tbuckley/cabot-search huggingface dataset:
Synergism between chemotherapy and alternating electric fields in the inhibition of cancer cell proliferation in-vitro
Authors: Rosa Schneiderman, Esther Shmueli, Eilon Kirson, Yoram Palti
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2276 

Currently the mainstay of cancer therapy is based on combinations of several chemotherapeutic protocols with the aim to increase efficacy while maintaining tolerable toxicity. The present study explores the in-vitro efficacy of combining chemotherapeutic treatment together with a new, non-toxic, anticancer modality (Kirson et al, Cancer Research, 2004;64:3288-3295); termed Tumor Treating Fields (TTFields). TTFields are specially tuned, low intensity, intermediate frequency alternating electric fields. TTFields, when generated by insulated external electrodes, have been shown to effectively inhibit cancer cell proliferation in tissue culture, animal tumor models and patients with brain tumors (glioblastoma multiforme) as well as skin metastases from breast carcinoma.

The inhibition of cancer cell proliferation, in human breast carcinoma cells (MDA-MB-231) in culture, was studied by applying TTFields of different intensities alone and in combination with different concentrations of the following chemotherapeutic agents: paclitaxel, doxorubicin and cyclophosphamide. The effects of chemo-TTField combinations were compared to the effect of each treatment modality alone. Similarly, the inhibitory efficacy of the TTFields - paclitaxel combinations was evaluated in human non-small cell lung cancer cells (H1299). Analysis of the results was performed by calculating Combination Index values, as derived from the median effect plots and by isobologram analysis.

It was found that the exposure of breast carcinoma and non-small cell lung carcinoma cell cultures to TTFields and paclitaxel, together, had the same inhibitory efficacy as exposure to paclitaxel alone at a concentration two orders of magnitude higher. Qualitatively similar results were obtained for cyclophosphamide and doxorubicin as well. Analysis of these results indicates that, depending on the field intensity and drug concentration, the efficacy of TTField-chemotherapy combinations varies between simple additivity for doxorubicin to overt synergism for cyclophosphamide and paclitaxel. We conclude that, since TTFields are not expected to contribute to systemic toxicity, treatment of cancer with TTFields - Chemotherapy combinations can cause significant potentiation of the efficacy of chemotherapeutic agents, while maintaining relatively low toxicity.
Combination chemotherapy using adriamycin, DTIC, cyclophosphamide, and actinomycin D for advanced soft tissue sarcomas: a randomized comparative trial. A phase III, Southwest Oncology Group Study (7613).
Authors: L H Baker, J Frank, G Fine, S P Balcerzak, R L Stephens, W J Stuckey, S Rivkin, J Saiki, J H Ward
Journal: Journal of Clinical Oncology (1987)

