tbuckley/cabot-search huggingface dataset:
<i>EGFR</i> Tyrosine Kinase Domain Mutations Are Detected in Histologically Normal Respiratory Epithelium in Lung Cancer Patients
Authors: Ximing Tang, Hisayuki Shigematsu, B. Nebiyou Bekele, Jack A. Roth, John D. Minna, Waun Ki Hong, Adi F. Gazdar, Ignacio I. Wistuba
Journal: Cancer Research (2005)

Abstract To determine whether EGFR tyrosine kinase domain mutations are early events in the pathogenesis of lung adenocarcinomas, we tested for the presence of EGFR mutations in histologically normal bronchial and bronchiolar epithelia from lung adenocarcinomas bearing the common EGFR mutations. DNA was extracted from microdissected tissue obtained from 21 tumors with known EGFR mutations, 16 tumors without mutation, and 90 sites of normal bronchial and bronchiolar epithelium from the same surgical specimens. With the use of PCR and direct DNA sequencing, EGFR mutations identical to the tumors were detected in the normal respiratory epithelium in 9 of 21 (43%) patients with EGFR mutant adenocarcinomas but none in patients without mutation in the tumors. The finding of mutations being more frequent in normal epithelium within tumor (43%) than in adjacent sites (24%) suggests a localized field effect phenomenon. Our findings indicate that mutation of the tyrosine kinase domain of EGFR is an early event in the pathogenesis of lung adenocarcinomas, and suggest EGFR mutations as an early detection marker and chemoprevention target.
Subcutaneous Growth and Transplantation of the RS 1 Rat Tumor Into Adult Unconditioned Golden Hamsters
Authors: I. Encut, Lidia Cioloca
Journal: JNCI Journal of the National Cancer Institute (1973)

The RS 1 rat tumor was heterotransplanted into adult, immunologically unconditioned golden hamsters by subcutaneous implantation of a tumor fragment. The histologic and chromosomal pattern of the RS 1 rat tumor was retained after serial hetero-transplantation. Some factors which may account for the apparently indefinite passage ability of this tumor in unconditioned hamsters were presented.
A reliable and long shelf-life in vitro cell model for studying goblet cell metaplasia in the human airways
Authors: Song Huang, Andreas Hohlbaum, Barbara Rattenstetter, Ludovic Wiszniewski, Samuel Constant
Journal: European Respiratory Journal (2012)

Goblet cell metaplasia, induced mainly by TH-2 cytokines like IL-13 and IL-4, is a common feature of several respiratory diseases such as asthma, COPD, and Cystic fibrosis. Recent clinic trials demonstrated that blocking IL-13 signaling seems to be an effective therapeutic strategy. In order to develop more efficient drugs, a reliable and reproducible in vitro cell model would be invaluable. Epithelix has developed a high quality in vitro cell model of the human airway epithelia (MucilAir) which can be maintained at a functional and homeostatic state for a year, allowing long term tests of drug candidates. In order to create an in vitro cell model of the airway goblet cell metaplasia, MucilAir was treated with IL-13 at different concentrations, ranging from 0.3 to 30 ng/ml. Using in situ Alcian Blue staining, as well as histological analysis, we demonstrated that MucilAir showed an increased goblet cell density after 14 days of IL-13 treatment, in a dose dependent manner. Furthermore, ELISA analysis revealed a concomitant increase of Eotaxin and Periostin released in the culture media as a function of IL-13 concentration. Despite some subtle morphological differences of the goblet cells between donors, the results from several different batches of MucilAir are very similar and therefore reproducible. Taken together, MucilAir is a relevant and reliable in vitro cell model for studying Goblet cell metaplasia, and for assessing the efficacy of drug candidates.
Influenza and pneumonia in Ukraine: An epidemiological survey
Authors: Yaroslav Dziublyk, Sergiy Soloviov
Journal: European Respiratory Journal (2013)

