tbuckley/cabot-search huggingface dataset:
OC-057 10 Years on from the improving outcomes guidance—development of a tertiary pancreatic cancer unit
Authors: M Johnstone, C M Halloran, P Ghaneh, R Sutton, J P Neoptolemos, M G T Raraty
Journal: Gut (2012)

<h3>Introduction</h3> In 2001 the National Institute for Clinical Excellence (NICE) published guidance on best practice for cancer services entitled Improving Outcomes Guidance (IOG). These guidelines specified centralisation, increased patient volume (&gt;200 referrals/year), improved resection rates (&gt;10%–15%) and reduced post-operative mortality rates (&lt;5%). We looked at the development of a regional tertiary pancreatic centre over the 10 years following this, and how practice has changed over this time. <h3>Methods</h3> A prospectively maintained database of all referrals with suspected pancreatic cancer to the Supra-Regional Pancreas Centre in Liverpool was interrogated to assess changes in practice and outcome from 2001 to 2010 inclusive. Data were analysed with χ<sup>2</sup> for trend for categorical data and log rank for survival data. <h3>Results</h3> 2076 patients with malignancy were referred, rising from 73 in 2001 to 364 in 2010. 511 resections for malignancy were performed (25%), ranging between 21% (42/182) in 2005 and 36% (33/87) in 2003 per year, with no trend over time. 710 patients underwent planned operation for malignancy over the 10-year period ranging from 41 procedures in 2001 and peaking at 97 in 2008, with 94 procedures in 2009 and 88 cases in 2010. The percentage of planned resections that had a successful resection increased from 51% (21/41) in 2001 to 90% (79/88) by 2010 (p&lt;0.001). The mortality from resection was 9/567 (2%) and overall was 5% (37/710) including palliative procedures. The 1 year survival rates of patients who underwent a successful resection improved from 65% (13/20) in 2001 to 76% (69/91) by 2009 (p=0.02). There has been a rise in the number of intraductal papillary mucinous neoplasm (IPMN) resected with none in 2001 increasing to 12 resections during 2009, 10 in 2010 and 212 patients currently undergoing surveillance for IPMN. The number of staging laparoscopies has remained fairly constant at around 27 per year, despite the increase in referrals, which reflects more stringent criteria in selecting these patients for laparoscopy. <h3>Conclusion</h3> Over the last 10 years we have seen centralisation of services, which was completed in 2007. This has led to an increase in volume of cancer referrals in line with IOG guidance. Although resection rates have stayed constant, this reflects the increasing number of patients referred with irresectable disease for other treatments, including chemotherapy and novel cancer trials. There has been an improvement in case selection as demonstrated by a reduction in the percentage of bypass procedures, reflecting better pre-operative staging of patients. This has also lead to an improved 1-year survival in those patients who had a successful resection. <h3>Competing interests</h3> None declared.
NPM-ALK transgenic mice spontaneously develop T-cell lymphomas and plasma cell tumors
Authors: Roberto Chiarle, Jerald Z. Gong, Ilaria Guasparri, Anna Pesci, Jonjing Cai, Jian Liu, William J. Simmons, Girish Dhall, Jennifer Howes, Roberto Piva, Giorgio Inghirami
Journal: Blood (2003)
Impact of meriolins, a new class of cyclin-dependent kinase inhibitors, on malignant glioma proliferation and neo-angiogenesis
Authors: M. Jarry, C. Lecointre, C. Malleval, L. Desrues, M.-T. Schouft, V. Lejoncour, F. Liger, G. Lyvinec, B. Joseph, N. Loaec, L. Meijer, J. Honnorat, P. Gandolfo, H. Castel
Journal: Neuro-Oncology (2014)