The term soft tissue sarcoma refers to a large variety of malignant tumors arising in extraskeletal connective tissues that connect, support, and surround discrete anatomic structures. All visceral organs also contain a connective stroma that can undergo malignant transformation. Because of the histological similarities of this group of tumors and their relative rarity, treatment prescriptions for patients that have disseminated disease are most often uniform. In this study, we asked the question whether adding a third drug (cyclophosphamide or actinomycin D) to Adriamycin (Adr [Adria Laboratories, Columbus, OH])-(3,3-dimethyl-1-triazeno)- imidazole-4-carboxamide (DTIC) would improve the response rate and/or survival. A unique feature of this cooperative group clinical trial was the mandatory pathology review of the histological material. All patients of the Southwest Oncology Group between June 1, 1976, and November 17, 1979, who had a biopsy-confirmed diagnosis of a soft tissue sarcoma with convincing clinical or biopsy-documented evidence of metastatic disease were eligible for the study. Patients were randomized to receive (1) Adr, 60 mg/m2 intravenously, day 1, and DTIC, 250 mg/m2 every 3 weeks (104 patients); (2) Adr and DTIC as in (1) and cyclophosphamide, 500 mg/m2, day 1 (112 patients); or (3) Adr and DTIC as in (1) and actinomycin D, 1.2 mg/m2, day 1, (119 patients). There was no statistically significant difference in response rates (33%, 34%, and 24%) (P = .25). Median durations of response were 31 weeks in the Adr-DTIC arm, 26 weeks in the cyclophosphamide-DTIC-Adr arm, and 23 weeks in the Adr-DTIC-Actinomycin D arm (P = .78). Median durations of survival were 37, 42, and 50 weeks, respectively. Again, no statistically significant differences were observed (P = .59). Toxicities from each of these treatment arms were formidable and were equivalent. Prognostic factor analysis showed a prognosis based on bone marrow reserve, sex, and pathology subtype favorable to patients.
The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity
Authors: Evie P.M. Broeders, Emmani B.M. Nascimento, Bas Havekes, Boudewijn Brans, Kay H.M. Roumans, Anne Tailleux, Gert Schaart, Mostafa Kouach, Julie Charton, Benoit Deprez, Nicole D. Bouvy, Felix Mottaghy, Bart Staels, Wouter D. van Marken Lichtenbelt, Patrick Schrauwen
Journal: Cell Metabolism (2015)
Impact of angiopoietin-1 in mesothelioma progression
Authors: Sophia Magkouta, Charis Moschos, Magda Spella, Maria-Eleni Vazakidou, Ioannis Psallidas, Apostolis Pappas, Georgios Stathopoulos, Ioannis Kalomenidis
Journal: European Respiratory Journal (2013)

Introduction: Angiopoietins-1 (Ang-1) is a key regulator of tumor angiogenesis and stimulates the proliferation and migration of malignant mesothelioma (MM) cells that express its receptor (Tie-2) in vitro. Despite this, the impact of Ang-1 in MM progression in vivo has not been examined before.  Aim: To elucidate the role of Ang-1 the progression of MM in vivo.  Materials and methods: Murine MM AE17 cells were transfected with Ang-1 overexpressing or control plasmid. Vector or Ang-1 overexpressing cells were intrapleurally injected to syngeneic C57BL/6 mice. Upon 15 days mice were sacrificed and tumor mass and pleural fluids were harvested and measured. Tumor cell proliferation, apoptosis and vessel density and maturity were assessed in tumor tissue sections by immunohistochemistry and immunofluorescence.  Results: Albeit AE17 cells express Tie-2 receptor the Ang-1 overexpressing (Ang-1-over) clone did not differ from control cells in terms of viability or migratory capacity. Mice bearing Ang-1-over tumors presented a significantly higher tumor mass compared to the control group (mean ± SEM 0.47±0.02 g vs 0.38±0.02 g, p=0.018). No significant difference in pleural fluid volumes was found. Moreover, Ang-1-over tumors presented higher proliferation (p=0.005) and lower apoptosis (p=0.046) rates. In addition, Ang-1-over tumors exhibited higher vessel density (p  Conclusions: Angiopoietin-1 promotes mesothelioma tumor mass progression by enhancing tumor cell proliferation and angiogenesis and attenuating apoptosis.
Protocols for in vivo measurement of the ion transport defects in cystic fibrosis nasal epithelium
Authors: PG Middleton, DM Geddes, EW Alton
Journal: European Respiratory Journal (1994)

