tbuckley/cabot-search huggingface dataset:
Transcriptional regulation by p53 during apoptosis.
Authors: Beverly M. Emerson, Joaquin M. Espinosa
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

SY08-02 

The tumor suppressor protein p53 regulates transcriptional programs that control the cellular response to stress resulting in cell cycle arrest, senescence or apoptosis. This is largely achieved through selective activation of subsets of p53 target genes that in combination direct specific cell fate decisions. In an effort to understand these processes, we have identified distinct stress- and promoter-specific mechanisms utilized by p53 to activate expression of its numerous responsive genes. We find that p53 functions in a temporal manner to regulate promoter activity both before and after stress. Before stress, p53 is required to establish a gradient of bound RNA polymerase II (RNAP II) among its target promoters. For example, high levels of a poised RNAP II complex already exists on the pro-cell cycle arrest p21 promoter before stress which is rapidly converted to an elongating form after DNA damage. By contrast, pro-apoptotic promoters such as Fas/APO1, PUMA, and PTEN contain very low levels of RNAP II but undergo stress-induction through efficient re-initiation. Surprisingly, we find that initiation factors TFIIB and TAFII250 assemble onto the p21 and Fas/APO1 promoters in a stress-specific manner that is dependent upon p53. Such differences in the composition and binding affinity of the basal transcription machinery may regulate the relative kinetics of expression of specific genes within the p53 program and ultimately determine cell fate. Human colon cancer cells undergo cell cycle arrest or apoptosis in response to different forms of stress. These distinct outcomes are correlated with very different kinetics of expression of p21 and PUMA. This may be modulated by the stress-specific recruitment of TAFII250 and rapid loss of TFIIB from the p21 promoter for high level, transient expression after UV radiation or retention of TFIIB for sustained transcription after doxorubicin-induced damage. We are currently exploring the mechanisms by which p53 controls the behavior and composition of basal transcription initiation and elongation complexes in response to specific stressors. Interestingly, our recent studies demonstrate that certain p53-regulated genes, such as p21 and PUMA, continue to be expressed in cells treated with compounds that shut down global RNA synthesis through inhibition of RNAP II phosphorylation. This reveals the existence of bypass mechanisms that preserve the p53 transcriptional response even under conditions in which most other promoters are susceptible to inactivation. We are examining the basis for these mechanisms and the possible involvement of novel activities that regulate RNAP II function on select p53 target promoters.
Anti-inflammatory Therapy after Selective Laser Trabeculoplasty
Authors: Delan Jinapriya, Mark D’Souza, Hussein Hollands, Sherif R. El-Defrawy, Isabella Irrcher, Donald Smallman, James P. Farmer, John Cheung, Todd Urton, Andrew Day, Xiaoquin Sun, Robert J. Campbell
Journal: Ophthalmology (2014)
Physics, Instrumentation, and Radiation Protection
Authors: P. Zanzonico, S. Heller
Journal: Clinical Nuclear Medicine (2008)

The underlying principles of nuclear medicine imaging involve the use of unsealed sources of radioactivity which are administered in the form of radiopharmaceuticals; the ionizing radiations which accompany the decay of the administered radioactivity can be detected and measured with specially designed instruments (e.g., survey meters, gamma cameras). In order to appreciate the scientific and technical basis of nuclear medicine imaging, this chapter reviews atomic and nuclear structure, radioactivity and radioactive decay, and interactions of radiation with matter. This is followed by a discussion of techniques for detection and measurement of radiation, design and operating principles of detection and imaging instruments, instrument quality control, and radiation protection.
A. Bateman, et al, Cancer Res., 60: 2492–2497, 2000.
Authors: Andrew Bateman, Francis Bullough, Stephen Murphy, Lisa Emiliusen, Dimitri Lavillette, François Loic Cosset, Roberto Cattaneo, Stephen J Russell, Richard Geoffrey Vile
Journal: Cancer Research (2000)

It has come to our attention that the data shown in Figure 3 of our manuscript (A. Bateman et al ., Cancer Res. 60: 1492–1497, 2000) are derived from a slightly different experimental protocol than those described in the following text from page 1496 (lines 28–35):

