tbuckley/cabot-search huggingface dataset:
Abstract 4938: APC in breast cancer: the ABCs of gene expression
Authors: Katia Fernandez Soto, Monica K. VanKlompenberg, Jennifer Cole, Jenifer R. Prosperi
Journal: Cancer Research (2015)

Abstract Breast cancer is the most common malignancy and cancer-related cause of death in non-smoking women in the United States. Due to the heterogeneity of this disease, the oncogenic and signaling pathways contributing to these tumors are distinct. The Adenomatous Polyposis Coli (APC) tumor suppressor is mutated or hypermethylated in up to 70% of sporadic breast cancers; however, the mechanism by which APC mutation impacts tumorigenesis remains unexplored. Up-regulation of the zinc finger transcription factor EGR-1 has been associated with cell invasion and enhanced drug resistance, which is an important property of cancer stem cells (CSCs). ALDH1 and STAT3 have been useful in the identification of CSCs, which are associated with poor clinical outcomes including increased tumor survival and invasion. We utilized two human breast cancer cell lines, MDA-MB-157 and DU4475, and cells isolated from the Mouse Mammary Tumor Virus-Polyoma middle T (MMTV-PyMT);ApcMin/+ mouse model. APC was knocked down in the MDA-MB-157 cells through shRNA lentiviral transduction, or transfected into DU4475 cells. First we looked at the expression of the transcription factor EGR-1 through Real-Time PCR in the MDA-MB-157 and DU4475 cell lines. Next, ALDH1 and STAT3 were measured in the MMTV-PyMT;ApcMin/+ mouse model and in MDA-MB-157 cells through western blots. In addition, an ALDEFLUOR assay was used to measure ALDH1 activity in the mouse model. To translate our findings to an in vivo model, we injected MMTV-PyMT;ApcMin/+ cells into the mammary fat pads of FVB-N syngeneic mice. EGR-1 expression was increased in both MDA-MB-157 APC-knockdown and DU4475 APC-mutant cells compared to cells expressing APC. In addition, STAT3 expression was found to be increased in MDA-MB-157 APC-knockdown and MMTV-PyMT;ApcMin/+ cells compared to MDA-MB-157 APC-wildtype and MMTV-PyMT;Apc+/+ cells. ALDH1 activity and tumor development were enhanced in ApcMin/+ cells compared to control cells. Combined, these data suggest that APC knockdown increases tumorigenic properties of cancer cells through EGR-1 overexpression and modulation of known cancer stem cell markers, ALDH1 and STAT3. Future studies will include measuring the expression of EGR-1 in the MMTV-PyMT;ApcMin/+ cells as well as ALDH1 in the human cell lines. Furthermore, because of the overexpression of these genes and markers, strategies designed to target positive populations might lead to more effective therapies of APC-mutant breast cancers. Citation Format: Katia Fernandez Soto, Monica K. VanKlompenberg, Jennifer Cole, Jenifer R. Prosperi. APC in breast cancer: the ABCs of gene expression. [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 4938. doi:10.1158/1538-7445.AM2015-4938
Current management of patients with Viral Haemorrhagic Fevers in the United Kingdom
Authors: N Crowcroft, D  W Brown, R Gopal
Journal: Eurosurveillance (2002)

