bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4031: Elevated expression of microRNAs in pancreatic carcinomas is correlated with poor prognosis
Authors: Greither Thomas , Grochola Philipp , Udelnow Andrej , Lautenschläger Christine , Eckert Alexander W. , Würl Peter , Taubert Helge W. 
Published: February 2011

Abstract
Pancreatic cancer is the eighth most common cancer and has an overall 5-year survival rate lower than 10 %. Due to their ability to regulate gene expression, microRNAs can act as oncogenes or tumour-suppressor genes and so have garnered interest as possible prognostic and therapeutic markers during the last decade. However, the prognostic value of microRNA expression in pancreatic cancer has not been thoroughly investigated.
We measured the levels of miR-155, miR-203, miR-210, miR-216, miR-217 and miR-222 by quantitative RT-PCR in a cohort of 56 microdissected pancreatic ductal adenocarcinomas (PDAC). These microRNAs were chosen as they had previously been shown to be differentially expressed in pancreatic tumours compared to normal tissues.
The possible association of microRNA expression and patients’ survival was examined using multivariate Cox's regression hazard analyses. Interestingly, significant correlations between elevated microRNA expression and overall survival were observed for miR-155 (RR = 2.50; p = 0.005), miR-203 (RR = 2.21; p = 0.017), miR-210 (RR = 2.48; p = 0.005) and miR-222 (RR = 2.05; p = 0.035). Furthermore, tumours from patients demonstrating elevated expression levels of all four microRNAs possessed a 6.2-fold increased risk of tumour-related death compared to patients whose tumours showed a lower expression of these microRNAs. This study provides the first evidence for an oncogenic activity of miR-155, miR-203, miR-210 and miR-222 in the development of pancreatic cancer as has been reported for other tumour types. Furthermore, the putative target genes for these microRNAs suggest a complex signalling network that can affect PDAC tumourigenesis and tumour progression.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4031.
Abstract 4038: Identification of microRNAs involved in colorectal cancer progression
Authors: Gariboldi Manuela , Lampis Andrea , Sokolova Viktorija , Pizzamiglio Sara , Reid James F. , Zanutto Susanna , Bertan Claudia , Perrone Federica , Verderio Paolo , Leo Ermanno , Pierotti Marco 
Published: February 2011

Abstract
MicroRNAs (miRNAs) are negative regulators of gene expression during various basic biological processes such as development, cellular differentiation, proliferation and apoptosis. Altered expression of miRNAs is associated with development and progression of various human cancers, where they mainly regulate the translation of oncogenes and of tumor suppressor genes. In colorectal cancer (CRC), these regulators complement the Vogelstein multi-step model of pathogenesis and have the potential of becoming a novel class of tumor biomarkers and of therapeutic targets.
To identify miRNAs deregulated in CRC that could be used for diagnosis and prognosis, we examined by Quantitative Real-Time PCR the global expression of 378 mature miRNAs in 40 CRCs and their paired non-tumor tissues. Non-parametric confidence intervals for each miRNA where calculated and twenty-four miRNAs whose expression is significantly altered in tumors respect to the normal tissue where identified (Bonferroni P&lt;0.05). Part of them, such as miR-21, miR-31 or miR-183 has been previously reported in CRC. MiR-135b, with the highest expression in the tumors is a promising tumor related miRNA. We subsequently evaluated the association of the 24 miRNAs with different clinical characteristics of the samples such as tumor site, disease status, TNM staging, expression of CEA and CA199, and presence of alterations in the molecular markers of CRC progression (APC, TP53, KRAS and loss of 18q arm). MiRNAs differently expressed among colon and rectum or higher in late stage tumors were identified. Expression levels of miR-31 were correlated to that of CA199 and miR-18a, miR-21 and miR-31 were associated with mutations in APC gene. Gene target predictions of these miRNAs pointed mainly the pathways related to CRC progression such as Wnt/TGFb, MAPK and TP53 signaling pathways. In addition, many of these miRNAs were predicted to target genes in the Vogelstein model.
This study has identified promising miRNAs to be used as biomarkers (for example in plasma) in diagnostic and prognostic settings of CRC. And, in addition it shows their direct involvement in the regulation of driving events of CRC carcinogenesis which should be explored further in biological models.
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 4038.
Abstract 4041: Lipofection of the designed plasmid expressing microRNA-7 has antitumor effect in gefitinib-resistant lung adenocarcinoma in vivo
Authors: Rai Kammei , Takigawa Nagio , Ito Sachio , Kashihara Hiromi , Ichihara Eiki , Kiura Katsuyuki , Yasuda Tatsuji , Shimizu Kenji , Tanimoto Mitsune 
Published: February 2011

