tbuckley/cabot-search huggingface dataset:
Abstract 3885: ITGA6 (CD49F) is directly regulated by hypoxia-inducible factors
Authors: Danielle L. Peacock, Luciana P. Schwab, Tiffany N. Seagroves
Journal: Cancer Research (2014)

Abstract Introduction: In response to hypoxic stress, tumors must adapt to the hostile microenvironment by regulating angiogenesis, cellular metabolism, cell survival and motility. The alpha subunits of the Hypoxia-Inducible Factors (HIF-1α and HIF-2α) are oxygen-responsive, master regulators of the hypoxic response. Over-expression of HIF-1α independently correlates with decreased survival of breast cancer patients, and a hypoxic core gene signature is enriched in triple negative breast cancers (TNBC) and HER2+ cancers relative to luminal tumors (ER+). In a variety of solid tumors, HIF-1α or HIF-2α also directly promotes tumor initiating cell (TIC) activity. Methods: Mammary tumor epithelial cells (MTECs) were established from late-stage tumors of MMTV-PyMT+; Hif1α floxed mice (which model ER-negative, luminal-like tumors), and exposed to either Adenovirus-β-gal or -Cre to create wild-type (WT) and knock-out (KO) cells, respectively. MDA-MB-231 cells (a model of TNBC) were generated in which either HIF1A or HIF2A or both genes (DKD) were knocked down (KD) via shRNA. Results: When PyMT+ MTECs were transplanted into female recipients, HIF-1 deletion reduced primary tumor growth by 60%, lung metastasis by 90% and TIC activity by &amp;gt;35-fold (Schwab et al. 2012). The expression of cell surface markers routinely used to enrich for TICs was assayed in PyMT+ and MDA-MB-231 cells. ITGA6 mRNA and CD49f protein expression were significantly decreased in response to HIF deletion at both normoxia and hypoxia. ChIP assays showed that either HIF-1 or HIF-2 bind to at least two HREs identified within the ITGA6 promoter. When WT PyMT tumors were sorted to enrich for CD49fhi cells, limiting dilution transplantation confirmed that TIC activity was increased relative to CD49low cells. Finally, data mining of breast cancer patient repositories showed that ITGA6 mRNA expression is independently and inversely correlated with overall and recurrence free survival. Conclusions: CD49f is a direct transcriptional target of HIF-1/HIF-2. Because CD49f is known to enrich for breast TICs, we suggest that HIF-dependent regulation of ITGA6 expression contributes at least partially to HIFs promotion of TIC activity in ER-negative breast cancers. Citation Format: Danielle L. Peacock, Luciana P. Schwab, Tiffany N. Seagroves. ITGA6 (CD49F) is directly regulated by hypoxia-inducible factors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3885. doi:10.1158/1538-7445.AM2014-3885
Alterations of Glycolipids of Human Leukemia Cell Line HL-60 During Differentiation
Authors: T Momoi, J Yokota
Journal: JNCI Journal of the National Cancer Institute (1983)

Alterations of glycolipids of human leukemia cell line HL-60 during differentiation were investigated. The neutral glycolipids of HL-60 cells are of the lacto-types such as lactosylceramide (LacCer) and lactoneotetraglycosylceramide (nLcOse4Cer). The gangliosides of HL-60 cells consisted of a mixture of the lacto-types and the gangliotypes. Chemical inducers of differentiation, 12-O-tetradecanoylphorbol 13-acetate (TPA) and dimethyl sulfoxide, altered the glycolipid profile; II3-α-acetylneuraminyl-lactosylceramide (GM3 ) increased in amount and LacCer and nLcOse4Cer decreased. Tunicamycin had no effect on the glycolipid synthesis. The GM3 accumulated more than tenfold in the TPA-induced macrophage-like cells. This accumulation could be due to the increased activity of LacCer sialyltransferase.
Randomized prospective clinical trial of high-dose epirubicin and dexrazoxane in patients with advanced breast cancer and soft tissue sarcomas.
Authors: M Lopez, P Vici, K Di Lauro, F Conti, G Paoletti, A Ferraironi, R Sciuto, D Giannarelli, C L Maini
Journal: Journal of Clinical Oncology (1998)