In the UK, suspected and confirmed cases of viral haemorrhagic fever are currently managed according to the 1996 Guidance of the Advisory Committee on Dangerous Pathogens, which describes an approach to the risk categorisation of suspected cases. It also provides guidance on patient management including transfer, laboratory investigations, infection control, and monitoring of contacts based on the risk assessment. Confirmed cases are managed in bed isolators (&amp;quot;Trexler units&amp;quot;), two of which are available in high security infectious disease units in the UK. This guidance is under review and may change. Recent experience has shown that communication and reassurance for health care workers and the public are major tasks in managing such cases.
A Phase I study of an HLA-DPB1*0401-restricted T cell receptor targeting MAGE-A3 for patients with metastatic cancers
Authors: Yong-Chen Lu, Linda Parker, Tangying Lu, Zhili Zheng, Xin Yao, Paul F Robbins, Pierre van der Bruggen, Christopher A Klebanoff, Christian S Hinrichs, Stephanie Goff, Richard Sherry, Udai Kammula, James C Yang, Steven A Rosenberg
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Adoptive transfer of genetically-modified T cells is being explored as a salvage treatment for patients with selected metastatic cancers. Most of the current strategies utilize MHC class I-restricted T cell receptor (TCR) or chimeric antigen receptor (CAR) technologies to
Bumetanide for neonatal seizures—back from the cotside
Authors: Ronit M. Pressler, Geraldine B. Boylan, Neil Marlow, Linda S. de Vries, Mats Blennow, Catherine Chiron, J. Helen Cross, Boubou Hallberg, Lena Hellström-Westas, Vincent Jullien, Barry Mangum, Brendan Murphy, Deirdre Murray, Gerard Pons, Janet Rennie, Mona C. Toet, Sarah Zohar
Journal: Nature Reviews Neurology (2015)
A Light-Driven Therapy of Pancreatic Adenocarcinoma Using Gold Nanorods-Based Nanocarriers for Co-Delivery of Doxorubicin and siRNA
Authors: Feng Yin, Chengbin Yang, Qianqian Wang, Shuwen Zeng, Rui Hu, Guimiao Lin, Jinglin Tian, Siyi Hu, Rong Feng Lan, Ho Sup Yoon, Fei Lu, Kuan Wang, Ken-Tye Yong
Journal: Theranostics (2015)

In this work, we report the engineering of polyelectrolyte polymers coated Gold nanorods (AuNRs)-based nanocarriers that are capable of co-delivering small interfering RNA (siRNA) and an anticancer drug doxorubicin (DOX) to Panc-1 cancer cells for combination of both chemo-and siRNA-mediated mutant K-Ras gene silencing therapy.Superior anticancer efficacy was observed through synergistic combination of promoted siRNA and DOX release upon irradiating the nanoplex formulation with 665 nm light.Our antitumor study shows that the synergistic effect of AuNRs nanoplex formulation with 665 nm light treatment is able to inhibit the in vivo tumor volume growth rate by 90%.The antitumor effect is contributed from the inactivation of K-Ras gene and thereby causing a profound synthesis (S) phase arrest in treated Panc-1 cells.Our study shows that the percentage of Panc-1 cells treated by nanoplex formulation with S phase is determined to be 35% and it is 17% much higher than that of Panc-1 cells without any treatments.The developed nanotherapy formulation here, that combines chemotherapy, RNA silencing and NIR window light-mediated therapy, will be seen to be the next natural step to be taken in the clinical research for improving the therapeutic outcomes of the pancreatic adenocarcinoma treatment.
Rate and mode differences between nuclear and mitochondrial small-subunit rRNA genes in mushrooms.
Authors: T D Bruns, T M Szaro
Journal: Molecular Biology and Evolution (1992)

Sequences from homologous regions of the nuclear and mitochondrial small-subunit rRNA genes from 10 members of the mushroom order Boletales were used to construct evolutionary trees and to compare the rates and modes of evolution. Trees constructed independently for each gene by parsimony and tested by bootstrap analysis have identical topologies in all statistically significant branches. Examination of base substitutions revealed that the nuclear gene is biased toward C-T transitions and that the distribution of transversions in the mitochondrial gene is strongly effected by an A-T bias. When only homologous regions of the two genes were compared, base substitutions per nucleotide were roughly 16-fold greater in the mitochondrial gene. The difference in the frequency of length mutations was at least as great but was impossible to estimate accurately because of their absence in the nuclear gene. Maximum likelihood was used to show that base-substitution rates vary dramatically among the branches. A significant part of the rate inconstancy was caused by an accelerated nuclear rate in one branch and a retarded mitochondrial rate in a different branch. A second part of the rate variability involved a consistent inconstancy: short branches exhibit ratios of mitochondrial to nuclear divergences of less than 1, while longer branches had ratios of approximately 4:1-8:1. This pattern suggests a systematic error in the branch length calculation. The error may be related to the simplicity of the divergence estimates, which assumes that all base positions have an equal probability of change.
Fucose-appended dendrimer/α-cyclodextrin conjugate as a novel NF-κB decoy carrier to Kupffer cells infulminant hepatitis mice induced by lipopolysaccharide
Authors: Keiichi Motoyama, Chiho Akao, Ryosuke Mitsuyasu, Taishi Higashi, Hidetoshi Arima
Journal: Asian Journal of Pharmaceutical Sciences (2015)
Interaction of complement and clusterin in renal injury.
Authors: R Correa-Rotter, T H Hostetter, K A Nath, J C Manivel, M E Rosenberg
Journal: Journal of the American Society of Nephrology (1992)

