bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2557: Role of microRNAs in breast cancer
Authors: El-Mahdy Hesham Abbas , Mansour Ossama Abdelmotaal , Badr Mohamed Mohamed , Elshimy Reham Aly 
Published: July 2017

Abstract
Background: Breast cancer (BC) is one of the most common cancer in women around the world and the second leading cause of death worldwide. MicroRNAs (miRNAs) expression participates in breast cancer.
Objectives: The purpose of this study is to investigate the expression of miR-133a and miR-155 in breast cancer serum and study their correlation with tumor suppressor protein (p53), carcinoembryonic antigen (CEA) and cancer antigen-15.3 (CA-15.3) concentrations in serum of breast cancer patients and also study their correlations with clinicopathological features.
Material and methods: In this study the expression of miR-133a and miR-155 in serum were measured using quantitative real-time polymerase chain reaction (qRT-PCR), P53 concentration was measured by enzyme-linked immunosorbent assays (ELISA), CEA and CA-15.3 concentration were measured using ARCHITECT immunoassay in women with breast cancer (n=60) and controls (n = 80).
Results: In this study miRNA-155 was significantly overexpressed (P&lt;0.001) while miR-133a had significant down expression (P&lt;0.001) in the serum of breast cancer patients compared to control serum. P53 had no significant correlations with any of the studied miRNAs. Carcinoembryonic antigen and CA-15.3 have significant higher concentration in the serum of breast cancer patients compared to control serum. A significant association was observed between miR-133a with tumor grade (P&lt;0.05) and miR-155 with lymph node involvement (P&lt;0.05). A significant correlation between miR-155 and CEA (P&lt;0.05). No correlations between miR-133a and P53, CEA, CA-15.3. By using receiver operating characteristic (ROC) curve, the two miRNAs showed higher sensitivity, specificity, positive predictive value and negative predictive value than routine markers.
Our Conclusion: These miRNAs have a significant signature in the pathogenesis of breast cancer and can be used as non-invasive potential biomarkers for breast cancer detection.
Note: This abstract was not presented at the meeting.
Citation Format: Hesham Abbas El-Mahdy, Ossama Abdelmotaal Mansour, Mohamed Mohamed Badr, Reham Aly Elshimy. Role of microRNAs in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2557. doi:10.1158/1538-7445.AM2017-2557
Abstract 256: Delta tocopherol inhibits urothelial tumorigenesis in the UPII mutant Ha-ras transgenic mouse model and induces apoptosis via activation of the ATF4/CHOP-DR5 pathway
Authors: Blair Christopher A. , Wu Maggie , Huynh Tim , Hu Hanze , Walia Arman , Yang Chung S. , Zi Xiaolin 
Published: July 2017

Abstract
Epidemiological studies have reported that Vitamin E intake was inversely related to the risk of multiple cancers including human urinary bladder cancer. Tocopherols (T) are the major forms of vitamin E in the U.S. diet, exist as α-T, β-T, γ-T and δ-T. Compared to α-T, the anti-cancer effect of other Ts and their mechanisms of action remain largely unknown. We have shown that δ-T is the most effective one among the Ts in reducing the viabilities of bladder cancer cell lines with IC50s of under 10 μM, whereas there is no or minimal effect of α-T at a concentration of up to 50 μM on the viability of bladder cancer cell lines. δ-T treatment of bladder cancer cell lines, RT4 and UMUC-3, resulted in apoptosis via marked induction of death receptor-5 (DR5) expression and then activation of caspase 3, 8, and 9 leading to PARP cleavage and apoptotic morphology. siRNA knockdown of DR5 expression significantly attenuated the apoptotic effects of δ-T in bladder cancer cells. Consistent with the above results, δ-T treatment significantly upregulated the expression of ER stress sensors PERK and IRE1α, as well as downstream components GRP78, ATF4, and CHOP. These results suggested that δ-T can induce endoplasmic reticulum stress and the Unfolded Protein Response, triggering its apoptotic effect. Furthermore, homozygous male UPII mutant Ha-ras transgenic mice that mimic the development and progression of human urothelial cell carcinoma (UCC) with H-ras activation were fed with vehicle control diet (n=20) or diet supplemented with δ-T (0.2% in diet) for 150 days (n=18). The δ-T diet significantly decreased the mean bladder weights (serves as a surrogate of tumor weight) of survived Ha-ras mutant mice by 56% (control vs δ-T, 0.259 ± 0.015 gram vs. 0.114 ± 0.012 gram, P&lt;0.0001) with no significant difference in overall body mass and no detectable indication of toxicity. Our results suggest that δ-T is a potent anti-cancer agent and deserves further investigation in preventing the recurrence and progression of non-muscle-invasive UCC.
Citation Format: Christopher A. Blair, Maggie Wu, Tim Huynh, Hanze Hu, Arman Walia, Chung S. Yang, Xiaolin Zi. Delta tocopherol inhibits urothelial tumorigenesis in the UPII mutant Ha-ras transgenic mouse model and induces apoptosis via activation of the ATF4/CHOP-DR5 pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 256. doi:10.1158/1538-7445.AM2017-256
Abstract 2566: Positive cross-regulatory loop links ZBTB7A to estrogen receptor alpha expression in breast cancer
Authors: Molloy Mary Ellen , Lewinska Monika , Nguyen ThanhThao , Yuan Zhi-Min 
Published: July 2017

