tbuckley/cabot-search huggingface dataset:
ISG15 Is a Critical Microenvironmental Factor for Pancreatic Cancer Stem Cells
Authors: Bruno Sainz, Beatriz Martín, Marianthi Tatari, Christopher Heeschen, Susana Guerra
Journal: Cancer Research (2014)

Cancer stem cells (CSC) are thought to play a major role in the development and metastatic progression of pancreatic ductal adenocarcinoma (PDAC), one of the deadliest solid tumors. Likewise, the tumor microenvironment contributes critical support in this setting, including from tumor stromal cells and tumor-associated macrophages (TAM) that contribute structural and paracrine-mediated supports, respectively. Here, we show that TAMs secrete the IFN-stimulated factor ISG15, which enhances CSC phenotypes in PDAC in vitro and in vivo. ISG15 was preferentially and highly expressed by TAM present in primary PDAC tumors resected from patients. ISG15 was secreted by macrophages in response to secretion of IFNβ by CSC, thereby reinforcing CSC self-renewal, invasive capacity, and tumorigenic potential. Overall, our work demonstrates that ISG15 is a previously unrecognized support factor for CSC in the PDAC microenvironment with a key role in pathogenesis and progression.
Pulmonary Vein Isolation as an End Point for Left Atrial Circumferential Ablation of Atrial Fibrillation
Authors: Kristina Lemola, Hakan Oral, Aman Chugh, Burr Hall, Peter Cheung, Jihn Han, Kamala Tamirisa, Eric Good, Frank Bogun, Frank Pelosi, Fred Morady
Journal: Journal of the American College of Cardiology (2005)
Expansion of human cardiac stem cells in physiological oxygen improves cell production efficiency and potency for myocardial repair
Authors: Tao-Sheng Li, Ke Cheng, Konstantinos Malliaras, Noriko Matsushita, Baiming Sun, Linda Marbán, Yiqiang Zhang, Eduardo Marbán
Journal: Cardiovascular Research (2010)

The ex vivo expansion of cardiac stem cells from minimally invasive human heart biopsies yields tens of millions of cells within 3–4 weeks, but chromosomal abnormalities were frequently detected in preliminary production runs. Here we attempt to avoid aneuploidy and improve cell quality by expanding human cardiac stem cells in physiological low-oxygen (5% O2) conditions, rather than in traditional culture in a general CO2 incubator (20% O2). Human heart biopsies (n = 16) were divided and processed in parallel to expand cardiac stem cells under 5% or 20% O2. Compared with 20% O2, 5% O2 culture doubled the cell production and markedly diminished the frequency of aneuploidy. Cells expanded in 5% O2 showed lower intracellular levels of reactive oxygen species, less cell senescence, and higher resistance to oxidative stress than those grown in 20% O2, although the expression of stem cell antigens and adhesion molecules was comparable between groups, as was the paracrine secretion of growth factors into conditioned media. In vivo, the implantation of 5% O2 cells into infarcted hearts of mice resulted in greater cell engraftment and better functional recovery than with conventionally cultured cells. The expansion of human adult cardiac stem cells in low oxygen increased cell yield, and the resulting cells were superior by various key in vitro and in vivo metrics of cell quality. Physiological oxygen tensions in culture facilitate the ex vivo expansion of healthy, biologically potent stem cells.
Multigene Panel Testing: Planning the Next Generation of Research Studies in Clinical Cancer Genetics
Authors: Mark Robson
Journal: Journal of Clinical Oncology (2014)

