tbuckley/cabot-search huggingface dataset:
HER3 Is Required for HER2-Induced Preneoplastic Changes to the Breast Epithelium and Tumor Formation
Authors: David B. Vaught, Jamie C. Stanford, Christian Young, Donna J. Hicks, Frank Wheeler, Cammie Rinehart, Violeta Sánchez, John Koland, William J. Muller, Carlos L. Arteaga, Rebecca S. Cook
Journal: Cancer Research (2012)

Abstract Increasing evidence suggests that HER2-amplified breast cancer cells use HER3/ErbB3 to drive therapeutic resistance to HER2 inhibitors. However, the role of ErbB3 in the earliest events of breast epithelial transformation remains unknown. Using mouse mammary specific models of Cre-mediated ErbB3 ablation, we show that ErbB3 loss prevents the progressive transformation of HER2-overexpressing mammary epithelium. Decreased proliferation and increased apoptosis were seen in MMTV-HER2 and MMTV-Neu mammary glands lacking ErbB3, thus inhibiting premalignant HER2-induced hyperplasia. Using a transgenic model in which HER2 and Cre are expressed from a single polycistronic transcript, we showed that palpable tumor penetrance decreased from 93.3% to 6.7% upon ErbB3 ablation. Penetrance of ductal carcinomas in situ was also decreased. In addition, loss of ErbB3 impaired Akt and p44/42 phosphorylation in preneoplastic HER2-overexpressing mammary glands and in tumors, decreased growth of preexisting HER2-overexpressing tumors, and improved tumor response to the HER2 tyrosine kinase inhibitor lapatinib. These events were rescued by reexpression of ErbB3, but were only partially rescued by ErbB36F, an ErbB3 mutant harboring six tyrosine-to-phenylalanine mutations that block its interaction with phosphatidyl inositol 3-kinase. Taken together, our findings suggest that ErbB3 promotes HER2-induced changes in the breast epithelium before, during, and after tumor formation. These results may have important translational implications for the treatment and prevention of HER2-amplified breast tumors through ErbB3 inhibition. Cancer Res; 72(10); 2672–82. ©2012 AACR.
Stat1 Deficiency in the Host Enhances Interleukin-12–Mediated Tumor Regression
Authors: Marina N. Torrero, Xueqing Xia, Williams Henk, Shry Yu, Shulin Li
Journal: Cancer Research (2006)

Abstract Signal transducer and activator of transcription 1 (Stat1) is considered a key transcription factor that inhibits tumorigenesis, and Stat1 activation in the host is required for interleukin-12 (IL-12)–mediated generation of CTL activity. Using syngeneic Stat1−/− C3H mice bearing SCCVII tumors in this study, we discovered opposite results. Stat1 deficiency in the host significantly enhances IL-12–mediated tumor regression, resulting in tumor eradication from 60% of SCCVII tumor–bearing mice and significant inhibition of tumor growth when compared with control treatment (P &amp;lt; 0.01). This effect is independent of both Stat1-activating cytokine IFN-γ and Stat1-downstream effector molecule FasL because neither neutralization of IFN-γ nor knocking out of FasL enhances or inhibits IL-12–mediated tumor regression. IL-12 induces a high intensity of tumor-specific CTL activity in Stat1-deficient mice (P &amp;lt; 0.01), increases the CD8 T-cell density in tumor bearing Stat1−/− mice, and induces a T-cell–dependent tumor regression. The increased CTL activity and the high-intensity infiltration of T cells into the tumors in IL-12–treated Stat1−/− mice are likely due to the longer survival than the same cells from wild-type mice. Together, the data show that inhibition of Stat1 expression in the host enhances tumor-local IL-12 gene therapy for regressing tumors. This conclusion provides a new concept for designing an effective treatment strategy. (Cancer Res 2006; 66(8): 4461-7)
Radiation-Induced Gene Translation Profiles Reveal Tumor Type and Cancer-Specific Components
Authors: Sandhya Kumaraswamy, Prakash Chinnaiyan, Uma T. Shankavaram, Xing Lü, Kevin Camphausen, Philip J. Tofilon
Journal: Cancer Research (2008)

