bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1290: The ability of the transcription factor p63 to induce selected gene expression modules associated with mesenchymal to epithelial transition of prostate cells
Authors: Olsen Jan Roger , Ke Xi-Song , Rostad Kari , Hellem Margrete R. , Qu Yi , Lin Biaoyang , Lorens James B. , Micklem David R. , Haugen Hallvard , Gravdal Karsten , Halvorsen Ole Johan , Akslen Lars A. , Rotter Varda , Oyan Anne Margrete , Kalland Karl H. 
Published: August 2012

Abstract
Genome-wide gene expression analysis identified p63 as one of the most consistently under-expressed transcription factors in prostate cancer samples compared to matched benign prostate tissue. Two alternative p63 promoters generate two different N-terminal variants, TA or ΔN which contains and lacks the transactivating domain, respectively. Differential splicing generates multiple additional isoforms. The activity and interactions of the different isoforms remain unresolved. Isoform-specific real-time quantitative PCR assays revealed that ΔNp63α is the predominant isoform in epithelial prostate tissues, but other isoforms are detectable. Our group has established an experimental cell culture model based upon primary, immortalized prostate epithelial cells (EP156T cells), where p63 was shut down when EP156T cells underwent epithelial-to-mesenchymal transition (EMT) to become EPT1 cells. Subsequently, several additional mesenchymal like cell subtypes with additional malignant features, including anchorage independent growth in soft agar and ability to grow at much higher density in monolayers, were derived from EPT1 cells. All of these subtypes exhibited very low p63 expression. To examine the potential of p63 to induce mesenchymal to epithelial transition (MET) in this EMT model, we have stably re-expressed the ΔNp63α and TAp63α isoforms in different mesenchymal like cells of the model using retroviral/lentiviral vector transductions. Genome-wide gene expression analyses and phenotypic cellular assays revealed that the ΔNp63α isoform induced re-expression of multiple genes involved in cell adhesion. But this was not associated with complete MET induction. Cells re-expressing ΔNp63α obtained an intermediate morphology with both epithelial and mesenchymal traits, and with actin filaments organized in stress fibers. ΔNp63α re-expression significantly compromised migratory but not invasive ability of the cells. Based upon these findings we want to investigate whether p63 may compromise epithelial to mesenchymal plasticity in an animal model of tumorigenic cells and if there is differential effect on primary tumor growth compared to metastatic growth.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1290. doi:1538-7445.AM2012-1290
Abstract 1293: Galectin-3 facilitates the stability of p21 protein through carbohydrate recognition domain in prostate cancer cells
Authors: Wang Yi , Raz Avraham 
Published: August 2012

Abstract
Galectin-3 (Gal-3), a β-galactoside-binding protein, has multiple functions such as regulating cell growth, apoptosis, angiogenesis, tumor metastasis and so on. p21cip/waf-1, a cyclin-dependent kinase inhibitor, also regulates apoptosis and cell growth as well. Gal-3 and p21 have some similar functions, and both of them play important roles in tumor progression. Here, we try to understand how Gal-3 regulates p21 protein in prostate cancer cells. Our study showed that the changes of expressions of Gal-3 and p21 in prostate cancer cells are parallel. Functions of Gal-3 in regulating apoptosis and cell growth are partially mediated by p21. Gal-3 protein helps to prevent the degradation of p21 protein and delay the turnover of p21 in prostate cancer cells. The protective effect of Gal-3 on the stability of p21 protein is attenuated by Gal-3 inhibitor lactose and modified citrus pectin, which suggests that carbohydrate recognition domain of Gal-3 is responsible for its effect on the stability of p21. Our study is helpful to further understand the molecular mechanisms of Gal-3 functions and demonstrate the crosslink between Gal-3 and p21 pathways.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1293. doi:1538-7445.AM2012-1293
Abstract 1297: Engrailed-2 (EN2) represses the transcription of the CST6 tumour suppressor gene in prostate cancer
Authors: Morgan Richard , Simpson Guy , Michael Agnieszka , Pandha Hardev S. 
Published: August 2012

Abstract
Engrailed-2 (EN2) is a homeodomain-containing transcription factor that is expressed in prostate and breast tumours but not in normal adult tissue. Although EN2 protein is known to be secreted by prostate tumours and is a potential urine based biomarker of this disease, its function in prostate tumours is unknown. In this study we have used siRNA-mediated knock down of EN2 as well as forced over expression in prostate cancer cells. Although neither treatment has a significant effect on cell survival, we identify two key transcriptional targets of EN2, the tumour suppressor gene CST6 and the Death Receptor ligand TRAIL, the transcription of which are repressed and activated by EN2, respectively. EN2 synergises with epigenetic changes to silence CST6, and may function to block CST6 expression very early in the development of malignancy. Further, we show that EN2 protein can regulate gene transcription in non-malignant prostate cells when supplied externally, indicating that EN2 secretion by prostate tumour cells may be able to modify its microenvironment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1297. doi:1538-7445.AM2012-1297
Abstract 1420: Microsomal prostaglandin E2 synthase 1 (mPGES-1) is expressed in neuroblastoma and may represent a novel target for therapy
Authors: Kock Anna , Rasmuson Agnes , Idborg Helena , Johnsen John Inge , Kogner Per 
Published: August 2012