Glioblastomas are the most frequent and most aggressive primary brain tumors in adults. The median overall survival is limited to a few months despite surgery, radiotherapy, and chemotherapy. It is now clearly established that hyperactivity of cyclin-dependent kinases (CDKs) is one of the processes underlying hyperproliferation and tumoral growth. The marine natural products meridianins and variolins, characterized as CDK inhibitors, display a kinase-inhibitory activity associated with cytotoxic effects. In order to improve selectivity and efficiency of these CDK inhibitors, a series of hybrid compounds called meriolins have been synthesized. The potential antitumoral activity of meriolins was investigated in vitro on glioma cell lines (SW1088 and U87), native neural cells, and a human endothelial cell line (HUV-EC-C). The impact of intraperitoneal or intratumoral administrations of meriolin 15 was evaluated in vivo on 2 different nude mice-xenografted glioma models. Meriolins 3, 5, and 15 exhibited antiproliferative properties with nanomolar IC50 and induced cell-cycle arrest and CDK inhibition associated with apoptotic events in human glioma cell lines. These meriolins blocked the proliferation rate of HUV-EC-C through cell cycle arrest and apoptosis. In vivo, meriolin 15 provoked a robust reduction in tumor volume in spite of toxicity for highest doses, associated with inhibition of cell division, activation of caspase 3, reduction of CD133 cells, and modifications of the vascular architecture. Meriolins, and meriolin 15 in particular, exhibit antiproliferative and proapoptotic activities on both glioma and intratumoral endothelial cells, constituting key promising therapeutic lead compounds for the treatment of glioblastoma.
Hepatitis B Reactivation in Patients With Previous Hepatitis B Virus Exposure Undergoing Rituximab-Containing Chemotherapy for Lymphoma: A Prospective Study
Authors: Wai-Kay Seto, Thomas S.Y. Chan, Yu-Yan Hwang, Danny Ka-Ho Wong, James Fung, Kevin Sze-Hang Liu, Harinder Gill, Yuk-Fai Lam, Albert K.W. Lie, Ching-Lung Lai, Yok-Lam Kwong, Man-Fung Yuen
Journal: Journal of Clinical Oncology (2014)

Patterns of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) -negative, antihepatitis B core antigen antibody (anti-HBc) -positive patients with lymphoma receiving rituximab-containing chemotherapy have not been well described.HBsAg-negative, anti-HBc-positive Chinese patients with undetectable serum HBV DNA (< 10 IU/mL), diagnosed with hematologic malignancies and receiving rituximab-containing chemotherapy, were prospectively monitored every 4 weeks for up to 2 years. Entecavir was started when HBV reactivation (defined as detectable HBV DNA) was encountered.Among 260 patients receiving rituximab-containing chemotherapy, 63 patients (24.2%) who were HBsAg negative and anti-HBc positive underwent follow-up for a median of 70 weeks (range, 6 to 104 weeks). The 2-year cumulative rate of HBV reactivation was 41.5%, occurring at a median of 23 weeks (range, 4 to 100 weeks) after rituximab treatment. The median HBV DNA level at reactivation was 43 IU/mL (range, 14 to 920 IU/mL). A baseline undetectable antibody to HBsAg (anti-HBs; < 10 mIU/mL) was the only significant risk factor that was positively associated with HBV reactivation (hazard ratio, 3.51; 95% CI, 1.37 to 8.98; P = .009). Patients with negative baseline anti-HBs, compared with those with positive anti-HBs, had a significantly higher 2-year cumulative rate of HBV reactivation (68.3% v 34.4%; P = .012). At HBV reactivation, all patients had normal ALT, and all patients but one were HBsAg negative. Entecavir successfully controlled HBV reactivation in all patients.A high rate of HBV reactivation was observed in HBsAg-negative, anti-HBc-positive patients undergoing rituximab-containing chemotherapy, with the risk of reactivation significantly higher in anti-HBs-negative patients. Periodic HBV DNA monitoring was an effective strategy in preventing HBV-related complications.
Excitatory Superficial Dorsal Horn Interneurons Are Functionally Heterogeneous and Required for the Full Behavioral Expression of Pain and Itch
Authors: Xidao Wang, Jie Zhang, Derek Eberhart, Rochelle Urban, Karuna Meda, Carlos Solorzano, Hiroki Yamanaka, Dennis Rice, Allan I. Basbaum
Journal: Neuron (2013)
Microglial p38α MAPK is critical for LPS-induced neuron degeneration, through a mechanism involving TNFα
Authors: Bin Xing, Adam D Bachstetter, Linda J Van Eldik
Journal: Molecular Neurodegeneration (2011)

