bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4950: miR-326 is critical for VEGF-C induced CTTN expression and metastasis of esophageal squamous cell carcinoma
Authors: Chiou Jean , Lin Chih-Chun , Jan Yi-Hua , Hsiao Michael , Su Jen-Liang 
Published: June 2012

Abstract
Esophageal cancer is a major cause of cancer deaths in most Asian countries, which is so called Asian esophageal cancer belt. Recent studies have demonstrated that, Cortactin (CTTN), a cytoskeletal protein frequently overexpressed in many types of human cancers including esophageal squamous cell carcinomas. Animal studies suggest that CTTN overexpression increases esophagus tumor aggressiveness, possibly through promotion of tumor invasion and metastasis. Vascular endothelial growth factor (VEGF)-C, ligand for the VEGF receptor-3, is critical for cancer metastasis through induces the formation of tumor-associated lymphatic vessels and facilitate the mobility of tumor cells. However, the detail molecular mechanisms involved in VEGF-C/VEGFR-3 axis-mediated tumor progression is not clear yet. Besides, the biological significance of the correlation between VEGF-C and CTTN in cancer cells is completely unknown. In this study, we found CTTN is critical for VEGF-C-mediated migration and invasion of esophageal squamous cell carcinoma (ESCC) cells. We also found that miR-326, which could target the 3’UTR of CTTN, is involved in VEGF-C-induced CTTN expression and subsequent migration and invasion of ESCC cells through an Src-dependent pathway. Taken together, our results show that VEGF-C up-regulates CTTN protein expression, resulting in enhanced cell invasion, tumorgenesis and metastasis through Src-mediated down-regulation the expression of miR-326.
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 4950. doi:10.1158/1538-7445.AM2011-4950
Abstract 4954: Comparison of miR expression patterns in plasma, serum, and cell line cMV
Authors: Pawlowski Traci L. , Yeatts Kimberly , Millis Meredith , Radebach Katrina , Kojima Yuka , Zhong Jason , Stark Adam , Kuslich Christine 
Published: June 2012

Abstract
Circulating microvesicles (cMV) isolated from either blood plasma or serum can yield genetic material sufficient for informative microRNA (miR) expression analysis. The ability to purify RNA from cMV isolated from several sources was compared, and the miR expression patterns were determined. cMV were isolated from the blood plasma and serum of men with and without prostate cancer, as well as from healthy and prostate tumor tissue and prostate cancer cell lines. Total RNA was extracted from the plasma and cell line cMV using the Qiagen miReasy kit and from the serum cMV using the ExoMir extraction method. The miR expression was determined for each source using Agilent V3 miRNA microarrays. Each sample (300 ng) was hybridized to the microarrays, and the acquired data were analyzed with the GeneSpring software package. Expression patterns for miR from cMV isolated from the plasma and serum of men with and without prostate cancer were evaluated for significant differences. Hierarchical clustering on both samples and genes demonstrated a distinct expression pattern for miR from plasma cMV compared with miR from cell line and tumor tissue cMV. These findings demonstrate that cMV isolated from the peripheral blood offer a unique and potentially clinically relevant source of miR for blood-based analysis.
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 4954. doi:10.1158/1538-7445.AM2011-4954
Abstract 499: High-level expression of the stem-cell marker CD133 in clear cell renal cell carcinoma with favorable prognosis
Authors: Kim Kyungeun , Ihm Hyojin , Ro Jae Y , Kang Sunghee , Kang Munjung , Cho Yong Mee 
Published: June 2012

