bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2210: Quantification of the relative amount of mouse and human DNA in cancer xenografts using species-specific gene length variations
Authors: Lin Ming-Tseh , Tseng Li-Hui , Kamiyama Hirohiko , Kamiyama Mihoko , Lim Phillip , Wheelan Sarah , Eshleman James 
Published: February 2011

Abstract
Human cancer cell lines and xenografts are valuable samples for whole-genome sequencing of human cancer. Tumors can be maintained by serial xenografting in athymic (nude) or severe combined immunodeficient (SCID) mice. Critical to next generation based sequencing is the relative proportions of human and mouse DNA. In the current study, we developed a molecular assay to quantify the relative contributions of human and mouse in mixed DNA samples. The assay was designed based on deletion/insertion variation between human and mouse genomes. The percentage of mouse DNA was calculated according to the relative peak heights of PCR products analyzed by capillary electrophoresis. Three markers from chromosomes 9 and 10 accurately predicted the mouse genome ratio and were combined into a multiplex PCR reaction. We used the assay to quantify the relative DNA amounts of 93 mouse xenografts used for a recently reported integrated genomic analysis of human pancreatic cancer. Of the 93 xenografts, the mean % of contaminating mouse DNA was 47%, ranging from 17% to 73%, with 43% of samples having greater than 50% mouse DNA. We then comprehensively compared the human and mouse genomes to identify 370 additional candidate gene loci demonstrating human-mouse length variation. With increasing use of whole genome sequencing of human cancers, this assay should be useful to monitor strategies to enrich human cancer cells from mixed human-mouse cell xenografts.
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 2210.
Abstract 2211: Array-comparative genomic hybridization identifies important recurrent copy number alterations in non-small cell lung cancer
Authors: Sriram Bajee K. , Larsen Jill E. , Francis Santiyagu M. Savarimuthu , Wright Casey M. , Clarke Belinda E. , Duhig Edwina E. , N Hayward K. , Bowman Rayleen V. , Yang Ian A. , Fong Kwun M. 
Published: February 2011

Abstract
Comprehensive knowledge of the genomic aberrations involved in NSCLC may deliver improved therapies, diagnostic and prognostic biomarkers. Recurrent copy number alterations (CNA) found in the same locus across a set of tumour samples are assumed to be the site of “driver” cancer genes. We hypothesize that whole genome array comparative genomic hybridization (aCGH) will identify recurrent regions of gains and loss in NSCLC containing candidate “driver” genes. Methods: DNA from fresh-frozen tumor tissue of 133 NSCLCs were obtained from The Prince Charles Hospital lung tumour bank. aCGH was performed using Agilent CGH 44B microarrays (Agilent Technologies). Recurrent CNAs were identified using the Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm, controlling for false discovery rates (q≤0.005). Focal (&lt;50% of chromosome arm) regions of amplification and deletion were identified by applying GISTIC with thresholds of log2 0.848 and −0.747, respectively, corresponding to 3.6 copies and 1.2 copies with stromal contamination of 30%. Results: Regions of amplification occurred in 3q26.33, 5p15.33, 8p11.23, 11q13.3 and 19q13.2 and deletions occurred in 3p11.2, 4p15.1, 4q34.3, 5q14.1, 6q22.31, 8p23.1, 9p21.3, 10q23.31, 11q25, 13q14.3, 15q14, 16q23.3, 17p12, 18q22.3, 21q21.3 and 22q13.33. The most significant CNA regions were deletion in 9p21.3 (q=1.20E-40) and amplification in 3q26.33 (q=1.13E-10). These regions contain known tumor suppressor genes (TSGs) (CDKN2A in 9p21.3) and oncogenes (SOX2 in 3q23.33). Conclusion: We have identified regions with recurrent CNAs in NSCLC many of which harbor known oncogenes and TSGs. Further validation will be performed using public datasets and independent test cohorts. Supported by: NHMRC Medical Postgraduate Scholarship 569762.
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 2211.
Abstract 2215: Association between acquired uniparental disomy and homozygous mutations and HER2/neu, ER, and PR status in breast cancer: Meta-analysis
Authors: Tuna Musaffe , Foekens John A. , Amos Christopher I. 
Published: February 2011