PURPOSE We conducted a randomized trial to evaluate primarily the cardioprotective effect of dexrazoxane (DEX) in patients with advanced breast cancer and soft tissue sarcomas (STS) treated with high-dose epirubicin (EPI). We wished also to determine the value of radioimmunoscintigraphy (RIS) in the assessment of anthracycline cardiotoxicity. PATIENTS AND METHODS Patients with breast cancer (n = 95) or STS (n = 34) received EPI 160 mg/m2 by intravenous (I.V.) bolus every 3 weeks with or without DEX 1,000 mg/m2 I.V. Cardiac monitoring included multigated radionuclide (MUGA) scans with determination of resting left ventricular ejection fraction (LVEF), and RIS with indium 111 antimyosin monoclonal antibodies. RESULTS In either disease, antitumor response rates, time to progression, and survival did not significantly differ between the two arms. There was little difference in noncardiac toxicity for the two treatment groups. All methods of cardiac evaluation clearly documented the cardioprotective effect of DEX. Four patients developed congestive heart failure (CHF), all in the EPI arm. The decrease in LVEF from baseline was significantly greater in the control group. An abnormal antimyosin uptake was observed early in both arms and progressively increased during treatment. However, this increase was significantly higher in the EPI group (P = .004). CONCLUSION DEX significantly protects against the development of cardiotoxicity when high single doses of EPI are used. Apparently, there was no evidence of an adverse impact of DEX on antitumor activity. Although RIS is a sensitive technique in detecting anthracycline cardiac damage, its specificity is low and it cannot be considered a primary test for guiding anthracycline treatment.
Real action in a virtual world
Authors: Melvyn A. Goodale
Journal: Behavioral and Brain Sciences (2001)

O'Regan &amp; Noë run into some difficulty in trying to reconcile their “seeing as acting” proposal with the perception and action account of the functions of the two streams of visual projections in the primate cerebral cortex. I suggest that part of the problem is their reluctance to acknowledge that the mechanisms in the ventral stream may play a more critical role in visual awareness and qualia than mechanisms in the dorsal stream.
Selection of a Low Antigenic Variant Subline From the TA3St Ascites Carcinoma by Repeated Passage of Antibody-Coated Cells Through Anti-immunoglobulin Columns&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: T Dallanis, G Klein, B Andersson
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Selection of a Low Antigenic Variant Subline From the TA3St Ascites Carcinoma by Repeated Passage of Antibody-Coated Cells Through Anti-immunoglobulin Columns Get access Tina Dalianis, Tina Dalianis Search for other works by this author on: Oxford Academic PubMed Google Scholar George Klein, George Klein Search for other works by this author on: Oxford Academic PubMed Google Scholar Birger Andersson Birger Andersson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 63, Issue 2, August 1979, Pages 383–388, https://doi.org/10.1093/jnci/63.2.383 Published: 01 August 1979 Article history Received: 22 June 1978 Revision received: 03 January 1979 Accepted: 29 January 1979 Published: 01 August 1979
Very low-dose warfarin prophylaxis to prevent thromboembolism in women with metastatic breast cancer receiving chemotherapy: an economic evaluation.
Authors: R Rajan, A Gafni, M Levine, J Hirsh, M Gent
Journal: Journal of Clinical Oncology (1995)

PURPOSE A recent double-blind, randomized trial demonstrated that very low-dose warfarin (VLDW) reduced the incidence of venous thromboembolism (VTE) without increasing the rate of bleeding in women with metastatic breast cancer receiving chemotherapy. We have evaluated the economic impact on the health care system of using VLDW in such patients. METHODS The records of patients entered onto the trial and a simultaneous, fully allocated, costing model for a tertiary care hospital in Hamilton, Canada were used to determine the difference in costs associated with the care of patients with and without VLDW. RESULTS The cost of providing VLDW was $ 21,854 (Canadian dollars) per 100 patients. This therapy led to a reduction in costs of $ 24,297 per 100 patients, thus saving the health care system $ 2,443 per 100 patients. In the sensitivity analysis, VLDW prophylaxis still did not increase health care costs unless the cost of VLDW was greatly increased, the cost of treating thromboembolic episodes was markedly reduced, or the incidence of either VTE or bleeding with VLDW was increased above the rates observed in the trial. CONCLUSION We conclude that for women receiving chemotherapy for metastatic breast cancer, the benefits of VLDW can be realized without increased health care costs.
Overcome the EGFR-TKIs resistance with cucurbitacin BE compound by targeting STAT3, ERK1/2 and AKT
Authors: Ming Liu, Lixia Zheng, Chen He, Jun Xu
Journal: European Respiratory Journal (2012)

Epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) is highly sensitive to EGFR tyrosine kinase inhibitors (TKIs) therapy, but acquired resistance eventually develops at about 9-12 months. Overcoming the drug resistance is of great clinical and scientific significance. In this study, We showed that STAT3,ERK1/2 and AKT were persistently activated in the resistant cells with T790M mutation(PC9/ER) and 52 tumor samples from EGFR-TKIs resistant NSCLC patients.The growth inhibition of the triterpenoid compound cucurbitacin BE (Cu BE) was tested in vitro and in vivo against PC9/GR cells. Cu BE can inhibit the growth of PC9 and PC9/GR cells in a dose- and time-dependent manner, resulting in G2/M phase arrest and apoptosis. This was associated with inhibition of activated Stat3,ERK1/2 and AKT, increased level of autophagy(LC3B expression), and down-regulated the expression of caspase 3 and survivin. Moreover, in a nude mouse tumor xenograft model, Cu BE decreased the PC9/GR tumor volume by 46.4% (P
Management of community acquired pneumoia (CAP): Knowledge, attitude and current practice of general practitioners (GPs) in urban areas of Pakistan
Authors: Saima Akhter, Ashok Pajwani, Nausheen Saifullah, Nadeem Rizvi
Journal: European Respiratory Journal (2012)

BACKGROUND:  CAP is a major burden with high prevalence and significant mortality and morbidity.Current evidences suggest that treatment of low risk patients in community is safe and reduce health costs by minimizing unnecessary hospital admissions and GPs can play an important role in primary care.  OBJECTIVE:  Our aim was to assess, at a community level, GPs knowledge about CAP and their assessment and prescription pattern.  METHODOLOGY:  A multicentre cross sectional survey was done in 10 cities of Pakistan from November 2011 to January 2012. A total of 110 GPs were recruited,with minimum of 3 years experience, and were not engaged with University teaching or research.Convenient sampling was done and data was collected on structured questionnaire.  RESULTS:  71% of GPs reported to work in high prevalence areas for respiratory ailments. Diagnosis of CAP was relied on physical examination in less than 5% of cases.  58% of GPs used PSI and 38% CURB 65 for assessment of severity but it was alarming to note that only 58% intend to treat severe pneumonia with IV antibiotics and there was reluctance for referral to hospital.  The majority(70%) of GPs claimed awareness of recent guidelines of CAP but the antibiotic class most prevalently used was oral macrolide(54%) in mild, oral quinolones(40%) in moderate and combinations of non antipseudomonal cephalosporin+Macrolide(55%) in severe cases.  CONCLUSION:  The major problems encountered were late referral of patients to hospital, poor knowledge of recent guidelines and prescription of inadequate regimens that in turn can lead to high mortality and morbidity and emergence of resistant bacteria as cause of CAP.
Doctors should refuse to check patients' immigration status, says BMA
Authors: T. Moberly
Journal: BMJ (2015)

UK doctors should refuse to check the immigration status of patients who come to them seeking healthcare, the BMA has said.

Delegates at the BMA’s annual representative meeting in Liverpool passed a motion on Wednesday 24 June stating, “NHS staff do not have any role in policing immigration.”

The motion, passed by an overwhelming majority of delegates, called on the BMA to “issue clear instructions that the role of the doctor is to provide medical care when it is needed and that doctors should not involve themselves in any monitoring of immigration status.” It also asked the …
Perinatal outcomes in pregnant women with asthma
Authors: Tatiana Luchnikova, Olga PriKhodko, Yuri Landyshex, Albina Babtseva, Elena Romantsova, Marina Pogrebnaya
Journal: European Respiratory Journal (2014)

