tbuckley/cabot-search huggingface dataset:
Phase II trial combining docetaxel and doxorubicin as neoadjuvant chemotherapy in patients with operable breast cancer
Authors: G. Ganem, M. Tubiana-Hulin, P. Fumoleau, M. Combe, J.-L. Misset, J.-M. Vannetzel, T. Bachelot, L.R. De Ybarlucea, V. Lotz, B. Bendahmane, V. Dieras
Journal: Annals of Oncology (2003)
Mass Spectrometry to Classify Non–Small-Cell Lung Cancer Patients for Clinical Outcome After Treatment With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Multicohort Cross-Institutional Study
Authors: Fumiko Taguchi, Benjamin Solomon, Vanesa Gregorc, Heinrich Roder, Robert Gray, Kazuo Kasahara, Makoto Nishio, Julie Brahmer, Anna Spreafico, Vienna Ludovini, Pierre P. Massion, Rafal Dziadziuszko, Joan Schiller, Julia Grigorieva, Maxim Tsypin, Stephen W. Hunsucker, Richard Caprioli, Mark W. Duncan, Fred R. Hirsch, Paul A. Bunn, David P. Carbone
Journal: JNCI Journal of the National Cancer Institute (2007)

Some but not all patients with non-small-cell lung cancer (NSCLC) respond to treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We developed and tested the ability of a predictive algorithm based on matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) analysis of pretreatment serum to identify patients who are likely to benefit from treatment with EGFR TKIs.Serum collected from NSCLC patients before treatment with gefitinib or erlotinib were analyzed by MALDI MS. Spectra were acquired independently at two institutions. An algorithm to predict outcomes after treatment with EGFR TKIs was developed from a training set of 139 patients from three cohorts. The algorithm was then tested in two independent validation cohorts of 67 and 96 patients who were treated with gefitinib and erlotinib, respectively, and in three control cohorts of patients who were not treated with EGFR TKIs. The clinical outcomes of survival and time to progression were analyzed.An algorithm based on eight distinct m/z features was developed based on outcomes after EGFR TKI therapy in training set patients. Classifications based on spectra acquired at the two institutions had a concordance of 97.1%. For both validation cohorts, the classifier identified patients who showed improved outcomes after EGFR TKI treatment. In one cohort, median survival of patients in the predicted "good" and "poor" groups was 207 and 92 days, respectively (hazard ratio [HR] of death in the good versus poor groups = 0.50, 95% confidence interval [CI] = 0.24 to 0.78). In the other cohort, median survivals were 306 versus 107 days (HR = 0.41, 95% CI = 0.17 to 0.63). The classifier did not predict outcomes in patients who did not receive EGFR TKI treatment.This MALDI MS algorithm was not merely prognostic but could classify NSCLC patients for good or poor outcomes after treatment with EGFR TKIs. This algorithm may thus assist in the pretreatment selection of appropriate subgroups of NSCLC patients for treatment with EGFR TKIs.
Epidermal Expression of the Translation Inhibitor Programmed Cell Death 4 Suppresses Tumorigenesis
Authors: Aaron P. Jansen, Corinne E. Camalier, Nancy H. Colburn
Journal: Cancer Research (2005)

