bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5103: Analysis of the role of “ATM” through “omics” analysis
Authors: Cheema Amrita K. , Jung Mira , Timofeeva Olga , Varghese Rency , Ressom Habtom , Dritschilo Anatoly 
Published: February 2011

Abstract
The human genetic disease, ataxia-telangiectasia (AT) is characterized by exquisite radiation sensitivity, neurological degeneration, immune deficiencies, genetic instability and predisposition to cancer. Furthermore, cells from patients with AT show disruption of the DNA damage response (DDR), a global signaling network that senses damage and coordinates cellular responses that include cell cycle regulation, transcription, DNA repair processes and apoptosis. Previously, AT5BIVA cells have been was established by SV40 immortalization of fibroblasts derived from an AT group D patient. We derived ATCL8 cells line was then derived by transfecting AT5BIVA with a vector carrying expressing the full- length wild type ATM. ATCL8 cells are and was found to be less sensitive to radiation resistant (D0=1.7 Gy) as compared tothan are the parental cell line AT5BIVA cells (D0=0.7 Gy).
We have used a systems approach to understand compare the baseline changes that occur at the genomics, proteomics and metabolomic levels in these two near isogenic cell lines and integrate the information to understand the correlation. The. mMicroarray analysies wereas carried performed out to compare investigate basal level changes in gene expression. between AT5BIVA and ATCL8. The p Proteomics analysies for the same system was donewere performed using a 2-D gels and mass spectrometry approach. Finally, metabolomic profilesing was performed were obtained using UPLC-ESI-TOF mass spectrometry followed by multivariate data analysis using (SIMCA-P and random forest) software. The mMetabolites which were found observed to be significantly different in ATCL8 as compared to AT5BIVA were then subjected to functional pathway analysies using the ingenuity software. The proteomics and the microarray data were then scored for the presence of proteins and genes which were a part of the predominant signaling pathways in the two cell lines as determined by metabolomic analysis.
The model system used in this study involves studyingof basal level changes in expression resulting from perturbations in a single gene and our results demonstrate the feasibility of such an the approach to correlate the changes found at all three levels of expression. The findings will be discussed in the context of the “AT” phenotype will be discussed.
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 5103.
Abstract 5133: Microtentacles and invadopodia: Functionally distinct plasma membrane protrusions of metastatic breast tumor cells separated mechanistically by c-Src
Authors: Balzer Eric M. , Whipple-Bettes Rebecca , Cho Edward H. , Matrone Michael A. , Mueller Susette C. , Martin Stuart S. 
Published: February 2011

Abstract
During metastasis, invading cells produce various actin-based membrane protrusions that promote directional migration and proteolysis of extracellular matrix (ECM). Our recent discovery of a filamentous actin (F-actin) component within thin tubulin-based microtentacle (McTN) protrusions in suspended MDA-MB-231 tumor cells prompted an investigation of whether these extensions are structural or functional analogs of invadopodia. We show here that MDA-MB-231s are capable of producing invadopodia and McTNs, both of which contain F-actin. Invadopodium formation was enhanced by expression of a constitutively-active c-Src kinase, and repressed by expression of dominant negative, catalytically inactive form of c-Src. In contrast expression of inactive c-Src significantly increased the McTN formation. Additionally, direct inhibition of c-Src with the SU6656 inhibitor compound significantly enhanced McTN formation, suppressed the appearance of F-actin cores and phospho-cortactin foci, and completely blocked focal degradation of extracellular matrix. These results identify McTNs and invadopodia as separate structures that provide unique and sequential contributions to metastatic progression, namely endothelial attachment and invasion, respectively.
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 5133.
Abstract 5138: The regulation of CD44 expression in malignant brain tumor cells
Authors: Raines Timothy A. , Debinski Waldermar , Martin Patrick M. 
Published: February 2011