Abstract
Neuroblastoma (NB) is an embryonic tumor of the sympathetic nervous system and it is the most common extracranial tumor affecting young children. Despite a very intensive treatment regimen high-risk neuroblastoma patients still have a poor prognosis. Neuroblastoma cells are enriched in arachidonic acid, over express COX-2 and produce prostaglandin E2 (PGE2) that acts as an autocrine or paracrine survival and proliferation factor by induction of Akt signaling. Downstream of the COX enzymes, specific synthases converts PGH2 into the different prostaglandins. Microsomal prostaglandin E2 synthase-1 (mPGES-1) specifically converts PGH2 to PGE2 and is thought to primarily couple to COX-2. The aim of this study is to investigate if inhibition of mPGES-1 could represent an alternative therapeutic approach to COX- inhibition in neuroblastoma. We could detect expression of mPGES-1 in a panel of seven human neuroblastoma cell lines. Stable knock down of mPGES-1 expression using shRNA significantly reduced the clonogenic capacity and treatment with the mPGES-1 inhibitor CAY1052 inhibited neuroblastoma cell growth in vitro. By immunohistochemistry and western blot we could also detect expression of COX-1, COX-2 and mPGES-1 in tumors from the transgenic TH-MYCN mouse model of neuroblastoma. Treatment of homozygous TH-MYCN mice with 10 mg/L diclofenac for two weeks, starting at the age of four weeks, significantly reduced tumour weight compared to untreated animals. Ex vivo analysis with LC-MS/MS of tumor tissues from diclofenac treated animals revealed a significant decreased level of COX metabolites compared to control. The expression of mPGES-1was not affected by the treatment. Furthermore the number of cells staining positive for cleaved caspase-3 were higher in the treated tumors indicating induced apoptosis. In conclusion, our results show that mPGES-1 is expressed in neuroblastoma therefore mPGES-1 might represent an alternative way of reducing NB growth through specific PGE2 inhibition.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1420. doi:1538-7445.AM2012-1420
Abstract 1439: Loss of expression of SWI/SNF subunits in high risk Wilms tumor is accompanied by global gene expression changes
Authors: Gadd Samantha L. , Gerhard Daniela S. , Smith Malcom A. , Auvil Jaime Guidry , Huff Vicki , Geller James I. , Dome Jeffrey , Huang Chiang-Ching , Perlman Elizabeth J. 
Published: August 2012

Abstract
Introduction: The TARGET initiative seeks to identify therapeutic targets through genomic sequencing supported by copy number and gene expression analysis. The High Risk Wilms Tumor TARGET project, currently in progress, includes the analysis of favorable histology (FH) tumors that relapsed and tumors with anaplasia (unfavorable histology). We report the identification of a group of Wilms tumors (WT) identified by a unique gene expression pattern. Methods and Results: 102 high risk WT (43 anaplastic, 59 relapsed FH) were analyzed using Affymetrix U133+2 chips. Unsupervised hierarchical analysis consistently selected 9 tumors (5 anaplastic, 4 FH) that shared a striking gene expression pattern. These patients presented at 15-96 months (median 51); 7 had a triphasic histology and 2 were blastemal predominate; 4 died of their disease. When the top differentially expressed genes (P&lt;0.0001) were analyzed with PANTHER, significant repression (p=5x10−7) of genes responsible for the regulation of chromatin architecture was apparent. Among the most significantly down-regulated were ARID1A (fold change (FC) 0.2, p=5.2x10−8) and SMARCA4 (BRG1, FC 0.16 p=9x10−6), among others. Transcriptomic analysis using hierarchical clustering based on chromosomal position displayed a unique pattern of alternating increased and decreased expression of small genetic regions for all chromosomes in this group. These findings may represent long-range genomic regulation that has been attributed to histone modifications and are in keeping with the role of the SWI/SNF chromatin remodeling complex. Analysis using the Affymetrix 6.0 SNP chip demonstrated LOH for 1p31 (ARID1A) and 19p13 (BRG1) in 2 and 1 of the 9 tumors, respectively. Global methylation analysis is underway. Conclusion: Mutations in several SWI/SNF subunits (including ARID1A, BRG1, SMARCB1, PBRM1) have been implicated in the development of a wide range of neoplasias. In normal cells, SWI/SNF subunit protein levels are tightly controlled in a coordinated fashion in order to maintain constant cellular levels. Little is known about the transcriptional regulation of these subunits. This report suggests that a subset of Wilms tumors show striking repression of many SWI/SNF subunits, resulting in a unique globally abnormal gene expression pattern that has not been previously described in tumors with ARID1A or SMARCB1 loss. Whole genomic or exomic sequencing of our tumor set is in progress.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1439. doi:1538-7445.AM2012-1439
Abstract 1458: Hyperthermia and radiotherapy in combination with curcumin prevent tumor cell migration and progression of breast cancer
Authors: Natarajan Mohan , Aravindan Sheeja , Herman Terence S. , Aravindan Natarajan 
Published: August 2012

