tbuckley/cabot-search huggingface dataset:
Restricted Usage of T-Cell Receptor Vα-Vβ Genes in Infiltrating Cells in Aortic Tissue of Patients With Takayasu’s Arteritis
Authors: YoshinoriSeko, OsamuSato, AtsuhikoTakagi, YusukeTada, HiroshiMatsuo, HideoYagita, KoOkumura, YoshioYazaki
Journal: Circulation (1996)

Background Infiltration by perforin-secreting killer lymphocytes, such as T cells and natural killer cells, has been shown to be involved in the pathogenesis of vascular cell damage in Takayasu’s arteritis. Methods and Results To investigate the immunological mechanisms involved, especially the nature of T-cell infiltration in Takayasu’s arteritis as well as atherosclerosis, we analyzed the expression of T-cell receptor (TCR) Vα and Vβ genes in infiltrating cells in the aortic tissue of patients with Takayasu’s arteritis and atherosclerotic aortic aneurysm by polymerase chain reaction (PCR). We also analyzed the expression of cytokine genes by PCR. We found that the repertoires of TCR Vα as well as Vβ gene transcripts in Takayasu’s arteritis were restricted. The infiltrating cells expressing Vα2, Vα16, Vα17, Vβ7, and Vβ13.1 were found in 3 of 4 patients. In contrast, TCR Vα-Vβ repertoires in atherosclerotic aortic aneurysm were polyclonal. There was no significant difference in the pattern of cytokine gen...
Abstract 16864: The Effect of Omega-3 Carboxylic Acids on Apolipoprotein CIII Containing Lipoproteins in Moderate to Severe Hypertriglyceridemia
Authors: AllysonMorton, JeremyFurtado, WilliamAmerine, DouglasKling, MichaelDavidson, FrankSacks
Journal: Circulation (2014)

Background: Apolipoprotein CIII, present on some HDL, LDL, and VLDL, promotes dyslipidemia and activates atherogenic processes. Lipoprotein subspecies containing apoCIII adversely affect CVD risk. For example, it has been shown that LDL with apoCIII is a stronger predictor of CVD than LDL without apoCIII, and that HDL with apoCIII is associated with increased CVD. Small studies have suggested that omega 3 fatty acids may reduce plasma total apoCIII in addition to their TG-lowering effects, but there is a lack of detailed analysis in regards to which lipoprotein subtypes are affected by treatment. We studied the effect of omega-3 carboxylic acids on apoCIII concentrations in HDL, LDL, and VLDL; and on the concentrations of subspecies of HDL, LDL, and VLDL that contain or do not contain apoCIII. Methods: We analyzed plasma samples from the EVOLVE trial (EpanoVa fOr Lowering Very high triglyceridEs), a 12 week double-blind study of 399 subjects with fasting TG between 500 mg/dl and 2000 mg/dl who were random...
Labor Induction versus Expectant Management in Low-Risk Nulliparous Women
Authors: William A. Grobman, Madeline M. Rice, Uma M. Reddy, Alan T.N. Tita, Robert M. Silver, Gail Mallett, Kim Hill, Elizabeth A. Thom, Yasser Y. El-Sayed, Annette Perez-Delboy, Dwight J. Rouse, George R. Saade, Kim A. Boggess, Suneet P. Chauhan, Jay D. Iams, Edward K. Chien, Brian M. Casey, Ronald S. Gibbs, Sindhu K. Srinivas, Geeta K. Swamy, Hyagriv N. Simhan, George A. Macones
Journal: New England Journal of Medicine (2018)

The perinatal and maternal consequences of induction of labor at 39 weeks among low-risk nulliparous women are uncertain.
Total IgE levels are linked to the response of chronic spontaneous urticaria patients to omalizumab
Authors: Karsten Weller, Tatevik Ohanyan, Tomasz Hawro, André Ellrich, Gordon Sussman, Jake Koplowitz, Ana M. Gimenez‐Arnau, Adriane Peveling‐Oberhag, Petra Staubach, Martin Metz, Marcus Maurer
Journal: Allergy (2018)

