tbuckley/cabot-search huggingface dataset:
A Molecular Signature of the Nottingham Prognostic Index in Breast Cancer
Authors: Kun Yu, Chee How Lee, Puay Hoon Tan, Ga Sze Hong, Siew Bok Wee, Chow Yin Wong, Patrick Tan
Journal: Cancer Research (2004)

Abstract The Nottingham prognostic index (NPI) is a widely used clinicopathological staging system for breast cancer prognostication. Using a step-wise classification approach where breast tumor expression profiles were first divided into general “molecular subtypes” [estrogen receptor (ER)+, ER−, ERBB2+], followed by an independent analysis of each subtype, we identified a 62-gene expression signature (NPI-ES) highly correlated to the NPI in ER+ tumors. The NPI-ES classified the majority of ER+ tumors into two distinct groups with high confidence and was significantly correlated to NPI status in two independent sets of ER+ tumors derived from different centers. The NPI-ES is comparable to the classical NPI in identifying patients likely to exhibit a poor clinical prognosis, as well as to a recently described “prognosis signature” for breast cancer. Our findings demonstrate how expression profiling can complement classical staging systems employing histopathological parameters scored over a continuous range of values.
Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case–control study
Authors: Owen A Ross, Alexandra I Soto-Ortolaza, Michael G Heckman, Jan O Aasly, Nadine Abahuni, Grazia Annesi, Justin A Bacon, Soraya Bardien, Maria Bozi, Alexis Brice, Laura Brighina, Christine Van Broeckhoven, Jonathan Carr, Marie-Christine Chartier-Harlin, Efthimios Dardiotis, Dennis W Dickson, Nancy N Diehl, Alexis Elbaz, Carlo Ferrarese, Alessandro Ferraris, Brian Fiske, J Mark Gibson, Rachel Gibson, Georgios M Hadjigeorgiou, Nobutaka Hattori, John PA Ioannidis, Barbara Jasinska-Myga, Beom S Jeon, Yun Joong Kim, Christine Klein, Rejko Kruger, Elli Kyratzi, Suzanne Lesage, Chin-Hsien Lin, Timothy Lynch, Demetrius M Maraganore, George D Mellick, Eugénie Mutez, Christer Nilsson, Grzegorz Opala, Sung Sup Park, Andreas Puschmann, Aldo Quattrone, Manu Sharma, Peter A Silburn, Young Ho Sohn, Leonidas Stefanis, Vera Tadic, Jessie Theuns, Hiroyuki Tomiyama, Ryan J Uitti, Enza Maria Valente, Simone van de Loo, Demetrios K Vassilatis, Carles Vilariño-Güell, Linda R White, Karin Wirdefeldt, Zbigniew K Wszolek, Ruey-Meei Wu, Matthew J Farrer
Journal: The Lancet Neurology (2011)
Confinement-optimized three-dimensional T cell amoeboid motility is modulated via myosin IIA–regulated adhesions
Authors: Jordan Jacobelli, Rachel S Friedman, Mary Anne Conti, Ana-Maria Lennon-Dumenil, Matthieu Piel, Caitlin M Sorensen, Robert S Adelstein, Matthew F Krummel
Journal: Nature Immunology (2010)
Inhibitory effect of imatinib on normal progenitor cells in vitro
Authors: Kerol Bartolovic, Stefan Balabanov, Ulrike Hartmann, Martina Komor, Andreas M. Boehmler, Hans-Jörg Bühring, Robert Möhle, Dieter Hoelzer, Lothar Kanz, Wolf-Karsten Hofmann, Tim H. Brümmendorf
Journal: Blood (2003)
The Wnt/β-catenin pathway regulates growth and maintenance of colonospheres
Authors: Shailender S Kanwar, Yingjie Yu, Jyoti Nautiyal, Bhaumik B Patel, Adhip PN Majumdar
Journal: Molecular Cancer (2010)