Kurianetal 1 accompanyingthiseditorialdescribestheresultsofan early deployment of this technology in the oncology clinic. The investigators performed multiplex testing using a custom panel on a collection of samples from women who had previously undergone evaluation for breast-ovarian cancer predisposition. Most of these women were affected by and had family histories of breast and/or ovarian cancer. As expected, the most common mutations observed were in BRCA1 and BRCA2, with nearly (but not quite) complete concordance with prior commercial testing. There were alsoanumberofindividualsinthegroupwhocarriedmutationsin other genes, including one woman with an unequivocal mutation in MLH1. The authors considered many of these additional findings to be “potentially actionable,” and concluded that multiplex testingresultedinchangesinrecommendationsforpreventivecare
Once-Daily Tiotropium Respimat® Improves Lung Function In Patients With Severe Symptomatic Asthma Independent Of Leukotriene Modifier Use
Authors: Ronald Dahl, Dennis E. Doherty, Jonathan Corren, Jill Karpel, Huib A.M. Kerstjens, Michael Engel, Petra Moroni-Zentgraf, Hendrik Schmidt, Shu Hashimoto
Journal: Journal of Allergy and Clinical Immunology (2014)
Surgical treatment of patellar tendon pain in athletes.
Authors: S Orava, L Osterback, M Hurme
Journal: British Journal of Sports Medicine (1986)

A series of surgically treated patellar tendon lesions among athletes is presented. The material was collected during 5 years from three sports injury clinics and from two hospitals. During this period the authors treated about 150 cases of jumper's knee, of which 34 cases were treated by operation. The athletes were mostly volley ball players, jumpers or runners. The operation revealed a necrotic focus of the patellar tendon in 21 cases, the retinaculum was thick and adherent in 16 patients and an exostosis of the patellar insertion was seen in two cases. The necrotic areas were excised, the thick and adherent retinaculum was divided and the exostoses were excised and drilled. Surgical treatment of chronic patellar tendon pains may give good results in selected cases.
Significance of <i>MYCN</i> Amplification in International Neuroblastoma Staging System Stage 1 and 2 Neuroblastoma: A Report From the International Neuroblastoma Risk Group Database
Authors: Rochelle Bagatell, Maja Beck-Popovic, Wendy B. London, Yang Zhang, Andrew D.J. Pearson, Katherine K. Matthay, Tom Monclair, Peter F. Ambros, Susan L. Cohn
Journal: Journal of Clinical Oncology (2008)

Purpose Treatment of patients with localized neuroblastoma with unfavorable biologic features is controversial. To evaluate the outcome of children with low-stage MYCN-amplified neuroblastoma and develop a rational treatment strategy, data from the International Neuroblastoma Risk Group (INRG) database were analyzed. Patients and Methods The database is comprised of 8,800 patients. Of these, 2,660 patients (30%) had low-stage (International Neuroblastoma Staging System stages 1 and 2) neuroblastoma, known MYCN status, and available follow-up data. Eighty-seven of these patients (3%) had MYCN amplified tumors. Results Patients with MYCN-amplified, low-stage tumors had less favorable event-free survival (EFS) and overall survival (OS) than did patients with nonamplified tumors (53% ± 8% and 72% ± 7% v 90% ± 1% and 98% ± 1%, respectively). EFS and OS were statistically significantly higher for patients whose tumors were hyperdiploid rather than diploid (EFS, 82% ± 20% v 37% ± 21%; P = .0069; OS, 94% ± 11% v 54% ± 15%; P = .0056, respectively). No other variable had prognostic significance. Initial treatment consisted of surgery alone for 29 (33%) of 87 patients. Details of additional therapy were unknown for 14 patients. Twenty-two patients (25%) underwent surgery and moderate-intensity chemotherapy; another 22 underwent surgery, intensive chemotherapy, and radiation therapy. Nine of the latter 22 underwent stem cell transplantation. Survival in patients who received transplantation did not differ from survival in those who did not receive transplantation. Conclusion Among patients with low-stage, MYCN-amplified neuroblastoma, outcomes of patients with hyperdiploid tumors were statistically, significantly better than those with diploid tumors. The data suggest that tumor cell ploidy could potentially be used to identify candidates for reductions in therapy. Further study of MYCN-amplified, low-stage neuroblastoma is warranted.
Postoperative radiation and concomitant bolus fluorouracil with or without additional chemotherapy with fluorouracil and high-dose leucovorin in patients with high-risk rectal cancer: A randomized phase III study conducted by the Hellenic Cooperative Oncology Group
Authors: G. Fountzilas, A. Zisiadis, U. Dafni, C. Konstantaras, G. Hatzitheoharis, A. Liaros, E. Athanassiou, N. Dombros, C. Dervenis, G. Basdanis, O. Gamvros, A. Souparis, E. Briasoulis, E. Samantas, A. Kappas, P. Kosmidis, D. Skarlos, N. Pavlidis
Journal: Annals of Oncology (1999)
Exploring a Phylogenetic Approach for the Detection of Correlated Substitutions in Proteins
Authors: Pierre Tuff, Pierre Darlu
Journal: Molecular Biology and Evolution (2000)