Here, we compared complete responders (CR) to non-responders (NR) and partial 18 responders (PR) to identify predictors for response.In total, we analyzed 85 patients 19 from 4 GA²LEN urticaria centers of reference and excellence (UCAREs) (5), 43 CR, 20 23 PR, and 19 NR to omalizumab treatment (Table 1).Complete, partial and non-21 response was defined as the reduction of signs and symptoms by ≥90%, by ≥30% 22 but <90%, and by <30% (physicians global assessment), respectively, after 2 four-23 weekly injections of omalizumab 300 mg.All centers provided data on NRs 24 comparing patient characteristics, laboratory values, and treatment response.In 25 addition, all centers were asked to provide data on at least one PR and CR per 26 entered NR.Because different methods of total IgE assessment with different 27 reference values were used, the total IgE-values were transferred to percentage 28 scores of the respective upper reference value.Total IgE levels of 0%-10%, >10%-29 50%, and >50%-100% were regarded as low normal, mid normal, and high normal, 30 whereas total IgE levels of >100%-250%, >250%-1000%, and >1000% were 31 regarded as slightly elevated, moderately elevated, and highly elevated.Statistical 32 analyses were done with SPSS (IBM SPSS Statistics, Version 22).33 No differences were found between the three responder groups (CR, PR, and NR) 34 Page 1 of 9 Allergy upregulating activity as an immunological marker to predict response to treatment 121 with omalizumab in patients with symptomatic chronic urticaria.
Abstract 3489: Comprehensive characterization of the SLC transporters in human cancer
Authors: Ruiping Wang, Shaojun Zhang, Andy Futreal, Linghua Wang
Journal: Cancer Research (2018)

Abstract Metabolic reprogramming has now been well recognized as one of 10 hallmarks of cancer. The plasma membrane transporters, that enable efficient cellular metabolism and aid in nutrient sensing, are receiving increasing attention in recent years. Membrane transporters include 3 main classes: ABC transporters, p-type ATPases, and the solute carrier family (SLC). The SLC group of transporters includes nearly 400 members organized into 52 families that mediate the transport of a wide variety of substrates across biological membranes. Until recently, little was known about the role of these SLC transporters in the mechanisms of cancer development and progression. Yet, the genomic landscape and clinical relevance of SLC transporters in human cancer have not been investigated systematically. We here performed a comprehensive characterization of 396 SLC transporters by integrating multi-platform data across over 30 tumor types from The Cancer Genome Atlas. We observed frequent dysregulation of SLC transporters across cancer types and identified cancer type- and subtype-specific expression signatures. We identified significant correlations of these SLC transporters with the activity of cancer metabolic pathways and explored their complex regulatory networks. We also investigated the role of SLC transporters in tumor metastasis. We further evaluated the potential clinical relevance of these SLC transporters and identified multiple SLC transporters that were significantly associated with patients' clinical outcomes. Our study provided an in-depth understanding of the role of SLC transporters in cancer metabolic reprogramming, elucidated their mechanisms in cancer development and metastasis, and provided novel biomarkers and potential therapeutic targets that can be further developed for future clinical applications. Citation Format: Ruiping Wang, Shaojun Zhang, Andy Futreal, Linghua Wang. Comprehensive characterization of the SLC transporters in human cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3489.
Abstract 3012: Urban neighborhood and residential factors associated with breast cancer in African American women: A systematic review
Authors: Brandi P. Smith, Zeynep Madak-Erdogan
Journal: Cancer Research (2018)

