tbuckley/cabot-search huggingface dataset:
Nuclear Factor-κB Signature of Inflammatory Breast Cancer by cDNA Microarray Validated by Quantitative Real-time Reverse Transcription-PCR, Immunohistochemistry, and Nuclear Factor-κB DNA-Binding
Authors: Steven J. Van Laere, Ilse Van der Auwera, Gert G. Van den Eynden, Hilde J. Elst, Joost Weyler, Adrian L. Harris, Peter van Dam, Eric A. Van Marck, Peter B. Vermeulen, Luc Y. Dirix
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer with high metastatic potential. In a previous study, we showed that IBC is a different form of breast cancer compared with non-IBC by cDNA microarray analysis. A list of 756 genes with significant expression differences between IBC and non-IBC was identified. In-depth functional analysis revealed the presence of a high number of nuclear factor-κB (NF-κB) target genes with elevated expression in IBC versus non-IBC. This led to the hypothesis that NF-κB contributes to the phenotype of IBC. The aim of the present study was to further investigate the role of NF-κB in IBC. Experimental Design: Immunohistochemistry and NF-κB DNA-binding experiments were done for all NF-κB subunits (RelA, RelB, cRel, NFkB1, and NFkB2) using IBC and non-IBC specimens. Transcriptionally active NF-κB dimers were identified by means of coexpression analysis. In addition, quantitative real-time reverse transcription-PCR for eight NF-κB target genes, selected upon a significant, 3-fold gene expression difference between IBC and non-IBC by cDNA microarray analysis, was done. Results: We found a significant overexpression for all of eight selected NF-κB target genes in IBC compared with non-IBC by quantitative real-time reverse transcription-PCR. In addition, we found a statistically elevated number of immunostained nuclei in IBC compared with non-IBC for RelB (P = 0.038) and NFkB1 (P &amp;lt; 0.001). Immunohistochemical data were further validated by NF-κB DNA-binding experiments. Significant correlations between immunohistochemical data and NF-κB DNA binding for RelA, RelB, NFkB1, and NFkB2 were found. Transcriptionally active NF-κB dimers, composed of specific combinations of NF-κB family members, were found in 19 of 44 IBC specimens compared with 2 of 45 non-IBC specimens (P &amp;lt; 0.001). In addition, we found evidence for an estrogen receptor (ER)–mediated inhibition of the NF-κB signaling pathway. NF-κB target genes were significantly elevated in ER− versus ER+ breast tumors. Also, the amount of immunostained nuclei for RelB (P = 0.025) and NFkB1 (P = 0.031) was higher in ER− breast tumors versus ER+ breast tumors. Conclusions: The NF-κB transcription factor pathway probably contributes to the phenotype of IBC and possibly offers new options for treatment of patients diagnosed with this aggressive form of breast cancer.
