tbuckley/cabot-search huggingface dataset:
Does dietary folate intake modify effect of alcohol consumption on breast cancer risk? Prospective cohort study
Authors: Laura Baglietto, Dallas R English, Dorota M Gertig, John L Hopper, Graham G Giles
Journal: BMJ (2005)

To evaluate the effect of dietary folate intake on the relation between alcohol consumption and breast cancer risk.Prospective cohort study.Melbourne, Australia.17,447 Anglo-Australian women resident in Melbourne, aged 40-69 years at recruitment in 1990-4, and followed up until 31 December 2003.Invasive breast cancers diagnosed during follow-up and ascertained through the Victorian cancer registry.537 invasive breast cancers were diagnosed. Compared with lifetime abstainers, the hazard ratio for breast cancer in women who consumed an average of 40 g or more of alcohol daily at baseline was 1.41 (95% confidence interval 0.90 to 2.23). No direct association was found between dietary folate intake and risk of breast cancer, but a high folate intake mitigated the excess risk associated with alcohol. The estimated hazard ratio of an alcohol consumption of 40 g/day or more was 2.00 (1.14 to 3.49) for women with intakes of 200 mug/day of folate and 0.77 (0.33 to 1.80) for 400 mug/day of folate (P = 0.04 for interaction between alcohol and folate).An adequate dietary intake of folate might protect against the increased risk of breast cancer associated with alcohol consumption.
Meta-analysis of human cancer microarrays reveals GATA3 is integral to the estrogen receptor alpha pathway
Authors: Brian J Wilson, Vincent Giguere
Journal: Molecular Cancer (2008)

The transcription factor GATA3 has recently been shown to be necessary for mammary gland morphogenesis and luminal cell differentiation. There is also an increasing body of data linking GATA3 to the estrogen receptor alpha (ERalpha) pathway. Among these it was shown that GATA3 associates with the promoter of the ERalpha gene and ERalpha can reciprocally associate with the GATA3 gene. GATA3 has also been directly implicated in a differentiated phenotype in mouse models of mammary tumourigenesis. The purpose of our study was to compare coexpressed genes, by meta-analysis, of GATA3 and relate these to a similar analysis for ERalpha to determine the depth of overlap.We have used a newly described method of meta-analysis of multiple cancer studies within the Oncomine database, focusing here predominantly upon breast cancer studies. We demonstrate that ERalpha and GATA3 reciprocally have the highest overlap with one another. Furthermore, we show that when both coexpression meta-analysis lists for ERalpha and GATA3 are compared there is a significant overlap between both and, like ERalpha, GATA3 coexpresses with ERalpha pathway partners such as pS2 (TFF1), TFF3, FOXA1, BCL2, ERBB4, XBP1, NRIP1, IL6ST, keratin 18(KRT18) and cyclin D1 (CCND1). Moreover, as these data are derived from human tumour samples this adds credence to previous cell-culture or murine based studies.GATA3 is hypothesized to be integral to the ERalpha pathway given the following: (1) The large overlap of coexpressed genes as seen by meta-analysis, between GATA3 and ERalpha, (2) The highest coexpressing gene for GATA3 was ERalpha and vice-versa, (3) GATA3, like ERalpha, coexpresses with many well-known ERalpha pathway partners such as pS2.
LYN Is a Mediator of Epithelial-Mesenchymal Transition and a Target of Dasatinib in Breast Cancer
Authors: Yoon-La Choi, Melanie Bocanegra, Mi Jeong Kwon, Young Kee Shin, Seok Jin Nam, Jung-Hyun Yang, Jessica Kao, Andrew K. Godwin, Jonathan R. Pollack
Journal: Cancer Research (2010)

