bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4723: Soluble L1-CAM in the ascites is a prognostic marker in ovarian cancer
Authors: Bondong Sandra , Hielscher Thomas , Zeimet Alain , Zeillinger Robert , Cadron Isabelle , Sehouli Jalid , Vergote Ignace , Mahner Sven , Speiser Paul , Braicu Ioana , Huszar Monica , Fogel Mina , Altevogt Peter 
Published: June 2012

Abstract
L1-cell adhesion molecule (L1-CAM) is a 200-220 kDa transmembrane protein that belongs to the immunoglobulin superfamily. It was initially found to be expressed on neuronal cells and is involved in axon outgrowth and guidance during central nervous system development. L1-CAM overexpression has been reported for various tumor entities, where it correlates with advanced stage disease, metastasis and chemoresistance. In mouse models, L1-CAM promotes tumor growth and facilitates experimental tumor metastasis. The extracellular part of the full length L1-CAM is subject to membrane proximal cleavage, which generates a soluble form of about 200kDa (sL1-CAM). L1-CAM cleavage and release of the soluble molecule has been shown to promote migration, adhesion and protection from apoptosis of ovarian cancer cells in vitro. The soluble L1-CAM can be detected in body fluids like saliva, serum or ascites.
In a multi-centric retrospective study with 270 ovarian cancer patients, we analysed tumor samples to quantify membrane bound full length L1-CAM as well as ascites for sL1-CAM to study the value of L1-CAM as a prognostic marker. We found that L1-CAM expression on the tumor correlated with sL1-CAM in the ascites (rho=0.41). Increased L1-CAM levels on the tumor and in the ascites correlated significantly with a reduced overall survival (univariate p=0.028; 0.022). Elevated ascitic L1-CAM levels were also associated with poor progression free survival (p&lt;0.0001) and remained an independent prognostic marker in multivariate analysis (p=0.0003). Furthermore, increased L1-CAM levels in the ascites correlated with an increased ascites volume (p=0.003). Patients with elevated L1-CAM levels in the tumor were at high risk for incomplete primary debulking (univariate p=0.01, multivariate p=0.04) and had an increased risk for lymph node metastases (p=0.004).
Given the in vitro role of L1-CAM in metastasis and invasion in addition to the findings of our study, we conclude that L1-CAM high expressing tumors show a more invasive phenotype which translates into a higher rate of incomplete debulking during upfront surgery. High levels of sL1-CAM in the ascites could serve as a reliable marker for prediction of early relapse and residual tumor burden in women suffering from ovarian 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 4723. doi:10.1158/1538-7445.AM2011-4723
Abstract 4740: Agonist anti-CD137 mAb act on tumor endothelial cells to enhance recruitment ofactivated T lymphocytes
Authors: Palazon Asis , Teijeira Alvaro , Martínez-Forero Iván , Hervás-Stubbs Sandra , Roncal Carmen , Dubrot Juan , Morales-Kastresana Aizea , Rouzaut Ana , Jure-Kunkel Maria , Melero Ignacio 
Published: June 2012

Abstract
Agonist monoclonal antibodies to the immune co-stimulatory molecule CD137, also known as 4-1BB, are presently in clinical trials for cancer treatment based on their co-stimulatory effects on primed T cells and perhaps other cells of the immune system. Here we provide evidence that CD137 is selectively expressed on the surface of tumor endothelial cells. Hypoxia upregulated CD137 on murine endothelial cells. Treatment of tumor-bearing immunocompromised Rag-/- mice with agonist
CD137 mAb did not elicit any measurable anti-angiogenic effects. In contrast, agonist mAb stimulated tumor endothelial cells, increasing cell surface expression of the adhesion molecules ICAM-1, VCAM-1 and E-selectin. When adoptively transferred into mice, activated T lymphocytes derived from CD137-deficient animals entered more avidly into tumor tissue after treatment with agonist mAb. This effect could be neutralized with anti-ICAM-1 and anti-VCAM-1 blocking antibodies. Thus, stimulation of CD137 not only enhanced T cell activation but also augmented their trafficking into malignant tissue, through direct actions on the blood vessels that irrigate the tumor. Our findings identify an additional mechanism of action that can explain the immunotherapeutic effects of agonist CD137 antibodies.
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 4740. doi:10.1158/1538-7445.AM2011-4740
Abstract 4750: Real-time imaging of 3-dimensional cancer cell movement in tissues
Authors: Digman Michelle , Aguilar Jose A. , Gratton Enrico , Suetsugu Atsushi , Hoffman Robert M. 
Published: June 2012