Prevalence and Risk Factors of Allergies in Turkey (PARFAIT): results of a multicentre cross-sectional study in adults
Authors: E. Kurt, S. Metintas, I. Basyigit, I. Bulut, E. Coskun, S. Dabak, F. Deveci, F. Fidan, H. Kaynar, E.Kunt Uzaslan, K. Onbasi, S. Ozkurt, G.Pasaoglu Karakis, S. Sahan, U. Sahin, K. Oguzulgen, F. Yildiz, D. Mungan, A. Yorgancioglu, B. Gemicioglu
Journal: European Respiratory Journal (2009)

The Prevalence and Risk Factors of Allergies in Turkey (PARFAIT) study was planned to evaluate the prevalence of and risk factors for asthma and allergic diseases in Turkey. The present analysis used data from 25,843 parents of primary school children, obtained from a cross-sectional questionnaire-based study. A total of 25,843 questionnaires from 14 centres were evaluated. In rural areas, the prevalences asthma, wheezing, allergic rhinitis and eczema in males were: 8.5% (95% confidence interval (CI) 7.9-9.1%), 13.5% (95% CI 12.8-14.2%), 17.5% (95% CI 16.7-18.2%) and 10.8% (95% CI 10.2-11.4%), respectively; and in females were: 11.2% (95% CI 10.9-11.8%), 14.7% (95% CI 14.3-15.1%), 21.2% (95% CI 20.4-22.0%) and 13.1% (95% CI 12.4-13.8%), respectively. In urban areas, the corresponding prevalences in males were: 6.2% (95% CI 5.8-6.6%), 10.8% (95% CI 10.3-11.3%), 11.7% (95% CI 11.4-12.0%) and 6.6% (95% CI 6.2-7.0%), respectively; and in females were: 7.5 % (95% CI 7.9-7.1%), 12.0% (95% CI 11.7-12.3%), 17.0% (95% CI 16.4-17.6%) and 7.3% (95% CI 6.9-7.7%), respectively. Having an atopic first-degree relative or any other atopic diseases had significant effects on the prevalence of allergic diseases. Housing conditions, such as living in a shanty-type house, visible moulds at home and use of wood or biomass as heating or cooking material were associated with one or more allergic diseases. Although genetic susceptibility is strongly associated, country- and population-based environmental factors may contribute to increased prevalence rates of allergic diseases.
alpha -Catenin expression is decreased in human gastric cancers and in the gastric mucosa of first degree relatives
Authors: J Yu
Journal: Gut (2000)

Clinical and experimental observations suggest that chronic lung disease is linked to respiratory viral infection. However, the long-term aspect of this relationship is not yet defined using a virus that replicates at properly high levels in humans and a corresponding animal model. In this study, we show that influenza A virus infection achieves 1 × 10<sup>6</sup>–fold increases in viral load in the lung and dose-dependent severity of acute illness in mice. Moreover, these events are followed by persistence of negative- and positive-strand viral RNA remnants for 15 wk and chronic lung disease for at least 26 wk postinfection. The disease is manifested by focal areas of bronchiolization and mucus production that contain increased levels of viral RNA remnants along with mucin Muc5ac and Il13 mRNA compared with uninvolved areas of the lung. Excess mucus production and associated airway hyperreactivity (but not fibrosis or emphysema) are partially attenuated with loss of IL-13 production or signaling (using mice with IL-13 or STAT6 deficiency). These deficiencies cause reciprocal increases in l17a mRNA and neutrophils in the lung; however, none of these disease endpoints are changed with IL-13/IL-17a compared with IL-13 deficiency or STAT6/IL-17a compared with STAT6 deficiency. The results establish the capacity of a potent human respiratory virus to produce chronic lung disease focally at sites of active viral RNA remnants, likely reflecting locations of viral replication that reprogram the region. Viral dose dependency of disease also implicates high-level viral replication and severity of acute infection as determinants of chronic lung diseases such as asthma and COPD with IL-13–dependent and IL-13/IL-17–independent mechanisms.
Phospholipase D activation in human natural killer cells through the Kp43 and CD16 surface antigens takes place by different mechanisms. Involvement of the phospholipase D pathway in tumor necrosis factor alpha synthesis.
