tbuckley/cabot-search huggingface dataset:
Human Epidermal Growth Factor Receptor 2 Assessment in a Case-Control Study: Comparison of Fluorescence In Situ Hybridization and Quantitative Reverse Transcription Polymerase Chain Reaction Performed by Central Laboratories
Authors: Frederick L. Baehner, Ninah Achacoso, Tara Maddala, Steve Shak, Charles P. Quesenberry, Lynn C. Goldstein, Allen M. Gown, Laurel A. Habel
Journal: Journal of Clinical Oncology (2010)

The optimal method to assess human epidermal growth factor receptor 2 (HER2) status remains highly controversial. Before reporting patient HER2 results, American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines mandate that laboratories demonstrate ≥ 95% concordance to another approved laboratory or methodology. Here, we compare central laboratory HER2 assessed by fluorescence in situ hybridization (FISH) and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using Oncotype DX in lymph node-negative, chemotherapy-untreated patients from a large Kaiser Permanente case-control study.Breast cancer specimens from the Kaiser-Genomic Health study were examined. Central FISH assessment of HER2 amplification and polysomy 17 was conducted by PhenoPath Laboratories (ratios > 2.2, 1.8 to 2.2, and < 1.8 define HER2 positive, HER2 equivocal, and HER2 negative, respectively). HER2 expression by RT-PCR was conducted using Oncotype DX by Genomic Health (normalized expression units ≥ 11.5, 10.7 to < 11.5, and < 10.7 define HER2 positive, HER2 equivocal, and HER2 negative, respectively). Concordance analyses followed ASCO/CAP guidelines.HER2 concordance by central FISH and central RT-PCR was 97% (95% CI, 96% to 99%). Twelve percent (67 of 568 patients) and 11% (60 of 568 patients) of patients were HER2 positive by RT-PCR and FISH, respectively. HER2-positive patients had increased odds of dying from breast cancer compared with HER2-negative patients. Polysomy 17 was demonstrated in 12.5% of all patients and 33% of FISH-positive patients. Nineteen of 20 FISH-positive patients with polysomy 17 were also RT-PCR HER2 positive. Although not statistically significantly different, HER2-positive/polysomy 17 patients tended to have the worst prognosis, followed by HER2-positive/eusomic, HER2-negative/polysomy 17, and HER2-negative/eusomic patients.There is a high degree of concordance between central FISH and quantitative RT-PCR using Oncotype DX for HER2 status, and the assay warrants additional study in a trastuzumab-treated population.
Delayed-Type Hypersensitivity Reaction With Iscador M Given in Combination With Cytotoxic Chemotherapy
Authors: Heather S. Shaw, Katherine B. Hobbs, Victoria L. Seewaldt, David J. Kroll
Journal: Journal of Clinical Oncology (2004)

GVHD.Such patients are rare, and it may therefore be difficult to collect a sufficient number of patients for a meaningful prospective study, even in a multicenter trial.I agree with Dr Mehta that there are more vital issues to address regarding HSCT.Some lessons may be learned from this report.Before including new treatment modalities in HSCT protocols, appropriate safety studies and proper prospective randomized studies enrolling enough patients to evaluate longterm TRM and overall survival are necessary.Furthermore, we have to rely on academic nonprofit studies.Doubleblind company-driven good clinical practice studies may disappear if data are in conflict with the interests of the stockholders.Not only at our unit, but also in one third of the European units, G-CSF was used as prophylaxis after HSCT, and we were encouraged only by a faster engraftment of ANC, with insufficient data to evaluate more vital end points.Retrospective analyses of large registries of patients, like those at EBMT and CIBMTR, will eventually help us understand the long-term ramifications of changing the regimen.
Micropuncture study of the effect of various diuretics on sodium reabsorption by the proximal tubules of the dog.
Authors: J H Dirks, W J Cirksena, R W Berliner
Journal: Journal of Clinical Investigation (1966)

The precise sites of action of various diuretics within the nephron have been the subject of numerous investigations and considerable debate for several decades. Inhibition of sodium transport in the proximal tubule has, at one time or another, been considered to play a major role in the action of virtually every group of diuretics. However, such actions on the proximal tubules have been inferred only from indirect evidence. The technique of micropuncture allows a more direct evaluation of the effects of pharmacologic agents on sodium reabsorption by the proximal tubules.
The Chloroplast Genome Sequence of Chara vulgaris Sheds New Light into the Closest Green Algal Relatives of Land Plants
Authors: Monique Turmel, Christian Otis, Claude Lemieux
Journal: Molecular Biology and Evolution (2006)