A great impact of influenza on community-acquired pneumonia (CAP) morbidity is widely recognized. However, a statistical data, reflecting the interrelation between these infections in Ukraine have never been presented before.   The aim  of the study was to reveal possible relationship between CAP and influenza morbidity rates for 2009-2011 epidemic seasons in Ukraine.   Materials and methods.  The official epidemiological data, published annually by Ministry of health of Ukraine Medical Statistics Center, Influenza Control Center and National institute of phthisiology and pulmonology, were analyzed. As a results the linear regression models of CAP morbidity were built for 4 regions of Ukraine (Kyiv, Vinnytsia, Ivano-Frankivsk and Dnipropetrivsk oblast). The correlation between the results of modeling and intensive influenza morbidity indices was evaluated using the Pearson’s correlation coefficient.   Results.  The highest pneumonia morbidity rate in Ukraine was in 2009-2010, exceeding corresponding value for 2008 by 24,2 % and 2011 – by 5 %. A significant correlation between intensive influenza morbidity, taken for each geographical region, and pneumonia regression model inclination was established (r=0,91).   Conclusion.  An existance of strong association between influenza outbreaks and high level of CAP incidence in different regions of Ukraine suggests the necessity of more closer epidemic monitoring and more intensive use of influenza preventive strategies in order to reduce the burden of low respiratory tract infections.
Abstract 313: Elucidation Of The Fibrotic Transcription Factors Gene Network Leading To Chagas Heart Disease
Authors: Pius N Nde, Aniekanabassi N Udoko, Candice A Johnson, Andrey Dykan, Girish Rachakonda, Fernando Villalta, Maria F Lima, Siddharth Pratap
Journal: Circulation Research (2014)

Background: Trypanosoma cruzi the causative agent of Chagas heart disease (CHD) remains incurable. The major pathology induced by the parasite is cardiac fibrosis leading to heart failure followed by death. The mechanisms of T. cruzi induced cardio-pathology remains largely unknown. We hypothesize that T. cruzi infection regulates the expression of profibrotic genes in human cardiac myocytes (HCM), tilting the heart towards a profibrotic phenotype seen in CHD patients. Methods and Results: To elucidate the molecular mechanisms of T. cruzi induced cardiac fibrosis, we challenged primary HCM with T. cruzi for two hours and purified total RNA for microarray. We investigated changes at the whole transcriptome level on an affymetrix platform. The arrays were done in triplicates at different time points; changes in gene expression greater than 2-fold and having a Benjamini and Hochburg false discovery rate corrected p-value &lt;0.05 were considered significant. The microarray data was validated using real-time PCR followed by PCR array and immunoblotting, to evaluate changes in the protein expression levels of fibrotic transcription factors. Protein expression levels were evaluated in triplicate and analyzed by ANOVA. The fibrotic interactome induced by T. cruzi in HCM was elucidated using Cytoscape. Our results indicate that exposure of HCM to T. cruzi upregulates the transcript levels of two transcription factors associated with fibrosis, SNAI1 (more than 2 fold up-regulated) and Early Growth Response protein 1, EGR1, (about four fold up-regulated). SNAI1 and EGR1 were increased at the protein level. Furthermore, we identified the first interactome regulating fibrosis in primary HCM induced by T. cruzi . Conclusions: This is the first report showing that T. cruzi upregulates the expression of profibrotic transcription factors in HCM early during the process of cellular infection and the operational fibrotic interactome. Thus, abnormal sustained expression of SNAI1 and EGR1 upregulate the expression of genes essential for conversion of HCM towards a profibrotic phenotype in CHD. Elucidation of the molecular mechanisms by which T. cruzi induces cardiac fibrosis will lead to the identification of new therapeutic targets for CHD.
The influence of diaphragm paralysis on regional ventilation
Authors: Glenn Leemans, Cedric Van Holsbeke, Jan De Backer, Rita Claes, Veronique Verplancke, Liesbeth Vervliet, Wim Vos, Wilfried De Backer
Journal: European Respiratory Journal (2014)

