bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4752: Cortactin and coronin 1B cooperate to promote tumor cell invasion in head and neck squamous cell carcinoma
Authors: Walk Elyse L. , Wu Hong , Garcia Marileila V. , Bear James E. , Weed Scott A. 
Published: June 2012

Abstract
Amplification of chromosome 11q13 in head and neck squamous cell carcinoma (HNSCC) is a common occurrence associated with poor patient prognosis. Within the core amplified region is the gene that encodes cortactin (CTTN), a filamentous (F)- actin binding protein and Src kinase substrate that stabilizes Arp2/3-F-actin branchpoints in dynamic cortical F-actin structures. CTTN amplification results in increased lymph node metastases and decreased survival rates in HNSCC patients. CTTN amplification in HNSCC cell lines enhances tumor cell motility and invasion. Chromosomal regions of varying length flanking the core 11q13 amplicon are often amplified in HNSCC, and contain several genes with the potential to cooperate with CTTN in regulating actin dynamics. One of these genes within the 11q13 region outside of the core amplicon is CORO1B (coronin 1B), an actin-binding protein that antagonizes cortactin function by promoting the breakdown of cortactin-stabilized Arp2/3-F-actin branches, resulting in impaired cell motility. Here we show that coronin 1B is a potential mediator of HNSCC invasion. CORO1B amplification and overexpression occurs in a subset of HNSCC patients with CTTN amplification. Coronin 1B localizes with cortactin within HNSCC invadopodia, ventral membranous protrusions responsible for degrading extracellular matrix to facilitate loco-regional invasion and extracapsular spread. RNAi-mediated coronin 1B knockdown decreases the number of invadopodia per cell, enhances cell spreading and reduces extracellular matrix degradation. These results collectively point to a potential role for coronin 1B in regulating HNSCC tumor cell invasion through modulating cortactin activity and invadopodia function. Our data also support a potential diagnostic function for CORO1B amplification in denoting a previously unidentified HNSCC subset that may display increased invasiveness in cases containing 11q13 amplification.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4752. doi:10.1158/1538-7445.AM2011-4752
Abstract 4753: The interaction of two metastasis suppressor genes, Nm23-H1 and Gelsolin, results in synergistic phenotypes
Authors: Marino Natascia , Marshall Jean-Claude A. , Collins Joshua , Zhou Ming , Veenstra Timothy , Steeg Patricia S. 
Published: June 2012

Abstract
Metastasis Suppressor Genes (MSGs) are able to inhibit metastasis without reducing primary tumor size. Nm23 was the first MSGs to be identified. The biochemical basis for the anti-metastatic effect of Nm23 has been subject of many studies but remains unresolved. We performed co-immunoprecipitation assays using flag-tagged constructs of both the human and murine forms of Nm23 (Nm23-H1 and Nm23-M1, respectively) over-expressed in the mouse mammary carcinoma cell line 4T1. Co-immunoprecipitation assays were also performed on tissue extracts of primary tumors and metastases obtained from Balb/C mice injected with these cell lines. Using Mass-Spectrometry, new binding partners were identified including the actin-binding protein Gelsolin. Gelsolin is an actin regulatory protein that modulates actin assembly and disassembly, and is believed to regulate cell motility in vivo through modulation of the actin network. Recently, Gelsolin has been added to the list of MSGs.
An interaction between Gelsolin and Nm23 was validated in a murine cell line (4T1- Nm23-H1/M1 clones) and in a human breast carcinoma cell lines (MCF-7). In the low- metastatic cells MCF-7 an interaction between endogenous Nm23-H1 and Gelsolin was observed. However, in the highly metastatic MDA-MB-435 and MDA-MB-231 cell lines the interaction was observed only after the over-expression of Nm23-H1. These results suggest that an Nm23-Gelsolin interaction may only take place when relatively high levels of Nm23 are expressed. We conclude that the interaction between Nm23-H1 and Gelsolin occurs in the non-metastatic state, where high levels of both proteins are present, and this interaction can contribute to the anti-metastatic property associated to Nm23.
Using cultures of MDA-MB-231 stably overexpressing Gelsolin, Nm23-H1 or both proteins, the biological role of this interaction was analyzed. The two metastasis suppressors, Nm23-H1 and Gelsolin, when overexpressed in the single stable clone did not affect the cell growth; however they cooperated in decreasing the cell growth. This is the first time overexpression of Nm23-H1 has decreased cell proliferatioin and suggests that combinations of MSGs may have distinct phenotypic effects. Moreover, overexpression of both Nm23-H1 and Gelsolin in MDA-MB-231 cells reduced cell migration and cell invasion compared to the clone overexpressing the empty vector or single suppressor genes. In summary, Nm23-H1 has been demonstrated to bind another Metastasis Suppressor, Gelsolin. Additive and synergistic effects of multiple Metastasis Suppressors were identified.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4753. doi:10.1158/1538-7445.AM2011-4753
Abstract 477: CD49fhi/CD90lo from primary human osteosarcoma cells are enriched for tumor initiating property
Authors: Penfornis Patrice , Cai David Z. , Harris Michael R. , Induru Spandana , Meyer Mark , Pochampally Radhika R. 
Published: June 2012