Abstract Background Recent evidence suggests that epithelial cancers, including colorectal cancer are driven by a small sub-population of self-renewing, multi-potent cells termed cancer stem cells (CSCs) which are thought to be responsible for recurrence of cancer. One of the characteristics of CSCs is their ability to form floating spheroids under anchorage-independent conditions in a serum-free defined media. The current investigation was undertaken to examine the role of Wnt/β-catenin pathway in regulating the growth and maintenance of colonospheres. Human colon cancer cells HCT-116 (p53 wild type; K-ras mutant), HCT-116 (p53 null; K-ras mutant) and HT-29 (p53 mutant) were used. Results Colonospheres formed in vitro exhibited higher expression of colon CSCs markers LGR5, CD44, CD166 and Musashi-1 along with putative CSC marker EpCAM, compared to the corresponding parental cancer cells and also exhibit the ability to form spheroids under extreme limiting dilution, indicating the predominance of CSCs in colonospheres. Colonospheres formed by HCT-116 cells show over 80% of the cells to be CD44 positive, compared to ≤ 1% in the corresponding parental cells. Additionally, colonospheres showed reduced membrane bound β-catenin but had increased levels of total β-catenin, cyclin-D1 and c-myc and down regulation of axin-1 and phosphorylated β-catenin. Increased expression of β-catenin was associated with a marked transcriptional activation of TCF/LEF. The latter was greatly decreased following down regulation of β-catenin by the corresponding siRNA, leading to a marked reduction in CD44 positive cells as well as colonospheres formation. In contrast, upregulation of c-myc, a down-stream effector of TCF/LEF greatly augmented the formation of colonospheres. Conclusion Our data suggest that colonospheres formed by colon cancer cell lines are highly enriched in CSCs and that Wnt/β-catenin pathway plays a critical role in growth and maintenance of colonospheres.
Quantitative DNA Fingerprinting May Distinguish New Primary Breast Cancer From Disease Recurrence
Authors: Benjamin L. Schlechter, Qiong Yang, Pamela S. Larson, Arina Golubeva, Rita A. Blanchard, Antonio de Las Morenas, Carol L. Rosenberg
Journal: Journal of Clinical Oncology (2004)

Approximately 10% of women with breast cancer develop a second breast tumor, either a new primary or a recurrence. Differentiating between these entities using standard clinical and pathologic criteria remains challenging. Ambiguous cases arise, and misclassifications may occur. We investigated whether quantitative DNA fingerprinting, based on allele imbalance (AI) or loss of heterozygosity (LOH), could evaluate clonality and distinguish second primary breast cancer from recurrence.We developed a scoring system based on the AI/LOH fingerprints of 20 independent breast tumors and generated a decision rule to classify any breast tumor pair as related or unrelated. We validated this approach on eight related tumors (cancers and synchronous positive lymph nodes). Finally, we analyzed paired tumors from 13 women (bilateral cancers, primary tumors and contralateral positive axillary lymph nodes, or two ipsilateral tumors). Each pair's genetic classification was compared with their clinical diagnosis and outcome.Each independent cancer had a unique fingerprint. Every tumor pair's relationship was quantifiable. Six of eight related tumor pairs were genetically classified correctly, two were indeterminate, and none were misclassified. Among the 13 women with two cancers, four of five clinically indeterminate pairs could be classified genetically. In three of 13 women, the pair's classification contradicted the clinical diagnosis. These women had bilateral cancers genetically classified as related and disease progression. This challenges the paradigm that bilateral cancers represent independent tumors. Overall, women with tumors genetically classified as related had poorer outcomes.Quantitative AI/LOH fingerprinting is a potentially valuable tool to improve diagnosis and optimize treatment for the growing number of second breast malignancies.
Effect of air pollution on daily mortality in Hong Kong.
Authors: C M Wong, S Ma, A J Hedley, T H Lam
Journal: Environmental Health Perspectives (2001)