The phylum Streptophyta comprises all land plants and six monophyletic groups of charophycean green algae (Mesostigmatales, Chlorokybales, Klebsormidiales, Zygnematales, Coleochaetales, and Charales). Phylogenetic analyses of four genes encoded in three cellular compartments suggest that the Charales are sister to land plants and that charophycean green algae evolved progressively toward an increasing cellular complexity. To validate this phylogenetic hypothesis and to understand how and when the highly conservative pattern displayed by land plant chloroplast DNAs (cpDNAs) originated in the Streptophyta, we have determined the complete chloroplast genome sequence (184,933 bp) of a representative of the Charales, Chara vulgaris, and compared this genome to those of Mesostigma (Mesostigmatales), Chlorokybus (Chlorokybales), Staurastrum and Zygnema (Zygnematales), Chaetosphaeridium (Coleochaetales), and selected land plants. The phylogenies we inferred from 76 cpDNA-encoded proteins and genes using various methods favor the hypothesis that the Charales diverged before the Coleochaetales and Zygnematales. The Zygnematales were identified as sister to land plants in the best tree topology (T1), whereas Chaetosphaeridium (T2) or a clade uniting the Zygnematales and Chaetosphaeridium (T3) occupied this position in alternative topologies. Chara remained at the same basal position in trees including more land plant taxa and inferred from 56 proteins/genes. Phylogenetic inference from gene order data yielded two most parsimonious trees displaying the T1 and T3 topologies. Analyses of additional structural cpDNA features (gene order, gene content, intron content, and indels in coding regions) provided better support for T1 than for the topology of the above-mentioned four-gene tree. Our structural analyses also revealed that many of the features conserved in land plant cpDNAs were inherited from their green algal ancestors. The intron content data predicted that at least 15 of the 21 land plant group II introns were gained early during the evolution of streptophytes and that a single intron was acquired during the transition from charophycean green algae to land plants. Analyses of genome rearrangements based on inversions predicted no alteration in gene order during the transition from charophycean green algae to land plants.
Heart conduction disturbance: an HLA-B27 associated disease.
Authors: A J Peeters, S ten Wolde, M I Sedney, R R de Vries, B A Dijkmans
Journal: Annals of the Rheumatic Diseases (1991)

In recent studies from Sweden an increased prevalence of HLA-B27 associated diseases and of HLA-B27 was found in an unselected group of men with permanently implanted pacemakers and with a heart block. Furthermore, a significantly increased prevalence of HLA-B27 was found in men with a pacemaker who had no clinical or radiological signs of HLA-B27 associated disease. To obtain more insight into the association between HLA-B27 and heart block, and the possible role of HLA-B27 in causing this block, a study was made of 35 patients with a pacemaker and heart block of unknown cause, selected from a total group of 350 men with pacemakers who were still alive at the time of the study. One of these 35 men had ankylosing spondylitis and two patients had an asymptomatic sacroiliitis, but all three were HLA-B27 negative. HLA-B27 was present in five (14%) patients, which is a significantly higher prevalence than in healthy controls (17/292, 6%). This percentage is equal to the percentage of HLA-B27 positivity found in the Swedish study on unselected men with an implanted pacemaker, in whom the presence of an HLA-B27 associated disease had been excluded. It suggests that factors other than HLA-B27 are important in the pathogenesis of heart block in most patients.
Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors
Authors: Andy J. Minn, Yibin Kang, Inna Serganova, Gaorav P. Gupta, Dilip D. Giri, Mikhail Doubrovin, Vladimir Ponomarev, William L. Gerald, Ronald Blasberg, Joan Massagué
Journal: Journal of Clinical Investigation (2005)

