tbuckley/cabot-search huggingface dataset:
Cyclooxygenase-2–Dependent Regulation of E-Cadherin: Prostaglandin E2 Induces Transcriptional Repressors ZEB1 and Snail in Non–Small Cell Lung Cancer
Authors: Mariam Dohadwala, Seok-Chul Yang, Jie Luo, Sherven Sharma, Raj K. Batra, Min Huang, Ying Lin, Lee Goodglick, Kostyantyn Krysan, Michael C. Fishbein, Longsheng Hong, Chi Lai, Robert B. Cameron, Robert M. Gemmill, Harry A. Drabkin, Steven M. Dubinett
Journal: Cancer Research (2006)

Elevated tumor cyclooxygenase-2 (COX-2) expression is associated with tumor invasion, metastasis, and poor prognosis in non-small cell lung cancer (NSCLC). Here, we report that COX-2-dependent pathways contribute to the modulation of E-cadherin expression in NSCLC. First, whereas genetically modified COX-2-sense (COX-2-S) NSCLC cells expressed low E-cadherin and showed diminished capacity for cellular aggregation, genetic or pharmacologic inhibition of tumor COX-2 led to increased E-cadherin expression and resulted in augmented homotypic cellular aggregation among NSCLC cells in vitro. An inverse relationship between COX-2 and E-cadherin was shown in situ by double immunohistochemical staining of human lung adenocarcinoma tissue sections. Second, treatment of NSCLC cells with exogenous prostaglandin E(2) (PGE(2)) significantly decreased the expression of E-cadherin, whereas treatment of COX-2-S cells with celecoxib (1 mumol/L) led to increased E-cadherin expression. Third, the transcriptional suppressors of E-cadherin, ZEB1 and Snail, were up-regulated in COX-2-S cells or PGE(2)-treated NSCLC cells but decreased in COX-2-antisense cells. PGE(2) exposure led to enhanced ZEB1 and Snail binding at the chromatin level as determined by chromatin immunoprecipitation assays. Small interfering RNA-mediated knockdown of ZEB1 or Snail interrupted the capacity of PGE(2) to down-regulate E-cadherin. Fourth, an inverse relationship between E-cadherin and ZEB1 and a direct relationship between COX-2 and ZEB1 were shown by immunohistochemical staining of human lung adenocarcinoma tissue sections. These findings indicate that PGE(2), in autocrine or paracrine fashion, modulates transcriptional repressors of E-cadherin and thereby regulates COX-2-dependent E-cadherin expression in NSCLC. Thus, blocking PGE(2) production or activity may contribute to both prevention and treatment of NSCLC.
Secondary acute myeloid leukaemia: results of conventional treatments. Experience of GIMEMA trials
Authors: L. Pagano, A. Pulsoni, M. Vignetti, M.E. Tosti, P. Falcucci, P. Fazi, L. Fianchi, A. Levis, A. Bosi, E. Angelucci, M. Bregni, A. Gabbas, A. Peta, P. Coser, F. Ricciuti, M. Morselli, M. Caira, R. Foà, S. Amadori, F. Mandelli, G. Leone
Journal: Annals of Oncology (2005)
Clinical features and effect of antiviral therapy on anti-liver/kidney microsomal antibody type 1 positive chronic hepatitis C
Authors: Silvia Ferri, Luigi Muratori, Chiara Quarneti, Paolo Muratori, Rita Menichella, Georgios Pappas, Alessandro Granito, Giorgio Ballardini, Francesco B. Bianchi, Marco Lenzi
Journal: Journal of Hepatology (2009)
Pulmonary hypertensive effects of lung inflation in chronic hypoxia: a study in rats
Authors: GR Barer, PC Russell, K Kapeller
Journal: European Respiratory Journal (1998)

