tbuckley/cabot-search huggingface dataset:
Rat <i>Mcs1b</i> Is Concordant to the Genome-Wide Association-Identified Breast Cancer Risk Locus at Human <i>5q11.2</i> and <i>MIER3</i> is a Candidate Cancer Susceptibility Gene
Authors: Aaron D. denDekker, Xin Xu, M. Derek Vaughn, Aaron H. Puckett, Louis L. Gardner, Courtney J. Lambring, Lucas Deschenes, David J. Samuelson
Journal: Cancer Research (2012)

Abstract Low-penetrance alleles associated with breast cancer risk have been identified in population-based studies. Most risk loci contain either no or multiple potential candidate genes. Rat mammary carcinoma susceptibility 1b (Mcs1b) is a quantitative trait locus on RN02 that confers decreased susceptibility when Copenhagen (COP)-resistant alleles are introgressed into a Wistar Furth (WF)-susceptible genome. Five WF.COP congenic lines containing COP RN02 segments were compared. One line developed an average of 3.4 ± 2.0 and 5.5 ± 3.6 mammary carcinomas per rat ± SD when females were Mcs1b-resistant homozygous and Mcs1b heterozygous, respectively. These phenotypes were significantly different from susceptible genotype littermates (7.8 ± 3.1 mean mammary carcinomas per rat ± SD, P = 0.0001 and P = 0.0413, respectively). All other congenic lines tested were susceptible. Thus, Mcs1b was narrowed to 1.8 Mb of RN02 between genetic markers ENSRNOSNP2740854 and g2UL2-27. Mammary gland-graft carcinoma susceptibility assays were used to determine that donor (P = 0.0019), but not recipient Mcs1b genotype (P = 0.9381), was associated with ectopic mammary carcinoma outcome. Rat Mcs1b contains sequence orthologous to human 5q11.2, a breast cancer susceptibility locus identified in multiple genome-wide association studies. Human/rat MAP3K1/Map3k1 and mesoderm induction early response (MIER; MIER3)/MIER3 are within these orthologous segments. We identified MIER3 as a candidate Mcs1b gene based on 4.5-fold higher mammary gland levels of MIER3 transcripts in susceptible compared with Mcs1b-resistant females. These data suggest that the human 5q11.2 breast cancer risk allele marked by rs889312 is mammary gland autonomous, and MIER3 is a candidate breast cancer susceptibility gene. Cancer Res; 72(22); 6002–12. ©2012 AACR.
Sleeve lobectomy for patients with non-small cell lung cancer
Authors: Takeshi Hanagiri, Tetsuro Baba, Yoshinobu Ichiki, Manabu Yasuda, Masakazu Sugaya, Kenji Ono, Hidetaka Uramoto, Mitsuhiro Takenoyama, Kosei Yasumoto
Journal: International Journal of Surgery (2009)
P-Glycoprotein-Mediated Drug Secretion in Mouse Proximal Tubule Perfused In Vitro
Authors: SHUICHI TSURUOKA, KOH-ICHI SUGIMOTO, AKIO FUJIMURA, MASASHI IMAI, YASUSHI ASANO, SHIGEAKI MUTO
Journal: Journal of the American Society of Nephrology (2001)