Abstract
Glioblastoma multiforme (GBM) is a highly aggressive brain tumor that demonstrates a high growth rate and the capacity to invade surrounding brain tissue. These characteristics result in a dismal prognosis for GBM patients. Current treatment options for GBM tumors involve surgical resection followed by radiation and/or chemotherapy. Disappointingly, GBM tumors are or become resistant to radiation and chemotherapy, and the invasiveness of GBM precludes curative removal of the tumor. GBM cells infiltration has been associated with the transmembrane glycoprotein, CD44, which is the principle cell surface receptor for hyaluronic acid (HA). The molecular mechanisms that regulate CD44 in GBM are not fully understood. However, CD44 protein expression has been associated with an AP-1 transcription factor, fos related antigen 1 (Fra-1), in another aggressive cancer, mesothelioma. Therefore, we investigated the regulation of CD44 expression in human glioma cells by Fra-1. Human GBM cell lines, U-251 MG, U-1242 MG, and A-172, were exposed to either epidermal growth factor (EGF, 20 ng/ml) or hepatocyte growth factor (HGF, 50 ng/ml) at varying time points and Western blot analysis was used to determine the protein expression of CD44 and Fra-1. CD44 and Fra-1 expression levels increased with longer exposures (4 to 24 hr) to EGF and HGF. To determine whether Fra-1 takes part in the regulation of CD44 expression, we utilized transient gene knockdown using siRNA directed against fra-1. fra-1-siRNA decreased Fra-1 expression in EGF- and HGF-treated GBM cells. Following EGF stimulation and fra-1-siRNA treatments, CD44 expression also decreased. However, HGF stimulation of fra-1-siRNA treated GBM cells showed no change in CD44 expression. These data suggest that Fra-1 regulation of CD44 expression is growth factor-specific. To investigate whether CD44-mediated cell adhesion is promoted by the expression of Fra-1, we analyzed GBM cell adhesion to HA. U-251 MG and U-1242 MG cell lines demonstrated an increase adherence to HA after growth factor simulation, 4hr and 24 hr respectively. This data is comparable to the initial western blot analysis of the GBM cells after growth factor simulation. However, A-172 cells did not adhere to HA regardless of growth factor stimulation. These data suggest that CD44 binding to HA is cell line specific. Taken together, our results suggest that CD44-mediated HA binding of GBM cells can be regulated by Fra-1 expression.
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 5138.
Abstract 5158: Differentiation of glioblastoma stem-like cells induced by retinoic acid
Authors: Ying Mingyao , Sang YingYing , Lal Bachchu , Sun Peng , Laterra John , Xia Shuli 
Published: February 2011

Abstract
We investigated the molecular and cellular responses of glioblastoma stem-like cells (GBM-SCs) to all-trans retinoic acid (RA)-induced differentiation. Four GBM-SC lines were used. Under neurosphere culture conditions, GBM-SCs grow as non-adherent neurospheres. RA (10 μmol/l) treatment for 48 h induced cells to adhere to culture surfaces and generate processes. RA inhibited G1/G0 to S transition, decreased cyclin D1 expression (50%) and increased p27 expression (2-fold). Immunofluorescence staining, western blot and flow cytometry analyses showed that RA induced the expression of differentiation markers Tuj1 and GFAP and inhibited nestin expression. RA treatment reduced the number of cells expressing CD133 from 44% to 10%. We measured the effects of RA on neurosphere number and size. RA treatment dramatically decreased (∼90%) the number of neurospheres &gt; 50 um diameter. Clonogenic assay showed that RA reduced the colony formation ability of GBM-SCs in soft agar. Microarray analysis was performed to determine the global gene expression profile of RA-induced GBM-SC differentiation. Data were analyzed using Significance Analysis of Microarrays (SAM) and the false discovery rate was set at 20%. Approximately 350 genes were altered after RA treatment for 48h; ∼20% were down-regulated and 80% were up-regulated. We selected 18 candidates and validated with real-time PCR. All 18 candidates exhibited the same pattern of up- or down-regulation by RA. Western blot analysis for some candidate gene products also confirmed the alteration by RA at the protein level. A web-based (portal.genego.com) molecular pathway analysis of RA-induced gene expression profiling identified several pathways altered during RA-induced differentiation process. The most prominent of them was Notch signaling. Notch pathway members Delta-like 1 (DLL1), Notch 1, NCID, NEXT and Notch 1 precursor were found to be down-regulated by RA. Only Delta-like 4 (DLL4) was up-regulated by RA. We also found that cyclin D, cyclin D1, PP2A and SMAD3, gene products involved in G1-S transition, were down-regulated by RA. This is consistence with our findings that RA induces cell cycle arrest. Numerous mechanisms involved in cell adhesion, cell-matrix interaction and cytoskeleton remodeling were also affected by RA. This analysis provides guidelines to further explore pathways and mechanisms during RA-induced GBM-SC differentiation. Our findings may be applicable to identify new molecular target applicable to differentiation therapies for glioblastomas. This will also stimulate the development of GBM stem cell based pre-clinical experimental models with the potential to improve mechanistic and pre-clinical therapeutic research.
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 5158.
Abstract 5163: Does melanoma metastasis recapitulate an embryonic neural crest invasion program
Authors: Bailey Caleb M. , Ythier Sylvain , Kulesa Paul M. 
Published: February 2011