Abstract The microarray analysis of total cellular RNA is a common method used in the evaluation of radiation-induced gene expression. However, profiling the cellular transcriptome does not take into account posttranscriptional processes that affect gene expression. To better define the genes whose expression is influenced by ionizing radiation, we used polysome-bound RNA to generate gene translation profiles for a series of tumor and normal cell lines. Cell lines were exposed to 2 Gy, polysome-bound RNA isolated 6 hours later, and then subjected to microarray analysis. To identify the genes whose translation was affected by radiation, the polysome-bound RNA profiles were compared with their corresponding controls using significance analysis of microarrays (&amp;lt;1% false discovery rate). From the statistically significant genes identified for each cell line, hierarchical clustering was performed by average linkage measurement and Pearson's correlation metric. Ingenuity Pathway Analysis was used for distributing genes into biological networks and for evaluation of functional significance. Radiation-induced gene translation profiles clustered according to tissue of origin; the cell lines corresponding to each tissue type contained a significant number of commonly affected genes. Network analyses suggested that the biological functions associated with the genes whose translation was affected by radiation were tumor type–specific. There was also a set of genes/networks that were unique to tumor or normal cells. These results indicate that radiation-induced gene translation profiles provide a unique data set for the analysis of cellular radioresponse and suggest a framework for identifying and targeting differences in the regulation of tumor and normal cell radiosensitivity. [Cancer Res 2008;68(10):3819–26]
To DNA or not to DNA? That Is the Question, When It Comes to Molecular Subtyping for the Clinic!
Authors: Serge J. Smeets, Ulrike Harjes, Wessel N. van Wieringen, Daoud Sie, Ruud H. Brakenhoff, Gerrit A. Meijer, Bauke Ylstra
Journal: Clinical Cancer Research (2011)

Genome-wide RNA expression profiling has yielded tumor subtypes with strong predictive or prognostic value for a wide variety of cancers. Recently, for breast cancer two RNA expression classifiers have been adopted by the World Health Organization (WHO) and approved by the Food and Drug Administration (FDA). Also on the basis of DNA copy number profiles, tumor subtypes with different prognosis have been described, but have not yet led to clinical implementation. The genomic revolution caused by next generation sequencing of DNA samples presents additional mutation, balanced translocations, single-nucleotide polymorphisms (SNP), and copy neutral loss of heterozygosity data simultaneously. We foresee a further boost of the potential of DNA profiling in the clinic when these multidimensional DNA factors will be implemented. Here we evaluate the current stratification power with DNA copy numbers. In a training and validation approach using data of 400 published breast cancer samples, we show that a DNA copy number classifier accurately classifies RNA expression subtypes. We consider this an important step forward for clinical implementation of genomic subtyping using DNA and discuss the extra dimensions upcoming techniques will bring to the DNA palette.
Exercise induced leg pain-chronic compartment syndrome. Is the increase in intra-compartment pressure exercise specific?
Authors: N Padhiar, J B King
Journal: British Journal of Sports Medicine (1996)

Intra-compartment pressure studies remain the main investigative method in diagnosing chronic compartment syndrome (CCS). Standard exercise protocols have been used to cause the raise in pressure measured in the laboratories. This case suggests that CCS cannot be excluded without the specific sports activity being used to raise the intracompartmental pressure.
Association of Poor Childhood Fear Conditioning and Adult Crime
Authors: Yu Gao, Adrian Raine, Peter H. Venables, Michael E. Dawson, Sarnoff A. Mednick
Journal: American Journal of Psychiatry (2009)

Objective Amygdala dysfunction is theorized to give rise to poor fear conditioning, which in turn predisposes to crime, but it is not known whether poor conditioning precedes criminal offending. This study prospectively assessed whether poor fear conditioning early in life predisposes to adult crime in a large cohort. Method Electrodermal fear conditioning was assessed in a cohort of 1,795 children at age 3, and registration for criminal offending was ascertained at age 23. In a case-control design, 137 cohort members with a criminal record were matched on gender, ethnicity, and social adversity with 274 noncriminal comparison members. Statistical analyses compared childhood fear conditioning for the two groups. Results Criminal offenders showed significantly reduced electrodermal fear conditioning at age 3 compared to matched comparison subjects. Conclusions Poor fear conditioning at age 3 predisposes to crime at age 23. Poor fear conditioning early in life implicates amygdala and ventral prefrontal cortex dysfunction and a lack of fear of socializing punishments in children who grow up to become criminals. These findings are consistent with a neurodevelopmental contribution to crime causation.
Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphoma
Authors: Stephan Mathas, Martin Janz, Franziska Hummel, Michael Hummel, Brigitte Wollert-Wulf, Simone Lusatis, Ioannis Anagnostopoulos, Andreas Lietz, Mikael Sigvardsson, Franziska Jundt, Korinna Jöhrens, Kurt Bommert, Harald Stein, Bernd Dörken
Journal: Nature Immunology (2005)
Can an endocytoscope system (ECS) predict histology in neoplastic lesions?
Authors: T. Eberl, G. Jechart, A. Probst, M. Golczyk, M. Bittinger, R. Scheubel, H. Arnholdt, R. Knuechel, H. Messmann
Journal: Endoscopy (2007)