Abstract Epithelial-mesenchymal transition (EMT), a switch of polarized epithelial cells to a migratory, fibroblastoid phenotype, is considered a key process driving tumor cell invasiveness and metastasis. Using breast cancer cell lines as a model system, we sought to discover gene expression signatures of EMT with clinical and mechanistic relevance. A supervised comparison of epithelial and mesenchymal breast cancer lines defined a 200-gene EMT signature that was prognostic across multiple breast cancer cohorts. The immunostaining of LYN, a top-ranked EMT signature gene and Src-family tyrosine kinase, was associated with significantly shorter overall survival (P = 0.02) and correlated with the basal-like (“triple-negative”) phenotype. In mesenchymal breast cancer lines, RNAi-mediated knockdown of LYN inhibited cell migration and invasion, but not proliferation. Dasatinib, a dual-specificity tyrosine kinase inhibitor, also blocked invasion (but not proliferation) at nanomolar concentrations that inhibit LYN kinase activity, suggesting that LYN is a likely target and that invasion is a relevant end point for dasatinib therapy. Our findings define a prognostically relevant EMT signature in breast cancer and identify LYN as a mediator of invasion and a possible new therapeutic target (and theranostic marker for dasatinib response), with particular relevance to clinically aggressive basal-like breast cancer. Cancer Res; 70(6); 2296–306
Inducible Nitric Oxide Synthase Contributes to Ventilator-induced Lung Injury
Authors: Xinqi Peng, Raja-Elie E. Abdulnour, Saad Sammani, Shwu-Fan Ma, Eugenia J. Han, Emile J. Hasan, Rubin Tuder, Joe G. N. Garcia, Paul M. Hassoun
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Inducible nitric oxide synthase (iNOS) has been implicated in the development of acute lung injury. Recent studies indicate a role for mechanical stress in iNOS and endothelial NOS (eNOS) regulation.This study investigated changes in lung NOS expression and activity in a mouse model of ventilator-induced lung injury.C57BL/6J (wild-type [WT]) and iNOS-deficient (iNOS(-/-)) mice received spontaneous ventilation (control) or mechanical ventilation (MV; VT of 7 and 20 ml/kg) for 2 hours, after which NOS gene expression and activity were determined and pulmonary capillary leakage assessed by the Evans blue albumin assay.iNOS mRNA and protein expression was absent in iNOS(-/-) mice, minimal in WT control mice, but significantly upregulated in response to 2 hours of MV. In contrast, eNOS protein was decreased in WT mice, and nonsignificantly increased in iNOS(-/-) mice, as compared with control animals. iNOS and eNOS activities followed similar patterns in WT and iNOS(-/-) mice. MV caused acute lung injury as suggested by cell infiltration and nitrotyrosine accumulation in the lung, and a significant increase in bronchoalveolar lavage cell count in WT mice, findings that were reduced in iNOS(-/-) mice. Finally, Evans blue albumin accumulation in lungs of WT mice was significant (50 vs. 15% increase in iNOS(-/-) mice compared with control animals) in response to MV and was prevented by treatment of the animals with the iNOS inhibitor aminoguanidine.Taken together, our results indicate that iNOS gene expression and activity are significantly upregulated and contribute to lung edema in ventilator-induced lung injury.
Looking forward: Getting research findings into practice: Making better use of research findings
Authors: A. Haines, A. Donald
Journal: BMJ (1998)

This is the first in a series of eight articles analysing the gap between research and practice

Series editors: Andrew Haines and Anna Donald

There is increasing interest in implementing research findings in practice both because of a growing awareness of the gap between clinical practice and the findings of research and also because of the need to show that public investment in research results in benefits for patients. Improved understanding of the reasons for the uptake of research findings requires insights from a range of disciplines. In order to promote the uptake of research findings it is necessary to identify potential barriers to implementation and to develop strategies to overcome them. Specific interventions that can be used to promote change in practice include using clinical guidelines and computerised decision support systems, developing educational programmes, communicating research findings to patients, and developing strategies for organisational change.

Interest in how best to promote the uptake of research findings has been fuelled by a number of factors including the well documented disparities between clinical practice and research evidence of effective interventions. Examples include interventions in the management of cardiac failure, secondary prevention of heart disease,1 atrial fibrillation,2 menorrhagia,3 and pregnancy and childbirth.4 In the United Kingdom the advent of the NHS research and development programme has led to greater involvement of NHS personnel in setting priorities5 and to the establishment of a programme to evaluate different methods of promoting the implementation of research findings.6 The concept of pay back on research7 has also been developed, resulting in a framework that can be used to assess the benefits arising from research.