Abstract
Mutations in genes that encode components of cellular signaling networks are a hallmark of cancer. However, sequencing the whole genome for each tumor sample is challenging. A novel form of abnormality called acquired uniparental disomy (aUPD) was recently found, which can pinpoint a region containing mutated genes predisposing to various cancers, therefore identifying a candidate region for subsequent next-generation. We conducted a large meta-analysis of genomic data from the Gene Expression Omnibus database to retrieve genome-wide regions of aUPD in breast tumor samples using approaches that can reliably detect aUPD. aUPD was identified in 40.57% of the samples. The most recurrent aUPD regions were located at chromosomes 17q, 3p, 13q, and 11q. These data suggest that multiple genes may be targeted for homozygous mutations. Then we found association between aUPD and homozygous point alterations by integrating our data with previously published mutation data on reference gene sequences in breast tumors. We also evaluated the data for any correlation between the most recurrent aUPD region at chromosome 17q and HER2/neu, ER, and PR status, and we found a statistically significant correlation between aUPD at chromosome 17q and HER2/neu-, ER- and PR-negative breast cancers. We conclude that aUPD is a common and nonrandom new molecular mechanism in breast tumorigenesis. Identifying UPD regions would be a more effective approach to take than randomly sequencing the genome for discovering novel candidate genes for mutation. An integrative view of aUPD and homozygous sequence alterations on a genome-wide scale should provide further valuable insights into breast tumorigenesis.
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 2215.
Abstract 222: Inhibition of cellular FLICE-inhibitory protein and induction of death receptor 5 expression is a major component of δ-tocotrienol-induced apoptosis in pancreatic cancer cells
Authors: Zhang Anying , Francois Rony A. , Hodul Pamela J. , Husain Kazim , Shivers Steven C. , Coppola Domenico , Sebti Said M. , Malafa Mokenge P. 
Published: February 2011

Abstract
Background: Previous pre-clinical studies have demonstrated that δ-tocotrienol, is the most bioactive natural vitamin E compound against pancreatic cancer. δ-Tocotrienol induces growth arrest and apoptosis in several human pancreatic cancer cell lines; however, the underlying mechanism remains unknown. In this study, we evaluated the role of the extrinsic and intrinsic apoptotic signaling pathways in δ-tocotrienol induced apoptosis and investigated the modulation of cellular FLICE-inhibitory protein (c-FLIP) and death receptor 5 (DR5) by δ-tocotrienol and the involvement of c-FLIP down-regulation and DR5 up-regulation in δ-tocotrienol-induced apoptosis.
Methods: We examined δ-tocotrienol induced apoptosis in human pancreatic cancer cell lines in vitro and in vivo. We used western blot and immunohistochemistry to determine the expression of DR4, DR5, Caspase 8, Caspase 9, Caspase 3, C-FLIPs and PARP. The effect of combination treatment with TRAIL and δ-tocotrienol was also determined. We examined the cellular effects of DR5 knockdown using small interfering RNA oligonucleotides, and c-FLIP overexpression using cDNA, on δ-tocotrienol-induced apoptosis using various assays.
Results: Delta-tocotrienol activated caspase-8 and its downstream caspases but not caspase-9, whereas caspase-8 specific inhibitor abrogated δ-tocotrienol-induced apoptosis indicating that δ-tocotrienol induces caspase-8-dependent apoptosis. c-FLIP was rapidly down-regulated by δ-tocotrienol in all of the tested cell lines. δ-Tocotrienol up-regulated DR4 and DR5 significantly and enhanced tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. Enforced expression of ectopic c-FLIP, and DR5 knockdown partially abolished δ-tocotrienol-induced apoptosis. δ-Tocotrienol inhibition of pancreatic tumor growth in SCID mice was associated with significant induction of apoptosis, activation of caspase 8, and down-regulation of c-FLIP expression.
Conclusion: We conclude that DR5 up-regulation and c-FLIP down-regulation contributes to δ-tocotrienol-induced apoptosis in pancreatic cancer cells.
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 222.
Abstract 2226: International Cancer Genome Consortium (ICGC)
Authors: Jennings Jennifer L. , Hudson Thomas J. 
Published: February 2011

