tbuckley/cabot-search huggingface dataset:
Abstract P1-04-03: A Role for Cyclin D1 in Neoplastic Transformation in MCF-7 Breast Cancer Cells Post p14ARF-p53 Induced Senescence
Authors: E McGowan, N Alling, R Shephard, D Yagoub, N Tran, P. Xia
Journal: Cancer Research (2010)

Abstract Many years of oncogenic insult and hormonal flux have important long-term implications for breast cancer emergence and progression. Premature-induced senescence is proposed to be a protective response against cancer development. We hypothesize that the senescence response can be subverted in some breast carcinomas, which exhibit latent hormone-dependent proliferative capacity. The ARF-p53 pathway has long been known to play an important role in tumour surveillance halting cell cycle progression to transiently or permanently stop aberrant cells from proliferating. It is well documented that disruption of this pathway is involved in tumourigenesis, in part, through inactivation of cyclin D1. Cyclin D1 plays an important role in breast cancer progression as a regulator of CDK4/6. In addition cyclin D1 has been reported to stimulate estrogen receptor (ER) activity independent of CDK4/6. Our initial observations showed that reactivation of ARF-p53-p21 is indeed a potent rapid inhibitor of cell proliferation in MCF-7 breast cancer cells with a senescent phenotype, however controversially cyclin D1 expression was increased and predominantly located in the nucleus. High expression of nuclear cyclin D1 and p14ARF inversely correlated with cell proliferation. Our studies showed that p14ARF regulated cyclin D1 at the post-transcriptional level. Furthermore, we have evidence from microRNA array analysis that microRNAs known to bind to the cyclin D1 3'UTR sequence were down regulated upon induction of p14ARF, contributing to cyclin D1 stability. We found that long-term exposure to p14ARF was not a failsafe barrier to tumour progression, senescent-like cells re-entering the cell cycle correlated with reduction of nuclear cyclin D1. Conversely, continuous p14ARF expression resulted in chaotic multinucleation and preceded neoplasia. These aberrant nuclei co-stained with cyclin D1 and Ki-67, a well-known marker of cell proliferation. These results suggest that induction of the p14ARF-p53 pathway does not entirely remove the threat of cancer resulting from hyperproliferative oncogenic signals and cyclin D1 plays a promiscuous role in prevention and progression. Arguably, in some breast cancers premature senescent cells may be precursor, or latent cancer cells. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-04-03.
A MOLECULAR ABNORMALITY OF URINARY MUCOPROTEIN IN CYSTIC FIBROSIS OF THE PANCREAS*
Authors: Myles Maxfield, William Wolins
Journal: Journal of Clinical Investigation (1962)

Since its first complete description in 1938 by Anderson, concepts of the pathogenesis of cystic fibrosis have been rapidly and continuously modified. The initial concept of pathology primarily in the pancreas had quickly to be extended to include primary pathology in other mucous-secreting glands because of clinical and histological evidence of abnormalities in the biliary tract and especially in the lungs. With the demonstration of the elevation of sweat electrolytes in this disorder, even this concept proved to be too limiting and had to be enlarged to include exocrine glands in general. It is the purpose of this report to demonstrate that the molecules of the urinary mucoprotein of Tamm and Horsfall have an abnormal structure in this disease. In this way we wish to present evidence pointing to the involvement of an organ not hitherto implicated in cystic fibrosis and, more importantly, evidence indicating the molecular nature of the fundamental abnormality in this hereditary disease.
Filaggrin null mutations are associated with increased asthma exacerbations in children and young adults
Authors: K. Basu, C. N. A. Palmer, B. J. Lipworth, W. H. Irwin McLean, A. Terron‐Kwiatkowski, Y. Zhao, H. Liao, F. J. D. Smith, A. Mitra, S. Mukhopadhyay
Journal: Allergy (2008)