Abstract
The cancer stem cell (CSC) model suggests that high levels of CSCs within a tumor are associated with poor prognosis. This study aims to investigate the expression of the stem cell marker CD133 in clear cell renal cell carcinoma (ccRCC) and its prognostic significance. The expression of CD133 was examined in 140 cases of ccRCC using immunohistochemistry. Ki-67 and Oct-4 were double immunostained with CD133 to evaluate the proliferative activity and the stemness of CD133-expressing cells, respectively. We observed CD133 expression in 45 cases (32.1%) and high levels of expression were associated with a macro-/microcystic pattern, no sarcomatoid changes, and non-metastatic disease. The Ki-67 labeling index tended to be lower in CD133-expressing ccRCCs compared with non-expressing tumors. CD133-expressing tumor cells rarely expressed Oct-4. CD133 was also highly expressed in renal intratubular neoplasia. This study demonstrated CD133 expression in pre-malignant and malignant renal diseases. We observed a high degree of CD133 expression in ccRCC with more differentiated morphology and non-metastatic disease, suggesting CD133 as a favorable prognostic marker. These results also imply that CD133 as a single marker may not be sufficient for CSC identification in ccRCC, and therefore, more specific CSC markers should be developed.
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 499. doi:10.1158/1538-7445.AM2011-499
Abstract 4996: The VEGF quadruplex-forming sequence inhibits lung cancer cell growth
Authors: Muench David , Thomas Shelia D. , Miller Donald M. , Sedoris Kara C. 
Published: June 2012

Abstract
Vascular endothelial growth factor (VEGF), commonly overexpressed in a variety of malignancies including lung cancer, is a key regulator of angiogenesis promoting tumor survival, growth, and metastasis. The promoters of several cancer-related genes, including VEGF, contain disproportionate sequences within nuclease hypersensitivity regions capable of forming quadruplex (four-stranded) DNA. The VEGF quadruplex-forming sequence (VEGF q), a polyG/polyC tract located in the proximal promoter region upstream of the transcription initiation site, has been implicated in the regulation of both basal and inducible VEGF expression. However, the biological role of this sequence remains unclear. We hypothesize that treatment of A549 non-small lung cancer cells with an oligonucleotide encoding VEGF q inhibits cell growth by decreasing VEGF expression and subsequent signaling through VEGF receptor 2 (FLK-1). To determine the biological role of VEGF on lung cancer cell proliferation, A549 cells were treated with VEGF q or the corresponding mutant sequence (MutVEGF), which lacks runs of two or more guanines. Our results demonstrate that VEGF q formed a parallel quadruplex structure and showed remarkable serum and intracellular stability. Confocal and flow cytometry analysis of cells treated with FITC-labeled VEGF q showed prominent uptake and nuclear/cytoplasmic localization in contrast to MutVEGF. Treatment of A549 cells with VEGF q caused a significant dose and time-dependent decrease in cell proliferation after 3 and 6 days (IC50&lt;5µM) as determined by MTT assay, which was not a result of cell cycle arrest. Matrigel analysis also showed a significant reduction in tumor invasiveness after 24 h with VEGF q treatment. Although uptake of VEGF q occurred in non-transformed Hs27 human fibroblast cells, no change in cell growth was evident, indicating that the anti-proliferative effects of VEGF q are specific for malignant cells. Inhibition of cell proliferation and invasion corresponded with decreased VEGF protein expression resulting in decreased FLK-1 signaling and phosphorylation of the target proteins ERK 1/2 and AKT. These results demonstrate striking growth inhibition and decreased invasion of A549 cells in response to VEGF q related to inhibition of VEGF expression and signaling through FLK-1 and have significant therapeutic implications for the treatment of non-small cell lung 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 4996. doi:10.1158/1538-7445.AM2011-4996
Abstract 5000: Tolerogenic transcription regulator Foxp3 controls the expression of immunosuppressive cytokines in melanoma cells
Authors: Olson Samuel Y. , Chen Cynthia , Marquez Diana C. , Bruhn Kevin W. , Craft Noah A. , Garban Hermes J. 
Published: June 2012