Relying on the passive diffusion of information to keep health professionals' knowledge up to date is doomed to failure in a global environment in which …
Estimating the Number of Paediatric Fevers Associated with Malaria Infection Presenting to Africa's Public Health Sector in 2007
Authors: Peter W. Gething, Viola C. Kirui, Victor A. Alegana, Emelda A. Okiro, Abdisalan M. Noor, Robert W. Snow
Journal: PLoS Medicine (2010)

Peter Gething and colleagues compute the number of fevers likely to present to public health facilities in Africa and the estimated number of these fevers likely to be infected with Plasmodium falciparum malaria parasites.
LOCALIZATION OF PNEUMOCOCCI IN THE LUNGS OF PARTIALLY IMMUNIZED MICE FOLLOWING INHALATION OF PNEUMOCOCCI
Authors: Ernest G. Stillman, Arnold Branch
Journal: The Journal of Experimental Medicine (1931)

1. When mice are passively immunized by the intraperitoneal injection of antipneumococcus horse serum or actively by the injection of heat-killed pneumococcus cultures, and are then alcoholized and sprayed with a culture of pneumococci of the same type as that of the bacteria employed in immunization, a considerable number die with localized lesions in the lungs. 2. If instead of injecting immune serum of the type corresponding to that of the bacteria employed in producing the infection, normal horse serum or immune serum of a heterologous type be injected, or if the animals be previously immunized by the injection of killed pneumococci of a heterologous type, none of the animals which die show any evidence of localization of the infection in the lung. 3. The occurrence of pulmonary lesions in alcoholized mice after spraying with a culture of pneumococci is the consequence of a general immunity of a very mild grade.
Regional distribution and alterations of lectin binding to colorectal mucin in mucosal biopsies from controls and subjects with inflammatory bowel diseases.
Authors: L R Jacobs, P W Huber
Journal: Journal of Clinical Investigation (1985)

Glycoconjugate composition of colorectal goblet cell mucin was characterized according to the anatomical distribution of lectin-binding sites in mucosal biopsies from 35 control subjects and 55 patients with inflammatory bowel disease. 24 of the controls had mucosal inflammation on biopsy, without clinical evidence of inflammatory bowel disease. These inflamed controls showed a similar rate of presence of lectin-binding sites as the normal noninflamed group. In the controls, the frequency of binding of Ricinus communis agglutinin I to galactosyl residues was consistently higher than that found with either Ulex europaeus agglutinin I to fucosyl or Dolichus biflorus agglutinin to N-acetyl galactosyl groups. A significant proximal to distal gradient for Ulex europaeus agglutinin I binding sites was identified in the controls group. These binding sites were present four times more often in the proximal colon than in the distal colon (P less than 0.025). In the ulcerative and Crohn's colitis groups, this gradient effect was lost, predominantly as a result of decreased availability of fucosyl residues in the proximal colon. In the descending colon of Crohn's colitis tissues, there was a complete absence of Dolichus biflorus agglutinin binding sites compared with the 62.5% incidence in the control group (P less than 0.05). These results demonstrate that the expression of lectin-binding sites in human large intestinal goblet mucin is specifically altered in inflammatory bowel disease, indicating that there are changes in glycosylation of colorectal mucin consistent with alterations in goblet cell differentiation.
Serum autoantibodies after liver transplantation. Prevalence and asssociated immunologic disorders
Authors: M. Salcedo, J. Vaquero, R. Bañares, M.R. Mahou, E. Alvarez, A. Hdez-Albújar, A. de Diego, S. Alonso, D. Rincón, G. Clemente
Journal: Journal of Hepatology (2001)
Soluble Mesothelin-Related Peptide and Osteopontin As Markers of Response in Malignant Mesothelioma
Authors: Paul Wheatley-Price, Boming Yang, Demetris Patsios, Devalben Patel, Clement Ma, Wei Xu, Natasha Leighl, Ronald Feld, B.C. John Cho, Brenda O'Sullivan, Heidi Roberts, Ming Sound Tsao, Martin Tammemagi, Masaki Anraku, Zhuo Chen, Marc de Perrot, Geoffrey Liu
Journal: Journal of Clinical Oncology (2010)

