bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1546: CD44 cleavage promotes anoikis resistance in oral squamous cell carcinoma
Authors: Qian Xu , Kamarajan Pachiyappan , Kapila Yvonne Lorraine 
Published: June 2012

Abstract
Background: CD44, a cell surface proteoglycan receptor, plays an important role in modulating oral squamous cell carcinoma (OSCC) cell functions. The recent identification of CD44 as a cancer stem cell marker led us to hypothesize that cleavage of CD44 may alter OSCC cell-matrix interactions and anoikis resistance, and thereby promote a metastatic phenotype in OSCC.
Methods: Anoikis-resistant cells were developed by maintaining human OSCC (UM-SCC 14A) cells under suspension culture conditions in polyhydroxyethylmethacrylate (poly-HEMA) coated plates. Anoikis sensitive control cells were maintained in adherent culture conditions. CD44 cleavage was blocked by the use of matrix metalloproteinase (MMP) chemical inhibitors, including ADAM-17 and ADAM-10. Western blot analysis was used to examine the relative levels of CD44 among the adherent and anoikis-resistant cells.
Results: This study showed that anoikis resistant OSCC cells exhibit higher levels of CD44 cleavage than their adherent counterparts. The study also showed that ADAM-10 and ADAM-17 chemical inhibitors blocked CD44 cleavage and the formation of anoikis-resistant multicellular aggregates in OSCC cells.
Conclusions: CD44 cleavage plays a crucial role in promoting the anoikis resistant phenotype in OSCC cells, suggesting that CD44 may significantly contribute to OSCC tumor initiation and metastasis. (Supported by NIH RO1 DE014429 to YLK)
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 1546. doi:10.1158/1538-7445.AM2011-1546
Abstract 1558: Paracrine signaling through Mycn enhances tumor-vascular microenvironment in neuroblastoma
Authors: Chanthery Yvan H. , Gustafson W. Clay , Weiss William A. 
Published: June 2012

Abstract
Neuroblastoma, a tumor of peripheral neural crest origin, numbers among the most common childhood cancers. Both amplification of the proto-oncogene MYCN and increased vascular density mark high-risk disease. Since angiogenesis is regulated by phosphatidylinositol-3’ kinase (PI3K), we tested a clinical PI3K inhibitor, NVP-BEZ235, in MYCN-dependent neuroblastoma. NVP-BEZ235 decreased angiogenesis in a primary human neuroblastoma (MYCN-amplified orthotopic xenograft), and improved survival in a transgenic mouse model for MYCN-driven neuroblastoma. Using both gain and loss of function approaches, we demonstrate that the anti-angiogenic efficacy of NVP-BEZ235 was critically dependent on Mycn, in vitro and in-vivo. Thus, clinical PI3K/mTOR inhibitors drive degradation of Mycn in tumor cells, with secondary paracrine blockade of tumor-vascular microenvironment. These observations argue that NVP-BEZ235 should be tested in children with high-risk, MYCN amplified neuroblastoma.
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 1558. doi:10.1158/1538-7445.AM2011-1558
Abstract 1563: M402, a heparan sulfate mimetic, inhibits taxane mediated mobilization of endothelial progenitor cells and their homing to tumors in a mouse model
Authors: Schultes Birgit C. , D'Alessandro Josephine S. , Chu Chia L. , Long Alison , Honan Christopher T. , Kishimoto Takashi K. 
Published: June 2012

