bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5214: Development of a microfiltration system for the improved detection and viable capture of metastatic circulating tumor cells
Authors: Harouaka Ramdane , Zhou Mingda , Zhang Jiayun , Khan Waleed J. , Zheng Siyang 
Published: June 2012

Abstract
The ability of metastatic cancer to release cells that travel through the circulatory system and invade different parts of the body accounts for over 90% of cancer related deaths. The fundamental challenge with detecting these circulating tumor cells (CTCs) in blood samples is the fact that they are so rare, with only a few tumors cells occurring among billions of blood cells. Since tumor cells are almost always significantly larger and more rigid than normal blood cells, size based separation has been demonstrated to be an effective method for CTC capture and enrichment. While useful for detection, size based techniques apply concentrated stresses that affect the viability of captured cells. We have incorporated novel spring structures into our microfilter design that mitigate the stresses experienced by CTCs during filtration to encourage their health and survival. The geometric design and filtration pressures have been optimized to maximize capture efficiency, enrichment against white blood cells, and tumor cell viability. This was achieved through repeated filtrations using a model system of fluorescently labeled cells from various established tumor cell lines spiked into healthy donor blood. The viability of captured cells has been confirmed through exclusion dye testing, and through the proliferation and culture of captured cells directly on the filter surface. The successful capture and primary culture of viable CTCs from clinical patient samples will allow unprecedented analysis and genetic testing of the cells directly responsible for metastasis. This could provide the basis for externally testing tumor cell response to a variety of anticancer drugs without having to expose a patient to the unnecessary cost and toxic effects of chemotherapy, thereby improving patient outcomes through the development of personalized treatment plans.
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 5214. doi:10.1158/1538-7445.AM2011-5214
Abstract 5230: Development of a series of genetically fluorescent human osteosarcoma cell lines with increasing spontaneous metastatic capability
Authors: Tome Yasunori , Kimura Hiroaki , Maehara Hiroki , Kanaya Fuminori , Bouvet Michael , Tsuchiya Hiroyuki , Hoffman Robert M. 
Published: June 2012

Abstract
In order to investigate the molecular pathogenesis of human osteosarcoma, a reliable metastatic osteosarcoma animal model is required. Here we report the development of a series of metastatic sublines (LM1-LM4) derived from a human osteosarcoma 143B parental cell line expressing GFP in the nucleus and RFP in the cytoplasm. The sublines have increasing ability to form pulmonary metastases in nude mice after intravenous injection. In vitro proliferation rates of all sublines were similar. When the 143B parental and the metastatic sublines were transplanted orthotopically in the tibia of nude mice, all cell lines were tumorigenic. Primary tumor growth and metastases were imaged with the OV100 Small Animal Imaging System (Olympus Corp., Tokyo, Japan). LM2 and LM3 had higher metastatic capability than the parental 143B. LM1 had higher metastatic capability than LM2 or LM3. LM4 cells resulted in the most pulmonary micrometastases. The number of pulmonary metastases was 8-fold higher in LM4 cells than that with 143B parental cells. This series of metastatic sublines should be a powerful tool to investigate genetic and other factors that promote or inhibit osteosarcoma metastasis and for evaluation of novel anti-metastatic drugs.
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 5230. doi:10.1158/1538-7445.AM2011-5230
Abstract 5231: Tilmaocept: A novel biotargeted agent for enhanced intraoperative discrimination of sentinel lymph nodes in breast cancer, melanoma, and head & neck SCC
Authors: Cope Frederick O. , Metz Wendy Rich , Blackburn Simon , Abbruzzese Bonnie , Orahood Richard 
Published: June 2012