Abstract
Foxp3 is a critical transcription regulator that is found commonly expressed in a subset of immunosuppressive CD4+/CD25+ T cells characterized as regulatory T cells (Tregs) in the immune system. Foxp3 is a member of the forkhead/winged-helix family of transcriptional regulators exhibiting both, activation and repression of transcription. Foxp3 is critically important for the development and function of Tregs and the consequent definition of immune-tolerance. Ectopic Foxp3 expression has been shown to -phenotypically and functionally- convert T cells to Tregs. Recently, we have characterized the expression of Foxp3 in a variety of human and mouse cancerous cells, either in tissue or in cultured cell lines. Although of cardinal importance, the specific role and mechanisms involved in the Foxp3-mediated immunosuppressive activity remains elusive. Thus, we hypothesize that tumor-derived Foxp3 is controlling the transcriptional expression of immunosuppressive cytokines by tumor cells and inducing immunotolerance in the tumor microenvironment. We have tested this hypothesis by interrogating the well-characterized B16-C57BL/6 syngeneic mouse model of melanoma. Foxp3-expressing B16-F0 cells (B16-Foxp3+) where specifically and stably knockdown for Foxp3 expression by lentivirus-mediated shRNA (B16-Foxp3-). In order to determine the specific role and mechanisms of melanoma-derived Foxp3 in controlling the expression of immunosuppressive cytokines generated by melanoma cells, we have evaluated the differential cytokine expression profile between the B16Foxp3+ and the B16-Foxp3- cultured cells using Multiplex Bead Immunoassay, Immunoblotting Assay of Proteins and Semiquantitative RT-PCR. Our results demonstrated that the suppression of expression of Foxp3 in melanoma cells showed a significant downregulation of a selected group of immunosuppressive cytokines, in particular IL-4, IL-6, IL-10, IL-12, TNF-alpha and GM-CSF. In contrast, Foxp3 did not have an appreciable effect on the expression of IL-1, IL-2, IL-5, and IFN-gamma. Altogether, our data suggest the specific role of tumor-derived expression of FOXP3 in the control of the expression of tolerogenic/immunosuppressive cytokines secreted by melanoma cells to the tumor microenvironment. Furthermore, selective suppression of Foxp3 expression and/or activity in cancerous cells may help to develop better and more effective targeted immunotherapy as treatment for malignant melanoma.
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 5000. doi:10.1158/1538-7445.AM2011-5000
Abstract 5008: Epidermal growth factor downregulates expression of neutrophil gelatinase-associated lipocalin (NGAL) through E-cadherin in pancreatic cancer cells
Authors: Tong Zhimin , Chakraborty Subhankar , Sung Bokyung , Kaur Sukhwinder , Aggarwal Bharat B. , Mani Sendurai , Bresalier Robert S. , Batra Surinder , Guha Sushovan 
Published: June 2012

Abstract
Background: Neutrophil gelatinase-associated lipocalin (NGAL), a member of the lipocalin family, is a secreted protein that is upregulated in multiple cancer types. Our group previously reported that NGAL overexpression significantly blocked invasion and angiogenesis in pancreatic ductal adenocarcinoma (PDAC). We and others have also demonstrated loss NGAL expression in advanced stages of PDAC. However, little is known about mechanisms that regulate NGAL expression in PDAC. As EGF-EGFR axis is significantly upregulated in PDAC, we examined EGF-mediated NGAL regulation in these cells.
Methods: NGAL-positive AsPC-1 and BxPC-3 cells were used as model system. Quantitative RT-PCR, western blot analysis, and immunofluorescence studies were used to investigate EGF-mediated effects on NGAL expression. E-cadherin expression was manipulated using lentiviral overexpression or shRNA constructs. NGAL promoter activity was assessed by luciferase-reporter assay and electrophoretic mobility shift assay (EMSA).
Results: NGAL expression was positively associated with tumor differentiation and was significantly downregulated after EGF treatment along with a concomitant reduction of E-cadherin expression in PDAC cells. E-cadherin downregulation was partly through the EGF receptor (EGFR)-dependent MEK1/2-ERK1/2 signaling pathway, which was demonstrated using pharmacologic inhibitors of EGFR (AG1478) and MEK1/2 (U0126 and PD98059). In addition, E-cadherin downregulation reduced NGAL expression in PDAC cells, whereas overexpression of E-cadherin led to increased NGAL expression and partly rescued inhibition of NGAL expression by EGF. Furthermore, EGF in part through E-cadherin reduced NGAL promoter activity by blocking NF-κB activation.
Conclusion: We demonstrated for the first time that EGF potently blocked NGAL expression in PDAC cells. This effect is partly mediated through activation of the EGFR-MEK1/2-ERK1/2 signaling pathway, which in turn downregulated E-cadherin with a subsequent reduction in NF-κB activation. Our findings illustrate a novel mechanism by which EGF regulates NGAL expression in PDAC.
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 5008. doi:10.1158/1538-7445.AM2011-5008
Abstract 5056: HuGAL-FR21, a humanized monoclonal antibody to Fibroblast Growth Factor Receptor 2, effectively inhibits the growth of gastric tumor xenografts
Authors: Park Hangil , Wang Lihong , Chhim Sophea , Ding Yi , Kim Jin 
Published: June 2012