In different weather conditions, constituents and concentrations of pollutants, personal exposure, and biologic responses to air pollution may vary. In this study we assessed the effects of four air pollutants on mortality in both cool and warm seasons in Hong Kong, a subtropical city. Daily counts of mortality, due to all nonaccidental causes, and cardiovascular and respiratory diseases were modeled with daily pollutant concentrations [24-hr means for nitrogen dioxide, sulfur dioxide, and particulate matter < 10 microm in aerodynamic diameter (PM(10)); 8-hr mean for ozone]. using Poisson regression. We controlled for confounding factors by fitting the terms in models, in line with those recommended by the APHEA (Air Pollution and Health: a European Approach) protocol. Exposure-response relationships in warm and cool seasons were examined using generalized additive modeling. During the cool season, for a linear extrapolation of 10th-90th percentiles in the pollutant concentrations of all oxidant pollutants, NO(2), SO(2), and O(3), we found significant effects on all the mortality outcomes under study, with relative risks (RR) of 1.04-1.10 (p < 0.038, except p = 0.079 for SO(2) on respiratory mortality). We observed consistent positive exposure-response relationships during the cool season but not during the warm season. The effects of PM(10) were marginally significant (RR = 1.06; p = 0.054) for respiratory mortality but not for the other outcomes (p > 0.135). In this subtropical city, local air quality objectives should take into account that air pollution has stronger health effects during the cool rather than warm season and that oxidant pollutants are more important indicators of health effects than particulates.
A Novel Ovarian Xenografting Model to Characterize the Impact of Chemotherapy Agents on Human Primordial Follicle Reserve
Authors: Ozgur Oktem, Kutluk Oktay
Journal: Cancer Research (2007)

Abstract Many chemotherapeutic agents, especially of the alkylating family, alter fertility in premenopausal females. However, it is not practically possible to quantify and characterize the impact of cancer drugs on ovarian reserve in a clinical setting. Thus, our specific aim was to develop a xenograft model to characterize the in vivo impact of chemotherapy agents on human ovary. Ovarian pieces from 24 weeks old abortuses were xenografted s.c. to severe combined immunodeficient mice (n = 52). Animals received either a single dose of 200 mg/kg of cyclophosphamide or the vehicle. Grafts were recovered from the control and treated mice 12 to 72 h after the cyclophosphamide injection and serially sectioned for primordial follicle counts. Apoptosis was assessed with terminal nucleotidyl transferase–mediated nick end labeling (TUNEL) assay. Platelet/endothelial cell adhesion molecule 1 (PECAM-1) staining, as well as intra-vital fluorescein-conjugated lectin and Evans blue labeling were done to assess microvasculature by confocal microscopy. Although there was 12% reduction in primordial follicle density by 12 h following treatment (P &amp;gt; 0.05), the follicle loss increased significantly at 24 h (53%, P &amp;lt; 0.01) and peaked at 48 h (93%, P &amp;lt; 0.0001). TUNEL staining peaked at 12 h, earlier than the diminishment in follicle numbers, and decreased thereafter. Xenograft vascularization pattern was similar to non-xenografted tissue, indicating appropriate in vivo drug delivery. The impact of cyclophosphamide on primordial follicle reserve in our human ovarian xenograft model is consistent with the clinical gonadotoxicity of this drug. Human ovarian xenografting is a promising model to characterize the gonadotoxic effects of current and emerging cancer drugs without a need for lengthy clinical studies. [Cancer Res 2007;67(21):10159–62]
Avoidance of endobronchial intubation
Authors: C. J. O'Connor
Journal: BMJ (2010)

<h3>Background</h3> Childhood maltreatment has been linked to preterm birth (&lt;37 weeks gestation) in some studies, but these findings have been inconsistent, and it remains unclear whether type, timing or severity of maltreatment are associated with risk of preterm birth. The aim of this observational study was to explore type of maltreatment (child and adolescent physical and sexual abuse and harsh parenting) as risk factors for preterm birth. <h3>Methods</h3> We examined these associations in a cross-sectional analysis of the Nurses’ Health Study II cohort of female nurses. Women completed a questionnaire about experiences of sexual abuse, physical abuse or harsh parenting, along with pregnancy outcomes. Logistic regression models adjusted for relevant covariates including age, race, alcohol and cigarette use during pregnancy, age at menarche, marital status, adult income, body mass index (kg/m<sup>2</sup>) at age 18, physical abuse in pregnancy, and childhood socioeconomic position. <h3>Results</h3> Among 51 434 first births, 4110 were preterm (8% of births). Forced sexual activity in childhood or adolescence was associated with a 22% increased odds of preterm birth (OR=1.22, 95% CI 1.10 to 1.35). Maltreatment involving sexual touch, physical abuse or harsh parenting was not associated with preterm birth in this sample. <h3>Conclusions</h3> Women who experience forced sexual activity in childhood or adolescence may have an increased likelihood of delivering preterm in adulthood.
State-of-the-Art Therapeutics: Hodgkin's Lymphoma
Authors: Joseph M. Connors
Journal: Journal of Clinical Oncology (2005)

