimor, H. M. Piper
Journal: Circulation Research (2000)

Abstract —Ventricular cardiomyocytes have previously been identified as potential target cells for parathyroid hormone–related peptide (PTHrP). Synthetic PTHrP peptides exert a positive contractile effect. Because systemic PTHrP levels are normally negligible, this suggests that PTHrP is expressed in the ventricle and acts as a paracrine mediator. We investigated the ventricular expression of PTHrP and its expression in cultured cells isolated from the ventricle, studied the release of PTHrP from hearts and cultures, and investigated whether this authentic PTHrP mimics the biological effects previously described for synthetic PTHrP on ventricular cardiomyocytes. We found PTHrP expressed in ventricles of neonatal and adult rat hearts. In cells isolated from adult hearts, we found PTHrP expression exclusively in coronary endothelial cells but not in cardiomyocytes. The latter, however, are target cells for PTHrP. PTHrP was released from isolated perfused hearts during hypoxic perfusion and from cultured coronary endothelial cells under energy-depleting conditions. This PTHrP was biologically active; ie, it exerted a positive contractile and lusitropic effect on cardiomyocytes. Authentic PTHrP was glycosylated and showed a slightly higher potency than synthetic PTHrP. These results suggest that PTHrP is an endothelium-derived modulator of ventricular function.
Brief Communication: The Relationship of Regression of Cirrhosis to Outcome in Chronic Hepatitis C
Authors: Vincent Mallet, Hélène Gilgenkrantz, Jeanne Serpaggi, Virginie Verkarre, Anaïs Vallet-Pichard, Hélène Fontaine, Stanislas Pol
Journal: Annals of Internal Medicine (2008)

Background: The effect of regression of cirrhosis in chronic hepatitis C is unknown. Objective: To evaluate the relation between regression of cirrhosis and clinical outcome in patients with chronic hepatitis C after antiviral therapy. Design: A cohort of patients with cirrhosis treated between 1988 and 2001. Setting: Hepatology unit of a tertiary care center in France. Patients: 96 patients with chronic hepatitis C and biopsy-proven cirrhosis (METAVIR score F4) who were treated with an interferon-based regimen and had at least 1 posttreatment liver biopsy. Patients were followed until November 2006. Measurements: Occurrence of a combined end point of liver-related events (ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatocellular carcinoma, or liver transplantation) and death in patients with regression of cirrhosis (defined as a decrease from 4 to ≤2 METAVIR units on posttherapy liver biopsy). Results: The median follow-up was 118 months (interquartile range, 86 to 138 months). Eighteen patients had regression of cirrhosis. The incidence of the combined end point per 100 patient-years was 0 in patients with regression of cirrhosis and 4 in patients without regression of cirrhosis (P = 0.002, log-rank test). The transplantation-free survival rate at 10 years was 100% in patients with regression of cirrhosis and 74.2% in patients without regression of cirrhosis (P = 0.025). Limitations: Selection of patients was retrospective; selection and survival biases may have influenced the estimates of the overall rate of regression of cirrhosis. The low number of patients who experienced regression of cirrhosis precludes analysis of factors that could predict regression of cirrhosis. Conclusion: Regression of cirrhosis occurs after antiviral therapy in some patients with chronic hepatitis C. Regression is associated with decreased disease-related morbidity and improved survival.
Immunohistochemical localisation of the matrix metalloproteinases MMP-3 and MMP-9 within the airways in asthma
Authors: B. Dahlen, J. Shute, P. Howarth
Journal: Thorax (1999)