Established Tumors Can Be
Abstract 15895: Durability of Linear Ablation Lesions and Their Relationship With Clinical Recurrence After Left Atrial Catheter Ablation in Patients With Persistent Atrial Fibrillation: Focused on Redo-Ablation Findings
Authors: Junbeom Park, Tae-Hoon Kim, Jin-Kyu Park, Jae-Sun Uhm, Jong-Youn Kim, Boyoung Joung, Moon-Hyoung Lee, Chun Hwang, Hui-Nam Pak
Journal: Circulation (2014)

Introduction: Linear ablation of left atrium (LA) mimicking catheter maze procedure has been known to be effective rhythm control strategy in persistent atrial fibrillation (AF). So we explored the bidirectional block (BDB) rate for LA ablations in de novo procedure and redo-procedure and compared their clinical outcomes. Methods: Among 1338 consecutive patients in Yonsei AF ablation Cohort, we included 236 patients with persistent AF (78.4% male, 58.7±10.7 years old) who underwent catheter ablation with consistent ablation protocol of circumferential pulmonary vein isolation (CPVI), cavotricuspid isthmus ablation (CTI), roof line (RL), posterior inferior line (PIL), and anterior line (AL). BDBs were checked in all LA ablation lesions in de novo and redo-ablations. Results: 1. In the de novo ablation procedure, BDB rates were 100% in CPVI, 100% in CTI, 92.3% in RL, 51.6% in PIL, and 76.4% in AL. In 72.4% of the patients, complete BDBs were achieved in all LA ablation lesions. 2. During 12.3±8.4 months fol...
Abstract 18950: PCSK9 and LDL-C Lowering Effect of SCAP Targeting siRNA in Mouse and Non-Human Primate Models
Authors: Kristian K Jensen, Marija Tadin-Strapps, Sheng-Ping Wang, Kithsiri Herath, James Hubert, Yanqing Kan, Ray Rosa, Daphne Szeto, Stephanie Williams, Dan Xie, Haihong Zhou, Gail Forrest, Stephen F Previs, David G McLaren, Laura Sepp-Lorenzino, Shirly Pinto
Journal: Circulation (2014)

SREBP cleavage-activating protein (SCAP) is a key protein in the regulation of lipid metabolism and a potential target for treatment of dyslipidemia. SCAP is required for activation of the transcription factors SREBP-1 and -2. SREBPs regulate the expression of genes involved in fatty acid and cholesterol biosynthesis as well as LDL-C clearance through regulation of LDL receptor and PCSK9 expression. Studies in rodent have demonstrated that genetic disruption of SCAP in the liver is associated with reduced plasma and liver cholesterol and triglyceride levels.   To further test the potential of SCAP as a novel target for treatment of dyslipidemia, rhesus monkeys were treated with a siRNA-LNP reagent targeting SCAP. A single dose of SCAP siRNA-LNP reagent resulted in up to 95% reduction in SCAP mRNA levels and suppression of SCAP mRNA was maintained at >75% up to day 28 after dosing. Inhibition of SCAP function was demonstrated by reduced expression of SREBP regulated genes and cholesterol and palmitate synthesis in the SCAP siRNA treated rhesus monkeys. A reduction in plasma PCSK9 was observed, which reached a maximum of 66% on day 16 after siRNA injection (167±65 ng/ml in the control siRNA group vs. 57±27 ng/ml in the SCAP siRNA treated group, N=9, p  In conclusion, inhibition of SCAP using a siRNA-LNP reagent caused a significant reduction in circulating PCSK9 and LDL-C in rodent and primate models. The data supports SCAP as a novel target for the treatment of dyslipidemia.
Abstract 15785: The Natural History of Doppler-Derived Left Ventricular Outflow Tract Gradients in Patients With Congenital Valvar Aortic Stenosis Before and After Balloon Valvuloplasty
Authors: Joseph D Kuebler, Jill Shivapour, Kimberlee Gauvreau, Steven D Colan, Doff B McElhinney, David W Brown
Journal: Circulation (2014)