Abstract
We have demonstrated that hyperthermia (HT)-induced nitric oxide regulates NF-kB, and that potentiates radiotherapy (RT)-induced breast cancer cell death. As a follow-up, in this study we investigated the efficacy of pharmacologically-safe bioactive curcumin (CUR) in combination with HT and therapeutic doses of radiation in regulating breast cancer progression. Human breast adenocarcinoma (MCF-7) cells were either mock-irradiated, exposed to 2Gy (IR), exposed to HT (43oC for 1 h) and /or treated with CUR in the presence or absence of radiation exposure. The treated/irradiated cells were examined for (i) transcriptional modulations of ninety three molecules that are directly involved in tumor invasion and metastasis; (ii) cellular localization of cMYC, p65, p53, MMP2 and MMP9; (iii) cellular migration; (iv) metabolic activity and (v) cell death. Compared to mock-IR control, QPCR profiling demonstrated a significant modulation of tumor invasion and metastasis molecules in IR exposed cells. Conversely, combinations like ‘HT with IR’, ‘CUR with IR’ or ‘CUR with HT’ robustly inhibited IR-induced and in parallel conferred IR suppressed tumor invasion and metastasis molecules in this setting. More importantly, CUR combined with both HT and IR significantly inhibited (through blocking seventy four genes) tumor invasion and metastasis molecules. Scratch wound assay demonstrated complete inhibition of tumor cell migration in CUR-HT-IR exposed cells as opposed to every stand alone and combinations investigated. Likewise, cytotoxic assay, MTT showed a significant cell killing with CUR-HT-IR exposure compared to all other groups. Furthermore, we observed significant and robust apoptotic characteristics in CUR-HT-IR exposed cells. These data together with our earlier report clearly demonstrate that CUR in combination with HT and IR may significantly inhibit breast cancer progression through combinatorial regulation of tumor invasion and metastasis molecules. The findings further imply that CUR may significantly enhance the IR dose reduction factor at least for the treatment of breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1458. doi:1538-7445.AM2012-1458
Abstract 1460: Comparison of radiosensitizing effects of several PARP inhibitors under clinical investigation
Authors: Yoo Stephen S. , Cerna David , Wilsker Deborah , Teicher Beverly A. , Coleman C. Norman 
Published: August 2012

Abstract
Targeting tumor DNA repair is an attractive strategy in selectively killing tumors while sparing normal tissues. Inhibiting Poly (ADP-ribose) polymerase (PARP) in cancers with BRCA1 and BRCA2 mutations has been shown to be a promising approach either as a single agent or in combination therapy with chemotherapeutics or ionizing radiation. To systematically compare the radiosensitizing efficacy of various PARP inhibitors we have evaluated the long-term cytotoxicity of ABT-888, AZD2281, MK4827, and BSI-201 in clonogenic survival assays in combination with ionizing radiation. For these studies we used the breast cancer cell lines MDA-MB 231 BR, a subline of MDA-MB-231 selected for its tendency to metastasize to brain (BRCA1+/−) and MX-1 (BRCA1 deletion and BRCA2 mutation). Furthermore, we have evaluated PARP inhibitors under normoxic and hypoxic conditions (21% O2 versus 0.1% O2). In MDA-MB 231 BR cells, at a clinically relevant and achievable concentration for ABT-888 (J Clin Oncol. 2009; 27(16)) and AZD2281(N Engl J Med. 2009; 361(2)), and at 1 uM MK4827 showed radiosensitizing effects under both normoxic and hypoxic conditions. BSI-201 at a clinically achievable concentration (ASCO 2010, Abstract 2012) did not exhibit radiosensitizing effects under the same conditions. When MX-1 cells were treated with BSI-201 under hypoxic conditions (0.1% O2) the cytotoxicity of BSI-201 was evident. Taken together, the results show that ABT-888, AZD2281 and MK4827 show promising radiosensitizing effects under both normoxic and hypoxic conditions whereas the cytotoxicity of BSI-201 was observed only under hypoxic conditions in BRCA1/2 mutant carrier MX-1cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1460. doi:1538-7445.AM2012-1460
Abstract 1472: Comprehensive evaluation of PEGylated gold nanorods for two photon photoluminescence image guided radiation therapy enhancement
Authors: Kumar Rajiv , Patel Janki , Korideck Houari , Berbeco Ross I. , Makrigiorgos Mike G. , Sridhar Srinivas 
Published: August 2012