Authors: M A Balboa, J Balsinde, J Aramburu, F Mollinedo, M López-Botet
Journal: The Journal of Experimental Medicine (1992)

We have recently described a novel glycoprotein, Kp43, expressed on the surface of human natural killer (NK) cells that appears to regulate their functional activity. In this report, signaling mechanisms through the Kp43 surface antigen have been studied. Incubation of interleukin 2 (IL-2)-treated NK cells with anti-Kp43 monoclonal antibody F(ab')2 fragments resulted in the time- and dose-dependent stimulation of NK cell phospholipase D. Phospholipase D activation through the Kp43 surface antigen was found to take place in the absence of polyphosphoinositide turnover and appeared not to depend on the presence of Ca2+ in the extracellular medium. On the other hand, signaling mechanisms through the CD16 receptor (FcR-III) on NK cells were comparatively studied. Stimulation of IL-2-treated NK cells with anti-CD16 monoclonal antibody F(ab')2 fragment also resulted in time- and dose-dependent activation of phospholipase D. However, CD16-triggered phospholipase D activation took place concomitant to phospholipase C-mediated polyphosphoinositide breakdown and showed a strong dependence on extracellular Ca2+. These results provide, to our knowledge, the first evidence for the presence of activatable phospholipase D in NK cells, as well as the first indication that distinct receptor-modulated pathways exist for activation of phospholipase D within the same cell type. On the other hand, phosphatidic acid, the physiologic product of phospholipase D action on phospholipids, was found to mimic the effect of anti-Kp43 monoclonal antibody regarding tumor necrosis factor alpha (TNF-alpha) biosynthesis and secretion by NK cells. Addition of phosphatidic acid vesicles to IL-2-treated NK cell cultures stimulated a TNF-alpha production that was abolished when the cells were previously treated with actinomycin D. Other phospholipids, including lysophosphatidic acid, were ineffective. However, phosphatidic acid-induced TNF-alpha production was strongly inhibited by the presence of propranolol, an inhibitor of phosphatidic acid phosphohydrolase. Moreover, in cells responding to phorbol myristate acetate, a compound that triggers activation of phospholipase D, TNF-alpha synthesis was also inhibited by propranolol. Thus, these data suggest a second messenger role for phosphatidic acid-derived diradylglycerol in the induction of TNF-alpha gene expression.
Serial Follow-Up and the Prognostic Significance of Reverse Transcriptase-Polymerase Chain Reaction—Staged Sentinel Lymph Nodes From Melanoma Patients
Authors: Udai S. Kammula, Ronald Ghossein, Satyajit Bhattacharya, Daniel G. Coit
Journal: Journal of Clinical Oncology (2004)

Reverse transcriptase-polymerase chain reaction (RT-PCR) may provide an extremely sensitive method for detection of occult nodal disease. We evaluated the role of a single-marker RT-PCR assay for tyrosinase mRNA in the detection of melanoma sentinel lymph node (SLN) metastases and correlated the results with long-term clinical outcome.One hundred twelve patients who underwent SLN biopsy for melanoma were prospectively analyzed. SLNs were bivalved, with half of each specimen evaluated by histologic methods and the other half evaluated by nested RT-PCR for tyrosinase.Fifteen patients (13%) had histologically positive SLNs, all of whom were also positive by RT-PCR (HISTO+/PCR+). Thirty-nine patients (35%) had SLNs that were negative by both histology and RT-PCR (HISTO-/PCR-). Fifty-eight patients (52%) were histologically negative but upstaged with a positive RT-PCR result (HISTO-/PCR+). Initially, at a median follow-up of 42 months, recurrence rates among the three cohorts were statistically different (HISTO+/PCR+, 53%; HISTO-/PCR+, 14%; and HISTO-/PCR-, 0%). However, at a longer median follow-up (67 months), recurrence rates for the HISTO-/PCR+ (24%) and HISTO-/PCR- (15%) groups were no longer statistically different (P =.25). The median time to relapse between the HISTO-/PCR+ and HISTO-/PCR- groups differed by 10 months (31 v 41 months, respectively).With extended follow-up of patients with histologically negative SLNs, detection of submicroscopic disease by tyrosinase RT-PCR does not define a subgroup that is at higher recurrence risk when compared with patients with RT-PCR-negative SLNs. Future studies evaluating molecular staging will require approximately 5 years of median follow-up to accurately define outcome for patients with occult melanoma metastases.
