tbuckley/cabot-search huggingface dataset:
Abstract 4376: Upregulation of miR-21 in cisplatin-resistant ovarian cancer via JNK-1/c-Jun pathway
Authors: Ileabett M. Echevarria, Joel Encarnacion, Fatma Valiyeva, Pablo Vivas
Journal: Cancer Research (2014)

Abstract Cisplatin has been the most accepted drug for the treatment of ovarian cancer for almost 40 years. Although the majority of patients with ovarian cancer respond to front-line platinum combination chemotherapy, many patients will develop cisplatin-resistance disease, which is extremely rapid and fatal. Although various mechanisms of cisplatin resistance have been postulated, the key molecules involved in such resistance have not been identified. MiRNAs are endogenously expressed small non-coding RNAs, which are evolutionarily conserved and function as post-transcriptional regulators of gene expression. Dysregulation of miRNAs have been associated with cancer initiation, progression and drug resistance. The oncogenic miRNA-21, one of the best-studied miRNAs, is upregulated in almost all human cancers. However, the regulation of miR-21 in cisplatin resistant ovarian cancer cells has not been assessed. In this study, we measured the miR-21 expression by real-time PCR and found upregulation of miR-21 in cisplatin resistant compared with cisplatin sensitive ovarian cancer cells. Chromatin immunoprecipitation studies demonstrated the association of the c-Jun transcription factor to the mir-21 DNA promoter regions. Blocking the JNK-1, the major activator of c-Jun phosphorylation, reduced the expression of miR-21 and increased the expression of its well-known target gene, PDCD4. Overexpression of miR-21 in cisplatin sensitive cells decreased PDCD4 levels and increased cell proliferation. Finally, targeting miR-21 reduced cell growth, proliferation and invasion of cisplatin resistant ovarian cancer cells. These results suggest that the JNK-1/c-Jun/miR-21 pathway contributes to the cisplatin resistance of ovarian cancer cells and demonstrated that miR-21 is a plausible target to overcome cisplatin resistance. Citation Format: Ileabett M. Echevarria, Joel Encarnacion, Fatma Valiyeva, Pablo Vivas. Upregulation of miR-21 in cisplatin-resistant ovarian cancer via JNK-1/c-Jun pathway. [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 4376. doi:10.1158/1538-7445.AM2014-4376
Corticosteroids significantly improve symptom score in patients with active pulmonary sarcoidosis over a two year follow up
Authors: Anna Warrington, Heather Milburn
Journal: European Respiratory Journal (2011)

Corticosteroids are used in sarcoidosis to relieve symptoms and modify disease progression. Most studies of the effects of corticosteroids have concentrated on changes in chest radiograph and lung function (PFT). A recent systematic review (Paramothayan, S. et al. Respir Med 2008;102:1-9) found no studies that reported the effects of corticosteroids on symptoms.   Objectives:  To investigate whether corticosteroids were associated with improved PFT or symptom score (SS) over a 2-year follow-up.   Methods:  PFT and SS before treatment were compared with results at 3, 12 and 24 months in 20 patients given oral corticosteroids for active pulmonary sarcoidosis. To calculate SS dyspnoea was valued 1-5 by severity, and all other symptoms were valued at 1. Data were collected from clinical records and results evaluated using a 2-tailed paired t-test.   Results:  14 females and 6 males aged 29-63 years were included; 13 black, 6 Caucasian, 1 Asian. Initial symptoms included dyspnoea (11), cough (8), skin changes (9), arthralgia (8), eye problems (7). SS improved significantly at all time points. Improvement in PFT was not statistically significant.   Conclusion:  Corticosteroids improved symptoms in sarcoidosis. This is a novel finding not assayed by other studies. It has potential importance for future management guidelines for pulmonary sarcoidosis.
Abstract 13732: Exercise Gas Exchange Patterns in Diabetes: Evidence From the EURO(pean) EX(ercise) Population-Based Study
Authors: Marta Pellegrino, Greta Generati, Francesco Bandera, Valentina Labate, Eleonora Alfonzetti, Marco Guazzi
Journal: Circulation (2014)

Introduction: Diabetes mellitus (DM) is a risk condition that may determine exercise limitation and reduced oxygen consumption (VO2).

