tbuckley/cabot-search huggingface dataset:
Abstract 573: Preclinical evaluation of JTX-2011, an anti-ICOS agonist antibody
Authors: Jennifer S. Michaelson, Christopher J. Harvey, Kutlu G. Elpek, Ellen Duong, Matthew Wallace, Chengyi J. Shu, Sriram Sathyanarayanan, Robert Mabry, Lindsey Shallberg, Tong Zi, Amit Deshpande, Stephen L. Sazinsky, Joshua Apgar, Deborah Law
Journal: Cancer Research (2016)

Abstract ICOS (inducible co-stimulator molecule) is a co-stimulatory molecule and a member of the CD28 superfamily expressed primarily on T lymphocytes. Analysis of cancer patient samples as well as rodent preclinical data have implicated a role for the ICOS pathway in cancer immunotherapy. We have generated a panel of anti-ICOS monoclonal antibodies with in vitro agonistic properties. The anti-ICOS antibodies are efficacious as monotherapies and in combination with anti-PD1 in multiple syngeneic tumor models. Mechanistic studies demonstrate that tumor regression is associated with enhanced ratios of cytotoxic CD8:T regulatory (Treg) cells as well as preferential reduction in ICOS-high Tregs in the tumor microenvironment. JTX-2011, a species cross-reactive high affinity humanized agonist monoclonal antibody, has been selected for development. Evaluation of JTX-2011 in nonhuman primate models will be presented, including data informing safety and PK parameters. Our preclinical data provides rational for clinical development of JTX-2011 as a cancer immunotherapeutic to be tested as both a monotherapy as well as in combination with immunotherapies in solid tumor indications. Citation Format: Jennifer S. Michaelson, Christopher J. Harvey, Kutlu G. Elpek, Ellen Duong, Matthew Wallace, Chengyi J. Shu, Sriram Sathyanarayanan, Robert Mabry, Lindsey Shallberg, Tong Zi, Amit Deshpande, Stephen L. Sazinsky, Joshua Apgar, Deborah Law. Preclinical evaluation of JTX-2011, an anti-ICOS agonist antibody. [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 573.
How Can a Valid Research Agenda for Patient-Reported Outcomes Be Defined Without Patient Input?
Authors: Lisa M. Kodadek, Brandyn D. Lau, Elliott R. Haut
Journal: JAMA Surgery (2016)

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Abstract 2499: Sox2 enhances breast tumor angiogenesis by promoting the transition of cancer cell to CD31+ and LYVE-1+ cells
Authors: Rongrong Wang, Xuefei Li, Yingxi Xu, Tongchao Sun, Weijun Su, Chenhua Yu, Xiaoli Dong, Rong Xiang, Na Li
Journal: Cancer Research (2016)

Abstract Angiogenesis plays an important role during the development of tumor. Sox2 is one of the transcription factors involved in tumorigenesis and metastasis. However, its function during the process of tumor angiogenesis and lymphogenesis is still poorly understood. Here, we demonstrated that down-regulation of Sox2 significantly reduced the tumor angiogenesis and lymphogenesis as reflected by attenuated immunofluorescence staining of CD31 and LYVE-1 and improved prognosis in xenograft models of breast tumor. Furthermore, Sox2 also promoted the recruitment of bone marrow derived endothelial progenitor cells (MDEPC) to tumor microenvironment. Most importantly, we demonstrated that some of CD31+ and LYVE-1+ cells were derived from Sox2+ cancer cells and silencing of Sox2 could inhibit this transition. We revealed that Sox2 promoted the expression of LYVE-1, VEGFs and enhanced the phosphorylation of VEGFR2 in breast cancer. ChIP-seq and dual-luciferase assay further revealed the binding of Sox2 protein on proximate promoter region of VEGFB and LYVE1 to regulate their transcriptional activities, disclosing the underlying molecular mechanism on the regulatory effects of Sox2 on angiogenesis and lymphogenesis. Our study indicated that Sox2 improved tumor angiogenesis and lymphogenesis through regulating the related genes and unveiled a novel function of Sox2 in tumor progression. Citation Format: Rongrong Wang, Xuefei Li, Yingxi Xu, Tongchao Sun, Weijun Su, Chenhua Yu, Xiaoli Dong, Rong Xiang, Na Li. Sox2 enhances breast tumor angiogenesis by promoting the transition of cancer cell to CD31+ and LYVE-1+ 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 2499.
Paludisme d’aéroport : quatre nouveaux cas dans la banlieue de Paris durant l’été 1999
Authors: D Lusina, F Legros, V Estève, M Klerlein, T Giacomini
Journal: Eurosurveillance (2000)