See also: Commentaire de travail de T. Eberl et al., pp. 497Endoscopy 2007; 39(06): 576-576DOI: 10.1055/s-0032-1306939
Calcineurin Signaling in Human Cardiac Hypertrophy
Authors: R. Sanders Williams
Journal: Circulation (2002)

n the basis of studies in cell and animal models, a great diversity of signaling molecules have been implicated in stimulus-response pathways by which hypertrophic growth of the myocardium is controlled.It remains unclear, however, which signal transduction pathways are pertinent to the common forms of cardiac hypertrophy that lead to heart failure and sudden death in humans.
In vivo study of scleroderma by non-invasive techniques
Authors: B. KALIS, J. RIGAL, F. LEONARD, J.L. LEVEQUE, O. RICHE, Y. CORRE, O. LACHARRIERE
Journal: British Journal of Dermatology (1990)

Journal Article In vivo study of scleroderma by non‐invasive techniques Get access B. KALIS, B. KALIS Département de Dermatologie, Hôpitl Sébastopol, Reims, France Mr B.Kalis, Departement de Dermatologié, Hôpital Sebastopol, Rue de Sébastopol, 51092 Reims, France Search for other works by this author on: Oxford Academic Google Scholar J. DE RIGAL, J. DE RIGAL Laboratoires de Recherche de L'Oreal, Aulnay sous Bois, France Search for other works by this author on: Oxford Academic Google Scholar F. LÉONARD, F. LÉONARD Département de Dermatologie, Hôpitl Sébastopol, Reims, France Search for other works by this author on: Oxford Academic Google Scholar J.L. LÉVÊQUE, J.L. LÉVÊQUE Laboratoires de Recherche de L'Oreal, Aulnay sous Bois, France Search for other works by this author on: Oxford Academic Google Scholar O. RICHE, O. RICHE Département de Dermatologie, Hôpitl Sébastopol, Reims, France Search for other works by this author on: Oxford Academic Google Scholar Y. LE CORRE, Y. LE CORRE Département de Dermatologie, Hôpitl Sébastopol, Reims, France Search for other works by this author on: Oxford Academic Google Scholar O. DE LACHARRIERE O. DE LACHARRIERE Département de Dermatologie, Hôpitl Sébastopol, Reims, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 122, Issue 6, 1 June 1990, Pages 785–791, https://doi.org/10.1111/j.1365-2133.1990.tb06267.x Published: 01 June 1990
No effect of oral N-acetylcysteine on the bioavailability of erythromycin and bacampicillin
Authors: O Paulsen, L Borgstrom, B Kagedal, M Walder
Journal: European Respiratory Journal (1988)

In vitro studies with N-acetylcysteine (NAC) solutions used for inhalation treatment have demonstrated inactivation of some antibiotics by NAC. Oral NAC treatment is increasingly common for long-term prophylaxis in chronic bronchitis. During exacerbations, treatment with oral antibiotics will often be given simultaneously. We assessed the effect of simultaneous oral administration of NAC on the bioavailability of two antibiotics in ten healthy volunteers. No effect of NAC was found on the bioavailability of ampicillin, after administration of the prodrug bacampicillin. A slight, but not significant statistical increase in erythromycin serum levels was seen with NAC. Acetylator phenotype did not influence the absorption of NAC, which seemed slightly reduced by bacampicillin, but significantly increased by erythromycin. No decrease of antibacterial activity of sera was found in vitro after the addition of NAC or the related thiol glutathione, employing micrococcus luteus and staphylococcus aureus as indicator organisms.
Effect of Glucose Variability on the Long-Term Risk of Microvascular Complications in Type 1 Diabetes
Authors: Eric S. Kilpatrick, Alan S. Rigby, Stephen L. Atkin
Journal: Diabetes Care (2009)

