bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3834: JKA97, a novel anti-cancer candidate, induces G1 arrest via up-regulation of p21 in a p53-independent manner
Authors: Wang Wei , Yang Xinyi , Zhang Xu , Wang Ming-hai , Sharma Horrick , Buolamwini John K. , Zhang Ruiwen 
Published: August 2012

Abstract
Breast cancer is one of the most commonly diagnosed cancers and the leading causes of cancer death in women worldwide. Natural product-oriented synthetic derivatives have played an important role in cancer drug discovery. JKA97, a benzylidene analog of harmine, is a novel anti-cancer candidate. The initial studies have shown its inhibitory effects on tumor growth in experimental models. However, the underlying molecular mechanisms are not fully elucidated. In this study, we determined the anti-cancer effects of JKA97 on human breast cancer in vitro and in vivo. Our data showed that, in a dose-dependent manner, JKA97 efficiently inhibited the growth and proliferation of human breast cancer cells with different p53 status, including MCF7 (p53 wild-type), MCF7 (p53 knockdown) and MDA-MB-468 (p53 mutant) cells. We also found that JKA97 induced apoptosis in human breast cancer cells independent of p53 and that JKA97 treatment resulted in G1 phase arrest in all the three breast cancer cell lines. In vivo, JKA97 significantly suppressed the growth of both breast cancer MCF7 and MDA-MB-468 xenograft tumors. Mechanistically, JKA97 modulated the levels of various cell-cycle regulators involved in G1 to S phase progression, such as p21, p27, cyclinE, and cyclinD1. Our results indicated that p21 and p27were up-regulated while cyclinE and cyclinD1 were down-regulated by JKA97 treatment. Using quantitative PCR and luciferase reporter assays, we demonstrated that the major mechanism for G1 phase arrest by JKA97 was induction of p21 at the transcriptional level, independent of p53. We further confirmed the role of p21 in JKA97-induced G1 phase arrest by using HCT116 cells with or without p21 expression. Taken together, these findings suggest that JKA97 inhibits human breast cancer by inducing cell cycle arrest through up-regulation of p21, regardless of p53 status. Considering that more than 50% human cancers have no or mutant p53 expression, our results provide a basis for further development of this compound as potential drug for breast cancer therapy. (This work was supported in part by NIH/NCI grants R01 CA112029 and R01 CA121211, R15 CA100102 and a grant (BCTR070731) from Susan G Komen for the Cure.)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3834. doi:1538-7445.AM2012-3834
Abstract 3975: Detecting patient mutomes by integrating DNA and RNA sequencing
Authors: Wilkerson Matthew D. , Sun Wei , Wang Kai , Cabanski Christopher R. , Hoadley Katherine A. , Liu Jinze , Prins Jan , Hayes D Neil 
Published: August 2012

Abstract
Personalized cancer medicine, the matching of therapies to a given patient's somatic alterations, depends on highly accurate and complete identification of patients’ somatic alterations, or their mutome. Advances in sequencing technologies (exome sequencing, RNAseq, and whole genome sequencing) have provided a means to examine large portions of the genetic content of patients’ cancers. Computational tools have arisen that make somatic mutation predictions utilizing particular sequencing assays; however, each sequencing assay has limitations and existing mutation detection tools exhibit less than ideal agreement when analyzing the same data. The task of identifying all somatic mutations in one patient's cancer remains a challenge to personalized cancer medicine. Typically, somatic mutation detection is performed utilizing DNA sequencing. Because RNA sequencing is often a component of genome characterization projects along with DNA sequencing, we sought to evaluate the possible added value of RNA sequencing in somatic mutation detection. We have developed an original computational method, UNCeqR, that makes patient-specific somatic mutation predictions utilizing RNA sequencing combined with DNA sequencing. DNA mutations and RNA mutations are statistically modeled separately and results are combined in a meta-analytic fashion, resulting in up to three predictions for a locus: DNA-only, RNA-only, and DNA+RNA. In addition to de novo genomewide mutation predictions, UNCeqR can query specific a priori mutations. UNCeqR was applied to The Cancer Genome Atlas (TCGA) lung squamous cell carcinoma sequencing data, consisting of Ilumina RNAseq and Illumina exome sequencing. Of annotated exons, 20% had very low to zero coverage in RNA and 5% had very low to zero coverage in DNA, indicating that both sequencing assays add new genomic territory for mutation detection. Limiting to regions with both DNA and RNA coverage, 56% of mutations detected from DNA were also predicted by RNA, providing an independent validation of these mutations. To evaluate if mutation detection using DNA+RNA is superior to detection using DNA-only, cancer specimen DNA and RNA reads were randomly split into subsamples. UNCeqR was executed on each of the subsamples and mutation agreement was compared among pairs of subsamples within regions of DNA and RNA coverage. Compared with the DNA-only method, DNA+RNA mutation detection exhibited a 42% relative increase in percent agreement across subsamples and a 230% relative increase in the number of mutations detected. Therefore, RNA sequencing adds positive value to somatic mutation detection via UNCeqR.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3975. doi:1538-7445.AM2012-3975
Abstract 3977: Meta-analysis of posttranslational modifications in cancer
Authors: Hornbeck Peter V. 
Published: August 2012

Abstract
PhosphoSitePlus (http://www.phosposite.org) is a comprehensive and easy-to-use resource that includes aggregated information about experimentally observed post-translational modifications (PTMs) observed in over thirty distinct types of cancer. Most of the cancer data is derived from over 900 mass spectrometric datasets of human disease tissues or cell lines, either reported in the literature or from studies performed at Cell Signaling Technology. The four most highly represented diseases are non-small cell lung carcinoma (269 datasets and over 5500 unique sites), breast cancers (99 datasets with over 2630 sites), acute myelogenous leukemia (70 datasets with over 1860 sites), and chronic myelogenous leukemia (115 datasets with over 1700 sites). Users can extract datasets associated with specific diseases, and analyze the data a number of newly-developed analytical tools. These include motif-analysis, permitting users to determine if specific kinases appear to be active in different diseases, and pathway analysis using novel Cytoscape plugins. Datasets and Cytoscape pathways corresponding to specific diseases and other data subsets can be downloaded from the site, enabling users to apply their own bioinformatics analyses to the information available at PhosphoSitePlus.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3977. doi:1538-7445.AM2012-3977
Abstract 3982: Cancer genome sequencing analysis, storage, discovery and delivery
Authors: Sanborn John Z. , Vaske Charles J. , Benz Stephen C. 
Published: August 2012

Abstract
Genome instability and structural rearrangement is a distinctive hallmark of the cancer genome. With next-gen sequencing technologies, our ability to measure structural rearrangements that occur throughout tumorigenesis and progression has improved significantly, while creating an urgent need for rearrangement discovery, analysis, and visualization methods to aid in our understanding of these events. We have developed a sequencing analysis pipeline that streamlines the discovery of an individual tumor's mutations, small indels, copy number alterations, allele-specific amplifications and deletions, and genomic rearrangements. Rearrangements are refined to base-pair precision using unmapped, putative split reads found in the vicinity of the breakpoint. Results are presented in an interactive, web-based genome browser that provides analysis and visualization of both high-level, processed results as well as the raw data from which they were derived. From the web-based interface, results from multiple samples can be aggregated into user-defined sample cohorts to help identify features that are shared among a significant number of the samples. Using this sequencing analysis pipeline, we discovered high-confident, small- and large-scale somatic events in 17 whole genome glioblastoma multiforme (GBM) tumor samples from The Cancer Genome Atlas (TCGA) project, using their matched normal sequences to filter out germline variants. Among many interesting structural aberrations identified in these samples, we find four samples exhibiting EGFR amplifications and the presence of the EGFRvIII mutant, characterized by the in-frame deletion of exons 2-7 to produce a constitutively active form of the receptor. Comparing the read support of the EGFRvIII-associated breakpoints to the number of normally-mapped reads in the neighborhood suggest that, in all cases, the EGFRvIII mutant emerges after the amplification of wild-type EGFR, existing as a small fraction of total number of EGFR copies. In other samples, evidence of high copy number amplicons containing both MDM2 and EGFR are discovered at detectable levels in the blood sequencing data, raising the possibility that patient-specific PCR-based assays could be developed to quantitate the presence of somatic rearrangements as a proxy to monitor the progression of brain tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3982. doi:1538-7445.AM2012-3982
Abstract 3983: Evaluation of data compression strategies for genetic variation calling using next generation sequencing data in normal and tumor samples
Authors: Xiao Chunlin , Yaschenko Eugene , Kimelman Mikhail , Rodarmer Kurt , Sherry Stephen 
Published: August 2012

Abstract
The per-base cost of whole genome sequencing has dropped dramatically due to recent advancement of next generation sequencing (NGS) technologies, and a number of large-scale re-sequencing projects, e.g. 1000 Genomes, ICGC, TCGA, GO-ESP, and CGCI etc., have been initiated to extend our knowledge of single nucleotide polymorphisms (SNPs), short insertions/deletions (INDELs) and structural variations (SVs), and relate these variants to human diseases. To date, various compression technologies, including NCBI's cSRA and EBI's CRAM etc., have been developed to significantly reduce the storage footprints and costs. However, whether or not such compression treatments have any impact on genetic variant callings has not been systematically assessed and validated with large scale NGS datasets as different calling algorithms for different variant classes (SNPs, INDELs, or SVs) may have different underlying data requirements. We have developed an integrated analysis framework (VarPipe) to profile genetic mutations using NGS data generated from various sequencing platforms in a uniform manner. This pipeline is also applied to the official data from 1000Genomes (normal samples) and Cancer Genome Characterization Initiative (tumor samples) projects to evaluate the compressions effects on variation callers. With defined quality metrics, the variant callsets from compression-treated and untreated data are carefully evaluated as well as compared to the official variation releases of the corresponding projects so that optimal compression strategy can be developed and recommended for variation detection using NGS data.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3983. doi:1538-7445.AM2012-3983
Abstract 3988: Aberrant NFKBIA expression in lung adenocarcinomas arising from never smokers
Authors: Furukawa Masashi , Soh Junichi , Toyooka Shinichi , Shien Kazuhiko , Maki Yuho , Muraoka Takayuki , Tanaka Norimitsu , Ueno Tsuyoshi , Asano Hiroaki , Tsukuda Kazunori , Yamane Masaomi , Oto Takahiro , Miyoshi Shinichiro 
Published: August 2012

Abstract
[Background] Lung cancer in never-smoker (NS) is known as a seventh cause of cancer-related death. Activating mutation of epidermal growth factor receptor (EGFR) gene is frequently observed in non-small-cell lung cancers (NSCLCs) with never smoking history and it is significantly associated with the sensitivity of EGFR tyrosine kinase inhibitor (EGFR-TKI). Recently, NFKBIA gene, a tumor suppressor gene, has been reported to be silenced by deletion in glioblastomas, and in NSCLCs, its expression level is associated with clinical outcome of EGFR-TKI therapy. In this study, we examined NFKBIA expression and the genetic alterations of EGFR, K-ras, EML4-ALK to investigate the inter-relationship between these genetic alterations and clinicopathological factors among lung adenocarcinomas in NS. [Material and Method] We obtained ninety seven lung adenocarcinomas samples in NS which were resected at our institution. Four NSCLC cell lines (NCI-H1299, NCI-H1650, HCC827, NCI-H1819) were also investigated. We examined NFKBIA expression using immunohistochemistory (IHC) in tumor samples and real time reverse transcriptional PCR (RT-PCR) in cell lines, respectively. Mutational statuses of EGFR and K-ras genes were determined using mutant-enriched PCR assay and direct sequencing, respectively. EML4-ALK fusion was screened by ALK IHC and confirmed using RT-PCR assay. The methylation status of NFKBIA gene is investigated by methylation specific PCR assay and bisulfite sequencing. [Result] NFKBIA expression was silenced in 36 out of 97 samples (37.1%). EGFR mutation, K-ras mutation, and EML4-ALK fusion were detected in 61.8%, 2.1%, and 1.0% of 97 samples, respectively. Of note, the silencing of NFKBIA expression was significantly frequent in EGFR wild-type patients than in EGFR mutant patients (p=0.0024), while there was no correlation between NFKBIA expression level and K-ras mutation or EML4-ALK fusion. Although NFKBIA expression was silenced in NCI-H1299 and NCI-H1650, NFKBIA expression was not restored after 5-Aza treatment in these cell lines. In addition, NFKBIA methylation was found in these two cell lines. [Conclusion] Our findings suggest that the degradation of NFKBIA expression is a frequent event in lung adenocarcinomas of NS and may mediate an important non-tobacco carcinogenic pathway especially among lung adenocarcinoma with wild-type EGFR.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3988. doi:1538-7445.AM2012-3988
Abstract 3994: Loss of STAT2 enhances the establishment of B16 melanoma tumors
Authors: Yue Chanyu , Gamero Ana M. 
Published: August 2012

Abstract
STAT2 is a key component of type I interferon (IFN-I) induced activation of the JAK/STAT signaling pathway. Several studies including ours have shown that STAT2 is a critical signaling mediator in the apoptotic and cell growth inhibitory effects of IFN-I. These findings suggest that STAT2 has tumor suppressive function. To investigate this further, the B16-F1 mouse melanoma cell line was used in a tumor transplantation model to interrogate the role of STAT2 in tumorigenesis. We found that STAT2 null mice injected subcutaneously with B16-F1 melanoma tumor cells showed accelerated tumor growth rate and grew larger tumors compared to those formed in wild type mice. We next compared the antitumor effects of IFN-I in wild type and STAT2 null mice administered intraperitoneally 3 days after tumor injection and given three times weekly until day 21 of the study. IFN-[[Unsupported Character - Symbol Font &#61538;]] therapy of STAT2 null mice was ineffective as tumors continued to grow at the same rate as in saline treated STAT2 null mice. In contrast, wild type mice that received IFN-[[Unsupported Character - Symbol Font &#61538;]] developed smaller tumors compared to saline treated control mice. Evaluation of B16 tumors established in wild type mice by Western blot analysis showed a marked reduction in the levels of STAT2 and STAT1 proteins. Similarly, B16 tumors established in STAT2 null mice also showed low levels of STAT1 protein. To determine whether tumor derived soluble factors were involved in decreasing STAT2 protein; supernatants collected from B16-F1 tumors incubated overnight with serum free medium were used to treat B16-F1 tumor cells grown in vitro. A decrease in STAT2 protein was evident when tumor supernatants derived from tumors established in wild type and STAT2 null mice were used. Taken together our findings reveal that host STAT2 restricts the establishment of melanoma tumors and soluble factors secreted by melanoma tumors reduce STAT2 protein levels thereby diminishing the antitumor effects of IFN.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3994. doi:1538-7445.AM2012-3994
Abstract 40: Targeting MLCK expression in cancer-associated fibroblasts disrupts tumor-stromal interactions in gastric cancer
Authors: Su Liping , Chen Lu , Chen Xuehua , Li Jianfang , Liu Bingya 
Published: August 2012

Abstract
Aim: Accumulating evidence has indicated that microenvironment consisting of stromal affects cancer progression. However, the mechanism by which cancer cells and fibroblasts, the major cell type in stromal, interact with each other during tumor development remains to be elucidated. Our aim is to identify the molecular mechanism involved in tumor-stromal cell interactions in human gastric cancer. Methods: The expression of Myosin Light Chain Kinase (MLCK) in gastric cancer-associated fibroblasts (CAF) was detected by quantitative RT-PCR. The effects of CAF, which was interfered with MLCK, on cell proliferation, apoptosis, migration and invasion in vitro were measured. Results: Primary fibroblast cultures were established from human gastric cancer. MLCK was upregulated in CAF compared with NF (fibroblasts from patient matching non-cancerous tissues). Small interfering RNA knockdown of MLCK in CAF impaired the augmenting effect of CAF on gastric cancer cell proliferation, and induced the apoptosis of gastric cancer cells (9.1+0.8 vs 22.3+1.4, p&lt;0.05). Moreover, the ability of stimulating gastric cancer cells migration (77.7+4.3 vs 61+4.2, p&lt;0.05) and invasion (60.9+1.5 vs 48.3+1.4, p&lt;0.05) in vitro by CAF was also inhibited when MLCK was knocked down. Furthermore, gastric cancer cells can also activate CAF in a MLCK-dependent manner. Conclusions: These findings indicate that MLCK mediates the cross-talk between tumor and stromal in gastric cancer, and suggest that targeting stromal cells for MLCK interference may be a therapeutic target in human gastric cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 40. doi:1538-7445.AM2012-40
Abstract 4000: Restoring LSAMP expression decreases the proliferation rate in osteosarcomas
Authors: Barøy Tale , Kresse Stine H. , Hopmeier Dahlia , Stabell Marianne , Skårn Magne , Myklebost Ola , Meza-Zepeda Leonardo A. 
Published: August 2012

Abstract
Osteosarcomas are the most common primary malignant tumors of bone. The tumors are highly aggressive with poor prognosis, and display complex genomic aberrations. Previously, our group has identified a frequently deleted region in 3q13.31 in osteosarcoma clinical samples and cell lines [1]. The deleted region contains non-coding RNA genes, pseudogenes and the gene encoding the limbic-system associated membrane protein (LSAMP). The latter has previously been reported to be a candidate tumor suppressor gene in other cancer types, and more recently in osteosarcomas. Interestingly, our data show that low expression of LSAMP is statistically correlated with shorter patient survival. To examine the possible function of LSAMP in osteosarcomas, the expression was restored in an osteosarcoma cell line with a homozygous deletion of the gene. Characterization of the cell line with restored LSAMP expression showed decreased proliferation rate, which is consistent with its suggested role as a tumor suppressor gene. The migration rate and colony forming capability of the cells were unaffected. Interestingly, gene expression profiling of the restored lines, showed up-regulation of three genes, all proposed to have a role in cancer biology. The results indicate that the LSAMP protein might up-regulate the transcription of these three genes, and that LSAMP alone, or in conjunction with other genes, suppresses tumors by reducing their proliferation rate. Together, our data strengthens the hypothesis of LSAMP being a tumor suppressor gene in osteosarcomas. 1. Kresse, S.H., et al., LSAMP, a Novel Candidate Tumor Suppressor Gene in Human Osteosarcomas, Identified by Array Comparative Genomic Hybridization. Genes Chromosomes & Cancer, 2009. 48(8): p. 679-693.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4000. doi:1538-7445.AM2012-4000