tbuckley/cabot-search huggingface dataset:
Improvement of Lung Tumor Radiotherapy Through Differential Chemoprotection of Normal and Tumor Tissue&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: John M. Yuhas
Journal: JNCI Journal of the National Cancer Institute (1972)

The radioprotective drug S-2-[3-aminopropylamino]ethyl-phosphorothioic acid (WR-2721) was studied as a possible improvement in the radiotherapy of primary urethan-induced lung tumors in the mouse. As in our observations of transplanted tumors, WR-2721 doubled the radiation resistance of the normal tissues in the radiation field but did not protect against lung tumors. Thus we conclude that the differential protection offered by WR-2721 is not the product of artificial factors found only in transplanted systems, and that it is a prime candidate for application to radiotherapy.
Dedifferentiation of Rat Mammary Myoepithelial-Like Cell Lines After Passage In Vivo or Cloning In Vitro&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S Jamieson, D J Dunnington, E J Ormerod, M J Warburton, P S Rudland
Journal: JNCI Journal of the National Cancer Institute (1986)

Myoepithelial-like cell lines from normal mammary glands of neonatal Ludwig Wistar rats, rat mammary (Rama) 401 and Rama 704E, were injected into fat pads of syngeneic animals or were single-cell cloned in vitro. Rama 401 produced tumors that were predominantly composed of elongated cells, while the subclones of both cell lines yielded multilayered structures of elongated cells when grown on floating 0.3% collagen gels in vitro. Immunocytochemical analysis of histologic sections for markers of myoepithelial cells revealed that anti-actin-myosin and human keratin sera failed to stain the Rama 401 tumor cells or subclones of both cell lines on collagen gels, but both were stained with antilaminin serum. Immunofluorescent analysis of cultures of Rama 401 tumors showed that the resulting elongated cells failed to stain with antikeratin serum, but abundant staining was observed with antilaminin and antivimentin sera, as in the tumors. Ultrastructural analysis of the Rama 401 tumor cells identified intermediate junctions and extracellular basement membrane-like material in the vicinity of plasma membrane-associated pinocytotic vesicles, but neither true desmosomes nor myofilamental bundles were observed. Thus growth of rat mammary myoepithelial-like cells as tumors in syngeneic animals or as subclones in vitro can lead to selective loss of myofilaments and prekeratin-containing intermediate filaments. Similar relatively undifferentiated elongated cells may be responsible for some of the cellular heterogeneity observed in certain carcinogen-induced rat mammary tumors.
Abstract 186: Identification of Novel Protein Kinase G I Alpha Antiremodeling Substrates in the Myocardium
Authors: Robert M Blanton, Robert A Baumgartner, Robrecht Thoonen, Shewit Giovanni, Suresh Govindan, Mark Aronovitz, Sakthivel Sadayappan, David A Kass, Richard H Karas
Journal: Circulation Research (2014)