Abstract
Sentinel lymph node (SLN) mapping and identification is a primary component of surgical therapies for breast cancers, melanomas, pediatric soft tissue sarcomas, and certain other cancers. The current standard of care for identifying SLNs to inject into a tumor (or near a tumor) a blue dye (often called “vital blue dye”), of which several are available, in conjunction with a radiolabeled (99mTc) tracer, available as either a technetium sulfur colloid or as a technetium labeled albumin formulation. The exact formulations used vary, especially between those used in the United States and Europe. All such compounds are effectively agents of passive transport in the lymphatic ducts and are “inert” with regard to any biomarker recognition specificity. Allegedly, such agents move passively from the tumor/tumor basin into lymph nodes with a presumptive tumor-node anatomic nexus and the nodes are elucidated as blue and/or radioactive, the former based on excision line-of-sight, the latter based on intraoperative evaluation with a gamma-detecting probe. But because such components do not bear any specificity, that is, bind or accumulate lymph nodes bearing targets, they either remain static at the injection site and/or quickly drain away, reducing their real-time clinical effectiveness.
A novel 99mTc-labeled, prospectively designed, low Mr molecule (99mTc DTPA Mannosyl Dextran; Tilmanocept) targeted as a ligand for the mannose binding receptor (MBR) of lymphatic reticuloendothelial cells and intended for real-time intraoperative gamma mapping of tumor-lymphatic nexuses has been synthesized and clinically tested in Phase 3 clinical studies in breast cancer and melanoma. The results of the development process and clinical testing indicate: 1) The prospective molecular designs resulted in safety and clinical performance characteristics that provided times from agent injection to patient evaluation that were significantly reduced compared to currently applied 99mTc-labeled agents; and 2) The specificity, sensitivity, and performance with regard to anatomic localization, false negative rates, and receptor retention exceed those of other colorimetric and 99mTc-labeled agents.
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 5231. doi:10.1158/1538-7445.AM2011-5231
Abstract 5243: Gene expression analysis of CRC liver metastases with different growth patterns
Authors: Van den Eynden Gert G. , Fiorentino Michelangelo , Van Laere Steven S. , Peeters Dieter S. , Trinh Xuan Bich , Dirix Luc Y. , Vermeulen Peter B. 
Published: June 2012

Abstract
Introduction: Liver metastases of colorectal cancer (CRC) grow according to different growth patterns (GPs) with different angiogenic properties. The aim of this study was to characterize these GPs on a molecular level using genome-wide gene expression analysis.
Materials and Methods: On 18 CRC liver metastases of which genome-wide gene expression data were available from a previous study (publicly available at GSE 10961), we assessed the GP using a haematoxylin-eosin and Gordon Sweet's reticulin stain. 7 metastases had a desmoplastic GP, 6 had a pushing GP and 3 had a replacement GP. Of 2 metastases the GP could not be assessed due to lack of sufficient material and these were excluded for further analysis. We used (hierarchical) cluster analysis, principal component analysis, significance/prediction analysis of microarrays and gene set enrichment analysis to study differences in gene expression between the different GPs.
Results: Principal component analysis and hierarchical cluster analysis showed significant gene expression differences between metastases with a desmoplastic and pushing GP (p=2.2e−16) and between metastases with a desmoplastic and replacement GP (p=2.2e−16). Gene set enrichment analysis demonstrated increased expression of biological processes, molecular functions, cellular components and KEGG pathways related to immune response, antigen processing, leucocyte activation and cell adhesion molecules in the metastases with a desmoplastic GP. Similar differences were found when metastases with a pushing GP were compared to metastases with a replacement GP and when the 3 groups were compared.
Conclusion: These results confirm on a molecular level that liver metastases of patients with CRC have a heterogeneous biology. Metastases with a desmoplastic GP appear to have upregulation of immunological processes, compared to metastases with a pushing or replacement GP. Further elucidation of these differences might lead to better understanding of host-tumour interactions in metastatic biology and new therapeutic strategies for patients with metastatic CRC.
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 5243. doi:10.1158/1538-7445.AM2011-5243
Abstract 5250: MUC1 expression is induced by Snai1 in an epithelial mesenchymal transition renal model
Authors: Gnemmi Viviane , Bouillez Audrey , Ringot Bélinda , Zini Laurent , Copin Marie-Christine , VanSeuningen Isabelle , Leroy Xavier , Perrais Michael , Sébastien Aubert 
Published: June 2012

