tbuckley/cabot-search huggingface dataset:
Pion, conventional therapy compared in radiation study
Authors: Phil Gunby
Journal: JAMA (1981)

One of the few clinically operational facilities for negative pi meson (pion) radiotherapy is starting comparison trials of pion and conventional radiation treatment for cancers of the bladder, rectum, oral cavity, and pharynx. The pion beam was activated seven years ago by University of New Mexico (Albuquerque) Cancer Research and Treatment Center personnel at the Clinton P. Anderson Meson Physics Facility within the Los Alamos Scientific Laboratory (<i>JAMA</i>[MEDICAL NEWS] 1979;241:2591, 1978;239:1014, 1974;229:14, and 1974;227:377-387). The 800-meV proton linear accelerator used in this work is the largest of its type anywhere. So far, according to Richard H. Stark, MS, a medical physicist involved in treatment planning, it appears that pion therapy not only requires fewer rad (approximately 5,000 vs 6,500 rad for conventional photon therapy) but also has about a 60% greater relative biological effect than conventional radiotherapy. Stark told a Radiological Society of North Americaaudience in Dallas audience in Dallas that
A Novel Epidermal Growth Factor Receptor Inhibitor Promotes Apoptosis in Non–Small Cell Lung Cancer Cells Resistant to Erlotinib
Authors: Thibault de La Motte Rouge, Lorenzo Galluzzi, Ken A. Olaussen, Yael Zermati, Ezgi Tasdemir, Thomas Robert, Hugues Ripoche, Vladimir Lazar, Philippe Dessen, Francis Harper, Gerard Pierron, Guillaume Pinna, Natalia Araujo, Annick Harel-Belan, Jean-Pierre Armand, Tai Wai Wong, Jean Charles Soria, Guido Kroemer
Journal: Cancer Research (2007)

Abstract Non–small cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) responds to EGFR tyrosine kinase inhibitors such as erlotinib. However, secondary somatic EGFR mutations (e.g., T790M) confer resistance to erlotinib. BMS-690514, a novel panHER/vascular endothelial growth factor receptor (VEGFR) inhibitor described here, exerted antiproliferative and proapoptotic effects on NSCLC cell lines, with prominent efficacy on H1975 cells expressing the T790M mutation. In this model, BMS-690514 induced a G1 cell cycle arrest, as well as ultrastructural hallmarks of apoptosis, mitochondrial release of cytochrome c, and activation of caspases involved in the intrinsic (e.g., caspase-2, caspase-3, caspase-7, and caspase-9), but not in the extrinsic (e.g., caspase-8), pathway. Caspase inhibition conferred partial protection against BMS-690514 cytotoxicity, pointing to the involvement of both caspase-dependent and caspase-independent effector mechanisms. Transcriptome analyses revealed the up-regulation of proapoptotic (e.g., Bim, Puma) and cell cycle inhibitory (e.g., p27Kip1, p57Kip2) factors, as well as the down-regulation of antiapoptotic (e.g., Mcl1), heat shock (e.g., HSP40, HSP70, HSP90), and cell cycle promoting [e.g., cyclins B1, D1, and D3; cyclin-dependent kinase 1 (CDK1); MCM family proteins; proliferating cell nuclear antigen (PCNA)] proteins. BMS-690514–induced death of H1975 cells was modified in a unique fashion by a panel of small interfering RNAs targeting apoptosis modulators. Down-regulation of components of the nuclear factor-κB survival pathway (e.g., p65, Nemo/IKKγ, TAB2) sensitized cells to BMS-690514, whereas knockdown of proapoptotic factors (e.g., Puma, Bax, Bak, caspase-2, etc.) and DNA damage–related proteins (e.g., ERCC1, hTERT) exerted cytoprotective effects. BMS-690514 is a new pan-HER/VEGFR inhibitor that may become an alternative to erlotinib for the treatment of NSCLC. [Cancer Res 2007;67(13):6253–62]
PAK-dependent STAT5 serine phosphorylation is required for BCR-ABL-induced leukemogenesis
Authors: A Berger, A Hoelbl-Kovacic, J Bourgeais, L Hoefling, W Warsch, E Grundschober, I Z Uras, I Menzl, E M Putz, G Hoermann, C Schuster, S Fajmann, E Leitner, S Kubicek, R Moriggl, F Gouilleux, V Sexl
Journal: Leukemia (2013)

