bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5017: T-cell repertoire turnover induced by anti-CTLA-4 antibody treatment in cancer patients
Authors: Fong Lawrence H. , Cha Edward , Klinger Mark , Hou Yafei , Cummings Craig , Ribas Antoni , Faham Malek 
Published: May 2015

Abstract
While treatment with anti-CTLA-4 antibody can induce clinical responses in advanced cancer patients, its effects on the breadth of the T cell response is unknown. We used a next-generation sequencing-based method to assess T cell repertoire diversity in 46 patients with metastatic castration resistant prostate cancer or metastatic melanoma. Peripheral blood mononuclear cells were obtained from patients prior to and during treatment with anti-CTLA-4 antibody. mRNA was amplified using locus-specific primer sets for T cell receptor (TCR) beta, and the amplified product was sequenced. Sequence reads were used to quantitate absolute TCR frequencies using standardized clonotype determination algorithms with normalization by spiked reference TCR sequences. Following clonotype quantitation, repertoire differences between serial samples were assessed by the Morisita index, a statistical measure of population dispersion. 97 paired samples were assessed, of which 46 (47%) had increases and 22 (23%) had decreases in TCR diversity by more than 2-fold. By comparison, none of 9 untreated sample pairs underwent more than a 2-fold change in diversity (P = 0.005, Fisher's exact test, two tailed). TCR repertoire differences between monthly samples were markedly higher than for time-matched controls. After the first treatment, median Morisita index between samples was 0.197 for treated samples versus 0.039 for untreated (P = 0.0005, Mann-Whitney U test). The median number of clones that significantly changed in abundance was 421 for treated versus 45 for controls. In patients with multiple time points, this rapid clonotype evolution continued through treatment. Whereas the number of clonotypes that increased with treatment was not associated with clinical outcome, improved overall survival was associated with maintenance of high frequency clones present at baseline. In contrast the highest frequency clonotypes fell with treatment in patients with shorter overall survival. Stably maintained clonotypes included T cells possessing high avidity TCR such as CMV-reactive T cells. Together, these results suggest that CTLA-4 blockade induces T-cell repertoire evolution and diversification. Moreover, improved clinical outcomes are associated with less clonotype loss, consistent with the maintenance of high frequency TCR clonotypes during treatment. These clones may represent the presence of pre-existing high avidity T cells that may be relevant in the anti-tumor response.
Citation Format: Lawrence H. Fong, Edward Cha, Mark Klinger, Yafei Hou, Craig Cummings, Antoni Ribas, Malek Faham. T-cell repertoire turnover induced by anti-CTLA-4 antibody treatment in cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5017. doi:10.1158/1538-7445.AM2014-5017
Abstract 5019: Irradiation and anti-B7-H1 provide synergistic treatment effects in murine cancer
Authors: Deng Liufu , Liang Hua , Burnette Byron , Beckett Micheal , Darga Thomas , Weichselbaum Ralph , Fu Yang-Xin 
Published: May 2015

Abstract
High dose ionizing irradiation (IR) results in direct tumor cell death and has been demonstrated to augment tumor-specific immunity that enhance tumor control both locally and distantly. However, local relapses often occur in patients and in established experimental tumors after treatment with IR suggesting that IR-induced immune responses are inadequate. Therapeutic blockade of the T cell negative regulator Programmed Death Ligand 1 (PD-L1, also named B7-H1) can enhance T cell effector function when PD-L1 is expressed in chronically inflamed tissues and tumors. Here, we demonstrate that PD-L1 is up-regulated in the tumor microenvironment after IR. Administration of anti-PD-L1 enhanced the efficacy of IR through a CD8+ T cell dependent mechanism. Concomitant with IR-mediated tumor regression, we observed that IR and anti-PD-L1 synergistically reduced the local accumulation of tumor-infiltrating Myeloid Derived Suppressor Cells (MDSCs), thus altering the tumor immune microenvironment. We demonstrate that CD8+ T cells, activated by combination therapy, mediate the reduction of MDSCs in tumors through the cytotoxic actions of TNF. Our data provide evidence for a close interaction between IR, T cells, and the PD-1/PD-L1 axis and establish the basis for the rational design of combination therapy with immune modulators and radiotherapy in the clinical setting.
Note: This abstract was not presented at the meeting.
Citation Format: Liufu Deng, Hua Liang, Byron Burnette, Micheal Beckett, Thomas Darga, Ralph Weichselbaum, Yang-Xin Fu. Irradiation and anti-B7-H1 provide synergistic treatment effects in murine cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5019. doi:10.1158/1538-7445.AM2014-5019
Abstract 5026: B7-H1 confers tumor chemoresistance by regulating MAPK/ERK activation
Authors: Orzechowski Amanda , Dong Haidong 
Published: May 2015