Protein kinase G I α (PKGIα) inhibits cardiac remodeling, and this effect requires the PKGIα leucine zipper (LZ) binding domain. However, PKGIα LZ-dependent cardiac substrates remain poorly understood. Clinical trials of PKGI activating drugs have been limited to date by hypotension arising from vascular PKGI activation. Therefore, we explored downstream PKGIα substrates in the heart which may inhibit remodeling, yet circumvent the hypotensive effects of systemic PKGI activation. A screen for PKGIα LZ-interacting proteins identified: 1)cardiac myosin binding protein-C (cMyBP-C) and 2) mixed lineage kinase 3 (MLK3). cMyBP-C is a cardiac myocyte protein known to inhibit remodeling when phosphorylated. Co-precipitations with cGMP-conjugated beads confirmed the PKGIα-cMyBP-C interaction. Purified PKGIα phosphorylated cMyBP-C in vitro at Ser-273, Ser-282, and Ser-302. cGMP induced cMyBP-C phosphorylation at these sites in COS cells transfected with WT PKGIα, but not in cells transfected with either LZ mutant PKGIα or kinase-inactive PKGIα. In hearts of 9 month old PKGIα Leucine Zipper mutant mice, which have LV hypertrophy (LVH) and diastolic dysfunction, we observed decreased phosphorylated cMyBP-C as well as decreased total cMyBP-C, compared with WT littermate hearts. We next tested the effect of MLK3, which interacts with PKGIα in the heart, on remodeling in vivo. We performed 7 day Transaortic Constriction (TAC) on MLK3 KO mice and WT littermates (n=5 shams, 8 TAC per genotype). MLK3 KO TAC mice had increased LVH (LV mass/tibia length 71.1 ± 2.7 g/cm KO TAC vs 62.1 ± 2.7 WT TAC; p&lt;0.05). Further, MLK3 KO mice developed overt CHF compared with WT littermates (LV end diastolic pressure 14.8 ± 1.9 mmHg KO TAC vs 7.7 ± 2.1 WT TAC, p &lt;0.05), as well as accelerated decrements in LV preload recruitable stroke work (36.6 ± 11.9 mmHg/ul KO TAC vs 94.6 ± 12.9 WT TAC, p&lt;0.05) and min dP/dt (-6292 ± 519 mmHg/s KO TAC vs −8157 ± 554 WT TAC , p &lt;0.05). We observed no differences in LV structure or function between sham genotypes. These studies reveal 2 novel PKGIα anti-remodeling substrates, and they support that exploring PKGIα substrates in the heart may identify novel therapeutic targets to inhibit cardiac remodeling but avoid excessive PKGI induced vasodilation.
Air quality evaluation and respiratory health effects according to weather conditions in a Korean cit
Authors: Tai Sun Park, Yoonki Hong, Woo Jin Kim
Journal: European Respiratory Journal (2014)

Objective

We evaluated air quality and investigated respiratory health effects according to four weather conditions (yellow dust haze, mist, and fog) in a city of Korea.

Methods

Air quality was evaluated for particulate matter 10 um (PM10), ozone (O3), nitrogen dioxide (NO2), and sulfur dioxide (SO2). Respiratory health effects were investigated with hospital visits for asthma or COPD. From January 2006 to April 2012, data of air quality and weather conditions from the Meteorological Administration, and hospital visits from National Health Insurance Corporation were analyzed.

Results

During the evaluation, yellow dust was 52 days, haze 167 days, mist 176 days, fog 51 days. Concentrations of PM10 were higher on days with all weather conditions. NO2 was lower in yellow dust days, and CO, NO2 SO2 were higher in the haze and mist. In fog days, there was no difference for air quality, except PM10.

Relative risk for hospital visits with asthma was 1.22 in 5 day after yellow dust weather, COPD was 1.38. In 1 day after mist weather, relative risk for hospital visits with asthma was 1.04, COPD was 1.12.

Conclusions

Weather conditions (yellow dust, haze, mist, and fog) consist of different air quality, and it affect for hospital visits for asthma or COPD after few days.
Predictive factors for antituberculosis treatment failure
Authors: Evelina Lesnic, Zlepca Vasile
Journal: European Respiratory Journal (2012)

The effectiveness of DOTS achieved 59% in Moldova in 2011. The result of an inadequate treatment is the treatment failure. Its increasing rate (7.5% in 2011) leads to accumulation of MDR sources in the population and puts more problems to the National TB Control Program. Treatment outcome depends by the social categories of patients, TB extension and co-morbidities. Aim of study is evaluation of predictive factors for anti-TB treatment failure (TF).