Introduction: Congenital aortic stenosis (AS) has been reported to manifest a slow rate of progression in mild disease with a greater likelihood of progression in patients with moderate-severe disease. The natural history of the Doppler estimated peak gradient (DEPG) in patients after balloon aortic valvuloplasty (BAV) has not previously been studied on a large scale. Methods: A retrospective review was performed of 360 patients from 1984-2012 with AS providing a total of 2051 echocardiograms before and after BAV. Patients were excluded if they had an intervention within the first 30 days of life. The relationships between the AS DEPG and several predictors (age at time of initial echocardiogram, valve morphology, and history of intervention) were explored using linear mixed effect models. The DEPG slope was then calculated in patients who had at least 2 echocardiograms before and after balloon dilation using linear regression modeling. Results: The rate of increase in the DEPG for all patients with AS was 5.6 mmHg per 10 years of age (p&lt;0.001). The DEPG increased over time regardless of age at presentation with the greatest mean increase in patients presenting from 10-14.9 years (n=59; 11.9 mmHg per 10 years; p&lt;0.001). Patients who went on to have a BAV or surgical intervention on the aortic valve had a significantly higher rate of AS progression than the overall patient cohort (n=59; 18.0 mmHg/10 years and n=36; 13.1 mmHg/10 years). Patients with a unicommissural (n=39) aortic valve had a significantly higher rate of progression compared to those with a bicommissural (n=270) aortic valve (8.1 mmHg/10 years and 4.5 mm Hg/10 years; p&lt;0.001). The median rate of progression in the post-BAV group was significantly lower than the median pre-BAV rate of progression (n=34; pre-BAV 3.97 (1.69-8.7) mmHg/year; post-BAV 0.40 (-1.80-3.88) mmHg/year; p&lt;0.01). Conclusions: The DEPG of native valve congenital aortic stenosis shows a slow, linear rate of progression prior to intervention. The rate of progression is significantly higher in patients with a unicommissural aortic valve as well as those patients that go on to have a BAV and/or surgical intervention. The rate of the DEPG progression is significantly lower after BAV.
Psychiatric reform revisited
Authors: GEORGE CHRISTODOULOU
Journal: World Psychiatry (2009)

The trend towards the establishment of community psychiatric services seems to be universal. However, before closing down a mental hospital, it is necessary to establish the appropriate alternative facilities in the community. Every de-institutionalization program should have a diachronic component, and cultural issues should be taken into consideration. Care for each patient has to be decided upon on the basis of the characteristics of that patient. Finally, de-institutionalization is just one aspect of psychiatric reform. Primary psychiatric prevention is equally or even more important.
Paleopathology. An Introduction to the Study of Ancient Evidences of Disease.
Authors: Roy Lee Moodie
Journal: JAMA (1924)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 4105: Prevalence of breast stem cells in high-risk benign breast lesions and association with breastfeeding
Authors: Rachel L. Atkinson, Fraser Symmans, Therese B. Bevers, Wendy A. Woodward, Abenaa M. Brewster
Journal: Cancer Research (2014)

Abstract Background: Invasive breast cancers contain a subpopulation of cancer stem cells that are thought to maintain the heterogeneity and self-renewing potential of the tumor. In our previously published data, we demonstrated that stem cells in normal adjacent tissues were associated with triple negative breast cancer. The objective of this study is to determine the presence of stem cells in high risk breast lesions. We hypothesized that stem cells in high-risk lesions and normal adjacent breast tissue may represent a biomarker for increased breast cancer risk. Methods: We identified biopsies from 42 high-risk women seen in the Cancer Prevention Center at The University of Texas MD Anderson Cancer Center between 1988-2011. We collected information on breast cancer risk factors. The biopsies contained high-risk lesions including ductal carcinoma in situ (DCIS) n=21, lobular carcinoma in situ (LCIS) n=5, atypical ductal hyperplasia (ADH) n=7 and atypical lobular hyperplasia (ALH) n=6. The tissues were fluorescently labeled for stem cell markers CD44/CD49f/CD133, and were scored positive if more then 1% cells were positive for all markers using an automated fluorescent microscopy software. The presence of stem cell markers was compared in the normal adjacent tissues and high-risk lesions from a subset of 25 patients. Results: We identified stem cells in 46% of samples containing DCIS, 67% of LCIS, 63% of ALH, and 70% of ADH. There was a 79% concordance in stem cell positive status between the high-risk lesion and adjacent normal tissue. Women with positive stem cell high-risk lesions had no significant difference in age at first birth (24.4 years vs 26.6 years p=0.3), parity (1.7 vs 1.9, p=0.5), or body mass index (27.8 vs 31.8, p=0.07) compared to women without positive stem cell high-risk lesions. Women with positive stem cell high-risk lesions had shorter breastfeeding duration than women without (2.4 months vs 9.0 months p= 0.05). Conclusion: This is the first report, to our knowledge, that stem cells are present in some high-risk lesions and their associated normal breast tissue. Correlation with future development of invasive breast cancer could lay the foundation for future targeted breast cancer prevention strategies. Citation Format: Rachel L. Atkinson, Fraser Symmans, Therese B. Bevers, Wendy A. Woodward, Abenaa M. Brewster. Prevalence of breast stem cells in high-risk benign breast lesions and association with breastfeeding. [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 4105. doi:10.1158/1538-7445.AM2014-4105
Abstract 18491: Metformin Lowers Circulating Adiponectin Levels in Patients with Myocardial Infarction
Authors: Megan V Cannon, Chris P Lexis, A Rogier van der Velde, Iwan C van der Horst, Erik Lipsic, Martin M Dokter, Dirk J van Veldhuisen, Pim van der Harst, Rudolf A de Boer
Journal: Circulation (2014)

