tbuckley/cabot-search huggingface dataset:
Platelet endothelial cell adhesion molecule-1 expression in blood cells from patients with chronic obstructive pulmonary disease
Authors: Ryo Kato, Shiro Mizuno, Makoto Kobayashi, Taku Oikawa, Ken Nakagawa, Kazuhiro Osanai, Maiko Kadowaki, Takeshi Ishizaki, Hirohisa Toga
Journal: European Respiratory Journal (2014)

Rationale: Endothelial progenitor cells (EPC) are are thought to play an important role in repair process of the endothelium in COPD patients. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is expressed at high levels on early and mature endothelial cells, and is also known as a marker of EPC.

Objective: we measured expression of PECANM-1 in blood samples from smokers to clarify the PECAM-1 can be used as a biomarker to detect COPD phenotypes.

Methods: 323 patients who have a smoking history (more than 10 pack years) were included in this study. 91 blood samples were from patients with normal lung function, the remainder of the samples were from patients with mild (n=67; GOLD I), moderate (n=103; GOLD II) and severe COPD (n=62; GOLD III and IV). The RNA from blood samples were extracted using PAX gene blood RNA kit and PECAM-1 mRNA expression were measured by real-time RT-PCR using LightCycler system. Analysis of chest HRCT images for emphysematous changes (%LAA) was performed using computer software (LungVison ver 2.1, Cybernet Systems CO. LTD.).

Results: PECAM-1 expressions from blood samples were significantly decreased in the moderate COPD patients compared with the age matched smoking control patients. However, there were no significant differences in the PECAM expression between severe COPD and smoking control patients.

Conclusion: the PECAM-1 expression from blood cells may be a biomarker of COPD in stable moderate COPD patients. The regain of PECAM expression in severe COPD could be explained by consequence of systemic inflammation, hypoxemia and frequency of complications such as cardiac vascular diseases.
Abstract 846: Patient Willingness to Participate in Genetic Research After a Myocardial Infarction
Authors: David E Lanfear, Philip G Jones, Sharon Cresci, Fengming Tang, Saif S Rathore, John A Spertus
Journal: Circulation (2008)

To achieve ‘Personalized Medicine’, identifying genetic associations with outcomes is essential. However, not all patients invited to participate in such studies agree. While existing data suggests race, gender, and education may influence this decision, correlates of patient willingness to participate in genetic studies remain incompletely understood. We assessed correlates of patient participation in the genetic substudy of TRIUMPH, a prospective myocardial infarction registry ongoing at 26 US hospitals. Patients enrolled in the first wave (4/05–12/06, N=1854) were analyzed. Factors examined included sociodemographics, financial status, social support, medical literacy, health status, depressive symptoms (PHQ-9, higher scores indicate greater depression) and 26 clinical variables. Predictors of participation were identified using hierarchical logistic regression adjusting for hospital. Variation in consent rates across hospitals was quantified by the median odds ratio (MOR), which compares the odds of consent between two randomly selected patients with identical covariates chosen from different hospitals. Most subjects consented to donation and storage of their genetic material (1,513, 81.6%). Participation rates varied greatly by site, ranging from 50% to 100%. After adjustment for possible confounding by patient factors, the MOR for hospitals was 4.5. Clinical characteristics were not associated with participation in univariate analysis (all p&gt;0.1). In multivariable analysis adjusted for hospital, the only significant predictors of consent were greater depressive symptoms (OR 1.41 per +5 PHQ points, 95% CI 1.19–1.67, p&lt;0.0001), and gender (OR 1.54 for males, 95% CI 1.16–2.04, p=0.0027). Roughly 80% of subjects enrolled in our study consented to genetic analysis. The strongest overall factor associated with participation was hospital. While we cannot rule out confounding by unmeasured characteristics, this suggests that variation in the way information is presented, or other site-specific factors, strongly influence patient participation in genetic studies. This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota &amp; Wisconsin).
Video-assisted thoracoscopic surgery decrease the physical performances of lung cancer patients: Short-term prospective study
Authors: Kunihiko Anami, Yoshiyasu Hirayama, Naoki Yamashita, Yoichi Tsukuda, Jun Horie
Journal: European Respiratory Journal (2014)

