tbuckley/cabot-search huggingface dataset:
Isolation and Characterization of Attached and Nonattached Populations of Rat Colon Epithelial Cells in Culture
Authors: Amitabha Mazumder, Rabindra N. Patnaik, Belur S. Bhagavan, Padmanabhan P. Nair
 5
Journal: JNCI Journal of the National Cancer Institute (1979)

Colon epithelial cells of Sprague-Dawley rats were isolated by the incubation of everted colon sacs aerobically in Puck's Saline F containing 0.5% hyaluronidase and a mixture of antibiotics (penicillin, streptomycin, and Fungizone). The complete removal of both mature absorptive and deep cryptal proliferating cells required about 2 hours of incubation. The yield of cells averaged about 153×106/rat, with a standard deviation of 12.9×106. Approximately 98% of these cells excluded trypan blue and were capable of sustained oxidation of [14C]glucose. When these cells were placed in short-term culture for about 16 hours in Eagle's minimum essential medium containing 15% calf serum and antibiotics (penicillin, streptomycin, and Fungizone), about 15±2% attached to the surface of the culture plate. Attached cells showed a 15-fold higher incorporation of [3H]thymidine into DNA than did nonattached cells. Thymidine kinase activity, generally associated with rapid growth and increased DNA synthesis, was mostly localized in the attached cells. Incorporation of [3H]uridine into RNA was distinctly higher in the attached cell population when compared to the nonattached population, although both populations of cells actively incorporated [14C]glycine into protein. Whereas total colon cells appeared heterogeneous in cytomorphology, the attached cells were more uniform and smaller and contained deeply hematoxylinophilic, round nuclei. With the use of short-term tissue culture techniques, we have separated a subpopulation of colon cells exhibiting characteristics compatible with the less differentiated immature cryptal cells.
Monitoring tumor response to ZD4190 therapy with an <sup>18</sup>F labeled angiogenesis imaging agent
Authors: M. S. Morrison, S. Ricketts, J. Barnett, M. Constantinou, J. Tessier, S. R. Wedge
Journal: Journal of Clinical Oncology (2007)

10507 Background: While a number of novel therapies are being developed to inhibit the growth or survival of tumor vasculature, there are limited methods available for measuring changes in tumor vascularity. In order to quantify tumour vascularity by PET imaging, we examined an 18 F-radiolabeled small peptide (AH111585) containing an RGD (Arg-Gly-Asp) sequence. This peptide binds with high affinity (nM) to avβ3 integrin, a cell adhesion receptor that is highly expressed on tumor neovasculature, but expressed at low levels on mature endothelium and epithelial cells. 18 F-AH111585 was used to examine the response of human lung tumor xenografts to treatment with ZD4190, a small molecule inhibitor of VEGF signaling. Methods: MicroPET (using 18 F-AH111585) and microCT imaging data was acquired pre and post 3 doses of ZD4190 (100 mg/kg, p.o., over 3 days) or vehicle in CD-1 nude mice bearing Calu-6 tumor xenografts. 18 F-AH111585 was administered 2 h prior to microPET imaging (10 min) to allow for tumor uptake and background tissue clearance. Tumor and background tissue uptake was determined from the images (expressed as %id/g). Results: Uptake of 18 F-AH111585 in Calu-6 tumors was reduced following 3 doses of ZD4190, with an average reduction of 31.8 ± 4.6 % (calculated from imaging ROI data), whereas increased 18 F-AH111585 uptake was observed in tumors of vehicle treated mice (average increase of 26.9 ± 9.4 %). The difference between treated and control group uptake was statistically significant (P&lt;0.01; two- tailed t-test). Tumor size (assessed via caliper measurement) remained comparable over the duration of treatment. Skeletal muscle, used as a reference tissue for ROI analysis, demonstrated equivalent uptake pre and post therapy. Conclusions: The data demonstrate that 18 F-AH111585 can detect changes in tumor uptake following acute treatment with a VEGF signaling inhibitor (ZD4190). The results suggest that this imaging agent may be useful for monitoring changes in tumor vascularity. No significant financial relationships to disclose.
Bronchiectasis but not emphysema is more prevalent in non-PiZ alpha-1 antitrypsin deficiency (AATD) COPD than in usual COPD
Authors: Ronald Dandurand, Tomás Carroll, Raúl San José Estépar, Jean Bourbeau, David Eidelman
Journal: European Respiratory Journal (2014)

