bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5015: TCR usage analysis in blood reveals different mechanisms of action of CTLA-4 and PD-1 blockade in patients
Authors: Robert Lidia , Harview Christina L. , Emerson Ryan , Mok Stephen , Homet Blanca , Comin-Anduix Begonya , Koya Richard C. , Robins Harlan , Tumeh Paul C. , Ribas Antoni 
Published: May 2015

Abstract
Immune-checkpoint blockade therapies are providing long-lasting responses in a subset of patients with malignant metastatic melanoma. In an effort to better understand the underlying mechanism, the T-cell population in peripheral blood mononuclear cells (PBMCs) was characterized. The complementarity determining region 3 (CDR3) of the rearranged T cell receptor variable ß chain genes (TCR Vß) was sequenced. This was performed using gDNA extracted from the PBMCs of twenty-one patients that were treated with antibody to Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) (tremelimumab) and seven patients that were treated with antibody to the Programmed Death-1 (PD-1) blockade (MK-3475) at baseline and at day 30-60 post first treatment. Four healthy donors were also sequenced as controls. Control PBMCs displayed random distribution with three patients showing a decrease and one showing an increase in the number of unique productive sequences (UPS) from baseline to the time after first cycle. In PBMCs from patients receiving the CTLA-4 antibody, two out of 21 samples showed a decrease in total number of UPS, while 19 out of 21samples experienced an increase. In PBMCs from patients receiving PD-1 antibody, the reponse was more similar to healthy donors as 5 out of 7 (71%) displayed a decrease and 2 out 7 (29%) an increase in total UPS from the pre to post timepoint. There was an increase in the absolute lymphocyte count (ALC) after CTLA-4 blockade therapy (p=0.03), but not in the samples from patients treated with PD-1 antibody (p=0.53). A direct correlation between ALC increase and increase in UPS for CTLA-4 blockade was ruled out (p=0.1 Spearman Correlation). When analyzing according to clinical response status, all responders to CTLA-4 blockade (4 out of 19) experienced an increase in the number of circulating clones. However, samples from clinical responders to PD-1 blockade showed an increase (2 out of 5) or decrease (1 out of 2) in the circulating pool. Considering the concerning toxicity profile for CTLA-4-blockade versus the mild toxicity for PD-1 antibodies, this data supports a model where CTLA-4 blockade induces a non-specific systemic expansion of T cells, while PD-1 blockade may have more specific effects directly in the tumor.
Citation Format: Lidia Robert, Christina L. Harview, Ryan Emerson, Stephen Mok, Blanca Homet, Begonya Comin-Anduix, Richard C. Koya, Harlan Robins, Paul C. Tumeh, Antoni Ribas. TCR usage analysis in blood reveals different mechanisms of action of CTLA-4 and PD-1 blockade in 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 5015. doi:10.1158/1538-7445.AM2014-5015
Abstract 5046: What do they do? Patient navigator actions and timely treatment within 30 days of diagnosis in Latinas with breast cancer: The Six Cities Study
Authors: Ramirez Amelie G. , Perez-Stable Eliseo J. , Talavera Gregory A. , Penedo Frank , Carrillo Emilio J. , Fernandez Maria E. , Holden Alan E. , Munoz Edgar , Gallion Kipling J. 
Published: May 2015

