tbuckley/cabot-search huggingface dataset:
Early Hematopoietic Events During Tumor Growth in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C L Hardy, L Balducci
Journal: JNCI Journal of the National Cancer Institute (1986)

Lewis lung carcinoma (LLC) of C57BL/6 mice, a transplantable tumor widely metastatic by 6–7 days post implant (PI), caused hematopoietic alterations such as progressive anemia (hemoglobin: day 1 PI, 11.0 g/dl; day 19 PI, 7.8 g/dl), neutrophilia (neutrophils: day 1 PI, 2 × 103/µl; day 19 PI, 22 × 103/µl), and marrow and splenic myeloid hyperplasia (marrow myeloid-to-erythroid ratio: day 1 PI, 1:1; day 7 PI, 3:1). Accompanying these changes were an increased concentration of marrow granulocyte-macrophage colony-forming units (culture) (GM-CFUc) (day 3 PI, LLC 185±27% of control; day 19 PI, LLC 265±10% of control) and accelerated cycling of these myeloid progenitors [day 3 PI, LLC 45.3±6.5% GM-CFUc in cycle vs, sham (media) injected 17.5±10.5%; day 7 PI, LLC 52.2±2.5% vs. sham (media) injected 29.8±9.8%; day 11 PI, LLC 56.2±4.4% vs. sham (media) injected 22.2±14%]. This study questioned whether enhanced hematopoiesis was a result of progressive tumor growth or whether the injection of tumor cells could evoke the response. By use of groups of C57BL/6 mice given an injection of live LLC cells, x-irradiated killed LLC cells, or media, the hematopoietic response to live LLC cells versus dead LLC cells could be dissected. A biphasic colony-stimulating activity (CSA) response in the sera of tumor bearers was found to account for the myelopoietic changes. The first wave of CSA from days 1 to 3 PI stimulated 168±3.7% more GM-CFUc than control sera and was likely released by dead cells of the tumor inoculum; the second wave from day 7 onward stimulated 220±7.6% more colonies and was a result of the enlarging tumor mass. Tumor growth was necessary for GM-CFUc proliferation, and the declining growth fraction at day 19 in LLC-bearing mice suggested that hematopoietic exhaustion was a consequence of tumor growth.
Detection of Replicating C-Type Viruses in Continuous Cell Cultures Established From Cows With Leukemia: Effect of the Culture Medium&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Jorge F. Ferrer, Neale D. Stock, Peck-sun Lin
Journal: JNCI Journal of the National Cancer Institute (1971)

Four long-term suspension cultures, initiated from thoracicduct or buffy-coat lymphocytes of cows with leukemia, were transferred from their regular medium [McCoy's SA medium supplemented with 20% heat-inactivated horse serum (M20HSI)] to Eagle's minimal essential medium supplemented with 20% heat-inactivated fetal calf serum (E20FSI). C-type particles were readily and consistently detected in 3 of the 4 cell lines. Mature and immature particles occurred extracellularly and within cytoplasmic vacuoles. Characteristic budding forms provided evidence for the replication and thus the viral nature of the particles. Cylindrical or tubular buds were also observed. Addition of phytohemagglutinin (PHA) to the E20FSI medium enhanced virus production in only 1 of these VLP-positive cell lines. Subsequent and more extensive examinations of 2 VLP-positive cell lines, grown in M20HSI, revealed replicating C-type virus, sbut consisderably fewer than observed when these cell lines were grown in E20FSI. The relationship of these particles to those observed in short-term, bovine buffy-coat cultures treated with PHA, as well as their possible significance in the etiology of bovine leukemia, remains to be determined.
Determinants of prognosis in late chronic-phase chronic myelogenous leukemia.
Authors: J Rodriguez, J Cortes, T Smith, S O'Brien, M B Rios, M Talpaz, H Kantarjian
Journal: Journal of Clinical Oncology (1998)

