bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1567: Pancreatic tumor cell secreted Cyr61/CCN1 enhances abnormal angiogenesis: A key event for metastasis
Authors: Mehta Smita , Majumder Monami , Haque Inamul , Banerjee Snigdha 
Published: June 2012

Abstract
CYR61/CCN1, a member of the cysteine rich 61/connective tissue growth factor/nephroblastoma over expressed (CYR61/CTFG/NOV) family of growth factors, is a pro-angiogenic factor that mediates diverse roles in development, cell proliferation, and tumorigenesis. In our previous studies, we have demonstrated that Cyr61 is highly expressed in aggressive pancreatic cancer cell lines. The objective of this study is to evaluate whether tumor cell-secreted Cyr61 is able to enhance the interactions of endothelial cells and vascular smooth muscle cells for remodeling of vasculature. To do so, we determined the impact of conditioned media (CM) of different pancreatic cancer cell lines and their side populations on in vitro and in vivo angiogenesis. The in vitro angiogenesis assay demonstrates that the CM of Cyr61 positive pancreatic cancer cells drastically altered the angiogenesis. CM induces deformed capillary-like structures as compared to regular media and this effect is cell type specific. Moreover, CM also drastically altered the attachment of vascular smooth muscle cells to the capillaries. These in vitro studies were further confirmed by in vivo gel foam assay in mice. The abnormal effects of CM can be overruled by nullifying the Cyr61 expression through Cyr61-specific shRNA or neutralizing Cyr61 antibody. Collectively, these studies suggest that Cyr61 could be a target molecule to normalize the angiogenesis to prevent metastatic growth.
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 1567. doi:10.1158/1538-7445.AM2011-1567
Abstract 1576: Prostaglandin I2 signaling regulates micro-metastasis in lung cancer
Authors: Minami Yoshinori , Okumura Shunsuke , Sasaki Takaaki , Kawabe Junichi , Endo Satoshi , Satoh Kazuhiro , Kitada Masahiro , Fujita Yuka , Hasebe Naoyuki , Ohsaki Yoshinobu 
Published: June 2012

Abstract
Background: Bone marrow-derived cells (BMDCs) play an important role in the initiation of neo-angiogenesis, and contribute to the diseases including ischemic diseases, retinopathy, and cancer. We have reported that BMDCs express prostaglandin I2 (PGI2) specific receptor, IP and the PGI2-IP signaling system maintains the function of BMDCs. Additionally, we have reported that the PGI2-IP signaling in BMDCs play an important role for tumor growth, by using mouse bone marrow transplanted models and tumor xenograft mouse models.
Objectives: The purpose of this study was to test the hypothesis that PGI2-IP signaling system regulates micro-metastasis in lung cancer.
Methods: In vitro study, 5-bromo-2’-deoxy-uridine (BrdU) cell proliferation assay and clonogenic cell assay were used to clarify the effect on lung cancer cell (A549, PC9) proliferation and cellular form in the existence of IP receptor agonist or antagonist. Human cytokine antibody array was performed to detect the expression of angiogenic cytokines and growth factors secreted by the treated cells.
In vivo study, we employed both a mouse lung metastasis model and a mouse bone marrow transplantation model. We used GFP-labeled or DsRed-labeled lung cancer cells to distinguish cancer cells from BMDCs. Lung cancer cells were injected into the tail vein of mice (ICR nu/nu), which were transplanted with bone marrow cells from GFP-labeled wild-type or IP knockout mice. Real-time RT-PCR was used to quantify lung metastasis of human cancer cells in nude mice, and the expression levels of housekeeping genes (human and mouse GAPDH) in the lungs were measured. Immunofluorescence assay was performed to evaluate angiogenesis in pulmonary metastatic tumors.
Results: In vitro study, PGI2-IP signaling didn't impair proliferation of lung cancer cells and production of angiogenic cytokines secreted by tumors.
In the mice lung metastasis model, micro-metastasis in lung cancer was regulated by PGI2-IP signaling system. RT-PCR assay showed that PGI2-IP signaling changed the expression levels of human lung cancer cells in mice lungs. In the immunofluorescence assay, PGI2-IP signaling influenced the expression of pericyte markers around the tumors.
Conclusions: The present study demonstrated that PGI2-IP signaling system regulates micro-metastasis in lung cancer. These results suggest that PGI2-IP system may become a novel therapeutic target in lung metastasis.
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 1576. doi:10.1158/1538-7445.AM2011-1576
Abstract 1577: The Impact of M1/M2 Tumor Associated Macrophage (TAM) Polarization on Cancer Progression in NSCLC
Authors: Hsiao Yi-Jing , Yu Sung-Liang , Chen Huei-Wen , Chen Jeremy J.W. , Yuan Ang , Yang Pan-Chyr 
Published: June 2012

