bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1448: Novel ALK5 inhibitor as an anti-metastasis agent in both breast cancer cells in vitro and MMTV/cNeu transgenic mice in vivo
Authors: Park Chul-Yong , Kang Bo M. , Kwon In H. , Moon So J. , Son Jee Y. , Yoon Eun J. , Kim Dae-Kee , Sheen Yhun Y. 
Published: February 2011

Abstract
We have synthesized novel ALK5 inhibitors and investigated their effects of on breast cancer cells as well as tumor bearing MMTV/cNeu transgenic mice and orthotopically injected mice. The treatment of ALK5 inhibitors into breast tumor bearing MMTV/cNeu transgenic mice and orthotopically injected mice inhibited lung metastasis compared to that of untreated animal. The level of ß-casein in the lung of the breast tumor bearing MMTV/cNeu transgenic mice and orthotopically injected mice were decreased by ALK5 inhibitor treatment. The levels of CXCR4, MMP2 and MMP9 were decreased in the lung and breast tumor of ALK5 inhibitors treated breast tumor bearing MMTV/cNeu transgenic mice and orthotopically injected mice. The action mechanisms of new ALK5 inhibitors were investigated in both breast cancer cells and breast cancer mice model. TGFß signaling, phosphorylated smad2/3 based from the western blot analysis in vitro and in vivo as well as confocal microscopic analysis in vitro was decreased by ALK5 inhibitors. And also, results from wound healing assay and invasion assay showed strong inhibition of TGFß action by new ALK5 inhibitors. This data strongly argue that ALK5 inhibitors have anti-metastasis effects via inhibiting ALK5 activity in vivo and in vitro. In order to gain further insight into the mechanism of ALK5 inhibitor, we have carried out experiment to examine the effects of ALK5 inhibitor in human breast cancer MDA-MB-231 cell. TGFß stimulated mesenchymal markers of epithelial mesenchymal transition (EMT), such as Snail, TWIST, N-cadherin and these were inhibited by ALK5 inhibitor concomitant treatment. Also, TGFß increased tumor invasion markers such as MMP2, and MMP9 which were inhibited by ALK5 inhibitor concomitant treatment. In addition, ALK5 inhibitors recover the level of E-cadherin, SnoN, Ski which were downregulated by TGFß treatment. In summary, ALK5 inhibitors have anti-metastatic effect on human breast cancer cells as well as tumor bearing MMTV/cNeu transgenic mice.
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 1448.
Abstract 1449: Chronic consumption of a high fat diet increases solid tumor growth and lung metastasis in BALB/c mice subcutaneously injected with CT26 colon cancer cells
Authors: Park Heesook , Song Hyerim , Park Jung Han Yoon 
Published: February 2011

Abstract
Epidemiological and laboratory animal studies suggest that dietary factors in general and specifically high dietary fat and calories increase the risk of colon cancer. In the present study, we determined whether dietary fat increases solid tumor growth and metastasis of colon cancer using a CT26 mouse colon cancer xenograft model. Four-week old, male BALB/c mice was fed a purified diet containing 34.9% (w/w) fat (high fat diet, HFD), or 4.3% fat (low fat diet, LFD) for a period of 16 weeks. After 16 weeks, CT26 colon cancer cells were injected subcutaneously into the animals’ right flank. 5 weeks after cell injection, animals were killed. The mean body weight was slightly increased in the HFD group (33.9 ± 0.46 g) as compared to the LFD group (31.9 ± 0.37 g). The weights of the liver, lung, and epididymal fat pad were also increased in animals fed the high fat diet. Solid tumor growth (tumor volumes and weights) and the number and volume of tumor nodules in the lung were markedly increased in the HFD group as compared to the LFD group. Immunohistochemical staining of tumor tissues revealed that the expression of proliferating cell nuclear antigen (PCNA), platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31, an angiogenesis marker), vascular endothelial growth factor, and phospho-tyrosine phosphatase (CD 45, a monocytes/macrophage marker) was markedly increased in the HFD group as compared to those in the LFD group. Results from cytokine array revealed that the expression of IFN-γ, IL-1ra, IL-16, CXCL9, MIP-2, CCL5, and TNF-α was up-regulated in the sera of the HFD group as compared to the LFD group. These results indicate that increases in angiogenesis, infiltration of monocytes and cytokine expression probably contribute to increased tumor growth and lung metastasis in mice fed the high fat diet.
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 1449.
Abstract 1453: Effect of systemic administration of chromogranin A on tumor metastatization in animal models
Authors: Dondossola Eleonora , Crippa Luca , Colombo Barbara , Gasparri Anna , Curnis Flavio , Corti Angelo 
Published: February 2011

