tbuckley/cabot-search huggingface dataset:
RAGE Mediates S100A7-Induced Breast Cancer Growth and Metastasis by Modulating the Tumor Microenvironment
Authors: Mohd W. Nasser, Nissar Ahmad Wani, Dinesh K. Ahirwar, Catherine A. Powell, Janani Ravi, Mohamad Elbaz, Helong Zhao, Laura Padilla, Xiaoli Zhang, Konstantin Shilo, Michael Ostrowski, Charles Shapiro, William E. Carson, Ramesh K. Ganju
Journal: Cancer Research (2015)

Abstract RAGE is a multifunctional receptor implicated in diverse processes including inflammation and cancer. In this study, we report that RAGE expression is upregulated widely in aggressive triple-negative breast cancer (TNBC) cells, both in primary tumors and in lymph node metastases. In evaluating the functional contributions of RAGE in breast cancer, we found that RAGE-deficient mice displayed a reduced propensity for breast tumor growth. In an established model of lung metastasis, systemic blockade by injection of a RAGE neutralizing antibody inhibited metastasis development. Mechanistic investigations revealed that RAGE bound to the proinflammatory ligand S100A7 and mediated its ability to activate ERK, NF-κB, and cell migration. In an S100A7 transgenic mouse model of breast cancer (mS100a7a15 mice), administration of either RAGE neutralizing antibody or soluble RAGE was sufficient to inhibit tumor progression and metastasis. In this model, we found that RAGE/S100A7 conditioned the tumor microenvironment by driving the recruitment of MMP9-positive tumor-associated macrophages. Overall, our results highlight RAGE as a candidate biomarker for TNBCs, and they reveal a functional role for RAGE/S100A7 signaling in linking inflammation to aggressive breast cancer development. Cancer Res; 75(6); 974–85. ©2015 AACR.
Response of myocardial metabolites to graded regional ischemia: 31P NMR spectroscopy of porcine myocardium in vivo.
Authors: S Schaefer, S A Camacho, J Gober, R G Obregon, M A DeGroot, E H Botvinick, B Massie, M W Weiner
Journal: Circulation Research (1989)

The changes in myocardial high energy phosphates and pH during regional ischemia, and their potential role in mediating functional abnormalities, is unclear. To determine the degree of regional blood flow reduction required to induce changes in high energy phosphates and pH, and to correlate these metabolic changes with alterations in blood flow, 31P nuclear magnetic resonance spectroscopy was employed in an in vivo porcine model of graded coronary stenosis. Simultaneous measurements of regional blood flow and phosphate compounds were made during various steady-state degrees of regional ischemia in which subendocardial blood flow was reduced by as much as 80%. ATP did not fall over the total range of graded ischemia, while phosphocreatine (PCr), inorganic phosphate (Pi), and pH all changed progressively after blood flow was reduced below 50% of normal. The ratio of PCr/Pi (a measure of the energy reserve of the myocardium) was strongly correlated to subendocardial blood flow (r = 0.94) and declined by 25% when blood flow was reduced by only 21% below normal. These findings indicate that PCr/Pi is a sensitive marker of ischemia and support the hypothesis that the in vivo energy status of the myocardium is closely coupled to myocardial blood flow.
New Insights into Tumor Microstructure Using Temporal Diffusion Spectroscopy
Authors: Daniel C. Colvin, Thomas E. Yankeelov, Mark D. Does, Zoe Yue, Chad Quarles, John C. Gore
Journal: Cancer Research (2008)

