tbuckley/cabot-search huggingface dataset:
Isolation and Properties of Cells Releasing C-Type Particles from BALB/c Embryo Cell Cultures2
Authors: P. J. Simons, Barbara J. Rankin, J. M. Papadimitriou
Journal: JNCI Journal of the National Cancer Institute (1972)

Cell lines were established from cultures of BALB/c embryos in which most of the cells were in a nondividing phase. A fusiform and a larger, polygonal cell were described. Both types were positive for the murine leukemia virus, group-specific (MuLV-gs) antigen when tested by immunodiffusion and complement fixation. C-type particles budded from both types of cells, and infectivity could be demonstrated. The large, polygonal cells had the properties of macrophages. The two lines behaved as transformed cells in vitro but were poorly tumorigenic. The only tumor, in a mouse inoculated with cell lines as a newborn, consisted of undifferentiated round and smaller osmiophilic cells. The tumor was positive for MuLV-gs antigen but was poorly transplantable. The possible role of MuLV-gs antigen in cell growth regulation isdiscussed.
Management of Patients With Cytogenetically Normal Acute Myeloid Leukemia Who Have Neither Favorable nor Unfavorable Markers
Authors: Alison R. Walker, Guido Marcucci
Journal: Journal of the National Comprehensive Cancer Network (2014)

The presence or absence of cytogenetic and molecular abnormalities present at the time of diagnosis of acute myeloid leukemia (AML) not only provides important prognostic information, but also directs decisions regarding postremission therapy. In no other group has molecular analysis been more important than for the 40% to 50% of newly diagnosed patients in whom clonal chromosomal aberrations are not detected. Patients with cytogenetically normal (CN) AML were once considered a homogenous group, but are now classified into molecularly defined subgroups with distinct clinical outcomes. Evaluating FLT3, NPM1, and CEBPA mutational status is a routine component of the diagnostic evaluation for all patients with CN-AML and is used to determine outcome risk. However, in patients with FLT3 wild-type/NPM1 wild-type/CEBPA wild-type CN-AML, the optimal postremission therapy has not been well defined. This article reviews treatment outcomes for this group of patients after chemotherapy and autologous and allogeneic stem cell transplantation. New recurrent somatic mutations and their prognostic significance in patients with FLT3 wild-type/NPM1 wild-type CN-AML are also addressed.
Circulating tumor cells (CTC) in a study of relapsed/recurrent advanced ovarian cancer: An exploratory analysis in the ova-301 phase III study of pegylated liposomal doxorubicin (PLD) compared with trabectedin and PLD
Authors: A. Poveda, S. B. Kaye, R. T. McCormack, S. Wang, D. Ricci, E. Broderick, T. Parekh, C. Lebedinsky, J. C. Tecero, B. J. Monk
Journal: Journal of Clinical Oncology (2009)

5551 Background: Circulating tumor cells (CTC) have demonstrated predictive and prognostic value among patients with metastatic breast, colorectal, and prostate cancer. In a phase III study of pegylated liposomal doxorubicin (PLD) with trabectedin (T) vs PLD for relapsed ovarian cancer, we assessed the affect of CTCs on progression free survival, (PFS) and overall survival (OS). Methods: CTCs were isolated from peripheral blood (10 mLs) using the CellSearch system and reagents (Veridex). A CTC is defined as EpCAM+, cytokeratin+, CD45-, and is positive for the nuclear stain DAPI. The normal reference range for CellSearch is &lt; 2 CTC/7.5 mLs of blood. Hazard ratios adjusted for known prognostic factors were estimated by Cox regression. Results: 216 subjects had baseline CTC measurements of which 111 (51.4%) were randomized to the PLD+T arm; 143/216 patients (66.2%) were platinum sensitive. Thirty-one/216 patients (14.4%) had 2 or more CTCs detected prior to the start of therapy (range 2–566). Univariate Cox regression analyses indicated that patient's &gt; 2 CTCs prior to therapy have 1.89 (p = 0.003) and 2.06 (p = 0.003) fold higher risk for progression and death respectively. Multivariate analyses that include baseline CTC, baseline CA125, platinum sensitivity status, largest diameter lesion, number of tumor lesions, ECOG PS, age, tumor histology, tumor grade and prior taxane show that patients with elevated baseline CTC have 1.58 (p = 0.058) and 1.54 (p = 0.096) fold higher risk for progression and death respectively. Conclusions: Results from this study indicate that although CTC detection in blood from relapsed recurrent ovarian cancer patients is relatively low, elevated numbers of CTCs imparts an unfavorable prognosis for patients. Multivariate analysis indicates that CTCs have prognostic value that is independent of established factors and thus provides a clinically useful tool for assessing prognosis in this difficult to treat patient population. [Table: see text]
Excess inhaled corticosteroid adherence may be a marker of uncontrolled asthma
Authors: Richard Martin, David Price, Jerry Krishnan, Jonathan D. Campbell, Leif Bjermer, Andrew McIvor, Gary Wong, Marc Miravitlles, Alison Chisholm, Annie Burden
Journal: European Respiratory Journal (2013)

Background: The relationship between adherence to inhaled corticosteroids (ICS) in excess of 100% and asthma control is unclear.

