tbuckley/cabot-search huggingface dataset:
Abstract 5128: Characterization of tumor immune microenvironment in response to PD-L1 therapy initiated at different time points post inoculation in syngeneic mouse models
Authors: Geeta Sharma, Susan Wu, Robert Mihalek, Ann Fiore, Matthew Gale, Christa Dias, Wendy Grant, Nidia Hernandez
Journal: Cancer Research (2016)

Abstract The tumor microenvironment is an important aspect of cancer biology that contributes to tumor initiation, progression and responses to therapy. Cells and molecules of the immune system are fundamental components of the tumor microenvironment which have been known to vary widely and are important in determining the anti-tumor immune response. The approval of immune checkpoint inhibitors like PD-1 and CTLA-4 antibodies has resulted in a lot of research activity in immune-oncology. Syngeneic mouse models have been utilized to understand the preclinical immune response as a surrogate to the clinical response. The timing of immune checkpoint inhibitor dosing is supposed to play an important role on the tumor growth in mouse models. In order to understand the correlation of tumor regression, survival and immune response in a preclinical mouse model, we evaluated the effect of different times of treatment initiation with Program Death Ligand-1 (PD-L1) on tumor volume, survival and tumor infiltrating leukocytes (TIL’s). Various dosing regimens evaluated included initiation of PD-L1 therapy on the day of inoculation, 6 and 12 days post inoculation. Tumors were collected from three different syngeneic mouse models (CT26, RENCA and B16F10) and profiled for the presence of tumor infiltrating leukocytes (TIL’s) using flow cytometry. Major sub-population of TIL's examined included T-regulatory cells (Treg’s), Tumor Associated Macrophages (TAM’s) and Myeloid Derived Suppressor Cells (MDSC’s). Finally, an attempt was made to identify any correlation or lack thereof between tumor growth and tumor immune microenvironment. Citation Format: Geeta Sharma, Susan Wu, Robert Mihalek, Ann Fiore, Matthew Gale, Christa Dias, Wendy Grant, Nidia Hernandez. Characterization of tumor immune microenvironment in response to PD-L1 therapy initiated at different time points post inoculation in syngeneic mouse models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5128.
Jewish Immigrants Of Middle Eastern Origin Have a Lower Incidence Of Multiple Myeloma Compared To Both North African and European Jews In a Cohort Of 746,200 Israeli Men Followed From Late Adolescence
Authors: Merav Leiba, Arnon Afek, Estela Derazne, Adi Leiba, Lital Keinan-Boker, Ari Shamiss, Arnon Nagler, Jeremy D. Kark
Journal: Blood (2013)
Intended Target of the Centers for Disease Control and Prevention Opioid Guidelines
Authors: Salimah H. Meghani
Journal: JAMA Oncology (2016)

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Mumps outbreak on the island of Anglesey, North Wales, December 2008-January 2009
Authors: C Roberts, G Porter-Jones, J Crocker, J Hart
Journal: Eurosurveillance (2009)

Twenty-three cases of clinical mumps in young people have been reported in North Wales over a five-week period since late December 2008. All cases have social links, and most of them have received two doses of mumps-containing vaccine.
Abstract LB-273: Identity card of tumor-infiltrating regulatory T cells in the context of tertiary lymphoid structures in lung cancer patients
Authors: Priyanka DEVI, Sylvain Leveugle, Jeremy Goc, Helene Kaplon, Claire Germain, Samantha Knockaert, Pierre Validire, Diane Damotte, Sandrine Katsahian, Wolf Herve Fridman, Catherine Sautes-Fridman, Myriam Lawand, Marie-Caroline Dieu-Nosjean
Journal: Cancer Research (2016)

