tbuckley/cabot-search huggingface dataset:
Abstract LB-350: IgG4 expressing B cells associate with poor survival in triple negative breast cancer
Authors: Nicole Flynn, Ugochukwu Amadi, Rajasekharan Somasundaram, Jennifer Sims-Mourtada
Journal: Cancer Research (2018)

Abstract Triple negative breast cancer (TNBC) is an aggressive form of breast cancer with high levels of lymphocyte infiltration. Although high levels of infiltrating B cells are present in TNBC, their role in progression of this disease is unclear. IgG4 is one of four subclasses of IgG and is the least abundant in healthy human serum. IgG4 has been found at higher percentages in both tissue and serum in cases of chronic inflammation, which promotes class switching to IgG4. Expression and secretion of IgG4 by B cells may be non-beneficial and potentially harmful in the cancer setting. Unlike the other subclasses of IgG, IgG4 does not activate complement dependent cytotoxicity and has a lower affinity for FcγR, thus resulting in a poor ability to engage immune effector cells and activate antibody-depended cell-mediated cytotoxicity. Additionally, IgG4 can compete with other IgG subclasses by binding to antigens and can sequestering IgG through Fc-Fc interactions, thus impairing potential anti-tumor antibody-mediated responses. As IgG4 expressing B cells have been shown to be associated with poor outcomes in other aggressive cancers such melanoma, glioblastoma and pancreatic cancer, we sought to determine the expression of IgG4 in TNBC. We performed immunohistological staining of IgG4 in paraffin-embedded tissue microarrays from 75 treatment-naive TNBC specimens obtained from women who underwent surgical resection of their tumors at the Helen F Graham Cancer Center and Research Institute from 2006-2007. We found that 69 % of TNBC cases contain IgG4+ cell infiltration. Moreover, the presence of IgG4+ cells is significantly correlated with poorer progression free (p&amp;lt;0.0003) and overall survival (p&amp;lt;0.0001) as determined by a Log-rank (Mantel-Cox) test. These findings indicate the presence of an immunosuppressive B cell population. Further study is needed to characterize these cells and to determine the significance of IgG4+ tumor infiltrating B cells, and their potential immunosuppressive role in the progression of TNBC. Citation Format: Nicole Flynn, Ugochukwu Amadi, Rajasekharan Somasundaram, Jennifer Sims-Mourtada. IgG4 expressing B cells associate with poor survival in triple negative breast 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 LB-350.
Abstract 1062: Downregulation of miR-200c stabilizes XIAP mRNA and contributes to invasion and lung metastasis of bladder cancer
Authors: Zhongxian Tian, Honglei Jin, Jingxia Li, Chao Huang, Chuanshu Huang
Journal: Cancer Research (2018)

Abstract Our previous studies have demonstrated that X-linked inhibitor of apoptosis protein (XIAP) plays a regulatory role in cancer invasion via mediation of RhoGDIα protein SUMOylation at Ser138 in colorectal cancer HCT116 cells. However, the alteration/association of XIAP in invasion, progression, and lung metastasis of bladder cancer (BC) as well as the molecular mechanisms leading to this XIAP alteration during BC development have not been explored yet. Herein, we found that XIAP was overexpressed in human high grade BCs, high metastatic human BC T24T cells, and in mouse invasive BCs. Mechanistic studies indicated that XIAP overexpression in the highly metastatic T24T cells was due to increased mRNA stability of XIAP in comparison to the parental non-metastatic T24 cells. Results from XIAP mRNA stability regulation revealed that miR-200c was profoundly downregulated in T24T cells and in highly invasive BCs, and that such miR-200c downregulation was mediated by CREB inactivation. Furthermore, miR-200c downregulation reduced its binding to the 3'-UTR region of XIAP mRNA, and resulted in its mRNA stabilization, protein overexpression, and invasive capabilities in T24T cells. Moreover, our results from XIAP-specific shRNA and miR-200c ectopic expression showed that suppression of XIAP profoundly attenuated lung metastasis of T24T cells in nude mice. In conclusion, our findings demonstrate the molecular basis leading to XIAP overexpression and the crucial role of XIAP in BC invasion in vitro and lung metastasis in nude mice. Citation Format: Zhongxian Tian, Honglei Jin, Jingxia Li, Chao Huang, Chuanshu Huang. Downregulation of miR-200c stabilizes XIAP mRNA and contributes to invasion and lung metastasis of bladder 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 1062.
Familial Hypertrophic Cardiomyopathy
Authors: GisèleBonne, LucieCarrier, PascaleRichard, BernardHainque, KettySchwartz
Journal: Circulation Research (1998)