Abstract
In breast development and tumorigenesis the biological functions of estrogen are mediated by estrogen receptor alpha (ERα). Approximately 70% of breast cancers are classified as ERα positive and are therefore candidates to receive various forms of endocrine therapy. De novo or acquired resistance to endocrine therapies limits their clinical effectiveness. Identification of novel targets is critical to combat disease progression. Our lab has recently discovered that ZBTB7A suppresses glycolysis by transcriptionally repressing key genes within the glycolytic pathway in various cancer types (Liu, X.S., et al. 2014). Currently, ZBTB7A is proposed to be an oncogene in breast cancer (Zu, X., et al. 2011), however its function in ERα positive breast cancers has yet to be fully addressed. Using publically available datasets, we found that in luminal breast cancers relapse free survival was improved for patients whose tumors expressed high levels of ZBTB7A. Gene expression analysis of TCGA datasets revealed that ZBTB7A and ERα are highly correlated in human breast tumors prompting us to evaluate their potential cross regulation. ERα mRNA and protein levels were significantly decreased upon ZBTB7A silencing both in MCF-7 and T47D breast cancer cell lines. Upon estradiol stimulation, ZBTB7A silencing reduced ERα target gene expression and estrogen response element driven luciferase reporter activity. Additionally, silencing of ZBTB7A inhibited estradiol-induced proliferation and decreased sensitivity to tamoxifen in MCF-7 and T47D cells. These data suggest that ZBTB7A may be required to mediate the pro-proliferative signal of estradiol through its regulation of ERα expression in breast cancer cell lines. To evaluate the potential regulation of ERα on ZBTB7A, ERα was silenced and ZBTB7A mRNA and protein expression were determined. ERα silencing had no effect on ZBTB7A mRNA levels, but led to decreased ZBTB7A protein expression. These effects on ZBTB7A protein expression were attenuated by the presence of the proteasomal inhibitor MG132. Together, these data suggest a model in which ZBTB7A promotes ERα expression at the transcript level while ERα stabilizes ZBTB7A post-transcriptionally conferring a positive feedback loop and sensitivity to estradiol and endocrine therapies. ZBTB7A may contribute to the transcriptional program maintaining a hormone and endocrine therapy responsive phenotype in breast cancer.
Citation Format: Mary Ellen Molloy, Monika Lewinska, ThanhThao Nguyen, Zhi-Min Yuan. Positive cross-regulatory loop links ZBTB7A to estrogen receptor alpha expression in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2566. doi:10.1158/1538-7445.AM2017-2566
Abstract 2569: BCL6 promotes glioma and serves as a novel therapeutic target
Authors: Xu Liang , CHEN Ye , Dutra-Clarke Marina , Mayakonda Anand , Hazawa Masaharu , Savinoff Steve E. , Doan Ngan , Said Jonathan W. , Yong William H. , Yang Henry , Ding Ling-Wen , Jiang Yan-Yi , Tyner Jeffrey W. , Ching Jianhong , Kovalik Jean-Paul , Müschen Markus , Breunig Joshua J. , Lin De-Chen , Koeffler Phillip 
Published: July 2017

