bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1441: Use of RFP and GFP transgenic nude mice to study the tumor microenvironment of liver metastasis
Authors: Suetsugu Atsushi , Osawa Yosuke , Nagaki Mashito , Saji Shigetoyo , Moriwaki Hisataka , Momiyama Masashi , Bouvet Michael , Hoffman Robert M. 
Published: February 2011

Abstract
The tumor microenvironment (TME) is critical for tumor progression in the liver. To examine the role of the TME in liver metastasis, we developed color-coded imaging of the TME using green fluorescent protein (GFP) transgenic and red fluorescent protein (RFP) transgenic nude mice, to investigate cancer-host-cell interaction. Non-colored human colon cancer cells (HCT-116, 2×106 / 50 µl) were injected in the spleen of GFP or RFP nude mice. Fluorescence imaging of the metastatic liver tumors used the Olympus OV100 small animal imaging system. The fluorescence area of the liver was measured and liver sections were stained with hematoxylin and eosin and desmin. HCT-116 cells formed tumor colonies in the liver 28 days after cell transplantation to the spleen. In the metastatic liver tumors in RFP nude mice, RFP-expressing stroma cells derived from the host animal appeared around the edge of HCT-116 tumors. The infiltration of RFP-expressing inflammatory cells was observed in the central necrotic area of the tumors. The fluorescence of the metastatic liver tumors in the GFP nude mice was weaker than that from the RFP mice. In the GFP mouse, only non-parenchymal cells of the liver had GFP fluoresecence. The GFP non-parenchymal cells greatly increased in the liver during tumor-colony growth and surrounded the metastatic tumors. Desmin positive cells predmoninated in the non-parenchymal and increased around the metastatic tumors suggesting that fibroblasts are greatly increased around the metastatic tumors in the liver and may have a role in tumor progression. This novel imaging model of the TME will enable the identification and characterization of stromal cells involved in cancer progression in the liver.
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 1441.
Abstract 1446: Effect of PF-03475952, a potent and neutralizing CD44 antibody, on cancer cell apoptosis in vitro and metastasis in two orthotopic models
Authors: Wang Yuli , Wang Jean , Li Gary , Jackson-Fisher Amy , Brett Simmons , Kraynov Eugenia , Li Baiyong , Pocalyko David 
Published: February 2011

Abstract
Effect of PF-03475952, a potent and neutralizing CD44 antibody, on cancer cell apoptosis in vitro and metastasis in two orthotopic models
Yuli Wang, Jean wang, Gary Li, Amy Jackson-Fisher, Brett Simmons, Eugenia Kraynov, Christy Ji, Baiyong Li, and David Pocalyko
Pfizer Global Research & Development, San Diego, CA 92121
CD44 is a cell surface glycoprotein that has multiple functions. It can act as a receptor for ligands such as hyaluronic acid and osteopontin. Additionally, it can function as co-receptor to modulate the activation of growth factor receptors such as c-met & ERBB. CD44 can also influence cell signaling through interaction with components of the actin cytoskeleton such as the ERM protein.
CD44 expression is increased in many types of human cancer. It is also a cell surface marker for cancer stem cells in breast cancer and HCC. In HCC, CD44 overexpression is a frequent event (∼30% based on several reports) and CD44 up regulation is associated with metastasis and poor patient survival. Down regulation of CD44 with RNAi knockdown or neutralizing antibody has been reported to reduce tumor metastasis, recurrence, and growth in different models.
PF-03475952 is a fully human IgG2 anti-CD44 monoclonal antibody that was initially developed as a potential therapeutic agent for rheumatoid arthritis. It was shown previously that the PF-03475952 can disrupt the interaction of CD44 with its ligand, hyaluronic acid. The antibody binding induces loss of CD44 from the cell surface, and inhibits LPS-induced cytokine release from various leukocytes.
In this report, we evaluated the potential of PF-03475952 as a cancer adjuvant therapy for HCC. HCC is the third most deadly forms of cancer world-wide with frequent early recurrence due to inter and extra hepatic metastasis. The effect of PF-03475952 on cancer metastasis was first demonstrated in an M24met melanoma model. The expression of CD44 and the effects of PF-03475952 on HCC cell lines were then characterized. In vitro, PF-03475952 was able to reduce cell adhesion and promote apoptosis in a CD44-dependent manner. More importantly, PF-03475952 can reduce lung metastasis in a CD44-positive HCC orthotopic model.
The study suggested that the CD44 neutralizing antibody, PF-03475952, could be an efficacious agent as adjuvant therapy to prevent cancer metastasis.
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 1446.
Abstract 1452: Examination of mechanisms involved in spontaneous melanoma metastasis to CNS
Authors: Cruz William , Man Shan , Jaramillo Maria , O'Connor-McCourt Maureen , Banville Myriam , Kerbel Robert S. 
Published: February 2011