Abstract
Treatment with certain anti-cancer agents, particularly taxanes and sunitinib, can lead to mobilization of pro-angiogenic factors and an acute mobilization of Endothelial Progenitor Cells (EPCs), which home to the viable tumor rim where they can enhance tumor vascularization. This phenomenon has been linked to rapid tumor regrowth following chemotherapy or treatment with specific angiogenesis inhibitors and may thus diminish the long-term efficacy of the treatment. EPCs are mobilized in response to circulating growth factors and chemokines (VEGFR, FGF, G-CSF, IL-6, SDF1α, etc.) that are induced by the drug or the progressing tumor. Many of these factors contain heparin binding domains for their anchorage to proteoglycans on cell surfaces or the extracellular matrix. We tested a novel heparan sulfate mimetic, M402, for its ability to inhibit EPC mobilization as well as EPC homing to the tumor as a result of interference with heparin-binding cytokines, chemokines and growth factors. In normal BALB/c mice, G-CSF and Docetaxel induced a significant increase in EPC within 8-24 h of dosing as compared to the saline control, while cisplatin or gemcitabine treatment did not show this effect. The docetaxel-induced EPC mobilization into the blood could be inhibited significantly by M402, similarly to an anti-VEGFR2 antibody (DC101). Analysis of the bone marrow microenvironment indicated that M402 does not inhibit the generation of EPCs but rather prevents the mobilization of EPCs from the bone marrow, likely through disruption of the SDF-1α/CXCR4 axis. M402 alone did not influence EPC mobilization in normal mice. However, in mice bearing orthotopic 4T1 breast carcinoma or Capan-2 pancreatic tumors, treatment with M402 normalized circulating EPCs otherwise mobilized by tumor-secreted factors, particularly G-CSF. Furthermore, M402 inhibited homing of EGFP labeled EPCs into SDF-1a loaded matrigel plugs or 4T1 tumors. The effect on EPCs correlated with decreased tumor angiogenesis as assessed by immuno-histochemistry and microCT. Furthermore, we observed synergistic anti-tumor activity of M402 with docetaxel in the 4T1 model. In conclusion, the experiments show that M402 could inhibit docetaxel or tumor-mediated EPC mobilization by trapping the EPCs in the bone marrow and inhibiting their recruitment into the tumor microenvironment. The data provide a scientific rationale for further studying the observed synergy of M402 with taxanes in cancer patients.
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 1563. doi:10.1158/1538-7445.AM2011-1563
Abstract 1564: Investigating the interaction of tumor xenografts with their microenvironment by combining human- and mouse- specific assays with high throughput RT-qPCR
Authors: Farren Matthew , Weston Susie , Brown Helen , Powell Steve , Shaw Robert , Smith Neil R. , Lovick Susan , Ashton Susan , Wedge Stephen R. , Barry Simon T. 
Published: June 2012

Abstract
Tumour growth is governed by the interaction with its microenvironment through pathways that regulate tumour cell function, angiogenesis, and recruitment of associated stromal cells and immune infiltrate. These complicated biological networks can be studied in tumour xenografts using a combination of gene expression, protein and histological analysis. The majority of gene expression studies either probe expression of specific transcripts by RT-qPCR, or use broad Affymetrix microarrays to examine 1000s of genes. RT-PCR experiments may be too focussed studying the interaction of a small number of pathways, while Affymetrix is often not sensitive enough to detect low abundance transcripts, or is limited by species specificity of the probe sets. For example studying tumour stromal and endothelial cells can be challenging because these cells comprise only a small proportion of the tumour. In this study we have used high throughput RT-qPCR to specifically analyse 180 human and mouse genes (or orthologues) thought to regulate key stromal/tumour interactions in a broad xenograft panel. This approach enabled us to determine the expression patterns of potential angiogenic, migratory and survival drives of a diverse range of tumour xenograft models. Across the xenograft panel these genes distinguished tumours with an Epithelial and Mesenchymal phenotype. Interestingly we find that the transcript profile of the supporting stroma (all murine transcripts) is similar between models and key genes cluster with physiological characteristics such vessel, stromal or inflammatory phenotypes. We also used this approach to assess pharmacodynamic changes in gene expression in the tumour and host compartments in response to a VEGF signalling inhibitor. Surprisingly there was little modulation in the expression of genes in the tumour cell compartment. However, there was a clear down regulation of transcripts corresponding to endothelial cells with a concomitant reduction in the tumour vasculature. This approach has enabled us to gain insight into pre-clinical models and the response to a host targetted therapy. The data provides information that enhances understanding that can be derived using histological analysis and standard protein expression.
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 1564. doi:10.1158/1538-7445.AM2011-1564
Abstract 157: Variability of microRNA measurements in breast ductal carcinomas
Authors: Grizzle William E. , Kerr Elizabeth H. , Parker Suzanne B. , Oelschlager Denise K. , McNally Lacey R. 
Published: June 2012

