tbuckley/cabot-search huggingface dataset:
Abstract 5562: BreastDefend enhances the effects of tamoxifen in estrogen receptor-positive human breast cancerin vitroand animal modelsin vivo
Authors: Shujie Cheng, Mark Alvarado, Jagadish Loganathan, Victor Castillo, Georg Sandusky, Isaac Eliaz, Daniel Sliva
Journal: Cancer Research (2015)

Abstract In this study we evaluated the combined effects of the natural product/dietary supplement BreastDefend (BD) and tamoxifen (TAM) on MCF-7 estrogen receptor-positive (ER+) human breast cancer cells in vitro and an orthotopic mouse model in vivo. BD has been studied previously in preclinical models, and shown to exert significant effects on MDA-MB-231 triple-negative breast cancer cells. The proliferation of MCF-7 cells was evaluated using MTT assays, whereas the expression of genes involved in the molecular mechanisms of cancer was evaluated using DNA microarrays. MCF-7 cells were stimulated with estradiol (10 nM) and treated with TAM (1 μM), BD (10 μg/ml), and the combination of TAM and BD for 3 days and 6 days. Compared with control, BD enhanced the anti-proliferative activity of TAM significantly (P &amp;lt; 0.05), and the combination of BD and TAM induced apoptosis. The results of DNA microarray analyses suggested that the pro-apoptotic activity of BD and TAM in MCF-7 cells was associated with the significant upregulation of BRAF (an oncogene that can block proliferation and induce apoptosis) and downregulation of BCL2 (an apoptosis inhibitor) and FN1 (fibronectin, a glycoprotein involved in tumorigenesis and metastasis) expression. In the orthotopic model MCF-7 cells were implanted into the mammary fat pads of female ovariectomized nude mice (n = 12-13). The mice received subcutaneous pellets that released estradiol and TAM, whereas BD was administered orally via intragastric gavage. All groups, including control, received estradiol. The combination of BD and TAM suppressed tumor size in vivo markedly compared with the BD and TAM alone groups. The inhibition of tumor growth was associated with the induction of the cell cycle inhibitor protein p21 in MCF-7-generated breast tumors. In summary, this study suggests that BD could be considered for use in clinical studies as an adjuvant therapy in conjunction with TAM for the treatment of ER+ human breast cancer. Citation Format: Shujie Cheng, Mark Alvarado, Jagadish Loganathan, Victor Castillo, Georg Sandusky, Isaac Eliaz, Daniel Sliva. BreastDefend enhances the effects of tamoxifen in estrogen receptor-positive human breast cancer in vitro and animal models in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5562. doi:10.1158/1538-7445.AM2015-5562
Immune Regulation of Cancer
Authors: Mary L. Disis
Journal: Journal of Clinical Oncology (2010)

Innate and adaptive immune system cells play a major role in regulating the growth of cancer. Although it is commonly thought that an immune response localized to the tumor will inhibit cancer growth, it is clear that some types of inflammation induced in a tumor may also lead to cancer proliferation, invasion, and dissemination. Recent evidence suggests, however, that some patients with cancer can mount an antitumor immune response that has the potential to control or eliminate cancer. Indeed, a so-called "immune response" signature has been described in malignancy that is associated with improved outcomes in several tumor types. Moreover, the presence of specific subsets of T cells, which have the capability to penetrate tumor stroma and infiltrate deep into the parenchyma, identifies patients with an improved prognosis. Immune-based therapies have the potential to modulate the tumor microenvironment by eliciting immune system cells that will initiate acute inflammation that leads to tissue destruction.
Atherosclerosis
Authors: Denham Harman
Journal: Circulation Research (1962)

