tbuckley/cabot-search huggingface dataset:
Simultaneous Suppression of Epidermal Growth Factor Receptor and c-erbB-2 Reverses Aneuploidy and Malignant Phenotype of a Human Ovarian Carcinoma Cell Line
Authors: Svetlana D. Pack, Özgül M. Alper, Kurt Stromberg, Meena Augustus, Metin Özdemirli, Anne M. Miermont, Greg Klus, Marek Rusin, Rebecca Slack, Neville F. Hacker, Thomas Ried, Zoltan Szallasi, Özge Alper
Journal: Cancer Research (2004)

Abstract Coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 in 47–68% of ovarian cancer cells indicate their strong association with tumor formation. We examined the effects of simultaneous antisense- or immunosuppression of EGFR and c-erbB-2 expression on the invasive phenotype, aneuploidy, and genotype of cultured human ovarian carcinoma cells (NIH:OVCAR-8). We report here that suppression of both EGFR and c-erbB-2 results in regression of aneuploidy and genomic imbalances in NIH:OVCAR-8 cells, restores a more normal phenotype, and results in a more normal gene expression profile. Combined with cytogenetic analysis, our data demonstrate that the regression of aneuploidy is due to the selective apoptosis of double antisense transfected cells with highly abnormal karyotype.
Identification of a blood-borne miRNA signature of synovial sarcoma
Authors: Alba Fricke, Prisca V. Ullrich, Jürgen Heinz, Dietmar Pfeifer, Jutta Scholber, Georg W. Herget, Oliver Hauschild, Peter Bronsert, G. Björn Stark, Holger Bannasch, Steffen U. Eisenhardt, David Braig
Journal: Molecular Cancer (2015)

Synovial sarcoma account for approximately 10 % of all soft-tissue tumors and occur most frequently in young adults. A specific translocation in this sarcoma induces fusion of the SYT gene on chromosome 18 to the SSX genes on chromosome X, leading to proliferation of the tumor cells. The need for non-invasive biomarkers indicating recurrence and activity of this disease has sparked research into short non-coding RNA known as microRNA (miRNA). Blood samples of patients with active synovial sarcoma and of synovial sarcoma patients in complete remission as well as of healthy donors and patients with active leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma were collected. Whole blood RNA was extracted and samples of patients with active synovial sarcoma and of healthy donors were analyzed using an Affymetrix GeneChip miRNA Array v. 4.0. qRT-PCR was carried out to confirm a panel of miRNAs which where differentially expressed in the miRNA array. This miRNA-panel was further evaluated in patients with synovial sarcoma in complete remission and patients with active leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma as well as in an independent cohort of synovial sarcoma patients. Unsupervised hierarchical clustering of the miRNA arrays separated patients with active synovial sarcoma from healthy controls. A panel of seven miRNAs (miR-99a-5p, miR-146b-5p, miR-148b-3p, miR-195-5p, miR-223-3p, miR-500b-3p and miR-505-3p) was further validated by qRT-PCR to be significantly upregulated in synovial sarcoma patients. Moreover, most of the analyzed miRNAs were shown to be significantly upregulated in synovial sarcoma patients compared to leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma patients. Validation of the miRNA panel in an independent cohort of synovial sarcoma patients confirmed higher expression levels compared to healthy controls and patients in complete remission. Our results have identified a specific whole blood miRNA signature that may serve as an independent biomarker for the diagnosis of local recurrence or distant metastasis of synovial sarcoma. It even distinguishes synovial sarcoma from other sarcoma subtypes, thus potentially serving as a specific biomarker for synovial sarcoma.
Health Status, Somatization, and Severity of Posttraumatic Stress Disorder in Vietnam Combat Veterans With Posttraumatic Stress Disorder
Authors: Jean C. Beckham, Scott D. Moore, Michelle E. Feldman, Michael A. Hertzberg, Angela C. Kirby, John A. Fairbank
Journal: American Journal of Psychiatry (1998)