Abstract. To examine the functional significance of durg-transporting P-glycoprotein (P-gp), studies were conducted in the isolated and perfused proximal tubule S2 segment from mice disrupting both mdr1a and mdr1b genes [mdr1a/1b(—)(—)] and their wild-type mice. Efflux of the intracellular fluorescence of rhodamine 123, a fluorescence substrate of P-gp, into the lumen was measured, and the decay half-time of the intracellular fluorescence (T 1/2 ) as an index of the drug-transporting P-gp activity was regarded. In the wild-type mice, the T 1/2 was 34 ± 4 s ( n = 36) at the basal period and was increased to 434 ± 41 s by the addition of luminal verapamil, a P-gp inhibitor. In the mdr1a/1b(—)(—) mice, the T 1/2 was 407 ± 16 s ( n = 10) at the basal period and was no longer affected by the luminal addition of verapamil. The digoxin content in the kidney after a repeated administration of the drug was markedly elevated in the mdr1a/1b(—)(—) mice. In conclusion, P-gp—mediated drug efflux capacity indeed exists in the apical membrane of proximal tubule cells from the wild-type mice, whereas it is absent in that of the mdr1a/1b(—)(—) mice.
Role of human chromosome 11 in determining surface antigenic phenotype of normal and malignant cells. Somatic cell genetic analysis of eight antigens, including putative human Thy-1.
Authors: W J Rettig, N C Dracopoli, P G Chesa, B A Spengler, H R Beresford, P Davies, J L Biedler, L J Old
Journal: The Journal of Experimental Medicine (1985)

The expression of eight serologically and biochemically distinct human cell surface antigens defined by monoclonal antibodies was examined on a panel of rodent-human somatic cell hybrids. Cosegregation was observed for human chromosome 11, and surface expression of all eight antigens was studied. Serological analysis of hybrids containing defined segments of human chromosome 11 permitted the regional assignment of genes controlling antigens JF23 (90 kD glycoprotein), G344 (25 kD), T43 (85 kD), A124, and NP13 to chromosome 11pter-q13, and of genes controlling Q14 (130 kD), MC139 (35 kD), and K117 (25 kD) to chromosome 11q13-qter. K117, the putative human Thy-1 antigen, was expressed at high levels in chromosome 11-containing hybrids constructed with mouse neuroblastoma cells, but showed little or no expression in hybrids constructed with mouse L cells. A similar pattern of expression in hybrids was found for MC139, an antigen shared by neuroectoderm-derived cells and normal and malignant T lymphocytes. T43 is a marker of malignant tumors (but not benign tumors) derived from a number of T43- epithelia, and the regional assignment of the T43 locus on chromosome 11 raises questions about its possible involvement in the specific rearrangements of this chromosome seen in human malignancies.
Enhanced production of nitric oxide by blood-dialysis membrane interaction.
Authors: A Amore, R Bonaudo, D Ghigo, M Arese, C Costamagna, P Cirina, B Gianoglio, L Perugini, R Coppo
Journal: Journal of the American Society of Nephrology (1995)

Nitric oxide (NO) is a powerful vasoactive product of endothelial origin, and one of its major effects is vasodilation, leading to hypotension. The role of NO in some complications of uremia is still debated. This study evaluated whether endothelial NO synthase activity could be modulated by the exposure of healthy blood to hemodialysis materials. In vitro hemodialysis sessions were performed with cuprophan and polymethylmethacrylate membranes. Blood samples from a healthy donor after recirculation for 0, 5, 15, 30, and 60 min were coincubated for 6 h with a murine endothelial cell line (t.End.1); mRNA for inducible NO synthase and enzyme activity, measured as (3H)citrulline produced from (3H)arginine, were detected. The release of interleukin (IL)-1 beta and tumor necrosis factor-alpha (TNF-alpha) from recirculating lymphomonocytes was measured, too. The NO synthase activity of endothelial cells was stimulated by blood dialyzed with cuprophan, peaking at 15 min (11-fold increase in comparison to the basal values), whereas polymethylmethacrylate was ineffective (P < 0.01 versus Cuprophan). Dialysis with cuprophan, but not with polymethylmethacrylate, induced in endothelial cells the expression of mRNA encoding for inducible NO synthase. The release of IL-1 beta and TNF-alpha after 6 h by recirculating lymphomonocytes paralleled the NO synthase activity profile in endothelial cells and was significantly higher after cuprophan exposure than after polymethylmethacrylate (P < 0.0001). In conclusion, the activity of endothelial NO synthase can be enhanced during the dialysis sessions by the interaction of lymphomonocytes with the membranes, possibly via TNF-alpha and IL-1 beta production.
Clinical applications of assessment of airway inflammation using induced sputum
Authors: I.D. Pavord, P.J. Sterk, F.E. Hargreave, J.C. Kips, M.D. Inman, R. Louis, M.M.M. Pizzichini, E.H. Bel, I. Pin, D.C. Grootendorst, K. Parameswaran, R. Djukanović
Journal: European Respiratory Journal (2002)