Abstract
Cerebral metastases occur in a majority of metastatic melanoma patients and are the major cause of mortality in those cases. Testing of novel therapeutic approaches has been slowed by the absence of appropriate preclinical models of spontaneous metastatic melanoma, particularly spontaneous CNS metastasis. To examine the efficacy of potentially promising treatment regimens, a highly visceral metastatic variant of the human melanoma WM239 cell line, named 6-4L, was developed and used to test the effectiveness of metronomic chemotherapy in the treatment of advanced metastatic disease. Concurrent low-dose cyclophosphomide/vinblastine led to significant disease control of mice with overt metastases in lungs, liver and lymph nodes. Among mice that survived the long-term treatment, 20% showed the presence of spontaneous brain metastases which likely emerged as a result of prolonged survival mediated by the therapy. From these, 2 cell lines (131/4-5B1 and 131/4-5B2) were generated which metastasize spontaneously to brain parenchyma. This constitutes the first model of heritable spontaneous melanoma brain metastasis by a human cell line from a subdermal transplant, without any therapeutic intervention. Characterization shows two salient functional alterations that may contribute to this phenotype 1) adhesion to brain-endothelial cells and 2) proliferation in the presence of brain-derived factors. When compared to poorly or highly metastatic cell lines (WM239A and 113/6-4L respectively), microarray analysis shows that 4-5B1/B2 cell lines have markedly different expression profiles. These cell lines show differential expression of 108 genes, thirteen of which share a common alteration for both brain-metastatic cell lines, including ednrb (endothelin receptor B) and bcl2a1 (BCL2-related protein A1), which stand out as potentially relevant. These molecules have been previously associated with increased proliferation in the presence of ENT-3; a peptide expressed in the brain, as well as resistance to TNF induced apoptosis and increased metastatic potential. Lentiviral vectors were used to induce stable upregulation of these genes in the otherwise non-brain metastatic parental 113/6-4L cell line. This upregulation mediated an increase in metastatic potential and, in the case of EDNRB, increased intracranial tumor growth. Future efforts will focus on characterizing the alterations in these cell lines, to confirm their clinical relevance and to test novel inhibitors for treating melanoma brain metastases.
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 1452.
Abstract 1456: Cerebrospinal fluid vascular endothelial growth factor in patients with brain metastases from breast cancer
Authors: Song Susan S. , Malchow Chris , Lok Edwin , Swanson Kenneth , Wong Eric T. 
Published: February 2011

Abstract
There is a rising incidence of brain metastases from breast cancer. Having an improved means of detecting and monitoring such brain metastases would be valuable. Using samples stored in our Cerebrospinal Fluid (CSF) Bank, we identified 176 samples from 71 patients with brain metastases from breast cancer. The CSF VEGF levels were measured using enzyme-linked immunosorbent assay and normalized to phosphate buffered saline. The highest CSF VEGF ratios from individual patients were correlated with patient survival. The median CSF VEGF ratio was 1.043, with a range of 0.575 to 22.060. At the time of analysis, 51 patients were deceased while 30 were alive, with a median survival of 4 months. The median survival of patients with CSF VEGF ratio ≤ 1.000 was 7 months (range 1 to 31 months) versus 2.5 months (range 0.5 to 60 months) for those with CSF VEGF &gt; 1.000. Furthermore, increasing CSF VEGF levels also appear to correlate with increasing number of brain metastases detected on magnetic resonance imaging. We conclude that VEGF is a potential biomarker in the CSF for brain metastases from breast cancer.
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 1456.
Abstract 1458: Orthotopic imageable peritoneal carcinomatosis GFP nude mouse model of human esophageal cancer
Authors: Gros Stephanie J. , Dohrmann Thorsten , Kaifi Jussuf T. , Bouvet Michael , Hoffman Robert M. , Izbicki Jakob R. 
Published: February 2011