Abstract
Development of resistance to chemotherapy and immunotherapy is a major obstacle in extending the survival of cancer patients. Although several molecular mechanisms have been identified that can contribute to chemoresistance, the role of immune checkpoint molecules in tumor chemoresistance has received little consideration. Elevated expression of B7-H1 (also named PD-L1) is predictive of an aggressive disease course, including increases in disease progression and cancer-related mortality in a variety of cancers (ovary, breast, liver, pancreas, esophagus, colon and lung). Although the aggressiveness of B7-H1 positive tumors has been attributed to B7-H1's immune-suppressive function, B7-H1 itself may be directly altering tumor cell intracellular signaling pathways promoting acquisition of drug resistance. It has been reported that overexpression of B7-H1 confers chemoresistance in human cancers. However, the mechanisms by which B7-H1 contributes to tumor chemoresistance have yet to be defined. We show that B7-H1 transfected tumor cells are resistant to chemotherapy. This resistance is due to increased activation of MAPK/ERK pathway in tumor cells with B7-H1 overexpression. Inhibition of ERK activation restored drug sensitivity of B7-H1 positive tumor cells. We further analyzed the downstream elements of B7-H1 signaling pathway and identified a new B7-H1 associated protein that is involved in DNA damage repair and MAPK/ERK activation mechanisms. We conclude that B7-H1 mediates tumor chemoresistance by enhancing the activation of MAPK/ERK pathway via its intracellular signaling pathway. Our studies may identify a novel pharmaceutical target for treatment of B7-H1 positive refractory tumor cells.
Citation Format: Amanda Orzechowski, Haidong Dong. B7-H1 confers tumor chemoresistance by regulating MAPK/ERK activation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5026. doi:10.1158/1538-7445.AM2014-5026
Abstract 5027: Identification of novel immune checkpoints as potential targets for cancer immunotherapy
Authors: Rotman Galit , Levy Ofer , Toporik Amir , Cojocaru Gady , Dassa Liat , Vaknin Ilan , Sameah-Greenwald Shirley , Barbiro Inbal , Fan Jinhong , Watson Susan , Hunter John , Neria Eyal , Levine Zurit 
Published: May 2015

Abstract
Members of the B7/CD28 family of immune checkpoints, such as CTLA4, PD1 and PDL-1, play critical roles in immune cell regulation and have emerged as promising drug targets for cancer immunotherapy. We hypothesize that additional immune checkpoints play a role as negative immune regulators and thus may serve as targets for therapeutic mAbs. Utilizing Compugen's predictive discovery platform, we identified novel members of this family that may serve as immune checkpoints. The therapeutic relevance of three of these proteins, CGEN-15001T, CGEN-15022, and CGEN-15049, was confirmed following the validation of their immunomodulatory properties and their expression in various cancers. Two of these proteins, CGEN-15001T and CGEN-15022, are the basis of a license and collaboration agreement recently signed with Bayer as targets for cancer immunotherapy. Here we present results obtained for an additional novel immune checkpoint, CGEN-15049. Following its ectopic expression on cancer cell lines, CGEN-15049 inhibits the activity of NK cells and cytotoxic T cells (CTLs). The fusion protein, consisting of the extracellular domain of CGEN-15049 fused to an IgG Fc domain, displays robust inhibition of T cell activation and enhances iTregs differentiation. IHC studies indicate that CGEN-15049 is expressed in tumor cells of numerous types of cancers, as well as in tumor infiltrating immune cells. Based on its immunomodulatory activities on immune cell types with key roles in cancer immune evasion, together with its expression pattern in cancer tissues, CGEN-15049 may serve as mAb target for cancer immunotherapy.
Citation Format: Galit Rotman, Ofer Levy, Amir Toporik, Gady Cojocaru, Liat Dassa, Ilan Vaknin, Shirley Sameah-Greenwald, Inbal Barbiro, Jinhong Fan, Susan Watson, John Hunter, Eyal Neria, Zurit Levine. Identification of novel immune checkpoints as potential targets for cancer immunotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5027. doi:10.1158/1538-7445.AM2014-5027
Abstract 5053: Preliminary results from the Reproducibility Project: Cancer Biology - a replication of 50 high-impact cancer cell biology papers from 2010-2012
Authors: William Gunn , Iorns Elizabeth , Silva Elizabeth , Nosek Brian 
Published: May 2015