Methods: The Respiratory Effectiveness Group conducted a real-life study using a US healthcare database to examine the association between ICS medication possession ratio (MPR) >100% (a proxy measure of excess adherence) and asthma control. Eligible patients were 12–80 yrs and initiated ICS as hydrofluoroalkane beclometasone (n=2578) or fluticasone (n=7734). Over the one-year period following ICS initiation, MPR was calculated as the number of days’ supply of ICS/365 x 100% (categorized as ≤100%; >100%). Measures of asthma control consisted of severe exacerbations (unscheduled hospital admission or ER attendance for asthma or an acute course of oral corticosteroids) and Risk Domain Asthma Control (RDAC: no admission, ER attendance, or outpatient hospital attendance for asthma; no acute oral corticosteroids prescriptions; no consultation, hospital admission, or ER attendance for a lower respiratory tract infection requiring antibiotics, and no hospital admission or ER attendance for lower respiratory reasons) during the same period.

Results: MPR>100% occurred in 7.2% of patients (n=742). Severe exacerbations were more common and RDAC attainment lower in patients with MPR >100% than in patients with MPR ≤100% (see table).

View this table:



Conclusions: In clinical practice, adherence to ICS in excess of the label-defined dosing interval appears to be a marker of poorer asthma control. A MPR >100% may be a simple tool to identify patients in need of more intensive evaluation.
Pharmaceutical Nanotechnology: Blended Nanoparticle System Based on Miscible Structurally Similar Polymers: A Safe, Simple, Targeted, and Surprisingly High Efficiency Vehicle for Cancer Therapy (Adv. Healthcare Mater. 8/2015)
Authors: Wei Tao, Jinxie Zhang, Xiaowei Zeng, Danny Liu, Gan Liu, Xi Zhu, Yanlan Liu, Qingtong Yu, Laiqiang Huang, Lin Mei
Journal: Advanced Healthcare Materials (2015)

On page 1203, a novel blended nanoparticle (NP) system for the delivery of anticancer drugs and its surprisingly high efficacy for cancer chemotherapy by blending a targeting polymer folic acid-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (FA-PEG-b-PLGA) and a miscible structurally similar polymer D-α-tocopheryl polyethylene glycol 1000 succinate-poly(lactide-co-glycolide) (TPGS-PLGA) are reported by X. Zeng, L. Huang, L. Mei, and colleagues. This blended NP system can be achieved through a simple and effective nanoprecipitation technique, possessing unique properties.
Affinity and size capture of circulating tumor cells: A platform for increased sensitivity
Authors: Peter J. Maimonis, Keith Merdek, Kurt Dietenhofer, Lucy Yen, Gary Palmer
Journal: Clinical Cancer Research (2010)