Abstract
ZBTB transcription factors orchestrate gene transcription during tissue development. However, their roles in glioblastoma multiforme (GBM) remain unexplored. Here, through a functional screening of ZBTB genes, we identify that BCL6 is required for GBM cell proliferation and is overexpressed in GBM samples. Using a somatic transgenic mouse model, Bcl6 confers the proliferative and invasive stimuli to glioma cells in vivo. Moreover, we discover AXL as a novel downstream target of BCL6. Through AXL, BCL6 enhances both MEK-ERK and S6K-RPS6 axes. Pharmacological inhibition of BCL6 activity effectively blocks GBM growth and inhibits AXL expression. Together, these findings uncover a novel glioma-promoting role of BCL6, and provide the rationale of targeting BCL6 as a potential therapeutic approach.
Citation Format: Liang Xu, Ye CHEN, Marina Dutra-Clarke, Anand Mayakonda, Masaharu Hazawa, Steve E. Savinoff, Ngan Doan, Jonathan W. Said, William H. Yong, Henry Yang, Ling-Wen Ding, Yan-Yi Jiang, Jeffrey W. Tyner, Jianhong Ching, Jean-Paul Kovalik, Markus Müschen, Joshua J. Breunig, De-Chen Lin, Phillip Koeffler. BCL6 promotes glioma and serves as a novel therapeutic target [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2569. doi:10.1158/1538-7445.AM2017-2569
Abstract 2574: The PICT-1 is required for USP7 to effectively stabilize p53 protein, and codon 389 polymorphism is a risk factor for ovarian cancer
Authors: Yoshimoto Masafumi , Tokuda Aoi , Yaginuma Yuji 
Published: July 2017

Abstract
The ovarian cancers causes the deaths of more than 100,000 women per year worldwide, and it is a complex disease, with multiple both histological subtypes and molecular characteristics recognized; therefore, overall survival rates have improved little in the last 30 years. We have to precisely identify genetic and molecular events which could serve as markers for early diagnosis or targets for new therapeutics for ovarian cancers.
The PICT-1 (also named GLTSCR2), one of the nucleolar proteins, has several tumor suppressor functions, such as the stabilization of PTEN and p53. Some studies reported that the loss of or low PICT-1 expression is the common alteration in many cancers, such as brain, skin, lung, esophageal, prostate, kidney, breast, and cervix, but its association with ovarian carcinogenesis has been unknown. Therefore, we investigated its alteration, regulation mechanism, and the effect for p53 stabilization in ovarian cancer.
We found that polymorphism on codon 389 (rs184994) was a statistically significant association with the risk of ovarian cancers. Furthermore, ectopic expression of PICT-1 was required for USP7 to effectively stabilize p53 protein. Because PICT-1 was reported to bind both p53 and MDM2 that enabled to form USP7-p53-MDM2 complex, we investigated whether PICT-1 was regulated by USP7-p53-MDM2 complex. Our results suggested that this complex was the important regulator for PICT-1. In the investigation of the role of PICT-1 that played in the ovarian carcinogenesis using immunohistochemical stainig, we found that PICT-1 protein levels decreased in ovarian cancer tissues compared to normal ovary, and there was a positive correlation between PICT-1 and USP7 protein expression. Our findings suggested that PICT-1 involved in exactly p53 regulation along with MDM2 and USP7, and PICT-1 should be considered as a potential target for therapeutic human cancers.
Citation Format: Masafumi Yoshimoto, Aoi Tokuda, Yuji Yaginuma. The PICT-1 is required for USP7 to effectively stabilize p53 protein, and codon 389 polymorphism is a risk factor for ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2574. doi:10.1158/1538-7445.AM2017-2574
Abstract 2576: Benzyl isothiocyanate potentiates p53 signaling and antitumor effects against breast cancer through activation of p53-LKB1 and p73-LKB1 axes
Authors: Nagalingam Arumugam , Xie Bei , Kuppusamy Panjamurthy , Muniraj Nethaji , Langford Peter , Győrffy Balázs , Saxena Neeraj , Sharma Dipali 
Published: July 2017