Abstract
Background: Breast cancer is the leading cause of cancer deaths in Latinas, primarily due to screening and treatment disparities. Patient navigation has emerged as an effective means to reduce these disparities, although how this is achieved is insufficiently documented.
Methods: We analyzed navigator logs of activities conducted on behalf of 42 navigated Latinas diagnosed with breast cancer from July 2008-January 2011. Women were navigated by locally trained navigators who resolved patient-reported barriers using one of 10 specific actions: referral, accompaniment, transportation, telephone support, records assistance, health education, appointment reminders, family support, translation services, or health care system intervention. We calculated the frequency of patient-reported barriers to cancer treatment, their association with navigator actions (correlation), and the association of these actions on time to primary treatment initiation within 30 days of confirmed diagnosis (Chi-squared analysis).
Results: Patients reported 323 potential barriers to care between diagnosis and initial treatment. Translation (44.3%), specific or generalized fear (14.9%), and transportation (6.5%) were the most commonly reported barriers. Barriers were resolved utilizing activities defined above as determined by navigators; some barriers were resolved with as few as one action. Correspondence (correlation) between reported barriers and navigator actions was high (r=0.985 to r=1.000). Five navigator actions were associated with earlier treatment relative to navigated women not utilizing these specific services (accompaniment: p=.006; transportation: p=.007; telephone support: p=.034; family support: p=.030; translation services: p=.004).
Conclusions: Specific patient navigation activities significantly increase the proportion of Latinas with breast cancer women who begin treatment within 30 days of diagnosis. It likely results in reduction of mortality in this group.
Citation Format: Amelie G. Ramirez, Eliseo J. Perez-Stable, Gregory A. Talavera, Frank Penedo, Emilio J. Carrillo, Maria E. Fernandez, Alan E. Holden, Edgar Munoz, Kipling J. Gallion. What do they do? Patient navigator actions and timely treatment within 30 days of diagnosis in Latinas with breast cancer: The Six Cities Study. [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 5046. doi:10.1158/1538-7445.AM2014-5046
Abstract 5051: Retrospective analysis of direct inpatient charges and mortality of leukemia pediatric patients with Methicillin-resistant Staphylococcus aureus, Candida, or Aspergillus infections in the United States
Authors: Nuño Tomas , Skrepnek Grant H. 
Published: May 2015

Abstract
Objective: The purpose of this study was to assess risk factors that are associated with inpatient charges and mortality rates with Methicilin-resistant Staphylococcus aureus (MRSA), Aspergillus, and Candida in children with leukemia. We hypothesize that MRSA and opportunistic fungal infections are associated with higher inpatient charges and worse outcomes relative to those without infections. Identifying the risk factors that affect mortality and inpatient charges of these infections should add to the current knowledge of treating and preventing these infections in immune compromised patients.
Methods: Retrospective cohort study using the Agency for Healthcare Research Quality's Healthcare Cost and Utilization Project 2009 KIDS database. Overall, 33,020 individual hospital visits were analyzed for pediatric leukemia patients.
Results: Predictors of increased mortality were: Age (OR=1.1, SE=0.02), MRSA (OR=7.2, SE=5.2), Aspergillus (OR=6.3, SE=2.1), Candida (OR=5.7, SE=1.3), and Deyo-Charlson comorbidity scores (OR=1.7, SE=0.13). Significant predictors of increased inpatient charges were: MRSA (OR=2.2, SE=0.35), Aspergillus (OR=2.7, SE=0.25), Candida (OR=2.3, SE=0.15), Female Sex (OR=1.1, SE=0.04), Deyo-Charlson comorbidity scores (OR=1.2, SE=0.04), Urban Hospitals (OR=1.9, SE=0.24), and the Southern Region (OR=0.84, SE=0.2=07). Significant predictors of increased length of stay were similar to predictors of inpatient charges.
Conclusions: Although uncommon in leukemia cases involving pediatrics or young adults, risks of higher mortality, length of stay, and inpatient charges were noted in cases involving MRSA, Aspergillus, and Candida. The burden of these illnesses requires further attention in order to improve outcomes among patients with leukemia.
Citation Format: Tomas Nuño, Grant H. Skrepnek. Retrospective analysis of direct inpatient charges and mortality of leukemia pediatric patients with Methicillin-resistant Staphylococcus aureus, Candida, or Aspergillus infections in the United States. [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 5051. doi:10.1158/1538-7445.AM2014-5051
Abstract 5062: Serum microRNA profiling in non-muscle invasive bladder cancer
Authors: Lian Jie , Lin Shu-Hong , Luo Sherri , Huang Maosheng , Gu Jian , Kamat Ashish M. , Dinney Colin P. , Wu Xifeng 
Published: May 2015

