tbuckley/cabot-search huggingface dataset:
Benefit/Risk Assessment for Breast Cancer Chemoprevention With Raloxifene or Tamoxifen for Women Age 50 Years or Older
Authors: Andrew N. Freedman, Binbing Yu, Mitchell H. Gail, Joseph P. Costantino, Barry I. Graubard, Victor G. Vogel, Garnet L. Anderson, Worta McCaskill-Stevens
Journal: Journal of Clinical Oncology (2011)

The Study of Tamoxifen and Raloxifene (STAR) demonstrated that raloxifene was as effective as tamoxifen in reducing the risk of invasive breast cancer (IBC) in postmenopausal women and had lower risks of thromboembolic events, endometrial cancer, and cataracts but had a nonstatistically significant higher risk of noninvasive breast cancer. There is a need to summarize the risks and benefits of these agents.Baseline incidence rates of IBC and other health outcomes, absent raloxifene and tamoxifen, were estimated from breast cancer chemoprevention trials; the Surveillance, Epidemiology and End Results Program; and the Women's Health Initiative. Effects of raloxifene and tamoxifen were estimated from STAR and the Breast Cancer Prevention Trial. We assigned weights to health outcomes to calculate the net benefit from raloxifene compared with placebo and tamoxifen compared with placebo.Risks and benefits of treatment with raloxifene or tamoxifen depend on age, race, breast cancer risk, and history of hysterectomy. Over a 5-year period, postmenopausal women with an intact uterus had a better benefit/risk index for raloxifene than for tamoxifen. For postmenopausal women without a uterus, the benefit/risk ratio was similar. The benefits and risks of raloxifene and tamoxifen are described in tables that can help identify groups of women for whom the benefits outweigh the risks.We developed a benefit/risk index to quantify benefits from chemoprevention with tamoxifen or raloxifene. This index can complement clinical evaluation in deciding whether to initiate chemoprevention and in comparing the benefits and risks of raloxifene versus tamoxifen.
The Multiple Roles of Osteoclasts in Host Defense: Bone Remodeling and Hematopoietic Stem Cell Mobilization
Authors: Orit Kollet, Ayelet Dar, Tsvee Lapidot
Journal: Annual Review of Immunology (2006)

Bone remodeling by bone-forming osteoblasts and bone-resorbing osteoclasts dynamically alters the bone inner wall and the endosteum region, which harbors osteoblastic niches for hematopoietic stem cells. Investigators have recently elucidated mechanisms of recruitment and mobilization; these mechanisms consist of stress signals that drive migration of leukocytes and progenitor cells from the bone marrow reservoir to the circulation and drive their homing to injured tissues as part of host defense and repair. The physical bone marrow vasculature barrier that is crossed by mobilized cells actively transmits chemotactic signals between the blood and the bone marrow, facilitating organ communication and cell trafficking. Osteoclasts play a dual role in regulation of bone resorption and homeostatic release or stress-induced mobilization of hematopoietic stem/progenitor cells. In this review, we discuss the orchestrated interplay between bone remodeling, the immune system, and the endosteal stem cell niches in the context of stem cell proliferation and migration during homeostasis, which are accelerated during alarm situations.
Phase II Study of Anti–Gastrin-17 Antibodies, Raised to G17DT, in Advanced Pancreatic Cancer
Authors: B. T. Brett, S. C. Smith, C. V. Bouvier, D. Michaeli, D. Hochhauser, B. R. Davidson, T. R. Kurzawinski, A. F. Watkinson, N. Van Someren, R. E. Pounder, M. E. Caplin
Journal: Journal of Clinical Oncology (2002)