We used bioluminescence imaging to reveal patterns of metastasis formation by human breast cancer cells in immunodeficient mice. Individual cells from a population established in culture from the pleural effusion of a breast cancer patient showed distinct patterns of organ-specific metastasis. Single-cell progenies derived from this population exhibited markedly different abilities to metastasize to the bone, lung, or adrenal medulla, which suggests that metastases to different organs have different requirements. Transcriptomic profiling revealed that these different single-cell progenies similarly express a previously described “poor-prognosis” gene expression signature. Unsupervised classification using the transcriptomic data set supported the hypothesis that organ-specific metastasis by breast cancer cells is controlled by metastasis-specific genes that are separate from a general poor-prognosis gene expression signature. Furthermore, by using a gene expression signature associated with the ability of these cells to metastasize to bone, we were able to distinguish primary breast carcinomas that preferentially metastasized to bone from those that preferentially metastasized elsewhere. These results suggest that the bone-specific metastatic phenotypes and gene expression signature identified in a mouse model may be clinically relevant.
Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial
Authors: Elisabeth Quoix, Rodryg Ramlau, Virginie Westeel, Zsolt Papai, Anne Madroszyk, Alain Riviere, Piotr Koralewski, Jean-Luc Breton, Erich Stoelben, Denis Braun, Didier Debieuvre, Hervé Lena, Marc Buyse, Marie-Pierre Chenard, Bruce Acres, Gisèle Lacoste, Bérangère Bastien, Annette Tavernaro, Nadine Bizouarne, Jean-Yves Bonnefoy, Jean-Marc Limacher
Journal: The Lancet Oncology (2011)
Characterization of heterotypic interaction effects in vitro to deconvolute global gene expression profiles in cancer
Authors: Martin Buess, Dimitry SA Nuyten, Trevor Hastie, Torsten Nielsen, Robert Pesich, Patrick O Brown
Journal: Genome biology (2007)

Abstract Background Perturbations in cell-cell interactions are a key feature of cancer. However, little is known about the systematic effects of cell-cell interaction on global gene expression in cancer. Results We used an ex vivo model to simulate tumor-stroma interaction by systematically co-cultivating breast cancer cells with stromal fibroblasts and determined associated gene expression changes with cDNA microarrays. In the complex picture of epithelial-mesenchymal interaction effects, a prominent characteristic was an induction of interferon-response genes (IRGs) in a subset of cancer cells. In close proximity to these cancer cells, the fibroblasts secreted type I interferons, which, in turn, induced expression of the IRGs in the tumor cells. Paralleling this model, immunohistochemical analysis of human breast cancer tissues showed that STAT1, the key transcriptional activator of the IRGs, and itself an IRG, was expressed in a subset of the cancers, with a striking pattern of elevated expression in the cancer cells in close proximity to the stroma. In vivo , expression of the IRGs was remarkably coherent, providing a basis for segregation of 295 early-stage breast cancers into two groups. Tumors with high compared to low expression levels of IRGs were associated with significantly shorter overall survival; 59% versus 80% at 10 years (log-rank p = 0.001). Conclusion In an effort to deconvolute global gene expression profiles of breast cancer by systematic characterization of heterotypic interaction effects in vitro , we found that an interaction between some breast cancer cells and stromal fibroblasts can induce an interferon-response, and that this response may be associated with a greater propensity for tumor progression.
Stratification of Intermediate-Risk Endometrial Cancer Patients into Groups at High Risk or Low Risk for Recurrence Based on Tumor Gene Expression Profiles
Authors: Sarah E. Ferguson, Adam B. Olshen, Agnès Viale, Richard R. Barakat, Jeff Boyd
Journal: Clinical Cancer Research (2005)

Endometrial cancers classified as "intermediate risk" based on clinical and/or pathologic features are associated with a 15% to 20% risk of recurrence. Here, we test whether global gene expression profiling can distinguish intermediate-risk tumors into high-risk and low-risk subgroups.Tumor specimens were obtained from 75 intermediate-risk endometrial cancer patients, 13 who had recurred and 62 who had not recurred with a median follow-up of 24 months. Gene expression profiles were obtained using the Affymetrix U133A GeneChip oligonucleotide microarray. The genes most associated with risk of recurrence were used to create a risk score using a leave-one-out cross-validation method and the univariate Cox proportional hazards regression model. Time to recurrence curves for the high-risk and low-risk subgroups were estimated using the Kaplan-Meier method, and the difference in time to recurrence between these two subgroups was tested using the log-rank test.There was a significant difference in time to recurrence between high-risk and low-risk patients using risk scores as defined above (P = 0.04). The estimated hazard ratio (95% confidence interval) was 3.07 (1.00-9.43).Patients with intermediate-risk endometrial cancers identified as high-risk for recurrence according to a gene expression-based risk score have a significantly increased risk for recurrence compared with those classified as low risk. These findings suggest that gene expression profiling can potentially contribute to the clinical classification and management of intermediate-risk endometrial cancers.
Inhibition of Myocardial Crossbridge Cycling by Hypoxic Endothelial Cells
Authors: Ajay M. Shah, Alexandre Mebazaa, Zhao-Kang Yang, Giovanni Cuda, Edward B. Lankford, Chris B. Pepper, Steven J. Sollott, James R. Sellers, James L. Robotham, Edward G. Lakatta
Journal: Circulation Research (1997)

