bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3826: Brevican absence and YKL-40 over-expression are associated to the mesenchymal profile and in vitro 3D-neurosphere growth of human glioma
Authors: Martinez Paloma Fernandez , Casans Cristina Zahonero , de la Rosa Natividad Pozo , Ayuso Angel , de Sola Rafael Garcia , Sanchez Juan Manuel Sepulveda , Gomez Pilar Sanchez 
Published: June 2012

Abstract
DNA microarray-based molecular profiling have recently uncovered two well-differentiated subsets of human glioma having distinct clinical outcome: those displaying neuronal lineage markers and having longer survival (proneural), and those enriched for neural stem cell markers and having short survival (mesenchymal). Genes allowing the distinction of both glioma subsets were herein used to further explore their clinical and biological significance with regard to survival and tumorigenic potential through 3D-neurosphere in vitro assay. Surgical samples from 72 patients with glioma (tumor tissue and tumor-unaffected brain tissue from the same patients) were used. The expression level of most relevant genes, including cancer stem cell markers, matrix and tumor progression genes were analyzed by quantitative RT-PCR. Brevican (BCAN), Delta-like 3 (DLL3) and oligodendrocyte lineage transcription factor 2 (Olig2) genes were associated to the proneural profile (Spearman correlation between them indicated a robust P-value: DLL3-BCAN: 2.17E-10; Olig2-BCAN: 6.94E-9; Olig2-DLL3: 5.03E-11). In contrast, Fibronectin 1 (FN1) and cartilage glycoprotein-39 (YKL-40) gene over-expression defined the mesenchymal profile in an effective way (Spearman correlation YKL-40-FN1 p-value: 2.65E-4). Survival increased by two-fold in patients having BCAN gene over-expression. Moreover, BCAN gene expression prevented in vitro growth of glioma cells as 3D-neurospheres. These data demonstrate a correlation between BCAN, DLL3 and Olig-2 gene expression and the proneural glioma profile, while absence of BCAN expression and YKL40 overexpression was associated to the mesenchymal profile and in vitro neurosphere growth of human glioma.
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 3826. doi:10.1158/1538-7445.AM2011-3826
Abstract 3830: Type 2 cGMP-dependent protein kinase regulates proliferation in the colon
Authors: Wang Rui , Kwon In-Kiu , Browning Darren D. 
Published: June 2012

Abstract
Signaling through cGMP has previously been found to play a role in tissue homeostasis in the intestinal mucosa but the mechanism is not known. Type 2 cGMP-dependent protein kinase (PKG2) is a major cGMP effector in the intestinal epithelium but its role in tissue homeostasis has not previously been examined. The present studies have tested the importance of PKG2 in the regulation of proliferation and differentiation in the mouse colon and in colon cancer cell lines. RT-PCR analysis confirmed that PKG2 is expressed in normal colon mucosa, and although there was no difference in colon tumors, it was undetectable in established colon cancer cell lines. Ectopic expression of PKG2 in LS174T and HT29 cells decreased colony formation in clonogenic assays. This effect of PKG2 on colon cancer cells was not due reduced cell viability but was associated with an increase in G1 arrested cells and increased expression of the differentiation markers CDX2 and MUC2. Consistent with an anti-proliferative and pro-differentiation role of PKG2 in the colon, we observed increased proliferation and larger crypt size in PKG2-/- mice compared to wild type siblings. In addition, there were significantly less mature goblet cells in PKG2-/- mice relative to controls when measured by histological staining with Alcian blue or by immunostaining with anti-MUC2 antibodies. Recent reports suggest that PKG2 might affect differentiation by regulating the transcriptional repressor Sox9. We found that PKG2 could phosphorylate Sox9 at Ser181 in both colon cancer cell lines and in the mouse colon at a position 2/3rd into the crypt. In the colon cancer cell lines, phosphorylation of Sox9 by PKG2 did not affect expression or nuclear localization, and was not sufficient for the regulation of MUC2 or CDX2 expression. The work presented here demonstrates a novel anti-proliferative and pro-differentiation role for PKG2 in the colon, which has an important function in tissue homeostasis. The ability of PKG2 to reduce growth and increase expression of MUC2 and CDX2 tumor suppressors suggests that PKG2 may have therapeutic significance in colon cancer.
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 3830. doi:10.1158/1538-7445.AM2011-3830
Abstract 3832: Defining molecular mechanisms controlling FES activation and microtubule binding as a potential strategy to limit mast cell recruitment to tumors via the SCF/KIT axis
Authors: Kwok Ester , Allingham John , Craig Andrew W. B. 
Published: June 2012