Since interferon alfa (IFN-A) became an established treatment in chronic myelogenous leukemia (CML), more patients are referred to tertiary centers in late chronic phase (ie, > 12 months after diagnosis). Trials conducted in this phase cannot be evaluated precisely unless the features that determine prognosis in late chronic-phase CML are identified. The purpose of this study is to define the prognostic determinants of late chronic-phase CML.From 1980 to 1997,257 consecutive CML patients referred in late chronic phase were studied. Their clinical characteristics at the time of referral and their association with survival were investigated. A staging model was designed.The median survival from time of referral was 43 months. Pretreatment characteristics associated with worse outcome included older age, poor performance status, splenomegaly, low albumin level, high percentage of blasts or basophils in peripheral blood (PB) or bone marrow, longer duration of chronic phase, and poor-risk group as defined by the Synthesis model. Prior exposure to IFN-A was not associated with worse outcome. By multivariate analysis, characteristics associated with shorter survival were age of 60 years or older, time from diagnosis of 3 years or greater, performance status of 1 or greater, PB basophils of 7% or greater, spleen 10 cm or greater, PB blasts 3% or greater, and albumin level less than 4 g/dL. A model that included age, duration of chronic phase, performance status, and PB basophils was generated. Patients with no, one, two, or three or greater adverse factors had median survivals of 71, 49, 26, and 19 months, respectively.A staging model for late chronic-phase CML can stratify patients in four groups with significantly different outcomes. If confirmed in independent populations, such a model could be considered in the analysis of future trials of treatment strategies in late chronic-phase CML.
Lung clearance index response in patients with CF with class III CFTR mutations
Authors: Mica Kane, Tanja Gonska, Renee Jensen, Julie Avolio, Michelle Klingel, Sanja Stanojevic, Felix Ratjen
Journal: Thorax (2016)

Ivacaftor (KALYDECO) is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that increases transmembrane chloride flux in vitro and leads to significant benefits in patients with cystic fibrosis (CF) with class III gating mutations.1–5 Ivacaftor is associated with sustained improvement in FEV1 and weight as well as reduced time to next pulmonary exacerbation.5–7 It has also been shown that 4 weeks of ivacaftor improves the lung clearance index (LCI) in patients with CF with preserved lung function.8

It is presently unclear whether LCI, a measure of ventilation inhomogeneity, provides additional information among patients with more impaired lung function as well as whether the sustained effectiveness of ivacaftor as demonstrated by improvements in the previously mentioned outcomes is also evident in the LCI response. The aim of this observational study was to assess the LCI before and after initiation of ivacaftor treatment over 6 months in patients with CF with a wider range of …
Traditional Prognostic Factors Used for Adjuvant Chemotherapy (Ct) Decisions in Early Stage Hr + , Her2– Breast Cancer in a Large International Survey (Magic) Among Breast Cancer Specialists
Authors: M. Martin, M. Aapro, C. Markopoulos, T. Mamounas, R. Rouzier, C. Thomssen, J.E. Bargallo Rocha, D. Rea, P. Neven, B. Linderholm, V. Smit, L. Landherr, A. Petrovsky, C. Svedman, M. De Laurentiis
Journal: Annals of Oncology (2014)
Oklahoma suspends executions after giving man wrong drug
Authors: Owen Dyer
Journal: BMJ (2015)

A convicted murderer executed this January in Oklahoma was given the wrong drug, and the state has suspended further executions only hours before the scheduled execution of another prisoner with the same substance.

Charles Warner received potassium acetate instead of the legally stipulated drug, potassium chloride, which the official execution log incorrectly recorded that he was given.

Potassium chloride is the third drug given in the state’s protocol, stopping the heart after midazolam has allegedly anaesthetized the prisoner and rocuronium bromide has paralyzed the muscles. Potassium acetate would also stop the heart but would act more slowly than potassium chloride, and a higher dose would be needed for the same effect.

Warner, convicted of murdering his roommate’s baby, said as the first drugs were injected, “My body is on fire.” But the potassium acetate, which would cause agonizing pain, would not have been injected until he was deemed unconscious some minutes later. Beyond his initial comment Warner showed no signs of suffering, although he took 18 minutes to be pronounced dead, which is longer than average.

Confusion reigns over who knew of the drug mix-up and when. …
The Respiratory Epithelium. V. Histogenesis of Lung Carcinomas in the Human&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Elizabeth M. McDowell, B. Vet. Med., Ph.D., Joseph S. McLaughlin, M.D., Dezso K. Merenyi, M.D., Richard F. Kieffer, M.D., Curtis C. Harris, M.D., Benjamin F. Trump, M.D.
 9
Journal: JNCI Journal of the National Cancer Institute (1978)

