tbuckley/cabot-search huggingface dataset:
Mechanisms of Resistance to Mammary Tumor Development in C57BL and I Strains of Mice. I. Noduligenesis, Tumorigenesis, and Characteristics of Nodules and Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S. Nandi, Sandra Haslam, Cheryl Helmich
Journal: JNCI Journal of the National Cancer Institute (1972)

Studies to determine the mechanisms of resistance to mammary tumor development in C57BL and I strains of mice are reported. Fragments of mammary tissues and whole mammary glands of C57BL and I mice were transplanted into parenchyma-free mammary fat pads and in subcutaneous sites of (C57BL × I)F1 (F1+) hosts infected with mammary tumor virus (MTV). Precancerous nodules developed in mammary transplants from both C57BL and I donors as well as in the in situ glands of F1+ hosts receiving noduligenic hormone treatment. Nodules arising in C57BL mammary transplants gave rise to hyperactive outgrowths and mammary tumors on transplantation into parenchyma-free fat pads of C57BL and (C57BL × I)F1 (F1−) hosts. These tumors were easily transplantable in subcutaneous sites of C57BL hosts. Tumors and hyperactive nodule outgrowths both contained MTV B particles, and the tumors also contained biologically infectious MTV. Nodules arising in I mammary transplants produced hyperactive outgrowths and tumors on transplantation into parenchyma-free fat pads of F1 hosts, but not in syngeneic MTV-free hosts. The tumors arising in I nodule transplants in F1− hosts were easily transplantable in I+ mice that had been foster-nursed on MTV-infected mothers, but not in I mice that had received milk from their own mothers. The I nodule outgrowths and tumors arising in F1− mice contained abundant MTV B particles, and such tumors also were positive in bioassays, even after transplantation first into I+ and then into I mice. It is suggested that the mechanisms of resistance to MTV-induced mammary tumor development are different in the I and C57BL strains.
Minute ventilation (V'E) and heart rate (HR) relationship during exercise in chronic cardiac and pulmonary diseases
Authors: Paolo Onorati, Paolo Marinelli, Patrizia Paoletti, Alessandro Maria Ferrazza, Gabriele Valli, Mattia Internullo, Dario Martolini, Paolo Palange
Journal: European Respiratory Journal (2012)

We have demonstrated in healthy subjects that the rate of increase in minute ventilation over heart rate (ΔV'E/ΔHR), during incremental exercise, is described by a bilinear response, with a slope's change at the ventilatory compensation point (VCP)( Onorati P., Eur J Appl Physiol, 2008; 104:87–94;Med Sci Sports Exerc 2012 in press ). We aimed at analyzing the exercise ΔV'E/ΔHR response in patients with chronic cardiopulmonary diseases. Methods. Patients with chronic obstructive pulmonary disease (COPD) (n=10) and cardiovascular diseases (CVD)(Pulmonary Arterial Hypertension, PAH, n=9; and Chronic Heart Failure, CHF, n=10) underwent one-minute incremental cycling exercise. Gas exchange, V'E, HR were measured breath-by-breath. ΔV'E/ΔHR response, before (S1) and after the VCP (S2) were computed by linear regression analysis. Results. In all patients we observed a linear response of the ΔV'E/ΔHR relationship; in COPD patients S1 was steeper vs PAH and CHF and approached maximal voluntary ventilation (MVV). S2 slope was observed manly in CVD patients and approached maximal predicted HR.

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A good agreement (Bland-Altman test) for VCP detection was observed between ΔV'E/ΔHR vs the ventilatory equivalent for CO2 (V'E/V'CO2) methods. Conclusions. In patients with COPD and CVD, the ΔV'E/ΔHR response during cycling incremental exercise can be utilized to discriminate between ventilatory and circulatory limitation.

