tbuckley/cabot-search huggingface dataset:
TRPM8 gene polymorphisms and their relation to cold airway hyperresponsiveness in patients with bronchial asthma
Authors: Denis E. Naumov, Julius M. Perelman, Viktor P. Kolosov, Vladimir N. Maksimov, Tatyana A. Potapova, Mikhail I. Voevoda, Xiangdong Zhou, Qi Li, Svetlana V. Naryshkina
Journal: European Respiratory Journal (2013)

Cold airway hyperresponsiveness (CAH) influences the clinical course of bronchial asthma (BA) leading to rapid deterioration of lung function in cold climate conditions. Transient receptor potential melastatin 8 (TRPM8) ion channels serve as a cold sensors and therefore may mediate airway constrictor responses to cold air. There are no data presented on the specific role of   TRPM8   gene in CAH development.    Objective:  The main goal of our study was to investigate whether the variability in   TRPM8   gene affects the state of CAH.    Methods:  123 patients with BA were recruited. All of them underwent lung function testing before and after 3-minute isocapnic cold air hyperventilation challenge (ICAH). Four SNPs of   TRPM8   gene were genotyped and tested for association with CAH: c.750G>C (rs11562975), c.1256G>A (rs7593557), c.3048C>T (rs11563208) and c.3174C>G (rs11563071).    Results:  GC genotype and C allele carriers for SNP c.750G>C were more frequently observed among the group with CAH (χ 2 =9.7, p=0.007). The odds ratio for CAH was estimated to be 3.73 95%CI (1.48; 9.37), p=0.005. Furthermore, GC heterozygotes had a prominent decrease in FEV 1  as compared to GG homozygotes (-12% (-16; -8.1) vs -6.45% (-11; -2.1), p 1 . The other SNPs except c.1256G>A showed some tendency to be related to CAH, which, however, was mostly statistically insignificant.    Conclusion:  GC variant of   TRPM8:c.750G>C   SNP predisposes to higher risk of CAH in patients with BA, which suggests a potential role of   TRPM8   as a novel gene in CAH development.
Association of SLC15A2 genomic variation with the response to sorafenib treatment: Whole-genome analysis in patients with hepatocellular carcinoma.
Authors: Bo Hyun Kim, Yeon-Su Lee, Byung Chul Kim, Aesun Shin, Jin Sook Kim, Seung-Hyun Hong, Jung-Ah Hwang, Jung Ahn Lee, Seungyoon Nam, Sung Hoon Lee, Jong Bhak, Joong-Won Park
Journal: Journal of Clinical Oncology (2015)

308 Background: Reliable biomarkers are required to predict patient response to sorafenib. We attempted to investigate genomic variations associated with responsiveness to sorafenib treatment in patients with unresectable hepatocellular carcinoma (HCC) and their functional relevance. Methods: We obtained blood samples from 4 strong and 3 poor responders to sorafenib treatment and subjected these samples to whole-genome analysis. Next, we performed validation tests for candidate single-nucleotide polymorphisms (SNPs) in the samples of 174 HCC patients who were treated with sorafenib, followed by in vitro functional analysis and in silico analyses of candidate SNPs. Results: On average, 90 gigabases/sample was generated at ~34X sequencing depth. In total, 1813 genomic variations were perfectly matched to sorafenib responses in the clinical data; 708 were located within regions for sorafenib-target genes or drug absorption, distribution, metabolism, and excretion (ADME)-related genes—36 within the coding regions and 6 identified as non-synonymous single-nucleotide variants from 4 ADME-related genes (ABCB1, FMO3, MUSK, and SLC15A2), which potentially cause functional alterations. Validation tests of 174 patients confirmed sequencing results and revealed that patients with the C/C genotype for rs2257212 in SCL15A2 displayed higher risk for cancer progression than did patients with C/T or T/T genotypes (HR: 2.18; 95% CI, 1.15–4.15; P = 0.018). In vitro functional analysis revealed that cells harboring C/C genotype for this SNP displayed lower response to sorafenib treatment than did cells harboring the T/T genotype. Structural prediction analysis revealed change in protein phosphorylation levels, potentially affecting sorafenib-associated enzymatic activity. Conclusions: SLC15A2 could be a robust biomarker of response to sorafenib treatment in HCC patients.
Genetic polymorphisms of k-ras gene in smoking related diseases
Authors: Radwa El-hefny, Alaa Shalaby, Olfat Shaker, Yousri Akl, Ahmed Al-halfawy, Assem Elessawy
Journal: European Respiratory Journal (2012)