Abstract Magnetic resonance images (MRI) that depict rates of water diffusion in tissues can be used to characterize the cellularity of tumors and are valuable in assessing their early response to treatment. Water diffusion rates are sensitive to the cellular and molecular content of tissues and are affected by local microstructural changes associated with tumor development. However, conventional maps of water diffusion reflect the integrated effects of restrictions to free diffusion at multiple scales up to a specific limiting spatial dimension, typically several micrometers. Such measurements cannot distinguish effects caused by structural variations at a smaller scale. Variations in diffusion rates then largely reflect variations in the density of cells, and no information is available about changes on a subcellular scale. We report here our experiences using a new approach based on Oscillating Gradient Spin-Echo (OGSE) MRI methods that can differentiate the influence on water diffusion of structural changes on scales much smaller than the diameter of a single cell. MRIs of glioblastomas in rat brain in vivo show an increased contrast and spatial heterogeneity when diffusion measurements are selectively sensitized to shorter distance scales. These results show the benefit of OGSE methods for revealing microscopic variations in tumors in vivo and confirm that diffusion measurements depend on factors other than cellularity. [Cancer Res 2008;68(14):5941–7]
Medroxyprogesterone acetate addition or substitution for tamoxifen in advanced tamoxifen-resistant breast cancer: a phase III randomized trial. Australian-New Zealand Breast Cancer Trials Group.
Authors: M J Byrne, V Gebski, J Forbes, M H Tattersall, R J Simes, A S Coates, J Dewar, M Lunn, C Flower, P G Gill, J Stewart
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine whether a strategy of adding medroxyprogesterone acetate (MPA) to tamoxifen (TAM) is superior to the substitution of MPA for TAM among women with advanced breast cancer and disease progressing on TAM. To assess the patterns or response and subsequent progression in sites and tissues according to prior involvement and treatment. PATIENTS AND METHODS Two-hundred-fifteen postmenopausal women with advanced breast cancer progressing on TAM after receiving TAM for at least six months were randomized: 109 to add MPA 500 mg/day orally (TAM + MPA), and 106 to stop TAM and to substitute MPA. RESULTS There were no significant differences between the groups with respect to complete plus partial response rates: TAM + MPA 10%, MPA 9%, median time to progression TAM + MPA 3.0 months, MPA 4.5 months, or median overall survival, TAM + MPA 17.2 months, MPA 18.4 months. In a multivariate model, prognostic factors significant for a shorter time to disease progression were worse for performance status, involvement of more than one tissue, prior radiotherapy, and shorter time from recurrence after primary therapy to randomization. Adjusting for these factors, treatment with TAM + MPA was associated with a higher relative risk for disease progression, with a hazards ratio of 1.31, but this was not significant (95% confidence interval, 0.98 to 1.74; P = .067). However, in an exploratory analysis, the time to disease progression, among patients with progesterone receptor positive (PR+) tumors, was 6.3 months with MPA versus 2.9 months with TAM + MPA, with a hazards ratio of 1.92 (95% confidence interval, 1.12 to 3.32; P = .02). There was a significant interaction, P = .04, between PR status and treatment, indicating an advantage to treatment substitution for those who have PR+ tumors. Tumor response occurred in 14% of assessed metastatic sites. Subsequent progression occurred in a new tissue alone in 13% of patients, in both new and previously involved (old) tissues in 76%, and in old tissues only in 11%. In 23% of patients, progression occurred only at a new site, in 50% at both old and new sites, and in 27% only at old sites. No significant differences in the patterns of response or progression were seen in the different treatment groups. CONCLUSION Among women with breast cancer whose disease is progressing after at least six months of treatment with TAM, there is no advantage to maintaining TAM when MPA is to be given. An overall effect of treatment on the pattern of failure at old sites or at new sites or tissues cannot be discerned.
STRATEGIES TO REDUCE DRIVING UNDER THE INFLUENCE OF ALCOHOL
Authors: William DeJong, Ralph Hingson
Journal: Annual Review of Public Health (1998)

▪ Abstract The purpose of this review is to update research on the prevention of alcohol-related traffic deaths since the 1988 Surgeon General's Workshop on Drunk Driving. Four primary areas of research are reviewed here: (a) general deterrence policies, (b) alcohol control policies, (c) mass communications campaigns, including advertising restrictions, and (d) community traffic safety programs. Modern efforts to combat drunk driving in the United States began with specific deterrence strategies to punish convicted drunk drivers, and then evolved to include general deterrence strategies that were targeted to the population as a whole. Efforts next expanded to include the alcohol side of the problem, with measures installed to decrease underage drinking and excessive alcohol consumption. In the next several years, greater efforts are needed on all these fronts. Also needed, however, are programs that integrate drunk driving prevention with other traffic safety initiatives.
Achalasia of the Esophagus
Authors: J. Spalding Schroder
Journal: JAMA (1967)