Abstract
Chromogranin A (CgA), an acidic glycoprotein present within secretory vesicles of many normal and neoplastic endocrine and neuroendocrine cells, is abnormally released in circulation in patients with neuroendocrine tumors. We have previously shown that local production of CgA can affect tumor growth by affecting the tumor microenvironment. Furthermore, we have recently shown that circulating CgA is increased also in a subpopulation of patients with non small cell lung cancer (NSCLC), with important prognostic implications. The present study was undertaken to investigate the role of CgA in tumor metastatization. We have found that systemic administration of CgA to mice can inhibit the number of lung metastasis formed by B16F10 mouse melanoma and by TS/A mouse mammary adenocarcinoma cells, when these cells were injected into the tail vein. The dose-response curve was bell-shaped, maximal effects being obtained with a dose of 0.2 ug/mouse administered daily (i.v for four days after tumor cell injection). Remarkably, this dose produced circulating levels similar to those found in NSCLC patients. The CgA1-78 N-terminal fragment (called vasostatin-1, VS-1) was sufficient to exert anti-metastatic effects in both models, suggesting that the N-terminal region of CgA contains a bioactive site. CgA could also inhibit B16F10 cell migration and invasion in vitro, and vessel formation in different in vitro and in vivo angiogenic assays. These results suggest that abnormal levels of circulating CgA in cancer patients can contribute to regulate tumor metastatization, possibly by affecting different steps of the metastatic cascade.
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 1453.
Abstract 1454: Telomerase-specific adenoviral labeling and treatment of hepatocellular carcinoma
Authors: Kishimoto Hiroyuki , Urata Yasuo , Fujiwara Toshiyoshi , Bouvet Michael , Hoffman Robert M. 
Published: February 2011

Abstract
We previously constructed telomerase-specific replication-selective adenoviruses OBP-301 (Telomelysin) and OBP-401 which contains the GFP gene (Telomelysin-GFP, TelomeScan). The replication of these adenoviruses is regulated by a human telomerase transcriptase (hTERT) promoter and allows specific targeting and labeling of tumor cells in vivo (Proc. Natl. Acad. Sci. USA, 1-6, 14514-14517, 2009 and Molecular Cancer Therapeutics 8, 3001-3008, 2009). The aim of this study was to validate systemic injection of these telomerase-specific replicating adenoviruses for in vivo hepatocellular carcinoma (HCC) GFP labeling and tumor-cell killing. We assessed the antitumor efficacy and the tumor labeling ability of the adenoviruses in an orthotopic mouse model using the Hep3B-GFP human HCC cell line. Biweekly i.v. treatment of OBP-301 caused a significant inhibition in liver tumor growth and showed a reduction in the number of liver tumor nodules compared to controls. To assess the GFP tumor labeling ability of OBP-401 for HCC, an orthotopic liver tumor model of unlabeled Hep3B was used. After i.v. injection of OBP-401, the liver tumors were labeled with GFP and visualized by fluorescence imaging. These results suggest that the two viruses, OBP-301 and OBP-401, when administrated systemically, are novel anticancer agents and labeling tools for HCC, respectively, with potential for human use.
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 1454.
Abstract 1457: Intraoperative contrast-enhanced ultrasonography using perflubutane for liver resection
Authors: Uetake Hiroyuki , Ishikawa Toshiaki , Mitsunori Yusuke , Tanaka Shinji , Arii Shigeki , Sugihara Kenichi 
Published: February 2011