Programmed cell death 4 (Pdcd4) is a novel repressor of in vitro transformation. Pdcd4 directly inhibits the helicase activity of eukaryotic translation initiation factor 4A, a component of the translation initiation complex. To ascertain whether Pdcd4 suppresses tumor development in vivo, we have generated transgenic mice that overexpress Pdcd4 in the epidermis (K14-Pdcd4). K14-regulated Pdcd4 expression caused a neonatal short-hair phenotype due to early catagen entry compared with matched wild-type siblings. In response to the 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) mouse skin carcinogenesis protocol, K14-Pdcd4 mice showed significant reductions in papilloma formation, carcinoma incidence, and papilloma-to-carcinoma conversion frequency compared with wild-type mice. The translational efficiency of an mRNA engineered to form a structured 5' untranslated region (UTR) was attenuated in primary keratinocytes when Pdcd4 was overexpressed. Pdcd4 inhibited by 46% TPA-induced activator protein-1 (AP-1)-dependent transcription, an event required for tumorigenesis. CDK4 and ornithine decarboxylase (ODC) are candidates for Pdcd4-regulated translation as their mRNAs contain 5'structured UTRs. In K14-Pdcd4 primary keratinocytes expressing activated Ha-Ras to mimic DMBA-initiated epidermis, ODC and CDK4 protein levels were decreased by 40% and 46%, respectively. Expression of a protein encoded by 5' unstructured mRNA showed no change. These results extend to an in vivo model the observations that Pdcd4 inhibits both translation initiation and AP-1 activation while decreasing benign tumor development and malignant progression. The K14-Pdcd4 mice seem to validate translation initiation as a novel target for cancer prevention.
Loss of Transforming Growth Factor Beta Type II Receptor Increases Aggressive Tumor Behavior and Reduces Survival in Lung Adenocarcinoma and Squamous Cell Carcinoma
Authors: Stephen P. Malkoski, Sarah M. Haeger, Timothy G. Cleaver, Karen J. Rodriguez, Howard Li, Shi-Long Lu, William J. Feser, Anna E. Barón, Daniel Merrick, Jessyka G. Lighthall, Hideaki Ijichi, Wilbur Franklin, Xiao-Jing Wang
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Lung adenocarcinoma and lung squamous cell carcinoma (SCC) are the most common non–small cell lung cancer (NSCLC) subtypes. This study was designed to determine whether reduced expression of TGFβ type II receptor (TGFβRII) promotes lung adenocarcinoma and SCC carcinogenesis. Experimental Design: We examined TGFβRII expression at the protein and mRNA levels in human NSCLC samples and assessed the relationship between TGFβRII expression and clinicopathologic parameters. To determine whether sporadic TGFβRII deletion in airway epithelial cells induces NSCLC formation, we targeted TGFβRII deletion alone and in combination with oncogenic KrasG12D to murine airways using a keratin 5 (K5) promoter and inducible Cre recombinase. Results: Reduced TGFβRII expression in human NSCLC is associated with male gender, smoking, SCC histology, reduced differentiation, increased tumor stage, increased nodal metastasis, and reduced survival. Homozygous or heterozygous TGFβRII deletion in mouse airway epithelia increases the size and number of KrasG12D-initiated adenocarcinoma and SCC. TGFβRII deletion increases proliferation, local inflammation, and TGFβ ligand elaboration; TGFβRII knockdown in airway epithelial cells increases migration and invasion. Conclusions: Reduced TGFβRII expression in human NSCLC is associated with more aggressive tumor behavior and inflammation that is, at least partially, mediated by increased TGFβ1 expression. TGFβRII deletion in mouse airway epithelial cells promotes adenocarcinoma and SCC formation, indicating that TGFβRII loss plays a causal role in lung carcinogenesis. That TGFβRII shows haploid insufficiency suggests that a 50% TGFβRII protein reduction would negatively impact lung cancer prognosis. Clin Cancer Res; 18(8); 2173–83. ©2012 AACR.
CO transfer capacity as a determining factor of survival for severe hypoxaemic COPD patients under long-term oxygen therapy
Authors: P Dubois, J Machiels, F Smeets, JP Delwiche, J Lulling
Journal: European Respiratory Journal (1990)

The transfer capacity for carbon monoxide is a commonly used method in clinical practice but is rarely considered as a prognostic factor for patients under long term oxygen therapy (LTOT). LTOT was applied to 217 stable, severely hypoxaemic (arterial oxygen tension (PaO2 less than 7.3 kPa or 55 mmHg) chronic obstructive pulmonary disease (COPD) patients, according to the usual recommendations. The average survival rate of this series is rather poor: 46% at 24 months. There is nevertheless an important difference between patients with a normal transfer coefficient and those with a decreased one (79% survival at 2 yrs as compared to 37%). On the other hand, the degree of airflow limitation has no prognostic value in the present series of very disabled patients. We can conclude that hypoxaemic COPD patients with a severely decreased transfer coefficient have a poor prognosis, even under LTOT, compared to patients with an equivalent impairment of airflow limitation and hypoxaemia but with a normal CO transfer factor/alveolar ventilation ratio (TLCO/VA).
Functional outcome of patients with chronic obstructive pulmonary disease and exercise hypercapnia
Authors: AA Simard, F Maltais, P LeBlanc
Journal: European Respiratory Journal (1995)