Bronchiectasis (BE) is associated with PiZ phenotypes of AATD. An association with non-PiZ phenotypes (SS, MS, MZ) is less certain. We wished to conduct a case-control study of BE prevalence among SS, MS and MZ genotypes vs. usual COPD. 16 subjects with non-PiZ phenotypes (NZ) (3 SS, 8 MS, 5 MZ) from community COPD screening for AATD had undergone chest CT scans. They were compared with 16 age, sex and FEV 1  matched COPD patients with AAT levelsl1.15g/L but MM genotype (MM) and 16 similarly matched COPD patients with serum AAT levels≥1.15g/L and not genotyped (NG). Spirometry, lung volumes and diffusing capacity (D Lco ) were measured within 5.9±5.2SD months of imaging. CT scans were read for BE using a visual grading system. Lung emphysema on CT scan was determined using  Airway Inspector  (www.airwayinspector.org) to measure lung %areal-950HU (LAA%). Group differences between continuous variables were determined with ANOVA and proportions with z-statistic. Gender was M30:F18, age 70±18 years (mean±SD), smoking history 47±26 pack-years, FEV 1  68±23 %predicted and FEV 1 /FVC 55±13 % in the 48 subjects. Serum AAT levels were NZ 0.89±0.01SE g/L, MM 0.90±0.05 and NG 1.59±0.07. BE on CT scan occurred in 13/16 NZ (3/3 SS, 6/8 MS, 4/5 MZ), 4/16 MM (p=0.00071) and 5/16 NG (p=0.00219). Groups were similar for spirometry, lung volumes and D Lco . LAA% did not differ between groups (NZ 12.3±3.7SE, MM 12.0±2.7, NG 11.0±3.2, p=0.97). In this small group of COPD patients, BE was present more often in non-PiZ phenotype AATD subjects than MM genotype subjects, or COPD subjects with normal serum AAT levels. This may be a novel observation requiring confirmation in larger populations.
Taking aspirin before coronary artery surgery does not increase deaths or bleeding, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

Taking aspirin before coronary artery surgery is not associated with an increased risk of death, bleeding, or thrombotic complications, a randomised trial1 has shown. The trial showed that there was no need for patients taking aspirin to stop before cardiac surgery.

Most patients with coronary artery disease take aspirin to reduce their risk of myocardial infarction, stroke, and death. Aspirin inhibits platelet …
Abstract 18494: Effect of Circumferential Pulmonary Vein Isolation on the Dominant Frequency in the Contralateral Pulmonary Vein during Atrial Fibrillation
Authors: Daisuke Horiuchi
Journal: Circulation (2014)

Introduction: The interaction of the electrical activities among the pulmonary veins (PVs) during atrial fibrillation (AF) is unclear. To define this, we examined how circumferential isolation (CPVI) of one-side PV influences to DF in the contralateral PV. Methods: The consecutive 46 patients (33 men; mean age, 60±12 years; 36 with paroxysmal AF) with induced or spontaneous sustained AF undergoing CPVI were studied. These patients were divided into two groups depending on which side PVs were isolated at the beginning of the procedure. In group A (n=34), CPVI was performed in the right side PVs at the beginning. In group B (n=12), CPVI was performed in the left side PVs at the beginning. CPVI in the right (or left) side PVs was performed while continuously recording 10 bipolar electrograms in the left (or right) superior PV using a circular catheter and 5 bipolar electrograms in the CS. Before and after right (or left) side CPVI, DF for a 30-second period was determined in each electrogram, and mean DFs in...
Effects of Chinese herbal medicine on cytochrome P450, a systematic review.
Authors: S. Bhowmik, W. Lu, D. S. Rosenthal
Journal: Journal of Clinical Oncology (2010)