 [1]: pending:yes
Nutritional aspects and asthma. Influence of malnutrition factors on severity of asthma
Authors: Zoran Stojanovic, Carlos Martinez Rivera, Carmen Centeno, Elena Molins, Estefania Sanchez, Caroline Becker, Marisa Rivera, Joan Ruiz Manzano, Josep Morera
Journal: European Respiratory Journal (2012)

While obesity is a risk factor for asthma that is increasingly studied, malnutrition in asthma is less known.  Objective:  To determine if nutritional aspects have an influence on severity of asthma.  Materials and methods:  We included 91 asthmatic patients and studied 4 aspects related with asthma: severe persistent asthma or not, obstructive or not, poorly controlled and >1 exacerbation/year or not. Nutritional status was measured by BMI, waist/hip ratio, albumin, prealbumin and bioimpedance. Systemic inflammation by Hb, hematocrit, CRP and Ddimer. Significant was p  Results:  Average age was 48 years, 21.2% men, 22.2% poorly controlled asthma, 45% had obstruction, 58% severe persistent asthma, 42.6% had >1 exacerbation/year. Older patients had more obstruction, severity, exacerbations and worse ACT. Higher Charlson index was associated with severity, obstruction and exacerbations. Increased CRP was related with obstruction (7.2 ±10 vs 2.8±3 p 1 exacerbation/year had lower percent of muscle mass (37.9±7.9 vs 42.9±8.3 p  Conclusions:  Lower percentage of muscle mass is associated with more exacerbations and low FFMI with obstruction in asthma. With more systemic inflammation, malnutrition has greater role, as in asthma with airflow obstruction.
MDA helminth control: more questions than answers
Authors: Graham F Medley, T Deirdre Hollingsworth
Journal: The Lancet Global Health (2015)

Soil transmitted helminths (STH) and schistosomiasis (SCH) have been recognised as important diseases for decades. Diagnostics, treatments and understanding were accrued throughout the 20th century, and reached the point where control and elimination appeared to be primarily a matter of implementation of mass drug administration (MDA) programmes [1]. However, in 2015, both STH and SCH remain global health problems, so perhaps we do not have the right tools, or we are not applying them effectively. To our knowledge, MDA for STH and SCH has never been demonstrated to eliminate infection without concomitant economic development. What are we missing?
Occurrence of Spontaneous Tumors in the Germfree F344 Rat 2
Authors: Miriam R. Sacksteder
Journal: JNCI Journal of the National Cancer Institute (1976)

The incidence of spontaneously occurring neoplasms was observed over 10 years in a colony of germfree F344 rats (78 males and 102 females) representing 10 generations of inbredding. Leukemia was the most common neoplasm (25.6% of males, 36% of females) followed by mammary tumors (11.5% of males, 19.6% of females). Various other tumors developed in 9% of the males and 5% of the females. The overall incidence of spontaneous tumors was comparable to that reported for conventional rats of different strains. This was particularly true of leukemia for which the most data were available. However, for unknown reasons, significantly fewer solid tumors were observed in germfree than in conventional male rats.
Changes in the lower airway bacterial community of from adult non-CF bronchiectasis population are significantly associated with exacerbations and the presence of Heamophilus influenza
Authors: Paul Purcell, Stephen Cummings, Hannah Jary, Anthony De Soyza, John Perry
Journal: European Respiratory Journal (2012)

Background : The aim was to investigate the polymicrobial communities in sputum samples derived from an adult non cystic fibrosis bronchiectasis (nCFBr) population using culture independent methods. The cohort consisted of 70 individuals with HRCT proven nCFBr. Twenty patients presented at the clinic for sputum collection with symptoms consistent with exacerbations, the remainder were clinically stable.

Methods : DNA was extracted from sputum samples of all patients (n=70). Universal primers were used to amplify the 16S and 28S rDNA, the resulting fragments were analysed by denaturing gradient gel electrophoresis. Demographic and culture data were used in constrained ordination analyses to identify any significant associations between these data and changes in the sputum microbiota.