Abstract
The aim of this study was to establish an imageable orthotopic GFP-expressing nude-mouse model of human esophageal cancer peritoneal carcinomatosis. Nude mice were orthotopically injected in the abdominal esophagus with stably transfected GFP- PT1590 human esophageal cancer cells. Tumor progression was visualized by fluorescence imaging. Fifty percent of the animals developed extensive peritoneal spread without a distinct primary tumor at the injection site. Continuous and metastatic spread to liver, lung, and lymph node was also observed. Fluorescence imaging enabled rapid and specific visualization of tumor progression without anaesthesia. Intraperitoneal and metastatic tumor spread of GFP-PT1590 esophageal carcinoma demonstrated a highly aggressive but heterogenous behaviour. Although injection of the esophageal carcinoma cell line PT1590-GFP did not lead to primary esophageal tumor development at the site of injection, 50% of the mice developed extensive peritoneal spread as well as lymph node and organ metastasis. The orthotopic cell injection model resulting in peritoneal carcinomatosis of esophageal adenocarcinoma, which can be visualized in real time using fluorescence imaging, will be a valuable tool for the study of esophageal cancer metastasis and its treatment.
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 1458.
Abstract 1471: Glycoprotein 90K suppresses Wnt signaling via ISGylation-dependent ubiquitination of β-catenin that needs interaction with CD9/CD82
Authors: Bae Jeong A , Lee Ji Hee , Sun Eun Gene , Bae Woo Kyun , Cho Sang Hee , Chung Ik Joo , Kim Kyung Keun 
Published: February 2011

Abstract
Backgrounds: Previously, we have observed that a tumor-associated 90K glycoprotein plays a potential tumor suppressor role in colorectal cancer (CRC) cells via antagonizing the canonical Wnt signaling pathway, which is functionally masked via interaction with extracellular galectin. Here, we investigated the signaling pathways of 90K action on CRC cells and its expression in human CRC tissues. Results: We identify a novel pathway comprising a secretory 90K and a CD9/CD82 tetraspanin web; in this pathway, 90K interacts with CD9/CD82, suppresses the Wnt/β-catenin signal via a novel proteasomal-ubiquitination mechanism of β-catenin that is dependent of ISG15 modification (ISGylation). In colon tissues from stage IV human CRC and invading cancer cells of corresponding metastatic liver tissues, in which β-catenin and galectin expression was higher, immunostained 90K and CD9/CD82 were lower than in adjacent hepatic tissues or colon tissues from stage I. Conclusions: 90K itself has antitumor activity in CRC cells via suppression of Wnt signaling with a novel mechanism of ISGylation-dependent ubiquitination of β-catenin when it interacts with CD9/CD82, but is downregulated in advanced CRC tissues. Our data suggest a strategy of strengthening this novel pathway with concomitant knockdown of galectins as a potential therapeutic approach to CRC progression.
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 1471.
Abstract 1472: Bcl-3 as a carcinogenic factor in non-endometrioid endometrial carcinoma
Authors: Lee Yoo-Kyung , Chung Hyun Hoon , Kim Jae Weon , Park Noh-Hyun , Kang Soon-Beom , Song Yong-Sang 
Published: February 2011

Abstract
Objectives : The aim of the study was to evaluate the Bcl-3 expression in normal endometrium, endometrial hyperplasia, and endometrial cancer.
Methods : Retrospectively collected paraffin blocks from 30 cases of normal endometrium, 16 of endometrial hyperplasia, 24 of endometrioid endometrial cancer, and 12 of non-endometrioid endometrial cancer were analyzed. Expression of Bcl-3 was assessed by immunohistochemistry. The staining pattern was correlated with clinicopathological variables.
Results : While none was positive in normal endometrium and endometrial hyperplasia and only 2 cases (8.3%) were positive for Bcl-3 in endometrioid endometrial cancer, 5 cases (41.7%) was positive in non-endometrioid endometrial cancer. Positive expression of Bcl-3 significantly correlated with non-endometrioid endometrial carcinoma (p=0.017), advanced stage (p=0.030), and high grade (p=0.001). Moreover, Bcl-3 positivity was associated with aggressive parameters including ovarian invasion (p=0.004), peritoneal cytology (p=0.029), lymphovascular space invasion (p=0.002), and lymph node metastases (p=0.029). In contrast, there was no significant correlation between expression of Bcl-3 and myometrial invasion or cervical invasion. In addition, Bcl-3 expression was not related to recurrence of disease.
Conclusion : Bcl-3 is strongly expressed in non-endometrioid endometrial cancer, but less frequently in endometrioid endometrial cancer and hyperplasia. It is suggested that Bcl-3 is related with the carcinogenesis of non-endometrioid endometrial cancer.
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 1472.
Abstract 1478: Role of Stat3 Ser727 phosphorylation in mouse hepatocarcinogenesis
Authors: Ogawa Katsuhiro , Miyakoshi Masaaki , Yamamoto Masahiro , Tanaka Hiroki , Yaginuma Yuji 
Published: February 2011