Dietary Fat Intake and Development of Specific Breast Cancer Subtypes
Authors: Sabina Sieri, Paolo Chiodini, Claudia Agnoli, Valeria Pala, Franco Berrino, Antonia Trichopoulou, Vassiliki Benetou, Effie Vasilopoulou, María-José Sánchez, Maria-Dolores Chirlaque, Pilar Amiano, J. Ramón Quirós, Eva Ardanaz, Genevieve Buckland, Giovanna Masala, Salvatore Panico, Sara Grioni, Carlotta Sacerdote, Rosario Tumino, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, Guy Fagherazzi, Petra H. M. Peeters, Carla H. van Gils, H. Bas Bueno-de-Mesquita, Henk J. van Kranen, Timothy J. Key, Ruth C. Travis, Kay Tee Khaw, Nicholas J. Wareham, Rudolf Kaaks, Annekatrin Lukanova, Heiner Boeing, Madlen Schütze, Emily Sonestedt, Elisabeth Wirfält, Malin Sund, Anne Andersson, Veronique Chajes, Sabina Rinaldi, Isabelle Romieu, Elisabete Weiderpass, Guri Skeie, Engeset Dagrun, Anne Tjønneland, Jytte Halkjær, Kim Overvard, Melissa A. Merritt, David Cox, Elio Riboli, Vittorio Krogh
Journal: JNCI Journal of the National Cancer Institute (2014)

We prospectively evaluated fat intake as predictor of developing breast cancer (BC) subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2), in a large (n = 337327) heterogeneous cohort of women, with 10062 BC case patients after 11.5 years, estimating BC hazard ratios (HRs) by Cox proportional hazard modeling. High total and saturated fat were associated with greater risk of ER+PR+ disease (HR = 1.20, 95% confidence interval [CI] = 1.00 to 1.45; HR = 1.28, 95% CI = 1.09 to 1.52; highest vs lowest quintiles) but not ER−PR− disease. High saturated fat was statistically significantly associated with greater risk of HER2− disease. High saturated fat intake particularly increases risk of receptor-positive disease, suggesting saturated fat involvement in the etiology of this BC subtype.
Risk of Fracture After Single Fraction Image-Guided Intensity-Modulated Radiation Therapy to Spinal Metastases
Authors: Peter S. Rose, Ilya Laufer, Patrick J. Boland, Andrew Hanover, Mark H. Bilsky, Josh Yamada, Eric Lis
Journal: Journal of Clinical Oncology (2009)

Single-fraction image-guided intensity-modulated radiation therapy (IG-IMRT) allows for tumoricidal treatment of traditionally radioresistant cancers while sparing critical adjacent structures. Risk of vertebral fracture after IG-IMRT for spinal metastases has not been defined.We evaluated 62 consecutive patients undergoing single fraction IG-IMRT at 71 sites for solid organ metastases. A neuroradiologist and three spine surgeons evaluated prospectively obtained magnetic resonance/computed tomography (CT) imaging studies for post-treatment fracture development and tumor recurrence.Fracture progression was noted in 27 vertebrae (39%). Multivariate logistic regression analysis showed that CT appearance, lesion location, and percent vertebral body involvement independently predicted fracture progression. Lesions located between T10 and the sacrum were 4.6 times more likely to fracture than were lesions above T10 (95% CI, 1.1 to 19.7). Lytic lesions were 6.8 times more likely to fracture than were sclerotic and mixed lesions (95% CI, 1.4 to 33.3). As percent vertebral body involvement increased, odds of fracture also increased. Patients with fracture progression had significantly higher narcotic use, change in Karnofsky performance score, and a strong trend toward higher pain scores. Local tumor progression occurred in seven patients and contributed to one fracture. Obesity, posterior element involvement, bisphosphonate use, and local kyphosis did not confer increased risk.Vertebral fracture is common after single fraction IG-IMRT for metastatic spine lesions. Lytic disease involving more than 40% of the vertebral body and location at or below T10 confer a high risk of fracture, the presence of which yields significantly poorer clinical outcomes. These results may help clinicians identify high-risk patients who would benefit from prophylactic vertebro- or kyphoplasty.