Abstract Background: The potential clinical value of evaluating circulating tumor cells (CTCs) from blood is clear. CTC analysis can aid in cancer diagnosis, prognosis, and treatment prediction. However, since CTCs are rare, current analysis is limited by low efficiencies. Variability of expression of cell surface antigens by CTCs make capture mechanisms based on antibody affinity less than ideal. We report here data from a CTC platform that combines affinity capture with size filtration capture. Methods: A spiked cell model was used, involving whole EDTA blood spiked with SKBR-3 human breast cancer cells. Two microfluidic chips were analyzed, a standard chip (T7) with constant gap size between posts, and a gradient chip (MA3) with a gap-size gradient between posts starting at 40 μ and decreasing to 12 μ. Chips were coated with either an anti-EpCAM monoclonal antibody or with no Ab. An anti-cytokeratin (CK) Ab in combination with a nuclear specific fluorescent stain on an automated cell imaging platform was used to identify CTCs. Results: 45% of cells were captured by size alone (MA3 with no Ab), 16% of cells were captured by affinity alone (T7 with MAb), and 65% of cells were captured by a combination of antibody affinity and size gradient (MA3 with MAb). This increased capture efficiency has been confirmed in clinical samples from patients with metastatic breast cancer, with a greater than 40% increase in capture efficiency utilizing both mechanisms. Whole blood from healthy donors run through either chip type yielded virtually no CTCs. FACS analysis showed that 75% of cultured SKBR-3 cells express high levels of EpCAM. This expression level will vary, as will, presumably, the relative contributions of the antibody capture mechanism and the size capture mechanism. A “heat map” analysis can demonstrate visually the relative contributions of each and these will be presented. Conclusions: The MA3 microfluidic chip captures CTCs using a combination of affinity and size filtration. This allows for the capture of CTCs with varying expression levels of EpCAM by exploiting the size differential between these CTCs and other blood elements. This dual-capture mechanism may allow for more efficient capture than affinity alone. Further work evaluating this platform in late-stage breast cancer patients is ongoing.
Comparison of peptide nucleic acid fluorescence in situ hybridization assays with culture-based matrix-assisted laser desorption/ionization-time of flight mass spectrometry for the identification of bacteria and yeasts from blood cultures and cerebrospinal fluid cultures
Authors: A. Calderaro, M. Martinelli, F. Motta, S. Larini, M.C. Arcangeletti, M.C. Medici, C. Chezzi, F. De Conto
Journal: Clinical Microbiology and Infection (2013)
Etiology of exacerbations in severe COPD patients with bronchial chronic colonization by pseudomonas
Authors: Marian Garcia-Nuñez, Laura Millares, Rafaela Ferrari, Vicente Perez-Brocal, Miguel Gallego, Javier Pomares, Conchita Monton, Mateu Espasa, Andres Moya, Eduard Monso
Journal: European Respiratory Journal (2013)

Airways in COPD patients can be colonized by PPM and chronic colonization by P.aeruginosa has been associated with impaired lung function and recurrent exacerbations.  OBJECTIVE  To analyse the bronchial microbiome in severe COPD patients with chronic colonization by P.aeruginosa when exacerbated compared to its stability.  METHOD  Sputum samples from 5 severe COPD patients colonized by P.aeruginosa were obtained during 6 stability and 7 exacerbation periods. Microbiome of the samples was determined using 16S rDNA gene 454 pyrosequencing. A change in baseline microbiota was identified when an increase of the relative abundance (RA) >10% was found in an exacerbation when compared to its baseline stability.  RESULTS  Most sequences were assigned in stable and exacerbation phases to the phyla Proteobacteria (46 vs 53%), Firmicutes (29 vs 53%), Bacteroidetes (10 vs 8%), Actinobacteria (9 vs 4%) and Fusobacteria (6 vs 4%). Pseudomonas RA during exacerbation increased form baseline in 1/7 exacerbations (14.3%) but decreased in 5/7 of them (71.4%). Microbial RA was increased for Stenotrophomonas in 1 episode, S.pneumoniae in 2, H.influenzae in 2, and Moraxella in 2, with 2 episodes with more increases in microbial RA >1 microorganism.  CONCLUSIONS  A high heterogeneity in the changes of bronchial microbioma was observed during an exacerbation in COPD patients colonized by P. aeuriginosa. An increase in the RA of Pseudomonas was only identified in less than one fifth of the episodes, suggesting than the role of P.aeuriginosa as etiologic agent of exacerbation in patients with chronic colonisation by this microorganisms should be reviewed.  Funded Fundacio Tauli, SOCAP, FUCAP I Menarini.
Strain and Sex Differences in N-Nitrosohexamethyleneimine Carcinogenesis in NZB, NZC, NZO, and NZY Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C M Goodall, W Lijinsky
Journal: JNCI Journal of the National Cancer Institute (1984)