Au cours de l’ete 1999, un nouveau regroupement de quatre cas de paludisme aeroportuaire a ete observe en France. L’analyse de ces cas souligne que le paludisme aeroportuaire, rare et de diagnostic difficile, peut etre observe en dehors de professions a risque, chez des sujets vivant a proximite d’un l’aeroport. Elle souligne egalement l’importance du respect des consignes de desinsectisation des avions venant de zone d’endemie palustre. Par ailleurs, elle montre l’importance des signes hematologiques indirects du paludisme, thrombopenie en particulier.
Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1
Authors: Wilfredo F Garcia-Beltran, Angelique Hölzemer, Gloria Martrus, Amy W Chung, Yovana Pacheco, Camille R Simoneau, Marijana Rucevic, Pedro A Lamothe-Molina, Thomas Pertel, Tae-Eun Kim, Haley Dugan, Galit Alter, Julie Dechanet-Merville, Stephanie Jost, Mary Carrington, Marcus Altfeld
Journal: Nature Immunology (2016)
Abstract 1454: IL-4 modulate the tumor microenvironment and response to cancer therapies
Authors: Shuku-ei A. Ito, Hidekazu Shirota, Chikashi Ishioka
Journal: Cancer Research (2016)

Abstract recent findings show that immune cells constitute a large fraction of the tumor microenvironment and modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL-4 in particular is up-regulated. Thus, we tested whether depletion of IL-4 affected in tumor immunity. Current results demonstrate that administration of neutralizing antibody against IL-4 enhances anti-tumor immunity and improve the response to Taxol-based chemotherapy and CpG ODN immunotherapy. Depletion of IL-4 also alter the tumor microenvironment, reducing the generation of immunosuppressive M2 macrophages and myeloid derived suppressor cells and enhancing tumor specific CTLs. These findings suggest that IL-4 impact anti-tumor immunity and constitute an attractive therapeutic target to reduce immune suppression in the tumor microenvironment and thus enhance the efficacy of cancer therapy. Citation Format: Shuku-ei A. Ito, Hidekazu Shirota, Chikashi Ishioka. IL-4 modulate the tumor microenvironment and response to cancer therapies. [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 1454.
Abstract 4309: Rare protein truncating and missense variants in ATM, CHEK2, PALB2, but not XRCC2, confer increased breast cancer risks
Authors: Brennan Decker, Jamie Allen, Craig Luccarini, Karen A. Pooley, Paul PD Pharoah, Alison M. Dunning, Douglas F. Easton
Journal: Cancer Research (2016)

