tbuckley/cabot-search huggingface dataset:
Reliability of EGFR mutations detection in NSCLC brain metastases by two different allele-specific PCR methods
Authors: Michal Skronski, Pawel Krawczyk, Kamila Wojas-Krawczyk, Bozena Jarosz, Tomasz Kucharczyk, Paulina Jagus, Marek Sawicki, Barbara Wilczynska, Tomasz Trojanowski, Janusz Milanowski, Joanna Chorostowska-Wynimko
Journal: European Respiratory Journal (2012)

Reliable detection of EGFR mutations in lung cancer metastases requires highly sensitive and robust molecular method.  Our aim was to assess effectiveness of two highly sensitive PCR methods in detection of EGFR activating mutations in FFPE samples of brain metastases from 142 NSCLC patients.  Isolated DNA was analyzed for EGFR exon 19 deletions and exon 21 L858R mutations by real-time PCR PNA-LNA PCR clamp and allele-specific PCR (ASP-PCR). If discrepant, results were re-evaluated by TaqMan genotyping. Direct sequencing analyses are ongoing.  All samples were successfully analyzed. In 37 samples (26%) DNA was of low quality and PCR pre-amplification was performed prior to PNA-LNA PCR clamp analysis. In total 11 out of 142 samples (8%) proved positive for EGFR activating mutations. 6 samples (55% of detected) were positive for exon 19 deletions (n=3) and L858R substitution (n=3) as assessed by both PNA-LNA PCR clamp and ASP-PCR. ASP-PCR, but not PNA-LNA PCR clamp, detected 3 further L858R mutations, whereas 1 L858R substitution and 1 rare A859T mutation were detected by PNA-LNA PCR clamp only. None of discrepant L858R substitutions were confirmed by TaqMan genotyping.  Different approach to molecular diagnostics represented by two highly sensitive methods employed in our study might be responsible for observed discrepancies. ASP-PCR utilizes allele-specific primers while in PNA-LNA PCR clamp method PNA probe inhibits wild type allele amplification. In FFPE samples with low tumor cells content, where direct sequencing is not applicable, it might be advisable to re-evaluate diagnostic results by another equally sensitive, but methodologically different diagnostic technique.
Do physicians use urinary pneumococcal antigen test (UPAT) appropriately
Authors: Vinod Palissery, Ajay Kamath, Catherine Tremlett
Journal: European Respiratory Journal (2012)

Introduction: UPAT is a useful test to identify the pneumococcal aetiology of pneumonia. The specificity and sensitivity are high in moderate to severe pneumonia (MSP). British Thoracic Society (BTS) recommends this test only in MSP. But as this test has become more accessible it is being used inappropriately in non severe pneumonia, infective exacerbation of asthma and COPD. The most important use of the test is in modifying the antibiotic regimen according to the result. We did this study to look at the utility of the test and how it altered clinical management.  Method: We conducted a retrospective analysis of medical records of all patients who had UPAT in a 6-month period between December 2007 and May 2008. The study was performed in a 1000 bed tertiary teaching hospital in United Kingdom. BTS CURB-65 scoring was used as a measure of severity of pneumonia.  Results: One hundred and eighteen patients had the test in the 6-month study period but only 37 patients met criteria for moderate to severe pneumonia (MSP). Rest of the patients had non-severe pneumonia, infective exacerbation of asthma/COPD/Bronchiectasis. Ten patients had positive results (8.4 %); 13.5 % positive results were in MSP group and 6.1 % in the other group. Most common antibiotic regimen commenced in our institution was amoxicillin and clarithromycin (41%). Modification in antibiotic regimen guided by the results was done only in three patients.  Conclusion: UPAT is used inappropriately and the test results are not effectively used in modifying management.
Induction of Interleukin-9-Producing Mucosal Mast Cells Promotes Susceptibility to IgE-Mediated Experimental Food Allergy
Authors: Chun-Yu Chen, Jee-Boong Lee, Bo Liu, Shoichiro Ohta, Pin-Yi Wang, Andrey V. Kartashov, Luke Mugge, J. Pablo Abonia, Artem Barski, Kenji Izuhara, Marc E. Rothenberg, Fred D. Finkelman, Simon P. Hogan, Yui-Hsi Wang
Journal: Immunity (2015)
Association between right ventricular dysfunction and diameter of right descending pulmonary artery on chest X-rays in pulmonary embolism
Authors: Yasin Abul, Savas Ozsu, Sait Karakurt, Beste Ozben, Ismet Durmus, Ahmet Toprak, Tevfik Ozlu, Turgay Celikel
Journal: European Respiratory Journal (2011)