The carcinogenic activity of N-nitrosohexamethyleneimine [(NHEX) CAS: 932-83-2; hexahydro-1-nitroso-1H-azepine] was studied in male and female mice of the four inbred strains NZB/BlGd, NZC/BlGd, NZO/BlGd, and NZY/BlGd. A total of 158 mice received NHEX treatment; 1,338 untreated controls were used, all kept under identical laboratory conditions for their natural life-spans. Beginning at age 50 days a 1.56-mM NHEX solution (200 mg/liter) was given instead of drinking water for 8 weeks, which resulted in nearly the same total dosage of 0.7 +/- 0.04 g or 5.7 +/- 0.2 mmol NHEX/kg body weight in both sexes of all four strains. In both sexes of all four strains the main types of tumors after NHEX treatment were squamous papillomas and carcinomas of the esophagus, squamous stomach, and oropharynx and hepatocellular carcinomas. Tumors of the hepatic bile ducts, glandular stomach, and lung and malignant lymphomas were also induced by NHEX, but these tumors had a predilection for certain strains only. The incidences of other tumors characteristic of the untreated mice in each particular strain, such as tumors of the ovary in NZC, tumors of the breast in NZY, and tumors of the duodenum in NZO, were not increased significantly by NHEX treatment. The incidence of main tumor types in NHEX-treated mice varied greatly between strains, e.g., esophageal papillomas and carcinomas in 81% of male NZC versus 32% in male NZB mice. Some marked sex differences also emerged in NHEX-treated animals, e.g., the occurrence of liver angiosarcomas only in males of three strains and the 53% incidence of hepatocellular tumors in male NZY mice compared to the absence of liver tumors in female NZY mice.
Diagnosis of Free-Wall Rupture by Left Ventricular Angiogram After Inferior ST-Segment–Elevation Myocardial Infarction
Authors: Yogesh N.V. Reddy, Mohammed Al-Hijji, Patricia J. Best, Lawrence J. Sinak, Rakesh M. Suri, Nkechinyere N. Ijioma, Sara J. Aberle, Deepi G. Goyal, Mandeep Singh
Journal: Circulation (2015)
Abstract 2105: Early Dilation/stenting of Pulmonary Vein Occlusion Following Catheter Ablation for Atrial Fibrillation Restores Pulmonary Flow and Prevents Associated Lung Diseases
Authors: Tamer S Fahmy, Luigi Di Biase, Oussama M Wazni, Jennifer E Cummings, Mohamed Kanj, Dhanujaya Lakkireddy, Chi Keong Ching, Rong Bai, Sergio Thal, Claude S Elayi, Mohamed Khan, Dimpi Patel, Subramanya K Prasad, Lucie Popova, David Martin, David J Burkhardt, Michelle Andrews-Williams, Robert A Schweikert, Walid Saliba, Patrick Tchou, Mauricio Arruda, Andrea Natale
Journal: Circulation (2006)

Introduction: Pulmonary vein occlusion (PVO) is a rare complication that can develop following radiofrequency catheter ablation (RFA) of atrial fibrillation (AF). As a consequence, arterial flow to...
Abstract 4039: Exploration of a potent E-Selectin antagonist (GMI-1271) as a potential novel therapeutic for treating breast cancer metastasis to the bone and lung
Authors: Mark Esposito, John L. Magnani, Yibin Kang
Journal: Cancer Research (2014)

Abstract The propensity of breast cancer to metastasize to the lung and bone with high frequency presents an attractive opportunity for specific therapeutic intervention. Targeting the initial steps of metastasis, such as survival in circulation, arrest, and extravasation, may constitute a more effective approach than treatment during the later steps. E-Selectin has been implicated as a pro-metastatic endothelial receptor which mediates the initial stages of tumor cell arrest and extravasation to the lung, liver and bone. We examined the ability of the potent E-selectin antagonist GMI-1271 (Kd = 0.54 μM) to inhibit E-selectin binding to lung and bone metastatic cells. Flow cytometry and ELISA analysis was used to evaluate the effects of GMI-1271 in vitro while treatment of bone and lung metastasis with GMI-1271 during the initial stages of metastatic seeding was used in xenograft models. Results demonstrated that metastatic breast cancer cells express carbohydrates ligands recognized by E-selectin as determined by interaction with E-selectin-Fc chimeric protein and the antibody HECA-452. GMI-1271 could significantly reduce metastatic breast cancer cell binding to E-selectin in vitro. Treatment of mice following intracardiac injection resulted in a significant reduction of mortality (HR = 0.29, p = 0.044) while treatment following tail vein injection demonstrated a directional increase in survival (p = 0.061 and p = 0.055). These results designate GMI-1271 as a potential therapeutic for treatment of late stage breast cancer. Citation Format: Mark Esposito, John L. Magnani, Yibin Kang. Exploration of a potent E-Selectin antagonist (GMI-1271) as a potential novel therapeutic for treating breast cancer metastasis to the bone and lung. [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 4039. doi:10.1158/1538-7445.AM2014-4039
Measurement of absolute myocardial blood flow with H215O and dynamic positron-emission tomography. Strategy for quantification in relation to the partial-volume effect.
Authors: H Iida, I Kanno, A Takahashi, S Miura, M Murakami, K Takahashi, Y Ono, F Shishido, A Inugami, N Tomura
Journal: Circulation (1988)