Abstract
Tumor microenvironment has important influences on tumor progression. One of the effectors is tumor-associated macrophages (TAMs) that are characterized as M1/M2 by their different immune responses, induced by Th1 and Th2.
In our study, we polarized THP-1 into classically (M1) and alternatively (M2) activated macrophages and evaluated some different markers to distinguish M1 and M2 subtype (M2a, M2c). M1 macrophage expressed high IL-1, IL-6, IL-12, IL23, TNF-α, and a surface maker CCR7; M2a and M2c macrophages expressed high IL-10 and a surface maker CD206, but expressed CD23 and CD163, respectively. Microarray analysis was used to evaluate the alteration of gene expression of lung cancer cell line (A549) after coculture with different subtype TAMs (M0, M1, M2a and M2c). Bioinformatics analysis indicated that TAMs mainly alter cell cycle, coagulation and cell adhesion pathways in tumor cells.
The M0, M2a and M2c promoted the invasion ability of A549 after coculture for 2days. Otherwise, M1 condition medium reduced cell viability and induced apoptosis of A549 but not H1299, the p53 null cell line. Moreover, the M2 macrophage condition medium but not M1 increased the drug resistance ability of A549 cells after long-term coculture. More importantly, in vivo tumorigenesis assay indicated that M2 can promote tumor growth and angiogenesis. Different subtypes of macrophages can modify behaviors of cancer cells and may contribute to tumor progression. Further studies in the detailed mechanisms involved in the interaction of TAMs and cancer cells will unveil the role of macrophages in tumor 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 1577. doi:10.1158/1538-7445.AM2011-1577
Abstract 1582: Identification of miRNAs that regulate breast cancer stem cells and spontaneous metastases in orthotopic mouse models
Authors: Liu Huiping , Bockhorn Jessica , Dalton Rachel , Olopade Olufunmilayo F. , Clarke Michael F. , Greene Geoffrey L. 
Published: June 2012

Abstract
To examine the role of microRNAs (miRNAs) in breast cancer progression, we profiled miRNA expression in both clinical breast tumors and human-in-mouse breast tumor models, where breast cancer stem cells (BCSCs) contribute to spontaneous metastasis. CD44+ cells from both primary tumors and lung metastases were highly enriched for tumor initiating cells. Based on the miRNA profile analyses, we identified a limited number of miRNAs that are differentially expressed in metastatic triple-negative breast tumors and that regulate BCSCs and tumor invasion in vitro. To facilitate miRNA functional studies in vivo, we also developed tumor imaging approaches by transducing BCSCs with optical reporter fusion genes (Luc2-eGFP or -tdTomato), which enabled both bioluminescence imaging (BLI) and FACS-based analysis and sorting. With non-invasive BLI approaches, as few as 10 cells of stably labeled BCSCs can be tracked in vivo. When optical reporters are expressed along with miRNA precursors or inhibitors, the effects of introduced miRNA candidates can be evaluated by selective imaging of the transduced tumor cells, thereby eliminating the noise of un-transduced cells. Using this model system and imaging technology, we have screened and identified miRNAs that regulate BCSCs (e.g. miR-200 family) and metastatic CSCs (MCSCs). Our metastatic cancer models, combined with non-invasive imaging techniques, comprise an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of MCSCs, to explore therapeutic strategies targeting metastasis in general, or to evaluate individual patient tumor cells and predict response to therapy.
Supported in part by the NIH T90, DOD BC087695 and Chicago Fellows Program at The University of Chicago (H.L.), University of Chicago Cancer Research Center Pilot Research Fund, UCMC/Northshore Collaborative Research Award and Ludwig Fund (G.L.G and H.L). NIH R01 and Breast Cancer Research Foundation (M.F.C. and H.L.).
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 1582. doi:10.1158/1538-7445.AM2011-1582
Abstract 1594: Significant in vivo activity of ENMD-2076, a novel inhibitor of Aurora receptor tyrosine kinases, alone and in combination with lenalidomide against plasma cell myeloma
Authors: Sandusky George E. , Rodgers Matt , Zhang ShuHong , Sinn Anthony , Pollok Karen , Farag Sherif 
Published: June 2012