The remarkable conservation of protein structure, compared with that of sequences, suggests that in the course of evolution, residue substitutions which tend to destabilize a particular structure must be compensated by other substitutions that confer greater stability on that structure. Several approaches have been designed to detect correlated changes in a set of homologous sequences. However, most of them do not take into account the phylogeny of the sequences, and it has been shown that their detection power is weak. It remains unclear whether coevolution could be a general process at the level of amino acids of proteins. In the present study, we analyze the phylogenetic reconstruction of 15 sets of homologous proteins to assess, under different conditions, whether a significant amount of coevolving sites can be detected. Two criteria are used to detect significantly cosubstituting sites. One criterion corresponds to that of Shindyalov, Kolchanov, and Sander. The second one is based on intensive simulations of evolution of protein sequences along a phylogeny to estimate the significance of the number of observed cosubstitutions for pairs of sites. Our results show an important sensitivity of the detection of cosubstituting sites to the model used for the phylogenetic reconstruction. Not considering the uncertainty associated with the reconstructed data might lead to detecting numerous false-positive pairs of sites. Finally, significant amounts of coevolving pairs could be found only when substitutions affecting the physicochemical properties of the amino acids were considered. Such results suggest evidence of a cosubstitution mechanism in protein evolution. However, the identification of nonambiguous coevolving sites is still unresolved.
Murine serum glycoprotein gp70 behaves as an acute phase reactant.
Authors: I Hara, S Izui, F J Dixon
Journal: The Journal of Experimental Medicine (1982)

A single intraperitoneal injection of bacterial lipopolysaccharide (LPS) or its lipid A component induced high levels of glycoprotein, gp70, in sera of several strains of mice within 24 h. This serum gp70 response induced by LPS was independent of the activation of B cells and the presence of T cells. However, serological and immunohistochemical studies demonstrated the production of gp70 by hepatic parenchymal cells and its subsequent release into the circulating blood. The expression of gp70 in the serum was enhanced not only by LPS but also other inducers of acute phase reactants (APR) such as turpentine oil or polyriboinosinic-polyribocytidylic acid. Further, the serum gp70 response was kinetically identical to those of APR. These results strongly suggest that (a) the liver may be the major source for serum gp70, (b) serum gp70 behaves like an APR, (c) its expression may be controlled by a mechanism similar to that for other APR, and (d) this glycoprotein apparently behaves as a normal host constituent and not a product of a viral genome.
PREPARATION AND PURIFICATION OF HUMAN INSULIN-I131; BINDING TO HUMAN INSULIN-BINDING ANTIBODIES
Authors: Solomon A. Berson, Rosalyn S. Yalow
Journal: Journal of Clinical Investigation (1961)