Abstract
[Background] Bevacizumab (Bmab) is now widely used for metastatic colorectal cancer (CRC) treatment in the world. Through the high response of metastatic CRC to Bmab combination therapy, neoadjuvant chemotherapy using Bmab plus FOLFOX is a new strategy for the treatment of liver metastasis. As liver metastases shows high shrinkage by Bmab plus FOLFOX therapy, intraoperative contrast-enhanced ultrasonography using perflubutane (SONAZOIDTM) is supposed to be effective for complete detection and resection of small metastatic lesion after chemotherapy. [Material and methods] Forty-five patients with metastatic CRC were underwent Bmab combination chemotherapy in our institute (response rate and disease control rate was 72% and 94%, respectively). Among them, 8 patient (18%) were underwent liver resection after Bmab+mFOLFOX6 treatment. Median cycle of preoperative chemotherapy was 6.5 (5-17). [Result] By CT angiography, 52 liver metastases were detected before chemotherapy and 27 after chemotherapy. By intraoperative contrast-enhanced ultrasonography using SONAZOIDTM, 31 liver tumors were detected and resected. In histological examination, 13 of the resected 31 lesion (41%) were without viable cancer cell (pCR). [Conclusion] Intraoperative contrast-enhanced ultrasonography was effective for complete resection of liver metastasis after Bmab plus FOLFOX therapy. High pCR rate for liver metastasis was observed by Bmab plus FOLFOX therapy.
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 1457.
Abstract 1459: Proteomic identification of a novel antitumor protein from myeloid-derived suppressor cells in breast cancer
Authors: Boutte Angela , Lin Charles 
Published: February 2011

Abstract
Myeloid derived suppressor cells (MDSCs) are significantly increased in hematopoietic organs of cancer patients and animals bearing tumors. The number of MDSCs is directly proportional to tumor malignancy. MDSCs infiltrate into tumors and facilitate tumor progression and metastasis. In searching for molecular mediators responsible for tumor metastasis, we used proteomics and mass spectrometry in combination with a mammary tumor model that includes two distinct tumor cell lines, 67NR and 4T1, which are derived from a single mammary tumor. While these cell lines form primary tumors with equivalent growth kinetics, they differ dramatically in their metastatic potential. MDSCs were isolated from spleens of tumor-bearing mice and compared for protein expression profiles using 2D-DIGE-MS. There was a significant reduction of a novel protein, neutrophilic granule protein (NGP), in MDSCs from 4T1- compared to 67NR- tumor-bearing mice. Further analysis showed that NGP was expressed in myeloid cells, but not in epithelial tumor cells. Addition of 4T1 tumor cell conditioned media decreased the gene expression in promyelocyte cells. Computational analysis of NGP indicates presence of a putative cystatin domain, a known cathepsin inhibitor site. Indeed, forced expression of NGP in cultured cells inhibited endogenous cathepsin B activity. Since cathepsins have been linked to tumor invasion and metastasis, we postulated that NGP has an anti-tumor role. To test this hypothesis, we generated 4T1 cells stably expressing NGP (4T1-NGP) or empty vector (4T1-Vec), and found that expression of NGP in tumor cells inhibited Matrigel invasion, but not cell proliferation. Furthermore, implantation of 4T1-NGP cells in mammary pad of syngeneic Balb/c mice resulted in a significant reduction of primary tumor growth and lung metastasis. Histological examination reveals reduced tumor angiogenesis and increased apoptosis. Collectively, this study identified a novel protein, NGP, in MDSCs acts as a negative mediator of tumor growth and metastasis, likely through inhibition of cathepsin activity. Down-regulation of NGP in the tumor microenvironment contributes to tumor growth and metastasis. NGP may act as a novel protease inhibitor and may be a therapeutic target for 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 1459.
Abstract 1465: Histone deacetylase inhibitor suberoylanilide hydroxamic acid blocks epithelial-mesenchymal transition exhibited by Tera-2 embryonal carcinoma cells with a stem cell phenotype
Authors: Chu Khoi , Player Audrey N. , Pickei Ross , Robertson Fredika M. 
Published: February 2011