The prognosis for advanced pancreatic cancer remains poor. Gastrin acts as a growth factor for pancreatic cancer. We describe the first study of the antigastrin immunogen G17DT in pancreatic cancer. Our aims were to determine the antibody response, safety, tolerability, and preliminary evidence of efficacy of G17DT in advanced pancreatic cancer.Thirty patients with advanced pancreatic cancer were immunized with three doses of either 100 micro g or 250 micro g of G17DT.In the whole group, 20 (67%) of 30 patients produced an antibody response. The 250- micro g dose resulted in a significantly greater response rate of 82% compared with 46% for the 100- micro g group (P =.018). The most significant side effects, seen in three patients, were local abscess and/or fever. The median survival for the whole group from the date of the first immunization was 187 days; median survival was 217 days for the antibody responders and 121 days for the antibody nonresponders. The difference in survival between the antibody responders and nonresponders was significant (P =.0023).Patients with advanced pancreatic cancer are able to mount an adequate antibody response to G17DT. The 250- micro g dose is superior to the 100- micro g dose, and it appears to be generally well tolerated. Antibody responders demonstrate significantly greater survival than antibody nonresponders. Phase III studies are currently underway in order to determine efficacy.
Effects of Alcohol and Sleep Restriction on Simulated Driving Performance in Untreated Patients With Obstructive Sleep Apnea
Authors: Andrew Vakulin, Stuart D. Baulk, Peter G. Catcheside, Nick A. Antic, Cameron J. van den Heuvel, Jillian Dorrian, R. Doug McEvoy
Journal: Annals of Internal Medicine (2009)

Background: Because of previous sleep disturbance and sleep hypoxia, patients with obstructive sleep apnea (OSA) might be more vulnerable to the effects of alcohol and sleep restriction than healthy persons. Objective: To compare the effects of sleep restriction and alcohol on driving simulator performance in patients with OSA and age-matched control participants. Design: Driving simulator assessments in 2 groups under 3 different conditions presented in random order. Setting: Adelaide Institute for Sleep Health, Sleep Laboratory, Adelaide, Australia. Participants: 38 untreated patients with OSA and 20 control participants. Measurements: Steering deviation, crashes, and braking reaction time. Intervention: Unrestricted sleep, sleep restricted to a maximum of 4 hours, and ingestion of an amount of 40% vodka calculated to achieve a blood alcohol level of 0.05 g/dL. Results: Patients with OSA demonstrated increased steering deviation compared with control participants (mean, 50.5 cm [95% CI, 46.1 to 54.9 cm] in the OSA group and 38.4 cm [CI, 32.4 to 44.4 cm] in the control group; P < 0.01) and significantly greater steering deterioration over time (group by time interaction, P = 0.02). The increase in steering deviation after sleep restriction and alcohol was approximately 40% greater in patients with OSA than in control participants (group by condition interaction, P = 0.04). Patients with OSA crashed more frequently than control participants (1 vs. 24 participants; odds ratio [OR], 25.4; P = 0.03) and crashed more frequently after sleep restriction (OR, 4.0; P < 0.01) and alcohol consumption (OR, 2.3; P = 0.02) than after normal sleep. In patients with OSA, prolonged eye closure (>2 seconds) and microsleeps (> 2 seconds of theta activity on electroencephalography) were significant crash predictors (OR, 19.2 and 7.2, respectively; P < 0.01). Braking reaction time was slower after sleep restriction than after normal sleep (mean, 1.39 [SD, 0.06] seconds vs. 1.22 [SD, 0.04] seconds; P < 0.01) but not after alcohol consumption. No group differences were found. Limitation: Simulated driving was assessed rather than on-road driving. Conclusion: Patients with OSA are more vulnerable than healthy persons to the effects of alcohol consumption and sleep restriction on various driving performance variables. Primary Funding Source: Australian National Health and Medical Research Council.
Processed and Unprocessed Red Meat Consumption and Incident Type 2 Diabetes Among French Women
Authors: Martin Lajous, Laura Tondeur, Guy Fagherazzi, Blandine de Lauzon-Guillain, Marie-Christine Boutron-Ruaualt, Françoise Clavel-Chapelon
Journal: Diabetes Care (2011)