Hypothesis: No study in literature has addressed the cardiopulmonary exercise testing (CPET) phenotype in diabetic subjects with normal left ventricular function. Their functional characterization by expired gas analysis may help to better define cardiovascular (CV) risk and to improve the timing of therapeutic interventions.

Methods: 442 asymptomatic subjects enrolled in the EURO EX trial, (mean age 60±14 years; male 49.3%; BMI 28±5.5 kg/m2) with different CV risk factors (hypertension 66%, dyslipidemia 50.2%, smoking habit 19.2%, diabetes 15.4%) underwent a maximal CPET with personalized ramp protocol.

Results: The population was divided into two groups according to the presence of diabetes. Diabetic subjects (n=68) were significantly older than non-DM subjects and showed a significant lower VO2 at peak exercise (16.3±4.1 vs 19.9±7.4 ml/kg/min), a steeper VE/VCO2 slope (27±3.7 vs 25.7±4) and an impaired heart rarte reserve (peak HR 123±27 vs 135±22 bpm) and recovery (HRR 12±6 vs 17±11 beats) and higher systolic blood pressure (SBP) at rest (142±22 vs 132±15 mmHg) and peak exercise (193±20 vs 184±22 mmHg). A significant difference in the VE/VCO2 slope, peak O2 pulse, SBP at rest and ΔVO2/ΔWR slope was maintained when a correction for confounding factors (BMI, age, gender, prevalence of dyslipidemia and hypertension) was applied.

Conclusions: Asymptomatic DM subjects with normal left ventricular function compared to non-diabetics show a reduced HRR and peak O2 pulse, an increased VE/VCO2 slope and higher SBP as a typical phenotype. These findings suggest that an impaired sympathovagal control may play a key role. Whether assessment of these variables may improve the risk-related definition and a timely metabolic control in this patients seems to be worth of further investigation.

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Eosinopenia of Acute Infection
Authors: David A. Bass, Thomas A. Gonwa, Pamela Szejda, M. Susan Cousart, Lawrence R. DeChatelet, Charles E. McCall
Journal: Journal of Clinical Investigation (1980)

One distinctive aspect of the response to acute inflammation involves a rapid and persistent decrease in the numbers of circulating eosinophils, yet the mechanisms of this eosinopenia are undefined. One possibility is that the abrupt eosinopenia may be the result of release of small amounts of the chemotactic factors of acute inflammation into the circulation. These studies were designed to examine the numbers of circulating eosinophils after an intravenous injection of zymosan-activated serum, partially purified C5a or the synthetic peptide, N-formyl-methionyl-leucyl-phenylalanine. Each of these factors caused a virtual disappearance of circulating eosinophils within 1 min, a transient return of eosinophils to ∼50% of control levels after 10-90 min, and a subsequent decrease which persisted for 5 h. In contrast, the numbers of circulating heterophils, although dropping transiently, rapidly returned and rose to elevated levels for 6 h after injection. The response was not caused by adrenal mediation as it occurred normally in adrenalectomized rabbits. Two chemotaxins of allergic inflammation, histamine and the tetrapeptide valine-glycine-serine-glutamic acid, did not cause significant eosinopenia.
Gene seems to induce metastasis
Authors: Abi Berger
Journal: BMJ (2000)

A single gene seems to play a critical part in inducing metastasis in melanoma tumours. Scientists at the Massachusetts Institute of Technology have identified a gene known to be important in regulating the cytoskeleton of cells that seems to control whether a primary melanoma tumour metastasises or not.