Abstract
Aurora kinases, particularly aurora A and aurora B, play a role in normal cell proliferation. Since an unusually high expression of Aurora kinases has been reported in tumor cells, they have become the target of a variety of novel anticancer drugs. One such drug, ENMD-2076, was studied in a translational research project involving a xenograft mouse model and a phase I clinical trial. The preclinical xenograft model evaluated multiple myeloma tumors in NOD/SCID mice treated with ENMD-2076, lenalidomide, and combinations of both drugs, and compared to an untreated vehicle control group. Immunohistochemistry (IHC) was used to predict the effectiveness of treatment for multiple myeloma based on caspase-3, Ki67, phospho-histone H3 (p-H3), and CD34 biomarker expression. IHC slides were quantified using both a traditional pathology hand count and an image analysis program (Image J). The Image J data closely mirrored the hand count for all four biomarkers. At the highest combined dosage, hand count data showed CD34 levels down 74.2% from the vehicle control. Ki67 and p-H3expression were down slightly, and caspase-3 was increased two fold in the combined drug treatment group. Comparing the two drugs, it was evident that the ENMD-2076 aurora kinase inhibitor had a stronger anti-angiogenic effect, while the Lenalidomide had a stronger apoptotic effect. Although the human clinical trial is still in its early stages, initial trends are consistent with results seen in this 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 1594. doi:10.1158/1538-7445.AM2011-1594
Abstract 1602: Mucinous adenocarcinoma developed from human fallopian tube epithelial cells through a combination of defined genetic modifications and tumor microenvironment
Authors: Mercado-Uribe Imelda , Shan Weiwei , Liu Jinsong 
Published: June 2012

Abstract
Epithelial ovarian cancer includes several distinct histologic types including serous, mucinous, endometrioid, and clear cell. The cell origin of these distinct epithelial ovarian cancers has been debated for many years. Recent studies have suggested that some ovarian and pelvic serous carcinomas could originate from the fimbrial end of distal fallopian tube, although direct experimental evidence supporting this hypothesis is still lacking. To test this hypothesis, we immortalized a normal human fallopian tubal epithelial (FTE) cell line by using a retrovirus-mediated infection expressing the early region of SV40 T/t antigen and the human telomerase reverse transcriptase. These immortalized FTEs were then transformed by ectopic expression of oncogenic human HRASV12. Tumorigenicity of the immortalized and/or transformed cells was subsequently tested by anchorage-independence assay and inoculation into nude mice via subcutaneous or intraperitoneal injections. As expected, the HRASV12-transformed FTEs produced tumors through both subcutaneous and intraperitoneal injections, while no tumor growth was observed in immortalized FTEs. To our surprise, however, while histopathologic examination of resulting tumor from subcutaneous injections revealed a largely undifferentiated carcinoma with focal mucin production, tumors from intraperitoneal injections showed mucinous adenocarcinoma with rich mucin production from an undifferentiated area. The mucinous differentiation of tumors was most prominent near the peritoneal fat and other peritoneal organs including the pancreas, spleen, and intestine. Immunohistochemical staining of tumor cells showed positive staining for the epithelial cell markers cytokeratin AE1/AE3 and CA125. Our study demonstrates that FTEs can generate mucinous adenocarcinoma through genetic modifications and that such mucinous differentiation is dependent on the peritoneal microenvironment. Thus, the experiment described here provided the first experimental evidence that fimbrial epithelial cells of the fallopian tube could be a potential source of ovarian mucinous adenocarcinoma, a distinct histologic entity of epithelial ovarian cancers whose origin is largely unknown.
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 1602. doi:10.1158/1538-7445.AM2011-1602
Abstract 1641: Targeting developmental regulators of zebrafish exocrine pancreas as a therapeutic approach in human pancreatic cancer
Authors: Yee Nelson S. , Chun Stephen G. , Zhou Weiqiang , Liang I-Chau 
Published: June 2012