Abstract—Hypertrophic cardiomyopathy is characterized by left and/or right ventricular hypertrophy, which is usually asymmetric and involves the interventricular septum. Typical morphological changes include myocyte hypertrophy and disarray surrounding the areas of increased loose connective tissue. Arrhythmias and premature sudden deaths are common. Hypertrophic cardiomyopathy is familial in the majority of cases and is transmitted as an autosomal-dominant trait. The results of molecular genetics studies have shown that familial hypertrophic cardiomyopathy is a disease of the sarcomere involving mutations in 7 different genes encoding proteins of the myofibrillar apparatus: β-myosin heavy chain, ventricular myosin essential light chain, ventricular myosin regulatory light chain, cardiac troponin T, cardiac troponin I, α-tropomyosin, and cardiac myosin binding protein C. In addition to this locus heterogeneity, there is a wide allelic heterogeneity, since numerous mutations have been found in all these ge...
The mode of action of anticholinergics in asthma
Authors: Reinoud Gosens, Nicholas Gross
Journal: European Respiratory Journal (2018)

Acetylcholine binds to muscarinic receptors to play a key role in the pathophysiology of asthma, leading to bronchoconstriction, increased mucus secretion, inflammation and airway remodelling. Anticholinergics are muscarinic receptor antagonists that are used in the treatment of chronic obstructive pulmonary disease and asthma. Recent in vivo and in vitro data have increased our understanding of how acetylcholine contributes to the disease manifestations of asthma, as well as elucidating the mechanism of action of anticholinergics. This review assesses the latest literature on acetylcholine in asthma pathophysiology, with a closer look at its role in airway inflammation and remodelling. New insights into the mechanism of action of anticholinergics, their effects on airway remodelling, and a review of the efficacy and safety of long-acting anticholinergics in asthma treatment will also be covered, including a summary of the latest clinical trial data.
Contraceptive Use Among Women at Risk for Unintended Pregnancy in the Context of Public Health Emergencies — United States, 2016
Authors: Karen Pazol, Sascha R. Ellington, Anna C. Fulton, Lauren B. Zapata, Sheree L. Boulet, Marion E. Rice, Shanna Cox, Lisa Romero, Eva Lathrop, Stacey Hurst, Charlan D. Kroelinger, Howard Goldberg, Carrie K. Shapiro-Mendoza, Regina M. Simeone, Lee Warner, Dana M. Meaney-Delman, Wanda D. Barfield, Leah Atwell, Rana Bayakly, Sarah Conklin, Harley T. Davis, Victoria Davis, Laurie Freyder, Christine Graham, Sarojini Kanotra, Sarah Khalidi, Georgette Lavetsky, Kristi Pier, Lauren Porter, Mina Qobadi, Sondra Reese, Chelsea L. Richard, Nagi Salem, Ruby A. Serrano-Rodríguez, Birgit A. Shanholtzer, Holly Sobotka, Amilcar Soto-Mercado, Carol L. Stone
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Ensuring access to and promoting use of effective contraception have been identified as important strategies for preventing unintended pregnancy (1). The importance of ensuring resources to prevent unintended pregnancy in the context of public health emergencies was highlighted during the 2016 Zika virus outbreak when Zika virus infection during pregnancy was identified as a cause of serious birth defects (2). Accordingly, CDC outlined strategies for state, local, and territorial jurisdictions to consider implementing to ensure access to contraception (3). To update previously published contraceptive use estimates* among women at risk for unintended pregnancy† and to estimate the number of women with ongoing or potential need for contraceptive services,§,¶ data on contraceptive use were collected during September-December 2016 through the Behavioral Risk Factor Surveillance System (BRFSS). Results from 21 jurisdictions indicated that most women aged 18-49 years were at risk for unintended pregnancy (range across jurisdictions = 57.4%-76.8%). Estimates of the number of women with ongoing or potential need for contraceptive services ranged from 368 to 617 per 1,000 women aged 18-49 years. The percentage of women at risk for unintended pregnancy using a most or moderately effective contraceptive method** ranged from 26.1% to 65.7%. Jurisdictions can use this information to estimate the number of women who might seek contraceptive services and to plan and evaluate efforts to increase contraceptive use. This information is particularly important in the context of public health emergencies, such as the recent Zika virus outbreak, which have been associated with increased risk for adverse maternal-infant outcomes (2,4-6) and have highlighted the importance of providing women and their partners with resources to prevent unintended pregnancy.
Identification of a Novel Role of T Cells in Postnatal Vasculogenesis
Authors: JinHur, Han-MoYang, Chang-HwanYoon, Choon-SooLee, Kyung-WooPark, Ji-HyunKim, Tae-YounKim, Ju-YoungKim, Hyun-JaeKang, In-HoChae, Byung-HeeOh, Young-BaePark, Hyo-SooKim
Journal: Circulation (2007)