Abstract Background The p38α MAPK isoform is a well-established therapeutic target in peripheral inflammatory diseases, but the importance of this kinase in pathological microglial activation and detrimental inflammation in CNS disorders is less well understood. To test the role of the p38α MAPK isoform in microglia-dependent neuron damage, we used primary microglia from wild-type (WT) or p38α MAPK conditional knockout (KO) mice in co-culture with WT cortical neurons, and measured neuron damage after LPS insult. Results We found that neurons in co-culture with p38α-deficient microglia were protected against LPS-induced synaptic loss, neurite degeneration, and neuronal death. The involvement of the proinflammatory cytokine TNFα was demonstrated by the findings that p38α KO microglia produced much less TNFα in response to LPS compared to WT microglia, that adding back TNFα to KO microglia/neuron co-cultures increased the LPS-induced neuron damage, and that neutralization of TNFα in WT microglia/neuron co-cultures prevented the neuron damage. These results using cell-selective, isoform-specific KO mice demonstrate that the p38α MAPK isoform in microglia is a key mediator of LPS-induced neuronal and synaptic dysfunction. The findings also provide evidence that a major mechanism by which LPS activation of microglia p38α MAPK signaling leads to neuron damage is through up-regulation of the proinflammatory cytokine TNFα. Conclusions The data suggest that selective targeting of p38α MAPK signaling should be explored as a potential therapeutic strategy for CNS disorders where overproduction of proinflammatory cytokines is implicated in disease progression.
In utero gene transfer of human factor IX to fetal mice can induce postnatal tolerance of the exogenous clotting factor
Authors: Simon N. Waddington, Suzanne M. K. Buckley, Megha Nivsarkar, Sarah Jezzard, Holm Schneider, Thomas Dahse, Geoff Kemball-Cook, Maznu Miah, Nick Tucker, Margaret J. Dallman, Mike Themis, Charles Coutelle
Journal: Blood (2003)
Aetiology of AIDS
Authors: MartinT. Schechter, KevinJ.P. Craib, JulioS.G. Montaner, ThinhN. Lee, MichaelV. O'Shaughnessy, KarenA. Gelmon, MichaelS. Ascher, HaynesW. Sheppard, Warren Winkelstein, Eric Vittinghoff, Keith Neal, A.G. Dalgleish
Journal: The Lancet (1993)
Differential Effects of Theophylline on Sympathetic Excitation, Hemodynamics, and Breathing in Congestive Heart Failure
Authors: Stefan Andreas, Hartwig Reiter, Lars Lüthje, André Delekat, Rolf W. Grunewald, Gerd Hasenfuss, Virend K. Somers
Journal: Circulation (2004)

Patients with heart failure have high levels of central sympathetic outflow and also have a high prevalence of sleep-related breathing disorders, predominantly central sleep apnea. The options for treating central sleep apnea in heart failure are limited and include theophylline. Whether theophylline alters sympathetic activity in heart failure patients is not known.Using a single-blinded, randomized, placebo-controlled study design, we investigated the sympathetic, hemodynamic, neurohumoral, and ventilatory effects of theophylline in patients with congestive heart failure compared with healthy control subjects closely matched for age, sex, and body mass index. Theophylline increased muscle sympathetic nerve activity and lowered transcutaneous CO2 in the control subjects but only lowered transcutaneous CO2 in the heart failure patients. Theophylline nearly doubled plasma renin concentration in both the healthy subjects (P<0.01) and the heart failure patients (P<0.02).Our study shows that in heart failure patients, there are differential effects of theophylline: in contrast to healthy subjects, theophylline does not increase sympathetic activity in heart failure, whereas increases in plasma renin and ventilation are still evident. These novel findings may have important implications for understanding the potential harmful and beneficial effects of theophylline and related substances in heart failure patients.
Research approaches to describe the mechanisms of injuries in sport: limitations and possibilities
Authors: T Krosshaug, T E Andersen, O-E O Olsen, G Myklebust, R Bahr
Journal: British Journal of Sports Medicine (2005)

A number of different methodological approaches have been used to describe the inciting event for sports injuries. These include interviews of injured athletes, analysis of video recordings of actual injuries, clinical studies (clinical findings of joint damage are studied to understand the injury mechanism, mainly through plain radiography, magnetic resonance imaging, arthroscopy, and computed tomography scans), in vivo studies (ligament strain or forces are measured to understand ligament loading patterns), cadaver studies, mathematical modelling and simulation of injury situations, and measurement/estimation from “close to injury” situations. In rare cases, injuries have even occurred during biomechanical experiments. This review describes each research approach and assesses its strengths and weaknesses in contributing to the understanding and prevention of sports injuries.
Influence of anatomic site and age on the replication and differentiation of rat adipocyte precursors in culture.
Authors: P Djian, A K Roncari, C H Hollenberg
Journal: Journal of Clinical Investigation (1983)