The preparation of I131-labeled human insulin from a lot of human insulin containing approximately 25% insulin by weight and its purification from labeled contaminants are described. The reaction of human insulin-I133 with insulinbinding antibodies in the serums of human subjects treated with commercial mixtures of animal insulins is demonstrated directly. Comparison of the binding of human insulin and beef insulin in antiserums from eight insulinresistant and nonresistant diabetic subjects revealed a lesser affinity' of antibody for human than for beef insulin in most cases, but considerable variability in this respect was encountered among different antiserums.
Honokiol Inhibits Epidermal Growth Factor Receptor Signaling and Enhances the Antitumor Effects of Epidermal Growth Factor Receptor Inhibitors
Authors: Rebecca J. Leeman-Neill, Quan Cai, Sonali C. Joyce, Sufi M. Thomas, Neil E. Bhola, Daniel B. Neill, Jack L. Arbiser, Jennifer R. Grandis
Journal: Clinical Cancer Research (2010)

This study aimed to investigate the utility of honokiol, a naturally occurring compound, in the treatment of head and neck squamous cell carcinoma (HNSCC) as well as its ability to target the epidermal growth factor receptor (EGFR), a critical therapeutic target in HNSCC, and to enhance the effects of other EGFR-targeting therapies.Human HNSCC cell lines and the xenograft animal model of HNSCC were used to test the effects of honokiol treatment.Honokiol was found to inhibit growth in human HNSCC cell lines, with 50% effective concentration (EC(50)) values ranging from 3.3 to 7.4 micromol/L, and to induce apoptosis, as shown through Annexin V staining. These effects were associated with inhibition of EGFR signaling, including downstream inhibition of mitogen-activated protein kinase, Akt, and signal transducer and activator of transcription 3 (STAT3), and expression of STAT3 target genes, Bcl-X(L) and cyclin D1. Furthermore, honokiol enhanced the growth inhibitory and anti-invasion activity of the EGFR-targeting agent erlotinib. Although HNSCC xenograft models did not show significant inhibition of in vivo tumor growth with honokiol treatment alone, the combination of honokiol plus cetuximab, a Food and Drug Administration-approved EGFR inhibitor for this malignancy, significantly enhanced growth inhibition. Finally, HNSCC cells rendered resistant to erlotinib retained sensitivity to the growth inhibitory effects of honokiol.These results suggest that honokiol may be an effective therapeutic agent in HNSCC, in which it can augment the effects of EGFR inhibitors and overcome drug resistance.
Early‐life house dust mite allergens, childhood mite sensitization, and respiratory outcomes
Authors: L. Casas, J. Sunyer, C. Tischer, U. Gehring, M. Wickman, R. Garcia‐Esteban, I. Lehmann, I. Kull, A. Reich, S. Lau, A. Wijga, J. M. Antó, T. S. Nawrot, J. Heinrich, T. Keil, M. Torrent
Journal: Allergy (2015)

Exposure to indoor allergens during early life may play a role in the development of the immune system and inception of asthma.To describe the house dust mite (HDM) allergen concentrations in bedroom dust during early life and to evaluate its associations with HDM sensitization, wheezing, and asthma, from birth to school age, in 5 geographically spread European birth cohorts.We included 4334 children from INMA-Menorca (Spain), BAMSE (Sweden), LISAplus and MAS (Germany), and PIAMA-NHS (the Netherlands). Dust samples were collected from bedrooms during early life and analyzed for Dermatophagoides pteronyssinus (Der p1) and Dermatophagoides farinae (Der f1). HDM concentrations were divided into four categories. Sensitization was determined by specific IgE. Wheezing and asthma information up to 8/10 years was collected through questionnaires. We performed mixed-effects logistic regression models and expressed associations as odds ratios with 95% confidence intervals.House dust mite concentrations varied across cohorts. Mean allergen concentrations were highest in INMA-Menorca (geometric mean (GM) Der p1 = 3.3 μg/g) and LISAplus (GM Der f1 = 2.1 μg/g) and lowest in BAMSE (GM Der p1 = 0.1 μg/g, Der f1 = 0.3 μg/g). Moderate and high HDM concentrations were significantly (P-values < 0.05) associated with 50-90% higher prevalence of HDM sensitization. No significant associations were observed with respiratory outcomes.Our study based on geographically spread regions, a large sample size, and a wide range of allergen concentration shows that HDM allergen concentrations vary across regions and that exposure during early life plays a role in the development of allergic sensitization but not in the development of respiratory outcomes.
Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap)
Authors: S. Dearden, J. Stevens, Y.-L. Wu, D. Blowers
Journal: Annals of Oncology (2013)