Objective:A two-part study was conducted to examine the health status of Vietnam veterans with posttraumatic stress disorder (PTSD). In part 1, veterans with and without PTSD were compared on health behaviors and on self-reported and physician-rated health problems. Consistency of self-report with physician rating for health problems across the two groups was compared. In part 2, the association between health status and PTSD symptom severity, depression, somatization, and health behaviors in PTSD patients was evaluated.Method:In part 1, 276 combat veterans (225 with PTSD and 51 without PTSD) provided health status information, and medical records were reviewed. In part 2, 225 PTSD patients completed standardized PTSD severity, somatization, and depression measures.Results:When analyses controlled for age, socioeconomic status, minority status, combat exposure, alcohol use, and pack-year history, veterans with PTSD reported and were rated as having a greater number of health problems than veterans without PTSD. Agreement between self-report and physician ratings for both groups ranged from low to moderate. Level of agreement between patient and physician was similar across groups. In the analysis of veterans with PTSD, somatization and PTSD symptom severity were significantly related to self-report of health problems, whereas only PTSD symptom severity was related to physician-rated health. Pack-year history was significantly related to self-reported health status in both groups.Conclusions:The presence and severity of PTSD in veterans were associated with greater physical health problems and conditions. Psychological variables (e.g., PTSD status, PTSD severity, somatization) and a behavioral variable (pack-year history) were related to health status. Am J Psychiatry 1998; 155: 1565-1569
Toll Gates and Traffic Arteries
Authors: Sarah C. Mullaly, Paul Kubes
Journal: Circulation Research (2004)

2][3] Disease onset is thought to be triggered by hypertension, high plasma concentrations of low-density lipoprotein (LDL) cholesterol, diabetes mellitus, or even infection. 1Endothelial injury by these factors is central to atherogenesis.Lesion susceptibility is greatest in those vascular regions with altered hemodynamics, such as the outer edges of arterial branches or curvatures.In these low-shear sites, endothelial proliferation, apoptosis, and permeability are all increased.In addition, the expression of adhesion molecules and chemokines increases, which facilitates the recruitment of monocytes, lymphocytes, and platelets from the circulation into the artery wall, resulting in the formation of an advanced, complicated lesion. 2,32][3] Although what initiates and maintains this inflammatory state is unclear, it is intriguing that both myocardial infarction and stroke are increased during acute infections 3 and numerous pathogens have been detected in human lesions.However, how pathogens contribute to atherosclerosis remains unclear.The detection of microbial infection and the initiation of the innate immune response are mediated via germlineencoded, pattern-recognition receptors, including the Tolllike receptors (TLRs), which recognize highly conserved pathogen-associated molecular patterns. 4 -7 The ligation of many TLRs, including TLR2 (summarized in the Figure ) and TLR4, results in the recruitment of the adaptor protein myeloid differentiation factor 88 (MyD88) followed by the subsequent activation of nuclear factor-B (NF-B) and the mitogen-activated protein kinases (MAPKs).This results in the production of a cascade of cytokines, chemokines, and other pro-inflammatory molecules that contribute to the inflammatory response and bacterial clearance.
Vitamin D Receptor Signaling in Podocytes Protects against Diabetic Nephropathy
Authors: Youli Wang, Dilip K. Deb, Zhongyi Zhang, Tao Sun, Weicheng Liu, Dosuk Yoon, Juan Kong, Yunzi Chen, Anthony Chang, Yan Chun Li
Journal: Journal of the American Society of Nephrology (2012)

Vitamin D and its analogs have antiproteinuric activity and podocytes express the vitamin D receptor, but whether vitamin D signaling in podocytes accounts for this renoprotection is unknown. To investigate this question, we used the 2.5 kb podocin promoter to target Flag-tagged human vitamin D receptor (hVDR) to podocytes in DBA/2J mice. After the induction of diabetes with streptozotocin, transgenic mice had less albuminuria than wild-type controls. In transgenic mice, a low dose of the vitamin D analog doxercalciferol prevented albuminuria, markedly attenuated podocyte loss and apoptosis, and reduced glomerular fibrosis, but it had little effect on the progression of diabetic nephropathy in wild-type mice. Moreover, reconstitution of VDR-null mice with the hVDR transgene in podocytes rescued VDR-null mice from severe diabetes-related renal damage. In culture, 1,25-dihydroxyvitamin D suppressed high-glucose–induced apoptosis of podocytes by blocking p38- and ERK-mediated proapoptotic pathways. Taken together, these data provide strong evidence that vitamin D/VDR signaling in podocytes plays a critical role in the protection of the kidney from diabetic injury.
EPHX1 polymorphisms, COPD and asthma in 47,000 individuals and in meta-analysis
Authors: J. Lee, B.G. Nordestgaard, M. Dahl
Journal: European Respiratory Journal (2010)

