tbuckley/cabot-search huggingface dataset:
An Increase in the Expression of Ribonucleotide Reductase Large Subunit 1 Is Associated with Gemcitabine Resistance in Non-Small Cell Lung Cancer Cell Lines
Authors: Jennifer D. Davidson, Liandong Ma, Michael Flagella, Sandaruwan Geeganage, Lawrence M. Gelbert, Christopher A. Slapak
Journal: Cancer Research (2004)

The mechanisms of resistance to the antimetabolite gemcitabine in non-small cell lung cancer have not been extensively evaluated. In this study, we report the generation of two gemcitabine-selected non-small cell lung cancer cell lines, H358-G200 and H460-G400. Expression profiling results indicated that there was evidence for changes in the expression of 134 genes in H358-G200 cells compared with its parental line, whereas H460-G400 cells exhibited 233 genes that appeared to be under- or overexpressed compared with H460 cells. However, only the increased expression of ribonucleotide reductase subunit 1 (RRM1), which appeared in both resistant cell lines, met predefined analysis criteria for genes to investigate further. Quantitative PCR analysis demonstrated H358-G200 cells had a greater than 125-fold increase in RRM1 RNA expression. Western blot analysis confirmed high levels of RRM1 protein in this line compared with the gemcitabine-sensitive parent. No significant change in the expression of RRM2 was observed in either cell line, although both gemcitabine-resistant cell lines had an approximate 3-fold increase in p53R2 protein. A partial revertant of H358-G200 cells had reduced levels of RRM1 protein (compared with G200 cells), without observed changes in RRM2 or p53R2. In vitro analyses of ribonucleotide reductase activity demonstrated that despite high levels of RRM1 protein, ribonucleotide reductase activity was not increased in H358-G200 cells when compared with parental cells. The cDNA encoding RRM1 from H358-G200 cells was cloned and sequenced but did not reveal the presence of any mutations. The results from this study indicate that the level of RRM1 may affect gemcitabine response. Furthermore, RRM1 may serve as a biomarker for gemcitabine response.
Renal responses to AT1 blockade in angiotensin II-induced hypertensive rats.
Authors: C T Wang, L X Zou, L G Navar
Journal: Journal of the American Society of Nephrology (1997)

Previous studies have shown that uninephrectomized rats infused chronically with low doses of angiotensin II (Ang II) develop progressive hypertension that is prevented by coadministration of losartan in the drinking water. The present study was performed to contrast the effects of chronic and acute losartan treatment in reversing the Ang II-mediated actions on arterial pressure and renal function. Ang II was infused subcutaneously via osmotic minipumps (40 ng/min) for 13 days in two groups (N = 10 and N = 6); one group also received losartan in the drinking water (30 mg/kg.day) throughout this period. Untreated rats (N = 6) and rats (N = 6) receiving only losartan served as control groups. Ang II-infused rats had higher mean arterial pressures (153 +/- 7 versus 107 +/- 3 mm Hg) and lower GFR (0.7 +/- 0.04 versus 0.98 +/- 0.06 mL/min.g) than Ang II-infused rats receiving losartan chronically. The Ang II-infused rats responded to acute doses of losartan (10 mg/kg) with progressive reductions in arterial pressure and significant increases in cortical blood flow (34 +/- 12% increase), renal plasma flow, GFR, and sodium excretion; however, the increases in renal blood flow and GFR were not sustained as systemic arterial pressure decreased. Because Ang II-infused rats receiving losartan chronically still exhibited decreases in RBF in response to a bolus dose of Ang II, further studies evaluated the effects of acute losartan treatment in rats treated chronically with losartan. Although arterial pressure decreased only slightly, demonstrating adequate systemic vascular blockade, there were still substantial and sustained increases in renal plasma flow, cortical blood flow (20 +/- 4% increase), GFR, and sodium excretion. In summary, the modest responses to acute losartan in Ang II-infused rats indicate that chronic Ang II infusions lead to alterations in renal function that are only partially reversible by acute losartan treatment. In contrast, chronic treatment with losartan prevents the Ang II-induced decrease in GFR. The renal responses to acute losartan in the Ang II-infused rats treated chronically with losartan suggest that substantive intrarenal actions of Ang II can be maintained even when the systemic vascular AT1 receptors are effectively blocked.
Effect of the Selective Estrogen Receptor Modulator Arzoxifene on Repopulation of Hormone-Responsive Breast Cancer Xenografts between Courses of Chemotherapy
Authors: Licun Wu, Ian F. Tannock
Journal: Clinical Cancer Research (2005)