Abstract
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is strikingly effective in tumors harboring activating EGFR mutations since the tumor cells depend on “oncogene addiction” to EGFR signaling that is inhibited effectively by a change in the affinity of ATP and EGFR-TKI to ATP binding site of mutated EGFR. Unfortunately, approximately 50% of patients who responded to EGFR-TKI acquired the resistance to EGFR-TKI due to additional mutation T790M in EGFR. Since T790M mutation restores the affinity of ATP to the ATP binding site of mutated EGFR, the oncogene addiction by EGFR pathway is presumed to sustain in the gefitinib-resistant cells harboring T790M mutation. MicroRNA-7 (miR-7) is predicted to suppress EGFR expression by targeting three sites in the 3′-untranslated region (UTR) of EGFR mRNA in silico. It was proved to be a potential tumor suppressor in EGFR-TKI-resistant lung adenocarcinoma cells by targeting the 3′-UTR of EGFR mRNA (#1396: Annual AACR meeting, 2009). The object of this experiment is to elucidate whether the miR-7 is effective or not in vivo. We established gefitinib-resistant lung adenocarcinoma cell line (RPC-9) carrying a secondary mutation T790M (Cancer Res 67: 7807-14, 2007) from gefitinib-sensitive EGFR mutated (delE746-A750 in exon 19) PC-9 cell line. RPC-9 cells (2 × 106) were injected s.c. into the backs of the female athymic mice at 7 week of age. At 1 week after injection, the mice were randomly assigned into one of three groups (five mice per group) that received either 3 μg/body of miR-7 expressing plasmid, control plasmid or mock using cationic liposome by direct injection. Marked tumor regression was observed within 2 weeks, and 60% of xenograft tumors disappeared. The immunostaining of residual tumor showed the suppression of EGFR expression on the tumor cells. To our knowledge, this is the first report to show the dramatic effect of miR-7 against EGFR-TKI resistant lung cancer model in vivo.Tumor size after treatment with miR-7 Day 1Day 5Day 11Day 18miR-710094.9445.7914.62*Control100144.0103.3242.6*tumor size(%), *p=0.00253, tumor diminished macroscopically in miR-7 group(3/5)
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 4041.
Abstract 4043: Targeting microRNA for the prevention and treatment of prostate cancer
Authors: Kumar Raj , Koduru Srinivas , Srinivasan Sowmyalakshmi , Rohr Jurgen , Damodaran Chendil 
Published: February 2011

Abstract
MicroRNAs (miRs) are small 20-24 nucleotide non-coding RNA molecules that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both stability and translation of mRNAs. The expression and activity of miRs vary in specific cell types and disease states. Several groups have investigated and determined the strong association between specific expression patterns of miRs and various stages of prostate cancer. Recent findings have highlighted the strong correlation between overexpression of miRs (21, 210, 125b, 221 and 222) and cancer development and progression. In this study we determined whether modulation of miR expression using a natural compound suppresses PCa growth. Previously we published that psoralidin inhibits prostate tumor growth and progression in both in vitro and in vivo models. While studying the expression patterns of a panel of miRs in control and psoralidin treated prostate cancer cells we found that psoralidin significantly inhibits expression of two specific miRNAs, miR-21 and miR-210 in turn resulting in the inhibition of EGFR-, MAPK- and PI3K-mediated prosurvival signaling and induction of JNK-mediated apoptosis in prostate cancer cells. Currently, we are overexpressing and inhibiting these two miRs to determine whether it modulates psoralidin-mediated effects on prostate cancer cells. The outcome of our study may provide encouraging data that may enable us to exploit miRs as therapeutic targets for the treatment of various malignancies.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4043.
Abstract 4045: Restoring miR-15a/16 in the NZB mouse model of chronic lymphocytic leukemia reduces disease and enhances drug sensitivity
Authors: Salerno Erica , Yuan Yao , Coffman Frederick D. , Scaglione Brian J. , Brown Brian D. , Bonci Desiree , Raveche Elizabeth S. 
Published: February 2011