Right ventricular dysfunction (RVD) has a prognostic significance on mortality in pulmonary embolism (PE). Echocardiographic measurement is user-dependent and requires experience. Cardiac biomarkers including troponin-T, BNP has been suggested to show RVD instead of echocardiography. However these markers are not available at all centers and they are known as expensive. Association between the grade of pulmonary hypertension and diameter of right descending pulmonary artery on PA chest X-rays (male<16 mm female <14 mm) has been shown previously. In present study, possible association between RVD in PE and diameter of right descending pulmonary artery on chest X-rays was investigated. 89 patients with the diagnosis of PE were included (M:F=41/48; age=65±13.5). Both diameter of right descending pulmonary artery on PA chest X-ray and RVD on echocardiography were measured. These two parameters were compared by pearson χ2, and sensitivity and spesificity of diameter of right descending pulmonary artery on PA chest X-ray for defining RVD was analyzed by ROC analysis. Diameter of right descending pulmonary artery on PA chest X-ray is more frequently increased in PE patients with RVD (p<0.001). The AUC was 0.76 for defining RVD by the diameter of right descending pulmonary artery on PA chest X-ray having sensitivity 78% and spesificity 63% at the diameter of 16.25 mm.

In conclusion, diameter of right descending pulmonary artery on PA chest X-ray may be used for the defining RVD which has prognostic importance in PE.
OM-85 shapes dendritic cell activation into a “pre-alert” phenotype
Authors: Daniela Bosisio, Laura Salogni, Natacha Nowak, Xenia Vaira, Patricia Jeandet, Gabriela Saborio, Silvano Sozzani
Journal: European Respiratory Journal (2011)

Background:  OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®) has proven efficacy in the prevention of recurrent infections of the airways and acute exacerbations in COPD. OM-85 is a lyophilized bacterial extract comprising fractions of 21 different inactivated bacterial strains. Previous work has shown that OM-85 acts as an immunostimulant, and that it may act on human dendritic cells (hDC). However, the molecular mechanisms through which OM-85 activates hDC remained largely unknown.   Aims:  Investigate the impact of OM-85 stimulation on hDC and identify the immune receptors implicated in OM-85 response.   Methods:  Primary and  in vitro  derived hDC were used to determine the precise OM-85 effects on DC biology. Stably transfected cell lines expressing human receptors were used to characterize OM-85 receptor-dependent activity.   Results:  In hDC, OM-85 induced the secretion of IL-6 and of several chemokines (i.e. CXCL8, CXCL6, CCL3, CCL20, CCL22) with a potency comparable to the prototypical activating stimulus LPS. OM-85 potentiated the effect of IFNγ in terms of IL-6, IL-12 and IL-10 release. The induction of selected chemokines by suboptimal doses of classical pro-inflammatory stimuli were boosted by the presence of OM-85. In addition, it was identified that OM-85 activates TLR2, NOD1 and NOD2 receptors in a significant, dose-response manner.   Conclusions:  OM-85 induces a mild and well shaped hDC activation through selected pattern recognition receptors. This activation may contribute to the generation of a “pre-alert state” resulting in an early protection towards incoming infection. These results provide new insights in the understanding of the mode of action of OM-85, opening new venues for further investigation.
Tumor Cytotoxicity In Vitro by Macrophages From Mice Infected With Mycobacterium bovis Strain BCG
Authors: Ronald P. Cleveland, Monte S. Meltzer, Berton Zbar
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Tumor Cytotoxicity In Vitro by Macrophages From Mice Infected With Mycobacterium bovis Strain BCG Get access Ronald P. Cleveland, Ronald P. Cleveland Search for other works by this author on: Oxford Academic PubMed Google Scholar Monte S. Meltzer, Monte S. Meltzer Search for other works by this author on: Oxford Academic PubMed Google Scholar Berton Zbar Berton Zbar Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 6, June 1974, Pages 1887–1895, https://doi.org/10.1093/jnci/52.6.1887 Published: 01 June 1974 Article history Received: 25 January 1974 Accepted: 04 March 1974 Published: 01 June 1974
Adolescent and Young Adult Colorectal Cancer
Authors: Joleen M. Hubbard, Axel Grothey
Journal: Journal of the National Comprehensive Cancer Network (2013)

