tbuckley/cabot-search huggingface dataset:
Analysis of &lt;italic&gt;N&lt;/italic&gt;-Ethyl-&lt;italic&gt;N&lt;/italic&gt;-nitrosourea-Induced Brain Carcinogenesis by Sequential Culturing During the Latent Period. II. Morphology of the Tumors Induced by Cell Cultures&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Penelope J. Claisse, P. L. Lantos, Joan P. Roscoe
 5
Journal: JNCI Journal of the National Cancer Institute (1978)

Pregnant BD IX rats were given ip injections of N-ethyl-N-nitrosourea (ENU) or buffer on day 15 or 16 of gestation, and cultures were prepared from the brains of fetuses and offspring at different times after treatment. Cultured cells were injected sc into syngeneic rats. Some of the cultures derived 2, 111–112, and 138–145 days after exposure to carcinogen were tumorigenic. They formed malignant growths which invaded and destroyed surrounding tissues. The neoplasms showed structural differences in various areas: The cells were dispersed at random in the wide extracellular space in the center of the tumors, whereas they were arranged in bundles at the periphery. Three groups of cells were distinguished: bipolar-fusiform, polygonal-stellate, and binucleate-multinucleate. The bipolar-fusiform cells could be divided into two separate populations by use of special stains; glioblasts showed occasional weak staining for glial fibers and collagen-producing cells. The polygonal-stellate and binucleate-multinucleate cells were all of astrocytic derivation with evidence of glial fiber production. Cellular pleomorphism correlated with the length of time after which the brains were removed following ENU treatment. Glial tumors derived from brains cultured 2 days after the administration of carcinogen were more pleomorphic than those produced by cell lines prepared 111–112 days and 138–145 days after treatment. Cellular pleomorphism decreased with increasing number of transfers in tumors from some cultures prepared 111–112 days and 138–145 days after injection, but not in those derived 2 days after treatment.
Abstract 852: ARRY-380, a potent, small molecule inhibitor of ErbB2, increases survival in intracranial ErbB2+ xenograft models in mice
Authors: Victoria Dinkel, Deborah Anderson, Shannon Winski, James Winkler, Kevin Koch, Patrice A. Lee
Journal: Cancer Research (2012)

Abstract ARRY-380 is an orally active, potent small molecule targeting ErbB2 inhibitor currently in clinical development in patients with ErbB2+ metastatic breast cancer (MBC). This compound has shown excellent activity in numerous SC mouse tumor models including breast (BT-474, MDA-MB-453), ovarian (SK-OV-3) and gastric (N87) carcinoma models. In breast cancer patients, brain metastases are a serious unmet medical need. Patients with ErbB2+ breast cancer have a significantly increased incidence of brain metastases following trastuzumab therapy. Here we demonstrate significant single agent activity of ARRY-380 in two ErbB2+ intracranial mouse xenograft models. For these studies, female nude mice received intracranial implantations of tumor cells (either NCI-N87 or BT-474) by direct injection into the brain parenchyma (via the sagittal suture). In pilot studies, we demonstrated that the blood brain barrier was not disrupted by mechanical injections and that increasing tumor burden correlates negatively with neurologic outcome, body weight and survival. In the N87 studies, animals received treatments beginning on Day 2 post-implantation and continuing for up to 6 weeks. Dose groups (n=12/group) were vehicle, ARRY-380 at MTD (75 mg/kg, PO, BID) or lapatinib at MTD (50 mg/kg, PO, BID). All animals in the vehicle- or lapatinib-treated groups did not survive beyond Day 22. In the ARRY-380-treated-group, 75% of the animals were alive on Day 43. Brain PK/PD was also evaluated in the N87 model. ARRY-380 and its active metabolite caused a significant reduction in brain pErbB2 (80%). In the BT-474 model, animals received treatments beginning on Day 2 post-implantation and continuing for up to 8 weeks. Dose groups (n=13/group) were vehicle, ARRY-380 at MTD (75 mg/kg, PO, BID), lapatinib at MTD (50 mg/kg, PO, BID) or neratinib at MTD (40 mg/kg, PO, QD). On Day 56, survival in the ARRY-380 group was 69% while survival rates in the vehicle, lapatinib or neratinib-treated groups were 23%, 8% and 23%, respectively. Thus ARRY-380 treatment significantly enhances survival in two ErbB2 driven intracranial tumor xenograft models, with superior activity compared to other ErbB2 agents in these studies. Additionally, ARRY-380 has demonstrated durable clinical activity in heavily pre-treated patients with ErbB2+ MBC. These preclinical and clinical data suggest that ARRY-380 may provide benefit to patients with ErbB2+ MBC with brain metastases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 852. doi:1538-7445.AM2012-852
C-Type Virus in Tumor Tissue of a Woolly Monkey (&lt;italic&gt;Lagothrix spp.&lt;/italic&gt;) With Fibrosarcoma&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Theilen, G. H., Gould, D., Fowler, M., Dungworth, D. L.
Journal: JNCI Journal of the National Cancer Institute (1971)