Abstract
The family of 22 fibroblast growth factors include potent mitogenic and angiogenic factors believed to play a role in the growth of many tumors. The various FGFs bind to only four tyrosine kinase signaling receptors, Fibroblast Growth Factor Receptors 1-4 (FGFR1-4). FGFR2 is a major cellular receptor for FGF2 (basic FGF), FGF7 (keratinocyte growth factor, KGF) and FGF10; and mutation or overexpression of FGFR2 is associated with a number of cancers, notably endometrial cancer and gastric carcinoma. In this study, we explored the therapeutic potential of the HuGAL-FR21 humanized monoclonal antibody (mAb) derived from our blocking anti-FGFR2 mAb, GAL-FR21.
We previously showed that GAL-FR21 binds to only the FGFR2IIIb isoform of FGFR2, which is expressed on epithelial tissues and thus more commonly on carcinomas. Using well-established humanization techniques, GAL-FR21 was humanized to create HuGAL-FR21, which binds human FGFR2IIIb with at least as high affinity as GAL-FR21. HuGAL-FR21, like GAL-FR21, also bound well to monkey and mouse FGFR2IIIb, facilitating study of this mAb in animal models. In functional assays, HuGAL-FR21 inhibited binding of FGF2, FGF7 and FGF10 to FGFR2IIIb as completely as GAL-FR21. And HuGAL-FR21 inhibited FGF7 or FGF10-induced proliferation of the Ba/F3 cells transfected with FGFR2IIIb, actually better than GAL-FR21. Finally, HuGAL-FR21 inhibited phosphorylation of cellular FGFR2 induced by FGF7 and FGF10 as well as GAL-FR21.
There are two major types of gastric cancer, well-differentiated and poorly differentiated, and published results show that many poorly differentiated tumors overexpress FGFR2, which is in fact the oncogenic driver for these tumors. We therefore tested the ability of HuGAL-FR21 to inhibit growth of xenografts of two cell lines, SNU-16 and OCUM-2M, derived from FGFR2-overexpressing, poorly differentiated gastric tumors. HuGAL-FR21, administered i.p. at 2.5 or 5 mg/kg twice per week, strongly inhibited the growth of established xenografts of both these cell lines. We conclude that FGFR2 is a promising molecular target, and that HuGAL-FR21 is a viable clinical candidate for the treatment of gastric and possibly other cancers.
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 5056. doi:10.1158/1538-7445.AM2011-5056
Abstract 5071: Application of a novel protein biomarker discovery platform to identify biomarkers for improved diagnosis of prostate cancer
Authors: McAndrew Michael , Wheeler Colin , Koopmann Jens , Uddin Ezam , Agashe Pooja , Workman Nick , Anson John 
Published: June 2012