Ras is a family of genes that have many biological functions but mainly control cell growth and development. Chemicals in cigarette smoke cause mutation in ras gene. Smoking causes lung cancer because the carcinogen bound strongly to the precise site in K-ras gene. Our aim of the study is to detect genetic polymorphism of K-ras gene in smoking related diseases.  The study included 50 patients, 20 with chronic obstructive pulmonary disease (COPD), 20 with lung cancer and 10 normal subjects. All patients and normal subjects were smokers. Serum samples were evaluated, DNA was extracted and mutational analyses performed using a PCR assay. Two (10%) out of 20 COPD patients and four (20%) out of 20 lung cancer patients had mutated k-ras gene, while there was no mutation in the control group. The mutation of k-ras gene was associated with smoking history, severity of COPD and cell type of lung cancer. Mutations were observed in heavy smokers in COPD (13.3%) and lung cancer (22.2%) patients. Moderate (14.3%) and severe (12.5%) obstruction in COPD patients were associated with mutations. All k-ras mutations were observed in non small cell lung cancer (NSCLC (95%).  In conclusion, k-ras mutation is detected in the lung cancer and COPD patients suggesting that COPD patients were in the early stages of developing cancer. For COPD patients the ras gene might be a biomarker for cancer as a screening of DNA in serum using a noninvasive technique.
Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities. Swedish Melanoma Study Group.
Authors: L Hafström, C M Rudenstam, E Blomquist, C Ingvar, P E Jönsson, B Lagerlöf, C Lindholm, U Ringborg, G Westman, L Ostrup
Journal: Journal of Clinical Oncology (1991)

A prospective randomized trial testing regional hyperthermic perfusion with melphalan has been conducted. Sixty-nine patients with recurrent malignant melanoma of the extremities were randomly allocated to surgery (36 patients) or surgery plus regional perfusion (33 patients). Prognostic variables concerning primary tumor as well as the recurrent disease were evenly distributed in the groups, excluding any bias in the randomization. Median tumor-free survival after randomization was 17 months in the perfusion group and 10 months in the control group. There were 15 locoregional recurrences in the perfusion group and 24 in the control group. The tumor-free survival curve was significantly (P = .044) better for the perfusion group than for the control group. Median survival time after randomization was 57 months in the perfusion group and 35 months in the control group. This difference was not significant. One patient died within 1 month after perfusion of pulmonary embolism. Regional hyperthermic perfusion after surgery of recurrent malignant melanoma should only be recommended in prospective and controlled trials, until its value has been proven in several randomized studies.
Abstract 2850: Biomarkers for detection of exfoliated tumor cells in the peritoneal cavity in rectal cancer
Authors: Annette T. Kristensen, Arne Solbakken, Stein G. Larsen, Karl-Erik Giercksky, Eivind Hovig, Ragnhild Lothe, Guro E. Lind, Marianne G. Guren, Kjersti Flatmark
Journal: Cancer Research (2014)

