bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 325: ITCH is a putative target for a novel 20q11.22 amplification detected in anaplastic thyroid carcinoma cells by array-based comparative genomic hybridization
Authors: Ishihara Takaya , Tsuda Hitoshi , Hotta Akiko , Kozaki Ken-ichi , Yoshida Akira , Yoshimura Hiroshi , Ito Koichi , Imoto Issei , Inazawa Johji 
Published: February 2011

Abstract
Anaplastic thyroid carcinoma (ATC) is one of the most virulent of all human malignancies, with a mean survival time among patients of less than a year after diagnosis. To date, however, cytogenetic information on this disease has been very limited. Significant genomic copy-number alterations, such as amplifications and homozygous losses, are useful landmarks for identifying oncogenes and tumor-suppressor genes (TSGs), respectively. We have performed bacterial artificial chromosome (BAC) array-based comparative genomic hybridization (array-CGH), which allows the high resolution, high throughput and quantitative copy-number analysis throughout the genome, in various cancers, and identified many novel cancer-related genes. In ATC, we have reported DUSP26 as a novel growth-promoting gene from an amplified region detected in ATC cell lines by the array-CGH using an in-house low-density cancer-targeting array (Yu Wei et al.,Oncogene 2007). In the course of a program to screen a panel of ATC cell lines for genomic copy-number aberrations using array-based comparative genomic hybridization, we identified a high-level amplification of the ITCH gene, which is mapped to 20q11.22 and belong to the HECT ubiquitin ligase family. The expression of ITCH was increased in four of 14 ATC cell lines (28.6%), including 8305C with a copy-number amplification of this gene, and six of seven primary cases (85.7%). Among the primary thyroid tumors, a considerable number of ITCH high expressers were found in ATC (40/45, 88.9%), papillary thyroid carcinoma (25/25, 100%), and papillary microcarcinoma (25/25, 100%). Furthermore, knockdown of ITCH by specific small interfering RNA significantly inhibited the growth of ITCH-overexpressing cells, whereas ectopic overexpression of ITCH promoted growth of ATC cell lines with a relatively weak expression. These observations indicate ITCH to be the most likely target for 20q11.22 amplification and to play a crucial role in the progression of thyroid carcinoma.
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 325.
Abstract 3253: Genetic loci that contribute to aristolochic acid nephropathy and associated upper urothelial cancer
Authors: Rosenquist Thomas A. , Strockbine Penelope , Grollman Arthur P. 
Published: February 2011

Abstract
Aristolochic acids (AA) are nitrophenanthrene carboxylic acids found in all Aristolochia species which have been used historically as herbal remedies throughout the world. AA are the suspected causative agent for aristolochic acid nephropathy (AAN), Balkan Endemic Nephropathy (BEN), and so-called Chinese Herb Nephropathy (CHN). Hallmarks of these disease entities are proximal tubule damage and interstitial fibrosis leading to end stage renal disease. At least half of all patients also develop cancers of the upper urothelial tract (UUC). Aristolochic acid-DNA adducts generate signature A:T-&gt;T:A transversions in TP53. Such mutations are rare in sporadic urothelial cancers but predominate in UUC from patients with BEN/AAN/CHN.
We have developed a mouse model for AAN that has enabled us to screen for quantitative trait loci (QTL) that increase the susceptibility to AA in mice. Two hundred F2 mice obtained by breeding C57Bl/6J (an AAN-resistant strain) and DBA/2J (an AAN-sensitive strain) were treated with a single dose of AA. Four days later urine was analyzed for markers of kidney function. Mice were then euthanized and tissues were collected for histology and DNA was isolated for analysis of AA-DNA adducts and genotyping.
Four QTL were identified; a major QTL, Aanq1(Chr4, 46-71MB), a pair of interacting QTL, Aanq2(Chr3, 116-128MB), and Aanq3 (Chr9, 113-122MB), and a minor QTL that acts additively with Aanq1, Aanq4(Chr6, 124-135MB). Further analyses of the QTL regions and their human orthologs will be presented.
The project described was supported by Award Number P01ES004068 from the National Institute of Environmental Health Sciences.
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 3253.
Abstract 3286: Overexpression of cornulin in histologically normal adjacent tissue predicts occult nodal metastases in head and neck cancer patients
Authors: Weinberger Paul M. , Merkley Mark , Jackson Lana , Dynan William S. 
Published: February 2011

