tbuckley/cabot-search huggingface dataset:
Neuroblastoma Cells Isolated from Bone Marrow Metastases Contain a Naturally Enriched Tumor-Initiating Cell
Authors: Loen M. Hansford, Amy E. McKee, Libo Zhang, Rani E. George, J. Ted Gerstle, Paul S. Thorner, Kristen M. Smith, A. Thomas Look, Herman Yeger, Freda D. Miller, Meredith S. Irwin, Carol J. Thiele, David R. Kaplan
Journal: Cancer Research (2007)

Abstract Neuroblastoma is a heterogeneous pediatric tumor thought to arise from the embryonic neural crest. Identification of the cell responsible for propagating neuroblastomas is essential to understanding this often recurrent, rapidly progressing disease. We have isolated and characterized putative tumor-initiating cells from 16 tumors and bone marrow metastases from patients in all neuroblastoma risk groups. Dissociated cells from tumors or bone marrow grew as spheres in conditions used to culture neural crest stem cells, were capable of self-renewal, and exhibited chromosomal aberrations typical of neuroblastoma. Primary spheres from all tumor risk groups differentiated under neurogenic conditions to form neurons. Tumor spheres from low-risk tumors frequently formed large neuronal networks, whereas those from high-risk tumors rarely did. As few as 10 passaged tumor sphere cells from aggressive neuroblastoma injected orthotopically into severe combined immunodeficient/Beige mice formed large neuroblastoma tumors that metastasized to liver, spleen, contralateral adrenal and kidney, and lung. Furthermore, highly tumorigenic tumor spheres were isolated from the bone marrow of patients in clinical remission, suggesting that this population of cells may predict clinical behavior and serve as a biomarker for minimal residual disease in high-risk patients. Our data indicate that high-risk neuroblastoma contains a cell with cancer stem cell properties that is enriched in tumor-initiating capacity. These cells may serve as a model system to identify the molecular determinants of neuroblastoma and to develop new therapeutic strategies for this tumor. [Cancer Res 2007;67(23):11234–43]
Two AHA Councils Become One
Authors: Thomas H. Hintze, Eduardo Marbán
Journal: Circulation Research (1999)

t the dawning of the new millennium, major changes in cardiovascular science lie on the horizon, including increased pay lines and a proposal to double the National Institutes of Health (NIH) budget in 5 years; major victories in the war against cigarette smoking by the American Heart Association (AHA) and an emphasis on outcomes research; the winding down of the Human Genome project; a reduction in the number of young people entering academic cardiovascular medicine; and the transition to a new editor at Circulation Research.Concurrent with all of these events and, perhaps, to better participate in these new directions, the Councils on Circulation and Basic Science, two of the thirteen councils of the AHA, have recently merged.The merger comes after a great deal of agonizing over the past several years, in fact, for more than 35 years, concerning the now artificial distinction between disciplines in basic cardiovascular sciences and the ensuing loss of individual identity due to the merging of so many scientific disciplines.Out of this reflection comes what we believe to be the best of the "old councils" and new energy and direction from their union.Council (Section) on Circulation: The Council on Circulation 1,2 was the first "section" of the AHA and was formed as the Section on Peripheral Circulation in 1935.Its function was to encourage investigation into the function of the circulation.At its first annual meeting in 1936, nine papers were presented on topics such as assessment of peripheral resistance, surgical treatment of hypertension, contrast arteriography, and intermittent claudication in man.The first chairman was George Brown, who died that year, and in his memory, the first George Brown Lecture was given by Walter Cannon in 1937.At that time, the journal for the Council was the American Heart Journal.After World War II, then as now, there was some soul-searching as to the purpose of the Section.It was stated by Irvine H.
Postoperative Adjuvant Therapy With Tamoxifen, Tegafur Plus Uracil, or Both in Women With Node-Negative Breast Cancer: A Pooled Analysis of Six Randomized Controlled Trials
Authors: Shinzaburo Noguchi, Hiroki Koyama, Junichi Uchino, Rikiya Abe, Shigeto Miura, Keizo Sugimachi, Kohei Akazawa, Osahiko Abe
Journal: Journal of Clinical Oncology (2005)