Rationale   Functional Respiratory Imaging (FRI) is able to personalize respiratory treatment based on regional ventilation in patients with unilateral diaphragmatic paralysis (UDP) (Van Holsbeke, Respiratory Care 2013). In this larger dataset we aimed to asses in detail the regional ventilation of the lung at the side of the paralysis.   Methods   5 patients with UDP were included in this trial. All patients underwent FRI to investigate regional ventilation. The lobar expansion from functional residual capacity (FRC) to total lung capacity (TLC) was considered as a measure for regional ventilation.   Results   For all patients (5 male, mean age 57±4.5 years, mean FEV1 58±9.0 %predicted) the reconstructed lobes at FRC and TLC can be found in figure 1. Diminished regional ventilation of the lung at the side of the paralysis was observed in all patients (mean 30.4±8.2 % of total), especially in the lower lobe (mean 6.9±5.8 % of total). A large heterogeneity in flow distribution towards the lower lobe at the side of the paralysis was observed (5.5-11.1-1.9-14.9-1.3% of total).   Conclusion   FRI shows clearly a diminished regional ventilation at the side of the paralysis with a large heterogeneity in flow distribution for the lower lobe at that side, with virtual no flow reaching in 2/5 patients. This could be of clinical importance since a disturbed local ventilatory status can be essential in clinical decision making between a conservative or surgical approach.
Dietary History Methods for Epidemiologic Studies: Application in a Case-Control Study of Vitamin A and Lung Cancer&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Jean H. Hankin, Laurence N. Kolonel, M. Ward Hinds
Journal: JNCI Journal of the National Cancer Institute (1984)

A dietary history method for use in a case-control study of vitamin A and lung cancer is described. The method was designed to obtain estimates of the usual frequencies and quantities of 84 major food sources of vitamin A and carotene consumed prior to symptoms of disease in cases and during the same time period in matched controls. Amounts were estimated from photographs of each item that showed three different quantities. The development of the questionnaire is described in detail, as well as the data collection and analysis. The results of the study showed that relative to those men with the highest intakes, the men who consumed less vitamin A or carotene had a higher risk for lung cancer in a general dose-response fashion. These findings were not apparent for females. Recommendations regarding dietary methodology for future studies concerning vitamin A and carotene intakes include further research on the validation and reproducibility of the dietary methods, identification of appropriate biological markers that reflect past exposures of vitamin A and carotene, and further research on the vitamin A and carotene content of available food items.
Hysteresis of the parathyroid hormone response to hypocalcemia in hemodialysis patients with low turnover aluminum bone disease.
Authors: A J Felsenfeld, D Ross, M Rodriguez
Journal: Journal of the American Society of Nephrology (1991)

During the study of parathyroid function in 19 hemodialysis patients with low turnover aluminum bone disease, it was observed that serum parathyroid hormone (PTH) levels were higher during the induction of hypocalcemia than during the recovery from hypocalcemia. This type of PTH response has been termed hysteresis. Hypocalcemia was induced during hemodialysis with a calcium-free dialysate. When the total serum calcium level decreased to 7 mg/dL, the dialysate calcium concentration was changed to 3.5 mEq/L and the dialysis session was completed. One week later, hypercalcemia was induced during hemodialysis with a high-calcium dialysate. The mean basal PTH level was 132 +/- 37 pg/mL (normal, 10 to 65 pg/mL; immunoradiometric (IRMA), Nichols Institute, San Juan Capistrano, CA) and increased to a maximal PTH level of 387 +/- 91 pg/mL during hypocalcemia. For the same ionized calcium concentration, the PTH level was higher during the induction of hypocalcemia than during the recovery from hypocalcemia. Conversely, for the same ionized calcium concentration, the PTH level was greater when hypercalcemia was induced from the nadir of hypocalcemia than when hypercalcemia was induced from basal serum calcium. The set point of calcium (defined as the serum calcium concentration required to reduce maximal PTH by 50%) was greater during the induction of hypocalcemia than during the recovery from hypocalcemia (4.44 +/- 0.10 versus 4.25 +/- 0.09 mg/dL; P = 0.03). The mean basal ionized calcium concentration and the mean ionized calcium concentration at the intersection of the two PTH-calcium curves were the same (4.61 +/- 0.13 versus 4.61 +/- 0.12 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 4491: One-Year Clinical Outcome of a Real World Experience in Patients Treated with a GenousTM EPC Capturing Stent
Authors: Margo Klomp, Marcel A Beijk, Niels J Verouden, Karel T Koch, Jose P Henriques, Jan Baan, Rene J van der Schaaf, Marije M Vis, Jan G Tijssen, Jan J Piek, Robbert J de Winter
Journal: Circulation (2008)
Clinical implications of the serum level of CD23 in patients with undifferentiated nasopharyngeal carcinoma.
Authors: G Rousselet, M Bachouchi, P Busson, F de Vathaire, H Wakasugi, G Schwaab, N Azli, J P Armand, E Cvitkovic, T Tursz
Journal: Journal of Clinical Oncology (1993)