Abstract
The International Cancer Genome Consortium (ICGC) is one of most ambitious biomedical research efforts since the Human Genome Project. The ICGC is coordinating an international-scale research effort to obtain a comprehensive description of genomic, transcriptomic and epigenomic changes in the major forms of cancer. This information will lead to better ways of diagnosing, treating and preventing cancer.
The ICGC was launched in April 2008, with the announcement of the proposed strategies and policies to the international scientific community to enable funding agencies and research groups to plan their participation within the ICGC. As of December 2009, the ICGC has received commitments from funding organizations in Asia, Australia, Europe and North America for the following cancer genome projects: breast cancer, Her2+ (France); breast cancer, multiple subtypes (United Kingdom); chronic lymphocytic leukemia (Spain); gastric adenocarcinoma (China), hepatocellular carcinoma, alcohol and associated etiologies (France); pediatric brain cancers - medulloblastoma and pilocytic astrocytoma (Germany); hepatocellular carcinoma, viral etiologies (Japan); oral cavity cancer (India), and pancreatic adenocarcinoma (Australia and Canada). Furthermore, the latest call for proposals published in the Health Theme of the European Union's 7th Research Framework Programme includes a research topic to support European participation in the ICGC. The ICGC projects will complement a large US-based pilot project called The Cancer Genome Atlas, which oversees projects related to glioblastoma multiforme, squamous carcinoma and serous adenocarcinoma. Over time, additional nations and organizations
Each project is expected to involve specimens from approximately 500 patients. Over the next ten years, the ICGC expects to produce comprehensive catalogues of the full range of genetic mutations involved in 50 types of cancer, with key factors being the ability to detect all mutated cancer genes, data at the level of individual DNA bases, application of common standards for pathology and technology and comparison data from matched, non-tumour tissue.
The ICGC's informed consent and ethical oversight policies state that cancer patients enrolled in an ICGC-related study should be informed that their participation is voluntary, that their clinical care will not be affected by their participation and that data obtained from analyses using their samples will be made available to the international research community.
ICGC projects will use common standards of data collection and analysis. The ICGC will make its data rapidly and freely available to the global research community.
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 2226.
Abstract 223: Apoptotic activity of Polygonum cuspidatum in KB human oral cancer cells through the downregulation of specificity protein 1
Authors: Shin Ji-Ae , Shim Jung-Hyun , Jeon Jae-Gyu , Cho Sung-Dae 
Published: February 2011

Abstract
Polygonum cuspidatum (Polygonaceae) has traditionally been used in folk medicine to improve oral public health. However, there are no reports related to its potential of controlling oral cancer. In this study, we evaluated the anti-tumorigenic effects and mechanisms of methanol extract and its fractions separated from Polygonum cuspidatum root in KB human oral cancer cells. The methanol extract of Polygonum cuspidatum (MEPC) inhibited the proliferation of KB cells in a dose- and time-dependent manner by inducing caspase-dependent apoptosis. Protein and mRNA expression levels and the transactivation of Specificity protein 1 (Sp1) were markedly decreased in KB cells treated with MEPC. Ethyl acetate fraction (EA) from MEPC was more potent than aqueous fraction (AQ) from MEPC to induce apoptosis. F2, F3 and F4 from EA differentially inhibited the growth of KB cells and it depends on the amount of Emodin in F2, F3 and F4. Moreover, Emodin inhibited KB cell growth and induced caspse-dependent apoptosis. Thus, the results from this study strongly suggest that MEPC, its fraction and Emodin may be potential bioactive materials to cause apoptosis mechanism via the down-regulation of Sp1 in KB human oral cancer cells.
This paper was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund, KRF-2008-331-E00260) and Bio R&D program through the Korea Science and Engineering Foundation funded by the Ministry of Education, Science and Technology (M10870050003-08N7005-00311).
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 223.
Abstract 2231: Detection of circulating tumor cells in peripheral blood of patients with renal cell carcinoma correlates with prognosis
Authors: Goebel Steffen , Bluemke Karen , Bilkenroth Udo , Meye Axel , Fuessel Susanne , Lautenschlaeger Christine , Melchior Andres , Heynemann Hans , Fornara Paolo , Taubert Helge 
Published: February 2011