Abstract Residential characteristics in urban neighborhoods impacts health and might be an important factor contributing to health disparities, especially in the African American population. The purpose of this systematic review is to understand the relationship between urban neighborhood and residential factors and breast cancer incidence and prognosis in African American women. Using PubMed and Web of Science, the existing literature was reviewed. Observational, cross-sectional, cohort, and prospective studies until February 2017 were examined. Studies including populations of African American women, setting in “urban” areas, and a measure of a neighborhood or residential factor were reviewed. Four parameters related to neighborhood or residential factors were extracted including: neighborhood socioeconomic status (nSES), residential segregation, spatial access to mammography, and residential pollution. Our analysis showed that African American women living in low nSES have greater odds of late stage diagnosis and mortality. Furthermore, African American women living in segregated areas (higher percentage of Blacks) have higher odds of late stage diagnosis and mortality compared to White and Hispanic women living in less segregated areas (lower percentage of Blacks). Late stage diagnosis was also shown to be significantly higher in areas with poor mammography access and areas with higher Black residential segregation. Lastly, residential pollution did not affect breast cancer risk in African American women. Overall, this systematic review provides a qualitative synthesis of major neighborhood and residential factors on breast cancer outcomes in African American women. Citation Format: Brandi P. Smith, Zeynep Madak-Erdogan. Urban neighborhood and residential factors associated with breast cancer in African American women: A systematic review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3012.
Activation of human aortic valve interstitial cells by local stiffness involves YAP-dependent transcriptional signaling
Authors: Rosaria Santoro, Denis Scaini, Luisa Ulloa Severino, Francesco Amadeo, Silvia Ferrari, Giacomo Bernava, Gloria Garoffolo, Marco Agrifoglio, Loredana Casalis, Maurizio Pesce
Journal: Biomaterials (2018)
Abstract 5880: Small-molecule modulators of PDE3/SLFN12 to kill cancer cells
Authors: Timothy A. Lewis, Luc de Waal, Xiaoyun Wu, Manuel Ellerman, Charlotte Kopitz, Antje Wengner, Knut Eis, Martin Lange, Adrian Tersteegen, Philip Lienau, Heidi Greulich, Matthew Meyerson
Journal: Cancer Research (2018)

Abstract We have previously reported1 our results with a small molecule called DNMDP which kills certain cancer cells by modulating the interaction of PDE3A and Schlafen 12 (SLFN12), a more recently discovered protein of unknown function. While DNMDP selectively inhibits PDE3, most PDE3 inhibitors have no cell killing effects and in fact rescue cancer cells from DNMDP-induced death. DNMDP is not suitable for advanced studies due to structural liabilities. Optimization of DNMDP to both increase activity and improve pharmacokinetic properties resulted in enantiomerically pure, low molecular weight, metabolically stable compounds which are active at low doses in animal models of cervical cancer and melanoma. While these compounds are selective PDE3A inhibitors and their biochemical activity mirrors their cellular activity, the activity of the compounds results not from PDE3 inhibition and increased cAMP levels, but from increased compound-induced binding of PDE3A to SLFN12, which most PDE3 inhibitors do not effect. Our results suggest that small molecule modulators of PDE3/SLFN12 binding may provide a novel treatment for the treatment of certain cancers. 1Nat. Chem. Bio. 2016, 12, 102-108. Citation Format: Timothy A. Lewis, Luc de Waal, Xiaoyun Wu, Manuel Ellerman, Charlotte Kopitz, Antje Wengner, Knut Eis, Martin Lange, Adrian Tersteegen, Philip Lienau, Heidi Greulich, Matthew Meyerson. Small-molecule modulators of PDE3/SLFN12 to kill cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5880.
Elevation of Prostate-Specific Markers After Cardiopulmonary Resuscitation
Authors: JeanetteKoller-Strametz, MonikaFritzer, MarianneGwechenberger, AlexanderGeppert, GottfriedHeinz, MarkusHaumer, MariaKoreny, GeraldMaurer, PeterSiostrzonek
Journal: Circulation (2000)