Abstract
As with many epithelial cancers, presence of nodal metastases in patients with Head and Neck Squamous Cell Carcinoma (HNSCC) predicts early recurrence and poor survival. Determination of occult metastases in the clinically N-zero (cN0) patient remains problematic and therefore prophylactic neck dissections are routinely performed for high risk cN0 patients. A cohort of 7 cN0 HNSCC patients who subsequently underwent planned neck dissection as part of their treatment was selected. Snap frozen tissue was enriched for tumor and adjacent normal tissue by laser capture microdissection. Total protein was extracted and separated by saturation-labeling 2D difference in-gel electrophoresis (2D-DIGE). Significance analysis of Microarray (SAM) method was used to evaluate for differential protein expression between patients with (n=3) and without (n=4) occult nodal metastases on neck dissection pathologic evaluation. Spot maps were generated for 14 gels (7 HNSCC, 7 normal) and relative abundance values calculated for each of 662 protein spots common to &gt;90% of gels. A 5% false discovery rate and 2-fold change were used as criteria for significance in the defintion of candidate biomarkers. Protein spots meeting these criteria were then extracted, digested and analyzed by liquid chromatography and tandem mass spectrometry to obtain protein identifications. For tumor tissue, there was no significant difference between groups. There were considerable differences in protein expression for normal adjacent tissue between patients with and without occult metastases, with 60 spots meeting criteria for significance (FDR&lt;0.05). There were 31 proteins underexpressed in occult metastases patients, with the top candidate being 11.9 fold lower in the occult metastasis group (adjusted q&lt;0.001). There were 29 proteins overexpressed, with the top candidate being 6.6 fold higher in the occult metastasis group (adjusted q&lt;0.001). This protein was identified as Cornulin, a 53 kDa calcium-binding protein of the s100 family recently identified as a novel HNSCC biomarker. Cornulin plays a known role as a cornification chaperone that is protective against acid stress in squamous epithelium. It is possible that elevated cornulin in surrounding normal tissue may reflect ongoing epithelial injury, predisposing developing tumors to aggressive behavior. In conclusion, we have identified overexpression of cornulin in adjacent normal tissue as a novel biomarker for tumors with occult metastases in the cN0 HNSCC patient population. Additionally, these data highlight the role that tumor-stroma interactions may play in the development of early nodal metastases.
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 3286.
Abstract 3294: The impact of occult nodal metastasis on the recurrence of esophageal squamous cell carcinoma
Authors: Morimoto Junya , Tanaka Hiroaki , Kubo Naoshi , Ohira Masaichi , Muguruma Kazuya , Noda Eiji , Amano Ryosuke , Inoue Toru , Yashiro Masakazu , Yamada Nobuya , Maeda Kiyoshi , Sawada Tetuji , Ishikawa Teturou , Hirakawa Kosei 
Published: February 2011

Abstract
Esophageal cancer (ESC) is an aggressive disease with a poor overall prognosis. Survival rate of patients with cStage II/III ESC who underwerrt surgical resection have been improved, whereas half of these patients frequently caused recurrences. It has been thought that the lymph node metastasis was deeply related to the relapse of ESC. However, clinical signification of micrometastases in lymph nodes remain unclear because of complexity in the procedure to detect micrometastasis. Here we report that the impact of micrometastasis in lymph nodes on the recurrence of ESC. The aim of this study was to confirm the relation between noccult nodal metastasis and recurrence of in resected cStage II/III ESC. A total of 98 patients with ESC resected at Osaka City University hospital between January 2000 and January 2007 were targeted. Micrometastasis was investigated with one-level cytokeratin immunohistochemistry(IHC)and routine histological assessment by hematoxylin-eosin sections. Judgment of micrometastasis was done with discovery of cluster cells. Uni-and multivariate analyses of the independent recurrect facters were performed using the Cox proportional hazards regression model.
A total of 6,172 lymph nodes(average 63) were examined from 98 patient, also 140 lymph nodes of micrometastasis(average 1.4) were detected. The micrometastasis was not possible to detect with routine histological assessment by hematoxylin-eosin sections. A clear difference of detected micrometastasis between relapse patients(45 patients,83%) and no relapse patient(15patients,34%) was admitted. In univariate analyses, curability(p=0.000),v facter(p=0.046),pN facter(p=0.026),pM facter(p=0.016),pStage(p=0.002),total metastatic lymph node count(p=0.000),total metastatic lymph node count added micrometastasis(p=0.000) were recurrence facters. In multivariate analyses, total metastatic lymph node count added micrometastasis were independent recurrence facters(Hazard ration 13.059,p=0.000) finally.
Therefore, the number of total metastatic lymph nodes with micrometastasis have pivotal impact on the recurrence of ESC.
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 3294.
Abstract 3313: Snail and slug-mediated epithelial mesenchymal transition in lung cancer cells
Authors: Daisuke Tamura , Arao Tokuzo Arao , Nagai Tomoyuki Nagai , Aomatsu Keiichi , Sakai Kazuko , Kudo Kanae , Kaneda Hiroyasu , Matsumoto Kazuko , Furuta Kazuyuki , Fujita Yoshihiko , Kotani Yoshikazu , Nishimura Yoshihiro , Saijo Nagahiro , Nishio Kazuto 
Published: February 2011