Introduction: Video-assisted thoracoscopic surgery (VATS) is considered as a minimally invasive method, and recently it has become a standard operative procedure for lung cancer. However, it is not clear how VATS affects physical performances and psychological function. The purpose of this prospective study was to clarify the short-term effect of VATS to physical performances and psychological functions in patients with lung cancer.  Methods: Participants with lung cancer were recruited (n = 18; mean ± SD age, 71.9 ± 6.9 years). We measured physical performances (pulmonary function, respiratory muscle strength, grip strength, knee extension strength, timed up and go test, 6-minutes walking test) and psychological functions (cancer fatigue scale, hospital anxiety depression scale, short-form 8 items health survey) at before and after VATS.  Results: The median length of hospital stay was 8.0 (range, 5.0-21.0) days. The %FVC (p  1.0  (p   Conclusion: VATS decreased the physical performances in patients with lung cancer in short-term. Therefore, it is necessary to provide effective postoperative rehabilitation to improve these decreased physical performances.
Pulmonary Hypertension in POEMS Syndrome
Authors: PHILIPPE LESPRIT, BERTRAND GODEAU, FRANCOIS-JÉRÔME AUTHIER, MARTIN SOUBRIER, MATHIEU ZUBER, CLAIRE LARROCHE, JEAN-PAUL VIARD, BERTRAND WECHSLER, ROMAIN GHERARDI
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare variant of plasma cell dyscrasia with multiple systemic manifestations. We followed the progress of 20 patients with POEMS syndrome in our institution over a 10-yr period. Pulmonary hypertension (PH) was observed in five patients. All patients suffered dyspnea on exertion, which always appeared during an exacerbation of POEMS syndrome. The typical echocardiographic signs of PH were observed in all of these patients, and the median pulmonary-artery systolic pressure was 57 mm Hg (range, 50 to 65 mm Hg). Mean pulmonary-artery pressure during right side heart catheterization in two patients was 32 mm Hg. No other explanation for the PH could be found. Overproduction of cytokines was found in all cases, with high serum concentrations of interleukin-1 β , interleukin-6, tumor necrosis factor- α , and vascular endothelial growth factor. We suggest that PH should be added to the list of symptoms of POEMS syndrome. Cytokines may mediate POEMS syndrome-associated PH, as proposed for the other systemic manifestations of this disorder.
Would RDW be a prognostic factor in pulmonary arterial hypertension
Authors: Can Sevinc, Kemal Can Tertemiz, Bahri Akdeniz, Aylin Ozgen Alpaydin, Ahmet Melih Birlik, Nezihi Baris
Journal: European Respiratory Journal (2014)

Aim and Methods:   Erythrocyte morphology is influenced by hematological pathologies, systemic inflammation, infective erythropoiesis and nutritional deficiencies. Erythrocyte morphology might be evaluated by “red blood cell (RBC) distribution width (RDW)”. We aimed to study the relationship of RDW with N-terminal pro-brain natriuretic peptide (NT-proBNP), 6 minute walk test (6MWT), pulmonary arterial pressure (PAP), arterial blood gases analysis in patients with pulmonary arterial hypertension (PAH) patients of our hospital   Results   Fifty-four female and 72 male patients whose mean age was 52 were included in the study. Mean follow-up duration was 20 months. According to PAH etiologies, 20 patients were diagnosed as iPAH, 14 as CTEPH, 24 were due to chronic cardiac disease, 10 were due to collagen vascular disease and 4 were due to other diseases. There were significant correlations between pretreatment RDW and functional capacity (FC), NT-proBNP, RV fractional area change, right ventricle Tei index, arterial oxygen saturation and CRP (p   Conclusion:   There are limited data upon the association between erythrocyte morphology and PAH parameters and mortality. In our center we observed a close relationship between RDW and routine follow-up and prognostic parameters of PAH as well as mortality.
Effect of tenofovir disoproxil fumarate on drug-resistant HBV clones
Authors: Eisuke Murakami, Masataka Tsuge, Nobuhiko Hiraga, Hiromi Kan, Takuro Uchida, Keiichi Masaki, Takashi Nakahara, Atsushi Ono, Daiki Miki, Tomokazu Kawaoka, Hiromi Abe, Michio Imamura, Hiroshi Aikata, Hidenori Ochi, C. Nelson Hayes, Tomoyuki Akita, Junko Tanaka, Kazuaki Chayama
Journal: Journal of Infection (2015)
Chemosensitivity Testing in V79 Spheroids: Drug Delivery and Cellular Microenvironment&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: R E Durand
Journal: JNCI Journal of the National Cancer Institute (1986)