An in vivo technique was developed for measuring the absolute myocardial blood flow with H215O and dynamic positron-emission tomography. This technique was based on a new model involving the concept of the tissue fraction, which was defined as the fraction of the tissue mass in the volume of the region of interest. The myocardium was imaged dynamically by positron-emission tomography, starting at the time of intravenous bolus injection of H215O. The arterial input function was measured continuously with a beta-ray detector. A separate image after C15O inhalation was also obtained for correction of the H215O radioactivity in the blood. The absolute myocardial blood flow and the tissue fraction were calculated for 15 subjects with a kinetic technique under region-of-interest analysis. These results seem consistent with their coronary angiographic findings. The mean value of the measured absolute myocardial blood flows in normal subjects was 0.95 +/- 0.09 ml/min/g. This technique detected a diffuse decrease of myocardial blood flow in patients with triple-vessel disease.
Abstract 16125: Pla2g7 is Crucial in Stem Cell Differentiation into Smooth Muscle Cells and Involves in Atherosclerosis
Authors: Qingzhong Xiao, Anna E Pepe, Qingbo Xu
Journal: Circulation (2010)

Background:  Accumulating evidence suggests that phospholipase A 2  group 7 (Pla2g7) is involved in cardiovascular development and vascular diseases because of its divergent functions in inflammation and oxidative stress/reactive oxygen species (ROS) balance. Our previous studies have demonstrated that embryonic stem (ES) cells can differentiate into smooth muscle cells (SMC) resulting from the maintenance of the ROS balance. In the present study, we aim to investigate the functional role of Pla2g7 in SMC differentiation.   Methods and Results:  When ES cells were cultivated on collagen IV-coated plates, Pla2g7 was up-regulated significantly in parallel with SMC marker genes (SM22, SM alpha-actin, calponin and SM myosin heavy chain) following 4–14 days of cell differentiation, and co-localized with SMC markers in the differentiated ES cells. Knockdown of Pla2g7 resulted in down-regulation of smooth muscle specific markers, while enforced expression of Pla2g7 enhanced SMC differentiation and increased ROS generation in a dose-dependent manner. Interestingly, free radical scavenger NMPG and flavoprotein inhibitor DPI, but not hydrogen peroxide inhibitor catalase, retard Pla2g7-induced SMC differentiation gene expression. Moreover, we demonstrated that overexpression of nuclear factor erythroid 2-related factor 3 (Nrf3) resulted in increase of Pla2g7 production, while knockdown Nrf3 ablated the Pla2g7 gene expression and enzyme activity. Most importantly, we further demonstrated that NAPDH oxidase 4 (Nox4), another important mediator for SMC differentiation and ROS generation, is required for Nrf3-indueced Pla2g7 gene expression. Finally, Pla2g7 is up-regulated in mature SMC phenotype switching in the culture, highly expressed in atherosclerotic lesions of apoE−/− mice and decreased significantly in the vessels after injury.   Conclusions:  Our findings demonstrated for the first time that Pla2g7 has a crucial role in SMC differentiation from stem cells, and the fine interactions between Nrf3, Nox4 and Pla2g7 is essential for ROS balance and SMC differentiation in vitro and in vivo, implicating that Pla2g7 could be potential new targets for switching SMC differentiation in vascular disease.
Tumor Growth and Neovascularization: An Experimental Model Using the Rabbit Cornea 2
Authors: Michael A. Gimbrone, Ramzi S. Cotran, Stephen B. Leapman, Judah Folkman
Journal: JNCI Journal of the National Cancer Institute (1974)

By intracorneal implantation of tumors in the eyes of rabbits, the early neovascular response to solid tumor growth could be directly observed. Fragments of homologous tumors—Brown-Pearce epithelioma and V2 carcinoma—were implanted into the avascular corneal stroma of rabbits at various distances from the limbus. Tumor growth and neovascular response of llmbal vessels were studied by: 1) Slit Lamp Stereomicroscopy, 2) histologic examination, 3) filling of vasculature with colloidal carbon, and 4) autoradiography after exposure to 3Hthymidine. Centrally placed tumors spread as thin plates until they reached within 2.5 ± 0.5 mm of the limbus, when new vessels began to grow from the limbal plexus toward the tumor edge. When tumors became vascularized, they grew rapidly into exophytic masses. Peripherally placed tumors evoked early neovascularization. The prevascular growth of incompatible rabbit homograft and mouse xenograft tumors suggested that the cornea, before its vascularization, was an immunologically privileged site for tumor growth. Intracorneal polyacrylamide gel implants containing tumor extracts elicited a specific pattern of corneal vascularization not observed with nonmalignant cell extracts. These experiments provide a new model for study of tumor growth and neovascularization in a site where there is anatomic separation of tumor cell stimulus from host vascular response; the technique of corneal gel implantation may be useful in the characterization of mediators of neovascularization.