OBJECTIVE This study analyzed data from the Epidemiology of Diabetes Interventions and Complications (EDIC) study to see whether longer-term follow-up of Diabetes Control and Complications Trial (DCCT) patients reveals a role for glycemic instability in the development of microvascular complications. RESEARCH DESIGN AND METHODS The mean area under the curve glucose and the within-day glucose variability (SD and mean amplitude of glycemic excursions [MAGE]) during the DCCT were assessed to see whether they contributed to the risk of retinopathy and nephropathy by year 4 of the EDIC. RESULTS Logistic regression analysis showed that mean glucose during the DCCT and mean A1C during EDIC were independently predictive of retinopathy (each P &amp;lt; 0.001) as well as A1C during EDIC of nephropathy (P = 0.001) development by EDIC year 4. Glucose variability did not add to this (all P &amp;gt; 0.25 using SD or MAGE). CONCLUSIONS Glucose variability in the DCCT did not predict the development of retinopathy or nephropathy by EDIC year 4.
Electron beam therapy for difficult cutaneous basal and squamous cell carcinoma
Authors: R.A. MILLER, MARGARET F. SPITTLE
Journal: British Journal of Dermatology (1982)

Electron beam therapy was used to treat twenty‐nine patients with squamous or basal cell carcinomas considered unsuitable for surgery or conventional superficial X‐ray therapy. Primary control failed in two patients at 2 and 5 years. Good cosmetic and functional results occurred in all patients treated. The advantages of this therapy in the management of cutaneous tumours which are difficult to treat are discussed.
Modified Mediterranean diet and survival
Authors: Eddie Vos
Journal: BMJ (2005)

Modified Mediterranean diet and survival Evidence for diet linked longevity is substantialEditor-The EPIC-elderly cohort study was designed to investigate the association between a modified Mediterranean diet and longer life expectancy among an elderly subpopulation (older than 60) that is part of the larger EPIC (European Prospective Investigation into Cancer and Nutrition) cohort. 1 2 Focusing the attention on a sample with a more restricted age range seems to reinforce previous findings on diet linked longevity, but important risk factors were not taken into account in collecting the data.Total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and blood pressure are well known determinants of cardiovascular disease.The study's outcomes are expressed in term of mortality, and cardiovascular disease remains the most important of all causes of death.The benefits of a healthy eating pattern with respect to these variables have been shown. 3he same might not be sustained if the total EPIC cohort were considered (aged 20-85). 2 Have the authors considered any possible statistical gain from including these risk factors in the analysis when considering the younger subgroup?We believe that the conclusions for participants older than 60 are stronger if the risk of cardiovascular disease in men and women after the menopause is considered.In a world in which people eat mainly processed foods that are rich in saturated fats, the analysis is a warning to adopt a healthier dietary pattern and, broadly, lifestyle changes.
Correlation of Levels of Oncostatin M Cytokine in Crevicular Fluid and Serum in Periodontal Disease
Authors: ManojKumar Thorat, Pradeep AR, Garima Garg
Journal: International Journal of Oral Science (2010)

The aim of this study was to measure the level of Oncostatin M (OSM) a gp130 cytokine in the gingival crevicular fluid (GCF) and serum of chronic periodontitis patients and to find any correlation between them before and after periodontal therapy (scaling and root planing, SRP). 60 subjects (age 25–50 years) were enrolled into three groups (n=20 per group), group I (healthy), group II (gingivitis) and group III (chronic periodontitis). Group III subjects were followed for 6–8 weeks after the initial periodontal therapy (SRP) as the group IV (after periodontal therapy). Clinical parameters were assessed as gingival index (GI), probing depth (PD), clinical attachment level (CAL), and radiographic evidence of bone loss. GCF and serum levels of OSM were measured by using Enzyme Linked Immunosorbent Assay (ELISA). It was found that mean OSM levels had been elevated in both the GCF and serum of chronic periodontitis subjects (726.65 ± 283.56 and 65.59 ± 12.37 pg·mL−1, respectively) and these levels were decreased proportionally after the periodontal therapy (95.50 ± 38.85 and 39.98 ± 16.69 pg·mL−1 respectively). However, OSM was detected in GCF of healthy subjects (66.15 ± 28.10 pg·mL−1) and gingivitis‐suffering subjects (128.33 ± 22.96 pg·mL−1) and was found as below the detectable limit (≈0.0 pg·mL−1) in the serum of same subjects. Significant correlation has been found between clinical parameters and GCF‐serum levels of OSM. Increased OSM level both in the GCF and serum, and the decreased levels after initial periodontal therapy (SRP) may suggest a use as an inflammatory bio‐marker in the periodontal disease.
Aryl Hydrocarbon Receptor Control of Adaptive Immunity
Authors: Francisco J. Quintana, David H. Sherr
Journal: Pharmacological Reviews (2013)