Was compared risk factors for TF in a study group (SG) of 110 patients with pulmonary TB failed after 5 months of DOTS and a control group (CG) of 100 patients cured with DOTS. Results: males 60% SG vs 50% CG, average age 35,6 SG vs 42,5 CG, unemployed 76% SG vs 48% CG, with bad living conditions 63% SG vs 48% CG (p<0.05). Were detected 80% of patients from both groups by passive way with known TB contact 26% SG vs 20% CG. All patients (100%) had destructive forms of TB with positive sputum, but bilateral extension had 84% of SG vs 24% in CG(p<0.05). Susceptibility test detected primary resistance in 55% SG vs 12% CG. Co-morbidities had 56% of SG vs 24% in CG, most frequent: alcoholism, hepatitis, diabetes, HIV infection. Noncompliance with treatment had 20% from SG vs 100% compliance in CG. Treatment outcome in SG: cured 42%, 30% dead,10% defaulted,18% continue another treatment regimen vs 100% cured in CG. Conclusions predictive factors for TF: are treatment not adapted to susceptibility testing, noncompliance with treatment, low social status, extensive TB with co-morbidities.
Lung clearance index and exercise capacity among children with bronchiectasis
Authors: Elpis Hatziagorou, Vasiliki Avramidou, Fotis Kirvassilis, Kalliopi Kontouli, Stafanos Nikopoulos, John Tsanakas
Journal: European Respiratory Journal (2012)

Background: In paediatric bronchiectasis, there has been limited experience on the relationship between disease severity, as assessed by exercise limitation and lung clearance index (LCI).  Aim: To compare LCI and exercise capacity among children with bronchiectasis.  Method: Fifteen stable children and adolescents with CF, 14 stable children with non-CF bronchiectasis and 15 healthy children and adolescents, participated in maximal incremental cardiopulmonary exercise testing using a cycle ergometer and they had an LCI assessment.  Results: The CF children9s mean age was 13.7 years, mean FEV 1  74.4% predicted. The 14 non-CF bronchiectasis children9s mean age was 13.8 years, mean FEV 1  75.1% predicted and the healthy children9s mean age was 13.6 years, mean FEV1 94.7%. Among CF patients there was evidence of exercise limitation, with mean Peak Aerobic Capacity (V9Opeak) 62.2 % predicted. Among the non-CF bronchiectasis patients there was evidence of exercise limitation, with mean V9Opeak 77.3 % predicted. Mean V9Opeak did not differ significantly among children with CF and non-CF bronchiectasis (p: 0.06). LCI was significantly increased among CF patients (mean LCI 13.7), compared to healthy children (p  Conclusions: Exercise testing and Multiple Breath Washout measurements can discriminate children with bronchiecatsis from healthy children. However, the burden of the disease is more prominent in children with CF compared with the non-CF bronchiectasis.
Gene Panel Testing for Inherited Cancer Risk
Authors: Michael J. Hall, Andrea D. Forman, Robert Pilarski, Georgia Wiesner, Veda N. Giri
Journal: Journal of the National Comprehensive Cancer Network (2014)

Next-generation sequencing technologies have ushered in the capability to assess multiple genes in parallel for genetic alterations that may contribute to inherited risk for cancers in families. Thus, gene panel testing is now an option in the setting of genetic counseling and testing for cancer risk. This article describes the many gene panel testing options clinically available to assess inherited cancer susceptibility, the potential advantages and challenges associated with various types of panels, clinical scenarios in which gene panels may be particularly useful in cancer risk assessment, and testing and counseling considerations. Given the potential issues for patients and their families, gene panel testing for inherited cancer risk is recommended to be offered in conjunction or consultation with an experienced cancer genetic specialist, such as a certified genetic counselor or geneticist, as an integral part of the testing process.
Teens who use e-cigarettes are more likely to take up smoking, US study finds
Authors: Michael McCarthy
Journal: BMJ (2015)

High school students who have used electronic (e) cigarettes are considerably more likely to take up smoking combustible tobacco products such as cigarettes, cigars, and hookahs, a US study published in JAMA has found.1

E-cigarettes are battery powered devices that deliver nicotine in an aerosol that can be inhaled. Manufacturers and some public health researchers argue that the devices offer a healthier alternative to smoking and can help current smokers reduce or stop their tobacco use. But others worry that the e-cigarettes, which are typically marketed to teens and young adults and flavoured to make them more appealing to young people, will addict young people to nicotine and lead them to take up smoking.