Meta-analyses were conducted to characterize patterns of mutation incidence in non small-cell lung cancer (NSCLC). Nine genes with the most complete published mutation coincidence data were evaluated. One meta-analysis generated a ‘mutMap’ to visually represent mutation coincidence by ethnicity (Western/Asian) and histology (adenocarcinoma [ADC] or squamous cell carcinoma). Another meta-analysis evaluated incidence of individual mutations. Extended analyses explored incidence of EGFR and KRAS mutations by ethnicity, histology, and smoking status. Genes evaluated were TP53, EGFR, KRAS, LKB1, EML4-ALK, PTEN, BRAF, PIK3CA, and ErbB2. The mutMap highlighted mutation coincidences occurring in ≥5% of patients, including TP53 with KRAS or EGFR mutations in patients with ADC, and TP53 with LKB1 mutation in Western patients. TP53 was the most frequently mutated gene overall. Frequencies of TP53, EGFR, KRAS, LKB1, PTEN, and BRAF mutations were influenced by histology and/or ethnicity. Although EGFR mutations were most frequent in patients with ADC and never/light smokers from Asia, and KRAS mutations were most frequent in patients with ADC and ever/heavy smokers from Western countries, both were detected outside these subgroups. Potential molecular pathology segments of NSCLC were identified. Further studies of mutations in NSCLC are warranted to facilitate more specific diagnoses and guide treatment.
Anti‐infliximab IgE and non‐IgE antibodies and induction of infusion‐related severe anaphylactic reactions
Authors: A. Vultaggio, A. Matucci, F. Nencini, S. Pratesi, P. Parronchi, O. Rossi, S. Romagnani, E. Maggi
Journal: Allergy (2009)

To cite this article: Vultaggio A, Matucci A, Nencini F, Pratesi S, Parronchi P, Rossi O, Romagnani S, Maggi E. Anti‐infliximab IgE and non‐IgE antibodies and induction of infusion‐related severe anaphylactic reactions. Allergy 2010; 65 : 657–661. Abstract Background: Infliximab is a chimeric monoclonal antibody against TNF‐α useful in the treatment of many chronic inflammatory diseases. Severe anaphylaxis has been reported during therapy, although the exact mechanism has not been fully defined. The reactions have been related to the infliximab immunogenicity and development of specific antibodies. Aims of the study: Evaluation of the development of IgE and non‐IgE antibodies to infliximab and their relationship with infusion reaction. Methods: Seventy‐one patients (11 reactives, 11 therapeutically nonresponders, and 49 unreactive therapeutically responders) and 20 non–infliximab‐exposed control subjects (ten rheumatoid arthritis, five spondyloarthropathies, five vasculitis) were evaluated for the presence of IgE (ImmunoCAP assay), IgM, and non–isotype‐specific (ELISA assays) anti‐infliximab antibodies. Sera were obtained at baseline and during the course of treatment, before each infliximab infusion. Results: Eleven out of 71 patients had a hypersensitivity reaction to infliximab. Non–isotype‐specific anti‐infliximab antibodies were detected in eight reactive and two nonresponder patients. Three patients with severe reactions displayed anti‐infliximab IgE antibodies and positive skin testing. Detectable levels of anti‐infliximab IgM antibodies were shown in three additional IgE‐ and skin testing‐negative patients. IgE and IgM antibodies to infliximab were not detectable in the two nonresponder patients. Antibodies developed before the 2nd and the 3rd infusion, and their appearance was strictly related to the timing of the reaction. Conclusions: This report indicates that in some patients with infliximab‐related severe reactions, IgE or IgM antibodies against infliximab were detectable. The majority of reactions could be predicted by the appearance of anti‐infliximab antibodies.
Lipid-laden macrophage index and inflammation in bronchoalveolar lavage fluids in children
Authors: M.Y. Kazachkov, M.S. Muhlebach, C.A. Livasy, T.L. Noah
Journal: European Respiratory Journal (2001)