Lung inflation was compared in isolated perfused lungs of control (C) and chronically hypoxic (CH) rats; in the latter, there is muscularization and loss of compliance in the pulmonary arterial system. During ventilation hypoxia, high alveolar pressure (Palv) elevated the pulmonary artery pressure (Ppa) less in C than in CH rats; Ppa fell during sustained inflation, rose on deflation, and after inflation hypoxic vasoconstriction was attenuated. Opposite changes took place in CH rats; Ppa often rose during inflation, fell on deflation, and after inflation hypoxic vasoconstriction was enhanced. Inflation also increased Ppa more in CH than C rats during air ventilation. Ppa/Palv relations measured during incremental inflation revealed normoxic tone in "extra-alveolar" vessels in both rat groups, which usually increased during hypoxia. In CH, but not C rats, there was also evidence for constriction in "alveolar" vessels during hypoxia. The effects of inflation were not changed by NO synthase blockade in either rat group. Pulmonary hypertensive effects of inflation in chronically hypoxic rats can be attributed to vascular remodelling.
FLT1 signaling in metastasis-associated macrophages activates an inflammatory signature that promotes breast cancer metastasis
Authors: Bin-Zhi Qian, Hui Zhang, Jiufeng Li, Tianfang He, Eun-Jin Yeo, Daniel Y.H. Soong, Neil O. Carragher, Alison Munro, Alvin Chang, Anne R. Bresnick, Richard A. Lang, Jeffrey W. Pollard
Journal: The Journal of Experimental Medicine (2015)

Although the link between inflammation and cancer initiation is well established, its role in metastatic diseases, the primary cause of cancer deaths, has been poorly explored. Our previous studies identified a population of metastasis-associated macrophages (MAMs) recruited to the lung that promote tumor cell seeding and growth. Here we show that FMS-like tyrosine kinase 1 (Flt1, also known as VEGFR1) labels a subset of macrophages in human breast cancers that are significantly enriched in metastatic sites. In mouse models of breast cancer pulmonary metastasis, MAMs uniquely express FLT1. Using several genetic models, we show that macrophage FLT1 signaling is critical for metastasis. FLT1 inhibition does not affect MAM recruitment to metastatic lesions but regulates a set of inflammatory response genes, including colony-stimulating factor 1 (CSF1), a central regulator of macrophage biology. Using a gain-of-function approach, we show that CSF1-mediated autocrine signaling in MAMs is downstream of FLT1 and can restore the tumor-promoting activity of FLT1-inhibited MAMs. Thus, CSF1 is epistatic to FLT1, establishing a link between FLT1 and inflammatory responses within breast tumor metastases. Importantly, FLT1 inhibition reduces tumor metastatic efficiency even after initial seeding, suggesting that these pathways represent therapeutic targets in metastatic disease.
Influenza vaccination in asthmatic children: effects on quality of life and symptoms
Authors: H.J. Bueving, J.C. van der Wouden, H. Raat, R.M.D. Bernsen, J.C. de Jongste, L.W.A. van Suijlekom-Smit, A.D.M.E. Osterhaus, G.F. Rimmelzwaan, M. Rutten-van Mölken, S. Thomas
Journal: European Respiratory Journal (2004)

This study aimed to detect the effect of influenza vaccination on quality of life, symptomatology and spirometry in asthmatic children. A randomised double-blind placebo-controlled trial in 696 (296 in 1999–2000 and 400 in 2000–2001) asthmatic children aged 6–18 yrs, which were vaccinated with either vaccine or placebo, was performed. Children participated for only one influenza season. They recorded symptoms in a diary and reported when symptom scores reached a predefined severity level. If this occurred research nurses visited them twice, first to take a pharyngeal swab and spirometry, and a week later to assess quality of life over the past illness week. Compared with placebo, vaccination improved health-related quality of life in the weeks of illness related to influenza-positive swabs. However, no effect was found for respiratory symptoms recorded in the diaries during those weeks. Similarly, no differences were found for quality of life in all weeks of illness or for respiratory symptoms throughout the seasons. Influenza vaccination was found to have a moderately beneficial effect on quality of life in influenza-positive weeks of illness in children with asthma.
Simultaneous Chemoradiotherapy Compared With Radiotherapy Alone After Induction Chemotherapy in Inoperable Stage IIIA or IIIB Non–Small-Cell Lung Cancer: Study CTRT99/97 by the Bronchial Carcinoma Therapy Group
Authors: Rudolf M. Huber, Michael Flentje, Michael Schmidt, Barbara Pöllinger, Helga Gosse, Jochen Willner, Kurt Ulm
Journal: Journal of Clinical Oncology (2006)