Abstract
Melanocytes derive from a highly invasive and pluripotent embryonic cell population called the neural crest. It has been proposed that melanocytes might be inherently predisposed to having invasive and metastatic attributes following neoplastic transformation as a result of their embryonic differentiation program. Metastatic melanoma cells are highly invasive and typically exhibit a high degree of plasticity, similar to their neural crest progenitors, but whether these cells recapitulate an embryonic invasion program related to their ancestral neural crest is unclear. We have shown that metastatic melanoma cells transplanted into the chick embryonic neural crest microenvironment invade into the host tissue, migrate along host neural crest cell migratory pathways, do not reform tumors, and can potentially be reprogrammed to a neural-crest-cell-like phenotype (Kulesa et al., 2006; Hendrix et al., 2007; Kasemeier-Kulesa et al., 2008). Here, we use the chick embryo neural crest microenvironment, combined with 2-photon photoactivation cell labeling and time-lapse microscopy, as a model to address the predisposition hypothesis in more detail. We find that melanoma cell orientation to the host cranial neural crest migratory routes and ellipticity of cell shape increase as cells stream out in distinct strand-like structures. Strand-like structures extend into the neural crest microenvironment, but give rise to individually invasive cells away from the neural tube. 2-photon photoactivation of PSCFP2, to discretely label small numbers of melanoma cells in ovo, reveals that the most invasive cells do not start at the tissue transplant periphery but may come from deep within the transplant. In vivo 2-photon time-lapse imaging confirms the unpredictable nature of melanoma dissemination and that some cells are more aggressively predisposed. These results indicate that melanoma metastasis resembles the neural crest migratory pattern but is unpredictable in the spatio-temporal order of invasion. We propose that the chick embryo transplant model is a valid, in vivo model of melanoma metastastasis.
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 5163.
Abstract 5169: The polycomb group protein BMI-1 cooperates with Yes-Associated Protein, YAP, to suppress cell contact inhibition in Ewing sarcoma cells
Authors: Hsu Jessie Hao-Ru , Hung Long , Lawlor Elizabeth R. 
Published: February 2011