Journal Article C-Type Virus in Tumor Tissue of a Woolly Monkey (Lagothrix spp.) With Fibrosarcoma Get access G. H. Theilen, G. H. Theilen Departments of Clinical Sciences and Pathology, School of Veterinary Medicine, University of California, Davis, California 95616 Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Gould, D. Gould Departments of Clinical Sciences and Pathology, School of Veterinary Medicine, University of California, Davis, California 95616 Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Fowler, M. Fowler Departments of Clinical Sciences and Pathology, School of Veterinary Medicine, University of California, Davis, California 95616 Search for other works by this author on: Oxford Academic PubMed Google Scholar D. L. Dungworth D. L. Dungworth Departments of Clinical Sciences and Pathology, School of Veterinary Medicine, University of California, Davis, California 95616 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 47, Issue 4, October 1971, Pages 881–889, https://doi.org/10.1093/jnci/47.4.881 Published: 01 October 1971 Article history Received: 03 May 1971 Accepted: 21 June 1971 Published: 01 October 1971
Abstract LB-273: Preclinical assesment of a novel CDC7 inhibitor: Genomewide RNAi screening identifies unique synergetic and resistance genes
Authors: Nancy Liu-Sullivan, Bhavneet Bhinder, David Shum, Christina Ramirez, Constantin Radu, Hakim Djaballah, Mark G. Frattini
Journal: Cancer Research (2011)

Abstract Despite extensive drug discovery efforts, drug-candidate failure and patients relapsing in the clinic remain as persistent problems. While insufficient drug-gene engagement leads to drug failure, de novo escape mutations give rise to patients relapsing, calling the need for systemic studies on how genes influence drug responsiveness. Towards this end, we have explored a functional short hairpin RNA (shRNA) based genomic screening platform aimed at interrogating drug-gene engagement and assessing its consequences on signaling pathways. We propose this concept as a novel way to evaluate drug candidates prior to clinical trials enabling liability assessment and predicting clinical outcome. We took advantage of the arrayed shRNA library produced in lentiviral particles and characterized by several obvious advantageous features including shRNA targeting one hairpin at a time and on the fly high content whole well microscopy imaging analysis. We carried out three parallel genomewide shRNA screens in the absence or presence of the novel CDC7 kinase inhibitor (MSK-777) at its IC20 and IC50 and have identified several gene candidates that influence MSK-777 sensitivity and resistance. These include synergizers that enhance MSK-777 sensitivity and rescuers that confer MSK-777 resistance. IPA analysis mapped clusters of these hits to multiple major pathways among them were the NF-kB pathway, the ubiquitin-proteasome pathway, DNA replication, and several epigenetic regulatory genes. We will present and discuss this concept together with the emerging pathways as a means to identify both key therapeutic targets and biomarkers of sensitivity and resistance. Thus, allowing for not only a broader applicability of assessing candidate genes that modulate specific drug agents, but also for the identification of a tailored and more efficacious therapeutic regimen to treat cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-273. doi:10.1158/1538-7445.AM2011-LB-273
Abstract 3166: Lung cancer bio-signatures in plasma based on the analysis of mouse models
Authors: Ayumu Taguchi, Katerina Politi, Sharon J. Pitteri, William W. Lockwood, Vitor M. Faça, Julien Sage, Christopher J. Kemp, Harold E. Varmus, Samir M. Hanash
Journal: Cancer Research (2011)