Abstract
The process of epithelial-mesenchymal transition (EMT) is associated with tumor progression. Tumor cells that undergo EMT have altered morphology and acquire a stem cell phenotype. Although there are numerous studies that demonstrate that shRNA approaches targeting specific transcription factors can block EMT, there are few pharmacological agents yet identified that can alter the process of EMT. Recent evidence suggests that the silencing of E-cadherin during EMT is dependent upon the activity of specific histone deacetylyase enzymes, which are known to regulate gene transcription. We used Tera-2 (HTB 106) embryonal carcinoma cells grown as 3 dimensional spheroids as a model of a tumor type characterized by a cancer stem cell phenotype. We observed that the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA; vorinostat; Zolinza®, Merck), which is FDA approved for treatment of cutaneous T cell lymphoma, significantly inhibited expression of over 55 distinct genes associated with EMT including those regulating responses to growth factors, adhesion, motility, and genes associated with maintenance/survival of stem cells, including Alpha 5 Integrin/fibronectin receptor alpha (ITGA5), Caldesmon 1 (CALD1), Epidermal growth factor receptor (EGFR), Forkhead box C2 (MFH-1, mesenchyme forkhead 1) (FOXC2), Glycogen synthase kinase 3 beta (GSK3 beta), Jagged 1 (JAG1), Integrin-linked kinase (ILK), Matrix metallopeptidase 2 (MMP2), Notch 1 homolog (NOTCH1), Platelet-derived growth factor receptor beta (PDGFb), Snail homolog 1 (SNAI1), Snail homolog 2 (SNAI2), Transcription factor 4 (TCF4), transforming growth factorβ1 (TGFβ1), Twist homolog 1 (Twist1), Wingless-type MMTC integration site family, member 5b (WNT5b), and Zinc finger E-box binding homeobox 2 (ZEB2). SAHA also altered the morphology of Tera-2 cells when cultured as adherent cells, which was associated with inhibited of both invasion, and anchorage independent growth in soft agar. In addition, SAHA inhibited the self-renewal capacity of Tera-2 tumor spheroids, which was associated with changes in expression of stem cell surface markers. Studies are ongoing to identify the HDAC enzymes that regulate expression of genes associated with the process of EMT and maintenance/survival of Tera-2 tumor spheroids that are targeted by SAHA. These studies suggest that HDAC inhibitors may be promising agents to reverse the process of EMT and may be potentially effective as inhibitors of tumor 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 1465.
Abstract 1468: Antagonism of platelet-derived growth factor receptor-α as a potential therapeutic for prostate cancer bone metastases
Authors: Russell Mike R. , Liu Qingxin , Lei Hetian , Kazlauskas Andrius , Fatatis Alessandro 
Published: February 2011