Abstract
The polycomb group family protein BMI-1 is frequently deregulated in cancer. BMI-1 has been shown to promote stemness and tumorigenicity largely through epigenetic repression of the CDKN2A locus, inhibiting the expression of cell-cycle inhibitors p16INK4A and p14ARF. We have previously shown that BMI-1 functions as an oncoprotein in Ewing sarcoma, promoting anchorage independent growth in vitro and tumorigenicity in vivo independently of CDKN2A repression. In the current study we have investigated the potential contribution of BMI-1 to loss of cell contact inhibition, a fundamental transforming property of cancer cells. Using cells that stably express an shRNA against BMI-1, we discovered that loss of BMI-1 expression restores contact inhibition to CDKN2A-null Ewing sarcoma cells. Significantly, although proliferation of cells in log phase growth is unaffected by loss of BMI-1, at high cell density BMI-1 knockdown cells undergo cell cycle arrest and death. In contrast, control vector-transduced cells continue to enter cell cycle and proliferate, avoiding contact inhibition. Although many signaling pathways are involved in mediating the cell contact inhibition response, inactivation of the Yes-Associated Protein (YAP), a key downstream target of the Hippo pathway, has been implicated in both Drosophila and mammalian cells. Intriguingly, our data show that, although the Hippo pathway is activated in response to increasing cell density, as evidenced by increasing YAP phosphorylation, YAP is not degraded in control cells that express high levels of BMI-1. In contrast, silencing BMI-1 expression results in loss of YAP protein at high cell density coincident with induction of contact inhibition. Together, these findings suggest that YAP is a novel downstream target of BMI-1 and that BMI-1-mediated stabilization of YAP renders cancer cells impervious to cell contact inhibition. Experiments are currently ongoing to elucidate the precise molecular mechanism linking BMI-1 to YAP; however, preliminary studies show that knockdown of BMI-1 has no effect on YAP1 transcript expression at either low or high cell density indicating that the effects of BMI-1 on YAP stabilization are most likely to be post-translational and indirect. Cancer cells escape cell contact inhibition to achieve unrestrained proliferation and enhanced invasive and metastatic properties. Our findings suggest that BMI-1 may be a key upstream mediator of this critical cancer-associated phenotype.
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 5169.
Abstract 5172: Role of CEACAM1 on cancer cell endothelial adhesion and liver metastasis in vivo
Authors: Chan Carlos H.F. , Arabzadeh Azadeh , DeMarte Luisa , Spicer Jonathan , Turbide Claire , Brodt Pnina , Beauchemin Nicole , Ferri Lorenzo E. 
Published: February 2011

Abstract
Background: There are emerging data to suggest that tumor over-expression of the carcinoembryonic antigen-related cell adhesion molecules (CEACAM1, 5 and 6) may influence cancer metastasis; however, the mechanisms for this are unclear. CEACAM1 was shown to bind homotypically to itself and heterotypically to CEACAM5 and CEACAM6. Since CEACAM1 is the only known CEACAM family member expressed on the hepatic endothelium, we hypothesized that CEACAM1 promotes cancer metastasis by directly mediating binding between circulating tumor cells and the sinusoidal endothelium.
Methods: Using intra-vital microscopy (IVM), a physiologically relevant model system to assess the early stages of liver metastasis in vivo, we have compared the hepatic endothelial adhesion of intra-splenically injected MC38 cells (mouse colon cancer cell line with minimal CEACAM1 expression) between Ceacam1+/+ and Ceacam1−/− mice. A CEACAM1-negative population of MC38 cells (MC38-null) was sorted out by FACS using specific anti-CEACAM1 antibodies. MC38-null cells were then infected with retroviruses produced from ψ2 packaging cells carrying pLXSN-CEACAM1 expression construct and infected cells were selected using neomycin-containing media. A CEACAM1-positive population of MC38 cells (MC38-CC1) was sorted out by FACS using specific anti-CEACAM1 antibodies. The migratory ability of MC38-null and MC38-CC1 cells were compared by IVM in Ceacam1+/+ mice as mentioned above. Liver metastasis assays were performed by means of intra-splenic injection of MC38 cells into the Ceacam1+/+ and Ceacam1−/− mice. Data expressed as mean ± SEM, student t-test determined significance (*p&lt;0.05).
Results: By using IVM, we observed a 3-fold decrease in hepatic sinusoidal endothelial adhesion of intra-splenically injected MC38-null cells in Ceacam1−/− mice compared to Ceacam1 +/+ mice (0.8±0.2 vs 2.5±0.3 adhered cells)*. Forced expression of CEACAM1 in MC38 cells however did not significantly increase hepatic endothelial adhesion in the Ceacam1+/+ mice (2.7±0.9 adhered MC38-CC1 cells vs 2.5±0.2 adhered MC38-null cells). Development of liver metastasis after intra-splenic injection of MC38-null cells was significantly reduced in the Ceacam1−/− mice (81% reduction in comparison to Ceacam1+/+ mice)*.
Conclusion: Sinusoidal endothelial cell, but not cancer cell, CEACAM1 expression supports liver metastasis by increasing the adherence of circulating tumor cells to hepatic endothelium. Further investigation will be required to dissect the exact mechanism of how endothelial CEACAM1 influence hepatic endothelial adhesion of 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 5172.
Abstract 5177: Assessment of EpCAM function in lung cancer progression
Authors: Seung Han Jee , Kim Youngwook , Park Keunchil , Ahn Myung-ju 
Published: February 2011