Filaggrin (FLG) null mutations are important genetic predisposing factors for atopic asthma and have recently been shown to influence controller and reliever medication needs in asthmatic children. Our objective was to study the role of FLG null alleles in asthma exacerbations.FLG mutations R501X and 2282del4 were assayed in 1135 individuals ranging from 3 to 22 years old with asthma from Tayside and Dumfries, Scotland. Asthma exacerbations over the previous 6 months were also studied.The FLG mutations were significantly associated with greater risk of exacerbations in children with asthma. Exacerbations were significant for the R501X but not the 2282del4 mutation and the combined genotype compared to the wild-type with odds ratios of 1.97 (95% CI, 1.19-3.22; P = 0.009) and 1.61 (95% CI, 1.08-2.40; P = 0.021), respectively. Individuals with FLG null alleles were more likely to require oral steroids (31.4%vs 19.5%; OR = 1.89; P = 0.021) for their exacerbations. There was also a 1.71-fold increased risk (42.6%vs 30%; P = 0.041) of school absence owing to asthma exacerbations in asthmatic individuals with FLG null mutation. On sub-group analysis, the effect of FLG mutations on asthma exacerbations is significant (P = 0.045) only for participants with relatively mild asthma controlled on inhaled steroids, with inhaled albuterol according to need.In addition to their effect on asthma medication requirements reported previously, there is an association between the presence of FLG null mutations and the risk of asthma exacerbations in asthmatic children and young adults.
<b> <i>In Situ</i> </b> Tumor Ablation Creates an Antigen Source for the Generation of Antitumor Immunity
Authors: Martijn H. M. G. M. den Brok, Roger P. M. Sutmuller, Robbert van der Voort, Erik J. Bennink, Carl G. Figdor, Theo J. M. Ruers, Gosse J. Adema
Journal: Cancer Research (2004)

Abstract Tumor-destructing techniques, like radiofrequency ablation (RFA), allow eradication of large tumors. Potentially, in situ tumor destruction also can provide the immune system with an antigen source for the induction of antitumor immunity. Antigen-presenting cells could take up antigens in the periphery after which they induce specific immune responses. Recent data show that especially antigen-presenting dendritic cells are crucial for the induction of potent immune responses. However, virtually nothing is known regarding the induction of immune responses after in situ tumor destruction in mice or humans. We used the well-defined murine B16-OVA melanoma cell line to develop a novel tumor model to explore: (a) the immunologic consequences of in situ tumor destruction; and (b) the efficacy of a combination approach of tumor destruction and immunostimulation. Applying this model system we demonstrate that following RFA, a weak but detectable immune response develops, directed against OVA, but also against a broader range of B16 antigens. Adoptive transfer experiments further indicate that antitumor reactivity can be transferred to naïve mice by splenocytes. To augment the response observed, we administered a blocking monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 at the time of tumor destruction. Interestingly, this strongly enhanced antitumor immunity, resulting in long-lasting tumor protection. These results illustrate that in situ tumor destruction can provide a useful antigen source for the induction of antitumor immunity, provided that additional immunostimulatory signals are coadministered.
MAPK overexpression is associated with anthracycline resistance and increased risk for recurrence in patients with triple-negative breast cancer
Authors: Y. Eralp, D. Derin, Y. Ozluk, E. Yavuz, N. Guney, P. Saip, M. Muslumanoglu, A. Igci, S. Kücücük, M. Dincer, A. Aydiner, E. Topuz
Journal: Annals of Oncology (2007)
Air pollution and mortality in the Netherlands: are the elderly more at risk?
Authors: P. Fischer, G. Hoek, B. Brunekreef, A. Verhoeff, J. van Wijnen
Journal: European Respiratory Journal (2003)

The association between daily mortality and short-term variations in the ambient levels of ozone (O 3 ), black smoke (BS), sulphur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), carbon monoxide (CO) and particulate matter was studied in the Netherlands. Daily total and cause-specific mortality counts (cardiovascular, chronic obstructive pulmonary disease (COPD) and pneumonia), air quality, temperature, relative humidity and influenza data were obtained from 1986–1994. The relationship between daily mortality and air pollution was modelled using Poisson regression analysis. All pollution mortality associations were adjusted for potential confounding due to long-term trends, seasonal trends, influenza epidemics, ambient temperature, ambient relative humidity, day of the week and holidays, using generalised additive models. Statistically significant associations were mostly found in the elderly, that is the age categories of 65–74 and ≥75 yrs for the pollutants PM 10 (particles with a 50% cut-off aerodynamic diameter of 10 µm), BS, SO 2 , NO 2 and CO. This may partly be due to a better precision of relative risk (RR) estimates for the larger numbers of deaths in these age groups. Significant associations for those &lt;65 yrs were found for O 3 (total and COPD mortality), PM 10 (pneumonia), NO 2 (pneumonia) and CO (pneumonia). RR estimates for deaths between 45–65 yrs tended to be smaller than those in &gt;65 yrs, with the exception of ozone; for cardiovascular mortality the RR for PM 10 , O 3 and CO were similar in these age groups. In conclusion, larger relative risks for air pollution were mostly found in the elderly except for ozone and for death-cause pneumonia which showed larger relative risk in younger age groups.
Mucus and bicarbonate secretion in the stomach and their possible role in mucosal protection.
Authors: A Allen, A Garner
Journal: Gut (1980)