Airway diseases account for a significant proportion of the respiratory physician's workload. Traditionally, conditions are classified according to clinical symptoms and abnormalities of function, although the major categories of airway disease (asthma, chronic cough and chronic obstructive pulmonary disease (COPD)) show considerable overlap in terms of both clinical picture and response to anti­inflammatory treatment with corticosteroids. All of the above conditions are associated with airway inflammation, although to date there has been little interest in its routine measurement in clinical practice. The recent development of simple, safe and valid noninvasive techniques for the assessment of airway inflammation has increased interest in such an approach 1, 2. A number of techniques are available, ranging from measurement of exhaled nitric oxide levels to performing differential cell counts and assessment of mediator concentrations in induced sputum. Relatively little is known about the relationship between these different markers, although it is likely that they measure different aspects of the inflammatory response 3. A clearer understanding is desirable since some techniques are more suited to routine clinical use than others. Induced sputum cell and mediator measurements are particularly well validated 1, and normal ranges from a relatively large adult population have been published 4.

The present article summarises clinical studies pointing to the usefulness of induced sputum analysis in the following conditions: 1) asthma; 2) cough; 3) COPD; and 4) other respiratory conditions.

Asthma is commonly associated with sputum eosinophilia. Up to 80% of corticosteroid­naive subjects 1, 2 and >50% of corticosteroid­treated subjects 5 with currently symptomatic asthma have a sputum eosinophil count that is outside the normal range. Subjects with severe acute asthma usually exhibit marked sputum eosinophilia, although predominant neutrophilia has been noted in some studies in which subjects …
Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma
Authors: F. Kanniess, K. Richter, S. Janicki, M.B. Schleiss, R.A. Jörres, H. Magnussen
Journal: European Respiratory Journal (2002)