Abstract
Accumulating data suggest that epithelial mesenchymal transition (EMT) is involved in cancer progression. Sarcomatoid carcinoma represents a high-grade transformation and an EMT-like pattern. Up to 8% of conventional renal cells cancers (cRCC) present with sarcomatoid carcinoma component that portends a worse prognosis. MUC1, a membrane-bound glycoprotein is known to be over-expressed in cRCC with correlation to prognosis. Indeed, we showed that MUC1 overexpression is correlated with a metastatic phenotype using tissue microarray sampling 27 cRCC of same TNM stage. Also, we demonstrated in a series of 15 RCC with sarcomatoid component, the loss of epithelial markers and the acquisition of mesenchymal markers compared to conventional carcinomatous areas. MUC1 was significantly overexpressed along with Snai1, a major actor of EMT, in sarcomatoid component. So, we hypothesized that MUC1 could be regulated by Snai1. Bioinformatic analyses revealed two Snai1 E-boxes at -84/-72 on MUC1 promoter. Cotransfection studies of MUC1 promoter and Snai1 expression vectors in renal cells lines showed an induction of MUC1 transcriptional activity by luciferase assays. Mutagenesis site-directed of both Snai1 E-boxes in renal cells lines induced loss MUC1 transcriptional activity. By chromatin immunoprecipation assay and gel shift analysis we will demonstrate a direct interaction between Snai1 and MUC1 promoter. In conclusion, all these data revealed that MUC1, usually considered as an epithelial marker, is overexpressed during cancer linked EMT process with a direct regulation by Snai1 suggesting that MUC1 plays a role in renal cancer progression.
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 5250. doi:10.1158/1538-7445.AM2011-5250
Abstract 5253: A model of tumor dormancy in Luminal A breast cancer
Authors: Sansone Pasquale , Shapiro Lauren , Chang Qing , Berishaj Marjan , Bromberg Jaqueline 
Published: June 2012

Abstract
Introduction: The clinical course and biologic features of metastasis vary extensively depending on the type of cancer. Latency is one of the most important variables in metastasis. Late-onset recurrences are frequently found in Luminal A (ER+/PR+/Her2-) breast cancer patients. In both ER+ tumors and ER+ breast cancer cell lines, tumor cells preferentially disseminate to the bone marrow where they are capable of remaining dormant. The identification of mechanisms that support the survival of disseminated cancer cells (DTCs) has clear implications for understanding the biology of latent metastatic disease.
Method: ER+ breast cancer cell lines expressing a GFP luciferase vector (for in vivo bioluminescent monitoring of tumor growth and dissemination) were orthotopically injected in the mammary fat pad (MFP) of mice. DTCs were isolated and characterized from the bone marrow and lungs after several months.
Results: The isolated DTCs from the bone and lung do not proliferate, are resistant to both chemo and hormonal therapy (HT) and are endowed with a highly invasive/disseminating capacity (loss of E-Cadherin and gain of EMT features). Moreover, these DTCs exhibit decreased expression of ER compared to the cancer cells within the primary tumor. Since ER activity is required for ER+ breast cancer cell growth in vitro and in vivo, our data suggest that loss of ER activity can be a mechanism of tumor dormancy in Luminal A breast cancer.
Conclusion: An understanding of the consequences of ER activity in terms of tumor dormancy and dissemination potential of ER+ breast cancer cells has implications for improving the treatment of latent metastatic disease.
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 5253. doi:10.1158/1538-7445.AM2011-5253
Abstract 5260: Heme oxygenase-1 is involved in prostate cancer cells-bone interaction
Authors: Ferrando Mercedes , Elguero Belén , Meiss Roberto , Tzelepi Vassiliki , De Siervi Adriana , Navone Nora , Vazquez Elba 
Published: June 2012