Abstract
We aim to test the hypothesis that histone deacetylases (HDACs) and RNA polymerase III (Polr3) cooperatively control exocrine pancreatic growth, and combined inhibition of HDACs and POLR3 produces enhanced growth suppression in pancreatic cancer. This hypothesis is based on the observations that HDACs and POLR3 play vital roles in fundamental cellular processes, and deregulation of these enzymes has been implicated in malignant transformation. Using chemical inhibitors of HDACs and POLR3, we examined the effect on exocrine pancreas during morphogenesis, and then translated the developmental findings to human pancreatic adenocarcinoma cultured cells. Hdacs and Polr3 are required for exocrine pancreatic epithelial proliferation during morphogenesis. In zebrafish larvae, combination of a Hdac inhibitor (Trichostatin A) and an inhibitor of Polr3 (ML-60218) synergistically prohibited expansion of exocrine pancreas. In human pancreatic adenocarcinoma cells, combination of the clinical HDAC inhibitor suberoyl-anilide hydroxamic acid (SAHA) and ML-60218 produced enhanced suppression of colony formation and proliferation, and induction of cell cycle arrest and apoptotic cell death. The enhanced cytotoxicity was associated with supra-additive induction of a pro-apoptotic regulator and the cyclin-dependent kinase inhibitors. tRNAs have been shown to have pro-proliferative and anti-apoptotic roles, and SAHA-stimulated expression of tRNAs was reversed by ML-60218. These findings demonstrate that chemically targeting developmental regulators in zebrafish can be translated into a potential therapeutic approach in human cancer, and suggest that counteracting the pro-malignant side effect of HDAC inhibitors can enhance their anti-tumor activity.
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 1641. doi:10.1158/1538-7445.AM2011-1641
Abstract 1642: TIP-1 regulates sensitivity of glioma cells to radio- and chemotherapeutic agents through modulating p53 stability and activation
Authors: Han Miaojun , Wang Hailun , Han Zhaozhong 
Published: June 2012

Abstract
Malignant gliomas represent one group of tumors that poorly respond to chemo- and radio-therapies because of the intrinsic or acquired resistance. Identification of novel molecules that are involved in the therapeutics resistance is critical to develop new therapeutic modalities. Our previous studies show that TIP-1 involves in tumor cells response to ionizing radiation (IR). In this study, we found that TIP-1 expression level correlates to the clinical staging and overall patient survival time after diagnosis of malignant gliomas. We hypothesized that TIP-1 is one novel predictive biomarker of glioma cell response to treatment, and targeting TIP-1 represents one novel strategy to combat the disease of high mortality. Studies on cell-based models indicated that TIP-1 deficiency resulted in the enhanced sensitivity of D54 and GL261 glioma cell lines to IR and chemotherapeutic agents, whereas ectopic expression of TIP-1 conferred resistance to the therapeutics in the cells. The data also showed that sensitivity of the glioma cell lines to IR correlates to stability and activation of p53 protein after IR treatment. Yeast two-hybrid screening identified C53/LZAP as one TIP-1 interacting protein within glioma cells. PDZ domain within TIP-1 binds to one classic type I PDZ-binding motif at the carboxyl terminus of C53/LZAP protein. C53/LZAP has been studied as one tumor suppressor and modulator of the cancer cell susceptibility to genotoxic stress including IR and several chemotherapeutic agents. C53/LZAP interacts with ARF and protects p53 from Mdm2-mediated protein degradation. Our data demonstrated that, after irradiation, presence of TIP-1 enhanced C53/LZAP interaction with ARF, thus promoted Mdm2-mediated p53 ubiquitination and resulted in less stable p53 protein. On the other hand, with absence of TIP-1 protein, IR treatment resulted in more stabilized and activated p53 protein that drives IR-induced apoptosis of the glioma cells. Taken together, our data suggests that TIP-1 is one novel modulator of p53 tumor suppressor and contributes to chemo- and radio-resistance of glioma cells. Therefore, targeting TIP-1 represents one novel approach for the improved therapy of malignant glioma.
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 1642. doi:10.1158/1538-7445.AM2011-1642
Abstract 1663: Identification of interleukin 4 receptor alpha (IL-4Rα) as a biomarker of advanced stage human bladder carcinoma
Authors: Joshi Bharat H. , Leland Pamela , Puri Raj K. 
Published: June 2012