Results : The presence of P. aeruginosa was significantly correlated with a reduced lung function. Bacterial profiles indicated a significantly different community was present in exacerbating patients compared to those that were clinically stable (P = 0.002). H. influenzae carriage also produced significant changes (P = 0.004) in community structure. Moreover, H. influenza e was never found in samples that harboured P. aeruginosa. Bacterial communities appeared to be randomly assembled. Fungal taxa were scarce.

Conclusions : Bacterial communities from adult non-CF bronchiectasis patients have distinct differences between exacerbating and clinically stable episodes. Persistent colonisation by P.aeruginosa is significantly associated with reduced lung function, and is negatively correlated with H. influenza carriage.
Geographical movement of doctors from education to training and eventual career post: UK cohort studies
Authors: Michael Goldacre, Jean Davidson, Jenny Maisonneuve, Trevor Lambert
Journal: Journal of the Royal Society of Medicine (2013)

To investigate the geographical mobility of UK-trained doctors.Cohort studies conducted by postal questionnaires.UK.A total 31,353 UK-trained doctors in 11 cohorts defined by year of qualification, from 1974 to 2008.Location of family home prior to medical school, location of medical school, region of first training post, region of first career post. Analysis for the UK divided into 17 standard geographical regions.The response rate was 81.2% (31,353/45,061; denominators, below, depended on how far the doctors' careers had progressed). Of all respondents, 36% (11,381/31,353) attended a medical school in their home region and 48% (10,370/21,740) undertook specialty training in the same region as their medical school. Of respondents who had reached the grade of consultant or principal in general practice in the UK, 34% (4169/12,119) settled in the same region as their home before entering medical school. Of those in the UK, 70% (7643/10,887) held their first career post in the same region as either their home before medical school, or their medical school or their location of training. For 18% (1938/10,887), all four locations - family home, medical school, place of training, place of first career post - were within the same region. A higher percentage of doctors from the more recent than from the older cohorts settled in the region of their family home.Many doctors do not change geographical region in their successive career moves, and recent cohorts appear less inclined to do so.
Phase I/II clinical and pharmacokinetic evaluation of liposomal daunorubicin.
Authors: P S Gill, B M Espina, F Muggia, S Cabriales, A Tulpule, J A Esplin, H A Liebman, E Forssen, M E Ross, A M Levine
Journal: Journal of Clinical Oncology (1995)

PURPOSE Since liposomal encapsulation of anticancer drugs may enhance antitumor activity while reducing toxicity in vitro, we evaluated liposomally encapsulated daunorubucin (DaunoXome; Vestar, Inc, San Dimas, CA) for safety, pharmacokinetics, and potential efficacy in patients with AIDS-related Kaposi's sarcoma (AIDS-KS). PATIENTS AND METHODS Forty patients with advanced AIDS-KS were accrued. Successive cohorts received DaunoXome at doses of 10, 20, 30, and 40 mg/m2 given once every 3 weeks, and 40, 50, and 60 mg/m2 given once every 2 weeks. Selected KS and solid-tumor patients underwent pharmacokinetic evaluation. RESULTS The area under the plasma concentration curve (AUC) ranged from 16.9 micrograms.h/mL to 375.3 micrograms./mL and the alpha half-life ranged from 7.8 to 8.3 hours at 10 mg/m2 to 60 mg/m2, respectively. Both pharmacokinetic profiles were significantly better compared with free daunorubicin. DaunoXome was well tolerated with no significant alopecia, mucositis, or vomiting. Neutropenia (&lt; 1,000/microL occurred in 17% of cycles and was severe (&lt; 500/microL) in only 2%. Anemia and thrombocytopenia were uncommon. Other adverse events included mild to moderate fatigue, nausea, and diarrhea. Even after cumulative doses greater than 1,000 mg/m2, no significant declines in cardiac function were observed. Twenty-two patients who received 50 and 60 mg/m2 were assessable for tumor response; 12 (55%) had a partial response (PR) or clinical complete response (CR). The median survival duration in all patients was 9 months. Prognostic factors for short survival were low CD4 lymphocyte counts (P = .004) and prior anthracycline therapy (P = .02). CONCLUSION DaunoXome has an improved pharmacokinetic profile compared with free daunorubicin, and is well tolerated. DaunoXome can be given safely at doses up to 60 mg/m2 every 2 weeks and has significant antitumor activity in patients with AIDS-KS.
Glycine and N-Methyl-d-Aspartate Receptors: Physiological Significance and Possible Therapeutic Applications
Authors: Wojciech Danysz, Chris G. Parsons
Journal: Pharmacological Reviews (1998)