<h3>BACKGROUND</h3> The matrix metalloproteinase (MMP) enzymes MMP-3 and MMP-9 have relevance to the chronic structural airway changes in asthma. These proteinases can be generated by structural and inflammatory cells, and have the ability to degrade proteoglycans and thus potentially enhance airway fibrosis and smooth muscle proliferation through their ability to release and activate latent matrix bound growth factors. <h3>METHODS</h3> Immunostaining for MMP-3 and MMP-9 as well as for mast cells, eosinophils, and neutrophils was undertaken in acetone fixed and glycolmethacrylate embedded endobronchial biopsy specimens obtained by fibreoptic bronchoscopy under local anaesthesia. The findings from 17 asthmatic subjects (nine with mild to moderate non-steroid treated asthma and eight with chronic persistent steroid-dependent asthma) were compared with those from eight healthy controls. The cell associated MMP immunoreactivity was co-localised to mast cells, eosinophils, or neutrophils and represented as cells/mm<sup>2</sup>, based on the area of the biopsy specimen. Extracellular matrix immunoreactivity was assessed by an image analysis system and visually with ranking and the two approaches were compared. <h3>RESULTS</h3> The biopsy specimens from asthmatic subjects contained significantly more eosinophils (p&lt;0.001) than those from the non-asthmatic subjects. Both MMP-9 and MMP-3 immunoreactivity could be identified in endobronchial biopsy specimens. Gelatinase B (MMP-9) immunoreactivity was prominent within the extracellular matrix as well as exhibiting distinct cell immunoreactivity which predominantly co-localised to neutrophils. Stromelysin (MMP-3) was co-localised to mast cells, eosinophils, and neutrophils as well as being present in the epithelium, the lamina reticularis and, to a lesser extent, the extracellular matrix. There was no significant difference in the extent of matrix immunoreactivity for either MMP-3 or MMP-9 between healthy controls or subjects with mild or severe asthma. <h3>CONCLUSION</h3> Although immunostaining cannot distinguish between active and inactive forms of MMPs, the presence of MMP-3 and MMP-9 within endobronchial biopsy specimens, the co-localisation to inflammatory cells of relevance to asthma (mast cells and eosinophils), and the identification of matrix binding, indicative of MMP-matrix interactions, points to the potential for disease related changes in MMP release that influence airway remodelling in asthma.
Effects of Hepatic Triglyceride Content on Myocardial Metabolism in Type 2 Diabetes
Authors: Luuk J. Rijzewijk, Jacqueline T. Jonker, Rutger W. van der Meer, Mark Lubberink, Hugo W. de Jong, Johannes A. Romijn, Jeroen J. Bax, Albert de Roos, Robert J. Heine, Jos W. Twisk, Albert D. Windhorst, Adriaan A. Lammertsma, Johannes W.A. Smit, Michaela Diamant, Hildo J. Lamb
Journal: Journal of the American College of Cardiology (2010)
Neurological sequelae in patients recovered from fulminant hepatic failure.
Authors: C J O'Brien, R J Wise, J G O'Grady, R Williams
Journal: Gut (1987)

Two teenage patients with fulminant hepatic failure progressing to grade 4 encephalopathy with clinical signs of cerebral oedema are described, in whom permanent neurological injury (involving the brain stem in one and the cerebral cortex in the other) was the sequel to an otherwise full recovery. The present day management of cerebral oedema may, as in these two cases, ensure the survival of patients with fulminant hepatic failure who would previously have been likely to die from the effects of raised intracranial pressure. As a result it is now possible more recovered cases will be seen with residual neurological deficits, a previously very rarely recorded event.
Retraction of: Statin enhances cytokine-mediated induction of nitric oxide synthesis in vascular smooth muscle cells
Authors: Yoshiyuki Hattori, Nobuo Nakanishi, Kikuo Kasai
Journal: Cardiovascular Research (2011)

This article has been retracted by the journal due to the fact that it contains data that are identical to those shown in a previously published article: In Fig. 2A, the photomicrographs of cells in (a) (“control”) and (b) (“LPS”) are the same as those shown in Fig. 1C (a) (“control”) and (b) (“TNFa”) of a previous article by this group (except that the image in (a) is turned 1808). In Fig. 2B, the leftmost three bands (for “Cont”, “LPS”, and “+ NOR3”) are the same as those shown Fig. 1B (for “Cont”, “TNFa”, and “TNFa + competitor”) of the previous article (except that the latter lanes are underexposed).
Cryptorchidism: a renewed plea.
Authors: C G Scorer
Journal: BMJ (1979)

acceptable" must be rejected.Any method of delivery that increases perinatal morbidity is open to challenge, particularly when that method is directly responsible for a perinatal mortality rate of 35 per 1000.In their second paper Drs Chiswick and James ignore the role of the active management of labour in avoiding the type of complications leading up to Kielland's delivery.Several papers have been published which conclusively demonstrate that these problems are avoid- able.-'-5None of the correspondents appear to recognise the essential difference between intracranial haemorrhage due to trauma and that due to asphyxia.Tentorial tears, which cause subdural haemorrhage, have been shown to be 11 times more common when forceps have been applied, with or without intrapartum hypoxia,6 and virtually all cases of gross intracranial haemorrhage occurring during labour are due to trauma.In contrast, asphyxial intracranial haemorrhage in the mature infant is characteristically subarachnoid and petechial.Finally, in the broader context of the role of Kielland's forceps in modern obstetrics my experience convinces me that they have no place.This personal experience is based on exposure to about 12 000 deliveries where labour was actively managed and Kielland's forceps unavailable (at the National Maternity Hospital, Dublin).
Numbers and numerosities: Absence of abstract neural realization doesn't mean non-abstraction
Authors: Rafael E. Núñez
Journal: Behavioral and Brain Sciences (2009)

