tbuckley/cabot-search huggingface dataset:
Ex vivo trans-differentiation of primary human alveolar epithelial cells type II by TGFb
Authors: Sebastian Marwitz, Gernot Zissel, Peter Zabel, Christian Kugler, Ekkehard Vollmer, Torsten Goldmann
Journal: European Respiratory Journal (2014)

Lung fibrosis, especially idiopathic pulmonary fibrosis (IPF) as an end-stage lung disease, is characterized by irreversible collagen-deposition from myofibroblasts in the alveolar interstitium. Since IPF is regarded as resistant to anti-inflammatory therapy, the 5-years-survival rate is comparable to lung cancer and transplantation often remains the only curative treatment option. Up to date several theories exist about the origin of collagen-secreting myofibroblasts and the involvement of the transforming growth factor beta (TGFb) pathway.Here we present an ex vivo approach to investigate the role of human primary alveolar cells type II (AECII) as possible targets of the TGFb pathway with implications for IPF pathophysiology. Primary human AECII were isolated from tumor-free lungs and stimulated with TGFb and SB431542 to verify the pathway specificity. Actin cytoskeleton remodelling was assessed by phalloidin staining to investigate TGFb-dependent changes in cell morphology. Furthermore, changes in transdifferentiation marker expression were analyzed by immunocytochemistry or immunofluorescence. Gene expression analysis was conducted by means of qRT-PCR and microarrays. Our data show a significantly regulated TGFb pathway as well as expression of transdifferentiation markers upon stimulation in human AECII. Actin cytoskelett-remodelling was observed and an increased expression of collagen synthesis on both, RNA and protein level. Gene ontology (GO) enrichment revealed a significant number of developmental, differentiation and collagen synthesis terms in AECII by stimulation with TGFb.
Abstract 3572: Acculturation is a Risk Factor for Higher Carotid Intimal Medial Thickness in Hispanic Americans. The Multi-Ethnic Study of Atherosclerosis
Authors: Matthew A Allison, Matthew Budoff, Nathan D Wong, Roger S Blumenthal, Pamela Schreiner, Michael H Criqui
Journal: Circulation (2007)

Background: The aim of this study was to determine if acculturation is a significant risk factor for carotid intimal medial thickness (CIMT) in Hispanic Americans.  Methods: Subjects were were 1,493 Hispanic participants from the Multi-Ethnic Study of Atherosclerosis (MESA). At the baseline MESA clinic visit, standardized protocols were used to quantify CIMT. The variable “generation” represents the degree of acculturation due to familial birthplace and was based on the number of relatives that were born in the U.S. Low generation number (e.g. 0) indicates fewer or no family members born in the U.S. while higher numbers (e.g. 3) indicate all or nearly all were born in the U.S.  Results: The mean (SD) age of the sub-sample was 61.3 (10.3) years and 52% were women. Thirty-one percent MESA Hispanics were born in the U.S. while 13.2% and 15.5% of their fathers and mothers, respectively, were born in the US. There were 68.8% of MESA Hispanics who were generation 0, 20.2% were generation 1, 7.2% generation 2 and 3.8% generation 3. With adjustment for age, sex, body mass index, cholesterol, smoking, diabetes and hypertension, the mean CIMT values increased significantly in each higher generation (p   Conclusions: Among Hispanics, acculturation defined by birthplace is significantly associated with CIMT independent of CVD risk factors. The more acculturated an individual becomes to the United States, the larger the burden of subclinical atherosclerosis.
Various Isozyme Gene Expression Patterns Among Human Colorectal Adenocarcinoma Cell Lines and Tissues&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: L P Rutzky, M J Siciliano
Journal: JNCI Journal of the National Cancer Institute (1982)