Since the finding by [Johnson and Ascher (1987)][1] demonstrating that glycine enhances electrophysiological responses mediated by N-methyl-d-aspartate (NMDA)b-sensitive glutamatergic receptors, considerable interest has been devoted to this topic (for reviews, see [Dingledine et al. , 1990][2]; [
Inhibition of Lymphoma 6C3HED by &lt;sc&gt;l&lt;/sc&gt;-Asparaginase From &lt;italic&gt;Serratia marcescens&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: John W. Boyd, Arthur W. Phillips
Journal: JNCI Journal of the National Cancer Institute (1971)

C3H mice bearing the 6C3HED lymphoma manifested complete regression of the tumor after the intraperitoneal administration of a single dose of purified l-asparaginase from Serratia marcescens. The blood clearance rate of this enzyme was delayed in these animals as it was in normal mice inoculated with the lactic dehydrogenase virus. Similar observations were made concurrently on Escherichia coli L-asparaginase which was less inhibitory to tumor growth than the enzyme from S. marcescens.
Gas exchange measures during six minute walk test are more sensitive to disease severity than walk distance
Authors: Norman Morris, Helen Seale, Bruce Johnson, Fiona Kermeen
Journal: European Respiratory Journal (2013)

Introduction: In pulmonary hypertension (PH) the 6-min walk distance (6MWD) differentiates patients based on WHO Functional Class (FC), however its relationship to other indices of disease severity such as pulmonary artery pressure (PAP) and vascular resistance (PVR) is unclear. There is evidence that indices of gas exchange obtained during exercise such as breathing efficiency (BE: VE/VECO2) and end tidal CO2 (PETCO2) relate to disease severity, hence the purpose of this study was to examine the relationship between disease severity and gas exchange measures made during a 6MWT. Method: 50 patients (49 ±17 yr, FC=2.2±0.5), completed a 6MWT whilst gas exchange was measured simultaneously. End exercise 6MWD, BE, PETCO2 and a non-invasive gas exchange estimate of pulmonary vascular capacitance (PCAP=oxygen pulse x PETCO2) were correlated with resting echocardiography measures of RV systolic pressure (RVSP). In a subgroup (n=15, FC=2.3±0.5, Category 1 PH) resting right heart catheterisations (RHC) were performed and PAP and PVR determined. Result: The mean 6MWD was 504±102m. There was no relationship between 6MWD and RVSP (70±23 mmHg, r=-0.15, p=0.51) however end exercise BE (42±10, r=0.63), PETCO2 (27.2±7.1 mmHg, r=-0.60) and PCAP (204 ± 107, r=-0.47) were significantly (p<0.01) related to RVSP. In the subgroup of RHC patients only end exercise PETCO2 (25.7±5.8 mmHg) and PCAP (186±94) were significantly correlated with PVR (PETCO2: r=-0.46, PCAP: r=-0.56) and PAP (PETCO2: r=-0.44, PCAP: r=-0.56). Conclusion: Non-invasive gas exchange measures may be a useful addition to the 6MWD and provide a more sensitive method for PH screening and tracking response to therapy.
Determining the fate of hepatic cells by lineage tracing: Facts and pitfalls
Authors: Frédéric P. Lemaigre
Journal: Hepatology (2014)