Abstract
Nanoparticle formulations of gold have shown a tremendous potential in various biomedical applications. The use of high atomic number (Z) materials presents an attractive approach in enhancing the therapeutic efficacy of the radiation therapy. The high Z number for gold (Z=79) makes them an ideal candidate for radiosensitization enhancement. The ability of the anisotropic gold nanorods to sustain the resonating surface plasmon with minimal damping results in highly efficient two-photon induced photoluminescence imaging. Here we present the synthesis and in vitro characterization of PEGylated gold nanorods as efficient radiosensitizing agents which can be imaged using inherent two-photon photoluminescence without a conjugated fluorophore. We have synthesized gold nanorods with an aspect ratio of 2.5 and functionalized the surface with different ratios of methoxy and amine PEG for modulating the charge and imparting the functional groups. The cellular uptake behavior in prostate cancer cell line PC3 was studied and the results indicated a robust uptake of the amine functionalized nanorods. The quantitative estimation of the nanorods uptake was performed with BCA assay as amount of nanorods present in per microgram of protein. Two photon photoluminescence imaging also confirmed a robust cellular uptake of the amine functionalized nanorods. The radiation damage enhancement of the gold nanorods was confirmed using PC3 cells. The cells treated with gold nanorods were irradiated with kilovoltage X-rays. A γH2AX assay was used for quantitation of the DNA damage with and without nanorods as controls. The results indicated an increased highly efficient DNA damage in cells treated with gold nanorods. The outcome of this research will enable further application of targeted nanorods in advanced animal models as efficient radiation dose enhancement agents wherein two-photon photoluminescence imaging will provide a real time assessment of the therapeutic response and disease progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1472. doi:1538-7445.AM2012-1472
Abstract 1481: microRNA mediated reprograming of fibroblasts into cancer associated fibroblasts in ovarian cancer
Authors: Mitra Anirban K. , Zillhardt Marion , Hua You-Jia , Tiwari Payal , Murmann Andrea E. , Peter Marcus E. , Lengyel Ernst 
Published: August 2012

Abstract
Cancer associated fibroblasts (CAFs) are a major constituent of the tumor stroma and promote the invasion and growth of cancer cells. However, the mechanism by which cancer cells transform normal fibroblasts into CAFs is unclear. While it is clearly established that microRNAs are deregulated in cancer and are involved in cellular reprograming, it is not known if they play a role in the transformation of normal fibroblasts into CAFs. Therefore, we investigated the novel possibility of microRNA mediated reprogramming of normal fibroblasts into CAFs. Primary CAFs extracted from the metastasis of patients with ovarian cancer and normal omental fibroblasts (NOFs) extracted from non-cancer patients were profiled for microRNA expression. The functional role of microRNAs in CAFs was established by assessing their ability to promote ovarian cancer co-invasion, colony formation and tumor growth in mice. The microRNA targets were identified using gene array analysis, validated by 3′UTR luciferase reporter assay, and functionally verified both in vitro and in mouse xenografts. Comparing CAFs and NOFs we found that, in ovarian cancer CAFs miR-31 and miR-214 were downregulated while miR-155 was upregulated as compared to normal or tumor-adjacent fibroblasts. Mimicking this deregulation by transfecting microRNAs and microRNA inhibitors induced a phenotypic and functional conversion of normal fibroblasts into CAFs, and the reverse experiment resulted in the reprograming of CAFs into normal fibroblasts. The microRNA induced CAFs and patient-derived CAFs shared multiple upregulated genes highly enriched in chemokines important for CAF function. The most highly upregulated chemokine, CCL5/RANTES, was found to be a direct target of miR-214. CCL5 was functionally important for both CAFs and normal fibroblasts reprogrammed into CAFs, in vitro and in mouse xenografts. These results indicate that tumor cells can reprogram fibroblasts to become CAFs through the regulation of their microRNAs, suggesting that targeting microRNA in stromal cells, as well as in tumor cells, could be beneficial for cancer treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1481. doi:1538-7445.AM2012-1481