Abstract
Prostate cancer metastasis is well characterized by its tropism to the bone with metastatic lesions being typically osteoblastic. Osteoblasts produce factors that promote growth and survival of prostate cancer cells, but the molecular nature of this interaction is still unknown. Previous reports from our laboratory documented that heme oxygenase-1 (HO-1) is expressed in primary prostate carcinomas and is localized in the nucleus. Recently, the involvement of HO-1 in bone metabolism has been reported. The aim of this study is to investigate the role of HO-1 in the interaction between prostate cancer cells and bone. We analyzed the expression of HO-1 by immunohistochemistry using a tissue microarray generated from 12 castrate-resistant prostate cancer specimens (MDA Anderson Cancer Center), growing as xenografts in male CB17 SCID wild or castrated mice. Each of these tumors led to clinically relevant biological models to study human prostate cancer progression. All samples showed cytoplasmic HO-1 staining of varying intensity. Intense positive nuclear staining was also detected in 3/5 tumors with neuroendocrine morphology. HO-1 expression was correlated with other markers such as PSA, AR and Ki-67 expression. Co-cultures of the osteolytic PC3 cancer cell line with PMO (primary mice osteoblasts) demonstrated that HO-1 induction in PC3 cells abolished the PC3-induced loss of osteoblasts and significantly increased Dickkopf-1 expression in tumor cells. Furthermore, using PC3-PMO co-cultures, we found that HO-1 induction in prostate cancer cells increased mRNA levels of Runx-2 and Cyclin D1 and diminished β-catenin protein expression in PMO. These results clearly indicate the involvement of HO-1 in the interaction between prostate cancer cells and bone. The study of the molecular mechanisms of this interaction will provide effective therapeutic interventions.
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 5260. doi:10.1158/1538-7445.AM2011-5260
Abstract 5261: Role of anterior gradient protein-2 in prostate cancer bone metastasis
Authors: Chanda Diptiman , Sawant Anandi , Isayeva Tatyana , Ponnazhagan Selvarangan 
Published: June 2012

Abstract
Skeletal metastasis is common in late stage prostate cancer, which leads to significant decline in the quality of life and mortality. In a recent study, we identified over-expression of anterior gradient protein (AGR2) in the PC3, bone metastatic prostate cancer cells following in vitro growth in bone marrow-conditioned medium. AGR2 is a secreted protein and originally reported for its role in the formation of forebrain and mucus-secreting cement gland in the frog Xenopus laevis. Role of AGR2 in carcinogenesis and metastasis is recently being investigated and reports indicate it is over-expressed in various adenocarcinomas and linked to poor survival. But no study has elucidated the role of AGR2 in bone metastasis. When AGR2 expression was compared between human prostate cancer cell lines obtained from bone (PC3), lymph node (LnCap) and brain (Du145) by RT-PCR and Western blot, highest level of AGR2 was observed in PC3 cells. To further confirm, PC3 cells expressing firefly luciferase were injected in athymic nude mice via intra-cardiac route and cells were retrieved from bone, adrenal, lung and heart 3 weeks later following organ dissemination. RT-PCR analysis indicated highest AGR2 expression in PC3 cells isolated from bone microenvironment, suggesting that AGR2 may have a potential role in prostate cancer bone metastasis. To correlate the relevance of this finding in humans, AGR2 immunohistochemistry was performed on human primary and metastatic prostate cancer tissue sections. Preliminary results indicate higher AGR2 expression in metastasized bone sections compared to primary prostate cancers. Additionally, AGR2 was stably silenced in the PC3 cells utilizing a short hairpin RNA and growth kinetics of the cell line was tested in vivo following intra-cardiac injection in a preclinical 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 5261. doi:10.1158/1538-7445.AM2011-5261
Abstract 5265: Development of a microfluidic device for tagless analysis of cell surface proteins directing lung metastasis
Authors: Vellanki Sri H. , Smith Robin L. , Tivari Samir , Kumar Rajan , Wieder Robert 
Published: June 2012