Chronic hypercapnia is associated with a poor prognosis in chronic obstructive pulmonary disease (COPD). Some patients are normocapnic at rest but retain CO2 during exercise. The significance of this abnormality on the course of the disease is unknown. Sixteen stable COPD patients (13 males and 3 females, aged 60 +/- 5 yrs, mean +/- SD) who had previously undergone pulmonary function tests and progressive exercise testing with arterial blood sampling at rest and maximal capacity, entered the study. At first evaluation (E1), subjects were normocapnic at rest (arterial carbon dioxide tension (Pa,CO2): 4.9-5.7 kPa, (37-43 mmHg)) and all presented exercise-induced hypercapnia (end-exercise Pa,CO2 &gt; 5.7 kPa (43 mmHg) with a minimal 0.5 kPa (4 mmHg) increase from resting value). The subjects were re-evaluated 24-54 months later (34 +/- 8 months) (second evaluation (E2)). At E2, forced expiratory volume in one second (FEV1) had decreased from 42 +/- 13 to 38 +/- 15% of predicted values, and mean resting Pa,CO2 had increased from 5.2 +/- 0.3 to 5.7 + 0.4 kPa. Maximal exercise capacity (Wmax) decreased between E1 and E2 from 76 +/- 30 to 56 +/- 22 W. Even if Wmax was lower at E2, end-exercise, Pa,CO2 was higher than at E1 (6.6 +/- 0.8 vs 6.4 +/- 0.5 kPa). At E2, eight subjects presented resting hypercapnia (group H), whilst the others remained normocapnic (Group N). Group H subjects had higher Pa,CO2, at Wmax than Group N and lower Wmax than Group N at E2.(ABSTRACT TRUNCATED AT 250 WORDS)
WDR5 Supports an N-Myc Transcriptional Complex That Drives a Protumorigenic Gene Expression Signature in Neuroblastoma
Authors: Yuting Sun, Jessica L. Bell, Daniel Carter, Samuele Gherardi, Rebecca C. Poulos, Giorgio Milazzo, Jason W.H. Wong, Rima Al-Awar, Andrew E. Tee, Pei Y. Liu, Bing Liu, Bernard Atmadibrata, Matthew Wong, Toby Trahair, Quan Zhao, Jason M. Shohet, Ygal Haupt, Johannes H. Schulte, Peter J. Brown, Cheryl H. Arrowsmith, Masoud Vedadi, Karen L. MacKenzie, Stefan Hüttelmaier, Giovanni Perini, Glenn M. Marshall, Antony Braithwaite, Tao Liu
Journal: Cancer Research (2015)

MYCN gene amplification in neuroblastoma drives a gene expression program that correlates strongly with aggressive disease. Mechanistically, trimethylation of histone H3 lysine 4 (H3K4) at target gene promoters is a strict prerequisite for this transcriptional program to be enacted. WDR5 is a histone H3K4 presenter that has been found to have an essential role in H3K4 trimethylation. For this reason, in this study, we investigated the relationship between WDR5-mediated H3K4 trimethylation and N-Myc transcriptional programs in neuroblastoma cells. N-Myc upregulated WDR5 expression in neuroblastoma cells. Gene expression analysis revealed that WDR5 target genes included those with MYC-binding elements at promoters such as MDM2. We showed that WDR5 could form a protein complex at the MDM2 promoter with N-Myc, but not p53, leading to histone H3K4 trimethylation and activation of MDM2 transcription. RNAi-mediated attenuation of WDR5 upregulated expression of wild-type but not mutant p53, an effect associated with growth inhibition and apoptosis. Similarly, a small-molecule antagonist of WDR5 reduced N-Myc/WDR5 complex formation, N-Myc target gene expression, and cell growth in neuroblastoma cells. In MYCN-transgenic mice, WDR5 was overexpressed in precancerous ganglion and neuroblastoma cells compared with normal ganglion cells. Clinically, elevated levels of WDR5 in neuroblastoma specimens were an independent predictor of poor overall survival. Overall, our results identify WDR5 as a key cofactor for N-Myc-regulated transcriptional activation and tumorigenesis and as a novel therapeutic target for MYCN-amplified neuroblastomas.
Classification and nomenclature of somatostatin receptors
Authors: D. Hoyer, G.I. Bell, M. Berelowitz, J. Epelbaum, W. Feniuk, P.P.A. Humphrey, A-M. O'Carroll, Y.C. Patel, A. Schonbrunn, J.E. Taylor, T. Reisine
Journal: Trends in Pharmacological Sciences (1995)

There is considerable controversy about the classification and nomenclature of somatostatin receptors. To date, five distinct receptor genes have been cloned and named chronologically according to their respective publication dates, but two were unfortunately given the same appellation (SSTR4). Consensually, a nomenclature for the recombinant receptors has been agreed according to IUPHAR guidelines (sst1, sst2, sst3, sst4, and sst5). However, a more informative classification is to be preferred for the future, employing all classification criteria in an integrated scheme. It is already apparent that the five recombinant receptors fall into two classes or groups, on the basis of not only structure but also pharmacological characteristics. One class (already referred to by some as SRIF1) appears to comprise sst2, sst3 and sst5 receptor subtypes. The other class (SRIF2) appears to comprise the other two recombinant receptor subtypes (sst1 and sst4). This promising approach is discussed but it is acknowledged that much more data from endogenous receptors in whole tissues are needed before further recommendations on somatostatin receptor nomenclature can be made.
Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial
Authors: E Furrie
Journal: Gut (2005)