Abstract During tumor growth, and possibly by manipulation during surgery, cells from rectal tumors may be shed into the peritoneal cavity. Such cells may contribute to development of metastatic disease, in the form of peritoneal carcinomatosis. Detection of cancer cells in the peritoneal cavity at the time of primary surgery might therefore be of value for prediction of disease recurrence with subsequent prognostic implications. We previously investigated the incidence of exfoliated cancer cells in peritoneal lavage fluid after resection of locally advanced rectal cancer (LARC). DNA from cells obtained by peritoneal lavage was analyzed with respect to mutations in hotspots of the K-RAS gene. K-RAS mutations were present in 30% of the primary tumors, and were detected in 8% of the lavage fluids examined. The presence of cells with K-RAS mutations in lavage fluid was associated with poor survival, suggesting that a molecular approach for detection of exfoliated tumor cells may be feasible, but K-RAS, although highly specific for detection of tumor cells, is insufficient as the only biomarker. Furthermore, since lavage fluid was collected only at the end of the surgical procedure, the relevance of spontaneous versus iatrogenic tumor cell exfoliation could not be determined. Based on these encouraging results, a prospective study was initiated, in which lavage is performed before and after surgical removal of the primary tumor to provide data regarding the cause of tumor cell exfoliation and their respective contributions to patient outcome. To increase detection sensitivity, a set of highly specific DNA methylation-based biomarkers is explored. In a pilot experiment, a panel of 12 biomarkers has been evaluated in primary tumors from 17 LARC patients using quantitative methylation specific polymerase chain reaction. Methylation of six genes, CNRIP1, MAL, SPG20, FBN1, SNCA and CDO1 was present at high frequencies in this cohort (in 55-88 % of the samples analyzed), and this biomarker panel has been selected for further comparative analysis in lavage samples. The presence of K-RAS, B-RAF and PIK3CA mutations is analyzed using denaturant capillary electrophoresis of PCR-amplified genes. Results from these genetic analyses of the primary tumors and lavage samples of 50 LARC patients will be presented. Citation Format: Annette T. Kristensen, Arne Solbakken, Stein G. Larsen, Karl-Erik Giercksky, Eivind Hovig, Ragnhild Lothe, Guro E. Lind, Marianne G. Guren, Kjersti Flatmark. Biomarkers for detection of exfoliated tumor cells in the peritoneal cavity in rectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2850. doi:10.1158/1538-7445.AM2014-2850
Adaptation of the GLI- 2012 spirometry reference equations for use in Indian children
Authors: Jane Kirkby, Sooky Lum, Janet Stocks, Rachel Bonner, Samatha Sonnappa
Journal: European Respiratory Journal (2014)

Background: The Global Lung Function Initiative (GLI) produced the first global all-age, multi-ethnic reference equations for spirometry (Quanjer, ERJ 2012) but lacked equations for South Asians.  Aim: To derive spirometry coefficients for Indian children based on GLI-2012 equations.  Methods: Identical anthropometry and spirometry were undertaken in healthy Indian children participating in the Size and Lung Function in Children study in London, UK and Bangalore, India. We have previously shown that anthropometry and lung function were similar between Indian children living in Bangalore city and those living in London (Kirkby, ERS-2013 abstract). Data from both centres were pooled to derive a new coefficient for Indian children using GLI software (www.lungfunction.org).  Results:Spirometry data from healthy Indian children l12y born in the UK (n=429) and India (n=382) were available. Compared to White children, FEV1 was 11% lower [mean (95%CI) -0.98z-scores (-0.99; -0.97)] in Indian children. A proportional reduction in FVC was observed such that FEV1/FVC was constant between groups (Figure1). After deriving and applying the new coefficients for Indian children, the mean (SD) for FEV1, FVC and FEV1/FVC z-scores approximated 0(1)  Conclusion: The derivation of GLI-coefficients from healthy Indian children will facilitate interpretation of spirometry data in Indian children with lung disease.
Prognostic Significance of a Novel Hypoxia-Regulated Marker, Carbonic Anhydrase IX, in Invasive Breast Carcinoma
Authors: Stephen K. Chia, Charles C. Wykoff, Peter H. Watson, Cheng Han, Russell D. Leek, Jaromir Pastorek, Kevin C. Gatter, Peter Ratcliffe, Adrian L. Harris
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To assess the frequency of expression and the prognostic significance of a hypoxia-regulated marker, carbonic anhydrase IX (CA IX), in a cohort of patients with invasive breast cancer. PATIENTS AND METHODS: CA IX expression was evaluated by immunohistochemistry with a murine monoclonal antibody, M75, in a series of 103 women treated surgically for invasive breast cancer. The majority of patients were treated with adjuvant hormonal or chemotherapy. The frequency of CA IX expression, its association with recognized prognostic factors, and the relationship with outcome was evaluated by univariate and multivariate statistical analyses. RESULTS: CA IX expression was present in 49 (48%) of 103 cases. The level of CA IX expression was found to be significantly associated with tumor necrosis (P &lt; .001), higher grade (P = .02), and negative estrogen receptor status (P &lt; .001). Furthermore, CA IX expression was associated with a higher relapse rate (P = .004) and a worse overall survival (P = .001). By multivariate analysis, CA IX was also shown to be an independent predictive factor for overall survival (hazard ratio, 2.61; 95% confidence interval, 1.01 to 6.75, P = .05). CONCLUSION: CA IX expression was associated with worse relapse-free survival and overall survival in an unselected cohort of patients with invasive breast carcinoma. The potential role of CA IX as a marker of hypoxia within breast carcinomas was also indicated by a significant association with necrosis. Further work assessing its prognostic significance in breast cancer is warranted, particularly interactions with radiotherapy and chemotherapy resistance.
Gene expression profile of necrotizing enterocolitis model in neonatal mice
Authors: Kyuwhan Jung, Jeong-Hyun Kim, Hyun Sub Cheong, Eun Shin, Seong-Ho Kim, Ji-Yeon Hwang, Eunyoung Lee, Mi-Ok Yoon, Seong-Hee Kim, Cherry Ann Sio, Hyoung Doo Shin, Sung-Eun Jung
Journal: International Journal of Surgery (2015)
Analysis of the cost-effectiveness of monotherapy versus fixed dose combination treatment of asthma in Republic of Moldova
Authors: Alexandru Corlateanu, Victor Botnaru, Ana Procoava, Olga Corlateanu
Journal: European Respiratory Journal (2013)