Abstract
Previously, we have demonstrated that a variety of human and murine cancer cell lines and tumor specimens overexpress Interleukin 4 receptor alpha (IL-4Rα) chain in vitro and in vivo. We have also shown that cancer cell lines and human bladder tumor specimens express high density IL-4Rα at mRNA and protein levels, which sensitized them in vitro and in vivo to a chimeric fusion immunotoxin consisting of circularly permutated IL-4 and a truncated Pseudomonas exotoxin [cpIL-4(38-37)-PE38KDEL]. In the present study, we have examined the expression of two receptor subunits of the IL-4R complex, IL-4Rα and IL-13Rα1, in 60 human bladder carcinoma tissue microarray (TMA) with different pathological grades by IHC and ISH analyses. The TMA consisted of either grade II papillary transitional cell carcinoma or grade I-III transitional cell carcinoma. By IHC analysis for IL-4Rα, we observed that 52/60 (84%) transitional cell carcinoma samples were ≥2+ staining intensity for IL-4Rα. Interestingly, Grade III TCC specimens were most strongly positive (3+) [18/29 (62%)] compared to Grade II specimens [4/26 (15%)]. Grade 1 specimens showed least positivity [5/5 (100%) and showed only 1+ staining intensity]. ISH results corroborated with the IHC findings, which demonstrated that Grade III tumors were more strongly positive (3+) for IL-4Rα mRNA compared to Grade II specimens [19/26 (73%) Grade III versus 4/26 (15%) Grade II, respectively]. 4/5 (80%) Grade I specimens showed 1+ staining and one sample was weakly positive (+/-). All samples expressed IL-13Rα1 at ≤1+ immunostaining intensity by both IHC and ISH analyses. Additional bladder cancer samples and normal or non-cancerous bladder specimens are being studied for IL-4Rα and IL-13Rα1 expression to confirm our observations. Taken together, these results suggest that IL-4Rα may have a role in disease aggressiveness and may serve as a biomarker of advanced stage 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 1663. doi:10.1158/1538-7445.AM2011-1663
Abstract 1686: Effect of echistatin on proliferation, migration, invasion and angiogenesis of integrin αvβ3-expressing human osteosarcoma
Authors: Tome Yasunori , Kimura Hiroaki , Sugimoto Naotoshi , Maehara Hiroki , Tsuchiya Hiroyuki , Kanaya Fuminori , Bouvet Michael , Hoffman Robert M. 
Published: June 2012

Abstract
Expression of integrin αvβ3 has been shown to be associated with tumor progression and metastasis in several types of cancer. To investigate the specific role of integrin αvβ3 expression in human osteosarcoma, we compared integrin αvβ3 expression in a series of osteosarcoma cell sublines (143B parental and LM1-LM4) with increasing metastatic potential. We quantified integrin αvβ3 expression using RT-PCR and Western-blotting. Integrin αvβ3 expression correlated with the metastatic potential of the cells, with the LM4 cells showing the highest expression and highest metastatic capability. LM4 in vitro cell proliferation decreased after treatment with echistatin, which is an antagonist of integrin αvβ3. In vitro migration and invasion of LM4 were also inhibited by echistatin. Tumor-induced angiogenesis by LM4 in the chick chorioallantoic membrane was also inhibited by echistatin. These data indicated that integrin αvβ3 overexpression may play a role in metastasis and that echistatin has potential as an inhibitor of cancer cell migration and 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 1686. doi:10.1158/1538-7445.AM2011-1686