Seven tissue-specific isozymes--lactate dehydrogenases A and B (LDHA and LDHB), esterases B2 and A4 (ESB2 and ESA4), creatine kinase B (CKB), and red blood cell and tissue forms of adenosine deaminases (ADA)--were examined in the human adenocarcinoma cell line LS174T and its subclones grown under a wide variety of conditions. Strong expressions of ESB2, ESA4 and CKB were stable in all material studied, as was a greater expression of LDHA than of LDHB. ADA isozyme expression varied with culture conditions. Identical expression of the five stable isozymes was observed in six surgical specimens of normal bowel mucosa, while cell lines derived from normal mucosa varied in the expression of these isozymes. An additional 23 colorectal cell lines, derived from primary or metastatic adenocarcinomas in different stages of invasiveness and differentiation from 18 individuals, were verified as to their origin by genetic signature analysis and similarly studied for isozyme expression. These lines had different, yet stable, gene expression patterns similar to differences observed among six adenocarcinoma surgical specimens. These differences could not be related to the number of passages that the cell lines were in culture nor to the stages of the tumors at the time that the cell lines were initiated or surgical samples tested. Gene expression patterns in adenocarcinomas differed, these differences might have been due to the origin of colorectal adenocarcinomas from different cell types within a heterogeneous mucosa, and the colorectal cell lines studied represented appropriate models for colon cancer.
Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood.
Authors: R J Packer, B Lange, J Ater, H S Nicholson, J Allen, R Walker, M Prados, R Jakacki, G Reaman, M N Needles
Journal: Journal of Clinical Oncology (1993)

PURPOSE This study investigates the response rate to and toxicity of carboplatin and vincristine in children with recurrent low-grade gliomas (LGGs) or patients younger than 60 months with newly diagnosed LGGs. PATIENTS AND METHODS Twenty-three children with recurrent and 37 children with newly diagnosed LGGs were treated with a 10-week induction cycle of carboplatin and vincristine, followed by maintenance treatment with the same drugs. Patients were evaluated for response to treatment and toxicity. RESULTS Twelve of 23 (52% +/- 10%; 95% confidence interval [CI], 0.32 to 0.72) assessable children with recurrent disease had an objective response to treatment, which included a greater than 50% reduction in tumor size in seven of 23 (30% +/- 10%; 95% CI, 0.10 to 0.50). Twenty-three of 37 (62% +/- .08; 95% CI, 0.46 to 0.78) of newly diagnosed patients had an objective response, 16 of 37 (43% +/- 0.08%; 95% CI, 0.27 to 0.59) with greater than 50% reduction in tumor size. The majority of those with an objective response had diencephalic tumors (n = 29), but children with thalamic (n = 2), cortical (n = 1), and brain stem (n = 2) LGGs also responded to treatment. Of the 35 patients with objective response to treatment, the maximum response was seen in 25 after completion of induction and in the remaining 10 after two to six cycles of maintenance treatment. Forty-nine of 53 (92% +/- .04%) patients who were stable or improved after induction remain without progressive disease (PD). Hematologic toxicity was common, but resulted in cessation of therapy in only one patient. Six children have been removed from the study because of allergic reactions, which were considered to be carboplatin-associated. CONCLUSION Carboplatin and vincristine have activity in children with recurrent and newly diagnosed progressive LGGs. Objective responses to treatment after chemotherapy can be seen. This drug regimen is relatively well tolerated, and further studies are indicated to define the role of this combination of drugs in children with newly diagnosed LGGs.
Elastin Stabilizes an Infarct and Preserves Ventricular Function
Authors: Tomohiro Mizuno, Terrence M. Yau, Richard D. Weisel, Chris G. Kiani, Ren-Ke Li
Journal: Circulation (2005)