Clusterin is a heterodimeric glycoprotein that has been associated with such diverse biologic functions as reproduction, cell regression, cell aggregation, and regulation of the cytolytic activity of the membrane attack complex of complement. Clusterin is a component of glomerular immune deposits in the kidney, and increased clusterin expression occurs in a number of renal injury states. To further explore the interaction between clusterin and complement, the requirement for an intact complement system for renal clusterin induction in an acute (folic acid nephropathy) and a chronic (subtotal renal ablation) model of renal injury was examined. After it was first demonstrated that folic acid increased renal clusterin mRNA in the rat, a species in which renal clusterin was highly inducible by other stimuli, the effects of folic acid (250 mg/kg ip) on clusterin mRNA and immunoreactivity were examined in mice sufficient and deficient for the fifth component of complement. Similar increases in clusterin mRNA and immunoreactivity were seen in both the C5-sufficient and C5-deficient mice compared with their respective vehicle-injected control groups. Renal clusterin mRNA was also increased to a similar extent in the remaining kidney of both C5-sufficient and C5-deficient mice 10 days after subtotal nephrectomy. In conclusion, the induction of clusterin after folic acid administration or subtotal nephrectomy was independent of the presence of an intact complement system, because similar increases in clusterin expression were observed in C5-sufficient and C5-deficient mice.
CRISPR-mediated Activation of Latent HIV-1 Expression
Authors: Prajit Limsirichai, Thomas Gaj, David V Schaffer
Journal: Molecular Therapy (2015)

Complete eradication of HIV-1 infection is impeded by the existence of cells that harbor chromosomally integrated but transcriptionally inactive provirus. These cells can persist for years without producing viral progeny, rendering them refractory to immune surveillance and antiretroviral therapy and providing a permanent reservoir for the stochastic reactivation and reseeding of HIV-1. Strategies for purging this latent reservoir are thus needed to eradicate infection. Here, we show that engineered transcriptional activation systems based on CRISPR/Cas9 can be harnessed to activate viral gene expression in cell line models of HIV-1 latency. We further demonstrate that complementing Cas9 activators with latency-reversing compounds can enhance latent HIV-1 transcription and that epigenome modulation using CRISPR-based acetyltransferases can also promote viral gene activation. Collectively, these results demonstrate that CRISPR systems are potentially effective tools for inducing latent HIV-1 expression and that their use, in combination with antiretroviral therapy, could lead to improved therapies for HIV-1 infection.
Noninvasive measurement of blood volume in hemodialysis patients.
Authors: D Schneditz, J M Roob, M Vaclavik, H Holzer, T Kenner
Journal: Journal of the American Society of Nephrology (1996)

Journal of the American Society of Nephrology : JASN 7(8):p 1241-1244, August 1996. | DOI: 10.1681/ASN.V781241
Underweight as a Predictor of Diabetes in Older Adults
Authors: Toshimi Sairenchi, Hiroyasu Iso, Fujiko Irie, Nobuko Fukasawa, Hitoshi Ota, Takashi Muto
Journal: Diabetes Care (2008)

A total of 39,201 men and 88,012 women aged 40–79 years who underwent health checkups in 1993 and who were free of diabetes were followed until the end of 2004 to examine an association between underweight and risk of diabetes. Incident diabetes was defined by a fasting blood glucose concentration ≥7.0 mmol/l or nonfasting glucose ≥11.1 mmol/l and/or diabetes treatment. The multivariable hazard ratio of diabetes adjusted for age, baseline blood glucose level, fasting status, and other confounding variables among subjects who had a BMI <18.5 kg/m2 compared with those with a BMI 18.5–24.9 kg/m2 was 1.32 (95% CI 1.12–1.56) in men aged 60–79 years and 1.31 (1.07–1.60) in women aged 60–79 years. Underweight may be associated with risk of diabetes among older adults.