Abstract
Alterations in the human 13q14 genomic region containing the microRNAS, mir-15a and mir-16-1 are present in a majority of human chronic lymphocytic leukemia (CLL). We have previously found the development of CLL in the New Zealand Black (NZB) murine model to be associated with a point mutation in the primary mir-15a/16-1 region, as well as a decrease in both mature miR-16 and miR-15a levels. Addition of exogenous miR-15a and miR-16 led to an accumulation of cells in G1 in both normal B cell and NZB-derived malignant B-1 cell lines. However, the NZB line had a significantly greater G1 accumulation, suggesting a restoration of cell cycle control upon exogenous miR-15a/16 addition. Our experiments demonstrated a reduction in protein levels of cyclin D1, a miR-15a/16 target and cell cycle regulator of G1/S transition, in the NZB cell line following miR-15a/16 addition. These miRNAs were shown to directly target the cyclin D1 3′UTR using a GFP lentiviral sensor. In vivo restoration of NZB with a miR-16-producing lentiviral vector resulted in the depletion of endogenous-transduced malignant aneuploid B-1 cells. In addition, experimentally increasing miR-16 in either a drug-resistant malignant NZB B-1 cell line or ex vivo splenic NZB B-1 cells augmented apoptosis induction by the following agents: genistein, a soy isoflavone tyrosine kinase inhibitor; nutlin, an MDM2 antagonist; and 2-fluoroadenine-9-B-D-arabinofuranoside, a purine nucleotide analog. Our data support a role for miR-16 in apoptosis induction, either alone, or in synergy with chemotherapeutic agents to increase their efficacy in murine CLL cells.
This research was funded in part by the NJCCR pre-doctoral fellowship awarded to E.S.
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 4045.
Abstract 4047: Mining of microRNA signatures in endometrial cancer
Authors: Wong Yick Fu , Cheung T.H. , Yim S.F. , Lau T.S. , Chan L.K.Y. , Ng S.W. , Chung T.K.H. 
Published: February 2011

Abstract
[Introduction] Endometrial cancer has now become the most common gynaecologic malignancy worldwide. About 80-90 % of endometrial cancer are endometrioid endometrial adenocarcinomas (EEC). MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression by inducing cleavage of the targeted messenger or by inhibiting translation. Our entire study was to mine miRNA signatures involved in EEC tumorigenesis and progression. Here we report a part of the results that is on miRNAs associated with endometrial cancer progression in vitro.
[Methods] We examined the expression of 365 mature miRNAs by real-time RT-PCR based plate assays in 52 EEC including 30 advanced- and 22 early-stage tumors, and compared that to 30 normal counterparts. To know about the deregulated miRNAs associated with endometrial cell behavior, miRNA inhibitor and pre-miRNA were used to inhibit up-regulated miRNA and induce down-regulated miRNA in highly invasive endometrial cancer cell line HEC-1A cells. Quantitative TaqMan RT-PCR was performed to measure miRNA levels in cells before and after treatment, respectively. Migration and invasion assays were carried out to evaluate effects of those deregulated miRNAs on invasion of endometrial cancer cells in vitro.
[Results] Supervised clustering analysis of global miRNA expression in endometrial caner and normal control identified 17 miRNAs up-regulated and 2 miRNAs down-regulated, respectively, in EEC. When the miRNA expression profiles in advanced stage tumors were compared to those in early stage tumors, 6 miRNAs were significantly over-expressed and one miRNA under-expressed in advanced stage tumors. Cell migration and invasion assay showed the ability of cell migration and invasion was significantly inhibited by anti-miR-7, anti-miR-194, anti-miR-449b and pre-miR-204 in HEC-1A cells in vitro.
[Conclusion] Unique miRNA signatures seem to be existed in ECC. Deregulated miRNAs miR-7, miR-194, miR-204 and miR-449b might mediate endometrial cancer progress. These miRNAs are potentially to be developed as novel diagnostic and/or prognostic molecular markers as well as candidate therapeutic targets of EEC.
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 4047.
Abstract 4062: Human peptide deformylase expression and activity in various cancers
Authors: Reindl Katie M. , Sorensen Karly 
Published: February 2011