Slow renewal of the epithelial cells by proliferation ensures homeostasis of the liver, but extensive proliferation may occur upon injury. When proliferation is impaired, transdifferentiation of mature cells or differentiation of stem cells allows production of new hepatocytes and cholangiocytes. While lineage tracings using cyclization recombinase (Cre) recombinase–mediated cell labeling represent the gold standard for defining cell fate, there are more variables than was initially realized. This led to controversies about the capacity of liver cells to switch their fate. Here, I review how cells are traced in the liver and highlight the experimental pitfalls that may cause misinterpretations and controversies. (H epatology 2015;61:2100–2103)
Abstract 16313: De-Activation of Mitogen-Activated Protein Kinases in Peripheral Blood Mononuclear Cells of Patients Undergoing Trans-Catheter Aortic Valve Implantation
Authors: Anna Franzone, Alessandro Cannavo, Cinzia Perrino, Marco Ferrone, Eugenio Stabile, Armando Pucciarelli, Giovanni Sorropago, Vincenzo Lucchetti, Paolo Rubino, Giovanni Esposito
Journal: Circulation (2011)

Trans-catheter aortic valve implantation (TAVI) is a promising technique for patients with severe aortic stenosis (AS) and high surgical risk. Since we have previously shown that Mitogen Activated ...
Management of chemotherapy-induced anemia in patients with lung cancer (LC): A comparative study of erythropoietic agents
Authors: Angelica Tiotiu, Christelle Clément-Duchêne, Pierre Vaillant, Pauline Barbier, Decebal Tiotiu, Yves Martinet
Journal: European Respiratory Journal (2012)

Chemotherapy-induced anemia is a frequent complication of LC.Platinum-based chemotherapies (CT) particularly impair erythropoietin production.One option for the management of this anemia is the administration of recombinant human erythropoietin (RHE) which stimulates red blood cell (RBC) formation.  We compared the efficacy and safety of two types of RHE: epoetin alpha (Eprex) and epoetin beta (NeoRecormon) in anemic patients with LC.Thirty eight patients (mean age 62 years) receiving CT for a LC (stage III and IV) with anemia (hemoglobin level≤11g/dl) were included: 19 patients in group 1 treated by Eprex 40000UI/week and 19 patients in group 2 treated by NeoRecormon 30000UI/week for 6 weeks. A hematopoietic response was defined as an increase in hemoglobin concentration ≥2g/dl or hemoglobin (Hb) concentration ≥12g/dl in the absence of a RBC transfusion.The mean Hb levels at baseline were identical: 10 g/dl in group 1 and 9.8 g/dl in group 2. Each group was divided into two subgroups (transfused and non-transfused). 15.8% of patients in the first group required a RBC transfusion versus 36.8% in the second group (p=0.26). The mean changes in hemoglobin level during treatment in non-transfused patients were 0.83 g/dl for group 1 (p=0.003) and 0.31 g/dl for group 2 (p=0.13) without statistical difference among groups (p=0.08). While 12.5% patients in group 1 had a significant hematopoietic response, none was observed in group 2. Two patients in group 2 developed thrombotic events.  The tested erythropoietic agents increased the Hb level in anemic patients with LC. In our study epoetin alpha was better in terms of efficacy and safety than epoetin beta.
A randomized study comparing chemotherapy alone with chemotherapy followed by radiotherapy in patients with pathologically staged IIIA Hodgkin's disease.
Authors: D Crowther, J Wagstaff, D Deakin, I Todd, P Wilkinson, H Anderson, G Blackledge, M Jones, J H Scarffe
Journal: Journal of Clinical Oncology (1984)