Introduction: Adiponectin is an adipokine and its levels are reduced in obesity, diabetes, and prevalent heart disease. However, the association of adiponectin and CV disease is complex, and studies have reported contradictory results with respect to the relation between adiponectin and CV disease. Furthermore, the oral antidiabetic agent, metformin, has multiple effects on metabolic parameters and is associated with better clinical outcomes compared to other antidiabetic agents. This study sought to determine the effects of metformin on adiponectin levels in patients with myocardial infarction (MI). Methods: The GIPS-III trial was a randomized, double-blind, placebo-controlled study conducted in 380 patients who underwent primary percutaneous coronary intervention (PCI) for a first time MI. The aim was to evaluate the efficacy of 4 months metformin treatment on preserving left ventricular function post-MI in non-diabetic patients. From 308 patients (mean age 58 ± 11 years, 78.9% male), both baseline and 4 month samples were available for plasma adiponectin measurement. Results: Placebo and metformin groups were well-matched, and metformin treatment had no effect on plasma glucose levels. Median baseline adiponectin level was 5057 ng/ml (IQR: 3325-7596) and median adiponectin level after 4 months was 4643 (IQR: 2768-6867). We observed a significant lowering of adiponectin levels following 4 months of metformin treatment compared to placebo (-629 versus -166, respectively; P=0.026). Baseline adiponectin levels were further assessed and divided into quartiles (Q1: 67 - 3297; Q2: 3352 - 5051; Q3: 5064 - 7549; Q4: 7643 -20118). Increasing adiponectin levels were associated with increased age (P=0.02), gender (higher in females, P&lt;0.001), lower BMI (P=0.01), elevated heart rate (P=0.03), as well as higher N-terminal pro-B-type natriuretic peptide levels both at baseline (P&lt;0.001) and at 4 months (P&lt;0.001). Conclusions: In this study, we show that treatment with metformin lowers circulating adiponectin levels. Metformin has been associated with improved CV outcomes, and the lowering of adiponectin may explain, at least in part, the cardioprotective effects of metformin.
Induction of epithelial to mesenchymal transition (EMT) by membrane type 1-Matrix metalloproteinase (MT1-MMP) is a prerequisite for cancer invasion
Authors: Jian Cao, Pallavi Kozarekar
Journal: Cancer Research (2006)

