bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2171: Weight change in relation to early breast cancer events in breast cancer patients
Authors: Kenéz Xuyian , Markkula Andrea , Simonsson Maria , Ingvar Christian , Rose Carsten , Jernström Helena C. 
Published: May 2015

Abstract
Background: Weight change may influence breast cancer prognosis. The aim was to investigate whether weight change between the preoperative and 1-year postoperative visit was associated with risk of early breast cancer events in a population-based cohort of breast cancer patients in Sweden.
Methods: Weight was measured by research nurses at the preoperative and the 1-year follow-up visits from 849 primary breast cancer patients operated between 2002 and 2011 in Lund, Sweden. Tumor characteristics, clinical data, and date of death were obtained from pathology reports, patient charts, and population registries.
Results: The median follow-up was three years and 79 early breast cancer events occurred during the follow-up period. In all patients, there was a non-significant tendency towards decreased risk of early events with weight loss (Ptrend = 0.11). Weight loss was significantly associated with lower risk of early events compared to stable weight or weight gain in patients with axillary nodal involvement (Ptrend = 0.012), but not in patients without axillary nodal involvement. Further analysis showed that weight loss was only significantly associated with lower risk of early events among patients younger than 70 years with axillary nodal involvement, while patients who had gained more than 5% of the preoperative weight had significantly earlier events compared to those with stable weight. The results remained significant after adjustment for age at diagnosis, natural logarithm of the preoperative weight, invasive tumor size, axillary nodal involvement, and ER status. Further adjustments for smoking and alcohol abstinence, ever use of hormone therapy, or for treatments did not materially change the result.
Conclusion: Weight loss was associated with significantly lower risk for early breast cancer events in patients younger than 70 years with axillary nodal involvement compared to stable weight or weight gain. If these results are confirmed, weight management may be incorporated in post-diagnosis management of breast cancer patients with axillary nodal involvement and have a significant beneficial impact on short-term prognosis.
Citation Format: Xuyian Kenéz, Andrea Markkula, Maria Simonsson, Christian Ingvar, Carsten Rose, Helena C. Jernström. Weight change in relation to early breast cancer events in breast 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 2171. doi:10.1158/1538-7445.AM2014-2171
Abstract 2211: Viral subtypes in hepatocellular carcinoma are associated with different mechanisms of WNT/CTNNB1 alteration
Authors: Covington Kyle R. , Donehower Lawrence A. , Creighton Chad , Slagle Betty L. , Goss John A. , Cotton Ronald T. , Gingras Marie-Claude , Shinbrot Eve , Guiteau Jacfranz J. , Nguyen Thao N. , Harring Theresa R. , Muzny Donna M. , Walker Kimberly , Doddapaneni HarshaVardhan , Gibbs Richard A. , Aburatani Hiroyuki , Shibata Tatsuhiro , Wheeler David A. ,   Japan ICGC HCC Project
Published: May 2015

Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers, especially in Asia, and regions of endemic hepatitis infection. The primary risk factors for HCC are chronic hepatitis infection by hepatitis C (HCV) or hepatitis B (HBV). We performed whole exome sequencing on 549 matched tumor and normal samples from three centers (BCM HGSC, RCAST, NCC) to identify somatic changes in protein coding regions and changes in copy number. Here we describe variants associated with specific viral etiologies in HCC.
We found TP53, CTNNB1, ARID1A, ARID2, and AXIN1 to be among the most frequently mutated genes in the entire dataset, implicating DNA damage, WNT signaling, and chromatin remodeling as recurrently altered pathways in HCC. Our validation rate for mutations in significantly mutated genes was over 95%. We identified 18 genes which differed significantly (p &lt; 0.05) in mutation frequency between viral subtypes. Of these, AXIN1 was mutated in over 15% of HBV-associated HCC but less than 5% of HCV and non-viral-associated HCC. Additionally, we performed GISTIC analysis based on read depth from our whole exome sequencing data. We found that WNT3A and MYC were significantly amplified and AXIN1 and TP53 were significantly deleted in HCV-associated HCC but not HBV or non-virus-associated HCC.
Our findings indicate that WNT/beta-catenin signaling is a frequently altered pathway in HCC. While aberrations in this pathway were present in all viral etiologies, HBV-associated HCC tended to mutate AXIN1 while HCV-associated HCC tended to have AXIN1 deletion. These differences may result from virus-specific oncogenic processes.
Citation Format: Kyle R. Covington, Lawrence A. Donehower, Chad Creighton, Betty L. Slagle, John A. Goss, Ronald T. Cotton, Marie-Claude Gingras, Eve Shinbrot, Jacfranz J. Guiteau, Thao N. Nguyen, Theresa R. Harring, Donna M. Muzny, Kimberly Walker, HarshaVardhan Doddapaneni, Richard A. Gibbs, Hiroyuki Aburatani, Tatsuhiro Shibata, David A. Wheeler, Japan ICGC HCC Project. Viral subtypes in hepatocellular carcinoma are associated with different mechanisms of WNT/CTNNB1 alteration. [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 2211. doi:10.1158/1538-7445.AM2014-2211
Abstract 2284: Cytotoxic and genotoxic effects of PEG-coated gold nanoparticles in HK-2 cells
Authors: Patlolla Anita K. , Epting Tammy , Thrasher Lisabeth , Tchounwou Paul B. 
Published: May 2015

Abstract
Biomolecular functionalization of gold nanoparticles (GNP's) have led to a dramatic expansion of their potential biomedical applications, including biosensorics, bioimaging, photothermal therapy, and targeted drug delivery. As the range of gold nanoparticle types and their applications continues to increase, human safety concerns are gaining attention, which makes it necessary to better understand the potential toxicity hazards of these novel materials. The main objective of this study was to determine the cytotoxic and genotoxic potential of poly-ethylene-glycol-coated gold nanoparticles (PEG-GNPs) in HK-2 cells. These cells were grown under sterile conditions in 96-well plate until 80% confluency. Four exposure concentrations (125, 250, 500 and 1000 µg/ml) of PEG-coated GNP's and a control were used. Following exposure to PEG-coated GNP's, cytotoxicity assay (MTS) was performed for 24 and 48 hrs using standard protocol. Genotoxic effects of GNP's were determined measuring DNA damage using comet assay. The results demonstrated a dose and time dependent decrease in cell viability with PEG-coated GNPs and an increase in percent DNA damage in exposed cells compared to control. The difference in the cytotoxic effect between 24 and 48 hrs was not statistically significant however, the genotoxic effect was statistically significant both in time and dose. The cellular findings reported here do suggest that GNPs has the potential to induce cell death and cause damage to DNA in HK-2 cells. However, more studies to clarify the role of encapsulation in the in vitro toxicity of GNP's, are required and parallel comparison is preferred.
Note: This abstract was not presented at the meeting.
Citation Format: Anita K. Patlolla, Tammy Epting, Lisabeth Thrasher, Paul B. Tchounwou. Cytotoxic and genotoxic effects of PEG-coated gold nanoparticles in HK-2 cells. [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 2284. doi:10.1158/1538-7445.AM2014-2284
Abstract 2298: Methylated gene markers discovered in nasopharyngeal carcinoma by differential methylation hybridization (DMH) in high density CpG island DNA chips
Authors: Cheng Wai Wai , Ngan Roger K.C. , Kwong Dora L.W. , Huang Tim H.M. , Ma Victor W.S. , Law Stephen C.K. , Tse Loretta , Busson Pierre , Tsao George S.W. , Lung Maria L. , Yip Timothy T.C. 
Published: May 2015