Cholesterol-induced rabbit atherosclerosis was inhibited by the antihistaminic, chlorpheniramine, given orally at a rate of either 2, 4, or 8 mg./day/rabbit. Two attempts, both unsuccessful, were made to demonstrate directly the expected chlorpheniramine-mediated decrease in the permeability of the rabbit aortic wall to serum constituents: (1) study of sudan-red-stained frozen sections of aortas from rabbits fed a high-cholesterol diet for a few days, with and without added chlorpheniramine, and (2) a study of the effect of chlorpheniramine on the permeability of the inner aspect of the aorta to I 13l -labeled serum albumin. A possible mechanism, based on aortic reaction to injury, is presented to account for the localization and development of atherosclerosis. This hypothesis led to the selection of chlorpheniramine for study as a possible atherosclerosis-inhibiting agent and underlies the belief that the atherosclerosis-inhibiting effect of this compound is due to inhibition of aortic reaction to injury.
Failure to Maintain Eye-Specific Segregation in nob, a Mutant with Abnormally Patterned Retinal Activity
Authors: Jay Demas, Botir T. Sagdullaev, Erick Green, Lisa Jaubert-Miazza, Maureen A. McCall, Ronald G. Gregg, Rachel O.L. Wong, William Guido
Journal: Neuron (2006)
Thrombocytopenia associated with low-molecular-weight heparin
Authors: Thomas Lecompte, Shao Kai Luo, Natalie Stieltjes, Chantal Lecrubier, MichelMeyer Samama, B. Tardy, F. Zeni, J. Reynaud, B. Tardy-Poncet, C. Comtet, J.C. Bertrand
Journal: The Lancet (1991)
Association Between Mammographic Density and Age-Related Lobular Involution of the Breast
Authors: Karthik Ghosh, Lynn C. Hartmann, Carol Reynolds, Daniel W. Visscher, Kathleen R. Brandt, Robert A. Vierkant, Christopher G. Scott, Derek C. Radisky, Thomas A. Sellers, V. Shane Pankratz, Celine M. Vachon
Journal: Journal of Clinical Oncology (2010)

Purpose Mammographic density and lobular involution are both significant risk factors for breast cancer, but whether these reflect the same biology is unknown. We examined the involution and density association in a large benign breast disease (BBD) cohort. Patients and Methods Women in the Mayo Clinic BBD cohort who had a mammogram within 6 months of BBD diagnosis were eligible. The proportion of normal lobules that were involuted was categorized by an expert pathologist as no (0%), partial (1% to 74%), or complete involution (≥ 75%). Mammographic density was estimated as the four-category parenchymal pattern. Statistical analyses adjusted for potential confounders and evaluated modification by parity and age. We corroborated findings in a sample of women with BBD from the Mayo Mammography Health Study (MMHS) with quantitative percent density (PD) and absolute dense and nondense area estimates. Results Women in the Mayo BBD cohort (n = 2,667) with no (odds ratio, 1.7; 95% CI, 1.2 to 2.3) or partial (odds ratio, 1.3; 95% CI, 1.0 to 1.6) involution had greater odds of high density (DY pattern) than those with complete involution (P trend &lt; .01). There was no evidence for effect modification by age or parity. Among 317 women with BBD in the MMHS study, there was an inverse association between involution and PD (mean PD, 22.4%, 21.6%, 17.2%, for no, partial, and complete, respectively; P trend = .04) and a strong positive association of involution with nondense area (P trend &lt; .01). No association was seen between involution and dense area (P trend = .56). Conclusion We present evidence of an inverse association between involution and mammographic density.
Discovering of Tumor‐targeting Peptides using Bi‐functional Microarray
Authors: Weizhi Wang, Zihua Wang, Xiangli Bu, Ren Li, Mingxing Zhou, Zhiyuan Hu
Journal: Advanced Healthcare Materials (2015)

A bi-functional microarray for in situ peptide screening is presented herein, from which an affinity peptide towards EpCAM is screened out for tumor cell capture. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Shared decision making in inflammatory bowel disease: helping patients understand the tradeoffs between treatment options
Authors: Corey A Siegel
Journal: Gut (2011)

The treatment of inflammatory bowel disease is becoming more complicated with new medications and new treatment paradigms. Although data are accumulating that the earlier use of immunomodulators and anti-tumor necrosis factor agents are more effective than the standard "step-up" pyramidal treatment algorithm, patients may not be comfortable with this more intensive therapeutic approach. The process of shared decision making engages patients in treatment decisions to optimize the chance that a chosen therapy matches their personal preferences for care. Decision aids are standard shared decision making tools, which are used to present evidence-based data in a patient-friendly manner to help patients with preference- sensitive decisions. Not all care decisions are preference-sensitive, and not all patients are interested in being part of a shared medical decision. The responsibility of the provider is to identify how much of a role patients want, and then determine which decisions need their input to provide the best patient-centered care. The overall goal is to involve patients in decisions so that they are educated about their options, confident in the plan, adherent to chosen therapy and ultimately have a better quality of life.
Risk of Acute Leukemia Following Epirubicin-Based Adjuvant Chemotherapy: A Report From the National Cancer Institute of Canada Clinical Trials Group
Authors: Michael Crump, Dongsheng Tu, Lois Shepherd, Mark Levine, Vivien Bramwell, Kathleen Pritchard
Journal: Journal of Clinical Oncology (2003)