Abstract Breast cancer (BC) is the most common malignancy in women and has a major heritable component that is driven by both common SNPs and rarer variants in susceptibility genes. However, the risks associated with most rare susceptibility alleles are not well estimated. We sequenced the coding regions of ATM, CHEK2, PALB2, and XRCC2 in 13,087 BC cases and 5,488 controls from East Anglia to characterize their role in BC risk in the largest sequencing study of these genes to date. We performed multiplexed microfluidic PCR target enrichment of 221 amplicons, covering 99.3% of the coding bases. Amplified DNA was barcoded, pooled, and sequenced on the Illumina HiSeq2000. Reads were demultiplexed, trimmed, and aligned to the hg19 reference sequence. Variants were called with GATK UnifiedGenotyper and filtered for missing data. Retained variants were annotated with CADD and VEP. Truncating variants, missense alleles, and other functional variant groups were assessed for association with BC risk using logistic regression. Truncating variants in ATM, CHEK2, and PALB2 increased overall BC risk, whereas XRCC2 variants did not (Table 1). The estimated relative risk was higher for PALB2 than ATM or CHEK2. While 88% of CHEK2 variant alleles were attributable to CHEK2*1100delC, other truncating alleles appeared to confer similar risks. CHEK2 truncating alleles were more strongly associated with risk of estrogen receptor (ER) positive disease than ER negative or triple negative disease. In contrast, PALB2 protein-truncating variants conferred similar relative risks for all subtypes. Analysis of rare missense variants suggested that specific subset of alleles in ATM (P = 0.012), CHEK2 (P = 0.009), and PALB2 (P = 0.017) may contribute to risk. Localization within known functional domains were a predictor of association among these variants. These results confirm that truncating variants in ATM, CHEK2, and PALB2 are associated with moderate BC risks, and exclude a large effect on risk from XRCC2 variants. Truncating Variant RiskATMATMCHEK2CHEK2PALB2PALB2XRCC2XRCC2ORP-ValueORP-ValueORP-ValueORP-ValueSEARCH Cases3.262.11E-053.345.18E-115.424.45E-080.940.9232ER Positive3.191.04E-043.719.11E-124.322.73E-050.870.8419ER Negative1.280.67431.560.23655.583.62E-040.880.9102Triple Negative2.850.14880.420.32217.500.0022NANA Citation Format: Brennan Decker, Jamie Allen, Craig Luccarini, Karen A. Pooley, Paul PD Pharoah, Alison M. Dunning, Douglas F. Easton. Rare protein truncating and missense variants in ATM, CHEK2, PALB2, but not XRCC2, confer increased breast cancer risks. [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 4309.
Abstract 4299: Short telomeres are associated with increased risk for arsenic-related skin lesions in Bangladesh
Authors: Chenan Zhang, Muhammad Kibriya, Farzana Jasmine, Shantanu Roy, Habibul Ahsan, Brandon L. Pierce
Journal: Cancer Research (2016)