The aim of this study was to examine whether, after preceding induction chemotherapy, simultaneous chemoradiotherapy is superior to radiotherapy alone.Patients with non-small-cell lung cancer in inoperable stage IIIA or IIIB received induction chemotherapy with two cycles of paclitaxel 200 mg/m2 and carboplatin area under the curve 6 every 3 weeks. Patients without progression at restaging after induction chemotherapy were randomly assigned to radiotherapy (60 Gy) or chemoradiotherapy (paclitaxel 60 mg/m2 weekly). The primary end point was overall survival; secondary end points were time to progression, response, and toxicity.Three hundred three patients entered the study, and 276 completed induction chemotherapy. Two hundred fourteen patients were randomly assigned (radiotherapy alone: n = 113; simultaneous chemoradiotherapy: n = 101). Median follow-up time of all randomly assigned patients was 13.6 months (interquartile range [IQR], 6.4 to 29.0 months), and median follow-up time of the subgroup of censored patients (n = 52) was 37.4 months (IQR, 5.9 to 57.0 months; maximum, 76.1 months). Toxicities during the induction phase were mild. During radiotherapy, overall toxicity rates were not significantly different between the two arms. Median survival times in the radiotherapy group and chemoradiotherapy group were 14.1 months (95% CI, 11.8 to 16.3 months) and 18.7 months (95% CI, 14.1 to 23.3 months; difference not statistically significant, P = .091). Median time to progression significantly favored simultaneous chemoradiotherapy (11.5 months; 95% CI, 8.3 to 14.7 months) versus radiotherapy alone (6.3 months; 95% CI, 5.0 to 7.6 months; P < .001, log-rank test).Induction chemotherapy followed by chemoradiotherapy with weekly paclitaxel is feasible. Response, time to progression, and survival favor chemoradiotherapy compared with radiotherapy alone.
The cell population in the cutaneous infiltrate of mycosis fungoides: in situ studies using monoclonal antisera
Authors: C.A. HOLDEN, E.W. MORGAN, D.M. MACDONALD
Journal: British Journal of Dermatology (1982)

T cell antigens were studied in cutaneous sections from five patients with mycosis fungoides (MF). The method allowed cell counting to be undertaken for each monoclonal antiserum. OKT3 (pan T cell) antiserum confirmed the predominantly T lymphocytic nature of the infiltrate, labelling the majority of infiltrating cells. OKT4 (helper/inducer) antiserum positively labelled 90% of the lymphocytes identified as OKT3 +. OKT8 (suppressor) antiserum marked only single or small groups of dermal lymphocytes, which comprised 24% of the cells identified as T lymphocytes. OKT6 (anti-Langerhans) showed positive labelling of dendritic cells in the epidermis and dermis. Fewer positively labelled epidermal dendritic cells were observed in sections from patients receiving PUVA, but no difference was found in the number of OKT6 positive dermal cells. The ratio of helper to suppressor cells in the dermal infiltrate significantly exceeded the normal circulating ratio.
The neural basis of cognitive development: A constructivist manifesto
Authors: Steven R. Quartz, Terrence J. Sejnowski
Journal: Behavioral and Brain Sciences (1997)

How do minds emerge from developing brains? According to “neural constructivism,” the representational features of cortex are built from the dynamic interaction between neural growth mechanisms and environmentally derived neural activity. Contrary to popular selectionist models that emphasize regressive mechanisms, the neurobiological evidence suggests that this growth is a progressive increase in the representational properties of cortex. The interaction between the environment and neural growth results in a flexible type of learning: “constructive learning” minimizes the need for prespecification in accordance with recent neurobiological evidence that the developing cerebral cortex is largely free of domain-specific structure. Instead, the representational properties of cortex are built by the nature of the problem domain confronting it. This uniquely powerful and general learning strategy undermines the central assumption of classical learnability theory, that the learning properties of a system can be deduced from a fixed computational architecture. Neural constructivism suggests that the evolutionary emergence of neocortex in mammals is a progression toward more flexible representational structures, in contrast to the popular view of cortical evolution as an increase in innate, specialized circuits. Human cortical postnatal development is also more extensive and protracted than generally supposed, suggesting that cortex has evolved so as to maximize the capacity of environmental structure to shape its structure and function through constructive learning.
NI-78 * LABEL-FREE MULTIPHOTON MICROSCOPY: A NOVEL TOOL FOR THE IMAGING OF BRAIN TUMORS
Authors: O. Uckermann, R. Galli, K. Geiger, E. Koch, G. Schackert, G. Steiner, M. Kirsch
Journal: Neuro-Oncology (2014)