Abstract
Functional reactivation of p53 pathway, although arduous, can potentially provide a broad-based strategy for cancer therapy owing to frequent p53 inactivation in human cancer. Using a phosphoprotein-screening array, we found that Benzyl Isothiocynate, (BITC) increases p53 phosphorylation in breast cancer cells and reveal an important role of ERK and PRAS40/MDM2 in BITC-mediated p53 activation. We show that BITC rescues and activates p53-signaling network and inhibits growth of p53-mutant cells. Mechanistically, BITC induces p73 expression in p53-mutant cells, disrupts the interaction of p73 and mutant-p53, thereby releasing p73 from sequestration and allowing it to be transcriptionally active. Furthermore, BITC-induced p53 and p73 axes converge on tumor-suppressor LKB1 which is transcriptionally upregulated by p53 and p73 in p53-wild-type and p53-mutant cells respectively; and in a feed-forward mechanism, LKB1 tethers with p53 and p73 to get recruited to p53-responsive promoters. Analyses of BITC-treated xenografts using LKB1-null cells corroborate in vitro mechanistic findings and establish LKB1 as the key node whereby BITC potentiates as well as rescues p53-pathway in p53-wild-type as well as p53-mutant cells. These data provide first in vitro and in vivo evidence of the integral role of previously unrecognized crosstalk between BITC, p53/LKB1 and p73/LKB1 axes in breast tumor growth-inhibition.
Citation Format: Arumugam Nagalingam, Bei Xie, Panjamurthy Kuppusamy, Nethaji Muniraj, Peter Langford, Balázs Győrffy, Neeraj Saxena, Dipali Sharma. Benzyl isothiocyanate potentiates p53 signaling and antitumor effects against breast cancer through activation of p53-LKB1 and p73-LKB1 axes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2576. doi:10.1158/1538-7445.AM2017-2576
Abstract 2580: Ceramide-rubusoside nano-micelles restores p53-mediated tumor suppression in p53R248W mutant ovarian cancer cells
Authors: khiste sachin K. , Liu Zhijun , Liu Yong-Yu 
Published: July 2017

Abstract
Ceramide (Cer), a sphingolipid metabolite, has crucial functions in anti-proliferation, cell differentiation and apoptosis. Cellular Cer levels highly correlates to therapeutic efficacy of anticancer drugs, however, the hydrophobicity Cer has limits to develop it as a therapeutic agent. Here, we report that Cer-rubusoside (Cer-RUB) nanomicelles enhanced Cer bioavailability and restored p53-mediated tumor suppression. These nanomicelles significantly increased the levels of NBD-C6-Cer by more than 50-fold in serum, 40-fold in tumor and 70-fold in lung of tumor-bearing mice (1 mg/kg, i.p., 24 hr), respectively. Cer-RUB (3 µM) significantly increased OVCAR-3 (p53 R248W) cell sensitivity to cisplatin, and the IC50 values decreased by 3-fold, even though these values were no significant changes in A2780 (wt p53) cells. Furthermore, Cer-RUB treatments (1 mg/kg, i.p. every 3 days for 24 days) significantly increased cisplatin efficacy in tumor growth-arrest in OVCAR-3 tumor-mice, and the tumor volumes reduced by 52% (1653 vs. 805 mm3) in combination with cisplatin, compared to cisplatin alone. We found that ovarian cancer stem cells (CD44+/CD133+) decreased by 10-fold (0.85 vs. 0.08% of total cells) in OVCAR-3 tumors treated with Cer-RUB combined with cisplatin, as compared to cisplatin alone, respectively. Western blotting showed that Cer-RUB treatments selectively increased the expression levels of phosphorylated p53 (Ser15), BAX and p21 in OVCAR-3 cancer cells and tumors, respectively. These studies indicates that the gain-of-function (GOF) of p53 R248W leads OVCAR-3 cell resistance to cisplatin and tumor growth. Cer-RUB can restore p53 and eliminates the GOF of p53 R248W in cancers.
Citation Format: sachin K. khiste, Zhijun Liu, Yong-Yu Liu. Ceramide-rubusoside nano-micelles restores p53-mediated tumor suppression in p53R248W mutant ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2580. doi:10.1158/1538-7445.AM2017-2580
Abstract 2582: KIRnome: KIR genotyping for whole genome/exome sequencing data
Authors: Kim Daeyoon , Yoon Sung-Soo , Koh Youngil , Lee Su Yeon , Yun Hongseok , Cho Sunghoon , Kim Hyung-Lae 
Published: July 2017

Abstract
In this study, we tried to develop valid KIR calling algorithm from WES/WGS data. As a consequence, here we suggest KIRnome (KIR typing for whole genome and exome sequencing) which is a KIR typing method for applying sequencing data such as WES/WGS. A total of 71 sequencing data (18 WES and 53 WGS data, respectively) and matched experimentally validated KIR genotype data are used to train and validate. Before developing this method, two types of allele references (genomic and coding, here after called gSeq and cSeq) are constructed by allele sequence of IPD/KIR. KIRnome consists of two part, first part is calculating normalized depth (here after called depth) of 16 KIR genes and considering allele reference length and second is estimating KIR type based on depth. In general, we get higher normalized depth when using genomic references for WGS data and using coding references for WES data. This coincides with scheme KIRnome and the characteristics of WGS and WES data. Given 71 samples of 3 data sets, we evaluated KIR genotyping performance of KIRnome per each KIR gene. For all 16 KIR genes, KIRnome shows &gt;=98.5% accuracy. When KIRnome performance was tested only in 13 WES samples, the accuracy slightly drops to 94%. We assume this is attributable to relatively small number of the samples. In conclusion, we developed a novel and unique method named KIRnome for KIR typing from NGS data. KIRnome could determine KIR genotype accurately from WES and WGS data respectively. We expect KIRnome would facilitate revealation of immunogenetic facts in various disease. Moreover, future generation of KIR specific NGS data and improved reference sequence information of KIR would enable KIRnome to type KIR at allele level in a near future.
Citation Format: Daeyoon Kim, Sung-Soo Yoon, Youngil Koh, Su Yeon Lee, Hongseok Yun, Sunghoon Cho, Hyung-Lae Kim. KIRnome: KIR genotyping for whole genome/exome sequencing data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2582. doi:10.1158/1538-7445.AM2017-2582
Abstract 2587: VCF2CNA: a tool for efficiently detecting copy number alteration using VCF genotype data
Authors: Putnam Daniel K. , Ma Xiaotu , Rice Stephen V. , Liu Yu , Zhang Jinghui , Chen Xiang 
Published: July 2017

Abstract
Whole genome sequencing (WGS) is increasingly used in both research and clinical settings. The Variant Call Format (VCF) specification is a widely adopted file format for genetic variation data exchange partially due to its smaller file size compared to raw WGS BAMs. Each variant in a typical VCF file contains its chromosome position, reference/alternative alleles and corresponding allele counts. This makes it possible to identify copy number alterations (CNAs). To this end, we developed VCF2CNA (http://vcf2cna.stjude.org), a web interface tool for CNA analysis from VCF files.
A user of VCF2CNA, uploads a VCF file via the provided web interface. The entire analysis runs remotely with an average run time of 23 minutes. Results are emailed to the user as either a downloadable link or file attachments. VCF2CNA also accepts input in the Mutation Annotation Format (MAF) and the variant file format produced by the Bambino program.
We analyzed 22 TCGA glioblastoma tumor/normal pairs by Illumina technology to evaluate VCF2CNA’s performance. It achieved high consistency (average F1-score: 0.952 ± 0.082) with CONSERTING, a tool that incorporated read-depth and SV data from raw BAMs for CNA detection. A segment-by-segment comparison between results from CONSERTING and VCF2CNA indicated that the latter was less sensitive to focal CNAs. This is expected because there is less information in the VCF input than in raw BAMs. Further analysis using samples with a “fractured genome” pattern revealed that VCF2CNA was more robust to library artifacts and produced relatively clean CNA profiles (on average 76.2-fold reduction compared to the number of segments reported by CONSERTING).
Finally, we analyzed 137 pediatric neuroblastoma samples from the TARGET project, sequenced by Complete Genomics, Inc. (CGI) technology. MYCN amplification has been clinically validated in 33 samples. VCF2CNA identified high amplitude MYCN gains in 32 samples and the remaining sample carried a low-level broad gain covering MYCN. For comparison, CGI’s HMM-based method reported MYCN gains in only 15 out of the 33 samples. VCF2CNA further identified two additional MYCN amplifications among the remaining samples. Collectively, our analysis suggests that VCF2CNA is a platform-independent, efficient, robust and accurate tool for general WGS-based CNA analysis. It further complements CONSERTING, which produces more accurate result in focal CNAs at the cost of significantly higher computational burden.
Citation Format: Daniel K. Putnam, Xiaotu Ma, Stephen V. Rice, Yu Liu, Jinghui Zhang, Xiang Chen. VCF2CNA: a tool for efficiently detecting copy number alteration using VCF genotype data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2587. doi:10.1158/1538-7445.AM2017-2587