In 90% of all cancers it is secondary tumours that ultimately cause death, so this finding has important implications for future targets for cancer therapy ( Nature 2000;406:532-5). Professor Richard Hynes, director of the Center for Cancer Research at the Massachusetts institute, and his colleagues set about looking for clues …
Culture systems for studying malignancy
Authors: Mina J. Bissell, James C. Bartholomew, Judah Folkman, Helene Smith, Martha Stampfer
Journal: Cancer Research (1979)

This paper is a meeting report of an international symposium on culture systems for studying malignancy. The four sessions of the symposium dealt with properties of transformed cells, the mechanisms of carcinogenesis, human cell systems and differentiation and malignancy. (KRM)
Long-term Use of Aspirin and Risk of Colorectal Cancer—Reply
Authors: Andrew T. Chan, Charles S. Fuchs
Journal: JAMA (2005)

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Abstract 1569: The nuclear export signal (NES) within CALM is necessary for CALM-AF10-induced leukemia
Authors: Mai Suzuki, Kazutsune Yamagata, Yukiko Aikawa, Toshio Watanabe, Issay Kitabayashi
Journal: Cancer Research (2014)

Abstract The CALM-AF10 fusion gene, which results from a t(10;11) translocation, is found in a variety of hematopoietic malignancies. Certain HOXA cluster genes and MEIS1 genes are upregulated in patients and mouse models that express CALM-AF10. Wild-type CALM primarily localizes in a diffuse pattern within the cytoplasm, whereas AF10 localizes in the nucleus; however, it is not clear where CALM-AF10 acts to induce leukemia. To investigate the influence of localization on leukemogenesis involving CALM-AF10, we determined the nuclear export signal (NES) within CALM that is necessary and sufficient for cytoplasmic localization of CALM-AF10. Mutations in the NES eliminated the capacity of CALM-AF10 to immortalize murine bone-marrow cells in vitro and to promote development of acute myeloid leukemia in mouse models. Furthermore, a fusion of AF10 with the minimal NES could immortalize bone-marrow cells and induce leukemia in mice. These results suggest that during leukemogenesis, CALM-AF10 plays its critical roles in the cytoplasm. Citation Format: Mai Suzuki, Kazutsune Yamagata, Yukiko Aikawa, Toshio Watanabe, Issay Kitabayashi. The nuclear export signal (NES) within CALM is necessary for CALM-AF10-induced leukemia. [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 1569. doi:10.1158/1538-7445.AM2014-1569
Abstract 17166: Myeloid-specific Deletion of the Glucocorticoid Receptor Increases Mitochondrial Oxidative Stress and Impairs Wound Healing After Myocardial Infarction
Authors: Jonas Neuser, Daniela Fraccarollo, Jan P Tuckermann, Paolo Galuppo, Johann Bauersachs
Journal: Circulation (2014)

Background: Glucocorticoid administration impairs ischemic wound healing by inhibiting inflammation and angiogenesis via a glucocorticoid receptor (GR)-mediated transcriptional response. However, there are also apparently contradictory reports claiming protective effects of glucorticoid administration after myocardial infarction (MI). We investigated the role of the GR in myeloid cells for infarct wound healing, using GR deficient mice (GRLysMCre). Methods and Results: MI was induced by permanent left coronary artery ligation in GRflox (wild-type [WT] controls) and GRLysMCre mice. The 7-day mortality was significantly lower in WT compared with GRLysMCre mice. At 7 days post MI, GRLysMCre mice exhibited significantly enhanced thinning and dilatation of the infarcted wall, LV chamber enlargement and functional deterioration. This was associated with altered granulation tissue formation and impaired neoangiogenesis at the site of ischemic injury. Multicolor flow cytometric analysis and immunohistochemical studies revealed at the 2nd day post infarction less infiltrating mononuclear cells [CD11bhigh and (CD49b, NK1.1, B220, CD90, Ly6G)low] in the healing myocardium of GRLysMCre mice. Mononuclear cells were identified as monocytes (F4/80, I-Ab, CD11c)low and as macrophages/dendritic cells (F4/80, I-Ab, CD11c)high. Monocytes lacking GR, isolated from peripheral blood and spleen by magnetic-activated cell sorting 1 day after MI, displayed reduced migration capacity and increased superoxide anion production in mitochondria, which was detected by HPLC-electrochemical analysis of Mito-2-hydroxy-E+. Moreover, at day 2 and 3 we found enhanced cellular and mitochondrial oxidative stress in the healing myocardium of GRLysMCre mice. Conclusions: Myeloid-specific deletion of the GR increasing mitochondrial oxidative stress alters wound healing and promotes infarct expansion. Our results suggest that the GR in myeloid cells play a crucial role during cardiac repair after myocardial infarction.
Effect of Incorporation of Pretreatment Serum Carcinoembryonic Antigen Levels Into AJCC Staging for Colon Cancer on 5-Year Survival
Authors: Pragatheeshwar Thirunavukarasu, Chetasi Talati, Sumeet Munjal, Kris Attwood, Stephen B. Edge, Valerie Francescutti
Journal: JAMA Surgery (2015)