Using a propagating cell culture system of adipocyte precursors from 70-400-g rats, we explored the possibility that regional variations in properties of adipose tissue may reflect site-specific characteristics intrinsic to the cells, rather than extracellular influences. Initially, studies were made of the nature of the fibroblastlike cells from perirenal adipose tissue stroma. Using colony-forming techniques, it was shown that these cells were adipocyte precursors; each confluent colony that was derived from a single cell displayed differentiated adipocytes. This characteristic was evident in cells from rats of all ages and persisted during secondary culture. At all ages of rats studied, perirenal cells replicated more rapidly than epididymal precursors, e.g., for 179-g rats the population-doubling times were 19.3 +/- 0.7 vs. 25.5 +/- 1.2 h (means +/- SEM, P less than 0.03). With aging of the rats, the replication rate of their perirenal cells decreased progressively. Under clonal conditions, the colony size distribution of both perirenal and epididymal precursors revealed heterogeneity in their capacity for replication, perirenal cells showing greater proliferation. These also differentiated more extensively by morphologic and enzymatic criteria. Age and site had effects that persisted through many cell generations; however, high-fat feeding had no perpetuating influence. The dissimilar properties of perirenal as compared with epididymal precursors may reflect differences in regulation of gene expression. The data are also compatible with a later development in embryological life of perirenal tissue. We suggest that the composition of the adipocyte precursor pool is an important determinant of the growth of adipose tissue that occurs in response to a nutrient load. Interregional or interindividual variation in composition may explain regional and individual differences in fat accumulation.
Less Toxic Chemotherapy Improves Uptake of All Lines of Chemotherapy in Advanced Non–Small-Cell Lung Cancer: A 10-Year Retrospective Population-Based Review
Authors: Cheryl Ho, Katherine Ramsden, Yongliang Zhai, Nevin Murray, Sophie Sun, Barbara Melosky, Janessa Laskin
Journal: Journal of Thoracic Oncology (2014)
Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart.
Authors: A M Feldman, A E Cates, W B Veazey, R E Hershberger, M R Bristow, K L Baughman, W A Baumgartner, C Van Dop
Journal: Journal of Clinical Investigation (1988)

Human heart failure is associated with a diminished contractile response to beta-adrenergic agonists. We hypothesized that alterations in the activity of a guanine nucleotide-binding regulatory protein (G protein) might be partially responsible for this abnormality. We therefore measured the activity of G proteins in failing human myocardium utilizing bacterial toxin-catalyzed ADP ribosylation. The activity of a 40,000-mol wt pertussis toxin substrate (alpha G40) was increased by 36% in failing human hearts when compared with nonfailing controls. In contrast, there was no change in the level of the stimulatory regulatory subunit (Gs). The increased activity in alpha G40 was associated with a 30% decrease in basal as well as 5'-guanylyl imidodiphosphate-stimulated adenylate cyclase activity. These data suggest that increased alpha G40 activity is a new marker for failing myocardium and may account at least in part for the diminished responsiveness to beta 1-adrenergic agonists in the failing human heart.
Diagnostic Specificity and Neuroanatomical Validity of Neurological Abnormalities in First-Episode Psychoses
Authors: Matcheri S. Keshavan, Richard D. Sanders, John A. Sweeney, Vaibhav A. Diwadkar, Gerald Goldstein, Jay W. Pettegrew, Nina R. Schooler
Journal: American Journal of Psychiatry (2003)