Abstract
Nasopharyngeal carcinoma (NPC) is a prevalent cancer in southern China and south east Asian countries. A variety of tumor suppressor (TS) genes including p16, RASSF1A, EDNRB, DAP-Kinase, RIZ1, E-Cadherin were found to be hypermethylated in NPC. This, however, could only be the tip of an iceberg. We made use of the high throughput differential methylation hybridization (DMH) technique in screening for methylated DNA markers in 244K CpG island DNA chip in three NPC xenografts (C15, C17, 99-186), a NPC tumor cell line (C666) versus an immortalized NP non-cancer cell line (NP69). This DMH screening discovered 100, 213, 372 and 977 genes respectively in 99-186, C17, C15 and C666 with ≥ 5 CpG sites in their gene promotors being methylated. Among these genes, 28 of them were found to have DNA methylation in all the 4 NPC xenografts/ tumor cell line. Bisulphite sequencing was performed in 17 pairs of tumor and normal biopsy samples from 17 NPC patients. This confirmed tumor specific methylation in the promotor regions of 8 gene markers, namely, NRP3, PCDH10, PENK, ADHFE1, IRX4, GSC, PFN2 & GFI1 with positive methylation ratios (+ve MR) in tumor biopsies of 86.7%, 85.7%, 80%, 72.7%, 54.5%, 50%, 41.7% &23.1% respectively and +ve MR of 18.2%, 0%, 0%, 0%, 0%, 37.5%, 12.5% & 0% respectively in normal biopsies. Methylation of CpG sites appears to occur either all or none with 15 to 45 consecutive CpG sites in these genes either all methylated or non-methylated in tumor biopsies probably indicating the need of methylation of a full cluster of CpG sites in order to affect the gene transcription of the discovered genes. Functions of the DMH identified genes includes cell adhesion (PCDH10), signal transduction (PENK), chloride ion binding (NPR3), regulation of DNA dependent transcription (IRX4) and xenobiotic metabolism (ADHFE1). In fact, PCDH10, PENK and GFI1 genes have been reported to be closely associated with NPC/esophageal carcinoma, pancreatic adenocarinoma and T-cell lymphoma respectively. Further analyses in these methylated markers could be useful in the diagnosis and study of etiology of NPC.
Citation Format: Wai Wai Cheng, Roger K.C. Ngan, Dora L.W. Kwong, Tim H.M. Huang, Victor W.S. Ma, Stephen C.K. Law, Loretta Tse, Pierre Busson, George S.W. Tsao, Maria Li Lung, Timothy T.C. Yip. Methylated gene markers discovered in nasopharyngeal carcinoma by differential methylation hybridization (DMH) in high density CpG island DNA chips. [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 2298. doi:10.1158/1538-7445.AM2014-2298
Abstract 23: bFGF induced VEGF expression and angiogenesis in human chondrosarcoma
Authors: Lin Kai-Wei , Tang Chih-Hsin 
Published: May 2015

Abstract
Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. Solid cancers cannot grow beyond a limited size without an adequate blood supply; cancers that express VEGF are able to grow and metastasize. In normal tissue, basic fibroblast growth factor (bFGF) is present in basement membranes and in the subendothelial extracellular matrix of blood vessels. It has been found that bFGF increased the formation of new blood vessels and angiogenesis during tumor growth and metastasis. However, the effect of bFGF in VEGF expression in human chondrosarcoma is largely unknown. In this study, we examined the effect of bFGF in VEGF expression in human chondrosarcoma. We found that the expression of bFGF and VEGF were correlated with tumor stage and significantly higher than that in normal cartilage. bFGF increased the VEGF expression and subsequently promoted migration and tub formation in endothelial progenitor cells (EPCs). Pretreatment of cells with p38, c-Src, or NF-κB inhibitor antagonized bFGF-induced VEGF expression and EPC migration as well as tube formation. Incubation with bFGF induced p38, c-Src and NF-κB phosphorylation. In addition knockdown bFGF decreased VEGF expression and also abolished chondrosarcoma conditional medium-mediated angiogenesis in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and matrigel-plug nude mice model in vivo. Furthermore, using xenograft tumor angiogenesis model, knockdown bFGF significantly reduced tumor growth and tumor-associated angiogenesis. Our results indicated that bFGF enhances the VEGF expression of chondrosarcoma cells. One of the mechanisms underlying bFGF-directed VEGF expression was through the p38/c-Src/NF-κB signal transduction pathway.
Citation Format: Kai-Wei Lin, Chih-Hsin Tang. bFGF induced VEGF expression and angiogenesis in human chondrosarcoma. [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 23. doi:10.1158/1538-7445.AM2014-23
Abstract 2379: 96-Well CometChip validation for simultaneous treatment and measurement of DNA damage in a single platform
Authors: Woodgate Sandra R. , Whittaker Clare , George Jay , Sobol Robert W. , Schamus-Haynes Sandy , Engelward Bevin P. , Ge Jing 
Published: May 2015

