bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1955: Bone-marrow-derived cells incorporate into the prostate during regrowth
Authors: Placencio Veronica R. , Sherrill Taylor P. , Yu Xiuping , Bhowmick Neil A. 
Published: February 2011

Abstract
It is necessary to understand mechanisms of castrate resistant prostate cancer development and progression. As prostate cancer transitions from androgen dependent to castrate resistant, subsequent recurrence involves increased growth of the cancer epithelial cells. Understanding prostate regrowth in a normal prostate will allow us to better understand growth in castrate resistant prostate cancer. We hypothesized that altered chemokine signaling which accompanies the loss and subsequent return of androgen signaling results in the recruitment of immune cells to the prostate microenvironment from the bone marrow. A chimeric mouse model with GFP-labeled bone marrow was used to allow us to identify bone marrow cells recruited to the prostate. We studied how bone marrow derived cells (BMDCs) contributed to an androgen refractory response, specifically prostate regrowth. In a similar mouse model we used GFP-labeled mesenchymal stem cells (MSCs) to study this specific subset of BMDCs in response to prostate regrowth. Host mice were castrated or left intact as a control. Testosterone was given to the chimeric mice. The intact and castrated control mice had a low number of BMDCs recruited to the prostate. However, three and seven days following exogenous testosterone administration resulted in a dramatic increase in BMDC recruitment during prostate regrowth. GFP labeled MSC cells were also recruited to the prostate at three days following treatment with exogenous testosterone. Interestingly, even after four weeks the fully regrown prostates retained BMDCs that appeared to be incorporated in the epithelial compartment. Double immunofluorescence staining showed that a subset of BMDCs gained the expression of androgen receptor; p63, a basal epithelial marker; and cytokeratin 8, a luminal epithelial marker, in the prostate. Rosa26 expressing MSCs injected into GFP mice showed prostate co-localization of ß-galactosidase and GFP, suggesting that MSCs fused with resident prostate epithelial cells during regrowth. The recruitment and eventual incorporation of BMDCs in the prostate suggests a mechanism for exogenous cells in castration-resistant prostate cancer growth. This result has implications for castrate-resistant prostate cancer growth, as it too may be a result of MSC recruitment, incorporation, and fusion. NIH grants F31 GM079879 (VRP), CA108646 and CA126505 (NAB).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1955.
Abstract 1960: Transgenic overexpression of Cdx1b in zebrafish induces metaplastic changes of gene expression in the squamous epithelium
Authors: Hu Bo , Liu Xiuping , Cole Gregory , Zhang Chengjin , Lee Ju-Ahng , Chen Xiaoxin (Luke) 
Published: February 2011

Abstract
Background and aims: Cdx2 has been suggested to play an important role in Barrett's esophagus (BE), or intestinal metaplasia (IM) in the esophagus. However, it is still unclear whether ectopic overexpression of Cdx2 may lead to IM in the esophagus in vivo. The aim of the present study was to investigate whether transgenic overexpression of Cdx1b, the functional equivalent of mammalian Cdx2 in zebrafish, may lead to IM of squamous epithelium in zebrafish.
Methods: We first characterized the histology of the upper gastrointestinal tract of zebrafish. A highly conserved promoter of zebrafish keratin 5 was cloned to drive transgenic expression of GFP. A transgenic zebrafish system was then developed by expressing Cdx1b gene under the control of zebrafish keratin 5 promoter (zK5p). Cdx1b expression in the squamous epithelium of transgenic zebrafish was analyzed by in situ hybridization, immunohistochemical staining and RT-PCR. Gene expression in the squamous epithelium of wild-type and transgenic zebrafish was analyzed by Affymetrix microarray and confirmed by in situ hybridization. Morphology, mucin expression, cell proliferation and apoptosis were analyzed by H&E staining, PAS Alcian blue staining, PCNA immunohistochemical staining and TUNEL assay as well.
Results: We found that zebrafish tongue was covered by a non-keratinized stratified squamous epithelium, which was similar to the oro-esophageal epithelium in humans. In situ hybridization showed that keratin 5, a marker of the basal cell layer of mammalian esophageal epithelium, was expressed in the squamous epithelium of zebrafish tongue. GFP expression in transgenic fish recapitulated endogenous zebrafish keratin 5 gene expression as shown by in situ hybridization. In Cdx1b transgenic zebrafish, Cdx1b was found to be overexpressed in the nuclei of squamous epithelial cells of the transgenic zebrafish. Cdx1b induced metaplastic changes in gene expression in the squamous epithelial cells, that is, up-regulation of intestinal differentiation markers and down-regulation of squamous differentiation markers. However, Cdx1b did not induce histological IM, or modulate cell proliferation and apoptosis in the squamous epithelium of transgenic zebrafish.
Conclusion: Transgenic overexpression of Cdx1b in the squamous epithelial cells induced metaplastic changes in gene expression, but failed to produce metaplastic changes in morphology. Cdx1b/Cdx2 may require cooperation of other genetic factors for induction of IM in squamous epithelium. In the present study, we first characterized the histology of the upper gastrointestinal tract of zebrafish.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1960.
Abstract 1966: In vivo detection of nucleotide lesions preceding mutation fixation
Authors: Mills Wilbur K. , Queimado Lurdes , Ramachandran Ilangovan , Friedberg Errol , Reis Antonio M. C. 
Published: February 2011

