tbuckley/cabot-search huggingface dataset:
Differential Killing of Human Carcinoma Cells Supplemented With n-3 and n-6 Polyunsaturated Fatty Acids&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M E Bégin, G Ells, U N Das, D F Horrobin
Journal: JNCI Journal of the National Cancer Institute (1986)

The effects of essential fatty acids on cell proliferation and cell viability of 3 human tumor and 4 normal cell lines were tested in vitro. It was found that n-3 and n-6 fatty acids supplemented at 20 micrograms/ml killed human breast, lung, and prostate cancer cells selectively. Normal human fibroblasts and other normal cells were not killed, but their rate of division was lowered. The most selective cytotoxic effects were obtained with fatty acids containing 3, 4, and 5 double bonds. The degree of inhibition of growth and/or loss of viability depended on a given fatty acid, on cell density, on fatty acid concentration, and on the type of cell. When eicosapentaenoate, gammalinolenate, or arachidonate was added to cocultures made of human cancer cells with normal fibroblasts, the cancer cells were selectively eliminated. These results, combined with the observation that certain fatty acids coupled to cytotoxic agents may enhance the cytotoxic activity, suggest that treatment of cancer with polyunsaturated fatty acids containing 3, 4, and 5 double bonds has potential clinical usefulness.
Treatment-Induced Pathologic Necrosis: A Predictor of Local Recurrence and Survival in Patients Receiving Neoadjuvant Therapy for High-Grade Extremity Soft Tissue Sarcomas
Authors: Fritz C. Eilber, Gerald Rosen, Jeffery Eckardt, Charles Forscher, Scott D. Nelson, Michael Selch, Frederick Dorey, Frederick R. Eilber
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine whether treatment-induced pathologic necrosis correlates with local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. PATIENTS AND METHODS: Four hundred ninety-six patients with intermediate- to high-grade extremity soft tissue sarcomas received protocol neoadjuvant therapy. All patients underwent surgical resection after neoadjuvant therapy and had pathologic assessment of tumor necrosis in the resected specimens. RESULTS: The 5- and 10-year local recurrence rates for patients with ≥ 95% pathologic necrosis were significantly lower (6% and 11%, respectively) than the local recurrence rates for patients with less than 95% pathologic necrosis (17% and 23%, respectively). The 5- and 10-year survival rates for the patients with ≥ 95% pathologic necrosis were significantly higher (80% and 71%, respectively) than the survival rates for the patients with less than 95% pathologic necrosis (62% and 55%, respectively). Patients with less than 95% pathologic necrosis were 2.51 times more likely to develop a local recurrence and 1.86 times more likely to die of their disease as compared with patients with ≥ 95% pathologic necrosis. The percentage of patients who achieved ≥ 95% pathologic necrosis increased to 48% with the addition of ifosfamide as compared with 13% of the patients in all the other protocols combined. CONCLUSION: Treatment-induced pathologic necrosis is an independent predictor of both local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. A complete pathologic response (≥ 95% pathologic necrosis) correlated with a significantly lower rate of local recurrence and improved overall survival.
Interleukin-6 and chondrocyte mineralisation act in tandem to promote experimental osteoarthritis
Authors: Sonia Nasi, Alexander So, Christèle Combes, Michel Daudon, Nathalie Busso
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> Basic calcium phosphate (BCP) crystal and interleukin 6 (IL-6) have been implicated in osteoarthritis (OA). We hypothesise that these two factors may be linked in a reciprocal amplification loop which leads to OA. <h3>Methods</h3> Primary murine chondrocytes and human cartilage explants were incubated with hydroxyapatite (HA) crystals, a form of BCP, and the modulation of cytokines and matrix-degrading enzymes assayed. The ability of IL-6 to stimulate chondrocyte calcification was assessed in vitro. The mechanisms underlying the effects of HA on chondrocytes were investigated using chemical inhibitors, and the pathways mediating IL-6-induced calcification characterised by quantifying the expression of genes involved in chondrocyte mineralisation. The role of calcification in vivo was studied in the meniscectomy model of murine OA (MNX), and the link between IL-6 and cartilage degradation investigated by histology. <h3>Results</h3> In chondrocytes, BCP crystals stimulated IL-6 secretion, further amplified in an autocrine loop, through signalling pathways involving Syk and PI3 kinases, Jak2 and Stat3 molecules. Exogenous IL-6 promoted calcium-containing crystal formation and upregulation of genes involved in calcification: the pyrophosphate channel Ank, the calcium channel Annexin5 and the sodium/phosphate cotransporter Pit-1. Treatment of chondrocytes with IL-6 inhibitors significantly inhibited IL-6-induced crystal formation. In meniscectomised mice, increasing deposits of BCP crystals were observed around the joint and correlated with cartilage degradation and IL-6 expression. Finally, BCP crystals induced proteoglycan loss and IL-6 expression in human cartilage explants, which were reduced by an IL-6 inhibitor. <h3>Conclusions</h3> BCP crystals and IL-6 form a positive feedback loop leading to OA. Targeting calcium-containing crystal formation and/or IL-6 are promising therapeutic strategies in OA.
Airway Bacterial Load and FEV<sub>1</sub> Decline in Patients with Chronic Obstructive Pulmonary Disease
Authors: Tom M. A. Wilkinson, Irem S. Patel, Mark Wilks, Gavin C. Donaldson, Jadwiga A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Chronic obstructive pulmonary disease (COPD) is characterized by an accelerated decline in lung function and progressive airway inflammation. Bacteria have been isolated from the lower airway of stable COPD patients, and airway inflammation has been related to bacterial load and type. The relationship between bacterial colonization, airway inflammation, and lung function decline remains uncertain. We studied 30 patients with COPD, mean (SD) FEV1 0.947 (0.329), 34.8% (13.6%) predicted, for 12 months. Sputum collected at recruitment and the end of the study was analyzed for cytokines and for quantitative bacteriology. The decline in FEV1 was 57.6 (137.6) ml year−1. Bacterial growth was identified in all subjects, with an initial count of 107.47(0.91) cfu ml−1 rising to 107.93(0.81) cfu ml−1 at the end of the study (p = 0.019). FEV1 decline was related to this increase in airway bacterial load (r = 0.59, p = 0.001). FEV1 decline was greater in subjects who exhibited a change in the colonizing bacterial type compared with those with persistence of a single bacterial species over the study period (p = 0.017). Higher sputum interleukin (IL-8) was associated with greater declines in FEV1 (p = 0.03). Rising airway bacterial load and species changes are associated with greater airway inflammation and accelerated decline in FEV1. Bacterial colonization in COPD is an important factor in disease progression.
Prognosis of patients with active tuberculosis requiring intensive care unit
Authors: Filiz Kosar, Levent Dalar, Emel Eryüksel, Sibel Yurt
Journal: European Respiratory Journal (2012)