One hundred human primary lung carcinomas were studied by light and electron microscopy and by light microscopic histochemistry to demonstrate mucosubstances. The tumors were classified histogenetically and were grouped into three major categories depending on their cell of origin: 1) tumors from basal and/or mucous cells; 2) tumors from neurosecretory cells; and 3) tumors from Clara cells. Most carcinomas (88%) arose from basal and/or mucous cells. These were subdivided into epidermoid carcinomas (21%), combined epidermoid and adenocarcinomas (46%), and adenocarcinomas (21%). The criteria for epidermoid differentiation included the presence of tonofilament bundles, poorly developed endoplasmic reticulum and Golgi apparatus, and well-developed desmosomes. The criteria for adeno differentiation included well-developed endoplasmic reticulum and Golgi apparatus, poorly developed desmosomes, the presence of extracellular and/or intracellular alveoli, and/or other evidence of cellular secretion such as secretory granules. In adenocarcinomas with extracellular alveoli, typical junctional complexes were also present at the luminal aspect where the cell apexes bordered the alveolus. With these criteria, combined epidermoid and adenocarcinomas were the most common type of lung carcinoma. We anticipate that the new data will clarify categories such as small cell anaplastic carcinoma and large cell carcinoma of the World Health Organization classification. In addition, the histogenetic classification of lung tumors may be of value in the future in studies of risk factors, prognosis, prevention, and treatment of lung cancer.
Aberrant Notch Signaling in the Bone Marrow Microenvironment of Acute Lymphoid Leukemia Suppresses Osteoblast-Mediated Support of Hematopoietic Niche Function
Authors: Weihuan Wang, Grant Zimmerman, Xiaoran Huang, Shuiliang Yu, Jay Myers, Yiwei Wang, Stephen Moreton, Joseph Nthale, Amad Awadallah, Rose Beck, Wei Xin, David Wald, Alex Y. Huang, Lan Zhou
Journal: Cancer Research (2016)

Abstract More than half of T-cell acute lymphoblastic leukemia (T-ALL) patients harbor gain-of-function mutations in the intracellular domain of Notch1. Diffuse infiltration of the bone marrow commonly occurs in T-ALL and relapsed B-cell acute lymphoblastic leukemia patients, and is associated with worse prognosis. However, the mechanism of leukemia outgrowth in the marrow and the resulting biologic impact on hematopoiesis are poorly understood. Here, we investigated targetable cellular and molecular abnormalities in leukemia marrow stroma responsible for the suppression of normal hematopoiesis using a T-ALL mouse model and human T-ALL xenografts. We found that actively proliferating leukemia cells inhibited normal hematopoietic stem and progenitor cell (HSPC) proliferation and homing to the perivascular region. In addition, leukemia development was accompanied by the suppression of the endosteum-lining osteoblast population. We further demonstrated that aberrant Notch activation in the stroma plays an important role in negatively regulating the expression of CXLC12 on osteoblasts and their differentiation. Notch blockade reversed attenuated HSPC cycling, leukemia-associated abnormal blood lineage distribution, and thrombocytopenia as well as recovered osteoblast and HSPC abundance and improved the hematopoietic-supportive functions of osteoblasts. Finally, we confirmed that reduced osteoblast frequency and enhanced Notch signaling were also features of the marrow stroma of human ALL tissues. Collectively, our findings suggest that therapeutically targeting the leukemia-infiltrated hematopoietic niche may restore HSPC homeostasis and improve the outcome of ALL patients. Cancer Res; 76(6); 1641–52. ©2016 AACR.
How one clinic's practice conforms with CSM's advice
Authors: C. Smith
Journal: BMJ (1996)

EDITOR,—In seeking to interpret for women the recent research showing an approximate doubling of the relative risk of venous thromboembolic disease in women taking oral contraceptives containing gestodene or desogestrel1 we need ways in which to explain the complicated and subtle statistical evidence.

John Guillebaud contends that we can reassure a woman who has been taking combined oral contraceptives for a considerable time that “as she has not had a venous thrombosis in these years she is particularly unlikely …
Emergence of a colistin-resistant KPC-3-producing Klebsiella pneumoniae ST512 clone in an Italian university hospital.
Authors: Beatrice Casini, A. Buzzigoli, Paola Valentini, M. Minacori, E. Tagliaferri, C. Tascini, Francesco Menichetti, Gaetano Pierpaolo Privitera
Journal: Clinical Microbiology and Infection (2012)
The Role of mTOR Inhibitors in the Treatment of Patients with Tuberous Sclerosis Complex: Evidence-based and Expert Opinions
Authors: Paolo Curatolo, Marit Bjørnvold, Patricia E. Dill, José Carlos Ferreira, Martha Feucht, Christoph Hertzberg, Anna Jansen, Sergiusz Jóźwiak, J. Christopher Kingswood, Katarzyna Kotulska, Alfons Macaya, Romina Moavero, Rima Nabbout, Bernard A. Zonnenberg
Journal: Drugs (2016)
Importance of Cardiac Magnetic Resonance in a Patient With Crohn’s Disease–Associated Constrictive Pericarditis
Authors: Walid Barake, Isabelle Vonder Muhll, David Ian Paterson
Journal: Circulation (2016)

