tbuckley/cabot-search huggingface dataset:
Abstract 2633: Adenosine analog enhances actions of 17-AAG
Authors: Fabiola Cervantes-Gomez, Ramadevi Nimmanapalli, Varsha Gandhi
Journal: Cancer Research (2010)

Abstract Heat shock protein 90 (HSP90) is a molecular chaperone that regulates the functional stability of client oncoproteins, which is driven by the binding and hydrolysis of ATP. The geldanamycin analog, 17-AAG, binds to the ATP pocket of HSP90 leading to the degradation of client proteins. However, 17-AAG also induces transcription of antiapoptotic HSP70 and HSP27 resulting in cell death resistance. The nucleoside analog 8-Chloro-Adenosine (8-Cl-Ado), currently in clinical trial, is a transcription inhibitor that gets metabolized into its cytotoxic form 8-Cl-ATP causing a parallel decrease of the cellular ATP pool. Based on its mechanisms of action we hypothesize that the combination of 17-AAG and 8-Cl-Ado will result in a favorable effect on cytotoxicity. % Cell Death Annexin V / 7-AAD TreatmentsHrsMM.1S8226-RPMIU2661)17-AAG 0.5 µM85452)17-AAG 0.5 µM202463)8-Cl-Ado 10 µM125324)8-Cl-Ado 10 µM2022825)17-AAG→8-Cl-Ado8→12 = 201511106)8-Cl-Ado→17-AAG12→8 = 205515197)8-Cl-Ado+17-AAG20421434 As shown in the Table, simultaneous or sequential combination (rows 6 and 7) were more than additive in multiple myeloma cell lines. With 17-AAG alone, there was a transcriptional induction of HSP90α, HSP90β, HSP70, HSC70 and HSP27 as measured by real time RT-PCR. With the drug combinations, there was no reduction of the 17-AAG-induced HSPs mRNA levels, rather a several fold increase was observed for the stress-inducible HSP70 and HSP27. In accordance, the protein levels of the HSPs were also increased when treated with 17-AAG but remained the same when 8-Cl-Ado was added. This suggests that the transcription inhibition by 8-Cl-Ado was not able to abrogate 17-AAG-mediated HSP induction. The transcript levels for client proteins (STAT3, Akt and c-Raf) remained at endogenous levels when treated with the drugs alone or in combination. However, the combination treatments resulted in a greater decline of the protein expression of STAT3 (1-60%), Akt (42-78%), and Raf-1 (25-85%). This may be due to the reduction in intracellular ATP levels after 8-Cl-Ado treatment, MM.1S (57%), 8226-RPMI (24%), and U266 (56%). Taken together, the increased cytotoxicity of 17-AAG and 8-Cl-Ado combination is mediated by the actions of 8-Cl-Ado on the cellular ATP pool and not due to its effect on transcription. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2633.
Improving quality of care: Challenges to implementing quality indicators
Authors: J. B. Owen, J. F. Wilson
Journal: Journal of Clinical Oncology (2006)

16030 Background: To assess the overall quality of cancer care, efforts seek consensus quality indicators that crosscut health services. Although pilot programs have collected and analyzed relevant clinical data, they have been unable to collect radiation oncology (RO) data detailed enough to assess the quality of services or to inform key decision makers. Quality Research in Radiation Oncology (QRRO) conducted retrospective surveys of national practice since 1973 with major positive impact on the quality of practice through recursive processes. Methods: From Donabedian’s model of quality assessment, QRRO analyzes crucial quality components by conducting Facilities, Process, and Outcomes Surveys. Survey design allows calculation of national averages for patients treated with RO and comparisons by key factors. Evolving data collection methods allow assessment of modern technologies. Methods start with definition and measurement of evidence-based quality indicators but allow greater detail and specification than most other quality measurement efforts. Results: QRRO showed that radiation dose affected outcomes for prostate cancer patients. Higher radiation doses were associated with improved local tumor control rates and treatment techniques affected toxicity rates. These results, presented widely in numerous venues, stimulated dose escalation clinical trials. Trials conducted in the USA all used QRRO results as critical data, providing the major impetus to test new directions in dose escalation and new methods to target delivery more precisely. National practice shifted to higher doses and use of conformal techniques. The dataset is unique in providing cross-sectional information on practice patterns with a wide variety of treatment approaches from many institutions and sufficient details of treatment delivery to allow examination of questions about quality and effects of techniques. Conclusions: Mounting societal demands for improvement in the quality of care, ever increasing complexity of radiation therapy, and escalating use of multi-modality treatment make continuing to measure, report, and improve quality of care in RO crucial to patients and the profession. Methods must keep pace with new technologies and techniques in radiation therapy. [Supported by NCI grant CA 65435]. No significant financial relationships to disclose.
Abstract 5222: Metabolomic patterns of tumors and metastases of human colon cancer xenografts
Authors: Ulrike S. Stein, Carsten Grötzinger, Katharina Detjen, Änne Eckardt, Jan Lisec, Lothar Willmitzer
Journal: Cancer Research (2011)