Abstract
Diagnostic analysis of the few tumor cells obtained by needle aspirates is currently limited to the cells’ morphologic characteristics. We are investigating tagless analysis of cell surface protein composition, when limited cell numbers are available, using a flow retardation microfluidic device. Expression of biologically significant cell surface proteins by individual cells is scored positive by achievement of flow retardation due to transient binding of cell surface proteins to cognizant antibodies immobilized on tandem patches of the channel. This permits repetitive queries of the same cell for several proteins that predict specific malignant behavior. We are adapting the model to LM2 cells, derived from lung metastases of MDA-MB-231 breast cancer cells, which selectively metastasize to the lung*. The original study identified 95 unique genes either overexpressed or underexpressed in LM2 cells compared to parental cells. Of these we identified three cell surface proteins, VCAM1, IL13RA2, and EMP1, as heterogeneously upregulated in a subset of LM2 cells and CXCR4, as downregulated in a subset of LM2 cells when compared with MDA-MB-231 cells. VCAM1 and IL13RA2 promote lung metastasis*. We sterile sorted LM2 cells into fractions expressing none, medium and high levels of these four proteins. We built a prototype microfluidic device able to retard the flow of streptavidin-coated silica oxide beads by immobilized biotin and used optical imaging and a tracking program for simultaneous analysis of multiple particles. We developed efficient and stable protein coating of microchannels and are generating patches with cognizant antibodies to these 4 antigens and to endothelial, macrophage, lymphocyte, fibroblast and endothelial cell markers as controls. We will correlate antigen expression levels with flow retardation efficiency. We will optimize shear rates affecting bond formation and shear stress affecting bond dissociation by optimizing velocity, viscosity, detergent and divalent cation concentrations to maximize cell separation. We will adapt the channel to select LM2 cells from excess controls in vitro and from tumor xenograft aspirates.
*Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL and Massague J (2005) Genes that mediate breast cancer metastasis to lung. Nature 436:518-524.
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 5265. doi:10.1158/1538-7445.AM2011-5265
Abstract 5270: Histone deacetylases 1, 6 and 8 are critical for invasion in breast cancer
Authors: Kang Jaeku , Kim Sun Young 
Published: June 2012

Abstract
Histone deacetylases (HDACs) are associated with the development and progression of cancer, but which HDAC isoforms play important roles in breast cancer metastasis is not known. Here, we identify the specific HDAC isoforms that are necessary for invasion and/or migration in human breast cancer cell lines. MDA-MB-231 cells were significantly more invasive and expressed higher levels of matrix metalloproteinase-9 (MMP-9) than MCF-7 cells. We compared the expression of HDAC isoforms between MCF-7 and MDA-MB-231 cells and found greater expression of HDAC4, 6 and 8 in MDA-MB-231 by RT-PCR and Western blot analyses. In addition, apicidin, a histone deacetylase inhibitor, was shown to attenuate the invasion, migration and MMP-9 expression in MDA-MB-231 cells. Using specific siRNAs directed against HDAC1, 4, 6 and 8, we show that inhibition of HDAC1, 6 and 8, but not HDAC4, are responsible for invasion and MMP-9 expression in MDA-MB-231 cells. We analyzed the invasiveness of MCF-7 cells overexpressing HDAC1, 4, 6 or 8 and found that overexpression of HDAC1, 6 or 8 increased invasion and MMP-9 expression. By developing HDAC isoforms as potential biomarkers for breast cancer metastasis, the present study can be extended to developing therapies for breast cancer invasion.
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 5270. doi:10.1158/1538-7445.AM2011-5270