Hyperinsulinemia and Cognitive Decline in a Middle-Aged Cohort
Authors: Sara E. Young, Arch G. Mainous, Mark Carnemolla
Journal: Diabetes Care (2006)

OBJECTIVE—Determining modifiable risks factors for cognitive decline and dementia are a public health priority as we seek to prevent dementia. Type 2 diabetes and related disorders such as hyperinsulinemia increase with aging and are increasing in the U.S. population. Our objective was to determine whether hyperinsulinemia is associated with cognitive decline among middle-aged adults without type 2 diabetes, dementia, or stroke in the Atherosclerosis Risk in Communities (ARIC) cohort. RESEARCH DESIGN AND METHODS—Middle-aged adults (aged 45–64 years at baseline) in the ARIC cohort had fasting insulin and glucose assessed between 1987 and 1989. Subjects with dementia, type 2 diabetes, or stroke at baseline were excluded from analysis. Three tests of cognitive function available at baseline and 6 years later were delayed word recall (DWR), digit symbol subtest (DSS), and first letter word fluency (WF). Cross-sectional comparisons and linear regression models were computed for cognitive tests at baseline and change in cognitive test scores to determine whether cognitive function was associated with two measures of insulin resistance, fasting insulin and homeostasis model assessment (HOMA). Linear regression models controlled for age, sex, race, marital status, education level, smoking status, alcohol use, depression, hypertension, and hyperlipidemia. RESULTS—In unadjusted and adjusted analyses, hyperinsulinemia based on fasting insulin and HOMA at baseline was associated with significantly lower baseline DWR, DSS, and WF scores and a greater decline over 6 years in DWR and WF. CONCLUSIONS—Insulin resistance is a potentially modifiable midlife risk factor for cognitive decline and dementia.
Allogeneic Bone Marrow Transplantation in Mevalonic Aciduria
Authors: Bénédicte Neven, Vassili Valayannopoulos, Pierre Quartier, Stéphane Blanche, Anne-Marie Prieur, Marianne Debré, Marie-Odile Rolland, Daniel Rabier, Laurence Cuisset, Marina Cavazzana-Calvo, Pascale de Lonlay, Alain Fischer
Journal: New England Journal of Medicine (2007)

Mevalonic aciduria is a rare, inborn error of isoprene biosynthesis characterized by severe, periodic attacks of fever and inflammation, developmental delay, ataxia, and dysmorphic features. This autosomal recessive disease is caused by a mutation in the mevalonate kinase gene that severely reduces mevalonate kinase activity. A 3-year-old boy with mevalonic aciduria whose condition had failed to improve with antiinflammatory treatment underwent allogeneic bone marrow transplantation from an HLA-identical sister who was a heterozygous carrier of the mutant gene. We observed sustained remission of febrile attacks and inflammation during a 15-month follow-up period.
Dietary Energy Restriction Modulates the Activity of AMP-Activated Protein Kinase, Akt, and Mammalian Target of Rapamycin in Mammary Carcinomas, Mammary Gland, and Liver
Authors: Weiqin Jiang, Zongjian Zhu, Henry J. Thompson
Journal: Cancer Research (2008)

Abstract Dietary energy restriction (DER) inhibits mammary carcinogenesis, yet mechanisms accounting for its protective activity have not been fully elucidated. In this study, we tested the hypothesis that DER exerts effects on intracellular energy sensing pathways, resulting in alterations of phosphorylated proteins that play a key role in the regulation of cancer. Experiments were conducted using the 1-methyl-1-nitrosourea–induced mammary cancer model in which rats were 0%, 20%, or 40% energy restricted during the postinitiation stage of carcinogenesis. Parallel experiments were done in non–carcinogen-treated rats in which effects of DER at 0%, 5%, 10%, 20%, or 40% in liver were investigated. In a DER dose–dependent manner, levels of Thr172 phosphorylated AMP-activated protein kinase (AMPK) increased in mammary carcinomas with a concomitant increase in phosphorylated acetyl-CoA-carboxylase, a direct target of AMPK, the phosphorylation of which is regarded as an indicator of AMPK activity. Levels of phosphorylated mammalian target of rapamycin (mTOR) decreased with increasing DER, and down-regulation of mTOR activity was verified by a