Presently Hodgkin's lymphoma can be cured in at least 80% of patients. The major challenge to the clinician in 2005 is how to cure the disease while inducing the least irreversible toxicity. This review focuses on clinical trials and institutional experiences to identify the best choice of treatment, individualized to the stage of the lymphoma permitting minimization of late toxicity such as infertility, premature menopause, cardiac disease, and most importantly, risk of second neoplasms. More than 90% of patients with limited Hodgkin's lymphoma can be cured with either short-course chemotherapy alone or even briefer chemotherapy followed by involved-field radiation. Accumulating evidence suggests that chemotherapy alone is suitable for the large majority of patients with limited disease. For the 80% of patients with advanced disease but without a large number of adverse prognostic factors, standard multi-agent chemotherapy with the well-established ABVD regimen (doxorubicin, bleomycin, vinblastine, and dacarbazine) provides the best balance of effectiveness and minimization of toxicity. More intensified regimens currently under investigation are appropriate for the 20% with numerous adverse prognostic factors. In 2005 it is insufficient to focus solely on cure of Hodgkin's lymphoma. The treatment program must maximize chance of cure and minimize late toxicity. Fortunately, brief chemotherapy alone or with radiation for patients with limited disease and standard ABVD chemotherapy for patients with advanced disease offer the appropriate balance of these two requirements. Patients with advanced disease plus multiple indicators of a poor prognosis and patients with disease that persists despite optimized primary treatment require specially intensified treatment.
Roux-en-Y Gastric Bypass Surgery, but Not Calorie Restriction, Reduces Plasma Branched-Chain Amino Acids in Obese Women Independent of Weight Loss or the Presence of Type 2 Diabetes
Authors: Mirjam A. Lips, Jan B. Van Klinken, Vanessa van Harmelen, Harish K. Dharuri, Peter A.C. ’t Hoen, Jeroen F.J. Laros, Gert-Jan van Ommen, Ignace M. Janssen, Bert Van Ramshorst, Bart A. Van Wagensveld, Dingeman J. Swank, Francois Van Dielen, Adrie Dane, Amy Harms, Rob Vreeken, Thomas Hankemeier, Johannes W.A. Smit, Hanno Pijl, Ko Willems van Dijk
Journal: Diabetes Care (2014)

Obesity and type 2 diabetes mellitus (T2DM) have been associated with increased levels of circulating branched-chain amino acids (BCAAs) that may be involved in the pathogenesis of insulin resistance. However, weight loss has not been consistently associated with the reduction of BCAA levels.We included 30 obese normal glucose-tolerant (NGT) subjects, 32 obese subjects with T2DM, and 12 lean female subjects. Obese subjects underwent either a restrictive procedure (gastric banding [GB], a very low-calorie diet [VLCD]), or a restrictive/bypass procedure (Roux-en-Y gastric bypass [RYGB] surgery). Fasting blood samples were taken for the determination of amine group containing metabolites 4 weeks before, as well as 3 weeks and 3 months after the intervention.BCAA levels were higher in T2DM subjects, but not in NGT subjects, compared with lean subjects. Principal component (PC) analysis revealed a concise PC consisting of all BCAAs, which showed a correlation with measures of insulin sensitivity and glucose tolerance. Only after the RYGB procedure, and at both 3 weeks and 3 months, were circulating BCAA levels reduced.Our data confirm an association between deregulation of BCAA metabolism in plasma and insulin resistance and glucose intolerance. Three weeks after undergoing RYGB surgery, a significant decrease in BCAAs in both NGT as well as T2DM subjects was observed. After 3 months, despite inducing significant weight loss, neither GB nor VLCD induced a reduction in BCAA levels. Our results indicate that the bypass procedure of RYGB surgery, independent of weight loss or the presence of T2DM, reduces BCAA levels in obese subjects.
Increasing hepatic cholesterol 7?-hydroxylase reduces plasma cholesterol concentrations in normocholesterolemic and hypercholesterolemic rabbits
Authors: G Xu, G Salen, S Shefer, G C Ness, L B Nguyen, G S Tint, T S Parker, J Roberts, A K Batta, T S Chen, Z Zhao, X Kong
Journal: Hepatology (1996)