In the study Adam M Leventhal, of Keck School of Medicine at the University of …
A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy
Authors: Paul Emery, Jiří Vencovský, Anna Sylwestrzak, Piotr Leszczyński, Wieslawa Porawska, Asta Baranauskaite, Vira Tseluyko, Vyacheslav M Zhdan, Barbara Stasiuk, Roma Milasiene, Aaron Alejandro Barrera Rodriguez, Soo Yeon Cheong, Jeehoon Ghil
Journal: Annals of the Rheumatic Diseases (2015)

To compare the efficacy and safety of SB4 (an etanercept biosimilar) with reference product etanercept (ETN) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy.This is a phase III, randomised, double-blind, parallel-group, multicentre study with a 24-week primary endpoint. Patients with moderate to severe RA despite MTX treatment were randomised to receive weekly dose of 50 mg of subcutaneous SB4 or ETN. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 24. Other efficacy endpoints as well as safety, immunogenicity and pharmacokinetic parameters were also measured.596 patients were randomised to either SB4 (N=299) or ETN (N=297). The ACR20 response rate at week 24 in the per-protocol set was 78.1% for SB4 and 80.3% for ETN. The 95% CI of the adjusted treatment difference was -9.41% to 4.98%, which is completely contained within the predefined equivalence margin of -15% to 15%, indicating therapeutic equivalence between SB4 and ETN. Other efficacy endpoints and pharmacokinetic endpoints were comparable. The incidence of treatment-emergent adverse events was comparable (55.2% vs 58.2%), and the incidence of antidrug antibody development up to week 24 was lower in SB4 compared with ETN (0.7% vs 13.1%).SB4 was shown to be equivalent with ETN in terms of efficacy at week 24. SB4 was well tolerated with a lower immunogenicity profile. The safety profile of SB4 was comparable with that of ETN.NCT01895309, EudraCT 2012-005026-30.
Electronic nose breathprints reflect BALF inflammatory cell counts in asthma
Authors: Niki Fens, Koen F. van der Sluijs, Marianne A. van de Pol, René Lutter, Peter J. Sterk
Journal: European Respiratory Journal (2013)

RATIONALE Airway inflammation in allergic asthma is predominantly eosinophilic. eNose breathprints can distinguish COPD from asthma (Fens 2009,2011) and sputum inflammatory markers in asthma and COPD are related to breathprints (Ibrahim 2011,Fens 2011).  HYPOTHESIS eNose breathprints capture markers of peripheral airway inflammation as derived from bronchoalveolar lavage fluid (BALF) in mild allergic asthma.  METHODS Breathprints, exhaled NO and inflammatory cell counts in BALF were obtained from 13 mild allergic, steroid-naive asthmatics and 11 healthy non-allergic controls. eNose (Cyranose 320) breathprints were analyzed by principal component (PC) analysis. The relationship between breathprints, NO and BALF inflammatory cell counts was analyzed using multivariate regression analysis (Sidak correction for multiple testing).  RESULTS Breathprints were significantly related to BALF neutrophils and eosinophils in all subjects. Significant correlations of breathprints with eosinophils, lymphocytes and macrophages were found for asthmatics (Table 1), and with neutrophils (PC3;R=0.71;p=0.015) for controls. NO was only associated with eosinophils in normals.  CONCLUSION Breathprints are related to inflammatory cell counts in BALF in mild allergic asthma, with eosinophils showing the strongest correlation. This suggests that peripheral airway inflammation in asthma can be assessed noninvasively.
Phase II trial of cediranib (AZD2171) in docetaxel-resistant, castrate-resistant prostate cancer (CRPC)
Authors: J. J. Karakunnel, J. L. Gulley, P. M. Arlen, M. Mulquin, J. J. Wright, I. B. Turkbey, P. Choyke, C. M. Ahlers, W. D. Figg, W. L. Dahut
Journal: Journal of Clinical Oncology (2008)