PURPOSE In contrast with other carcinoma cells, cells from nude mice transplanted undifferentiated carcinoma of nasopharyngeal type (UCNT) release the soluble fragment of the CD23 antigen (sCD23). We sought to study the level of sCD23 in sera of untreated UCNT patients. PATIENTS AND METHODS Pretherapeutic sera from 65 consecutive, locally advanced, initially nonmetastatic UCNT patients were assayed for sCD23. Patients were treated with a neoadjuvant chemotherapy/full-dose radiotherapy sequence. The mean follow-up duration is 50.5 months (range, 28 to 77). The Cox proportional hazards model was used to study the association between sCD23 levels and clinical signs and disease evolution. RESULTS sCD23 levels showed an association with disease-free survival (DFS; P = .08) and overall survival (OVS; P = .08). Patients with sCD23 levels greater than a cutoff value of 0.6 ng/mL (greater cutoffs were found to be equally significant, but less sensitive), have a relative risk (RR) of relapse of 3.3 (95% confidence interval, 1.6 to 6.9; P = .002), and an RR of death of 2.9 (95% confidence interval, 1.2 to 7.3; P = .02), when taking other prognostic factors into account. CD23 does not correlate with either the response to treatment or the development of metastases, but appears to be related to local control (cutoff, 0.6 ng/mL; RR = 5.1 [95% confidence interval, 1.2 to 21.7]; P = .02). CONCLUSION The serum level of sCD23 appears to be an independent prognostic factor for initially nonmetastatic, locally advanced UCNT patients, treated with chemotherapy and radiotherapy. Our data indicate an association between this marker and local relapses. Thus, a simple enzyme-linked immunoadsorbent assay (ELISA) could help to identify a high-risk group among nonmetastatic UCNT patients. CD23 could be a marker for two groups of UCNT tumors, with distinct biologic characteristics and clinical behaviors.
Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma
Authors: Matthew H Law, D Timothy Bishop, Jeffrey E Lee, Myriam Brossard, Nicholas G Martin, Eric K Moses, Fengju Song, Jennifer H Barrett, Rajiv Kumar, Douglas F Easton, Paul D P Pharoah, Anthony J Swerdlow, Katerina P Kypreou, John C Taylor, Mark Harland, Juliette Randerson-Moor, Lars A Akslen, Per A Andresen, Marie-Françoise Avril, Esther Azizi, Giovanna Bianchi Scarrà, Kevin M Brown, Tadeusz Dębniak, David L Duffy, David E Elder, Shenying Fang, Eitan Friedman, Pilar Galan, Paola Ghiorzo, Elizabeth M Gillanders, Alisa M Goldstein, Nelleke A Gruis, Johan Hansson, Per Helsing, Marko Hočevar, Veronica Höiom, Christian Ingvar, Peter A Kanetsky, Wei V Chen, Maria Teresa Landi, Julie Lang, G Mark Lathrop, Jan Lubiński, Rona M Mackie, Graham J Mann, Anders Molven, Grant W Montgomery, Srdjan Novaković, Håkan Olsson, Susana Puig, Joan Anton Puig-Butille, Abrar A Qureshi, Graham L Radford-Smith, Nienke van der Stoep, Remco van Doorn, David C Whiteman, Jamie E Craig, Dirk Schadendorf, Lisa A Simms, Kathryn P Burdon, Dale R Nyholt, Karen A Pooley, Nick Orr, Alexander J Stratigos, Anne E Cust, Sarah V Ward, Nicholas K Hayward, Jiali Han, Hans-Joachim Schulze, Alison M Dunning, Julia A Newton Bishop, Florence Demenais, Christopher I Amos, Stuart MacGregor, Mark M Iles
Journal: Nature Genetics (2015)
Effect of Oral Contraceptives on the Mammary Glands of Rhesus Monkeys: A Preliminary Report
Authors: Victor A. Drill, David P. Martin, E. Ross Hart, Robert G. McConnell
Journal: JNCI Journal of the National Cancer Institute (1974)