4356  experimental and clinical evidence has demonstrated that MT1-MMP may serve as a master regulator of cancer dissemination. The mechanism underlying this process remains to be defined. While, recent reports on the role of MT1-MMP in cell migration and invasion in three dimensional (3D) type I collagen gels have expanded our understanding of cancer cell invasion, some of the data appear contradictory. Epithelial-to-mesenchymal transition (EMT) has emerged as a critical step in the conversion of early stage tumors into invasive malignancies. Employing our previously established stable cell lines {human prostate cancer (LNCaP), breast cancer (MCF-7) and fibrosarcoma (HT1080) cells} expressing “pathophysiologic” level of MT1-MMP-GFP (MT1-GFP) chimera as well as GFP control cells cultivated in either 2D plastic dishes or 3D native type I collagen gels, we examined the role of MT1-MMP in promoting epithelial cancer cell EMT. expression of MT1-MMP in all three cell lines promotes cell proliferation in 3D cultures, but not in 2D cultures. Enzymatic activity of MT1-MMP is a prerequisite for enhanced cell proliferation suggesting that cellular degradation of surrounding collagen is a prerequisite for enhanced cell proliferation. GFP-expressing LNCaP and MCF-7 cells cultivated in 3D type I collagen gels gradually formed spherical aggregates, whereas cells expressing MT1-GFP display a scattered growth pattern. MT1-MMP-induced cell scattering was abrogated by targeted inhibition of either the catalytic domain (TIMP-2, but not TIMP-1) or the hemopexin domain (recombinant MT1-hemopexin protein), indicating a specific role for each domain of MT1-MMP in cancer cell scattering. Inhibition of MT1-MMP-induced phenotypic changes (fibroblast-like morphology and cell scattering), however, was reversed upon withdrawal of inhibitors. MT1-MMP transfected LNCaP and MCF-7 cells also degraded the cell-cell adherins junction molecule, E-cadherin. In contrast to epithelial cells (LNCaP, MCF-7), HT1080 cells which are mesenchymal in origin displayed a scattered growth pattern in 3D collagen gels. Transfection of HT1080 cells with MT1-MMP or treatment with high dose TIMP-2, did not alter the scattered growth pattern of HT1080 cells, thus consistent with previous observations that mesenchymal cell invasion is independent of MMP activity. Given these data, it appears that MT1-MMP is responsible for converting LNCaP and MCF-7 cells (epithelial origin) to a mesenchymal phenotype. We hypothesize that MT1-MMP degradation of E-cadherin and collagen leads to mesenchymal-associated morphologic changes in 3-D collagen gels and promotes cancer cell migration and proliferation, thus recapitulating EMT. The central role of MT1-MMP in epithelial cancer progression provides a stimulus for development of specific inhibitors as treatment of early stage cancer.
Germ Cell Tumors and Other Pineal Region Tumors
Authors: Geneviève Legault, Jeffrey C. Allen
Journal: Neuro-Oncology (2012)

The predominant pineal region neoplasm in patients <25 years is a germ cell tumor (GCT) while pineal parenchymal (PPT) and glial tumors are more common in adulthood. Treatment planning requires histologic confirmation. Tumor marker profiles (β-hCG, AFP) in serum and/or lumbar CSF may facilitate diagnosis for GCT and cure rates are high following combinations of chemotherapy (CHT) and radiation therapy. PPT include pineocytoma, PPT of intermediate differentiation and pineoblastoma. Pineocytomas are surgically curable but curative therapy for pineoblastoma requires CHT and radiation therapy.
Successful and long-lasting treatment of solar urticaria with ultraviolet A rush hardening therapy
Authors: E. Masuoka, A. Fukunaga, K. Kishigami, H. Jimbo, M. Nishioka, Y. Uchimura, K. Taguchi, N. Ohgou, C. Nishigori
Journal: British Journal of Dermatology (2012)

Solar urticaria (SU) is a photodermatosis that is thought to be caused through the effects of mast cell mediators released because of an altered chromophore, possibly a photoallergen recognized by IgE. Phototherapy for SU to induce a tolerant state appears to be most effective, but is often time consuming and provides only short-lived remission. Ultraviolet (UV) A rush hardening has been successful and less time consuming in serum factor-negative patients with SU. However, the mechanism of action and long-lasting effects of UVA rush hardening therapy remain unclear.We aimed to evaluate whether UVA rush hardening exhibits long-lasting therapeutic effects in serum factor-positive patients with SU and to examine the action mechanism of tolerance.Two serum factor-positive patients with SU were exposed to multiple UVA irradiations at 1-h intervals per day for 2 or 3 days. Intradermal injection of their in vitro-irradiated autologous serum or compound 48/80 and a prick test for histamine were performed before and after UVA rush hardening.The two serum factor-positive patients with SU benefited greatly from UVA rush hardening, as documented by a marked increase in minimal wealing dose, and remained symptom free without using sunscreen in their daily life. Intradermal injection of in vitro-irradiated autologous serum induced wealing before hardening, but not in tolerized skin after hardening. The responses to compound 48/80 and histamine were unaltered.UVA rush hardening is an effective and long-lasting treatment even in serum factor-positive patients with SU. The mechanism of tolerance may involve continued blockade of photoallergen binding to IgE on mast cells, rather than depletion of mast cell mediators or histamine tachyphylaxis.