To evaluate the relation of processed and unprocessed red meat and incident type 2 diabetes.We conducted a prospective study among 66,118 disease-free French women with dietary information from a validated questionnaire. Between 1993 and 2007, we identified 1,369 cases of incident diabetes. Multivariate analyses were adjusted for age, education, region, smoking, BMI, hypertension, hypercholesterolemia, physical activity, parental history of diabetes, menopause, hormone replacement therapy, alcohol, calories, n-3 fatty acids, carbohydrates, coffee, fiber, and fruits and vegetables.Comparing the highest category of processed meat intake, ≥5 servings/week (median, 48 g/day), to the lowest, <1 serving/week (median, 5 g/day), processed meat was significantly associated with incident diabetes (hazard ratio 1.30 [95% CI 1.07-1.59], P trend = 0.0007; for 1 serving/day, 1.29 [1.14-1.45]). Unprocessed red meat was not associated with diabetes.In this large prospective cohort of French women, a direct association was observed only for processed red meat and type 2 diabetes.
Intravenous Transfusion of Endothelial Progenitor Cells Reduces Neointima Formation After Vascular Injury
Authors: Nikos Werner, Stefan Junk, Ulrich Laufs, Andreas Link, Katrin Walenta, Michael Böhm, Georg Nickenig
Journal: Circulation Research (2003)

Endothelial cell damage is one important pathophysiological step of atherosclerosis and restenosis after angioplasty. Accelerated reendothelialization impairs neointima formation. We evaluated the role of intravenously transfused endothelial progenitor cells (EPCs) on reendothelialization and neointima formation in a mouse model of arterial injury. Spleen-derived mouse mononuclear cells (MNCs) were cultured in endothelial basal medium. A total of 91.8+/-3.2% of adherent cells showed uptake of acetylated low-density lipoprotein (Dil-Ac-LDL) and lectin binding after 4 days. Immunostaining and long-term cultures confirmed the endothelial progenitor phenotype. To determine the effect of stem cell transfusion on reendothelialization, mice received either fluorescent-labeled spleen-derived MNCs or in vitro differentiated EPCs intravenously after endothelial injury of the carotid artery. Transfused cells were strictly restricted to the injury site, and lectin binding confirmed the endothelial phenotype. Homing of transfused cells to the site of injury was only detectable in splenectomized mice. Cell transfusion caused enhanced reendothelialization associated with a reduction of neointima formation. Systemically applied spleen-derived MNCs and EPCs home to the site of vascular injury, resulting in an enhanced reendothelialization associated with decreased neointima formation. These results allow novel insights in stem cell biology and provide additional information for the treatment of vascular dysfunction and prevention of restenosis after angioplasty. The full text of this article is available online at http://www.circresaha.org.
A Role for <i>VAV1</i> in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis
Authors: Maja Jagodic, Celine Colacios, Rita Nohra, Anne S. Dejean, Amennai Daniel Beyeen, Mohsen Khademi, Audrey Casemayou, Lucille Lamouroux, Christine Duthoit, Olivier Papapietro, Louise Sjöholm, Isabelle Bernard, Dominique Lagrange, Ingrid Dahlman, Frida Lundmark, Annette B. Oturai, Helle B. Soendergaard, Anu Kemppinen, Janna Saarela, Pentti J. Tienari, Hanne F. Harbo, Anne Spurkland, Sreeram V. Ramagopalan, Dessa A. Sadovnick, George C. Ebers, Maria Seddighzadeh, Lars Klareskog, Lars Alfredsson, Leonid Padyukov, Jan Hillert, Michel Clanet, Gilles Edan, Bertrand Fontaine, Gilbert J. Fournié, Ingrid Kockum, Abdelhadi Saoudi, Tomas Olsson
Journal: Science Translational Medicine (2009)