Abstract
Epithelial-Mesenchymal Transition (EMT) has been classified as a unique process by which epithelial cells undergo remarkable morphologic changes characterized by a transition from epithelial cobblestone phenotype to elongated fibroblastic phenotype (mesenchymal phenotype) leading to increased motility and invasion. Accumulating evidence indicates that EMT-inducible transcription factors such as Snail homologues (Snail1, 2, and 3) and several basic helix-loop-helix factors Twist, are poor prognostic factors and associated with chemoresistance in oncology.
The aim of this study was to investigate the involvement of SNAI-mediated EMT and its malignant potential in lung cancer cells. We introduced SNAI1 or SNAI2 gene into A549 or PC-9 lung cancer cell lines and established stable cell lines A549/GFP, /SNAI1, /SNAI2, PC-9/GFP, /SNAI1 and /SNAI2. Overexpression of SNAI1 and SNAI2 clearly mediated the EMT-related morphological changes including the cell scattering and the elongation of cell-shape. Real-time RT PCR demonstrated that overexpression of SNAI1 and SNAI2 markedly down-regulated the mRNA levels of E-cadherin about 1/2 to 1/100 compared with GFP-expressing control cell lines. The mRNA upregulation of N-cadherin, fibronectin 1 and Vimentin, which changes are characteristic of EMT, were also observed. We are now investigating its oncogenic properties, gene expression changes by microarray analysis and chemoresistance using these stable SNAI1 or SNAI2 transfectants.
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 3313.
Abstract 3316: CD44High head and neck cancer cells demonstrate increased cell growth and chemotherapeutic resistance
Authors: Wu Arthur W. , Basak Saroj K. , Lai Chi , Veena Mysore S. , Wang Marilene B. , Srivatsan Eri S. 
Published: February 2011

Abstract
Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is a tumor made up of a heterogeneous population of cancer cells. Differences in individual cell phenotype may extrapolate to clinical behavior at the tumor level. CD44 is a cell surface marker highly expressed in putative cancer stem cells. Here, we demonstrate that fluorescence activated cell sorting (FACS) for the CD44 cell surface marker isolates a population of HNSCC cells with increased growth rate, colony forming ability, and chemoresistance. Methods: FACS was used to isolate CD44High and CD44Low cells from the HNSCC cell line SCC1. CD44High, CD44Low and unsorted cells were compared with respect to cell growth using the MTT assay for 8 days. They were also seeded into agar and grown for 6 weeks to determine colony forming potential. Sorted and unsorted cells were also compared for their sensitivity to cisplatin (20 µM). Live cells were measured using the MTT assay and compared to untreated cells at the same time point in order to calculate relative growth rates. Additionally, SCC1 cells were analyzed using FACS with and without cisplatin to determine changes in the population of CD44High cells. Primary tumor specimens and normal controls were analyzed for various cancer stem cell markers via immunohistochemistry. Results: CD44High SCC1 cells grew the fastest in culture with CD44Low cells growing significantly slower. Unsorted cells had a similar growth rate to CD44High cells, which is not surprising given that CD44High cells made up roughly 60% of the total population. CD44High cells in soft agar developed significantly more colonies with a larger average colony size after 6 weeks in culture compared to unsorted and CD44Low cells. CD44High SCC1 cells also were less sensitive to cisplatin with no difference in cell growth between treated and untreated cells. Using FACS to analyze unsorted cells after treatment with cisplatin, we observed enrichment in the CD44High cell population. Control non-cancer specimens demonstrated expression of p16 with low levels of BMI and CD44 on immunohistochemical analysis. Poorly differentiated HNSCC tumors demonstrated absence of p16, high BMI, and high CD44. Conclusion: The cell surface marker CD44 is expressed in a subset of HNSCC cells that have higher growth rates, tumorogenicity, and resistance to chemotherapy. These HNSCC stem cells may be the reason for resistance and recurrence. Understanding the mechanism behind their specific phenotype will be valuable in advancing treatments for HNSCC.
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 3316.
Abstract 3317: Study of response in neural stem cells after cerebral irradiation
Authors: Kong Doo-Sik , Joo Kyung Min , Nam Do-Hyun 
Published: February 2011