Abstract Previous studies have shown that cardiac endothelial cells release substances that influence myocardial contraction. Since P o 2 is an important stimulus that modulates endothelial function, we investigated the effects of acute moderate hypoxia and reoxygenation on the release of cardioactive factors by endothelial cells. Endothelial cells cultured from several vascular beds were superfused with normoxic (equilibrated with room air; P o 2 , ≈160 mm Hg) or hypoxic (P o 2 , 40 to 50 mm Hg) physiological buffer solution, and the superfusates were reequilibrated to a P o 2 of ≈160 mm Hg and then tested for their effects on various myocardial assays. Endothelial cell viability and buffer ionic composition were unaltered after the superfusion procedures. The superfusates of hypoxic endothelial cells induced rapid, potent, reversible inhibition of isolated cardiac myocyte contraction without reducing cytosolic Ca 2+ transients. This activity was not lost after heating (95°C) and was present in low molecular weight ( M r , &lt;500) superfusate fractions. Hypoxic endothelial superfusate reduced unloaded shortening velocity of human skinned soleus muscle fibers. It markedly depressed in vitro actin motility over cardiac myosin and reduced the rate of actin-activated cardiac myosin ATPase activity but had no effect on corresponding smooth muscle myosin assays. Reoxygenation of hypoxic endothelial cells resulted in loss of this inhibitory activity. These data indicate that cultured endothelial cells respond to acute moderate hypoxia by releasing an unidentified substance(s) that inhibits myocardial crossbridge cycling, independent of Ca 2+ or other second messenger signaling pathways. Such a mechanism could have important implications for the regulation of oxygen supply-demand balance in the heart and be relevant to conditions such as myocardial hibernation.
Immunodetection of DNA Repair Endonuclease ERCC1-XPF in Human Tissue
Authors: Nikhil R. Bhagwat, Vera Y. Roginskaya, Marie B. Acquafondata, Rajiv Dhir, Richard D. Wood, Laura J. Niedernhofer
Journal: Cancer Research (2009)

Abstract The high incidence of resistance to DNA-damaging chemotherapeutic drugs and severe side effects of chemotherapy have led to a search for biomarkers able to predict which patients are most likely to respond to therapy. ERCC1-XPF nuclease is required for nucleotide excision repair of helix-distorting DNA damage and the repair of DNA interstrand crosslinks. Thus, it is essential for several pathways of repair of DNA damage by cisplatin and related drugs, which are widely used in the treatment of non–small cell lung carcinoma and other late-stage tumors. Consequently, there is tremendous interest in measuring ERCC1-XPF expression in tumor samples. Many immunohistochemistry studies have been done, but the antibodies for ERCC1-XPF were not rigorously tested for antigen specificity. Herein, we survey a battery of antibodies raised against human ERCC1 or XPF for their specificity using ERCC1-XPF–deficient cells as a negative control. Antibodies were tested for the following applications: immunoblotting, immunoprecipitation from cell extracts, immunofluorescence detection in fixed cells, colocalization of ERCC1-XPF with UV radiation–induced DNA damage in fixed cells, and immunohistochemistry in paraffin-embedded samples. Although several commercially available antibodies are suitable for immunodetection of ERCC1-XPF in some applications, only a select subset is appropriate for detection of this repair complex in fixed specimens. The most commonly used antibody, 8F1, is not suitable for immunodetection in tissue. The results with validated antibodies reveal marked differences in ERCC1-XPF protein levels between samples and cell types. [Cancer Res 2009;69(17):6831–8]
Left Ventricular Remodeling and Ventricular Arrhythmias After Myocardial Infarction
Authors: Martin St John Sutton, Douglas Lee, Jean Lucien Rouleau, Steven Goldman, Ted Plappert, Eugene Braunwald, Marc A. Pfeffer
Journal: Circulation (2003)