Tuberculosis remains an important health problem. The aim of this sudy to determine the mortality rate of patients with active tuberculosis requiring intensive care unit.  We conducted an observational study. Patients with confirmed active tuberculosis admitted to ICU between May 2010 and January 2012 were identified and enrolled. Clinical data and mortality rate were recorded.  A total of 19 tuberculosis patients admitted to ICU were included. Mean Acute Physiology and Chronic Health Evaluation (APACHE) II score at admission was 17.00 ±7,7. Twelve patients (63 %) required mechanical ventilation. The mortality was 12 of 19 (63 %). The reasons associated with ICU admission were massive hemoptysis in two patients, empyema in one patients, active tuberculosis and sepsis in nine patients, tuberculous meningitis in one patients and tuberculosisand/or pneumonitis in others. High APACHE II score and invasive mechanical ventilation use were significiantly associated mortality (p  These data indicate a high mortality of patients with tuberculosis requiring intensive care unit care and further studies needed to determine associated risk factors.   Keywords:  mortality, tuberculosis, intensive care.
Stromal protein expression in breast cancer is differentially regulated by TGF-&amp;bgr;1
Authors: M. Van Bockstal, K. Lambein, M. Van Gele, E. De Vlieghere, R. Limame, G. Braems, M. Bracke, H. Denys, L. Libbrecht, O. De Wever
Journal: Annals of Oncology (2015)
Four tobacco companies plan action against UK government over standard packaging
Authors: C. Dyer
Journal: BMJ (2015)

Tobacco companies have launched a multi-billion pound legal claim against the UK government for losses as a result of a law that will require them to sell their cigarettes in plain packaging.