Background: Asthma is one of the most common chronic diseases in the world and its prevalence continues to increase. Despite the availability of effective asthma controller medications, many asthma patients in Republic of Moldova are still not meeting therapeutic goals because of the poor disease management.  The aim of this study was to assess the cost-effectiveness of ICS monotherapy versus fixed dose combination treatment of asthma in Republic of Moldova.  Methods: For retrospective pharmacoecomonic analysis there was used the data of clinical and population-based trials, monitoring of drug prices and sales and health care resources.  Results:  In Republic of Moldova the average monthly cost of SAL/FP represents 352 Lei (∼22 €) and monotherapy with ICS costs 287 Lei (∼17.9 €). Health care costs (unscheduled physician visits, hospitalization, emergency visit, SABA) and QOL measures were 76 Lei (4.8 €) and 0.75 for controlled asthma; 12686 Lei (793 €) and 0.49 for uncontrolled asthma. The annual costs per patient were higher for ICS monotherapy than for SAL/FP (8583 Lei / 536 € versus 7464 Lei/466 €). SAL/FP in comparison with ICS monotherapy was associated with an expected increase of QALYs per patient (0.68 QALYs vs. 0.65 QALYs). The cost-utility analysis demonstrated that SAL/FP was dominant (less costly and more effective in terms of QALYs gained).  Conclusion: Pharmacoeconomic analysis demonstrates that salmeterol/fluticasone propionate administered via a single inhaler represents a cost-effective treatment strategy in comparison with ICS monotherapy.
The effect of Theophylline in patients with allergic rhinitis: A double-blind, randomised, crossover study
Authors: Prasanna Sankaran, Claire Brockwell, Andrew Wilson
Journal: European Respiratory Journal (2014)

Background   Allergic rhinitis and Asthma are considered as 9one airway disease9. Theophylline is used as a bronchodilator in asthma and also has anti-inflammatory properties. We hypothesize that low dose theophylline in persistent allergic rhinitis improves total nasal symptom score (TNSS).   Methods   We conducted a double-blind, randomised placebo controlled crossover study of Theophylline 200 mgs twice a day for 4 weeks in 21 patients with persistent rhinitis. Primary outcome was change in TNSS. Secondary endpoint measures were differences in peak nasal inspiratory flow,Sino-Nasal Outcome Test. Participants continued with their intra nasal steroids and antihistamines.   Results   There was no significant differences in TNSS, peak nasal inspiratory flow or sino-nasal outcome test between treatment periods but there was a non-significant improvement with Theophylline treatment period  Nasal scrape samples were stained with HDAC2 antibodies and the signals were very week during immunostaining. The intention-to-treat analysis results for both the primary and secondary outcomes were in keeping with the per protocol analysis   Conclusion   Low-dose Theophylline had no significant effects on total nasal symptom scores, rhinosinusitis symptoms questionnaire and nasal patency assessed using peak nasal inspiratory flow. There was a non-significant improvements in the total nasal symptom scores and sino-nasal outcome test.
Urinary Excretion of Estrone, Estradiol, and Estriol in Postmenopausal Women With Primary Breast Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C E Morreal, T L Dao, T Nemoto, P A Lonergan
Journal: JNCI Journal of the National Cancer Institute (1979)