Purpose: Cyclophosphamide, epirubicin, and fluorouracil (CEF), compared with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy. has lead to an improvement in relapse-free and overall survival in premenopausal women with node-positive breast cancer. We undertook this analysis to more accurately define the estimate of risk of secondary acute leukemia (sAL) following epirubicin-containing chemotherapy regimens. Patients and Methods: We assessed the conditional probability of sAL among 1,545 women who received adjuvant (n = 1,477) or neoadjuvant (n = 68) chemotherapy in four National Cancer Institute of Canada Clinical Trials Group trials from 1990 to 1999. The risks associated with epirubicin-containing regimens (CEF or epirubicin and cyclophosphamide [EC]) and other regimens (doxorubicin and cyclophosphamide [AC] or CMF) were determined. Results: A total of 10 cases of sAL were observed (eight acute myelogeneous leukemia, two acute lymphoblastic leukemia): seven among women treated with CEF, two who had received AC, and one following CMF. Using competing risk statistics, the conditional probability of sAL was 1.7% (95% confidence interval [CI], 0.5 to 3.6) among 539 women treated with CEF chemotherapy at a follow-up of 8 years, 0.4% (95% CI, 0% to 1.3%) among the 678 who received CMF, and 1.3% (95% CI, 0% to 4.7%) among the 231 treated with AC. The conditional probability of death from breast cancer at 8 years for the entire group of women treated with epirubicin-containing regimens in all four trials was approximately 34.9%. Conclusion: CEF chemotherapy for breast cancer carries a small increased risk of sAL compared with CMF. These estimates of acute leukemia risk are important in discussing treatment with women, especially patients with a lower risk of death from breast cancer, such as those with node-negative breast cancer.
Therapeutical Experiences with the Digestive Ferments
Authors: F. A. Lees
Journal: BMJ (1880)

CASE xv.-Operation was done March 27th, too recently to report anything more than the primary result.The husband, himself an experienced medical man, writes, June ioth, I879 " The menopause is complete.I am very sanguine of a. perfect recovery of mind, as soon as she is accustomed to the great change from the operation."
Hepatic vein thrombosis in Behçet's disease
Authors: Eric Bismuth, Antoine Hadengue, Pascal Hammel, Jean-Pierre Benhamou
Journal: Hepatology (1990)

We describe four patients with hepatic vein thrombosis caused by Behçet's disease and review the 17 previously published cases. In addition, we compared these 21 cases of hepatic vein thrombosis to our 24 cases of hepatic vein thrombosis caused by primary myeloproliferative disorders. In patients with Behçet's disease, a male predominance (male/female ratio, 19:1) contrasted with the female predominance found in patients with hepatic vein thrombosis complicating primary myeloproliferative disorders (sex ratio = 1:3). The mean age at clinical onset was younger in patients with Behçet's disease than in those with primary myeloproliferative disorders (29 vs. 35 yr). Obstruction of the inferior vena cava was found in 90% of patients with hepatic vein thrombosis caused by Behçet's disease. Inferior vena caval thrombosis appears to be the main pathophysiological mechanism of hepatic vein thrombosis in patients with Behçet's disease. Unlike patients with primary myeloproliferative disorders who often had a progressive course, one third of patients with Behçet's disease had acute liver failure and died within 2 wk of clinical onset. These findings suggest that, in patients with Behçet's disease, hepatic vein thrombosis is a sudden event usually related to the extension of a caval thrombus to the ostium of the hepatic veins.(HEPATOLOGY 1990;11:969–974.).
PKC/Raf/MEK/ERK signaling pathway modulates native-LDL-induced E2F-1 gene expression and endothelial cell proliferation
Authors: G Pintus
Journal: Cardiovascular Research (2003)