The American Joint Committee on Cancer (AJCC) has proposed the inclusion of pretreatment serum carcinoembryonic antigen (CEA) levels (C stage) into the conventional TNM staging system of colon cancer. The latter proposal has yet to be widely adopted because of the lack of long-term survival estimates of after C-stage incorporation into AJCC staging.To evaluate whether long-term overall and cancer-specific survival is affected by inclusion of C stage into the standard AJCC TNM staging and to study the implications on survival estimates.We performed a retrospective study of all patients diagnosed as having histologically proven colonic adenocarcinoma from January 1, 2004, through December 31, 2005, from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. We stratified each AJCC stage as C0 (normal) or C1 (elevated) based on the pretreatment serum CEA level. Median follow-up was 71 months.Five-year estimates of overall and disease-specific survival and hazard ratios (HRs) for estimates of risk of overall and disease-specific mortality.A total of 16 619 patients were evaluated, and of these, 8878 patients had C0 disease and 7741 had C1 disease. C1 stage was independently associated with a 51% and 59% increased risk of overall (HR, 1.51; 95% CI, 1.44-1.59; P < .001) and disease-specific mortality (HR, 1.59; 95% CI, 1.49-1.69; P < . 001) at a median follow-up of 71 months. Analysis of survival of the AJCC stages subdivided as C0 or C1 revealed a significant worse prognosis of C1 AJCC stages compared with the respective C0 AJCC stages. The magnitude of change in survival was large enough to cause clustering of survival estimates of C1 vs C0 cancers across various AJCC stages. Analysis of patients with stage I, II, and III cancer revealed that node-negative C1 disease was associated with prognosis similar or worse than node-positive C0 disease.Inclusion of C stage into the AJCC TNM staging of colon cancer revealed significant differences dependent on C stage in terms of 5-year survival. C-stage inclusion resulted in substantial change in survival estimates, with C1 status portending a prognosis to certain stages similar to or worse than higher AJCC TNM stages with C0 status. We recommend routine pretreatment CEA testing as standard of care in colon cancer and use of C stage for multimodality treatment planning and risk stratification in prospective studies and randomized clinical trials.
Persistent Environmental Pollutants and Couple Fecundity: The LIFE Study
Authors: Germaine M. Buck Louis, Rajeshwari Sundaram, Enrique F. Schisterman, Anne M. Sweeney, Courtney D. Lynch, Robert E. Gore-Langton, José Maisog, Sungduk Kim, Zhen Chen, Dana B. Barr
Journal: Environmental Health Perspectives (2012)

Evidence suggesting that persistent environmental pollutants may be reproductive toxicants underscores the need for prospective studies of couples for whom exposures are measured.We examined the relationship between selected persistent pollutants and couple fecundity as measured by time to pregnancy.A cohort of 501 couples who discontinued contraception to become pregnant was prospectively followed for 12 months of trying to conceive or until a human chorionic gonadotrophin (hCG) test confirmed pregnancy. Couples completed daily journals on lifestyle and provided biospecimens for the quantification of 9 organochlorine pesticides, 1 polybrominated biphenyl, 10 polybrominated diphenyl ethers, 36 polychlorinated biphenyls (PCBs), and 7 perfluorochemicals (PFCs) in serum. Using Cox models for discrete time, we estimated fecundability odds ratios (FORs) and 95% CIs separately for each partner's concentrations adjusting for age, body mass index, serum cotinine, serum lipids (except for PFCs), and study site (Michigan or Texas); sensitivity models were further adjusted for left truncation or time off of contraception (≤ 2 months) before enrollment.The adjusted reduction in fecundability associated with standard deviation increases in log-transformed serum concentrations ranged between 18% and 21% for PCB congeners 118, 167, 209, and perfluorooctane sulfonamide in females; and between 17% and 29% for p,p´-DDE and PCB congeners 138, 156, 157, 167, 170, 172, and 209 in males. The strongest associations were observed for PCB 167 (FOR 0.79; 95% CI: 0.64, 0.97) in females and PCB 138 (FOR = 0.71; 95% CI: 0.52, 0.98) in males.In this couple-based prospective cohort study with preconception enrollment and quantification of exposures in both female and male partners, we observed that a subset of persistent environmental chemicals were associated with reduced fecundity.
Abstract 17268: Echocardiographic Predictors of Cardiopulmonary Exercise Test Performance in Hypertrophic Cardiomyopathy
Authors: Carolyn M Larsen, Caroline A Ball, Virginia B Hebl, Jeffrey B Geske, Kevin C Ong, Konstantinos C Siontis, Thomas P Olson, Thomas G Allison, Steve R Ommen
Journal: Circulation (2014)