Chinese hamster V79 multicell spheroids growing in tissue culture exhibit many of the same properties as solid tumors outgrowing their blood supply, including the spontaneous development of both noncycling and hypoxic cell populations expected to be resistant to many chemotherapeutic agents. Cell-sorting techniques were used to select cells as a function of their position (depth) within the spheroid to test this prediction. "Sensitivity profiles" of cells from various regions within spheroids after treatment with doxorubicin, bleomycin, 5-fluorouracil, carmustine, cisplatin, chlorambucil, and mitomycin are presented. Additionally, exposure of preseparated cells was used to distinguish inherent sensitivity from environmental or locational factors. For these drugs, penetration was a problem only for doxorubicin; in contrast, the microenvironment in the intact spheroid had a much greater influence on cell sensitivity.
Diagnostics of congenital pneumonia
Authors: Lydmila Gurina
Journal: European Respiratory Journal (2014)

In the Republic of Belarus congenital infections caused by neonatal mortality come second after congenital abnormalities. Early diagnostics of congenital infections is an urgent problem of medicine. Congenital pneumonia of neonates does not have any clinical evidence.

The objective of the research was early diagnostics of congenital pneumonia of full-term neonates.

151 full-term neonates born in clinical maternity in Grodno, the Republic of Belarus, were examined. The children were divided into three groups on the basis of full clinical-laboratory and tool inspection (the 2nd and the 3rd are the main groups). Congenital pneumonia was a criterion of inclusion in the second group (the 2nd group, n=45). Noninfectious pathology (cerebral ischemia) was a criterion of inclusion in the third group (the 3rd group, n=83). Healthy neonates formed the first group (the 1st group is a group of comparison, n=23). With the help of spectrophotometric method the activity of the elastase proteases in umbilical blood serum was determined. ROC analysis of studied indicators was carried out.

The results of the research showed that the level of elastase activity in umbilical blood serum of neonates with congenital pneumonia was considerably higher than of healthy babies and neonates with noninfectious pathology (p<0,05). The activity of elastase of neonates with congenital pneumonia was 0,81 (0,78/0,88) me/mkl, of neonates with cerebral ischemia – 0,59 (0,54/0,74) me/mkl, of healthy neonates - 0,37 (0,31/0,41) me/mkl.

With the help of ROC analysis it was found that congenital pneumonia is diagnosticated with the level of blood serum's elastase activity of more than 0,76 me/mkl with diagnostic sensitivity of 81%, diagnostic specificity of 91%.
Abstract 4229: The anti-estrogen effect of metformin in ERα+ breast cancer and tamoxifen resistant cell lines
Authors: Jinkyoung Kim, Jiyun Lee, Soonyoung Jang, Chungyeul Kim, Aeree Kim
Journal: Cancer Research (2014)

Abstract Anti-estrogen therapy is still the most important systemic treatment to manage estrogen responsive breast cancer. Tamoxifen resistance is a major obstacle in treatment of ER-positive breast cancer. Recently, metformin, which is a biguanide derivative which is commonly used in the treatment of type II diabetes, has been emerged as a potential anti-cancer agent. We investigated if metformin had anti-estrogen effect in ER-positive breast cancer cell lines which are MCF-7, MDA-MB-361 as well as tamoxifen resistant cells (TR-MCF-7). Metformin inhibited the cell proliferation and the expression of ERα in dose-dependent manner in MCF-7 and TR-MCF-7 cells. Under stimulation of 17β-estradiol (E2), metformin inhibited the cell proliferation and expression of mRNA and protein of ERα in MCF-7 and TR-MCF-7 cells, while tamoxifen didn't affect E2 induced cell proliferation and ERα expression. This result indicates that metformin, as anti-estrogen agent, is superior to tamoxifen for targeting ER in breast cancer. We also identified that metformin inhibited E2 induced cell proliferation and expression of mRNA and protein of ERα in MDA-MB 361 cell line (ER+/Her-2+). We also analyzed estrogen responsive element (ERE) activity using by luciferase assay and identified metformin suppressed E2-inducible luciferase activity and expression of direct ER-regulated genes, such as c-myc, Cyclin D1 and pS2 and FOXA1, which were not inhibited by tamoxifen. In conclusion, metformin has a direct anti proliferative effect and anti-estrogen effect in MCF-7, TR-MCF-7 as well as MDA-MB-361 cell lines. These results suggest that metformin can be used as anti- estrogen in ER positive breast cancer (luminal A &amp; B) and tamoxifen resistant breast cancer. Citation Format: Jinkyoung Kim, Jiyun Lee, Soonyoung Jang, Chungyeul Kim, Aeree Kim. The anti-estrogen effect of metformin in ERα+ breast cancer and tamoxifen resistant cell lines. [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 4229. doi:10.1158/1538-7445.AM2014-4229
Transplacental Induction of Tumors in Sprague-Dawley Rats With Crude Cycad Material&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Maria Spatz, Gert L. Laqueur
Journal: JNCI Journal of the National Cancer Institute (1967)