5136 Introduction: There is no standard therapy for prostate cancer patients who have progressed following docetaxel therapy. VEGF is implicated in tumor blood vessel formation and disease progression in solid tumors. Cediranib, an oral, small molecule inhibitor of VEGF receptor tyrosine kinases, is being evaluated at a dose of 20 mg daily in patients with prostate cancer resistant to docetaxel and hormonal therapy. Methods: Patients have clinical and/or radiographic evidence of progression on docetaxel with no limit on the number of prior chemotherapy regimens or radioisotopes. Response imaging is assessed every 2 months. Simon two stage optimal design was utilized. Primary objective is a 30% 6 month probability of progression free survival as determined by clinical (not PSA rise alone) and radiographic criteria. If 2 or more patients are progression-free at 6 months, the cohort will be expanded to 35 evaluable patients. Patients receiving cediranib were scanned by DCE-MRI pre- and post-treatment. A two compartment model was used to analyze the volume transfer. Results: First stage response goals have been exceeded and full study accrual of 35 patients is ongoing. Eighteen patients have been enrolled (2 PR/ 11 evaluable patients, 9 on trial [1–10 months]). Significant decreases in lymph node metastases as well as in lung, liver and bone lesions have been documented. PSA levels have not corresponded with imaging responses. Adverse events have been similar to other VEGFR inhibitors: hypertension, dysphonia, fatigue. Grade 3 toxicities included vomiting (1), prolonged QTc (2), muscle weakness (1). Preliminary data from DCE-MRI (14 patients): baseline to cycle 1 decreases in forward rate (11/14, median change = 23.1%) and reverse rate (9/14, median change = 60.3%). Targeted lesions: bone (7) and soft tissue (7). Conclusion: Cediranib appears to be a promising drug in CRPC post docetaxel based on the compound's tolerability and efficacy. Preliminary data suggests that cediranib has a direct effect on the microcirculation and vasculature. There has been an early correlation between clinical response and DCE-MRI changes. Additional accrual is required to characterize the response rate, discrepancy between PSA and imaging and determine clinical correlation for DCE- MRI. No significant financial relationships to disclose.
Clinical characteristics of the smooth tubercle bacilli ‘Mycobacterium canettii’ infection suggest the existence of an environmental reservoir
Authors: J.-L. Koeck, M. Fabre, F. Simon, M. Daffé, é. Garnotel, A.B. Matan, P. Gérôme, J.-J. Bernatas, Y. Buisson, C. Pourcel
Journal: Clinical Microbiology and Infection (2010)

Over a 3-year follow-up, 30 out of the 318 unique Mycobacterium tuberculosis complex isolates recovered in the Republic of Djibouti had a smooth-type morphology and were Niacine-negative, the characteristics of 'Mycobacterium canettii' strains. Unlike M. tuberculosis, 'M. canettii' grew on nutrient-poor media at 30°C, and possessed characteristic lipids. They were isolated from respiratory and extra-respiratory sites from patients with typical forms of tuberculosis. Most cases resolved with antibiotic therapy but in two human immunodeficiency virus-positive patients 'M. canettii' infection led to septicaemia and death. No cases of human-to-human transmission were observed. The proportion of tuberculosis cases caused by 'M. canettii' was higher among French patients than among Djiboutian patients. Patients with 'M. canettii' were significantly younger than those with tuberculosis caused by other M. tuberculosis complex strains. Smooth tubercle bacilli could be misidentified as non-tuberculous mycobacteria and appear to be limited to the Horn of Africa. Their characteristics are consistent with the existence of non-human sources of infection.
The combination of elevated FeNO and blood eosinophils relate to reduced lung function and increased bronchial responsiveness in young asthmatics
Authors: Andrei Malinovschi, Lennart Nordvall, Borres Magnus, Janson Christer, Kjell Alving
Journal: European Respiratory Journal (2014)