Progress reportMucus and bicarbonate secretion in the stomach and their possible role in mucosal protection How the gastric mucosa is able to withstand intraluminal acid, which can attain concentrations approaching 155 mM H+ under conditions of maximal stimulation, remains an unanswered question.The concept of the gastric mucosa as a limiting barrier to ion diffusion developed from an appreciation that the concentration of electrolytes in the stomach varies with the rate of secretion.Thus gastric juice has a high Na+ and a low H+ concentration at low secretory rates, while at high secretory rates the reverse is found.1In addition it is well known that a reduction in H+ and gain in Na+ occurs after instillation of exogenous acid into the ligated stomach or gastric pouch.23 Teorell4 considered the gastric mucosa as a diffusion barrier and described events at the mucosal surface in terms of an exchange diffusion between H+ in the lumen and Na+ in the mucosa.In contrast, Hollander5 proposed a two component barrier consisting of the mucus layer lining the gastric mucosa together with the subjacent layer of epithelial cells and suggested that the reduction in H+ concentration resulted from dilution and neutralisation by a Na+ containing non-acid secretion or leakage of interstitial fluid.The gastric mucosal barrier was sytematically studied by Davenport,6 who considered it to be formed by the apical membrane of the surface epithelial cells together with the tight junctions linking adjacent cells.Com- petent tight junctions prevent diffusion of the gastric contents into the mucosa with loss of H+ from the lumen and entry of Na+ limited by this ion barrier.Numerous compounds which damage the stomach, including salicylates, alcohol, and bile salts, increase the permeability of the barrier inducing diffusion of acid into the mucosa with subsequent development of haemor- rhage and mucosal erosion.8 7 Whether or not back-diffusion of acid is a normal physiological process is uncertain and, indeed, a recent review of the question concluded that there is no direct evidence that the disappearance of H+ from the lumen of the stomach is caused by back-diffusion.9Whereas Davenport ascribed to mucus the chief function of lubri- cation, Heatley10 suggested that mucus played a major role in protecting the gastric epithelium by providing an unstirred layer on the surface of the mucosa.He proposed that H+ diffusing in from the gastric lumen is neu- tralised by HCO3 secreted from the mucosa.Thus the mucus gel could provide an unstirred layer which maintains HCO3 at the mucosal surface and prevents it from mixing with bulk HCI in the lumen of the stomach.Until now there has been a lack of appropriate data to enable assessment of these hypotheses on the nature of mucosal protection.However, recent work on two aspects of the mucosal barrier-namely, the structure of the mucus gel11 1213 and the demonstration of an active HCO3 secretion by surface epithelial cells14 15 16 -has provided important new insights at the molecular
Adult human neural crest–derived cells for articular cartilage repair
Authors: Karoliina Pelttari, Benjamin Pippenger, Marcus Mumme, Sandra Feliciano, Celeste Scotti, Pierre Mainil-Varlet, Alfredo Procino, Brigitte von Rechenberg, Thomas Schwamborn, Marcel Jakob, Clemente Cillo, Andrea Barbero, Ivan Martin
Journal: Science Translational Medicine (2014)

HOX -negative, differentiated neural crest–derived adult cells from the nasal septum display self-renewal capacity and environmental plasticity and are compatible for articular cartilage repair.
Adjuvant immunotherapy with BCG in squamous cell bronchial carcinoma.
Authors: H M Jansen, T H The, N G Orie
Journal: Thorax (1980)