This paper reports the five-year follow-up (range, 1-8 years) of 56 patients with pathologic stage IIIA Hodgkin's disease randomized for chemotherapy alone or chemotherapy followed by radiotherapy to previous areas of disease (26 treated with mustine, vinblastine, procarbazine, and prednisolone [MVPP] alone, 30 with MVPP and radiotherapy). Of the 56 patients 53 (95%) achieved a complete remission with chemotherapy and of these only five (9%) have relapsed; three died of Hodgkin's disease. There was no improvement in relapse-free survival associated with the uses of radiotherapy following chemotherapy but in view of the small numbers of relapses and the excellent results following chemotherapy alone, a significant improvement could not be expected. The use of MVPP alone can be recommended as an alternative therapy for patients with stage IIIA Hodgkin's disease. This avoids both the physical and psychologic morbidity associated with the high relapse rate following extensive primary radiotherapy and the necessity of combined modality treatment for about half these patients. The question of whether radiotherapy should be given to areas of previous bulk following chemotherapy has not yet been answered in this trial which is continuing.
Pancreatic Cancer Cell Migration and Metastasis Is Regulated by Chemokine-Biased Agonism and Bioenergetic Signaling
Authors: Ishan Roy, Donna M. McAllister, Egal Gorse, Kate Dixon, Clinton T. Piper, Noah P. Zimmerman, Anthony E. Getschman, Susan Tsai, Dannielle D. Engle, Douglas B. Evans, Brian F. Volkman, Balaraman Kalyanaraman, Michael B. Dwinell
Journal: Cancer Research (2015)

Abstract Patients with pancreatic ductal adenocarcinoma (PDAC) invariably succumb to metastatic disease, but the underlying mechanisms that regulate PDAC cell movement and metastasis remain little understood. In this study, we investigated the effects of the chemokine gene CXCL12, which is silenced in PDAC tumors, yet is sufficient to suppress growth and metastasis when re-expressed. Chemokines like CXCL12 regulate cell movement in a biphasic pattern, with peak migration typically in the low nanomolar concentration range. Herein, we tested the hypothesis that the biphasic cell migration pattern induced by CXCL12 reflected a biased agonist bioenergetic signaling that might be exploited to interfere with PDAC metastasis. In human and murine PDAC cell models, we observed that nonmigratory doses of CXCL12 were sufficient to decrease oxidative phosphorylation and glycolytic capacity and to increase levels of phosphorylated forms of the master metabolic kinase AMPK. Those same doses of CXCL12 locked myosin light chain into a phosphorylated state, thereby decreasing F-actin polymerization and preventing cell migration in a manner dependent upon AMPK and the calcium-dependent kinase CAMKII. Notably, at elevated concentrations of CXCL12 that were insufficient to trigger chemotaxis of PDAC cells, AMPK blockade resulted in increased cell movement. In two preclinical mouse models of PDAC, administration of CXCL12 decreased tumor dissemination, supporting our hypothesis that chemokine-biased agonist signaling may offer a useful therapeutic strategy. Our results offer a mechanistic rationale for further investigation of CXCL12 as a potential therapy to prevent or treat PDAC metastasis. Cancer Res; 75(17); 3529–42. ©2015 AACR.
MYC Is a Major Determinant of Mitotic Cell Fate
Authors: Caroline Topham, Anthony Tighe, Peter Ly, Ailsa Bennett, Olivia Sloss, Louisa Nelson, Rachel A. Ridgway, David Huels, Samantha Littler, Claudia Schandl, Ying Sun, Beatrice Bechi, David J. Procter, Owen J. Sansom, Don W. Cleveland, Stephen S. Taylor
Journal: Cancer Cell (2015)

Taxol and other antimitotic agents are frontline chemotherapy agents but the mechanisms responsible for patient benefit remain unclear. Following a genome-wide siRNA screen, we identified the oncogenic transcription factor Myc as a taxol sensitizer. Using time-lapse imaging to correlate mitotic behavior with cell fate, we show that Myc sensitizes cells to mitotic blockers and agents that accelerate mitotic progression. Myc achieves this by upregulating a cluster of redundant pro-apoptotic BH3-only proteins and suppressing pro-survival Bcl-xL. Gene expression analysis of breast cancers indicates that taxane responses correlate positively with Myc and negatively with Bcl-xL. Accordingly, pharmacological inhibition of Bcl-xL restores apoptosis in Myc-deficient cells. These results open up opportunities for biomarkers and combination therapies that could enhance traditional and second-generation antimitotic agents.