The companies claim that forcing them to use unbranded packages amounts to deprivation of highly valuable intellectual property. They say that the law, which is expected to come into force in May 2016, amounts to illegal seizure of their trademarks by the state.

Philip Morris International and British American Tobacco have filed papers at the High Court in London, and Imperial Tobacco and Japan Tobacco International have signalled that they intend to follow suit. …
Nutrition and Eye Cancer in Cattle&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: David E. Anderson, L. S. Pope, Dwight Stephens
Journal: JNCI Journal of the National Cancer Institute (1970)

The association between nutrition and ocular squamous-cell carcinoma and its precursor lesions was investigated with data derived from a 20-year experiment involving 435 range beef cows. The animals were exposed to a variety of winter feeding programs for 1–15 years. A high level of feeding compared to a low level had an important effect on increasing lesion manifestation as well as its rate of increase with age. More animals with more advanced lesions were observed at earlier ages in the higher feeding levels than in a medium or low level. With the cessation of a feeding trial, the lesion manifestation decreased compared with animals remaining on trial. These decreases were more pronounced in the higher levels than in the low feeding level. Animals fed at a high level were also heavier and larger and had a lower survival rate than those fed at a low level, The age-adjusted disposal rate for eye cancer was higher with high levels of feeding (14%) than in the low level (1.5%). Animals fed at a high level also calved earlier and were reproductively superior to those fed at a low level.
Abstract 15409: Inactivation of 14-3-3 Protein Exacerbates Cardiac Dysfunction and Reduces Survival in Mice with Myocardial Infarction
Authors: Rajarajan Amirthalingam Thandavarayan, Somasundaram Arumugam, Flori R Sari, Vijayasree V Giridharan, Vijayakumar Sukumaran, Arun Prasath Lakshmanan, Vivian Soetikno, Ma Meilei, Tetsuya Konishi, Kenichi Watanabe
Journal: Circulation (2011)

Introduction: 14-3-3 family members are dimeric phosphoserine-binding proteins that participate in signal transduction and checkpoint control pathways. For instance, modulations of 14-3-3 protein e...
Antibiotics promote inflammation through the translocation of native commensal colonic bacteria
Authors: Kathryn A Knoop, Keely G McDonald, Devesha H Kulkarni, Rodney D Newberry
Journal: Gut (2015)

Antibiotic use is associated with an increased risk of developing multiple inflammatory disorders, which in turn are linked to alterations in the intestinal microbiota. How these alterations in the intestinal microbiota translate into an increased risk for inflammatory responses is largely unknown. Here we investigated whether and how antibiotics promote inflammation via the translocation of live native gut commensal bacteria.Oral antibiotics were given to wildtype and induced mutant mouse strains, and the effects on bacterial translocation, inflammatory responses and the susceptibility to colitis were evaluated. The sources of the bacteria and the pathways required for bacterial translocation were evaluated using induced mutant mouse strains, 16s rRNA sequencing to characterise the microbial communities, and in vivo and ex vivo imaging techniques.Oral antibiotics induced the translocation of live native commensal bacteria across the colonic epithelium, promoting inflammatory responses, and predisposing to increased disease in response to coincident injury. Bacterial translocation resulted from decreased microbial signals delivered to colonic goblet cells (GCs), was associated with the formation of colonic GC-associated antigen passages, was abolished when GCs were depleted and required CX3CR1(+) dendritic cells. Bacterial translocation occurred following a single dose of most antibiotics tested, and the predisposition for increased inflammation was only associated with antibiotics inducing bacterial translocation.These findings reveal an unexpected outcome of antibiotic therapy and suggest that bacterial translocation as a result of alterations in the intestinal microflora may provide a link between increasing antibiotic use and the increased incidence of inflammatory disorders.
Combined etoposide and 5-azacitidine in children and adolescents with refractory or relapsed acute nonlymphocytic leukemia: a Pediatric Oncology Group Study.
Authors: N Hakami, A T Look, P C Steuber, J Krischer, R Castleberry, R Harris, Y Ravindranath, T J Vietti
Journal: Journal of Clinical Oncology (1987)