To determine the relationship of oral contraceptive use and breast cancer, 96 rhesus monkeys were administered either Enovid-E (2.5 mg norethynodrel and .1 mg mestranol) or Ovulen (1 mg ethynodiol diacetate and .1 mg mestranol) cyclically for 5 years at doses of 1, 10 and 50 times the human dose. The animals' progress was compared with a control group of 32 monkeys. General physical and mammary gland examinations were conducted before treatment and monthly thereafter. During the 5 year study period none of the treated animals demonstrated clinical evidence of mammary gland lesions, no deaths from breast malignancy occurred, and no palpable breast nodules were found.
Antibody-Dependent Cellular Cytotoxicity in Blood Monocytes and Alveolar Macrophages in Patients With Lung Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: G McLennan, P G Gill, N J De Young
Journal: JNCI Journal of the National Cancer Institute (1985)

Antibody-dependent cellular cytotoxicity (ADCC), mediated by blood monocytes (MNC) and pulmonary alveolar macrophages (PAM) obtained from 31 patients with lung cancer and 13 control subjects, was determined. The ADCC of the PAM obtained from patients with lung cancer was significantly less (40% reduction) than that of the control group. This finding was demonstrated over the range of effector-to-target cell ratios. The ADCC of blood MNC from the cancer patients was not different from that of control subjects and in both groups the ADCC of blood MNC was significantly greater than that of lung macrophages. Comparison of PAM ADCC in smokers and nonsmokers within the control group suggested that the lower activity in cancer patients was not simply an effect of smoking.
Meeting the referral criteria to the rapid access lung cancer clinic: A 10-year audit
Authors: Syed M.H. Kazmi, Mohammed Hussain, Martin Ledson, Colin Smyth, Martin Walshaw
Journal: European Respiratory Journal (2012)

INTRODUCTION:

Although targeting patients with agreed criteria (where the risk of cancer is high) under the “two week wait” rule to fast-track lung cancer clinics allows an efficient and timely diagnosis, the referral of other patients to such services will potentially waste valuable healthcare resources. To look at this further we studied the trends in referral to our dedicated rapid access lung cancer clinic since its inception in 2001.

METHOD:

We audited referrals in 2001, 2009 and 2011, looking for their compliance with the nationally agreed referral criteria, and their subsequent placement and outcome.

RESULTS:

There was an increase in referrals that did not meet the agreed criteria with time.

![Figure][1] 



Of those that did not meet the agreed criteria, in 2001: 10 were returned to the referrer, 18 redirected to a general chest clinic, and 3 were already under specialist care (2009: 15, 51, and 17; 2011: 44, 108, and 12 respectively).

Subsequently 9 (3%) were diagnosed with lung cancer (8 at follow-up and only 1 on re-referral 18 months later with haemoptysis).

CONCLUSION:

These results show that a significant and increasing proportion of referrals are made outside the agreed national criteria and may have been more appropriately referred elsewhere. We are seeking to educate our colleagues to ensure that these scarce and expensive healthcare resources are best used for this unfortunate patient population.

 [1]: pending:yes
Efficacy of talc pleurodesis in patients with malignant pleural effusions
Authors: Inmaculada Alfageme, Nuria Reyes, Javier Gallego, Juan Cotera, Isabel Caballero, Desire Macias
Journal: European Respiratory Journal (2011)

The aim of this study was to analyze complications and survival after talc pleurodesis for recurrent malignant pleural effusion.   Methods:  All patients with proven malignant pleural effusion who received talc pleurodesis from January 2004 to August 2010 were included in a retrospective analysis. Talc pleurodesis was performed with talc slurry if the pleural effusion was known previously as neoplastic or under medical thoracoscopic with talc poudrage if the pleural effusion was undiagnosed at this moment. The procedure was performed only if a pulmonary reexpansion was proved in the previous day. Postoperative pleural drainage was used until fluid output was less than 100 ml/24 h.   Results:  54 patients (30 male and 24 female) with mean age 65.9±12.5 (range 36-91) years were included. The most common primary cancer sites were lung (13 cases), mesothelioma (9), gynecological (7), digestive (8), and unknown primary (9). Six patients (11%) developed thrombosis (four in the cava vein), Two patients developed empiema and other two bronchopleural fistula. In 7 cases pleurodesis was ineffective and in nine cases pleural effusion relapsed. In 17 cases was complete success (32%) and in 21 partial success (39%). Patients with Karfnosfky index (KI) > 60% had greater survival [10.71 months 95%CI (7.34 -14.08)] than patients with KI less than 60% [2.52 months 95%CI (0.20 -4.84)]  KI more than 60% is a useful criteria to select candidates to talc pleurodesis.