<h3>Background</h3> Cardiovascular disease is the major cause of excessive mortality in rheumatoid arthritis (RA). The endothelial dysfunction represents the earlier manifestation of Atherosclerosis and it predicts cardiovascular events. The effect of tumor necrosis factor alpha blockers and anti-CD20 (Rituximab) on endothelial function in RA patients has already been studied. It seems that both the anti-TNF alpha and Rituximab improved endothelial function after a 12-week treatment, even if the anti-TNF alpha effect is transient. The aim of the present study was to assess whether tocilizumab (anti-IL6) therapy affected the endothelial function in RA patients too. <h3>Objectives</h3> To evaluate endothelial function in Tocilizumab treated rheumatoid arthritis refractory to tumor-necrosis-factor alpha inhibitor theraphy. <h3>Methods</h3> Five consecutive RA patients (5 women; age range 38-51 years) without other cardiovascular risk factors were enrolled. These patients received intravenous tocilizumab every 28 days (mean of treatment 8,8 months). Flow-mediated endothelium-dependent vasodilatation (FMD%) was measured at day 0 prior to the tocilizumab infusion and at week 12 (before the infusion) by brachial ultrasonography. Normal range of FMD% value is between 5% and 10%. <h3>Results</h3> At week 12, FMD% values decreased in three out of five patients (mean ± SD 4,83±3,37%, range 2,46 - 11,89%); in one patient no FMD% values variation was found. On the contrary, in the other patient we observed an increase (range 3,94 - 5.62). In two out of three patients the decreased FMD% value was a little higher than the lower limit of normal; in the other one, it was less than 5% (2,46%). <h3>Conclusions</h3> Our study demonstrates an active effect of tocilizumab on endothelial function in RA patients refractory to TNFalpha blockers. Further data needs to establish what kind of effect on endothelial function is mediated by tocilizumab. <h3>Disclosure of Interest</h3> None Declared
A New Method to Assay Protease Based on Amyloid Misfolding: Application to Prostate Cancer Diagnosis Using a Panel of Proteases Biomarkers
Authors: Hao Li, Yue Huang, Bin Zhang, Dawei Yang, Xiaoli Zhu, Genxi Li
Journal: Theranostics (2014)

This paper reports a sensitive method with electrochemical technique to detect various proteases, which can be used for the diagnosis of prostate cancer.For the proposed assay method, the working electrode is modified with the peptide probes for the target proteases.These probes contain the substrate sequence of target proteases, as well as the seed peptide sequence that can accelerate the misfolding of amyloid-beta.If there are proteases in the test solution, after protease cleavage of the substrate peptides, the distal seed peptide will be removed from the electrode surface.So, in the absence of proteases, the seed peptides can initiate and accelerate amyloid-beta misfolding on the electrode surface.Consequently, the formed aggregates strongly block the electron transfer of the in-solution electroactive species with the electrode, resulting in suppressed signal readout.Nevertheless, in the presence of proteases, enzyme cleavage may lead to greatly mitigated protein misfolding and evident signal enhancement.Since the contrast in signal readout between the two cases can be amplified by using the protein misfolding step, high sensitivity suitable for direct detection of proteases in serum can be achieved.These results may suggest the feasibility of our new method for the detection of a panel of proteases in offering detailed diagnosis of prostate cancer and a better treatment of the cancer.
Ophthalmologic heterogeneity in subjects with gyrate atrophy of choroid and retina harboring the L402P mutation of ornithine aminotransferase
Authors: Katja E Peltola, Kirsti Näntö-Salonen, Olli J Heinonen, Satu Jääskeläinen, Kaarlo Heinänen, Olli Simell, Eeva Nikoskelainen
Journal: Ophthalmology (2001)
Effective treatment of frontal hyperhidrosis with botulinum toxin A
Authors: I. Kinkelin, M. Hund, M. Naumann, H. Hamm
Journal: British Journal of Dermatology (2000)

Background Focal hyperhidrosis is a common condition mostly confined to the axillae, palms and soles. In some individuals, predominantly men, increased sweating of the forehead may be the major complaint and may interfere with the person's quality of life. Botulinum toxin A has been shown to be a very effective treatment for focal hyperhidrosis of the axillae and palms. Objectives To assess the response in 10 men suffering from frontal hyperhidrosis treated with botulinum toxin A. Methods Botulinum toxin A Botox® was injected at multiple sites evenly distributed over the forehead (mean dose 86 mouse units) . Results The mean ± SEM amount of sweat was significantly reduced, 4 weeks after treatment, from 173·8 ± 38·6 mg min−1 to 53·7 ± 17·6 mg min−1. The effect lasted at least 5 months in nine of the 10 patients. All patients subjectively judged the treatment as very effective. Minor side‐effects included painful injections and a transient weakness of forehead muscles without ptosis. Conclusions In this study, we provide evidence that botulinum toxin A is an effective and safe treatment for frontal hyperhidrosis.
The course of neurocognitive functioning in high-grade glioma patients1
Authors: Ingeborg Bosma, Maaike J. Vos, Jan J. Heimans, Martin J.B. Taphoorn, Neil K. Aaronson, Tjeerd J. Postma, Henk M. van der Ploeg, Martin Muller, W. Peter Vandertop, Ben. J. Slotman, Martin Klein
Journal: Neuro-Oncology (2006)