VAV1 plays a role in regulating proinflammatory cytokines, which underlie the susceptibility for developing experimental autoimmune encephalomyelitis and multiple sclerosis.
Circulating Levels of Secretory Type II Phospholipase A <sub>2</sub> Predict Coronary Events in Patients with Coronary Artery Disease
Authors: Kiyotaka Kugiyama, Yasutaka Ota, Keiji Takazoe, Yasushi Moriyama, Hiroaki Kawano, Yuji Miyao, Tomohiro Sakamoto, Hirofumi Soejima, Hisao Ogawa, Hideki Doi, Seigo Sugiyama, Hirofumi Yasue
Journal: Circulation (1999)

Background —The circulating levels of secretory nonpancreatic type II phospholipase A 2 (sPLA 2 ) are increased in various chronic inflammatory diseases and the increase in the levels correlates with the disease severity. sPLA 2 may possibly play a role in atherogenesis and is highly expressed in atherosclerotic arterial walls that are known to have inflammatory features. Thus, this study prospectively examined whether circulating levels of sPLA 2 may have a significant risk and prognostic values in patients with coronary artery disease (CAD). Methods and Results —Plasma levels of sPLA 2 were measured in 142 patients with CAD and in 93 control subjects by a radioimmunoassay. The sPLA 2 levels had a significant and positive relations with serum levels of C-reactive protein, a marker of systemic inflammation, and with the number of the traditional coronary risk factors associated with individuals. Multivariate logistic regression analysis showed that higher levels of sPLA 2 (&gt;246 ng/dL; 75th percentile of sPLA 2 distribution in controls) were a significant and independent risk factor for the presence of CAD. In multivariate Cox hazard analysis, the higher levels of sPLA 2 were a significant predictor of developing coronary events (ie, coronary revascularization, myocardial infarction, coronary death) during a 2-year follow-up period in patients with CAD independent of other risk factors, including CRP levels, an established inflammatory predictor. Conclusions —The increase in circulating levels of sPLA 2 is a significant risk factor for the presence of CAD and predicts clinical coronary events independent of other risk factors in patients with CAD; these results may reflect possible relation of sPLA 2 levels with inflammatory activity in atherosclerotic arteries.
Differentiation Between Papillary and Nonpapillary Renal Cell Carcinomas by DNA Analysis
Authors: G. Kovacs, L. Wilkens, T. Papp, W. d. Riese
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Differentiation Between Papillary and Nonpapillary Renal Cell Carcinomas by DNA Analysis Get access Gyula Kovacs, Gyula Kovacs * Lab-oratory of Cytogenetics, Institute of Pathology, Albert-Ludwigs-University, Fed-eral Republic of Germany.Freiburg *Correspondence to: Dr. Gyula Kovacs, Institute of Pathology, Albert-Ludwigs-University, Albert Str. 19, D-7800 Freiburg, Federal Republic of Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Ludwig Wilkens, Ludwig Wilkens Lab-oratory of Cytogenetics, Institute of Pathology, Albert-Ludwigs-University, Fed-eral Republic of Germany.Freiburg Search for other works by this author on: Oxford Academic PubMed Google Scholar Thilo Papp, Thilo Papp Lab-oratory of Cytogenetics, Institute of Pathology, Albert-Ludwigs-University, Fed-eral Republic of Germany.Freiburg Search for other works by this author on: Oxford Academic PubMed Google Scholar Werner de Riese Werner de Riese Department of Urology, HannoverMedical School, Federal Republic ofGermany.Freiburg Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 7, 5 April 1989, Pages 527–530, https://doi.org/10.1093/jnci/81.7.527 Published: 05 April 1989 Article history Received: 17 November 1988 Revision received: 04 January 1989 Accepted: 23 January 1989 Published: 05 April 1989
Comparing coping strategies, accident history and driving simulator (MiniUoLDS) outcome in obstructive sleep apnoea syndrome (OSAS) patients and controls
Authors: Akshay Dwarakanath, Dipansu Ghosh, Samantha Jamson, Mark Elliott
Journal: European Respiratory Journal (2014)