Background— After a myocardial infarction, the injured region becomes fibrotic and the myocardial scar may expand if the ventricular wall lacks elasticity. Cardiac dilatation may precipitate the vicious cycle of progressive heart failure. The present study evaluated the functional benefits of increasing elastin within a myocardial scar using cell based gene therapy. Methods and Results— A myocardial infarction was generated by ligation of the left anterior descending artery in rats. Six days later, 2×10 6 syngeneic rat endothelial cells transfected with the rat elastin gene (elastin group, n=14) or an empty plasmid (control group, n=14) were transplanted into the infarct scar. Cardiac function, left ventricular (LV) volume, and infarct size were monitored over 3 months by echocardiography, Langendorff measurements, and planimetry. Elastin deposition was evaluated in the cells and in the infarct region by Western blot assay and by histological examination. Recombinant elastin was found in the scar in the elastin group but not the control group during the 3 months after cell transplantation. Histological assessment demonstrated organized elastic fibers within the infarct region. LV volume and infarct size were significantly smaller ( P &lt;0.05) in the elastin group than in the control group. Cardiac function evaluated by echocardiography and during Langendorff perfusion was significantly better ( P &lt;0.05) in the elastin group than in the control group. Conclusions— Expressing recombinant elastin within the myocardial scar reduced scar expansion and prevented LV enlargement after a myocardial infarction. Altering matrix remodeling after an infarct preserved the LV function for at least 3 months.
Abstract 9165: Short and Long-Term Case Fatality of Thoracic Aortic Dissection: A Thirteen Year Statewide Study
Authors: Daniel M Shindler, Sampada K Gandhi, Jerry Q Cheng, Nora M Cosgrove, Yingzi Deng, Javier Cabrera, John B Kostis
Journal: Circulation (2011)

Objectives. We examined in-hospital and long-term case fatality in patients aged ≥ 20 years admitted with a first-time diagnosis of thoracic aortic dissection (AoD) to all non-federal hospitals in New Jersey (NJ) between 1995 and 2007 using a statewide database. Methods. The Myocardial Infarction Data Acquisition System (MIDAS) database was used to identify demographic characteristics, comorbidities and the presence of hypertension (HT) and diabetes mellitus (DM) among AoD patients. Deaths were ascertained by matching the MIDAS records to death information from NJ Death Registration Files. Results. The 2,373 cases of AoD observed during the study period were categorized into four groups: DM alone (n=41), HT alone (n=1,499), both DM and HT (n=237), neither of the conditions (n=596). Mortality from the index admission was high in all groups: 16.9% died in hospital, 19.6% within 30 days, 30.4% within 1 year and 43.8% within 5 years (Figure 1A). Figures 1B, 1C and 1D show the survival probability among 4 groups using Kaplan-Meier estimates. After adjusting for all covariates in the model, important predictors of mortality among all AoD patients were prior history of: hypertension, chronic renal disease, atrial fibrillation and arrhythmia. Of those who were discharged alive, 16.2% died within 1 year and 32.4% died within 5 years. Approximately 64% of the post discharge deaths were due to a cardiovascular cause, mostly comprised of coronary heart disease (35.6%), aortic aneurysm or dissection (33.4%) and cerebrovascular disease (9.3%). The remaining 36% of the post discharge deaths were due to a non-cardiovascular cause such as cancer, COPD, and renal disease. Conclusions. Thoracic aortic dissection patients, including a previously unstudied diabetic subgroup, have a poor five year prognosis. A majority of the post-discharge deaths were due to a cardiovascular cause and a significant proportion of those were due to recurrent aortic dissection.
A New Prognostic Index In Diffuse Large B-Cell Lymphoma Using Serum Albumin: A Pilot Study Evaluating The Albumin Adjusted-International Prognostic Index (A-IPI)
Authors: Samir Dalia, Julio C Chavez, Celeste M. Bello, Paul A. Chervenick, Bryan J Little, Najla H Al Ali, Lubomir Sokol, Eduardo M. Sotomayor, Ji-Hyun Lee, Kate Fisher, Zachary Thompson, Bong-jin Choi, Bijal D. Shah
Journal: Blood (2013)
Abstract 1602: Clobetasol treatment of vulvar carcinoma cell lines influences growth rates
Authors: Jani E. Lewis, Mehek Mehta, Alison Treichel, Sean Colligan, Vinh Nguyen, David C. Foster
Journal: Cancer Research (2014)