Changes in tissue composition caused by brain tumor growth involve a series of complex biochemical alterations which can be imaged on unstained native tissue using multiphoton microscopy: We used coherent anti-Stokes Raman scattering (CARS) imaging that resonantly excites the symmetric stretching vibration of CH2 groups at 2850 cm−1 and visualizes lipid content in combination with imaging of endogenous two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) to discern different types of tumors from normal tissue in unstained, native brain samples. Experimental brain tumors were induced in nude mice NMRI nu/nu (n = 25) by stereotactic implantation of glioblastoma (U87), melanoma (A375) and breast cancer (MCF-7) cell lines. Label-free multiphoton microscopy of brain cryosections provided exhaustive information of the tumor morphochemistry. The tumor border was defined with cellular resolution by a strong reduction of CARS signal intensity to 61% (glioblastoma), 71% (melanoma) and 68% (breast cancer). This reduction of lipid content within the tumor was confirmed by Raman spectroscopy. Micrometastases infiltrating normal tissue (size 50 - 200 µm) were identified in glioblastoma and melanoma. Additionally, multiphoton microscopy proved a reduction of CARS signal intensity in all human glioblastoma samples analyzed (to 72%, n = 6). Additionally, relevant SHG and TPEF signals were detected in human primary and secondary brain tumor samples and enabled to image variations in tumor associated vasculature, fibrosis, necrosis and nuclear size and density. All primary or secondary brain tumors investigated were characterized by a lower intensity of the CARS signal, therefore offering a simple tool for objective tumor detection and delineation. The combination of techniques allows retrieving a quantity of information on native unstained tissue which is comparable to H&E staining. Therefore, label-free multiphoton microscopy has the potential to become a technology routinely used intraoperatively for inspection and by neuropathology for frozen section equivalent assessment of brain tumors.
Relation between distal airspace size, bronchiolar attachments, and lung function.
Authors: D Lamb, A McLean, M Gillooly, P M Warren, G A Gould, W MacNee
Journal: Thorax (1993)

<h3>Background</h3> Experimental and observational studies have raised concerns that giving intravenous (IV) iron to patients, such as individuals receiving maintenance hemodialysis, might increase the risk of infections. The Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial randomized 2141 patients undergoing maintenance hemodialysis for ESKD to a high-dose or a low-dose IV iron regimen, with a primary composite outcome of all-cause death, heart attack, stroke, or hospitalization for heart failure. Comparison of infection rates between the two groups was a prespecified secondary analysis. <h3>Methods</h3> Secondary end points included any infection, hospitalization for infection, and death from infection; we calculated cumulative event rates for these end points. We also interrogated the interaction between iron dose and vascular access (fistula versus catheter). <h3>Results</h3> We found no significant difference between the high-dose IV iron group compared with the lose-dose group in event rates for all infections (46.5% versus 45.5%, respectively, which represented incidences of 63.3 versus 69.4 per 100 patient years, respectively); rates of hospitalization for infection (29.6% versus 29.3%, respectively) also did not differ. We did find a significant association between risk of a first cardiovascular event and any infection in the previous 30 days. Compared with patients undergoing dialysis with an arteriovenous fistula, those doing so <i>via</i> a catheter had a higher incidence of having any infection, hospitalization for infection, or fatal infection, but IV iron dosing had no effect on these outcomes. <h3>Conclusions</h3> The high-dose and low-dose IV iron groups exhibited identical infection rates. Risk of a first cardiovascular event strongly associated with a recent infection.
High Survival and Organ Function Rates After Primary Chemoradiotherapy for Intermediate-Stage Squamous Cell Carcinoma of the Head and Neck Treated in a Multicenter Phase II Trial
Authors: Ezra E.W. Cohen, Daniel J. Haraf, Marcy A. List, Masha Kocherginsky, Bharat B. Mittal, Fred Rosen, Bruce Brockstein, Rosalyn Williams, Mary Ellyn Witt, Kerstin M. Stenson, Merrill S. Kies, Everett E. Vokes
Journal: Journal of Clinical Oncology (2006)