Abstract
MicroRNAs (miRNAs) are associated with the development of nearly all cancers and serum miRNAs are promising biomarkers for early detection, diagnosis, and prognosis of cancer. We sought to identify serum miRNAs as potential diagnostic biomarkers for bladder cancer. To this end, global miRNA profiling was performed on sera in a pilot sample set containing matched non-muscle-invasive bladder cancer (NMIBC) and healthy controls to identify highly abundant serum miRNAs. Eighty nine miRNAs were stably detectable in cases and controls and selected for further testing. These 89 miRNAs were simultaneously quantified by high-throughput Taqman analysis using the Fluidigm BioMark™ HD System in a discovery set (140 NMIBC patients and 139 control subjects) and a validation set (140 NMIBC patients and 139 control subjects). In the discovery phase, 12 miRNAs showed significant differential expression between NMIBC patients and controls. In the validation phase, expression of one miRNA, miR-409-3p, remained significantly down-regulated in patients with NMIBC as compared to controls. The risk estimates of bladder cancer for miR-409-3p by tertile distributions in controls showed a significant trend for increased risk at the highest tertile for the whole sample set (odds ratio (OR) = 2.26; 95% confidence interval (CI) =1.42-3.59; P = 5.95 × 10−4) as well as for age &gt; 65 (OR = 2.32; 95% CI =1.24-4.34; P =4.60 × 10−3) and ever smokers (OR = 2.34; 95% CI =1.31-4.18; P =4.05 × 10−3). Analyses of joint effects of this risk factor showed that the OR was statistically significantly elevated to 5.21 (95% CI =2.72-10.00; P =6.84 × 10−7) for the sample set including both the lowest level of miR-409-3p and ever smokers. Thus the differential expression miR-409-3p in serum distinguishes NMIBC and controls and may contribute to bladder cancer development.
Citation Format: Jie Lian, Shu-Hong Lin, Sherri Luo, Maosheng Huang, Jian Gu, Ashish M. Kamat, Colin P. Dinney, Xifeng Wu. Serum microRNA profiling in non-muscle invasive bladder 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 5062. doi:10.1158/1538-7445.AM2014-5062
Abstract 5065: Fine-mapping the HOXB region detects common variants tagging a rare coding allele: Evidence for synthetic association in prostate cancer
Authors: Kote-Jarai Zsofia , Saunders Edward , Dadaev Tokhir , Leongamornlert Daniel , Jugurnauth-Little Sarah , Tymrakiewicz Malgorzata , Govindasami Koveela , Wiklund Fredrik , Olama Ali Amin Al , Benlloch Sara ,   The PRACTICAL Consortium, Easton Douglas , Muir Keneth , Eeles Rosalind 
Published: May 2015

Abstract
The HOXB13 gene has been implicated in prostate cancer susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 prostate cancer cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with prostate cancer risk, described by rs117576373, OR 1.30, P = 2.62×10-14. Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene, G84E, rs138213197, which has been identified recently as a moderate penetrance prostate cancer susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.
Citation Format: Zsofia Kote-Jarai, Edward Saunders, Tokhir Dadaev, Daniel Leongamornlert, Sarah Jugurnauth-Little, Malgorzata Tymrakiewicz, Koveela Govindasami, Fredrik Wiklund, Ali Amin Al Olama, Sara Benlloch, The PRACTICAL Consortium, Douglas Easton, Keneth Muir, Rosalind Eeles. Fine-mapping the HOXB region detects common variants tagging a rare coding allele: Evidence for synthetic association in prostate 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 5065. doi:10.1158/1538-7445.AM2014-5065
Abstract 5067: An expressed retrogene of master embryonic stem cell factor OCT4 alters prostate cancer susceptibility
Authors: Breyer Joan , Dorset Daniel , Clark Travis , Bradley Kevin , Wahlfors Tiina , McReynolds Kate , Maynard William , Chang Sam , Cookson Michael , Smith Joseph , Schleutker Johanna , Dupont William , Smith Jeffrey R. 
Published: May 2015