Abstract
MicroRNAs (miRNAs) are a newly identified class of molecules involved in the post transcriptional regulation of genetic information. Multiple approaches have been developed to measure miRNAs including the measurement of miRNAs in paraffin embedded tissue. There have been few reported studies of the reproducibility of miRNA measurements, especially in paraffin embedded tissues, and how such measurements might vary due to tissue heterogeneity and/or analytical variability. We used microdissected paraffin embedded samples of ductal carcinoma of the breast enriched to a tumor nuclear cellularity of at least 80% to determine the reproducibility of analysis of miRNAs extracted from paraffin sections. From each of 3 microdissected paraffin embedded tissues, six 10μ paraffin sections were cut and combined as one specimen and the following six 10μ sections were combined as a second specimen from the same case. While the sections were adjacent, this would incorporate variation due to tissue heterogeneity over 0.12mm of the specimen that was analyzed. All six specimens were blinded and 1500 miRNAs including miRNAs from mice, rats and plants as controls were analyzed by High Throughput Genomics (HTG) considering each of these 6 specimens as an independent specimen. Even with tissue heterogeneity, the correlations of the values of miRNA of the three pairs of specimens were 0.96, 0.90 and 0.83; the 12 correlations between specimens of different cases did not excel 0.9 and only 2 exceeded 0.8. Results of combining alternative paraffin sections into 2 specimens from these same cases and laser capture microdissection specimens are pending to separate differences due to variation in tissue from analytical variables. Of note, the 22 most upregulated miRNAs (X20 to X30 basal levels) in these breast ductal carcinomas include the following: Let 7b, Let 7f, 1225-3P, 1228, 1237, 1280, 1281, 1308, 16, 1826, 191, 200c, 23a, 27a, 574-5p, 638, 663b, 720, 768-3P, 768-5P, 886-5P, and 92a. These studies are continuing and laser capture microdissection results will be incorporated in the study.
Supported in part by the Breast SPORE at UAB (CA089019-09) and a grant from the Susan G Komen foundation (BCTR0600484).
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 157. doi:10.1158/1538-7445.AM2011-157
Abstract 1579: TGF-β blockade controls ascites by preventing abnormalization of lymphatic vessels in orthotopic human ovarian carcinoma model
Authors: Liao Shan , Liu JieQiong , Jain Rakesh K. , Xu Lei 
Published: June 2012

Abstract
Ovarian cancer is characterized by the rapid growth of solid intraperitoneal tumors and accumulation of ascites, the ascites being the clinical presentation of end-stage disease. The role of Transforming Growth Factor beta (TGF-β) in tumor progression has been well studied. However, the role of TGF-β in lymphatic vessel function remains far from understood. We study the effect and mechanisms of TGF-β blockade in human ovarian cancer. We report that blocking tumor and host TGF-β signaling can significantly inhibit the growth of both VEGF- and IL-8-dependent human ovarian tumors. More importantly, we have shown that TGF-β blockade significantly decreases the volume of ascites by both inhibiting ascites formation and preventing impairment of lymphatic vessel drainage, thus demonstrating its potential as a promising new treatment for malignant ascites. Since a number of agents that target the TGF-β-pathway are in clinical trials, the results of the proposed study could be rapidly translated to the clinic.
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 1579. doi:10.1158/1538-7445.AM2011-1579
Abstract 158: Expression of miR-205 is significantly associated with prognosis of endometrial cancer
Authors: Karaayvaz Mihriban , Zhang Cecilia , Mehmood Saira , Georgakopoulos Penelope , Burke Stephanie , Shroyer Kenneth , Liang Sharon , Ju Jingfang 
Published: June 2012

Abstract
Background: microRNAs (miRNAs) have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. As a result, miRNAs represent important diagnostic biomarkers for the advancement of cancer and potential therapeutic approaches. They may be up-regulated or down-regulated in various tumor types, thus act as oncogenes or tumor suppressors. Although accumulating evidence suggests the role of aberrant miRNA expression in endometrial carcinogenesis, there is still limited data available about the endrometrial miRNAs. Endometrial cancer is characterized by frequently infiltrating tumors, and one of the most important molecular alterations in this process is through epithelial-mesencymal transition (EMT). Several studies implicated the role of miRNAs targeting the critical players during EMT. The goal of this study is to investigate the clinical utility of selected key miRNAs in archival FFPE tissue samples of patients with endometrial cancer. In this study, the expression of miR-26a, miR-205, miR-200c, miR-192, miR-215, let-7g, miR-21, miR-181b were quantified from 20 stage I, 2 stage II, 5 stage III, 8 stage IV endometrial cancer patients (endometrioid-type endometrial cancer (EEC), endometrial serous carcinoma(ESC), clear cell carcinoma(CCC) undifferentiated carcinoma (UDC), malignant mullerian mixed tumor (MMMT)) with up to 15 years clinical follow up information.
Methods: Using archival FFPE tissues, areas of tumor and normal tissues were identified according to the corresponding hematoxylin and eosin stained sections, and cores of 1.5 mm in diameter were extracted. Total RNAs were isolated from 35 paired endometrial tumor and adjacent normal tissue specimens by using Trizol based approach. The expression levels of miRNAs were quantified by using real-time qRT-PCR analysis.
Results: The expression of miR-205 (p=0.0002) and miR-200c (p&lt;0.0001) were significantly elevated in endometrial cancer tissue specimens when compared to adjacent normal tissues. Kaplan-Meier survival analysis indicated that low levels of miR-205 expression (hazard ratio, 0.309; log rank test, p=0.018) is closely associated with better patient's overall survival.
Conclusions: miR-205 holds a great potential as a prognostic biomarker in endometrial 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 158. doi:10.1158/1538-7445.AM2011-158
Abstract 1580: Molecular mechanisms of OSM-induced VEGF in breast cancer
Authors: Nandakumar Madhuri , Fox Ryan , Jorcyk Cheryl 
Published: June 2012