Abstract
Inappropriate activation of signal transducer and activator of transcription 3 (Stat3) occurs with extreme frequency in a wide variety of cancers including HCC, and constitutive Stat3 activation in hepatocytes was demonstrated to accelerate hepatocarcinogenesis, while repression of Stat3 activation suppresses hepatocarcinogenesis. Diverse factors such as cytokines, growth factors and oncoproteins can activate Stat3, where phosphorylation of the conserved tyrosine residue at the C-terminus (Y705) results in the Stat3 homodimer or the heterodimer with Stat1, and phosphorylation of the serine residue on the transactivation domain (S727) contributes to its maximal transcriptional activity. The activated Stat dimers bind to specific DNA-response elements in the promoter of target genes and thereby induce unique gene expression programs cooperating with other transcription factors and cofactors. We investigated Stat3 activation in mouse hepatocarcinogenesis induced by neonatal treatment with diethylnitrosamine (DEN) and found that Stat3 phosphorylation occurred by two steps, where S727 phosphorylation was seen in the preneoplastic stage, whereas Y705 phosphorylation was further associated with malignant progression. In mouse HCC cells, serum treatment induced Ser727 phosphorylation via MAPK activation, associating with cell proliferation and Stat3 nuclear translocation, whereas IL-6 induced Tyr705 phosphorylation via JAK activation without stimulating cell proliferation and the Stat3 nuclear translation. On the other hand, the Ser727 phosphorylation dead Stat3 (S727A), in which the serine residue was replaced by alanine, reduced the cell proliferation and Stat3 nuclear translocation, while the Ser727-phosphorylation mimic Stat3 (S727D), in which the serine residue was replaced by aspartic acid, enhanced the cell proliferation and Stat3 nuclear translocation. To further investigate the role of Stat3 Ser727 phosphorylation, the Stat3 knockdown HCC cell lines were established by introducing the Stat3 siRNA into the mouse HCC cells. These cell lines showed retarded growth and less attachment to the substrate forming spheroidal aggregates, whereas the parent cells showed rapid proliferation and attached to the substrate with extended morphology. cDNA array analysis revealed that the Stat3 knockdown cells showed variety of gene expression changes relating to cell survival and growth, and RT-PCR demonstrated that the expression of EGFR, FGFR and E-cadherin was markedly reduced in the Stat3 knockdown cells. Our findings indicate that the Ser727-phosphorylated Stat3 plays an important role from the early stage in mouse hepatocarcinogenesis, presumably by controlling cellular growth and survival.
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 1478.
Abstract 1480: Characterization of C35, a novel protein binding partner of p73, in gynaecological cancers
Authors: Wong Sanna Ching-shan , Leung Thomas Ho-yin , Chan Karen Kar-loen , Ngan Hextan Yuen-sheung 
Published: February 2011

Abstract
The p53 family protein p73 encodes pro-apoptotic (TAp73) and anti-apoptotic (DNp73) isoforms. The functional role of the two isoforms in cancer development is still unclear. In this study, by yeast-2-hybrid screening using DNp73 as a bait, we identified C35 (C17orf37) as a novel protein interacting partner of p73. C35 was mapped to chromosome 17q12. It was overexpressed in breast cancer and prostate cancer. Its expression was positively correlated with the grade and stage of breast cancer progression. A recent study reported that C35 promotes cell migration and invasion in prostate cancer cells. However, the significance of C35 in cancer development remains to be elucidated. In this study, we focused on the functional role of C35 in gynaecological cancers. The binding of C35 and DNp73 was confirmed by co-immunoprecipitation. Quantitative real-time PCR revealed that mRNA expression of C35 in ovarian and cervical cancer cell lines was higher than that in normal cell lines. In addition, mRNA expression of C35 was significantly higher in ovarian cancer clinical samples than that in normal samples (p&lt;0.0001, t-test). To investigate the function of C35, SiHa and OV2008 cells stably expressing C35 were established. The protein expression of C35 was confirmed by western blot analysis. In studying the effect of C35 on cell transforming ability, soft agar assay was performed. The result showed that the number of colonies formed by the C35 stable clones was significantly higher than those formed by the parental cells and control vector stably transfected cells. In addition, the size of the colonies formed by the C35 stable clones was larger. Wound healing assay and transwell migration assay were performed to investigate the effect of C35 on cell migration rate. We found that the migration rate of the C35 stable clones was higher than that of the parental cells and vector transfected cells. XTT assay revealed that the proliferation rate of the C35 stable clones was higher than that of the parental cells and vector controls. In summary, our findings suggested that C35 is overexpressed in ovarian cancer. C35 likely exerts its oncogenic roles to enhance transformation, cell migration and cell proliferation in gynaecological cancers. Further study of the significance of the DNp73-C35 interaction may give insight into their oncogenic properties.
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 1480.