Abstract Regulatory T cells (Tregs) exert various suppressive mechanisms to dampen the host immune response which can help tumor cells to escape immune surveillance. However, the prognostic value of tumor-infiltrating Tregs (Ti-Tregs) is controversial. We described, tumor-associated tertiary lymphoid structures (TLS) in lung cancers, shown that they are critical for the local coordination and polarization of protective immunity and are able to imprint the behavior of intra-tumoral CD8+ T cells. The aim of the study was to determine the role of Ti-Tregs in the shaping of the local immune response in the context of TLS. We studied the differentiation, activation, immunosuppression, and immune checkpoint (ICP) status of Ti-Tregs in different areas of human lung tumors on a prospective cohort of 50 lung cancer specimens. In lung cancer patients, CD3+FoxP3+ cells were detected in different zones of the tumor i.e. the tumor stroma (TLS and non-TLS areas) and to a lesser extend in tumor nests. They express CD4 and all markers of human Tregs. As observed for conventional CD4+ T cells, Ti-Tregs show central-memory and effector-memory phenotype. Based on the expression of activation, immunosuppression and ICP (gene and protein level), Tregs exhibit a fully activated phenotype in tumor compared to distant sites of NSCLC patients. Interestingly, Ti-Tregs display a common phenotype in TLS versus out TLS but with some key specificities regarding immune checkpoint expression. In conclusion, the presence of several Ti-Treg subsets in lung tumor suggests they may use distinct mechanisms to exert their immunosuppressive functions in the different tumor areas. Citation Format: Priyanka DEVI, Sylvain Leveugle, Jeremy Goc, Helene Kaplon, Claire Germain, Samantha Knockaert, Pierre Validire, Diane Damotte, Sandrine Katsahian, Wolf Herve Fridman, Catherine Sautes-Fridman, Myriam Lawand, Marie-Caroline Dieu-Nosjean. Identity card of tumor-infiltrating regulatory T cells in the context of tertiary lymphoid structures in lung cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-273.
Abstract 1752: Dietary fat intake during adolescence and breast density among young women
Authors: Seungyoun Jung
Journal: Cancer Research (2016)

Abstract BACKGROUND: Lack of association between fat intake and breast cancer risk in cohort studies might be attributed to disregard of temporal effects during adolescence when breasts develop and are particularly sensitive to stimuli. We prospectively examined associations between adolescent fat intakes and breast density. METHOD: Among 177 women who participated in the Dietary Intervention Study in Children, dietary intakes at ages 10-18 were assessed on five occasions by 24-hour recalls and averaged. We calculated geometric mean and 95% confidence intervals for MRI-measured breast density at ages 25-29 across quartiles of fat intake using linear mixed-effect regression. RESULTS: Comparing women in the extreme quartiles of adolescent fat intakes, percent dense breast volume (%DBV) was positively associated with saturated fat (mean = 16.4% vs. 21.5%; Ptrend&amp;lt;0.001). Conversely,%DBV was inversely associated with monounsaturated fat (25.0% vs. 15.8%; Ptrend&amp;lt;0.001) and the ratio of polyunsaturated fat to saturated fat (P/S ratio; 19.1% vs. 14.3%; Ptrend:&amp;lt;0.001). When examining intake by pubertal stages,%DBV was inversely associated with intake of polyunsaturated fat (20.8% vs. 16.4%; Ptrend = 0.04), long-chain omega-3 fat (17.8% vs. 15.8%; Ptrend&amp;lt;0.001), and P/S ratio (22.5% vs. 16.1%; Ptrend&amp;lt;0.001) before menarche, but not after. These associations observed with%DBV were consistently observed with absolute dense breast volume but not with absolute non-dense breast volume. CONCLUSIONS: In our study, adolescent intakes of higher saturated fat and lower mono- and polyunsaturated fat are associated with higher breast density measured approximately 15 years later. IMPACT: The fat subtype composition in adolescent diet may be important in early breast cancer prevention. Citation Format: Seungyoun Jung. Dietary fat intake during adolescence and breast density among young women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1752.
Uncovering Haematopoietic System Dynamics and Single Multipotent Progenitors Activity In Vivo In Humans by Retroviral Tagging.
Authors: Luca Biasco, Cristina Baricordi, Stefania Merella, Cynthia Bartholomae, Alessandro Ambrosi, Danilo Pellin, Clelia Di Serio, Christof Von Kalle, Manfred Schmidt, Alessandro Aiuti
Journal: Blood (2010)
Re: Jabbarvand et al.: Endophthalmitis occurring after cataract surgery: outcomes of more than 480 000 cataract surgeries, epidemiologic features, and risk factors (Ophthalmology 2016;123:295-301)
Authors: Vivek Dave, Siddharth Dikshit, Mudit Tyagi, Chandra S. Garudadri, Sayan Basu
Journal: Ophthalmology (2016)
Streamlining ethical review of data intensive research
Authors: David Townend, Edward S Dove, Dianne Nicol, Jasper Bovenberg, Bartha M Knoppers
Journal: BMJ (2016)