Abstract
FES protein-tyrosine kinase (PTK) is activated downstream of the KIT receptor in mast cells, and promotes mast cell migration towards Stem cell factor (SCF), the ligand for KIT. Recently, tumor-derived SCF has been implicated in promoting mast cell recruitment leading to increased tumor vascularity and poor prognosis. FES is also a potential therapeutic target in leukemias driven by oncogenic KIT receptors that are constitutively active. Thus, defining FES activation and signaling mechanisms could lead to development of FES inhibitors as potential therapeutics in mast cell-involved tumors or KIT-driven leukemias. FES was previously shown to phosphorylate Tubulin, and localize to microtubules (MTs) in an SH2 domain-dependent manner. We hypothesized that defects in MT reorganization in FES-deficient mast cells may account for the observed defects in migration towards SCF. To map potential MT binding site(s) in FES, we performed MT binding assays, and identified two modes of FES binding, one via the N-terminal F-BAR/FX domains, and also via the SH2 domain. Interestingly, mutations predicted to disrupt oligomerization of the F-BAR/FX domains enhanced MT binding in vitro, and MT localization in vivo. Using in vitro kinase assays, we show that FES preferentially phosphorylates soluble tubulin compared to MTs, suggesting that FES recruitment to MTs may depend on their phosphorylation by other PTKs (such as Src family PTKs). In mast cells treated with SCF, FES co-localizes with MTs, including some localization to the MT organizing center (MTOC). We are currently comparing MTOC orientation in polarized wild-type and FES-deficient mast cells, and examining MT subsets marked by γ-tubulin, acetylation, and detyrosination. In conclusion, we find that FES interacts directly with MTs in vitro, and co-localizes with MTs in vivo, and hypothesize that disruption of FES-MT interaction and/or activation will be relevant therapeutic targets to limit mast cell recruitment in solid tumors, and growth of KIT-driven leukemias.
Funded by an operating grant from Canadian Institutes for Health Research (MOP82882) to AWBC.
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 3832. doi:10.1158/1538-7445.AM2011-3832
Abstract 3835: Multiple stimulants target different phosphoinositide 3-kinase (PI3K) classes in breast cancer cell lines
Authors: Ehrmantrout Kimberly K. , Thompson James E. , Branch Angie M. 
Published: June 2012

Abstract
Phosphoinositides (PIPs) are an integral part of multiple cell signaling pathways and are metabolized by kinases, phosphatases, and phospholipases. PIPs produced by the activities of phosphoinositide 3-kinase (PI3K) serve as second messengers in cell survival, growth, motility, immune response, inflammation, and apoptosis. Conversely, abnormal production of these signaling lipids leads to proliferative, metabolic, and inflammatory disorders. It is critical to know the absolute and relative concentration of individual PIPs in cell samples, however this analysis is difficult due to their low abundance and the inherent physical properties of lipids. Experiments to measure PIPs have involved radiolabeling cells, extraction of radioactive products, and separation using thin-layer chromatography. The amount of PIPn extracted from cell lysates was determined by means of a standard competitive ELISA format, eliminating the need for radioactivity. Using specific antibodies and binding proteins we developed assays able to differentiate closely related PIPs. These nonradioactive assays employ synthetic di-C16 lipids as standards and are able to measure as little as 0.1 pmol of lipid. Cell-extracted PIPs were added as competitors in these quantitative ELISAs. We used the human breast cancer cell lines MDA-MB-231 and MDA-MB-468 (PTEN deficient) as a model system to evaluate multiple activators of PI3K pathways by looking at levels of PI(3)P, PI(3,4)P2 and PI(3,4,5)P3. Using growth factors, hyperosmolarity, and oxidative stress we found that different stimulants targeted different classes of PI3K. All three classes of PI3K were more active in PTEN deficient cell line (468 cells) than PTEN+/+ (231 cells). We found that all stimulants used increased PI3K products. Pre-incubation with wortmannin, a known PI3K inhibitor, decreased PIPn levels. We propose that hyperactivation of class I and class II PI3K in the absence of PTEN regulation (468 cells) leads to excessive 3’ phosphorylated phosphoinositide levels that are known to activate Akt, We expect the ability to quantify individual phosphoinositides from cells will help assign specific biological functions to these important lipid second messengers.
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 3835. doi:10.1158/1538-7445.AM2011-3835
Abstract 3838: Mitogen-activated protein kinase phosphatase-1 deficiency increases susceptibility to 4-nitroquinoline 1-oxide-induced neoplasia in murine squamous oral epithelium
Authors: Zhang Xiaoyi , Yu Hong , Kirkwood Keith L. 
Published: June 2012