Neurological abnormalities are frequently seen in patients with first-episode psychotic disorders but are generally considered to be diagnostically nonspecific, neurologically nonlocalizing, and, hence, "soft." This study examined the neuroanatomical correlates and diagnostic specificity of abnormal findings on the neurological examination in first-episode schizophrenia and other psychotic disorders.Neuroleptic-naive patients with schizophrenia (N=90) and with nonschizophrenia psychoses (N=39) and carefully matched healthy subjects (N=93) were compared on total and factor scores for a reliable subset of Neurological Evaluation Scale items. The relationship between neurological examination abnormalities and alterations in the relevant brain structures as assessed by magnetic resonance imaging was examined in a subset of subjects.Factor scores for repetitive motor task abnormalities were higher in both patient groups, relative to the healthy group, and did not distinguish between the patient groups. Factor scores for abnormalities in cognitively demanding and perceptual tasks were markedly higher in the schizophrenia group, relative to both comparison groups, and were not different between the nonschizophrenia psychoses group and the healthy comparison group. Higher scores for the cognitive/perceptual abnormalities factor were correlated with smaller volumes of the left heteromodal association cortex.Neurological signs may serve as expedient bedside measures that are potentially useful in the assessment of idiopathic psychoses, and cognitive/perceptual neurological signs may have a measure of diagnostic specificity. These findings provide neurobiological validation of abnormal findings on the neurological examination. These abnormalities may reflect discrete neuroanatomical alterations in schizophrenia and may have a localizing value.
Frailty Phenotypes, Disability, and Outcomes in Adult Candidates for Lung Transplantation
Authors: Jonathan P. Singer, Joshua M. Diamond, Cynthia J. Gries, Jamiela McDonnough, Paul D. Blanc, Rupal Shah, Monica Y. Dean, Beverly Hersh, Paul J. Wolters, Sofya Tokman, Selim M. Arcasoy, Kristy Ramphal, John R. Greenland, Nancy Smith, Pricilla Heffernan, Lori Shah, Pavan Shrestha, Jeffrey A. Golden, Nancy P. Blumenthal, Debbie Huang, Joshua Sonett, Steven Hays, Michelle Oyster, Patricia P. Katz, Hilary Robbins, Melanie Brown, Lorriana E. Leard, Jasleen Kukreja, Matthew Bacchetta, Errol Bush, Frank D’Ovidio, Melanie Rushefski, Kashif Raza, Jason D. Christie, David J. Lederer
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation.To examine the construct and predictive validity of frailty phenotypes in lung transplant candidates.In a multicenter prospective cohort, we measured frailty with the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). We evaluated construct validity through comparisons with conceptually related factors. In a nested case-control study of frail and nonfrail subjects, we measured serum IL-6, tumor necrosis factor receptor 1, insulin-like growth factor I, and leptin. We estimated the association between frailty and disability using the Lung Transplant Valued Life Activities disability scale. We estimated the association between frailty and risk of delisting or death before transplant using multivariate logistic and Cox models, respectively.Of 395 subjects, 354 completed FFP assessments and 262 completed SPPB assessments; 28% were frail by FFP (95% confidence interval [CI], 24-33%) and 10% based on the SPPB (95% CI, 7-14%). By either measure, frailty correlated more strongly with exercise capacity and grip strength than with lung function. Frail subjects tended to have higher plasma IL-6 and tumor necrosis factor receptor 1 and lower insulin-like growth factor I and leptin. Frailty by either measure was associated with greater disability. After adjusting for age, sex, diagnosis, and transplant center, both FFP and SPPB were associated with increased risk of delisting or death before lung transplant. For every 1-point worsening in score, hazard ratios were 1.30 (95% CI, 1.01-1.67) for FFP and 1.53 (95% CI, 1.19-1.59) for SPPB.Frailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death.
MET Signaling Regulates Glioblastoma Stem Cells
Authors: Kyeung Min Joo, Juyoun Jin, Eunhee Kim, Kang Ho Kim, Yonghyun Kim, Bong Gu Kang, Youn-Jung Kang, Justin D. Lathia, Kwang Ho Cheong, Paul H. Song, Hyunggee Kim, Ho Jun Seol, Doo-Sik Kong, Jung-Il Lee, Jeremy N. Rich, Jeongwu Lee, Do-Hyun Nam
Journal: Cancer Research (2012)

Abstract Glioblastomas multiforme (GBM) contain highly tumorigenic, self-renewing populations of stem/initiating cells [glioblastoma stem cells (GSC)] that contribute to tumor propagation and treatment resistance. However, our knowledge of the specific signaling pathways that regulate GSCs is limited. The MET tyrosine kinase is known to stimulate the survival, proliferation, and invasion of various cancers including GBM. Here, we identified a distinct fraction of cells expressing a high level of MET in human primary GBM specimens that were preferentially localized in perivascular regions of human GBM biopsy tissues and were found to be highly clonogenic, tumorigenic, and resistant to radiation. Inhibition of MET signaling in GSCs disrupted tumor growth and invasiveness both in vitro and in vivo, suggesting that MET activation is required for GSCs. Together, our findings indicate that MET activation in GBM is a functional requisite for the cancer stem cell phenotype and a promising therapeutic target. Cancer Res; 72(15); 3828–38. ©2012 AACR.
An open-label, single-arm study assessing safety and efficacy of panitumumab in patients with metastatic colorectal cancer refractory to standard chemotherapy
Authors: E. Van Cutsem, S. Siena, Y. Humblet, J.-L. Canon, J. Maurel, E. Bajetta, B. Neyns, D. Kotasek, A. Santoro, W. Scheithauer, S. Spadafora, R.G. Amado, N. Hogan, M. Peeters
Journal: Annals of Oncology (2007)
BaHoF 5 nanoprobes as high-performance contrast agents for multi-modal CT imaging of ischemic stroke
Authors: Jing Wang, Dalong Ni, Wenbo Bu, Qian Zhou, Wenpei Fan, Yue Wu, Yanyan Liu, Lekang Yin, Zhaowen Cui, Xiaoxue Zhang, Hua Zhang, Zhenwei Yao
Journal: Biomaterials (2015)