Abstract
Oncostatin M (OSM) is an interleukin-6 (IL-6) family cytokine that has been shown to induce expression of vascular endothelial growth factor (VEGF) in astroglioma and in hepatocellular and breast carcinoma. It is also known to induce VEGF in non-cancerous cells such as cardiac myocytes, hepatocytes, and smooth muscle cells. Under hypoxic conditions, VEGF expression is known to be dependent on the transcription factor hypoxia-inducible factor 1 alpha (HIF1α). Our current studies were designed to determine whether VEGF expression induced by OSM and other IL-6 family members, including IL-6 and leukemia inhibitory factor (LIF), is likewise dependent on HIF1α in human breast cancer cells. To analyze VEGF expression levels, MDA-MB-231 and T47D human breast cancer cells were cultured in the presence or absence of OSM, IL-6, and LIF, with or without a HIF1α siRNA, for 12 to 72 hrs. All three cytokines significantly induced HIF1α expression by Western blot analysis at each time point in both MDA-MD-231 and T47D cells. Conditioned media from these experiments was also analyzed using ELISA to determine HIF1α-induced VEGF expression. Treatment with OSM resulted in a two- to three-fold induction of secreted VEGF, while treatment with IL-6 and LIF showed no significant induction. In addition, OSM-induced VEGF expression was independent of HIF1α in MDA-MB-231 cells. This was indicated by unchanged secreted VEGF levels despite the reduction of HIF1α expression in siRNA treated groups. In T47D cells however, HIF1α siRNA-treatment for 72 hrs reduced VEGF levels by 40% suggesting that OSM-induced HIF1α may be partially responsible for VEGF expression in this cell line. To summarize, it is important to note that IL-6 and LIF did not induce VEGF expression in two commonly used human breast cancer cell lines, MDA-MB-231 and T47D. Furthermore, OSM-induced VEGF was not dependent on HIF1α in MDA-MB-231 cells, suggesting regulation of VEGF by an alternative molecular mechanism. Investigations are in progress to better understand mechanisms utilized by breast cancer cells for OSM-induced VEGF expression. Future results could lead to the potential design of OSM-targeted therapeutics. Funded by NIH R15CA137510, ACS RSG-09-276-01-CSM, Susan G. Komen for the Cure KG100513, and NIH/NCRR P20RR016454.
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 1580. doi:10.1158/1538-7445.AM2011-1580
Abstract 1584: Characterization of 28 patient-derived colorectal cancer xenografts and analysis for predictive response markers to current standard treatment
Authors: Becker Michael , Rivera-Markelova Maria , Merk Johannes , Sers Christine T. , Slisow Wassilij , Rosenthal Andre , Hinzmann Bernd , Schlag Peter M. , Hoffmann Jens , Fichtner Iduna 
Published: June 2012

Abstract
Improved methods for the preclinical characterization of anti-cancer drugs in larger panels of primary lung cancer xenograft models have recently described (Fichtner et al. Clin Cancer Res. 2008;14(20):6456-68). These models consider more thoroughly the heterogeneity and genetic instability of tumors in a way ultimately enabeling treatment decisions on an individualized basis.
The approach is based on large scale screening for activity in new in vivo models combined with extensive characterization of these models (gene expression and mutations). Bioinformatic methods are then used to further evaluate the mechanism of action of new drugs, to investigate possible resistance mechanisms and provide a rationale for combination therapies.
Here we describe the development of a panel of primary patient derived colorectal cancer models. Primary colon carcinoma tissue samples were collected using a standardised procedure. Tumour pieces were transplanted onto immunodeficient mice immediately after surgery. A panel of 28 stably passagable colon cancer xenografts could be established as permanent tumour models. The results obtained so far, show that these patient-derived colon cancer models feature a high coincidence with the original tumour regarding histology and gene expression profiling. Response analysis according to clinical trial criteria revealed that the standard drug Oxaliplatin induce a overall response in 8 of the 28 xenograft models.
Gene expression analyses were performed to identify predictive profiles for Oxaliplatin sensitivity. As one example, the effectiveness of Oxaliplatin seems to be related to the differential expression of genes which products are involved in the wnt pathway.
The analysis of drug sensitivity in this set of models together with bioinformatics coorelations will provide hypotheses for further studies to identify patients that will more likely benefit from a drug as well as provide a rationale for combinations to be tested in clinical trials.
These new approaches may help to better integrate research results in clinical development and may increase the success of new anti-cancer drugs in clinical studies.
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 1584. doi:10.1158/1538-7445.AM2011-1584