Abstract Prognostic assessment of colon cancer metastasis and intervention in metastatic disease represent critical clinical challenges. Metabolomic platforms now offer the potential for a systematic survey of the metabolic profile of tumor tissues, which may allow to link key metabolites to distinct aspects of tumor biology such as metastatic capacity. Here we addressed these issues by testing the hypothesis that metastatic disease is characterized by distinct metabolites. In preparation for subsequent analyses of human tumor samples from existing tissue collections, here we employed human colon cancer lines harboring metastatic capacities to induce cancer xenografts in mice. In a first set of experiments using human colon xenografts, and applying GC-MS based metabolomics technology, we characterized the metabolite patterns of the primary tumors and of liver metastases, as well as of the mouse spleens (organ of transplantation) and the mouse livers (main target organ of distant metastasis). Subjecting the metabolite data to a Principal Component Analysis resulted in the separation of the samples into four clusters discriminating on the one hand mouse from human tumor xenograft tissues. Furthermore, mouse spleen was easily separated from mouse liver. More importantly, we identified clearly distinct metabolomic clusters comprising the primary tumor samples vs. the liver metastasis although originating from the same human colon cancer cell line. These different metabolic profiles of primary tumors and metastases were highly reproducible between independent experiments and were conserved in primary tumors or metastases of different size, suggesting they offer a representation of distinct biological features, rather than reflect tumor cell mass or common features of the tumor cell microenvironment. In addition, defined metabolites were identified that are characteristic for particular mouse organs (spleen vs. liver), and for discrimination of mouse tissues vs. human xenograft tumors. Moreover, metabolites were identified that allow discrimination of the primary tumor vs. its corresponding liver metastasis, although both tissues originate from the same human colon cancer cells. We also addressed methodological topics, such as the influence of time until sample cryo-asservation, time of storage, size and amount of the tissue samples, and reproducibility in independent in vivo experiments, on the metabolomic patterns and specific metabolites. In summary, we identified metabolomic patterns as well as defined metabolites that allow discrimination of the primary tumor vs. its corresponding liver metastasis of colon cancer xenografts in mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5222. doi:10.1158/1538-7445.AM2011-5222
A Prospective Evaluation of an Angiotensin-Converting–Enzyme Gene Polymorphism and the Risk of Ischemic Heart Disease
Authors: Klaus Lindpaintner, Marc A. Pfeffer, Reinhold Kreutz, Meir J. Stampfer, Francine Grodstein, Fran LaMotte, Julie Buring, Charles H. Hennekens
Journal: New England Journal of Medicine (1995)