Abstract
Objective: Ionizing irradiation causes cell death but also birth and migration of new neurons within sites of cerebral damage. The cellular environment that induces neuronal regeneration and migration after irradiation has not been defined yet. The aim of this study was to evaluate the neuronal response after irradiation injury induced by gamma knife radiosurgery.
Methods: We used a model of long-distance migration of newly transplanted neural stem cells from the subependymal zone on the other hemisphere to that on the ipsilateral side after irradiation using gamma knife radiosurgery for the purpose of defining the cellular cues that induce neuronal regeneration after CNS injury.
Results: In vitro and in vivo studies showed that irradiation induced neurogenesis from transplanted GFP-tagged neural stem cells and migration of newly born neurons into a unique neurovascular niche. Within this neurovascular niche, newly born, immature neurons were closely associated with the remodeling vasculature. The relationship between neurogenesis and angiogenesis is causally linked through vascular production of CD31 and VEGF receptor-2.
Conclusions: These experiments defined a novel brain environment for neuronal regeneration after irradiation using gamma knife radiosurgery and identified molecular mechanisms that are shared between angiogenesis and neurogenesis during functional recovery from brain injury.
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 3317.
Abstract 3323: Induction of apoptosis in glioma cells by downregulation of X-linked inhibitor of apoptosis protein (XIAP)
Authors: Dasari Venkata Ramesh , Kaur Kiranpreet , Fassett Daniel , Klopfenstein Jeffrey D. , Dinh Dzung H. , Gujrati Meena , Rao Jasti S. 
Published: February 2011

Abstract
XIAP (X-linked inhibitor of apoptosis protein) is one of the most important members of the family of apoptosis inhibitors. XIAP blocks apoptosis by inhibiting both the initiator (caspase 9) and effector (caspase 3) caspases, and therefore, prevents cell death induced by various triggers. One mechanism through which tumor cells are believed to acquire resistance to apoptosis is by overexpression of XIAP. When XIAP is overexpressed, cancer cells are rendered resistant to apoptosis, both intrinsically and in response to chemotherapy and radiotherapy. It is upregulated in various malignancies, including human glioblastoma. It promotes invasion, metastasis, growth, and survival of malignant cells. In order to downregulate XIAP in glioma cells, we used human umbilical cord blood mesenchymal stem cells (hUCB) and siRNA of XIAP (siXIAP). We observed the effect of both hUCB and siXIAP on two malignant glioma cell lines (SNB19 and U251) and two glioma xenograft cell lines (4910 and 5310). In either case, proliferation of the glioma cells was significantly inhibited. Both treatments increased cytotoxicity of glioma cells and led to cell death. However, cytotoxicity is more significant in siXIAP treatments compared to hUCB cocultures. Both hUCB and siXIAP induced TNF-alpha-mediated apoptosis in glioma cells, which was confirmed by TUNEL assay, FACS analyses and immunoblotting. Apoptosis is characterized by loss of mitochondrial membrane potential and upregulation of mitochondrial apoptotic protein BAD. Cell death of glioma cells is marked by downregulation of Akt and phospho-Akt molecules. Taken together, our results indicate the therapeutic potential of XIAP and hUCB in treating malignant gliomas.
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 3323.
Abstract 3326: BEZ235 enhances radiosensitization via blockade of PI3-kinase/mTOR pathway in cisplatin-selected non-small cell lung cancer stem cells
Authors: Kim Kwang Woon , Jung Dae Kwang , Lu Bo 
Published: February 2011

Abstract
Purpose: Most drug resistance cancer cells have resisted to radiation therapy. In this study, we hypothesized that a dual inhibitor of PI3-kinase/ the downstream mammalian target of rapamycin (mTOR), BEZ235, could potentially enhance radiosensitization in cisplatin-selected non- small cell lung cancer stem cells.
Methods: Clonogenic assay was used to determine radiosensitivity. Stem cell marker was detected with CD133 antibody. P-AKT, P-mTOR and P-S6R were detected by Western Blotting. Cell cycle was performed using flow cytometry. Autophagy was determined by punctuate localization of GFP-LC3 fusion protein, which observed under a confocal fluorescence microscope in vitro.
Results: Basal CD133 which is a marker of stem cell, P-Akt, p-mTOR and P-S6R proteins were enhanced in cisplatin-selected non- small cell lung cancer stem cells (CSNSCLCSTC) when compared to parental non-small cell lung cancer (H460) cells. Cisplatin-selected non- small cell lung cancer stem cells mediate less radiation sensitivity when compared with parental cells in clonogenic assay(DER=0.82, p=0.02). However BEZ235 obviously enhanced sensitivity of cisplatin-selected non- small cell lung cancer stem cells to radiation (DER=1.2, p=0.01). Therefore, this enhanced radiosensitization was associated with a downregulation of PI3-kinase/mTOR signaling pathway and an increase in characteristic punctuate localization of GFP-LC3 as a marker for autophagy, suggesting that G2/M inhibition and autophagy were induced simultaneously.
Conclusions: These findings may be utilized as a novel strategy to enhance radiation therapy in drug-selected non-small cell lung cancer stem cells showing radioresistance.
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 3326.