Abstract
The epithelial cell adhesion molecule (EpCAM) is expressed on the basolateral membrane of the majority of epithelial tissues and it is upregulated or expressed de novo in various carcinomas. Several studies showed that high level EpCAM expression is associated with poor survival and tumor grading.
EpCAM remains an attractive cancer therapeutic target. Until recently, however, molecular impact of EpCAM on cancer signaling processes and growth regulation has not been clearly understood. We show here that inhibition of EpCAM by inducible shRNA resulted in a change of cell cycle profile and decreased cellular proliferation in non-small cell lung cancer cells. Cancer cells were apparently arrested in G1 phase, and subsequent western blotting experiments showed that p27 protein increased upon EpCAM inhibition.
To test whether EpCAM depletion would also lead to changes in tumor progression in vivo, we assessed the effect of EpCAM shRNA induction in lung cancer animal xenograft model. EpCAM knock-down led to almost complete tumor progression in vivo. Additional studies showed that inhibition of EpCAM expression was related to decreased microvessel density, revealed by CD31 immunohistochemical staining.
Overall, the data presented here suggest that EpCAM can be another therapeutic target of lung cancer. Development of inhibitory modality of EpCAM function needs to be tested further alone or in combination of other therapeutic reagents.
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 5177.
Abstract 5183: Correlation of cell adhesion molecules expression and prognosis in clinically localized prostate cancer
Authors: Júnior José Pontes , Ribeiro-Filho Leopoldo Alves , Reis Sabrina Thalita , de Oliveira Luiz Carlos Neves , Dall'Oglio Marcos , Leite Kátia R M , Srougi Miguel 
Published: February 2011

Abstract
Introduction and objective: E-cadherin and others adhesion molecules are responsible for the maintenance of the epithelial phenotype. Some studies have reported correlation between alterations in cell adhesion molecules expression and carcinogenesis, but their role in the prostate cancer is not clear. Our aim is to study the expression profiles of E-cadherin and catenins in localized prostate cancer and evaluate their association with recurrence after surgical treatment
Methods: For this case-control study, we selected 111 patients with localized tumor submitted to radical prostatectomy. 60 of these patients have not presented recurrence after a median follow-up of 123 months. Recurrence was defined as a PSA level above 0.4ng/ml. E-cadherin and α, β and µ-catenins expression was evaluated by immunohistochemistry in a Tissue Microarray containing two samples from each tumor. We employed a semiquantitative analysis and considered normal when the expression was strong and diffusely positive. We correlated expression with recurrence using the χ2 test and p&lt;0.05 was considered significant.
Results: We observed normal expression for E-cadherin and α, β and µ-catenins in 77%, 42, 18% and 8% of patients respectively (figure 1). Correlation the expression of cell adhesion molecules with cancer recurrence after radical prostatectomy in the univariate analysis we found that these expressions were not associated with tumor outcome after surgery with more than ten years follow up (table1). Conclusions: In the present study we have shown a profile of cell adhesion molecules expression in localized prostate cancer who underwent surgery. Furthermore, we found that the expressions were not correlated with recurrence, which do not qualify these proteins as potential markers of prognosis for this tumor.
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 5183.