bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5325: Localized tumor growth in bone: Quantification of tumor burden, bone destruction, and weight-bearing capability in MDA-MB-231 human mammary carcinoma xenograft-bearing immunodeficient rats
Authors: Brune Kellie A. , Misener Elizabeth A. , Shannon Harlan , Wolos Jeffrey A. 
Published: June 2012

Abstract
Metastatic bone disease is common in multiple myeloma, breast, prostate, and lung cancer patients and is a frequent cause of morbidity in advanced disease. Metastatic bone tumors destroy bone and cause severe bone remodeling which leads to structural weakening and bone fractures and often results in severe bone pain in a large percentage of patients.
These studies examined tumor growth, bone erosion, and pain in a nude rat model. A surgical defect was created in the tibia, exposing the marrow cavity. Luciferase-expressing MDA-MB-231 mammary tumor cells were injected into the exposed bone cavity. Rats inoculated with tumor cells were treated with either doxorubicin (3 mg/kg/week, iv) or risedronate (80 ug/kg/day, ip). Animals were monitored weekly for tumor burden by optical imaging and for bone erosion by CT. In addition to clinical observations, weight bearing was measured using an incapacitance tester with separate force transducers for each hind paw.
Compared to controls, rats treated with doxorubicin demonstrated a significant decease in luminescence, indicating tumor growth inhibition (bone protection). Decreased luminescence correlated with sparing of the bone as measured by CT. In contrast, the bisphosphonate, risedronate, had limited effect on tumor growth, but preserved bone integrity. In both treatments, protection of bone was associated with normalization of weight-bearing. This finding supports the premise that pain in metastatic bone cancer is attributable to bone loss (destruction) and remodeling. Weight-bearing data correlated directly with clinical observations This model, leveraging multiple imaging modalities, enables longitudinal and quantitative assessment of tumor growth; bone loss, remodeling and sparing, and weight-bearing in test animals that provides a sensitive and robust screening tool to evaluate compounds for anti-tumor, bone-sparing and pain amelioration effects.
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 5325. doi:10.1158/1538-7445.AM2011-5325
Abstract 5326: Quantitative molecular profiling of biomarkers for pancreatic cancer with quantum dots
Authors: Searson Peter C. , Lee Kwan Hyi 
Published: June 2012

Abstract
The detection of cancer biomarkers is important for diagnosis, disease stage forecasting, and clinical management. Since tumor populations are inherently heterogeneous, a key challenge is the quantitative profiling of membrane biomarkers, rather than secreted biomarkers, at the single cell level. The detection of cancer biomarkers is also important for imaging and therapeutics since membrane proteins are commonly selected as targets. Many methods for detection of membrane proteins yield ensemble averages and hence have limited application for analysis of heterogeneous populations or single cells. Fluorescence-based methods allow detection at the single cell level, however, photobleaching presents a major limitation in obtaining quantitative information. Quantum dots overcome the limitations associated with photobleaching, however, the development of quantum dot – antibody (QD-Ab) conjugates that allow quantitative profiling of biomarkers has remained challenging. Here we demonstrate quantitative in vitro profiling and multiplexing of molecular biomarkers associated with precursor lesions of pancreatic adenocarcinoma using QD-Ab conjugates. We demonstrate quantitative spatial profiling of several biomarkers for pancreatic cancer, including mesothelin, prostate stem cell antigen, and claudin-4 in several pancreatic cancer cell lines and a normal pancreas cell line. We also show tumor targeting in a mouse model.
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 5326. doi:10.1158/1538-7445.AM2011-5326
Abstract 5329A: Micro-CT enables microlocalization and quantification of Her2-targeted gold nanoparticles within tumor regions
Authors: Hainfeld James F. , O'Connor Michael J. , Dilmanian Avraham , Slatkin Daniel N. , Adams Douglas J. , Smilowitz Henry M. 
Published: June 2012