In a previous study, men with a history of myocardial infarction were found to have an increased prevalence of homozygosity for the deletional allele (D) of the angiotensin-converting-enzyme (ACE) gene. The D allele is associated with higher levels of ACE, which may predispose a person to ischemic heart disease. We investigated the association between the ACE genotype and the incidence of myocardial infarction, as well as other manifestations of ischemic heart disease, in a large, prospective cohort of U.S. male physicians.In the Physicians' Health Study, ischemic heart disease as defined by angina, coronary revascularization, or myocardial infarction developed in 1250 men by 1992. They were matched with 2340 controls according to age and smoking history. Zygosity for the deletion-insertion (D-I) polymorphism of the ACE gene was determined by an assay based on the polymerase chain reaction. Data were analyzed for both matched pairs and unmatched samples, with adjustment for the effects of known or suspected risk factors by conditional and nonconditional logistic regression, respectively.The ACE genotype was not associated with the occurrence of either ischemic heart disease or myocardial infarction. The adjusted relative risk associated with the D allele was 1.07 (95 percent confidence interval, 0.96 to 1.19; P = 0.24) for ischemic heart disease and 1.05 (95 percent confidence interval, 0.89 to 1.25; P = 0.56) for myocardial infarction, if an additive mode of inheritance is assumed. Additional analyses assuming dominant and recessive effects of the D allele also failed to show any association, as did the examination of low-risk subgroups.In a large, prospectively followed population of U.S. male physicians, the presence of the D allele of the ACE gene conferred no appreciable increase in the risk of ischemic heart disease or myocardial infarction.
Cutaneous Metastasis Revealing a Widely Disseminated Follicular Thyroid Carcinoma
Authors: SAMI BOUGHATTAS, HABIB HASSINE, KAOUTHER CHATTI, RACHED JOMAA, HABIB ESSABBAH
Journal: Clinical Nuclear Medicine (2002)

BOUGHATTAS, SAMI M.D.; HASSINE, HABIB M.D.; CHATTI, KAOUTHER M.D.; JOMAA, RACHED M.D.; ESSABBAH, HABIB M.D. Author Information
Effect of Systemic Glucocorticoids on Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Dennis E. Niewoehner, Marcia L. Erbland, Robert H. Deupree, Dorothea Collins, Nicholas J. Gross, Richard W. Light, Paula Anderson, Nancy A. Morgan
Journal: New England Journal of Medicine (1999)

Although their clinical efficacy is unclear and they may cause serious adverse effects, systemic glucocorticoids are a standard treatment for patients hospitalized with exacerbations of chronic obstructive pulmonary disease (COPD). We conducted a double-blind, randomized trial of systemic glucocorticoids (given for two or eight weeks) or placebo, in addition to other therapies, for exacerbations of COPD. Most other care was standardized over the six-month period of follow-up. The primary end point was treatment failure, defined as death from any cause or the need for intubation and mechanical ventilation, readmission to the hospital for COPD, or intensification of drug therapy.
LOWER SERUM CHLORIDE IS ASSOCIATED WITH LOWER DIURETIC EFFICIENCY AND ADVERSE POST-DISCHARGE OUTCOMES: INSIGHTS FROM ROSE-AHF
Authors: Justin Lee Grodin, Jie-Lena Sun, Kevin Anstrom, Horng Chen, Randall Starling, Jeffrey Testani, Wai Hong Tang
Journal: Journal of the American College of Cardiology (2016)
P209Interleukin 27 in carotid atherosclerosis
Authors: I Gregersen, E Askevold, S Holm, M Skjelland, K Krogh Sorensen, A Yndestad, P Aukrust, B Halvorsen
Journal: Cardiovascular Research (2014)

Aim: Interleukin 27 is a member of the IL-12 family of cytokines and is secreted as a heterodimer consisting of Epstein-Barr-induced gene 3 product (EBI3) and p28. The IL-27 receptor is also a heterodimer composed of IL-27Rα and gp130, in which both units are required for signal transduction. IL-27 has both pro- and anti-inflammatory properties and is involved in several different inflammatory diseases. There are only few reports on IL-27 in atherosclerotic disease and the regulation of IL-27 in atherosclerosis is not fully understood. In this study we examine IL-27 levels in carotid atherosclerotic disease as well as effects of this cytokine on a relevant cell line. Methods: Plasma levels of IL-27 were measured by ELISA in patients with carotid stenosis (n=135) and in healthy controls (n=20). Expression of IL-27 and IL-27R were analyzed by qPCR and immunohistochemistry in plaques from the same patient group. TNF-α –activated THP-1 monocytes were used to study relevant effects of IL-27 in vitro. Results: Plasma levels of IL-27 were significantly elevated in patients with carotid atherosclerotic disease compared to healthy controls. IL-27 and IL-27R mRNA expression were significantly elevated in plaques when compared to control vessels. Protein expression in the carotid plaque was confirmed by immunohistochemistry. In vitro, IL-27 (100 ng/ml) induced production of pro-inflammatory cytokines from TNF-α activated THP-1 cells. Conclusions: We demonstrate increased levels of circulating IL-27 and expression of IL-27 and IL-27R in plaque from patients with carotid atherosclerosis. Our in vitro findings may suggest a pro-inflammatory role for IL-27, which can possibly be linked to atherosclerotic disease development.
Preliminary Therapy Evaluation of <sup>225</sup>Ac-DOTA-c(RGDyK) Demonstrates that Cerenkov Radiation Derived from <sup>225</sup>Ac Daughter Decay Can Be Detected by Optical Imaging for <i>In Vivo</i> Tumor Visualization
Authors: Darpan N. Pandya, Roy Hantgan, Mikalai M. Budzevich, Nancy D. Kock, David L. Morse, Izadora Batista, Akiva Mintz, King C. Li, Thaddeus J. Wadas
Journal: Theranostics (2016)