Background—Prostate-specific antigen (PSA), acid phosphatase (AP), and prostatic acid phosphatase (PAP) are serum markers for adenocarcinoma of the prostate gland. Previous studies indicated that prostatic ischemia may also produce elevations of PSA. Cardiopulmonary resuscitation (CPR) is frequently associated with profound tissue hypoperfusion. The present study investigated whether PSA, AP, and PAP are influenced by prolonged CPR. Methods and Results—PSA, AP, and PAP were assessed immediately, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after prolonged CPR (>5 minutes) in 14 male and 5 female patients. No changes were noted in women. In men, serum levels increased significantly after CPR and gradually decreased to near baseline values after 7 days. PSA, AP, and PAP values above the normal range were observed in 63%, 71%, and 64% of all patients, respectively. Compared with survivors, nonsurvivors exhibited higher peak serum levels of PSA (98.6±14.3 versus 1.1±2.2 μg/L; P<0.03), AP (57.0±71 ve...
Abstract 19305: Diabetes Mellitus and Ischemic Heart Disease Susceptibility: Which is the Influence of Genetic Polymorphisms for Katp Channels?
Authors: Paolo Severino, Alessandra Cinque, Nicolò Salvi, Giorgio Calabrese, Alessandra Armato, Maria Laura De Marchis, Raffaele Palmirotta, Massimo Mancone, Francesco Fedele
Journal: Circulation (2014)

Background: Evidences show that diabetes mellitus (DM) lead to higher risk for ischemic heart disease (IHD). Recently, we proposed that genetic polymorphisms (SNP) of coronary ion channels might be involved in IHD. We showed that the genotype distribution of SNP rs5215 for Kir6.2 subunit of ATP-dependent potassium (KATP) channels moderately deviated from the HW equilibrium and that rs5215_GG is linked to IHD susceptibility: it might have a ‘‘protective’’ role in IHD genesis. Moreover, previous studies described that SNP rs5215_GG is strongly correlated with DM and hyperinsulinism in human. Aim and methods: In the present study, we hypothesized that SNP rs5215_GG for Kir6.2 subunit for KATP channels had some influences in the susceptibility of DM to IHD. We performed a subgroup analysis about the influence of rs5215_GG in diabetic patients on our previous population, i.e. 242 patients candidates to elective or emergency coronary angiography for acute coronary syndrome or chronic angina, of which 155 with CAD, 46 with microvascular dysfunction and 41 with anatomically and functionally normal coronary arteries (control group). Results: Among 242 patients, comparing subjects with DM to those without, there was not any significant difference in the prevalence of rs5215_GG. However, among 33 subjects without DM with normal coronary arteries, SNP rs5215_GG had a higher prevalence compared to those in the CAD group (10/33; 30.3%; p= 0.0277) as well as non-diabetic patients in the microvascular dysfunction group (9/33; 27.2%; p= 0.0295). Discussion and conclusion: The variant rs5215_GG results in the substitution of isoleucine (I) residue with valine (V) in the Kir6.2 subunit of KATP channels. Our results confirm that rs5215_GG might decrease susceptibility to IHD in patients without DM. In fact, rs5215_GG was confirmed to be present more frequently in patients without DM presenting anatomically and functionally normal coronary arteries. We believe that absence of DM is protective against IHD genesis and it might be improved by coronary KATP channels expressing rs5215_GG. Taken together, our data ratify the possibility that ion channels play a key role in coronary homeostasis and that SNP encoding for ion channels are involved in IHD pathophysiology.
CK2 Phosphorylates the Angiotensin-Converting Enzyme and Regulates Its Retention in the Endothelial Cell Plasma Membrane
Authors: KarinKohlstedt, FirouzehShoghi, WernerMüller-Esterl, RudiBusse, IngridFleming
Journal: Circulation Research (2002)