An intensive regimen of combined etoposide (VP-16) and 5-azacitidine (5-Az) was used to treat 96 children and adolescents with refractory or relapsed acute nonlymphocytic leukemia (ANLL). Patients were given two sequential five-day courses of VP-16, 250 mg/m2 for three days, followed by 5-Az, 300 mg/m2 for two days. An additional five-day course was administered if marrow aplasia was not evident by day 13. A complete remission rate of 45% was achieved with a median of two courses of VP-16 and 5-Az. The outcome of induction therapy was not influenced by prior treatment, blast cell morphology, or disease status on study entry (refractory or relapsed). Twenty-seven patients have relapsed after remission periods of 35 to 920 days (median, 110 days); seven others are free of leukemia for up to 519 days. The effectiveness of VP-16/5-Az combination therapy in patients refractory to anthracyclines and cytarabine indicates a potential role for these compounds in first-line treatment of patients with ANLL.
Abstract 409: Incidence and Prognostic Impact of Persistent Microvascular Obstruction as Assessed by Cardiac Magnetic Resonance in the Setting of Non ST Segment Elevation Myocardial Infarction
Authors: Alexandre Cochet, Luc Lorgis, Alain Lalande, Marianne Zeller, Paul Walker, Claude Touzery, Jean-Eric Wolf, Francois Brunotte, Yves Cottin
Journal: Circulation (2009)
Effects on health care utilisation of early pulmonary rehabilitation on hospitalisation for an acute exacerbation of chronic respiratory disease
Authors: Neil Greening, Johanna Willams, Theresa Harvey-Dunstan, Fayyaz Hussain, John Bankart, Emma Chaplin, Emma Vincent, Rudo Chimera, Mike Morgan, Sally Singh, Michael Steiner
Journal: European Respiratory Journal (2013)

Introduction : Hospitalisation for acute exacerbations of chronic respiratory disease (AECRD) are important events and are associated with future increased health care utilisation.

Aim : Establish the effects of a pulmonary rehabilitation (PR) programme starting during hospitalisation for an AECRD.

Methods : A 2 centre, single-blinded, randomised, control trial comparing a six week PR, including home based rehabilitation following hospital discharge, starting on hospitalisation with usual care was conducted. Primary outcome was hospitalisation rate at 12 months. The number of hospital days and time to first readmission were also recorded.

Results : 389 patients were recruited. There was no difference in hospitalization rate at 12 months (Intervention 59.9% vs Control 57.5%, p=0.434). A reduction in hospital days was seen in the intervention group (Incidence Rate Ratio 0.705, 95% CI 0.512-0.971, p=0.032). Figure one shows the cumulative number of hospital days against subsequent admissions (17.9% difference). There was no difference in time to first readmission.

![Figure][1] 



Conclusions : Early PR did not affect hospitalisation rate however a significant reduction in the number of hospital days was seen in the intervention group. Early pulmonary rehabilitation may lessen the impact of hospital readmission.

 [1]: pending:yes
Nintedanib reduces bleomycin-induced lung inflammation and fibrosis in mice
Authors: Lutz Wollin, Isabelle Maillet, Valérie Quesniaux, Bernhard Ryffel
Journal: European Respiratory Journal (2013)

Introduction: In a Phase II clinical trial, 12 months’ treatment with nintedanib (BIBF 1120) reduced the rate of decline in FVC in patients with idiopathic pulmonary fibrosis (IPF) by 68.4% versus placebo, which approached statistical significance.  Aim: To explore its mode of action, nintedanib was tested in a preventive and therapeutic mouse model of lung inflammation and fibrosis.  Methods: Lung fibrosis was induced in mice by a single intratracheal administration of bleomycin. Nintedanib was administered by gavage q.d. at 30 mg/kg or 60 mg/kg from day 0 to day 14 (preventive treatment) or from day 7 to 21 (therapeutic treatment).  Results: After 14 days, bleomycin caused increased macrophages and lymphocytes in the BALF and elevated IL-1β, TIMP-1 and collagen levels in the lung. Histology revealed chronic inflammation and fibrosis. At day 21, the pathology was very similar to day 14, but histology revealed slightly increased inflammation and fibrosis and TIMP-1 levels were nearly doubled. Preventive nintedanib treatment significantly reduced lymphocytes but not macrophages. Furthermore, IL-1β, TIMP-1, and lung collagen were significantly reduced. Histological analysis showed significantly diminished lung inflammation and fibrosis. Therapeutic treatment at 60 mg/kg caused similar inhibitory effects compared to preventive treatment, but at 30 mg/kg the effect size was smaller.  Conclusion: Nintedanib, when used as preventive or therapeutic treatment, effectively reduced lung inflammation and fibrosis in mice. The anti-inflammatory and anti-fibrotic features of nintedanib may impact the progressive course of fibrotic lung diseases like IPF.
Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials
Authors: S Burdett, Mkb Parmar, LA Stewart, RL Souhami, R. Arriagada, DJ Girling, JP Pignon, Torri, AH Brichet, JJ Lafitte, B Dautzenberg, M Debevec, Kovac, RJ Stephens, A Gregor, S Piantadosi, P. Rocmans, Paul Van Houtte, M Wang
Journal: The Lancet (1998)
A New Human Breast Carcinoma Cell Line (PMC42) With Stem Cell Characteristics. III. Hormone Receptor Status and Responsiveness
Authors: R H Whitehead, S J Quirk, A A Vitali, J W Funder, R L Sutherland, L C Murphy
Journal: JNCI Journal of the National Cancer Institute (1984)