Achalasia of the esophagus is characterized by lack of neuromuscular coordination, which results in an absence of normal peristalsis in the body of the esophagus and a failure of relaxation of the lower segment. It is a frequent cause of esophageal obstruction. Symptoms of achalasia include dysphagia, regurgitation (nocturnal overflow), substernal discomfort, recurrent pulmonary infection, and weight loss. The diagnosis of achalasia is established by esophagoscopy, x-ray examinations (routine posterioanterior and lateral views), barium swallow and cinefluoroscopy, and esophageal motility studies. Treatment consists of bougienage, forceful dilation, and Heller esophagocardiomyotomy.
Farming from a new perspective: remote sensing comes down to earth.
Authors: W C Holton
Journal: Environmental Health Perspectives (2000)

Farmers strive to increase the yield of their fields by adding nutrients and water to the land, and using pesticides to control insects and disease. In addition to bountiful harvests, the results of their endeavors may include elevated amounts of fertilizers in surface waters and aquifers and potential risk to themselves and their neighbors from exposure to pesticides. Precision agriculture is the use of modern information technologies such as geographic information systems, the global positioning system, and remote sensing from the air to reduce the environmental effects of these chemicals while enhancing the productivity of farming. By combining crop yield maps with soil survey maps and remote sensing output, farmers can identify areas that need more or less fertilizer, water, or pesticide.
Antitumor compounds from tunicates
Authors: Kenneth L. Rinehart
Journal: Medicinal Research Reviews (2000)

Of the six marine-derived compounds that have reached clinical trials as antitumor agents three-didemnin B, Aplidine, and ecteinascidin 743-are derived from tunicates. Di-demnin B (DB), a cyclic depsipeptide from the compound tunicate Trididemnum solidum, was the first marine-derived compound to enter Phases I and II clinical trials. The Phase II studies, sponsored by the U. S. National Cancer Institute, indicated complete or partial remissions with non-Hodgkins lymphoma, but cardiotoxicity caused didemnin B to be dropped from further study. The closely related dehydrodidemnin B (DDB, Aplidine) was isolated in 1988 from a second colonial tunicate, Aplidium albicans, and spectroscopic studies assigned a structural formula in which a pyruvyl group in DDB replaced the lactyl group in DB and syntheses of DDB have been achieved. Aplidine is more active than DB and lacks DB's cardiotoxicity. It was introduced by PharmaMar into Phase I clinical trials in January 1999. The second family of tunicate-derived antitumor agents are the ecteinascidins (ETs), from the mangrove tunicate Ecteinascidia turbinata. The antitumor extracts of E. turbinata were first described in 1969, but the small amount of ETs in E. turbinata prevented their isolation for over a decade. The structures of ETs have been assigned mainly by spectroscopy. Phase II clinical trials with ET 743 are underway. Future supplies of ET's should be available from aquaculture or synthesis.
Effects of lysine-acetylsalicylate (LAS) treatment in nasal polyposis: two controlled long term prospective follow up studies
Authors: E Nucera, D Schiavino, A Milani, M Del Ninno, C Misuraca, A Buonomo, C D'Ambrosio, G Paludetti, G Patriarca
Journal: Thorax (2000)

Nasal polyposis is a multifactorial disease with a complex and still not completely understood pathogenesis. In more than one third of cases it is associated with intolerance to acetylsalicylic acid (aspirin, ASA) or to other non-steroidal anti-inflammatory drugs (NSAIDs).1 In as many as 20% of cases nasal polyposis is also associated with the presence of bronchial asthma and/or rhinitis, configuring the so-called ASA triad or aspirin disease.2 

Nasal polyps may benefit from medical treatment (corticosteroids) and surgery,3 but they frequently relapse soon after surgery4-9 with significant morbidity and high social and medical costs. Unfortunately, the effect of treatment with steroids is also often temporary.3 10-16 

In the last two decades it has been observed that, in aspirin sensitive patients, oral aspirin desensitisation (followed by long term aspirin treatment) often results in an improvement in the clinical course of nasal polyposis.17-21 We have shown that aspirin sensitive patients with nasal polyposis have a higher rate of positive nasal provocation tests (rhinomanometric measure of nasal airflow reduction after exposure to the drug) with lysine-acetylsalicylate (LAS) than aspirin sensitive patients without nasal polyps.22-24 Moreover, LAS has been found to have an in vitro non-specific antiproliferative, dose dependent effect on the growth of fibroblasts of both nasal polyps and normal skin.23 We have shown that long term topical (endonasal) treatment with LAS prevents the recurrence of nasal polyps after polypectomy with satisfactory results.24 

In this paper we present and discuss the definitive results obtained in two controlled long term prospective follow up studies dealing with the evaluation of relapse rates in nasal polyposis.