Background— The colony number of early endothelial progenitor cells (EPCs) has been used as a quantitative indicator of the number of EPCs in the blood or as a biological marker of cardiovascular diseases. In the present study, we found a subset of T cells that were localized at the center of the EPC colony and played a pivotal role in colony formation and differentiation of early EPCs. Methods and Results— We found that CD3+CD31+CXCR4+ T cells (referred to as angiogenic T cells in the present study) constituted the center of EPC colonies during cultures of human peripheral blood mononuclear cells. These angiogenic T cells were required for colony formation and differentiation of early EPCs. They secreted high levels of angiogenic cytokines such as vascular endothelial growth factor, interleukin-8, and matrix metalloproteinases. Angiogenic T cells showed superior angiogenic potential to the other subset of T cells in the experiments with regard to Matrigel tube formation, adhesion, transendothelial migrat...
Use of topical antipsoriatic drugs in Denmark: a nationwide drug utilization study
Authors: M.T. Svendsen, M.S. Ernst, K.E. Andersen, F. Andersen, H. Johannessen, A. Pottegård
Journal: British Journal of Dermatology (2018)

The reported real-life use of prescribed topical antipsoriatic drugs is conflicting and based on heterogeneous data sources.To describe the utilization of topical antipsoriatic drugs among patients with psoriasis in Denmark.A drug utilization study was performed based on nationwide Danish health registry data. We identified patients who received a first-time hospital diagnosis of psoriasis and redeemed at least one topical drug prescription in the period 2005-2015 (n = 7743). Patients were followed for 3 years from the time of diagnosis. Use of topical and systemic antipsoriatic drugs was described, specified by the type of treatment.The total use of topical drugs was divided between corticosteroids with calcipotriol (31%), calcipotriol (6·5%), very potent corticosteroids (24%), potent corticosteroids (30%), moderate corticosteroids (7·2%) and corticosteroids with antimicrobials (1·6%). There was a 19% reduction in the overall use of topical drugs during the study period. Use increased around the time of diagnosis and the majority of patients redeemed more than two packages of topical drugs during the first year after being diagnosed. Regional differences in patients' use of topical drugs varied considerably. The distribution of use of topical drugs was uneven, with a minority of all patients (25%) using 70% of the total amount of topical treatment. There was a 70% increase in the use of methotrexate over the study period. Biologics were used by up to 6%.The study provides further evidence that the use of topical antipsoriatic drugs shows considerable heterogeneity over time and regional practices, and differences between patients.
Targeting ability of self-assembled nanomedicines in rat acute limb ischemia model is affected by size
Authors: Masamitsu Suhara, Yutaka Miura, Horacio Cabral, Daisuke Akagi, Yasutaka Anraku, Akihiro Kishimura, Masaya Sano, Takuya Miyazaki, Noriko Nakamura, Ayako Nishiyama, Kazunori Kataoka, Hiroyuki Koyama, Katsuyuki Hoshina
Journal: Journal of Controlled Release (2018)