This case highlights the rare association of pericarditis with inflammatory bowel disease.T2-weighted pericardial imaging can be helpful in the evaluation of pericardial disease by cardiac magnetic resonance and may be predictive of response to medical treatment.These results should be confirmed in a larger study or case series.
Tetrapod phylogeny inferred from 18S and 28S ribosomal RNA sequences and a review of the evidence for amniote relationships.
Authors: S B Hedges, K D Moberg, L R Maxson
Journal: Molecular Biology and Evolution (1990)

The 18S ribosomal RNAs of 21 tetrapods were sequenced and aligned with five published tetrapod sequences. When the coelacanth was used as an outgroup, Lissamphibia (living amphibians) and Amniota (amniotes) were found to be statistically significant monophyletic groups. Although little resolution was obtained among the lissamphibian taxa, the amniote sequences support a sister-group relationship between birds and mammals. Portions of the 28S ribosomal RNA (rRNA) molecule in 11 tetrapods also were sequenced, although the phylogenetic results were inconclusive. In contrast to previous studies, deletion or down-weighting of base-paired sites were found to have little effect on phylogenetic relationships. Molecular evidence for amniote relationships is reviewed, showing that three genes (beta-hemoglobin, myoglobin, and 18S rRNA) unambiguously support a bird-mammal relationship, compared with one gene (histone H2B) that favors a bird-crocodilian clade. Separate analyses of four other genes (alpha-crystallin A, alpha-hemoglobin, insulin, and 28S rRNA) and a combined analysis of all sequence data are inconclusive, in that different groups are defined in different analyses and none are strongly supported. It is suggested that until sequences become available from a broader array of taxa, the molecular evidence is best evaluated at the level of individual genes, with emphasis placed on those studies with the greatest number of taxa and sites. When this is done, a bird-mammal relationship is most strongly supported. When regarded in combination with the morphological evidence for this association, it must be considered at least as plausible as a bird-crocodilian relationship.
Does ‘healing’ benefit patients with chronic symptoms? A quasi-randomized trial in general practice
Authors: Michael Dixon
Journal: Journal of the Royal Society of Medicine (1998)

This study was designed to examine the effects of a healer seeing chronically ill patients in a large semirural practice. The 57 patients were allocated alternately either to receive ten weekly healing sessions or to become waiting-list controls. Two weeks after completion of ‘healing’ 22 (81%) of the 27 study patients thought their symptoms had improved and 15 of these thought they had improved substantially. Study patients scored better than controls on both measures of symptoms (P &lt; 0.05, P &lt; 0.01), on anxiety and depression ratings (P &lt; 0.01, P &lt; 0.05) and on general function measured by the Nottingham Health Profile (P &lt; 0.01). Treatment differences were still evident three months later for one of the measures of symptom change (P &lt;0.05) and for both anxiety and depression ratings (P &lt; 0.01, P &lt; 0.05). The percentages of natural killer cells (CD16, CD56) did not change greatly in either group. These results suggest that healing may be an effective adjunct for the treatment of chronically ill patients presenting in general practice. They do not distinguish between any specific effects of spiritual healing and non-specific effects such as relaxation; for further investigation, randomized controlled trials will be needed.
Alemtuzumab levels impact acute GVHD, mixed chimerism, and lymphocyte recovery following alemtuzumab, fludarabine, and melphalan RIC HCT
Authors: Rebecca A. Marsh, Adam Lane, Parinda A. Mehta, Lisa Neumeier, Sonata Jodele, Stella M. Davies, Alexandra H. Filipovich
Journal: Blood (2015)
Authors’ reply to Gachi, Mullie and colleagues, and Weatherburn
Authors: Cuilin Zhang, Wei Bao, Deirdre K Tobias, Jorge E Chavarro, Frank B Hu
Journal: BMJ (2016)

We appreciate the interest in our recent article on pre-pregnancy potato consumption and risk of gestational diabetes mellitus (GDM).1 Below we provide responses to a few major points raised by readers

Pre-pregnancy consumption of potato in our study did not include sweet potato.2 Sweet potato consumption in our study population was too low (~95% consumed <1 serving a week) for us to reliably evaluate its association with the risk of GDM. The role of pre-pregnancy sweet potato consumption in the development of GDM warrants further investigation. We are aware that sweet potato—which is rich in complex carbohydrates, dietary fibre, β carotene, vitamin C, vitamin B6, anthocyanin, and minerals—is considered to be a nutritious vegetable.3 Studies in animal models indicated that sweet potatoes have hypoglycaemic effects through ameliorating oxidative stress and inflammation and improving pancreatic β cells mass.4 In humans, sweet potato has been used in traditional medicine for the treatment of type 2 diabetes. However, data from randomised controlled trials and large observational studied on the efficacy of sweet potato in glycaemic control in humans are insufficient and inconclusive.3