The transcription factor STAT5 (signal transducer and activator of transcription 5) is frequently activated in hematological malignancies and represents an essential signaling node downstream of the BCR-ABL oncogene. STAT5 can be phosphorylated at three positions, on a tyrosine and on the two serines S725 and S779. We have investigated the importance of STAT5 serine phosphorylation for BCR-ABL-induced leukemogenesis. In cultured bone marrow cells, expression of a STAT5 mutant lacking the S725 and S779 phosphorylation sites (STAT5SASA) prohibits transformation and induces apoptosis. Accordingly, STAT5SASA BCR-ABL+ cells display a strongly reduced leukemic potential in vivo, predominantly caused by loss of S779 phosphorylation that prevents the nuclear translocation of STAT5. Three distinct lines of evidence indicate that S779 is phosphorylated by group I p21-activated kinase (PAK). We show further that PAK-dependent serine phosphorylation of STAT5 is unaffected by BCR-ABL tyrosine kinase inhibitor treatment. Interfering with STAT5 phosphorylation could thus be a novel therapeutic approach to target BCR-ABL-induced malignancies.
Points: Chemoprophylaxis of malaria in Africa
Authors: D B A Hutchinson, J A Farquhar
Journal: BMJ (1983)

December, p 1617) of a patient in whom atenolol treatment apparently precipitated renal artery thrombosis.Recent reports suggest that the angiotensin converting enzyme inhibitor captopril may cause the same complication in patients with pre-existing renal artery stenosis.Oelkers' has described two patients with renovascular hypertension who developed renal artery occlusion during treatment with captopril, and, according to Hollenberg,' about 10% of patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney developed rapidly progressive renal failure during the first few weeks of treatment with captopril.Half of these patients recovered renal function with a reduction in dosage of captopril.No details of the remaining patients were given, but one might speculate that some or all of them may also have developed renal artery thrombosis.
Regulation of biliary cholesterol secretion. Functional relationship between the canalicular and sinusoidal cholesterol secretory pathways in the rat.
Authors: F Nervi, I Marinović, A Rigotti, N Ulloa
Journal: Journal of Clinical Investigation (1988)

The functional interrelationship between biliary cholesterol secretion, sinusoidal lipoprotein cholesterol secretion and bile salt synthesis was studied in the rat. Diosgenin, fructose, and colestipol in the diet were used to, respectively, influence biliary cholesterol output, VLDL production and bile salt synthesis. In the acute bile fistula rat, biliary cholesterol output was 700% increased by diosgenin and 50% decreased by fructose. In the rats fed both diosgenin and fructose, biliary cholesterol secretion was increased only by approximately 200%, whereas biliary bile salts and phospholipid outputs were unchanged. In the isolated perfused liver, VLDL-cholesterol output was 50% reduced by diosgenin alone, but was unchanged following feeding of diosgenin plus fructose. However, the livers of rats fed diosgenin plus fructose exhibited a 700% increase in VLDL-triglyceride production and a 200% increase in VLDL-cholesterol output. A significant reciprocal relationship between VLDL-cholesterol secretion and the coupling ratio of cholesterol to bile salts in bile was observed. Colestipol added to the diet maintained both sinusoidal and biliary cholesterol outputs within the normal range. In the chronic bile fistula rat, colestipol increased bile salt synthesis by 100% while diosgenin and fructose diets had no effect. Similarly, the addition of fructose to the colestipol diet did not decrease bile salt synthesis. These data suggest a reciprocal relationship between biliary cholesterol secretion and hepatic secretion of cholesterol as VLDL particles. The free cholesterol pool used for bile salt synthesis seems functionally unrelated to the pool from which VLDL-cholesterol and biliary cholesterol originate. These findings support the idea that metabolic compartmentalization of hepatic cholesterol is a major determinant of the quantity of cholesterol available for recruitment by the bile salt-dependent biliary cholesterol secretory mechanism.
Supersensitivity of atherosclerotic artery to constrictor effect of cigarette smoke extract
Authors: S Sugiyama
Journal: Cardiovascular Research (1998)