The presence of lipids in alveolar macrophages has been used clinically as an indicator of aspiration, a process associated with increased lung inflammation in animal models. The hypothesis is that the quantity of lipids in alveolar macrophages, measured as lipid-laden index (LLI), would correlate with lung inflammation in paediatric patients. Children with chronic respiratory symptoms (21 cystic fibrosis (CF), 24 non-CF) underwent flexible bronchoscopy with bronchoalveolar lavage (BAL) and 24-h intraoesophageal pH monitoring for clinical indications. Total cell counts, number and per cent of neutrophils and macrophages, and LLI were determined in the bronchoalveolar lavage fluids (BALF) from all children. BALF were also obtained from eight healthy, young nonsmoking adults for comparison. LLI in non-CF children were 6.9 +/- 3.5 (mean +/- SEM) which were higher than LLI in healthy adults (1.0 +/- 0.4), (p=0.045). Children with CF had very high LLIs (19.2 +/- 4.5) compared with both healthy adults (p=0.014) and children without CF (p=0.045). LLI did not correlate with airway inflammation in any group. LLI in children with abnormal pH probes had a tendency to be higher than in children with normal pH probes, but the difference was not significant (p=0.098). It is concluded that the lipid-laden index was significantly elevated in children with chronic respiratory symptoms compared with healthy adults, and in children with cystic fibrosis compared with those who have other chronic respiratory conditions. However, the lipid-laden index did not correlate with the quantity of bronchoalveolar lavage fluid inflammation. The lipid-laden index in children may, in part, reflect processes other than aspiration, such as airways obstruction.
Loss of function and inhibitory effects of human CSX/NKX2.5 homeoprotein mutations associated with congenital heart disease
Authors: Hideko Kasahara, Bora Lee, Jean-Jacques Schott, D. Woodrow Benson, J.G. Seidman, Christine E. Seidman, Seigo Izumo
Journal: Journal of Clinical Investigation (2000)

CSX/NKX2.5 is an evolutionarily conserved homeodomain-containing (HD-containing) transcription factor that is essential for early cardiac development. Recently, ten different heterozygous CSX/NKX2.5 mutations were found in patients with congenital heart defects that are transmitted in an autosomal dominant fashion. To determine the consequence of these mutations, we analyzed nuclear localization, DNA binding, transcriptional activation, and dimerization of mutant CSX/NKX2.5 proteins. All mutant proteins were translated and located to the nucleus, except one splice-donor site mutant whose protein did not accumulate in the cell. All mutants that had truncation or missense mutations in the HD had severely reduced DNA binding activity and little or no transcriptional activation function. In contrast, mutants with intact HDs exhibit normal DNA binding to the monomeric binding site but had three- to ninefold reduction in DNA binding to the dimeric binding sites. HD missense mutations that preserved homodimerization ability inhibited the activation of atrial natriuretic factor by wild-type CSX/NKX2.5. Although our studies do not characterize the genotype-phenotype relationship of the ten human mutations, they identify specific abnormalities of CSX/NKX2.5 function essential for transactivation of target genes.
The Prime Study: Survival Outcomes for Patients with RAS/BRAF Wild-Type Metastatic Colorectal Cancer, by Baseline ECOG Performance Status
Authors: Peeters Marc, Siena Salvatore, Tabernero Josep, Douillard Jean-Yves, Koukakis Reija, Terwey Jan-Henrik, Sidhu Roger
Journal: Annals of Oncology (2014)