Abstract Chronic exposure to arsenic, a human carcinogen, has been shown in epidemiologic studies to increase the risk of arsenical skin lesions (keratosis and melanosis) as well as cancer (including non-melanoma skin cancer). Recent studies suggest that the mechanism of arsenic's toxicity may be related to telomere dysfunction, including altered telomere length (TL), and differential expression of genes involved in telomere maintenance. However, prior studies of arsenic exposure, TL, and skin lesion tend to be small and cross-sectional in nature. In this study, we investigated the association between arsenic exposure and TL (measured by qPCR as T/S ratio), as well as TL and subsequent risk of skin lesion in individuals who are exposed to naturally contaminated drinking water with a wide range of arsenic levels in the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh (2000-2009). In all laboratory analyses, we attempted to randomize samples across plate positions, and in statistical analyses, we controlled for any residual confounding by plate or plate position. All TL data generated showed a strong inverse association with age. In a random sample of the baseline cohort (n = 649), we observed a positive association between water arsenic levels and TL (Ptrend = 0.035), with beta estimates of 0.001, 0.023, and 0.025 for water arsenic levels of 10.1-50ug/L, 50.1-150ug/L and 150+ug/L, respectively, compared to &amp;lt;10ug/L. However the association was not replicated in an independent random sample (n = 1181, Ptrend = 0.176) with beta estimates of 0.007, -0.004, and -0.017. In a nested case-control study comparing skin lesion incident cases diagnosed across a nine year period with sex- and age-matched controls (448 cases and 462 controls), we observed higher incident skin lesion risk with shorter TL (Ptrend = 4.6E-5), with odds ratios of 3.05, 1.30, and 1.21 for the first (shortest), second, and third TL quartiles compared to the longest. Our findings show that arsenic exposure is not strongly associated with TL, indicating that TL is likely not the main mode of action for arsenic's carcinogenic toxicity. However, TL is inversely associated with skin lesion risk, suggesting that short TL may be a biomarker of susceptibility for arsenical skin lesions independent of arsenic exposure. Citation Format: Chenan Zhang, Muhammad Kibriya, Farzana Jasmine, Shantanu Roy, Habibul Ahsan, Brandon L. Pierce. Short telomeres are associated with increased risk for arsenic-related skin lesions in Bangladesh. [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 4299.
P0899 : Preclinical profile of the pan-genotypic HCV NS3/4A protease inhibitor GS-9857
Authors: J.G. Taylor, T. Appleby, O. Barauskas, X. Chen, H. Dvory-Sobol, R. Gong, J. Lee, E. Nejati, B. Schultz, Y. Wang, C. Yang, M. Yu, S. Zipfel, K. Chan
Journal: Journal of Hepatology (2015)
Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders
Authors: Asbjørg Stray-Pedersen, Hanne Sørmo Sorte, Pubudu Samarakoon, Tomasz Gambin, Ivan K. Chinn, Zeynep H. Coban Akdemir, Hans Christian Erichsen, Lisa R. Forbes, Shen Gu, Bo Yuan, Shalini N. Jhangiani, Donna M. Muzny, Olaug Kristin Rødningen, Ying Sheng, Sarah K. Nicholas, Lenora M. Noroski, Filiz O. Seeborg, Carla M. Davis, Debra L. Canter, Emily M. Mace, Timothy J. Vece, Carl E. Allen, Harshal A. Abhyankar, Philip M. Boone, Christine R. Beck, Wojciech Wiszniewski, Børre Fevang, Pål Aukrust, Geir E. Tjønnfjord, Tobias Gedde-Dahl, Henrik Hjorth-Hansen, Ingunn Dybedal, Ingvild Nordøy, Silje F. Jørgensen, Tore G. Abrahamsen, Torstein Øverland, Anne Grete Bechensteen, Vegard Skogen, Liv T.N. Osnes, Mari Ann Kulseth, Trine E. Prescott, Cecilie F. Rustad, Ketil R. Heimdal, John W. Belmont, Nicholas L. Rider, Javier Chinen, Tram N. Cao, Eric A. Smith, Maria Soledad Caldirola, Liliana Bezrodnik, Saul Oswaldo Lugo Reyes, Francisco J. Espinosa Rosales, Nina Denisse Guerrero-Cursaru, Luis Alberto Pedroza, Cecilia M. Poli, Jose L. Franco, Claudia M. Trujillo Vargas, Juan Carlos Aldave Becerra, Nicola Wright, Thomas B. Issekutz, Andrew C. Issekutz, Jordan Abbott, Jason W. Caldwell, Diana K. Bayer, Alice Y. Chan, Alessandro Aiuti, Caterina Cancrini, Eva Holmberg, Christina West, Magnus Burstedt, Ender Karaca, Gözde Yesil, Hasibe Artac, Yavuz Bayram, Mehmed Musa Atik, Mohammad K. Eldomery, Mohammad S. Ehlayel, Stephen Jolles, Berit Flatø, Alison A. Bertuch, I. Celine Hanson, Victor W. Zhang, Lee-Jun Wong, Jianhong Hu, Magdalena Walkiewicz, Yaping Yang, Christine M. Eng, Eric Boerwinkle, Richard A. Gibbs, William T. Shearer, Robert Lyle, Jordan S. Orange, James R. Lupski
Journal: Journal of Allergy and Clinical Immunology (2016)
Abstract 1903: A genetic variation in microRNA target site of ETS2 is associated with clinical outcomes of paclitaxel-cisplatin chemotherapy in non-small cell lung cancer
Authors: SON JI WOONG, Shin Yup Lee, Chang Ho Kim, Jae Yong Park
Journal: Cancer Research (2016)