We tested the hypothesis that two well-characterised functional polymorphisms of the microsomal epoxide hydrolase gene ( EPHX1 ), T113C and A139G , may influence susceptibility to chronic obstructive pulmonary disease (COPD) and asthma. We genotyped participants from the Copenhagen City Heart Study (n = 10,038) and the Copenhagen General Population Study (n = 37,022) for the T113C and A139G variants in the EPHX1 gene and measured lung function and recorded COPD hospitalisation and asthma and smoking history. Finally, we meta-analysed results from 19 studies including 7,489 COPD cases and 42,970 controls. The OR for spirometry-defined COPD or COPD hospitalisation did not differ from 1.0 for any of the EPHX1 genotypes or phenotypes overall, or in smokers or nonsmokers separately (p-value for trend 0.18–0.91). Likewise, EPHX1 genotypes or phenotypes did not associate with risk of asthma (p-value for trend 0.46–0.98). In meta-analysis, random effects OR for COPD in T113C heterozygotes and homozygotes versus non-carriers were 1.17 (0.99–1.38) and 1.38 (1.09–1.74), respectively. Corresponding values for A139G were 0.93 (0.83–1.05) and 0.89 (0.78–1.02). Our results indicate that genetically reduced microsomal epoxide hydrolase activity is not a major risk factor for COPD or asthma in the Danish population; however, meta-analysis cannot completely exclude a minor effect on COPD risk.
THE PHARMACOLOGY AND TOXICOLOGY OF POLYPHENOLIC-GLUTATHIONE CONJUGATES
Authors: Terrence J. Monks, Serrine S. Lau
Journal: The Annual Review of Pharmacology and Toxicology (1998)

▪ Abstract Polyphenolic-glutathione (GSH) conjugates and their metabolites retain the electrophilic and redox properties of the parent polyphenol. Indeed, the reactivity of the thioether metabolites frequently exceeds that of the parent polyphenol. Although the active transport of polyphenolic-GSH conjugates out of the cell in which they are formed will limit their potential toxicity to those cells, once within the circulation they can be transported to tissues that are capable of accumulating these metabolites. There are interesting physiological similarities between the organs that are known to be susceptible to polyphenolic-GSH conjugate-mediated toxicity. In addition, the frequent localization of γ-glutamyl transpeptidase to cells separating the circulation from a second fluid-filled compartment coincides with tissues that are susceptible either to polyphenolic-GSH conjugate-induced toxicity or to quinone and reactive oxygen species–induced toxicity. Polyphenolic-GSH conjugates therefore contribute to the nephrotoxicity, nephrocarcinogenicity, and neurotoxicity of a variety of polyphenols.
CD28 Costimulation Overcomes Transforming Growth Factor-β–Mediated Repression of Proliferation of Redirected Human CD4+ and CD8+ T Cells in an Antitumor Cell Attack
Authors: Heike Koehler, David Kofler, Andreas Hombach, Hinrich Abken
Journal: Cancer Research (2007)