Patients with intermediate-stage squamous cell carcinoma of the head and neck traditionally have been treated with initial surgical resection followed by radiotherapy (RT) alone or chemoradiotherapy. A previous study in this patient population reported a 91% locoregional control rate and 65% overall survival (OS) rate at 5 years, with chemoradiotherapy used as primary treatment. This study was undertaken to assess whether shortening treatment duration with hyperfractionated RT would be feasible and improve locoregional control, organ preservation, and progression-free survival.Eligible patients with stage II or III disease received fluorouracil, hydroxyurea, and RT given twice daily on a week-on/week-off schedule. Quality-of-life scores were measured using three validated indexes.All 53 patients enrolled are included in the analysis, with a median follow-up of 42 months (range, 5 to 98 months). Grade 3 or 4 in-field mucositis was observed in 77% and 9%, respectively. No patients required surgical salvage at the primary tumor site (pathological complete response rate, 100%). The 3-year progression-free and OS rates are 67% and 78%, respectively. The 3-year disease-specific mortality rate is 7%. At the time of analysis, 87% of surviving patients do not require enteral feeding support. Quality-of-life and performance assessment indicated that, although acute treatment toxicities were severe, most patients returned to pretreatment function by 12 months.Concurrent chemoradiotherapy with hyperfractionated RT is feasible in this patient population and yields high local control and cure rates. Compared with our historical control using once-daily fractionation, hyperfractionation is accompanied by increased acute in-field toxicity.
Impact of Sodium and Ultrafiltration Profiling on Hemodialysis-Related Symptoms
Authors: MATTHEW J. OLIVER, LLOYD J. EDWARDS, DAVID N. CHURCHILL
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Dialysate sodium and ultrafiltration profiling are two methods to reduce symptoms during hemodialysis. The objective of the study was to determine the efficacy of combining these techniques to reduce symptoms in chronic hemodialysis patients. Blood volume changes were measured to determine whether any benefit of profiling could be explained through this mechanism. Patients were randomized to profiled dialysate sodium and ultrafiltration or constant dialysate sodium and ultrafiltration. The study was a two-period, two-treatment, crossover design with repeated measures. The primary outcome was hypotension and/or symptomatic events observed by the dialysis nurse. Secondary outcomes were symptom survey scores, weights, BP, and blood volume changes. Thirty-three patients were randomized. On standard treatment, 30.6% of dialysis sessions were symptomatic compared with 20.4% on profiled treatments. The odds ratio for the development of hypotension or symptomatic event on profiled treatments was 0.61 (95% confidence interval, 0.39 to 0.96) compared with standard treatment. Patients had lower symptom scores by questionnaire in both the intradialytic and the interdialytic periods during profiled treatments. Predialysis weight was greater during profiled treatments by 0.3 kg ( P = 0.008), but there were no differences in postdialysis weight, BP, or thirst. There was no difference in maximum decrease in blood volume during the two treatments (standard, -11.2%; profiled, -10.0%; P = 0.08), but there was a significant difference in the rate of change in blood volume (standard, -2.96%/h; profiled, -1.96%/h; P &lt; 0.001). Decrease in blood volume, rate of change in blood volume, and predialysis weights were not associated with hypotension or symptomatic dialysis sessions. In conclusion, dialysate sodium and ultrafiltration profiling significantly reduces hemodialysis-related symptoms. Profiling reduces the slope of the blood volume curve during dialysis, but blood volume changes are not predictive of symptomatic events for an individual patient.
Inhibition of Sphingosine 1-Phosphate Receptor 2 Protects against Renal Ischemia-Reperfusion Injury
Authors: Sang Won Park, Mihwa Kim, Kevin M. Brown, Vivette D. D’Agati, H. Thomas Lee
Journal: Journal of the American Society of Nephrology (2011)

Activation of the sphingosine 1-phosphate receptor 1 (S1P(1)R) protects against renal ischemia-reperfusion (IR) injury and inflammation, but the role of other members of this receptor family in modulating renal IR injury is unknown. We found that a selective S1P(2)R antagonist protected against renal IR injury in a dose-dependent manner. Consistent with this observation, both S1P(2)R-deficient mice and wild-type mice treated with S1P(2)R small interfering RNA had reduced renal injury after IR. In contrast, a selective S1P(2)R agonist exacerbated renal IR injury. The S1P(2)R antagonist increased sphingosine kinase-1 (SK1) expression via Rho kinase signaling in renal proximal tubules; the S1P(2)R agonist decreased SK1. S1P(2)R antagonism failed to protect the kidneys of SK1-deficient mice or wild-type mice pretreated with an SK1 inhibitor or an S1P(1)R antagonist, suggesting that the renoprotection conferred by S1P(2)R antagonism results from pathways involving activation of S1P(1)R by SK1. In cultured human proximal tubule (HK-2) cells, the S1P(2)R antagonist selectively upregulated SK1 and attenuated both H(2)O(2)-induced necrosis and TNF-α/cycloheximide-induced apoptosis; the S1P(2)R agonist had the opposite effects. In addition, increased nuclear hypoxia inducible factor-1α was critical in mediating the renoprotective effects of S1P(2)R inhibition. Finally, induction of SK1 and S1P(2)R in response to renal IR and S1P(2)R antagonism occurred selectively in renal proximal tubule cells but not in renal endothelial cells. Taken together, these data suggest that S1P(2)R may be a therapeutic target to attenuate the effects of renal IR injury.