The first is a six year follow up study of patients with nasal polyps who underwent long term intranasal LAS treatment after surgical polypectomy in comparison with matched controls (patients who underwent …
P37 Muscle mass in COPD patients receiving angiotensin II receptor blockers and ACE-inhibitors
Authors: S. S. C. Kon, M. S. Patel, A. L. Clark, K. A. Ingram, R. P. Fowler, P. Marns, J. L. Canavan, N. S. Hopkinson, M. I. Polkey, W. D. C. Man
Journal: Thorax (2011)

<h3>Background</h3> Skeletal muscle dysfunction is well recognised in chronic obstructive pulmonary disease (COPD) and is associated with increased morbidity and mortality. Considerable circumstantial evidence supports a role for renin-angiotensin systems in skeletal muscle turnover. Angiotensin II (ATII) administration causes cachexia through several biological mechanisms. Angiotensin converting enzyme inhibitors (ACE-I) block the conversion of angiotensin I to ATII. Previous pilot studies have shown that the administration of ATII receptor blockers (ARB) or ACE-I to COPD patients may increase quadriceps strength and peak work rate (Andreas <i>et al</i>, 2006; Di Marco <i>et al</i>, 2010). We hypothesised that in an unselected COPD population referred for pulmonary rehabilitation (PR), those receiving ARB or ACE-I drugs would have preserved muscle mass. <h3>Methods</h3> Data from 373 consecutive COPD patients (213M: 160F; mean age 68.3; median FEV<sub>1</sub> 41% predicted) referred to an outpatient pulmonary rehabilitation programme were analysed. Patients were divided into those receiving either an ARB or ACE-I and controls (those receiving neither drug). Fat free mass (FFM; measured by bioelectric impedance analysis), incremental shuttle walk (ISW), Chronic Respiratory Disease Questionnaire (CRDQ), MRC Dyspnoea score (MRC) and COPD assessment test (CAT) were measured. Between group differences were compared using Mann–Whitney U or unpaired t-test. <h3>Results</h3> Data are presented as median (25<sup>th</sup>, 75<sup>th</sup> centiles), and summarised in Abstract P37 table 1. 130 COPD patients from this cohort were taking either an ACE-I (n=82), ARB (n=45) or both (n=3). The groups were matched for gender distribution and long-term oral corticosteroid use. Compared with the control COPD patients, those on ACE-I or ARB were older, had better FEV<sub>1</sub> % predicted but similar ISW, CRDQ, MRC and CAT. However, the patients receiving ACE-I or ARB had significantly higher fat free mass (FFM) and fat free mass index (FFMI). <h3>Conclusions</h3> In an unselected COPD cohort referred for pulmonary rehabilitation, patients on ACE-I or ARB appear to have increased muscle mass compared with those receiving neither drug. Future longitudinal studies and randomised controlled trials are required to further define the effect of ACE-I and ARB in COPD.
Neoplastic and Antineoplastic Effects of -Carotene on Colorectal Adenoma Recurrence: Results of a Randomized Trial
Authors: J. A. Baron, B. F. Cole, L. Mott, R. Haile, M. Grau, T. R. Church, G. J. Beck, E. R. Greenberg
Journal: JNCI Journal of the National Cancer Institute (2003)