Abstract
Background and Purpose: Unrepaired DNA damage likely originates a large fraction of human cancer. However, a direct correlation between DNA damage and specific mutations is lacking. To identify in vivo nucleotide lesions that can act as the precursors of neoplastic mutations, we investigated the origin of specific tumor signature mutations previously reported on codon 122 of the p53 tumor suppressor gene (Trp53) in UVB radiation induced mouse skin tumors. Methods: The dorsal skin of wild-type (WT) and repair defective (Xpc−/− Trp53+/−) mice was shaved and exposed to a single dose of 4.8 kJ/m2 UVB radiation. Skin from unirradiated and irradiated animals was excised surgically at specific time points (0, 24 and 48 h after irradiation) and used for DNA extraction. A novel primer-anchored PCR based damage-detection methodology developed in our laboratory was used to identify and map DNA damage on the transcribed (TS) and non-transcribed strand (NTS) of the Trp53 gene. Results: Twenty-four and 48 h after UVB-radiation, significant levels of unrepaired nucleotide lesions persisted in genomic DNA of Xpc−/− Trp53+/− compared with WT mice. We observed that most of the damage blocked the primer-extension, yielding early stops. Additionally, most of the damage affecting Trp53 codon 122 in Xpc−/− Trp53+/− mice occurred in the NTS and strictly localized to 2 nucleotides. Importantly, a small percentage of the damage observed at these nucleotides allowed DNA polymerase bypass with misincorporation. Significantly, these lesions were detected precisely in the two nucleotides of Trp53 codon 122 that were found mutated in 64% of all tumors arising in this genotype. These results support the model that the tumor mutations at this site arise from error-prone bypass of long-lasting, unrepaired DNA lesions. Conclusions: We demonstrate a significant correlation between the persistence of precisely localized nucleotide lesions and the later establishment of tumor mutations at those specific nucleotides. Using a novel primer-anchored DNA damage methodology, we identified and mapped for the first time in vivo polymerase by-passable nucleotide lesions. Given the mutagenic potential of these lesions, the wide application of this novel technique for the identification of those lesions and the quantification of in vivo DNA damage might have major implications for early detection of cancer precursor lesions and evaluation of prevention strategies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1966.
Abstract 1967: UvrABC excision of interstrand crosslink mitomycin C-DNA lesion induces double-stranded DNA breaks
Authors: Weng Mao Wen , Zheng Yi , Jasti Vijay P. , Champeil Elise , Tomasz Maria , Wang Yin sheng , Basu Ashis K. , Tang Moon Shong 
Published: February 2011

Abstract
Mitomycin C (MC) forms at least nine different covalent DNA adducts including an N2-2’-deoxyguanosine monoadduct (MC-mono-dG) and inter- and intrastrand bis-adducts with 2’-deoxyguanosine (dG) in vivo. Inter-strand cross-linked (ICL) dG-MC-dG-DNA adducts can prevent strand separation, and therefore, the MC antitumor activity is most likely derived from formation of ICL-MC adducts. In Escherichia coli cells, UvrABC, the nucleotide excision repair (NER) enzyme complex can repair ICL psoralen lesions that cause DNA bending. The mechanism and the consequence of NER of ICL dG-MC-dG lesions that do not induce DNA bending remain unclear. In order to compare the NER of MC-mono-dG with an ICL dG-MC-dG adduct, we constructed DNA fragments containing the adducts in the same DNA sequence context. We determined that UvrABC incises only at the strand containing MC-mono-dG adduct. In contrast, UvrABC makes three types of incisions on a site specific ICL dG-MC-dG adduct: type 1 (40 %), a single 5’ incision on one strand and 3’ incision on the other; type 2 (21 %), dual incisions on one strand and a single incision on the other strand; and type 3 (39%), dual incisions on both strand of both 5’ and 3’ sides of the ICL dG-MC-dG adduct. These three types of incisions occur with similar kinetics. An important consequence of these incisions is formation of DNA double-stranded breaks (DSB). Contrary to conventional model, we also found that UvrA, UvrA+UvrB and UvrA+UvrB+UvrC bind to MC-modified DNA specifically and form complexes that include UvrA. No UvrB- and UvrB+UvrCDNA complexes were observed. Our findings challenge the current UvrABC incision model of ICLs. We propose that NER of ICL dG-MC-dG adduct produces DSB, a lethal event that contributes to MC antitumor activity, and causes a non-homologous end-to-end joining that leads to DNA translocation and deletion mutations.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1967.
Abstract 197: The KRAB-containing zinc finger protein ZNF545 is a functional tumor suppressor exerting proapoptotic and antiproliferation abilities with frequent epigenetic inactivation in multiple carcinomas
Authors: Cheng Yingduan , Liang Pei , Geng Hua , Cheng Suk Hang , Ng Margaret H L , Chan Anthony T c , Tao Qian 
Published: February 2011