Abstract Selective inhibition of repopulation of clonogenic tumor cells between courses of chemotherapy has potential to improve the effectiveness of treatment. Here we study arzoxifene, a short-acting selective estrogen receptor modulator, for its potential to inhibit repopulation in estrogen-dependent human breast cancer MCF-7 xenografts between courses of chemotherapy. Proliferation of tumor cells was evaluated by cyclin D1 expression and uptake of 5-bromo-2′-deoxyuridine. Arzoxifene decreased cell proliferation in xenografts. To model adjuvant treatment of human breast cancer, MCF-7 cells were injected s.c. into nude mice and four groups of mice received the following treatments beginning after implantation: (a) control (vehicle solution); (b) arzoxifene alone, 5 days per week by oral gavage for 3 weeks; (c) 5-fluorouracil (5-FU) or paclitaxel i.p. weekly, for 3 doses; and (d) arzoxifene following each cycle of chemotherapy. The incidence of tumors with volume ≥50 mm3 was determined as a function of time. MCF-7 xenografts developed in 100% of control mice by 4 weeks after implantation. Paclitaxel or 5-FU alone had minor effects to delay the appearance of xenografts whereas arzoxifene alone caused longer delay. Combined treatment with arzoxifene given between cycles of 5-FU or paclitaxel had substantial effects, with ∼50% tumor incidence by 5 weeks. Our results indicate that arzoxifene can inhibit repopulation of hormone-responsive MCF-7 breast cancer xenografts when given between courses of chemotherapy. The scheduling of short-acting hormonal agents between courses of adjuvant chemotherapy for human breast cancer has potential to improve the outcome of treatment.
Prognosis of Japanese Metastatic Renal Cell Carcinoma Patients in the Cytokine Era: A Cooperative Group Report of 1463 Patients
Authors: Sei Naito, Naoki Yamamoto, Tatsuya Takayama, Masatoshi Muramoto, Nobuo Shinohara, Kenryu Nishiyama, Atsushi Takahashi, Ryo Maruyama, Takashi Saika, Senji Hoshi, Kazuhiro Nagao, Shingo Yamamoto, Issei Sugimura, Hirotsugu Uemura, Shigehiko Koga, Masayuki Takahashi, Fumio Ito, Seiichiro Ozono, Toshiro Terachi, Seiji Naito, Yoshihiko Tomita
Journal: European Urology (2009)
31P magnetic resonance spectroscopy in dilated cardiomyopathy and coronary artery disease. Altered cardiac high-energy phosphate metabolism in heart failure.
Authors: S Neubauer, T Krahe, R Schindler, M Horn, H Hillenbrand, C Entzeroth, H Mader, E P Kromer, G A Riegger, K Lackner
Journal: Circulation (1992)