New treatments for cystic fibrosis (CF), including gene therapy, are currently being assessed. These aim to correct the basic defects of increased sodium absorption and decreased chloride secretion in airway epithelia. Assessment of these bioelectric parameters, particularly in the nasal epithelium, is likely to be used as a measure of treatment efficacy. However, the optimal in vivo protocol to discriminate cystic fibrosis from non-cystic fibrosis subjects is unclear. We have, therefore, compared three protocols for measurement of the cystic fibrosis ion transport defects in vivo in the nasal epithelium. Sodium absorption was measured using both the baseline potential difference and the response to the sodium channel blocker, amiloride. Chloride secretion was assessed in the presence of amiloride, using perfusion with isoprenaline, or terbutaline, or a low chloride solution followed by isoprenaline. Baseline potential difference (PD) and the absolute response to amiloride clearly differentiated the increased sodium absorption in the cystic fibrosis subjects. The responses both to terbutaline (delta PD: non-CF: -0.8 (SEM 0.7) mV; CF: -3.6 (0.5) mV) and isoprenaline (non-CF: 1.5 (0.6) mV; CF: -2.9 (0.6) mV) differentiated the two groups of subjects, but there was considerable overlap of values. Perfusion with a low chloride solution (non-CF: 12.6 (1.2) mV; CF: 0.6 (0.4) mV), as well as subsequent perfusion with isoprenaline (non-CF: 10.0 (1.1) mV; CF: -1.4 (0.4) mV) allowed clear separation of the two groups, with no overlap of values. Some CF subjects showed a transient hyperpolarization to these stimuli, which could clearly be differentiated from the sustained responses seen in non-cystic fibrosis subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Disease management program for COPD patients with frequent exacerbations
Authors: A. Marin, M. Rivera, G. Bonet, R. Hervas, L. Merlos, J. Ruiz-Manzano
Journal: European Respiratory Journal (2012)

OBJECTIVES  To determine if a disease management program focused on early recognition and self-treatment of COPD exacerbations can reduce hospital admissions due to COPD exacerbation.  METHODS  We included outpatients with stable COPD who had two or more COPD exacerbations in the previous year. Patients attended an individual education session conducted by a specialized respiratory nurse that included general information about COPD, direct observation of inhaler techniques, smoking cessation counselling and encouragement of regular exercise. Subjects were instructed to recognized signs and symptoms of an exacerbation and to begin action plan medications for symptoms that were substantially worse than usual. Each subject received an individualized written medical action plan and the telephone number to contact the case manager. The nurse made monthly phone calls to patients. Scheduled medical visits were made every three months and after exacerbation.  RESULTS  31 patients were included in the program (94% male; mean age 74 SD 7 years; post-bronchodilator FEV1% predicted 39 SD 11; 100% ex-smokers). The average duration of follow-up was 13.5 (3.5) months. During this period of time a mean of 8 DS 4 phone calls and 5 SD 2 medical visits were made. The frequency of hospitalizations and emergency visits for COPD were lower than the previous year before beginning the program (mean 0.26 SD 0.6 vs. 0.97 SD 1.1; p=0.000). The total COPD exacerbations were significantly lower than the previous year (mean 2.35 SD 1.8 vs. 3.61 SD 1.4; P=0.001)  CONCLUSIONS  A disease management program focused on early recognition and self-treatment of COPD exacerbations can reduce hospital admissions due to COPD exacerbation.
Book: Di Bella: the Man, the Cure, a Hope for All
Authors: A. Berger
Journal: BMJ (1999)

Vincenzo Brancatisano (translated by Vicki Satlow) Quartet Books, £7, pp 137 ISBN 0 7043 8093 5 Rating: ![Graphic][1]</img>![Graphic][2]</img> Despite the enormous leaps taken by science and medical technology in recent times, the myths that surround cancer remain intact, for patients at least. Cancer remains the bogeyman of medicine in the 20th century and still brings the fear of God into people in a way I have not seen with any other disease. And, despite all I have heard and read about Di Bella's cure for cancer, I remain sceptical about what doctors really have to offer. I was hoping that … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
Abstract 14266: Magnetic Resonance Imaging for Patients with Implanted Cardiac Devices: Prospective Study to Assess Safety and Utility
Authors: Saman Nazarian, Rozann Hansford, Ariel Roguin, Dorith Goldsher, Menekhem M Zviman, Albert C Lardo, Brian S Caffo, Kevin Frick, Michael A Kraut, Ihab Kamel, Hugh Calkins, Ronald D Berger, David A Bluemke, Henry R Halperin
Journal: Circulation (2010)