Tumors have been induced transplacentally by crude cycad meal containing 3% cycasin fed to rats at various periods of gestation. The over-all relative incidence of neoplasia in the offspring was 18.5%. The interval necessary for tumor production was essentially the same as that previously reported in immature and adult rats fed crude cycad material, cycasin, or the aglycone of cycasin. Frequent sites of neoplasia were brain and jejunum, organs rarely involved by tumors in earlier feeding experiments in rats. No teratogenic effects were found among the rats dying during the immediate postpartum period or later in life. The death rate among newborn rats exposed in utero was 42%. Hypoplastic mammary glands and a decreased suckling stimulus normally necessary to maintain lactation appeared to be important causes for the early deaths.
Pharmacokinetics of tobramycin nebulizer solution (300mg/4ml) administered by Pari e-Flow rapid vs Pari LC plus nebulizer in patients with cystic fibrosis and Pseudomonas aeruginosa infection
Authors: Mirco Govoni, Gianluigi Poli, Helen Cicirello, Debora Santoro, Daniela Acerbi, Jozef Ruzicka
Journal: European Respiratory Journal (2012)

Background:  New generation nebulizers are increasingly used to reduce the time required for inhalation, potentially improving patient compliance.   Objectives:  To compare the pharmacokinetic (PK) profile of tobramycin nebulizer solution (TNS) 300mg/4mL (Bramitob®) administered with the Pari e-Flow rapid versus the Pari LC plus nebulizer.   Methods:  Randomized, crossover trial, enrolling 27 cystic fibrosis (CF) patients with chronic  Pseudomonas aeruginosa  infection. Patients received two twice-daily, 28-day treatment periods with TNS 300mg/4mL delivered by either nebulizer, separated by a 4-week wash-out. Blood and sputum samples were collected on days 1 and 28 over the first 12 and 8 hours, respectively. Primary endpoints were plasma tobramycin maximum concentration (C max ) and area under the curve (AUC 0-t ) on day 28.   Results:  27 patients were randomized and 25 completed the study. Patients were 18-47 (mean 25.5) years old. On Day 28, the geometric mean ratios (e-Flow rapid:LC Plus) for plasma tobramycin C max  and AUC 0-t  were 0.85 (90% CI 0.61-1.19) and 0.87 (90% CI 0.65-1.18), respectively, while the geometric mean ratios for sputum tobramycin C max  and AUC 0-t  were 1.40 (90% CI 0.86-2.27) and 1.37 (90% CI 0.80-2.33), respectively. Nebulization time was significantly shorter for the eFlow rapid as compared to the LC plus: 5.7±2.0 versus 12.1±2.2 min (mean ± SD on day 28).   Conclusion:  Plasma and sputum PK data support comparable pulmonary delivery of TNS 300 mg/4mL in CF patients using different nebulizers with a shorter nebulization time for the Pari e-Flow device.  Supported by: Chiesi Farmaceutici.
Treatment failure of hospitalized patients with COPD exacerbation using systemic corticosteroids plus antibiotics: Role of early inflammatory predictors
Authors: Ernesto Crisafulli, Arturo Huerta, Mónica Guerrero, Alexandra Gimeno, Raquel Martinez, Néstor Soler, Laia Fernández, Rosario Menéndez, Antoni Torres
Journal: European Respiratory Journal (2014)

Background 

Pharmacological treatment of hospitalized patients with COPD exacerbation includes antibiotics and systemic corticosteroids. During treatment a proportion of patients show worsening of symptoms that characterized a treatment failure; the aim of our study was to determine clinical and inflammatory predictors of treatment failure.