Background and objectives : The interactions of low-density lipoprotein (LDL) with the endothelium are thought to play a major role in the development of atherosclerosis. Due to this reason, the molecular sequelae of events resulting from native LDL (N-LDL) interaction with human endothelial cells (HECs) are largely under investigation. Methods and results : Here, we report that the exposure of serum-free HECs to different concentrations of N-LDL-cholesterol (LDL-chol) elicited a time- and dose-dependent induction of DNA synthesis. The exposure of serum-free HECs to N-LDL was able to elicit a time- and dose-dependent increase of protein kinase C (PKC) activity that, along with the activation of the Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway, leads to an increase in E2F-1 gene expression. In addition, the treatment of HECs with N-LDL was also able to induce both E2F-1 gene transcription and protein expression. These N-LDL-aroused responses were dramatically counteracted by PKC inhibition or down regulation. Similarly to what observed for Raf/MEK/ERK activation and E2F-1 gene expression, the inhibition of PKC as well as its down regulation, significantly lowered the DNA synthesis induced by N-LDL in serum-free HECs. Conclusions : These results suggest that the activation of PKC/Raf/MEK/ERK-mediated events controlling E2F-1 gene expression by N-LDL may represent an important mechanism in the regulation of HECs proliferation during normal and pathological processes.
Echocardiographic findings in primary Sjogren's syndrome
Authors: P. MANGANELLI, P. BERNARDI, U. TALIANI, C. CAMINITI
Journal: Annals of the Rheumatic Diseases (1997)

Primary Sjogren’s syndrome (pSS) is a chronic autoimmune disease characterised by lymphocytic infiltration of the salivary and lacrimal glands.1 Similar lymphocytic infiltrates may invade visceral organs, and this results in several extraglandular manifestations.1 Among these, a clinically overt heart disease is very rare.2-4 However, recent echocardiographic studies showed that asymptomatic cardiac involvement is frequent in pSS. Thus, Rantapaa-Dahlqvist and colleagues5 reported signs of present or previous pericarditis in nine of 27 (33%) pSS patients. Of the echocardiographic measurements, the right ventricular anterior wall and the left ventricular posterior wall were significantly smaller in patients with pericarditis than in those without pericardial serositis. Moreover, in the pericarditis patients, the regional fractional shortening of the left ventricle was …
Epidermal Growth Factor Receptor in Non–Small-Cell Lung Carcinomas: Correlation Between Gene Copy Number and Protein Expression and Impact on Prognosis
Authors: Fred R. Hirsch, Marileila Varella-Garcia, Paul A. Bunn, Michael V. Di Maria, Robert Veve, Roy M. Bremnes, Anna E. Barón, Chan Zeng, Wilbur A. Franklin
Journal: Journal of Clinical Oncology (2003)

The epidermal growth factor receptor (EGFR) is frequently overexpressed in non-small-cell lung carcinoma (NSCLC), and EGFR inhibitors are promising new therapeutic agents. The molecular mechanisms responsible for EGFR overexpression are poorly understood.Gene copy number and protein status of EGFR were investigated in microarrayed tumors from 183 NSCLC patients, including squamous cell carcinoma (SCC; 89 patients) and non-SCC (94 patients) histologies. Protein expression was assessed by immunohistochemistry on a scale from 0 to 400 (percentage of positive cells x staining intensity). Gene and chromosome 7 copy numbers were identified by fluorescent in situ hybridization (FISH).EGFR protein overexpression was observed in 62% of the NSCLC (25% scored 201 to 300; 37% scored 301 to 400), more frequently in SCC than non-SCC (82% v 44%; P <.001), and in 80% of the bronchioloalveolar carcinomas. The prevalent FISH patterns were balanced disomy (40%) and trisomy (38%) for EGFR gene and chromosome 7 (40%), whereas balanced polysomy was seen in 13% and gene amplification was seen in 9% of the patients. Gene copy number correlated with protein expression (r = 0.4; P <.001). EGFR overexpression or high gene copy numbers had no significant influence on prognosis.EGFR overexpression is frequent in NSCLC, is most prominent in SCC, and correlates with increased gene copy number per cell. High gene copy numbers per cell showed a trend toward poor prognosis. It will be important to evaluate EGFR gene and EGFR protein status and signal protein expression to properly interpret future clinical trials using EGFR inhibitors.
Role of p73 in Alzheimer disease: lack of association in mouse models or in human cohorts
Authors: Badri Vardarajan, David Vergote, Fadel Tissir, Mark Logue, Jing Yang, Nathalie Daude, Kunie Ando, Ekaterina Rogaeva, Joseph Lee, Rong Cheng, Jean-Pierre Brion, Mahdi Ghani, Beipei Shi, Clinton T Baldwin, Satyabrata Kar, Richard Mayeux, Paul Fraser, André M Goffinet, Peter St George-Hyslop, Lindsay A Farrer, David Westaway
Journal: Molecular Neurodegeneration (2013)