The effect of bile acid depletion and replacement with glycodeoxycholic acid on plasma cholesterol concentrations, hepatic low–density lipoprotein (LDL) receptor binding and messenger RNA (mRNA) levels, and hepatic activities and mRNA levels for 3–hydroxy–3–methylglutaryl coenzyme A (HMG–CoA) reductase and cholesterol 7α–hydroxylase was investigated in 19 New Zealand white (NZW) and 15 Watanabe heritable hyperlipidemic (WHHL) rabbits. Bile acid depletion was produced by external bile drainage for 5 days, which maximized cholic acid synthesis. Replacement was achieved by infusing glycodeoxycholic acid intraduodenally for 24 hours so that the hepatic bile acid flux reached prefistula levels. Plasma and liver cholesterol concentrations were 13 times and 50% greater, respectively, hepatic LDL receptor–mediated binding was 26% less, and cholesterol 7α–hydroxylase activity and mRNA levels were 62% and 86% less in WHHL than NZW rabbits. After bile drainage, plasma cholesterol concentrations decreased 29% in NZW rabbits and 40% in WHHL rabbits and were associated with a 2.1–fold increase in hepatic LDL receptor–mediated binding in the NZW rabbits, but there was no change in the WHHL rabbits. Cholesterol 7α– hydroxylase activity and mRNA levels increased three and four times in NZW and WHHL rabbits, respectively, although liver cholesterol levels remained unchanged. Replacement with exogenous glycodeoxycholic acid increased plasma cholesterol concentrations 1.7 times in NZW rabbits and decreased enhanced cholesterol 7α–hydroxylase activity 54%, mRNA levels 86%, cholic acid synthesis 38%, and hepatic LDL receptor– mediated binding 57% in NZW rabbits. Bile acid depletion stimulated cholic acid synthesis by up–regulating cholesterol 7α–hydroxylase to use cholesterol and reduce plasma concentrations substantially in both NZW and WHHL rabbits, although LDL receptors did not function in WHHL rabbits. Glycodeoxycholic acid replacement inhibited elevated cholesterol 7α–hydroxylase, cholic acid synthesis, and hepatic LDL receptor binding to reestablish baseline plasma cholesterol levels in NZW rabbits. Hypercholesterolemia in WHHL rabbits was related to the combination of dysfunctional LDL receptors and inhibited cholesterol 7α–hydroxylase. Plasma cholesterol concentrations were reduced significantly when cholesterol 7α–hydroxylase was stimulated even in the absence of LDL receptor function.
Event-Free Survival at 24 Months Is a Robust End Point for Disease-Related Outcome in Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy
Authors: Matthew J. Maurer, Hervé Ghesquières, Jean-Philippe Jais, Thomas E. Witzig, Corinne Haioun, Carrie A. Thompson, Richard Delarue, Ivana N. Micallef, Frédéric Peyrade, William R. Macon, Thierry Jo Molina, Nicolas Ketterer, Sergei I. Syrbu, Olivier Fitoussi, Paul J. Kurtin, Cristine Allmer, Emmanuelle Nicolas-Virelizier, Susan L. Slager, Thomas M. Habermann, Brian K. Link, Gilles Salles, Hervé Tilly, James R. Cerhan
Journal: Journal of Clinical Oncology (2014)

Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data.Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France.In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL.Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.