Abstract
Human peptide deformylase (hsPDF) expression has been detected in human cells, but it is unclear if the enzyme is functional. Our hypothesis is that hsPDF is functional in human cells. The objectives of this study were to 1) quantify hsPDF transcript levels in normal and cancerous cells and tissues and 2) determine the effects of hsPDF inhibition on the proliferation of normal and cancerous cells. Quantitative real-time PCR was used to measure hsPDF mRNA levels in normal and cancerous cell lines and tissues. Increases in hsPDF mRNA expression were seen in most cancer cell lines compared to the normal. hsPDF was up-regulated in most, but not all, cancer tissues compared to the normal, with the greatest differences observed in breast, colon, and lung tissues. Various cancer and normal cell lines were treated with increasing concentrations of a known PDF inhibitor, actinonin, and cell proliferation was assessed. The antiproliferative effects of actinonin were greater in prostate, colon, and breast cancer cell lines than in the normal cell lines. These results suggest that hsPDF is up-regulated in certain cancers, and that it may play an active role in the proliferation of human cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4062.
Abstract 407: Molecular characterization of invasive subpopulations from an esophageal squamous cell carcinoma cell line
Authors: Wu I-Chen , Chen Yu-Kuei , Wu Deng-Chyang , Wu Ming-Tsang 
Published: February 2011

Abstract
Background: Once diagnosed, esophageal cancer has a very low overall 5-year survival rate. This study investigates the mechanisms behind the invasiveness and severity of esophageal squamous cell carcinoma (ESCC). Materials and Methods: We used Transwell Invasion Chamber to subdivide one Taiwanese esophageal squamous cancer cell line CE81T/VGH into sublines (CE81T-0, CE81T-1, CE81T-2, CE81T-3, and CE81T-4) in four rounds of assays, identified the most invasive ones, and measured various factors related to their invasiveness. Results: CE81T-1, CE81T-2, CE81T-3, and CE81T-4 sublines were significantly more invasive than the parental cell (CE81T/VGH) and CE81T-0 subline. CE81T-1 and CE81T-4, the sublines we chose to study further, had significantly greater colony forming ability (3.5-2.7 fold) and wound migrating activity (1.95-2.6 fold) than the parental cell in vitro (p&lt; 0.01). They also displayed greater tumorigenesis in immunodeficiency BALB/c Foxlnn mice than the parental cell. We found an inverse correlation between expression of TIMP-2 (tissue inhibitor of metalloproteinase-2) and invasive ability and a significant positive correlation between expressions of MMP-1 (matrix metalloproteinase-1), vimentin, and p-Src (pY416) in these cell lines and their invasiveness (all p&lt; 0.05). Conclusion: The subline model may be used to study the molecular and genetic mechanisms underlying the invasion and metastasis of ESCC.
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 407.
Abstract 4070: Mutant tristetraprolin enhances growth factor downregulation and inhibition of cell growth in malignant glioma
Authors: Suswam Esther A. , Shacka John J. , Zhang Xiaowen , Lu Liang , Li Xuelin , Zheng Lei , Si Ying , King Peter H. 
Published: February 2011