Background: Most patients with implantable pacemakers and defibrillators are currently denied magnetic resonance imaging (MRI) due to safety concerns. We performed a study to define the safety and ...
Comorbidity in patients with COPD in Russia
Authors: Nina Karoli, Andrey Rebrov
Journal: European Respiratory Journal (2013)

Comorbidities are frequent throughout the lifespan of COPD patients, and are ultimately responsible for many deaths.  The aim of our study was evaluated frequently of comorbidities in patients with COPD.  We performed retrospective analysis history of 125 patients with COPD (mean age 54,93±0,63 yrs). We studied all comorbidity diseases in patients with COPD and performed analysis of the Charlson Comorbidity Index (CCI) with W.H. Hall modification. COPD was diagnosed according GOLD criteria. 39.2% was with COPD I-II stage and 60.8% was with COPD III-IV stage.  Patients with COPD had 3,49±0,22 chronic comorbidity condition. Cardiovascular diseases are most frequently comorbidities in pts with COPD (MI had 11,2% pts, angina pectoris 13,6%, arterial hypertension 59,2% and heart failure 20,0% pts). CCI was 2,82±0,14 in patients with COPD. CCI in patients with COPD I-II stages was 2,40±0,19 and in pts with COPD III-IV stages was 3,11±0,18 (p 2  (r=-0.47, p  So comorbidities are frequently in patients with COPD and In conclusion early detection of concomitant diseases in patients with COPD is important and should be considered carefully when initiating therapy.
Cough variant asthma may be a incipience of bronchial asthma
Authors: Yasushi Obase, Terufumi Shimoda, Mikio Oka, Reiko Kishikawa, Tomoaki Iwanaga
Journal: European Respiratory Journal (2012)

Cough variant asthma (CVA) is characterized by chronic cough that persists for more than two months and suggested to be a precursor of bronchial asthma (BA).  To analogize if the position of cough variant asthma is early or mild stage of the classical bronchial asthma analyzed according to the airway inflammation, bronchial hyperresponsiveness, airway obstructive damage, newly diagnosed 46 cough variant asthma patients and 57 bronchial asthma patients naive to oral or inhaled corticosteroids and free of asthma execerbation were subjected to spirometry, impulse oscillometry (IOS), bronchial hyperesponsiveness test, induction of sputum, and measurement of fractional exhaled nitric oxide (FeNO).  Spirometry revealed lower values of FEV1.0/FVC, FEV1.0 %pred, V50 %pred, and V25 %pred in patients with BA than in those with CVA (p  All measures of central and peripheral airway obstruction, eosinophilic inflammation, and airway hyperresponsiveness were milder in patients with CVA than in those with BA but paralleled with intermittent asthma. Our data suggest that CVA is an allergic and inflammatory precursor of BA.
Phase II Study of Irinotecan Plus Cisplatin in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Russell F. DeVore, David H. Johnson, Jeffrey Crawford, Jennifer Garst, Isaiah W. Dimery, John Eckardt, S. Gail Eckhardt, Gary L. Elfring, Larry J. Schaaf, Cristy K. Hanover, Langdon L. Miller
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate the antitumor efficacy and safety of a combination of irinotecan (CPT-11) and cisplatin in patients with inoperable non–small-cell lung cancer (NSCLC). A secondary objective was to characterize the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38. PATIENTS AND METHODS: Patients with stage IIIB or IV NSCLC were treated with repeated 4-week courses comprising CPT-11 (60 mg/m 2 ) administered on days 1, 8, and 15, and a single dose of cisplatin (80 mg/m 2 ) after CPT-11 administration on day 1. RESULTS: Fifty-two patients were enrolled, including 33 men and 19 women. The median age was 61 years (range, 29 to 79 years). Southwest Oncology Group performance status was 0 in 12 patients, 1 in 32 patients, and 2 in eight patients. Eleven and 41 patients had stage IIIB and IV disease, respectively. Objective responses occurred in 28.8% of patients (15 of 52; 95% confidence interval, 16.5% to 41.2%). The median survival duration was 9.9 months (range, 1.6 to 30.8 months). The 1-year survival rate was 37%. Grade 3/4 adverse events consisted primarily of nausea (32.7% ) or vomiting (13.5%), late-onset diarrhea (17.3%), and neutropenia (46.1%). The study design led to preferential modification of CPT-11 doses, resulting in CPT-11 dose attenuations to ≤ 40 mg/m 2 in the majority of patients (31 of 52; 60%), whereas dose reductions of cisplatin were uncommon. CPT-11 pharmacokinetic parameters were comparable to those reported previously in single-agent studies. CONCLUSION: CPT-11/cisplatin is an active combination regimen with manageable toxicity in the therapy of stage IIIB/IV NSCLC. Future studies should be designed with schedules and dose modification provisions that avoid unnecessary CPT-11 dose reductions to exploit more directly the therapeutic synergy of these agents.
Up-regulation of HIV coreceptors CXCR4 and CCR5 on CD4+ T cells during human endotoxemia and after stimulation with (myco)bacterial antigens: the role of cytokines
Authors: Nicole P. Juffermans, William A. Paxton, Pascale E. P. Dekkers, Annelies Verbon, Evert de Jonge, Peter Speelman, Sander J. H. van Deventer, Tom van der Poll
Journal: Blood (2000)
Contribution of lung function tests in asthma screening: About a respresentative population
Authors: Ines Saada, Jouda Cherif, Sonia Toujani, Hafedh Zakhama, Yacine Ouahchi, Ben Salah Nozha, Bechir Louzir, Jalloul Daghfous, Nedia Mehiri, Majed Beji
Journal: European Respiratory Journal (2012)