Abstract
Osteosarcoma (OS) is one of the most prolific forms of cancer among adolescents, resulting in a severe decrease in life expectancy unless detected early. Though several previous studies have suggested various tumor-initiating properties of osteosarcoma, major limitations for understanding have been observed due the OS's restrictive ability to expand in in vivo models. In this study, we are reporting the use of primary osteosarcoma cells for characterizing the tumor initiating property. Human OS samples were collected during biopsies or surgeries, expanded in vitro, phenotyped for multiple cell-surface markers by Fluorescence Activated Cell Sorting (FACS) analysis and then injected subcutaneously into nu/nu mice. We observed that cells showing an expression of the CD49fhi/CD90lo cell surface marker produced a more aggressive tumor. In vitro treatment of this cell population with amiloride, a potassium-sparing diuretic, decreased the cells ability to express the CD49f protein. In vivo, amiloride treatment also dramatically decreased tumor growth when injected into nu/nu mice when compared to controls, indicating that CD49fhi/CD90lo is an important marker in tumor initiation. The transfection of CD49fhi cells with a shCD49f lentiviral construct showed a 20% decrease in their overall ability to migrate in a trans-well assay, and experienced a two-fold decrease in their capability to form colonies (CFU assay). Subcutaneous injections of the transfected cells expressing shRNA for CD49f reduced tumor growth by 30% compared to controls. In conclusion, our data suggests that the CD49fhi/CD90lo cell population is linked to a more aggressive osteosarcoma tumor growth and that this cell surface marker could be a potential candidate for the characterization of TICs in osteosarcoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 477. doi:10.1158/1538-7445.AM2011-477
Abstract 4775: Role of FoxM1 survival pathway in primary effusion lymphoma cells
Authors: Ahmed Maqbool , Hussain Azhar R. , Ahmed Saeeda O. , Bu Rong , Thangavel Saravanan , Platanias Leonidas C. , Al-Kuraya Khawla S. , Uddin Shahab 
Published: June 2012

