tbuckley/cabot-search huggingface dataset:
Near IR Heptamethine Cyanine Dye–Mediated Cancer Imaging
Authors: Xiaojian Yang, Chunmeng Shi, Rong Tong, Weiping Qian, Haiyen E. Zhau, Ruoxiang Wang, Guodong Zhu, Jianjun Cheng, Vincent W. Yang, Tianmin Cheng, Maged Henary, Lucjan Strekowski, Leland W.K. Chung
Journal: Clinical Cancer Research (2010)

Near-IR fluorescence imaging has great potential for noninvasive in vivo imaging of tumors. In this study, we show the preferential uptake and retention of two hepatamethine cyanine dyes, IR-783 and MHI-148, in tumor cells and tissues.IR-783 and MHI-148 were investigated for their ability to accumulate in human cancer cells, tumor xenografts, and spontaneous mouse tumors in transgenic animals. Time- and concentration-dependent dye uptake and retention in normal and cancer cells and tissues were compared, and subcellular localization of the dyes and mechanisms of the dye uptake and retention in tumor cells were evaluated using organelle-specific tracking dyes and bromosulfophthalein, a competitive inhibitor of organic anion transporting peptides. These dyes were used to detect human cancer metastases in a mouse model and differentiate cancer cells from normal cells in blood.These near-IR hepatamethine cyanine dyes were retained in cancer cells but not normal cells, in tumor xenografts, and in spontaneous tumors in transgenic mice. They can be used to detect cancer metastasis and cancer cells in blood with a high degree of sensitivity. The dyes were found to concentrate in the mitochondria and lysosomes of cancer cells, probably through organic anion transporting peptides, because the dye uptake and retention in cancer cells can be blocked completely by bromosulfophthalein. These dyes, when injected to mice, did not cause systemic toxicity.These two heptamethine cyanine dyes are promising imaging agents for human cancers and can be further exploited to improve cancer detection, prognosis, and treatment.
Gut in 2007
Authors: R Spiller
Journal: Gut (2007)

Another good year for Gut 

The first issue of the New Year is a good time to look back on past achievements and forward to the future. Gut continues to be a popular journal for authors and readers alike. 2006 was an exceptionally busy year with over 2400 manuscripts submitted, a 33% increase since 2003. Approximately half our manuscripts come from Europe, with most of the remainder coming equally from the USA, Japan and Asia. The criteria for acceptance are entirely uniform and the acceptance rate by country is increasingly similar. In spite of the steady rise in the number of manuscripts, the median time to decision for all manuscripts remains under 30 days, while the median time to first decision for reviewed manuscripts is around 40 days. As we only publish around 1 in 8 of manuscripts submitted, it makes sense for us to reject without review those that we think have little chance of success. These make up about one third of all manuscripts: all such papers are read by at least one associate editor and myself before the decision is made. The remaining manuscripts are sent out for review, most of which are …
Identification of Nectin-4 Oncoprotein as a Diagnostic and Therapeutic Target for Lung Cancer
Authors: Atsushi Takano, Nobuhisa Ishikawa, Ryohei Nishino, Ken Masuda, Wataru Yasui, Kouki Inai, Hitoshi Nishimura, Hiroyuki Ito, Haruhiko Nakayama, Yohei Miyagi, Eiju Tsuchiya, Nobuoki Kohno, Yusuke Nakamura, Yataro Daigo
Journal: Cancer Research (2009)