Introduction   Any driver who starts to feel tired while driving should have a rest, but some may use various strategies to stay alert.A questionnaire was devised to assess various frequently used coping strategies between OSAS patients and controls and this was compared it with previous accident history,sleepiness while driving and MiniUoLDS outcome.   Methods   97 (52+/-11 yrs,ESS-13+/- 8,ODI-38+/- 26) untreated OSAS patients and 35 controls (61+/-11 yrs,ESS-5+/- 3) completed a questionnaire,which included previous accident history,sleepiness while driving and ten coping strategies they adapt in order to stay awake in the last one year.They were asked to rate on a scale,from “not frequently” to “frequently”.All performed a 90km motorway driving simulation.   Results   OSAS patients as compared to controls frequently use coping strategies (P-0.004,OR-3.6),were more likely to fail the MiniUoLDS (P-0.04,OR-9.3) and admit sleepiness while driving (P-0.02,OR-8.5).  However there was no difference in the accident history between the two groups (P-0.89).   Conclusion   OSAS patients report frequent use of coping strategies and those who frequently used such strategies failed the MiniUoLDS.Asking about such strategies may aid the clinician in identifying the patients at risk.
Modeling synthetic lethality
Authors: Nolwenn Le Meur, Robert Gentleman
Journal: Genome biology (2008)

Synthetic lethality defines a genetic interaction where the combination of mutations in two or more genes leads to cell death. The implications of synthetic lethal screens have been discussed in the context of drug development as synthetic lethal pairs could be used to selectively kill cancer cells, but leave normal cells relatively unharmed. A challenge is to assess genome-wide experimental data and integrate the results to better understand the underlying biological processes. We propose statistical and computational tools that can be used to find relationships between synthetic lethality and cellular organizational units.In Saccharomyces cerevisiae, we identified multi-protein complexes and pairs of multi-protein complexes that share an unusually high number of synthetic genetic interactions. As previously predicted, we found that synthetic lethality can arise from subunits of an essential multi-protein complex or between pairs of multi-protein complexes. Finally, using multi-protein complexes allowed us to take into account the pleiotropic nature of the gene products.Modeling synthetic lethality using current estimates of the yeast interactome is an efficient approach to disentangle some of the complex molecular interactions that drive a cell. Our model in conjunction with applied statistical methods and computational methods provides new tools to better characterize synthetic genetic interactions.
Erdheim–Chester disease
Authors: Montserrat Juanós-Iborra, Javier Solanich-Moreno, Albert Selva-O'Callaghan
Journal: Annals of the Rheumatic Diseases (2013)

We read with interest the excellent study published by Cavalli et al 1 in Annals of the Rheumatic Diseases and wish to voice our concerns. Although heterogeneity is the rule in the clinical presentation of patients with Erdheim–Chester disease (ECD), …
Multicenter Phase II Trial of Sunitinib in the Treatment of Nongastrointestinal Stromal Tumor Sarcomas
Authors: Suzanne George, Priscilla Merriam, Robert G. Maki, Annick D. Van den Abbeele, Jeffrey T. Yap, Timothy Akhurst, David C. Harmon, Gauri Bhuchar, Margaret M. O'Mara, David R. D'Adamo, Jeffrey Morgan, Gary K. Schwartz, Andrew J. Wagner, James E. Butrynski, George D. Demetri, Mary L. Keohan
Journal: Journal of Clinical Oncology (2009)