Abstract
Our knowledge of how cells move in 3D in tissues is limited due to the lack of imaging methods that can produce 3D images fast enough and with sufficient resolution. Cancer cells migrate in 3D by forming adhesion points at the end of very long cellular protrusions. These protrusions are very thin and it is difficult to visualize adhesions along the protrusion surface. Conventional 3D stack reconstruction has relatively low resolution unless it is done using many frames. This results in a very slow acquisition in 3D confocal microscopy. Faster methods of 3D data acquisition (spinning disk microscopy) cannot be easily implemented since there is significant amount of scatter in tissues. A major obstacle in imaging adhesions is to find and track them so that they will not go out of focus. We are developing a new method which is based on orbiting imaging around cellular protrusions to visualize protein dynamics during extravasation. A feedback mechanism controls the center of the orbit to be at the center of the fluorescence distribution. A program reconstructs the shape of the protrusions in 3D. The fluorescence intensity in one or more channels is also simultaneously measured. The fluorescence intensity of one channel is used to paint the protrusion shape, which results in the 3D reconstruction of the protrusion. During the orbit, the second channel of the microscope measures the second harmonic generation (SHG) signal. We then correlated the appearance of bright fluorescence spots on the protrusion surface with the points of contact of the protrusion. This method will enable imaging of cancer cell invasion in 3-dimentions in live mice in real time.
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 4750. doi:10.1158/1538-7445.AM2011-4750
Abstract 476: Defining two populations of prostate cancer cells with distinct molecular, biological, and tumor-propagating properties
Authors: Qin Jichao , Liu Xin , Laffin Brian , Chen Xin , Choy Grace , Jeter Collene , Calhoun-Davis Tammy , Li Hangwen , Ivanov Ivan , Palapattu Ganesh , Pang Shen , Huang Jiaoti , Suraneni Mahipal , Tang Dean G. 
Published: June 2012

Abstract
Prostate cancer (PCa) is a heterogeneous malignancy containing different types of tumor cells. The cellular basis underlying PCa cell heterogeneity and functional importance of different PCa cell populations in maintaining tumor homeostasis and mediating castration-resistant progression remain poorly understood. By whole-genome microarray analysis, time-lapse videomicroscopy, serial tumor transplantations, and other functional assays, here we report the distinct molecular, cell biological, and tumor-propagating properties of PCa cells that express high (i.e., PSA+) and low (PSA−/lo) levels of PSA. PSA−/lo PCa cells are relatively quiescent and resistant to multiple stresses, exhibit high clonogenic potential, and possess long-term tumor-propagating capacity in intact male mice. They preferentially express stem cell-associated genes and epigenetic profiles and can generate PSA+ cells by either asymmetric or symmetric cell division. Of great clinic significance, PSA−/lo PCa cells can initiate robust tumor development in fully castrated hosts and survive experimental androgen-deprivation therapy. In contrast, PSA+ PCa cells, despite being highly tumorigenic in androgen-proficient hosts, possess more limited tumor-propagating capacity, mainly undergo symmetric division, and are sensitive to castration. Our data together suggest that the two populations of PCa cells appear to play differential roles in tumor maintenance and PSA−/lo cells may represent an important source of castration-resistant PCa cells. Our findings have important implications in understanding PCa cell heterogeneity, tumor response to the mainstay antiandrogen therapies, and emergence of castration-resistant PCa.
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 476. doi:10.1158/1538-7445.AM2011-476
Abstract 4774: Epimorphin inhibits mammary epithelial cell apoptosis through induction of IKBKE
Authors: Khauv Davitte , Cichon Magdalena , Radisky Derek 
Published: June 2012

Abstract
Epimorphin is a stromally produced factor that plays a role in normal mammary branching morphogenesis, but deregulated expression of epimorphin can have oncogenic consequences, although the oncogenic processes activated by epimorphin have not been elucidated. We had previously found that treatment of cultured mammary epithelial cells with epimorphin blocked activation of cell death pathways by a variety of apoptotic stimuli. These results implicated a potential role for epimorphin for inhibition of cellular apoptosis, a critical stage of tumor development. To identify potential mediators by which epimorphin could be affecting cell death pathways, we used a transcriptional profiling approach comparing mammary epithelial cells treated with epimorphin versus untreated cells. We found that epimorphin treatment led to significantly increased expression of IKBKE, which inhibits apoptosis through activation of NF-kappaB and which has recently been characterized as a key breast cancer oncogene. We found that epimorphin specifically blocks induction of apoptosis and activation of caspase-3 in cells treated with tumor necrosis factor-alpha, and that this activity was linked to epimorphin-mediated activation of IKBKE. We also found that knockdown of IKBKE blocked epimorphin-mediated induction of branching morphogenesis, implicating activation of IKBKE by epimorphin as a critical function for its normal morphogenic activities as well. These studies provide insight into an additional and unexpected linkage between mammary gland developmental processes and breast 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 4774. doi:10.1158/1538-7445.AM2011-4774
Abstract 4777: Loss of death receptor 5 expression in plasmacytic MALT lymphoma is associated with genetic aberrations
Authors: Anees Mariam , Horak Peter , Müllauer Leonhard , Streubel Berthold , Raderer Markus , Krainer Michael 
Published: June 2012