Abstract
The 96-Well CometChip System is a high-throughput platform to simultaneously treat and measure DNA damage induced by different treatments, or among different cell types on a single slide using the comet assay. The CometChip is a consumable consisting of specifically sized micron pores patterned into agarose layered on a treated microscope slide. Ninety-six (96) separate wells are created by inserting the CometChip into a reusable 96-Well CometChip System, a magnetically-sealed cassette suitable for tissue culture incubators. Cells added to each well are captured by gravity into micropores and excess cells aspirated leaving an array of non-overlapping cells. Multiple experimental conditions are performed in parallel by the addition of different chemicals to respective wells. Once treatment is complete the CometChip is removed from the cassette and processed using standard alkaline comet conditions and imaging systems.
A distributable CometChip requires precision manufacturing to ensure robust and reproducible performance. CometChip tolerances were investigated and compared to normal comet using cryopreserved comet control cells with known levels of DNA damage. After setting specifications, 96-Well CometChips with 30 micron pores were distributed to evaluate both intra and inter-chip variations between laboratories. To assure experimental consistency between labs, magnetically sealable cassettes, cryopreserved control cells and identical electrophoresis systems were provided to each lab. Data is presented to demonstrate the feasibility of manufacturing the CometChip for reproducible results based on the coefficients of variance (CVs) obtained between different wells and laboratories. In addition, data will be presented demonstrating the absence of cross talk between CometChip wells using the 96-Well CometChip System. (Work was supported by R44ES021116).
Citation Format: Sandra R. Woodgate, Clare Whittaker, Jay George, Robert W. Sobol, Sandy Schamus-Haynes, Bevin P. Engelward, Jing Ge. 96-Well CometChip validation for simultaneous treatment and measurement of DNA damage in a single platform. [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 2379. doi:10.1158/1538-7445.AM2014-2379
Abstract 2392: The role of ATM in lytic infection of EBV in nasopharyngeal epithelial cells
Authors: Tsao George Sai-Wah , Hau Pok Man 
Published: May 2015

Abstract
Epstein-Barr virus (EBV), a type of oncogenic herpesvirus, is associated with human malignancies. Previous studies have shown that reactivation of EBV in infected cells induces ATM-dependent DNA damage response (DDR). The functional role and involvement of ATM activation during lytic induction remains obscure. In this study, the essential role of ATM for viral DNA replication was examined in EBV-infected nasopharyngeal epithelial cells. Induction of lytic EBV infection triggers ATM activation and localization of DDR proteins at the viral replication compartments. Suppression of ATM activity using siRNA approach or specific chemical inhibitor diminished EBV DNA replication and production of infectious virion in EBV-infected cells induced to undergo lytic infection. Phosphorylation of Sp1 is a downstream event of ATM activation. The phosphorylation of Sp1 at serine 101 residue is crucial in promoting the accretion of EBV replication proteins at the replication compartment to facilitate viral DNA replication. Depletion of Sp1 suppresses viral DNA replication and localization of EBV replication proteins to the replication compartments. Our studies support an important role of ATM activation in lytic infection of EBV. Phosphorylation of Sp1 is an essential process mediating the recruitment of EBV replication protein to replication compartments. Our study highlights the importance of DDR pathway in lytic infection of EBV and suggests the potential application of specific DDR inhibitors to control the EBV replication in infected cells.
Funding support: Research Grant Council of Hong Kong (GRF #779312 & 779713; AoE/M-06/08).
Note: This abstract was not presented at the meeting.
Citation Format: George Sai-Wah Tsao, Pok Man Hau. The role of ATM in lytic infection of EBV in nasopharyngeal epithelial cells. [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 2392. doi:10.1158/1538-7445.AM2014-2392
Abstract 2411: Rapamycin sensitizes cancer cells to growth inhibition by the PARP inhibitor olaparib
Authors: Osoegawa Atsushi , Gills Joell J. , Kawabata Shigeru , Sugio Kenji , Dennis Phillip A. 
Published: May 2015