The present study aimed at comparing the effects of a dose reduction of inhaled corticosteroids on lung function, indirect measures of airway inflammation and clinical scores during treatment with a leucotriene receptor antagonist. In 50 patients (mean forced expiratory volume in one second (FEV 1 ) 94% predicted), steroid doses (800 µg beclomethasone dipropionate) were first reduced to 50% and then to 25%, for 6 weeks each. One group received a placebo and the other group received montelukast (10 mg). The first reduction did not cause significant effects. During the second, FEV 1 and peak expiratory flow decreased in both groups (p&lt;0.001). Daytime symptoms were not altered with placebo but were reduced by montelukast (p&lt;0.05). Night-time symptoms were slightly elevated with placebo (p&lt;0.05) but not montelukast, as well as the use of supplemental salbutamol. Changes in provocative concentration of methacholine causing a 20% fall in FEV 1 (PC 20 ), sputum eosinophils and exhaled nitric oxide were mostly nonsignificant for both placebo and montelukast. These data demonstrate that a 75% reduction in the dose of steroid given to patients with asthma led to a deterioration in lung function not prevented by montelukast, whereas changes in clinical state seemed to favour montelukast treatment. It therefore appears that potential effects of montelukast, in the presence of low-dose steroids, could not be attributed to single indices of lung function or airway inflammation.
Tet2 Loss Leads to Increased Hematopoietic Stem Cell Self-Renewal and Myeloid Transformation
Authors: Kelly Moran-Crusio, Linsey Reavie, Alan Shih, Omar Abdel-Wahab, Delphine Ndiaye-Lobry, Camille Lobry, Maria E. Figueroa, Aparna Vasanthakumar, Jay Patel, Xinyang Zhao, Fabiana Perna, Suveg Pandey, Jozef Madzo, Chunxiao Song, Qing Dai, Chuan He, Sherif Ibrahim, Miloslav Beran, Jiri Zavadil, Stephen D. Nimer, Ari Melnick, Lucy A. Godley, Iannis Aifantis, Ross L. Levine
Journal: Cancer Cell (2011)
Cognitive Decline among Patients with Chronic Obstructive Pulmonary Disease
Authors: William W. Hung, Juan P. Wisnivesky, Albert L. Siu, Joseph S. Ross
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Prior research has suggested an association between chronic obstructive pulmonary disease (COPD) and the development of cognitive decline; however, these studies have been cross-sectional or small case series.To determine whether COPD increases the risk of cognitive decline among older adults surveyed in a large, population-based longitudinal cohort.We included data from the 1996 to 2002 waves of the Health and Retirement Study, a biennial nationally representative survey. We studied respondents who completed cognitive testing in 1996 and at least one subsequent survey, and excluded those with unknown history of COPD. Clinical history of COPD was based on self-report; severity was categorized based on use of oxygen or disease-related activity limitations. Our primary outcome was cognitive performance, measured using a validated 35-point scale. We examined the effect of COPD on cognition using multivariable mixed linear models accounting for repeated measurements, adjusted for sociodemographic and clinical characteristics.A total of 4,150 adults were included in our study. Among them, 12% reported a history of COPD (29% severe, 71% nonsevere disease). On repeated measurement, mean cognition scores of older adults with both severe and nonsevere COPD were significantly lower when compared with adults without COPD (2.6 points [P < 0.001] and 0.9 points [P < 0.001], respectively). After multivariable adjustment, mean scores of adults with severe COPD remained lower (0.9 point [P < 0.001]), whereas mean score of adults with nonsevere COPD was no longer different (P = 0.39) when compared with adults without COPD.Severe COPD was associated with lower cognitive performance on standardized measurement over time.
Expression of ER-α36, a Novel Variant of Estrogen Receptor α, and Resistance to Tamoxifen Treatment in Breast Cancer
Authors: Liang Shi, Bin Dong, Zhongwu Li, Yunwei Lu, Tao Ouyang, Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Tie Fan, Benyao Lin, Zhaoyi Wang, Yuntao Xie
Journal: Journal of Clinical Oncology (2009)

Purpose Recently, a 36-kDa variant of estrogen receptor α (ER-α66), ER-α36, has been identified and cloned. ER-α36 predominantly localizes on the plasma membrane and in the cytoplasm and mediates a membrane-initiated “nongenomic” signaling pathway. Here, we investigate the association between ER-α36 expression and tamoxifen resistance in patients with breast cancer. Patients and Methods ER-α36 protein expression in tumors from 896 women (two independent cohorts, 1 and 2) with operable primary breast cancer was assessed using an immunohistochemistry assay. Results In the first cohort of 710 consecutive patients, overexpression of ER-α36 was associated with poorer disease-free survival (DFS) and disease-specific survival (DSS) in patients with ER-α66–positive tumors who received tamoxifen treatment (chemotherapy plus tamoxifen or tamoxifen alone, n = 307). In contrast, ER-α36 was not associated with survival in patients with ER-α66–positive tumors who did not receive tamoxifen (chemotherapy alone, n = 129) and in patients with ER-α66–negative tumors whether they received tamoxifen (n = 73) or not (n = 149). In the second cohort of 186 patients who only received tamoxifen as adjuvant therapy, overexpression of ER-α36 was significantly associated with poorer DFS and DSS in 156 ER-α66–positive patients from this cohort, and ER-α36 remained an independent unfavorable factor for both DFS and DSS in these 156 patients by a multivariate analysis (DFS: hazard ratio [HR] = 5.47; 95% CI, 1.81 to 16.51; P =. 003; DSS: HR = 13.97; 95% CI, 1.58 to 123.53; P = .018). Conclusion Women with ER-α66–positive tumors that also express high levels of ER-α36 are less likely to benefit from tamoxifen treatment.
Points: Not all clinical assistants should have tenure
Authors: A G S Bailey, J. Walter
Journal: BMJ (1984)