Peripheral artery disease (PAD) is one of the most spreading diseases all over the world. The treatment strategies are limited to surgical or endovascular procedures for final stage chronic PAD or acute limb ischemia, and no pharmacological approaches have been achieved to prevent the worsening of chronic PAD or to regenerate the tissues of acute limb ischemia. Therefore, the improvement of therapeutic strategy is strongly demanded in clinics. Here, we adopted an acute hindlimb ischemia model in rats, which provides concomitant inflammatory response, to evaluate the application of drug delivery system against PAD. Through comparative experiments by using different-sized nanomedicine analogues, polyion complex (PIC) micelles with 30 nm diameter and PIC vesicles with 100- and 200-nm diameter (PICs-30, −100, −200 respectively), we found the size-dependent accumulation and retention in the collateral arteries. In contrast to PICs-30 and -200, histological analysis showed that PICs-100 were around the arterioles and co-localized with macrophages, which indicates that the PICs-100 can achieve moderate interaction with phagocytes. Our data suggests that controlling the size of nanomedicines has promise for developing novel angiogenic treatments toward the effective management of collateral arteries.
Abstract 856: Selection of radiosensitizers based on HRAS mutation in bladder cancer
Authors: Michael M. Fisher, Adam D. Swick, Kwangok P. Nickel, Randall J. Kimple
Journal: Cancer Research (2018)

Abstract Purpose/Objective(s): The ability of activated HRAS to promote radiation resistance and predict for sensitivity to potential radiosensitizers was tested in a bladder cancer model system. Materials/Methods: Mutations in HRAS, KRAS, and NRAS were analyzed using cBioPortal in a bladder cancer cohort (TCGA). We employed a panel of urothelial carcinoma cell lines-T24 (HRASG12V), J82 and 5637 (RASWT). Cell growth and survival was tested with colony formation and proliferation assays. Radiation survival was assessed by clonogenic survival assay. Immunoblots were used to confirm mutant HRAS expression, and target activation/knockdown in overexpression and knockdown studies. Radiosensitization of mutant-HRAS bladder cancer was tested using a flank cell line xenograft model in nude mice. Results: Approximately 10% of bladder cancers feature alterations in one of three RAS genes; mutations in HRAS comprise greater than 50% of these. An HRAS activating (G12V) mutation was detected in T24. Consistent with known roles for activated RAS, T24 is relatively insensitive to both cetuximab and radiation. Using both in vivo and in vitro studies, cetuximab exhibited no radiosensitization of T24. Treatment with cetuximab lowered AKT, but not ERK activation. Direct inhibition of the MEK/ERK or PI3K/MTOR pathway by selumetinib or BEZ235, respectively, decreased target protein activation and resulted in significant growth inhibition compared to control (p&amp;lt;0.05). Treatment with either selumetinib or BEZ235 radiosensitized HRASG12V expressing cells (SER 1.3-1.8), but had more modest effects on cells with wild-type HRAS. siRNA knockdown of HRAS radiosensitized T24, but not J82 or 5637 cells relative to non-targeting control. The combination of selumetinib and radiation therapy delayed the growth of T24 tumors in vivo. Conclusions: Over 10% of bladder cancers feature alterations in the RAS family of genes. These mutations can lead to resistance to cetuximab, either as a single treatment or as a radiosensitizer. Inhibition of downstream MEK/ERK and PI3K/MTOR pathways can radiosensitize tumors with activating mutations in HRAS. Identification of additional mutation/drug combinations that result in radiosensitization may be valuable to advance the design of personalized radiation therapy. Citation Format: Michael M. Fisher, Adam D. Swick, Kwangok P. Nickel, Randall J. Kimple. Selection of radiosensitizers based on HRAS mutation in bladder 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 856.
Deficiency of GATA3-Positive Macrophages Improves Cardiac Function Following Myocardial Infarction or Pressure Overload Hypertrophy
Authors: Mingjie Yang, Lei Song, Lai Wang, Ada Yukht, Haley Ruther, Fuqiang Li, Minghui Qin, Homayon Ghiasi, Behrooz G. Sharifi, Prediman K. Shah
Journal: Journal of the American College of Cardiology (2018)
Giant Abdominal Aortic Aneurysm
Authors: NicolaMumoli, ClaudioInvernizzi, RiccardoLuschi, GiovanniCarmignani, AlbertoCamaiti, LorenzoBocci, SimonaMilianelli, GianluigiOcchipinti, PatrizioChiavistelli, FabrizioOrlandi, GiovanniNiccoli
Journal: Circulation (2010)
Role of Ca2+-Independent Phospholipase A2 and Store-Operated Pathway in Urocortin-Induced Vasodilatation of Rat Coronary Artery
Authors: TarikSmani, AlejandroDomínguez-Rodríguez, AbdelkrimHmadcha, EvaCalderón-Sánchez, AngélicaHorrillo-Ledesma, AntonioOrdóñez
Journal: Circulation Research (2007)