We have recently reported in a population-based study the independent and additive information of the fraction of exhaled NO (FeNO) and blood eosinophil (B-Eos) count in relation to asthma, wheeze and asthma exacerbations. In the present study, we investigated FeNO and B-Eos in relation to lung function, bronchial responsiveness and asthma symptoms in an asthma cohort.

FeNO, B-Eos, FEV1 and PD20 methacholine were measured in 410 subjects (10-34 years; 209 women) with asthma and ongoing treatment.

Subjects with both elevated FeNO (>25 ppb) and B-Eos (>0.3x109/L) had lower FEV1% (p<0.001), more nighttime dyspnea (p=0.02) and lower PD20 (p<0.001) than subjects with normal FeNO and B-Eos, as well as lower PD20 than subjects with either high FeNO or high B-Eos (both p<0.001) (Table 1). These results were consistent after adjusting for gender, age, height, weight, IgE sensitization to aeroallergens, and current ICS dose.

View this table:

Table 1. Asthma characteristics in relation to FeNO and B-Eos





In conclusion, additive information of two inflammatory biomarkers, exhaled nitric oxide and blood eosinophils, was found with regard to reduced lung function, increased bronchial responsiveness and nighttime dyspnea in young asthmatics. This suggests that these patients may be in need of biomarker-directed asthma treatment.
Evaluation of Safety, Tolerability, Pharmacokinetics and Efficacy of Dabrafenib, a Braf Inhibitor, in Japanese Patients with Braf V600 Mutation-Positive Advanced Solid Tumors: a Phase I Study
Authors: N. Yamazaki, Y. Kiyohara, S. Yoshikawa, N. Yamamoto, A. Tsutsumida, H. Nokihara, K. Namikawa, Y. Fujiwara, A. Suzuki, A. Mukaiyama, T. Tamura
Journal: Annals of Oncology (2014)
Correlation between thymidine phosphorylase expression and prognosis in human renal cell carcinoma.
Authors: Y Imazano, Y Takebayashi, K Nishiyama, S Akiba, K Miyadera, Y Yamada, S Akiyama, Y Ohi
Journal: Journal of Clinical Oncology (1997)

PURPOSE Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and has angiogenic activity. We examined whether TP expression in renal cell carcinoma (RCC) is associated with microvessel density as a marker of angiogenesis, clinicopathologic characteristics, and outcome. PATIENTS AND METHODS The enzymatic activity and expression of TP were examined in 18 RCCs and 19 kidney tissues not grossly involved with tumor from 24 patients with 13 paired samples and 11 unpaired samples by spectrophotometry and immunoblotting. The relationship between TP expression and microvessel density was assessed by immunohistochemistry in 133 RCCs. RESULTS The median enzymatic activity of TP in RCCs was nine fold higher than that in nonneoplastic kidney tissues (P &lt; .001). Similar results were obtained by immunoblot analysis. According to the TP staining profile, tumors were classified as no or low, intermediate, or high TP-expressing tumors. TP positivity was significantly correlated with microvessel density. TP expression was correlated with tumor grade, but there was no significant association between TP expression and other clinicopathologic characteristics. TP expression as a prognostic variable was studied using Cox's proportional hazards model. TP overexpression was an independent prognostic factor (hazards ratio, 3.95; 95% confidence interval, 0.98 to 15.89; P = .039) as were nodal category, metastases category, tumor grade, and venous invasion. CONCLUSION These findings suggest that TP expression is correlated with microvessel density in RCC and is an unfavorable independent prognostic factor. The future development and characterization of TP inhibitors may provide a novel approach to the therapy of RCC.