P73 belongs to the p53 family of cell survival regulators with the corresponding locus Trp73 producing the N-terminally distinct isoforms, TAp73 and DeltaNp73. Recently, two studies have implicated the murine Trp73 in the modulation in phospho-tau accumulation in aged wild type mice and in young mice modeling Alzheimer's disease (AD) suggesting that Trp73, particularly the DeltaNp73 isoform, links the accumulation of amyloid peptides to the creation of neurofibrillary tangles (NFTs). Here, we reevaluated tau pathologies in the same TgCRND8 mouse model as the previous studies.Despite the use of the same animal models, our in vivo studies failed to demonstrate biochemical or histological evidence for misprocessing of tau in young compound Trp73+/- + TgCRND8 mice or in aged Trp73+/- mice analyzed at the ages reported previously, or older. Secondly, we analyzed an additional mouse model where the DeltaNp73 was specifically deleted and confirmed a lack of impact of the DeltaNp73 allele, either in heterozygous or homozygous form, upon tau pathology in aged mice. Lastly, we also examined human TP73 for single nucleotide polymorphisms (SNPs) and/or copy number variants in a meta-analysis of 10 AD genome-wide association datasets. No SNPs reached significance after correction for multiple testing and no duplications/deletions in TP73 were found in 549 cases of AD and 544 non-demented controls.Our results fail to support P73 as a contributor to AD pathogenesis.
Hormones, genetic factors, and gender differences in cardiovascular disease
Authors: J Rossouw
Journal: Cardiovascular Research (2002)

Time for primary review 31 days. 

On average, women develop heart disease some 10–15 years later than men. This raises the question of whether there is some aspect of ‘femaleness’ which reduces risk, or whether there is some aspect of ‘maleness’ that raises risk. To date, most attention has been focused on the hypothesis that endogenous estrogen is cardioprotective in women [1]. Rising rates of coronary heart disease (CHD) after the menopause, and after oophorectomy, are among the strands of evidence in humans that endogenous estrogen may prevent CHD [2]. However, upon closer examination this evidence is not persuasive, and in fact the evidence is amenable to alternative explanations.

During the first 3 decades of adult life, low-density lipoprotein (LDL) cholesterol levels are lower in women than men, and this may contribute to the delayed onset of CHD in women. A more widely held explanation for the later onset of CHD in women is their higher high-density lipoprotein (HDL) cholesterol levels, attributed to higher endogenous estrogen levels in women. However, the difference in HDL cholesterol between women and men is an androgen effect, not an estrogen effect. Up to puberty, young men and women have similar HDL cholesterol levels. At puberty, concurrent with the rise in endogenous testosterone levels, the HDL cholesterol levels in young men decline to the adult level [3,4]. A 20% difference in HDL cholesterol levels predicts at least a 20% difference in CHD rates in the short term, and may predict even larger differences in CHD rates over a lifetime [5]. Thus, the entire gender difference in CHD risk may indeed be due to the lifelong difference in HDL cholesterol levels; however, this difference is a consequence of having the Y chromosome. During fetal development, the Y chromosome directs the formation of … 

* Tel.: +1-301-435-6669; fax: +1-301-480-5158 rossouwj{at}nih.gov
Chlorhexidine body washing to control antimicrobial-resistant bacteria in intensive care units: a systematic review
Authors: Lennie P. G. Derde, Mirjam J. D. Dautzenberg, Marc J. M. Bonten
Journal: Intensive Care Medicine (2012)

Infections caused by antimicrobial-resistant bacteria (AMRB) are increasing worldwide, especially in intensive care units (ICUs). Chlorhexidine body washing (CHG-BW) has been proposed as a measure to limit the spread of AMRB. We have systematically assessed the evidence on the effectiveness of CHG-BW in reducing colonization and infection with AMRB in adult ICU patients.