Abstract Vulvar cancer is an aggressive cancer often masked by diseases such as the vulvar rash known as lichen sclerosis (LS). Ultrapotent corticosteroids such as clobetasol are commonly used to treat LS but there is debate over the safety of long-term clobetasol use and development of vulvar cancer. Growing cells from LS biopsies has proven difficult so our objective was to decipher if clobetasol promotes changes in vulvar cancers in vitro that parallel the formation of more aggressive cancer types. Previously we have shown that clobetasol actually promotes transformation of one vulvar cancer cell line into a more aggressive phenotype. Our present studies used MTT assays to examine the effect that short-term (72 hours) and long-term (4 weeks) clobetasol treatment had on the growth rate of vulvar cancer cell lines. Our preliminary data indicates that the growth response varies between cell lines with at least two cell lines displaying increased cell growth after extended treatment with clobetasol when compared to controls. Citation Format: Jani E. Lewis, Mehek Mehta, Alison Treichel, Sean Colligan, Vinh Nguyen, David C. Foster. Clobetasol treatment of vulvar carcinoma cell lines influences growth rates. [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 1602. doi:10.1158/1538-7445.AM2014-1602
Epidemiological trends in invasive aspergillosis in France: the SAIF network (2005–2007)
Authors: O. Lortholary, J.-P. Gangneux, K. Sitbon, B. Lebeau, F. de Monbrison, Y. Le Strat, B. Coignard, F. Dromer, S. Bretagne
Journal: Clinical Microbiology and Infection (2011)
Effect of aclidinium bromide on static lung function and hyperinflation in patients with moderate to severe COPD
Authors: Henrik Watz, Kai M. Beeh, Helgo Magnussen, Luis de Theresa, Diana Jarreta, Cynthia Caracta, Esther Garcia Gil
Journal: European Respiratory Journal (2013)

INTRODUCTION:  Improvements in static lung mechanics and hyperinflation are important therapeutic goals in COPD.   AIMS:  To investigate the effects of aclidinium on static lung function and hyperinflation in patients with COPD.   METHODS:  This double-blind, randomized, crossover study compared aclidinium bromide 400 µg BID (metered dose; equivalent to aclidinium 322 µg BID delivered dose) with placebo, each for 3 weeks, in 112 patients with moderate to severe COPD (FEV 1  1.50 L, 56.7% pred). Efficacy variables included: change from baseline in trough inspiratory capacity (IC), FEV 1  and IC/total lung capacity (TLC); trough and 2-hour post-dose functional residual capacity (FRC), residual volume (RV), and specific airway conductance (sGaw); and 2-hour post-dose TLC.   RESULTS:  see table.   CONCLUSIONS:  Aclidinium significantly improved static lung hyperinflation in COPD patients.
Effect of Insulin on Glucose Uptake by Normal and Neoplastic Mouse Mammary Tissues in Organ Culture&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: R. L. Moretti, K. B. DeOme
Journal: JNCI Journal of the National Cancer Institute (1962)

The glucose uptake of expiants of normal prelactating mammary lobules and of spontaneous mammary adenocarcinomas of C3H/Crgl mice was compared in organ culture in the presence and absence of insulin. In the absence of insulin the normal explants used little or no glucose after the 1st day, whereas tumor explants used glucose at a high rate throughout the 5-day culture period. The presence of insulin resulted in an increase in the daily glucose uptake by normal explants but had no effect on tumor explants. As the concentration of insulin was increased from 0 to 40 µg per ml, normal explants showed a corresponding increased rate of glucose uptake; at concentrations above 40 µg per ml, the rate decreased. Tumor explants showed no response to insulin at any concentration.
LUX-Lung 3: A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations.
Authors: James Chih-Hsin Yang, Martin H. Schuler, Nobuyuki Yamamoto, Kenneth John O'Byrne, Vera Hirsh, Tony Mok, Sarayut Lucien Geater, Sergey V Orlov, Chun-Ming Tsai, Michael J. Boyer, Wu-Chou Su, Jaafar Bennouna, Terufumi Kato, Vera Gorbunova, Ki Hyeong Lee, Riyaz N.H. Shah, Dan Massey, Robert M. Lorence, Mehdi Shahidi, Lecia V. Sequist
Journal: Journal of Clinical Oncology (2012)