Abstract
Introduction: We investigated the expression profiles of TNF-Related Apoptosis Inducing Ligand (TRAIL) pathway components and the mechanisms underlying TRAIL-induced apoptosis in MALT lymphoma. In lymphoid malignancies these have been only explored in a few non Hodgkin lymphomas and in multiple myeloma so far. In view of this, we have performed a pilot study to assess the potential role of TRAIL-pathway in MALT lymphoma with and without plasmacytic differentiation.
Methodology: We assessed paraffin embedded specimens from 20 patients diagnosed with MALT lymphoma and treated at the Medical University of Vienna for the expression of the key components of TRAIL pathway including TRAIL, death receptors 4 and 5 (DR4 and DR5) and the long form of the FLICE inhibitory protein (FLIPL) by immunohistochemistry. In addition, we also investigated MALT-lymphoma associated genetic aberrations including t(11;18)(q21;q21), t(14;18)(q32;q21) involving IGH and MALT1, t(1;14)(p22;q32), t(3;14)(q14;q32) involving FOXP1 and IGH and trisomies 3 and 18 by reverse transcriptase polymerase chain reaction and fluorescence in situ hybridization.
Results: We observed a general loss of expression of key TRAIL components in MALT lymphomas with plasmacytic differentiation which were present in normal infiltrating plasma cells. DR4 expression was totally absent from 65.6% of the lymphoma tissues and only weakly present in the remaining 34.4%. DR5 was expressed by only 32.25% of the MALT lymphoma tissues. Out of these, DR5 was expressed by infiltrating regular plasma cells in 50% of cases, by plasmacytic lymphoma cells themselves in 40% and by both types of cells in the remaining 10%. Interestingly, MALT lymphomas expressing DR5 had a normal cytogenetic status while samples with absent or week DR5 expression displayed translocation t(11;18) and trisomy 3, 8 and/or 18. The DR5 loss was significantly correlated with cytogenetic abnormalities (R = -0.488, p=0.008). FLIPL was moderately expressed in 18.75% of our samples while TRAIL was present only in 6.25% of the tissues.
Conclusion: Loss of expression of TRAIL pathway components is a common event in MALT lymphomas with plasmacytic differentiation. Moreover, DR5 expression in particular correlates with the presence of MALT-associated cytogenetic anomalies.
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 4777. doi:10.1158/1538-7445.AM2011-4777
Abstract 4803: Epigenome signatures during gastric carcinogenesis detected by MBD-seq and RRBS technologies
Authors: Kim Hee-Jin , Haam Keeok , Kang Tae-Wook , Kim Seon-Young , Noh Seung-Moo , Song Kyu-Sang , Kim Yong Sung 
Published: June 2012

Abstract
DNA methylation plays an important role in the control of eukaryotic gene expression. Many tumor suppressor genes are silenced by aberrant DNA hypermethylation during carcinogenesis, while genome-wide DNA hypomethylation has been observed in human neoplasia, although the extent of this correlation still remains obscure. Hence DNA methylation profiling of a whole genome is essential to our understanding of its relevance for normal development and diseases including cancer. Recently two genome-wide DNA methylation assays combined with a next-generation sequencing (NGS) platform can be useful to establish the methylation map for a whole genome of cancer cell. One of the methods use affinity based assay to enrich for methylated DNA, called a ‘MBD-seq’ (methylated DNA binding domain sequencing: Nucleic Acids Res. 2010; 38: 391-9). Another one is ‘RRBS’ (reduced representation bisulfite sequencing: Nat Methods. 2010; 7: 133-6) which generates nucleotide resolution of DNA methylation from bisulfite sequencing library that enrich for CpG-dense regions by methylation-insensitive restriction digestion. In this study, we applied the two different methods to the same batch of genomic DNAs of normal gastric mucosa, intestinal metaplasia, and gastric tumor which were isolated microscopically using a laser microdissection system (PALM) with frozen clinical samples of one patient with intestinal type gastric cancer. The epigenome signatures during gastric carcinogenesis will be compared and presented here.
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 4803. doi:10.1158/1538-7445.AM2011-4803
Abstract 4808: Detection of aberrant DNA methylation in saliva samples as a predictor of recurrence in head and neck squamous cell carcinoma patients
Authors: de Carvalho Ana Carolina , Rettori Marianna M. , Maia Danielle C. C. , Carvalho Andre L. , Kowalski Luiz P. , Vettore Andre L. 
Published: June 2012