<b>Background and aims:</b> Ulcerative colitis (UC) is an acute and chronic inflammatory disease of the large bowel with unknown aetiology. The immune response against normal commensal microorganisms is believed to drive inflammatory processes associated with UC. Therefore, modulation of bacterial communities on the gut mucosa, through the use of probiotics and prebiotics, may be used to modify the disease state. <b>Methods:</b> A synbiotic was developed for use in UC patients combining a probiotic, <i>Bifidobacterium longum</i>, isolated from healthy rectal epithelium, and a prebiotic (Synergy 1), a preferential inulin-oligofructose growth substrate for the probiotic strain. Treatment was employed in a double blinded randomised controlled trial using 18 patients with active UC for a period of one month. Clinical status was scored and rectal biopsies were collected before and after treatment, and transcription levels of epithelium related immune markers were measured. <b>Results:</b> Sigmoidoscopy scores (scale 0–6) were reduced in the test group (start 4.5 (1.4), end 3.1 (2.5)) compared with placebo (start 2.6 (2.1), end 3.2 (2.2)) (p = 0.06). mRNA levels for human beta defensins 2, 3, and 4, which are strongly upregulated in active UC, were significantly reduced in the test group after treatment (p = 0.016, 0.038, and 0.008, respectively). Tumour necrosis factor α and interleukin 1α, which are inflammatory cytokines that drive inflammation and induce defensin expression, were also significantly reduced after treatment (p = 0.018 and 0.023, respectively). Biopsies in the test group had reduced inflammation and regeneration of epithelial tissue. <b>Conclusions:</b> Short term synbiotic treatment of active UC resulted in improvement of the full clinical appearance of chronic inflammation in patients receiving this therapy.
Stimulation of the intestinal Cdx2 homeobox gene by butyrate in colon cancer cells
Authors: C Domon-Dell
Journal: Gut (2002)

The transcription factor encoded by the intestinal Cdx2 homeobox gene and treatment with sodium butyrate (NaB), a byproduct of fibre fermentation by colonic bacteria, exert similar effects on colon cancer cell lines as they both inhibit cell growth and stimulate cell differentiation and apoptosis.To investigate whether NaB regulates expression of the Cdx2 gene in colon cancer cell lines.Human adenocarcinoma cell lines Caco2 and HT29 were grown in the presence or absence of NaB. Cells were analysed for Cdx2 mRNA expression by reverse transcription-polymerase chain reaction, for protein expression by western blotting and electromobility shift assays, and for transcriptional activity of the Cdx2 promoter by transfection with luciferase reporter plasmids.In HT29 and Caco2 cells, NaB stimulated Cdx2 mRNA and protein expression as well as transcriptional activity of the Cdx2 promoter. Stimulation of the activity of the Cdx2 promoter by NaB was dose and time dependent. The Cdx2 promoter contains discrete regions that participate in or inversely that blunt the stimulatory effect exerted by NaB. In addition, NaB stimulated the transcriptional activity of the Cdx2 promoter downregulated by oncogenic ras.This study is the first report of an intestine specific transcription factor, Cdx2, stimulated by butyrate. Thus it provides a new mechanism whereby butyrate controls proliferation and differentiation of colon cancer cells.
Recurrence of exhausting hiccup in a patient treated with chemotherapy for metastatic colon cancer
Authors: D Errante
Journal: Gut (2005)

A 61 year old man was surgically treated for a pT3 Nl-G2 MO adenocarcinoma of the colon in February 2003. Immediately after surgery, an enteric fistula occurred that caused a delay in administration of adjuvant treatment.

At the start of adjuvant chemotherapy (CT) in May 2003, CEA level was 18.2 ng/ml and a new work-up with computed tomography scan of the thorax and abdomen revealed the early appearance of two metastatic lesions in the liver. The patient underwent liver metastasectomy and in July 2003 was started on post-surgical systemic CT with the FOL-FIRI (leucovorin, 5-fluorouracil, irinotecan) regimen every 14 …
Detection of antibodies to Candida albicans germ tubes in heroin addicts with systemic candidiasis
Authors: M.J. Linares, M.R. Javier, J.L. Villanueva, F. Solís, J. Torre-Cisneros, F Rodríguez, J.M. Kindelán, M. Casal
Journal: Clinical Microbiology and Infection (2001)
Characterising the individual performance responses to mild illness in international swimmers
Authors: D B Pyne, W G Hopkins, A M Batterham, M Gleeson, P A Fricker
Journal: British Journal of Sports Medicine (2005)