Although the overall incidence of colorectal cancer (CRC) in adolescents and young adults (AYAs) is low, it has seen an increase over the past 2 to 3 decades, which contrasts with the trend of decreased incidence in the older population. This phenomenon is conceivably caused by a lack of routine CRC screening in the young population and lifestyle issues, including the obesity epidemic and dietary factors. Hereditary genetic syndromes (eg, familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer syndrome) and known predisposing medical conditions (eg, inflammatory bowel disease) account for only a minority of CRC cases in AYA. Younger patients with CRC commonly present with more advanced disease at diagnosis and exhibit specific molecular and clinical characteristics associated with a distinct biologic phenotype of CRC compared with older individuals. Matched for stage, however, the prognosis of patients with young-onset CRC is similar to or better than that for older patients. A surprising paucity of data exists on outcomes associated with modern systemic cytotoxic and biologic therapy specifically in young patients with CRC. The toxicity pattern of these treatments, however, differs between young and older patients, partly because of the lower rate of pertinent comorbidities in younger adults. Issues regarding surgical management in the setting of hereditary syndromes and fertility preservation while on therapy are of particular importance to the younger patient population. Future studies should seek to increase understanding of the distinct tumor biology of AYA patients with CRC and the consequences of treatment interventions to optimize outcomes for this population.
Clinical Course of Stage IV Epithelial Ovarian Cancer
Authors: Richard T. Penson, Steven J. Skates, Arlan J. Fuller, Michael V. Seiden
Journal: Journal of Clinical Oncology (1999)

Article Tools Correspondence Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.10.3361 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10506641 Clinical Course of Stage IV Epithelial Ovarian Cancer Richard T. PensonxRichard T. PensonSearch for articles by this author , Steven J. SkatesxSteven J. SkatesSearch for articles by this author , Arlan J. Fuller JrxArlan J. Fuller JrSearch for articles by this author , Michael V. SeidenxMichael V. SeidenSearch for articles by this author Show More Massachusetts General Hospital, Boston, MA https://doi.org/10.1200/JCO.1999.17.10.3361 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Brain Metastases in Patients With Germ Cell Tumors: Prognostic Factors and Treatment Options—An Analysis From the Global Germ Cell Cancer Group
Authors: Darren R. Feldman, Anja Lorch, Andrew Kramar, Costantine Albany, Lawrence H. Einhorn, Patrizia Giannatempo, Andrea Necchi, Aude Flechon, Helen Boyle, Peter Chung, Robert A. Huddart, Carsten Bokemeyer, Alexey Tryakin, Teodoro Sava, Eric William Winquist, Ugo De Giorgi, Jorge Aparicio, Christopher J. Sweeney, Gabriella Cohn Cedermark, Jörg Beyer, Thomas Powles
Journal: Journal of Clinical Oncology (2015)

Purpose To define characteristics, treatment response, and outcomes of men with brain metastases (BM) from germ cell tumors (GCT). Patients and Methods Data from 523 men with BM from GCT were collected retrospectively from 46 centers in 13 countries by using standardized questionnaires. Clinical features were correlated with overall survival (OS) as the primary end point. Results BM were present at initial diagnosis in 228 men (group A) and at relapse in 295 men (group B). OS at 3 years (3-year OS) was superior in group A versus group B (48% v 27%; P &lt; .001). Multiple BM and the presence of liver or bone metastasis were independent adverse prognostic factors in both groups; primary mediastinal nonseminoma (group A) and elevations of α-fetoprotein of 100 ng/mL or greater or of human chorionic gonadotropin of 5,000 U/L or greater (group B) were additional independent adverse prognostic factors. Depending on these factors, the 3-year OS ranged from 0% to 70% in group A and from 6% to 52% in group B. In group A, 99% of patients received chemotherapy; multimodality treatment or high-dose chemotherapy was not associated with statistically improved survival in multivariable analysis. In group B, only 54% of patients received chemotherapy; multimodality treatment was associated with improved survival compared with single-modality therapy (hazard ratio, 0.51; 95% CI, 0.36 to 0.73; P &lt; .001), as was high-dose compared with conventional-dose chemotherapy (hazard ratio, 0.41; 95% CI, 0.24 to 0.70; P = .001). Conclusion Men with BM from GCT have poor OS, particularly if additional risk factors are present. High-dose chemotherapy and multimodality treatment seemed to improve survival probabilities in men with BM at relapse.
Pattern of respiratory muscle recruitment during walking in active and less physically-active COPD patients
Authors: Maroula Vasilopoulou, Eleni Kortianou, Zafeiris Louvaris, Stavroula Spetsioti, Ioannis Nasis, Andreas Asimakos, Theodora Vasilogiannakopoulou, Spyros Zakynthinos, Ioannis Vogiatzis
Journal: European Respiratory Journal (2013)

Aim: To investigate whether walking movement intensity is associated with the pattern of respiratory muscle recruitment in COPD.