Abstract
Genetic association studies of prostate and other cancers have identified a major risk locus at chromosome 8q24, but a causal gene and a mechanism for cancer predisposition has remained elusive. The locus harbors the POU5F1B retrogene and several non-coding RNA genes, and is also proximal to the MYC oncogene. The open reading frame of the retrogene is preserved with 96% identity to that of the parent POU5F1 gene on chromosome 6, encoding the master embryonic stem cell factor Oct4. We observed that 8q24 risk alleles are significantly correlated with reduced expression of the POU5F1B retrogene in normal prostate tissue. The alleles were not correlated with the expression of MYC or other flanking genes in normal prostate tissue. Predicted deleterious POU5F1B missense germline variants were also associated with risk of prostate cancer. Thus, two independent lines of genetic evidence support a potential causal role for POU5F1B in the transformation of normal prostate tissue. A plausible hypothesis of POU5F1B function is dysregulation of Oct4; POU5F1 is transcriptionally regulated by the encoded Oct4 transcription factor. The POU5F1B retrogene on 8q24 and POU5F1 on 6p21 were significantly co-expressed. These results suggest that a pathway critical to self-renewal of embryonic stem cells may also have a role in the origin of cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Joan Breyer, Daniel Dorset, Travis Clark, Kevin Bradley, Tiina Wahlfors, Kate McReynolds, William Maynard, Sam Chang, Michael Cookson, Joseph Smith, Johanna Schleutker, William Dupont, Jeffrey R. Smith. An expressed retrogene of master embryonic stem cell factor OCT4 alters prostate cancer susceptibility. [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 5067. doi:10.1158/1538-7445.AM2014-5067
Abstract 507: ERβ1 decreases breast cancer cell survival by regulating the unfolded protein response
Authors: Thomas Christoforos , Rajapaksa Gayani , Nikolos Fotis , Bado Igor , Gustafsson Jan-Ake 
Published: May 2015

Abstract
Estrogen receptors (ERs) regulate cellular processes that influence the development and response of breast cancer to hormonal therapy. Unfolded protein response (UPR) has been identified as a key mechanism that determines endocrine responsiveness and cellular survival in breast cancer. UPR assists the cells to cope with the stress caused by the accumulation of unfolded proteins in the endoplasmic reticulum (ER). Although ERα is known to affect the cellular response to ER stress, the role of ERβ in regulating the UPR has not been investigated. Here we show that the wild-type ERβ (ERβ1) enhanced apoptosis in breast cancer cells in response to treatment with the ER stress inducers thapsigargin and bortezomib. Targeting the Bcl-2 in the ER of the ERβ1-expressing cells prevented the apoptosis induced by ER stress but not by non-ER stress apoptotic stimuli indicating that ERβ1 promotes ER stress-regulated apoptosis. ERβ1 promoted ER stress-induced apoptosis by suppressing the inositol-requiring enzyme-1 (IRE-1) pathway of the UPR. ERβ1 repressed the transcription of the IRE-1α gene and the subsequent splicing of the X-box binding protein-1 (XBP-1). These results suggest a potential role of ERβ1 in influencing stress and therapy response in breast cancer by regulating the UPR.
Citation Format: Christoforos Thomas, Gayani Rajapaksa, Fotis Nikolos, Igor Bado, Jan-Ake Gustafsson. ERβ1 decreases breast cancer cell survival by regulating the unfolded protein response. [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 507. doi:10.1158/1538-7445.AM2014-507
Abstract 5085: Inducing multipolarity of acentrosomal mitotic spindles as a novel tumor-specific targeting strategy revealed by the antimitotic effect of mdivi-1
Authors: Wang Jingnan , Qian Wei , Shuda Masahiro , Li Jianfeng , Santana-Santos Lucas , Sobol Robert W. , Houten Bennett Van 
Published: May 2015