BACKGROUND The purpose of this work was to further define the value of cardiac 31P magnetic resonance (MR) spectroscopy for patients with coronary artery disease and dilated cardiomyopathy. METHODS AND RESULTS Blood-corrected and T1-corrected 31P MR spectra of anteroseptal myocardium were obtained at rest using image-selected in vivo spectroscopy localization, a selected volume of 85 +/- 12 cm3, and a field strength of 1.5 T. Nineteen volunteers had a creatine phosphate (CP)/ATP ratio of 1.95 +/- 0.45 (mean +/- SD) and a PDE/ATP ratio of 1.06 +/- 0.53; in four patients with left anterior descending coronary artery (LAD) stenosis, six patients with chronic anterior wall infarction, and four patients with chronic posterior wall infarction, CP/ATP and phosphodiester (PDE)/ATP ratios did not differ from those in volunteers. Twenty-five measurements of 19 patients with dilated cardiomyopathy yielded a CP/ATP of 1.78 +/- 0.51 and a PDE/ATP of 0.98 +/- 0.56 (p = NS versus volunteers). When these patients were grouped according to the severity of heart failure, however, CP/ATP was 1.94 +/- 0.43 in mild (p = NS versus volunteers) and 1.44 +/- 0.52 in severe DCM (p &lt; 0.05), respectively. No correlation was found between CP/ATP and left ventricular ejection fraction or fractional shortening, but correlation of CP/ATP with the New York Heart Association (NYHA) class was significant (r = 0.60, p &lt; 0.005). Six patients with dilated cardiomyopathy were studied repeatedly before and after 12 +/- 6 weeks of drug treatment leading to clinical recompensation with improvement of the NYHA status by 0.8 +/- 0.3 classes. Concomitantly, CP/ATP increased from 1.51 +/- 0.32 to 2.15 +/- 0.27 (p &lt; 0.01), whereas PDE/ATP did not change significantly. CONCLUSIONS Cardiac high-energy phosphate metabolism at rest is normal in LAD stenosis and chronic myocardial infarction in the absence of heart failure. The CP/ATP ratio has low specificity for the diagnosis of dilated cardiomyopathy. However, CP/ATP correlated with the clinical severity of heart failure and may improve during clinical recompensation.
The Sympathetic Nervous System Induces a Metastatic Switch in Primary Breast Cancer
Authors: Erica K. Sloan, Saul J. Priceman, Benjamin F. Cox, Stephanie Yu, Matthew A. Pimentel, Veera Tangkanangnukul, Jesusa M.G. Arevalo, Kouki Morizono, Breanne D.W. Karanikolas, Lily Wu, Anil K. Sood, Steven W. Cole
Journal: Cancer Research (2010)

Metastasis to distant tissues is the chief driver of breast cancer-related mortality, but little is known about the systemic physiologic dynamics that regulate this process. To investigate the role of neuroendocrine activation in cancer progression, we used in vivo bioluminescence imaging to track the development of metastasis in an orthotopic mouse model of breast cancer. Stress-induced neuroendocrine activation had a negligible effect on growth of the primary tumor but induced a 30-fold increase in metastasis to distant tissues including the lymph nodes and lung. These effects were mediated by β-adrenergic signaling, which increased the infiltration of CD11b(+)F4/80(+) macrophages into primary tumor parenchyma and thereby induced a prometastatic gene expression signature accompanied by indications of M2 macrophage differentiation. Pharmacologic activation of β-adrenergic signaling induced similar effects, and treatment of stressed animals with the β-antagonist propranolol reversed the stress-induced macrophage infiltration and inhibited tumor spread to distant tissues. The effects of stress on distant metastasis were also inhibited by in vivo macrophage suppression using the CSF-1 receptor kinase inhibitor GW2580. These findings identify activation of the sympathetic nervous system as a novel neural regulator of breast cancer metastasis and suggest new strategies for antimetastatic therapies that target the β-adrenergic induction of prometastatic gene expression in primary breast cancers.
Possible Link Between Zinc Intake and Colon Cancer
Authors: M. K. Song, M. C. Y. Heng, R. Rolandelli, M. E. Ament, M. K. Heng
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Possible Link Between Zinc Intake and Colon Cancer Get access Moon K. Song, Moon K. Song Research and Medical Services, Sepulveda DVA Medical CenterNorth Hills, CalifDepartment of Pediatrics, University of California at Los Angeles (UCLA) School of Medicine Correspondence to: Moon K. Song, Ph.D., 151-C7, Sepulveda DVA Medical Center, 16111 Plummer St., North Hills, CA 91343. Search for other works by this author on: Oxford Academic PubMed Google Scholar Madalene C. Y. Heng, Madalene C. Y. Heng Research and Medical Services, Sepulveda DVA Medical Center; and Department of Medicine, UCLA School of Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar Rolando Rolandelli, Rolando Rolandelli Research and Surgical Services, Sepulveda DVA Medical Center; and Department of Surgery, UCLA School of Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar Marvin E. Ament, Marvin E. Ament Department of Pediatrics, UCLA School of Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar Ming K. Heng Ming K. Heng Research and Medical Services, Sepulveda DVA Medical Center; and Department of Medicine, UCLA School of Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 8, 21 April 1993, Pages 667–669, https://doi.org/10.1093/jnci/85.8.667 Published: 21 April 1993 Article history Received: 09 September 1992 Revision received: 08 January 1993 Accepted: 03 February 1993 Published: 21 April 1993
Remembrance of Immunology Past: Conversations with Herman Eisen
Authors: Herman N. Eisen, Sondra Schlesinger
Journal: Annual Review of Immunology (2015)