Abstract
Gold nanoparticles are of interest as potential in vivo diagnostic and therapeutic agents, as X-ray contrast agents, drug delivery vehicles and radiation enhancers. The aim of this study was to quantitatively determine their targeting and microlocalization in mouse tumor models after intravenous injection by using micro- CT. Gold nanoparticles (15 nm) were coated with polyethylene glycol and covalently coupled to anti-Her2 antibodies (Herceptin). In vitro, conjugates incubated with Her2+ (BT-474) and Her2- (MCF7) human breast cancer cells showed specific targeted binding with a Her2+ to Her2- gold ratio of 39.4± 2.7:1. Nude mice, simultaneously bearing subcutaneous Her2+ and Her2- human breast tumors in opposite thighs were prepared. Gold nanoparticles alone, conjugated to Herceptin or to a non-specific antibody were compared. After intravenous injection of the gold nanoparticles, gold concentrations were determined by atomic absorption spectroscopy. Microlocalization of gold was carried out by calibrated micro-CT, giving both the radiodensities and gold concentrations in tumor and non-tumor tissue. All gold nanoparticle constructs showed accumulation, predominantly at tumor peripheries. However, the Herceptin-gold nanoparticles showed the best specific uptake in their periphery (15.8± 1.7% injected dose g-1), 1.6-fold higher than Her2- tumors and 22-fold higher than surrounding muscle. Imaging readily enabled detection of small, 1.5-mm-thick tumors. In this pre-clinical study, antibody-targeted 15 nm gold nanoparticles showed preferential uptake in cognate tumors, but even untargeted gold nanoparticles enhanced the visibility of tumor peripheries and enabled detection of millimeter-sized tumors. Micro-CT enabled quantification within various regions of a tumor.
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 5329A. doi:10.1158/1538-7445.AM2011-5329A
Abstract 5331: CHK1 inhibition enhances chemosensitivity of p53 deficient osteosarcoma cells
Authors: Xu Gufeng , Wang Hongmei , Rainusso Nino C. , Flores Ricardo J. , Triche Timothy , Man Tsz-Kwong , Lau Ching C. 
Published: June 2012

Abstract
Osteosarcoma is the most common malignant bone tumor in children. Using expression profiling, we have previously identified a 45-gene chemoresistance signature in osteosarcoma that can predict tumor response to neo-adjuvant chemotherapy. One of the signature genes is CHEK1, which was expressed significantly higher in osteosarcomas that respond poorly to neoadjuvant chemotherapy. CHEK1 encodes a Serine/threonine-protein kinase CHK1 that regulates both G2/M and S phases of the cell cycle mainly through phosphorylation of CDC25, and particularly controls the entry into mitosis. In this study, we used two independent short hairpin RNA (shRNA) constructs to knock-down CHEK1 expression in a p53-mutated osteosarcoma cell line 143B and a p53- wild type osteosarcoma cell line U2OS. The results show that the stably transduced CHEK1 knock-down 143B cells, but not U2OS cells, became more sensitive to both doxorubicin and cisplatin treatment relative to the parental or scrambled control cells. The results of the cytotoxicity assay were confirmed by clonogenic assay using 143B and U2OS stable transfectants. Using a CHK1 inhibitor UCN-01, we found that mutation status of p53 in different osteosarcoma cells lines correlated with their sensitivity to doxorubicin or cisplatin in the presence of UCN-01. Using flow cytometry, we also validated the activity of UCN-01 in abolishing the cell cycle arrest induced by doxorubicin or cisplatin treatment in 143B cells.
In summary, our results confirm that CHEK1 expression is not only a potential biomarker for predicting chemoresistance in osteosarcoma, but also potentially represents a therapeutic target for overcoming chemoresistance in osteosarcoma with the use of small molecule CHK1 inhibitors. Further experiments involving in vivo orthotropic xenograft mouse model with both CHEK1 knock-down osteosarcoma cells and CHK1 inhibitors is underway.
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 5331. doi:10.1158/1538-7445.AM2011-5331
Abstract 5332: Evaluation of GD2 expression in patients with osteosarcoma
Authors: Tarim John , Sowers Rebecca S. , Piperdi Sajida , Khanna Chand , Gorlick Richard G. 
Published: June 2012

Abstract
GD2 is a disialoganglioside that is expressed on the cell surface in specific normal and malignant human tissues. Tumor specific cell surface antigens serve as important targets in cancer therapy. Anti-GD2 therapy using antibodies targeted to the cell surface antigen GD2 to induce antibody-dependent cellular cytotoxicity has been proven effective in treating GD2 expressing tumors like neuroblastoma and melanoma. Prior studies of osteosarcoma have shown GD2 to be expressed in malignant cells of osteosarcoma patients. In this study, the expression of GD2 in osteosarcoma will be evaluated further. A previously created and described tissue microarray was stained with 14.G2a, a murine monoclonal anti-GD2 antibody that was obtained from the National Cancer Institute. The intensity and location of tissue staining were assessed by a comparison between the positive and negative control slides. To evaluate GD2 expression quantitatively a cell-based ELISA was performed on different osteosarcoma patient derived cell cultures. The results of the tissue microarray showed that 34.8% of patient samples stained positive for GD2 while 60.9% of samples showed intermediate staining and only 4.3% of samples showed negative staining for GD2 (n=88). Nearly all of the osteosarcoma cell lines (n=24) showed levels of GD2 expression comparable to the neuroblastoma and fibrosarcoma cell lines and in some cases GD2 expression was significantly greater. Anti-GD2 therapy has been proven effective in treating patients with neuroblastoma and melanoma. The findings in this paper indicate that osteosarcomas express GD2 to a similar extent as neuroblastomas. These results would suggest clinical trials are worthwhile to further evaluate the benefit of anti-GD2 therapy in patients with osteosarcoma.
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 5332. doi:10.1158/1538-7445.AM2011-5332
Abstract 5335: The histone deacetylase inhibitor MS-275 sensitizes osteosarcoma cells and osteosarcoma lung metastases to FasL-induced cell death by the downregulation c-FLIP
Authors: Rao-Bindal Krithi , Kleinerman Eugenie S. 
Published: June 2012