e13150 Background: Interactions of cytochrome P450 (CYP), especially CYP3A4, between chemotherapy agents and other xenobiotics can cause potential adverse effects during cancer treatment. Furthermore, Chinese herbal medicine (CHM) has been increasingly used by cancer patients during chemotherapy. The purpose of this study is to systematically examine available literature on the effects of CHM on CYP3A4. Methods: Relevant research articles published prior to May 31, 2009 in PubMed and The Natural Medicines Comprehensive Database were searched using the MeSH terms “Cytochrome P-450 CYP3A”, “Drugs, Chinese Herbal”, and “Medicine, East Asian Traditional”, and CHM names obtained from “Chinese Herbal Medicine: Materia Medica”, a widely used CHM textbook. Articles in non-English languages and herbs infrequently used in practice were excluded upon review. Full texts were obtained for further analysis and effects on CYP450 of each studied herb were evaluated. Results: Of the 483 herbs/herbal mixtures searched, 47 (10%) have been studied for their interactions with CYP450 in 42 research articles, consisting of 30 in vitro and 25 in vivo tests in all. Among these herbs, 38 (81%), 10 (21%), and 15 (32%) exhibited inhibition, induction, and no effect on CYP450, respectively. Ten herbs (Ginkgo biloba, Pueraria lobata, Saposhnikovia divaricata, Citrus aurantium fruit, Curcuma longa, Panax ginseng, Glycyrrhiza uralensis, Glycyrrhiza glabra, Evodia rutaecarpa, Schisandra chinensis) and 2 mixtures (PC-SPES and Shoseiryuto) showed conflicting results with CYP450. Among the 26 herbs and mixtures studied with CYP34A, 15 (58%), 5 (19%), and 8 (31%) exhibited inhibition, induction, and no effect, respectively. Three herbs (Ginkgo biloba, Evodia rutaecarpa, Schisandra chinensis) showed conflicting results with CYP3A4. Conclusions: Chinese herbs and their mixtures may alter functions of CYP450, and the majority of studied herbs show a potential inhibitory effect on CYP3A4. Future studies are needed to further understand the impact of using CHM on the safety of patients undergoing chemotherapy. No significant financial relationships to disclose.
Adherence to standard therapy for the treatment of childhood CNS tumors in Argentina. An audit perspective
Authors: E. G. Rivarola, G. L. Chantada, L. Ezcurdia, A. Negro, E. Gil Deza, D. Cascallar, D. Santillán, S. Carnaval, E. Morgenfeld, F. G. Gercovich
Journal: Journal of Clinical Oncology (2004)

8573 Background: There are no national protocols for the treatment of children with CNS tumors in Argentina, so patients receive individualized treatment at each center. The aim of this study was to evaluate, from an audit perspective, the treatment prescribed to children with CNS tumors belonging to a large health insurance organization in Argentina. Methods: The files of all patients with CNS tumors for whom their oncologists requested chemotherapy from 2000 to 2003 were retrieved. All patients were treated at prestigious institutions. The PDQ Cancer Information Treatment Summaries posted at the National Cancer Institute of USA web site was used to define standard therapy. Results: Requests of chemotherapy for 24 children treated at 8 different referral centers were received. There were 10 cases of medulloblastoma, 7 gliomas, 5 ependymomas, 1 malignant rhabdoid-teratoid tumor and 1 anaplastic tumor not otherwise specified. This case was excluded because no standard therapy is available. Overall, 9/10 children younger than 3 years of age received standard Baby's combination. Seventeen out of 23 patients received standard combinations as first line treatment while in 6/23 patients experimental treatment was prescribed. These included 1 children with brainstem glioma, 3 children with ependymoma and 1 one year old child with glioma that received an experimental combination. Even though the role of temozolomide is not clear in children, this drug was requested for 3 patients with glioma (1 baby) as first line and 2 for second line therapy (ependymoma and glioma). Topotecan was requested for 2 patients with ependymoma. All patients with medulloblastoma received standard therapy. Conclusions: Despite all patients were treated at prestigious centers, 46% of children with CNS tumors other than medulloblastoma received unproven first line therapy. “Off guidelines” treatments with unproven agents outside a clinical trial such as temozolomide and topotecan were requested for 30% of the cases. According to ethical principles, it is our feeling that all children with malignancies outside a controlled clinical trial should receive standard therapies. No significant financial relationships to disclose.
Abstract P036: Parathyroid Hormone is Associated with All-Cause and Cardiovascular Mortality: The Hoorn Study
Authors: Adriana J van Ballegooijen, Ilse Reinders, Marjolein Visser, Jacqueline M Dekker, Giel Nijpels, Coen D Stehouwer, Stefan Pilz, Ingeborg A Brouwer
Journal: Circulation (2013)