Abstract
Background: Cytokines and pro-inflammatory factors have critical roles in shaping the malignant transformation that gives rise to head and neck squamous cell carcinoma (HNSCC). Mitogen-activated protein kinases (MAPKs), such as p38, JNK, and ERK, relay information from extracellular signals to control the diverse cellular processes of carcinogenesis. These kinases are negatively regulated by MAPK phosphatases (MKPs), the founding member being mitogen-activated protein kinase phosphatase-1 (MKP-1). Initial studies demonstrated significant over-expression of MKP-1 in human epithelial tumors only in the early phases of disease with levels falling progressively in tumors of higher histological grade and in metastases. We hypothesize low levels of MKP-1 in the HNSCC tumor microenvironment generate high levels of inflammation which promote tumor development and progression.
Methods: To address how regulation of inflammatory cytokine expression via MKP-1 activity may affect HNSCC development and progression, we examined the effects of MKP-1 deficiency on a well characterized model for oral squamous cell carcinoma (OSCC), a subset of HNSCC. MKP-1-/- and wild-type mice were treated with 4-nitroquinoline 1-oxide (4NQO), a surrogate for tobacco exposure, in drinking water for 16 weeks and monitored by oral examination for an additional 16 weeks. Tumor size was assessed by volumetric measurement. Histological grading of the tumors and inflammation were performed in a blinded manner by two collaborating pathologists.
Results: Our studies demonstrated significantly earlier onset of 4NQO-induced OSCC in MKP-1-/- mice compared with wild-type controls. Tumor size and histological grade were found to be more severe in the MKP-1-/- mice. In addition, tissues surrounding the tumors demonstrated a significantly higher degree of inflammation in MKP-1-/- mice. Remarkably, development of esophageal squamous carcinomas was dramatically enhanced in MKP-1-/- mice treated with 4NQO.
Conclusion: These studies demonstrate increased susceptibility of MKP-1-/- mice to 4NQO-induced neoplasia, suggesting an important role for MKP-1 as a negative regulator of HNSCC development. Further work will be done to characterize mechanisms of regulation by assessing levels of MAPK activity and characterizing the pro- and anti-inflammatory milieu of the tumor tissues and supportive stroma. Elucidating the regulation of inflammatory mediators in the tumor microenvironment may reveal critical tumor suppressive interactions mediated by MKP-1 which are lost during cancer initiation and progression.
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 3838. doi:10.1158/1538-7445.AM2011-3838
Abstract 3844: K-Ras is required for maintaining survivin protein stability in human cancer cells harboring mutant but not wild type K-Ras
Authors: Tecleab Awet , Sebti Said M. 
Published: June 2012