Research that crosses international borders and analyses large volumes of data from multiple sources is growing.Such data intensive research-for example, precision medicine studies driven by genomic research and DNA sequencing-creates difficult governance challenges, one of which is repetitive and inefficient ethical review.There is no clear evidence that review of the same study by multiple research ethics committees better protects participants, particularly for research analysing large aggregate datasets.International, data intensive research may require different assessment from research that risks physical harm to participants. 1 2 However, concerns about liability mean that local ethics committees-and their administrators and institutional lawyers-tend to insist on reviewing research protocols themselves, rather than "delegating" review to another ethics committee or otherwise recognising outside reviews.These concerns are some of the main barriers to reform of the ethics review system for international research. 3We argue that the concerns are more perception than reality.
Denosumab in Postmenopausal Women with Low Bone Mineral Density
Authors: Michael R. McClung, E. Michael Lewiecki, Stanley B. Cohen, Michael A. Bolognese, Grattan C. Woodson, Alfred H. Moffett, Munro Peacock, Paul D. Miller, Samuel N. Lederman, Charles H. Chesnut, Douglas Lain, Alan J. Kivitz, Donna L. Holloway, Charlie Zhang, Mark C. Peterson, Pirow J. Bekker
Journal: New England Journal of Medicine (2006)

Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162) binds RANKL with high affinity and specificity and inhibits RANKL action.The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open-label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase.Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent.In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment for osteoporosis. (ClinicalTrials.gov number, NCT00043186.).
Methicillin-resistant Staphylococcus aureus (MRSA)
Authors: R Köck, K Becker, B Cookson, J E van Gemert-Pijnen, S Harbarth, J Kluytmans, M Mielke, G Peters, R L Skov, M J Struelens, E Tacconelli, A Navarro Torné, W Witte, Alex Friedrich
Journal: Eurosurveillance (2010)
Abstract 3591: Expression of 14-3-3 gamma stabilizes polyploidization in NSCLC cells
Authors: Cecil J. Gomes, Michael Harman, Sara Centuori, Charles Wolgemuth, Jesse Martinez
Journal: Cancer Research (2016)

Abstract In normal lung tissue the expression levels of 14-3-3 gamma are very low and tightly regulated, however, in cancer it is evident that 14-3-3 gamma's expression patterns become deregulated and significantly elevated. In patients with advanced non-small cell lung cancer (NSCLC), increased expression of this isoform is associated with poorer survival and significantly correlates with lymph node and distant metastasis. These data prompted us to analyze TCGA's NSCLC gene expression dataset, and it is clear that 14-3-3 gamma's expression continues to increase in the progression from early to late stage cancers. Taken together, these data suggest that overexpression of 14-3-3 gamma is correlated with a more aggressive tumor phenotype, an observation also seen with breast and hepatocellular carcinoma. The focus of this study is to elucidate the mechanism(s) causing these more aggressive cancer phenotypes. We have previously shown that overexpressing 14-3-3 gamma in human lung cancer cells harboring very low levels of endogenous 14-3-3 gamma and no wildtype p53 results in a stable subpopulation of cells with polyploid DNA content. Interestingly, approximately 40% of lung adenocarcinomas present with hyper-triploid karyotypes, and even a higher percentage, 40-60%, have inactivation of p53. It is well established that polyploid tumors have the capacity to increase tumorigenicity by allowing resistance to conventional therapies and also permitting elevated tolerance to chromosomal instability (CIN). This leads us to hypothesize that in the absence of p53, NSCLC tumors overexpressing 14-3-3 gamma result in a polyploid population of cells that may be influencing the aggressiveness of the tumor. Further in vitro analysis of these 14-3-3 gamma induced tetraploid cells show that they have a prolonged mitosis with significantly more lagging chromosomes in anaphase than their diploid counterparts, indicating an increase in chromosomal instability (CIN). After isolating isogenic tetraploid clones with or without 14-3-3 gamma expression, the stability of the tetraploid cell state was assessed. Clones not expressing 14-3-3 gamma quickly reverted back to a pseudo-diploid state, whereas overexpression of 14-3-3 gamma significantly prolonged the tolerance of tetraploidy and eventually resulted in an aneuploid cell state. Our data suggests that overexpression of 14-3-3 gamma increases tumorigenicity through the stabilization of a polyploid cell state. Citation Format: Cecil J. Gomes, Michael Harman, Sara Centuori, Charles Wolgemuth, Jesse Martinez. Expression of 14-3-3 gamma stabilizes polyploidization in NSCLC cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3591.
Abstract 1637: 22(S)-Hydroxycholesterol, an antagonist of LXR, inhibits breast cancer cell migration
Authors: Sewon Hwang, Tae Young Na, Hyelin Na, Minho Lee, Mi-Ock Lee
Journal: Cancer Research (2016)