Introduction: The major difficulty in epidemiological studies of asthma is due to the methods used to formulate the diagnosis. Studies conducted through questionnaires related frequencies often higher than those of objective tests including measurement of flow rates or airway hyperresponsiveness. we show through this study the contribution of spirometry in the diagnosis of asthma.  Methods: A cross-sectional survey, single pass, representative of the general population was carried out in the capital of Tunisia in subjects aged from 2 to 50 years. Informed consent was obtained. Prevalence was determinate through questionnaires, validated and used in international surveys, corresponding to the asthma screening and lung function tests. Spirometry was performed only in subjects reporting respiratory or atopy symptoms. Statistical analysis was performed using SPSS 18.0.  Results: The study included 4470 subjects. There was 40.2% male and 59.8% female. Current asthma prevalence was 6.8% in adults and 5.9% in children. Lung function tests were normal in 92% of cases (839 subjects). There was an airflow obstruction disorder in 11 individuals, 7 of which were reversible. Fifty subjects gain more than 12% in forced expiratory volume (FEV1). Of these, 20 did not report symptoms of asthma but had symptoms of atopy. We deduce that 19.6% of asthmatics had a reversibility and 6,8% were asymptomatics.  Conclusions: In the absence of gold standard, it is difficult to define asthma in epidemiological studies. If the measure of bronchial hyperresponsiveness has a specificity similar to questionnaires on asthma symptoms, it is also less sensitive.
Lenalidomide Maintenance After Stem-Cell Transplantation For Multiple Myeloma: Follow-Up Analysis Of The IFM 2005-02 Trial
Authors: Michel Attal, Valérie Lauwers-Cances, Gérald Marit, Denis Caillot, Thierry Facon, Cyrille Hulin, Philippe Moreau, Claire Mathiot, Murielle Roussel, Catherine Payen, Pascale Olivier, Hervé Avet-Loiseau
Journal: Blood (2013)
Late-breaking abstract: High flow oxygen therapy decreases endotracheal intubation requirement in patients with ALI or ARDS
Authors: Guillaume Schnell, Claire Andrejak, Bouchra Lamia, Bénédicte Toublanc, Jean-François Muir, Antoine Cuvelier, Vincent Jounieaux
Journal: European Respiratory Journal (2011)