Abstract
The lack of reproducibility of preclinical research is a significant and growing problem which slows basic research and leads to fruitless clinical trials. An increasing number of reports have found discrepancies in published preclinical studies across scientific disciplines. For example:
* Amgen found that 47 of 53 “landmark” oncology publications could not be reproduced.
* Bayer found that their internal results contradicted academic publications in 43 of 67 oncology and cardiovascular projects.
* Dr. John Ioannidis and his colleagues found that of 432 publications purporting sex differences in hypertension, multiple sclerosis, or lung cancer, only one data set was reproducible.
These studies, and the many others that report similar results, highlight a significant problem in the development of new therapies to treat disease. With increasing reports of discrepancies in preclinical publications, pharmaceutical companies are being forced to re-evaluate their reliance on academic research. In fact, Bayer recently decided to halt nearly two-thirds of target-validation projects.In this session, we'll report the work we have done to address this issue. We will bring together researchers and representatives from funders and publishers to discuss the issue of reproducibility. We will share funder and publisher initiatives to promote reproducibility and also discuss research practices that lead to more reproducible research such as using proper statistical tests, reporting all experimental data, experimental blinding, and identification and validation of research reagents. We'll also share preliminary results from an Arnold Foundation-funded study to replicate the 50 most high impact cancer biology studies from 2010-1012.
Reproducibility ResearchAmgen47 of 53 “landmark” oncology publications could not be reproducedBayerinternal results contradicted academic publications in 43 of 67 oncology and cardiovascular projectsDr. John Ioannidis and colleagues432 publications purporting sex differences in hypertension, multiple sclerosis, or lung cancer, only one data set was reproducible
Note: This abstract was not presented at the meeting.
Citation Format: Gunn William, Elizabeth Iorns, Elizabeth Silva, Brian Nosek. Preliminary results from the Reproducibility Project: Cancer Biology - a replication of 50 high-impact cancer cell biology papers from 2010-2012. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5053. doi:10.1158/1538-7445.AM2014-5053
Abstract 5054: Smoking prevention intervention with school classes at a university hospital by thoracic surgeon und pulmonologist
Authors: Tomaszek Sandra , Schuurmans Macé M. , Schneiter Didier , Weder Walter , Hillinger Sven 
Published: May 2015