Abstract The T-cell–mediated antitumor immune response is frequently repressed in the tumor environment by an immunologic barrier, the predominant mediators of which are thought to be interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). We explored the effect of these cytokines on the individual T-cell effector functions on antigen engagement during an antitumor cell attack. Isolated CD4+ and CD8+ T cells were antigen-specifically redirected toward carcinoembryonic antigen (CEA)-positive tumor cells by expression of a recombinant T-cell receptor (immunoreceptor), which triggers T-cell activation via CD3ζ on binding to CEA. Immunoreceptor-activated T cells secrete IFN-γ, proliferate, and lyse CEA+ but not CEA− tumor cells. Whereas IL-10 has no direct effect on immunoreceptor-triggered effector functions, TGF-β represses proliferation of both CD4+ and CD8+ T cells but neither IFN-γ secretion nor specific cytolytic activities. CD28 costimulation, however, overcomes TGF-β–mediated repression in T-cell proliferation. Consequently, T cells redirected by a combined CD28-CD3ζ signaling immunoreceptor are largely resistant to TGF-β–mediated repression. This is reflected in vivo by a more pronounced antitumor activity of T cells against TGF-β–secreting tumors when redirected by a costimulatory CD28-CD3ζ than by a CD3ζ signaling immunoreceptor. [Cancer Res 2007;67(5):2265–73]
Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial
Authors: Sube Banerjee, Jennifer Hellier, Michael Dewey, Renee Romeo, Clive Ballard, Robert Baldwin, Peter Bentham, Chris Fox, Clive Holmes, Cornelius Katona, Martin Knapp, Claire Lawton, James Lindesay, Gill Livingston, Niall McCrae, Esme Moniz-Cook, Joanna Murray, Shirley Nurock, Martin Orrell, John O'Brien, Michaela Poppe, Alan Thomas, Rebecca Walwyn, Kenneth Wilson, Alistair Burns
Journal: The Lancet (2011)
Ki-67 Staining Is a Strong Predictor of Distant Metastasis and Mortality for Men With Prostate Cancer Treated With Radiotherapy Plus Androgen Deprivation: Radiation Therapy Oncology Group Trial 92–02
Authors: A. Pollack, M. DeSilvio, L.-Y. Khor, R. Li, T.I. Al-Saleem, M.E. Hammond, V. Venkatesan, C.A. Lawton, M. Roach, W.U. Shipley, G.E. Hanks, H.M. Sandler
Journal: Journal of Clinical Oncology (2004)

Purpose The Ki-67 staining index (Ki67-SI) has been associated with prostate cancer patient outcome; however, few studies have involved radiotherapy (RT) -treated patients. The association of Ki67-SI to local failure (LF), biochemical failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall death (OD) was determined in men randomly assigned to short term androgen deprivation (STAD) + RT or long-term androgen deprivation (LTAD) + RT. Patients and Methods There were 537 patients (35.5%) on Radiation Therapy Oncology Group (RTOG) 92-02 who had sufficient tissue for Ki67-SI analysis. Median follow-up was 96.3 months. Ki67-SI cut points of 3.5% and 7.1% were previously found to be related to patient outcome and were examined here in a Cox proportional hazards multivariate analysis (MVA). Ki67-SI was also tested as a continuous variable. Covariates were dichotomized in accordance with stratification and randomization criteria. Results Median Ki67-SI was 6.5% (range, 0% to 58.2%). There was no difference in the distribution of patients in the Ki-67 analysis cohort (n = 537) and the other patients in RTOG 92-02 (n = 977) by any of the covariates or end points tested. In MVAs, Ki67-SI (continuous) was associated with LF (P = .08), BF (P = .0445), DM (P &lt; .0001), CSD (P &lt; .0001), and OD (P = .0094). When categoric variables were used in MVAs, the 3.5% Ki67-SI cut point was not significant. The 7.1% cut point was related to BF (P = .09), DM (P = .0008), and CSD (P = .017). Ki67-SI was the most significant correlate of DM and CSD. A detailed analysis of the hazard rates for DM in all possible covariate combinations revealed subgroups of patients treated with STAD + RT that did not require LTAD. Conclusion Ki67-SI was the most significant determinant of DM and CSD and was also associated with OD. The Ki67-SI should be considered for the stratification of patients in future trials.
Evaluation of pseudoprogression in patients with glioblastoma multiforme using dynamic magnetic resonance imaging with ferumoxytol calls RANO criteria into question
Authors: M. Nasseri, S. Gahramanov, J. P. Netto, R. Fu, L. L. Muldoon, C. Varallyay, B. E. Hamilton, E. A. Neuwelt
Journal: Neuro-Oncology (2014)