In the present study, we enrolled 181,863 nondiabetic Japanese subjects (58,402 men and 123,461 women) from community residents aged 40–79 years who underwent health checkups in 1993 conducted by the local governments under the Japan Health Laws. We excluded 19,201 men and 35,449 women who did not participate in the 1994 survey, thereby ensuring that the subjects were followed up for at least 1 year. A total of 39,201 men and …
Transfusion of fresher vs older red blood cells in hospitalized patients: a systematic review and meta-analysis
Authors: Paul E. Alexander, Rebecca Barty, Yutong Fei, Per Olav Vandvik, Menaka Pai, Reed A. C. Siemieniuk, Nancy M. Heddle, Neil Blumberg, Shelley L. McLeod, Jianping Liu, John W. Eikelboom, Gordon H. Guyatt
Journal: Blood (2015)
Association of Hospital and Physician Characteristics and Care Processes With Racial Disparities in Procedural Outcomes Among Contemporary Patients Undergoing Coronary Artery Bypass Grafting Surgery
Authors: Rajendra H. Mehta, David M. Shahian, Shubin Sheng, Sean M. O’Brien, Fred H. Edwards, Jeffery P. Jacobs, Eric D. Peterson
Journal: Circulation (2015)

Background— Previous studies have reported that black patients undergoing coronary artery bypass surgery had worse outcomes than white patients, even after accounting for patient factors. The degree to which clinician, hospital, and care factors account for these outcome differences remains unclear. Methods and Results— We evaluated procedural outcomes in 11 697 blacks and 136 362 whites undergoing isolated coronary artery bypass surgery at 663 Society of Thoracic Surgery Database participating sites (January 1, 2010 to June 30, 2011) adjusted for patients’ clinical and socioeconomic features, hospital and surgeon effects, and care processes (internal mammary artery graft and perioperative medications use). Relative to whites, blacks undergoing coronary artery bypass surgery were younger, yet had higher comorbidities and more adverse presenting features. Blacks were also more likely to be treated at hospitals with higher risk-adjusted mortality. The use of internal mammary artery was marginally lower in blacks than in whites (93.3% versus 92.2%, P &lt;0.0001). Unadjusted mortality and major morbidity rates were higher in blacks than in whites (1.8% versus 2.5%, P &lt;0.0001) and (13.6% versus 19.4%, P &lt;0.0001), respectively. These racial differences in outcomes narrowed but still persisted after adjusting for surgeon, hospital, and care processes in addition to patient and socioeconomic factors (odds ratio, 1.17; 95% confidence interval, 1.00–1.36 and odds ratio, 1.26; 95% confidence interval, 1.19–1.34, respectively). Conclusions— The risks of procedural mortality and morbidity after coronary artery bypass surgery were higher among black patients than among white patients. These differences were in part accounted for by patient comorbidities, socioeconomic status, and surgeon, hospital, and care factors, as well, as suggested by the reduction in the strength of the race-outcomes association. However, black race remained an independent predictor of outcomes even after accounting for these differences.
Human Germline CRISPR-Cas Modification: Toward a Regulatory Framework
Authors: Niklaus H. Evitt, Shamik Mascharak, Russ B. Altman
Journal: The American Journal of Bioethics (2015)