Abstract Genetically engineered mouse models of cancer have been shown to recapitulate many of the molecular and biological features of human cancer. To identify plasma proteins that show altered abundance during lung cancer development, we applied in-depth quantitative proteomic analysis to plasma from three mouse models of lung adenocarcinoma driven by mutant EGFR, Kras or induced by urethane exposure; a mouse model of small cell lung cancer (SCLC); models of pancreatic, ovarian, colon, prostate and breast cancer; and two mouse models of inflammatory disease as confounders. Plasma proteins from mice with disease and age-matched littermate controls were analyzed by mass spectrometry (MS). Whole cell lysates and conditioned media from 12 lung adenocarcinoma cell lines were also analyzed by MS to identify enriched proteins in conditioned media in common with proteins with increased levels in plasmas from lung tumor bearing mice. Proteins corresponding to 3744 non-redundant IPIs (International Protein Index) that represented protein products from 2260 unique genes were quantified in one or more experiments. Unsupervised hierarchical clustering of plasma proteins revealed clustering of the four lung cancer models and the two breast cancer models, suggesting that protein signatures in the blood are organ-type specific. Fifty-eight percent of the elevated proteins in plasmas from mice with lung adenocarcinoma were identified in conditioned media of one or more human lung cell lines. A biosignature based on plasma proteins regulated by the Titf1/Nkx2-1 transcription factor was identified in plasmas from mouse models of lung adenocarcinoma. In addition, protein network analysis showed that many proteins whose abundance is altered in the plasma of the lung cancer mouse model engineered to express mutant human EGFR are associated with EGFR. A plasma protein signature that is enriched in proteins associated with neuroendocrine development was also identified in a SCLC model. Exploratory studies in human lung cancer and control plasmas of candidate markers identified in mouse models yielded altered levels in lung cancer plasmas concordant with findings in mouse models. Our studies of mouse models have identified plasma based signature for lung cancer that reflect developmental and signaling pathways applicable to human lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3166. doi:10.1158/1538-7445.AM2011-3166
Book: Spores, Plagues and History: The Story of Anthrax
Authors: Itzhak Brook
Journal: BMJ (2004)

This book begins dramatically with compelling information about the bioterrorism attack involving anthrax sent through the postal system in the United States in 2001. Holmes describes the patients' cases in great detail, combining medical descriptions (radiological and clinical pictures) with the drama of the events as they emerged. He then summarises the use of anthrax, as well as other microbes, as agents of bioterrorism and warfare agents. More generally, he discusses epidemics throughout history, both ancient and modern: during the time of Moses and the 10 great plagues of Egypt; the plague of Athens in 430 bc; the Black Death epidemic of the Middle Ages; and the development of “woolsorter's disease” (inhalational anthrax) during the industrial revolution.​revolution.




Figure 1



Chris Holmes

Durban House, $15.95, pp 227 ISBN 1 930754 45 0 www.durbanhouse.com

Rating: ★★★




Holmes also considers the role and life history of the great pioneers in medicine—Robert Koch and Louis Pasteur—in the discovery of the causes and pathogenesis of anthrax, tuberculosis, cholera, rabies, and other infectious diseases; the development and use of biological weapons in the 20th century by Japan and the former Soviet Union; the American biological weapons programme; the accidental anthrax epidemic at Sverdlovsk in the Ural mountains in 1979; and Saddam Hussein's development of a biological weapons programme in the 1990s and the efforts to curtail and destroy it. He concludes by reviewing the medical preparedness and preventive capability of the United States in the event of bioterrorism.

The author presents interesting theories relating to major historical events and discusses the role of plagues in these events. He correlates historical evidence with clinical and medical signs and symptoms that substantiate his conclusions. He builds up an intricate body of evidence and conclusions that add a new dimension to history. For example, he suggests that Alexander the Great was intentionally exposed to anthrax and died as a result.

A well written book, it skilfully intertwines medical, journalistic, historical, poetic, and theatrical styles. Holmes uses lay and medical terminology, and his book is suitable for reading by the general public as well as the medical community. The book is educational and entertaining.
Embryonic ζ-Globin Chains in Adults: a Marker for α-Thalassemia-1 Haplotype Due to a &gt;17.5-kb Deletion
Authors: David H.K. Chui, Shiu C. Wong, Siu-Wah Chung, Margaret Patterson, Sunita Bhargava, Man-Chiu Poon
Journal: New England Journal of Medicine (1986)