The daily excretion of estrone, estradiol, and estriol was determined for 22 normal women and 35 women with primary breast cancer. The excretion of the hormones (measured in microgram/24 hr) in the breast cancer group was elevated and showed a statistical significance of P less than 0.001. The same wide difference between the 2 groups was also noted when excretion was expressed in terms of the body area of the individuals and when women of similar ages were compared.
Bone Marrow Transplantation in Adult Thalassemic Patients
Authors: G. Lucarelli, R.A. Clift, M. Galimberti, E. Angelucci, C. Giardini, D. Baronciani, P. Polchi, M. Andreani, D. Gaziev, B. Erer, A. Ciaroni, F. D’Adamo, F. Albertini, P. Muretto
Journal: Blood (1999)
Periodontal health through public health – the case for oral health promotion
Authors: Richard G. Watt, Poul E. Petersen
Journal: Periodontology 2000 (2012)

Abstract Periodontal diseases are highly prevalent, particularly amongst socially disadvantaged populations, impact on quality of life and are costly to treat. Clinical treatments and chairside preventive approaches alone will never adequately address this problem. Indeed in many parts of the developing world clinical care and chairside prevention are both unaffordable and inappropriate for the control of periodontal diseases. A paradigm shift away from the individualized treatment approach to a population public health model is needed to promote periodontal health and, in particular to address social inequalities in periodontal status. Public health measures need to focus on the underlying determinants of periodontal diseases. Poor hygiene, tobacco use, psychosocial factors and related systemic diseases are the main risk factors for periodontal diseases. Public health interventions need to tackle these factors but also must recognize and act upon the distal underlying influences that determine and pattern these identified risks. Recognition also needs to be placed on the interlinking and common risk factors shared by periodontal diseases and other chronic conditions. A complementary range of public health policies acting at local, regional, national and international levels need to be implemented to achieve sustainable improvements in oral health. To be effective these policies need to link across the broader public health agenda and require public engagement and support. Clinicians, public health practitioners, commercial organizations and professional groups all have an important role to play in promoting periodontal health.
Validity of early MRI structural damage end points and potential impact on clinical trial design in rheumatoid arthritis
Authors: Joshua F Baker, Philip G Conaghan, Paul Emery, Daniel G Baker, Mikkel Østergaard
Journal: Annals of the Rheumatic Diseases (2015)

Objective To evaluate the construct validity of the rheumatoid arthritis MRI score (RAMRIS) erosion evaluation as structural damage end point and to assess the potential impact of incorporation in clinical trials. Methods In a randomised trial of early methotrexate-naïve RA (GO-BEFORE), RAMRIS scores were determined from MRIs and van der Heijde-Sharp (vdHS) scores from radiographs, at baseline, week 12, week 24 and week 52. Progression in damage scores was defined as change &gt;0.5. Associations of X-ray and MRI outcomes with clinical features were evaluated for convergent validity. Iterative Wilcoxon rank sum tests and tests of proportion estimated the sample size required to detect differences between combination therapy (methotrexate+golimumab) and methotrexate-monotherapy arms in (A) change in damage score and (B) proportion of patients progressing. Results Patients with early MRI progression had higher DAS28, C reactive protein (CRP) and vdHS at baseline, and higher 2-year HAQ. Associations were similar to those with 1-year vdHS progression. Differences in change in structural damage between treatment arms achieved significance with fewer subjects when 12-week or 24-week MRI erosion score was the outcome (150 patients; 100 among an enriched sample with baseline-synovitis &gt;5) compared with the 52-week vdHS (275 patients). Differences in the proportion progressing could be detected in 234 total subjects with 12-week MRI in an enriched sample whereas 1-year X-ray required between 468 and 1160 subjects. Conclusions Early MRI erosion progression is a valid measure of structural damage that could substantially decrease sample size and study duration if used as structural damage end point in RA clinical trials.