Abstract
Primary effusion lymphoma (PEL) is associated with Kaposi sarcoma herpesvirus (KSHV) but its pathogenesis is poorly understood. Many KSHV-associated products can deregulate cellular pathways commonly targeted in cancer. The clinical features and natural history of PELs differ greatly from those observed in other lymphomas. The failure to improve outcomes with treatment intensification indicates the need for the introduction of new therapeutic options. Forkhead Box M1 (FoxM1) is a transcription factor that regulates the expression of a number of genes that are involved in cell cycle regulation and metastasis. Over-expression of FoxM1 has been shown in a variety of cancer however its role has not been fully elucidated in PELs. We found that FoxM1 is constitutively expressed in PELs and treatment of PELs with thiostrepton; a specific inhibitor of FoxM1 inhibits cell viability and induces apoptosis in a dose dependent manner. In addition, thiostrepton treatment also efficiently blocks formation of colonies on agarose plates as well as inhibits cell invasion and migration of PEL cell. Thiostrepton treatment causes down-regulation of FoxM1, MMP-2 and MMP-9 in PEL cells leading to activation of the intrinsic apoptotic pathway. Thiostrepton treatment causes conformational changes of Bax protein, leading to loss of mitochondrial membrane potential and release of cytochrome c to the cytosole. This leads to activation of caspase-9, caspase-3, and polyadenosin-5’-diphosphate-ribose polymerase (PARP) cleavage leading to caspase-dependent apoptosis. Altogether, this data demonstrates the possible role of FoxM1 in pathogenesis of PELs and raise the possibility that incorporation of thiostrepton in treatment regimens for primary effusion lymphomas may improve the overall survival of patients suffering from this malignancy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4775. doi:10.1158/1538-7445.AM2011-4775
Abstract 4801: Comprehensive genome methylation analysis in bladder cancer; identification and validation of novel methylated genes and application of these as urinary tumor markers
Authors: Reinert Thomas , Modin Charlotte , Lamy Philippe , Wojdacz Tomasz K. , Hansen Lise L. , Wiuf Carsten , Borre Michael , Dyrskjøt Lars , Ørntoft Torben F. 
Published: June 2012

Abstract
Cancer of the urinary bladder is one of the major cancers being the fifth most common neoplasm in the industrialised countries. Urothelial carcinomas account for more than 90% of all bladder cancers. The majority of bladder cancers are non-muscle invasive cancers characterized by frequent recurrences after resection and up to 25% will develop an aggressive phenotype. We investigated the methylation in bladder cancer with respect to location in genome, consistency, variation in metachronous tumors, impact on transcripts, chromosomal location, and usefulness as urinary markers of bladder cancer.
In this study, a microarray assay with more than 27.000 CpG sites was utilized to analyze methylation in 56 samples. Independent validations were performed in 63 samples by methylation-sensitive high-resolution melting (MS-HRM) and bisulfite sequencing. Transcript levels were analyzed using expression microarrays, and pathways using dedicated software. DNA from 40 urinary specimens was analyzed by MS-HRM.
Our results show that global methylation patterns were established within and outside CpG-islands. Differential methylation (p&lt;0.0001 to p&lt;0.05) was identified in 1588 genes between normals and cancers, in 1019 genes with stage specific methylation, and in 149 genes as progression markers. We validated methylation of eight genes, the tumor markers ZNF154 (p&lt;0.0001), HOXA9 (p&lt;0.0001), and POU4F2 (p&lt;0.0001) and the progression marker TBX4 (p&lt;0.002). The methylation of metachronous tumors was relatively stable and targeted to certain pathways. The correlation to expression was not stringent. Chromosome 21 showed most differential methylation (p&lt;0.0001) and specifically hypomethylation of keratins, which together with keratin like proteins were epigenetically regulated. In DNA from voided urine we detected differential methylation of ZNF154 (p&lt;0.0001), POU4F2 (p&lt;0.0001), and HOXA9 (p&lt;0.0044), achieving 94% sensitivity and 100% specificity.
Our results suggest that both hypo- and hyper methylation is stage dependent, over-represented at chromosome 21, and has a restricted influence on transcript levels in general, but clearly on keratins. The methylated genes are highly promising urinary cancer markers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4801. doi:10.1158/1538-7445.AM2011-4801
Abstract 4806: Claudin downregulation in head and neck squamous cell carcinoma (HNSCC) may be caused by aberrant promoter methylation
Authors: Nagado Aline A. , de Carvalho Ana Carolina , Lessa Roberta C. , Lourenço Silvia V. , Coutinho-Camillo Claudia M. , Buim Marcilei E.C. , Soares Fernando A. , Carvalho André L. , de Oliveira André Luiz Vettore 
Published: June 2012