Hemolysates from adults with the alpha-thalassemia-1 haplotype due to the greater than 17.5-kb deletion of both alpha-globin genes from the same chromosome were found to contain embryonic zeta (zeta)-globin chains (alpha-globin-like chains), as determined by a specific and sensitive radioimmunoassay and an electrophoretic technique. zeta-Globin chains were not present in hemolysates from adults with deletion of a single alpha-globin gene from one or both chromosomes. These results indicate that zeta-globin chains, which can be assayed by immunologic techniques, can serve as markers for the alpha-thalassemia-1 haplotype due to the greater than 17.5-kb deletion. The ability to detect zeta-globin chains may be useful in populations in which the gene frequency of the greater than 17.5-kb deletion is high, for screening couples at risk of having offspring with homozygous alpha-thalassemia.
Efficacy and Safety of Ecallantide Treatment for HAE Attacks in Patients Treated with Both Ecallantide and Placebo
Authors: W.R. Lumry, H.H. Li, A.J. MacGinnitie, J.A. Bernstein, D.F. Soteres, M. Riedl, T.J. Craig, M. Campion, W.E. Pullman
Journal: Journal of Allergy and Clinical Immunology (2012)
Abstract 1934: Molecular mechanism of abnormal localization of nucelolin on cell-surface of gastric cancer cells, with regard to Ras signaling pathway
Authors: Tatsuro Watanabe, Kazuya Hirano, Masatoshi Beppu, Kensei Yamaguchi, Atsushi Takahashi, Hirota Fujiki, Masami Suganuma
Journal: Cancer Research (2011)

Abstract Our intensive study of TNF-α inducing protein (Tipα), a carcinogenic factor secreted from H. pylori, revealed that nucleolin acts as a receptor of Tipα in a mouse gastric cancer cell line (MGT-40). Although nucleolin is a major nucleolar protein, nucleolin was found in the cell membrane by cell fractionation and on the cell-surface by flow cytometrical analysis. We further found that nucleolin shuttles Tipα from cell surface to the cytosol, resulting in expression of TNF-α gene, an endogenous tumor promoter. Moreover, a large amount of nucleolin was found in the membrane fraction of MGT-40 cells, but not in that of mouse normal glandular stomach. These results suggest that abnormal localization of nucleolin occures in gastric cancer, as an associated process of carcinogenesis. In the light of this evidence, we think that the abnormal localization of nucleolin on cell surface produces the optimal carcinogenic environment for Tipα binding in gastric cancer development by H. pylori infection. Experimentally we found that large amounts of nucleolin were expressed on the surface of four human gastric cancer cell lines (MKN-45, MKN-74, AGS, and KATOIII), with smaller amounts on that of another cell line (MKN-1), although the total amounts of nucleolin were almost the same among these five cell lines. It is important to note that the amounts of cell-surface nucleolin are correlated well with those of Ras-GTP form, the active form of Ras protein in these cell lines, and we confirmed that MKN-1 cells had the lowest amounts of Ras-GTP form among the five lines. Moreover, the treatment of AGS cells with okadaic acid, a tumor promoter and inhibitor of protein phosphatases 1 and 2A, reduced the amount of nucleolin localized on cell-surface, indicating that abnormal localization of nucleolin on cell surface can be induced by Ras signaling pathway and post-translational modifications. Thus, we discuss the relationship between the abnormal localization of nucleolin and the disorder in the Ras signaling pathway in gastric cancer development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1934. doi:10.1158/1538-7445.AM2011-1934
Aortic Dissection during Diagnostic Aortography
Authors: Samad Ghaffari, Leili Pourafkari
Journal: New England Journal of Medicine (2010)

A 30-year-old man presented to our clinic for evaluation of newly diagnosed hypertension. On examination, he had an apical systolic ejection click, a grade 2/6 systolic murmur, and weak femoral pulses. The difference in blood pressure between his arms and legs was 60 mm Hg. Echocardiography revealed coarctation of the aorta and a bicuspid aortic valve with mild stenosis. (See the Supplementary Appendix, available with the full text of this article at NEJM.org, for a chest radiograph showing the consequences of coarctation.) Catheterization through the right femoral artery was performed in preparation for stenting of the coarctation. Contrast material was injected . . .
P789 EARLY VIROLOGICAL RESPONSE IS THE MAIN PREDICTOR OF VIRAL ERADICATION IN HCV HAEMODIALYSIS PATIENTS TREATED WITH PEGYLATED INTERFERON PLUS RIBAVIRIN
Authors: M. Rendina, A. Tucci, A. Castellaneta, N.M. Castellaneta, M. Zappimbulso, C. Chiala', G. Leandro, A. di Leo
Journal: Journal of Hepatology (2014)
P73 Preliminary results of the Study of Acute Liver Transplant (SALT): NSAID exposure and risk of acute liver failure leading to transplantation in 7 European countries
Authors: D. Thorburn, E. Gulmez, S. Lignot, D. Larrey, C. de Vries, S. Perez-Gutthann, J. L. Montastruc, M. Sturkenboom, J. Benichou, G. Velo, A. Caputi, F. Salvo, F. Hamoud, S. Micon, R. Lassalle, J. Jove, G. P. Pageaux, Y. Horsmans, J. Bernuau, F. Bissoli, B. Stricker, A. Gatta, E. Monteiro, I. Vafiadis, A. McCormick, H. Metselaar, E. Sen, A. Nightingale, P. Blin, N. Moore
Journal: Gut (2011)