decrease in the phosphorylation state of two mTOR targets, 70-kDa ribosomal protein S6 kinase (p70S6K) and eukaryote initiation factor 4E binding protein 1 (4E-BP1). Coincident with changes in mTOR phosphorylation, levels of activated protein kinase B (Akt) were also reduced. Similar patterns were observed in mammary glands and livers of non–carcinogen-treated rats. This work identifies components of intracellular energy sensing pathways, specifically mTOR, its principal upstream regulators, AMPK and Akt, and its downstream targets, p70S6K and 4E-BP1, as candidate molecules on which to center mechanistic studies of DER. [Cancer Res 2008;68(13):5492–9]
Effectiveness and Cost-Effectiveness of Dialectical Behaviour Therapy for Self-Harming Patients with Personality Disorder: A Pragmatic Randomised Controlled Trial
Authors: Stefan Priebe, Nyla Bhatti, Kirsten Barnicot, Stephen Bremner, Amy Gaglia, Christina Katsakou, Iris Molosankwe, Paul McCrone, Martin Zinkler
Journal: Psychotherapy and Psychosomatics (2012)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; A primary goal of dialectical behaviour therapy (DBT) is to reduce self-harm, but findings from empirical studies are inconclusive. The aim of this study was to assess the effectiveness and cost-effectiveness of DBT in reducing self-harm in patients with personality disorder. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Participants with a personality disorder and at least 5 days of self-harm in the previous year were randomised to receive 12 months of either DBT or treatment as usual (TAU). The primary outcome was the frequency of days with self-harm; secondary outcomes included borderline personality disorder symptoms, general psychiatric symptoms, subjective quality of life, and costs of care. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Forty patients each were randomised to DBT and TAU. In an intention-to-treat analysis, there was a statistically significant treatment by time interaction for self-harm (incidence rate ratio 0.91, 95% CI 0.89–0.92, p &lt; 0.001). For every 2 months spent in DBT, the risk of self-harm decreased by 9% relative to TAU. There was no evidence of differences on any secondary outcomes. The economic analysis revealed a total cost of a mean of 5,685 GBP (6,786 EUR) in DBT compared to a mean of 3,754 GBP (4,481 EUR) in TAU, but the difference was not significant (95% CI –603 to 4,599 GBP). Forty-eight per cent of patients completed DBT. They had a greater reduction in self-harm compared to dropouts (incidence rate ratio 0.78, 95% CI 0.76–0.80, p &lt; 0.001). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; DBT can be effective in reducing self-harm in patients with personality disorder, possibly incurring higher total treatment costs. The effect is stronger in those who complete treatment. Future research should explore how to improve treatment adherence.
Early events in Epstein-Barr virus infection provide a model for B cell activation.
Authors: D A Thorley-Lawson, K P Mann
Journal: The Journal of Experimental Medicine (1985)

We have used Epstein-Barr virus (EBV) infection in vitro to delineate two distinct stages in B cell activation. Previous studies have shown that the BLAST-2 (EBVCS) (EBV cell surface) activation antigen is expressed on a small fraction of B cells within 24 h of stimulation with a variety of agents, including mitogens and EBV. In this study, we have been able to isolate the BLAST-2 (EBVCS)+ cells early after activation/infection with EBV. These cells are small B cells that are actively synthesizing RNA but not DNA, and are, therefore, clearly distinct from large proliferating lymphoblasts. In addition, they contain multiple copies of the EBV genome, express the viral nuclear antigen (EBNA) and, most importantly, proceed to undergo transformation when placed back in culture. By comparison, the BLAST-2 (EBVCS)- population does not undergo transformation, even though a fraction of these cells are activated for RNA synthesis and express EBNA. Thus, using the EBV system, we have been able to show directly that an activated B cell first expresses the BLAST-2 (EBVCS) antigen concomitant with an increase in RNA synthesis, and then subsequently proceeds to differentiate into a proliferating lymphoblast.