PMC42 is a new human breast carcinoma cell line. In this report the content of estrogen, progesterone, and glucocorticoid receptors in PMC42 has been determined. The estrogen receptor content (1,750 cytoplasmic sites and 350 nuclear sites) was lower than that described for MCF7 and T47D. The cells would not proliferate in serum-free medium without the addition of beta-estradiol (optimum concentration 10(-8) M) or progesterone (5 X 10(-8) M). The addition of both hormones induced a more than additive increase in proliferation (P less than .005, n = 18). Similarly, addition of insulin or hydrocortisone induced proliferation; however, in this case, the effect of the hormones together was only additive. The addition of tamoxifen (10(-6) M) led to a significant decrease in cell numbers and inhibited the stimulatory effects of 10(-8) M beta-estradiol.
Abstract P213: Habitual Coffee Intake, Blood Pressure and Risk of Stroke: a Meta-analysis of Prospective Studies
Authors: Pasquale Strazzullo, Lanfranco D'Elia, Giulia Cairella, Francesca Garbagnati, Giovanni Rossi, Luca Scalfi
Journal: Circulation (2014)

Background: Prospective cohort studies estimated the predictive role of exposure to coffee consumption and risk of hypertension (HP) or cerebrovascular disease, with contrasting results. Therefore, we carried out a meta-analysis to assess the relation between habitual coffee intake and risk of HP and stroke in the general population. Methods: We performed a systematic search for prospective studies published without language restrictions between 1966 and July 2013. Inclusion criteria were: original article, prospective design, adult general population study, assessment of coffee intake as baseline exposure, assessment of HP or stroke as outcome, and follow-up of at least 2 years. To evaluate risks of HP and stroke, relative risks and 95% confidence intervals for “low-moderate” (2-3 cups/d), “high”(4-6) and “very high”(&gt;6) compared with “reference” (0-1) coffee intake categories were extracted and pooled using a random effect model. Heterogeneity, publication bias, subgroup and meta-regression analyses were performed. Results: Four studies for HP (171,460 participants and 39,851 HP diagnoses) and 10 for stroke (969,656 participants with 12,990 events) met the inclusion criteria. Coffee intake was assessed by dietary questionnaire. In pooled analyses, “low-moderate” and “high” coffee intake were both inversely associated with the risk of stroke (RR=0.84, 95% C.I. 0.78 to 0.91 and 0.83, 0.72 to 0.96, respectively) but not with risk of HP. “Very high” coffee intake was not significantly associated with either risk of stroke or of HP. There was significant heterogeneity between studies, while some evidence of publication bias was detected only in the analysis of HP risk. Sub-group analysis suggested an influence of gender and of geographic location, and meta-regression analysis detected age at baseline and length of follow-up as further sources of heterogeneity. Decaffeinated coffee consumption was not related to risk of stroke or HP. Conclusions: This meta-analysis of the available prospective studies showed that habitual coffee intake is not associated with higher risk of HP in the general population and that moderate-high coffee consumption is inversely associated with risk of stroke. A protective effect of coffee consumption towards cerebrovascular disease might be exerted through mechanisms independent of changes in blood pressure.