Abstract
Background: Tristetraprolin (TTP) negatively regulates short-lived mRNAs by binding to AU-rich elements in the 3′ untranslated region (3′UTR). A number of mRNA targets, including vascular endothelial growth factor (VEGF), and interleukin (IL)-8, play an important role in tumor progression. We have shown previously that TTP downregulates IL-8 and VEGF in malignant glioma (MG) cells via RNA destabilization. In primary glioblastoma tumors, TTP is heavily phosphorylated which may render the protein less active. Hypothesis: We postulate that the destabilizing effect of TTP on target growth factor mRNAs is held in check by hyperphosphorylation which leads to altered subcellular localization and protein stability. Methods: Wild-type TTP and two mutant forms in which select serines were exchanged with alanines were cloned with a Flag epitope into pTRE2 and pEGFP vectors. U251 Tet On MG cells were transfected with pTRE2–TTP plasmids to produce stable clones. TTP expression was induced using doxycycline. Cellular location was assessed by fluorescence microscopy and Western blotting. Protein stability was measured by assessment of TTP levels following cycloheximide treatment. VEGF and IL-8 mRNA and protein levels were measured by qRT-PCR and ELISA. For assessment of RNA half-lives, cells were treated with actinomycin D. Cell growth, proliferation and cell viability were assessed using biochemical assays, soft agar, and Trypan Blue method. Results: Both IL-8 and VEGF mRNA levels were significantly lowered in the mutant TTP clones compared to wild-type. Half-lives of these mRNAs were also shortened, and ELISA analysis showed a correspondingly greater decrease in protein expression. There was a marked impact on cellular phenotype with greater inhibition of proliferation and loss of cell viability. A Soft agar colony formation was decreased by five-fold in mutant clones versus wild-type and a greater than ten-fold decrease versus the parent cell line. With TNF-α, there was a significant shift of mutant TTP to the nuclear compartment compared to WT TTP. Treatment with cycloheximide revealed that the WT TTP was less stable compared to dephosphorylated mutant. Conclusion: Removal of key serine residues from TTP enhances its function as an RNA destabilizer of VEGF and IL-8 mRNs and as a negative regulator of tumor cell growth in MG.
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 4070.
Abstract 4072: Overexpression of FOXO1 increased sensitivity to Tamoxifen in MCF7 cells, and is associated with estrogen receptor α (ERα) expression
Authors: Shang Xiying , Wu Yanyuan , Sarkissyan Marianna , Koeffler H Phillip , Vadgama Jaydutt V. 
Published: February 2011

Abstract
The transcription factor FOXO1, which belongs to the Forkhead family, plays an important role in promoting cellular apoptosis in cancer cells. Clinical data from our laboratory suggested that breast cancer subtypes vary in their FOXO1 expression, and this difference may contribute to differential response to drug therapy. Our goal is to investigate the mechanisms associated with FOXO1 expression and anti-estrogen therapy in ERα positive breast cancer cells (MCF7 cells). First, we examined the FOXO1 expression in different Akt transfected clones, and the results showed that FOXO1 expression decreased in MCF7/AA cells (active Akt), but significantly increased in MCF7/DN cells (dominant negative Akt). Next, we examined FOXO1 expression in the Tamoxifen resistant cells (MCF7/TAMR cells). FOXO1 expression decreased in MCF7/TAMR cells, compared to MCF7/wildtype cells. To further explore the association between FOXO1 expression and the response to Tamoxifen in MCF7 cells, we established FOXO1 overexpression clones (MCF7/FOXO1), and checked the cell growth rate under Tamoxifen treatment. The results showed that MCF7/FOXO1 cells had better response to Tamoxifen, when compared with the vector transfected cells (MCF7/pcDNA3). Since Tamoxifen is an antagonist of the ERα receptor, we examined the relationship between ERα and FOXO1. We used the ERα knockdown cells (MCF7/antisense hERα cells) as a model, and found the high Akt, but low FOXO1 expression in these cells. In summary, our study demonstrates that FOXO1 is inversely related to Akt and ERα and improves sensitivity of Tamoxifen treatment in MCF7 breast cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4072.