Abstract Background: Recently, crosslinking, ligation, and sequencing of hybrids (CLASH) provided direct observation of transcriptome-wide miRNA-target pairs. The present study was performed to investigate the association of single nucleotide polymorphisms (SNPs) located in the miRNA target sites, which were experimentally verified by CLASH, with the clinical outcome of first line paclitaxel-cisplatin chemotherapy in advanced non-small cell lung cancer (NSCLC). Methods: Eighty SNPs in miRNA target sites of cancer related genes selected from 18,500 miRNA:target interactions in CLASH data were investigated in 379 advanced NSCLC patients using a sequenom mass spectrometry-based genotype assay. Quantitative reverse transcription-polymerase chain reaction and luciferase assay were conducted to examine functional relevance of potentially functional SNPs in miRNA target sites. Results: Of the 80 SNPs analyzed, 16 SNPs were significantly associated with the clinical outcome after chemotherapy. Among these, ANAPC1 rs3814026C&amp;gt;T, ETS2 rs461155A&amp;gt;G, SORBS1 rs7081076C&amp;gt;A and POLR2A rs2071504C&amp;gt;T were found to be significantly associated with both chemotherapy response and survival. Notably, the relative expression level of ETS2 was significantly associated with rs461155A&amp;gt;G genotypes in both tumor and paired normal lung tissues (Ptrend = 4 × 10-7,and3×10-4,respectively). Consistently, a decreased expression of the reporter gene for the G allele of rs461155 compared with the A allele was observed by luciferase assay. Conclusion: These findings suggest that the four SNPs, especially ETS2 rs461155A&amp;gt;G, could be used as biomarkers predicting the response and survival of NSCLC patients treated with first-line paclitaxel-cisplatin chemotherapy. Citation Format: SON JI WOONG, Shin Yup Lee, Chang Ho Kim, Jae Yong Park. A genetic variation in microRNA target site of ETS2 is associated with clinical outcomes of paclitaxel-cisplatin chemotherapy in non-small cell lung cancer. [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 1903.
Abstract 86: Functional effects of MutL homolog 1 promoter polymorphism in prostate cancer
Authors: Shinichiro Fukuhara, Yozo Mitsui, Yutaka Hashimoto, Taku Kato, Ryan K. Wong, Varahram Shahryari, Soichiro Yamamura, Shahana Majid, Sharanjot Saini, Guoren Deng, Rajvir Dahiya, Yuichiro Tanaka
Journal: Cancer Research (2016)

Abstract The mutL homolog (MLH1) gene protects the integrity of the genome by correcting erroneous insertions, deletions and mismatches that occur during DNA replication. Proper MLH1 expression is thus essential for the health of the cell and deficiency can result in mutation and genomic instability, which ultimately may lead to cancer. Polymorphisms in the promoter region can lead to altered gene expression and we tested the hypothesis that MLH1 promoter variants can affect levels as well as be a risk for prostatic cancer. Two polymorphic sites were analyzed, rs1800734 (A to G) and rs4647203 (G to A). A luciferase reporter construct containing the MLH1 promoter region was utilized and site-directed mutagenesis was performed to create rs1800734 and rs4647203 variants. Activity was tested using DU145, PC3 and LNCaP prostatic cells and interestingly, the rs1800734 G variant resulted in significantly decreased luciferase levels in all three cell lines compared to A (P&amp;lt;0.01). No difference however, was seen for the rs4647203 variant. To determine whether rs1800734 can affect clinical expression levels, benign prostatic hyperplasia specimens were evaluated for MLH1 expression by immunohistochemistry. A significantly lower H score was observed for the GG genotype compared to AA (P&amp;lt;0.01). To further explore the clinical relevance of rs1800734, a case-control study was performed using DNA extracted from normal healthy, BPH, and prostate cancer patients from a Japanese population by sequence-specific PCR and sequencing. Results of experiments showed a trend for the variant G allele to be associated with prostate cancer when compared to normal controls (P&amp;lt;0.1). However, no differences were observed between BPH and controls as well as between stages or grades of prostate cancer. The MLH1 promoter polymorphism is thus capable of altering expression and associated with prostate cancer, and these results are important in understanding its role in this disease. Citation Format: Shinichiro Fukuhara, Yozo Mitsui, Yutaka Hashimoto, Taku Kato, Ryan K. Wong, Varahram Shahryari, Soichiro Yamamura, Shahana Majid, Sharanjot Saini, Guoren Deng, Rajvir Dahiya, Yuichiro Tanaka. Functional effects of MutL homolog 1 promoter polymorphism in prostate cancer. [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 86.