Abstract
Purpose. The aim of this study was to evaluate the clinical relevance of the presence of disseminated tumor cells in peripheral blood [so called circulating tumor cells (CTCs)] for renal cell carcinoma (RCC) patients.
Methods. 233 peripheral blood samples from 154 RCC patients were investigated for the presence of disseminated tumor cells (DTCs) by autoMACS technique and immunocytochemical (ICC) staining of cytokeratin. The frequency of CTCs was analyzed statistically for correlation with relevant clinical data.
Results. Two kinds of tumor cells were detected: those with expression of cytokeratin 8/18 (CK+), but also cells without a detectable CK+ expression, which we called large blue stained (Bl+) cells with a tumor-like morphology. After following the CD45 autoMACS depletion protocol, we identified CTCs in 96 out of 233 peripheral blood samples (41%), which originated from 81 out of 154 (53%) RCC patients. A significant correlation between the detection of CTCs and positive lymph node status (p&lt;0.001; chi2-test) and the presence of synchronous metastases at the time of primary tumor resection (p=0.014; chi2-test) was found. In a multivariate Cox's regression hazard model, presence of CK+ CTCs was significantly correlated with poor overall survival for RCC patients (RR=2.3; P=0.048).
Conclusions. The presence of CTCs correlated to lymph node status and presence of synchronous metastases in RCC. It is important to evaluate CK+ and Bl+ tumor cells together to determine the role of CTCs in tumor behavior and disease progression. Detection of CK+ CTCs in peripheral blood is a significant and independent prognostic factor for RCC.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 2231.
Abstract 2235: Immunohistochemical analysis of RUNX2 in human colon cancer
Authors: Sase Tomohiko , Suzuki Takashi , Miura Kou , Onodera Yoshiaki , Sato Ryuichirou , Karasawa Hideaki , Yamamura Akihiro , Kimura Syunichi , Egawa Shinichi , Shibata Chikashi , Sasaki Iwao , Sasano Hironobu 
Published: February 2011

Abstract
[Background] Runt-related transcription factor (RUNX) family comes to attract attention in a field of differentiation and carcinogenesis. However, the RUNX2 expression in human colon cancer has not been fully analyzed. Therefore, we immunohistochemically analyzed the RUNX2 expression in human colon cancer. [Method] Primary colon cancer specimens were obtained from 158 colon cancer patients. All patients had undergone operations at Tohoku University Hospital, from 1994 to 2000. The formalin-fixed paraffin-embedded tissue sections were used for immunohistochemical analysis. [Result] RUNX2 was detected exclusively in nuclear of cancer cells, and 66.5% of cancer tissues were positive for RUNX2 (105/158 cases). Statistical analysis demonstrated that positive RUNX2 status was significantly associated with poor survival (Log-lank test: P=0.0178). In addition, RUNX2-positve patients had higher incidence of lymph node and liver metastasis compared to RUNX2-negative patients (P=0.0147 and 0.0038, respectively) [Discussion] RUNX2 may therefore play an important role in metastatic ability of human colon cancer.
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 2235.
Abstract 2237: Expression of the trefoil protein TFF3 in human breast cancers
Authors: Ahmed Ahmed Roshdi Hamed , May Felicity EB , Tilby Michael J. 
Published: February 2011