The aim of the research is to study the state of health of children recently born of women with bronchial asthma. We analyzed 340 cases over the last 20 years (group 1). The comparison group includes 140 newborns of women who do not have chronic respiratory diseases (group 2). Pregnant women of group 1 showed greater incidence of complications than in the control group. Pregnancy with bronchial asthma caused the increase of diagnosed placental insufficiency, chronic intrauterine fetal hypoxia, and premature birth. Pregnancy complications are often observed in patients with uncontrolled course of asthma. Physical development of newborns in group 1 was lower than in group 2. The frequency of disharmonious development was more common in children of mothers with severe asthma (p <0,05), indicating the intrauterine fetal suffering . The prevailing diseases in newborns of group 1 include cerebral ischemia (65.2 %), localized inflammation of the skin (37.2%), post hypoxic cardiomyopathy (22%), intrauterine growth retardation (19.3 %), which differed significantly from the corresponding figures of group 2. The polyorganic character of system damage was found in 70% of group 1 infants, and only in 11% of group 2. Severity status of newborns in group 1 correlated with worsening of asthma during pregnancy, the frequency of birth of healthy children being significantly reduced. Thus, the perinatal outcomes in patients with asthma depend on the severity of the disease and the level of control during the gestation period. Babies born to mothers with asthma are characterized by high frequency of disharmonious development, greater polyorganic morbidity of systems, which necessitate preventive measures during the gestational period.
Are 6MWD and FEV1 the most clinically relevant measures
Authors: Matthew A. Rutter, Jennifer A. Colbourne, Jonathan P. Fuld, Karl P. Sylvester
Journal: European Respiratory Journal (2012)

Six minute walk tests (6MWT) are used to assess exercise tolerance and widely used to assess the response to interventions. The six minute walk distance (6MWD) is used clinically to describe the patients9 ability to tolerate exercise and is often used in comparison to FEV1. Although FEV1 and 6MWD performed concomitantly correlate, FEV1 in certain patient populations can remain stable over time whilst 6MWD can vary. Our aim was to determine if any additional lung function parameters and values obtained during a 6MWT could be used for clinical interpretation. A retrospective analysis of 312 patients who undertook full lung function, which comprised of spirometry, gas transfer and body plethysmography and a 6MWT, utilising pulse oximetry and Borg score. The correlation between 6MWD and FEV1 was r=0.487, p
Pathology of the Spread of L1210 Leukemia in the Central Nervous System of Mice and Effect of Treatment With Cytoxan
Authors: Louis B. Thomas, Michael A. Chirigos, Stewart R. Humphreys, Abraham Goldin
Journal: JNCI Journal of the National Cancer Institute (1962)

L1210 leukemia and the amethopterin-resistant subline, L1210 FR-9, grow diffusely in the subarachnoid space and dura after intracerebral inoculation in mice. The distribution of leukemia in the meninges in these animals is similar to leukemic-cell infiltrates in the meninges of patients with acute leukemia. Intracerebrally inoculated leukemia spreads to extracranial organs and tissues by two routes: (1) hematogenously and (2) by direct extension through tissues which surround cranial and spinal nerves and blood vessels. The median survival time of mice inoculated intracerebrally with leukemia was 8 to 9 days. Extensive deposits of leukemic cells were observed in the liver, spleen, and bone marrow at the time these animals died or were killed. Cytoxan injected subcutaneously in animals inoculated with leukemia intracerebrally prolonged the survival time of the animals and completely destroyed the leukemic cells in the liver, spleen, bone marrow, and dura, whereas the leukemic cells in the subarachnoid space continued to proliferate. Therefore, the prolonged survival in the Cytoxan-treated animals is apparently related to the effect of the drug on leukemic cells in the systemic organs and tissues and in the dura. The anatomical zone, where the antileukemic effectiveness of systemically injected Cytoxan against leukemic cells extending from the intracranial tissues stops, is illustrated and is referred to as a “therapeutic barrier.” Certain discrete areas of the brain, the area postrema, the tuber cinereum, and the walls of the supraoptic recess of the third ventricle were diffusely infiltrated by leukemic cells in the mice inoculated intracerebrally, in contrast to the brain and spinal-cord tissues generally. Some of the histologic and biochemical factors which might be related to this are mentioned. L1210 and L1210 FR-9 inoculated subcutaneously in mice reach the subarachnoid space as a result of direct spread from the dura in and through the perivascular and perineural tissues. This occurs late in the course of the disease. In other words, the tissue barriers at the capillary bed (the “blood-brain barrier”) and in the choroid plexus (the “blood-cerebrospinal fluid barrier”) prevent the passage of leukemic cells directly into the brain and into the cerebrospinal fluid.
Improvements in lung cancer surgery
Authors: Trond-Eirik Strand, Kristian Bartnes, Hans Rostad
Journal: European Respiratory Journal (2011)