Abstract
Epigenetic silencing of tumor suppressor gene is frequently involved in tumor development. Some zinc finger proteins (ZFPs) involved in tumorigenesis are down-regulated through CpG methylation in multiple carcinomas. Here, through genome wide-screening, we identified a novel KRAB domain-containing zinc finger protein (KRAB-ZFP), ZNF545, downregulated in multiple tumor cell lines including nasopharyngeal, esophageal, colon, stomach, liver, kidney, breast, cervix, and prostate carcinomas, in contrast to its broad expression in normal tissues. The promoter of ZNF545 contains a typical CpG island and is frequently methylated in multiple carcinoma cell lines. Transcriptional silencing of ZNF545 could be reversed by pharmacologic demethylation or genetic demethylation, indicating a direct epigenetic silencing mechanism. ZNF545 was also frequently methylated in primary tumors of NPC and ESCC, but less frequently in normal epithelial tissues and paired surgical marginal normal tissues. ZNF545 was found to be a transcriptional repressor when fused to Gal4-binding domain, as determined by the luciferase assay. Ectopic expression of ZNF545 in silenced cancer cell lines significantly inhibited their colony formation, proliferation and induced apoptosis, indicating that ZNF545 can function as a tumor suppressor. ZNF545 also can inhibit the activity of NF-KappaB and AP-1, which play an important role in tumorigenesis. We further found that ZNF545 was located in the nucleus and sequestered in the nucleolus in some cells. ZNF545 could co-localize with KAP1 and heterochromatin protein, so we proposed that ZNF545 could inhibit tumorigenesis, at least partially through downregulating the transcription of target genes, or regulating nucleolus function such as ribosome biogenesis. The tumor specific-silencing of ZNF545 could serve as an epigenetic biomarker for common cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 197.
Abstract 1980: Transcriptional profiling in peripheral blood mononuclear cells of patients with pancreatic cancer identifies several genes with potential diagnostic and prognostic implications
Authors: Baine Micahel , Chakraborty Subhankar , Smith Lynette , Mallya Kavita , Sasson Aaron , Batra Surinder 
Published: February 2011

Abstract
Background: Pancreatic cancer is one of the most lethal human malignancies, being the fourth most common cause of cancer-related mortality in the Western world and fifth most common worldwide. Despite advancements in understanding the pathogenesis of this malignancy, no reliable screening test currently exists for pancreatic cancer. As a result, the majority of patients present with advanced stage disease contributing to a poor prognosis. Owing to their accessibility, peripheral blood mononuclear cells (PBMCs) are a rich source of potential biomarkers for diagnosis and predicting patient outcome. The question of whether the gene expression profile in PBMCs of pancreatic cancer patients could be useful for its detection has not been examined. Hence, we tested the hypothesis that global gene expression profiling of PBMCs from pancreatic cancer patients could be useful to identify genes potentially useful as specific, early, surrogate biomarkers in the diagnosis of lethal pancreatic cancer.
Experimental design: We evaluated the transcriptional profile in PBMCs of 35 patients with pancreatic adenocarcinoma and compared it to that of 33 healthy controls using a Phalanx whole genome microarray containing probes for 39,200 genes. The Universal human reference was used as the reference against which all samples were normalized. We further validated the results of the microarray by quantitative real time PCR using SYBR green based chemistry. The normalization of the data was performed using the BRB Array tool software (http://linus.nci.nih.gov/BRB-ArrayTools.html)
Results: After normalization and filtering the genes (criteria: false discovery rate &lt;10%, confidence level 90%), 21,671 genes remained for analysis. 530 genes were found to be differentially expressed in pancreatic cancer patients (p&lt;0.05). 78 of these genes had at least a 1.5 fold change (up or down-regulation) in expression compared to that in the control PBMCs. The expression of two significantly upregulated genes (GAPDH, ASGR2) and four significantly down-regulated genes (DYRK2, MS4A1, EDG1, GRAMD1C) were validated via quantitative PCR. There was an 83% correlation between the microarray and qPCR results for these genes.
Conclusion: The present study represents the first example of gene expression profiling in the PBMCs of pancreatic cancer patients with the aim of identifying patterns of gene expression for diagnostic and prognostic purposes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1980.
Abstract 199: HPV-16 E6 silencing of p16INK4a in human cervical cancer cells
Authors: Yeung Chi Lam Au , Tsang Tsun Yee , Co Ngai Na , Yau Pak Lun , Kwok Tim Tak 
Published: February 2011