PURPOSE To evaluate the potential benefit of continuous daily dosing sunitinib in patients with advanced nongastrointestinal stromal tumor (GIST) sarcomas. PATIENTS AND METHODS A total of 53 patients with advanced non-GIST soft tissue sarcomas received sunitinib 37.5 mg daily. Primary end point was Response Evaluation Criteria in Solid Tumors defined response. Secondary end points were stable disease at 16 and 24 weeks. [(18)F]-fluorodeoxyglucose positron emission tomography was performed on a subset of 24 patients at baseline and after 10 to 14 days of therapy. Results Forty-eight patients were eligible for response. One patient (desmoplastic round cell tumor [DSRCT]) achieved a confirmed partial response (PR) and remained on study for 56 weeks. Ten patients (20%) achieved stable disease for at least 16 weeks. Metabolic PR was seen in 10 (47%) of 21 of patients. Metabolic stable disease was seen in 11 (52%) of 21. There were no unexpected toxicities observed. CONCLUSION Sunitinib demonstrated notable evidence of metabolic response in several patients with non-GIST sarcoma. The relevance of disease control observed in subtypes with an indolent natural history is unknown, however, the durable disease control observed in DSRCT, solitary fibrous tumor, and giant cell tumor of bone suggests that future evaluation of sunitinib in these subtypes may be warranted.
The expanding world of stem cell modeling of Huntington's disease: creating tools with a promising future
Authors: Jacqueline M Ward, Albert R La Spada
Journal: Genome Medicine (2012)

Deconstructing the mechanistic basis of neurodegenerative disorders, such as Huntington's disease (HD), has been a particularly challenging undertaking, relying mostly on post-mortem tissue samples, non-neural cell lines from affected individuals, and model organisms. Two articles recently published in Cell Stem Cell report first the generation and characterization of induced pluripotent stem cell (iPSC)-derived models for HD, and second, the genetic correction of a disease-causing CAG expansion mutation in iPSCs from individuals with HD. Taken together, these two studies provide a framework for the production and validation of iPSC materials for human neurodegenerative disease research and yield crucial tools for investigating future therapies.
Dietary Glycemic Load and Risk of Colorectal Cancer in the Women's Health Study
Authors: Susan Higginbotham, Zuo-Feng Zhang, I-Min Lee, Nancy R Cook, Edward Giovannucci, Julie E Buring, Simin Liu
Journal: JNCI Journal of the National Cancer Institute (2004)

Although diet is believed to influence colorectal cancer risk, the long-term effects of a diet with a high glycemic load are unclear. The growing recognition that colorectal cancer may be promoted by hyperinsulinemia and insulin resistance suggests that a diet inducing high blood glucose levels and an elevated insulin response may contribute to a metabolic environment conducive to tumor growth. We prospectively followed a cohort of 38 451 women for an average of 7.9 years and identified 174 with incident colorectal cancer. We used baseline dietary intake measurements, assessed with a semiquantitative food-frequency questionnaire, to examine the associations of dietary glycemic load, overall dietary glycemic index, carbohydrate, fiber, nonfiber carbohydrate, sucrose, and fructose with the subsequent development of colorectal cancer. Cox proportional hazards models were used to estimate relative risks (RRs). Dietary glycemic load was statistically significantly associated with an increased risk of colorectal cancer (adjusted RR = 2.85, 95% confidence interval [CI] = 1.40 to 5.80, comparing extreme quintiles of dietary glycemic load; Ptrend = .004) and was associated, although not statistically significantly, with overall glycemic index (corresponding RR = 1.71, 95% CI = 0.98 to 2.98; Ptrend = .04). Total carbohydrate (adjusted RR = 2.41, 95% CI = 1.10 to 5.27, comparing extreme quintiles of carbohydrate; Ptrend = .02), nonfiber carbohydrate (corresponding RR = 2.60, 95% CI = 1.22 to 5.54; Ptrend = .02), and fructose (corresponding RR = 2.09, 95% CI = 1.13 to 3.87; Ptrend = .08) were also statistically significantly associated with increased risk. Thus, our data indicate that a diet with a high dietary glycemic load may increase the risk of colorectal cancer in women.