The relation between left ventricular (LV) remodeling and ventricular arrhythmias after myocardial infarction is poorly documented. We investigated the relations between LV size, hypertrophy, and function and ventricular arrhythmias in 263 patients from the Survival and Ventricular Enlargement (SAVE) study, using quantitative 2D echocardiography and ambulatory ECG monitoring after myocardial infarction.Transthoracic 2D echocardiograms and arrhythmia monitoring were performed at baseline (mean, 11 days) and 1 and 2 years after infarction. LV size, short-axis muscle (mass) area (LVMA), and function were quantified from 2D echocardiograms. The prevalence of ventricular tachycardia (VT) and frequent ventricular ectopy (premature ventricular contractions [PVCs] >10/h) was assessed from ambulatory ECG. VT and PVCs >10/h occurred in 20% and 29% of patients at baseline, in 22% and 35% at 1 year and 23% and 39% at 2 years, respectively. VT and PVCs >10/h at baseline and 1 and 2 years were significantly related to LV size, LVMA, and function. Furthermore, changes in LV size and function from baseline to 2 years predicted both VT and PVCs >10/h. The study was underpowered to detect treatment effect of ACE inhibitors and beta-adrenergic receptor blockers but did not alter the relations between ventricular arrhythmias, LV size, and function.Quantitative echocardiographic assessment of LV size, LVMA, and function and changes in these measurements over time predict ventricular arrhythmias after infarction. Altered LV architecture and function during postinfarction LV remodeling provide an important substrate for triggering high-grade ventricular arrhythmias.
Use of fMRI to Predict Recovery From Unipolar Depression With Cognitive Behavior Therapy
Authors: Greg Siegle
Journal: American Journal of Psychiatry (2006)

Objective: In controlled treatment trials, 40%–60% of unmedicated depressed individuals respond to cognitive behavior therapy (CBT). The authors examined whether pretreatment neural reactivity to emotional stimuli accounted for this variation. Method: Unmedicated depressed individuals (N=14) and never depressed comparison subjects (N=21) underwent fMRI during performance of a task sensitive to sustained emotional information processing. Afterward, depressed participants completed 16 sessions of CBT. Results: Participants whose sustained reactivity to emotional stimuli was low in the subgenual cingulate cortex (Brodmann’s area 25) and high in the amygdala displayed the strongest improvement with CBT. Conclusions: The presence of emotion regulation disruptions, which are targeted in CBT, may be the key to recovery with this intervention.
Short-term use of clarithromycin in lower respiratory tract infections may increase long-term risk of cardiovascular mortality and morbidity
Authors: Haider Al-Najjar
Journal: Thorax (2013)

Short-term use of clarithromycin in lower respiratory tract infections may increase long-term risk of cardiovascular mortality and morbidityMacrolides are commonly prescribed for chronic obstructive pulmonary disease (COPD) exacerbations and community-acquired pneumonia.The short-term cardiovascular effects, probably due to QT prolongation, are well documented and some studies have implicated macrolides with increased mortality in patients with pre-existing coronary disease.This study evaluated the association between clarithromycin use and cardiovascular events in patients treated for lower respiratory tract infections in a secondary analysis of two prospective cohort studies.The EXODUS dataset enrolled 1343 patients aged over 40 admitted with COPD exacerbations to 12 hospitals in the UK from 2009 to 2011.The Edinburgh pneumonia cohort included 1631 patients admitted to hospital with radiologically confirmed community-acquired pneumonia from 2005 to 2009.Both datasets were reviewed for cardiovascular events at 1 year (defined as hospital admission for acute coronary syndrome, decompensated cardiac failure, serious arrhythmia or sudden cardiac death).There were 268 events in the COPD cohort and 171 in the pneumonia cohort.The use of clarithromycin was associated with an increased risk of cardiovascular events at 1 year in both the cohorts after adjustment for confounders, with a HR of 1.5 (95% CI 1.13 to 1.97) for COPD and 1.68 (1.18 to 2.38) for pneumonia.This remained significant after propensity-adjusted analysis to correct for patients with more severe illness being given clarithromycin.It is of interest to note that the increased risk was only significant in those receiving ≥7 days of clarithromycin, older patients (>60 for COPD, >70 for pneumonia) and those with pre-existing cardiovascular disease.The increased risk was not seen in patients with COPD treated with alternative antibiotics (β lactams and doxycycline).While this study is observational in nature, the results are troubling, particularly given the trend towards prescribing long-term macrolides to prevent COPD exacerbations and further studies need to be performed to explore this potential risk.