The theranostic potential of (225)Ac-based radiopharmaceuticals continues to increase as researchers seek innovative ways to harness the nuclear decay of this radioisotope for therapeutic and imaging applications. This communication describes the evaluation of (225)Ac-DOTA-c(RGDyK) in both biodistribution and Cerenkov luminescence imaging (CLI) studies. Initially, La-DOTA-c(RGDyK) was prepared as a non-radioactive surrogate to evaluate methodologies that would contribute to an optimized radiochemical synthetic strategy and estimate the radioactive conjugate's affinity for αvβ3, using surface plasmon resonance spectroscopy. Surface plasmon resonance spectroscopy studies revealed the IC50 and Ki of La-DOTA-c(RGDyK) to be 33 ± 13 nM and 26 ± 11 nM, respectively, and suggest that the complexation of the La(3+) ion to the conjugate did not significantly alter integrin binding. Furthermore, use of this surrogate allowed optimization of radiochemical synthesis strategies to prepare (225)Ac-DOTA-c(RGDyK) with high radiochemical purity and specific activity similar to other (225)Ac-based radiopharmaceuticals. This radiopharmaceutical was highly stable in vitro. In vivo biodistribution studies confirmed the radiotracer's ability to target αvβ3 integrin with specificity; specificity was detected in tumor-bearing animals using Cerenkov luminescence imaging. Furthermore, tumor growth control was achieved using non-toxic doses of the radiopharmaceutical in U87mg tumor-bearing nude mice. To our knowledge, this is the first report to describe the CLI of αvβ3 (+) tumors in live animals using the daughter products derived from (225)Ac decay in situ. This concept holds promise to further enhance development of targeted alpha particle therapy.
THE SAFETY OF PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS TURNED DOWN FOR SURGICAL REVASCULARIZATION: INSIGHTS FROM THE BLUE CROSS BLUE SHIELD OF MICHIGAN CARDIOVASCULAR CONSORTIUM
Authors: Devraj Sukul, Milan Seth, Simon Dixon, Mark Zainea, Nicklaus Slocum, Elizabeth Pielsticker, Hitinder Gurm
Journal: Journal of the American College of Cardiology (2016)
How Employers Are Responding to the ACA
Authors: Robert Galvin
Journal: New England Journal of Medicine (2016)