Introduction: Patients with hypertrophic cardiomyopathy (HCM) have lower peak oxygen uptake (VO2) than healthy peers. The mechanism of peak VO2 limitation in HCM has not been fully elucidated. Hypothesis: We assessed the hypothesis that resting echocardiographic parameters are predictive of peak VO2 in HCM. Methods: A retrospective review of adult HCM patients seen at a tertiary referral center from 2006-2012 was performed. Patients who underwent a comprehensive echocardiogram and cardiopulmonary treadmill exercise test within 1 week were included. Multivariate modeling was used to identify predictors of peak VO2 adjusting for age, sex, body mass index, beta blocker use, diabetes, smoking, systolic blood pressure, and obstructive HCM. Results: Five hundred and forty one patients met the inclusion criteria. The average age was 52 +/- 0.65 years, 62% were male, 78% had obstructive HCM, and 42% were NYHA class III or IV. Independent predictors of peak VO2 included averaged left ventricular (LV) longitudinal peak systolic strain (p&lt;0.01) and right ventricular systolic pressure (RVSP) (p&lt;0.01) (Figure 1). Obstructive versus non-obstructive HCM, grade of diastolic dysfunction, LV mass and wall thickness, left atrial volume index, right ventricular dysfunction and moderate or greater mitral or tricuspid regurgitation were not independent predictors of peak VO2. Conclusions: In conclusion, higher RVSP and less negative LV longitudinal peak systolic strain were moderate independent predictors of lower peak VO2. These findings confirm the hypothesis that resting echocardiographic parameters are predictive of peak VO2 in HCM. Further study of the relationship between echocardiographic findings and outcomes on cardiopulmonary exercise testing may help elucidate the mechanisms of exercise limitation in HCM.
Abstract 9404: Acute Coronary Syndrome-Like ST-T Changes on Admission Electrocardiogram Predicts 30-Day Mortality in Patients With Type A Acute Aortic Dissection
Authors: Masami Kosuge, Keiji Uchida, Yoshihisa Karube, Toshiaki Ebina, Kiyoshi Hibi, Munetaka Masuda, Satoshi Umemura, Kazuo Kimura
Journal: Circulation (2014)

Introduction: In patients with Stanford type A acute aortic dissection (AAD), acute coronary syndrome (ACS)-like ST-T changes such as ST segment elevation (STE), depression (STD) or negative T wave (Neg T) often occur at presentation. However, its clinical implication remains unclear. Methods: We studied the relation admission ECG findings to clinical features at presentation and 30-day mortality in 277 patients with type A AAD who were admitted within 12 h from symptom onset. Emergency surgery was performed in 251 patients (91%). Results: Patients were divided into the 3 groups according to ECG findings on admission: ACS-like ST-T changes (n=140) [STE (n=14) and STD/Neg T (n=126)]; normal ECG (n=84), and ECG confounders (n=53) [right bundle branch block or left ventricular hypertrophy]. Age, sex, time to admission, and the rate of emergency surgery were similar in the 3 groups. ACS-like ST-T changes were more frequently associated with pericardial effusion (45% vs 10%, 32%), cardiac tamponade (27% vs 2%,...