Abstract Gene expression profile analysis of lung cancers revealed the transactivation of an immunoglobulin-like molecule Nectin-4 in the majority of non–small cell lung cancers (NSCLC). Immunohistochemical staining of 422 NSCLCs showed that a high level of Nectin-4 expression was associated with poor prognosis for NSCLC patients (P &amp;lt; 0.0001), and multivariate analysis confirmed its independent prognostic value (P &amp;lt; 0.0001). We established an ELISA to measure serum Nectin-4 and found that serum Nectin-4 levels were significantly higher in NSCLC patients than in healthy volunteers. The proportion of the serum Nectin-4–positive cases was 88 of 164 (53.7%) NSCLCs, whereas only 3 of 131 (2.3%) healthy volunteers were falsely diagnosed as positive, which was superior to carcinoembryonic antigen (CEA) and cytokeratin 19-fragment (CYFRA21-1) in sensitivity and specificity. A combined ELISA for both Nectin-4 and CEA increased sensitivity and classified 65.0% of lung adenocarcinomas as positive with false-positive rate of 4.6%. The use of both Nectin-4 and CYFRA21-1 classified 68.3% of lung squamous cell carcinomas as positive with false-positive rate of 6.1%. Treatment of lung cancer cells with small interfering RNAs against Nectin-4 suppressed its expression and cell growth. In addition, exogenous expression of Nectin-4 increased the lamellipodia formation and the invasive ability of mammalian cells through activation of small GTPase Rac1. Nectin-4 might play a significant role in lung carcinogenesis, and it should be a new candidate serum and tissue biomarker, as well as a therapeutic target. [Cancer Res 2009;69(16):6694–703]
Cadmium-Induced Leydig Cell Tumors of Rat Testis: Morphologic and Cytochemical Study2
Authors: Janardan Reddy, Donald Svoboda, Daniel Azarnoff, Ramesh Dawar
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Cadmium-Induced Leydig Cell Tumors of Rat Testis: Morphologic and Cytochemical Study Get access Janardan Reddy, Janardan Reddy Search for other works by this author on: Oxford Academic PubMed Google Scholar Donald Svoboda, Donald Svoboda Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniel Azarnoff, Daniel Azarnoff Search for other works by this author on: Oxford Academic PubMed Google Scholar Ramesh Dawar Ramesh Dawar Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 3, September 1973, Pages 891–903, https://doi.org/10.1093/jnci/51.3.891 Published: 01 September 1973 Article history Received: 05 March 1973 Accepted: 14 May 1973 Published: 01 September 1973
Contact allergens and sodium lauryl sulphate upregulate vascular endothelial growth factor in normal keratinocytes
Authors: S. PALACIO, D. SCHMITT, J. VIAC
Journal: British Journal of Dermatology (1997)

In allergic and irritant contact dermatitis, keratinocytes are major target cells that can be activated to take part in local reactions by secreting soluble mediators. Among the growth factors produced by keratinocytes, vascular endothelial growth factor (VEGF) is a powerful inducer of permeability of endothelial cells, and is involved in inflammation. We determined whether different contact allergens, dinitrosulphobenzene (DNSB), para‐phenylenediamine (pPD) and the metals nickel and chromium, as distinct from cobalt, which has been shown to mimic the effects of hypoxia, can modify the basal level of VEGF in normal human keratinocytes when tested at various, non‐toxic concentrations. The effects of an irritant, sodium lauryl sulphate (SLS), and of hydrocortisone were also tested. Our results showed an intense dose‐dependent upregulation of VEGF release by keratinocytes after treatments by metals, pPD and SLS. DNSB induced only a moderate increase of VEGF. Hydrocortisone reduced the basal level as well as the nickel‐induced upregulation of VEGF. These findings suggest that contact allergens and irritants probably upregulate VEGF in keratinocytes by different mechanisms and may contribute directly to the microvascular hyperpermeability which characterizes both contact and irritant dermatitis.
Efficient Selection of Branch-Specific Models of Sequence Evolution
Authors: Julien Y. Dutheil, Nicolas Galtier, Jonathan Romiguier, Emmanuel J.P. Douzery, Vincent Ranwez, Bastien Boussau
Journal: Molecular Biology and Evolution (2012)