Objective: The aim of this study was to assess whether contractile response of arteries to aqueous component of cigarette smoke extract (CSE) may be modulated in atherosclerotic arteries. Methods: Thoracic aortas were isolated from control rabbits and from 1.5% cholesterol-fed rabbits, all of which had visible advanced atheromatous surface changes on the aortas. CSE was prepared by bubbling main stream of smoke from one cigarette with filter into 2 ml of phosphate-buffered saline. The thoracic aortic rings were suspended in organ chambers and tested with CSE (0.01–3.0 μl/ml buffer in the organ chamber) after precontraction with 0.1 μmol/l of phenylephrine (PE). Results: The contractile response to CSE was significantly greater in atherosclerotic aortas than in control aortas (the maximal contraction expressed as % of the precontraction; control aortas 10.8±2.8%, atherosclerotic aortas 42.6±4.7%; P<0.01). The magnitude of the precontractions by PE was not different between control and atherosclerotic aortas. Exogenous addition of superoxide dismutase (SOD) significantly attenuated the CSE-induced contraction in both control and atherosclerotic aortas and pretreatment of aortic rings with diethyldithiocarbamate to deplete of endogenous vascular CuZn-SOD activity potentiated the CSE-induced contraction in control aortas, while it had no significant effect in atherosclerotic aortas. The vascular SOD activity was significantly lower in atherosclerotic aortas than in control aortas ((U/mg protein): control aortas 38.2±3.3, atherosclerotic aortas 18.5±2.4; P<0.01). Conclusion: These results indicate that atherosclerotic arteries may be supersensitive to the constrictor effect of superoxide anion derived from CSE. The decrease in endogenous vascular SOD activity may partly contribute to the increased susceptibility to oxidative stress in atherosclerotic arteries.
Second Hand Smoke Exposure and Survival in Early-Stage Non–Small-Cell Lung Cancer Patients
Authors: Wei Zhou, Rebecca S. Heist, Geoffrey Liu, Kofi Asomaning, David P. Miller, Donna S. Neuberg, John C. Wain, Thomas J. Lynch, David C. Christiani
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Second hand smoke (SHS) exposure is associated with higher risk of lung cancer. However, the role of SHS in lung cancer survival is not clear. Experimental Design: We examined the association between self-reported SHS exposure before diagnosis and overall survival and recurrence-free survival in 393 early-stage non–small-cell lung cancer patients. SHS exposure was analyzed by both duration and location of exposure using log-rank test and Cox proportional hazard models, adjusting for covariates including pack-years of smoking. Results: The median follow-up time was 66 months (range, 0.2-140 months). There were 135 recurrences and 213 deaths. The 5-year overall survival rates were 71% [95% confidence interval (95% CI), 62-81%], 61% (51-72%), 49% (38-60%), and 47% (37-58%), respectively, for patients with the lowest to highest quartile of SHS exposure durations (P &amp;lt; 0.001, log-rank test), with the adjusted hazard ratio (AHR) of 1.57 (95% CI, 1.02-2.41) for the highest versus lowest quartile of SHS exposure durations (Ptrend = 0.04). For different SHS exposure locations, a stronger association was found for SHS exposure at work (AHR of the highest versus lowest quartile, 1.71; 95% CI, 1.12-2.61; Ptrend = 0.03) than for exposure at home (AHR, 1.26; 95% CI, 0.86-1.86; Ptrend = 0.20) or leisure places (AHR, 1.28; 95% CI, 0.83-1.95; Ptrend = 0.16). Similar associations were observed when SHS exposure durations were dichotomized into two or three groups and between SHS exposure and recurrence-free survival. Conclusions: SHS exposure is associated with worse survival in early-stage non–small-cell lung cancer patients, especially for SHS exposure at the work.
Effect of Replacement of Potassium by Rubidium on the Transmembrane Action Potential and Contractility of Human Papillary Muscle
Authors: KAILASH PRASAD, JOHN C. CALLAGHAN
Journal: Circulation Research (1969)

The effects of extracellular rubidium chloride (1, 2, 4, and 8 mM) on simultaneously recorded transmembrane action potentials and contractions of human papillary muscle in potassium-free solutions were investigated. In KCl-free solution, reduction in the duration of the action potential at the 25% and 50% levels of repolarization was associated with an increase in the force of contraction. Exposure of the muscle to rubidium chloride led to an increase in the duration of the action potential at 25% and 50% levels of repolarization associated with a corresponding decrease in the force of contraction. A decrease in the force of contraction was more usually associated with an increase in the duration of the action potential at the 25% level of repolarization than at the 50% level. No appreciable change in the duration of the action potential at the 90% level of repolarization was observed. Increases in the duration associated with corresponding decreases in the force of contraction were concentrationdependent. Rubidium chloride (8 mM) produced a conduction delay and inexcitability in the muscle. It has been suggested that in KCl-free solution the reduction in the duration of the action potential and an increase in the force of contraction were associated with inhibition of membrane ATPase. Also, the increases in the duration of the action potential accompanied by decreases in the force of contraction were associated with rubidium chloride-induced stimulation of membrane ATPase in human myocardium.
Mechanisms of Tumor Regression and Resistance to Estrogen Deprivation and Fulvestrant in a Model of Estrogen Receptor–Positive, HER-2/<i>neu</i>-Positive Breast Cancer
Authors: Suleiman Massarweh, C. Kent Osborne, Shou Jiang, Alan E. Wakeling, Mothaffar Rimawi, Syed K. Mohsin, Susan Hilsenbeck, Rachel Schiff
Journal: Cancer Research (2006)