This article reports the results of a pooled analysis of six randomized trials conducted to study the efficacy of uracil and tegafur (UFT) in the adjuvant treatment of node-negative breast cancer patients.Six randomized controlled trials on node-negative breast cancer patients were conducted from 1992 through 1995 in Japan that included the three, three-arm trials (control [no adjuvant], UFT, and tamoxifen [TAM] groups) and the three, four-arm trials (control, UFT, TAM, and UFT plus TAM groups). Pooled analysis was performed on the data obtained from these six trials (involving 2,934 patients).Overall survival was compared between the UFT group (including both the UFT group and the TAM plus UFT group) and the non-UFT group (control group and TAM group). A significant difference (P = .04) was observed in 5-year survival rates between the UFT (95.9%) and the non-UFT (94.0%) groups. Overall survival was also compared between the TAM group (TAM group and TAM plus UFT group) and the non-TAM group (control group plus UFT group). The 5-year survival rate (95.2%) in the TAM group was not significantly different from that (93.9%) in the non-TAM group, but the subset analysis showed a significant (P = .01) improvement in the estrogen receptor-positive subset.Adjuvant UFT improves the overall survival of node-negative breast cancer patients. Given that UFT has milder adverse effects, it is suggested that UFT can be a useful alternative to doxorubicin and cyclophosphamide, or cyclophosphamide, methotrexate, and fluorouracil in the adjuvant treatment for node-negative breast cancer.
Studies of defective tolerance induction in NZB mice. Evidence for a marrow pre-T cell defect.
Authors: C A Laskin, P A Smathers, J P Reeves, A D Steinberg
Journal: The Journal of Experimental Medicine (1982)

NZB mice manifest a defect in tolerance induction by deaggregated heterologous gamma globulins. We have used an adoptive transfer system to study the defect. Thymectomized, intact, or thymectomized recipients given thymic epithelial grafts were studied after lethal irradiation and reconstitution with NZB, DBA/2, or (NZB x DBA(F1 marrow depleted of mature T cells. NZB thymocytes were responsible for the tolerance defect of NZB mice. The information for the defect was present in the NZB marrow prethymocyte. That defect could only be expressed when there was further maturation in association with a thymus. However, the normal DBA/2 thymic epithelium served as well as the abnormal NZB thymic epithelium. These studies resolve existing conflicts as to whether the NZB marrow or thymus is responsible for the loss of tolerance in association with autoimmunity.
αEβ7 integrin interaction with E-cadherin promotes antitumor CTL activity by triggering lytic granule polarization and exocytosis
Authors: Audrey Le Floc'h, Abdelali Jalil, Isabelle Vergnon, Béatrice Le Maux Chansac, Vladimir Lazar, Georges Bismuth, Salem Chouaib, Fathia Mami-Chouaib
Journal: The Journal of Experimental Medicine (2007)

Various T cell adhesion molecules and their cognate receptors on target cells promote T cell receptor (TCR)–mediated cell killing. In this report, we demonstrate that the interaction of epithelial cell marker E-cadherin with integrin αE(CD103)β7, often expressed by tumor-infiltrating lymphocytes (TILs), plays a major role in effective tumor cell lysis. Indeed, we found that although tumor-specific CD103+ TIL-derived cytotoxic T lymphocyte (CTL) clones are able to kill E-cadherin+/intercellular adhesion molecule 1− autologous tumor cells, CD103− peripheral blood lymphocyte (PBL)-derived counterparts are inefficient. This cell killing is abrogated after treatment of the TIL clones with a blocking anti-CD103 monoclonal antibody or after targeting E-cadherin in the tumor using ribonucleic acid interference. Confocal microscopy analysis also demonstrated that αEβ7 is recruited at the immunological synapse and that its interaction with E-cadherin is required for cytolytic granule polarization and subsequent exocytosis. Moreover, we report that the CD103− profile, frequently observed in PBL-derived CTL clones and associated with poor cytotoxicity against the cognate tumor, is up-regulated upon TCR engagement and transforming growth factor β1 treatment, resulting in strong potentiation of antitumor lytic function. Thus, CD8+/CD103+ tumor-reactive T lymphocytes infiltrating epithelial tumors most likely play a major role in antitumor cytotoxic response through αEβ7–E-cadherin interactions.
Managing impotence in diabetes. No need for separate service.
Authors: M A Miller, J Y Jeremy, C S Thompson
Journal: BMJ (1993)

education for general practitioners was also provided.People concerned about possible lesions were encouraged to consult their general practitioner, who could refer those with suspect lesions direct to a pigmented lesion clinic, avoiding the waiting list for appointments to dermatology clinics.The effect of these campaigns on incidence by stage and on mortality are still being evaluated; preliminary results from western Scotland indicate some possible benefit to women but not yet to men.2
Is a 2-week steroid trial after initial negative investigation for malignancy useful in differentiating autoimmune pancreatitis from pancreatic cancer? A prospective outcome study
Authors: S-H Moon, M-H Kim, D H Park, C Y Hwang, S J Park, S S Lee, D W Seo, S K Lee
Journal: Gut (2008)