Urocortin has been shown to produce vasodilatation in several arteries, but the precise mechanism of its action is still poorly understood. Here we demonstrate the role of store operated Ca2+ entry (SOCE) regulated by Ca2+-independent phospholipase A2 (iPLA2) in phenylephrine hydrochloride (PE)-induced vasoconstriction, and we present the first evidence that urocortin induces relaxation by the modulation of SOCE and iPLA2 in rat coronary artery. Urocortin produces an endothelium independent relaxation, and its effect is concentration-dependent (IC50≈4.5 nmol/L). We show in coronary smooth muscle cells (SMCs) that urocortin inhibits iPLA2 activation, a crucial step for SOC channel activation, and prevents Ca2+ influx evoked by the emptying of the stores via a cAMP and protein kinase A (PKA)–dependent mechanism. Lysophophatidylcholine and lysophosphatidylinositol, products of iPLA2, exactly mimic the effect of the depletion of the stores in presence of urocortin. Furthermore, we report that long treatment w...
Abstract P115: How Many Coronary Heart Disease Deaths In Poland In 2020 Might Be Prevented By Further Reductions In Population Risk Factor Levels?
Authors: PiotrBandosz, MariaGuzman-Castillo, SimonCapewell, TomaszZdrojewski, JuliaCritchley, MarcinRutkowski, MartinO'Flaherty
Journal: Circulation (2014)

Background: Poland has experienced one of the most dramatic declines in coronary heart disease (CHD) mortality rates in recent decades. This decline reflects the use of evidence based treatments and, crucially, population wide changes in diet. Our aim is to explore the potential for further gains in Poland by achieving population wide reductions in smoking, dietary salt and saturated fat intake and physical inactivity levels. Methods: A validated and updated policy model was used to forecast potential decreases in CHD deaths by 2020 as consequence of lifestyle and dietary changes in the population. Data from the most recent Polish risk factor survey was used for the baseline (2011). We modeled two different policy scenarios regarding possible future changes in risk factors: A) conservative scenario: reduction of smoking prevalence and physically inactivity rates by 5% between 2011 and 2020, and reduction of dietary consumption of energy from saturated fats by 1% and of salt by 10%. B) ideal scenario: redu...
CD4+ T Cells Promote the Transition From Hypertrophy to Heart Failure During Chronic Pressure Overload
Authors: FannyLaroumanie, VictorineDouin-Echinard, JoffreyPozzo, OlivierLairez, FlorenceTortosa, ClaireVinel, ChristineDelage, DenisCalise, MarianneDutaur, AngeloParini, NathaliePizzinat
Journal: Circulation (2014)

Background—The mechanisms by which the heart adapts to chronic pressure overload, producing compensated hypertrophy and eventually heart failure (HF), are still not well defined. We aimed to investigate the involvement of T cells in the progression to HF using a transverse aortic constriction (TAC) model. Methods and Results—Chronic HF was associated with accumulation of T lymphocytes and activated/effector CD4+ T cells within cardiac tissue. After TAC, enlarged heart mediastinal draining lymph nodes showed a high density of both CD4+ and CD8+ T-cell subsets. To investigate the role of T cells in HF, TAC was performed on mice deficient for recombination activating gene 2 expression (RAG2KO) lacking B and T lymphocytes. Compared with wild-type TAC mice, RAG2KO mice did not develop cardiac dilation and showed improved contractile function and blunted adverse remodeling. Reconstitution of the T-cell compartment into RAG2KO mice before TAC enhanced contractile dysfunction, fibrosis, collagen accumulation, and...