Introduction Higher parathyroid hormone (PTH) concentrations have been associated with increased cardiovascular disease (CVD) mortality, although data in the general population are scarce. Hypothesis We hypothesize that higher serum PTH concentrations are associated with all-cause and CVD mortality in a prospective, population-based cohort of older men and women. Methods We included 633 participants of the Hoorn Study, a population-based cohort with oversampling of subjects with impaired glucose regulation; mean age 70.1±6.6 years, 50.7% female. Serum intact PTH concentrations were measured using a 2-site immunoassay. Outcomes were all-cause and CVD mortality based on clinical files and coded according to the ICD-9. We used Cox-regression to estimate survival curves and hazard ratios (HR 95% CI) for all-cause and CVD mortality adjusted for potential confounders using season-specific PTH quartiles. Results During a median follow-up of 7.8 years, 112 participants died, of which 26 deaths (23%) were due to CVD. Survival curves showed an impaired survival for all-cause (Log-rank p=0.054) and CVD mortality (Log-rank p=0.022) for people in the highest PTH quartile (Figure 1). In a multivariate model adjusted for age, sex, smoking, education level, BMI, glucose status, systolic blood pressure, anti-hypertensive drug use, the highest PTH quartile was associated with higher all-cause mortality; HR 1.98 (1.08, 3.64). Kidney function (estimated glomerular filtration rate and micro-albuminuria) attenuated the PTH risk association, but risk persisted; HR 1.93 (95% CI 1.04, 3.58). The results for CVD mortality showed a similar pattern, although the association was only significant in a threshold model (Quartile 4 vs. Quartile 1-3) HR 2.56 (1.11, 5.94). Conclusion In conclusion, among older men and women, higher PTH concentrations are associated with higher mortality risk. We suggest to evaluate whether individuals with high PTH concentrations benefit from therapeutic approaches targeted to decrease PTH concentrations.
Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3
Authors: Howard I. Scher, Michael J. Morris, Walter M. Stadler, Celestia Higano, Ethan Basch, Karim Fizazi, Emmanuel S. Antonarakis, Tomasz M. Beer, Michael A. Carducci, Kim N. Chi, Paul G. Corn, Johann S. de Bono, Robert Dreicer, Daniel J. George, Elisabeth I. Heath, Maha Hussain, Wm. Kevin Kelly, Glenn Liu, Christopher Logothetis, David Nanus, Mark N. Stein, Dana E. Rathkopf, Susan F. Slovin, Charles J. Ryan, Oliver Sartor, Eric J. Small, Matthew Raymond Smith, Cora N. Sternberg, Mary-Ellen Taplin, George Wilding, Peter S. Nelson, Lawrence H. Schwartz, Susan Halabi, Philip W. Kantoff, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2016)

Evolving treatments, disease phenotypes, and biology, together with a changing drug development environment, have created the need to revise castration-resistant prostate cancer (CRPC) clinical trial recommendations to succeed those from prior Prostate Cancer Clinical Trials Working Groups.An international expert committee of prostate cancer clinical investigators (the Prostate Cancer Clinical Trials Working Group 3 [PCWG3]) was reconvened and expanded and met in 2012-2015 to formulate updated criteria on the basis of emerging trial data and validation studies of the Prostate Cancer Clinical Trials Working Group 2 recommendations.PCWG3 recommends that baseline patient assessment include tumor histology, detailed records of prior systemic treatments and responses, and a detailed reporting of disease subtypes based on an anatomic pattern of metastatic spread. New recommendations for trial outcome measures include the time to event end point of symptomatic skeletal events, as well as time to first metastasis and time to progression for trials in the nonmetastatic CRPC state. PCWG3 introduces the concept of no longer clinically benefiting to underscore the distinction between first evidence of progression and the clinical need to terminate or change treatment, and the importance of documenting progression in existing lesions as distinct from the development of new lesions. Serial biologic profiling using tumor samples from biopsies, blood-based diagnostics, and/or imaging is also recommended to gain insight into mechanisms of resistance and to identify predictive biomarkers of sensitivity for use in prospective trials.PCWG3 moves drug development closer to unmet needs in clinical practice by focusing on disease manifestations most likely to affect prognosis adversely for therapeutics tested in both nonmetastatic and metastatic CRPC populations. Consultation with regulatory authorities is recommended if a trial is intended to seek support for drug approval.
Fitness effects of amino acid replacements in the beta-galactosidase of Escherichia coli.
Authors: A M Dean, D E Dykhuizen, D L Hartl
Journal: Molecular Biology and Evolution (1988)