The analysis of extant sequences shows that molecular evolution has been heterogeneous through time and among lineages. However, for a given sequence alignment, it is often difficult to uncover what factors caused this heterogeneity. In fact, identifying and characterizing heterogeneous patterns of molecular evolution along a phylogenetic tree is very challenging, for lack of appropriate methods. Users either have to a priori define groups of branches along which they believe molecular evolution has been simila or have to allow each branch to have its own pattern of molecular evolution. The first approach assumes prior knowledge that is seldom available, and the second requires estimating an unreasonably large number of parameters. Here we propose a convenient and reliable approach where branches get clustered by their pattern of molecular evolution alone, with no need for prior knowledge about the data set under study. Model selection is achieved in a statistical framework and therefore avoids overparameterization. We rely on substitution mapping for efficiency and present two clustering approaches, depending on whether or not we expect neighbouring branches to share more similar patterns of sequence evolution than distant branches. We validate our method on simulations and test it on four previously published data sets. We find that our method correctly groups branches sharing similar equilibrium GC contents in a data set of ribosomal RNAs and recovers expected footprints of selection through dN/dS. Importantly, it also uncovers a new pattern of relaxed selection in a phylogeny of Mantellid frogs, which we are able to correlate to life-history traits. This shows that our programs should be very useful to study patterns of molecular evolution and reveal new correlations between sequence and species evolution. Our programs can run on DNA, RNA, codon, or amino acid sequences with a large set of possible models of substitutions and are available at http://biopp.univ-montp2.fr/forge/testnh.
Epigenetic Epidemiology of the Developmental Origins Hypothesis
Authors: Robert A. Waterland, Karin B. Michels
Journal: Annual Review of Nutrition (2007)

Extensive human epidemiologic and animal model data indicate that during critical periods of prenatal and postnatal mammalian development, nutrition and other environmental stimuli influence developmental pathways and thereby induce permanent changes in metabolism and chronic disease susceptibility. The biologic mechanisms underlying this “developmental origins hypothesis” are poorly understood. This review focuses on the likely involvement of epigenetic mechanisms in the developmental origins of health and disease (DOHaD). We describe permanent effects of transient environmental influences on the developmental establishment of epigenetic gene regulation and evidence linking epigenetic dysregulation with human disease. We propose a definition of “epigenetic epidemiology” and delineate how this emerging field provides a basis from which to explore the role of epigenetic mechanisms in DOHaD. We suggest strategies for future human epidemiologic studies to identify causal associations between early exposures, long-term changes in epigenetic regulation, and disease, which may ultimately enable specific early-life interventions to improve human health.
STANDARDS OF VISION FOR SCHOLARS AND TEACHERS IN COUNCIL SCHOOLS
Authors: N. B. Harman
Journal: BMJ (1923)

M BaJf anaesthetic, some of them actually demonstrating it at scientific meetings, anid we received many inquiries from all over the country for more information.It was decided, however, not to recommetnd butyn for use in dentistry until we should have the evidence of many thousand cases to support the statements of its advantage reported to us by the various investigators.. . .Several hunidred dentists have used butyn in probably more than 10,000 cases of dental operations.It has run the gamut of infiltration, nerve blocking, topical application, pressure anaesthesia, pulp anaesthesia, in fact, practically every use to which a dentist might put a local anaesthetic, and has come through with high honours.Now we feel justified in presenting butyn to the dental profession, strictly on its merits as evidenced by actual clinical experience."
Safety and Efficacy of 24-h Closed-Loop Insulin Delivery in Well-Controlled Pregnant Women With Type 1 Diabetes
Authors: Helen R. Murphy, Kavita Kumareswaran, Daniela Elleri, Janet M. Allen, Karen Caldwell, Martina Biagioni, David Simmons, David B. Dunger, Marianna Nodale, Malgorzata E. Wilinska, Stephanie A. Amiel, Roman Hovorka
Journal: Diabetes Care (2011)

To evaluate the safety and efficacy of closed-loop insulin delivery in well-controlled pregnant women with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII).
Disciplinary stereotypes and reinventing the wheel on culture
Authors: David P. Kennedy
Journal: Behavioral and Brain Sciences (2007)

Gintis argues that disciplinary models of human behavior are incompatible. However, his depiction of the discipline of anthropology relies on a broad generalization that is not supported by current practice. Gintis also ignores the work of cognitive anthropologists, who have developed theories and methods that are highly compatible with the perspective advocated by Gintis.
Glycoprotein IIb/IIIa Inhibitors in the Elderly
Authors: Gilles Montalescot
Journal: Circulation (2006)