Abstract
Purpose: Smoking prevention in schoolchildren with the aim to inform and prevent smoking initiation has been widely studied and has shown variable results. Interventions provided by physicians in a hospital setting have been rarely reported. Here we show the feasibility and gain of knowledge of our smoking prevention project in a hospital setting.
Methods: Interventions performed from November 2009 - February 2013 were evaluated. Overall 470 children participated in our preventive intervention. A 7-item questionnaire was provided to the school classes (Grades 6 to 10) before and after a two-hour smoking prevention intervention consisting of anatomical models, oral presentations, videos, patient interviews and hands-on lung function tests. The goal was to show the anatomical and physiological basics as well as age-based information about the harms of smoking. During the intervention the children have been motivated to be actively involved. Class selection has been performed for groups of children in a highly vulnerable phase of age before smoking initiation.
Results: The baseline questionnaire was completed by 457 children, the one after intervention by 426. The knowledge about which organs are affected by smoking increased from 6.8-99.6% to 65.5-99.5% (p&lt;0.01). While only 59.5% knew that only a minority of people is able to quit smoking successfully, 94.1% answered the question correctly after intervention (p&lt;0.001). Prior to the intervention only 78.1% believed that minor tobacco consumption is not damaging which increased to 89.4% after the teaching session (p&lt;0.05). Smoking hookah was believed to be less harmful than cigarettes by 30.2% of children decreasing to 7.7% after the intervention (p&lt;0.001).
Conclusion: Information on health effects provided by lung specialists in the hospital leads to a statistically significant increase in knowledge as assessed by a short questionnaire. The intervention is feasible and well received. This kind of interventions might help to prevent schoolchildren from smoking in a highly vulnerable phase of age.
Citation Format: Sandra Tomaszek, Macé M. Schuurmans, Didier Schneiter, Walter Weder, Sven Hillinger. Smoking prevention intervention with school classes at a university hospital by thoracic surgeon und pulmonologist. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5054. doi:10.1158/1538-7445.AM2014-5054
Abstract 5057: The role of health locus of control and self-efficacy beliefs in sunscreen use: Evidence from 2012 Health Information National Trends Survey
Authors: He Xiaofei 
Published: May 2015

Abstract
Sun exposure has been identified as a cause of skin cancer (Armstrong & Kricker, 2001). Extensive empirical evidence shows that sunscreen use was associated with lower skin cancer incidence (Green et al., 1999, 2011). However, only 32% U.S. adults used sunscreen regularly (NCI, 2010); the percentage was even lower (21.7%) among adolescents (Eaton et al., 2012). To reduce skin cancer burden, sunscreen use promotion should be enhanced.
Locus of control, the extent to which people believe they have control over their lives with external and internal dimensions (Rotter, 1954), is a significant predictor of behavioral changes (Bundek et al., 1993). Internal locus of control, i.e., beliefs that reinforcements are dependent upon one's own behavior, is positively related with behavioral changes, e.g., weight loss (O'Bryan, 1972) and health information seeking (Wallston & Maides, 1976), etc. Self-efficacy, the extent to which one believes to be capable of performing the recommended behavior (Bandura, 1977), is a robust predictor for behavioral changes including smoking cessation (Norman, 1994) and AIDS prevention (Yzer, 1998), etc.
However, little research focuses on the role of locus of control and self-efficacy in promoting sunscreen use by using nationally representative cross-sectional data. The present study bridges this gap by examining the following two hypotheses:
H1: People with high external locus of control were less likely to use sunscreen.
H2: People with high health self-efficacy were more likely to use sunscreen.
Results show that people high in external locus of control were less likely to use sunscreen (B=-0.160, p=0.001) and people high in health self-efficacy were more likely to use sunscreen (B= 0.331, p=0.046), both of which were statistically significant. Males, Pacific Islanders, homemakers, and non-immigrants were more likely to use sunscreen. The findings attest to the necessity of enhancing people's internal locus of control and self-efficacy with the purpose of promoting sunscreen use. Public health efforts could be allocated based on the socio-demographic findings.
Citation Format: Xiaofei He. The role of health locus of control and self-efficacy beliefs in sunscreen use: Evidence from 2012 Health Information National Trends Survey. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5057. doi:10.1158/1538-7445.AM2014-5057
Abstract 5076: Rapid assessment of AML genes for mutation detection and copy number variation
Authors: Andersen Mark , Rhodes Kate , Roman Steve , VanLoy Cristina , Broomer Adam , Allen Michael , Topacio Denise , Liu Guoying , Hyland Fiona 
Published: May 2015