Abstract
The issues surrounding the use of prostate-specific antigen (PSA) in the diagnosis of prostate cancer (PCa) are well documented and the need for a molecular diagnostic test with greater discriminatory power is clear. The development of autoantibodies associated with prostate cancer has also been described. In general, the appearance of such antibodies can precede disease symptoms by many years, making them attractive as potential biomarkers for early diagnosis.
We have developed a unique “functional protein” array platform which utilises correctly folded proteins and has the ability to display native, discontinuous epitopes. The reproducibility of the platform is exceptionally good, making it possible to screen statistically meaningful numbers of samples. Following on from a successful pilot study, where panels of autoantibody biomarkers exhibiting a specificity and sensitivity for PCa superior to PSA were identified using the platform1, we have validated this approach in a large-scale analytical study.
The current analytical study involving approximately 1800 samples was primarily designed to identify panels of biomarkers with the ability to distinguish between PCa (n=400) and control samples from patients with benign prostatic hypertrophy (BPH, n=406). BPH can present with similar symptoms to PCa and can also result in elevated PSA levels. Additional sample cohorts included prostatitis, other cancers of various origin and non-disease/healthy controls (n=400). All samples were age, ethnicity and gender matched.
The products of 1296 unique genes (1330 proteins), chosen for their association with disease, signal transduction and cancer autoimmunity, are immobilized on each array. Serum samples (n=1781) were analysed using the arrays as described previously1. Data were split into test and training sets and analyzed with several classification algorithms to identify classifiers which would successfully distinguish case from control samples. Data were repeatedly split into test and training sets and analysis cycles repeated until a stable set of classifiers was identified. At the time of writing, data is still under analysis; however, early indications are encouraging and suggest that panels of biomarkers with a performance that significantly exceeds that of PSA may be identified. Full results of the study will be presented.
1 McAndrew et al Development of a panel of biomarkers for the diagnosis of prostate cancer (2010) Molecular Diagnostics in Cancer Therapeutic Development conference
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 5071. doi:10.1158/1538-7445.AM2011-5071
Abstract 5093: The molecular genetics of radiogenic breast cancer
Authors: Wade Mark A. , Batey Michael A. , Rand Vikki , Russell Lisa J. , Bacon Chris M. , Allan James M. , May Felicity E.B 
Published: June 2012

Abstract
The aim of this study is to identify the underlying molecular genetic mechanisms of radiation induced breast carcinogenesis. Studies have shown that women exposed to ionising radiation at a young age are more at risk of developing breast cancer than older women exposed to the same level of radiation. Higher levels of estrogen are present in young women and estrogen has a known transforming effect on breast epithelial cells. One hypothesis suggests that radiation and estrogen synergise to drive breast epithelial cell transformation. We have developed an in vitro model of radiation-induced breast epithelial cell transformation in order to investigate genetic alterations associated with breast cell transformation.
The immortalised, non-transformed breast epithelial cell line MCF-10A was exposed to fractionated doses of X-rays in the presence or absence of exogenous estrogen. We have shown that radiation treated cells display evidence of transformation, including loss of contact inhibition, increased cell invasion, disrupted acini formation and tumor formation in immunocompromised Rag2−/− γ−/− mice. Analysis of radiation treated cells by SNP array karyotyping identified focal gene deletion (EP300 and OCT-1) and amplification (c-MYC) which may be linked to radiation-induced breast cell transformation. Gene deletion and amplification was confirmed by Fluorescent In Situ Hybridization analysis and alterations in expression have been confirmed by western analysis.
EP300 is a transcriptional co-activator and a putative tumor suppressor. Somatic mutations in EP300 have been found in solid tumours and the gene is located in a region of chromosome 22 affected by loss of heterozygosity in numerous cancers. Oct-1 encodes an octamer binding transcription factor that has been associated with regulating DNA damage response through interactions with BRCA1 and GADD45. c-MYC is a known proto-oncogene that encodes a transcription factor involved in cell proliferation, cell cycle regulation and apoptosis.
Analysis of our in vitro model of radiation-induced breast epithelial cell transformation has identified genetic alterations that have established roles in mediating cellular response to DNA damage and which might be key events in the development of radiogenic breast 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 5093. doi:10.1158/1538-7445.AM2011-5093