Herman Eisen and Sondra Schlesinger spent several days together in September 2007 in Woods Hole, Massachusetts, talking about immunology, focusing on his remembrances of the field over the more than 60 years of his involvement. This article is an abridged version of those discussions (the full version is available on the Annual Reviews website). It is both an oral history and a written memory of some important but selected areas of immunology.
Insulin Resistance, Inflammation, and Serum Fatty Acid Composition
Authors: José-Manuel Fernández-Real, Montserrat Broch, Joan Vendrell, Wifredo Ricart
Journal: Diabetes Care (2003)

Fatty acids (FAs) have been involved in the development of chronic inflammatory conditions such as insulin resistance and obesity. However, the relation among insulin resistance, obesity, inflammatory activity (circulating interleukin [IL]-6) and dietary FAs has been scarcely studied in otherwise healthy subjects.We aimed to study these interactions in 123 overweight (BMI 26.9 +/- 2.4 kg/m(2) [means +/- SD]) subjects and 109 lean (BMI 21.7 +/- 1.7 kg/m(2), P < 0.000001) subjects. IL-6 was measured by immunoassay and FA by gas liquid cromatography.The percentage of saturated FAs (r = 0.30, P = 0.01) and omega-6 FAs (r = -0.32, P = 0.001) were significantly associated with circulating IL-6, whereas the percentage of omega-3 FAs correlated negatively with C-reactive protein in overweight subjects (P = 0.04). Saturated-to-omega-3 and saturated-to-omega-6 FA ratios were significantly and positively associated with C-reactive protein (P < 0.0001) and IL-6 (P < 0.001), respectively. In contrast, none of these associations reached statistical significance in lean subjects. Those subjects in the most insulin-sensitive quintile (homeostasis model assessment value) showed a significantly higher percentage of linoleic acid (C18:2 varpi6) (P = 0.03) and a significantly lower level of araquidic (C20:0) (P = 0.04), behenic (C22:0) (P = 0.009), lignoceric (C24:0) (P = 0.02), and nervonic (C24:1 varpi9) (P = 0.001) FAs than the remaining subjects. In parallel, the most insulin-sensitive subjects showed significantly decreased C-reactive protein (P = 0.03). Serum C-reactive protein was significantly associated with percent linoleic acid and eicosapentaenoic acid in nonsmoking men (P = 0.03 and P = 0.04, respectively) and with docosahexaenoic acid in nonsmoking women (r = -0.46, P < 0.0001). We constructed a multivariant regression analysis to predict circulating IL-6. Age, BMI, waist-to-hip ratio (WHR), smoking status, and the relation of saturated to omega-6 or saturated to omega-3 FAs were considered as independent variables separately in men and women. In overweight men, the ratio of saturated to omega-3 FAs (P = 0.01), but not age, sex, BMI, WHR, or smoking status, independently contributed to 17% of IL-6 variance. In lean men, smoking status (P = 0.02), but not the remaining variables, contributed to 8% of IL-6 variance.Dietary FAs (as inferred from plasma FA concentration) seem to be linked to inflammatory activity in overweight subjects and in subjects with insulin resistance. Being overweight modulates the relation of FAs to inflammatory markers.
Tenocyte hypercellularity and vascular proliferation in a rabbit model of tendinopathy: contralateral effects suggest the involvement of central neuronal mechanisms
Authors: Gustav Andersson, Sture Forsgren, Alexander Scott, James Edmund Gaida, Johanna Elgestad Stjernfeldt, Ronny Lorentzon, Håkan Alfredson, Clas Backman, Patrik Danielson
Journal: British Journal of Sports Medicine (2010)