High flow oxygen (HFO) therapy is able to deliver up to 60L/min of a heated and humidified air-oxygen mixture through nasal cannulae and to provide small amount of positive end-expiratory pressure. Our objective was to assess the outcome of patients admitted for acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) who were treated by HFO and to determine if HFO could decrease endotracheal intubation rate.  We retrospectively selected 38 consecutive patients (median age 57 yrs) admitted in ICU for ALI (n=5, 13%) or ARDS (n=33, 87%) and who underwent HFO (Optiflow®, Fisher & Paykel, France) at admission (PaO2 = 65 mmHg, PaO2/FiO2 = 110±71 mmHg). Most of our population (26/38 patients, 68%) resolved their acute episode with HFO. In this group, invasive ventilation was not required and this decision was not stated on EOL care (success group). PaO2/FiO2 at admission was found higher in the success group (126 vs. 76 mmHg, p=0.04). Failure patients (12/38, 32%) exhibited more comorbidities (Charlson9s score = 4.5 vs. 2.5, p=0.034) and appeared more severe at admission (SAPS2 = 45 vs. 31, p=0.0054). After 24 hours, the %FiO2 under HFO was significantly lower in the success group (50% vs. 70%, p=0.004). The hospitalization length was similar in both groups (p=0.28). Hospital mortality rate was significantly higher in the failure group than in the success group ((92% vs. 4%, p  In conclusion, HFO may avoid endotracheal intubation during ALI/ARDS and its usefulness in hypoxemic respiratory failure needs further investigations.
Inhalation of antibiotics in cystic fibrosis
Authors: DJ Touw, RW Brimicombe, ME Hodson, HG Heijerman, W Bakker
Journal: European Respiratory Journal (1995)

Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis. However, its contribution to the improvement of lung function, infection and quality of life is not well-established. All articles published from 1965 until the present time concerning the inhalation of antibiotics in cystic fibrosis were collected by computerized literature search and analysed. Effective aerosol delivery is compromised by nebulizers with limited capacity to produce particles in the respirable range. Twelve studies concerning maintenance treatment were published. Four uncontrolled studies evaluating antibiotic aerosol maintenance treatment in stable patients indicated a beneficial effect in terms of reducing the number of hospital admissions. Eight placebo-controlled studies were found; six of these showed a significant improvement of lung function in the treatment group. Four studies showed a reduction of the number of hospital admissions. In some studies, there was a considerable negative effect of the nebulized placebo solution on the outcome, probably due to the improper choice of its osmolarity. Studies with antibiotic aerosols as adjunct to intravenous therapy in cystic fibrosis patients with an acute exacerbation showed no enhancement of the clinical effects of the intravenous antibiotic by the aerosol; sputum colony counts, however, were lower. Toxicity studies carried out so far have shown no renal or ototoxicity; however, long-term toxicity studies still have to be performed using higher dosages. Introduction or selection of resistant bacteria is relatively rare, but remains a matter of concern. Aerosol maintenance treatment with an appropriate antibiotic in high enough dosage can be recommended for patients with cystic fibrosis chronically infected with P. aeruginosa, and may improve lung function and reduce the number of hospital admissions due to an acute exacerbation.
Treatment, trial participation and survival in adult acute myeloid leukemia: a population-based study in the Netherlands, 1989–2012
Authors: A G Dinmohamed, O Visser, Y van Norden, N M A Blijlevens, J J Cornelissen, G A Huls, P C Huijgens, P Sonneveld, A A van de Loosdrecht, G J Ossenkoppele, B Löwenberg, M Jongen-Lavrencic
Journal: Leukemia (2015)