CRISPR germline editing therapies (CGETs) hold unprecedented potential to eradicate hereditary disorders. However, the prospect of altering the human germline has sparked a debate over the safety, efficacy, and morality of CGETs, triggering a funding moratorium by the NIH. There is an urgent need for practical paths for the evaluation of these capabilities. We propose a model regulatory framework for CGET research, clinical development, and distribution. Our model takes advantage of existing legal and regulatory institutions but adds elevated scrutiny at each stage of CGET development to accommodate the unique technical and ethical challenges posed by germline editing.
Postmenopausal Female Hormone Use and Estrogen Receptor–Positive and –Negative Breast Cancer in African American Women
Authors: Lynn Rosenberg, Traci N. Bethea, Emma Viscidi, Chi-Chen Hong, Melissa A. Troester, Elisa V. Bandera, Christopher A. Haiman, Laurence N. Kolonel, Andrew F. Olshan, Christine B. Ambrosone, Julie R. Palmer
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Use of estrogen with progestin (combination therapy) is associated with increased incidence of estrogen receptor–positive (ER+) breast cancer in observational studies and randomized trials among postmenopausal white women. Whether this is also the case among African American women is not established.
Hemichoreoathetosis in Neurosarcoidosis
Authors: Ali Ataya, Eloise Harman
Journal: New England Journal of Medicine (2015)

A 39-year-old black man presented with progressively worsening involuntary movements of the left arm that had been sudden in onset. A physical examination revealed chorea of the left upper arm and athetosis of the fingers of the left hand, shown in a video.
Following the Trail From Genotype to Phenotypes
Authors: Catherine Lord, Jeremy Veenstra-VanderWeele
Journal: JAMA Psychiatry (2015)

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Human Cortical Distal Nephron
Authors: Helena Lagger Biner, Marie-Pierre Arpin-Bott, Johannes Loffing, Xiaoyan Wang, Mark Knepper, Steve C. Hebert, Brigitte Kaissling
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The exact distributions of the different salt transport systems along the human cortical distal nephron are unknown. Immunohistochemistry was performed on serial cryostat sections of healthy parts of tumor nephrectomized human kidneys to study the distributions in the distal convolution of the thiazide-sensitive Na-Cl cotransporter (NCC), the β subunit of the amiloride-sensitive epithelial Na channel (ENaC), the vasopressin-sensitive water channel aquaporin 2 (AQP2), and aquaporin 3 (AQP3), the H+ ATPase, the Na-Ca exchanger (NCX), plasma membrane calcium-ATPase, and calbindin-D28k (CaBP). The entire human distal convolution and the cortical collecting duct (CCD) display calbindin-D28k, although in variable amounts. Approximately 30% of the distal convolution profiles reveal NCC, characterizing the distal convoluted tubule. NCC overlaps with ENaC in a short portion at the end of the distal convoluted tubule. ENaC is displayed all along the connecting tubule (70% of the distal convolution) and the CCD. The major part of the connecting tubule and the CCD coexpress aquaporin 2 with ENaC. Intercalated cells, undetected in the first 20% of the distal convolution, were interspersed among the segment-specific cells of the remainder of the distal convolution, and of the CCD. The basolateral calcium extruding proteins, Na-Ca exchanger (NCX), and the plasma membrane Ca2+-ATPase were found all along the distal convolution, and, in contrast to other species, along the CCD, although in varying amounts. The knowledge regarding the precise distribution patterns of transport proteins in the human distal nephron and the knowledge regarding the differences from that in laboratory animals may be helpful for diagnostic purposes and may also help refine the therapeutic management of electrolyte disorders.
Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials
Authors: K. Fizazi, T.W. Flaig, M. Stöckle, H.I. Scher, J.S. de Bono, D.E. Rathkopf, C.J. Ryan, T. Kheoh, J. Li, M.B. Todd, T.W. Griffin, A. Molina, C.H. Ohlmann
Journal: Annals of Oncology (2015)
Analysis of predictive and prognostic factors in 290 patients treated with oncolytic adenoviruses
Authors: Kristian Taipale, Ilkka Liikanen, Anniina Koski, Anna Kanerva, Minna Oksanen, Akseli Hemminki
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts After years of development, oncolytic viruses are nearing a breakthrough into clinical use. In order to facilitate the implementation of this new form of immunotherapy, all existing clinical experience must be utilized to optimize treatment strategies, improve patient selection