Abstract The Liver X Receptor (LXR) is a well-established ligand-regulated transcription factor involved in cholesterol homeostasis, lipid metabolism, and inflammation. Recent studies have reported a strong antiproliferative effect of LXRs in multiple types of cancer including prostate, colon, lung, and breast cancer. However, little is known about its association with cancer metastasis. Therefore we aimed to investigate the potential of LXR ligands in the context of breast cancer cell migration, and its underlying molecular mechanism. We first performed 2D-migration assay in 4T1 breast cancer cells. Treatment of an LXR antagonist significantly reduced the rate of 4T1 cell migration. However, LXR agonists such as T0901317, GW3965 did not have much effect. Next, we investigated the molecular mechanism of cell migration. Since the degree of invasion and metastasis of breast carcinoma is well correlated with elevated expression of metastasis-associated protein 1 (MTA1), we examined whether MTA1 expression could be regulated by LXR ligands. Interestingly, when LXR agonists were treated, increased protein expression of MTA1 and its downstream target protein HIF-1α was observed in MCF7, MDA-MB-231, and 4T1-Luc breast cancer cell lines. Transient expression of LXRα demonstrated the same results as well. Furthermore, the treat of 22(S)-HC down-regulated MTA1 and HIF-1α protein expressions. Together, our findings indicate that LXR influences migratory pattern of breast cancer cells, which may affect metastatic property of breast cancer cells via LXR-dependent regulation of MTA1 and HIF-1α expression. Citation Format: Sewon Hwang, Tae Young Na, Hyelin Na, Minho Lee, Mi-Ock Lee. 22(S)-Hydroxycholesterol, an antagonist of LXR, inhibits breast cancer cell migration. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1637.
Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2
Authors: Marc Humbert, J Gerry Coghlan, Hossein-Ardeschir Ghofrani, Friedrich Grimminger, Jian-Guo He, Gabriela Riemekasten, Carmine Dario Vizza, Annette Boeckenhoff, Christian Meier, Janethe de Oliveira Pena, Christopher P Denton
Journal: Annals of the Rheumatic Diseases (2016)

Background The 12-week, phase III Pulmonary Arterial hyperTENsion sGC-stimulator Trial (PATENT)-1 study investigated riociguat in patients with pulmonary arterial hypertension (PAH). Here, we present a prospectively planned analysis of the safety and efficacy of riociguat in the subgroup of patients with PAH associated with connective tissue disease (PAH-CTD). Methods Patients with PAH-CTD were further classified post hoc as having PAH associated with systemic sclerosis or PAH-other defined CTD. In PATENT-1, patients received riociguat (maximum 2.5 or 1.5 mg three times daily) or placebo. Efficacy endpoints included change from baseline in 6-minute walking distance (6MWD; primary endpoint), haemodynamics and WHO functional class (WHO FC). In the long-term extension PATENT-2, patients received riociguat (maximum 2.5 mg three times daily); the primary endpoint was safety and tolerability. Results In patients with PAH-CTD, riociguat increased mean 6MWD, WHO FC, pulmonary vascular resistance and cardiac index. Improvements in 6MWD and WHO FC persisted at 2 years. Two-year survival of patients with PAH-CTD was the same as for idiopathic PAH (93%). Riociguat had a similar safety profile in patients with PAH-CTD to that of the overall population. Conclusions Riociguat was well tolerated and associated with positive trends in 6MWD and other endpoints that were sustained at 2 years in patients with PAH-CTD. Trial registration numbers PATENT-1 ( NCT00810693 ), PATENT-2 ( NCT00863681 ).
The Authors' reply: Figure 1
Authors: Aleixo M Muise, Ramzi Fattouh, Grace Y Lam, Sandeep Dhillon, John H Brumell
Journal: Gut (2011)

We read with interest the letter by Somasundaram et al 1 in response to our paper ‘NADPH oxidase complex and IBD candidate gene studies: identification of a rare variant in NCF2 that results in reduced binding to RAC2’ that further demonstrates the importance of the NADPH oxidase complex genes in the pathogenesis of Crohn's disease. Their letter provides interesting confirmatory data that complement our findings, which already clearly demonstrate the role of the NADPH oxidase complex in inflammatory bowel disease (IBD).2 However, there are a number of important issues that require further clarification.

1.  Somasundaram et al suggest that our study did not show the association between reactive oxygen species (ROS) production and IBD.1 Our study clearly shows that ROS production is important …