Methods 

Prospective data on 110 hospitalized patients with COPD exacerbation, all treated with antibiotics and systemic corticosteroids, were collected during a 30-month period; on the seventh day of hospitalization, patients were then divided into treatment failure (n=16) or success (n=94). Measures of inflammatory serum biomarkers were recorded on admission to hospital (day 1) and at day 3; data on clinical, laboratory, microbiological, and severity, as well data on mortality and readmission, evaluated at 30 and 90 days and at 1 year, were also recorded.

Results 

High serum levels of C-reactive protein (CRP), procalcitonin (PCT), tumour necrosis factor-alpha (TNF-α), interleukin (IL) 8, and IL-10 were found at day 1 in the treatment failure group; moreover, a longer length of hospital stay and a higher prevalence of patient deaths and re-admission were found.

At admission, a CRP value ≥100 mg/L and a PCT value ≥0.16 ng/L were independent variables increasing risk of treatment failure.

Conclusions 

CRP and PCT measured at admission predict treatment failure of hospitalized patients with COPD exacerbation treated with antibiotics and systemic corticosteroids.
Abstract SY18-03: Therapeutically targeting the p53 pathway using miRNA-based approaches in mouse models of cancer
Authors: Elsa R. Flores
Journal: Cancer Research (2015)

Abstract The tumor suppressor gene, p53, is commonly mutated or lost in human cancer, and p53 reactivation has been shown to suppress tumors in-vivo. This strategy has proven difficult to implement therapeutically. One alternative strategy to overcome p53 loss is to manipulate the p53 family members, p63 and p73, which interact with p53 extensively to suppress tumorigenesis. Both p63 and p73 are composed of multiple isoforms. The isoforms can be placed into two groups: the TA isoforms, which structurally resemble p53 and act as tumor suppressors, and the ΔN isoforms, which bind to p53, TAp63, and TAp73 and inhibit their function, thus acting as oncogenes. Many current therapeutic strategies to target p53 focus on p53 solely, ignoring the existence of the other p53 family members. Over the last decade, we have learned that this family of genes acts together to suppress tumorigenesis and metastasis; therefore, a clear understanding of the cross talk between the p53 family as a whole is needed to effectively treat cancers with alterations in the p53 family of genes. Recently, my laboratory has shown that in vivo inactivation of ΔNp63 or ΔNp73 in the p53-deficient mouse model of thymic lymphoma leads to massive tumor regression and increased survival through upregulation of TAp63 and TAp73 and subsequent transactivation of a large network of genes and miRNAs identified through RNA sequencing (Venkatanarayan et al., Nature, 2014 Nov 17, doi: 10.1038/nature13910). Importantly, we have previously shown that Dicer and DGCR8 are transcriptional targets of p63 (Su et al., Nature, 2010 Oct 21;467(7318):986-90 and Chakravarti et al., Proc Natl Acad Sci U S A, 2014 Feb 4;111(5):E572-81. doi: 10.1073/pnas.1319743111). To identify inhibitors of ΔNp63 or ΔNp73 as a means to identify compounds that may be used to target the p53 pathway therapeutically, we screened a drug library of more than 850 FDA approved compounds. We found several small molecules that were able to reduce ΔNp63 protein stability and a specific set of miRNAs essential for the effectiveness of the drugs. In vivo analyses of these compounds as well as of these miRNA inhibitors have shown their efficacy in counteracting tumor formation and progression in genetically engineered mouse models deficient for p53 and in patient derived xenograft (PDX) mouse models with tumors that have p53 mutations. In summary, we have now identified multiple modalities to therapeutically target the p53 pathway through manipulation of p63 and p73. Citation Format: Elsa R. Flores. Therapeutically targeting the p53 pathway using miRNA-based approaches in mouse models of cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY18-03. doi:10.1158/1538-7445.AM2015-SY18-03