Abstract
Claudins are a family of transmembrane proteins that compose the tight junctions, playing an essential role in cell-to-cell adhesion, maintenance of cell polarity and recruiting signaling proteins. The expression of these proteins has been found to be altered in several human cancers, suggesting that this family of proteins might represent potential molecular markers for cancer detection, diagnosis and therapy. We analyzed the expression profile of a claudin member gene in Head and Neck Squamous Cell Carcinomas (HNSCC) cases using Real-Time PCR, and found low expression in 78% of the evaluated cases. The expression of this gene was restored in an HNSCC cell line after treatment with the demethylating agent 5-Aza-2′-Deoxycytidine. After that, we designed primers for methylation analysis (MSP) and examined the expression and methylation status of this gene in several cell lines. A positive correlation between the expression level and methylation pattern was found. Besides, preliminary analyses of aberrant methylation status in HNSCC and normal samples showed 100% of specificity and 24% of sensitivity. This result suggests that aberrant methylation of claudin members could play a major role in the expression control of this gene.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4806. doi:10.1158/1538-7445.AM2011-4806
Abstract 4817: Altered DNA methylation in human lung cell line A549 after treatment with a standard mixture of particulate matter
Authors: Rota Federica , Dioni Laura , Cantone Laura , Baccarelli Andrea , Bertazzi Pier Alberto 
Published: June 2012

Abstract
BACKGROUND: Numerous health studies have shown acute and chronic particulate air pollution (PM, particulate matter) exposures to be associated with lung cancer, as well as with lung growth impairment, chronic obstructive pulmonary disease (COPD), and asthma. Toxicology studies have shown that PM is only a weak mutagen. Whether PM induces DNA methylation alterations, a primary mechanism in cell transformation, has never been studied in lung epithelial cells. In our study, we found a significative modification of P16 DNA methylation after PM treatement.
AIM: To investigate PM on 8 cancer and inflammatory genes (TLR-4, CD14, IFNγ, TNFα, RASSF1A, APC, p53, p16) in A549 human alveolar basal epithelial cells.
METHODS: A549 cells were treated with a complex standard mixture of particulate matter (NIST-National Institute of Standards and Technology- Standard Reference Material [SRM] 1648a). SRM 1648a treatments were performed with increasing doses of total mixture (15, 31, 62, 125, and 250 μg/ml) dissolved in colture medium. We used untreated cells as a negative control. Only concentrations that did not affect cell viability were considered. The cells were harvested after 2, 6, 12, 24, and 48 hours of continuous exposure, washed with phosphate buffered saline, and stored as cell pellet at -80°C until DNA extraction. DNA methylation was measured by means of bisulfite-Pyrosequencing. All the experiments were conducted in triplicate to confirm repeatability of our results.
RESULTS: Using a t-test assuming that the two distributions have the same variance, we found an increase in p16 methylation for a dose of 15 μg/ml (p16 mean(untreated-treated)=0,83; p-value=0,05); an hypomethylation for a dose of 62 μg/ml (p16 mean(untreated-treated)=−0,77; p-value=0,004) as well as for a dose of 250 μg/ml (p16 mean(untreated-treated)=−0,78; p-value=0,01). We observed also an increase in APC methylation for a dose of 250 μg/ml (APC mean(untreated-treated)=2,90; p-value=0,02). CONCLUSION: This finding indicates that different levels of exposure to PM can induce changes in the DNA methylation levels in vitro. Our hypothesis is that exposure to PM can cause changes in the gene-specific DNA methylation levels thus enhancing cancerogenesis. Additional studies are required to better define the epigenetic mechanisms by which PM and similar environmental agents induce changes in DNA methylation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4817. doi:10.1158/1538-7445.AM2011-4817
Abstract 482: High CD44/CD24 expressive cells presented cancer stem cell characteristics and undergo mitochondrial resetting and metabolic shift in nasopharyngeal carcinoma
Authors: Shen Yao-An , Wei Yau-Huei , Chen Yann-Jang 
Published: June 2012