Objective To determine whether there are objective findings of tendinosis in a rabbit tendinopathy model on exercised and contralateral (non-exercised) Achilles tendons. Design Four groups of six New Zealand white rabbits per group were used. The animals of one (control) group were not subjected to exercise/stimulation. Interventions Animals were subjected to a protocol of electrical stimulation and passive flexion–extension of the right triceps surae muscle every second day for 1, 3 or 6 weeks. Main Outcome Measures Tenocyte number and vascular density were calculated. Morphological evaluations were also performed as well as in-situ hybridisation for vascular endothelial growth factor (VEGF) messenger RNA. Results There was a significant increase in the tenocyte number after 3 and 6 weeks of exercise, but not after 1 week, in comparison with the control group. This was seen in the Achilles tendons of both legs in experimental animals, including the unexercised limb. The pattern of vascularity showed an increase in the number of tendon blood vessels in rabbits that had exercised for 3 weeks or more, compared with those who had exercised for 1 week or not at all. VEGF-mRNA was detected in the investigated tissue, with the reactions being more clearly detected in the tendon tissue with tendinosis-like changes (6-week rabbits) than in the normal tendon tissue (control rabbits). Conclusions There were bilateral tendinosis-like changes in the Achilles tendons of rabbits in the current model after 3 weeks of training, suggesting that central neuronal mechanisms may be involved and that the contralateral side is not appropriate as a control.
Detection of the complement fragment C5a in inflammatory exudates from the rabbit peritoneal cavity using radioimmunoassay.
Authors: P J Jose, M J Forrest, T J Williams
Journal: The Journal of Experimental Medicine (1983)

We describe a radioimmunoassay for rabbit C5a and its use to obtain evidence of extravascular C5a generation in two inflammatory reactions in the peritoneal cavity. These observations, together with the potent activity of C5a in inducing increased microvascular permeability involving circulating PMN leukocytes, strengthen the case for considering C5a an important inflammatory mediator. These findings offer an explanation for the many different experimental inflammatory reactions where oedema formation can be suppressed either by systemic depletion of complement or by depletion of circulating PMN leukocytes.
Bevacizumab Beyond Progression in Metastatic Colorectal Cancer Patients Receiving a First-Line Treatment Containing Bevacizumab: Update of Bebyp Trial by Gono
Authors: Lisa Salvatore, Gianluca Masi, Fotios Loupakis, Chiara Cremolini, Marta Schirripa, Lorenzo Fornaro, Cristina Granetto, Emanuela Miraglio, Francesco Di Costanzo, Lorenzo Antonuzzo, Lorenzo Marcucci, Samanta Cupini, Corrado Boni, Maria Banzi, Silvana Chiara, Daniela Garbarino, Chiara Valsuani, Andrea Bonetti, Luca Boni, Alfredo Falcone
Journal: Annals of Oncology (2013)
Carbohydrate Nutrition, Insulin Resistance, and the Prevalence of the Metabolic Syndrome in the Framingham Offspring Cohort
Authors: Nicola M. McKeown, James B. Meigs, Simin Liu, Edward Saltzman, Peter W.F. Wilson, Paul F. Jacques
Journal: Diabetes Care (2004)