Abstract
The anti-apoptotic protein survivin is maintained at high levels in cancer cells relative to normal cells. The mechanism by which this occurs is ill-understood. Here we show in several human cancer cell lines including those derived from pancreatic, lung and ovarian cancers that knocking down K-Ras expression by siRNA results in decreased survivin levels in cancer cells harboring mutant but not wild type K-Ras. K-Ras knockdown decreases survivin mRNA and protein levels by 50% and 85%, respectively, suggesting that K-Ras regulates survivin transcription as well as protein stability. Consistent with this K-Ras knockdown decreases the levels of ectopically-expressed Myc-tagged survivin. Further support for the ability of K-Ras to regulate the protein stability of survivin is also supported by the fact that the proteasome inhibitor Velcade partially inhibits K-Ras siRNA from decreasing the levels of survivin. Taken together, the data suggest that K-Ras is a contributor to the maintenance of high levels of survivin in human cancer cells which harbor mutant but not wild type K-Ras.
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 3844. doi:10.1158/1538-7445.AM2011-3844
Abstract 3873: Genetic and epigenetic determinants of outcome in locally advanced head-and-neck cancer
Authors: Nigro Cristiana Lo , Gasco Milena , Vivenza Daniela , Lattanzio Laura , Monteverde Martino , Comino Alberto , Syed Nelofer , Crook Tim , Merlano Marco 
Published: June 2012

Abstract
Despite improved outcome, optimal protocols of combined modality treatments have not been identified in advanced Head and Neck squamous cell carcinoma (HNSCC). Nor has it been established which subgroup of patients will benefit from integrated treatments. Because of the significant treatment-related toxicity, it is critical to design treatments according to molecular predictors in order to maximise therapeutic anti-tumour effect and minimise toxicity. We have investigated the potential utility of candidate predictive biomarkers in a large, homogenous cohort of patients treated in our centre.
One-hundred-eighty-three paraffin-embedded specimens were obtained from 160 patients (136 males and 24 females, median age 0 58 years) with stage III-IV, locally advanced, unresectable HNSCC collected at S. Croce General Hospital since1999. All patients were treated with radical, cisplatin-based, chemo-radiotherapy regimens. P53 mutations in exons 4-10, polymorphism P72R in p53 gene and MDM2 single nucleotide polymorphism (SNP) 309 were analysed by sequencing and pyrosequencing. EGFR expression and HPV status were determined by ICH. Methylation in the CpG island of Dab-2 and DUPS2 was analyzed both by MSP and pyrosequencing.
We previously showed that a functional SNP in the apoptosis signalling domain of p53 influences clinical response of HNSCC to chemotherapy. We now have investigated the hypothesis that, in addition to molecular genetic determinants, methylation profiling can identify distinct subtypes of HNSCC.
p53 mutations were found in 48.5% of samples. Distribution of alleles at codon 72 in p53 was as follows: RR = 50%, RP = 40%, PP = 10%. Distribution of alleles MDM2 SNP309 was: TT =35%, TG = 43%, GG = 22%. Methylation in the Dab-2 and DUPS2 CpG islands was present in 35% and 31%, respectively.
We are currently correlating these data with objective response rate, progression-free survival and overall survival. The final statistical analysis will be presented.
We report the incidence of mutations, SNPs and epigenetic profiling in specific genes in HNSCC. We shall identify correlations with clinical outcome parameters.
The project was partially supported by AIRC grant to M.G.
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 3873. doi:10.1158/1538-7445.AM2011-3873
Abstract 3877: FTSJ2, a putative ribosomal RNA methyltransferase, suppressed cell invasion and migration in cancer cell line
Authors: Lai Cheng-Wei , Lin Ken-Yo , Liou Fang-Jiue , Chen Hsiao-Ling , Cheng Ju-Chien , Chen Chuan-Mu 
Published: June 2012