In malignant mesothelioma (MM), radiologic assessment of disease status is difficult. Both soluble mesothelin-related peptide (SMRP) and osteopontin (OP) have utility in distinguishing MM from benign pleural disease. We evaluated whether SMRP and OP also correlated with the disease course of MM.Serial plasma samples from patients with MM were prospectively collected, and SMRP and OP levels were measured. Radiologic tests across time periods showing disease progression, stability, or shrinkage were compared with corresponding changes in SMRP/OP levels.From 41 patients, 165 samples were collected (range, 2 to 10; median 4). At study entry, 37 of 41 patients had measurable disease, of whom 92% (34 of 37) had elevated baseline SMRP levels; four of 41 patients had no evidence of recurrence and each had normal baseline SMRP levels. In 21 patients receiving systemic therapy, percentage change in SMRP more than 10% correlated with the radiologic assessment by a trained thoracic radiologist (P < .001), by formal Response Evaluation Criteria in Solid Tumors (RECIST; P = .008), or by modified RECIST (P < .001). All seven patients who underwent surgical resection with negative margins had elevated preoperative SMRP levels that fell to normal postoperatively. Rising SMRP was observed in all patients with radiologic disease progression. No associations were found with OP.Percentage changes in SMRP levels, but not changes in OP levels, are a potentially useful marker of disease course. These findings should be validated prospectively for a role as an objective adjunctive measure of disease course in both clinical trials and clinical practice.
2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation
Authors: Craig T. January, L. Samuel Wann, Joseph S. Alpert, Hugh Calkins, Joaquin E. Cigarroa, Joseph C. Cleveland, Jamie B. Conti, Patrick T. Ellinor, Michael D. Ezekowitz, Michael E. Field, Katherine T. Murray, Ralph L. Sacco, William G. Stevenson, Patrick J. Tchou, Cynthia M. Tracy, Clyde W. Yancy
Journal: Circulation (2014)

work of the writing committee, without commercial support.Writing committee members volunteered their time for this activity.Guidelines are official policy of both the ACC and AHA.In an effort to maintain relevance at the point of care for clinicians, the Task Force continues to oversee an ongoing process improvement initiative.As a result, in response to pilot projects, several changes to this guideline will be apparent
Intravitreal Therapy in Bilateral Neovascular Age-Related Macular Degeneration
Authors: Daniel Barthelmes, Richard J. Walton, Jennifer J. Arnold, Ian L. McAllister, Judy M. Simpson, Anna Campain, Alex P. Hunyor, Robyn Guymer, Rohan W. Essex, Nigel Morlet, Mark C. Gillies
Journal: Ophthalmology (2014)
Hsp90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin Prevents Synovial Sarcoma Proliferation via Apoptosis in <i>In vitro</i> Models
Authors: Jefferson Terry, Joanna M. Lubieniecka, Wanda Kwan, Suzanne Liu, Torsten O. Nielsen
Journal: Clinical Cancer Research (2005)

Abstract Synovial sarcoma is a soft tissue malignancy with a poor prognosis; many patients will die from this disease within 10 years of diagnosis, despite treatment. Gene expression profiling and immunohistochemistry studies have identified oncogenes that are highly expressed in synovial sarcoma. Included in this group are receptor tyrosine kinases such as epidermal growth factor receptor, insulin-like growth factor receptor 1, fibroblast growth factor receptor 3, KIT, and HER2. Inhibitors of these growth-promoting receptors are likely to inhibit proliferation of synovial sarcoma; however, the effect of receptor tyrosine kinase inhibitors on synovial sarcoma is largely unknown. We assessed the ability of the following receptor tyrosine kinase inhibitors to halt proliferation and induce apoptosis in synovial sarcoma monolayer and three dimensional spheroid in vitro models: gefitinib (Iressa), NVP-AEW541, imatinib mesylate (Gleevec), SU5402, PRO-001, trastuzumab (Herceptin), and 17-allylamino-17-demethoxygeldanamycin (17-AAG). Gefitinib, NVP-AEW541, and imatinib inhibited proliferation only at relatively high concentrations, which are not clinically applicable. 17-AAG, which destabilizes multiple receptor tyrosine kinases and other oncoproteins through heat shock protein 90 inhibition, prevented proliferation and induced apoptosis in synovial sarcoma monolayer models at concentrations achievable in human serum. 17-AAG treatment was also associated with receptor tyrosine kinase degradation and induction of apoptosis in synovial sarcoma spheroid models. 17-AAG was more effective than doxorubicin, particularly in the spheroid models. Here we provide in vitro evidence that 17-AAG, a clinically applicable drug with known pharmacology and limited toxicity, inhibits synovial sarcoma proliferation by inducing apoptosis, and thus has potential as a systemic therapy for this disease.
In Vivo Imaging of Partially Reversible Th17 Cell-Induced Neuronal Dysfunction in the Course of Encephalomyelitis
Authors: Volker Siffrin, Helena Radbruch, Robert Glumm, Raluca Niesner, Magdalena Paterka, Josephine Herz, Tina Leuenberger, Sabrina M. Lehmann, Sarah Luenstedt, Jan Leo Rinnenthal, Gregor Laube, Hervé Luche, Seija Lehnardt, Hans-Joerg Fehling, Oliver Griesbeck, Frauke Zipp
Journal: Immunity (2010)
Photoaffinity Labeling of Peptide Hormone Receptors*
Authors: E. HAZUM
Journal: Endocrine Reviews (1983)