Diagnosis of pseudoprogression in patients with glioblastoma multiforme (GBM) is limited by Response Assessment in Neuro-Oncology (RANO) criteria to 3 months after chemoradiotherapy (CRT). Frequency of pseudoprogression occurring beyond this time limit was determined. Survival comparison was made between pseudoprogression and true progression patients as determined by using perfusion magnetic resonance imaging with ferumoxytol (p-MRI-Fe). Fifty-six patients with GBM who demonstrated conventional findings concerning for progression of disease post CRT were enrolled in institutional review board-approved MRI protocols. Dynamic susceptibility-weighted contrast-enhanced p-MRI-Fe was used to distinguish true progression from pseudoprogression using relative cerebral blood volume (rCBV) values. rCBV of 1.75 was assigned as the cutoff value. Participants were followed up using RANO criteria, and survival data were analyzed. Twenty-seven participants (48.2%) experienced pseudoprogression. Pseudoprogression occurred later than 3 months post CRT in 8 (29.6%) of these 27 participants (ie, 8 [14.3%] of the 56 patients meeting the inclusion criteria). Overall survival was significantly longer in participants with pseudoprogression (35.2 months) compared with those who never experienced pseudoprogression (14.3 months; P < .001). Pseudoprogression presented after 3 months post CRT in a considerable portion of patients with GBM, which raises doubts about the value of the 3-month time limit of the RANO criteria. Accurate rCBV measurement (eg, p-MRI-Fe) is suggested when there are radiographical concerns about progression of disease in GBM patients, regardless of any time limit. Pseudoprogression correlates with significantly better survival outcomes.
Adult respiratory distress syndrome after limited resection of adenocarcinoma of the lung.
Authors: S el Bayadi, D B Ettensohn, J Yashar
Journal: Thorax (1990)

Two cases of the adult respiratory distress syndrome developed after limited resection for lung carcinoma. No other known precipitants were evident. The adult respiratory distress syndrome is a clinical expression of acute lung injury that may arise from various insults and include air and blood borne factors. Tumour related blood borne factors may have contributed to lung injury in these cases.
Hemodynamics of Collateral Vasodilatation following Femoral Artery Occlusion in Anesthetized Dogs
Authors: STANLEY L. ROSENTHAL, ARTHUR C. GUYTON
Journal: Circulation Research (1968)

Dilatation of collateral blood vessels was studied following occlusion of the femoral artery in anesthetized dogs. This was achieved by measuring pressure and flow in the anterior tibial artery distal to the occlusion and pressure in the femoral artery proximal to the occlusion. Dilatation of the collateral vessels to the anterior tibial artery was estimated by the increase in the conductance of the collaterals from the minimum value measured 8 to 10 seconds following onset of the occlusion. Conductance rose 277 ± 67 (SEM)% during the first 70 seconds following occlusion and an additional 178 ± 66% during the ensuing hour. When the femoral artery was reopened after a 2-minute period of occlusion, the collaterals reconstricted to their preocclusion size in 12 to 14 minutes. Elimination of circulatory reflexes by total spinal anesthesia did not alter the course of collateral vasodilatation. However, when systemic arterial pressure was lowered to approximately 45 mm Hg for 8 minutes prior to occlusion, the collaterals dilated almost completely even before the occlusion was instituted, indicating that tissue ischemia is in some way related to collateral vasodilatation.
Applicability of the Single-Breath Carbon Monoxide Diffusing Capacity in a Norwegian Community Study
Authors: IDA WELLE, GEIR EGIL EIDE, PER BAKKE, AMUND GULSVIK
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The test of single-breath diffusing capacity for carbon monoxide (DLCO) has been widely used in population surveys. However, little is known about the effect of meeting or failing to meet the criteria for acceptability of this test. The American Thoracic Society (ATS) recommends a breathholding time of 9 to 11 s, two measurements within +/- 10% or 3 ml CO(STPD)/min/mm Hg of the average DLCO, and an inspiratory vital capacity (IVC) of at least 90% of the largest previously measured forced vital capacity (FVC) as criteria for this test. The objective of the present study was to examine the extent to which these criteria were met in a community study. To do this, a random sample of 3,740 persons, aged 15 to 70 yr, of the general population of the city of Bergen and 11 surrounding municipalities on the southwest coast of Norway were enrolled in a two-phase cross-sectional study. In the second phase, a stratified sample (n = 1,512) of the respondents to the postal questionnaire used for recruitment for the study (n = 3,370) were invited to a clinical and respiratory physiologic examination that included the DLCO test. The attendance rate was 84% (1,275 of 1,512). In the examination, all subjects were able to maintain a breathholding time of 9 to 11 s, and 98% had two DLCO values within +/- 10% or 3 ml CO(STPD)/min/mm Hg of the average DLCO. The criterion of an IVC of at least 90% of FVC in the two tests was met by 68% of the subjects. Younger age was an independent predictor of failure to meet the required criteria. Thus, only two-thirds of the participants fulfilled all of the ATS criteria for the DLCO test, the main reason for failure being an IVC of less than 90% FVC. This should not necessarily lead to the exclusion from further analysis of those failing to meet this criterion.