Two genetic procedures were used to obtain amino acid replacements in the lacZ-encoded beta-galactosidase in Escherichia coli. Amino acid replacements could be obtained without regard to their effects on lactase activity by selecting spontaneous mutations that relieved the strong polarity of six nonsense mutations. When streaked on MacConkey-lactose indicator plates, approximately 75% of these mutants gave strong red lactose-fermenting colonies, and 25% gave white nonfermenting colonies. Mutants from 11 other nonsense codons were isolated directly using MacConkey-lactose indicator plates, on which positive color indication requires only 0.5% of the wildtype lactase activity. Among the total of 17 codons, 25 variant beta-galactosidases were identified using electrophoresis and thermal denaturation studies. The fitness effects of these variant beta-galactosidases were determined using competition experiments conducted with lactose as the sole nutrient limiting the growth rate in chemostat cultures. Three of the replacements were deleterious, one was selectively advantageous, and the selective effects of the remaining 21 were undetectable under conditions in which the smallest detectable selection coefficient was approximately 0.4%/generation.
Increase in Tumor Vascular Area Due to Increased Blood Flow by Angiotensin II in Rats
Authors: K Hori, M Suzuki, I Abe, S Saito, H Sato
Journal: JNCI Journal of the National Cancer Institute (1985)

For further elucidation of the microhemodynamics in tumor tissue, the “vascular level,” percentage of the vascular area to tissue area, was measured in DONRYU rats. Changes in the vascular level due to angiotensin II were analyzed by a point-counting method in normal and tumor tissues within a rat transparent chamber. The vascular level in normal subcutis changed from 21.8 to 18.6% when the mean arterial pressure was elevated from 102.3 to 155.9 mmHg. The coefficient of change due to angiotensin II was 0.85. The vascular level in tumor tissue was distributed inhomogeneously from 0 to 48.5% with an average of 19.7%. It increased to 33.9% (range: 8.7–57.6%) with an elevation of the mean arterial blood pressure from 103.5 to 150.8 mmHg. The coefficient of change due to angiotensin II was 2.08 in tumor tissue. Moreover, the tumor vascular level increased at a higher rate in the areas with a lower vascular level.
P03 The use of BRUM1 resequencing microarray to identify mutations in patients with neonatal cholestasis
Authors: J Hartley, C Bruce, R Brown, K McKay, U Bauman, E Sturm, B Udd, P Mckiernan, D McMullen, J Mansson, F McDonald, E Maher, A Knisely, C Hendriksz, D Kelly, P Gissen
Journal: Gut (2010)

Introduction  Neonatal cholestasis is the presenting clinical feature of serious and potentially life limiting liver diseases such as progressive familial intrahepatic cholestasis (PFIC), arthrogryposis-renal-cholestasis (ARC) syndrome and Niemann Pick C (NPC) disease. A single rapid molecular test to confirm the diagnosis would reduce the delay from molecular genetic investigation at multiple diagnostic centres thus facilitating optimal clinical management and counselling. We have designed a resequencing microarray (BRUM1) capable of simultaneously sequencing multiple genes associated with neonatal cholestasis.  Aim  To assess the utility of BRUM1 as a first-line molecular investigation for patients with neonatal cholestasis in whom an inherited causes is suspected.  Method  DNA from 95 infants with neonatal cholestasis in whom an inherited cause was suspected was amplified by PCR and hybridised to BRUM1 (validated against reference sequencing with 98.9% agreement (CI 0.97 to >0.99)) for simultaneous sequencing of the main causes of inherited disease in this group which included ATP8B1, ABCB11, ABCB4, VPS33B, VIPAR, NPC1 and NPC2. Children with known α-1 antitrypsin deficiency or Alagille syndrome were not included.  Results  30 infants had pathogenic mutations, which cause neonatal cholestasis. 23 of the mutations were novel.  In this cohort of patients, 30.5% of infants with neonatal cholestasis had a genetic diagnosis confirmed by BRUM1. The average time to diagnosis was 5–25 days.  Conclusion  A specific and rapid genetic diagnosis in infants with a phenotype of neonatal cholestasis can be made using a single resequencing microarray, to optimise clinical management and facilitate appropriate counselling of families.
Immunodiagnosis of Colorectal Cancer: Clinical Evaluation of Tennessee Antigen (Tenagen)<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: O F Dent, P H Chapuis, J E Payne, J Meyer, A M Sutherland, K J Goulston
Journal: JNCI Journal of the National Cancer Institute (1983)

Blood samples from 172 consecutive patients undergoing complete colon investigations to exclude colorectal cancer (CC) were examined for levels of Tennessee antigen, i.e., Tenagen (Tg), and carolnoembryonic antigen. Patients included 48 with CC, 34 with adenomataus polyps, 14 with colitis, and 76 with no organic mucosal disease. All patients were investigated by the one clinical and histopathology department. Laboratory estimations were performed blindly. Although there were some statistically significant differences among average values, the degree of overlap among the groups of patients precludes the practical application of Tg in the diagnosis of CC.