Autoimmune pancreatitis (AIP) is a peculiar type of chronic pancreatitis that responds dramatically to steroid therapy. To date, there are no worldwide consensus criteria for AIP. Different criteria with institutional preference (HISORt, revised Kim and the revised Japanese criteria) are being used to diagnose AIP, and there is controversy regarding the inclusion of steroid responsiveness in the diagnostic criteria. In contrast to the HISORt and revised Kim criteria, the revised Japanese criteria do not include steroid responsiveness as a diagnostic component.This study was performed to evaluate whether "a 2-week steroid trial and subsequent assessment of its response" is a useful diagnostic tool for the differentiation of AIP from pancreatic cancer. A further aim was to discover the surgical and clinical outcome for a patient who followed the treatment algorithm based on the steroid responsiveness.From January 2004 to June 2007, in the setting of clinically suspected AIP, 22 consecutive patients with atypical imaging for AIP, while not meeting the classic imaging criteria for pancreatic cancer, were challenged to undergo 2 weeks of steroid therapy (0.5 mg/kg of oral prednisolone per day). After the 2-week steroid trial, steroid responsiveness was assessed based on a marked improvement of narrowing of the main pancreatic duct and a reduction of the pancreatic mass. The steroid trial was continued in the case of positive steroid responsiveness, whereas surgical exploration was conducted in the case of negative steroid responsiveness. The final diagnosis was made by surgical exploration or long-term clinical and radiological follow-up.All patients (n = 15) who responded to steroids were diagnosed as having AIP, whereas all patients (n = 7) who did not show a response to steroids were confirmed as having pancreatic cancer. Complete resection was possible in all (6/6; 100%), except one individual who refused surgery.In the clinical setting of suspected AIP with the continued need for differentiation from pancreatic cancer due to atypical imaging for AIP, "a 2-week steroid trial and subsequent assessment of its response" may be helpful in confirming the diagnosis of AIP without negative consequences for resectable pancreatic cancer. However, a steroid trial should be performed carefully only by specialists in pancreatology.
Open-Label, Multicenter, Randomized, Phase III Study Comparing Oral Topotecan/Cisplatin Versus Etoposide/Cisplatin As Treatment for Chemotherapy-Naive Patients With Extensive-Disease Small-Cell Lung Cancer
Authors: John R. Eckardt, Joachim von Pawel, Zsolt Papai, Antoaneta Tomova, Valentina Tzekova, Theresa E. Crofts, Sarah Brannon, Paul Wissel, Graham Ross
Journal: Journal of Clinical Oncology (2006)

This open-label, randomized, multicenter phase III study compared oral topotecan/intravenous cisplatin (TC) with intravenous (IV) etoposide/cisplatin (PE) in patients with untreated extensive-disease small-cell lung cancer (ED-SCLC).A total of 784 patients were randomly assigned to either oral topotecan 1.7 mg/m2/d x 5 with IV cisplatin 60 mg/m2 on day 5 (n = 389) or IV etoposide 100 mg/m2/d x 3 with IV cisplatin 80 mg/m2 on day 1 (n = 395) every 21 days.Overall survival (primary end point) was similar between groups (P = .48; median: TC, 39.3 weeks v PE, 40.3 weeks). One-year survival was 31% (95% CI, 27% to 36%) in both groups and the difference of -0.03 (95% CI, -6.53 to 6.47) met the predefined criteria of < or = 10% absolute difference for noninferiority of TC relative to PE. Response rates were similar between groups (TC, 63% v PE, 69%). Time to progression was slightly but statistically longer with PE (log-rank P = .02; median: TC, 24.1 weeks v PE, 25.1 weeks). The regimens were similarly tolerable. Grade 3/4 neutropenia occurred more frequently with PE (84% v 59%), whereas grade 3/4 anemia and thrombocytopenia occurred more frequently with TC (38% v 21% and 38% v 23%, respectively). Lung Cancer Symptom Scale scores were statistically better with PE, but the differences were small and of debatable clinical significance.Oral topotecan with cisplatin provides similar efficacy and tolerability to the standard (etoposide with cisplatin) in untreated ED-SCLC and may provide greater patient convenience compared with intravenous etoposide and cisplatin.
Bile acid malabsorption in Crohn's disease and indications for its assessment using SeHCAT.
Authors: H Nyhlin, M V Merrick, M A Eastwood
Journal: Gut (1994)