Mr Richard Earlam has provided us with a clear exposition of the current mismanagement of oesophageal carcinoma in a regional hospital service (23 June, p 1892).Most doctors would agree that at presentation most cases of oesophageal carcinoma are incurable.'The aim of any treatment, therefore, is effective palliation-that is, relief of dysphagia-with consequent low morbidity and mortality.2The treatment statistics detailed by Mr Earlam clearly show that this goal is not being achieved in the North East Thames region.It is likely that the hospital management of oesophageal carcinoma will improve only when all patients with this condition are urgently referred to multidisciplinary teams established in regional specialist centres.
Abstract P3-06-01: Association between metformin use and improved survival in breast cancer patients: A population-based study
Authors: YR Li, J Tchou
Journal: Cancer Research (2013)

Abstract Background: Long-term use of AMP-kinase agonist Metformin, the first-line oral hypoglycemic agent, has recently been shown to be associated with both a decreased incidence of and improved survival following diagnosis of breast and other solid tumors. However, the sample size of most reported studies has been limited and has not been able to clearly delineate if there are molecular subtype-dependent effects. Method: We implemented a population-based, retrospective case-control analysis of the effect of metformin on breast cancer outcomes. We comprehensively searched the electronic medical records of all female patients who were cared for within the University of Pennsylvania Health System between the years 1997 and 2013. To ensure the accuracy of patient selection, we focused our preliminary analysis on only patients (n = 20,684) who received an ICD9 code for breast cancer (BC) on at least 2 separate in-person visits. We assessed the use of metformin by identifying those patients who have at least a record of a metformin prescription both before the first breast cancer diagnosis ICD9 code and after the first breast cancer diagnosis visit. Overall survival was determined by assessing a combination of electronic medical record of patient expiration and the SSN Death Certificate Index. Statistical tests, including chi-sq and cox-hazard modeling were implemented in R, Graphpad Prism or EXCEL. Results: In the preliminary analysis, we identified a total of 29,251 female patients either diagnosed or reported a history of BC within the UPHS EMRs. Stratifying by per patient visits, we limited the subsequent analysis to the 20,684 BC patients with at least 2 in-person visits where BC was recorded as a diagnosis code. Of these, there were 534 patients who had a record of metformin prescription prior to and after the first BC diagnosis code and 20,150 BC patients who did not. We found that with a mean follow up of (6.40 years), there were a total of 8 deaths (1.28%) in metformin users and 526 deaths (2.62%) among the no metformin users. Using a two-tailed chi-sq test, we found that metformin use was significantly associated with improved overall survival rates (98.50 vs 96.94%, p&amp;lt;0.05). We are currently assessing the role of age, ethnicity, the presence of diabetes, health metrics related to insulin resistance, and the use of other metabolic regulators (insulin, sulfonylurea) using a cox-hazard proportional risk model. Conclusion: Our preliminary analyses suggest that metformin use before and following diagnosis may be protective against overall mortality among women diagnosed with breast cancer. A more refined Cox proportional hazard modelling is ongoing, which will shed light on how factors such as the use of other metabolic agents, age, and breast cancer subtype may interact with metformin's effect on overall and disease-free BC survival. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-01.
Effect of Cadmium Exposure on Primary Tumor Growth and Cell-Mediated Cytotoxicity in Mice Bearing MSB Sarcomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: N I Kerkvliet, L D Koller, L G Baecher, J A Brauner
Journal: JNCI Journal of the National Cancer Institute (1979)