Abstract
Aberrant DNA methylation (hypermethylation) at CpG islands within promoter regions is an epigenetic mechanism involved in the transcriptional silencing of several tumor suppressor genes. The presence of hypermethylation is commonly reported in different human cancers and might be useful as a molecular marker for tumor cell detection and for early detection of tumor recurrence. Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent types of cancer and the lack of early detection and the high incidence of locoregional recurrence lead to high mortality rates. Therefore, the identification of new molecular markers to be used as diagnostic and prognostic indicators is of paramount importance in reducing these recurrence rates. The aim of this study was to evaluate promoter hypermethylation of tumor suppressor genes using Quantitative Methylation-Specific PCR (Q-MSP) in tumor and salivary rinse samples as a mean to detect epigenetic alterations specific to HNSCC. Tumor samples were collected from 150 patients at the time of surgery while salivary rinses were collected before and after the last curative treatment and during the follow up (every 6 months for 2 years). The hypermethylation profile of 24 genes was analyzed and allowed the selection of a panel of 5 specific and sensitive genes. At least one of these genes was found methylated in 61% of the salivary rinse samples collected before treatment, suggesting that this panel could be useful as a diagnostic tool. Patients harboring aberrant DNA methylation of these genes in the post-treatment salivary rinse showed worse 3-year overall survival (p=0.035) and 3-year free from local recurrence survival (p=0.043). Thus, our results support the idea that the evaluation of gene methylation profile in saliva, a non-invasive method of sample collection, could be a good prognostic indicator of HNSCC recurrence.
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 4808. doi:10.1158/1538-7445.AM2011-4808
Abstract 481: In vivo imaging identifies that myf5+ embryonal rhabdomyosarcoma-propagating cells are dynamically reorganized during tumor growth
Authors: Ignatius Myron S. , Chen Eleanor , Elpek Natalie , Nielsen Petur , Linardic Corinne , Mempel Thorsten , Langenau David M. 
Published: June 2012

Abstract
Embryonal rhabdomyosarcoma (ERMS) is a devastating pediatric cancer with specific features of muscle differentiation. Here, we use a transgenic zebrafish model of RAS-induced ERMS and show that myf5+ ERMS cells possess self-renewal potential, confirming that ERMS is a cancer stem cell driven disease. The ERMS-initiating cell is molecularly similar to an activated satellite cell and expresses myf5, m-cadherin, and c-met. To directly visualize tumor-initiating cells in vivo, fluorescent transgenic zebrafish were created that express myf5-GFP, myogenin-h2b-mRFP, and mylz2-lyn-cyan. These transcription factors are expressed during distinct stages of muscle/ERMS development and transgenic reporter lines using these gene promoters allow self-renewing cells to imaged in live animals by confocal microscopy. myf5-GFP+ ERMS-initiating cells from early stage tumors lie in immediate proximity to muscle fibers where normal satellite cells reside. However, as tumors grow, the niche is greatly expanded with the number of myf5-GFP+ cells increasing by 10-fold per fiber. By late stages of tumor growth, myf5-GFP+ ERMS cells are re-localized into a new tumor-specific stem cell niche that is no longer associated with fibers and is separated from more differentiated myogenin+ and myogenein/mylz2 double positive tumor cells. Analysis of human ERMS showed that tumors also contain regional niches of differentiated and undifferentiated cells. Time-lapse imaging of live zebrafish showed that myf5-GFP+ ERMS cells move only locally within the tumor and remain largely confined to stable self-renewing niches. By contrast, myogenin+ cells move dynamically throughout tumors and colonize new areas for tumor growth by both migration through the tissue and entry into the vasculature system. Following colonization by myogenin+ cells, self-renewing myf5+ cells are recruited to new areas of tumor growth. Our findings reconcile the clinical observation that myogenin-positivity in RMS correlates with poor outcome, because it is these cells that intravasate into blood vessels, invade new areas of tumor growth, and recruit slow moving self-renewing cells to newly colonized areas. Taken together, our in vivo imaging studies provide unprecedented access to directly visualize tumor growth in real-time and to define the kinetics of self-renewal and tumor dissemination as has never been assessed in any experimental 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 481. doi:10.1158/1538-7445.AM2011-481