Abstract HER-2/neu in breast cancer is associated with tamoxifen resistance, but little data exist on its interaction with estrogen deprivation or fulvestrant. Here, we used an in vivo xenograft model of estrogen receptor (ER)-positive breast cancer with HER-2/neu overexpression (MCF7/HER-2/neu-18) to investigate mechanisms of growth inhibition and treatment resistance. MCF7/HER-2/neu-18 tumors were growth inhibited by estrogen deprivation and with fulvestrant, but resistance developed in 2 to 3 months. Inhibited tumors had reductions in ER, insulin-like growth factor-I receptor (IGF-IR), phosphorylated HER-2/neu (p-HER-2/neu), and phosphorylated p42/44 mitogen-activated protein kinase (p-MAPK). p27 was increased especially in tumors sensitive to estrogen deprivation. Tumors with acquired resistance to these therapies had complete loss of ER, increased p-HER-2/neu, increased p-MAPK, and reduced p27. In contrast, IGF-IR and phosphorylated AKT (p-AKT) levels were markedly reduced in these resistant tumors. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib, which can block EGFR/HER-2/neu signaling, significantly delayed the emergence of resistance to both estrogen deprivation and fulvestrant. Levels of p-MAPK and p-AKT decreased with gefitinib, whereas high ER levels were restored. Eventually, however, tumors progressed in mice treated with gefitinib combined with estrogen deprivation or fulvestrant accompanied again by loss of ER and IGF-IR, increased p-HER-2/neu, high p-MAPK, and now increased p-AKT. Thus, estrogen deprivation and fulvestrant can effectively inhibit HER-2/neu-overexpressing tumors but resistance develops quickly. EGFR/HER-2/neu inhibitors can delay resistance, but reactivation of HER-2/neu and signaling through AKT leads to tumor regrowth. Combining endocrine therapy with EGFR/HER-2/neu inhibitors should be tested in clinical breast cancer, but a more complete blockade of EGFR/HER-2/neu may be optimal. (Cancer Res 2006; 66(16): 8266-73)
Abstract 1723: Can histologic patterns of pulmonary adenocarcinoma reflect histologic grade, one of the most important factors of cancer prognosis?
Authors: Ilseon Hwang, Keon Uk Park, Jin Young Kim, Eunyoung Ha
Journal: Cancer Research (2012)

Abstract Background: Pulmonary adenocarcinoma shows highly heterogeneous histologic pattern. Histologic pattern is suggested to be an important prognostic factor, therefore predominant histologic pattern is emphasized in 2010 IASLC/ATS/ERS classification of pulmonary adenocarcinoma. However, there are a few papers on the prognosis of pulmonary adenocarcinoma according to histologic patterns, especially in various stages. The aim of this study is to evaluate prognosis according to histologic patterns in pulmonary adenocarcinoma with various stages. Methods: We examined 125 cases of surgically resected pulmonary adenocarcinomas with various stages from January 1998 to December 2007. Invasive adenocarcinomas were classified into histologic subtypes which are lepidic, papillary, acinar, solid and micropapillary patterns by 2010 IASLC/ATS/ERS classification. Invasive adenocarcinoma was divided into 2010 classification (I), predominant and second predominant pattern (II), predominant and the worst pattern (III), and modified predominant pattern (IV). Results: Proportions of predominant lepidic, papillary, acinar, solid and micropapillary patterns were 11 (9.3%), 8 (6.8%), 54 (45.8%), 38 (32.2%) and 7 (5.9%), respectively. All histologic classification systems were not correlated with clinical manifestations including age, tumor size, T stage, N stage or recurrence. However, all histologic classification systems were significantly correlated with overall survival rates (p=0.010, 0.044, 0.001, and 0.013) by Kaplan-Meier survival test. In Cox proportional hazard model, histologic pattern was independent factor of prognosis on classification according to I, III, IV (p=0.017, 0.006 and 0.023). Conclusion: Histologic pattern is an independent prognostic factor in pulmonary adenocarcinoma with various stages and histologic patterns of pulmonary adenocarcinoma reflect the degree of histologic differentiation, one of the most important prognostic factor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1723. doi:1538-7445.AM2012-1723
1043. Intravenous (I.V.) Administration of Manganese Superoxide Dismutase-Plasmid Liposome (MnSOD-PL) Complex Protects Mice from Whole Body Irradiation
Authors: Michael W. Epperly, Yunyun Niu, Joel S. Greenberger
Journal: Molecular Therapy (2006)