Abstract
The purpose of this study was to determine the effects of the histone deacetylase inhibitor, MS-275, on the Fas signaling pathway and susceptibility of osteosarcoma (OS) to FasL-induced cell death. OS metastasizes almost exclusively to the lungs. We have shown that Fas expression by OS cells inversely correlates with their metastatic potential. Fas+ cells are rapidly eliminated when they enter the lungs via interaction with FasL, which is constitutively expressed in the lungs. OS cells that are Fas− escape this FasL-induced apoptosis and survive in the lung microenvironment. Moreover, upregulation of Fas expression on established OS lung metastases results in tumor regression. Therefore, agents that upregulate Fas or activate the Fas signaling pathway may have therapeutic potential. These investigations utilized the Fas− metastatic osteosarcoma cell lines LM7 and CCH-OS-D. Treatment of OS cells with 2µM MS-275 sensitized cells to FasL-induced cell death in vitro, as quantified by MTT, trypan blue and clonogenic assays. We have demonstrated that blocking Fas signaling by transfecting cells with a FADD dominant-negative (FDN) plasmid, inhibited MS-275-induced sensitization to FasL-mediated cell death, suggesting the involvement of the Fas pathway in this mechanism. We found that treatment of OS cells in vitro did not alter the expression of Fas on the cell surface, rather it resulted in the downregulation of the anti-apoptotic protein, c-FLIP (cellular FLICE-inhibitory protein), which was determined to be a result of MS-275-induced downregulation of FLIP mRNA. Downregulation of c-FLIP correlated with caspase activation and induction of apoptosis. Treatment of nu/nu-mice with established OS lung metastases with oral MS-275 resulted in tumor regression, increased apoptosis and a significant inhibition of c-FLIP expression in tumors. Histopathological examination of mice receiving oral MS-275 showed no evidence of toxicity. Overall, these data suggest that the mechanism by which MS-275 sensitizes OS cells and OS lung metastases to FasL-induced cell death may be by a direct reduction in the expression of c-FLIP.
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 5335. doi:10.1158/1538-7445.AM2011-5335
Abstract 5336: Macrophage migration inhibitory factor (MIF) plays roles in proliferation, survival and migration of Ewing tumor cells through the activation of several tyrosine kinases
Authors: Kang Hyung Gyoo , Liu Xian Fang , Sorensen Poul HB , Triche Timothy J. 
Published: June 2012

Abstract
In normal cells, expression of cytokines and their mediated cell signaling pathways are tightly and accurately regulated. But in many tumors, it has been shown that cytokine signaling pathways are deregulated. Thus, identification and understanding of deregulated cytokines and their related pathways can provide the unique and promising opportunity for better-targeted therapies of cancer. MIF has been known to be a proinflammatory cytokine but recently it was shown that MIF plays roles in proliferation, survival and apoptosis in several tumors. In order to study the effects and molecular mechanisms of MIF on Ewing tumor cell growth and survival we established MIF deficient Ewing tumor cell lines using shRNA method. In our study it was found that the decreased MIF expression is significantly correlated to morphological change, deregulation of differentiation, decrease of proliferation and increase of apoptosis in Ewing tumor cells. Then several signal pathways were investigated to elucidate the molecular mechanism of MIF functions in Ewing tumor cells. It has been found that MIF is involved in the activation of Jak/Stat and Src pathways that regulate activation of Akt and Erk, which play key roles in the cell survival and proliferation. Related to the morphological change and mobility change in MIF-deficient cells it was found that Rac1 activation is highly regulated by MIF in Ewing tumors. In addition, it was found that activation of several kinases is closely related to the expression of MIF in Ewing tumors. Therefore our data implies that MIF might functionally contribute to Ewing tumor cell growth, survival, proliferation and metastasis, which suggests that MIF might be a promising target of Ewing tumor cells therapy.
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 5336. doi:10.1158/1538-7445.AM2011-5336
Abstract 5341: Combinatorial regulation of E2F target genes by the oncogenic ETS transcription factor EWS-FLI1
Authors: Schwentner Raphaela , Kauer Maximilian , Bilke Sven , Jug Gunhild , Meltzer Paul S. , Kovar Heinrich 
Published: June 2012