We evaluated the course of neurocognitive functioning in newly diagnosed high-grade glioma patients and specifically the effect of tumor recurrence. Following baseline assessment (after surgery and before radiotherapy), neurocognitive functioning was evaluated at 8 and 16 months. Neurocognitive summary measures were calculated to detect possible deficits in the domains of (1) information processing, (2) psychomotor function, (3) attention, (4) verbal memory, (5) working memory, and (6) executive functioning. Repeated-measures analyses of covariance were used to evaluate changes over time. Thirty-six patients were tested at baseline only. Follow-up data were obtained for 32 patients: 14 had a follow-up at 8 months, and 18 had an additional follow-up at 16 months. Between baseline and eight months, patients deteriorated in information-processing capacity, psychomotor speed, and attentional functioning. Further deterioration was observed between 8 and 16 months. Of 32 patients, 15 suffered from tumor recurrence before the eight-month follow-up. Compared with recurrence-free patients, not only did patients with recurrence have lower information-processing capacity, psychomotor speed, and executive functioning, but they also exhibited a more pronounced deterioration between baseline and eight-month follow-up. This difference could be attributed to the use of antiepileptic drugs in the patient group with recurrence. This study showed a marked decline in neurocognitive functioning in HGG patients in the course of their disease. Patients with tumor progression performed worse on neurocognitive tests than did patients without progression, which could be attributed to the use of antiepileptic drugs. The possibility of deleterious effects is important to consider when prescribing antiepileptic drug treatment.
Community-acquired pathogens associated with prolonged coughing in children: a prospective cohort study
Authors: F.G.A. Versteegh, G.J. Weverling, M.F. Peeters, B. Wilbrink, M.T.M. Veenstra-van Schie, J.M. van Leeuwen-Gerritsen, E.A.N.M. Mooi-Kokenberg, J.F.P. Schellekens, J.J. Roord
Journal: Clinical Microbiology and Infection (2005)
Safety, Pharmacokinetics, and Antitumor Activity of AMG 386, a Selective Angiopoietin Inhibitor, in Adult Patients With Advanced Solid Tumors
Authors: Roy S. Herbst, David Hong, Linnea Chap, Razelle Kurzrock, Edward Jackson, Jeffrey M. Silverman, Erik Rasmussen, Yu-Nien Sun, Don Zhong, Yuying C. Hwang, Jeffrey L. Evelhoch, Jonathan D. Oliner, NgocDiep Le, Lee S. Rosen
Journal: Journal of Clinical Oncology (2009)

Purpose AMG 386 is an investigational peptide-Fc fusion protein (ie, peptibody) that inhibits angiogenesis by preventing the interaction of angiopoietin-1 and angiopoietin-2 with their receptor, Tie2. This first-in-human study evaluated the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of AMG 386 in adults with advanced solid tumors. Patients and Methods Patients in sequential cohorts received weekly intravenous AMG 386 doses of 0.3, 1, 3, 10, or 30 mg/kg. Results Thirty-two patients were enrolled on the study and received AMG 386. One occurrence of dose-limiting toxicity was seen at 30 mg/kg: respiratory arrest, which likely was caused by tumor burden that was possibly related to AMG 386. The most common toxicities were fatigue and peripheral edema. Proteinuria (n = 11) was observed without clinical sequelae. Only four patients (12%) experienced treatment-related toxicities greater than grade 1. A maximum-tolerated dose was not reached. PK was dose-linear and the mean terminal-phase elimination half-life values ranged from 3.1 to 6.3 days. Serum AMG 386 levels appeared to reach steady-state after four weekly doses, and there was minimal accumulation. No anti–AMG 386 neutralizing antibodies were detected. Reductions in volume transfer constant (K trans ; measured by dynamic contrast-enhanced magnetic resonance imaging) were observed in 10 patients (13 lesions) 48 hours to 8 weeks after treatment. One patient with refractory ovarian cancer achieved a confirmed partial response (ie, 32.5% reduction by Response Evaluation Criteria in Solid Tumors) and withdrew from the study with a partial response after 156 weeks of treatment; four patients experienced stable disease for at least 16 weeks. Conclusion Weekly AMG 386 appeared well tolerated, and its safety profile appeared distinct from that of vascular endothelial growth factor–axis inhibitors. AMG 386 also appeared to impact tumor vascularity and showed antitumor activity in this patient population.
Dukes A carcinoma after colonic interposition for oesophageal stricture.
Authors: A D Houghton, M Jourdan, I McColl
Journal: Gut (1989)

The management of caustic and peptic oesophageal strictures refractory to medical treatment and repeated dilatations continues to be a challenge. Colonic interposition with subtotal oesophagectomy is felt by many surgeons to be the best treatment. Complications in the short and long term are, however, frequent. We report a case of a colonic carcinoma originating in a colonic interposition and growing up into the oesophageal remnant.