Abstract
Poly (ADP-ribose) polymerase inhibitors (PARPi) have been developed and tested in a context of combining them with drugs that inhibit double-stranded (ds) DNA repair, because PARPi impair single-stranded (ss) DNA break repair, resulting in activation of dsDNA break repair machinery. Rapamycin, an mTOR inhibitor, has been widely prescribed for more than a decade, and recent studies revealed its ability to inhibit dsDNA break repair. The combination of the PARPi, olaparib, and rapamycin synergistically inhibited cell proliferation in non-small cell lung cancer (NSCLC) cells, as well as triple negative breast cancer (TNBC) cells that have BRCA1 mutations. Rad51, which forms a polymer on ssDNA upon dsDNA breaks, plays an essential role in homologous recombination. Olaparib induced Rad51 focus formation and rapamycin successfully inhibited it both in vivo and in vitro, suggesting this combination worked through blocking both ssDNA break repair and dsDNA break repair, resulting in cells that cannot go through G2/M checkpoint. The protein level of PARP was predictive for both PAR activity and Rad51 focus formation with this combination. Collectively, these data suggest that this combination could have a therapeutic potential to inhibit cancer with high PARP expression, or in combination with cytotoxic chemotherapy or radiation.
Citation Format: Atsushi Osoegawa, Joell J. Gills, Shigeru Kawabata, Kenji Sugio, Phillip A. Dennis. Rapamycin sensitizes cancer cells to growth inhibition by the PARP inhibitor olaparib. [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 2411. doi:10.1158/1538-7445.AM2014-2411
Abstract 2413: Unstable genomes and the average cancer cell
Authors: Abdallah Batoul , Stevens Joshua B. , Horne Steven , Liu Guo , Heng Henry HQ 
Published: May 2015

Abstract
The high degree of multi-level heterogeneity represents a key challenge for cancer research. Despite its importance, both the theoretical concepts and appropriate tools for proper quantitative analysis are underdeveloped. Specifically, the characterization of heterogeneity in cancer cell populations of different genomic stabilities, and its effect on systems dynamics are poorly understood. We use a single-cell and population-based assays to describe an instability-mediated mechanism where genome heterogeneity drastically affects cell growth, and cannot be accurately measured using conventional averages. First, we show that most unstable cancer cell populations exhibit high levels of karyotype heterogeneity, where it is difficult, if not impossible, to karyotypically clone cells. Second, by comparing stable and unstable cell populations, we show that instability-mediated karyotype heterogeneity leads to growth heterogeneity, where outliers dominantly contribute to population growth and exhibit shorter cell cycles. Predictability of population growth is more difficult for heterogeneous cell populations than for homogenous cell populations. Since “outliers” play an important role in cancer evolution, where genome instability is the key feature, averaging methods used to characterize cell populations are misleading. We conclude: 1) the karyotype cannot be cloned when genome instability is high, and caution is needed for single cell analysis for cell populations that are not genetically identical; 2) the “average” cancer cell does not exist, as the statistical mean does not accurately describe systems behavior, especially genome instability is high; and 3) single cell analysis is needed when cells are not genomically identical. Our results not only provide an explanation for population heterogeneity but also explain how genome-level heterogeneity contributes to drug resistance and cancer evolution.
Note: This abstract was not presented at the meeting.
Citation Format: Batoul Abdallah, Joshua B. Stevens, Steven Horne, Guo Liu, Henry HQ Heng. Unstable genomes and the average cancer cell. [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 2413. doi:10.1158/1538-7445.AM2014-2413