In vivo MSB tumor growth and cell-mediated cytotoxicity (CMC) to MSB tumor cells in vitro were studied in male C57BL/6 mice exposed to 0, 3, 30, or 300 ppm Cd as CdCI2 in their drinking water for 21 weeks prior to and during tumor growth. CMC was assessed on days 5, 12, and 19 post tumor injection with the use of both a,51Cr release assay and a 51Cr post-label assay. Cd exposure significantly inhibited the growth of MSB tumors in vivo and enhanced the levels of CMC in the tumor-bearing hosts. Peak levels of CMC on day 12 post tumor injection were significantly increased in Cd-exposed animals. However, whereas the inhibition of tumor growth was directly dependent on the dose of Cd, the enhancement of CMC was Inversely related to dosage. These data suggested that other mechanisms in addition to increased CMC were involved in tumor growth inhibition. Possible factors such as direct inhibition of tumor growth by Cd and decreased serum blocking levels in Cd-exposed animals are discussed.
Increased serum IL-33 levels may indicate vascular involvement in systemic sclerosis
Authors: Sarah Terras, Elisabeth Opitz, Rose K C Moritz, Stefan Höxtermann, Thilo Gambichler, Alexander Kreuter
Journal: Annals of the Rheumatic Diseases (2012)

Interleukin 33 (IL-33) belongs to the IL-1 family and was found in smooth muscle cells, epithelial cells, fibroblasts, keratinocytes, endothelial cells, dendritic cells and activated macrophages.1 IL-33 binds the orphan receptor ST2 and induces gene expression of Th2-associated cytokines. Treatment of wild-type mice with IL-33 led to changes in vessels, digestive tract and lungs.2 

Manetti et al 3 recently investigated serum IL-33 levels by means of an ELISA in 58 patients with systemic sclerosis (SSc) and 30 healthy individuals. They observed that serum IL-33 was significantly increased in patients with SSc as compared with healthy controls. They also found that serum IL-33 levels were associated with early disease stage and microvascular involvement as determined by capillaroscopy. The study of Manetti et al 3 prompted us to investigate serum IL-33 …
Cytokine Activation of Nuclear Factor κB in Vascular Smooth Muscle Cells Requires Signaling Endosomes Containing Nox1 and ClC-3
Authors: Francis J. Miller, Mohammed Filali, Gina J. Huss, Bojana Stanic, Ali Chamseddine, Thomas J. Barna, Fred S. Lamb
Journal: Circulation Research (2007)

Reactive oxygen species (ROS) are mediators of intracellular signals for a myriad of normal and pathologic cellular events, including differentiation, hypertrophy, proliferation, and apoptosis. NADPH oxidases are important sources of ROS that are present in diverse tissues throughout the body and activate many redox-sensitive signal transduction and gene expression pathways. To avoid toxicity and provide specificity of signaling, ROS production and metabolism necessitate tight regulation that likely includes subcellular compartmentalization. However, the constituent elements of NADPH oxidase-dependent cell signaling are not known. To address this issue, we examined cytokine generation of ROS and subsequent activation of the transcription factor nuclear factor κB in vascular smooth muscle cells (SMCs). Tumor necrosis factor-α and interleukin (IL)-1β stimulation of SMCs resulted in diphenylene iodonium-sensitive ROS production within intracellular vesicles. Nox1 and p22 phox , integral membrane subunits of NADPH oxidase, coimmunoprecipitated with early endosomal markers in SMCs. ClC-3, an anion transporter that is primarily found in intracellular vesicles, also colocalized with Nox1 in early endosomes and was necessary for tumor necrosis factor-α and interleukin-1β generation of ROS. Cytokine activation of nuclear factor κB in SMCs required both Nox1 and ClC-3. We conclude that in response to tumor necrosis factor-α and interleukin-1β, NADPH oxidase generates ROS within early endosomes and that Nox1 cannot produce sufficient ROS for cell signaling in the absence of ClC-3. These data best support a model whereby ClC-3 is required for charge neutralization of the electron flow generated by Nox1 across the membrane of signaling endosomes.