Abstract
Expression of the trefoil protein TFF3 in human breast cancers
The purpose of this study is to investigate expression of the trefoil factor family protein, TFF3 in a large series of human breast cancers. Trefoil factors are small secreted proteins that are expressed in mucus secreting epithelia. They are involved in mucosal protection in part by stimulation of cell motility. It has been proposed that the motogenic actions of trefoil proteins may facilitate tumor cell invasion and metastasis. Expression of TFF3 mRNA is regulated by estrogen in human breast cancer cell lines and strong association between estrogen receptor and TFF3 mRNA expression has been demonstrated in breast tumors by expression microarray analyses.
A tissue microarray was constructed from 300 primary breast tumors and 76 metastatic deposits of breast tumors from patients who presented in the northern region of England between 2002 and 2003. TFF3 expression was evaluated by immunohistochemistry with an antibody raised against correctly-folded human TFF3 protein. Each sample was analyzed in duplicate. The intensity of the immunoreactions in 1,000 tumor cells was evaluated as: absent, weak, moderate or strong. The association of TFF3 expression with various clinico-pathological features and with estrogen receptor protein expression was tested statistically with SPSS software (p&lt;0.01).
Clear TFF3 expression is demonstrated in normal and malignant breast epithelial cells. There is no expression in stromal, endothelial or immune cells. Expression of TFF3 varied enormously between tumor samples. TFF3 expression is highest in mucinous and tubular breast adenocarcinomas. TFF3 is expressed at higher levels in lobular than in ductal breast cancers. TFF3 expression is associated strongly with estrogen receptor expression. There is a negative association between TFF3 expression and tumor grade. There is however a positive association between TFF3 expression and presence of vascular invasion and TFF3 expression is higher in metastatic breast tumor cells than in primary breast tumor cells.
This is the first report of TFF3 protein expression in a large series of human breast tumors. The strong association between TFF3 and estrogen receptor suggests that TFF3 expression is dependent on estrogen in a significant proportion of breast tumors. The high expression of TFF3 in breast tumors with vascular invasion and in metastatic breast tumor cells supports the hypothesis that TFF3 predisposes towards breast cancer cell invasion.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 2237.
Abstract 2238: A novel prognostic marker in patients with squamous cell carcinoma of the tongue: high endothelial venules
Authors: Lee Ser Yee , Ooi Aik Seng , Qian Chao-Nan , Hwang Siok Gek , Teh Bin Tean , Soo Khee-Chee 
Published: February 2011

Abstract
AIMS: To evaluate tumor-induced vascularization in regional lymph nodes (LN) of patients with tongue carcinoma by studying the morphological and functional alterations of high endothelial venules (HEV) and its correlation to clinico-pathological features.
BACKGROUND: Squamous cell carcinoma (SCC) of the tongue is one of the most prevalent tumors of the head and neck region. The extent of LN metastasis is a major determinant for the staging and the most reliable adverse prognostic factor. Primary tumors can induce lymphatics and vasculature reorganizations within sentinel LN before the arrival of cancer cells and these key blood vessels are identified as HEV. The morphological altera[[Unsupported Character - Codename &shy;]]tion of HEV in the presence of a cancer, coupled with the increased proliferation rate of the endothelial cells, results in a functional shift of HEV from immune response mediator to blood-flow carrier.
METHODS: This study is based on 65 consecutive patients with tongue SCC who underwent primary surgical treatment at Singapore General Hospital from January 2001 to December 2005. The patients were categorized into 2 groups (Cases and Controls) based on the presence of malignancy in their cervical lymph nodes. A review of the patients’ pathological and clinical data was performed from a prospective database. Immunohistochemical staining of the tissue blocks for HEV and high-power-field image analysis were performed and analyzed with correlation to the patients’ clinico-pathological features.
RESULTS: The total number of HEVs is significantly associated to disease-free interval when controlling for the group (p=0.022) as well as combining both groups as one cohort (p=0.023). There also a similar association comparing the HEV parameters to overall survival.
CONCLUSION: Our results suggest that the HEV possibly plays a key role in the pathogenesis of lymphatic and subsequent distant metastases. Confirmation of this hypothesis would offer a novel therapeutic approach to preventing metastasis by blocking the remodeling processes of HEV in LN.
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 2238.