Patients with Crohn9s disease who suffer from longstanding diarrhoea that does not respond to conventional treatment pose a common clinical problem. Bile acid malabsorption is a possible cause, although its prevalence and clinical importance is unclear. This paper explores the clinical indications for referring patients with Crohn9s disease for bile acid assessment and the extent of bile acid malabsorption in this selected group of patients. The selenium labelled bile acid SeHCAT was used to assess the effect of disease on the integrity of the enterohepatic circulation. Altogether 76% of the patients referred for bile acid assessment had longstanding diarrhoea that had not responded to conventional anti-diarrhoeal treatment or an increase in steroid therapy as their sole or predominant symptom. Ninety per cent of patients with bowel resections, almost exclusively ileocaecal, had abnormal SeHCAT retention (&lt; 5% at seven days). Twenty eight per cent of patients with Crohn9s disease who had not undergone resection 28% had a SeHCAT retention &lt; 5%, signifying bile acid malabsorption. Nineteen of 22 patients given cholestyramine treatment subsequent to the SeHCAT test had a good symptomatic response. In conclusion, the prevalence of bile acid malabsorption in this selected group with Crohn9s disease is sufficiently high to justify performing the SeHCAT test in order to separate the various differential diagnoses.
Quantitation of GD2 Synthase mRNA by Real-Time Reverse Transcriptase Polymerase Chain Reaction: Clinical Utility in Evaluating Adjuvant Therapy in Neuroblastoma
Authors: Irene Y. Cheung, M. Serena Lo Piccolo, Brian H. Kushner, Kim Kramer, Nai-Kong V. Cheung
Journal: Journal of Clinical Oncology (2003)

Minimal residual disease (MRD) is one of the final hurdles to cancer cure. Because therapy (myeloablation, immunotherapy, or differentiation) for MRD is applied at the time of clinical remission, objective surrogate markers are needed to gauge treatment efficacy.Using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) of GD2 synthase (beta1,4-N-acetylgalactosaminyltransferase, EC 2.4.1.92) mRNA, we evaluated MRD response to anti-GD2 monoclonal antibody 3F8 adjuvant therapy, namely, one cycle of radioimmunotherapy using iodine-131 ((131)I)-3F8 plus one cycle of unlabeled 3F8 in 45 stage 4 neuroblastoma patients (newly diagnosed or without prior relapse) on the N7 protocol at Memorial Sloan-Kettering Cancer Center. The prognostic effect of MRD in their bone marrows before and after this phase of adjuvant therapy on progression-free survival (PFS) and overall survival (OS) was also analyzed.Before 3F8 treatment, 24 of 45 patients were in complete remission (CR), 12 were in very good partial remission (VGPR), and nine were in partial remission (PR), according to criteria from International Neuroblastoma Staging System plus (131)I-3F8 scan; 71% had detectable tumor cells in marrow by real-time RT-PCR. Of the 32 positive patients, 20 became negative after therapy, with a 63% efficacy. When patients were stratified by CR/VGPR versus PR, GD2 synthase positivity was prognostic when detected before 3F8-targeted therapy (PFS, P =.045 and OS, P =.010). Persistent marker positivity was also predictive of PFS (P =.035) and OS (P =.027). Patients who succumbed to the disease had transcript levels four times higher than those who remain alive.GD2 synthase mRNA is a useful surrogate marker for evaluating adjuvant treatment efficacy in neuroblastoma with prognostic potential.
The impact of depression in recovery and outcome of patients hospitalized for COPD exacerbation
Authors: Andriana Papaioannou, Konstantinos Bartziokas, Stamatoula Tsikrika, Foteini Karakontaki, Emmanouil Kastanakis, Aikaterini Haniotou, Vlassios Poluchronopoulos, Konstantinos Kostikas
Journal: European Respiratory Journal (2011)