Abstract
Traditional antimitotic drugs for cancer chemotherapy often have undesired toxicity to healthy tissue, limiting clinical application. Developing tumor-specific antimitotic strategies is necessary to improve the efficacy of drugs in the selective eradication of tumor cells. In this study, we discovered mdivi-1 (mitochondrial division inhibitor-1), which was originally reported as an inhibitor of mitochondrial fission protein dynamin-related protein 1 (Drp1), specifically disrupts M phase cell cycle progression only in human tumor cells and not in non-transformed fibroblasts and epithelial cells. The antimitotic effect of mdivi-1 is Drp1-independent, as M phase abnormality induced by mdivi-1 was observed in both Drp1 wild-type and Drp1 knockout MEF cells. We also identified that the tumor transformation process required for the antimitotic effect of mdivi-1 is downstream of SV40 large T and small t antigens - but not hTERT-mediated immortalization. Mdivi-1 induces multipolar mitotic spindles in tumor cells regardless of centrosome number. Acentrosomal spindle poles, which do not contain bona-fide centrosome components γ-tubulin and centrin-2, were found to contribute to the spindle multipolarity. The formation of such aberrant mitotic spindles leads to gross genome instability and apoptotic cell death through Bax/Bak-mediated mitochondrial outer membrane permeabilization (MOMP). Gene expression profiling comparing non-transformed and transformed cells revealed that the genes involved in assembly of acentrosomal spindles are highly up-regulated in tumor cells, thus providing the mechanism underlying the preferential formation of acentrosomal multipolar spindles in tumor cells compared to normal cells after mdivi-1 treatment. Taken together, our studies imply that mdivi-1 represents a novel class of quinazolinone compounds that function as acentrosomal spindle inducers (ASI). We suggest that promoting the assembly of multipolar mitotic spindles composed of acentrosomal poles could serve as a novel strategy in achieving a tumor-specific antimitotic effect.
(Work was supported by P30CA047904, GM087798, UPCI and PA Dept of Health CURE program)
Note: This abstract was not presented at the meeting.
Citation Format: Jingnan Wang, Wei Qian, Masahiro Shuda, Jianfeng Li, Lucas Santana-Santos, Robert W. Sobol, Bennett Van Houten. Inducing multipolarity of acentrosomal mitotic spindles as a novel tumor-specific targeting strategy revealed by the antimitotic effect of mdivi-1. [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 5085. doi:10.1158/1538-7445.AM2014-5085
Abstract 5086: BEX protein attenuates the mitotic checkpoint and induces preneoplastic aneuploidy
Authors: Lee Jin-Kwan , Ha Geun-Hyoung , Lee Janet , Lee Chang-Woo 
Published: May 2015

Abstract
The mitotic checkpoint plays a critical role in preventing chromosome missegregation and the adaptation of aneuploid cells. BubR1 kinase is a member of the mitotic checkpoint machinery. To understand the function of BubR1-mediated mitotic checkpoint, we have screened a novel BubR1-interating protein, BEX, by performing yeast two-hybrid systems. Here, we show that overexpression of BEX protein with sustained spindle poison results in a production of aneuploid cells and less apoptotic cell death. Inhibition of BubR1 expression increases aneuploid cell populations, whereas knockdown of both BEX and BubR1 avoid polyploidy by undergoing apoptosis in BubR1-depleted aneuploid cells. In addition, forced BEX expression significantly induces the colony forming potential and accelerates the proliferation rate. Interestingly, BEX is localized on X chromosome, and seems to be selectively expressed at cancer cells and tissues. These results indicate that BEX expression leads to mitotic dysfunction, and contributes to unstable chromosome aneuploid cells to be preneoplastically adapted.
Citation Format: Jin-Kwan Lee, Geun-Hyoung Ha, Janet Lee, Chang-Woo Lee. BEX protein attenuates the mitotic checkpoint and induces preneoplastic aneuploidy. [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 5086. doi:10.1158/1538-7445.AM2014-5086