Background:  Recent trends in outcomes of lung cancer treatment might challenge recommendations for acceptable care.   Methods:  Using data from the Cancer Registry of Norway, we analyzed outcomes and quality indicators of lung cancer surgery in the periods 1994-1995, 2000-2001 and 2006-2007.   Results:  A total of 2201 patients were operated on during the study periods. Surgery was performed at 24 hospitals during the first two periods and at 13 in the last. Resection rates varied among counties from 7% to 31%. From the first to the last period, national resection rates increased from 16% to 19% (p for trend=0.001) and one-year survival increased from 73% to 82%. The proportion of resected patients in pStage I-II decreased from 87% to 83% (p for trend=0.048), the proportion of pneumonectomies from 27% to 15% (p for trend   Conclusions:  Important aspects of lung cancer surgery have improved in recent years and the recommendations for certain quality indicators are challenged. The most important is that the resection rates should be further increased towards a putative optimum exceeding 25%.
The combined conventional bronchoscopic methods are still useful in diagnosis of sarcoidosis
Authors: Lukasz Kasper, Krzysztof Sladek, Jerzy Soja, Mariusz Duplaga, Filip Mejza, Magdalena Mikos, Piotr Grzanka, Boguslaw Papla, Romana Tomaszewska
Journal: European Respiratory Journal (2011)

Introduction:  At present EBUS-TBNA and EUS-FNA methods are suggested as the best methods in diagnosis of sarcoidosis. Until now a lot of pulmonologists use the standard endoscopic procedures to confirm this disease. In our study we present the results of the combined conventional bronchofiberoscopic methods such as endobronchial biopsy (EBB), transbronchial lung biopsy (TBLB), transbronchial needle aspiration (TBNA) in diagnosis of patients with suspicion of sarcoidosis.   Material and methods:  53 patients with suspicion of sarcoidosis (in stage 1 to 3) were sent to Division of Bronchoscopy for all 2009 year. The all patients were underwent bronchoscopy with simultaneous all three bronchoscopic methods. The presence of noncaseating epithelioid cell granulomas that correspond to clinical and radiological picture of sarcoidosis was obtained in 94.33%. In only one patient the sarcoidosis was confirmed by EBUS-TBNA, and two others with acute sarcoidosis still remain under clinical observation.   Conclusions:  The results of combined bronchoscopic biopsies are comparable to the results from EBUS and EUS studies. It might suggest that the combined conventional bronchoscopic methods are still useful and recommended to confirm sarcoidosis suspicion.
Antitumor Effects of Antibody-Diphtheria Toxin Conjugates: Use of Hapten-Coated Tumor Cells as an Antigenic Target&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Frederick L. Moolten, Neva J. Capparell, Sidney R. Cooperband
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Antitumor Effects of Antibody-Diphtheria Toxin Conjugates: Use of Hapten-Coated Tumor Cells as an Antigenic Target Get access Frederick L. Moolten, Frederick L. Moolten Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neva J. Capparell, Neva J. Capparell Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118 Search for other works by this author on: Oxford Academic PubMed Google Scholar Sidney R. Cooperband Sidney R. Cooperband Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 49, Issue 4, October 1972, Pages 1057–1062, https://doi.org/10.1093/jnci/49.4.1057 Published: 01 October 1972 Article history Received: 28 February 1972 Accepted: 07 June 1972 Published: 01 October 1972
A comparison of the frequency of cough with laughter in asthmatic and non asthmatic patients
Authors: Christopher Leahy, Bernard Leahy
Journal: European Respiratory Journal (2012)

Cough is a frequent symptom in asthmatic patients.Cough may be induced by typical asthma triggers such as allergens,exertion or change in atmospheric temperature.This study investigates the symptom of cough with laughter as an asthmatic symptom.  Patients attending a general adult respiratory clinic were routinely asked if they experienced cough with laughter.Seventy four consecutive patients with a single respiratory diagnosis were included.The patients were divided into two groups-patients with asthma and those with another respiratory diagnosis.  The asthma group had forty three patients with a mean age of 57.7 years,twenty seven were female and sixteen male.  The non asthma group had thirty one patients with a mean age of 63.9 years,sixteen were male and fifteen female.In this second group their diagnoses were chronic obstructive pulmonary disease in eleven,pulmonary fibrosis in eight,sarcoidosis in five,bronchiectasis in two,hyperventilation in two and one each of carcinoma of bronchus,tuberculosis and sleep apnoea.  In the asthma group forty two of the forty three patients had the symptom of cough with laughter.  In the non asthma group one of the thirty one patients had the symptom of cough with laughter.  The symptom of cough with laughter is highly significantly associated with a diagnosis of asthma compared to other respiratory diagnoses(p