Our study was not designed to look at the underlying mechanisms of the observed positive association between pre-pregnancy potato intake and GDM risk; future studies will elucidate these.5 Evidence suggests that the potato’s high glycaemic index …
Breast Tumor Kinase (Brk/PTK6) Is Induced by HIF, Glucocorticoid Receptor, and PELP1-Mediated Stress Signaling in Triple-Negative Breast Cancer
Authors: Tarah M. Regan Anderson, Shi Hong Ma, Ganesh V. Raj, John A. Cidlowski, Taylor M. Helle, Todd P. Knutson, Raisa I. Krutilina, Tiffany N. Seagroves, Carol A. Lange
Journal: Cancer Research (2016)

Cancer cells use stress response pathways to sustain their pathogenic behavior. In breast cancer, stress response-associated phenotypes are mediated by the breast tumor kinase, Brk (PTK6), via the hypoxia-inducible factors HIF-1α and HIF-2α. Given that glucocorticoid receptor (GR) is highly expressed in triple-negative breast cancer (TNBC), we investigated cross-talk between stress hormone-driven GR signaling and HIF-regulated physiologic stress. Primary TNBC tumor explants or cell lines treated with the GR ligand dexamethasone exhibited robust induction of Brk mRNA and protein that was HIF1/2-dependent. HIF and GR coassembled on the BRK promoter in response to either hypoxia or dexamethasone, indicating that Brk is a direct GR/HIF target. Notably, HIF-2α, not HIF-1α, expression was induced by GR signaling, and the important steroid receptor coactivator PELP1 was also found to be induced in a HIF-dependent manner. Mechanistic investigations showed how PELP1 interacted with GR to activate Brk expression and demonstrated that physiologic cell stress, including hypoxia, promoted phosphorylation of GR serine 134, initiating a feed-forward signaling loop that contributed significantly to Brk upregulation. Collectively, our findings linked cellular stress (HIF) and stress hormone (cortisol) signaling in TNBC, identifying the phospho-GR/HIF/PELP1 complex as a potential therapeutic target to limit Brk-driven progression and metastasis in TNBC patients.
Carcinogenesis Bioassay of Technical-Grade Piperonyl Butoxide in F344 Rats2
Authors: Richard H. Cardy, Roger A. Renne, John W. Warner, Robert L. Cypher
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Carcinogenesis Bioassay of Technical-Grade Piperonyl Butoxide in F344 Rats Get access Richard H. Cardy, Richard H. Cardy 4 3NCI Frederick Cancer Research Center, Frederick. Md. 21701. 4Address reprint requests to Dr. Cardy at his present address: Department of Pathology, Litton Bionetics, 5516 Nicholson Lane Kensington, Md. 20795. Search for other works by this author on: Oxford Academic PubMed Google Scholar Roger A. Renne, Roger A. Renne 5Experimental Pathology Laboratories, Herndon, Va. 22070. Search for other works by this author on: Oxford Academic PubMed Google Scholar John W. Warner, John W. Warner 3NCI Frederick Cancer Research Center, Frederick. Md. 21701. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert L. Cypher Robert L. Cypher 3NCI Frederick Cancer Research Center, Frederick. Md. 21701. 6We gratefully acknowledge the contributions of Dr. Walter Zielinski, NCI Frederick Cancer Research Center, for analysis and stability testing of the chemical. We also thank Mr. Charles Riggs, NCI Frederick Cancer Research Center, for portions of the statistical analysis. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 62, Issue 3, March 1979, Pages 569–578, https://doi.org/10.1093/jnci/62.3.569 Published: 01 March 1979 Article history Received: 29 March 1978 Accepted: 21 September 1978 Published: 01 March 1979
Poland’s new conservative government to scrap IVF programme
Authors: Jarosław Adamowski
Journal: BMJ (2015)

Poland’s health minister, Konstanty Radziwill, has said that the state run in vitro fertilisation (IVF) programme will end halfway through 2016. 

The decision, which will shorten the programme by two and a half years, came two months after the parliamentary elections that led to a new government being formed by the conservative Law and Justice party. The new prime minister, Beata Szydlo, promised during the electoral campaign to halt the state funded IVF …