Abstract
Cancer stem cells (CSCs) are a rare subset cancer cells with self-renewal property and cause many difficulties in clinical treatment. CSCs have been found in different tumors by specific surface markers. However, the surface marker of CSC remains unknown in various cancer types, including in nasopharyngeal carcinoma (NPC). Here, we took advantage of CSC's properties, such as chemoresistance, radioresistance, and the ability to form tumor spheres, to isolate CSCs from NPC cell lines. Combining these three isolation methods, and surface marker screening, we identified that NPC CSCs had high level of CD44 and CD24 surface antigen expression. We then validated the CD44/CD24 high positive as NPC CSC surface marker. In cell proliferation assay by MTT test, tumorigenity assay in soft agar and in vivo xenotransplantation, and radioresistant assay, CD44/CD24 high positive cells expressed significant CSC properties compared with CD44/CD24 double negative and parental NPC cells. We further found that CSCs underwent mitochondria resetting, including the distribution, quantity, and quality of mitochondria. Metabolic shift that largely relied on glycolysis also occured in CSCs. They predominately ultilized glycolysis instead of mitochondrial respiration to meet energy demand. Inhibiting glycolysis or treating antioxidants suppresses the viability and malignant traits of CSCs which provides therapeutic implication in NPC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 482. doi:10.1158/1538-7445.AM2011-482
Abstract 4821: Somatic variation scoring and validation for large-scale cancer genome sequencing
Authors: Pant Krishna P. , Lincoln Steve , Baccash Jonathan , Halpern Aaron L. , Nazarenko Igor , Carnevali Paolo , Ballinger Dennis G. 
Published: June 2012

Abstract
Complete Genomics has sequenced the genomes of over 100 tumor-normal sample pairs from a variety of cancers (e.g. Lee, et al., Nature 465: 473-477, 2010) using a unique high throughput sequencing platform (Drmanac, et al., Science 327:78-81, 2010). We have assembled a tool set to investigate somatic mutations in these samples, including small variations (SNVs, deletions, insertions and substitutions), as well as larger structural variations, copy number variations and regions of LOH (Loss of Heterozygosity). Included in this sample set are 12 cancer cell lines and matched normal cell lines obtained from the American Type Tissue Culture collection (ATCC), comprising 10 breast cancers and 2 lung cancers. We have developed and characterized somatic variation scoring methods for each variant class that can be tuned for particular applications and sample types. Comparative analyses with previously published data show high specificity and sensitivity of somatic variation detection. We will discuss the application of these methods for somatic variation analysis in larger cancer genome studies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4821. doi:10.1158/1538-7445.AM2011-4821
Abstract 4848: Genetic profile of invasive breast cancer vasculature using laser capture microdissection (LCM) to capture vessels
Authors: Jones Dylan T. , Lechertier Tanguy , Herbert John , Bicknell Roy , Jones Louise J. , Harris Adrian L. , Hodivala-Dilke Kairbaan 
Published: June 2012

Abstract
Tumor angiogenesis is vital for tumor growth and progression. Defining genes that are involved in tumor driven angiogenesis may yield therapeutically important targets for cancer therapy.
We have developed and optimized a rapid 25 minute immunohistochemical staining method using CD31 antibody (Pecam1) specific to endothelial cells in vessels on sections from frozen human breast cancer (n=3) and normal breast (n=3), followed by laser capture microdisection (LCM) of vessels. Good quality RNA was extracted amplified, and fluorescently labeled cDNA was synthesized and hybridized onto Affymetrix U-133 Plus 2.0 array.
Using this methodology, we were able to elucidate the genetic profile of tumor associated vessels from invasive breast cancer and compare it with vessels in normal breast tissue. This technique has the advantage over other methods in analyzing genetic profile of tissue as it analyses the genetic profile of isolated cell population and eliminates genes expressed by surrounding tissue, allowing for the detection of low expression of genes that were not detected in whole tumor arrays.
Using false discovery rate statistical analysis (q&lt;0.05) of microarray data, we identified 64 upregulated and 6 downregulated genes in breast cancer associated vessels. With Ingenuity Pathway analysis the top molecular and cellular functions include 11 genes involved in Cellular Assembly and Organization, 9 in Cellular Function and Maintenance and 8 in Protein Synthesis. Canonical pathway analysis revealed 3 genes involved in Ephrin Receptor signaling, 3 in Integrin signaling, 2 in VEGF signaling and 2 in TGF-β signaling. Differentiated genes were compared to Expression Sequence Tags from endothelial and non-endothelial libraries; three genes were specific to endothelial cells only (q&lt;0.05). Using Immunohistochemistry we have validated expression of two genes in breast vessels.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4848. doi:10.1158/1538-7445.AM2011-4848