OBJECTIVE—The aim of this study was to examine the relation between carbohydrate-related dietary factors, insulin resistance, and the prevalence of the metabolic syndrome in the Framingham Offspring Cohort. RESEARCH DESIGN AND METHODS—We examined cross-sectional associations between carbohydrate-related dietary factors, insulin resistance, and the prevalence of the metabolic syndrome in 2,834 subjects at the fifth examination (1991–1995) of the Framingham Offspring Study. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated using the following formula (fasting plasma insulin × plasma glucose)/22.5. The metabolic syndrome was defined using the National Cholesterol Education Program criteria. RESULTS—After adjustment for potential confounding variables, intakes of total dietary fiber, cereal fiber, fruit fiber, and whole grains were inversely associated, whereas glycemic index and glycemic load were positively associated with HOMA-IR. The prevalence of the metabolic syndrome was significantly lower among those in the highest quintile of cereal fiber (odds ratio [OR] 0.62; 95% CI 0.45–0.86) and whole-grain (0.67; 0.48–0.91) intakes relative to those in the lowest quintile category after adjustment for confounding lifestyle and dietary factors. Conversely, the prevalence of the metabolic syndrome was significantly higher among individuals in the highest relative to the lowest quintile category of glycemic index (1.41; 1.04–1.91). Total carbohydrate, dietary fiber, fruit fiber, vegetable fiber, legume fiber, glycemic load, and refined grain intakes were not associated with prevalence of the metabolic syndrome. CONCLUSIONS—Whole-grain intake, largely attributed to the cereal fiber, is inversely associated with HOMA-IR and a lower prevalence of the metabolic syndrome. Dietary glycemic index is positively associated with HOMA-IR and prevalence of the metabolic syndrome. Given that both a high cereal fiber content and lower glycemic index are attributes of whole-grain foods, recommendation to increase whole-grain intake may reduce the risk of developing the metabolic syndrome.
Immunological and genetic links in Crohn's disease
Authors: F SHANAHAN
Journal: Gut (2000)

See article on page 58 

Current consensus holds that the pathogenesis of Crohn's disease involves the interacting elements of multigenic host susceptibility factors and environmental priming from the enteric microflora.1 2 Tissue damage is mediated by the immune system, although the contributory mechanisms are still unclear, and may be multiple or varied in different individuals. In addition, many immunological alterations in patients with Crohn's disease seem to have no direct role in mediating tissue injury and are frequently dismissed as epiphenomena. The history of medical discovery is replete with examples of overlooked clues hitherto dismissed as unimportant. Could some of the antibody markers in Crohn's disease yet provide useful clues to disease aetiology and pathogenesis? Could some of these phenomena be manifestations of the linkage across genetic, immunological and environmental contributions to aetiopathogenesis?

Marker antibodies have attracted considerable attention as putative manifestations of the disease related immune response in inflammatory bowel disease.3 The relative specificity of some of these antibodies for either Crohn's disease …
Spirituality and Religion in the “Art of Dying”
Authors: Lois M. Ramondetta, Deborah Sills
Journal: Journal of Clinical Oncology (2003)

Article Tools ART OF ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.01.109 Journal of Clinical Oncology - published online before print November 1, 2016 PMID: 14645439 Spirituality and Religion in the “Art of Dying” Lois M. RamondettaxLois M. RamondettaSearch for articles by this author , Deborah SillsxDeborah SillsSearch for articles by this author Show More From the Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX. https://doi.org/10.1200/JCO.2003.01.109 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology