bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1152: Clinical relevance of elevated microsatellite alterations at selected tetranucleotide repeats in colorectal adenocarcinomas
Authors: Katkoori Venkat R. , Shanmugam Chandrakumar , Sthanam Meenakshi , Callens Tom , Messiaen Ludwine M. , Bumpers Harvey L. , Manne Upender , Birdsong George G. , Samuel Temesgen 
Published: August 2012

Abstract
Purpose: Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) are frequently observed in various cancers, including colorectal cancers (CRCs). The incidence of EMAST and its clinical relevance with respect to patient race, however, have not been studied. Therefore, we assessed the frequency and clinical relevance of EMAST and microsatellite instability (MSI) in African-American (AA) and non-Hispanic Caucasian (NHCA) CRC patients. Methods: We analyzed 166 CRCs, collected from the University of Alabama at Birmingham and Grady Memorial hospitals. The EMAST and MSI status of the CRCs was evaluated using seven tetranucleotide microsatellite markers (MYCL1, D8S321, D9S242, D9S747, D20S82, D20S85, L17686) and five National Cancer Institute-recommended MSI markers (BAT25, BAT26, D2S123, D5S346, D17S250). This was accomplished by polymerase chain reactions using marker-specific primers. The status for EMAST and MSI was considered positive if at least two EMAST- or MSI-specific loci were found to be unstable. The EMAST and MSI phenotypes were correlated with clinicopathologic features and patient survival. Results: The overall incidence of EMAST was 46% (77 of 166 cases); AA patients had a higher incidence (62 of 124, 50%) relative to NHCA patients (15 of 42, 36%). Analyses based on tumor location and patient race showed that, for AAs, EMAST was more common in colonic tumors (60 of 114, 53%) than in tumors of NHCAs (10 of 32, 31%). In contrast, only 20% of rectal tumors in AAs (2 of 10) demonstrated EMAST, as compared to NHCA (5 of 10, 50%) patients. Combined analysis (both racial groups) showed that 16% (26 of 166) of cases exhibited both EMAST and the phenotype, MSI-high. Furthermore, for AA patients, but not NHCA patients, EMAST was associated with mucinous CRCs (χ2p = 0.02 and χ2p = 0.56, respectively). NHCA patients who had EMAST had lower median survival (24 months) relative to those without EMAST (55 months). In contrast, the AA patients did not demonstrate an appreciable difference in median survival. Conclusions: These findings suggest that, for AA patients, CRCs with EMAST are associated with the MSI-high phenotype and mucinous tumors. For NHCA patients, EMAST is associated with short survival. This work was supported by grants from the NCI/NIH (2U54-CA118948, R01-CA98932, and R03-CA139629).
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 1152. doi:1538-7445.AM2012-1152
Abstract 1161: The role of MED12 exon 2 mutations in histopathological variants of uterine leiomyoma
Authors: Mäkinen Netta , Arola Johanna , Vahteristo Pia , Lehtonen Heli J. , Bützow Ralf , Aaltonen Lauri A. 
Published: August 2012

Abstract
Uterine leiomyomas, or fibroids, are benign tumors affecting millions of women worldwide. They arise from the overgrowth of smooth muscle and connective tissue. Regardless of their benign nature, leiomyomas can cause considerable morbidity, such as abdominal pain, excessive bleeding, pregnancy complications and even infertility. They also pose a considerable socio-economic impact and are the most common cause for hysterectomy. Based on histopathology, uterine leiomyomas can be divided into various subtypes. Cellular, atypical and mitotically active fibroids are examples of relatively rare variants of common leiomyomas. Rarely, fibroids may undergo malignant transformation and develop into a leiomyosarcoma. We recently showed that MED12 (mediator complex subunit 12) exon 2 is mutated in approximately 70% of uterine leiomyomas (ref 1). The mutation hot spot affects an evolutionary conserved region of the MED12 protein. MED12 is part of a 26-subunit protein complex, which is thought to regulate global as well as gene-specific transcription by bridging DNA regulatory elements to the RNA polymerase II initiation complex. To study the frequency of MED12 exon 2 mutations in different histopathological variants of uterine leiomyoma, we analyzed 105 fibroids and 61 leiomyosarcomas by direct sequencing. Both rare histopathological variants and leiomyosarcomas harbored significantly less MED12 exon 2 mutations than common leiomyomas. The driver mutations underlying these lesions remain to be characterized. (1) N Mäkinen et al. (2011) MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science 14, 252-255.
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 1161. doi:1538-7445.AM2012-1161
Abstract 1162: SIX1 protein expression selectively identifies blastemal elements in Wilms tumor
Authors: Sehic Daniel , Karlsson Jenny , Sandstedt Bengt , Gisselsson David 
Published: August 2012

Abstract
Background. Wilms tumour (WT) is the most common renal neoplasm in children. Histologically, most WTs consist of three tissue elements: blastema, epithelium, and stroma. Some cases also show diffuse or focal anaplastic features. Previous studies have shown that a predominance of blastemal cells in post-chemotherapy WT specimens is associated with a poor clinical course. However, there is currently no molecular marker for blastemal cells, and risk stratification for post-nephrectomy treatment is therefore often based on clinico-histological parameters alone. Procedure. In the present study, three public gene expression microarray datasets, including 82 WTs and 8 normal foetal kidneys, were used to establish a consensus gene expression profile of WT. By bioinformatic analyses, 17 genes overexpressed in WT compared to foetal kidney were then selected for evaluation of their protein expression in WT cell lines and in the different histological components in paraffin-embedded WT tissue sections by immunofluorescence. Results. Most of the evaluated proteins were expressed in all three common histological components. A prominent exception was SIX1, being expressed predominantly in blastemal elements in 24/25 paediatric cases containing blastema. Anaplastic elements exhibited highly variable SIX1-positivity. The SIX2 protein, known to be co-expressed with SIX1 during nephrogenesis, only exhibited blastemal-predominant expression in half of the SIX2 evaluated cases. Conclusions. Genes highly expressed in WT compared to foetal kidney are generally overexpressed in all of the three common WT tissue elements. An exception is the predominant expression of SIX1 in blastemal cells, hereby identifying this protein as a candidate marker for blastema.
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 1162. doi:1538-7445.AM2012-1162
Abstract 1164: MTUS1 as a potential progression marker at chromosome 8p in bladder cancer
Authors: Rogler Anja Paola , Hoja Sabine , Ekici Arif , Wullich Bernd , Goebell Peter , Hartmann Arndt , Stöhr Robert 
Published: August 2012

Abstract
Aims and background: The search for sensitive and specific progression and recurrence markers in bladder cancer is a major focus of many urological research groups. The aim of this study was to identify biomarkers on chromosome 8p in papillary urothelial carcinoma that give evidence for progression from non-invasive pTa to invasive pT1 stage. Candidate genes should be analyzed functionally in cell lines and validated immunohistochemically using tissue micro arrays. Material and methods: To find new progression markers 19 papillary urothelial carcinomas (9 pTa and 10 pT1) were investigated with array comparative genomic hybridization (aCGH) on Affymetrix Genome-Wide Human SNP Array 6.0. Therefore, tumor slides were manually microdissected, genomic DNA was isolated and DNA was hybridized on Affymetrix Chip together with reference DNA from 167 tumor-free patients. Computational analysis was performed with free Software “Genotyping-Console” from Affymetrix. MTUS1 gene and protein expression were investigated in bladder cancer cell lines and tumor tissue using qRT-PCR, Western blot and immunohistochemistry. Results: aCGH revealed more chromosomal aberrations overall as well as more deletions on chromosome 8p in pT1 tumors (50%) compared to pTa tumors (11%). Several putative progression-associated genes could be identified on 8p, for example SLC7A2, PDGFL, MTUS1, FGL1 and PCM1. MTUS1 (microtubule associated tumor suppressor 1) was chosen for further analysis, as in other tumor types this gene is known to be associated with frequent loss of heterozygosity at 8p22. However, to our knowledge, not much is known about its role in bladder cancer. Western blot analysis revealed expression of different isoforms in cell lines (140, 80 and 60 kDa) and tumor tissue (mainly 80kDa). Immunohistochemical staining of 128 papillary and 236 advanced tumors showed conflicting results compared to the aCGH findings. Conclusion: Whereas loss of genetic material at 8p22 harboring the MTUS1 gene is significantly associated with a pT1 stage in papillary urothelial carcinoma, pT1 tumors showed a significantly higher MTUS1 expression than pTa tumors as was shown by immunohistochemistry. At least in the pT1 group, expression loss contributed to worse overall survival, suggesting MTUS1 as a prognostic marker. Functional effects of MTUS1 overexpression will be analyzed in the future in RT112 cell line.
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 1164. doi:1538-7445.AM2012-1164
Abstract 1171: Identification of p53 target genes by ChIP-Seq and transcriptome analysis combined with genome-wide p53-binding motif analysis in silico
Authors: Idogawa Masashi , Sasaki Yasushi , Shinomura Yasuhisa , Imai Kohzoh , Tokino Takashi 
Published: August 2012

Abstract
p53 is one of the most important tumor suppressor genes. In approximately half of all human cancers, p53 is inactivated as a direct result of mutations in the p53 gene. Furthermore, mutation or deletion of p53 is related to poor prognosis and resistance to chemotherapy and radiation. The activation of p53 is induced by a variety of cell stresses, such as DNA damage, oncogene activation, spindle damage and hypoxia. Activated p53 transactivates a number of genes, many of which are involved in DNA repair, cell cycle arrest and apoptosis. In this study, we tried to identify novel p53 target genes by the combination of chromatin-immunoprecipitation, transcriptome analysis and a search of p53 binding motif in silico. We infected lung cancer cell, H1299 (p53 null) with adenovirus vectors expressing FLAG-tagged p53, p63g and p73b, and then performed chromatin-immunoprecipitation (ChIP) with FLAG antibody. The immunoprecipitated DNA was subjected to next-generation sequencing (ChIP-Seq). The short sequences generated by ChIP-Seq were aligned to the human genome sequence and peaks which indicate the binding of p53 family protein were detected by several algorithms. We also searched p53 binding motif, RRRCWWGYYY appeared inside genes and 10k base upstream from its transcription start site, and selected ChIP-Seq peaks of which genomic positions include p53 binding motif. Furthermore we analyzed mRNA expression of H1299 cells by cDNA microarray including several long intergenic non-coding RNAs (lincRNAs) and next-generation sequencing (RNA-Seq). We combined three categories of data, mRNA expression, ChIP-Seq peaks and p53 binding motif in silico. As a result, we found several genes which are upregulated by p53 family proteins and have ChIP-Seq peaks with p53 binding motif in promoter regions or gene bodies. These genes included not only well-known p53 target genes such as p21 and MDM2 but also novel candidate genes. In addition, ChIP-PCR and reporter assay confirmed the binding and responsiveness to p53. Thus, our approach identified several novel target genes induce by p53. We are now analyzing the role of these genes in p53 response pathway.
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 1171. doi:1538-7445.AM2012-1171
Abstract 1178: Allele specific p53 mutant synthetic lethality
Authors: Yu Xin , Vazquez Alexei , Levine Arnold J. , Carpizo Darren R. 
Published: August 2012

Abstract
Rescuing the function of mutant p53 is an attractive cancer therapeutic strategy. The NCI60 database has reported the growth inhibition of over 47,000 compounds in a panel of 60 human tumor cell lines with the p53 mutational status known. We hypothesized that we could use the NCI60 dataset as an “in silico” screen to identify compounds with activity in cell lines containing mutant p53. We identified three compounds from the thiosemicarbazone family and validated this methodology for two of the three. Both compounds demonstrate a marked sensitivity in cell lines carrying a p53-175 allele while at the same time are relatively nontoxic to cells wildtype for p53. Mechanistic studies reveal that one of the compounds restores a wildtype structure and function to the p53-175 mutant. These findings extend to p53R172H knock-in mutant mice as well as to the inhibition of xenograft tumor growth in a 175-allele specific, mutant p53 dependent manner. Together these data both validate a bioinformatics approach to the identification of compounds with activity in cell lines expressing mutant p53, and identify two compounds that demonstrate allele specific mutant p53 synthetic lethality.
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 1178. doi:1538-7445.AM2012-1178
Abstract 1185: Plakoglobin (β-catenin) interacts with the transcription factor p53 and regulates the expression of genes involved in tumorigenesis and metastasis
Authors: Aktary Zackie , Pasdar Manijeh 
Published: August 2012

Abstract
Plakoglobin (β-catenin) and β-catenin are highly homologous proteins that function in cell-cell adhesion and signaling. Both proteins exist in a cadherin-associated form, which mediates adhesion, and in a distinct cytosolic/nuclear form, which plays a signaling role. Despite their interactions with common cellular partners, β-catenin has well documented oncogenic potential while plakoglobin expression is generally associated with tumor/metastasis suppression. The underlying mechanisms for this activity of plakoglobin are unclear. We previously showed that plakoglobin expression in oral squamous carcinoma cells (SCC9-PG) resulted in a mesenchymal-epidermoid transition, which was concurrent with increased N-cadherin and decreased β-catenin levels. Comparison of the RNA and protein profiles of SCC9 cells and SCC9-PG transfectants identified a number of differentially expressed proteins and transcripts, which suggested that plakoglobin regulates gene expression. Closer analysis of the mRNA profiles of SCC9 and SCC9-PG cells identified several p53 target genes that were differentially expressed upon plakoglobin expression, suggesting that plakoglobin may regulate gene expression in conjunction with p53. Here, we describe the ability of plakoglobin to regulate three potential p53 target genes: the tumor and metastasis suppressors 14-3-3α and Nm23 and the tumor promoter SATB1. We show, by RT-PCR and Western blot, that plakoglobin expression results in increased 14-3-3σ and Nm23 and decreased SATB1 mRNA and protein levels. Co-immunoprecipitation experiments show that plakoglobin and p53 interact, and that these interactions occur in both the cytoplasm and the nucleus. Chromatin immunoprecipitation and Electrophoretic mobility shift assays (EMSA) indicate that plakoglobin and p53 associate with the promoters of these target genes. Finally, luciferase reporter assays confirm that plakoglobin regulates the expression of these p53 target genes. Taken together, the results of these studies provide strong evidence that plakoglobin plays an active role in regulating gene expression, a function that has not often been associated with plakoglobin.
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 1185. doi:1538-7445.AM2012-1185
Abstract 132: MicroRNA expression profiling in tumorigenic prostate cancer cells and tumor suppressive functions of let-7
Authors: Liu Can , Kelnar Kevin , Vlassov Alexander , Brown David , Tang Dean 
Published: August 2012

Abstract
Most human tumors contain a small population of cells with stem cell properties, called cancer stem cells (CSCs), which are believed to be responsible for tumor initiation, metastasis, resistance to clinical therapy and relapse. It's crucial to understand the regulatory mechanisms unique to CSCs, so that we may design CSC-specific therapeutics. Recent discoveries of microRNA (miRNA) have provided a new avenue in understanding the regulatory mechanisms of cancer. In our previous studies, we have showed miR-34a under-expression in prostate CSC populations, and its critical role in negatively regulating prostate tumor development and metastasis. However, detailed profiling process was not presented due to space limit. Here, we presented the detailed miRNA expression profiling process and results, together with functional studies of let-7. By quantitative RT-PCR, we dicovered miRNA expressions profiles specific to the prostate cancer (PCa) stem/progenitor populations, i.e., CD44, CD133, α2β1 and side population from thee prostate xenograft models (LAPC9, LAPC4, and Du145). Functional annotation of let-7, one of the commonly under-expressed miRNAs in PCa stem/progenitor populations, showed that over-expression of let-7 inhibited proliferation and clonal expansion of prostate cancer cells in vitro. In addition, over-expression of let-7 by a lentiviral vector suppressed tumor development in mice. To further understand how these miRNAs are differentially expressed in the stem/progenitor population of PCa cells, we took miR-34a as an example, and explored p53 and c-Myc regulation in the CD44+ and CD44- populations, but failed to draw a connection.
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 132. doi:1538-7445.AM2012-132
Abstract 1323: Liver-specific knockout mice and liver-derived cell lines provide insights into potential roles for the GP73/GOLM1 HCC serum biomarker - association with sustained cell proliferation
Authors: Arora Gunisha , Flores Rosalba , Wright Lorinda , Fimmel Claus J. , Bode Barrie P. 
Published: August 2012

Abstract
Golgi Protein-73kDa (GP73/GOLM1) is a resident cis Golgi Type II membrane protein that is nearly undetectable in normal liver, but whose expression is upregulated in hepatocellular carcinoma (HCC) and whose circulating levels increase in the plasma of patients with chronic liver disease and HCC. As such, it is the subject of ongoing clinical trials investigating its use as a serum biomarker for HCC. GP73/GOLM1 is cleaved by a proprotein convertase and secreted by proliferating cells, an activity possibly elevated in cancer, yet its biological role in the liver and in the pathogenesis of HCC remains unclear. In order to investigate possible biological roles for GP73/GOLM1, liver-specific knockout mice (C57BL/6) were generated using the Cre-loxP system, characterized by a “floxed” GOLM1 gene and Cre recombinase driven by the albumin promoter. GP73/GOLM1 Cre+/−genotypes were confirmed by PCR analysis. GP73/GOLM1Fl/Fl/Cre(+) animals showed no obvious biological phenotype compared to their Cre(-) littermates, and exhibited normal growth, behavior, and successful mating, suggesting that hepatic GP73/GOLM1 is not vital for normal physiological function, as might be hypothesized from its normally low expression in the liver. Previous studies indicated that GP73/GOLM1 expression was not upregulated in post-hepatectomy liver regeneration, suggesting that its activated expression in the liver is linked to inflammatory or carcinogenic processes rather than transiently increased mitosis. Examination of GP73/GOLM1 expression in 14 human HCC cell lines revealed similar expression levels in epithelial and mesenchymal cell lines, and in an SV40-transformed nontumorigenic human liver epithelial cell line. Rodent in vitro models of hepatocellular transformation revealed equal GP73/GOLM1 expression levels in nontumorigenic parent cell lines and their transformed tumorigenic derivatives. Collectively, the data from the in vivo and in vitro models thus far do not support a direct association of GP73/GOLM1 expression with liver mitogenesis or differentiation, but rather suggest that its expression may be linked to a sustained commitment to cell proliferation - such as occurs in cell lines, liver disease and cancerous transformation, promoted by an inflammatory microenvironment. Possible mechanistic roles for GP73/GOLM1 in HCC development and progression are currently being tested in carcinogenesis models with liver-specific knockout mice. A website on GP73/GOLM1 has also been established as a resource for the research community interested in the study of this protein.
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 1323. doi:1538-7445.AM2012-1323