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that belongs to the family of basic helix-loop-helix transcription factors. Although the AhR was initially recognized as the receptor mediating the pathologic effects of dioxins and other pollutants, the activation of AhR by endogenous and environmental factors has important physiologic effects, including the regulation of the immune response. Thus, the AhR provides a molecular pathway through which environmental factors modulate the immune response in health and disease. In this review, we discuss the role of AhR in the regulation of the immune response, the source and chemical nature of AhR ligands, factors controlling production and degradation of AhR ligands, and the potential to target the AhR for therapeutic immunomodulation.
The impact of exercise reconditioning on breathlessness in severe chronic airflow limitation.
Authors: D E O'Donnell, M McGuire, L Samis, K A Webb
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Exercise in chronic airflow limitation (CAL) is often limited by symptoms before the physiologic boundaries of maximal ventilatory or cardiovascular capacities are attained. Symptom amelioration should translate directly into improved exercise performance. We studied the impact of a 6-wk supervised multimodality endurance exercise program (EXT) on perceived breathlessness (B) and leg effort (LE) and sought a physiologic rationale for symptom improvement. Thirty patients with CAL (FEV1/FVC = 42 +/- 2%, mean +/- SEM) were tested before and after EXT. Their responses were compared with those of a matched control group (n = 30; FEV1/FVC = 44 +/- 2%) after a nonintervention period. Testing included pulmonary function tests, chronic dyspnea evaluation (Baseline/Transition Dyspnea Index [BDI/TDI]), and graded cycle exercise with cardioventilatory monitoring and Borg scaling of B and LE. Spirometry did not change (delta) post-EXT. EXT significantly (p < 0.001) reduced chronic breathlessness (TDI = +2.8 +/- 0.3) compared with control (TDI = 0.0 +/- 0.3). Exertional symptoms of B and LE also fell (p < 0.01) after EXT (slopes of B and LE relative to VO2 fell by 14 and 23%, respectively; delta B/VO2 was associated with delta LE/VO2, r = 0.52, p < 0.01). Post-EXT slopes of B over ventilation (VE) also decreased by 10% (p < 0.025). Total cycle work increased 142 +/- 70% (p < 0.001) post-EXT and correlated primarily with delta B/VO2 (r = -0.64, p < 0.001). The best correlate of delta B/VO2 was delta VE/VO2 (r = 0.47, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Immune Selection for Altered Antigen Processing Leads to Cytotoxic T Lymphocyte Escape in Chronic HIV-1 Infection
Authors: Rika Draenert, Sylvie Le Gall, Katja J. Pfafferott, Alasdair J. Leslie, Polan Chetty, Christian Brander, Edward C. Holmes, Shih-Chung Chang, Margaret E. Feeney, Marylyn M. Addo, Lidia Ruiz, Danni Ramduth, Prakash Jeena, Marcus Altfeld, Stephanie Thomas, Yanhua Tang, Cori L. Verrill, Catherine Dixon, Julia G. Prado, Photini Kiepiela, Javier Martinez-Picado, Bruce D. Walker, Philip J.R. Goulder
Journal: The Journal of Experimental Medicine (2004)

Mutations within cytotoxic T lymphocyte (CTL) epitopes impair T cell recognition, but escape mutations arising in flanking regions that alter antigen processing have not been defined in natural human infections. In human histocompatibility leukocyte antigen (HLA)-B57+ HIV-infected persons, immune selection pressure leads to a mutation from alanine to proline at Gag residue 146 immediately preceding the NH2 terminus of a dominant HLA-B57–restricted epitope, ISPRTLNAW. Although N-extended wild-type or mutant peptides remained well-recognized, mutant virus–infected CD4 T cells failed to be recognized by the same CTL clones. The A146P mutation prevented NH2-terminal trimming of the optimal epitope by the endoplasmic reticulum aminopeptidase I. These results demonstrate that allele-associated sequence variation within the flanking region of CTL epitopes can alter antigen processing. Identifying such mutations is of major relevance in the construction of vaccine sequences.