To determine individual differences in the impact of illness on the change in performance of swimmers in international competitions.Subjects were members of the Australian swimming team (33 male and 39 female, aged 15-27 years). Swimmers provided a weekly seven day recall of symptoms of illness during final six weeks of preparations for international competition over a three year period. Swimmers were categorised as either ill (one or more episodes of illness) or healthy. The measure of performances was the international point score. Mean changes in points score were calculated for healthy and ill swimmers between a national championship and an international competition ( approximately 16 weeks later). Likelihoods of substantial effects of illness on an individual's true change in performance (beneficial/trivial/harmful) were estimated from means and standard deviations, assuming a smallest substantial change of 6 points.Illness was reported before international performances by 38% of female and 35% of male swimmers. For female swimmers the change in performance was -3.7 (21.5) points (mean (SD)) with illness and -2.6 (19.0) points when healthy; for male swimmers the changes were -1.4 (17.5) points with illness and 5.6 (13.2) points when healthy. The likelihoods that illness had a substantial beneficial/trivial/harmful effect on performance of an individual swimmer were 32%/31%/37% for female and 17%/31%/52% for male participants (90% confidence limits approximately +/-10% to 20%).Although mild illness had only a trivial mean effect on female swimmers and a small harmful mean effect on male swimmers, there were substantial chances of benefit and harm for individuals.
Hodgkin's disease occurring in primary Sjogren's syndrome.
Authors: J.M Martín-Santos, L Carretero, A Armentia, E Alonso, I Gil
Journal: Annals of the Rheumatic Diseases (1990)

A 57 year old woman with a 13 year history of mouth dryness, keratoconjunctivitis sicca, and recurrent bronchial infections presented with multiple lymphadenopathies. Histological diagnosis was Hodgkin's disease. B and T cell lymphomas are well known complications of Sjögren's syndrome. This case provides evidence that Hodgkin's disease may also be associated with this syndrome.
Mechanical Load-Dependent Regulation of Gene Expression in Monocrotaline-Induced Right Ventricular Hypertrophy in the Rat
Authors: Harald Kögler, Oliver Hartmann, Kirsten Leineweber, Phuc Nguyen van, Peter Schott, Otto-Erich Brodde, Gerd Hasenfuss
Journal: Circulation Research (2003)

Rats treated with monocrotaline (MCT) develop pulmonary hypertension. Their right ventricles (RVs) exhibit severe pressure overload-induced hypertrophy, whereas the left ventricles (LVs) are normally loaded. In contrast, enhanced neuroendocrine stimulation during the transition to heart failure affects both ventricles. We assessed gene expression levels of Ca2+-regulating proteins in RVs and LVs of control and MCT rats in transition to heart failure to identify biomechanical load-regulated genes. In MCT RVs, both mRNA and protein levels of the Ca2+-ATPase of the sarcoplasmic/endoplasmic reticulum (SERCA2a) were reduced by 36% (P=0.001) and 17% (P=0.016), respectively, compared with control RVs. Phospholamban and ryanodine receptor mRNA levels likewise were reduced (by 27% [P=0.05] and 21% [P=0.011], respectively) in MCT RVs, whereas sarcolemmal Na+-Ca2+ exchanger expression was not altered. MCT LVs exhibited no significant expression changes compared with control LVs. Isometrically contracting MCT intact RV trabeculae showed enhanced baseline force development. Although control RV preparations exhibited a positive force-frequency relationship, MCT RVs showed a negative force-frequency relationship and blunted postrest potentiation. Contractile function of MCT LV trabeculae was normal. Maximum Ca2+-activated tension was enhanced by 64% in permeabilized RV MCT preparations (P=0.013). beta-Myosin heavy chain protein was upregulated in MCT RVs (P<0.001) but unaltered in MCT LVs. Degradation of troponin T was prominent in MCT RVs, a phenomenon not observed in the LV. Enhanced biomechanical load is necessary to induce the gene expression changes associated with the hypertrophic phenotype of the pressure-overloaded RV. Neuroendocrine factors, which equally affect both chambers, are not sufficient to alter the expression of Ca2+-cycling proteins.
A Critical Period for Experience-Dependent Remodeling of Adult-Born Neuron Connectivity
Authors: Matteo Bergami, Giacomo Masserdotti, Silvio G. Temprana, Elisa Motori, Therese M. Eriksson, Jana Göbel, Sung Min Yang, Karl-Klaus Conzelmann, Alejandro F. Schinder, Magdalena Götz, Benedikt Berninger
Journal: Neuron (2015)