Methods: 18 patients underwent a treadmill walking test at a speed corresponding to each patient’s average movement intensity of walking. This was captured by a DynaPort Minimod triaxial accelerometer during a 7-day period. Based on the median movement intensity of the whole COPD sample (1.8 m/s2) patients were evenly divided into those with a speed lower (FEV1%pred: 45±6) or greater (FEV1%pred: 53±5) than 1.8m/s2. Compartmental chest wall volume variations, representing rib cage muscle as well as diaphragm and expiratory abdominal muscle activities, were computed by OEP.

Results : Active compared to less active patients [median 2.0 (CI: 1.92-2.08 m/s2) vs 1.6 (CI: 1.52-1.65) m/s2] demonstrated greater increases in tidal volume from baseline (1.0±0.2 vs 0.6±0.1 L). This was a result of greater volume increases in the abdominal (0.44±0.08 vs 0.15±0.06 L) than the rib cage (0.55±0.13 vs 0.45±0.11) compartments. Groups differed in terms of the increase in end-expiratory abdominal volume from baseline (0.06±0.04 vs 0.19±0.04 L, p=0.045) reflecting greater expiratory abdominal muscle recruitment in physically active patients. However, no group differences were seen in end-inspiratory abdominal volume changes from baseline suggesting similar diaphragmatic muscle action.

Conclusion: Patients adopting greater movement intensity exhibit more profound expiratory abdominal muscle activation that allows them to exhibit greater tidal volumes.

This work was funded by Innovative Medicines Initiative Joint Undertaking (IMU-JU # 115011) and by Thorax Foundation.
Effect of Host Immune Capability on Radiocurability and Subsequent Transplantability of a Murine Fibrosarcoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H B Stone, L J Peters, L Milas
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Effect of Host Immune Capability on Radiocurability and Subsequent Transplantability of a Murine Fibrosarcoma Get access Helen B. Slone, Helen B. Slone 4 4Address reprint requests to Dr. Stone at her present address: Department of Radiology and Radiation Biology, Colorado State University, Fort Collins, Colo. 80523. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lester J. Peters, Lester J. Peters Search for other works by this author on: Oxford Academic PubMed Google Scholar Luka Milas Luka Milas Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 63, Issue 5, November 1979, Pages 1229–1235, https://doi.org/10.1093/jnci/63.5.1229 Published: 01 November 1979 Article history Received: 17 January 1979 Accepted: 23 April 1979 Published: 01 November 1979
Phase I and pharmacologic study of irinotecan and etoposide with recombinant human granulocyte colony-stimulating factor support for advanced lung cancer.
Authors: N Masuda, M Fukuoka, S Kudoh, K Matsui, Y Kusunoki, M Takada, K Nakagawa, T Hirashima, H Tsukada, T Yana
Journal: Journal of Clinical Oncology (1994)

PURPOSE We conducted a phase I trial of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, and recombinant human granulocyte colony-stimulating factor (rhG-CSF) support because of the overlapping neutrophil toxicity of both drugs. The aim was to determine the maximum-tolerated dose of CPT-11 combined with a fixed dose of etoposide in patients with advanced lung cancer, as well as the dose-limiting toxicities of this combination. PATIENTS AND METHODS Twenty-five patients with stage III or IV lung cancer, 15 (60%) with prior chemotherapy, were treated at 4-week intervals using CPT-11 (90-minute intravenous infusion on days 1, 8, and 15) plus etoposide (80 mg/m2 intravenously on days 1 to 3). In addition, rhG-CSF (2 micrograms/kg/d) was given from day 4 to day 21, except on the days of CPT-11 administration. The starting dose of CPT-11 was 60 mg/m2, and it was escalated in 10-mg/m2 increments until the maximum-tolerated dose was reached. RESULTS The maximum-tolerated dose of CPT-11 was 90 mg/m2, since two of the three patients developed grade 3 to 4 leukopenia or grade 3 to 4 diarrhea during the first cycle of treatment at this dose level. Diarrhea and leukopenia were the dose-limiting toxicities, while thrombocytopenia was only a moderate problem. Elimination of CPT-11 was biphasic, with a mean +/- SD beta half-life of 18.17 +/- 9.09 hours. The mean terminal half-life of 7-ethyl-10-hydroxycamptothecin (SN-38; the major metabolite of CPT-11) was 43.40 +/- 37.84 hours. There was one complete response (5%) and eight partial responses (38%) among 21 assessable patients, for an overall response rate of 43%. The response rates for small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) were 58% (seven of 12 patients) and 22% (two of nine patients), respectively. CONCLUSION The combination of CPT-11 and etoposide with rhG-CSF support seems to be active against lung cancer, especially SCLC, with acceptable toxicity. The recommended dose for phase II studies in previously untreated patients is 80 mg/m2 of CPT-11 (days 1, 8, and 15) and 80 mg/m2 of etoposide (days 1 to 3) plus 2 micrograms/kg of rhG-CSF (days 4 to 21, except when CPT-11 is given). In addition, 70 mg/m2 of CPT-11 appears to be the appropriate dose for previously treated patients receiving this regimen.
Autocrine-Paracrine Endothelin System in the Physiology and Pathology of Steroid-Secreting Tissues
Authors: Gastone G. Nussdorfer, Gian Paolo Rossi, Ludwik K. Malendowicz, Giuseppina Mazzocchi
Journal: Pharmacological Reviews (1999)