Abstract
Aberrant promoter methylation and silencing of tumor suppressor genes such as p16INK4a were reported in association with cervical carcinogenesis. Persistent infection with high-risk human papillomavirus (HPVs), such as HPV-16, contributes significantly towards the cervical cancer development. One of the HPV-16 early proteins E6 is considered to function as an oncoprotein. In the present study, the role of HPV-16 E6 in the regulation of p16INK4a silencing was investigated.
Knockdown of E6 in HPV-16 positive human cervical carcinoma SiHa cells by the technique of small interfering RNA (siRNA) led to an increase in p16INK4a mRNA expression as assessed by quantitative RT-PCR analysis. Addition of DNA demethylating agent, 5-aza-2’-deoxyctidine, also had similar effect. Moreover, by methylation-specific PCR analysis, hypo-methylation of p16INK4a promoter was detected in HPV-16 E6 knockdown SiHa cells. The results indicated that HPV-16 E6 may regulate the expression of p16INK4a through promoter methylation. By Western blot analysis, the expression of DNA methyltransferase DNMT1 was repressed in HPV-16 E6 knockdown SiHa cells while it was induced in HPV-16 E6 over-expressed cells. In addition, decrease in p16INK4a mRNA expression and hyper-methylation of its promoter were observed in SiHa cells upon DNMT1 cDNA transfection.
To sum up, HPV-16 E6 silencing of p16INK4a may be through the upregulation of DNMT1 which in turn induces the hyper-methylation of p16INK4a promoter and thus suppresses p16INK4a expression. This pathway may be one of the possible mechanisms for the oncogenic function of HPV-16 E6 in human cervical cancer development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 199.
Abstract 1991: Integrated analysis of copy number alteration and RNA expression profile in pediatric diffuse intrinsic pontine glioma
Authors: Zarghooni Maryam , Bartels Ute , Bouffet Eric , Hawkins Cynthia 
Published: February 2011

Abstract
DIPG is one of the most devastating of pediatric malignancies and one for which no effective therapy exists. A major contributor to the failure of therapeutic trials is the assumption that biologic properties of childhood brainstem tumors are identical to adult high-grade gliomas. A better understanding of the biology of DIPG itself is needed in order to develop agents targeted more specifically to these children's disease. Here we address this lack of knowledge by performing the first high-resolution, DNA- and RNA-microarray analysis of pediatric DIPG.
Nine DIPGs were prospectively collected at post-mortem following consent for research purposes. Four pre-treatment surgical samples were also retrieved from our pathology archives. All samples were hybridized to Affymetrix SNP-arrays (250k or 6.0). Nine samples were also hybridized to the HumanRef-8 v3.0 (DASL) or HumanWG-6 v3.0 expression beadchip from Illumina. Data were analyzed using the Copy Number Analysis Tool (Affymetrix) and Partek Genomics Suite using HMM and segmentation algorithm for copy number and clustering algorithm for gene expression.
DASL and Whole genome beadchip from Illumina have 18,404 probes in common. Those common probes were selected in the two data sets and the gene intensities related to those probes were pulled out for each sample separately. The differentially expressed genes were then identified using one-way ANOVA. For each sample, a gene list was created containing genes having a fold change between 2 and −2. The intersection of the seven gene lists was found using a Venn diagram. In total 234 genes were found that are differentially expressed in all seven samples.
The gene expression and gene copy number data were then integrated. In total 5 genes show correlation between copy number and gene expression in all seven samples.
Among the 234 differentially expressed genes, Ingenuity pathway analysis identified 63 genes associated with different aspect of cancer including proliferation, metastasis, polyploidization, neoplasia, adhesion, migration, survival, acidification, attachment, cell cycle progression, differentiation, growth and invasion.
Our data provides the first, comprehensive, genomic analysis of pediatric DIPG. A thorough understanding of the genetic abnormalities in DIPG is a crucial first step in the development of targeted therapies for this devastating group of tumors. This is of particular importance for DIPG given the lack of efficacy of current treatment regimens and the dismal prognosis for these patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1991.