n Western countries, persons 75 years of age or older constitute Ϸ5% of the population but account for more than one third of those with acute coronary syndromes.In addition, one third of this elderly population has exerciseinduced silent ischemia.The elderly population is projected to be more than 3 times larger in 2050 as today.The lower fertility rate and reduced mortality account for the aging of global population now and during the coming 50 years. 1However, this problem is not a problem for the richest countries only, and, according to the World Health Organization, the developing countries are actually more vulnerable to cardiovascular diseases, which have increased by more than 120% in the last 30 years compared with a 50% increase in developed countries over the same period.Better information and education of the elderly population, better access to healthcare services, earlier detection of coronary artery disease, better quality of care delivered to the elderly, and extrapolation to older persons of modern, evidence-based medicine, and often of modern aggressive care successfully tested in younger populations, are leading to dramatic changes in the management of this segment of the population.The painful consequence is that health systems will be stretched as the number of elderly patients increases.There will be a need for more investment in treatments of coronary artery disease, development of more aggressive prevention, and evaluation of the best cost-effective measures in this group of patients.
Global analysis of mRNA stability in the archaeon Sulfolobus
Authors: Anders F Andersson, Magnus Lundgren, Stefan Eriksson, Magnus Rosenlund, Rolf Bernander, Peter Nilsson
Journal: Genome biology (2006)

Abstract Background Transcript half-lives differ between organisms, and between groups of genes within the same organism. The mechanisms underlying these differences are not clear, nor are the biochemical properties that determine the stability of a transcript. To address these issues, genome-wide mRNA decay studies have been conducted in eukaryotes and bacteria. In contrast, relatively little is known about RNA stability in the third domain of life, Archaea. Here, we present a microarray-based analysis of mRNA half-lives in the hyperthermophilic crenarchaea Sulfolobus solfataricus and Sulfolobus acidocaldarius , constituting the first genome-wide study of RNA decay in archaea. Results The two transcriptomes displayed similar half-life distributions, with medians of about five minutes. Growth-related genes, such as those involved in transcription, translation and energy production, were over-represented among unstable transcripts, whereas uncharacterized genes were over-represented among the most stable. Half-life was negatively correlated with transcript abundance and, unlike the situation in other organisms, also negatively correlated with transcript length. Conclusion The mRNA half-life distribution of Sulfolobus species is similar to those of much faster growing bacteria, contrasting with the earlier observation that median mRNA half-life is proportional to the minimal length of the cell cycle. Instead, short half-lives may be a general feature of prokaryotic transcriptomes, possibly related to the absence of a nucleus and/or more limited post-transcriptional regulatory mechanisms. The pattern of growth-related transcripts being among the least stable in Sulfolobus may also indicate that the short half-lives reflect a necessity to rapidly reprogram gene expression upon sudden changes in environmental conditions.
Targeting ERBB Receptors Shifts Their Partners and Triggers Persistent ERK Signaling through a Novel ERBB/EFNB1 Complex
Authors: Paola D. Vermeer, Paul L. Colbert, Bryant G. Wieking, Daniel W. Vermeer, John H. Lee
Journal: Cancer Research (2013)

Abstract Most squamous cell carcinomas of the head and neck (HNSCC) overexpress ERBB1/EGFR, but EGF receptor (EGFR)-targeted therapies have yielded disappointing clinical results in treatment of this cancer. Here, we describe a novel interaction between EGFR and the ligand EphrinB1 (EFNB1), and we show that EFNB1 phosphorylation and downstream signaling persists in the presence of cetuximab. Mechanistically, cetuximab drives a shift in EGFR dimerization partners within the signaling complex, suggesting that targeted drugs may trigger partner rearrangements that allow persistent pathway activation. EFNB1 attenuation slowed tumor growth and increased survival in a murine model of HNSCC, suggesting a substantial contribution of EFNB1 signaling to HNSCC development. Together, our findings suggest that EFNB1 is part of the EGFR signaling complex and may mediate drug resistance in HNSCC as well as other solid tumors. Cancer Res; 73(18); 5787–97. ©2013 AACR.
Imatinib Mesylate in Advanced Dermatofibrosarcoma Protuberans: Pooled Analysis of Two Phase II Clinical Trials
Authors: Piotr Rutkowski, Martine Van Glabbeke, Cathryn J. Rankin, Wlodzimierz Ruka, Brian P. Rubin, Maria Debiec-Rychter, Alexander Lazar, Hans Gelderblom, Raf Sciot, Dolores Lopez-Terrada, Peter Hohenberger, Allan T. van Oosterom, Scott M. Schuetze
Journal: Journal of Clinical Oncology (2010)