Soluble angiotensin-converting enzyme (ACE) is derived from the membrane-bound form by proteolytic cleavage of its C-terminal domain. Because intracellular events might be involved in the regulation of the cleavage process, we determined whether the cytoplasmic tail of ACE is phosphorylated and whether this process regulates secretion. Immunoprecipitation of ACE (180 kDa) from 32P-labeled endothelial cells revealed that ACE is phosphorylated. Phosphorylation was not observed in endothelial cells overexpressing a mutant form of ACE (ACEΔS, all five cytoplasmic serine residues replaced by alanine). CK2 coprecipitated with ACE from endothelial cells, and CK2 phosphorylated both ACE and a peptide corresponding to the cytoplasmic tail. Mutation of serine1270 within the CK2 consensus sequence almost abolished ACE phosphorylation. In ACE-overexpressing endothelial cells, ACE was mostly localized to the plasma membrane. However, no ACE was detected in the plasma membrane of ACEΔS-overexpressing cells, although a ...
Indoor microbiota and the development of asthma by age 10.5 years: a birth cohort study
Authors: A. M. Karvonen, P. Kirjavainen, M. Taubel, B. Jayaprakash, R. Adams, J. E. Sordillo, D. R. Gold, A. Hyvarinen, S. Remes, Erika von Mutius, J. Pekkanen
Journal: Allergy (2017)
Kub5-Hera<i>RPRD1B</i> Deficiency Promotes “BRCAness” and Vulnerability to PARP Inhibition in BRCA-proficient Breast Cancers
Authors: Edward A. Motea, Farjana J. Fattah, Ling Xiao, Luc Girard, Amy Rommel, Julio C. Morales, Praveen Patidar, Yunyun Zhou, Andrew Porter, Yang Xie, John D. Minna, David A. Boothman
Journal: Clinical Cancer Research (2018)

Identification of novel strategies to expand the use of PARP inhibitors beyond BRCA deficiency is of great interest in personalized medicine. Here, we investigated the unannotated role of Kub5-HeraRPRD1B (K-H) in homologous recombination (HR) repair and its potential clinical significance in targeted cancer therapy.Functional characterization of K-H alterations on HR repair of double-strand breaks (DSB) were assessed by targeted gene silencing, plasmid reporter assays, immunofluorescence, and Western blots. Cell survival with PARP inhibitors was evaluated through colony-forming assays and statistically analyzed for correlation with K-H expression in various BRCA1/2 nonmutated breast cancers. Gene expression microarray/qPCR analyses, chromatin immunoprecipitation, and rescue experiments were used to investigate molecular mechanisms of action.K-H expression loss correlates with rucaparib LD50 values in a panel of BRCA1/2 nonmutated breast cancers. Mechanistically, K-H depletion promotes BRCAness, where extensive upregulation of PARP1 activity was required for the survival of breast cancer cells. PARP inhibition in these cells led to synthetic lethality that was rescued by wild-type K-H reexpression, but not by a mutant K-H (p.R106A) that weakly binds RNAPII. K-H mediates HR by facilitating recruitment of RNAPII to the promoter region of a critical DNA damage response and repair effector, cyclin-dependent kinase 1 (CDK1).Cancer cells with low K-H expression may have exploitable BRCAness properties that greatly expand the use of PARP inhibitors beyond BRCA mutations. Our results suggest that aberrant K-H alterations may have vital translational implications in cellular responses/survival to DNA damage, carcinogenesis, and personalized medicine.
Prevalence of dyslipidaemia among adults in Africa: a systematic review and meta-analysis
Authors: Jean Jacques Noubiap, Jean Joel Bigna, Jobert Richie Nansseu, Ulrich Flore Nyaga, Eric Vounsia Balti, Justin B Echouffo-Tcheugui, André Pascal Kengne
Journal: The Lancet Global Health (2018)