Endothelins (ETs)2 are a family of endogenous peptides, mainly secreted by endothelial cells, which exert a potent vasoconstrictor and pressor activity, acting through two classes of receptors named ETA and ETB. ETs were originally isolated from porcine aortic endothelium ([Yanagisawa et al., 1988][
Procalcitonin as etiological marker of severe community-acquired pneumonia
Authors: Kseniia Bielosludtseva, Tetyana Pertseva, Tetyana Kyreeva
Journal: European Respiratory Journal (2013)

Aim: to study the diagnostic value of procalcitonin (PCT) at patients (pts) with severe community-acquired pneumonia (sCAP) depending on the identified pathogen.  Methods: 54 patients with verified sCAP (age 54,1±2,6, men–38, women–16), general data, HIV-test, pathogens’ identification in sputum, scoring SMRT-CO scale, serum PCT level before antibiotic therapy.  Results: all pts were in serious condition, the number of points according to SMART was 6,0±0,2. We could identify the pathogen at 32 (59,3%) pts. According to the etiology they were retrospectively divided into groups (gr): 1–Gr+ bacteria, Gr-bacteria, Pneumocystis pneumonia at HIV-positive pts. PCT levels in pts of gr 1 and 2 were higher than normal (0,1 ng/ml) more than in 60 and 500 times respectively. It differed significantly from PCT level in gr 3, at which it does not exceed the norm. We found that PCT level at Gr-pathogens was more than at Gr+ in 8 times.  Conclusions: PCT level can be an etiological marker of sCAP: 1) sharp increase of PCT (up to 50 ng/ml) may be a marker of Gr-pathogen, 2) increasing up to 7 ng/ml is a marker of Gr+ bacterial agent; 3) normal PCT level may accompanies Pneumocystis pneumonia at HIV-positive pts and may point on prolongation of diagnostic search for determination the cause of acute respiratory failure.
Prevalence of asthma in Latin American middle-aged and older adults and its overlap with diagnosis of COPD
Authors: Ana Maria Menezes, Pedro Hallal, Maria Montes de Oca, Adriana Muino, Maria Victorina Lopez Varela, Carlos Talamo, Jose R.B. Jardim, Gonzalo Valdivia, Rogelio Perez-Padilla
Journal: European Respiratory Journal (2011)

Objective:  To evaluate the prevalence of asthma using self-reported and spirometric criteria and to analyze the overlap in asthma and COPD diagnoses.   Methods:  Multicenter study (PLATINO) in five Latin America cities: Sao Paulo, Mexico City, Montevideo, Santiago and Caracas. Individuals aged 40 + years performed pre and post-BD spirometry and answered to ISAAC. Significant reversibility was defined as a difference between post and pre-BD FEV1 or FVC; those with a 200 ml and 12% or more differences were classified as having significant reversibility.   Results:  Questionnaires and pre and post-BD spirometry were available for 5,183 individuals. Out of 1,242 individuals reporting wheezing in the last 12 months, only 184 (14.8%) also had significant reversibility by spirometry. Out of 532 subjects with significant reversibility, 34.6% also reported wheezing in the last year. As a consequence, asthma by both wheezing and reversibility affected exactly 3.6% of the sample. By analyzing COPD, based on the fixed ratio criterion, and asthma by the most specific criterion (wheezing + reversibility), out of 728 individual with COPD, only 96 (13.2%) also presented asthma. Out of the 184 individuals with asthma, 52% also had COPD. Taking these two variables together, 96 individuals, representing 1.9% of the sample, had both asthma and COPD.   Conclusion:  Wheezing in the last 12 months alone does not correlate strongly with reversibility in spirometry. COPD and asthma diagnoses are mostly independent; its overlap affected only 1.9% of the sample. However, out of all asthmatic subjects, over half also presented COPD.