Local administration of MnSOD-PL has been demonstrated to protect normal tissues from irradiation damage including: oral cavity, esophagus, lung, bladder and intestines. To determine whether systemic administration of MnSOD-PL protected the bone marrow from irradiation-induced damage, C57BL/6NHsd female mice were injected intravenously with MnSOD-PL (100 μg plasmid DNA). Groups of the mice were irradiated 24 hours later to 9 Gy, 9.5 Gy or 9.75 Gy whole body irradiation. Following irradiation, the mice were weighed on a daily basis and watched for signs of irradiation- induced hematologic damage. Control mice irradiated to either 9.5 Gy or 9.75 Gy demonstrated a loss of body weight while mice injected with the MnSOD-PL showed no changes in body weight. Mice injected with MnSOD-PL before irradiation demonstrated protection against irradiation with stabilized body weight and increased survival compared to control irradiated mice (p=0.0402 at 9.5 Gy or p = 0.0016 at 9.75 Gy). Therefore, I.V. administration of MnSOD-PL protects mice from bone marrow toxicity of whole body irradiation. Joel S. Greenberger, MD is a co-owner of and holds equity in Automated Cell, Inc., Pittsburgh, PA.
A Stage-for-Stage and Grade-for-Grade Analysis of Cancer-Specific Mortality Rates in Renal Cell Carcinoma According to Age: A Competing-Risks Regression Analysis
Authors: Maxine Sun, Firas Abdollah, Marco Bianchi, Quoc-Dien Trinh, Claudio Jeldres, Zhe Tian, Shahrokh F. Shariat, Hugues Widmer, Kevin Zorn, Mani Menon, Francesco Montorsi, Paul Perrotte, Pierre I. Karakiewicz
Journal: European Urology (2011)
Accuracy of endoscopic ultrasound elastography used for differential diagnosis of focal pancreatic masses: a multicenter study
Authors: A. Săftoiu, P. Vilmann, F. Gorunescu, J. Janssen, M. Hocke, M. Larsen, J. Iglesias-Garcia, P. Arcidiacono, U. Will, M. Giovannini, C. Dietrich, R. Havre, C. Gheorghe, C. McKay, D. Gheonea, T. Ciurea
Journal: Endoscopy (2011)

See also: Commentaire de travail de A. S'ftoiu et al., pp. 596Endoscopy 2011; 43(07): 647-647DOI: 10.1055/s-0031-1291785
Type II Diabetes Mellitus: Interface Between Clinical and Epidemiological Investigation
Authors: Michael P Stern
Journal: Diabetes Care (1988)

The field of cardiovascular disease and atherosclerosis has been enriched by a fruitful interplay between basic and clinical scientists and epidemiologists. Such interaction has been less highly developed in the field of diabetes. I present an epidemiological perspective on certain problems in type II (non-insulin-dependent) diabetes research and point out some potentially useful directions for future interdisciplinary efforts involving both basic and clinical scientists and epidemiologists. Early research on diabetes has been marred by variable case definitions. The demonstration in numerous epidemiological studies that plasma glucose has a bimodal distribution in populations has contributed to the widely accepted National Diabetes Data Group (NDDG) and the nearly identical World Health Organization (WHO) definitions of diabetes. This development has markedly ameliorated many of the difficulties resulting from variable case definitions. Appreciation of the phenomenon of bimodality has also contributed to a better understanding of impaired glucose tolerance. Many studies on the pathogenesis of type II diabetes take the form of case-control (i.e., cross-sectional) studies. The weaknesses of this research design are well known to epidemiologists. Prospective studies, a much stronger research design for inferring causal relationships, are much less common in the field of diabetes than in the field of cardiovascular disease and atherosclerosis. Recently, however, two prospective studies have helped define the role of serum insulin levels and insulin resistance as diabetes risk factors. These studies were carried out in small, relatively isolated populations, and there is a great need to replicate these findings in larger, more representative populations and to further evaluate the relative role of insulin secretion and insulin resistance as diabetes risk factors. Because characterization of these metabolic parameters by modern techniques is complex and expensive, such studies will probably have to be carried out in high-risk populations in which the sample-size requirements are more modest.