The burden of dyslipidaemia in Africa remains inadequately characterised. We aimed to estimate the prevalence of dyslipidaemia in African adults from hospital-based and community-based studies.In this systematic review and meta-analysis, we searched MEDLINE via PubMed, Embase, African Journals Online, and African Index Medicus for studies published between Jan 1, 1980, and July 31, 2017, without language restriction. We assessed methodological quality of all cross-sectional studies reporting on the prevalence of elevated concentrations of total cholesterol, LDL cholesterol, or triglycerides, or low concentrations of HDL cholesterol in adults residing in African countries. We excluded reports on Africans living outside Africa, studies of individuals selected on the basis of existing dyslipidaemia or those including children and adolescents, and case series with a small sample size. The most frequently used cutoffs in the included studies were chosen for the subgroup analysis. We used random-effect model meta-analysis to derive the pooled prevalence of elevated total cholesterol, low HDL cholesterol, elevated LDL cholesterol, and elevated triglyceride concentrations. This study is registered with PROSPERO, number CRD42014015376.181 studies (309 207 participants) were included in the meta-analysis. The pooled prevalence of dyslipidaemia in the general population from population-based studies was 23·6% (95% CI 18·4-29·2) for elevated concentrations of total cholesterol with a cutoff of at least 5·2 mmol/L, 41·1% (33·0-49·4) for low concentrations of HDL cholesterol with a cutoff of less than 1·0 mmol/L, 25·7% (16·2-36·6) for elevated concentrations of LDL cholesterol with a cutoff of at least 3·3 mmol/L, and 16·5% (11·8-21·6) for elevated concentrations of triglycerides with a cutoff of at least 1·7 mmol/L.The prevalence of dyslipidaemia is high in the general adult population in Africa. Ongoing efforts to reduce cardiovascular diseases in Africa should integrate effective detection and treatment of dyslipidaemia.None.
Abstract 4114: Development and application of 18F-labeled Tenascin-C aptamer for cancer imaging
Authors: Jun Young Park, Ye Lim Cho, Ju Ri Chae, Ga Eul Chu, Won Gil Cho, Sang Wun Kim, Won Jun Kang
Journal: Cancer Research (2018)

Abstract Aptamers are synthetic single-stranded DNA or RNA that can be held together with complementary sequences by base-pairing. Tenascin-C is an extracellular matrix protein that is overexpressed in cancer tissues. Herein, we investigate the biological characteristics of Tenascin-C aptamer as potential tumor imaging agents. Cy5 or F-18 labeled Tenascin-C aptamers were prepared through hybridization-based labeling method using complementary oligonucleotide platform. Immunoblot analysis was performed on U-251 MG, U-87 MG, C6 and NCI-H460 cell lines to confirm the expression of tenascin-C. In vitro binding specificity of Tenascin-C aptamers was evaluated using confocal microscopy. In vivo biodistribution properties and PET Imaging of the 18F-labeled Tenascin-C were determined in C6 tumor-bearing nude mice. High levels of tenascin-C protein were detected in C6, U-251 MG. and U-87 MG cell lines. However, tenascin-C protein levels were undetectable in NCI-H460 cells. Confocal fluorescence microscopy images showed that Cy5-labeled Tenascin-C aptamer bound specifically to tenascin-C protein expressing cell lines including C6, U-251 MG and U-87 MG, however, not bound to NCI-H460 cells. Tumor uptake of 18F-labeled Tenascin-C aptamer was 1.64 ± 0.36 at 30 min after injection in C6 tumor xenografts. C6 tumors were clearly visualized by microPET imaging in a tumor-bearing mouse at 60 after injection. Tenascin-C aptamer was successfully labeled with F-18 labeled complementary oligonucleotide by base-pair hybridization. In vitro data showed that the cODN platform-hybridized Tenascin-C aptamer was selectively bound to target tumor cells. In addition, C6 tumor xenografts in mice were clearly visualized on microPET imaging. Our study demonstrated that Tenascin-C may be a useful target molecule for the imaging of malignant gliomas. Citation Format: Jun Young Park, Ye Lim Cho, Ju Ri Chae, Ga Eul Chu, Won Gil Cho, Sang Wun Kim, Won Jun Kang. Development and application of 18F-labeled Tenascin-C aptamer for cancer imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4114.