<h3>Introduction</h3> The risk of acute liver failure (ALF) related to NSAIDs is still discussed and the European Medicines Agency requested a study investigating this. University Bordeaux Segalen conducted the study independently. <h3>Aim</h3> To estimate the incidence rates of ALF leading to registration for liver transplantation (LT) in patients exposed to NSAIDs. <h3>Method</h3> Multinational, multicentre, case-population study performed in France, Greece, Ireland, Italy, the Netherlands, Portugal, and the UK retrospectively evaluating a 3-year period (2005–2007) in adults. Data of ALF cases were sought through liver transplant registries and hospital records. Demographic and clinical data were collected for all ALF cases and drug use information was collected for the exposure window of 30 days prior to index date (ID, initial symptoms of liver disease). For ALF cases exposed to NSAIDs (ATC code M01A), rate per million treatment-years (tt-yrs) was calculated using sales data from IMS. Poisson CIs (95% CI) were estimated. <h3>Results</h3> In the seven participating countries, 62 LT centres were identified and contacted, five were excluded (four paediatric, one oncology), and 50 actively contributed data before database lock. Among the 8824 patients identified from LT lists for the period 2005–2007, 500 were cases of ALF: 197 with identified clinical cause, 21 with incomplete or unavailable medical files, and 241 drug-exposed without identified clinical cause. Among the latter, 34 were exposed to at least one NSAID, 123 exposed to other drugs, and 84 were acute drug intoxications. Mean age of NSAID-exposed ALF cases was 43.8 years, 24 were female. Event rates per million treatment-years were 4.4 (95% CI 3.0 to 6.1) for all NSAIDs pooled, 5.6 (2.4 to 11.1) for nimesulide (8 cases), 5.8 (2.8 to 10.6) for ibuprofen (10 cases), 4.5 (1.5 to 10.4) for diclofenac (5 cases), and 4.7 (1.0 to 13.6) for ketoprofen (3 cases). 71 of the 157 non-intoxication cases had been exposed to paracetamol (9.8 per million treatment-years, 95% CI 7.7 to 12.4), and 83 of the 84 intoxications. <h3>Conclusion</h3> In seven countries over 3 years only 34 NSAID-exposed ALF cases leading to registration for LT were identified with no differences in incidence rates per million tt-yrs among the most used NSAIDs. Non-overdose paracetamol-associated liver failure was twice more common.
Chronic pancreatitis caused by a swallowed orthodontic device
Authors: Maximilian Tiller, Wolfgang Schepp, Felix Gundling, Jochen Tuerck
Journal: Endoscopy (2014)

A 37-year-old woman was admitted to our hospital for endosonography because of a pancreatic duct dilatation. Originally, this dilatation had been noted during magnetic resonance imaging (MRI) ([Fig. 1]) for epigastric pain recurring episodically over a period of years. Endoscopically, we found a metallic object trapped inside the papilla Vateri ([Fig. 2]). Endosonography revealed calcifications in the pancreatic head ([Fig. 3]) suggesting chronic pancreatitis. The metallic object was removed endoscopically with a snare and was found to be a Kobayashi ligature ([Fig. 4]). This device is used by orthodontists and is fixed by drilling it into dental braces. Our patient reported that a dental brace had been implanted at the age of 12. The extracted ligature was not drilled, substantiating the suspicion that it had been ingested before fixation to the brace, and probably swallowed during the implantation procedure. After extraction of the ligature from the papilla, our patient's clinical symptoms improved remarkably. In summary, our patient suffered from chronic pancreatitis caused by obstruction of the papilla Vateri by an orthodontic device implanted years earlier.
TOLL-LIKE RECEPTOR 4 FUNCTION IS ESSENTIAL FOR INCREASING OXIDATIVE STRESS, AND PROMOTING THE INFLAMMATION AND GLOMERULAR SCLEROSIS BY ANGIOTENSIN II
Authors: Seiji Umemoto, Tadashi Okamoto, Koichi Yoshimura, Toshihiro Sakumura, Tomoaki Murata, Tohru Fukai, Masafumi Yano, Masunori Matsuzaki
Journal: Journal of the American College of Cardiology (2016)