In two large, randomized prevention trials, supplementation with beta-carotene increased the risk of lung cancer. Subjects in these studies were predominantly cigarette smokers, and the adverse effects were concentrated among those who also drank alcohol. Although beta-carotene supplementation appeared not to increase the risk of cancer generally, it is not clear if smoking and/or alcohol use alters the effect of beta-carotene on carcinogenesis at sites outside the lung.We studied the effect of beta-carotene supplementation on colorectal adenoma recurrence among subjects in a multicenter double-blind, placebo-controlled clinical trial of antioxidants for the prevention of colorectal adenomas. A total of 864 subjects who had had an adenoma removed and were polyp-free were randomly assigned (in a factorial design) to receive beta-carotene (25 mg or placebo) and/or vitamins C and E in combination (1000 mg and 400 mg, respectively, or placebo), and were followed with colonoscopy for adenoma recurrence 1 year and 4 years after the qualifying endoscopy. A total of 707 subjects had two follow-up examinations and provided smoking and alcohol use data. Adjusted multivariate risk ratios (RRs) and 95% confidence intervals (CIs) were used to assess the effects of beta-carotene on adenoma recurrence.Among subjects who neither smoked cigarettes nor drank alcohol, beta-carotene was associated with a marked decrease in the risk of one or more recurrent adenomas (RR = 0.56, 95% CI = 0.35 to 0.89), but beta-carotene supplementation conferred a modest increase in the risk of recurrence among those who smoked (RR = 1.36, 95% CI = 0.70 to 2.62) or drank (RR = 1.13, 95% CI = 0.89 to 1.43). For participants who smoked cigarettes and also drank more than one alcoholic drink per day, beta-carotene doubled the risk of adenoma recurrence (RR = 2.07, 95% CI = 1.39 to 3.08; P for difference from nonsmoker/nondrinker RR <.001).Alcohol intake and cigarette smoking appear to modify the effect of beta-carotene supplementation on the risk of colorectal adenoma recurrence.
Radiological tumor size decrease at week 6 is a potent predictor of outcome in chemorefractory metastatic colorectal cancer treated with cetuximab (BOND trial)
Authors: H. Piessevaux, M. Buyse, W. De Roock, H. Prenen, M. Schlichting, E. Van Cutsem, S. Tejpar
Journal: Annals of Oncology (2009)
Effect of Adrenalectomy upon the Pressor Action of Potassium in Hypotensive, Potassium-Deficient Rats
Authors: S. CHARLES FREED, RAY H. ROSENMAN, MALCOLM K. SMITH
Journal: Circulation Research (1954)

The administration of potassium to hypotensive, potassium-deficient rats results in a prompt restoration of their lowered blood pressure to normotensive levels. Similar repletion of the potassium deficit in adrenalectomized rats is only partially effective in restoring the blood pressure to normotensive levels. The spontaneous retention of potassium which occurs in potassium-deficient rats following adrenalectomy fails to restore lowered blood pressures to normotensive values.
Histone Deacetylase Inhibitors Have a Profound Antigrowth Activity in Endometrial Cancer Cells
Authors: Noriyuki Takai, Julian C. Desmond, Takashi Kumagai, Dorina Gui, Jonathan W. Said, Sadie Whittaker, Isao Miyakawa, H. Phillip Koeffler
Journal: Clinical Cancer Research (2004)

Abstract Purpose: HDAC inhibitors (HDACIs) have been shown to inhibit cancer cell proliferation, stimulate apoptosis, and induce cell cycle arrest. Our purpose was to investigate the antiproliferative effects of the HDACIs [suberoyl anilide bishydroxamine, valproic acid (VPA), trichostatin A, and sodium butyrate] against six endometrial cancer cell lines. Experimental Design: Endometrial cancer cells were treated with a variety of HDACIs, and the effect on cell growth, cell cycle, and apoptosis was measured. The ability of VPA to inhibit the growth of endometrial tumors growing in immunodeficient mice was also assessed. Results: Clonogenic assays showed that all cancer cell lines were sensitive to the growth inhibitory effect of HDACIs. Cell cycle analysis indicated that treatment with HDACIs decreased the proportion of cells in S phase and increased the proportion of cells in the G0-G1 and/or G2-M phases of the cell cycle. Terminal deoxynucleotidyl transferase-mediated nick end labeling assays showed that HDACIs induced apoptosis. This was concomitant with altered expression of genes related to malignant phenotype, including an increase in p21Waf1, p27Kip7, and E-cadherin and a decrease in Bcl-2 and cyclin-D1 and -D2. Chromatin immunoprecipitation analysis revealed a remarkable increase in levels of acetylated histones associated with the p21 promoter after suberoyl anilide bishydroxamine treatment. In nude mice experiments, VPA inhibited significantly human uterine tumor growth without toxic side effects. Conclusions: These results suggest that HDACIs are effective in inhibiting growth of endometrial cancer cells in vitro and in nude mice, without toxic side effects. The findings raise the possibility that HDACIs may prove particularly effective in treatment of endometrial cancers.