Abstract
Ewing's sarcoma (ESFT) is a highly aggressive pediatric cancer of the bone characterized by the chimeric ETS transcription factor EWS-FLI1 as a result of a chromosomal translocation. By whole genome gene expression and ChIP-seq analyses we obtained evidence that EWS-FLI1 directly binds 50% of E2F target genes and possibly cooperates with E2F transcription factors. Furthermore, several E2F factors were themselves found to be direct targets of EWS-FLI1. To unravel the hierarchical structure of this EWS-FLI1/E2F transcriptional network module we performed luciferase reporter gene assays in combination with DNA motif mutation analyses and ChIP-PCR.
The promoter regions of ten candidates for direct target genes of EWS-FLI1 and E2F factors were chosen for in-depth analysis. Corroborating the transcriptomic data, promoter activity of all ten genes showed reduced levels upon knockdown of EWS-FLI1.
By chromatin immunoprecipitation, we confirmed that EWS-FLI1 directly binds to the promoter regions. For some of those genes, mutation of only a single ETS binding site leads to a reduction of luciferase activity comparable to knockdown of EWS-FLI1 (for example the E2F promoters).
For the other selected EWS-FLI1 target candidates, mutation analysis and ChIP-PCR revealed more complex regulatory patterns.
In one example, simultaneous mutation of two ETS binding sites within the region directly bound by EWS-FLI1 resulted in a significant reduction of transcriptional activity. However, mutation of the single E2F binding site rendered the promoter completely insensitive to EWS-FLI1 regulation. Furthermore, ChIP-PCR revealed that upon EWS-FLI1 repression an EWS-FLI1 induced activating E2F factor is exchanged for a repressing E2F factor on the promoter of this gene. Our results imply that EWS-FLI1 uses several modes of interaction with E2F factors to control shared target genes.
This study was supported by grant 22328-B09 from the Austrian Science Fund FWF.
R. Schwentner is a recipient of a DOC-fFORTE-fellowship of the Austrian Academy of Sciences.
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 5341. doi:10.1158/1538-7445.AM2011-5341
Abstract 5343: Aberrant activation of hedgehog signaling confers a poor prognosis in embryonal and fusion gene negative alveolar rhabdomyosarcoma
Authors: Zibat Arne , Missiaglia Edoardo , Rosenberger Albert , Pritchard-Jones Kathy , Shipley Janet , Hahn Heidi , Fulda Simone 
Published: June 2012

Abstract
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and comprises two major histological subtypes: alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS). The hedgehog (Hh) pathway has recently been implied in tumor formation and progression of various cancers. In the current study we investigated whether Hh pathway activation presents a general feature also of RMS and whether it bears prognostic impact. Here, we report that marker genes of active Hh signaling, i.e. Patched1 (Ptch1), Gli1, Gli3 and Myf5, are elevated in two distinct cohorts of RMS patients with a total number of 235 primary samples. Interestingly, all these marker genes of active Hh signaling were expressed at significantly higher levels in specific subtypes of RMS, i.e. ERMS and fusion gene negative ARMS, compared to fusion gene positive ARMS. Consistently, Gli1 expression correlates with Ptch1 expression in ERMS and fusion gene negative ARMS, but not in fusion gene positive ARMS. In addition, expression levels of MyoD1 are significantly lower in ERMS and fusion gene negative ARMS, pointing to an inverse association of Hh activation and early muscle differentiation in primary RMS samples. In support of this notion, the addition of Shh inhibits muscle differentiation in parallel experiments in muscle satellite cells and myoblasts. Moreover, we identify Myf5 is as a novel excellent class predictor for RMS by receiver operating characteristic (ROC) analysis. Most importantly, high expression of Ptch1 or low MyoD1 expression significantly correlate with reduced cumulative survival in fusion gene negative RMS (P&lt; 0.004) underscoring the clinical relevance of these findings. By identifying aberrant Hh activation in specific subgroups of RMS, our study has important implications for the development of molecular targeted therapies, such as small molecule Hh inhibitors, in RMS.
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 5343. doi:10.1158/1538-7445.AM2011-5343