Abstract
Prostate adenocarcinoma is the second leading cause of cancer death among men, due primarily to the fact that the majority of prostate cancers will eventually spread to the skeleton. Metastatic dissemination requires a complex series of coordinated events that result in cells that escape from the primary tumor into the circulation and eventually colonize distant organs. The ability of disseminated cancer cells to evolve into metastases of clinically significant size depends strongly on their compatibility with, and ability to utilize, this new micro-environment. We previously showed that bone-metastatic prostate cancer cells exposed to human bone marrow respond by activation of cell survival pathways, such as PI3K/Akt., and that these events are mediated by the alpha-receptor for platelet-derived growth factor (PDGFRα). We also have shown that prophylactic antagonism of this receptor using IMC-3G3, a monoclonal, humanized antibody currently in phase II trials, was able to significantly reduce tumor burden in an in vivo model of skeletal metastasis.
Here we show that IMC-3G3 can be used in a curative manner to reduce the growth of previously established skeletal lesions. In addition, we have successfully combined this antibody with zoledronic acid, a bisphosphonate commonly used to treat skeletal metastases, with encouraging results. Interestingly, treatment with a monoclonal antibody targeting only host PDGFRα failed to show any significant difference over saline treated mice.
Lastly, we sought to dissect the mechanism by which PDGFRα may exert its role within the bone microenvironment. We provide evidence that soluble components of human bone marrow can activate PDGFRα through a mechanism that does not require the canonical binding of PDGF ligand(s) to the receptor. To establish the relevance of this phenomenon in vivo, we employed a PDGFRα mutant lacking the extracellular ligand-binding domain. Our studies show that this truncated PDGFRα was able to restore bone-metastatic potential of prostate cancer cells as effectively as the full-length form of the receptor. In addition, we have found that expression of PDGFRα, and its related signaling events, results in the regulation of a specific set of genes that we believe may aid in the survival and growth of metastatic prostate cancer cells within the bone. Studies to understand the contribution of several of these putative bone metastatic genes are currently underway in our laboratory.
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 1468.
Abstract 1470: 15-Deoxy-Δ12,14-prostaglandin J2 up-regulates expression of p53 and p21 through Nrf2-driven heme oxygenase-1 induction in human breast cancer (MCF-7) cells
Authors: Kim Do-Hee , Song Na-Young , Na Hye-Kyung , Kim Eun-Hee , Surh Young-Joon 
Published: February 2011

Abstract
Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that has antioxidant and cytoprotective functions. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand of peroxisome proliferator-activated receptor γ (PPARγ), has been reported to induce HO-1 and other antioxidant enzymes in certain cell lines. In the present work, we investigated the effects of HO-1 on the expression of p53 and p21 induced by 15d-PGJ2 in human breast cancer (MCF-7) cells. Treatment of MCF-7 cells with 15d-PGJ2 (30 μM) led to time-dependent increases in the expression of p53 and p21 as well as HO-1. The up-regulation of p53 and p21 expression by 15d-PGJ2 was abrogated by pharmacological inhibition with zinc protophophyrin (10 μM) or si-RNA knock down of HO-1. Nrf2, a basic-leucine zipper transcription factor, plays a key role in regulating the up-regulation of many antioxidant enzymes including HO-1. In MCF-7 cells transfected with NRF2 si-RNA, 15d-PGJ2 failed to induce expression of p53, p21 and HO-1. In addition, HO-1 inducers, such as cobalt protoporphyrin (25 μM) and hemin (10 μM), upregulated the expression of p53 and p21 without eliciting any apparent cytotoxicity. HO-1 degrades heme to produce iron, biliverdin, and carbon monoxide. We hypothesize that iron, a by-product of HO-1-catalyzed reactions, could mediate 15d-PGJ2-induced expression p53 and p21. Up-regulation of p53 and p21 expression by 15d-PGJ2 was abrogated by the iron chelator desferrioxamine (25 μM) in MCF-7 cells. Iron released from heme by HO-1 activity is mostly in the ferrous (Fe2+) form. When MCF-7 cells were treated with the iron-specific chelator phenanathroline (10 μM), 15d-PGJ2-induced expression of p53 and p21 was attenuated. However, p53 induction by 15d-PGJ2 was not affected by GW9662, a PPARγ antagonist. In addition, levels of the iron-sequestering protein H-ferritin were induced by 15d-PGJ2 in MCF-7 cells. Addition of the antioxidant N-acetylcysteine lowered the 15d-PGJ2-mediated H-ferritin levels. Recently, it has been reported that p21 as a positive regulator of Nrf2 extends the prosurvival function of p53 through recruitment of stress-response genes. Up-regulation of p53 and p21 expression via Nrf2-driven HO-1 induction and subsequent release of iron together with elevated expression of H-ferritin may confer resistance to oxidative damage in MCF-7 cells.
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 1470.