Abstract
Targeted sequencing using the Ion AmpliSeq™ Library kit combined with the Ion PGM™ sequencing instrument is a fast and effective method to identify genetic variants in cancer samples. A new targeted primer panel for amplification of genes involved in Acute Myeloid Leukemia (AML) has been developed by Life Technologies. The panel covers 19 genes characterized using over 300 specific primer pairs in two highly multiplexed PCRs. To demonstrate the coverage efficiency, we evaluated libraries prepared from whole blood and isolated genomic DNA. When libraries from 4 individuals were run on a single Ion 318™ Chip, the average coverage depth was &gt;3000x, with &gt;97% of the target bases covered &gt;500X. Additionally, &gt;90% of reads were on-target. The panel was tested on control samples and analyzed using the Ion Reporter™ Software, and expected variants, including copy number variations (CNVs) were detected with high sensitivity and specificity.
Citation Format: Mark Andersen, Kate Rhodes, Steve Roman, Cristina VanLoy, Adam Broomer, Michael Allen, Denise Topacio, Guoying Liu, Fiona Hyland. Rapid assessment of AML genes for mutation detection and copy number variation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5076. doi:10.1158/1538-7445.AM2014-5076
Abstract 5087: Peli 1 targets BubR1 for ubiquitinational degradation and induces aneuploidy transformation
Authors: Kim Suhyeon , Park Hye-Young , Song Ha Rim , Go Heounjeong , Cho Hyeseong , Chung Doo Hyun , Lee Chang-Woo 
Published: May 2015

Abstract
Disruption of the BubR1-mediated function negatively impacts mitotic checkpoint control, increases chromosomal instability, and is associated with infertility, life span and cancer. Therefore, BubR1 plays an important role in preventing abnormal mitotic cells with chromosomal aneuploidy from achieving neoplastic aneuploidy, however it remains unclear how the signalling activates or inactivates the BubR1 function during the neoplastic transformation. Here, we report that Peli 1, a new family of signal-responsive E3 ubiquitin ligase, directly interacts with BubR1. This interaction promotes the ubiquitin-mediated degradation, and prevents the kinetochore association of BubR1. In addition, cells expressing Peli 1 led to severe mitotic defects and displayed severe chromosomal aneuploidy in vitro and in vivo. Together, these results suggest that Peli 1 expression acts as a potent causative signalling against chromosome integrity by mediating the ubiquitinational degradation of BubR1, and thus contributes to the development of neoplastic chromosome aneuploidy.
Citation Format: Suhyeon Kim, Hye-Young Park, Ha Rim Song, Heounjeong Go, Hyeseong Cho, Doo Hyun Chung, Chang-Woo Lee. Peli 1 targets BubR1 for ubiquitinational degradation and induces aneuploidy transformation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5087. doi:10.1158/1538-7445.AM2014-5087
Abstract 5090: Estrogen receptor-alpha promotes multi-centrosomes by inhibition of BRCA1-Rad51 binding
Authors: Jung Youn-Sang , Chun Ho-Young , Woo Tae-Gyun , Park Bum-Joon 
Published: May 2015

Abstract
Von Hippel Lindau gene (VHL) is frequently deleted in renal cell carcinoma and known to be negative regulator of Hypoxia inducible factor-1 (HIF-1). However, its tumor suppressive functions has not been fully explained by HIF-1 suppression, because loss of pVHL is appeared in initial stage of RCC tumorigenesis and induces the defect in cytokinesis or centrosome instability. Concerning this, we previously revealed that estrogen receptor-alpha is primary target of E3 ligase function of pVHL. In this study, we demonstrate that ER-α is responsible for mitotic defect and drug resistance in VHL-deficient cells. Activated ER-α can interact with BRCA1 or Rad51 and disrupt the BRCA1-Rad51-mediated centrosome maintaining. Thus, VHL-deficient cells, like as BRCA1-deficient cells, possessed multi-centrosome and multi-nucleated phenotypes. In addition, multi-centrosomal features rendered the resistance to Taxol. Since it is mediated by ER-α in nucleus, blocking of ER-α translocation by specific inhibitor, Faslodex, can ameliorate multi-centrosomes and induce Taxol sensitivity in RCC and BRCA1-deficient breast cancers. These results suggest that pVHL is critical for proper cell division and suppression of ER-α in RCC and BRCA1-deficient breast cancer is one of useful strategy for improving the drug sensitivity.
Citation Format: Youn-Sang Jung, Ho-Young Chun, Tae-Gyun Woo, Bum-Joon Park. Estrogen receptor-alpha promotes multi-centrosomes by inhibition of BRCA1-Rad51 binding. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5090. doi:10.1158/1538-7445.AM2014-5090