Abstract The neural realization of number in abstract form is implausible, but from this it doesn't follow that numbers are not abstract. Clear definitions of abstraction are needed so they can be applied homogenously to numerical and non-numerical cognition. To achieve a better understanding of the neural substrate of abstraction, productive cognition – not just comprehension and perception – must be investigated.
Effect of Afterload on Force-Velocity Relations and Contractile Element Work in the Intact Dog Heart
Authors: Herbert J. Levine, Stanley A. Forwand, Kevin M. Mclntyre, Eliot Schechter
Journal: Circulation Research (1966)

The effects of heightened afterload on force-velocity relations and on contractile element work of single systoles were examined in the intact dog heart. The force-velocity curve described during the course of a normal systole represents a composite of curves, each with its own projected isometric force determined by instantaneous changes in fiber length. During the first systole following an afterload intervention, reciprocal changes in force and velocity were observed together with an extension of the projected isometric-force. The effect of afterload on contractile element work was determined by: (1) the direction and magnitude of the afterload, and (2) the afterload of the control beat itself. When the control beat was lightly loaded, an increase in afterload increased contractile element work by two additive mechanisms: (1) an increase in mean isometric force, and (2) a shift of force-velocity relations to positions of greater power and work production. In normally loaded control beats, an increase in afterload resulted in a decrease in contractile element work, despite the fact that mean isometric force was increased. In this instance, force-velocity relations were shifted to positions where less power and work could be achieved. Thus, the normal systole appears to function at the apex of the contractile element work-load curve (near 60% of the isometric load). Evidence is presented which suggests that the apparent maximum active state of the entire left ventricle is generally achieved within 30 to 50 msec after the onset of pressure rise, and that its decay is accompanied by abrupt divergence of the force-velocity relations from the inverse curve of that beat. A sudden increase in afterload does not appear to influence the duration of the maximum active state, although the duration of positive contractile element work is shortened and that of negative contractile element work prolonged.
Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia
Authors: Thomas P Hellyer, Andrew Conway Morris, Daniel F McAuley, Timothy S Walsh, Niall H Anderson, Suveer Singh, Paul Dark, Alistair I Roy, Simon V Baudouin, Stephen E Wright, Gavin D Perkins, Kallirroi Kefala, Melinda Jeffels, Ronan McMullan, Cecilia M O'Kane, Craig Spencer, Shondipon Laha, Nicole Robin, Savita Gossain, Kate Gould, Marie-Hélène Ruchaud-Sparagano, Jonathan Scott, Emma M Browne, James G MacFarlane, Sarah Wiscombe, John D Widdrington, Ian Dimmick, Ian F Laurenson, Frans Nauwelaers, A John Simpson
Journal: Thorax (2014)

<h3>Background</h3> Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare. <h3>Objectives</h3> We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP. <h3>Methods</h3> A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at &gt;10<sup>4</sup> colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1β), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination. <h3>Results</h3> Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (p&lt;0.001). The area under the receiver operator characteristic curve for IL-1β was 0.81; IL-8, 0.74; MMP-8, 0.76; MMP-9, 0.79 and HNE, 0.78. A combination of IL-1β and IL-8, at the optimal cut-point, excluded VAP with a sensitivity of 100%, a specificity of 44.3% and a post-test probability of 0% (95% CI 0% to 9.2%). <h3>Conclusions</h3> Low BALF IL-1β in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.
Analysis of data from the ERA-EDTA Registry indicates that conventional treatments for chronic kidney disease do not reduce the need for renal replacement therapy in autosomal dominant polycystic kidney disease
Authors: Edwin M. Spithoven, Anneke Kramer, Esther Meijer, Bjarne Orskov, Christoph Wanner, Fergus Caskey, Frederic Collart, Patrik Finne, Damian G. Fogarty, Jaap W. Groothoff, Andries Hoitsma, Marie-Béatrice Nogier, Maurizio Postorino, Pietro Ravani, Oscar Zurriaga, Kitty J. Jager, Ron T. Gansevoort
Journal: Kidney International (2014)