Interview with Dr. Robert Galvin on the effects of the Affordable Care Act on employer-sponsored insurance. (10:03)Download Although it's still early in the game, employers are making key decisions about health care coverage that affect patients, providers, and insurers. So far, under the “play-or-pay” model created by the Affordable Care Act, almost all employers have continued to play.
Serum Selenium Level in Relation to In Situ Cervical Cancer in Australia
Authors: K.E. Brock, G. Gridley, J. S. Morris, W. C. Willett
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Serum Selenium Level in Relation to In Situ Cervical Cancer in Australia Get access K.E. Brock, K.E. Brock Cumberland College of Health Sciences, University of SyndneyAustralia Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Gridley, G. Gridley * Environmental Epidemiology Branch, Division of Cancer Etiology, National Cancer InstituteBethesda, Md * Correspondence to: G. Gridley, MS, Executive Plaza North, Room 443, National Institutes of Health, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. S. Morris, J. S. Morris University of Missouri Research Reactor FacilityColumbia, Mo Search for other works by this author on: Oxford Academic PubMed Google Scholar W. C. Willett W. C. Willett Departments of Epidemiology and Nutrition, Harvard School of Public HealthBoston, Mass Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 4, 20 February 1991, Pages 292–293, https://doi.org/10.1093/jnci/83.4.292 Published: 20 February 1991 Article history Received: 26 September 1990 Revision received: 15 November 1990 Accepted: 29 November 1990 Published: 20 February 1991
Postural Cerebral Hypoperfusion Related to Brain Atrophy After a Modified Fontan Operation
Authors: K Hayashida, Y Hirose, N Kume, Y Nishioeda, I H Cho, Y Shimotsu, K Fukuchi, Y Ono
Journal: Clinical Nuclear Medicine (1998)

A brain CT in a 7-year-old girl who had a modified Fontan procedure 5 years earlier revealed cortical atrophy, especially in the frontal areas. Upright brain SPECT was performed because she had frequent episodes of headache and vomiting when standing that were relieved when she was recumbent. Brain SPECT revealed postural cerebral hypoperfusion in the frontal areas and basal ganglia. The postural cerebral hypoperfusion may be related to the Fontan operation, with associated neuron damage and brain atrophy because the frontal areas might be highly susceptible to a reduction in blood flow. The patient may have experienced the postural cerebral hypoperfusion repeatedly during the 5 years since the operation. Upright imaging using Tc-99m HMPAO brain SPECT can be applied to pediatric patients to detect postural cerebral hypoperfusion after undergoing cardiac surgery that may affect cerebral blood flow.
Effects of <i>in Utero</i> Exposure to Arsenic during the Second Half of Gestation on Reproductive End Points and Metabolic Parameters in Female CD-1 Mice
Authors: Karina F. Rodriguez, Erica K. Ungewitter, Yasmin Crespo-Mejias, Chang Liu, Barbara Nicol, Grace E. Kissling, Humphrey Hung-Chang Yao
Journal: Environmental Health Perspectives (2015)

BackgroundMice exposed to high levels of arsenic in utero have increased susceptibility to tumors such as hepatic and pulmonary carcinomas when they reach adulthood. However, the effects of in utero arsenic exposure on general physiological functions such as reproduction and metabolism remain unclear.ObjectivesWe evaluated the effects of in utero exposure to inorganic arsenic at the U.S. Environmental Protection Agency (EPA) drinking water standard (10 ppb) and at tumor-inducing levels (42.5 ppm) on reproductive end points and metabolic parameters when the exposed females reached adulthood.MethodsPregnant CD-1 mice were exposed to sodium arsenite [none (control), 10 ppb, or 42.5 ppm] in drinking water from gestational day 10 to birth, the window of organ formation. At birth, exposed offspring were fostered to unexposed dams. We examined reproductive end points (age at vaginal opening, reproductive hormone levels, estrous cyclicity, and fertility) and metabolic parameters (body weight changes, hormone levels, body fat content, and glucose tolerance) in the exposed females when they reached adulthood.ResultsArsenic-exposed females (10 ppb and 42.5 ppm) exhibited early onset of vaginal opening. Fertility was not affected when females were exposed to the 10-ppb dose. However, the number of litters per female was decreased in females exposed to 42.5 ppm of arsenic in utero. In both 10-ppb and 42.5-ppm groups, arsenic-exposed females had significantly greater body weight gain, body fat content, and glucose intolerance.ConclusionOur findings revealed unexpected effects of in utero exposure to arsenic: exposure to both a human-relevant low dose and a tumor-inducing level led to early onset of vaginal opening and to obesity in female CD-1 mice.CitationRodriguez KF, Ungewitter EK, Crespo-Mejias Y, Liu C, Nicol B, Kissling GE, Yao HH. 2016. Effects of in utero exposure to arsenic during the second half of gestation on reproductive end points and metabolic parameters in female CD-1 mice. Environ Health Perspect 124:336–343; http://dx.doi.org/10.1289/ehp.1509703