THE MECHANISMS involved in cellular response to a particular hormone-receptor interaction are complex. The intricacy of these biological systems stems from the fact that cells are multicomponent. The classical biochemical approach of isolation and characterization of proteins does not always reveal the transient interactions that occur in the natural environment of the cells. Photoaffinity labeling provides an important experimental tool for the detection and isolation of membrane components (e.g., binding sites for hormones) and for the elucidation of interactions involved in biological processes at the molecular level (1–9). This review describes some properties of photoreactive cross-linking reagents and the applications of photoaffinity derivatized hormones to highlight the potential uses of this technique for studying complex biological systems. These include: identification of receptor macromolecules; photoaffinity inactivation of receptors; persistent activation of biological functions; and localization and cellular processing of receptors. The most useful and widely used cross-linking reagents are the photoactive aryl azides which have the convenient property of becoming reactive only after photolysis.
Comparison of Two Creatinine-Based Estimating Equations in Predicting All-Cause and Cardiovascular Mortality in Patients With Type 2 Diabetes
Authors: Giovanni Targher, Giacomo Zoppini, William Mantovani, Michel Chonchol, Carlo Negri, Vincenzo Stoico, Alessandro Mantovani, Francesca De Santi, Enzo Bonora
Journal: Diabetes Care (2012)

To compare the performance of two glomerular filtration rate (GFR)-estimating equations in predicting the risk of all-cause and cardiovascular mortality in type 2 diabetic patients.We followed 2,823 type 2 diabetic outpatients for a period of 6 years for the occurrence of all-cause and cardiovascular mortality. GFR was estimated using the four-variable Modification of Diet in Renal Disease (MDRD) study equation and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.At baseline, an estimated GFR (eGFR) <60 mL/min/1.73 m(2) was present in 22.0 and 20.2% of patients using the MDRD study equation and the CKD-EPI equation, respectively. A total of 309 patients died during the follow-up (152 patients from cardiovascular causes). Both creatinine-based equations were associated with an increased risk of all-cause and cardiovascular mortality. However, the CKD-EPI equation provided a more accurate risk prediction of mortality than the MDRD study equation. Receiving operating characteristic curves showed that the areas under the curve (AUCs) for all-cause mortality (AUC 0.712 [95% CI 0.682-0.741]) and cardiovascular mortality (0.771 [0.734-0.808]) using eGFR(CKD-EPI) were significantly greater (P < 0.0001 by the z statistic) than those obtained by using eGFR(MDRD) (0.679 [0.647-0.711] for all-cause mortality and 0.739 [0.698-0.783] for cardiovascular mortality).Our findings suggest that the estimation of GFR using the CKD-EPI equation more appropriately stratifies patients with type 2 diabetes according to the risk of all-cause and cardiovascular mortality compared with the MDRD study equation.
Standards of care for treatment of recurrent glioblastoma—are we there yet?
Authors: Michael Weller, Timothy Cloughesy, James R. Perry, Wolfgang Wick
Journal: Neuro-Oncology (2012)

Newly diagnosed glioblastoma is now commonly treated with surgery, if feasible, or biopsy, followed by radiation plus concomitant and adjuvant temozolomide. The treatment of recurrent glioblastoma continues to be a moving target as new therapeutic principles enrich the standards of care for newly diagnosed disease. We reviewed PubMed and American Society of Clinical Oncology abstracts from January 2006 to January 2012 to identify clinical trials investigating the treatment of recurrent or progressive glioblastoma with nitrosoureas, temozolomide, bevacizumab, and/or combinations of these agents. At recurrence, a minority of patients are eligible for second surgery or reirradiation, based on appropriate patient selection. In temozolomide-pretreated patients, progression-free survival rates at 6 months of 20%–30% may be achieved either with nitrosoureas, temozolomide in various dosing regimens, or bevacizumab. Combination regimens among these agents or with other drugs have not produced evidence for superior activity but commonly produce more toxicity. More research is needed to better define patient profiles that predict benefit from the limited therapeutic options available after the current standard of care has failed.