Dermatofibrosarcoma protuberans (DFSP) is a dermal sarcoma typically carrying a translocation between chromosomes 17 and 22 that generates functional platelet-derived growth factor B (PDGFB).Two distinct phase II trials of imatinib (400 to 800 mg daily) in patients with locally advanced or metastatic DFSP were conducted and closed prematurely, one in Europe (European Organisation for Research and Treatment of Cancer [EORTC]) with 14-week progression-free rate as the primary end point and the other in North America (Southwest Oncology Group [SWOG]) with confirmed objective response rate as the primary end point. In the EORTC trial, confirmation of PDGFB rearrangement was required, and surgery was undertaken after 14 weeks if feasible. The SWOG study confirmed t(17;22) after enrollment.Sixteen and eight patients were enrolled onto the EORTC and SWOG trials, respectively. Tumor size ranged from 1.2 to 49 cm. DFSP was located on head/neck, trunk, and limb in seven, 11, and six patients, respectively, and was classic, pigmented, and fibrosarcomatous DFSP in 13, one, and nine patients, respectively. Metastases were present in seven patients (lung involvement was present six patients). Eleven patients (4%) had partial response as best response, and four patients had progressive disease as best response. Median time to progression (TTP) was 1.7 years. Imatinib was stopped in 11 patients because of progression, one patient because of toxicity, and two patients after complete resection of disease. Median overall survival (OS) time has not been reached; 1-year OS rate was 87.5%.Imatinib is active in DFSP harboring t(17;22) including fibrosarcomatous DFSP, with objective response rate approaching 50%. Response rates and TTP did not differ between patients taking 400 mg daily versus 400 mg twice a day.
Endothelial Growth Factor Receptors in Human Fetal Heart
Authors: Taina A. Partanen, Taija Makinen, Johanna Arola, Toshio Suda, Herbert A. Weich, Kari Alitalo
Journal: Circulation (1999)

Background —Endothelial receptor tyrosine kinases include 3 members of the vascular endothelial growth factor receptor (VEGFR) family and 2 members of the angiopoietin receptor (Tie) family. In addition, the VEGF 165 isoform binds to neuropilin-1 (NP-1), a receptor for collapsins/semaphorins. The importance of these receptors for vasculogenesis and angiogenesis has been shown in gene-targeted mice, but so far, little is known about their exact expression patterns in the human vasculature. Methods and Results —Frozen sections of human fetal heart were stained immunohistochemically with receptor-specific monoclonal (VEGFR, Tie) or polyclonal (NP-1) antibodies. The following patterns were observed: The endocardium was positive for VEGFR-1, VEGFR-2, NP-1, Tie-1, and Tie-2 but negative for VEGFR-3. The coronary vessels were positive for Tie-1, Tie-2, VEGFR-1, and NP-1 and negative for VEGFR-2 and VEGFR-3. Myocardial capillaries and epicardial blood vessels stained for VEGFR-1, VEGFR-2, NP-1, and Tie-1; myocardial capillaries and epicardial veins weakly for Tie-2; and epicardial lymphatic vessels for VEGFR-2 and VEGFR-3, weakly for Tie-1 and Tie-2, but not for VEGFR-1 or NP-1. Conclusions —The results demonstrate differential expression of the endothelial growth factor receptors in distinct types of vessels in the human heart. This information is useful for the understanding of their roles in physiological and pathological processes and for their diagnostic and therapeutic application in cardiovascular medicine.
Breast Cancer Methylomes Establish an Epigenomic Foundation for Metastasis
Authors: Fang Fang, Sevin Turcan, Andreas Rimner, Andrew Kaufman, Dilip Giri, Luc G. T. Morris, Ronglai Shen, Venkatraman Seshan, Qianxing Mo, Adriana Heguy, Stephen B. Baylin, Nita Ahuja, Agnes Viale, Joan Massague, Larry Norton, Linda T. Vahdat, Mary Ellen Moynahan, Timothy A. Chan
Journal: Science Translational Medicine (2011)

Breast cancer methylomes contribute to metastatic potential, modulate the metastasis transcriptome, and predict disease outcome.