Abstract
The E. coli heat shock protein which is called ribosomal RNA large subunit methyltransferase J (RrmJ) responsible for the 2’-O-ribose methylation of A-loop U2552 in the 23S rRNA. This gene is highly conserved from Prokaryota to Eukaryota. In human, three closed homologues of RrmJ have been identified and designated as FTSJ1, FTSJ2 and FTSJ3. In this study, we characterized mammalian FTSJ2 from the amino acid sequences alignment to the mitochondrial localization, and suggested the similar function to RrmJ. The RT-PCR results showed that there were much lower FTSJ2 mRNA expression in eight hepatoma cell lines (HepG2, Hep3B, HHCM, Huh7, 22T, 59T, SK-Hep1, PLC/PRF/5) and one medulloblastoma cell line (Te671), compared with the expression level in normal liver tissue. Subsequently, after the medulloblastoma cells were transfected with FTSJ2 overexpression vector, the FTSJ2-overexpressed Te671 cells (FTSJ2/Te671) showed the inhibition effects of cell migration and invasion in vitro. In addition, this also caused the rearrangement of F-action in FTSJ2/Te671 detected by immunofluorescence. However, recent study showed that FTSJ2 may involve in tumourigenesis, and FTSJ2 gene was activated in non-small cell lung cancer. Thus, we proposed that FTSJ2 may play different roles in different tissues during tumourigenesis through the catalysis of ribosomal RNA methylation in mitochondria.
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 3877. doi:10.1158/1538-7445.AM2011-3877
Abstract 3881: Genetic alterations in intrahepatic cholangiocarcinoma- revealed by array CGH, SKY and gene expression microarray
Authors: Weng Wen-Hui , Tsao Lee-Cheng , Pang Yeu-Jye , Pang See-Tong , Yeh Chun-Nan 
Published: June 2012

Abstract
Cholangiocarcinoma (CCA) is an adenocarcinoma of the biliary tract, which is considered to be an incurable and rapidly lethal disease. A major problem with CCA surveillance is the lack of reliable biomarkers, therefore, still less no significant aspects of client-centered therapy in clinical treatment so far. Here, we established a 25th week thioacetamide (TAA)-induced cholangiocarcinoma rat cell line model named Chang Gung CCA (CGCCA), aim to figure out the early alterations of cytogenetics, molecular and protein expressed characteristics of CCA. Array comparative genomic hybridization (aCGH) and Spectral karyotyping (SKY), gene expression microarray and immunohistochemistry were performed on either rat CCA tissues or CGCCA cell line in this study. Our results showed complicated alterations of genetic gain or loss on different chromosomal regions could be observed. The data compared with the gene expression profile, thirty-three genes aberrations could be further identified; for example, tumor metastasis-related genes ANXA1 and CLCA3, the genes MMP7 and MMP12 are related with tumor invasion, and proliferation-related genes PKM2 and OSMR have been pinpointed; The number of chromosome ranging between 50 to 56 diplody (2n); despite the apparently high incidence of chromosomal translocation was revealed by cytogenetic analyses, ring and/or giant rod marker chromosomes were detected in almost every CGCCA cells, and the genetic materials are mainly included chromosomes 4 and 8. Herein, we concluded ANXA1, CLCA3, MMP7, MMP12, PKM2 and OSMR genes could be considered as potential biomarkers for the risk of disease. Supernumerary ring or giant rod marker chromosomes could also be considered as a characteristic may be involved in the late stage of CCA. However, the genes involved in the tumorigenesis should be further investigated the function of the genes. In order to verify the clinical significance and potentially to be as therapeutic targets in the future, to confirm onto a series of human CCA tissues are necessary.
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 3881. doi:10.1158/1538-7445.AM2011-3881
Abstract 3882: The comparison of genomic instability between epidermal growth factor receptor(EGFR) mutation status of lung adenocarcinoma
Authors: Lai Yi-Ling , Yuan Shin-Sheng , Chen Hsuan-Yu , Yu Sung-Liang , Li Ker-Chau , Yang Pan-Chyr 
Published: June 2012

Abstract
We investigated how different the patients of lung adenocarcinoma with and without EGFR activating mutation are in the genomes of their cancer cells. We conducted EGFR mutation test for 141 patients and used high-density even-coverage CGH arrays to chart the sites of DNA copy number alteration (CNA) in primary adenocarcinomas of each patient. We analyzed the site distribution of the most notable alterations from various perspectives and revealed several leading characteristics that converged on chromosome 7p. The clinical relevance of our findings was confirmed by conducting a survival study on an independent group of 114 patients, wherein a gene-signature that used the average copy numbers of 6 genes on 7p as measured by genomic real-time rt-PCR, showed statistical significance in predicting the overall survival and the relapse-free survival for the EGFR-mutation patients but not for the EGFR-wild-type patients. Our findings suggest that chromosome 7p contains very rich information for deciphering the pivotal genomic component contributing to the heterogeneity of lung adenocarcinoma.
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 3882. doi:10.1158/1538-7445.AM2011-3882