Background:  Depression has been associated with worsening of COPD symptoms and quality of life, more exacerbations and increased mortality.   Objectives:  To evaluate prospectively the impact of depressive symptoms on admission on the outcomes of patients hospitalized for COPD exacerbations (ECOPD).   Methods:  We studied prospectively 151 patients admitted to hospital for ECOPD. Depression symptoms were evaluated with Becks Depression Inventory. Pulmonary function tests, arterial blood gases and COPD assessment test (CAT) score, were recorded on the day of their admission and 3, 10 and 40 days later. Patients were evaluated monthly for one year.   Results:  Duration of hospitalization was longer in patients with high depressive symptoms [5 (3, 6) vs 12 (10, 14), p 1 , blood gases, dyspnea and CAT score (p 1  as well as ADO and DOSE indexes on stability compared to patients with less depressive symptoms (41.5±10.7 vs 62.5±20.0, 4.8±1.3 vs 4.1±1.2 and 3.5±1.2 vs 1.9±1.2 respectively; p 2/year) had a higher score in Becks Depression Inventory compared to non-frequent exacerbators (22.2±13.1 vs 9.1±4.2 p   Conclusions:  Depressive symptoms in patients admitted for ECOPD have significant impact on their recovery and are related to worse survival and more new ECOPD during the following year.
Lung cancer deaths from indoor radon and the cost effectiveness and potential of policies to reduce them
Authors: A. Gray, S. Read, P. McGale, S. Darby
Journal: BMJ (2009)

<b>Objective</b> To determine the number of deaths from lung cancer related to radon in the home and to explore the cost effectiveness of alternative policies to control indoor radon and their potential to reduce lung cancer mortality. <b>Design</b> Cost effectiveness analysis. <b>Setting</b> United Kingdom. <b>Data sources</b> Epidemiological data on risks from indoor radon and from smoking, vital statistics on deaths from lung cancer, survey information on effectiveness and costs of radon prevention and remediation. <b>Main outcome measures</b> Estimated number of deaths from lung cancer related to indoor radon, lifetime risks of death from lung cancer before and after various potential interventions to control radon, the cost per quality adjusted life year (QALY) gained from different policies for control of radon, and the potential of those policies to reduce lung cancer mortality. <b>Results</b> The mean radon concentration in UK homes is 21 becquerels per cubic metre (Bq/m<sup>3</sup>). Each year around 1100 deaths from lung cancer (3.3% of all deaths from lung cancer) are related to radon in the home. Over 85% of these arise from radon concentrations below 100 Bq/m<sup>3</sup> and most are caused jointly by radon and active smoking. Current policy requiring basic measures to prevent radon in new homes in selected areas is highly cost effective, and such measures would remain cost effective if extended to the entire UK, with a cost per QALY gained of £11 400 ( €12 200; $16 913). Current policy identifying and remediating existing homes with high radon levels is, however, neither cost effective (cost per QALY gained £36 800) nor effective in reducing lung cancer mortality. <b>Conclusions</b> Policies requiring basic preventive measures against radon in all new homes throughout the UK would be cost effective and could complement existing policies to reduce smoking. Policies involving remedial work on existing homes with high radon levels cannot prevent most radon related deaths, as these are caused by moderate exposure in many homes. These conclusions are likely to apply to most developed countries, many with higher mean radon concentrations than the UK.
Electroencephalographic spectral analysis: detection of cortical activity changes in sleep apnoea patients
Authors: K. Dingli, T. Assimakopoulos, I. Fietze, C. Witt, P.K. Wraith, N.J. Douglas
Journal: European Respiratory Journal (2002)

There are no visible electroencephalographic (EEG) changes at the termination of some apnoeas and hypopnoeas. This study tests the hypothesis that cortical activity fluctuates at apnoea/hypopnoea termination, despite the lack of visible changes. To detect these changes, EEG spectral analysis was performed and centred around the end of apnoeas/hypopnoeas in 15 sleepy patients. Ten second windows were applied and comparisons were conducted between the normalised power of the same frequency bands before and after termination of each apnoea/hypopnoea. Comparisons were performed within patients between apnoeas/hypopnoeas and periods of undisturbed sleep as well as between patients and healthy subjects during sleep. Normalised theta power (4–8 Hz) decreased significantly at apnoea/hypopnoea termination. No significant changes were found between consecutive periods of undisturbed sleep across the 15 patients. During nonrapid eye movement sleep, changes were detected irrespective of arousal visibility. During rapid eye movement sleep, nonarousal apnoeas/hypopnoeas were not accompanied by any significant spectral power changes. Theta power was significantly lower across patients compared to healthy subjects (p=0.03) and was correlated to the apnoea/hypopnoea index (rho=0.6, p=0.008). The authors conclude that electroencephalographic spectral analysis improves detection of changes at apnoea/hypopnoea termination. Further validation is needed to determine whether it improves correlation between nocturnal measures and daytime symptoms.