LBA7500 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Recent Advances in Tumor Ablation for Hepatocellular Carcinoma
Authors: Tae Wook Kang, Hyunchul Rhim
Journal: Liver Cancer (2015)

Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC.
Survival of breast cancer patients receiving adjunctive psychosocial support therapy: a 10-year follow-up study.
Authors: G A Gellert, R M Maxwell, B S Siegel
Journal: Journal of Clinical Oncology (1993)

PURPOSE The impact of an adjunctive psychosocial support program on length of survival with breast cancer was evaluated in a retrospective cohort study. The duration of observation of survival was extended 10 years beyond a previous study of the same cohort of patients. PATIENTS AND METHODS One hundred two nonparticipants were individually matched to 34 participants on major prognostic factors. Both groups were monitored from the date of cancer diagnosis (1971 through 1980) until March 1991. The support program consisted of weekly cancer peer support and family therapy, individual counseling, and use of positive mental imagery. Survival analysis controlled for the effects of other major prognostic factors in the outcome of breast cancer. RESULTS The mean +/- SD survival time from date of cancer diagnosis to last date of follow-up was 96.0 +/- 53.2 months in the participant group compared with 85.1 +/- 63.4 months in the nonparticipant group, a nonsignificant difference (P = .1). Median survival was 84.0 months for participants (95% confidence interval [CI], 59 to 133) and 66.0 months for nonparticipants (95% CI, 48 to 105). A second analysis restricted nonparticipants to those who had a survival time &gt; or = that of the matched case at time of entry into the support program. Survival increased to a mean of 101.1 months (median, 105.0; 95% CI, 71 to 132) for nonparticipants and remained unchanged for participants, also a statistically nonsignificant difference (P = .9). CONCLUSION While the program may have beneficial effects on quality of life, this study does not indicate a significant favorable impact on survival with breast cancer or that the program is serving as a social locus for the gathering of exceptional survivors.
Metabolic Syndrome: A Definition in Progress
Authors: Hoong Sern Lim, Jeetesh V. Patel, Gregory Y.H. Lip
Journal: Circulation (2004)

We applaud the National Heart, Lung and Blood Institute and the American Heart Association in their efforts to define and outline the pathophysiology of the complex and still ill-defined metabolic syndrome. 1Although there is little doubt that obesity is closely linked to many components of the metabolic syndrome, we must also acknowledge that much of the data available on the metabolic syndrome are derived from (large) registries and post hoc analyses of clinical studies 2,3 that are not specifically designed to address the relationship between obesity, measures of insulin resistance, other associated features of the metabolic syndrome, and eventual cardiovascular outcome.These studies provide useful associations but do not establish the temporal relationship between obesity, insulin resistance, and other independent factors (such as serum lipid levels).In the absence of an established temporal relationship (cause preceding effect) and clinical trials documenting improved cardiovascular outcome with reduced insulin resistance, we fear that the Committee's description of "3 aetiological categories," which implies a 1-way causal relationship, may be presumptuous (at this point in time) and may conceal a more complex pathophysiology.Finally, body mass index (BMI), though widely used, is not sensitive to adverse levels of obesity in all populations across different ethnic groups.Indeed, South Asians have higher upper body and visceral fat for a given BMI when compared with people of European descent. 4Hence, obesity should be defined in the context of specific ethnic population, which is reflected in the recent World Health Organisation recommendation of a lower BMI in South Asians (BMI over 23 kg/m 2 classed as overweight).The concept of "primary insulin resistance," as proposed by the Committee, has not been clearly defined, detracts from the ethnic-specific anthropometric differences, and risks introducing further confusion.